TJTES 2020-5 by KAREPUBLISHING

ISSN 1306 - 696X

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi

Volume 26 | Number 5 | September 2020

www.tjtes.org

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi Editor-in-Chief Mehmet Kurtoğlu Editors M. Mahir Özmen Mehmet Eryılmaz Publication Coordinator Mehmet Eryılmaz Former Editors Ömer Türel, Cemalettin Ertekin, Korhan Taviloğlu, Recep Güloğlu Section Editors Anaesthesiology & ICU Güniz Meyancı Köksal, Mert Şentürk Cardiac Surgery Münacettin Ceviz, Murat Güvener Neurosurgery Ahmet Deniz Belen, Mehmet Yaşar Kaynar Ophtalmology Cem Mocan, Ali Hakan Durukan Ortopedics and Traumatology Mahmut Nedim Doral, Ali Erşen Plastic and Reconstructive Surgery Figen Özgür, Atakan Aydın Pediatric Surgery Aydın Yağmurlu, Ebru Yeşildağ Thoracic Surgery Alper Toker, Akif Turna Urology Ali Atan, Öner Şanlı Vascular Surgery Cüneyt Köksoy, Mehmet Kurtoğlu Emergency Medicine Burak Katipoğlu, Bülent Erbil Gynecology and Obstetrics Recep Has, Kazım Emre Karaşahin

www.tjtes.org

THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ President (Başkan) Vice President (2. Başkan) Secretary General (Genel Sekreter) Treasurer (Sayman) Members (Yönetim Kurulu Üyeleri)

Orhan Alimoğlu Mehmet Eryılmaz Ali Fuat Kaan Gök Gökhan Akbulut Osman Şimşek Münevver Moran Adnan Özpek

ISSUED BY THE TURKISH ASSOCIATION OF TRAUMA AND EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ YAYIN ORGANI Owner (Ulusal Travma ve Acil Cerrahi Derneği adına Sahibi) Editorial Director (Yazı İşleri Müdürü) Managing Editor (Yayın Koordinatörü) Publication Secretary (Yayın Sekreteri) Emblem (Amblem) Correspondence address (Yazışma adresi) Tel Fax (Faks)

Orhan Alimoğlu Orhan Alimoğlu M. Mahir Özmen Kerem Ayar Metin Ertem Ulusal Travma ve Acil Cerrahi Dergisi Sekreterliği Şehremini Mah., Köprülü Mehmet Paşa Sok., Dadaşoğlu Apt., No: 25/1, 34104 Şehremini, İstanbul +90 212 - 531 12 46 - 588 62 46 +90 212 - 586 18 04

p-ISSN 1306-696x • e-ISSN 1307-7945 • Included in Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), DOAJ, EBSCO, and Turkish Medical Index (Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), DOAJ, EBSCO ve TÜBİTAK ULAKBİM Türk Tıp Dizini’nde yer almaktadır.) Publisher (Yayımcı): KARE Yayıncılık (KARE Publishing) • www.kareyayincilik.com • Design (Tasarım): Ali Cangül • Graphics (Grafikler): Edibe Çomaktekin • Linguistic Editor (İngilizce Editörü): Suzan Atwood • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): September (Eylül) 2020 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

www.tjtes.org

INFORMATION FOR THE AUTHORS The Turkish Journal of Trauma and Emergency Surgery (TJTES) is an official publication of the Turkish Association of Trauma and Emergency Surgery. It is a peer-reviewed periodical that considers for publication clinical and experimental studies, case reports, technical contributions, and letters to the editor. Six issues are published annually.

manuscript title, author names and institutions and correspondence address, abstract in Turkish (for Turkish authors only), and title and abstract in English are uploaded to the Journal Agent system in the relevant steps. The main text includes Introduction, Materials and Methods, Results, Discussion, Acknowledgments, References, Tables and Figure Legends.

As from 2001, the journal is indexed in Index Medicus and Medline, as from 2005 in Excerpta Medica and EMBASE, as from 2007 in Science Citation Index Expanded (SCI-E) and Journal Citation Reports / Science Edition, and as from 2014 in EBSCOhost. Our impact factor in SCI-E indexed journals is 0.643 (JCR 2019). It is cited as ‘Ulus Travma Acil Cerrahi Derg’ in PubMed.

The cover letter must contain a brief statement that the manuscript has been read and approved by all authors, that it has not been submitted to, or is not under consideration for publication in, another journal. It should contain the names and signatures of all authors. The cover letter is uploaded at the 10th step of the “Submit New Manuscript” section, called “Upload Your Files”.

Submission of a manuscript by electronic means implies: that the work has not been published before (except in the form of an abstract or as part of a published lecture, review, or thesis); that it is not under consideration for publication elsewhere; and that its publication in the Turkish Journal of Trauma and Emergency Surgery is approved by all co-authors. The author(s) transfer(s) the copyright to the Turkish Association of Trauma and Emergency Surgery to be effective if and when the manuscript is accepted for publication. The author(s) guarantee(s) that the manuscript will not be published elsewhere in any other language without the consent of the Association. If the manuscript has been presented at a meeting, this should be stated together with the name of the meeting, date, and the place.

Abstract: The abstract should be structured and serve as an informative guide for the methods and results sections of the study. It must be prepared with the following subtitles: Background, Methods, Results and Conclusions. Abstracts should not exceed 200 words.

Manuscripts must be submitted in English. All submissions are initially reviewed by the editor, and then are sent to reviewers. All manuscripts are subject to editing and, if necessary, will be returned to the authors for answered responses to outstanding questions or for addition of any missing information to be added. For accuracy and clarity, a detailed manuscript editing is undertaken for all manuscripts accepted for publication. Final galley proofs are sent to the authors for approval. Unless specifically indicated otherwise at the time of submission, rejected manuscripts will not be returned to the authors, including accompanying materials. TJTES is indexed in Science Citation Index-Expanded (SCI-E), Index Medicus, Medline, EMBASE, Excerpta Medica, and the Turkish Medical Index of TUBITAK-ULAKBIM. Priority of publications is given to original studies; therefore, selection criteria are more refined for reviews and case reports. Submission Fee: In order to further improve the quality and accessibility of the journal, a fee will be charged as a contribution to the cost of production. This fee will be charged during the process of application of submitted articles and will be charged regardless of eventual acceptance/rejection of the manuscript. Foreign authors can complete the article submission process after depositing USD 100.- to the USD account below. The article number released at the last stage of the article upload process must be written in the bank shipment description section. Recipient: ULUSAL TRAVMA VE ACIL CERRAHI DERNEGI IKTISADI ISLETMESI IBAN: TR02 0006 4000 0021 0490 9277 35 (USD) Turkish authors can complete the article submission process after depositing 500.- TL to the account below. The article number released at the last stage of the article upload process must be written in the bank shipment description section. Alıcı: ULUSAL TRAVMA VE ACİL CERRAHİ DERNEĞİ İKTİSADİ İŞLETMESİ IBAN: TR37 0006 4000 0021 0491 5103 66 (Türk Lirası Hesabı) Open Access Policy: Full text access is free. There is no charge for downloading the full text of printed material. Manuscript submission: TJTES accepts only on-line submission via the official web site (please click, www.travma.org.tr/en) and refuses printed manuscript submissions by mail. All submissions are made by the on-line submission system called Journal Agent, by clicking the icon “Online manuscript submission” at the above mentioned web site homepage. The system includes directions at each step but for further information you may visit the web site (http://www.travma.org/en/journal/). Manuscript preparation: Manuscripts should have double-line spacing, leaving sufficient margin on both sides. The font size (12 points) and style (Times New Roman) of the main text should be uniformly taken into account. All pages of the main text should be numbered consecutively. Cover letter,

Figures, illustrations and tables: All figures and tables should be numbered in the order of appearance in the text. The desired position of figures and tables should be indicated in the text. Legends should be included in the relevant part of the main text and those for photomicrographs and slide preparations should indicate the magnification and the stain used. Color pictures and figures will be published if they are definitely required and with the understanding that the authors are prepared to bear the costs. Line drawings should be professionally prepared. For recognizable photographs, signed releases of the patient or of his/her legal representatives should be enclosed; otherwise, patient names or eyes must be blocked out to prevent identification. References: All references should be numbered in the order of mention in the text. All reference figures in the text should be given in brackets without changing the font size. References should only include articles that have been published or accepted for publication. Reference format should conform to the “Uniform requirements for manuscripts submitted to biomedical journals” (http://www.icmje.org) and its updated versions (February 2006). Journal titles should be abbreviated according to Index Medicus. Journal references should provide inclusive page numbers. All authors, if six or fewer, should be listed; otherwise the first six should be listed, followed by “et al.” should be written. The style and punctuation of the references should follow the formats below: Journal article: Velmahos GC, Kamel E, Chan LS, Hanpeter D, Asensio JA, Murray JA, et al. Complex repair for the management of duodenal injuries. Am Surg 1999;65:972-5. Chapter in book: Jurkovich GJ. Duodenum and pancreas. In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: McGraw-Hill; 2000. p. 735-62. Our journal has succeeded in being included in several indexes, in this context, we have included a search engine in our web site (www.travma.org.tr) so that you can access full-text articles of the previous issues and cite the published articles in your studies. Review articles: Only reviews written by distinguished authors based on the editor’s invitation will be considered and evaluated. Review articles must include the title, summary, text, and references sections. Any accompanying tables, graphics, and figures should be prepared as mentioned above. Case reports: A limited number of case reports are published in each issue of the journal. The presented case(s) should be educative and of interest to the readers, and should reflect an exclusive rarity. Case reports should contain the title, summary, and the case, discussion, and references sections. These reports may consist of maximum five authors. Letters to the Editor: “Letters to the Editor” are only published electronically and they do not appear in the printed version of TJTES and PUBMED. The editors do not issue an acceptance document as an original article for the ‘’letters to the editor. The letters should not exceed 500 words. The letter must clearly list the title, authors, publication date, issue number, and inclusive page numbers of the publication for which opinions are released. Informed consent - Ethics: Manuscripts reporting the results of experimental studies on human subjects must include a statement that informed consent was obtained after the nature of the procedure(s) had been fully explained. Manuscripts describing investigations in animals must clearly indicate the steps taken to eliminate pain and suffering. Authors are advised to comply with internationally accepted guidelines, stating such compliance in their manuscripts and to include the approval by the local institutional human research committee.

YAZARLARA BİLGİ Ulusal Travma ve Acil Cerrahi Dergisi, Ulusal Travma ve Acil Cerrahi Derneği’nin yayın organıdır. Travma ve acil cerrahi hastalıklar konularında bilimsel birikime katkısı olan klinik ve deneysel çalışmaları, editöryel yazıları, klinik olgu sunumlarını ve bu konulardaki teknik katkılar ile son gelişmeleri yayınlar. Dergi iki ayda bir yayınlanır. Ulusal Travma ve Acil Cerrahi Dergisi TÜBİTAK TR Dizinde taranmaktadır, ayrıca uluslararası indekslerde, 2001 yılından itibaren Index Medicus, PubMed’de, 2005 yılından itibaren EMBASE’de, 2007 yılından itibaren Web of Science, Science Citation Index-Expanded’de (SCI-E), 2014 yılından itibaren de EBSCOhost indeksinde dizinlenmektedir. 2018 Journal Citation Report IF puanımız 0.643 olmuştur. Dergide araştırma yazılarına öncelik verilmekte, bu nedenle derleme veya olgu sunumu türündeki yazılarda seçim ölçütleri daha dar tutulmaktadır. PUBMED’de dergi “Ulus Travma Acil Cerrahi Derg” kısaltması ile yer almaktadır. Dergiye yazı teslimi, çalışmanın daha önce yayınlanmadığı (özet ya da bir sunu, inceleme, ya da tezin bir parçası şeklinde yayınlanması dışında), başka bir yerde yayınlanmasının düşünülmediği ve Ulusal Travma ve Acil Cerrahi Dergisi’nde yayınlanmasının tüm yazarlar tarafından uygun bulunduğu anlamına gelmektedir. Yazar(lar), çalışmanın yayınlanmasının kabulünden başlayarak, yazıya ait her hakkı Ulusal Travma ve Acil Cerrahi Derneği’ne devretmektedir(ler). Yazar(lar), izin almaksızın çalışmayı başka bir dilde ya da yerde yayınlamayacaklarını kabul eder(ler). Gönderilen yazı daha önce herhangi bir toplantıda sunulmuş ise, toplantı adı, tarihi ve düzenlendiği şehir belirtilmelidir. Dergide İngilizce yazılmış makaleler yayınlanır. Tüm yazılar önce editör tarafından ön değerlendirmeye alınır; daha sonra incelenmesi için danışma kurulu üyelerine gönderilir. Tüm yazılarda editöryel değerlendirme ve düzeltmeye başvurulur; gerektiğinde, yazarlardan bazı soruları yanıtlanması ve eksikleri tamamlanması istenebilir. Dergide yayınlanmasına karar verilen yazılar “manuscript editing” sürecine alınır; bu aşamada tüm bilgilerin doğruluğu için ayrıntılı kontrol ve denetimden geçirilir; yayın öncesi şekline getirilerek yazarların kontrolüne ve onayına sunulur. Editörün, kabul edilmeyen yazıların bütününü ya da bir bölümünü (tablo, resim, vs.) iade etme zorunluluğu yoktur. Makale Gönderim Ücreti (Submission Fee): Dergimizin maliyetine katkı olarak, gönderilen makalelerde “başvurusu sırasında; kabul/red şartına bağlı olmaksızın” ücretlendirme yapılacaktır. Türk yazarlar aşağıdaki hesaba 500.- TL yatırdıktan sonra makale gönderim işlemini tamamlayabilirler. Alıcı: Ulusal Travma ve Acil Cerrahi Derneği IBAN: TR37 0006 4000 0021 0491 5103 66 (T. İş Bankası) (Banka gönderisi açıklama kısmına, makale yükleme işlemi sırasında son aşamadaki çıkacak makale numarası mutlaka yazılmalıdır). Açık Erişim İlkesi: Tam metinlere erişim ücretsizdir. Yayınlanan basılı materyali tam metni indirmek için herhangi bir ücret alınmaz. Yazıların hazırlanması: Tüm yazılı metinler 12 punto büyüklükte “Times New Roman” yazı karakterinde iki satır aralıklı olarak yazılmalıdır. Sayfada her iki tarafta uygun miktarda boşluk bırakılmalı ve ana metindeki sayfalar numaralandırılmalıdır. Journal Agent sisteminde, başvuru mektubu, başlık, yazarlar ve kurumları, iletişim adresi, Türkçe özet ve yazının İngilizce başlığı ve özeti ilgili aşamalarda yüklenecektir. İngilizce yazılan çalışmalara da Türkçe özet eklenmesi gerekmektedir. Yazının ana metnindeyse şu sıra kullanılacaktır: Giriş, Gereç ve Yöntem, Bulgular, Tartışma, Teşekkür, Kaynaklar, Tablolar ve Şekiller. Başvuru mektubu: Bu mektupta yazının tüm yazarlar tarafından okunduğu, onaylandığı ve orijinal bir çalışma ürünü olduğu ifade edilmeli ve yazar isimlerinin yanında imzaları bulunmalıdır. Başvuru mektubu ayrı bir dosya olarak, Journal Agent sisteminin “Yeni Makale Gönder” bölümünde, 10. aşamada yer alan dosya yükleme aşamasında yollanmalıdır. Başlık sayfası: Yazının başlığı, yazarların adı, soyadı ve ünvanları, çalışmanın yapıldığı kurumun adı ve şehri, eğer varsa çalışmayı destekleyen fon ve kuruluşların açık adları bu sayfada yer almalıdır. Bu sayfaya ayrıca “yazışmadan sorumlu” yazarın isim, açık adres, telefon, faks, mobil telefon ve e-posta bilgileri eklenmelidir. Özet: Çalışmanın gereç ve yöntemini ve bulgularını tanıtıcı olmalıdır. Türkçe özet, Amaç, Gereç ve Yöntem, Bulgular, Sonuç ve Anahtar Sözcükler başlıklarını; İngilizce özet Background, Methods, Results, Conclusion ve Key words başlıklarını içermelidir. İngilizce olarak hazırlanan çalışmalarda da Türkçe özet yer almalıdır. Özetler başlıklar hariç 190210 sözcük olmalıdır.

Tablo, şekil, grafik ve resimler: Şekillere ait numara ve açıklayıcı bilgiler ana metinde ilgili bölüme yazılmalıdır. Mikroskobik şekillerde resmi açıklayıcı bilgilere ek olarak, büyütme oranı ve kullanılan boyama tekniği de belirtilmelidir. Yazarlara ait olmayan, başka kaynaklarca daha önce yayınlanmış tüm resim, şekil ve tablolar için yayın hakkına sahip kişilerden izin alınmalı ve izin belgesi dergi editörlüğüne ayrıca açıklamasıyla birlikte gönderilmelidir. Hastaların görüntülendiği fotoğraflara, hastanın ve/veya velisinin imzaladığı bir izin belgesi eşlik etmeli veya fotoğrafta hastanın yüzü tanınmayacak şekilde kapatılmış olmalıdır. Renkli resim ve şekillerin basımı için karar hakemler ve editöre aittir. Yazarlar renkli baskının hazırlık aşamasındaki tutarını ödemeyi kabul etmelidirler. Kaynaklar: Metin içindeki kullanım sırasına göre düzenlenmelidir. Makale içinde geçen kaynak numaraları köşeli parantezle ve küçültülmeden belirtilmelidir. Kaynak listesinde yalnızca yayınlanmış ya da yayınlanması kabul edilmiş çalışmalar yer almalıdır. Kaynak bildirme “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” (http:// www.icmje.org) adlı kılavuzun en son güncellenmiş şekline (Şubat 2006) uymalıdır. Dergi adları Index Medicus’a uygun şekilde kısaltılmalıdır. Altı ya da daha az sayıda olduğunda tüm yazar adları verilmeli, daha çok yazar durumunda altıncı yazarın arkasından “et al.” ya da “ve ark.” eklenmelidir. Kaynakların dizilme şekli ve noktalamalar aşağıdaki örneklere uygun olmalıdır: Dergi metni için örnek: Velmahos GC, Kamel E, Chan LS, Hanpeter D, Asensio JA, Murray JA, et al. Complex repair for the management of duodenal injuries. Am Surg 1999;65:972-5. Kitaptan bölüm için örnek: Jurkovich GJ. Duodenum and pancreas. In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th ed. New York: McGraw-Hill; 2000. p. 735-62. Sizlerin çalışmalarınızda kaynak olarak yararlanabilmeniz için www.travma.org.tr adresli web sayfamızda eski yayınlara tam metin olarak ulaşabileceğiniz bir arama motoru vardır. Derleme yazıları: Bu tür makaleler editörler kurulu tarafından gerek olduğunda, konu hakkında birikimi olan ve bu birikimi literatüre de yansımış kişilerden talep edilecek ve dergi yazım kurallarına uygunluğu saptandıktan sonra değerlendirmeye alınacaktır. Derleme makaleleri; başlık, Türkçe özet, İngilizce başlık ve özet, alt başlıklarla bölümlendirilmiş metin ile kaynakları içermelidir. Tablo, şekil, grafik veya resim varsa yukarıda belirtildiği şekilde gönderilmelidir. Olgu sunumları: Derginin her sayısında sınırlı sayıda olgu sunumuna yer verilmektedir. Olgu bildirilerinin kabulünde, az görülürlük, eğitici olma, ilginç olma önemli ölçüt değerlerdir. Ayrıca bu tür yazıların olabildiğince kısa hazırlanması gerekir. Olgu sunumları başlık, Türkçe özet, İngilizce başlık ve özet, olgu sunumu, tartışma ve kaynaklar bölümlerinden oluşmalıdır. Bu tür çalışmalarda en fazla 5 yazara yer verilmesine özen gösterilmelidir. Editöre mektuplar: Editöre mektuplar basılı dergide ve PUBMED’de yer almamakta, ancak derginin web sitesinde yayınlanmaktadır. Bu mektuplar için dergi yönetimi tarafından yayın belgesi verilmemektedir. Daha önce basılmış yazılarla ilgili görüş, katkı, eleştiriler ya da farklı bir konu üzerindeki deneyim ve düşünceler için editöre mektup yazılabilir. Bu tür yazılar 500 sözcüğü geçmemeli ve tıbbi etik kurallara uygun olarak kaleme alınmış olmalıdır. Mektup basılmış bir yazı hakkında ise, söz konusu yayına ait yıl, sayı, sayfa numaraları, yazı başlığı ve yazarların adları belirtilmelidir. Mektup bir konuda deneyim, düşünce hakkında ise verilen bilgiler doğrultusunda dergi kurallarına uyumlu olarak kaynaklar da belirtilmelidir. Bilgilendirerek onay alma - Etik: Deneysel çalışmaların sonuçlarını bildiren yazılarda, çalışmanın yapıldığı gönüllü ya da hastalara uygulanacak prosedür(lerin) özelliği tümüyle anlatıldıktan sonra, onaylarının alındığını gösterir bir cümle bulunmalıdır. Yazarlar, bu tür bir çalışma söz konusu olduğunda, uluslararası alanda kabul edilen kılavuzlara ve T.C. Sağlık Bakanlığı tarafından getirilen yönetmelik ve yazılarda belirtilen hükümlere uyulduğunu belirtmeli ve kurumdan aldıkları Etik Komitesi onayını göndermelidir. Hayvanlar üzerinde yapılan çalışmalarda ağrı, acı ve rahatsızlık verilmemesi için neler yapıldığı açık bir şekilde belirtilmelidir. Yazı gönderme - Yazıların gönderilmesi: Ulusal Travma ve Acil Cerrahi Dergisi yalnızca www.travma.org.tr adresindeki internet sitesinden on-line olarak gönderilen yazıları kabul etmekte, posta yoluyla yollanan yazıları değerlendirmeye almamaktadır. Tüm yazılar ilgili adresteki “Online Makale Gönderme” ikonuna tıklandığında ulaşılan Journal Agent sisteminden yollanmaktadır. Sistem her aşamada kullanıcıyı bilgilendiren özelliktedir.

TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 26

Number - Sayı 5 September - Eylül 2020

Contents - İçindekiler Experimental Studies - Deneysel Çalışma 651-656 The effects of ozone on the acute phase of intestinal ischemia-reperfusion injury in rats Sıçanlarda ozonun bağırsak iskemi-reperfüzyon hasarının akut evresi üzerine etkisi Dere Günal Y, Boybeyi Türer Ö, Atasoy P, Kısa Ü, Aslan MK 657-662 Does ß-glucan can have a protective role against oxidative stress in the experimental sepsis model in rats? ß-glukan, sıçanlarda deneysel sepsis modelinde oksidatif strese karşı koruyucu rol oynayabilir mi? Demir M, Köse K, Yazıcı C, Sözüer EM 663-670 The efficacy of curcumin on PDGF expression and NF-kappa B pathway: TNBS-induced colitis Kurkumin’in PDGF ekspresyonu ve NF-kappa B üzerindeki etkisi: TNBS kolit modeli Altınel Y, Yalçın Ş, Ercan G, Yavuz E, Erçetin C, Gülçiçek OB, Çelik A, Özkaya G, Uzun H

Original Articles - Orijinal Çalışma 671-677 The completeness of the registration system and the economic burden of fatal injuries in Iran İran’da kayıt sisteminin bütünlüğü ve ölümcül yaralanmaların ekonomik yükü Ghodsi Z, Saadat S, Barzegar A, Alaeddini F, Rahimi-Movaghar V, Zafarghandi M, Sheikhazadi A, Sari AA, Salamati P 678-684 Efficacy of stomach-partitioning on gastric emptying in patients undergoing palliative gastrojejunostomy for malign gastric outlet obstruction Malign mide çıkış obstrüksiyonu nedeniyle palyatif gastrojejunostomi uygulanan hastalarda mide bölücü cerrahinin mide boşalmasına etkisi Yıldırım R, Candaş B, Usta MA, Türkyılmaz S, Çalık A, Güner A 685-692 The impacts of the COVID-19 outbreak on emergency department visits of surgical patients COVID-19 salgınının cerrahi hastaların acil servis başvuruları üzerine etkisi Göksoy B, Akça MT, İnanç ÖF 693-698 Penetrating cardiac trauma in stab wounds: A study of diagnostic accuracy of the cardiac area Kesici-delici alet yaralanmalarında penetran kardiyak travma: Kardiyak bölgenin doğru tanısına ilişkin bir çalışma Muñoz JHM, Dussan O, Ruiz F, Rubiano AM, Puyana JC 699-704 Diagnostic value of serum pentraxin 3 level in children with acute appendicitis Akut apandisitli çocuklarda serum pentraksin 3 düzeyinin tanısal değeri Duman L, Cesur Ö, Kumbul Doğuç D, Çelik S, Karaibrahimoğlu A, Savaş MÇ 705-712 Liver transplant versus non-liver transplant patients underwent appendectomy with presumed diagnosis of acute appendicitis: Case-control study Akut apandisit ön tanısı ile apendektomi yapılan karaciğer transplantlı ve transplant dışı hastaların karşılaştırılması: Olgu kontrol çalışması Sarıcı KB, Akbulut S, Koç C, Tuncer A, Yılmaz S 713-718 Does being a refugee affect prognosis in patients who underwent surgery due to peptic ulcer perforation? Peptik ülser perforasyonunun cerrahi tedavisinde mülteci olmak prognozu etkiler mi? Geriye dönük klinik çalışma Çıtlak G, Yurtteri ME, Soytaş Y, Yüksel S, Dinçer M, Ferlengez E 719-727 Guideline implementation and raising awareness for unintended perioperative hypothermia: Single-group “before and after” study İstenmeyen perioperatif hipotermi için farkındalık oluşturmak ve kılavuz implementasyonu: Tek gruplu “önce ve sonra” çalışması Şenkal S, Kara U 728-734 The concordance of optic nerve sheath diameter measurements with the clinical course in children with traumatic head injury Kafa travmalı çocuklarda optik sinir kılıf çapı ölçümlerinin klinik seyir ile uyumu Kavak RP, Özdemir M, Kavak N, Ertan N, Külah B 735-741 Relationship of mortality with neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume in patients undergoing acute abdominal surgery Akut karın cerrahisi geçiren hastalarda, nötrofil-lenfosit oranı, trombosit-lenfosit oranı ve ortalama trombosit hacminin mortalite ile ilişkisi Çolakoğlu ŞM, Genç Moralar D, Tok Çekmecelioğlu B, Hergünsel GO 742-745 Treatment of acute appendicitis: Urgent surgery or emergent surgery? Akut apandisit tedavisinde acil cerrahi veya gecikmiş cerrahinin yeri Bozkurt E, Celayir MF

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TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 26

Number - Sayı 5 September - Eylül 2020

Contents - İçindekiler 746-753 Comparison of early and delayed diagnosis of mortality in ERCP perforations: A high-volume patient experience ERCP perforasyonlarında erken ve gecikmiş tanının mortalite ile karşılaştırılması: Yüksek hacimli hasta deneyimi Borazan E, Konduk BT 754-759 Sedoanalgesia modality during laser photocoagulation for retinopathy of prematurity: Intraoperative complications and early postoperative follow-up Prematüre retinopatisinde lazer fotokoagülasyon sırasında sedoanaljezi yöntemi: İntraoperatif komplikasyonlar ve erken postoperatif takip Saylan S, Akdoğan A, Kader Ş, Tuğcugil E, Beşir A, Kola M, Aslan Y 760-764 The role of C-reactive protein to lymphocyte ratio in the differentiation of acute and perforated appendicitis Akut ve perfore apandisit ayırımında C-reaktif protein lefosit oranının rolü Koyuncu S, İsmail O 765-768 Pediatric head traumas: A different perspective Pediyatrik kafa travmaları: Farklı bir bakış açısı Yaşar S, Kırık A, Durmaz MO 769-776 The value of inflammatory markers in diagnosing acute appendicitis in pregnant patients Gebe hastalarda enflamatuvar belirteçlerin akut apandisit tanısı koymadaki değeri Akbaş A, Aydın Kasap Z, Hacım NA, Tokoçin M, Altınel Y, Yiğitbaş H, Meriç S, Okumuş B 777-783 Factors affecting the mortality at patients with burns: Single centre results Yanıklı hastalarda mortaliteyi etkileyen faktörler: Tek merkez sonuçları Temiz A, Albayrak A, Peksöz R, Dışcı E, Korkut E, Tanrıkulu Y, Albayrak Y 784-788 The efficacy of continuous lumbar drainage in post-traumatic cerebrospinal fluid fistulas Posttravmatik beyin omurilik sıvısı fistüllerinde kontinü lomber drenajın etkinliği Kırık A, Yaşar S 789-797 Intraperitoneal rupture of the hydatid cyst disease: Single-center experience and literature review Hidatik kist hastalığının periton içine rüptürü: Tek merkez deneyimi ve literatür analizi Koç C, Akbulut S, Şahin TT, Tuncer A, Yılmaz S 798-804 The mid-term effects on quality of life and foot functions following pilon fracture Pilon kırıkları sonrası ayak fonksiyonları ve hayat kalitesinde orta dönem etkenler Yaradılmış YU, Okkaoğlu MC, Kılıç A, Haberal B, Demirkale İ, Altay M 805-810 Management of thoracolumbar injury classification and severity score of 4 (TLICS=4) thoracolumbar vertebra fractures: Surgery versus conservative treatment Torakolomber yaralanma sınıflaması ve ciddiyet skoru 4 (TLICS = 4) olan torakolomber vertebra kırıklarının yönetimi: Cerrahi mi, konservatif tedavi mi? Karaali E, Çiloğlu O, Duramaz A, Kuşvuran Özkan A, Ekiz T 811-817 Comparison of functional outcomes in patients fixed with dynamic hip screw and proximal femur nail-anti-rotation in A1 and A2 type intertrochanteric femur fractures A1 ve A2 tipi femur intertrokanterik kırıklarında kayan kalça vidası ve proksimal femur çivisi-antirotasyon ile tespit sonrası hastaların fonksiyonel sonuçlarının karşılaştırılması Sevinç HF, Çırpar M, Canbeyli İB, Dağlar B, Oktaş B, Durusoy S 818-825 Injury mechanisms of ankle fractures with dislocation and analysis of differences on functional outcome Ayak bileği kırıklarına eşlik eden çıkıkların yaralanma mekanizmaları ve fonksiyonel sonuçlarındaki farklılıkların incelenmesi Yaradılmış YU, Öğük C, Okkaoğlu MC, Ateş A, Demirkale İ, Altay M

Case Reports - Olgu Sunumu 826-828 Tension gastrothorax secondary to trauma in the emergency room: A case report Acil serviste travmaya sekonder tansiyon gastrotoraks: Bir olgu sunum Algın A, Erdoğan MÖ, Sarıaydın M, Bozan K, Özdemir S, İnan İ 829-832 Hemorrhagic adrenal myelolipoma after trauma to left adrenal gland: A case report Sol adrenal bezde travma sonrası hemorajik adrenal miyelolipom: Olgu sunumu Chen TH, Lai PF, Hsu YH

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EXPERIMENTAL STUDY

The effects of ozone on the acute phase of intestinal ischemia-reperfusion injury in rats Yasemin Dere Günal, M.D.,1 Özlem Boybeyi Türer, M.D.,2 Üçler Kısa, M.D.,4 Mustafa Kemal Aslan, M.D.1

Pınar Atasoy, M.D.,3

Department of Pediatric Surgery, Kırıkkale University Faculty of Medicine, Kırıkkale-Turkey

Department of Pediatric Surgery, Hacettepe University Faculty of Medicine, Ankara-Turkey

Department of Pathology, Kırıkkale University Faculty of Medicine, Kırıkkale-Turkey

Department of Biochemistry, Kırıkkale University Faculty of Medicine, Kırıkkale-Turkey

ABSTRACT BACKGROUND: In this study, we aimed to examine the therapeutic effects of ozone on the acute phase of intestinal ischemia-reperfusion (I/R) injury in rats to resemble clinical practice. METHODS: Eighteen Wistar albino rats were assigned to control (CG, n=6), sham (SG, n=6) and ozone groups (OG, n=6). A midline laparotomy was performed and a superior mesenteric artery (SMA) in the SG and OG was occluded with a 0/0 catgut suture, but in the CG, the incision was closed without any intervention. Tissue oxygenation was monitored with a tissue oxygenation monitor to achieve the same grade during intestinal ischemia. The incision was closed and, in the OG, ozone/oxygen mixture (0.7 mg/kg) was injected intraperitoneally, 20 minutes before reperfusion. Surgical incision was reopened and reperfusion was achieved after 60 minutes of ischemia in the SG and OG. After 60 minutes of reperfusion, 2 cm small intestine segment was sampled for histopathological assessment of the intestinal mucosal damage (Chiu score) and biochemical assessment of oxidative stress markers (nitric oxide: NO, malondialdehyde: MDA, superoxide dismutase: SOD) in all groups. RESULTS: The Chiu scores of the SG and OG were statistically increased than that of the CG (p=0.002; and p=0.002, respectively). Chiu score in the OG was higher compared to that in the SG, but not statistically significant (p=0.175). MDA levels were statistically higher in the SG and OG than that of the CG (p=0.004; and p=0.010, respectively). However, the difference between the SG and OG was not statistically significant (p=0.522). SOD and NO levels were not significantly different between groups (p=0.451 and p=0.056, respectively). CONCLUSION: Contrary to the literature, single-dose ozone therapy did not reduce the oxidative stress or improve the ischemic damage in intestinal I/R injury in rats. Further evaluation with different doses in different time periods is needed for potential clinical use. Keywords: Experimental; Intestine; ischemia/reperfusion injury; ozone.

INTRODUCTION Intestinal I/R injury is an urgent and severe condition with high morbidity and mortality rates because it results in multiple organ failure, intestinal atrophy, sepsis and vascular protein and fluid leakage.[1,2] The common clinical causes of intestinal I/R injury include necrotizing enterocolitis in newborns, malrotation and volvulus, intussusception, septic shock, incarcerated inguinal hernia, trauma, mesenteric artery embo-

lism, and severe burns in children.[3–6] It has been shown that the end products of anaerobic metabolism and accumulation of toxic products due to the inadequate distribution of blood flow and oxygen lead to primary ischemic damage.[1,2,5] Furthermore, the reactive oxygen free radicals cause damage to the tissue directly or the cellular antioxidant systems in reperfusion injury.[1,3,5] Although most of the recent studies on the treatment of I/R injury are intended to prevent the tissues from the destructive effects of this reperfusion injury,

Cite this article as: Dere Günal Y, Boybeyi Türer Ö, Atasoy P, Kısa Ü, Aslan MK. The effects of ozone on the acute phase of intestinal ischemiareperfusion injury in rats. Ulus Travma Acil Cerrahi Derg 2020;26:651-656. Address for correspondence: Yasemin Dere Günal, M.D. Kırıkkale Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, Kırıkkale, Turkey Tel: +90 318 - 444 40 71 E-mail: drderegunal@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(5):651-656 DOI: 10.14744/tjtes.2020.48672 Submitted: 06.08.2020 Accepted: 25.08.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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no effective therapeutic regimen has yet been described in the medical literature.[2,4,6–8] Ozone (O3) is a colorless gas having a characteristic odor at room temperature, consisting of three oxygen atoms. Ozone has adverse effects on the human body, such as damage to cells and tissues, because of its strong oxidation activity, especially at high concentrations.[9–11] However, ozone can act as an antioxidant agent at low doses, decreasing tissue oxidative stress parameters, such as lipid peroxidation, protein oxidation, and nitrite/nitrate, and increasing the activity of enzymes, which are cellular antioxidants, such as catalase and glutathione peroxidase. Furthermore, it may also affect the production and release of proinflammatory cytokines from inflammatory cells and activate the immune and neuroendocrine systems by increasing the blood circulation and oxygen delivery at low doses.[2,6–8,12–15] Due to these antioxidant and anti-ischemic effects, clinical studies have suggested that ozone therapy is useful to treat many diseases, including peritonitis, wound infections, burns, skin ulcers, and gangrene.[6,7] However, there are few experimental studies regarding the effects of ozone on intestinal I/R injury and also there is a lack of standardization among them. We conducted this study to experimentally investigate the effects of ozone in the acute stage of an intestinal I/R injury model in rats by trying to simulate the clinical scenario.

MATERIALS AND METHODS This experimental study was carried out according to the guides of the laboratory animals in the studies determined by the Local Ethical Committee (Approval Number: 4613-0014). Eighteen Wistar albino male adult rats were used, which weighed 250±50 g in this study. The rats were fed with tap water and ad libitum food in a 12 h day/night cycle at 22°C. The rats were randomly assigned to three groups as follows: - Control group (CG, n=6): Laparotomy was performed, but intestinal I/R injury was not developed and no chemical was administered. - Sham group (SG, n=6): Laparotomy and intestinal I/R injury were performed. - Ozone group (OG, n=6): Laparotomy, intestinal I/R injury, and intraperitoneal 95% oxygen plus 5% ozone gas mixture (0.7 mg/kg) (Evozone Basic Plus, Germany) infusion 20 minutes before the reperfusion was performed.

rotomy was performed under sterile conditions, following the interference with a midline incision. Afterwards, the SMA in the SG and OG was exposed and occluded with a 0/0 catgut suture as described previously,[4] but in the CG, the incision was closed without any intervention. In the SG and OG, the tissue oxygenation monitor (MoorVMS-OXY, Moor Instruments, UK) was used to achieve the same grade of intestinal ischemia (Fig. 1). Tissue oxygenation was monitored during intestinal ischemia and was expressed as percentages. It was also observed macroscopically that the pulsation of the SMA stopped, and the color of the small intestine became purple. We appropriately closed the surgical incision layers after SMA occlusion. In the OG, the ozone/oxygen mixture (0.7 mg/kg)[16] was injected intraperitoneally, 20 minutes before reperfusion. Surgical incision was reopened and reperfusion was achieved by opening the catgut knots on the SMA carefully, after 60 minutes of intestinal ischemia in the SG and OG. Then, the incision was closed again. After 60 minutes of the reperfusion period, ischemic small intestine segment measuring 2 cm (15 cm closer to the ileocecal valve) of each rat was sampled for histopathological examination of the mucosal damage (Chiu score)[17] and biochemical investigation of markers of oxidative stress (nitric oxide: NO, malondialdehyde: MDA, superoxide dismutase: SOD). The half part of the intestine was kept in 10% buffered formaldehyde at room temperature for histopathological analysis, and the remaining part was kept at -80°C in dry air for biochemical analysis. The rats were sacrificed by exsanguination.

Histopathological Analyses Routine light microscopic tissue examination was applied to all the tissue samples. Serial sections (5 µm thick) were stained with haematoxylin-eosin and analyzed by a light microscope (Leica® Microsystems, Wetzlar GmbH). The sections were examined by an experienced pathologist who was blinded to the groups. For histopathological examination of the intestinal I/R injury, the grading system according to Chiu was applied to all samples (Table 1).[17] (a)

(b)

Surgical Procedures The rats were anesthetized with an intraperitoneal injection of 40 mg/kg ketamine hydrochloride (Ketalar®, Pfizer, USA) and 5 mg/kg xylazine hydrochloride (Rompun® 2%, Bayer, Germany). All animals were fixed in the supine position on the operating table after applying a sedation anesthesia, and abdominal lapa652

Figure 1. The experimental model. (a) The superior mesenteric artery is prepared for occlusion and. (b) The measurement of bowel perfusion using tissue oxygenation monitor. Note that the color of the small intestine became purple after the SMA was occluded.

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Table 1. Histopathologic grades of colonic tissue (Chiu scoring system[17]) Grade

Histopathologic finding

Normal mucosal villi

Development of a subepithelial space, usually at the

tip of the villus, with capillary congestion

Extension of the subepithelial space with the

moderate lifting of the epithelial layer

III

Massive epithelial lifting down the sides of villi

Denuded villi with lamina propria, dilated capillaries

exposed, increased cellularity of the lamina propria

Digestion and disintegration of the lamina propria,

hemorrhage and ulceration

cedure according to Miranda et al.[19] The nitrate content was quantified by reducing nitrate with vanadium (III), using the Griess reaction to reflect the total nitrate and nitrite in the specimen. Serial dilutions of Na nitrate were made to achieve standard concentration. The results were given as µmol/g protein. SOD levels were quantified using an ELISA (Cayman Chemical Company, USA). The results were given as U/mg protein.

Statistical Analysis

Biochemical Analyses All samples were kept in dry air at -80 °C. A homogenate was prepared for all tissues with saline solution in ice (1 mL) and was then centrifuged at 1500 g for 10 min at 4 °C. After centrifugation, MDA, NO, and SOD levels were determined in all the supernatants. MDA levels, a standard curve of MDA (1,1,3,3-tetraethoxypropane) levels were defined using the method of Armstrong and al-Awadi.[18] and results were given as nmol/mg protein. NO levels were measured using a spectrophotometric pro-

Kruskal-l Wallis test was used for histopathological grades and MDA levels that did not show the normal distribution and inhomogeneous variations between the groups. The Mann-Whitney U test was used for post hoc evaluation of differences between the groups. One-Way ANOVA test was used for NO and SOD levels that were normally distributed and homogenous among the groups. Statistical significance was set at p-values lower than 0.05.

RESULTS Tissue oxygenation in the CG ranged from 94% to 98%, while during intestinal ischemia, it ranged from 35% and 45% in the SG and OG measured using the tissue oxygenation monitor. The results of the biochemical and histopathological examinations are presented in Table 2 and Figure 2. The harvested in-

Table 2. The median values of biochemical results

NO (µmol/g protein)

MDA (nmol/mg protein)

SOD (U/mg protein)

Chiu Scores

Control group

2.17 (0.35–5.19)

2.49 (1.60–3.33)α,β

4.25 (3.82–4.56)

0 (0–0)γ,θ

Sham group

2.71 (0.12–6.93)

6.40 (2.81–19.12)α

4.56 (3.05–6.57)

2 (1–4)γ

Ozone group

3.78 (1.80–4.82)

6.43 (3.55–13.81)

3.33 (2.65–3.98)

4 (1–5)θ

12.00 10.00 8.00 6.00 4.00

Superoxide dismutase (U/mg protein)

14.00

α α,β

2.00 .00

Nitric oxide (μmol/g protein)

Malondialdehyde (nmol/mg protein)

NO, MDA, SOD and Chiu scores of the groups (interquartile ranges within brackets). The statistically significant differences were indicated with small Greek letters (α, β, γ, θ: p<0.05). NO: Nitric oxide; MDA: Malondialdehyde; SOD: Superoxide dismutase.

6.00 4.00 2.00 .00

OG Groups

7000 6000 5000 4000 3000 2000 CG

OG Groups

Figure 2. The median values of MDA, NO and SOD between the groups: α and β represent the significant difference. NO: Nitric oxide; MDA: Malondialdehyde; SOD: Superoxide dismutase; CG: Control group, SG: Sham group, OG: Ozone group.

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Dere GĂźnal et al. The effects of ozone on the acute phase of intestinal ischemia-reperfusion injury in rats

Figure 3. The light microscope findings of intestinal samples (H&E Ă&#x2014;100). CG: Normal findings. OG: Shedding at the ends of intestinal villi and increased mononuclear cell infiltration in the mucosa. Large epithelial lifting from the villi and cellular increase in the lamina propria. SG: Mucosal edema and capillary congestion with focal epithelial separations on the tips of the villi.

testines were observed macroscopically to be edematous and discolored. The specimens were graded using the Chiu score for the histopathological evaluation of intestinal injury (Table 2). The Chiu scores were compatible with the macroscopic appearance. A significant increase was found in the SG and OG when the Chiu score was compared to the CG (p=0.002; and p=0.002, respectively). Although not significant, the Chiu score in the OG was higher compared to that of the SG (p=0.175). Representative microscopic views of the groups are shown in Figure 3. The median values of the MDA levels were statistically higher in the SG and OG than that of the CG (p=0.004; and p=0.010, respectively). However, the difference between the SG and OG was not statistically significant (p=0.522). The median values of NO were numerically higher in the OG than the other groups, while the median values of SOD were numerically lower, but this was not statistically significant (p=0.056; and p=0.451, respectively).

DISCUSSION It has been demonstrated that cellular necrosis and apoptosis occurring in the ischemic environment produces proinflammatory substances from the polymorphonuclear cells, such as nitrogen- and oxygen-derived free radicals, prostaglandins, thromboxanes, prostacyclins, interleukins, tumor necrosis factor, and leukotrienes. These superoxide and hydroxyl radicals enter into the lipid peroxidation reaction that can destroy the cell membrane and its permeability. This cell membrane destruction particularly induces the development of cell death and the release of the free radicals, protease enzymes, and peroxides. These substances also increase further tissue damage.[1,2,6] The published data reveal inconsistencies in the effects of ozone on apoptosis and cell death. Many studies have suggested that ozone stimulates cell death. [20] The way of cell damage due to ozone has not yet been fully understood. One study has suggested that ozone stimulates lipid peroxidation, causing oxidative stress and DNA injury. MDA is indicative of lipid peroxidation in tissues, and increased levels represent oxidative damage.[21] In the present study, MDA levels of the ischemic rats (SG and OG) were 654

significantly higher than the control rats (CG). However, the MDA levels of the OG were statistically similar to those of the SG, suggesting that ozone has no protective effect on lipid peroxidation in the cell membrane after intestinal I/R injury in the rat. Borrego et al.[22] demonstrated in a study regarding cisplatin-induced nephrotoxicity in rats that SOD and other antioxidants may decrease because of the increased H2O2, which could be increased by high dose ozone application. Furthermore, it has been shown in in vivo studies that high-dose ozone applied to the ischemic/hypoxic tissue could lead to decreased antioxidant enzyme levels.[2] In the present study, the SOD levels of the OG were lower than the other groups numerically, but this was not statistically significant. The absence of a long-term I/R damage may have caused this result. Additionally, the degradation of antioxidant enzymes could increase if the ischemia and reperfusion time increases.[13] It is reported that ozone seriously compromises cell membrane integrity and short-term repeated doses up-regulate cellular plasticity by inducing anti-apoptotic pathways.[23] In the present study, histopathological examination revealed that the Chiu scores of the CG were significantly lower than the SG. Similar to our previous experience, these findings provide that the intestinal I/R injury model applied in this study is successful and acceptable.[4] Therefore, we can assume that occlusion of the SMA for an hour which provides intestinal tissue oxygenation of between 35% and 45%, leads to significant I/R damage in the intestine. Although a significant difference was not found, the median value of the Chiu score in the OG tended to increase compared to the SG. It can be concluded that a single-dose ozone therapy neither decreases the oxidative damage nor improves the evidence of the ischemic damage in intestinal I/R injury in rats, even though some worsening is observed. Recently, ozone has been shown to have positive effects on antioxidant and histopathological parameters in intestinal I/R injuries with 1 mg/kg doses per day for five days, when given prophylactically before an ischemic injury was created in rats. [6] Given that it is very difficult to make a quick diagnosis of those patients within minutes, the preconditioning use of ozone will not be suitable for actual clinical practice, particuUlus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Dere Günal et al. The effects of ozone on the acute phase of intestinal ischemia-reperfusion injury in rats

larly in emergency cases. Since intestinal ischemia is usually an emergency condition, our aim was to assess the acute effects of single dose of the ozone. Thus, we designed our study with a delayed administration of ozone once the intestinal ischemia had occurred. Similarly, Haj et al.[7] gave an equal mixture of ozone and oxygen in 0.7 mg/kg daily doses both intraperitoneally and intraluminally (50/50) for 72 hours after intestinal I/R injury in rats. They found successful results, including significantly increased intestinal villus height, decreased enterocyte apoptosis, and enhanced intestinal recovery.[7] Isik et al.[2] demonstrated that ozone has protective effects on mesenteric artery ischemia in rats if it is given intraperitoneally in 0.5 mg/kg single dose, 15 minutes after the ischemia. They stated that they would plan a prospective clinical study and use ozone therapy during the surgeries of real-time patients. [2] Contrary to these promising studies, our results did not show any therapeutic benefit of ozone but showed its oxidative effect. This may suggest that the therapeutic dose range of ozone is narrow. Intraperitoneal administration of ozone is generally more efficient than oral administration.[2] Since ozone is administered under ischemic conditions, the high oxygen pressure gradient will cause ozone to be transfused into the intestinal wall through passive diffusion. Therefore, ozone is effective in the entire ischemic intestine.[24] In our study, the measured intestinal tissue oxygenation below 45% and the application of ozone in the late period of ischemia may cause the oxygen gradient in the intestine to increase further and more ozone to be transfused into the intestinal wall by passive diffusion. Consequently, this high dose ozone may have caused more damage to the intestinal wall. Given that it is unlikely to diagnose these patients at the 15th minute of ischemia in clinical practice, ozone can worsen bowel damage in the late period of ischemia, when intestinal tissue perfusion remarkably decreases. Previous studies provide evidence that ozone has protective effects on intestinal I/R damage.[2,6,7] However, it should be noted that the amount of injury may vary depending on the compression pressure applied to the SMA and the duration of the ischemia. There are not enough data in the literature about the degree of intestinal ischemia developing after the SMA occlusion with any methods. It was decided that the SMA is occluded when the SMA pulsation stopped and the color of the intestine changed into the purple. Although the applied force is considered to be the same, the amount of tissue ischemia created may vary. Unlike the other studies mentioned above, a tissue oxygenation monitor was used to achieve similar to SMA compression in all subjects in this study. Although we could not physically measure the force applied to the SMA, we obtained the same tissue perfusion in all intestine using this device. Besides this, our results in contradiction with the literature may be related to the dose of ozone (in single or repetitive doses), the route of application and the time of administration. It is obvious that more studies Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

are required to determine the appropriate dosage range and time of administration of ozone therapy to be used in clinical practice. This study has some limitations. Since this study aimed to explore the possible useful effects of single-dose ozone in the acute stage of intestinal I/R injury, it did not involve the longterm effects of repeated doses of ozone therapy. Additionally, lack of ultrastructural changes associated with inflammatory response and apoptosis in the intestine after I/R and ozone therapy is a hindrance to have more precise conclusions. In this study, we used tissue oxygen level measurement only to standardize the ischemia level and did not compare this measurement with post-reperfusion. Considering that ozone therapy was ineffective in the acute stage of intestinal I/R injury, we think that the difference between tissue oxygenation did not affect the results between the groups. However, we believe that this study will inspire future research investigating tissue oxygenation changes, studying long-term ischemia-reperfusion models with different substances.

Conclusion In conclusion, single-dose ozone therapy did not increase the antioxidant enzymes to reduce the oxidative stress and did not improve the evidence of the ischemic damage in intestinal I/R injury in rats. Although ozone is reported to be an effective antioxidant in previous clinical and experimental studies, further evaluation with different doses in different time periods, including ischemic and/or reperfusion periods, is needed to be used for clinical purposes.

Acknowledgment Authors thank to Bülent Bakar, M. D. Associate Professor from Kırıkkale University, Medical Faculty, Department of Neurosurgery, for the statistical analysis and evaluations of the results. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Y.D.G.; Design: Y.D.G., Ö.B.T.; Supervision: Y.D.G., M.K.A.; Fundings: Y.D.G.; Materials: Y.D.G., Ö.B.T., P.A., Ü.K.; Data: Y.D.G., P.A., Ü.K.; Analysis: Y.D.G., Ö.B.T.; Literature search: Y.D.G.; Writing: Y.D.G.; Critical revision: Y.D.G., Ö.B.T., M.K.A. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Cerqueira NF, Hussni CA, Yoshida WB. Pathophysiology of mesenteric ischemia/reperfusion: a review. Acta Cir Bras 2005;20:336–43. 2. Isik A, Peker K, Gursul C, Sayar I, Firat D, Yilmaz I, et al. The effect of ozone and naringin on intestinal ischemia/reperfusion injury in an exper-

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Dere Günal et al. The effects of ozone on the acute phase of intestinal ischemia-reperfusion injury in rats imental model. Int J Surg 2015;21:38−44. 3. Vollmar B, Menger MD. Intestinal ischemia/reperfusion: microcirculatory pathology and functional consequences. Langenbecks Arch Surg 2011;396:13−−29. 4. Boybeyi O, Dere Gunal Y, Atasoy P, Kısa U, Aslan MK. The effect of colchicine and low-dose methotrexate on intestinal ischemia/reperfusion injury in an experimental model. J Pediatr Surg 2014;49:1471−4. 5. Mallick IH, Yang W, Winslet MC, Seifalian AM. Ischemia-reperfusion injury of the intestine and protective strategies against injury. Dig Dis Sci 2004;49:1359−77. 6. Onal O, Yetisir F, Sarer AE, Zeybek ND, Onal CO, Yurekli B, et al. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat. Mediators Inflamm 2015;2015:792016. 7. Haj B, Sukhotnik I, Shaoul R, Pollak Y, Coran AG, Bitterman A, et al. Effect of ozone on intestinal recovery following intestinal ischemia-reperfusion injury in a rat. Pediatr Surg Int 2014;30:181−8. 8. Oztosun M, Akgul EO, Cakir E, Cayci T, Uysal B, Ogur R, et al. The effects of medical ozone therapy on renal ischemia/reperfusion injury. Ren Fail 2012;34:921−5. 9. Bocci V, Borrelli E, Travagli V, Zanardi I. The ozone paradox: ozone is a strong oxidant as well as a medical drug. Med Res Rev 2009;29:646−82. 10. Elvis AM, Ekta JS. Ozone therapy: A clinical review. J Nat Sci Biol Med 2011;2:66−70. 11. Himuro H. The Effect of Ozone on Colonic Epithelial Cells. Kurume Med J 2018;64:75−81. 12. Fedakâr Senyücel M, Ayva ES, Aslan MK, Boybeyi O, Soyer T, Aksoy N, et al. Comparison of the effect of contrast medium, air, and ozone on ischemia/reperfusion injury due to experimental intussusception model. Turk J Med Sci 2013;43:637−41. 13. Aslan MK, Boybeyi Ö, Şenyücel MF, Ayva Ş, Kısa Ü, Aksoy N, et al. Protective effect of intraperitoneal ozone application in experimental ovarian ischemia/reperfusion injury. J Pediatr Surg 2012;47:1730−4. 14. Rodríguez ZZ, Guanche D, Alvarez RG, Rosales FH, Alonso Y, Schulz S. Preconditioning with ozone/oxygen mixture induces reversion of some

indicators of oxidative stress and prevents organic damage in rats with fecal peritonitis. Inflamm Res 2009;58:371−5. 15. Koca K, Yurttaş Y, Yıldız C, Caycı T, Uysal B, Korkmaz A. Effect of hyperbaric oxygen and ozone preconditioning on oxidative/nitrosative stress induced by tourniquet ischemia/reperfusion in rat skeletal muscle. Acta Orthop Traumatol Turc 2010;44:476−83. 16. Guven A, Gundogdu G, Vurucu S, Uysal B, Oztas E, Ozturk H, et al. Medical ozone therapy reduces oxidative stress and intestinal damage in an experimental model of necrotizing enterocolitis in neonatal rats. J Pediatr Surg 2009;44:1730−5. 17. Chiu CJ, McArdle AH, Brown R, Scott HJ, Gurd FN. Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal. Arch Surg 1970;101:478−83. 18. Armstrong D, al-Awadi F. Lipid peroxidation and retinopathy in streptozotocin-induced diabetes. Free Radic Biol Med 1991;11:433−6. 19. Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001;5:62−71. 20. Kosmider B, Loader JE, Murphy RC, Mason RJ. Apoptosis induced by ozone and oxysterols in human alveolar epithelial cells. Free Radic Biol Med 2010;48:1513−24. 21. Pompella A. Biochemistry and histochemistry of oxidant stress and lipid peroxidation. Int J Vitam Nutr Res 1997;67:289−97. 22. Borrego A, Zamora ZB, González R, Romay C, Menéndez S, Hernández F, et al. Protection by ozone preconditioning is mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats. Mediators Inflamm 2004;13:13−9. 23. Brink CB, Pretorius A, van Niekerk BP, Oliver DW, Venter DP. Studies on cellular resilience and adaptation following acute and repetitive exposure to ozone in cultured human epithelial (HeLa) cells. Redox Rep 2008;13:87–100. 24. Gao C, Xu L, Chai W, Sun X, Zhang H, Zhang G. Amelioration of intestinal ischemia-reperfusion injury with intraluminal hyperoxygenated solution: studies on structural and functional changes of enterocyte mitochondria. J Surg Res 2005;129:298−305.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sıçanlarda ozonun bağırsak iskemi-reperfüzyon hasarının akut evresi üzerine etkisi Dr. Yasemin Dere Günal,1 Dr. Özlem Boybeyi Türer,2 Dr. Pınar Atasoy,3 Dr. Üçler Kısa,4 Dr. Mustafa Kemal Aslan1 Kırıkkale Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, Kırıkkale Hacettepe Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, Ankara Kırıkkale Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, Kırıkkale 4 Kırıkkale Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Kırıkkale 1 2 3

AMAÇ: Klinik uygulamalara benzer şekilde sıçanlarda ozonun intestinal iskemi-reperfüzyon (I/R) hasarının akut fazı üzerindeki terapötik etkilerini incelemeyi amaçladık. GEREÇ VE YÖNTEM: On sekiz Wistar albino sıçanı kontrol (CG, n=6), sham (SG, n=6) ve ozon gruplarına (OG, n=6) ayrıldı. Laparatomiyi takiben SG ve OG’de süperiyor mezenterik arter (SMA) 0/0 katgut dikişle oklüde edildi, ancak CG’de herhangi bir girişim yapılmadan insizyon kapatıldı. Eşit derecede bağırsak iskemisi elde etmek için bir doku oksijenasyon monitörü kullanıldı. İnsizyon kapatıldı ve OG’de, reperfüzyondan 20 dakika önce ozon/oksijen karışımı (0.7 mg/kg) intraperitoneal olarak enjekte edildi. SG ve OG’de 60 dakikalık iskemi sonrası cerrahi insizyon tekrar açıldı ve reperfüzyon sağlandı. Atmış dakikalık reperfüzyondan sonra tüm gruplarda bağırsak mukozal hasarının (Chiu skoru) histopatolojik değerlendirmesi ve oksidatif stres belirteçlerinin (nitrik oksit: NO, malonildialdehit: MDA, süperoksit dismutaz: SOD) biyokimyasal değerlendirmesi için 2 cm’lik ince bağırsak segmenti örneklendi. BULGULAR: Chiu skorları SG ve OG’de CG’ye göre istatistiksel olarak yüksekti (sırasıyla, p=0.002 ve p=0.002). Chiu skoru OG’de SG’ye göre daha yüksekti, ancak istatistiksel olarak anlamlı değildi (p=0.175). MDA düzeyleri SG ve OG’de CG’ye göre istatistiksel olarak daha yüksekti (sırasıyla p=0.004 ve p=0.010). Ancak, SG ve OG arasındaki fark istatistiksel olarak anlamlı değildi (p=0.522). SOD ve NO düzeyleri açısından gruplar arasında anlamlı olarak fark yoktu (sırasıyla, p=0.451 ve p=0.056). TARTIŞMA: Literatürün aksine, tek doz ozon tedavisi, sıçanlarda bağırsak I/R hasarında oksidatif stresi azaltmadı ve iskemik hasarı iyileştirmedi. Potansiyel bir klinik kullanım için farklı zaman aralıklarında farklı dozları içeren daha ileri değerlendirmeler yapılması gerekmektedir. Anahtar sözcükler: Bağırsak; deneysel; iskemi/reperfüzyon hasarı; ozon. Ulus Travma Acil Cerrahi Derg 2020;26(5):651-656

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doi: 10.14744/tjtes.2020.48672

Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

EXPERIMENTAL STUDY

Does ß-glucan can have a protective role against oxidative stress in the experimental sepsis model in rats? Meltem Demir, M.D.,1

Kader Köse, M.D.,2

Cevat Yazıcı, M.D.,2

Department of Medical Biochemistry, İstinye University Faculty of Medicine, İstanbul-Turkey

Department of Medical Biochemistry, Erciyes University Faculty of Medicine, Kayseri-Turkey

Department of General Surgery, Erciyes University Faculty of Medicine, Kayseri-Turkey

Erdoğan Mütevelli Sözüer, M.D.3

ABSTRACT BACKGROUND: Very high mortality rate in sepsis may be related to oxidative stress. This study was conducted on the rats to investigate the presence of oxidative stress and also the potential protective effects of the ß-glucan in the intra-abdominal sepsis model formed by cecal ligation-perforation (CLP). METHODS: In this study, 30 Male rats were equally divided into three groups as “Sham”, “Sepsis” and “ß-Glucan”. Only laparotomy was performed in the Sham group, and sepsis was induced by CLP in Sepsis and ß-Glucan groups. Following CLP, a single dose of 4 mg ß-glucan/kg was also intraperitoneally administered to the β-Glucan group. Blood and tissue (liver, lung and kidney) samples were taken from Sepsis and ß-Glucan groups after sepsis development determined at the end of the 48th hour, also from the Sham group. The levels of myeloperoxidase (MPO) and advanced oxidation protein products (AOPP) were determined in plasma samples, and the malondialdehyde (MDA) was measured in plasma and tissues. RESULTS: MPO and AOPP were higher in both the Sepsis and ß-Glucan groups; however, plasma and tissue MDA levels were higher only in the Sepsis group than the Sham group (p<0.05). However, when compared to the Sepsis group, all parameters measured, except kidney MDA, were significantly lower in the ß-Glucan group (p<0.05). CONCLUSION: To our knowledge, this is the first study to investigate the AOPP levels in the CLP sepsis model, ROS produced by the reaction of MPO derived from neutrophils may form oxidative damage to the proteins, compared to the lipids, and ß-glucan may be used as an alternative agent for sepsis treatment. Keywords: Advanced oxidation protein products; B-Glucan; myeloperoxidase; reactive oxygen species; sepsis.

INTRODUCTION Sepsis-induced multiple organ dysfunctions are the major cause of death in critical care units.[1–3] The high mortality rate in sepsis mostly arises from gram-negative bacteria endotoxins, which cause secretion of cytokines by inducing the immune system, has also been suggested to be related to oxidative stress due to the generation of reactive oxygen species (ROS)[4–6] Despite the growing evidence that ROS is important during sepsis development, whether oxidative stress causes or propagates the pathogenesis of sepsis remains unclear.[5] Thus, it represents a potential therapeutic target.[6] ROS abla-

tion for the treatment of sepsis could be useful in the clinical setting of sepsis-induced multiple organ failure.[4] Clinical[7,8] and experimental[4,9,10] studies have demonstrated that ß-glucan may be beneﬁcial in the treatment of sepsis. Pretreatment with ß-glucan in septic rats may have therapeutic potential to ameliorate clinical symptoms due to excessive production of proinﬂammatory cytokines during acute septic complications. [11] A previous report from our team,[12] investigating the protective effects of ß-glucan on lung injury after cecal ligation and puncture (CLP) in rats, has been shown that ß-glucan treatment decreased lung damage according to both morphological and functional criteria in an experimental sepsis model.

Cite this article as: Demir M, Köse K, Yazıcı C, Sözüer EM. Does ß-glucan can have a protective role against oxidative stress in the experimental sepsis model in rats?. Ulus Travma Acil Cerrahi Derg 2020;26:657-662. Address for correspondence: Meltem Demir, M.D. İstinye Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, İstanbul, Turkey Tel: +90 850 - 283 60 00 E-mail: meldemir52@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):657-662 DOI: 10.14744/tjtes.2019.79002 Submitted: 02.08.2019 Accepted: 29.12.2019 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Demir et al. Does ß-glucan can have a protective role against oxidative stress in the experimental sepsis model in rats?

In the present study, as a follow-up of the previous report, [12] the experimental CLP sepsis model was used to demonstrate the increased ROS production by activated neutrophils, which leads to oxidative stress in sepsis, through the oxidations of lipids and proteins. Therefore, plasma Myeloperoxidase (MPO) activity as a neutrophil activation marker, and oxidative stress markers, such as plasma advanced oxidation protein products (AOPP) levels for protein oxidation, and malondialdehyde (MDA) levels for lipid peroxidation in both plasma and tissue samples obtained from liver, lung and kidney were determined in septic rats. In addition, the possible protective effects of ß-glucan on these parameters were investigated and discussed its potential therapeutic effects on this rat model.

MATERIALS AND METHODS The protocol of this study was approved by Erciyes University Animal Research Local Ethics Committee. This study was conducted on male Wistar albino rats grown at Hakan Çetinsaya Experimental and Clinical Research Center of University.

Study Groups A total of 30 male rats, guaranteed to be free of particular pathogens and were acclimatized for one week before the experiments, weighing 250–300 g, were kept on the 12-hour light/dark cycle and at normal room temperature and moisture during this study. The rats, kept in standard wire cages and fed ad libitum with standard pellet chow and tap water, were randomly divided into three groups of 10 rats each to form “Sham”, “Sepsis” and “ß-Glucan” groups.

Study Design The rats were weighed before this study, and the doses of water-soluble ß-glucan (Beta-D-glucan, Sigma, St. Louis, Mo., USA) and ketamine HCl (Ketalar®, Parke-Davis, USA; 50 mg/ mL) were adjusted to be applied per kilogram (kg) of rat weight intraperitoneally (ip). The rats were allowed to take only water for 12 hours before the operation. All surgical procedures were carried out under ip ketamine anesthesia (50 mg/kg) and in sterile conditions. In the Sham group, laparotomy was performed through a lower-midline incision, and the cecum was manipulated without being ligated or perforated. CLP procedure was applied to both Sepsis and ß-Glucan groups, as previously described in detail12. A single dose of 4 mg β-glucan/kg was also administered ip to the ß-Glucan group, while two other groups were given equal volumes of saline. After surgery, the rats, which were received their cages and provided ad libitum fed, were followed up for 48 hours. In the rats which were applied CLP with a preliminary study, sepsis was identified after 48 hours by the assessment of the cell content and morphology of bronchoalveolar lavage (BAL) 658

fluid;[12] therefore, blood samples were taken, and liver, lung and kidney tissues were removed from all groups under ketamine anesthesia at the end of 48 hours following laparotomy.

Biochemical Analyses Plasma samples were kept at –70°C until the determinations of MPO, MDA and AOPP levels. The tissue samples were washed with ice-cold saline, until the clearance of blood, and dried with filter paper; then, tissue portions were suspended and homogenized in ice-cold 0.15 mol/L phosphate buffer, pH 7.4 (10% wt/vol). Homogenates were stored at –70°C until MDA measurements. Plasma MPO activity was conducted by the kinetic observation of o-dianisidine oxidation under the existence of H2O2 at 460 nm. MPO activity was calculated using the molar extinction coefficient of 1.13 x 104 M-1 cm-1 of oxidized o-dianisidine.[13] The results were expressed as units of enzyme activity per liter of plasma (U/L). AOPP levels were designated by the measurement of liberated triiodide ions at 340 nm during KI oxidization by cross-linking products created by chlorinated oxidants with plasma proteins, and AOPP levels were expressed as micromoles of chloramine-T equivalents per liter of plasma (µmol/L).[14] MDA levels in plasma and tissue homogenates were assessed by the spectrophotometrical method of Ohkawa et al.,[15] where in MDA couples to thiobarbituric acid to form pink chromogen compound, which has a maximum absorbance at 540 nm. During measurement, plasma samples were used directly. Thawed samples of tissue homogenates (10% wt/vol) were mixed by vortex, centrifuged at 20.000 g for 15 min at +4°C. The supernatants were used for MDA measurement on the same day. MDA levels were expressed as micromoles per liter (μmol/L) and nanomoles per gram of wet tissue weight (nmol/g), in plasma and tissue samples, respectively.

Statistical Analyses The data were analyzed using Statistical Products and Service Solution package (SPSS, for Windows, 16 versions, Chicago, IL., USA). The normality of measured parameters was assessed using the Shapiro–Wilk test, and all data were determined to conform to a normal distribution. Comparison of the data was made by the analysis of variance (ANOVA) and post-ANOVA (Scheffe’s procedure) tests among three groups. Furthermore, bivariate comparisons were made using Pearson correlation coefficients (r) in the parameters of study groups. Data were presented as means ± SD at the tables, and the difference was considered significant at p<0.05.

RESULTS Since one rat of the Sepsis group died on the second postoperative day due to generalized peritonitis revealed by autopsy, Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Demir et al. Does ß-glucan can have a protective role against oxidative stress in the experimental sepsis model in rats?

Table 1. MPO, AOPP and MDA values of the study groups Parameters

Study Groups Sham Group (n=10)

Sepsis Group (n=9)

ß-Glucan Group (n=10)

Plasma MPO (U/L)

65.4±17.9

136.4±27.0* 98.5±27.0*,‡

Plasma AOPP (μmol/L)

34.4±8.6

146.4±31.8* 93.6±12.1*,‡

Plasma MDA (µmol/L)

1.8±0.5

3.6±0.8* 1.9±0.4‡

Lung MDA (nmol/g tissue)

72.4±17.9

118.8±23.6* 75.8±18.3‡

Liver MDA (nmol/g tissue)

64.5±18.3

116.3±29.6* 76.6±16.8‡

Kidney MDA (nmol/g tissue)

81.6±17.1

114.6±25.1* 93.6±20.9

n: Number of rats. Data presented as means±standard deviation. Significant statistical comparisons: Sham group vs Sepsis or ß-Glucan groups (*p<0.05) by post-ANOVA test. Sepsis group vs ß-Glucan group (‡p<0.05) by post-ANOVA test. MPO: Myeloperoxidase; AOPP: Advanced oxidation protein products; MDA: Malondialdehyde.

Table 2. Significant correlations between parameters measured in the study groups Biochemical parameters

Sham Group (n=10)

Sepsis Group (n=9)

r p r p

Plasma: myeloperoxidase – AOPP

0.752

0.012

0.797

0.01

Plasma malondialdehyde – Lung malondialdehyde

0.856

0.001

0.900

0.001

–

0.754

0.019

0.650

0.042

0.864

0.003

Plasma malondialdehyde – Kidney malondialdehyde Lung malondialdehyde – Kidney malondialdehyde n: Number of rats. AOPP: Advanced oxidation protein products.

this study was completed with 29 rats. No statistical difference was found among study groups concerning weight, both at the beginning and the end of this study (p>0.05). Plasma MPO activity and AOPP levels and MDA in plasma and tissue samples were shown in Table 1. When compared to the Sham group, MPO and AOPP were found significantly increased in both the Sepsis and ß-Glucan groups (p<0.05); however, plasma and tissue MDA levels were higher only in Sepsis group (p<0.05). When the Sepsis group was compared to the ß-Glucan group, except kidney MDA, all parameters measured were significantly lower in the ß-Glucan group (p<0.05). There was a relative decrease in kidney MDA level, but it was not statistically significant (p>0.05). Only significant correlations among the parameters of the study groups are shown in Table 2. Plasma MPO activity was positively correlated with AOPP levels, and there were significantly positive correlations between plasma and lung MDA, and also lung – kidney MDA levels in both the Sham and the Sepsis groups (p<005).

DISCUSSION In the present study, plasma AOPP and MPO levels were found to be higher in septic rats. To our knowledge, there has been no study measuring plasma AOPP in experimental Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

sepsis by inducing CLP. On the other hand, clinical studies, and also experimental studies in different animal species, and different types of sepsis models except CLP, have been shown to increase in plasma AOPP and MPO levels.[16] Selmeci et al. has suggested that plasma AOPP measurement is especially suitable for monitoring oxidative stress in critically ill patients even at daily intervals since AOPP exhibited rapid responses in both directions. Additionally, increased AOPP levels have been reported in critically ill patients, induced by the overproduction of ROS and the subsequent depletion of the antioxidant endogenous stores. In experimental studies, plasma AOPP levels were higher in dogs infected with Rangelia vitalii,[17] and a signiﬁcant increase in plasma; AOPP levels was also measured in the rats inoculated with infective blood by Trypanosoma evansi.[18] The finding of high AOPP levels in septic rats can be explained in the way that chlorinated oxidants, HOCl and chloramines are only produced by phagocytic cells in vivo, which migrate to lungs that cause the formation AOPP. Supporting this view, since chloramines have been reported to increase membrane permeability,[19] these oxidants may be assumed to pass from tissue to plasma. In an experimental obstructive jaundice model induced by choleduct ligation,[20] and in mediastinitis model by methicillin-resistant Staphylococcus aureus,[21] serum MPO activity was found to be higher in the rats. Mühl 659

Demir et al. Does ß-glucan can have a protective role against oxidative stress in the experimental sepsis model in rats?

et al.[22] and Kothari et al.[23] found increased plasma MPO levels in patients with sepsis; and suggested that neutrophil activation occurring during inflammation and sepsis could be detected by plasma MPO released into the blood, which may be a good biomarker of the neutrophil proliferation and severity of inflammation (Fig. 1).[23] MDA levels in liver, lung and kidney tissues, and also in plasma were found higher and the correlations between MDA levels in plasma, lung and kidney were also obtained in septic rats in the present study, indicating the sepsis as a cause of oxidative damage in the liver, kidney and lung tissues; demonstrated by the increased lipid peroxidation. Increased MDA levels in the liver,[4,9–11] lung,[4,9,10,24–27] and kidney tissues,[4,9,10,24,26] and also in plasma[4,9,10] were reported in CLP-induced septic rats. Furthermore, Koksal et al.[10] reported that plasma MDA was correlated to MDA in liver, lung, and kidney in septic rats induced by CLP; and suggested that increased oxidative stress in tissues in parallel with plasma may be important mechanisms due to the output of free radicals. Furthermore, in the present study, for the first time, decreases in plasma MPO and AOPP values with ß-glucan administration were found to be statistically significant concerning the efficacy of treatment. These findings may suggest that ß-glucan suppresses the severity of sepsis, and regarding these results, inflammation following induction of sepsis was decreased by ß-glucan. Obviously, lower neutrophil accumulation will result in lower tissue inflammation. As seen in the first part of the present study,[12] lower neutrophil and higher monocyte percentages were observed by ß-glucan administration, compared to septic rats. When considering decreased percentages of neutrophils, these findings may be explained as the ß-glucan that may prevent both inflammation and also MPO release from activated phagocytic cells to plasma. Additionally, the formation of chloramines by MPO mediated reactions, which may oxidize proteins, may be captured by ß-glucan and in this manner; the oxidative damage secondary to respiratory burst may be partially prevented. There are contrasting views about the relationship between MDA, oxidative stress and sepsis. Namely, Lorente et al.[28] reported that increased serum MDA levels were associated

Figure 1. Respiratory burst and formation of chloramines.

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with severity and mortality in septic patients, irrespective of site of the infection, type of micro-organism, or dysfunctional organ system, suggesting that lipid peroxidation was attributable to the general host response rather than a pathogen- or organ-specific reaction. Otherwise, the considerable overlap between sepsis survivors and non-survivors limits the utility of MDA in clinical practice.[1] According to Weiss and Deutschman,[6] lipid peroxidation is not specific to sepsis and may be affected by comorbid conditions, diet, and lifestyle behaviors, and also its shorter half-life and the lack of stability, and the use of non-specific/non-sensitive methods affect the reliability of the MDA results.[6,29] Therefore, further study is required to validate the utility of MDA as a prognostic biomarker in sepsis.[6] On the other hand, during severe sepsis or organ failure, the body response fails to protect itself. An intense study of oxygen radical-mediated mechanisms may lead to improved therapies in sepsis treatment.[5] Although the antioxidant therapies in sepsis remains an attractive but unproven strategy;[6] the use of biological mediators or pharmacological agents with antioxidant properties is gradually increasing to strengthen the endogenous defense system in many diseases involving oxidative stress in their pathogenesis. The studies have focused on the ß-glucan molecule because of the beneficial effects on the immune system and the lack of toxic or adverse effects.[2] Although major discrepancies exist, several mechanisms are proposed for the protective effects of ß-glucan treatment, some of them are related to antioxidant capacity and free-radical scavenger activity, and anti-inflammatory properties of the molecule.[2,4,30] Systemic administration of ß-glucans has been shown to enhance host protection against infections in humans and animal models, such as sepsis and associated organ injury. Clinical studies have shown that glucan therapy can reduce hospitalization time, post-operative infection and mortality rates in high-risk patients undergoing major thoracic or abdominal surgery[7,8] and suggested that intake of glucans in trauma surgical patients will increase the chance of survival via decreasing the frequencies of septic complications. Additionally, in a clinical ex-vivo study, it has been shown that ß-glucan could protect an endothelial monolayer from damage that arises from neutrophils obtained from septic patients exert a dramatic compromise of endothelial barrier integrity.[31] Similarly, when investigated in vitro effects of ß-glucan on oxidative stress by lipopolysaccharide associated with oxidative damages of human blood platelets; TBARS, protein carbonyl levels and nitration of tyrosine residues in proteins of platelets were found to be lower in the presence of ß-glucan.[32] These findings are also in accordance with the present study that ß-glucan administration was associated with significantly reversing the high MDA levels in tissues and plasma of a rat model where sepsis was induced by CLP. In conclusion, although sepsis cannot be simplified to ROS pathology alone, in this first study in which AOPP levels in sepsis model are investigated; it may be suggested that the Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Demir et al. Does ß-glucan can have a protective role against oxidative stress in the experimental sepsis model in rats?

oxidants produced by MPO derived from neutrophils are more likely to cause oxidative damage to proteins than lipids, and ß-glucan with anti-inflammatory and antioxidant effects may be a promising candidate with further clinical and experimental trials for sepsis therapy. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: M.D., K.K., C.Y., E.M.S.; Design: M.D., K.K., C.Y.; Supervision: M.D., K.K.; Fundings: M.D., K.K.; Materials: M.D., K.K., C.Y., E.M.S; Data: M.D., K.K., C.Y., E.M.S; Analysis: M.D., K.K., C.Y.; Literature search: M.D., K.K., C.Y., E.M.S; Writing: M.D., K.K.; Critical revision: M.D., K.K., C.Y., E.M.S. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Samraj RS, Zingarelli B, Wong HR. Role of biomarkers in sepsis care. Shock 2013;40:358−65. 2. Ercan M, Ozdemir S. The contribution to studies of the effect of β-glucan on plasma viscosity in rat sepsis model. Med Sci Discover 2015;2:148– 53. 3. Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, et al. The Timing of Early Antibiotics and Hospital Mortality in Sepsis. Am J Respir Crit Care Med 2017;196:856−63. 4. Sener G, Toklu H, Ercan F, Erkanli G. Protective effect of beta-glucan against oxidative organ injury in a rat model of sepsis. Int Immunopharmacol 2005;5:1387−96. 5. Crimi E, Sica V, Williams-Ignarro S, Zhang H, Slutsky AS, Ignarro LJ, et al. The role of oxidative stress in adult critical care. Free Radic Biol Med 2006;40:398−406. 6. Weiss SL, Deutschman CS. Elevated malondialdehyde levels in sepsis something to ‘stress’ about?. Crit Care 2014;18:125. 7. Babineau TJ, Hackford A, Kenler A, Bistrian B, Forse RA, Fairchild PG, et al. A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-glucan) in high-risk surgical patients. Arch Surg 1994;129:1204−10. 8. Dellinger EP, Babineau TJ, Bleicher P, Kaiser AB, Seibert GB, Postier RG, et al. Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group. Arch Surg 1999;134:977−83. 9. Ritter C, Andrades M, Frota Júnior ML,Bonatto F, Pinho RA, Polydoro M, et al. Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation. Intensive Care Med 2003;29:1782−9. 10. Koksal GM, Sayilgan C, Aydin S, Oz H, Uzun H. Correlation of plasma and tissue oxidative stresses in intra-abdominal sepsis. J Surg Res 2004;122:180−3. 11. Senoglu N, Yuzbasioglu MF, Aral M, Ezberci M, Kurutas EB, Bulbuloglu E, et al. Protective effects of N-acetylcysteine and beta-glucan pretreatment on oxidative stress in cecal ligation and puncture model of sepsis. J Invest Surg 2008;21:237−43. 12. Babayigit H, Kucuk C, Sozuer E, Yazici C, Kose K, Akgun H. Protective effect of beta-glucan on lung injury after cecal ligation and puncture in rats. Intensive Care Med 2005;31:865−70. 13. Bradley PP, Priebat DA, Christensen RD, Rothstein G. Measurement of

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cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982;78:206−9. 14. Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, et al. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 1996;49:1304−13. 15. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351−8. 16. Selmeci L, Seres L, Antal M, Lukács J, Regöly-Mérei A, Acsády G. Advanced oxidation protein products (AOPP) for monitoring oxidative stress in critically ill patients: a simple, fast and inexpensive automated technique. Clin Chem Lab Med 2005;43:294−7. 17. França RT, Da Silva AS, Costa MM, Paim FC, Paim CB, Thomé GR, et al. Relationship between oxidative stress and clinical-pathological aspects in dogs experimentally infected with Rangelia vitalii. Res Vet Sci 2012;93:1309−13. 18. Da Silva AS, Paim FC, Santos RC, Sangoi MB, Moresco RN, Lopes ST, Jaques JA, Baldissarelli J, Morsch VM, Monteiro SG. Nitric oxide level, protein oxidation and antioxidant enzymes in rats infected by Trypanosoma evansi. Exp Parasitol 2012;132:166–70. 19. Ogino T, Packer L, Maguire JJ. Neutrophil antioxidant capacity during the respiratory burst: loss of glutathione induced by chloramines. Free Radic Biol Med 1997;23:445−52. 20. Erkol H, Kahramansoy N, Kordon Ö, Büyükaşık O, Serin E, Kükner A. Effect of beta-glucan in lung damage secondary to experimental obstructive jaundice. Turk J Gastroenterol 2012;23:38–45. 21. Sacar S, Sacar M, Aybek H, Turgut H, Onem G, Cevahir N, et al. Comparison of the therapeutic efficacy of linezolid and vancomycin and correlation of serum and tissue malondialdehyde and myeloperoxidase in an experimental mediastinitis model. J Surg Res 2009;152:89−95. 22. Mühl D, Woth G, Drenkovics L, Varga A, Ghosh S, Csontos C, et al. Comparison of oxidative stress & leukocyte activation in patients with severe sepsis & burn injury. Indian J Med Res 2011;134:69–78. 23. Kothari N, Keshari RS, Bogra J, Kohli M, Abbas H, Malik A, et al. Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis. J Crit Care 2011;26:435.e1−7. 24. Andrades M, Ritter C, Moreira JC, Dal-Pizzol F. Oxidative parameters differences during non-lethal and lethal sepsis development. J Surg Res 2005;125:68−72. 25. Ozturk E, Demirbilek S, Begec Z, Surucu M, Fadillioglu E, Kirimlioglu H, et al. Does leflunomide attenuate the sepsis-induced acute lung injury? Pediatr Surg Int 2008;24:899–905. 26. Andrades M, Ritter C, de Oliveira MR, Streck EL, Fonseca Moreira JC, Dal-Pizzol F. Antioxidant treatment reverses organ failure in rat model of sepsis: role of antioxidant enzymes imbalance, neutrophil infiltration, and oxidative stress. J Surg Res 2011;167:e307–13. 27. Zolali E, Hamishehkar H, Maleki-Dizaji N, Majidi Zolbanin N, Ghavimi H, Kouhsoltani M, et al. Selenium effect on oxidative stress factors in septic rats. Adv Pharm Bull 2014;4: 289–93. 28. Lorente L, Martín MM, Abreu-González P, Domínguez-Rodriguez A, Labarta L, Díaz C, et al. Sustained high serum malondialdehyde levels are associated with severity and mortality in septic patients. Crit Care 2013;17:R290. 29. Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A. Biomarkers of oxidative damage in human disease. Clin Chem 2006;52:601−23. 30. Du B, Lin C, Bian Z, Xu B. An insight into anti-inflammatory effects of fungal beta-glucans. Trends Food Sci Technol 2015;41:49–59. 31. Fox ED, Heffernan DS, Cioffi WG, Reichner JS. Neutrophils from critically ill septic patients mediate profound loss of endothelial barrier integrity Crit Care 2013;7-17:R226. 32. Saluk J, Bijak M, Ponczek MB, Nowak P, Wachowicz B. (1→3)-β-D-Glucan reduces the damages caused by reactive oxygen species induced in human platelets by lipopolysaccharides. Carbohydr Polym 2013;97:716– 24.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

ß-glukan, sıçanlarda deneysel sepsis modelinde oksidatif strese karşı koruyucu rol oynayabilir mi? Dr. Meltem Demir,1 Dr. Kader Köse,2 Dr. Cevat Yazıcı,2 Dr. Erdoğan Mütevelli Sözüer3 1 2 3

İstinye Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, İstanbul Erciyes Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, Kayseri Erciyes Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Kayseri

AMAÇ: Sepsiste çok yüksek mortalite oranı oksidatif stres ile ilişkili olabilir. Bu çalışma fareler üzerinde, çekal ligasyon-perforasyon (CLP) ile oluşturulan karıniçi sepsis modelinde oksidatif stresin varlığını ve ayrıca ß-glukanın potansiyel koruyucu etkisini araştırmak için yapılmıştır. GEREÇ VE YÖNTEM: Otuz erkek sıçan eşit olarak “Sham”, “Sepsis” ve “ß-Glukan” olarak üç gruba ayrıldı. Sham grubunda sadece laparotomi yapıldı, Sepsis ve ß-Glukan gruplarında CLP ile sepsis oluşturuldu. ß-Glukan grubuna CLP’yi takiben intraperitonal olarak tek bir doz 4 mg ß-glukan/ kg verildi. Sepsis gelişiminden sonra 48. saatin sonunda Sepsis ve ß-Glukan gruplarından ve Sham grubundan kan ve doku (karaciğer, akciğer ve böbrek) örnekleri alındı. Plazma örneklerinde miyeloperoksidaz (MPO) ve ileri oksidasyon protein ürünleri (AOPP) seviyeleri belirlendi ve plazma ve dokularda malondialdehit (MDA) ölçüldü. BULGULAR: MPO ve AOPP, Sepsis ve ß-Glukan gruplarında daha yüksekti; ancak plazma ve doku MDA düzeyleri sadece Sepsis grubunda Sham grubundan daha yüksekti (p<0.05). Bununla birlikte, Sepsis grubuyla karşılaştırıldığında, böbrek MDA değeri hariç ölçülen tüm parametreler, ß-Glukan grubunda anlamlı olarak daha düşüktü (p<0.05). TARTIŞMA: CLP sepsis modelinde AOPP düzeylerini araştırmak için yapılan bu ilk çalışmada; nötrofillerden salgılanan MPO reaksiyonu ile üretilen ROS, lipitlere kıyasla proteinlerde oksidatif hasar oluşturabilir ve ß-glukan, sepsis tedavisi için alternatif bir ajan olarak kullanılabilir. Anahtar sözcükler: ß-Glukan; ileri oksidasyon protein ürünleri; miyeloperoksidaz; reaktif oksijen türleri; sepsis. Ulus Travma Acil Cerrahi Derg 2020;26(5):657-662

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doi: 10.14744/tjtes.2019.79002

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EXPERIMENTAL STUDY

The efficacy of curcumin on PDGF expression and NF-kappa B pathway: TNBS-induced colitis Yüksel Altınel, M.D.,1 Şenay Yalçın, M.D.,2 Gülçin Ercan, M.D.,1 Erkan Yavuz, M.D.,1 Candaş Erçetin, M.D.,1 Osman Bilgin Gülçiçek, M.D.,1 Atilla Çelik, M.D.,1 Güven Özkaya, M.D.,3 Hafize Uzun, M.D.4 1

Department of General Surgery, Bağcılar Training and Research Hospital, İstanbul-Turkey

Department of Pathology, Bağcılar Training and Research Hospital, İstanbul-Turkey

Department of Biostatistics, Uludağ University Faculty of Medicine, Bursa-Turkey

Department of Biochemistry, Cerrahpaşa University Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: Curcumin is an antioxidant and anti-inflammatory molecule known to be a potent inhibitor of nuclear factor kappa B (NF-kappa B). In this study, we aimed to investigate the therapeutic effects of curcumin on colitis induced by a 2,4,6-trinitrobenzene sulfonic acid (TNBS). METHODS: After the induction of colitis under anesthesia, 42 rats were divided into six groups as follows; the curcumin oral group, curcumin (20 mg/kg); the corn oil oral group, corn oil (20 mg/kg) using gastric gavage, the curcumin rectal group, curcumin; the corn oil rectal group, corn oil; the control group, 1 mL saline solution (0.9% NaCl) were administered using the rectal route. In the sham group, only rectal catheterization was performed. At the end of the seven day, the blood and intestinal tissue samples were obtained for histopathological examination and for MPO, MDA, NO, PDGF, IL-6, TNF-alpha, NF-kappaB. RESULTS: The macroscopic damage score was significantly higher in curcumin oral, corn oil oral and saline groups when compared to the sham group (p<0.05). The significant differences between groups were evaluated using the biochemical analysis of intestinal tissue for IL-6, NO, NF-κB, PDGF, TNF-α, MDA, MPO (p<0.05). NF-κB levels of blood in curcumin oral, curcumin rectal, sham, corn oil oral, corn oil rectal groups were significantly increased when compared to saline rectal group (p≤0.001). NF-κB serum levels of corn oil rectal and control group (p≤0.001) were lower than the sham group (p=0.012). CONCLUSION: The effects of curcumin improved possibly by modulating the NF-κB signaling pathway should be considered against colitis alone or in combination with the conventional anti-colitic therapies in future studies. Keywords: Anti-inflammatory; anti-oxidant; colitis; curcumin; NF-kappaB.

INTRODUCTION Inflammatory Bowel Diseases (IBD), usually referring to Ulcerative colitis or Chron’s Disease, are determined by increased production of inflammatory cytokines, epithelial cell apoptosis and immune cell infiltration causing to the disruption of intestinal epithelial structure. The intestinal damage of IBD had a growing body of evidence determines that the abnormal production of reactive oxygen species (ROS) and dif-

ferentiated antioxidant defense participation.[1,2] Nowadays, various drugs, including mesalamine, sulfasalazine, corticosteroids and immunomodulators, are used to be a part of the treatment of IBD patients. However, there are many side effects of these drugs and complications of diseases that show the unmet needs for the safety of the maintenance therapy.[3,4] Curcumin derived from the root of the turmeric plant (Curcuma longa) appears to be the therapeutic compounds of

Cite this article as: Altınel Y, Yalçın Ş, Ercan G, Yavuz E, Erçetin C, Gülçiçek OB, et al. The efficacy of curcumin on PDGF expression and NF-kappa B pathway: TNBS-induced colitis. Ulus Travma Acil Cerrahi Derg 2020;26:663-670. Address for correspondence: Yüksel Altınel, M.D. Bağcılar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 440 40 00 E-mail: dryukselaltinel@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):663-670 DOI: 10.14744/tjtes.2019.45570 Submitted: 09.02.2019 Accepted: 01.12.2019 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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pharmacological actions, including anti-tumor, anti-oxidant, anti-proliferative and anti-inflammatory effects.[5,6] Curcumin has an effect on modulating the inhibition of the tumor necrosis factor alfa (TNF-α) induced nuclear kappa-B (NF-kB) activation pathways.[7,8] Also, it has preventive and therapeutic effects in murine colitis models, including trinitrobenzene sulfonic acid (TNBS)-, dextran sulfate sodium (DSS)-, and dinitrobenzene sulfonic acid (DNB)-induced colitis by inhibiting NF-kB.[9,10] The transmural inflammation of colitis induced by trinitrobenzene sulphonic acid (TNBS) affects the intestinal motor apparatus, and subsequently, a loss of myenteric and submucosal neurons adjacent to intestinal smooth muscle cells (ISMC) leading to changes in cell number.[11–14] There are many pluripotent activities of curcumin helping to these effects, such as a potent inhibitor of and platelet-derived growth factor PDGF-stimulated proliferation and pro-inflammatory factors, such as the cytokines IL-1 and TNF-α and mesenchymal growth factors, such as insulin-like growth factor (IGF).[15–17] Therefore, we conducted the present study to further approach the inflammation of colonic mucosa and investigate the possible preventive and therapeutic effects of curcumin considering new alternative therapy. Especially, we investigated the efficacy of different methods like the oral or rectal route of the curcumin treatment in this experimental model through the pathways of myeloperoxidase (MPO) activity and lipid peroxidation malondialdehyde (MDA).

MATERIALS AND METHODS Animals Forty-two female Wistar Hannover rats weighing 300 to 500 g were used in this study. The animals were kept in a restricted access room with controlled temperature and light cycle. The animals were fed on standard rat chow, allowed access to tap water ad libitum. The rats were housed in individual standard cages. The study protocol was in accordance with the guidelines for animal research and approved by the Animal Ethical and Research Committee of Bagcilar Research and Training Hospital.

Reagents

There were six groups consisting of seven rats for each: (1) control group: rats were treated with daily rectal single dose of saline (1 mL, 0.9% NaCl) using feeding tube from day one to day 7; (2) oral curcumin group: rats were treated with daily single dose of curcumin (20 mg/kg) which was dissolved in corn oil (1 mg/mL) by gastric gavage for seven days following the induction of colitis; (3) rectal curcumin group: rats were treated with daily rectal single dose of curcumin (20 mg/kg) which was dissolved in corn oil (1 mg/mL) by feeding tube for seven days following the induction of colitis; (4) sham group: no colitis was induced, only rectal insertion of feeding tube was performed once a day from day 1 to day 7; (5) oral corn oil group: rats were treated with daily single dose of corn oil (20 mg/kg) by gastric gavage for seven days following the induction of colitis; (6) rectal corn oil group: rats were treated with daily rectal single dose of corn oil (20 mg/kg) by feeding tube for seven days following the induction of colitis. At postoperative 7th day, after their weight measurements, finally, all rats under general anesthetized with intramuscular ketamine (50 mg/ kg; Ketalar, Pfizer Inc.) and xylazine (10 mg/kg, Ronpum, Bayer AG), were performed laparotomy and total colectomy after inspection for adhesions and were sacrificed by an intra-cardiac puncture to get blood samples for nuclear kappa-B (NF-kB), nitric oxide (NO), platelet-derived growth factor (PDGF), interleukin 6 (IL-6), tumor necrosis factor alfa (TNF-α). When tissue samples were obtained, macroscopic damage was scored on a scale of 0 to 13 modified from a description by Wang et al.[18] (Table 1) by the same pathologist who was Table 1. Macroscopic scoring of mucosal damage in colitis Macroscopic damage

Score

Ulceration and inflammation None 0 Local hyperemia, no ulcer

One site of ulcer not accompanied by congestion

or thickening of the intestinal wall One site of ulcer accompanied by inflammation

≥2 sites of ulcer accompanied by inflammation

1 cm > inflamed segment + ulcer site ≥2

1 cm < inflamed segment + ulcer site ≥2

The trinitro-benzene sulfonic acid (TNBS) (5% w/v, 40 mg) and Curcumin were purchased from Sigma Chemical Co., St. Louis, USA. Other agents used in this study were all of the analytical grades.

2 cm ≤ inflamed segment (the score increases

Experimental Protocol

None 0

On the day of induction, the mixture of 0.6 mL of TNBS and 0.25 mL of 50% ethanol was instilled into the lumen of the colon by 6 F feeding tube, which was inserted rectally until the tip was 8 cm proximal to the anus. Then, 0.5 mL of air was given to ensure that the whole mixture was instilled into the lumen of the colon. 664

7–10

1 with each 1 cm enlargement of the inflamed segment) Adhesions Mild (easy to separate colon from other tissues)

Severe 2 Diarrhea None 0 Present 1

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blinded to the group assignment of the rats. Later, the tissue samples were fixed with 10% formaldehyde solution. Tissue samples of 5 mm in length were taken from 8 cm distal segments of total colectomy specimens. All samples were embedded in paraffin wax, and sections were taken and stained with hematoxylin-eosin (HE). All sections were evaluated using light microscopy and scored on a scale of 0 to 10, as described by Wang et al.[18] (Table 2) in a blinded fashion by the same pathologist. Serum IL-6, TNF-α levels nuclear kappa-B (NF-Κb), nitric oxide (NO) and platelet-derived growth factor (PDGF) were analyzed with ELISA using rat kits (InvitrogenTM Rat Immunoassay Kit; Invitrogen Corporation, Carlsbad, California, USA).

Lipid Peroxidation Determination The colonic tissue for the determination of MDA and NO substances were homogenized in-cold PBS (pH 7.4) and centrifuged at 3000 rpm for 10 min at 4°C. The last supernatant was collected at 20°C until analysis with corresponding assay kits according to the manufacturer’s guide. The colon tissue samples were homogenized in 10% KCI (1.10g/mL) in a glass-glass homogenizer. Homogenate was added into the mixture, which consisted of 8.1% sodium dodecyl sulfate, 0.82% thiobarbituric acid, and acetate buffer (3M, pH 3.5), and the reaction was evaluated at 532 nm by the spectrophotometer. Results were identified as µmol/L using a standard curve.

Statistical Analysis Myeloperoxidase Activity Assay Myeloperoxidase (MPO) is a biochemical sample of neutrophil infiltration into intestinal tissues and was used to determine colitis. Tissue samples were homogenized in 10 volumes of ice-cold potassium phosphate buffer (50 Mm K2HPO4, pH 6.0) containing hexadecyltrimethylammonium bromide (0.5%, g/mL). One unit of the enzyme activity was established as the amount of MPO present per gram of tissue weight that causes a change in absorbance of 10 min at 460 nm (37°C). The MPO activity in the supernatant was evaluated by the assay kit, depending on its provider’s instructions. Table 2. Microscopic scoring of colitis Histological lesion

Score

Ulcer None

Ulcer <3 mm

Ulcer >3 mm

Inflammation None

Mild

Severe

Granuloma None

Present

Depth of the disease None

Submucosal layer

Muscular layer

Serosal layer

Fibrosis None

Mild

Severe

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Data were expressed as means ± standard error of the mean (SEM). Statistical analyses were performed using the Statistical Package for Social Sciences version 10.01(SPSS, Chicago, IL, USA). Overall comparisons between the groups were made using 1-way analyses of variance (ANOVA). The Kruskal-Wallis test followed by the Mann-Whitney U test was used for statistical evaluation, and p<0.05 was accepted as a level of significance.

RESULTS There were no statistically significant differences in weight loss between all groups. Also, when we evaluated the intra-abdominal adhesion, there were no statistically significant differences among the groups.

Biochemical Assessment The biochemical analysis of blood samples for PDGF, TNF-α, MPO did not show any significant difference among groups (Table 3). NF-kB levels of blood in curcumin oral, curcumin rectal, sham, corn oil oral, corn oil rectal groups were significantly increased when compared to saline rectal group (p≤0.001). NF-kB serum levels of corn oil rectal and control group (p≤0.001) were lower than the sham group (p=0.012). The significant differences between groups were evaluated by the analysis of intestinal tissue sampling for IL-6, NO, NF-kB, PDGF, TNF-α, MDA, MPO (p<0.05) (Table 4). Tissue NF-kB level of curcumin oral group was lower than curcumin rectal (p≤0.001), sham (p≤0.001) and corn oil oral groups (p=0.030). Tissue NF-kB level of curcumin rectal group was higher than saline rectal (p=0.005), curcumin oral (p≤0.001) and corn oil rectal (p=0.045) groups. The sham group for tissue NF-kB level was higher than saline rectal (p≤0.001), curcumin oral (p≤0.001), corn oil oral (p=0.037) and corn oil rectal (p≤0.001) groups. The tissue level of PDGF of the sham group was higher than the saline rectal (p=0.003), curcumin oral (p≤0.001), corn oil oral (p=0.004) and corn oil rectal (p≤0.001) groups. The 665

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tissue level of PDGF in the curcumin oral group was significantly lower when compared to the curcumin rectal group (p=0.048).

Pro-Inflammatory Cytokine Release IL-6 serum levels in corn oil oral group were significantly increased when compared to corn oil rectal (p=0.033) and saline rectal (p=0.035) groups. IL-6 tissue level of the sham group was significantly higher than all other groups (p<0.05). TNF- α tissue level of the corn oil oral group was higher than the saline rectal (p=0.020) and corn oil rectal (p=0.033) groups. The TNF-α tissue level of the curcumin oral group was lower than the curcumin rectal (p=0.001) and sham (p=0.004) groups. The TNF-α tissue level in the curcumin rectal group was higher when comparing to the saline rectal (p≤0.001), curcumin oral (p≤0.001) and corn oil rectal (p≤0.001). The TNF-α tissue level of the sham group was higher than the saline rectal (p≤0.001), curcumin oral (p=0.004) and corn oil rectal (p≤0.001).

The Inflammatory Response MPO tissue level of the sham group was significantly higher than the saline rectal (p=0.033) and curcumin oral (p=0.005) groups.

Colonic Oxidative Differentiation MDA serum level of the saline rectal group was lower than the sham group (p=0.017), curcumin rectal (p=0.015) and corn oil oral group (p=0.010). MDA tissue level of the sham group was significantly higher than the curcumin oral group (p=0.013). NO serum level of the curcumin oral group was significantly higher than the saline rectal group (p=0.037). NO tissue level of the sham group was higher than curcumin oral (p=0.002) and corn oil rectal (p=0.038) groups.

Histopathological Findings (Table 5) The macroscopic damage score was significantly higher in curcumin oral (p=0.016), corn oil oral (p=0.016) and saline rectal (p=0.006) groups when compared to the sham group. However, no significant difference was found between curcumin and corn oil groups. Even if it was not statistically significant, the macroscopic and microscopic damage scores of the curcumin rectal group were more decreased than the curcumin and corn oil groups except the sham group (Fig. 1). Microscopic damage score was significantly higher in curcumin oral (p=0.02), saline rectal (p=0.015) and corn oil oral (p=0.019)

Table 3. The biochemical analysis of blood samples (mean-standard deviation) Biochemical

s_IL6

s_NO

s_NFkB s_PDGF s_TNF-α s_MDA s_MPO

Saline rectal

156.74±21.40 72.66±22.94 1.50±0.46 2.52±0.28 143.92±55.19 1.27±0.09 19.81±1.82

Curcumin oral

164.57±19.16 105.49±28.92 3.91±0.71 2.62±0.79 186.39±39.68 1.63±0.27 20.36±2.51

Curcumin rectal 187.61±19.45 97.24±17.10 3.83±0.51 2.98±0.40 174.53±39.74 1.70±0.24 21.25±3.17 Sham

165.70±31.86 97.98±12.66 4.32±0.56 2.71±0.31 193.81±18.52 1.69±0.27 22.73±2.85

Corn oil oral

206.60±51.05

Corn rectal

156.28±20.33 80.89±19.62 3.32±0.43 3.08±0.65 181.65±37.00 1.45±0.22 20.33±3.00

90.91±9.83

3.93±0.39

2.91±0.66

191.89±20.90

1.72±0.19

23.01±1.93

0.017 0.036 <0.001 0.364 0.158 0.004 0.126

IL-6, NO, NF-kB, PDGF, MPO, MDA: (µM/l), TNF-α (pg/ml). Data are means±SEM. *: p<0.05, statistically significant. IL6: Interleukin 6; NO: Nitric oxide; NFkB: Nuclear kappa-B; PDGF: Platelet-derived growth factor; TNF-a: Tumor necrosis factor alfa; MDA: Malondialdehyde; MPO: Myeloperoxidase.

Table 4. The analysis of intestinal tissue sampling (mean-standard deviation), (pg/g tissue) Tissue

t_IL6

t_NO

t_NFkB t_PDGF t_TNF-α t_MDA t_MPO

Saline rectal

130.88±61.79 55.68±5.33 1.83±0.68 1.83±0.95 99.56±33.21 1.11±0.51 12.55±5.67

Curcumin oral

98.48±56.79 33.24±11.09 1.50±0.39 1.20±0.66 129.53±39.46 0.94±0.43 10.51±4.62

Curcumin rectal 197.74±53.88 60.33±27.19 3.22±1.11 2.92±0.55 243.54±92.06 1.55±0.22 18.64±5.85 Sham

339.09±122.03 71.59±17.63 3.77±0.69 4.14±2.18 234.36±47.89 1.88±0.92 21.43±2.83

Corn oil oral

203.51±43.02

Corn rectal

124.11±19.59 43.49±17.99 2.13±0.45 1.41±0.10 104.82±17.44 1.11±0.19 18.12±8.18

<0.001

51.65±13.36 0.003

2.65±0.32

1.85±0.59

188.44±28.55

1.31±0.28

14.12±1.22

<0.001 <0.001 <0.001 0.013 0.003

*: p<0.05, statistically significant. IL6: Interleukin 6; NO: Nitric oxide; NFkB: Nuclear kappa-B; PDGF: Platelet-derived growth factor; TNF-a: Tumor necrosis factor alfa; MDA: Malondialdehyde; MPO: Myeloperoxidase.

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Table 5. The histopathological comparison of groups, mean (min–max) Histopathological Macroscopic Microscopic Inflammatory Crypt Ulcer Granuloma damage score damage score cell infiltration abscess Saline rectal

3 (2–4)

8 (4–9)

3 (2–3)

1 (0–2)

2 (1–2)

Curcumin oral

2 (1–4)

7 (4–9)

3 (2–3)

1 (0–2)

2 (1–2)

Curcumin rectal

1 (0–3)

1 (0–9)

1 (0–3)

0 (0–3)

0 (0–2)

1 (0–2)

Sham

0 (0–1)

0 (0–9)

0 (0–2)

0 (0–0)

Corn oil

3 (1–4)

8 (3–9)

3 (1–3)

2 (0–3)

2 (0–2)

Corn rectal

2 (1–4)

4 (3–9)

2 (1–3)

1 (0–3)

0 (0–2)

5 (0–2)

0.001

0.003

0.105 0.005 0.006

*: p<0.05, statistically significant.

groups than the sham group. The inflammatory cell accumulation and ulceration were significantly higher in the curcumin oral group than the sham group (p=0.019/p=0.009) (Fig. 2). Furthermore, the corn oil oral and saline rectal groups’ inflammatory cell accumulation was significantly higher than the

sham group (p=0.031/p=0.011). However, there was no statistical significance. The inflammatory cell, ulcer and granuloma formation of the curcumin rectal group had slightly decreased levels comparing to the corn oil and curcumin groups except for the sham group. Granuloma formation of saline rectal (p=0.049) and curcumin oral (p=0.008) group was significantly higher than the sham group. In addition to that, the mucosal disruption of the sham group was significantly lower than the curcumin oral (p=0.04) and saline rectal (p=0.004) groups.

DISCUSSION

Figure 1. The rectal curcumin administration; normal intestinal tissue (HEx4).

Figure 2. The administration of oral curcumin; the area of ulcer (HEx4).

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This study aims to investigate the efficacy of different treatment methods like oral or rectal routes of the curcumin medication for IBD model. The TNBS colitis had granulomas with infiltration of inflammatory cells over the intestinal layers. Similar to our study, the saline rectal group has more than other groups. Although there are various reagents (such as DSS, and acetic acid) to contribute the colitis experiments, TNBS has the useful potential in the clinic for the management of the human diseases.[19–21] The outcomes of curcumin on chemically induced colitis experiments have been precisely determined in the literature. However, it is not established yet, which therapy regimen (oral or rectal) is efficient for the treatment modalities of colitis. The initiation and maintenance of inflammation in IBD have been established by NO overproduction and upregulation of inducible nitric oxide synthase (iNOS). Furthermore, the Nuclear kappa-B (NF-kB) has been primarily activated by oxidative stress. Additionally, TNF-α has a potential initiation for NF-kB in monocytes and then, IL-6 is expressed by the regulation of NF-kB.[22] The anti-inflammatory effects of curcumin are predominantly expressed by the inhibition of the pathways and mediators, such as NF-kB and TNF-α initiated oxidative stress. The treatment of curcumin has beneficial effects on decreasing the level of NO and MDA in the colonic mucosa.[22,23] According to our findings, we had similar outcomes in curcumin oral group when comparing to other groups for the levels of MPO, MDA, NO, IL-6, TNF-α, NF-kB. However, there was a dilemma; it was not statistically significant, but the macro667

Altınel et al. The efficacy of curcumin on PDGF expression and NF-kappa B pathway: TNBS-induced colitis

scopic and microscopic damage scores of the curcumin rectal group decreased more than the curcumin oral and corn oil groups. Although the decrease of IL-6 in the curcumin oral group was higher than the curcumin rectal group, the microscopic damage score suggesting that topical-rectal administration of curcumin might have some more beneficial effects on anti-inflammatory efficiency. The severity of the inflammatory injuries has been evaluated by morphological injury and histological variations. One of the markers of the acute inflammatory response is MPO that accomplishes the activity of neutrophils. The elevated MPO levels of the acetic acid-induced colitis were reduced by the treatment of curcumin correlated with the histopathological findings, such as inflammatory cell infiltration.[2,24,25] However, we had discordance in the histopathological and the colon samples for MPO levels when comparing oral and rectal routes of curcumin treatment. The scores of histopathological findings were lower in curcumin rectal; on the other hand, the tissue samples were lower in the curcumin oral rectal groups when comparing MPO. Additionally, our oral curcumin therapy group MPO results were concordant with the findings of enema containing study by Kadri and et al.[26] Maybe the longer study periods are needed to evaluate the different types of administration of curcumin therapies or scoring systems for the pathological findings. MDA is a good indicator of the oxidative stress and the lipid peroxidation process. The colonic MDA is in the increasing range of both human and animal models for ulcerative colitis, similar to our current study results.[24] Moreover, we evaluated the treatment of curcumin, causing the reduction of MDA levels in the rats with colitis like other studies. This conclusion could be one of the results of the reduction in neutrophil infiltration by curcumin effects in the colonic samples.[2,10] The anti-inflammatory effects of curcumin have an influence on the treatment of colitis related to the inhibition of NF-kB pathways and its antioxidant contents. The cellular signaling pathways induced apoptosis are containing the Bcl-2 family of proto-oncogenes, transcription factor NF-kB and TNF-α. [2] There is a study related to ROS-induced cytotoxicity, including the oxidants and epithelial apoptosis by inhibiting the neutrophil and macrophages in the TNF-α colitis model.[27] Controversially, in our study, it was not exactly well-matched with these findings. The tissue NF-kB and TNF-α levels of the curcumin oral group was lower than other groups, and it was not statistically significant. However, the histopathological correlation was observed by the curcumin rectal group. Unlike some studies,[2,27] we had a deficiency to succeed at the finding of the epithelial cell apoptosis by Bcl-2 immunohistochemical dye in which there was no meaningful evaluation performed by our pathologist to mention. During inflammatory reactions, some of the reactive oxygen species (ROS) production generated when PDGF binds to its 668

receptor and oxidized a cysteine residue in the active site of phosphates following the transduction of PDGF-signaling.[28] The phosphatase inhibition and reduction of PDGF signaling occurred as a result of anti-oxidant effects.[29] Due to the antioxidant properties of curcumin, the PDGF stimulated ROS generation in cultured VSMC was inhibited by the effects of both curcumin and bisdemethoxy curcumin that was the differential effects of these compounds on PDGF-signaling.[28,29] When we concerned about the similar pathways, the biochemical findings that we obtained from our experiment, was correlated with the literature. The amount of PDGF for the curcumin oral group was 1.20±0.66 (mean-standard error) lower than the other groups. However, histopathologically, the curcumin rectal group showed more improvement among the inflammatory changes considering the influence of the anti-oxidant effects of curcumin. Furthermore, it was reported that curcumin has some analogs and nano-formulations properties for potentialenhancement of their therapeutic administrations.[22] That could be considered as a beneficial point for further improvements of any doses and routes in curcumin treatments like our study. Despite its various alterations in results of experimental studies, there is a wide range of clinical applications of curcumin in some case series and small clinical trials for every stage of IBD follow up, such as Hanai et al.[8,22] In the study of Hanai et al.,[8] they had safe and effective clinical conclusions of the curcumin treatment for ulcerative colitis patients, besides its undetermined dosages and combined components of medication for curcumin administration. Especially, that is the primary start point of view of our study to figure out the different dosages and the application routes comparing the literature. In conclusion, the results of this study suggest that substantially the curcumin may be considered to improve the histopathological findings on the rectal route and the biochemical antioxidant and anti-inflammatory assessments of the oral route. Although we did not perform both types of administration and additionally different doses compared to literature, there were no exact solutions determined mainly for clinical usage. As far as we concerned, further research with different doses may be beneficial to undertake the therapeutic components of curcumin into clinical use.

Acknowledgments This study was presented as a poster at the 2016 ASCRS Annual Scientific Meeting in Los Angeles, CA.

Funding This study was supported by the Research Fund of Bagcilar Research and Training Hospital. The authors received no financial support for the authorship and publication of this article. Ethics Committee Approval: Approved by the local ethics committee. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Altınel et al. The efficacy of curcumin on PDGF expression and NF-kappa B pathway: TNBS-induced colitis

Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Y.A.; Design: Y.A., H.U.; Supervision: H.U.; Fundings: G.E., E.Y.; Materials: O.B.G., A.Ç.; Data: Y.A., Ş.Y.; Analysis: G.Ö.; Literature search: Y.A., C.E.; Writing: Y.A.; Critical revision: Y.A., H.U. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Funding: This study was supported by the Research Fund of Bagcilar Training and Research Hospital.

REFERENCES 1. Sartor RB. Mucosal immunology and mechanisms of gastrointestinal inﬂammation. In: Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. Feldman M, Friedman LS, Brandt LJ, editors. Philadelphia, PA: WB Saunders; 2002. pp.21–51. 2. Topcu-Tarladacalisir Y, Akpolat M, Uz YH, Kizilay G, Sapmaz-Metin M, Cerkezkayabekir A, et al. Effects of curcumin on apoptosis and oxidoinflammatory regulation in a rat model of acetic acid-induced colitis: the roles of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. J Med Food 2013;16:296–305. 3. Hanauer SB. Medical therapy for ulcerative colitis 2004. Gastroenterology 2004;126:1582–92. 4. Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006;12:S3–9. 5. Calabrese V, Butterfield DA, Stella AM. Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer’s disease. Ital J Biochem 2003;52:177–81. 6. Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, et al. Chemopreventive and therapeutic effects of curcumin. Cancer Lett 2005;223:181–90. 7. Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Mol Pharmacol 2006;69:195–206. 8. Hanai H, Iida T, Takeuchi K, Watanabe F, Maruyama Y, Andoh A, et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 2006;4:1502–6. 9. Jian YT, Mai GF, Wang JD, Zhang YL, Luo RC, Fang YX. Preventive and therapeutic effects of NF-kappaB inhibitor curcumin in rats colitis induced by trinitrobenzene sulfonic acid. World J Gastroenterol 2005;11:1747–52. 10. Deguchi Y, Andoh A, Inatomi O, Yagi Y, Bamba S, Araki Y, et al. Curcumin prevents the development of dextran sulfate Sodium (DSS)-induced experimental colitis. Dig Dis Sci 2007;52:2993–8. 11. Sanovic S, Lamb DP, Blennerhassett MG. Damage to the enteric nervous system in experimental colitis. Am J Pathol 1999;155:1051–7. 12. Lourenssen S, Wells RW, Blennerhassett MG. Differential responses of intrinsic and extrinsic innervation of smooth muscle cells in rat colitis. Exp Neurol 2005;195:497–507.

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13. Marlow SL, Blennerhassett MG. Deficient innervation characterizes intestinal strictures in a rat model of colitis. Exp Mol Pathol 2006; 80:54– 66. 14. Flynn RS, Murthy KS, Grider JR, Kellum JM, Kuemmerle JF. Endogenous IGF-I and alphaVbeta3 integrin ligands regulate increased smooth muscle hyperplasia in stricturing Crohn’s disease. Gastroenterology 2010;138:285–93. 15. Nair DG, Miller KG, Lourenssen SR, Blennerhassett MG. Inflammatory cytokines promote growth of intestinal smooth muscle cells by induced expression of PDGF-Rβ. J Cell Mol Med 2014;18:444–54. 16. Hua Y, Dolence J, Ramanan S, Ren J, Nair S. Bisdemethoxycurcumin inhibits PDGF-induced vascular smooth muscle cell motility and proliferation. Mol Nutr Food Res 2013;57:1611–8. 17. Yang X, Thomas DP, Zhang X, Culver BW, Alexander BM, Murdoch WJ, et al. Curcumin inhibits platelet-derived growth factor-stimulated vascular smooth muscle cell function and injury-induced neointima formation. Arterioscler Thromb Vasc Biol 2006;26:85–90. 18. Wang H, Ouyang Q, Hu RW. Establishment of a trinitrobenzene sulfonic acid-induced rat colitis model. Chin J Gastroenterol 2001;6:7–10. 19. Jurjus AR, Khoury NN, Reimund JM. Animal models of inflammatory bowel disease. J Pharmacol Toxicol Methods 2004;50:81–92. 20. Dong WG, Liu SP, Yu BP, Wu DF, Luo HS, Yu JP. Ameliorative effects of sodium ferulate on experimental colitis and their mechanisms in rats. World J Gastroenterol 2003;9:2533–8. 21. Vicario M, Crespí M, Franch À, Amat C, Pelegrí C, Moretó M. Induction of Colitis in Young Rats by Dextran Sulfate Sodium. Dig Dis Sci 2005;50:143–50. 22. Sreedhar R, Arumugam S, Thandavarayan RA, Karuppagounder V, Watanabe K. Curcumin as a therapeutic agent in the chemoprevention of inflammatory bowel disease. Drug Discov Today 2016;21:843–9. 23. Midura-Kiela MT, Radhakrishnan VM, Larmonier CB, Laubitz D, Ghishan FK, Kiela PR. Curcumin inhibits interferon-γ signaling in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 2012;302:G85– 96. 24. El-Abhar HS, Hammad LN, Gawad HS. Modulating effect of ginger extract on rats with ulcerative colitis. J Ethnopharmacol 2008;118:367–72. 25. Ung VY, Foshaug RR, MacFarlane SM, Churchill TA, Doyle JS, Sydora BC, et al. Oral administration of curcumin emulsified in carboxymethyl cellulose has a potent anti-inflammatory effect in the IL-10 gene-deficient mouse model of IBD. Dig Dis Sci 2010;55:1272–7. 26. Kadri CJ, Pereira JA, Campos FG, Ortega MM, Bragion CB, Martinez CA. Anti-inflammatory effects of enemas containing an oily extract of curcumin in an experimental model of diversion colitis. Histol Histopathol 2017;32:161–9. 27. Mouzaoui S, Rahim I, Djerdjouri B. Aminoguanidine and curcumin attenuated tumor necrosis factor (TNF)-α-induced oxidative stress, colitis and hepatotoxicity in mice. Int Immunopharmacol 2012;12:302–11. 28. Rhee SG, Kang SW, Jeong W, Chang TS, Yang KS, Woo HA. Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins. Curr Opin Cell Biol 2005;17:183–9. 29. Kappert K, Sparwel J, Sandin A, Seiler A, Siebolts U, Leppänen O, et al. Antioxidants relieve phosphatase inhibition and reduce PDGF signaling in cultured VSMCs and in restenosis. Arterioscler Thromb Vasc Biol 2006;26:2644–51.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Kurkumin’in PDGF ekspresyonu ve NF-kappa B üzerindeki etkisi: TNBS kolit modeli Dr. Yüksel Altınel,1 Dr. Şenay Yalçın,2 Dr. Gülçin Ercan,1 Dr. Erkan Yavuz,1 Dr. Candaş Erçetin,1 Dr. Osman Bilgin Gülçiçek,1 Dr. Atilla Çelik1 Dr. Güven Özkaya,3 Dr. Hafize Uzun4 Bağcılar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Bağcılar Eğitim ve Araştırma Hastanesi, Patoloji Kliniği, İstanbul Uludağ Üniversitesi Tıp Fakültesi, Biyoistatistik Anabilim Dalı, Bursa 4 Cerrahpaşa Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, İstanbul 1 2 3

AMAÇ: Kurkumin, nükleer faktör kappa B’nin (NF-kappa B) güçlü bir inhibitörü olduğu bilinen antioksidan ve antienflamatuvar bir moleküldür. Kurkumin’in 2,4,6-trinitrobenzen sülfonik asit (TNBS) ile indüklenen kolit modeli üzerindeki etkisini araştırmayı amaçladık. GEREÇ VE YÖNTEM: Anestezi altında kolit indüksiyonundan sonra, 42 sıçan altı gruba ayrıldı; kurkumin oral grup, kurkumin (20 mg/kg); mısır yağı oral grubu, mısır yağı (20 mg/kg) mide gavajı yoluyla, kurkumin rektal grubu, kurkumin; mısır yağı rektal grubu, mısır yağı. Kontrol grubuna 1 mL salin solüsyonu (%0.9 NaCl) rektal yolla uygulandı. Sham grubunda sadece rektal kateterizasyon yapıldı. Yedi gün sonunda, histopatolojik inceleme ve MPO, MDA, NO, PDGF, IL-6, TNF-alfa, NF-kappa B için kan ve bağırsak doku örnekleri alındı. BULGULAR: Makroskobik hasar skoru, kurkumin oral, mısır yağı oral ve salin gruplarında sham grubuna göre anlamlı olarak yüksek bulundu (p<0.05). Gruplar arasındaki anlamlı fark, IL-6, NO, NF-kB, PDGF, TNF-α, MDA, MPO intestinal dokunun biyokimyasal analizinde değerlendirildi (p<0.05). Kurkumin oral, kurkumin rektal, sham, mısır yağı oral, mısır yağı rektal gruplarında NF-kB kan seviyeleri, salin rektal grubuna göre anlamlı olarak arttı (p=0.001). Mısır yağı rektal ve kontrol grubunun NF-kB serum seviyeleri (p≤0.001) sham grubundan düşük bulundu (p=0.012). TARTIŞMA: Kurkumin’in, NF-kB sinyal yolundaki duzenleyici etkisi muhtemelen iyileştirici özelliği ile gelecekteki çalışmalarda tek başına kolite karşı veya konvansiyonel anti-kolitik tedaviler de kombinasyon halinde düşünülmelidir. Anahtar sözcükler: Antienflamatuvar; anti-oksidan; kolit; kurkumin; NF-kB. Ulus Travma Acil Cerrahi Derg 2020;26(5):

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doi: 10.14744/tjtes.2019.45570

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ORIGIN A L A R T IC L E

The completeness of the registration system and the economic burden of fatal injuries in Iran Zahra Ghodsi, PhD.,1 Soheil Saadat, M.D.,1 Abdolrazagh Barzegar, M.D.,2 Farshid Alaeddini, M.D.,1 Vafa Rahimi-Movaghar, M.D.,1 Mohammadreza Zafarghandi, M.D.,1 Ardeshir Sheikhazadi, M.D.,3 Ali Akbari Sari, M.D.,4 Payman Salamati, M.D.1 1

National Trauma Registry of Iran, Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran-Iran

Department of Forensic Medicine, Legal Medicine Research Center, Legal Medicine Organization, Tehran-Iran

Department of Forensic Medicine, Tehran university of Medical Sciences, Faculty of Medicine, Tehran-Iran

Department of Health Management and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran-Iran

ABSTRACT BACKGROUND: The present study aims to calculate completeness of the current registration system of fatal injuries in the legal Medicine Organization (LMO) and to estimate the economic burden of fatal injuries at the national level of Iran. METHODS: We estimated the completeness of registered fatal injuries using a three-source capture-recapture method among the Legal Medicine Organization, health departments and Traffic police in Hamedan County (HC) from June 22, 2015 to June 21, 2016. We also estimated the economic burden of fatal injuries using Years of Life Lost (YLL) during one year. Then, using appropriate statistical methods, we generalized the estimates to the national level. RESULTS: There were 487 registered fatal injuries in the LMO of HC. The male to female ratio was 2.89. Road Traffic Crashes (RTC) and suicide pertained 45 and 21 percent of deaths, respectively. The completeness of fatal injuries registration was estimated at 86.9%. Based on LMO information of HC, the percentage of fatal injuries numbering errors at the national level was estimated 1.1 times that was reported by LMO in the same period (41,936 vs. 36442). YLL and the economic burden of fatal injuries were estimated 1,706,373 years and 8,692,264,432 US$ at the national level, respectively. CONCLUSION: The completeness of the current registration system of fatal injuries is good. The economic burden of fatal injuries, especially due to motor vehicle crashes in Iran, is substantial. Strategies, legislative actions, and preventive programs should be considered to decrease the number of fatal injuries in our country. Keywords: Economic burden; Iran; injuries; mortality.

INTRODUCTION Although the long-term impact understanding of fatal injuries on societies has stayed as a gap, the profound and specific impact of them from different aspects is not covered on any one.[1,2] The heavy contribution of fatal road traffic crashes, the most common injury-related death, among aged 15â&#x20AC;&#x201C;29 or mainly occurrence of suicide and homicide in men aged 15â&#x20AC;&#x201C;44 years reveal the importance of socioeconomic burden of years of lost life in particular for lost productivity years.[1,3,4]

Premature mortality that arises from fatal injuries imposes substantial economic consequences.[1,5,6] Cost assessment in the US showed that approximately 33% of the total $671 billion costs of all injuries which had been spent in medical and work-loss were related to fatal injuries.[7] However, it is not only difficult to calculate their exact quantitative costs due to the inability to estimate of intangible costs but also expensive because they are relying on registries and population-based studies.[2,8] Calculating and interpretation of economic burden of fatal injuries in different regions of the world helps

Cite this article as: Ghodsi Z, Saadat S, Barzegar A, Alaeddini F, Rahimi-Movaghar V, Zafarghandi M, et al. The completeness of the registration system and the economic burden of fatal injuries in Iran. Ulus Travma Acil Cerrahi Derg 2020;26:671-677. Address for correspondence: Payman Salamati, M.D. Sina Trauma And Surgery Research Center, Sina Hospital, Imam Khomeini Avenue 11367 Tehran, Iran. Tel: +98 2166757001 E-mail: psalamati@tums.ac.ir Ulus Travma Acil Cerrahi Derg 2020;26(5):671-677 DOI: 10.14744/tjtes.2019.34903 Submitted: 07.12.2018 Accepted: 11.11.2019 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Ghodsi et al. The completeness of the registration system and the economic burden of fatal injuries in Iran

The posed burden of fatal injuries in Iran needs to evaluate the costs based on the more exact number of injury-related mortality to plan prevention and reduction of fatal injuries. It is considered that the magnitude of the economic burden of fatal injuries in a local setting is required for identifying the needs, design specific interventions and raise the scale as a part of approach steps.[2,3] Furthermore, effective interventions should be based on accurate and reliable evidence. The present study aimed to estimate economic burden and the error calculating of registered fatal injuries, after completeness assessing through the capture-recapture method in the country using the Legal Medicine Organization data of Hamadan County for one year.

Sex

Male

Female

76+

71–75

66–70

61–65

56–60

51–55

46–50

41–45

36–40

31–35

26–30

21–25

16–20

11–15

Age groups (15)

Low and middle-income countries are worst-affected by fatal injuries where economic inequality occurs at higher levels, and at the same time, the report of deaths information and cause of deaths is categorized as a moderate level.[3,4,12] Due to weak health information sources to capture accurate data, few policies or injury prevention measurements at the national level in use originate in these countries.[2,10] Furthermore, economic burden studies on fatal injuries often are insignificant in these settings, whereas injuries often have significant implications and should be taken into account to better understand the burden.[2]

The cost of injury-related mortality in HC was estimated as follows: the potential years of life lost based on Iranian life expectancy at the age of death reported by the World Health Organization[13] was multiplied by the average annual income per person (based on the World Bank’s annual report of “average domestic income per capita for 2016 and 2017” that was $5,094 USD).[14] This gives the total lost income for every fatality in HC. Dividing the sum of “the total lost income for every fatality” by the number of fatalities gives the “average income loss per every fatal injury” (AILFI). The AILFI estimated above was multiplied

Age groups (15)

policymakers and health planners to alternative strategies, allocate health resources and set priorities, underscoring the needs for the most appropriate interventions and cost-benefit to prevent and control injury-related mortality.[4,9–11] However, the estimating of related costs of fatal injuries depend on the data quality and completeness of injury-related death registries.[12]

11–15

6–10

<=5

Count

Figure 1. The distribution of 487 fatal injuries by sex and age in Legal Medicine Organization in Hamedan County from 2016 to 2017.

Homicide Undetermind (2%) (4%)

MATERIALS AND METHODS The number of fatal injuries referred to the LMO in HC was recorded from 22 June 2016 to 21 June 2017 and the age-sex distribution and cause of death of fatalities were extracted. A three capture-recapture method was applied to estimate under-reporting fatal injuries in the LMO resource in HC. The completeness of the registered fatal injuries number in the LMO was obtained by comparing it with the health department and the Traffic Police to detect unregistered deceased in the LMO resource. To realize the best log-linear model, HILOGLINEAR was used in SPSS 21. To estimate the real number of fatal injuries at the national level based on the percentage of calculating errors in HC, the number and annual incidence of injury-related mortality were calculated during the study period in the County. The national number and rate of fatal injuries were estimated, assuming the same conditions, based on percent errors calculating in Hamedan County, and then it was compared with the LMO report for the same period. 672

Suicide (21%) Road traffic incident (45%)

Other (3%) Poisoning (16%)

Fall (6%) Burn (smoke/ fire/flames (3%)

Drowning/ submersion (0%)

Figure 2. The distribution of 487 fatal injuries by cause of death in Legal Medicine Organization in Hamedan County from 2016 to 2017.

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by â&#x20AC;&#x153;corrected total injury fatalityâ&#x20AC;? to estimate the total lost income due to fatal injuries (TLIFI). The research deputy of Tehran University of Medical Sciences (TUMS) Ethical Committee approved the present study. The ethical code was 1395.370.

RESULTS Four hundred eighty-seven fatal injuries were recorded in HC during the study period; at the same time, there were 31 unreported deceased, who was identified by the health de-

partment and the Traffic Police resources. Figures of 1 and 2 show the age-sex and cause of death distribution of recorded fatalities, respectively. Table 1 shows the distribution of cause of death by age groups. The most common external cause of death was MVC, The results in different age groups showed that 34.7% of death arose from MVC occurred in the age group of 26 to 45 years; one-third and one-quarter of fatal falls occurred in the age group of over 65 and 46 to 65 years, respectively. The highest percentage of deaths from burns occurred in the

Table 1. The distribution of the 487 fatal injuries by cause of death and age in Legal Medicine Organization in Hamedan County from 2016 to 2017 Cause of death count % within mechanism

Age groups (year) <=5

6-15

16-25

26-45

Total 46-65

>65

Motor vehicle crashes 10 12 34 77 59 30 222 Fall of height Cold weapon Drowning Burn Drug poisoning Poison poisoning Suffocation Hanging Electrocution Firearm Hypoxia Drug abuse Hard hit Other Total

4.5% 5.4% 14.9% 34.7% 26.6% 13.5% 100.0% 1 2 4 6 8 11 32 3.1% 6.3% 12.5% 18.8% 25.0% 34.4% 100.0% 0 0 1 7 0 0 8 0.0% 0.0% 12.5% 87.5% 0.0% 0.0% 100.0% 2 1 2 0 1 0 6 33.3% 16.7% 33.3% 0.0% 16.7% 0.0% 100.0% 0 1 0 6 3 6 16 0.0% 6.25% 0.0% 37.5% 18.7% 37.5% 100.0% 0 1 12 13 4 1 31 0.0% 3.2% 38.7% 41.9% 12.9% 3.2% 100.0% 1 0 9 7 7 2 26 3.8% 0.0% 34.6% 26.9% 26.9% 7.7% 100.0% 0 0 1 0 0 1 2 0.0% 0.0% 50.0% 0.0% 0.0% 50.0% 100.0% 0 3 11 21 13 2 50 0.0% 6.0% 22.0% 42.0% 26.0% 4.0% 100.0% 0 0 1 2 2 0 5 0.0% 0.0% 20.0% 40.0% 20.0% 0.0% 100.0% 0 0 0 5 1 1 7 0.0% 0.0% 0.0% 71.4% 14.3% 14.3% 100.0% 1 3 8 6 2 1 21 4.8% 14.3% 38.0% 28.6% 9.5% 4.8% 100.0% 0 0 10 27 10 2 48 0.0% 0.0% 20.8% 56.2% 20.8% 4.2% 100.0% 0 0 0 5 1 2 8 0.0% 0.0% 0.0% 62.5% 12.5% 25% 100.0% 2 0 0 2 0 0 4 50.0% 0.0% 0.0% 50.0% 0.0% 0.0% 100.0% 17 23 93 183 111 59 487

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age group of 26 to 45 years and over 65 years with a similar percentage. The highest percentage of drug abuse and drug poisoning deaths occurred between the ages of 26 and 45 and from other poisonings to the age of 16 to 25 years. The highest and lowest numbers of hanging deaths were seen in the age group of 26 to 45 and years years or less, respectively. Using log-linear analysis, we estimated 42 fatal injuries that would be hidden from the LMO, the health department and the Police Traffic resources. Thus, the completeness of the LMO was estimated at 86.9 percent. The total YLL due to fatal injuries in HC was 19,816 (Table 1). Therefore, the total lost income due to fatal injuries in HC was $100,942,704 USD, and the AILFI was $207,274.5 USD. According to the LMO, the number of deaths due to injuries was 36,442 for the year 1395[15] in the country. The corrected total injury fatality (including those not detected by the LMO) was estimated as (36,442/0.869) = 41,936. Therefore, YLL WAS estimated 1,706,373 years and the TLIFI for whole country could be estimated as (41936 × 207274.5) = $8,692,264,432 USD (Table 2).

DISCUSSION The present study examined the completeness of registered fatal injuries and the estimated economic burden of injury-associated deaths at the national level with the use of the Legal Medicine Organization data source of Hamedan County for one year. It estimated the percentage of calculating errors of fatal injuries at the national level based on the number of cases in the County. Fatal injuries were caused as a massive burden at the national level and mostly by fatal RTC, which is the most cause of death associated with injuries in Iran (19.9 per 100,000).[15] There were about 13 percent of unreported fatal injuries in the LMO of HC. However, the LMO is the main reliable source to detect the external cause of death.[16] All assumptions of the capture-recapture include closed population; independence, homogeneity, and sufficient information were considered in the study.[17,18] In a study in Ethiopia, the capture of fatal road traffic injuries by the Police and hospital sources was approximately 60% and 31.5-33.4%, respectively. [19] A study conducted in Iran showed 65% reported deaths by the LMO source and death registration system (DRS).[17] Incomplete identification of the cause of death, incorrect

Table 2. Frequency distribution and percentage of the lost years of life (YLL) by sex in different age groups in Hamadan County from 22 June 2016 to 21 June 2017 Sex/age (year) <1

Male

Female

Frequency Percent YLL Frequency Percent YLL 4

.8 298

1.0 383

1–4

2 .4 149.2 4 .8 306.4

5–9

.8 282.8

1.6 582.4

10–14

7 1.4 460.6 6 1.2 407.4

15–19

20–24 25–29 30–34

36 7.5 1684.8 15 3.1 724.5

35–39

32 6.7 1347.2 11 2.3 477.4

5.3 1583.4

1.0 314.5

8.5 2300.1

1.4 406.7

11.2 2781

1.8 478.8

40–44

7.1 1268.2

1.0 193

45–49

4.1 652

1.0 169

50–54

3.9 532

.2 29

55–59

27 5.5 637.2 11 2.3 268.4

60–64

65–69

12 2.5 182.4 11 2.3 173.8

3.5 328.1

.8 79.6

70–74

1.2 68.4

.4 24

75–79

1.4 58.8

.8 34.8

80–84

9 1.8 55.8 8 1.6 52

85≤

Total

1.0 22.5

.8 18.8

362 74.6 14692.5 125 25.4 5123.5

YLL: Years of the life lost.

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coding and low quality reporting all could be assumed as the main factors.[16] Team related training, exact supervising, and use of the automatic system; all could be mention as effective factors.[20] However, Iran is among medium quality deaths data based on the WHO classification.[12] In the present study within groups of fatal injuries, the distribution of burden was changed strongly in different ages. Of the total YLL due to fatal injuries, 14.5% of them were among children aged 0–14 years, 82% among adults (15–64 years), which was accounted as productive years and 3.5% among the elderly (65 years or more). The economic burden that arose from all fatal injuries was also affected by sex: about three-quarters of the total economic burden of fatal injuries were resulted in men. Thus, the male to female ratio of all injuries was about 2.9:1. Table 1 shows the most YLL was observed at 20–24 and 30–34 aged groups of men and women, respectively, so the highest economic burden belongs to these groups. In Polinder et al.’s[21] study the highest loss in YLL was observed in men aged between 15–64 years. In assessing fatal injuries number errors at the national level based on in Hamadan County, it was estimated 1.1 times that was reported by the LMO in the same period at the national level (41,936 vs. 36442).[15] Despite the cases are representative for the composition of the Iranian population by age and sex, there is widely affected variation risks of fatal injury in a different region of the country based on a socioeconomic demographic index, culture, geographical location and external cause of deaths at different provinces.[22–26] Failure to correct coding by doctors due to inadequate training, failure to meet the standards for completing the death certificate, and the low quality of the deaths coding all could be considered as the main reasons for the low reporting of the causes of death.[15] However, the access to accurate and valid data helps the best decision to decrease costs resulted in injury-related deaths based on the more exact number of reported fatal injuries of registries.[12] A study showed a 25 percent difference in injury-related mortality statistics between CDC WONDER and GBD 2015 estimates, and percent difference was varied considerably across the cause of death. It is recommended that efforts be made to improve the coding of the cause of death and reduce garbage code to obtain accurate and reliable information on the causes of death.[27] The present study showed that the cost per death in RTC was about 199,924 US$. Fatal RTC is the main cause of death associated with injuries in Iran (19.9 per 100,000).[15] In Najafi et al.’s[6] study the cost per death that arose from a transport accident was 72,571 US$. However, the age of the deceased at the time of death could have an effect on YLL. The results emphasize on special attention and control of fatal road traffic crashes, and the development of strategies for effective interventions and management of prevention programs at health sectors and planners.

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We know that the cost of premature deaths is not limited to lost income only, but we want to raise that, in a country with 40.6 billion $ in export earnings in 2016, at least $ 8.7 billion was lost due to fatal injuries.[28] This highlights the need for health policymakers to pay special attention to the significant costs, lost and to allocate resources for preventive interventions, especially in specific areas. An average of 5.5 million barrels of oil per day of fuel is consumed annually in the country, and we can consider using fuel as a source of risk caused by RTC, with a $ 4.5 billion imposed cost due to fatal RTC.[29] As a result, the adoption of risk-based tax measures can be considered solely to improve traffic safety. The present study had some strength. First, the fatal injury data, as derived from the LMO database where we were represented deceased, died following injury; and delayed injury-related deaths were considered. Second, the economic burden calculations were included in all fatal injuries and it was not restricted to some mechanism or intent. The most important limitation of the current study was that the calculated cost of injuries resulting in death was limited to loss of income. Second, we assumed that the distribution of age-related and sex of fatal injuries in other parts of the country are similar to that of Hamedan, yet there was no reason to exist. Moreover, as a constraint, in the present study, we assumed that under-reporting at the national level is similar to Hamedan. It is based on the assumption that reporting of fatal injuries resulting from an organization where applies the same regulations throughout the country. It is recommended to assess and compare the economic burden of fatal injury on the other province. Based on the present study, there is under-reporting at fatal injuries registration sources. Also, the lost income of fatal injuries in Iran is substantial and the imposed economic burden is notable. It is important to calculate the real cost of the economic burden of fatal injuries and estimate the percentage of calculating errors. This allows health planners to base their decisions on a more accurate capture and facilitate to identify the best preventive interventions.

Acknowledgment The present study is based on the thesis of Zahra Ghodsi to achieve a PhD degree, which was conducted under the supervision of Professor Payman Salamati. We appreciate the personnel of the LMO, especially Mr. Javad Hemati, Health Department, EMS, and Police, who have cooperated in this study. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: P.S.; Design: P.S.; Supervision: P.S.; Fundings: The work was funded and supported by Sina Trauma and Surgery Research Center- Tehran University of Medical Sciences, Thesis code: 9311598018; Materials: 675

Ghodsi et al. The completeness of the registration system and the economic burden of fatal injuries in Iran

P.S., Z.G.; Data: Z.G., P.S., A.B.; Analysis: S.S., F.A., A.A.S.; Literature search: Z.G.; Writing: Z.G., S.S., P.S., V.R.M.; Critical revision: P.S., R.M., A.S., M.Z. Conflict of Interest: None declared. Financial Disclosure: The work was funded and supported by Sina Trauma and Surgery Research Center-Tehran University of Medical Sciences, Thesis code: 9311598018.

REFERENCES 1. World Health Organization. Injuries and Violence: The Facts 2014. Available from: https://www.who.int/violence_injury_prevention/key_ facts/en/. Geneva, Switzerland: WHO; 2014. 2. Bachani AM, Zhang XJ, Allen KA, Hyder AA. Injuries and violence in the Eastern Mediterranean Region: a review of the health, economic and social burden. East Mediterr Health J 2014;20:64352. 3. World Health Organization. 10 facts about violence prevention. Available from: http://www.who.int/features/factfiles/violence/en/. Geneva, Switzerland: WHO; 2017. 4. World Health Organization. Road traffic injuries. Available from: http:// www.who.int/news-room/fact-sheets/detail/road-traffic-injuries. Geneva, Switzerland: WHO; 2018. 5. Rezaei S, Arab M, Karami Matin B, Akbari Sari A. Extent, consequences and economic burden of road traffic crashes in Iran. J Inj Violence Res 2014;6:57−63. 6. Najafi F, Karami-Matin B, Rezaei S, Khosravi A, Soofi M. Productivity costs and years of potential life lost associated with five leading causes of death: Evidence from Iran (2006-2010). Med J Islam Repub Iran 2016;30:412. 7. Florence C, Haegerich T, Simon T, Zhou C, Luo F. Estimated Lifetime Medical and Work-Loss Costs of Emergency Department-Treated Nonfatal Injuries--United States, 2013. MMWR Morb Mortal Wkly Rep 2015;64:1078−82. 8. Yang L, Lam LT, Liu Y, Geng WK, Liu DC. Epidemiological profile of mortality due to injuries in three cities in the Guangxi Province, China. Accid Anal Prev 2005;37:137−41. 9. Saadat S, Yousefifard M, Asady H, Moghadas Jafari A, Fayaz M, Hosseini M. The Most Important Causes of Death in Iranian Population; a Retrospective Cohort Study. Emerg (Tehran) 2015;3:16−21. 10. World Health Organization. National injury prevention policies, strategies and plans of action. Available from: http://www.who.int/violence_injury_prevention/policy/introduction/en/. Geneva, Switzerland: WHO; 2018. 11. Khosravi A, Taylor R, Naghavi M, Lopez AD. Mortality in the Islamic Republic of Iran, 1964-2004. Bull World Health Organ 2007;85:607−4. 12. World Health Organization. World Health Statistics 2017: Monitoring health for the SDGs, Sustainable Development Goals. Available from: https://www.who.int/gho/publications/world_health_statistics/2017/ en/. Geneva, Switzerland: WHO; 2017. 13. World Health Organization. Life tables by country Iran (Islamic Republic of ). 2015. Available from: https://apps.who.int/gho/data/view. main.60760.

676

14. The World Bank. Iran Overview 2018. Available from: https://www. worldbank.org/en/country/iran/overview. 15. Iranian Legal Medicine Organization. Statistical Yearbook of the Forensic Medicine Organization 2016 [cited 2016 May 10]. Available from: http://www.lmo.ir. 16. Khosravi A, Aghamohammadi S, Kazemi E. Guidance for recording and classifying causes of death. 1st edition. Tehran: Ministry of Health, Treatment and Medical Education, Deputy Minister of Health, Network Management, 2016. 17. Zavareh DK, Mohammadi R, Laflamme L, Naghavi M, Zarei A, Haglund BJA. Estimating road traffic mortality more accurately: use of the capture-recapture method in the West Azarbaijan Province of Iran. Int J Inj Control Sa 2008;15:9−17. 18. Bierrenbach A. Capture Recapture. Available from: https://www.who. int/tb/advisory_bodies/impact_measurement_taskforce/meetings/ ie_oct09_capture_recapture.pdf. Accessed May 27, 2020. 19. Abegaz T, Berhane Y, Worku A, Assrat A, Assefa A. Road traffic deaths and injuries are under-reported in Ethiopia: a capture-recapture method. PLoS One 2014;9:e103001. 20. World Health Organization. Improving Mortality Statistics through Civil Registration and Vital Statistics Systems, Strategies for country and partner support. Available from: https://www.who.int/healthinfo/civil_registration/CRVS_MortalityStats_Guidance_Nov2014.pdf?ua=1. Geneva, Switzerland: WHO; 2014. 21. Polinder S, Haagsma JA, Toet H, van Beeck EF. Epidemiological burden of minor, major and fatal trauma in a national injury pyramid. Br J Surg 2012;99:114−21. 22. Azizpour Y, Asadollahi K, Sayehmiri K, Kaikhavani S, Abangah G. Epidemiological survey of intentional poisoning suicide during 1993-2013 in Ilam Province, Iran. BMC Public Health 2016;16:902. 23. Najafi F, Beiki O, Ahmadijouybari T, Amini S, Moradinazar M, Hatemi M, et al. An assessment of suicide attempts by self-poisoning in the west of Iran. J Forensic Leg Med 2014;27:1−5. 24. Kristiansen T, Lossius HM, Rehn M, Kristensen P, Gravseth HM, Røislien J, et al. Epidemiology of trauma: a population-based study of geographical risk factors for injury deaths in the working-age population of Norway. Injury 2014;45:23−30. 25. De Leo D, Milner A, Fleischmann A, Bertolote J, Collings S, Amadeo S, et al. The WHO START study: suicidal behaviors across different areas of the world. Crisis 2013;34:156−63. 26. Jamshidi F, Fathi G, Davoodzadeh H. Investigation Paraquat Poisoning in Southwest of Iran - from Sign to Mortality and Morbidity. Arch Med Sadowej Kryminol 2017;67:35−45. 27. Wu Y, Cheng X, Ning P, Cheng P, Schwebel DC, Hu G. Comparing U.S. Injury Death Estimates from GBD 2015 and CDC WONDER. Int J Environ Res Public Health 2018;15:87. 28. Iran (IRN) Exports, Imports and Trade Partners. Available from: https://atlas.media.mit.edu/en/profile/country/irn/. Accessed May 27, 2020. 29. The Iran Project. Oil Minister: Fuel consumption volume in Iran equivalent to 5.5m BPD. 2018. Available from: https://theiranproject.com/ blog/2018/02/06/oil-minister-fuel-consumption-volume-iran-equivalent-5-5m-bpd/.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

İran’da kayıt sisteminin bütünlüğü ve ölümcül yaralanmaların ekonomik yükü Dr. Zahra Ghodsi,1 Dr. Soheil Saadat,1 Dr. Abdolrazagh Barzegar,2 Dr. Farshid Alaeddini,1 Dr. Vafa Rahimi-Movaghar,1 Dr. Mohammadreza Zafarghandi,1 Dr. Ardeshir Sheikhazadi,3 Dr. Ali Akbari Sari,4 Dr. Payman Salamati1 İran Ulusal Travma Sicili, Sina Travma ve Cerrahi Araştırma Merkezi, Tahran Tıp Bilimleri Üniversitesi, Tahran-İran Yasal Tıp Araştırma Merkezi, Adli Tıp Örgütü, Adli Tıp Bölümü, Tahran-İran 3 Tahran Tıp Bilimleri Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, Tahran-İran 4 Tahran Tıp Bilimleri Üniversitesi Halk Sağlığı Fakültesi, Sağlık Yönetimi ve Ekonomi Bölümü, Tahran-İran 1 2

AMAÇ: Bu çalışmanın amacı, Yasal Tıp Teşkilatı (LMO) içerisinde ölümcül yaralanmaların mevcut kayıt sisteminin bütünlüğünü hesaplamak ve İran’da ulusal düzeyindeki ölümcül yaralanmaların ekonomik yükünü tahmin etmektir. GEREÇ VE YÖNTEM: 22 Haziran 2015–21 Haziran 2016 tarihleri arasında Hamedan Bölgesi’nde (HC) Yasal Tıp Teşkilatı, sağlık departmanları ve trafik polisi arasında üç kaynaklı yakalama-yeniden yakalama yöntemi kullanılarak kaydedilen ölümcül yaralanmaların bütünlüğünü değerlendirildi. Ayrıca, bir yıl boyunca Kaybedilmiş Yıllar (KY) ölçütü kullanarak ölümcül yaralanmaların ekonomik yükü de değerlendirildi. Ardından, uygun istatistiksel yöntemleri kullanarak tahminleri ulusal düzeyde genelleştirdik. BULGULAR: Hamedan Bölgesi LMO’sunda 487 kayıtlı ölümcül yaralanma vardı. Erkek/kadın oranı 2.89 idi. Karayolu Trafik Kazaları (RTC) ve intihar, ölümlerin sırasıyla yüzde 45 ve yüzde 21’ini oluşturmaktaydı. Ölümcül yaralanma kayıt bütünlüğünün %86.9 olduğu tahmin edilmektedir. Hamedan Bölgesi’nin LMO bilgilerine dayanarak, ulusal düzeydeki ölümcül yaralanma numaralandırma hatalarının yüzdesinin, aynı dönemde LMO tarafından bildirilenin 1.1 katı olduğu tahmin edilmektedir (41.936’e karşı 36442). Kaybedilmiş yıllar ve ölümcül yaralanmaların ekonomik yükünün ulusal düzeyde sırasıyla 1.706.373 yıl ve 8.692.264.432 ABD doları olduğu tahmin edilmektedir. TARTIŞMA: Ölümcül yaralanmalara ait mevcut kayıt sisteminin bütünlüğü iyidir. İran’da özellikle motorlu taşıt kazaları nedeniyle ölümcül yaralanmaların ekonomik yükü büyüktür. Ülkemizdeki ölümcül yaralanma sayısını azaltmak için stratejiler, yasal eylemler ve önleyici programlar göz önünde bulundurulmalıdır. Anahtar sözcükler: Ekonomik yük; İran; mortalite; yaralanmalar. Ulus Travma Acil Cerrahi Derg 2020;26(5):671-677

doi: 10.14744/tjtes.2019.34903

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ORIGIN A L A R T IC L E

Efficacy of stomach-partitioning on gastric emptying in patients undergoing palliative gastrojejunostomy for malign gastric outlet obstruction Reyyan Yıldırım, M.D.,1 Bahar Candaş, PhD.,2 Serdar Türkyılmaz, M.D.,1 Adnan Çalık, M.D.,1

Mehmet Arif Usta, M.D.,1 Ali Güner, M.D.1

Department of General Surgery, Karadeniz Technical University Faculty of Medicine, Trabzon-Turkey

Department of Surgical Disease Nursing, Karadeniz Technical University Faculty of Health Sciences, Trabzon-Turkey

ABSTRACT BACKGROUND: Palliative efficacy of conventional gastrojejunostomy in palliation of malignant gastric outlet obstruction is debatable. This study aims to compare the outcomes of conventional gastrojejunostomy and stomach-partitioning gastrojejunostomy and to explore the factors influencing the delayed gastric emptying after surgery in patients with malignant gastric outlet obstruction. METHODS: The study subjects were divided into the following two groups based on whether the stomach was partitioned or not: Conventional gastrojejunostomy and stomach-partitioning gastrojejunostomy. All demographic data, patient characteristics, postoperative outcomes, including delayed gastric emptying grade and 30-day complications were collected. Following the comparison of the clinical outcomes, risk factors for delayed gastric emptying were determined by regression models. RESULTS: Fifty-three patients were included in this study. Of these, 37 patients underwent conventional gastrojejunostomy, whereas 16 patients underwent stomach-partitioning gastrojejunostomy. Patient demographics and baseline characteristics were comparable between groups. Although 10 (27%) patients in the conventional gastrojejunostomy group had delayed gastric emptying grade B-C, no patient in the stomach-partitioning gastrojejunostomy group experienced this condition. There was no difference between the groups concerning hospital stay and complications. In multivariate regression analysis, having distant metastasis (OR=0.156, 95%CI 0.034–0.720, p=0.017) and stomach-partitioning (OR=0.127, 95%CI 0.025–0.653, p=0.014) were found as independent factors for the delayed gastric emptying. CONCLUSION: In patients with malignant gastric outlet obstruction, compared with conventional gastrojejunostomy, stomach-partitioning may provide favorable clinical outcomes by improving gastric emptying. Keywords: Delayed gastric emptying; gastric outlet obstruction; stomach-partitioning gastrojejunostomy.

INTRODUCTION Gastric outlet obstruction (GOO) is a clinical syndrome that arises because of any benign or malignant process leading to an obstruction at the level of the stomach outlet.[1–3] Symptoms of GOO can be the main impediment in attaining a better quality of life by patients. Although the traditional treatment choice for GOO is gastrojejunostomy (GJ), less invasive endoscopic treatment options, such as dilatation and endolu-

minal stenting, have also been used.[4,5] However, owing to the possibility of long-term stent-related complications, surgical GJ is usually recommended as a palliative option for patients with long-life expectancy.[6–8] Conventional GJ is commonly performed with side-to-side loop jejunal anastomosis to the proximal part of the obstruction; however, studies have demonstrated that conventional GJ may not provide acceptable palliation in some patients because of impaired gastric emptying.[9,10] According to recent reports, up to 47% of the

Cite this article as: Yıldırım R, Candaş B, Usta MA, Türkyılmaz S, Çalık A, Güner A. Efficacy of stomach-partitioning on gastric emptying in patients undergoing palliative gastrojejunostomy for malign gastric outlet obstruction. Ulus Travma Acil Cerrahi Derg 2020;26:678-684. Address for correspondence: Ali Güner, M.D. Karadeniz Teknik Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Trabzon, Turkey Tel: +90 462 - 377 56 13 E-mail: draliguner@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(5):678-684 DOI: 10.14744/tjtes.2020.14668 Submitted: 27.09.2019 Accepted: 27.01.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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patients experienced delayed gastric emptying (DGE) after conventional GJ; therefore, the palliative efficacy of conventional GJ is debatable.[11,12] Stomach-partitioning GJ (SPGJ) has been developed to improve the outcomes of the GJ procedure.[12–14] In this technique, the stomach is partially partitioned to eliminate the risk of a blowout of the closed-loop in the distal stomach.[11] There are some case series that have assessed the efficacy of SPGJ.[14–17] Besides, some comparative studies suggested that SPGJ may improve DGE compared to conventional GJ.[11–13] However, patients included in the studies had various clinicopathological features that may have the potential to influence the outcomes. Improvement of DGE was evaluated only by considering the type of GJ, without considering other crucial factors. In this study, we aimed to compare the outcomes of conventional and stomach-partitioning GJ and to explore the factors influencing the DGE in patients undergoing palliative gastrojejunostomy for malign GOO.

MATERIALS AND METHODS Patients and Data Collection We retrospectively reviewed the electronic medical records of patients who underwent a bypass for GOO between March 2013 and February 2019. GOO is diagnosed based on recurrent symptoms of epigastric abdominal pain and postprandial vomiting that arose from mechanical obstruction confirmed radiologically (upper gastrointestinal series or contrast-enhanced computerized tomography) or endoscopically at the level of the stomach outlet. The GOO score was calculated based on a scoring system defined by Adler (GOO score: 0 = no oral feed, 1 = liquids only, 2 = soft solids, and 3 = complete diet).[1] The main inclusion criteria were a GOO score of 0–2 and having undergone only GJ without any resection as surgical treatment. Of the 64 patients treated with GJ, patients with benign disease (n=2) and who underwent concomitant biliary bypass during the same surgical procedure (n=9) were excluded from the analyses. All the data regarding patient demographics and preoperative clinical data were collected. Comorbidities were evaluated using the Charlson comorbidity index (CCI).[18] Postoperative short-term outcomes, including the length of hospital stay, postoperative GOO score, and the presence of DGE, DGE grade, complications, and operative mortality were also collected. Postoperative GOO scores were assessed approximately two weeks after surgery. The primary outcome of this study was the presence of DGE, and the DGE grade was calculated based on the grading system defined by the International Study Group of Pancreatic Surgery (nasogastric tube requirement and ability to tolerate foods are used).[19] Grades B and C were defined as clinically significant DGE. Prolonged hospitalization was defined as a hospital stay longer than 10 days. Adverse events occurring within 30 days of Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

the surgery (or within the hospitalization period for patients who stayed in the hospital for >30 days) were classified as postoperative complications and were classified according to the Clavien–Dindo classification system.[20] Complications of ≥grade 3 were classified as major. Mortality occurring within 30 days after the surgery was defined as operative mortality. Signed informed consent was obtained from all patients before surgery. Ethical permission for this study was obtained from the ethical committee.

Surgical Procedures In this study population, conventional GJ was performed using two reconstruction techniques. In both the techniques, the proximal jejunal loop was anastomosed to the stomach (side-to-side manner and at least 3–5 cm proximal from the distal tumor) using a single, 60-mm linear stapling device via the conventional loop Billroth-II GJ technique (Fig 1a). For conventional Roux-en-Y GJ, in addition to the loop GJ technique, the ascending part of the jejunal limbs was divided just before the GJ anastomosis site and anastomosed to the descending part of the jejunum, 25–30 cm distal to the GJ anastomosis using a stapling device (Fig 1b).[21] For SPGJ, the stomach was partially divided using linear stapling devices from the greater curvature side of the proximal stomach, and 1–2 cm from the lesser curvature side was left undivided. After gastric division, GJ was performed with a linear stapling device in Roux-en-Y fashion, as previously described (Fig. 2).[11] For the laparoscopic surgery, a similar technique was used using five ports, and all anastomoses were completed intracorporeally with linear stapling devices.[22] The decision for reconstruction technique and approach was decided based on the surgeon’s preference.

Statistics and Ethics Continuous variables are presented as mean ± standard deviation for the parametric distribution and as median (25th-75th percentile) for the nonparametric distribution. Chi-square test or Fisher exact test, Student’s t-test and Mann-Whitney (a)

(b)

Figure 1. Schematic illustrations of conventional gastrojejunostomy. (a) Billroth-II gastrojejunostomy; (b) Roux-en-Y gastrojejunostomy.

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was assessed.[23] Based on this assessment, all continuous variables except for age were found to be linearly related to the logit of the dependent variable. For univariate analyses, a binary logistic regression test was used. All potential confounding factors were entered into the multivariate logistic regression model using a backward stepwise approach to explore the risk factors for the presence of the DGE. All p-values were two-sided, and statistical significance was defined as p<0.05. R software (R Foundation for Statistical Computing, Vienna, Austria) with required packages was used for statistical analyses. Figure 2. Schematic illustration of Roux-en-Y stomach-partitioning gastrojejunostomy.

test were used for comparing the groups based on the type and characteristics of the data. The linearity of the continuous variables concerning the logit of the dependent variable

RESULTS Fifty-three patients who met the criteria were included in the analyses. Of these, 37 patients underwent conventional GJ, whereas 16 patients underwent SPGJ. Patient demographics and baseline characteristics were comparable between the groups (Table 1). For operative data, two patients in the SPGJ group underwent laparoscopic surgery while an open

Table 1. Patient demographics and baseline characteristics Variables Age (years), mean±SD

Conventional GJ (n=37)

Stomach-partitioning GJ (n=16)

p-value

68.7±14.4

62.7±10.2

0.135 0.933

Sex, n (%)

Male

25 (67.6)

11 (68.8)

Female

12 (32.4)

5 (31.2)

Charlson comorbidity index, mean±SD

5.9±2.3

5.1±2.4

0.287

Hemoglobin (g/dL), mean±SD

11.3±2.3

11.3±1.8

0.969

Albumin (g/dL), mean±SD

3.3±0.6

3.4±0.6

0.470 0.656

Preoperative transfusion, n (%)

28 (75.7)

13 (81.2)

Yes

9 (24.3)

3 (18.8)

Origin of malignancy, n (%)

Gastroduodenal

20 (54.1)

13 (81.2)

Pancreaticobiliary

17 (45.9)

3 (18.8)

0.061

Reason for non-resection, n (%)

Locally-advanced

25 (67.6)

10 (62.5)

0.721

Distant metastasis

12 (32.4)

6 (37.5)

Preoperative chemotherapy, n (%)

33 (89.2)

13 (81.2)

Yes

4 (10.8)

3 (18.8)

0.419

Score 0

19 (51.4)

7 (43.8)

Score 1

12 (32.4)

7 (43.8)

Score 2

6 (16.2)

2 (12.4)

37 (100)

14 (87.5)

Preoperative GOO score, n (%)

0.729

Approach, n (%)

Open

Laparoscopy

–

0.087

2 (12.5)

Data were presented as mean±standard deviation or number of patients (percentage). GJ: Gastrojejunostomy; GOO: Gastric outlet obstruction; SD: Standard deviation.

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approach was used in all remaining patients; there was no statistically significant difference between groups concerning the approach. All patients in the SPGJ group underwent Roux-en-Y reconstruction, while 21 (56.8%) patients in the conventional GJ group underwent Roux-en-Y reconstruction. Postoperative clinical outcomes are presented in Table 2. There was no difference between the groups concerning the length of hospital stay, all complication rate, major complication rate, reoperation rate, and operative mortality. Three patients required reoperation, all belonging to the conventional GJ group. One patient had ongoing GOO-related concerns; therefore, Billroth-II was converted to Roux-en-Y reconstruction. One patient experienced anastomotic leakage and was operated again. One patient was re-operated because of intraabdominal bleeding (bleeding from the gastroepiploic vessels) for hemostasis. Although there was no statistically significant difference concerning operative mortality among the groups, operative mortality was observed in four patients (10.8%) in the conventional GJ group. The mean age and the mean CCI score were 83.5±3.8 years and 8.3±2.1 in patients experienced operative mortality, respectively. In patients without operative mortality, the mean age and the mean CCI score were 65.6±13.1 years and 5.5±2.3, respectively. There was a statistically significant difference between the patients who experienced the operative mortality or did not, concerning the age (p=0.009) and the CCI score (p=0.022). Post-operative GOO scores, the incidence of DGE and DGE grades differed between the groups. Two weeks after surgery, all patients in the SPGJ group were able to eat soft solids or

complete diet, while 24.3% (9/37) of patients in the conventional GJ group still had a GOO score of 0 or 1. Incidences of DGE in the conventional GJ group and SPGJ group were 70.3% and 18.8%, respectively. No patients in the SPGJ group experienced clinically significant DGE (grade B or C), while 10 (27%) of the patients in the conventional group experienced clinically significant DGE. Univariate regression analysis demonstrated that the presence of distant metastasis rather than locally-advanced malignancy as a reason for non-resection, Roux-en-Y reconstruction rather than Billroth-II reconstruction and stomach-partitioning are better prognostic factors for the DGE (Table 3). In multivariate regression analysis, having distant metastasis (OR=0.156, 95%CI 0.034–0.720, p=0.017) and stomach-partitioning (OR=0.127, 95%CI 0.025–0.653, p=0.014) were found as independent factors for the DGE.

DISCUSSION In the present study, we compared the outcomes of conventional and stomach-partitioning GJ in the palliation of malignant GOO and also explored the factors influencing the DGE after surgical treatment of the GOO. We found that SPGJ may provide satisfactory postoperative GOO scores and may decrease the incidence of the DGE after surgery. Although the SPGJ group showed exceptional improvement in the ability of oral feeding, complication rates and hospital stay were comparable between the two groups. We also found that the presence of the unresectable locally-advanced malignancy regardless of the origin increased the incidence of the DGE.

Table 2. Postoperative clinical outcomes Variables

Conventional GJ (n=37)

Stomach-partitioning GJ (n=16)

p-value

Hospital stay (days)

8 (7–14)

8 (8–10)

0.822

Prolonged hospitalization, n (%)

13 (35.1)

3 (18.8)

0.233

All complications, n (%)

15 (40.5)

6 (37.5)

0.835

Major complications, n (%)

9 (24.3)

1 (6.3)

0.123

Reoperation, n (%)

3 (8.1)

–

0.545

Operative mortality, n (%)

4 (10.8)

–

0.303 0.030

Postoperative GOO score, n (%)

Score 0–1

9 (24.3)

–

Score 2–3

28 (75.7)

16 (100)

26 (70.3)

3 (18.8)

0.001

11 (29.7)

13 (81.2)

0.006

Presence of DGE, n (%) Grades of DGE, n (%)

Grade A

16 (43.2)

3 (18.8)

Grade B

4 (10.8)

–

Grade C

6 (16.2)

–

Data were presented as median (25 -75 percentile) or number of patients (percentage). GJ: Gastrojejunostomy; GOO: Gastric outlet obstruction; DGE: Delayed gastric emptying. th

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Table 3. Regression analysis of risk factors for delayed gastric emptying Variables

Univariate analysis

OR (95% CI)

p-value

Multivariate analysis OR (95% CI)

p-value

Age

<70 vs. ≥70

1.556 (0.517–4.680)

0.432

Sex

male vs. female

0.900 (0.283–2.863)

0.858

Charlson comorbidity index

0.932 (0.740–1.173)

0.548

Hemoglobin

0.929 (0.716–1.204)

0.576

Albumin

0.570 (0.222–1.462)

0.242

Preoperative transfusion

no vs. yes

0.783 (0.216–2.840)

0.709

Origin of malignancy

PB vs GD

0.982 (0.322–2.997)

0.974

Reason for non-resection

locally-advanced vs. distant

0.261 (0.078–0.869)

0.029

0.156 (0.034–0.720)

0.017

metastasis Preoperative chemotherapy

no vs. yes

0.281 (0.049–1.606)

0.154

Preoperative GOO score

Score 0-1 vs. score 2

0.438 (0.093–2.063)

0.297

Type of reconstruction

Billroth-II vs. Roux-en-Y

0.176 (0.043–0.723)

0.016

Stomach-partitioning

Conventional vs. SP

0.098 (0.023–0.412)

0.001

0.127 (0.025–0.653)

0.014

GOO: Gastric outlet obstruction; PB: Pancreaticobiliary; GD: Gastroduodenal; SP: Stomach-partitioning; OR: Odds ratio; CI: Confidence interval.

We found that no patients in the SPGJ group experienced clinically significant DGE, although 27% of the patients in the conventional group showed clinically significant DGE. Besides, nine patients (24.3%) in conventional GJ group were unable to eat soft/complete diet two weeks after the surgery and all required additional nutritional support after discharge, while no patients in the SPGJ group required supplemental nutrition. In the theoretical basis of SPGJ, stomach partitioning may facilitate the direct passage from the proximal stomach to the jejunum. Previous reports, including two meta-analyses of retrospective series, support this theory and have shown that stomach-partitioning alleviates DGE, and patients who have undergone stomach-partitioning may tolerate oral intake better without GOO recurrence.[9,13,24,25] However, because the DGE may be attributable to multiple clinicopathological features, we aimed to move the current evidence one step forward. Type of reconstruction has been found as a prognostic factor in univariate analysis; however, it lost its prognostic power after adjustment for other factors. This finding contradicts the studies reporting that Roux-en-Y is superior to Billroth-II reconstruction following distal gastrectomy.[26,27] However, we only used Roux-en-Y reconstruction in the SPGJ group, and the surgeon’s preference may have caused a misinterpretation of the results. Multivariate analysis showed that there are two prognostic factors for the DGE. First, patients who have the locally-advanced disease may experience DGE more than the patients who underwent palliative surgery due to distant metastasis. Second, regardless of the reconstruction technique, stomach-partitioning, which is a surgically modifiable factor, provides better gastric emptying outcomes. We believe that, for a better understanding of the underlying causes of DGE following palliative GJ, patient- and tumor-related factors should be evaluated in further studies. 682

A meta-analysis has evaluated the influence of stomach-partitioning on postoperative complications.[9] Although there was a trend toward a decrease in the incidences of complications in the SPGJ group, there was not a significant difference between treatment arms. In the present study, correspondingly, we found no difference between the two groups concerning the complications despite the decrease in number in the SPGJ group. From the technical perspectives, because the distinction between two techniques is only dividing the stomach partially with a linear stapler device, an increase in surgical complication rates is unexpected. Besides, because the SPGJ has the potential to decrease the reintervention rates, a decrease in the incidence of the complication can be expected. However, there is no evidence demonstrating less complication in the SPGJ group, so far. Current studies, including our study, possibly have an insufficient sample size for detecting an effect and lead to false-negative outcomes. Large-scale studies with sufficient power are warranted to answer this question. We believe that published studies so far can be considered as a part of the development stage (Stage 2a) of the IDEAL framework, and because the safety and efficacy have been demonstrated in the studies, it is now time to move forward to the exploration stage (Stage 2b).[28] Unlike in previous studies, the operative mortality rates in our study were high.[14,15,22] In total, 4 (7.5% of all cohort) patients died in the 30-day postoperative period, and the higher mortality rate in our study warrants further evaluation and should be highlighted. Because the number of events is low, it was not possible to analyze the predictive factors for mortality in the presented study. However, we analyzed some patient characteristics and found that, for the patients who experienced operative mortality, the mean age was Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

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83.5 years (65.6 for those who survived), and the mean CCI score was 8.3 (5.5 for those who survived). None of them had a surgery-related complication and all died because of systemic complications and comorbid diseases unrelated to the surgery. Although we found no difference concerning the mortality between the groups, the presented outcomes underline the importance of patient selection for surgical palliation in the decision-making process. Although the current treatment guidelines for malignant GOO recommend GJ over endoluminal stenting in patients with a reasonable prognosis, we believe that endoscopic treatment options may be preferred in the elderly population, particularly for unfit patients.[8] The retrospective nature and relatively small sample size were the main limitations of the presented study. With the increasing use of endoscopic treatment modalities and neoadjuvant treatment options, the number of patients requiring surgical bypass has decreased over time. In addition to the reduction in the number of patients requiring surgical palliation, deciding bypass during surgery makes it impossible to obtain the informed consent of patients. Such obstacles make it difficult to conduct an appropriate prospective randomized study; therefore, it will be challenging to obtain high-level evidence in the era of retrospective series. Besides, a systematic difference between the baseline characteristics of the groups is inevitable in non-randomized studies. Although patient demographics and baseline characteristics are comparable in the presented study, adding a multivariable regression analysis provided us independence of the groups for proper evaluation of risk factors for the DGE.

search: R.Y., M.A.U., A.G.; Writing: R.Y., B.C., A.G.; Critical B.C, S.T., A.G. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Adler DG, Baron TH. Endoscopic palliation of malignant gastric outlet obstruction using self-expanding metal stents: experience in 36 patients. Am J Gastroenterol 2002;97:72−8. 2. Gibson JB, Behrman SW, Fabian TC, Britt LG. Gastric outlet obstruction resulting from peptic ulcer disease requiring surgical intervention is infrequently associated with Helicobacter pylori infection. J Am Coll Surg 2000;191:32−7. 3. Shone DN, Nikoomanesh P, Smith-Meek MM, Bender JS. Malignancy is the most common cause of gastric outlet obstruction in the era of H2 blockers. Am J Gastroenterol 1995;90:1769−70. 4. Nagaraja V, Eslick GD, Cox MR. Endoscopic stenting versus operative gastrojejunostomy for malignant gastric outlet obstruction-a systematic review and meta-analysis of randomized and non-randomized trials. J Gastrointest Oncol 2014;5:92−8. 5. Chandrasegaram MD, Eslick GD, Mansfield CO, Liem H, Richardson M, Ahmed S, et al. Endoscopic stenting versus operative gastrojejunostomy for malignant gastric outlet obstruction. Surg Endosc 2012;26:323−9. 6. Khashab M, Alawad AS, Shin EJ, Kim K, Bourdel N, Singh VK, et al. Enteral stenting versus gastrojejunostomy for palliation of malignant gastric outlet obstruction. Surg Endosc 2013;27:2068−75. 7. Jeurnink SM, Steyerberg EW, van Hooft JE, van Eijck CH, Schwartz MP, Vleggaar FP, et al. Surgical gastrojejunostomy or endoscopic stent placement for the palliation of malignant gastric outlet obstruction (SUSTENT study): a multicenter randomized trial. Gastrointest Endosc 2010;71:490−9.

There are some published series demonstrating the benefits of the stomach-partitioning; however, to our knowledge, this is the first study analyzing multiple factors that have the potential to influence gastric emptying after surgery. Despite the presented valuable findings, we believe that there are some core outcomes, such as the quality of life, hospital-free survival, tumor bleeding in follow-up, and using stomach-partitioning as a part of neoadjuvant treatment, to be answered in future comparative studies.

8. National Comprehensive Cancer Network. Gastric Cancer (Version 2.2018). Available at: http://www.nccn.org/professionals/physician_ gls/pdf/gastric.pdf. Accessed February 23, 2018.

In conclusion, stomach-partitioning may provide favorable clinical outcomes by improving gastric emptying compared to conventional GJ in patients requiring surgical palliation of GOO. However, these promising outcomes should be confirmed in future prospective comparative studies.

11. Ernberg A, Kumagai K, Analatos A, Rouvelas I, Swahn F, Lindblad M, et al. The Added Value of Partial Stomach-partitioning to a Conventional Gastrojejunostomy in the Treatment of Gastric Outlet Obstruction. J Gastrointest Surg 2015;19:1029−35.

Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: R.Y., B.C, S.T., A.G.; Design: R.Y., B.C, S.T., A.G.; Supervision: M.A.U., S.T., A.Ç., A.G.; Fundings: A.G.; Materials: R.Y., S.T., A.Ç.; Data: R.Y., B.C., M.A.U., A.Ç., A.G.; Analysis: R.Y., B.C., A.G.; Literature Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

9. Kumagai K, Rouvelas I, Ernberg A, Persson S, Analatos A, Mariosa D, et al. A systematic review and meta-analysis comparing partial stomach partitioning gastrojejunostomy versus conventional gastrojejunostomy for malignant gastroduodenal obstruction. Langenbecks Arch Surg 2016;401:777−85. 10. Shyr YM, Su CH, Wu CW, Lui WY. Randomized trial of gastrojejunostomy with duodenal partition versus antrectomy in unresectable periampullary cancer. Zhonghua Yi Xue Za Zhi (Taipei) 2001;64:443−50.

12. Usuba T, Misawa T, Toyama Y, Ishida Y, Ishii Y, Yanagisawa S, et al. Is modified Devine exclusion necessary for gastrojejunostomy in patients with unresectable pancreatobiliary cancer?. Surg Today 2011;41:97−100. 13. Oida T, Mimatsu K, Kawasaki A, Kano H, Kuboi Y, Amano S. Modified Devine exclusion with vertical stomach reconstruction for gastric outlet obstruction: a novel technique. J Gastrointest Surg 2009;13:1226−32. 14. Kwon SJ, Lee HG. Gastric partitioning gastrojejunostomy in unresectable distal gastric cancer patients. World J Surg 2004;28:365−8. 15. Suzuki O, Shichinohe T, Yano T, Okamura K, Hazama K, Hirano S, et

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Yıldırım et al. Efficacy of stomach-partitioning on gastric emptying in patients undergoing palliative GJ for malign GOO al. Laparoscopic modified Devine exclusion gastrojejunostomy as a palliative surgery to relieve malignant pyloroduodenal obstruction by unresectable cancer. Am J Surg 2007;194:416−8. 16. Kubota K, Kuroda J, Origuchi N, Kaminishi M, Isayama H, Kawabe T, et al. Stomach-partitioning gastrojejunostomy for gastroduodenal outlet obstruction. Arch Surg 2007;142:607−11. 17. Arciero CA, Joseph N, Watson JC, Hoffman JP. Partial stomach-partitioning gastrojejunostomy for malignant duodenal obstruction. Am J Surg 2006;191:428−32. 18. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373−83. 19. Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2007;142:761−8. 20. Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 2009;250:187−96. 21. Szymanski D, Durczynski A, Nowicki M, Strzelczyk J. Gastrojejunostomy in patients with unresectable pancreatic head cancer - the use of Roux loop significantly shortens the hospital length of stay. World J Gastroenterol 2013;19:8321−5.

22. Kushibiki T, Ebihara Y, Hontani K, Tanaka K, Nakanishi Y, Asano T, et al. The Surgical Outcomes of Totally Laparoscopic Stomach-partitioning Gastrojejunostomy for Gastric Outlet Obstruction: A Retrospective, Cohort Study. Surg Laparosc Endosc Percutan Tech 2018;28:e49−53. 23. Box GEP, Tidwell PW. Transformation of the independent variables. Technometrics 1962;4:531−50. 24. Kaminishi M, Yamaguchi H, Shimizu N, Nomura S, Yoshikawa A, Hashimoto M, et al. Stomach-partitioning gastrojejunostomy for unresectable gastric carcinoma. Arch Surg 1997;132:184−7. 25. Lorusso D, Giliberti A, Bianco M, Lantone G, Leandro G. Stomach-partitioning gastrojejunostomy is better than conventional gastrojejunostomy in palliative care of gastric outlet obstruction for gastric or pancreatic cancer: a meta-analysis. J Gastrointest Oncol 2019;10:283−91. 26. Cai Z, Zhou Y, Wang C, Yin Y, Yin Y, Shen C, et al. Optimal reconstruction methods after distal gastrectomy for gastric cancer: A systematic review and network meta-analysis. Medicine (Baltimore) 2018;97:e10823. 27. Zong L, Chen P. Billroth I vs. Billroth II vs. Roux-en-Y following distal gastrectomy: a meta-analysis based on 15 studies. Hepatogastroenterology 2011;58:1413−24. 28. Hirst A, Philippou Y, Blazeby J, Campbell B, Campbell M, Feinberg J, et al. No Surgical Innovation Without Evaluation: Evolution and Further Development of the IDEAL Framework and Recommendations. Ann Surg 2019;269:211−20.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Malign mide çıkış obstrüksiyonu nedeniyle palyatif gastrojejunostomi uygulanan hastalarda mide bölücü cerrahinin mide boşalmasına etkisi Dr. Reyyan Yıldırım,1 Dr. Bahar Candaş,2 Dr. Mehmet Arif Usta,1 Dr. Serdar Türkyılmaz,1 Dr. Adnan Çalık,1 Dr. Ali Güner1 1 2

Karadeniz Teknik Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Trabzon Karadeniz Teknik Üniversitesi Sağlık Bilimleri Fakültesi, Cerrahi Hastalıklar Hemşireliği Anabilim Dalı, Trabzon

AMAÇ: Malign mide çıkış tıkanıklığı palyatif tedavisinde konvansiyonel gastrojejunostominin palyatif etkinliği tartışmalıdır. Bu çalışmanın amacı, konvansiyonel gastrojejunostomi ile mide bölücü gastrojejunostominin sonuçlarını karşılaştırmak ve malign mide çıkış tıkanıklığı olan hastalarda cerrahi sonrası gecikmiş mide boşalmasını etkileyen faktörleri araştırmaktır. GEREÇ VE YÖNTEM: Çalışma grubu midenin bölünüp bölünmeme durumuna göre konvansiyonel gastrojejunostomi ve mide bölücü gastrojejunostomi olarak iki gruba ayrıldı. Tüm demografik veriler; hasta özellikleri ve gecikmiş mide boşalma derecesi ile 30 günlük komplikasyonları içeren ameliyat sonrası sonuçlar toplandı. Klinik sonuçların karşılaştırılmasının ardından, gecikmiş mide boşalması için risk faktörleri regresyon modelleri kullanılarak belirlendi. BULGULAR: Elli üç hasta çalışmaya alındı. Otuz yedi hastaya konvansiyonel gastrojejunostomi, 16 hastaya ise mide bölücü gastrojejunostomi uygulandı. Hastaların demografik ve temel özellikleri gruplar arasında benzerdi. Konvansiyonel gastrojejunostomi grubunda 10 (%27) hastada grade B-C gecikmiş mide boşalması mevcut iken, mide bölücü gastrojejunostomi grubunda hiçbir hastada bu durum gözlenmedi. Gruplar arasında hastanede yatış süresi ve komplikasyonlar açısından fark yoktu. Çok değişkenli regresyon analizinde uzak metastaz varlığı (OR=0.156, %95 GA 0.034–0.720, p=0.017) ve mide bölünmesi (OR=0.127, %95 GA 0.025–0.653, p=0.014) gecikmiş mide boşalması için bağımsız faktörler olarak bulundu. TARTIŞMA: Malign mide çıkış tıkanıklığı olan hastalarda, mide bölücü gastrojejunostomi konvansiyonel gastrojejunostomi ile karşılaştırıldığında, mide boşalmasını iyileştirerek olumlu klinik sonuçlar sağlayabilir. Anahtar sözcükler: Gecikmiş mide boşalması; mide bölücü gastrojejunostomi; mide çıkış obstrüksiyonu. Ulus Travma Acil Cerrahi Derg 2020;26(5):678-684

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doi: 10.14744/tjtes.2020.14668

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ORIGIN A L A R T IC L E

The impacts of the COVID-19 outbreak on emergency department visits of surgical patients Beslen Göksoy, M.D.,

Muhammed Tahir Akça, M.D.,

Ömer Faruk İnanç, M.D.

Department of General Surgery, Şehit Prof. Dr. İlhan Varank Sancaktepe Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: The novel Coronavirus Disease 2019 (COVID-19) formed the basis for emergency department visits. This study aims to evaluate the effects of the pandemic on emergency department visits of surgical patients. METHODS: The hospital database records of general surgery patients who presented at the emergency department in the period of March 2020-May 2020 (pandemic period) and March 2019–May 2019 (non-pandemic period) were retrospectively analyzed and compared. The primary outcome of this study was the emergency department visit rate of patients requiring a general surgery consultation. Secondary outcomes of this study were patient complaints, diagnosis and treatments, treatment rejection rate, triage category data, the effects of age and gender, and the hospitalization rate. RESULTS: In this study, 618 patients were included: 265 patients from the pandemic period and 353 patients from the non-pandemic period. The analysis and comparison revealed that during the pandemic period, the presentation rate of female patients was lower than that of male patients (45.5% vs. 55.5%, respectively, p=0.045). The triage category rates of patient visits to the hospital during the pandemic period were higher in yellow and red, and lower in green (p<0.01). The incidence of a surgical pathology finding was higher during the pandemic period (p=0.019). The incidence of diseases related to the gastrointestinal tract was higher during the pandemic period (p=0.011). The rate of open surgery in the pandemic period was higher than that of the non-pandemic period (80.5% vs. 32.7%, respectively; p<0.01). The treatment rejection rate was also higher in the pandemic period compared with the non-pandemic period (20% vs. 3.7%, respectively; p<0.01, r). In addition, the hospitalization period was shorter in the pandemic period (p=0.021). CONCLUSION: A 25% reduction in the number of surgical patient visits to the emergency department was observed during the COVID-19 outbreak. The biggest decrease was seen in patients with a green triage code and female patients. It is significant to evaluate the effects of the pandemic on surgical patients visited the emergency department to manage the post-epidemic period and to prepare for possible future epidemic periods. Keywords: COVID-19; emergency department visit; emergency surgery.

INTRODUCTION Coronavirus Disease 2019 (COVID-19) stemming from severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) was declared as a pandemic by the world health organization (WHO) on March 11, 2020.[1] After that, prevention of the spread of the pandemic has been the primary goal. A wide range of individual protection measures has been undertaken all over the world. Both the WHO and health authorities have made some recommendations (e.g., handwashing,

avoiding crowded areas, paying attention to social distance and use of face masks) to protect members of the public in the face of this insidious disease transmitted through droplets and to reduce its spread.[2] COVID-19 affects all age groups; however, it progresses more severely in the elderly and individuals with additional diseases. [3] Naturally, institutions providing health services, particularly emergency services, where the first contact with the patient is established, are the riskiest environment and healthcare

Cite this article as: Göksoy B, Akça MT, İnanç ÖF. The impacts of the COVID-19 outbreak on emergency department visits of surgical patients. Ulus Travma Acil Cerrahi Derg 2020;26:685-692. Address for correspondence: Beslen Göksoy, M.D. Şehit Prof. Dr. İlhan Varank Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 216 - 606 33 00 E-mail: beslengoksoy@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):685-692 DOI: 10.14744/tjtes.2020.67927 Submitted: 13.07.2020 Accepted: 25.08.2020 Online: 11.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Göksoy et al. The impacts of the COVID-19 outbreak on emergency department visits of surgical patients

personnel is the most likely to become infected during the period of infectivity. The behavior of the patient population that visits the emergency department, which is a significant element of healthcare, is affected by external changes that arise from natural disasters and pandemics. For example, previous studies have shown that a pandemic of the severe acute respiratory syndrome (SARS) directly affected the visits of patients in emergency departments.[4,5] According to the official data of the Turkish Ministry of Health, the first COVID-19 case in Turkey was recorded on March 11, 2020, and the first death was reported on March 17, 2020.[6] During the early period of the pandemic, emergency departments in Turkey and all over the world focused on COVID-19. Recommendations for compliance with social distancing and quarantine rules made by local administrations and developing an understanding of the severity of the disease caused some public anxiety and affected hospital visits, especially to emergency departments. Less urgent conditions (e.g., acute cholecystitis and perianal area diseases), and patients requiring urgent intervention, such as trauma and acute abdomen are among, the most crucial reasons for emergency department visits. Postponing the appointments of the patients due to the COVID-19 outbreak may put patients who require urgent surgery at a higher risk of morbidity and mortality. Understanding the impacts of adjourned applications due to pandemic can help improve treatment strategies and health systems in future outbreaks. The present study aims to evaluate the effects of the COVID-19 outbreak on surgical patients who presented at an emergency department of a pandemic hospital.

MATERIALS AND METHODS Study Design and Population This was a retrospective, observational study. This study was conducted in a tertiary healthcare institution with a380-bed capacity, where an average of 700,000 patient visits is seen every year at the emergency department. The study parameters were evaluated in two periods: the pandemic period and the non-pandemic period. The pandemic period studied comprised two months from the date when the hospital was declared a pandemic hospital, and the first case of COVID-19 was seen: i.e., March 15, 2020–May 15, 2020. The non- pandemic period used was the same interval in the previous year: March 15, 2019–May 15, 2019. The hospital computer database records of patients who visited the emergency department and were consulted to general surgery between the dates specified were retrospectively analyzed (records during the pandemic period were prospectively maintained). The standard triage classification using three color-coded categories of green, signifying not urgent; yellow, indicating an urgent need; and red, designating the very urgent cases was implemented.[7] 686

Treatment rejection was defined as patients who were not administered any treatment because they did not accept the recommended medical or surgical treatment and/or hospitalization and left the hospital voluntarily. An elderly category was used to define and evaluate patients aged 65 years or more. The admission complaints of the patients were evaluated under six main headings: gastrointestinal system, perianal region, breast, inguinal region, exposure to trauma, and other complaints. The diagnoses of the patients were assessed using seven categories: non-surgical pathology, hepatobiliary system diseases, gastrointestinal system diseases, hernia, breast diseases, benign perianal area diseases, and other. Patients without a surgical pathology finding were defined as patients who did not receive any treatment. The patients who received treatment were divided into two categories: outpatient treatment (oral antibiotic and/or analgesic treatment) and inpatient treatment (medical treatment or surgery). Inclusion criteria for both study periods included patients over the age of 18 who visited the emergency department and were consulted to general surgery. Patients under the age of 18 and patients who were consulted to general surgery during their follow-up (other than trauma) were excluded from this study. This study was approved by the Ethics Committee of Süreyyapaşa Chest Diseases and Chest Surgery Training and Research Hospital (Protocol number: 116.2017.166).

Outcomes The primary outcome of this study was the emergency department presentation rate of patients requiring a general surgery consultation. Secondary outcomes were the proportion of patients who underwent emergency surgery and received medical treatment, the patient admission complaints, the diagnoses and treatments, the treatment rejection rate, triage categories, the effects of age and gender on emergency admission, and the hospitalization rate. The rate of patients who were not found to have a general surgical pathology but who were hospitalized or transferred to other branches was also examined. The outcome criteria for the two periods were compared. In addition, a subgroup analysis was conducted to further examine patients who presented during the pandemic period to assess the impacts of the patients who were infected with COVID-19 at the time of admission or after admission (during inpatient treatment), and patients whose visits were delayed due to fear of becoming infected with COVID-19 virus.

Statistical Analysis In addition to descriptive statistical methods (mean, SD, median, frequency, ratio, minimum, maximum), the Student’s t-test was used for the comparison of two groups of variables with normal distribution, and the Mann-Whitney U test was employed in 2-group comparisons of variables Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

RESULTS This study was conducted with 618 patients (265 patients in the pandemic period, and 353 patients in the non-pandemic period). The mean age of the patients was 46.20±19.42 years. The number of visits to the emergency department of surgical patients during the pandemic and non-pandemic periods is shown in Figure 1. The comparison revealed some differences. The rate of male patients who went to the hospital during the pandemic period was greater than females (55.5% vs. 45.5%, respectively; p=0.045) (Fig. 2). The rate of study patients with a yellow or red triage code increased during the pandemic period and there were fewer green-coded patients relative to the non-pandemic period (p<0.01) (Fig. 3). The demographic data and triage categories of the patients are shown in Table 1. There was no statistically significant difference between the two periods according to admission complaints (Table 2). The incidence of a surgical pathology finding in patients in the pandemic period was higher than in the non-pandemic period (p=0.019). The incidence of gastrointestinal system disease finding in patients in the pandemic period was higher than in the non-pandemic period (p=0.011). In this study, 14 patients were diagnosed with complicated acute appendicitis: nine (64.2%) patients in the pandemic period and five patients (35.8%) in the non-pandemic period. Details of the admission diagnoses are provided in Table 3. The rate of open surgery during the pandemic period was higher than the non-pandemic period (p<0.01). The rate of patients declining treatment was statistically significantly higher during the pandemic period than in the non-pandemic period (p<0.01). Patients were also hospitalized for a shorter-term during the pandemic period when compared with the non-pandemic period (p=0.021) (Table 4). A general surgical pathology finding was not detected in 24 patients (3.9%) (n=22 in the pandemic period, and n=2 in the non-pandemic period), but they were hospitalized or referred to other branches.

Subgroup Analysis During the pandemic period, 12 (4.5%) patients stated that they had delayed their arrival due to the fear of becoming infected with the COVID-19 virus. Surgical pathology was detected in 11 patients (91.6%) (n=10 acute appendicitis, and Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Pandemic period Non-pandemic period

16 14 12 10 8 6 4 2 0

3/15

3/22

3/29

4/6

4/13

4/20

4/27

5/3

5/10

5/15

Date

Figure 1. Daily patient visits to the emergency department requiring general surgery consultation from March 15 to May 15 for the years 2019 to 2020.

Female 60

55.5

50 Ratio (%)

with non-normal distribution (e.g., age and length of hospital stay). The Pearson chi-square test and Fisher’s exact test were used to comparing qualitative data (e.g., the patient admission complaints and diagnoses). Statistical significance was determined at p<0.05. NCSS 2007 software (NCSS, LLC, Kaysville, UT, USA) was used for the statistical analysis.

General surgery consultations per day

Göksoy et al. The impacts of the COVID-19 outbreak on emergency department visits of surgical patients

Male

52.7 47.3

45.5

40 30 20 10 0

Pandemic period

Non-pandemic period

Figure 2. Distribution of the pandemic and non-pandemic period by sex. Pandemic period

Non-pandemic period

15% 33%

12%

60%

73% 7%

Emergency triage colors

Figure 3. Distribution of the triage categories by the pandemic and non-pandemic period.

n=1 acute cholecystitis) who had deferred their treatment. Seven of the patients diagnosed with acute appendicitis were cases of complicated acute appendicitis. COVID-19 infection was detected in 11 (4.1%) of the patients during the pandemic period (n=10 at the time of admission, n=1 after admission). The mean length of the hospital stay of the patients with the COVID-19 infection was longer than that of those without (6.43±3.21 days and 2.68±1.92 days, respectively; p<0.01). 687

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Table 1. Demographic characteristics and triage categories Age (years), mean±SD

Non-pandemic period (n=353)

Pandemic period (n=265)

Total (n=618)

46.20±19.42

44.83±19.28

46.20±19.42

<65, n (%)

277 (78.5)

213 (80.4)

490 (79.3)

≥65, n (%)

76 (21.5)

52 (19.6)

128 (20.7)

0.385 0.563

Sex, n (%)

Female

186 (52.7)

118 (45.5)

304 (49.2)

Male

167 (47.3)

147 (55.5)

314 (50.8)

Triage category, n (%)

0.045*

Green

117 (33.1)

40 (15.1)

157 (25.4)

Yellow

212 (60.1)

193 (72.8)

405 (65.5)

Red

24 (6.8)

32 (12.1)

56 (9.1)

0.001**

SD: Standard deviation. aStudent’s t-test; bPearson Chi-Square Test; *P<0.05; **P<0.01.

Table 2. Patient admission complaints presenting to the emergency department Patient complaints Gastrointestinal complaints

Non-pandemic period (n=353)

Pandemic period (n=265)

Total (n=618)

244 (69.1)

187 (70.6)

431 (69.7) 347 (56.1)

Only abdominal pain

205 (58)

142 (53.6)

Abdominal pain and nausea/vomiting

11 (3.1)

20 (7.5)

31 (5)

Abdominal pain and diarrhea

9 (2.5)

7 (2.6)

16 (2.6)

†

0.699

Other

19 (5.4)

18 (6.8)

37 (6)

Groin pain

24 (6.8)

9 (3.4)

33 (5.3)

0.063

Perianal region

34 (9.6)

29 (10.9)

63 (10.2)

0.594

Only anorectal pain

16 (4.5)

22 (8.3)

38 (6.1)

Only rectal bleeding

13 (3.7)

7 (2.6)

20 (3.2)

Anorectal pain and bleeding

5 (1.4)

0 (0.0)

5 (0.8)

Breast pain

8 (2.3)

4 (1.5)

12 (1.9)

0.500

Trauma

31 (8.8)

23 (8.7)

54 (8.7)

0.964

0.347

Road traffic accident

12 (3.4)

11 (4.5)

23 (3.7)

Firearm injuries

5 (1.4)

2 (0.7)

7 (1.1)

Sharp instrument injuries

7 (2)

3 (1.1)

10 (1.6)

‡

Other

7 (2)

7 (2.6)

14 (2.3)

Other

12 (3.4)

13 (4.9)

25 (4.0)

Other included abdominal pain and constipation, only constipation, abdominal pain and fever, only nausea-vomiting. ‡Other included fall from a high level, accidental fall of an object, assault and battery, electric shock, burn wounds and foreign body swallowing. §Other included armpit swelling, nail pain, backache, wound discharge, bloody emesis, respiratory distress, fainting. bPearson Chi-Square Test; *P<0.05.

†

DISCUSSION In this study, we found a reduction in the number of general surgery patients admitted to the emergency department during the COVID-19 pandemic period compared with the non-pandemic period. The greatest decrease in triage categories was observed in green-coded patients, and gender comparison revealed that the number of female patients 688

seen decreased significantly. In the pandemic period, the rate of detection of a surgical pathology was higher. The most prominent difference in diagnosis was seen in diseases of the gastrointestinal tract, and the incidence increased significantly during the pandemic period. In addition, we found that the rate of open surgery increased during the pandemic period. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Göksoy et al. The impacts of the COVID-19 outbreak on emergency department visits of surgical patients

Table 3. Patient admission diagnoses in the emergency department Disease diagnoses

Non-pandemic period (n=353)

Pandemic period (n=265)

Total (n=618)

Non-surgical pathology

101 (28.6)

54 (20.4)

155 (25.1)

Hepatobiliary system diseases

72 (20.4)

62 (23.4)

134 (21.7)

22 (6.2)

21 (7.9)

43 (7.0)

Acute cholecystitis

Acute biliary pancreatitis

21 (5.9)

18 (6.8)

39 (6.3)

Biliary colic

18 (5.1)

10 (3.8)

28 (4.5)

11 (3.1)

13 (5)

24 (3.9)

Gastrointestinal system diseases

82 (23.2)

86 (32.5)

168 (27.2)

‡

Acute appendicitis

48 (13.6)

45 (17)

93 (15)

Ileus

13 (3.7)

15 (5.7)

28 (4.5)

9 (2.5)

10 (3.8)

19 (3.1)

7 (2)

10 (3.8)

17 (2.8)

†

Other

Gastroenteritis

Sigmoid diverticulitis

5 (1.4)

6 (2.2)

11 (17.8)

Hernia

Other

23 (6.5)

12 (4.5)

35 (5.7)

Non-strangulated inguinal hernia

12 (3.4)

6 (2.3)

18 (2.9)

Non-strangulated umbilical hernia

6 (1.7)

2 (0.8)

8 (1.3)

Other

6 (1.7)

4 (1.5)

9 (1.4)

Breast diseases

6 (1.7)

3 (1.1)

9 (1.5)

Mastitis

4 (1.1)

1 (0.4)

5 (0.8)

Breast abscess

2 (0.6)

2 (0.8)

4 (0.6)

Benign perianal area diseases

31 (8.8)

23 (8.7)

54 (8.7)

16 (4.5)

8 (3)

24 (3.9)

Haemorrhoids

Perianal abscess

8 (2.3)

4 (1.5)

12 (1.9)

Acute pilonidal abscess

5 (1.4)

8 (3)

13 (2.1)

Other

Other diagnosis

€

2 (0.6)

3 (1.1)

5 (0.8)

38 (10.8)

25 (9.4)

63 (10.2)

0.019*

0.370

0.011*

0.290

0.560

0.964

0.588

Other included cholelithiasis, cholangitis and choledocholithiasis. ‡Included perforated appendicitis (n=5) and plastrone appendicitis (n=4) in the pandemic period, and perforated appendicitis (n=3) and plastrone appendicitis (n=2) in the non-pandemic period. §Other included peptic ulcer perforation and bleeding, and diverticular bleeding. ψOther included strangulated inguinal hernia, strangulated umbilical hernia, strangulated incisional hernia, non-strangulated incisional hernia. ¶Other included anal fissure, gluteal abscess. €Other included burn wounds, epiploic appendicitis, subcutaneous abscess-hematoma, mesenteric volvulus-panniculitis, rectus sheath hematoma, intra-abdominal abscess, solid organ injury, onychocryptosis, intramural hematoma of the duodenum, metastatic cancers, surgical site infection and sebaceous cyst. b Pearson Chi-Square Test; *P<0.05. †

In the event of disasters, such as earthquakes, severe storms, and forest fires, emergency department visits, primarily those patients requiring surgery, tend to increase.[8–10] The situation is different in the presence of epidemic disease. Striking examples were seen during the SARS epidemic period when the rate of emergency department visits decreased by 40% to 51.6%.[5,11,12] In a recent study conducted in Portugal, it was found that the total incidence of emergency department visits within a a month period (March 2020) during the COVID-19 outbreak decreased 48%, and the greatest decrease (50%) was patients in the yellow-coded triage category.[13] In our study, we detected a 25% reduction in the emergency presentations of general surgery patients during the pandemic period. Analysis of Figure 1 reveals that the biggest decrease Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

occurred in the first 30 days of the pandemic, and particularly the first two weeks of April when the pandemic was the most intense. After the second week of April, the presentation rate approached that of the non-pandemic period. A decrease was observed in all of the triage categories during the pandemic period, notably the green-coded patients (from 33% to15%). The proportion of yellow- and red-coded patients increased, and that of patients without a surgical pathology decreased. There are several possible reasons for the reduction in the number of non-emergency patient admissions we observed. First, patients were reluctant to go to the hospital due to the risk of infection. A second reason is related to the quarantine decisions made by local governments to prevent the spread of the virus. Patients also chose alternative means of treatment, such as home care, and going to other hospitals they thought 689

Göksoy et al. The impacts of the COVID-19 outbreak on emergency department visits of surgical patients

Table 4. Comparison of the treatments by periods

Pandemic period n (%)

Non-pandemic period n (%)

Total n (%)

Total treatment

157 (59.2)

247 (70.0)

404 (65.4)

0.006*

Treatment type

Outpatient treatment

73 (46.5)

121 (49.0)

194 (48.0)

Inpatient treatment

84 (53.5)

126 (51.0)

210 (52.0)

126

210

Medical

43 (51.2)

77 (61.1)

120 (57.1)

Surgical

41 (48.8)

49 (38.9)

90 (42.9)

Open surgery

33 (80.5)

16 (32.7)

49 (54.4)

0.625

0.155

0.001**

Laparoscopic surgery

8 (19.5)

33 (67.3)

41 (45.6)

Declining the treatment

53 (20.0)

13 (3.7)

66 (10.7)

Length of hospital stay (day, Mean±SD)

2.99±2.28

4.00±3.27

3.60±2.95

0.001** 0.021*

SD: Standard deviation. bPearson Chi-Square Test; cMann-Whitney U Test. *P<0.05. **P<0.01.

to be less risky. Finally, news in social media indicating the increasing rate of infection among healthcare professionals added to anxiety among patients. Despite strict quarantine rules (in Turkey, a curfew was imposed on people over the age of 65 on March 21, 2020), a significant decrease in the proportion of patients older than 65, and trauma patients were not seen. In our study, the proportion of patients who had no surgical pathology result but were hospitalized in other branches was greater than that seen in the non-pandemic period. This suggests us that patients who presented at the emergency department during the pandemic period had more severe illnesses without any other alternatives for treatment. In a study of 3009 patients that investigated the relationship between gender and pain, anxiety, and stress in emergency department visits, the findings showed that anxiety and stress were more frequently detected in female patients (p<0.001). [14] In our study, we observed that the number of female patients was slightly greater than that of male patients during the non-pandemic period. We found a significant decrease in female patients during the pandemic period. This may be related to the risk of infection during the pandemic and increased anxiety and stress in female patients. Generally, there is a decrease in trauma cases during disease outbreaks.[12] In contrast to the literature, the lack of any decrease in trauma patients in our study may have been because not every trauma case (especially sports injuries, child trauma, and some traffic accidents) is consulted to general surgery. The findings of other branches of service need to be examined in more detail. The incidence of diseases related 690

to the gastrointestinal tract, the category with the greatest difference in the diagnosis of patients, increased significantly during the pandemic period compared with the non-pandemic period (32.5% vs. 23.2%). The incidence of complicated acute appendicitis (perforated or plastron appendicitis) may have been higher during the pandemic period due to delayed admission or referrals to outpatient treatment at an initial visit. We found that the rate of cases with complicated acute appendicitis during the pandemic period was 64.2% and onethird were patients who stated that they had delayed presentation due to the pandemic outbreak. The number and proportion of patients with gastrointestinal system diseases, such as gastroenteritis, ileus, and diverticulitis, increased during the pandemic period. Measures implemented by local governments (e.g., quarantine rules and curfews) and by some professional groups and businesses to support working at home, as well as social media alerts, have led to individuals spending most of their time at home to prevent contracting the disease and its spread. A more sedentary life and unbalanced diet may have contributed to the increase in diseases related to the gastrointestinal tract during the pandemic period. Another remarkable result of this study is the 16.3% increase in the treatment rejection rate seen during the pandemic period. The addition of a section on the consent forms required before hospitalization or surgery notifying patients of the risk of COVID-19 infection and a restriction in the number of relatives who could accompany the patient due to strict infection rules are possible causes of the increase in the rejection rate. There was a surgical pathology finding in the majority of patients who stated that they had delayed presentation due to fear of infection with COVID-19, and about half of these Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Göksoy et al. The impacts of the COVID-19 outbreak on emergency department visits of surgical patients

patients declined treatment. Also, in these patients, 70% of the cases with acute appendicitis were complicated acute appendicitis. This result indicates that fear of the pandemic can affect patient morbidity. The effects of postponed admissions may be dramatic, especially in cases of diseases that require emergency treatment. Although there are some suggestions of a preference for open surgery rather than a laparoscopic approach in surgical treatment related to COVID-19, the evidence is still insufficient. [15] We observed that the open surgery rate increased significantly in the pandemic period compared with the non-pandemic period. Only one of the patients who underwent open appendectomy had a COVID-19 infection. The patient was hospitalized for five postoperative days and administered oral medical treatment consisting of azithromycin (250 mg tab four times a day), hydroxychloroquine (400 mg tab twice a day), and oseltamivir (75 mg tab twice a day). All patients with a surgical pathology finding in the pandemic period were evaluated preoperatively with computed tomography, and swabs were taken from the nasopharynx and oropharynx of the patients with suspected COVID-19 infection. All surgeries were performed as recommended in the literature (e.g., using protective equipment, avoiding smoke and aerosol exposure).[16] Although there is insufficient evidence that open surgery is more reliable, there is a preference among surgeons and other operating room personnel due to anxiety and uncertainty. Although there was no significant difference between the periods in the rate of inpatients, the duration of hospitalization was shorter during the pandemic period. The average length of the hospital stay of patients infected with COVID-19 during the pandemic period was longer than that of non-infected patients. Even when emergency surgical pathologies were resolved, treatment for infection caused a prolonged hospital stay in this group. The results of this study have valuable implications. A significant reduction in emergency service presentations of approximately one-third of non-emergency patients (especially in the green-coded triage category) during the pandemic period is important because it allows attention to be directed to more urgent patients. Based on this, how many patients “do not really urgent” visit to the emergency departments in normal times? Is one of the questions that come to mind? There was a partial decrease in visits by patients evaluated in the yellow-coded triage category, which constitutes the majority of emergency presentations. Delayed treatment of these patients who have more urgent needs may lead to increased severity of disease and negative effects, including requiring urgent surgery, which causes an increased disease burden. This pandemic outbreak may lead to the emergence of new approaches in the treatment of some surgical diseases. We do not yet know whether these predictions will be correct. To better understand the current situation, we thought it would Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

be interesting to evaluate the post-pandemic period, and we planned to conduct a study to compare the pandemic period and the post-pandemic period.

Limitations The records that have been kept prospectively during the pandemic period are the strength of this study. This study has some limitations. First of all, this was a single-center study, and it may not be appropriate to make generalizations about other pandemic hospitals. Second, some patients who went to the emergency department may have left the hospital voluntarily without consulting general surgery or they were discharged by the emergency medicine physicians, given the risk of contamination. Finally, some patients may have gone to the emergency department of other hospitals they found less risky. The COVID-19 outbreak has led to a review of national health systems around the world. It is significant to evaluate the effects of the pandemic on surgical patients admitted to the emergency department in the post-pandemic period, which will assist with preparation for possible future outbreaks. In conclusion, during the COVID-19 outbreak, we observed a 25% reduction in the emergency department visits of surgical patients. The most severe decline was seen in the green-coded triage group and in female patients. Understanding that hospitals are risky placesas in hospital-acquired infections may reduce unnecessary visits. However, individuals who require emergency surgery do not hesitate to present at the emergency department. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: B.G., Ö.F.İ., M.T.; Design: B.G., Ö.F.İ., M.T.; Supervision: B.G.; Fundings: B.G.; Materials: B.G., Ö.F.İ., M.T.; Data: B.G., Ö.F.İ., M.T.; Analysis: B.G., Ö.F.İ., M.T.; Literature search: B.G.; Writing: B.G., Ö.F.İ., M.T.; Critical revision: B.G., Ö.F.İ., M.T. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. World health Organization. WHO Director-General’s opening remarks at the media briefing on COVID-19 - 11 March 2020. Available from: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020. 2. World health Organization. Coronavirus disease (COVID-19) advice for the public. Available from: https://www.who.int/emergencies/diseases/ novel-coronavirus-2019/advice-for-public. 3. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, Chi-

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Göksoy et al. The impacts of the COVID-19 outbreak on emergency department visits of surgical patients na: a retrospective cohort study. Lancet 2020;395:1054−62. 4. Chen WK, Cheng YC, Chung YT, Lin CC. The impact of the SARS outbreak on an urban emergency department in Taiwan. Med Care 2005;43:168−72. 5. Huang HH, Yen DH, Kao WF, Wang LM, Huang CI, Lee CH. Declining emergency department visits and costs during the severe acute respiratory syndrome (SARS) outbreak. J Formos Med Assoc 2006;105:31−7. 6. T.C Sağlık Bakanlığı Korona Tablosu. Available from: https://covid19. saglik.gov.tr/ 7. Brouns SHA, Mignot-Evers L, Derkx F, Lambooij SL, Dieleman JP, Haak HR. Performance of the Manchester triage system in older emergency department patients: a retrospective cohort study. BMC Emerg Med 2019;19:3. 8. Stryckman B, Walsh L, Carr BG, Hupert N, Lurie N. Impact of Superstorm Sandy on Medicare Patients' Utilization of Hospitals and Emergency Departments. West J Emerg Med 2017;18:1035−41. 9. Moitinho de Almeida M, Schlüter BS, van Loenhout JAF, Thapa SS, Kumar KC, Singh R, et al. Changes in patient admissions after the 2015 Earthquake: a tertiary hospital-based study in Kathmandu, Nepal. Sci Rep 2020;10:4956. 10. Shusterman D, Kaplan JZ, Canabarro C. Immediate health effects of an

urban wildfire. West J Med 1993;158:133−8. 11. Chen TA, Lai KH, Chang HT. Impact of a severe acute respiratory syndrome outbreak in the emergency department: an experience in Taiwan. Emerg Med J 2004;21:660−2. 12. Man CY, Yeung RS, Chung JY, Cameron PA. Impact of SARS on an emergency department in Hong Kong. Emerg Med (Fremantle) 2003;15:418−22. 13. Santana R, Sousa JS, Soares P, Lopes S, Boto P, Rocha JV. The Demand for Hospital Emergency Services: Trends during the First Month of COVID-19 Response. Port J Public Health 2020;38:30−6. 14. Patel R, Biros MH, Moore J, Miner JR. Gender differences in patient-described pain, stress, and anxiety among patients undergoing treatment for painful conditions in the emergency department. Acad Emerg Med 2014;21:1478−84. 15. Vigneswaran Y, Prachand VN, Posner MC, Matthews JB, Hussain M. What Is the Appropriate Use of Laparoscopy over Open Procedures in the Current COVID-19 Climate?. J Gastrointest Surg 2020;24:1686−91. 16. Gök AFK, Eryılmaz M, Ozmen MM, Alimoglu O, Ertekin C, Kurtoglu MH. Recommendations for Trauma and Emergency General Surgery Practice During COVID-19 Pandemic. Ulus Travma Acil Cerrahi Derg 2020;26:335−42.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

COVID-19 salgınının cerrahi hastaların acil servis başvuruları üzerine etkisi Dr. Beslen Göksoy, Dr. Muhammed Tahir Akça, Dr. Ömer Faruk İnanç Şehit Prof. Dr. İlhan Varank Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul

AMAÇ: Coronavirus Hastalığı 2019 (COVID-19) acil servis başvurularının temelini oluşturmuştur. Bu çalışma pandeminin acil servise başvuran genel cerrahi hastalarına etkisini değerlendirmeyi amaçlamaktadır. GEREÇ VE YÖNTEM: Mart 2020–Mayıs 2020 (pandemi dönemi) ile Mart 2019–Mayıs 2019 (pandemi olmayan dönem) tarihleri arasında acil servise başvuran genel cerrahi hastalarının kayıtları hastane bilgisayar tabanlı veritabanından geriye dönük olarak incelendi. Birincil sonuç acil servis başvuru oranlarıdır. İkincil sonuçlar hastaların başvuru şikayetleri, tanı ve tedavileri, tedavi red oranları, triyaj kategorileri, yaş ve cinsiyetin acil servis başvuru oranlarına etkisi ve hastanede yatış oranlarıdır. Sonuçlar her iki dönemde karşılaştırılmıştır. BULGULAR: Çalışma pandemi döneminde 265 hasta, pandemi olmayan dönemde 353 hasta olmak üzere toplam 618 hastayla yapıldı. Pandemi döneminde kadın hastaların başvuru oranı, erkek hastalara göre daha düşüktü (sırasıyla, %45.5’e karşı %55.5, p=0.045). Pandemi döneminde hastaneye başvuran hastaların triyaj kategorilerinin sarı ve kırmızı olma oranı daha yüksek, yeşil olma oranı ise daha düşüktü (p<0.01). Pandemi dönemindeki hastalarda cerrahi patoloji görülme oranı daha fazlaydı (p=0.019). Pandemi döneminde tanısı gastrointestinal sistem hastalıkları olan hastaların oranı daha yüksekti (p=0.011). Pandemi döneminde açık ameliyat oranı pandemi olmayan döneme göre daha yüksekti (sırasıyla, %80.5’e karşı %32.7, p<0.01). Tedavi red oranı pandemi döneminde pandemi olmayan döneme göre daha yüksekti (sırasıyla, %20’ye karşı %3.7, p<0.01). Hastanede yatış süreleri pandemi döneminde daha düşüktü (p=0.021). TARTIŞMA: COVID-19 salgını sırasında cerrahi hastaların acil servis başvurularında %25 oranında azalma saptandı. En büyük düşüş yeşil alan başvurularında ve kadın hasta başvurularında görüldü. Pandeminin acil servise başvuran cerrahi hastalar üzerindeki etkisini değerlendirmek hem salgın sonrası dönemde hem de olası gelecek salgın dönemlerine hazırlık açısından önemlidir. Anahtar sözcükler: Acil cerrahi; acil servis başvuruları; COVID-19. Ulus Travma Acil Cerrahi Derg 2020;26(5):685-692

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doi: 10.14744/tjtes.2020.67927

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ORIGIN A L A R T IC L E

Penetrating cardiac trauma in stab wounds: A study of diagnostic accuracy of the cardiac area Jorge Hernan Montenegro Muñoz, M.D.,1 Oscar Dussan, M.D.,2 Andres M. Rubiano, M.D.,4 Juan C. Puyana, M.D.5

Francisco Ruiz, M.D.,3

Meditech Foundation, Clinical Research Group, Neiva-Colombia

Department of General Surgery, South Colombian University, Neiva-Colombia

Department of General Surgery, South Colombian University/Hernando Moncaleano Hospital, Neiva-Colombia

Meditech Foundation / El Bosque University, Neurosciences Institute, Bogota-Colombia

Department of Surgery, Division of Trauma, University of Pittsburgh, Pittsburgh-USA

ABSTRACT BACKGROUND: Stab wounds (SW) to the thorax raises suspicion for cardiac injuries; however, the topographic description is variable. The present study aims to evaluate different topographical descriptions within the thorax and establish their diagnostic value in penetrating cardiac trauma by SW. METHODS: Medical records of all patients admitted to our center with thoracic SW from January 2013 to June 2016 were included in this study. Diagnostic value potential was measured using different areas of the thorax described in the literature. RESULTS: In this study, we analyzed 306 cases. Thirty-eight (12.4%) patients had a cardiac injury managed surgically. Death by cardiac injury occurred in seven (18.4%) patients. The cardiac area defined between the right mid-clavicle line until the left anterior axillary line, and between 2nd and 6th intercostal spaces was the more accurate. It has sensitivity of 97.3%, specificity 72%, positive predictive value 33%, negative predictive value 99.4% and accuracy 75.1% for penetrating cardiac trauma. ROC was 0.894 IC 95% (0.760–0.901). CONCLUSION: Among the thoracic areas, topographical limits between the right mid-clavicle line and the left anterior axillary line, and between 2nd and 6th intercostal spaces are the more accurate and are highly indicative of cardiac injury in patients with SW to the thorax. Keywords: Diagnosis; penetrating cardiac trauma; stab wound; trauma.

INTRODUCTION Penetrating cardiac trauma remains an injury with high mortality but can be salvageable. Despite immense progress in the area of trauma care, more than 90% of patients may die before reaching the emergency room.[1,2] Due to the low frequency of these cases and thus the difficulty in acquiring sufficient experience in their management, it can be easy to miss a diagnosis of cardiac injury. Penetrating cardiac injuries represent around 0.1% of all trauma admissions, representing less than 10 cases per year for the majority of hospitals in many regions of the world.[3,4]

During the last two decades, the advent of real-time ultrasound and the use of echocardiography mode B or M in emergency departments has revolutionized management and algorithms for thoracic injuries, in particular those corresponding to the anterior wall of the chest.[5] The use of Focused Assessment with Sonography for Trauma (FAST) and subxiphoid pericardial window (SPW) was introduced and led to significant changes in the timing for surgical approach, especially in centers were the initial diagnosis was routinely performed clinically.[6] In countries with a high incidence of violence like Colombia, early case series noted that 85% of the penetrating injuries were stab wounds (SW) and 12%

Cite this article as: Muñoz JHM, Dussan O, Ruiz F, Rubiano AM, Puyana JC. Penetrating cardiac trauma in stab wounds: A study of diagnostic accuracy of the cardiac area. Ulus Travma Acil Cerrahi Derg 2020;26:693-698. Address for correspondence: Jorge Hernan Montenegro Muñoz, M.D. Calle 7A#44-95 760036 Cali - Colombia Tel: +573006154775 E-mail: jorgehmontenegrom@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):693-698 DOI: 10.14744/tjtes.2020.70503 Submitted: 04.08.2018 Accepted: 02.02.2020 Online: 10.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Muñoz et al. Penetrating cardiac trauma in stab wounds: A study of diagnostic accuracy of the cardiac area

were from firearms.[5,7] However, in studies performed, more recently, 47% of the wounds were SW and 42% from a firearm, with mortality levels from a firearm being the highest.[8] Publications from countries with low volumes of chest trauma have been published, including numbers like 14 cases over 20 years, highlighting that cardiac injuries are relatively rare, but with high mortality, requesting the application of clear guidelines with the aim of improving the survival of the patients.[9] However, there is not yet a statistically validated definition for the different “Cardiac areas” or “Cardiac Box” found in the literature, making it difficult to design diagnostic and management protocols for penetrating stab wounds in cardiac trauma. The present study aims to evaluate different topographic descriptions of the thorax and cardiac area and establish their diagnostic value for cardiac injury in penetrating trauma.

MATERIALS AND METHODS This study was approved by the local Ethics Committee and conformed to the principles of the Declaration of Helsinki.

Study Design A cross-sectional retrospective study was conducted reviewing medical records of patients admitted to Neiva University Hospital with SW, which caused the thoracic penetrating injury (TPI) during the period from 2013 to 2016. This was defined as an injury that penetrates the pleural or pericardial cavity. Inclusion criteria 1. Patient with an SW in the anterior or posterior region of the thorax. 2. Age older than 14 years. 3. Admission during the period of evaluation. Exclusion criteria 1. Tangential or superficial SW. 2. Patients who arrived without signs of life. 3. Incomplete information in physical and electronic medical records. 4. Pregnancy

including the epigastrium, and between the two mid-clavicular lines. Topographical area B (the Cambridge-anatomical area[11]) is located from the 3rd to the 6th intercostal space on the right sternal edge and the left from the 2nd intercostal space 2 cm lateral to the sternal border until the 5th intercostal space in the midclavicular line. Topographical area C (Cardiac Zone[12]) is located from right anterior axillary line anteriorly across the precordium to the posterior left chest ending in the midline at the spinous processes, with the superior margin being the supraclavicular areas and the inferior margin being the costal margins, including the upper epigastrium. Topographical area D (proposed area) is located from the 2nd to the 6th intercostal space between the right midclavicular line and the left anterior axillary line. The gold standard for confirmation of cardiac injury was surgical findings. In those patients who had no cardiac injury, this was confirmed by Echocardiogram, FAST, SPW or chest x-ray in order to give satisfactory confirmation of the absence of injury. This information was confirmed through the medical records, imaging studies and surgical reports.

Statistical Analysis Data were expressed as the mean value and its standard deviation. The diagnostic value for cardiac injury of each topographical thoracic area was calculated using sensitivity, specificity, accuracy, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and ROC with 95% CI. SPSS software (SPSS version 19, Chicago, IL, United States) was applied for statistical analyses.

RESULTS After reviewing the medical record of the 306 patients, 38 patients were found with cardiac injury diagnosed during the surgical intervention to be included in this study (Fig. 1).

333 patients were admitted to

27 medical records were

emergency department with

excluded from this study:

SW that caused a TPI.

• 7 did not correspond to the Diagnosis • 8 did not correspond with the identification of the patient

Test Methods A review of the literature was conducted to determine the different topographical areas of the thorax that were described when attempting to determine the possibility of cardiac injury from an SW. We found two different descriptions that were used by different national and international studies. These areas were identified for this study as A, B and C. A new area identified as D was also proposed from the pilot test carried out at the start of this research. The limits of topographical area A (the Cardiac Box[10]) are between the superior aspect of the clavicles and inferior costal margin, 694

• 6 did not have complete 306 medical records of patients with SW that caused a TPI were review.

information • 6 presented letter unreadable

38 patients with SW that caused a TPI had injury cardiac.

Figure 1. Flow of participants in this study. SW: Stab wounds; TPI: Thoracic penetrating injury.

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Muñoz et al. Penetrating cardiac trauma in stab wounds: A study of diagnostic accuracy of the cardiac area

Table 1. Distribution of the patient with penetrating cardiac injury Variable

Survivor n (%)=31

Die n (%)=7

Total n (%)=38

29.7±9.7

41.1±18.6

31.8±11.5

Admission data

Age (year)

Sex (male/female)

30/1 5/2 35/3

Systolic pressure blood (mmHg)

86.1±25.5

40.5±41

77.7±33.5

Heart rate (bpm)

101±23.8

76.8±53.9

96.5±32

Shock index

Injury Severity Score

1.3 2.9 1.4 18±8.5

44±15.2

30±12.3

Diagnosis, n (%)

Surgery

19 (61.3)

7 (100)

26 (68.4)

Focused assessment with sonography for trauma

6 (19.4)

6 (15.8)

Subxiphoid pericardial window

5 (16.1)

5 (13.2)

Echocardiogram

1 (3.2)

1 (2.6)

Cardiac injury, n (%)

Right atrium

4 (12.9)

1 (14.3)

5 (13.2)

Right ventricle

20 (64.5)

4 (57.1)

24 (63.2)

Left atrium

1 (3.2)

1 (2.6)

Left ventricle

6 (19.4)

2 (28.6)

8 (21.1)

15.5±10.1

31.7±16.5

18.9±12.2

Size of cardiac lesion (mm)

The majority of patients were male [292 (95.4%)]; the average age was 30.4±11.6 years, a median of 28 years, the minimum age was 15 and maximum of 75 years. 38 (12.4%) of the patients were identified with cardiac Injury, all injuries being located in the anterior wall of the thorax; the average age of these patients was 31.8±11.5 years, minimum age of 15 and maximum of 60 years and 35 (92.1%) were men. At

admission to the emergency department, systolic blood pressures mean (SBP) was 77.7±33.5 mmHg and the mean heart rate (HR) was 96.5±32 beats per minute; the shock index (SI) average was 1.4. The location of the lesions to the heart was in 24 (63.2%) cases the right ventricle, five (13.2%) cases in the right atrium, 8 (21.1%) in the left ventricle and 1 (3.3%) in the left atrium. The average size of the cardiac lesions was 18.9±12.2 mm. In-hospital mortality rate was 7 (18.4%) cases; 4 (57.1%) had a lesion to the right ventricle, 2 (28.5%) to the left ventricle and 1 (14.2%) to the right atrium (Table 1). The following table shows an analysis of the patients within the study, their injuries and outcomes (Fig. 2). The diagnostic value for cardiac injury of each topographical thoracic areas evaluated is described in the following Table (Table 2).

DISCUSSION

Figure 2. Relationship between areas evaluated and the topographical location of the lesions in the thorax. Non mortal Injuries (yellow points) and mortal injuries (red points). Area A (yellow box), area B (blue box), area C (orange box) and area D (green box).

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A high clinical suspicion of cardiac injury (CI), which occurs in the 6.4% stab wounds to the chest,[13] is important due to the high mortality and the increase in survival rates if intervention comes early. In low and middle-income countries centers without access to radiological studies are still the primary location for the diagnosis and management of these injuries. [14,15] The cardiac area has an important clinical significance due to its ability to help in the development of management algorithms with or without the use of technologies for imag695

Muñoz et al. Penetrating cardiac trauma in stab wounds: A study of diagnostic accuracy of the cardiac area

Table 2. Description of the diagnostic value for CI of each topographical thoracic area evaluated Area evaluated

SEN (%)

SPE (%)

VPP (%)

VPN (%)

Accuracy (%)

LR +

LR -

AUC ROC

IC 95%

Area A

89.4

66.4

27.4

97.8

69.2

2.6

0.1

0.779

0.710–0.849

Area B

55.2

86.5

36.8

93.1

82.6

4.1

0.5

0.709

0.610–0.808

Area C

100

17.9

14.7

100

28.1

1.2

0.590

0.505–0.674

Area D

97.3

99.4

75.1

3.47

0.03

0.847

0.797–0.897

SEN: Sensitivity; SPE: Specificity, PPV: Positive predictive value; NPV: Negative predictive value; LR+: Positive likelihood ratio; LR-: Negative likelihood ratio; AUC ROC: Area under curve ROC.

ing (FAST, SPW, thoracoscopy). Given that decision-making should be done quickly to reduce mortality in this type of injury, it is important to define the limits of this area as a diagnostic screening test. In a review of the literature, studies evaluating their diagnostic value are not easy to find. The area has been previously referred to as the “cardiac proximity”,[16] “cardiac box”,[10] “heart silhouette”,[17] “precordium” and “cardiac zone”,[12] terms all used to describe an area of the thorax in which the penetrating wounds are at risk of causing injury to the heart.[18] The population in this study is similar to the population described in other studies, being mostly male and of an economically active age.[9,10,12,14] The site more affected in the heart is the right ventricle by its previous position with similar frequency to the literature (62%), followed by the left ventricle that causes high mortality.[19–21] Mortality reported in studies of CI secondary to stab wounds is on average 21.9% (range 8–22%) which is higher than the mortality found in our study (18.4%) and higher than other mortality described in other Colombian trauma centers (8.8%).[14] Most of the patients in our study reached the hospital in a haemodynamically unstable state and with a CI greater than 30 mm. Different methods diagnostics (creatine kinase (CK)-MB or CKMB ratio, troponin I and troponin T, electrocardiogram) have been evaluated remain limited to its value diagnosis and applied with greater frequency in patients with blunt cardiac injuries and hemodynamically stable.[22–24] Focused assessment with sonography for trauma patients (FAST) and the Focused cardiac ultrasound (FOCUS) have been associated with a decrease of mortality as it leads to early diagnosis and timely management.[6,25] Most of these studies have been conducted to evaluate ultrasound methods and include multiples types of injuries like knives and firearms. According to these studies, two-thirds of the patients with a CI have entry wounds into the skin between the left anterior axillary line and the left sternal edge.[26] Another study shows the highest mortality from cardiac injury by stab wounds outside of the precordial region (25%), in contrast, to stab wounds located in the cardiac area (4%). In these studies, they recommend a re-thinking of the actual cardiac areas described in the thorax to improve the index of suspicion 696

for the detection of CI and recommend a new “Cardiac zone”.[12,27] On assessing the diagnostic value of the three areas, it was shown that the cardiac area described as the Cambridge anatomical area (Area B) had lower sensitivity but a higher specificity (86.5%) than the other areas. Nicol et al.[12] proposes an area (Area C) that was evaluated with sensitivity and negative predictive value perfect (100%), despite which would exclude the wound outside the thorax as possible cardiac injury should be considered a small area with similar value diagnosis to suspect a cardiac injury taking considerations about the trauma mechanism as described the literature. In two cases reported, the lesions are located lateral to the right mid-clavicular line and another superior to the left clavicle suggesting that CI should be anticipated even when a wound is not in the cardiac area.[28] This type of injury requires that the defined cardiac area has adequate sensitivity and NPV to guide the management. In comparison with the previously defined areas, the area described by the new proposal (area D) was found to have a sensitivity of 97.3%, a VPN of 99.4%, and an improved area under the curve ROC (0.847 CI 95% 0.797–0.897). It is believed that this proposed “Cardiac area” can better guide the process of identifying cardiac injury in those patients with penetrating trauma to the thorax.

Limitations The main limitation of this study is the small sample size. There is not analysis for excluded patients with incomplete data in the medical record. Further studies are required to validate our findings in a bigger population.

Conclusion Among the thoracic areas evaluated, the topographical limits between the right midclavicular line and the left anterior axillary line and between 2nd and 6th intercostal spaces are the most accurate and highly indicative of cardiac injury in patients with stab wounds to the thorax. Ethics Committee Approval: Approved by the local ethics committee. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Muñoz et al. Penetrating cardiac trauma in stab wounds: A study of diagnostic accuracy of the cardiac area

Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: J.H.M.M., O.D., A.M.R.; Design: J.H.M.M., O.D., A.M.R., F.R., J.C.P.; Supervision: A.M.R., F.R., J.C.P.; Materials: J.H.M.M., O.D., A.M.R., F.R., J.C.P.; Data: J.H.M.M., O.D., A.M.R., F.R., J.C.P.; Analysis: J.H.M.M., A.O., A.M.R.; Literature search: .H.M.M., O.D., A.M.R., F.R., J.C.P.; Writing: .H.M.M., O.D., A.M.R., F.R., J.C.P.; Critical revision: .H.M.M., O.D., A.M.R., F.R., J.C.P. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Campbell NC, Thomson SR, Muckart DJ, Meumann CM, Van Middelkoop I, Botha JB. Review of 1198 cases of penetrating cardiac trauma. Br J Surg 1997;84:1737−40. 2. Carr JA, Buterakos R, Bowling WM, Janson L, Kralovich KA, Copeland C, et al. Long-term functional and echocardiographic assessment after penetrating cardiac injury: 5-year follow-up results. J Trauma 2011;70:701−4. 3. Morse BC, Mina MJ, Carr JS, Jhunjhunwala R, Dente CJ, Zink JU, et al. Penetrating cardiac injuries: A 36-year perspective at an urban, Level I trauma center. J Trauma Acute Care Surg 2016;81:623−31. 4. Asensio JA, Garcia-Nunez LM, Petrone P, Duran D, Vara AD, Weston JS, et al. Cardiac injuries. In: Current therapy of trauma and surgical critical care. Asensio JA, Trunkey DD, editors. Philadelphia: Mosby Elsevier; 2008.p.304−15. 5. Rozycki GS, Feliciano DV, Ochsner MG, Knudson MM, Hoyt DB, Davis F, et al. The role of ultrasound in patients with possible penetrating cardiac wounds: a prospective multicenter study. J Trauma 1999;46:543−51; discussion 551−2. 6. Kong VY, Oosthuizen G, Sartorius B, Sartorius B, bruce J, Clarke DL. Penetrating cardiac injuries and the evolving management algorithm in the current era. J Surg Res 2015;193:926−32. 7. Ferrada R, Rodriguez A. Trauma cardiac. Rev Col Cirugia 2001;16:5−15. 8. Karrel R, Shaffer MA, Franaszek JB. Emergency diagnosis, resuscitation, and treatment of acute penetrating cardiac trauma. Ann Emerg Med 1982;11:504−17. 9. Ngatchou W, Surdeanu I, Ramadan AS, Essola B, Youatou P, Guimfacq V, et al. Penetrating cardiac injuries in Belgium: 20 years of experience in university hospitals in Brussels. Acta Chir Belg 2013;113:275−80. 10. Asensio JA, Stewart BM, Murray J, Fox AH, Falabella A, Gomez H, et al. Penetrating cardiac injuries. Surg Clin North Am 1996;76:685−724. 11. Wilcox BR, Cook AC, Anderson RH. Surgical anatomy of the heart. 3rd edition. Cambridge, UK: Cambridge University Press; 2005.

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12. Nicol AJ, Navsaria PH, Beningfield S, Hommes M, Kahn D. Screening for occult penetrating cardiac injuries. Ann Surg 2015;261:573−8. 13. Asensio JA, Roldan G, Petrone P, Forno W, Rowe V, Salim A. Cardiac Trauma. J Trauma 2001;3:69−77. 14. Hernandez F, Correa J. Trauma Precordial Penetrante ¿Ventana Pericárdica vs Eco?. [Article in Spanish]. Colombia: Universidad del Valle press, 2010. 15. Moore H, Demner S, Caro A. Trauma Precordial. [Article in Spanish]. Rev Col Cirugia 1989;17:23. 16. Meyer DM, Jessen ME, Grayburn PA. Use of echocardiography to detect occult cardiac injury after penetrating thoracic trauma: a prospective study. J Trauma 1995;39:902−9. 17. Grewal H, Ivatury RR, Divakar M, Simon RJ, Rohman M. Evaluation of subxiphoid pericardial window used in the detection of occult cardiac injury. Injury 1995;26:305−10. 18. Demetriades D. Cardiac wounds. Experience with 70 patients. Ann Surg 1986;203:315−7. 19. Altun G, Altun A, Yilmaz A. Hemopericardium-related fatalities: a 10year medicolegal autopsy experience. Cardiology 2005;104:133−7. 20. Gosavi S, Tyroch AH, Mukherjee D. Cardiac Trauma. Angiology 2016;67:896−901. 21. Ezzine SB, Bouassida M, Benali M, Ghannouchi M, Chebbi F, Sassi S, et al. Management of penetrating cardiac injuries in the Department of surgery, Mohamed Thahar Maamouri Hospital, Tunisia: report of 19 cases. Pan Afr Med J 2012;11:54. 22. Salim A, Velmahos GC, Jindal A, Chan L, Vassiliu P, Belzberg H, et al. Clinically significant blunt cardiac trauma: role of serum troponin levels combined with electrocardiographic findings. J Trauma 2001;50:237−43. 23. Clancy K, Velopulos C, Bilaniuk JW, Collier B, Crowley W, Kurek S, et al; Eastern Association for the Surgery of Trauma. Screening for blunt cardiac injury: an Eastern Association for the Surgery of Trauma practice management guideline. J Trauma Acute Care Surg 2012;73:S301−6. 24. Collins JN, Cole FJ, Weireter LJ, Riblet JL, Britt LD. The usefulness of serum troponin levels in evaluating cardiac injury. Am Surg 2001;67:821−6. 25. Mandavia DP, Hoffner RJ, Mahaney K, Henderson SO. Bedside echocardiography by emergency physicians. Ann Emerg Med 2001;38:377−82. 26. Seamon MJ, Haut ER, Van Arendonk K, Barbosa RR, Chiu WC, Dente CJ, et al. An evidence-based approach to patient selection for emergency department thoracotomy: A practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg 2015;79:159−73. 27. Stranch EW, Zarzaur BL, Savage SA. Thinking outside the box: re-evaluating the approach to penetrating cardiac injuries. Eur J Trauma Emerg Surg 2017;43:617−22. 28. Claassen CW, O’connor JV, Gens D, Sikorski R, Scalea TM. Penetrating cardiac injury: think outside the box. J Trauma 2010;68:E71−3.

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Muñoz et al. Penetrating cardiac trauma in stab wounds: A study of diagnostic accuracy of the cardiac area

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Kesici-delici alet yaralanmalarında penetran kardiyak travma: Kardiyak bölgenin doğru tanısına ilişkin bir çalışma Dr. Jorge Hernan Montenegro Muñoz,1 Dr. Oscar Dussan,2 Dr. Francisco Ruiz,3 Dr. Andres M Rubiano,4 Dr. Juan C. Puyana5 Meditech Vakfı, Klinik Araştırma Grubu, Neiva-Kolombiya Güney Kolombiya Üniversitesi, Genel Cerrahi Anabilim Dalı, Neiva-Kolombiya Güney Kolombiya Üniversitesi / Hernando Moncaleano Hastanesi, Genel Cerrahi Anabilim Dalı, Neiva-Kolombiya 4 Meditech Vakfı / El Bosque Üniversitesi, Nörobilim Enstitüsü, Bogota-Kolombiya 5 Pittsburgh Üniversitesi, Cerrahi Anabilim Dalı, Travma Bölümü, Pittsburgh-ABD 1 2 3

AMAÇ: Torakstaki kesici ve delici alet yaralanmaları (SW) kardiyak yaralanma şüphesini akla getirmekle beraber bunlara ilişkin tomografik açıklamalar değişkenlik gösterir. Bu çalışma, toraks içindeki farklı tomografik tanımlamaları değerlendirilmesi ve SW’nin penetran kardiyak travmasındaki tanı değerlerinin saptanması amaçlanmaktadır. GEREÇ VE YÖNTEM: Ocak 2013 - Haziran 2016 tarihleri arasında merkezimize torasik SW ile başvuran tüm hastaların tıbbi kayıtları bu çalışmaya alındı. Bunların tanı değeri potansiyelleri literatürde açıklanan farklı toraks alanları kullanılarak ölçüldü. BULGULAR: Üç yüz altı olgu analiz edildi. Otuz sekiz (%12.4) hastada cerrahi olarak yönetilen kalp yaralanması vardı. Kardiyak yaralanma nedeniyle ölüm 7 (%18.4) hastada meydana geldi. Sağ ön klavikula çizgisi ile sol ön aksiller çizgiye kadar, 2. ve 6. interkostal boşluklar arasında tanımlanan kalp alanı daha doğruydu. Penetran kardiyak travmada %97.3, özgüllük %72, pozitif prediktif değer %33, negatif prediktif değer %99.4 ve %75.1 hassasiyete sahiptir. ROC 0.894 IC %95 (0.760–0.901) idi. TARTIŞMA: Torasik bölgeler arasında, sağ orta klavikula çizgisi ile sol ön aksiller çizgisi ve 2. ve 6. interkostal boşluklar arasındaki topografik sınırlamalar daha kesindir ve toraks ile SW hastalarında kalp yaralanmasının yüksek göstergesidir. Anahtar sözcükler: Penetran kalp travması; stab yara; tanı; travma. Ulus Travma Acil Cerrahi Derg 2020;26(5):693-698

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doi: 10.14744/tjtes.2020.70503

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ORIGIN A L A R T IC L E

Diagnostic value of serum pentraxin 3 level in children with acute appendicitis Levent Duman, M.D.,1 Özkan Cesur, M.D.,1 Duygu Kumbul Doğuç, M.D.,2 Seda Çelik, M.D.,2 Adnan Karaibrahimoğlu, Ph.D.,3 Mustafa Çağrı Savaş, M.D.1 1

Department of Pediatric Surgery, Süleyman Demirel University Faculty of Medicine, Isparta-Turkey

Department of Biochemistry, Süleyman Demirel University Faculty of Medicine, Isparta-Turkey

Department of Biostatistics and Medical Informatics, Süleyman Demirel University Faculty of Medicine, Isparta-Turkey

ABSTRACT BACKGROUND: Appendicitis is one of the most common surgical emergencies. Early diagnosis of appendicitis is important in children because any delay in treatment substantially leads to complicated appendicitis. In this study, we aimed to test the diagnostic value of pentraxin 3 (PTX3) level in children with acute appendicitis and to investigate whether there is a relationship between the progression of the disease and PTX3 level. METHODS: This prospective study included 70 children. They were divided into three groups as follows: group 1 (appendicitis; n=37), group 2 (abdominal pain; n=25), group 3 (control; n=8). Demographic data, medical history, the time from the onset of symptoms to blood sampling, operative and pathological findings of the patients were noted, and white blood cell (WBC), C-reactive protein (CRP) and PTX3 values were measured. RESULTS: The mean WBC, CRP and PTX3 values were found to be significantly increased in the appendicitis group (p<0.001). PTX3 has the highest diagnostic value (AUC=0.828), specificity (88%) and positive predictive value (90%) in the appendicitis group. WBC values did not show a significant correlation with the time periods (p=0.999). The mean CRP level of the appendicitis group in 24–48 hours was found to be higher than in 0–24 hours, but this was marginally significant (p=0.068). On the other hand, PTX3 value was significantly correlated with the time periods (p<0.05). CONCLUSION: This study showed that PTX3 is a valuable inflammatory biomarker in the diagnosis of acute appendicitis and also documented that PTX3 is useful for predicting the progression of the disease. Keywords: Abdominal pain; appendicitis; children; pentraxin 3.

INTRODUCTION Abdominal pain is a common entity in the pediatric population. Although right lower quadrant (RLQ) pain principally brings to mind appendicitis worldwide, RLQ usually remains a diagnostic dilemma for the clinicians in children because many non-surgical conditions also cause RLQ pain and clinically mimic appendicitis.[1] Although laboratory tests showing inflammation, and radiological studies are helpful diagnostic tools, the results sometimes do not support the diagnosis in the initial phase of appendicitis and may cause a delay in the

treatment, which is associated with increased risk of complicated appendicitis. In this respect, new diagnostic tools are needed to differentiate the early phase of appendicitis from nonspecific abdominal pain. Appendicitis is a suppurative inflammatory process of the vermiform appendix. C-reactive protein (CRP) is an inflammatory biomarker, which has been widely used in the diagnosis of appendicitis in daily practice.[2] CRP reaches its peak level within the first 48 hours of the inflammatory process. [3–5] For this reason, negative CRP values obtained in the early

Cite this article as: Duman L, Cesur Ö, Kumbul Doğuç D, Çelik S, Karaibrahimoğlu A, Savaş MÇ. Diagnostic value of serum pentraxin 3 level in children with acute appendicitis. Ulus Travma Acil Cerrahi Derg 2020;26:699-704. Address for correspondence: Levent Duman, M.D. Süleyman Demirel Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, 32260 Isparta, Turkey Tel: +90 246 - 211 92 49 E-mail: leduman@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):699-704 DOI: 10.14744/tjtes.2020.23258 Submitted: 19.08.2019 Accepted: 05.02.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Duman et al. Diagnostic value of serum PTX3 level in children with acute appendicitis

phase of appendicitis may be misleading. Recently, pentraxin 3 (PTX3) has been started to use as a diagnostic tool in inflammatory conditions. PTX3 is a protein from the same family with CRP, but its blood levels increase more rapidly than CRP during acute inflammation.[6,7] In this respect, we hypothesized that PTX3 might be a potential diagnostic tool for early diagnosis of acute appendicitis. We designed a prospective, controlled clinical trial to test the diagnostic value of PTX3 for acute appendicitis in children and to investigate whether there is a relationship between the progression of the disease and PTX3 level.

Determination of PTX3 Levels

MATERIALS AND METHODS

Statistical Analysis

Ethical Approval

Data were analyzed using SPSS software for Windows (release 20.0; SPSS Inc., Chicago, IL, USA). Numerical data were expressed as mean ± standard deviation of the mean and categorical data were expressed as frequencies (percentages). Statistical comparisons among the groups were made by Kruskal-Wallis and Mann-Whitney U tests for numerical variables due to the continuous variables that were not distributed normally, and the Chi-square test for categorical variables. The optimum cut-off value, sensitivity, specificity and predictive values of the studied biomarkers were determined by the receiver operation characteristic (ROC) analysis with 95% CI. The area under the ROC curve (AUC) of 0.5 to 0.7 is considered low, 0.7 to 0.8 is considered acceptable, 0.8 to 0.9 is considered excellent, and more than 0.9 is considered outstanding diagnostic value.[8] P values less than 0.05 were considered to be statistically significant.

Permission from the institutional review board was obtained before this prospective clinical trial (IRB approval number: 04.07.2018-127). Informed consent was obtained from one of the parents of each patient before the study.

Study Groups This study was performed between July 2018 and April 2019 on 95 children (87 consecutive children who presented to the emergency service with RLQ pain suggesting acute appendicitis, and eight healthy children). On admission, all children were examined by an experienced pediatric surgeon. Demographic data (age and sex), medical history, the time from the onset of symptoms to blood sampling, WBC counts and CRP levels at admission, operative and pathological findings of the patients were noted. A total of 25 children who documented complicated appendicitis (n=11), negative appendectomy (n=1), RLQ pain lasting more than 48 hours (n=5), Meckel’s diverticulitis (n=1), mesenteric lymphadenitis (n=1), RLQ pain with acute tonsillitis (n=2) and urinary tract infection (n=1), and a history of antibiotic usage in the 10 days preceding admission (n=3) were excluded from this study. The remaining 70 children were divided into three groups as follows: 1) Appendicitis group (n=37) included patients undergoing appendectomy in whom the diagnosis was confirmed by histopathological examination, 2) Abdominal pain group (n=25) included other patients who were observed for suspected acute appendicitis without any medication and discharged after abdominal pain completely resolved, 3) Control group (n=8) included only healthy children. Patients with appendicitis were further divided into two subgroups according to the duration of symptoms as RLQ pain lasting less than 24 h (n=28) and between 24–48 h (n=9).

Collection of Blood Samples Blood samples were obtained from the patients for analysis of the serum PTX3 at the same time with WBC and CRP samples. They were centrifugated for 10 minutes at 3000 rpm. Plasma was separated and stored at -80 °C until used for biochemical assay. 700

PTX3 levels were measured using an enzyme-linked immunosorbent assay commercial kit (Human PTX3 Elisa Kit, Shanghai YL Biotech Co., Ltd., Shanghai, China) according to recommendations of the manufacturer. The absorbance of the samples was measured using a microplate reader (Rayto RT-6000 Microplate Reader, China) at a 450 nm wavelength. A standard chart was prepared using absorbance values obtained against standard concentrations. Results were calculated using this chart and were expressed as nanograms per milliliters (ng/mL).

RESULTS The demographic data, the time from the onset of abdominal pain to blood sampling, and the mean WBC, CRP and PTX3 values of the study groups are given in Table 1. There was no statistically significance between the groups concerning age, sex, and time (p>0.05). Distribution of the biomarker values among the groups were also shown in Fig. 1. The mean WBC, CRP and PTX3 values were found to be significantly increased in the appendicitis group when compared with the others (p<0.001). The mean WBC, CRP and PTX3 values by the time periods (0–24 and 24–48 h) in the appendicitis group are shown in Table 2. Although CRP and PTX3 values were found to be increased by the time periods, this increase was significant only for PTX3 (p<0.05). The predictive power of the studied biomarkers in the diagnosis of acute appendicitis and ROC curve analyses are given in Table 3 and Fig. 2, respectively. PTX3 has the highest diagnostic value (AUC=0.828) in children with acute appendicitis.

DISCUSSION Appendicitis is the most common surgical abdominal emergency in childhood. Although clinical, laboratory and radiological features of appendicitis have been well documented, its definitive diagnosis may be elusive in children at the time Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Duman et al. Diagnostic value of serum PTX3 level in children with acute appendicitis

Table 1. The mean values of the demographic data, time periods, and inflammatory biomarkers

Group 1 (n=37)

Age (years) Sex (male/female), n (%) Time (h)

Group 2 (n=25)

Group 3 (n=8)

12.14±3.47

11.68±3.24

8.88±3.52

0.119

26 (70%)/11 (30%)

15 (60%)/10 (40%)

5 (63%)/3(37%)

0.479

0.068

15.86±9.19

12.32±9.68

White blood cell (cell/µL)

16108±3684*

12004±6387

7125±1044 <0.001

C-reactive protein (mg/L)

31.64±38.50*

7.65±15.98

0.57±0.59 <0.001

Pentraxin 3 (ng/mL)

14.35±7.32*

6.88±2.93

4.33±0.34 <0.001

*Significant as p<0.001.

of initial assessment.[1] Misdiagnosis may lead to complications on the one hand or an unnecessary surgery on the other. Both consequences are not desired in the management of appendicitis. Thus, many studies, like the present study, have focused on new diagnostic tools that can differentiate acute appendicitis from other non-surgical causes of abdominal pain. Children with appendicitis more commonly present with perforation than adults.[1] A previous study demonstrated that the prevalence of perforation is 7% within the first 24 hours after the onset of symptoms, 38% when symptoms are present less than 48 hours, and 98% when symptoms are present for more than 48 hours.[9] This finding clearly shows that increased duration of symptoms is associated with an increased risk of perforation. Especially the first 24-48 hours are critical to a definitive diagnosis and treatment. The concentration of inflammatory markers, such as CRP, increases with the duration and the severity of the inflammatory process.[10] Thus, patients with longer duration of symptoms are expected to have higher values. However, the duration of symptoms has been ignored in the vast majority of biomarker studies in appendicitis. The measurements at different times produce different values. In this respect, significant results can be achieved with higher values obtained from patients with a longer duration of symptoms, while lower values obtained in patients presenting earlier may result in insignificant results. Therefore, the duration of symptoms was considered in the

Table 2. The mean inflammatory biomarker values of the appendicitis group by time periods

0–24 h

24–48 h

White blood cell (cell/µL)

16221±4049 15755±2356 0.999

C-reactive protein (mg/L)

20.94±22.72 64.92±57.30 0.068

Pentraxin 3 (ng/mL)

12.73±6.52

19.40±7.74* 0.020

*Significant as p<0.05.

present study to obtain more accurate results, and to investigate the relationship between the progression of the disease and the level of studied markers. Appendicitis causes a systemic inflammatory response, so inflammatory biomarkers, such as WBC and CRP, have long been used in the diagnosis.[11] Although the increase in WBC is generally accepted as an early sign of appendix inflammation, elevated or normal values of WBC are not reliable to diagnose or exclude appendicitis. Because patients with many other conditions, such as gastroenteritis, mesenteric lymphadenitis and infections, may have an elevated WBC.[2] Moreover, it is not surprising that children with appendicitis may have WBC within normal limits.[12] The previous studies showed that the sensitivity of WBC in the diagnosis of acute appendicitis ranges between 62% and 97% and the specificity ranges between 53% and 80%.[2,11–14] WBC showed an ac-

80.00 55

20000 15000

60.00 40.00 54

10000

20.00

5000

.00 1

2 Groups

30.00

PTX3 (mg/mL)

25000

CRP (mg/L)

WBC (cells/μL)

30000

**24

2 Groups

20.00 27

10.00

.00 1

2 Groups

Figure 1. Distribution of the WBC, CRP and PTX3 values among the groups. WBC: White blood cell; CRP: C-reactive protein; PTX3: Pentraxin 3.

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Duman et al. Diagnostic value of serum PTX3 level in children with acute appendicitis

Table 3. Predictive power of the WBC, CRP and PTX3 in the diagnosis of acute appendicitis

Cut-off value

White blood cell

AUC

Sensitivity

5.65

(67.99–93.81) (54.87–90.64) (71.72–91.33) (59.58–87.19)

0.809 72.97 84.00 87.10 67.74

9.31

(55.88–86.21) (63.92–95.46) (72.91–94.42) (54.62–78.56)

0.828 72.97 88.00 90.00 68.75 *

NPV

Pentraxin 3

PPV

83.78 76.00 83.78 76.00 0.778*

12750

C-reactive protein

Specificity

(55.88–86.21) (68.78–97.45) (75.36–96.36) (55.96–79.21)

Significant as p<0.001. Values in parentheses are 95% confidence intervals. AUC: Area under ROC curve; PPV: Positive predictive value; NPV: Negative predictive value.

ceptable diagnostic value (AUC=0.778) for acute appendicitis with 83.78% sensitivity and 76% specificity in the present study. Our results also supported the previous meta-analyses suggesting that WBC is more sensitive but less specific than CRP in the early stage of acute appendicitis.[2,15] Another finding of our study was that mean WBC values did not show a significant correlation with the time periods (p=0.999). This finding suggests that WBC is not a useful parameter to show the severity of appendiceal inflammation; in other words, the progression of the disease. PTXs are acute-phase proteins that play major roles in the humoral arm of innate immunity and serve as markers of inflammation.[16] Based on the primary structure, they are divided into two subfamilies as short and long PTXs. CRP is a classic short PTX that is produced by hepatocytes in response to cytokine stimulation triggered by a bacterial infection, trauma, tissue necrosis, and most forms of inflammation.[7] The results from previous studies showed that CRP is not an ideal diagnostic tool for ruling out or determination of acute appendicitis, and has more diagnostic accuracy in detecting complicated appendicitis.[14,17–19] Although the sensitivity of CRP in the ROC Curve

1.0

WBC CRP PTX3 Reference line

Sensitivity

0.8

0.6

0.4

0.2

0.0 0.0

0.2

0.4 0.6 1-Specificity

0.8

1.0

Figure 2. ROC curve analyses of the diagnostic value of serum WBC, CRP and PTX3 for acute appendicitis in children. WBC: White blood cell; CRP: C-reactive protein; PTX3: Pentraxin 3.

702

diagnosis of acute appendicitis ranged between 35% and 86% and the specificity ranges between 57% and 93% in the literature,[11,12,19–21] a CRP cut-off value of 5.65 produced 72.97% sensitivity, 84% specificity, and an excellent diagnostic value (AUC=0.809) in our study. Our results addressed that CRP is still a helpful inflammatory biomarker in the diagnosis of acute appendicitis in children. Some studies suggested that its level increases in appendicitis, which is related to the severity of appendiceal inflammation.[22,23] On the other hand, the mean CRP levels in 24–48 hours of appendicitis group were found to be higher in our study, but this was marginally significant (p=0.068). This result may be interpreted as CRP has a low or moderate value in showing the progression of the disease. PTX3 is the prototype of long PTXs that is produced at local sites where the primary inflammation occurs.[7] Its blood levels are low in normal conditions but increase rapidly during acute inflammation.[24,25] Production of PTX3 is mediated by early proinflammatory cytokines, such as interleukin (IL)-1 and tumor necrosis factor-α in endothelial cells and mononuclear phagocytes. However, a previous study reported that PTX3 is stored in a ready-made form in specific granules of neutrophils, and is rapidly released within minutes to sites where tissue damage or microbial stimulation are occurring. [26] In contrast, the production of CRP has a slower time course than PTX3 because it is mediated by the secondary cytokine IL-6 and is produced only in the liver.[7,16] Therefore, PTX3 is expected to increase earlier than CRP in the course of acute inflammation. In this respect, PTX3 is a potential early diagnostic marker of inflammation and tissue damage. To our knowledge, only two clinical studies examined the role of PTX3 in the diagnosis of acute appendicitis to date.[14,27] The first preliminary study in adults propounded that PTX3 levels were significantly higher in patients with acute appendicitis (mean 3.28 ng/ml) than non-specific abdominal pain group (mean 1.31 ng/ml), and PTX3 showed an acceptable diagnostic value (AUC=0.739). However, this study obtained confusing results with three different cut-off values of PTX3.[27] The first study in children achieved very ambitious results in which a PTX3 cut-off value 5.6 produced 91.8% sensitivity, 90.7% specificity, and an outstanding diagnostic value (AUC=0.979), and concluded that a high PTX3 level is a strong indicator of Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

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appendicitis.[14] In our study, a PTX3 cut-off value of 9.31 produced 72.97% sensitivity and 88% specificity, and an excellent diagnostic value (AUC=0.828). However, the present study is novel in two aspects. First, the above-mentioned studies did not investigate the time from the onset of symptoms to blood sampling (disease progression bias). Second, PTX3 value was significantly correlated with the time periods (p<0.05). This result suggests that PTX3 is a useful biomarker in showing progression of the disease. Many potential biomarkers, such as procalcitonin, bilirubin, mean platelet volume, D Dimer and calprotectin, have been studied in the diagnosis of appendicitis.[2,28–31] Although some studies have found significant results with various diagnostic value, their role in the diagnosis still contains some controversies, and most have not still been used in daily practice. Although studies about the diagnostic role of PTX3 in appendicitis are limited, the promising results of our study suggest that PTX3 may find a place in daily practice in the future due to its high diagnostic value.

Conclusion The present study showed that PTX3 is a valuable inflammatory biomarker in the diagnosis of acute appendicitis and may also be useful in predicting the progression of the disease. However, the results of the test should be interpreted carefully in conjunction with a medical history, physical examination, and radiological studies, and further prospective clinical studies, including a larger number of patients, are needed to achieve more accurate results. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: L.D.; Design: L.D.; Supervision: M.Ç.S.; Materials: L.D., Ö.C.; Data: L.D., Ö.C., D.K.D., S.Ç., M.Ç.S.; Analysis: A.K.; Literature search: L.D., Ö.C.; Writing: L.D., M.Ç.S.; Critical revision: L.D., M.Ç.S. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

5. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest 2003;111:1805−12. 6. Peri G, Introna M, Corradi D, Iacuitti G, Signorini S, Avanzini F, et al. PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans. Circulation 2000;102:636−41. 7. Daigo K, Mantovani A, Bottazzi B. The yin-yang of long pentraxin PTX3 in inflammation and immunity. Immunol Lett 2014;161:38−43. 8. Hosmer DW, Lemeshow S. Area under the ROC curve. In: Applied Logistic Regression. Hosmer DW, Lemeshow S, editors. 2nd edition. New York, USA: John Wiley and Sons; 2000.p.160−4. 9. Rothrock SG, Pagane J. Acute appendicitis in children: emergency department diagnosis and management. Ann Emerg Med 2000;36:39−51. 10. Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol 2018;9:754. 11. Buyukbese Sarsu S, Sarac F. Diagnostic value of white blood cell and C-reactive protein in pediatric appendicitis. Biomed Res Int 2016;2016:6508619. 12. Grönroos JM. Do normal leucocyte count and C-reactive protein value exclude acute appendicitis in children? Acta Paediatr 2001;90:649−51. 13. Shafi SM, Afsheen M, Reshi FA. Total leucocyte count, C-reactive protein and neutrophil count: diagnostic aid in acute appendicitis. Saudi J Gastroenterol 2009;15:117−20. 14. Oztan MO, Aksoy Gokmen A, Ozdemir T, Müderris T, Kaya S, Koyluoglu G. Pentraxin-3: A strong novel biochemical marker for appendicitis in children. Am J Emerg Med 2019;37:1912−6. 15. Andersson RE. Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg 2004;91:28−37. 16. Magrini E, Mantovani A, Garlanda C. The Dual Complexity of PTX3 in Health and Disease: A Balancing Act?. Trends Mol Med 2016;22:497−510. 17. Jangjoo A, Varasteh AR, Bahar MM, Meibodi NT, Aliakbarian M, Hoseininejad M, et al. Is C-reactive protein helpful for early diagnosis of acute appendicitis? Acta Chir Belg 2011;111:219−22. 18. Amalesh T, Shankar M, Shankar R. CRP in acute appendicitis--is it a necessary investigation?. Int J Surg 2004;2:88−9. 19. Sack U, Biereder B, Elouahidi T, Bauer K, Keller T, Tröbs RB. Diagnostic value of blood inflammatory markers for detection of acute appendicitis in children. BMC Surg 2006;6:15. 20. Benito J, Acedo Y, Medrano L, Barcena E, Garay RP, Arri EA. Usefulness of new and traditional serum biomarkers in children with suspected appendicitis. Am J Emerg Med 2016;34:871−6. 21. Asfar S, Safar H, Khoursheed M, Dashti H, al-Bader A. Would measurement of C-reactive protein reduce the rate of negative exploration for acute appendicitis?. J R Coll Surg Edinb 2000;45:21−4.

REFERENCES

22. Shakhatreh HS. The accuracy of C-reactive protein in the diagnosis of acute appendicitis compared with that of clinical diagnosis. Med Arh 2000;54:109−10.

1. Dunn JCY. Appendicitis. In: Pediatric Surgery. Coran AG, Caldamone A, Adzick NS, Krummel TN, Laberge JM, Shamberger R, editors. 7th edition. Philadelphia: Elsevier Saunders; 2012.p.1255−63.

23. Gavela T, Cabeza B, Serrano A, Casado-Flores J. C-reactive protein and procalcitonin are predictors of the severity of acute appendicitis in children. Pediatr Emerg Care 2012;28:416−9.

2. Yu CW, Juan LI, Wu MH, Shen CJ, Wu JY, Lee CC. Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis. British J Surg 2013;100:322−9.

24. Yamasaki K, Kurimura M, Kasai T, Sagara M, Kodama T, Inoue K. Determination of physiological plasma pentraxin 3 (PTX3) levels in healthy populations. Clin Chem Lab Med 2009;47:471−7.

3. Pepys MB. C-reactive protein fifty years on. Lancet 1981;1:653−7. 4. Ledue TB, Rifai N. Preanalytic and analytic sources of variations in C-reactive protein measurement: implications for cardiovascular disease risk assessment. Clin Chem 2003;49:1258−71.

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25. Inforzato A, Jaillon S, Moalli F, Barbati E, Bonavita E, Bottazzi B, et al. The long pentraxin PTX3 at the crossroads between innate immunity and tissue remodelling. Tissue Antigens 2011;77:271−82. 26. Jaillon S, Peri G, Delneste Y, Frémaux I, Doni A, Moalli F, et al. The humoral pattern recognition receptor PTX3 is stored in neutrophil granules

703

Duman et al. Diagnostic value of serum PTX3 level in children with acute appendicitis and localizes in extracellular traps. J Exp Med 2007;204:793−804. 27. Aygun A, Katipoglu B, İmamoglu M, Demir S, Yadigaroglu M, Tatli O, et al. Diagnostic Value of Plasma Pentraxin-3 in Acute Appendicitis. J Invest Surg 2019;32:143−8. 28. Motie MR, Nik MM, Gharaee M. Evaluation of the diagnostic value of serum level of total bilirubin in patients with suspected acute appendicitis. Electron Physician 2017;9:4048−54. 29. Fan Z, Zhang Y, Pan J, Wang S. Acute Appendicitis and Mean Plate-

let Volume: A Systemic Review and Meta-analysis. Ann Clin Lab Sci 2017;47:768−72. 30. Cayrol J, Miguez MC, Guerrero G, Tomatis C, Simal I, Marañón R. Diagnostic accuracy and prognostic utility of D Dimer in acute appendicitis in children. Eur J Pediatr 2016;175:313−20. 31. Ambe PC, Gödde D, Bönicke L, Papadakis M, Störkel S, Zirngibl H. Calprotectin could be a potential biomarker for acute appendicitis. J Transl Med 2016;14:107.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut apandisitli çocuklarda serum pentraksin 3 düzeyinin tanısal değeri Dr. Levent Duman,1 Dr. Özkan Cesur,1 Dr. Duygu Kumbul Doğuç,2 Dr. Seda Çelik,2 Dr. Adnan Karaibrahimoğlu,3 Dr. Mustafa Çağrı Savaş1 1 2 3

Süleyman Demirel Üniversitesi Tıp Fakültesi, Çocuk Cerrahisi Anabilim Dalı, Isparta Süleyman Demirel Üniversitesi Tıp Fakültesi, Biyokimya Anabilim Dalı, Isparta Süleyman Demirel Üniversitesi Tıp Fakültesi, Biyoistatistik ve Tıbbi Bilişim Anabilim Dalı, Isparta

AMAÇ: Apandisit en sık görülen cerrahi acillerden biridir. Çocuklarda apandisitin erken tanısı önemlidir, çünkü tedavideki herhangi bir gecikme büyük ölçüde komplike apandisite yol açar. Bu çalışmada, akut apandisitli çocuklarda pentraksin 3 (PTK3) düzeyinin tanısal değerini ve hastalığın ilerlemesi ile PTK3 seviyesi arasında bir ilişki olup olmadığını araştırmayı amaçladık. GEREÇ VE YÖNTEM: Bu çalışmaya 70 çocuk alındı. Çocuklar 3 gruba ayrıldı: Grup 1 (apandisit; n=37), grup 2 (karın ağrısı; n=25), grup 3 (kontrol; n=8). Demografik veriler, tıbbi öykü, semptomların başlangıcından kan örneklemesine kadar geçen süre, hastaların ameliyat ve patolojik bulguları kaydedildi ve beyaz küre (BK), C-reaktif protein (CRP) ve PTK3 değerleri ölçüldü. BULGULAR: Apandisit grubunda ortalama BK, CRP ve PTK3 değerleri anlamlı olarak yüksek bulundu (p<0.001). Apandisit grubunda PTK3 en yüksek tanı değerine (AUC=0.828), özgüllüğe (%88) ve pozitif öngörü değerine (%90) sahipti. BK değerleri zaman dilimleri ile anlamlı bir korelasyon göstermedi (p=0.999). Apandisit grubunda 24–48 saatteki ortalama CRP değeri, 0–24 saattekinden daha yüksek bulundu, ancak bu sınırda anlamlı idi (p=0.068). Diğer taraftan, PTK3 değeri zaman dilimleri ile anlamlı olarak korele idi (p<0.05). TARTIŞMA: Bu çalışma, PTK3’ün akut apandisit tanısında değerli bir enflamatuvar biyobelirteç olduğunu göstermiş ve ayrıca hastalığın ilerlemesini tahmin etmek için de yararlı olduğunu belgelemiştir. Anahtar sözcükler: Apandisit; çocuklar; karın ağrısı; pentraksin 3. Ulus Travma Acil Cerrahi Derg 2020;26(5):699-704

704

doi: 10.14744/tjtes.2020.23258

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ORIGIN A L A R T IC L E

Liver transplant versus non-liver transplant patients underwent appendectomy with presumed diagnosis of acute appendicitis: Case-control study Kemal Barış Sarıcı, M.D., Sami Akbulut, M.D., Adem Tuncer, M.D., Sezai Yılmaz, M.D.

Cemalettin Koç, M.D.,

Department of Surgery and Liver Transplant Institute and, İnönü University Faculty of Medicine, Malatya-Turkey

ABSTRACT BACKGROUND: This study aims to compare liver transplant and non-liver transplant patients who underwent appendectomy with a presumed diagnosis of acute appendicitis. METHODS: Demographic and clinicopathological features of 13 liver transplant recipients (transplant group) who underwent posttransplant appendectomy with a presumed diagnosis of acute appendicitis were compared with the features of 52 non-liver transplant patients (non-transplant group). They underwent appendectomy with a presumed diagnosis of acute appendicitis during the same time period. The transplant group was matched at random in a 1: 4 ratio with the non- transplant group. While the continuous variables were compared using the Mann Whitney-U test, categorical variables were compared with Fisher’s exact test. A p-value of less than 0.05 was considered statistically significant. RESULTS: A total of 65 patients aged between one year and 84 years were included in this study. While the age of the 52 patients (32 male and 20 female) in the non- transplant group ranged from 17 years to 84 years, the age of the 13 patients (nine male and four female) in the transplant group ranged from one year to 64 years. Statistically significant differences were noted between both groups concerning WBC (p=0.002), neutrophil (p=0.002), lymphocyte (p=0.032), platelets (p=0.032), RDW (p=0.001), CRP (p=0.009), PNR (p=0.042), WNR (p=0.03), and appendiceal length (p<0.001). The negative appendectomy rate was relatively higher in transplant than the non-transplant group but this difference was not statistically significant (30.8% vs. 21.2%; p=0.477). Perforated acute appendicitis occurred more frequently in the transplant group; however, this difference was not statistically significant (30.8% vs. 9.6%; p=0.070). CONCLUSION: WBC and neutrophil were lower in the LT group; however, the CRP and RDW were higher in the LT group. Further, perforation and negative appendectomy rates were higher in the LT group, although this difference was not statistically significant. Keywords: Liver recipients; acute appendicitis; Liver transplantation; negative appendectomy; perforated appendicitis.

INTRODUCTION Acute appendicitis (AAp) is one of the most common causes of admission to emergency units, and appendectomy is one of the most frequently performed surgical procedures in the world.[1] The lifetime risk of an AAp episode is 8.6% in male and 6.7% in female patients.[1–5] Epidemiologic studies state that the risk of undergoing an appendectomy at any point in their lives in male and female patients is 12% and 23%,

respectively.[1] Parameters, such as leukocyte count, neutrophil count, C-reactive protein (CRP) level, some interleukins (IL), procalcitonin level, and the findings of physical examination, used in the diagnosis of AAp depend on the extent of the host response to the inflammation in the body. Despite the contradicting findings in the literature, there is a general consensus that AAp signs and symptoms in an immunocompromised individual may differ from AAp signs and symptoms in an immunocompetent patient.[6–8] Thus, it has been sug-

Cite this article as: Sarıcı KB, Akbulut S, Koç C, Tuncer A, Yılmaz S. Liver transplant versus non-liver transplant patients underwent appendectomy with presumed diagnosis of acute appendicitis: Case-control study. Ulus Travma Acil Cerrahi Derg 2020;26:705-712. Address for correspondence: Sami Akbulut, M.D. İnönü Üniversitesi Tıp Fakültesi, Karaciğer Nakli Enstitüsü ve Genel Cerrahi Anabilim Dalı, Malatya, Turkey Tel: +90 422 - 341 06 60 E-mail: akbulutsami@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):705-712 DOI: 10.14744/tjtes.2020.52368 Submitted: 06.01.2020 Accepted: 14.02.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Sarıcı et al. Liver transplant versus non-liver transplant patients underwent appendectomy with presumed diagnosis of AAp

gested that transplant patients may have a higher rate of late diagnosis and risk of fatal complications, such as perforation and abscess formation, due to immunosuppressive therapy received in the postoperative period.[7] The present study aims to compare the demographic and clinicopathologic data of the immunosuppressed liver transplant (LT) recipients who underwent an appendectomy due to AAp to that of their non-transplant counterparts who underwent appendectomy during the same period. This study will provide an indirect means of investigation of the effects of immunosuppressive therapy on the signs and symptoms of inflammation in AAp.

MATERIALS AND METHODS Between March 2002 and October 2019, a total of 2442 patients underwent LT in Inonu University Liver Transplant Institute, and 13 (0.53%) of these patients underwent appendectomy with a presumed diagnosis of AAp after LT. This group was defined as the LT group (n=13). A control group was created for comparison with the transplant group, and this group was defined as the non-LT group (n=52). The non-LT group comprised patients who presented to our emergency unit with abdominal pain in the same time period and underwent appendectomy with the presumed diagnosis of AAp. Patients with a history of corticosteroid, chemotherapeutic agent, or other immunosuppressive drug use for any reason were not included in the non-LT group. The LT group was matched at random in a 1:4 ratio with the non-transplant group (G*Power 3.1.9.2 software; effect size=0.7, two-tailed, power: 81.8%, Df:63, critical t=1.349, non-centrality parameter=2.257). To minimize the bias risk, the non-LT group (control group) was enrolled by a surgeon who was not related to this study. Both groups were compared concerning age (years), sex (male, female), white blood cell (WBC) count, neutrophil count, lymphocyte count, platelets, red cell distribution width (RDW), platelet distribution width (PDW), mean corpuscular hemoglobin (MCH), mean platelet volume (MPV), mean corpuscular volume (MCV), bilirubin level, CRP level, white cell neutrophil ratio (WNR), white cell lymphocyte ratio (WLR), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), platelet to the neutrophil ratio (PNR), appendix diameter (mm), appendix length (mm), presence of acute appendicitis, ultrasonographic findings, and histopathological findings.

Immunosuppression for LT Recipients Intravenous methylprednisolone was administered immediately after the completion of the hepatic artery anastomosis during liver graft implantation. Thereafter, peroral steroid treatment was initiated on a postoperative day one and tapered from 100 mg/day to 0.25 mg/kg/day and stopped 3-6 months after surgery, except in patients with autoimmune diseases. Cyclosporine was only prescribed in pediatric patients who underwent LT due to acute liver failure or neurological Wilson’s disease. Mycophenolate mofetil and tacrolimus were usually initiated on postoperative day 3. Tacrolimus 706

was the first choice for immunosuppressive therapy in most cases except in patients with renal dysfunction or hepatorenal syndrome. In patients with impaired or deteriorated renal function, tacrolimus was stopped or tapered and everolimus was added until renal function improved.

Statistical Analysis The statistical analyses were performed using IBM SPSS Statistics v25.0 (Statistical Package for the Social Sciences, Inc, Chicago, IL, USA). The quantitative variables were expressed as, median and min-max. The qualitative variables were reported as number and percentage (%). Kolmogorov-Smirnov test was used to determine whether the quantitative variables showed normal distribution. Mann Whitney-U test was used to compare the quantitative variables. Fisher’s exact tests were used to compare qualitative variables because the minimum expected count was less than 5 for all compared parameters. A p-value of less than 0.05 was considered statistically significant. Patient medical records were retrospectively reviewed after obtaining approval from Inonu University institutional review board for non-interventional studies (Approval No: 2019/16-381).

RESULTS A total of 65 patients (41 male and 24 female) aged between one year and 84 years were included in this case-control study. While the age of the 52 patients (32 male and 20 female) in the non- transplant group ranged from 17 years to 84 years, the age of the 13 patients (nine male and four female) in the LT group ranged from one year to 64 years. Patients in the LT group underwent appendectomy with a preliminary diagnosis of AAp a median 339 days (min-max: 20–2023 days) after LT. While living donor LT was performed in 10 patients in the LT group, deceased donor LT was performed in the remaining three patients. Eleven of the patients in the LT group were adults, and the remaining two were in the pediatric age group (one and eight years). There was no statistically significant difference between the groups concerning age (p=0.163), sex (p=0.753), PDW (p=0.700), MCH (p=0.115), MPV (p=0.611), MCV (p=0.081), TBil (p=0.528), NLR (p=0.228), PLR (p=0.682), WLR (p=0.412), diameter of appendix (p=0.717), presence of acute appendicitis according to histopathological findings (p=0.477), ultrasonographic findings (p=0.139), and detailed histopathological findings (p=0.064). However, statistically significant difference was noted between the groups with respect to WBC count (p=0.002), neutrophil count (p=0.002), lymphocyte count (p=0.032), platelet count (p=0.032), RDW (p=0.001), CRP level (p=0.009), PNR (p=0.042), WNR (p=0.03), and appendix length (p<0.001). The negative appendectomy rate was relatively higher in the LT group than in the non-LT group, but this difference was not statistically significant (30.8% vs. 21.2%; p=0.477). SimilarUlus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Sarıcı et al. Liver transplant versus non-liver transplant patients underwent appendectomy with presumed diagnosis of AAp

ly, the clinical and histopathologically-proven perforated AAp rate was higher in the LT group than in the non-LT group; however, this difference also was not statistically significant (30.8% vs. 9.6%; p=0.070). There was no significant difference

between the two groups in terms of postoperative wound infection, wound dissociation, intra-abdominal abscess, and adjacent organ injury. In both groups, the subcutaneous collection was treated with simple drainage in only one patient.

Table 1. Comparison of the LT and No-LT appendectomy groups in terms of continuous variables Patients’ characteristics

LT Group (n=13)

Age, median (min–max)

No-LT Group (n=52)

42 (1–67)

30 (17–84)

0.163

7.5 (2.5–25)

12.5 (6.2–27)

0.002

Neutrophil, median (min–max)

5.2 (2–20.7)

10.2 (3.9–22.3)

0.002

Lymphocyte, median (min–max)

1.3 (0.4–1.9)

1.8 (0.2–5.6)

0.032

WBC, median (min–max)

Platelets, median (min–max)

147 (76–503)

237 (53–443)

0.032

14.7 (12.8–17.6)

13.1 (11.5–18)

0.001

PDW, median (min–max)

14.8 (9–18.8)

14.8 (8.7–17.6)

0.700

MCH, median (min–max)

27 (17.9–32.9)

29 (19.6–31.5)

0.115

RDW, median (min–max)

MPV, median (min–max)

9.4 (6.8–11.5)

9.2 (5.4–11.9)

0.611

MCV, median (min–max)

82.5 (62.6–99.5)

85.4 (68.4–94.2

0.081

TBil, median (min–max)

1 (0.2–2.3)

0.8 (0.2–3.7)

0.528

CRP, median (min–max)

6.1 (0.3–20.7)

0.8 (0.1–16.7)

0.009

NLR, median (min–max)

5 (2.3–12.4)

5.4 (1.4–29.5)

0.228

PLR, median (min–max)

169 (49–429)

139 (29–1020)

0.682

PNR, median (min–max)

32 (14.5–58.1)

22.4 (8.5–95.6)

0.042

WLR, median (min–max)

6.3 (4–13.9)

6.7 (2.8–31)

0.412

WNR, median (min–max)

1.4 (1.1–1.7)

1.2 (0.7–2.3)

0.030

47 (30–80)

70 (45–110)

<0.001

8 (5–40)

10 (5–30)

0.717

Appendix length (mm), median (min–max) Appendix diameter (mm), median (min–max)

LT: Liver transplantation; WBC: White blood cell; RDW: Red cell distribution width; PDW: Platelet distribution width; MCH: Mean corpuscular hemoglobin; MPV: Mean platelet volume; MCV: Mean corpuscular volume; CRP: C-reactive protein; NLR: Neutrophil to lymphocyte ratio; PLR: Platelet to lymphocyte ratio; PNR: Platelet to neutrophil ratio; WLR: White cell lymphocyte ratio; WNR: White cell neutrophil ratio; Min: Minimum; Max: Maximum.

Table 2. Comparison of the LT and No-LT appendectomy groups concerning categorical variables Patients’ characteristics Sex

LT Group (n=13)

No-LT Group (n=52)

p 0.753

Male

9 (69.2)

32 (61.5)

Female

4 (30.8)

20 (38.5)

Yes

9 (69.2)

41 (78.8)

4 (30.8)

11 (21.2)

AAp Perforation

Yes

4 (30.8)

5 (9.6)

9 (69.2)

47 (90.4)

Ultrasonographic findings

AAp (+)

3 (33.3)

32 (64.0)

AAp (-)

6 (66.7)

18 (36.0)

Histopathological findings

AAp

5 (38.5)

36 (69.2)

AAp (perforated)

4 (30.8)

5 (9.60)

Appendix vermiformis

0 (0.00)

5 (9.60)

Fibrous obliteration

1 (7.70)

2 (3.80)

Lymphoid hyperplasia

3 (23.1)

4 (7.70)

0.477 0.070 0.139 0.064

AAp: Acute appendicitis; LT: Liver transplantation.

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Comparison of the LT and No-LT appendectomy groups in terms of continuous and categorical variables were summarized in Table 1 and Table 2.

DISCUSSION AAp is the most common disease requiring emergency surgical therapy worldwide and its current global incidence is 100– 151 per 100.000 population.[9,10] Conversely, its incidence following solid organ transplantation is low compared to that in the normal population. However, as the frequency of solid organ transplantation is increasing with enhanced survival due to recent advancements in immunosuppressive therapy, the incidence of AAp in this subgroup of patients is increasing.[5,8,9,11] The first publication regarding AAp in patients with LT was published in 2005 by Abt et al.,[11] and since then, 14 articles have been published with one being a review article. [2–16] Our literature review with 33 LT patients who received appendectomy for AAp has been summarized in Table 3. The studies in the field show that AAp incidence in patients with LT ranges between 0.09%–0.67%.[4,6,8,9,11,15] De’Angelis et al.[5] found that AAp developed in 0.29% of the transplant patients and 38.9% of them had undergone an LT. In our opinion, the term incidence used for documenting AAp occurrence following solid organ transplantation is inappropriate, considering its low rate of occurrence. In fact, we believe “prevalence” is a better term to define the frequency of this disease in transplant patients. It has been suggested by many researchers that the classical signs and symptoms of AAp, such as right lower quadrant pain, loss of appetite, nausea and vomiting, and fever, are not observed in transplant patients due to the suppressive effects of immunosuppressive therapy, which in turn delay the diagnosis and increase the complication rates observed. On the contrary, some researchers state that in this subgroup of patients, the signs and symptoms of the disease are not different; rather, the severity of the symptoms may be altered. [4,6–8] It has been suggested that combined immunosuppressive therapy used, especially in the early post-transplant period, could mask the symptoms of AAp by suppressing the inflammatory response and result in atypical manifestations of the disease.[7] Furthermore, graft-related complications encountered in the early post-transplant period could also mask the clinical manifestations of the AAp.[9] As a result of the literature analysis we performed, fever-related data of 21 patients were retrieved, and 66.7% of these patients developed a fever during AAp episodes. In our case-control study, we found that 23.7% of the patients with LT had a fever during the development of AAp. In the literature, the interval between LT and development of AAp was reported to be 8–5430 days, and in 24.2% of the patients, AAp developed in the first 15 days following LT. Our case-control study showed that in 7.7% of the patients, AAp 708

developed in the first postoperative month. Thus, based on our results, we disagree with the idea of the other researchers[7] proposing that AAp develops in the early postoperative period in LT patients. Some researchers have proposed that immunosuppressive therapy reduces the leukocyte count and suppresses the inflammatory response leading to a delayed diagnosis of AAp. [7,8,14] The opponents of this hypothesis state that there is, in fact, no difference concerning leukocyte count between transplanted and non-transplanted patients with AAp. Sheppard and colleagues[6] have stated that leukocytosis was observed in 73% of the LT patients with AAp, comparable to that in the non-transplanted patient population, and their hypothesis was supported by Savar et al.[4] Our literature review showed that 28 of the 33 patients reported had data regarding leukocyte count, and 71.4% of these patients had leukocytosis (>10.000 cells/mm3). In our case-control study, leukocytosis was observed in 30% of the LT patients in contrast to 76.9% of the non-transplant patients during the study period. The results of the study by Fonseca-Neto et al.[8] are consistent with the findings obtained in our study. All in all, our results and the results of previous studies regarding this subject are contradictory. However, in our experience of over 2500 cases of LT, leukocyte levels in the post-transplant period are lower than the normal range observed in the general population as a result of immunosuppressive therapy. The diagnosis of AAp in LT patients requires evaluation of anamnesis, physical examination findings, laboratory values, and imaging studies. The differential diagnosis in LT patients with AAp should include intraabdominal infections, gastrointestinal perforations, biliary fistula, graft-related complications, rejection, and vascular thrombosis.[8,9,15] As previously discussed, the leukocyte count and inflammatory response are reduced in immunosuppressed individuals. On the contrary, some studies state that inflammatory markers, such as RDW and CRP level, are elevated significantly in LT patients in contrast to non-transplant patients. However, when analyzed in detail, these parameters were found to be especially increased in complicated cases.[17] Therefore, although statistically not significant, a higher perforation rate in the LT patients may explain the elevated CRP and RDW levels. Further, even though ultrasonography is a very effective diagnostic tool when performed by experienced personnel, abdominal computerized tomography is both effective in diagnosing complications related to the transplanted graft and also has higher sensitivity (91% vs. 78%) and specificity (90% vs. 83%) when compared to ultrasonography.[6,8] Radiological studies are especially useful in post-transplant patients in whom leukocytosis is not observed.[9,15] The majority of researchers have found no difference concerning the etiopathogenetic factors of AAp between transplant and non-transplant patients.[8,9,15] However, there are Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

2002-2014

Brazil

F M

Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

USA

2010

2005

Ceulemans et al.

Savar et al.

1996-2004

Abt et al.

USA

2005

1 56

9 15

1989-2002

USA

Belgium

2011

Turkey

Aktas et al.

F M

M M

63 33

2000-2007

43 52

China

2010-2013

2003-2013

2012

2011

Quartey et al.

Wu et al.

Brazil

Taiwan

2014

Andrade et al.

Wei et al.

58 M 50

2015

McCarty et al.

38 F 41 M

USA

HCC

NASH

PFIC-II

HHE

HBV

HCC

PSC+ALF

HCV+HCC

PSC

Alcoholic

Autoimmune

49 F

2016

Foncesa-Neto et al.

USA

2017

58 40

1998-2013

China

Sheppard et al.

2017

Study Age Sex Etiology Period

Huang et al.

References Year Country NS

Total LT 2

Total App NS

925

426 5

1 0.54

0.23

817

150

0.49

0.67

3287

0.21

14 hours-3 days

0.09

16 hours

7 days

48 hours

24 hours

12 hours

Several hours

7 days

21 days

24 hours

21-5430

2935

2977

1598

1050

809

231

574

1560

720

240

180

570

1380

720

3650

2.3-26.400

10.580

18.080

6.810

5.470

11.200

4.600

14.900

20.390

18.400

21.000

18.000

19.000

17.000

13.600

5.456

12.060

6.100

12.500

14.000

11.000

App From LT to WBC (%) App (days)

Sudden onset

Duration of symptoms

Table 3. Summary of the published articles on acute appendicitis after liver transplantation in the literature

Yes (n=6)

Yes

Fever (≥37.5°C)

Yes

Tachycardia

Sarıcı et al. Liver transplant versus non-liver transplant patients underwent appendectomy with presumed diagnosis of AAp

709

710

US (n=8) CT (n=7)

Ceulemans et al.

Savar et al.

Abt et al.

Yes (n=4)

Yes

Appendectomy (Open)

Appendectomy (Open; n=7)

Appendectomy (Open)

Appendectomy (Lap)

Appendectomy (Open)

Appendectomy (Lap)

Appendectomy (Open)

Appendectomy (Lap)

Appendectomy (Converted)

Appendectomy (Lap)

Wound infection (n=2)

Sepsis

Wound infection?

Postoperative complications

AAp (n=8)

AAp

AAp (CMV+)

AAp

Histopathological findings

3-12 days

210-2220

540

870

1200

1860

2520

150

360

270

Combined

Single

Combined

Induced

Combined

Single

Combined

Hospital Follow up Immunosupp. stay (day) (day) regimens

Alive (n=8)

Alive (n=7)

Alive

Dead

Alive

Status

LT: Liver transplantation; HCC: Hepatocellular carcinoma; HBV: Hepatitis B virus; HCV: Hepatitis C virus; ALF: Acute liver failure; NASH: Nonalcoholic steatohepatitis; PSC: Primary sclerosing cholangitis; HHE: Hepatic hemangioendothelioma; PFIC-II: Progressive familial intrahepatic cholestasis; CMV: Cytomegalovirus; CT: Computed tomography; US: Ultrasonography; AAp: Acute appendicitis; NS: Not-stated; Lap: Laparoscopic.

Aktas et al.

Examination

Quartey et al.

Wu et al.

CT (No-diagnostic)

Wei et al.

Andrade et al.

Yes

McCarty et al.

Yes No

Foncesa-Neto

et al.

Yes

Diagnostic Perforation Surgery tools

Sheppard et al.

Huang et al.

References

Table 3. Summary of the published articles on acute appendicitis after liver transplantation in the literature (continued)

Sarıcı et al. Liver transplant versus non-liver transplant patients underwent appendectomy with presumed diagnosis of AAp

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Sarıcı et al. Liver transplant versus non-liver transplant patients underwent appendectomy with presumed diagnosis of AAp

some opponents of this opinion.[6] In fact, luminal obstruction and bacterial overgrowth are the two triggering factors in the development of clinical AAp.[8] Our literature review revealed that only one LT patient had acute appendicitis due to CMV infection.[13] Further, CMV-associated AAp is more common after kidney and bone marrow transplantation. The gold standard therapeutic option for AAp is open or laparoscopic appendectomy. The timing of appendectomy depends on the development of complications (pylephlebitis, periappendicular abscess, and plastron) at the time of diagnosis. The basic principles of management for AAp in LT patients are the same as those for non-transplant patients. Our literature review showed that 27 transplanted patients had received open appendectomy, whereas five transplanted patients underwent laparoscopic appendectomy.[2,6,7,13,14] In the remaining patient, a perforation was noticed during laparoscopic exploration and the operation was converted to open surgery.[3] Although laparoscopic surgery is recommended in the early postoperative period, laparoscopic appendectomy may also be performed many years after the transplant surgery.[2,6,7,13,14] The first trocar should always be placed under direct vision during laparoscopic appendectomy. In the open approach, if the diagnosis is confirmed in the preoperative period, a McBurney incision is preferred. Conversely, in cases with uncertain diagnoses, the old incision or midline incision should be used for the exploration of the abdomen.[15] In the present case-control study, 12 LT patients underwent operation through the McBurney incision, and one patient received a paramedian incision for an appendectomy. The most dreaded complications of appendicitis in transplant patients are perforation and intraabdominal sepsis. The rate for perforation in the non-transplant population ranges between 4–41.5%, whereas it was reported to be 0–50% in LT patients.[8,11,18] Abt et al.[11] showed that in LT patients in whom the diagnosis was delayed or the admission was delayed by three days, the perforation rate was 75%. This is supported by many other researchers.[2,9] Our literature review showed that among the 26 patients with documented operative parameters, the perforation rate was 30.7%, and no mortality case was noted.[3,7,8,11] In previous literature, during the 4–2220 days of follow up, only one case of mortality related to AAp was observed.[9] In the present study, 30.8% of the 13 LT patients developed perforation and none of the patients died. In our opinion, the main causes of perforation were the non-specific symptoms observed in the patients enrolled and late admission to the emergency department. Conversely, a high negative appendectomy rate in our institution may be attributable to our decision to operate in LT patients suspected to have AAp to avoid any complications. In conclusion, to our knowledge, this study is the first study to compare AAp in LT patients to that in the normal population. WBC and neutrophil counts that are biomarkers of inflammation were lower in LT patients; however, the CRP Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

level and RDW, markers of severe appendicitis, were higher in the LT patients. Although AAp has been known to be more frequent in the early post-transplant period, we showed that it may occur at any time following LT. Further, the rates of perforation and negative appendectomy were higher in LT patients than in the normal population, although this difference was not statistically significant. We believe that our results are relevant as, to our knowledge, this is the first and largest study on this subject concerning design and the number of cases reported. In addition, since AAp after LT is a very rare clinical entity, the multicentric study should be designed to comprehensively evaluate AAp in transplanted patients. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.A., A.T.; Design: S.A., K.B.S.; Materials: K.B.S., C.K., A.T.; Data: K.B.S., C.K., A.T.; Analysis: S.A.; Literature search: S.A., C.K., A.T.; Writing: S.A.; Critical revision: S.A., S.Y. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Akbulut S, Koc C, Kocaaslan H, Gonultas F, Samdanci E, Yologlu S, et al. Comparison of clinical and histopathological features of patients who underwent incidental or emergency appendectomy. World J Gastrointest Surg 2019;11:19−26. 2. Quartey B, Dunne J, Cryer C. Acute appendicitis post liver transplant: a case report and literature review. Exp Clin Transplant 2012;10:183−5. 3. Aktas S, Sevmis S, Karakayali H, Ozcay F, Coskun M, Bilezikci B, et al. Acute appendicitis after diaphragmatic hernia after pediatric liver transplant. Exp Clin Transplant 2011;9:63−7. 4. Savar A, Hiatt JR, Busuttil RW. Acute appendicitis after solid organ transplantation. Clin Transplant 2006;20:78−80. 5. de’Angelis N, Esposito F, Memeo R, Lizzi V, Martìnez-Pérez A, Landi F, et al. Emergency abdominal surgery after solid organ transplantation: a systematic review. World J Emerg Surg 2016;11:43. 6. Sheppard SE, Marecki HL, Psoinos CM, Movahedi B, Furman MJ, Bozorgzadeh A, et al. Acute Appendicitis after Liver Transplantation: A Case Report and Review of the Literature. Int J Organ Transplant Med 2017;8:208−12. 7. Huang JF, Ma JF, Gong Y, Yu LL, Cui CX, Yang LX, et al. Acute Appendicitis in the Early Stage after Orthotopic Liver Transplantation. Chin Med J (Engl) 2017;130:1253−4. 8. Fonseca-Neto OC, Lima HC, Melo PS, Melo PS, Lemos R, Leitão L, et al. Acute apendicitis in liver transplant recipients. Arq Bras Cir Dig 2016;29:30−2. 9. Andrade RO, Pires RS, Silva RE, Mello FPT, Sousa CCT, Basto ST, et al. Acute Appendicitis after Liver Transplant: A Case Report and Review of the Literature. Open J Organ Transplant Surg 2014;4:29−32. 10. Ferris M, Quan S, Kaplan BS, Molodecky N, Ball CG, Chernoff GW, et al. The Global Incidence of Appendicitis: A Systematic Review of Population-based Studies. Ann Surg 2017;266:237−41.

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Sarıcı et al. Liver transplant versus non-liver transplant patients underwent appendectomy with presumed diagnosis of AAp 11. Abt PL, Abdullah I, Korenda K, Frank A, Peterman H, Stephenson GR, et al. Appendicitis among liver transplant recipients. Liver Transpl 2005;11:1282−4. 12. Ince V, Barut B, Ozdemir F, Ersan V, Kutluturk K, Gonultas F, et al. The management of acute appendicitis in liver transplant patients: How effective is the Alvarado score? North Clin Istanb 2017;4:262−6. 13. McCarty TP, Lee RA, Herfel BM, Pappas PG. Cytomegalovirus appendicitis in solid organ transplant patients, two cases and a review. J Clin Virol 2015;66:48−50. 14. Wei CK, Chang CM, Lee CH, Chen JH, Yin WY. Acute appendicitis in organ transplantation patients: a report of two cases and a literature review. Ann Transplant 2014;19:248−52.

15. Wu L, Zhang J, Guo Z, Tai Q, He X, Ju W, et al. Diagnosis and treatment of acute appendicitis after orthotopic liver transplant in adults. Exp Clin Transplant 2011;9:113−7. 16. Ceulemans P, Wybaillie E, Monbaliu D, Aerts R, Pirenne J. Acute appendicitis after liver transplantation: a case report and review of the literature. Acta Chir Belg 2010;110:335−8. 17. Akturk OM, Cakir M, Yildirim D, Akinci M. C-reactive protein and red cell distribution width as indicators of complications in patients with acute appendicitis. Arch Clin Exp Med 2019;4:76−80. 18. Balogun OS, Osinowo A, Afolayan M, Olajide T, Lawal A, Adesanya A. Acute perforated appendicitis in adults: Management and complications in Lagos, Nigeria. Ann Afr Med 2019;18:36−41.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut apandisit ön tanısı ile apendektomi yapılan karaciğer transplantlı ve transplant dışı hastaların karşılaştırılması: Olgu kontrol çalışması Dr. Kemal Barış Sarıcı, Dr. Sami Akbulut, Dr. Cemalettin Koç, Dr. Adem Tuncer, Dr. Sezai Yılmaz İnönü Üniversitesi Tıp Fakültesi, Karaciğer Nakli Enstitüsü ve Genel Cerrahi Anabilim Dalı, Malatya

AMAÇ: Bu çalımanın amacı akut apandisit ön tanısıyla apendektomi olmuş karaciğer transplantlı ve transplant dışı hastaları karşılaştırmaktır. GEREÇ VE YÖNTEM: Posttransplant dönemde akut apandisit ön tanısıyla apendektomi yapılan 13 karaciğer transplantlı hasta (transplant grubu) ile aynı dönemde apendektomi olmuş transplant dışı 52 hasta (non-transpalnt grubu) demografik ve klinikopatolojik özellikler yönünden karşılaştırıldı. Transplant ve non-transplant gruplar 1:4 rastgele eşleştirme yöntemi kullanılarak oluşturuldu. Devamlı değişkenlerin karşılaştırılmasında MannWhitney U-testi kullanılırken kategorik değişkenlerin karşılaştırılmasında Fisher kesin testi kullanıldı. P değeri <0.05 istatistiksel anlamlılık sınırı olarak kabul edildi. BULGULAR: Bu çalışmaya yaşları 1 ile 84 yıl arasında değişen toplam 65 hasta alındı. Non-transplant grubundaki 52 hastanın (32 erkek ve 20 kadın) 17 ile 84 yıl arasında değişirken transplant grubundaki 13 hastanın (9 erkek ve 4 kadın) yaşları 1 ile 64 yıl arasında değişmekteydi. Gruplar arasında WBC (p=0.002), nötrofil (p=0.002), lenfosit (p=0.032), trombosit (p=0.032), RDW (p=0.001), CRP (p=0.009), PNR (p=0.042), WNR (p=0.03) ve apendiks uzunluğu (p<0.001) açısından istatistiksel olarak anlamlı farklılıklar saptandı. Negatif apendektomi oranı transplant grubunda nisbeten daha yüksek olmakla birlikte bu farklılık istatistiksel olarak anlamlı değildi (%30.8 ve %21.2; p=0.477). Perfore apandisit transplant grubunda çok daha sık görülmekle birlikte bu farklılık istatistiksel olarak anlamlı değildi (%30.8 ve %9.6; p=0.070). TARTIŞMA: WBC ve nötrofil LT grubunda daha düşüktü; CRP ve RDW LT grubunda daha yüksekti. Perforasyon ve negatif apendektomi oranları LT grubunda daha yüksekti, ancak bu fark istatistiksel olarak anlamlı bulunmamıştır. Anahtar sözcükler: Akut apandisit; karaciğer alıcıları; karaciğer nakli; negatif apendektomi; perfore apandisit. Ulus Travma Acil Cerrahi Derg 2020;26(5):705-712

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doi: 10.14744/tjtes.2020.52368

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ORIGIN A L A R T IC L E

Does being a refugee affect prognosis in patients who underwent surgery due to peptic ulcer perforation? Gamze Çıtlak, M.D.,1 Mustafa Ertuğrul Yurtteri, M.D.,1 Yiğit Soytaş, M.D.,1 Sercan Yüksel, M.D.,1 Mürşit Dinçer, M.D.,2 Ekrem Ferlengez, M.D.1 1

University of Health Sciences, Haseki Training and Research Hospital, Department of General Surgery, İstanbul-Turkey

Department of General Surgery, Fırat University Faculty of Medicine, Elazığ-Turkey

ABSTRACT BACKGROUND: Although Turkey hosts the largest number of Syrian immigrants, the interpretation of their health problems seems to be inadequate and understudied. In this study, we aimed to investigate whether being a refugee is a prognostic factor or not for peptic ulcer perforation (PUP). METHODS: A retrospective study was designed in Turkish Citizen patients and the refugees to compare the prognosis who underwent surgery for PUP. After ethical committee approval, the data of 143 patients, constituting 130 males and 13 females, operated for PUP, were collected. Patients’ files, surgery notes and outpatient policlinic data were evaluated. RESULTS: In this study, 105 patients were Turkish Citizen, while the remaining 38 patients were refugees. Eight (7.6%) Turkish and one (2.6%) refugee patient died. There was no statistical significance between the two groups concerning mortality (p=0.445). Age, perforation diameter and localization, need of reoperation, nasogastric tube detention time, CRP, hematocrit, albumin, creatinine, BUN levels were found statistically significant for mortality. CONCLUSION: Although being a refugee has been identified as a risk in the etiopathogenesis of peptic ulcer disease, we found that being a refugee in Turkey is not a negative prognostic factor for PUP. Keywords: Morbidity; mortality; peptic ulcer perforation; refugee.

INTRODUCTION Peptic ulcer disease refers to an insult to the mucosa of the upper digestive tract resulting in ulceration that extends beyond the mucosa and into the submucosal layers. Peptic ulcers disease most commonly occur in the stomach and duodenum. While most of peptic ulcers are initially asymptomatic, clinical manifestations range from mild dyspepsia to complications, including gastrointestinal system bleeding, perforation, and gastric outlet obstruction.[1] Peptic ulcer perforation (PUP) had a high mortality rate before the 1950s. However, nowadays, the mortality rate is decreased due to some factors like technological progress in

medicine and easy reach to the health service. Patients experiencing ulcer perforation usually have a peptic ulcer disease or gastritis history, and most of them have also used proton pump inhibitors (PPI). PUP is known as a young smoker disease. Mainly stress, young age, smoking, usage of some medicines like non-steroidal anti-inflammatory drugs (NSAIDs) and helicobacter pylori infections have been accused in etiology. PUP is a common surgical emergency worldwide, with mortality rates up to 30%. PUP is the most common cause of emergency surgery among the complications of the gastroduodenal ulcers. Morbidity and mortality in PUP occur due

Cite this article as: Çıtlak G, Yurtteri ME, Soytaş Y, Yüksel S, Dinçer M, Ferlengez E. Does being a refugee affect prognosis in patients who underwent surgery due to peptic ulcer perforation? Ulus Travma Acil Cerrahi Derg 2020;26:713-718. Address for correspondence: Yiğit Soytaş, M.D. Sağlık Bilimleri Üniversitesi, Haseki Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 529 44 00 E-mail: yigitsoytas@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):713-718 DOI: 10.14744/tjtes.2020.44902 Submitted: 01.10.2019 Accepted: 13.06.2020 Online: 15.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Çıtlak et al. Does being a refugee affect prognosis in patients who underwent surgery due to PUP?

to secondary peritonitis and sepsis. Helicobacter pylori and the use of NSAIDs are common causes. Due to the differences between countries in age, sex, localization of perforation and underlying causes, mortality rates also vary. Early surgery, either by laparoscopic or open repair and proper sepsis management is essential for a good outcome. Selected patients can be managed non-operatively or with novel endoscopic approaches.[2,3] Since 2011, the conflict in Syria has led to the migration of over five million refugees to Turkey and this number seems to be increased in the future. Only 6.1% of the Syrian refugees live in temporary shelters.[4] Most of them also have a problem because there is a minimal similarity between Turkish and Arabic languages. Also, some of these refugees are fugitive and have no registration to the Turkish State and Health System. Being homeless and unemployment usually lead to a poor environment concerning health. Due to the factors listed above, it is possible that refugees in Turkey admit to the hospital later than Turkish citizens do. Because of this condition, we thought that being a refugee could have been a prognostic factor for PUP.

MATERIALS AND METHODS This retrospective clinical trial was conducted at the University of Health Sciences Haseki Training and Research Hospital. Clinical Ethical Committee approval was received from the University of Health Sciences Haseki Training and Research Hospital (18.10.2017-533). The patients who were diagnosed and treated by the General Surgery Department for PUP between January 2014 and January 2017 were included in this study. The patients were evaluated in two groups constituting of Turkish citizen and refugee patients. In addition to clinical examination, the diagnosis was established by the help of biochemical laboratory findings, such as leucocyte count, c reactive protein (CRP) blood plasma level, plasma amylase, hematocrit (Htc) level, creatinine, albumin, blood urea nitrogen (BUN) values, and radiological techniques like posterior-anterior chest and abdominal X-ray and if necessary computed tomography were used as imaging modalities. Patients’ sex, age, nation, PUP localization, perforation diameter, operation techniques (open Graham patch, laparoscopic Graham patch and others), duration of hospital stay, duration of nasogastric tube usage, oral nutrition starting time, need of re-operation, complications and mortality were recorded. All data were analyzed by SPSS 15.0 for Windows. Descriptive statistics were carried out, and a comparison of two groups was made by the Mann-Whitney U and Chi-square tests for comparisons of numerical variables that do not provide a normal distribution. Predictive factors were examined by logistic regression analysis. The statistical significance level was considered as p<0.05. 714

RESULTS The mean age was 40.0±17.6 (15–93) years. The total number of PUP patients was 143. Most of these patients were men (n=130). While 105 (73.4%) were Turkish citizen, and 38 (26.6%) were refugees. Pre-pyloric, post-pyloric and other sites, such as antrum, were the localizations of the perforations in 78 (54.5%), 62 (43.4%) and 3 (21%) patients, respectively. Mean duration of hospital stay was 6.8±3.4 (1–21) days. Six (4.2%) of the patients had reoperation because of complications like evisceration and intraabdominal abscess. A pneumoperitoneum image on an abdominal X-ray was present in 42 (29.4%) patients. Also, 128 of patients had posterior-anterior chest X-ray and 64 (44.8%) of all patients had a pneumoperitoneum image on chest X-ray 95 of patients had an abdominal computed tomography (CT) and 76 (53.5%) of all patients had a pneumoperitoneum image on CT. Mortality rate was 6.3% (n=9) (Table 1). Abdominal X-ray assessment revealed statistical significance, because pneumoperitoneum presence at abdominal X-ray was 50% (n=19) in Turkish and 21.9% (n=23) in refugee patients (p=0.13). There was no statistical significance between mortality and the nation (Table 2). Age, perforation diameter, reoperation and complication rates were statistically significantly higher in mortal patients (p<0.001, p<0.001, p=0.003, p<0,001, respectively). The mortality rate of patients with other types of surgery was higher than Graham patch surgery. In laboratory evaluations, CRP, creatinine, BUN, amylase values were significantly high, whereas Htc and albumin values were statistically significantly low (Table 3). For the factors determining mortality, the number of days of nasogastric tube usage, post-pyloric localization and perforation diameter were the most significant factors in the model consisting of variables p<0.250 in the Single Variable analysis for logistic regression (p=0.003, p=0.038, p=0.001, respectively) (Table 4). There were no statistically significant differences in biochemical evaluations between the two groups.

DISCUSSION PUP is more common in men than in women, and it is the most common form of a benign reason for acute abdomen, which needs emergency surgery after counted than acute appendicitis, creating a major health issue. Changes in living standards and medical usage, such as steroids, stress and smoking, contribute to perforation formation. Several studies have demonstrated that Helicobacter pylori infection increases PUP rates. PPI may be used daily in routine by patients for chronic gastritis. The previous studies showed no increased risk of PUP by the increased age. Also, it is reported that the length of smoking and usage of NSAIDs increases the risk of PUP.[5–7] Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Çıtlak et al. Does being a refugee affect prognosis in patients who underwent surgery due to PUP?

Table 1. Demographic, biochemical and radiological findings of the groups

Sex Male 130 90.9 Female 13 9.1 Age, Mean±SD 40.0±17.6 (15–93) Nation Turkish 105 73.4 Others 38 26.6 Localization Pre-pyloric 78 54.5 Post-pyloric 62 43.4 Other (e.g., Antrum) 3 2.1 Perforation diameter (mm) 7.6±5.9 (2–30) Operation Graham Patch 123 86.0 Technique Laparoscopic Graham Patch 10 7.0 Other (e.g., Antrectomy) 10 7.0 Duration of hospital stay 6.8±3.4 (1–21) Starting time of oral nutrition 4.0±1.8 (2–18) Nasogastric tube usage day 3.6±2.5 (1–18) Re-operation No 137 95.8 Yes 6 4.2 Complication No 122 85.3 Yes 21 14.7 Leucocytes 14.9±7.3 (3.47–75) C-reactive protein 55.7±97.8 (0.18–500) Hematocrit 42.0±6.6 (15.9–62) Albumin 3.87±0.78 (1.23–5.4) Creatinine 0.97±0.83 (0.21–8.79) Blood urea nitrogen 40.0±29.4 (15.8–234) Amylase 81.4±69.5 (21–731) Abdominal Direct X–Ray None 21 14.7 Pneumoperitoneum 42 29.4 Air–liquid level 5 3.5 Normal 75 52.4 Chest X-Ray None 12 8.4 Pneumoperitoneum 64 44.8 Normal 66 46.2 Computed tomography None 47 33.1 Pneumoperitoneum 76 53.5 Free liquid 8 5.6 Contrast extralumination 6 4.2 Normal 5 3.5 Mortality No 134 93.7 Yes 9 6.3

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Table 2. Comparison of the features patients’ nations

Nation

Turkish Others

n % n %

Re-operation No Yes

100 95.2 37 97.4 1.000 5 4.8 1 2.6

Complication No

89 84.8 33 86.8 0.756

Yes

16 15.2 5 13.2

Abdominal Direct x-ray None

17 16.2 4 10.5

Pneumoperitoneum

23 21.9 19 50.0 0.013

Air-liquid level

4 3.8 1 2.6

Normal

61 58.1 14 36.8

PALX None

10 9.5 2 5.3 0.183

Pneumoperitoneum

42 40.0 22 57.9

Normal

53 50.5 14 36.8

CT None

33 31.7 14 36.8 0.331

Pneumoperitoneum

53 51.0 23 60.5

Free liquid

7 6.7 1 2.6

Contrast extralumination 6 5.8 0 0.0 Normal

5 4.8 0 0.0

Mortality No

97 92.4 37 97.4 0.445

Yes

8 7.6 1 2.6

Kanno et al.[5] found that 87 (27%) of 329 peptic ulcers emerged from refugee shelters, and the majority (76 of 87) of them was the bleeding type. Multivariate regression showed that residence in a shelter was a strong risk factor for ulcer bleeding, independent of the progressiveness of ulcer diseases. Accommodation in a refugee shelter can be a strong risk factor for ulcer bleeding after a large-scale disaster since acid-suppressive drugs are supposed to decrease the risk for stress-induced ulcer bleeding. Although the trial was above actually related to ulcer bleeding risks, it shows us indirectly the PUP rate can be increased in the refugee population, too. Despite that opinion in our trial, we found that there was no statistical significance between refugees and Turkish citizens. There had been several reports about the increase of peptic ulcers under a large-scale from disaster to war. It was still unclear that severe psychological stress itself caused peptic ulcer independently of two major causes, which are Helico715

Çıtlak et al. Does being a refugee affect prognosis in patients who underwent surgery due to PUP?

Table 3. A multivariate analyses for mortality

Mortality

No Yes n

Mean±SD

Sex

Male

122 91.0

8 88.9

Female

12 9.0

1 11.1

Age

38.1±15.9 (35)

69.3±17.2 (70)

Nation

Turkish

97 72.4

8 88.9

Others

37 27.6

1 11.1

Localization

Pre-pyloric

76 56.7

2 22.2

Post-pyloric

55 41.0

7 77.8

Others

3 2.2

0 0.0

Perforation(mm)

6.8±4.6 (5)

19.3±9.4 (20)

Operation

Graham Patch

118

88.1

55.6

Lap Graham Patch

7.5

0.0

Other (e.g., Antrectomy)

4.5

44.4

0.587 <0.001 0.445 0.151

<0.001 0.003

Duration of hospital stay

6.7±3.2 (6)

8.4±5.9 (10)

0.621

Starting of oral nutrition

4.0±1.9 (4)

3.9±0.4 (4)

0.587

Nasogastric tube duration

3.4±1.9 (3)

7.7±6.1 (5)

0.085

Re-operation

131 97.8

Yes

3 2.2

6 66.7

Complication

119 88.8

3 33.3

Yes

15 11.2

6 66.7

0.003

3 33.3 <0.001

Leucocytes

14.7±7.4 (13.9)

16.6±6.2 (15.7)

0.287

C-reactive protein

50.8±94.9 (8.7)

128.2±117.6 (110.4)

0.021

Hematocrit

42.3±6.1 (42.7)

37.6±11.4 (38.3)

0.026

Albumin

3.98±0.67 (4.2)

2.29±0.70 (2.11)

<0.001

Creatinine

0.92±0.81 (0.8)

1.73±0.88 (1.57)

<0.001

Blood urea nitrogen

37.1±26.4 (32)

83.8±38.4 (97)

<0.001

Amylase

78.3±67.4 (65.8)

128.5±87.3 (115)

0.099

Abdominal direct X-ray

None

19 14.2

2 22.2

Pneumoperitoneum

42 31.3

0 0.0

Air-liquid level

Normal

69 51.5

3.0

11.1

6 66.7

Chest X-Ray

None

11 8.2

1 11.1

Pneumoperitoneum

62 46.3

2 22.2

Normal

61 45.5

6 66.7

Computed tomography

None

46 34.3

1 12.5

Pneumoperitoneum

73 54.5

3 37.5

Free liquid

4.5

25.0

3.0

25.0

Contrast extralumination

Normal

5 3.7

bacter pylori infection and nonsteroidal anti-inflammatory drug. Disaster (psychological) stress possibly induces peptic 716

0.065

0.343

0.014

0 0.0

ulcer independently of two major causes described above. Moreover, people living in a refugee shelter immediately afUlus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Çıtlak et al. Does being a refugee affect prognosis in patients who underwent surgery due to PUP?

Table 4. Logistic regression analysis for factors determining mortality

95% CI

1.031

0.961

Enter Model

Age

0.392

Localization pre-pyloric

0.292

1.106

Post-pyloric

0.117

9.327

0.573

151.846

Other (e.g., Antrectomy)

0.999

0.000

Perforation (mm)

0.027

1.268

1.027

1.565

Operation Graham Patch

0.324

Laparoscopic Graham patch

0.999

0.000

Other (e.g., Antrectomy)

0.133

7.002

0.552

88.868

Nasogastric tube duration

0.020

1.361

1.050

1.764

Nation (Others)

0.569

2.290

0.132

39.637

Backward Model

Localization pre-pyloric

0.117

Post-pyloric

0.038 19.218 1.171 315.289

Other (e.g., Antrectomy)

0.999

0.000

Perforation (mm)

0.001

1.312

1.120

1.536

Nasogastric tube duration

0.003

1.436

1.132

1.823

ter a disaster are a strong risk group of peptic ulcer bleeding.[5] Carlsson et al.[8] also found that war is a reason for post-traumatic stress disease and some of the outcomes were symptoms of depression and anxiety. We also know that anxiety and depression may cause peptic ulcer disease and its complications. In Dovjak et al.’s[7] trial, they found that the mortality in elderly patients over the age of 80 years with peptic ulcers in the case of complications, such as bleeding and perforation, is higher than the general population. In our trial, we also found that mortality increases with the age of patients. Duodenal ulcers are associated with Helicobacter pylori infections in 90% of cases and in 70% of gastric ulcers.[7] In Varcus et al.’s[3] trial and review, there were 32 studies included, counting 3488 patients with Laparoscopic patch and 5208 with Graham patch. LPR patients had shorter hospital stays. They also emphasized the increased mortality rate in Graham patch patients because of their tendency to be more shocked or with higher ASA at presentation. In our series, there was no difference concerning mortality. In Mohsina et al.’s[9] clinical trial, they evaluated the feasibility and efficacy of ERAS pathways in patients undergoing emergency simple closure of perforated duodenal ulcer. In this trial, patients with refractory shock, ASA class ≥3, and perforation size ≥1 cm were excluded. Ninety-nine patients were included and 49 and 50 patients were included in standard care and ERAS group, respectively. The duration of hospital stay in the Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

ERAS group was significantly shorter. There was a significant reduction in postoperative morbidity, such as postoperative nausea, vomiting and pulmonary complications. This trial shows us early nasogastric tube extraction and starting oral nutrition may reduce the morbidity and mortality rate. This was also a lack of our trial, and that should be surveyed in the future, too. In our study, patients who underwent laparoscopic Graham patch have no mortality, and it was statistically significant. However, no clinical significance was considered because laparoscopic surgery was performed in appropriate patients. Wang et al.[10] found that there was no significant difference in baseline data between the laparoscopic patch and Graham patch (all p>0.05). No significant differences in operation time, the morbidity of postoperative complication, mortality, reoperation probability, nasogastric decompression time, fluid diet recovery time and hospitalization cost were found between two groups (all p>0.05). According to several studies, being a refugee is a risk factor for peptic ulcer disease and its complication; therefore, we decided to investigate whether being a refugee was a prognostic factor for PUP. However, we found there was no difference between refugees and Turkish citizens concerning mortality and morbidity. In our study, we found a similar prognosis between Turkish patients and refugees. We thought that, as a government policy, uncharged emergency healthcare and easy admission to hospital might be the reason for a similar prognosis between two groups. 717

Çıtlak et al. Does being a refugee affect prognosis in patients who underwent surgery due to PUP?

Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: G.Ç., S.Y., Y.S.; Design: S.Y., Y.S.; Supervision: G.Ç., E.F.; Materials: M.D., M.E.Y., E.F.; Data: M.E.Y., E.F.; Analysis: G.Ç., S.Y., Y.S.; Literature search: M.D., Y.S., M.E.Y.; Writing: G.Ç., S.Y., E.F.; Critical revision: G.Ç., Y.S. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Stern E, Sugumar K, Journey JD. Peptic Ulcer Perforated. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2020. 2. Søreide K, Thorsen K, Harrison EM, Bingener J, Møller MH, Ohene-Yeboah M, et al. Perforated peptic ulcer. Lancet 2015;386:1288−98. 3. Varcus F, Paun I, Duta C, Dobrescu A, Frandes M, Tarta C. Laparoscopic repair of perforated peptic ulcer. Minerva Chir 2018;73:188−93.

4. Ergönül Ö, Tülek N, Kayı I, Irmak H, Erdem O, Dara M. Profiling infectious diseases in Turkey after the influx of 3.5 million Syrian refugees. Clin Microbiol Infect 2020;26:307−12. 5. Kanno T, Iijima K, Koike T, Abe Y, Shimada N, Hoshi T, et al. Accommodation in a refugee shelter as a risk factor for peptic ulcer bleeding after the Great East Japan Earthquake: a case-control study of 329 patients. J Gastroenterol 2015;50:31−40. 6. Kanno T, Iijima K, Koike T, Shimosegawa T. Relationship between disaster stress and peptic ulcers. [Article in Japanese]. Nihon Rinsho 2015;73:1209−14. 7. Dovjak P. Duodenal ulcers, gastric ulcers and Helicobacter pylori. [Article in German]. Z Gerontol Geriatr 2017;50:159−69. 8. Carlsson J, Sonne C, Vindbjerg E, Mortensen EL. Stress management versus cognitive restructuring in trauma-affected refugees-A pragmatic randomised study. Psychiatry Res 2018;266:116−23. 9. Mohsina S, Shanmugam D, Sureshkumar S, Kundra P, Mahalakshmy T, Kate V. Adapted ERAS Pathway vs. Standard Care in Patients with Perforated Duodenal Ulcer-a Randomized Controlled Trial. J Gastrointest Surg 2018;22:107−16. 10. Wang Q, Ge B, Huang Q. A prospective randomized controlled trial of laparoscopic repair versus open repair for perforated peptic ulcers. [Article in Chinese]. Zhonghua Wei Chang Wai Ke Za Zhi 2017;20:300−3.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Peptik ülser perforasyonunun cerrahi tedavisinde mülteci olmak prognozu etkiler mi? Geriye dönük klinik çalışma Dr. Gamze Çıtlak,1 Dr. Mustafa Ertuğrul Yurtteri,1 Dr. Yiğit Soytaş,1 Dr. Sercan Yüksel,1 Dr. Mürşit Dinçer,2 Dr. Ekrem Ferlengez1 1 2

Sağlık Bilimleri Üniversitesi, Haseki Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Fırat Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Elazığ

AMAÇ: Türkiye çok sayıda Suriyeli göçmene ev sahipliği yapmasına rağmen, sağlık sorunlarının yorumlanması yetersiz ve anlaşılmamış gibi görünmektedir. Mülteci olmanın, peptik ülser perforasyonu (PUP) hastalığı için prognostik bir faktör olup olmadığını araştırmayı amaçladık. GEREÇ VE YÖNTEM: Türkiye Cumhuriyeti vatandaşı ve mülteci olan hastaların PUP açısından prognozlarını karşılaştırmak için retrospektif bir çalışma tasarlandı. PUP nedeniyle ameliyat edilen 130 erkek ve 13 kadından oluşan 143 hastanın 105’i Türk, geri kalan 38’i mülteci idi. Hastaların dosyaları, ameliyat notları ve poliklinik verileri değerlendirildi. BULGULAR: Sekiz (%7.6) Türk vatandaşı ve bir (%2.6) mülteci hastada mortalite saptandı ve iki grup arasında mortalite açısından istatistiksel bir anlamlılık saptanmadı (p=0.445). Yaş, perforasyon çapı ve lokalizasyonu, reoperasyon ihtiyacı, nazogastrik dekompresyon süresi, CRP, hematokrit, albümin, kreatinin, BUN düzeyleri mortalite açısından istatistiksel olarak anlamlı bulundu. TARTIŞMA: Bir mülteci olmak, peptik ülser hastalığının etiyopatogenezinde bir risk olarak tanımlanmış olmasına rağmen, Türkiye’de mülteci olmanın PUP için negatif bir prognostik faktör olmadığını tespit ettik. Anahtar sözcükler: Morbidite; mortalite; mülteci; peptik ülser perforasyonu. Ulus Travma Acil Cerrahi Derg 2020;26(5):713-718

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doi: 10.14744/tjtes.2020.44902

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ORIGIN A L A R T IC L E

Guideline implementation and raising awareness for unintended perioperative hypothermia: Single-group “before and after” study Serkan Şenkal, M.D.,1

Umut Kara, M.D.2

Department of Anesthesiology and Reanimation, Health Sciences University, Gülhane Faculty of Medicine, Ankara-Turkey

Department of Anesthesiology and Reanimation, Health Sciences University, Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: Unintended Perioperative Hypothermia (UPH) is defined as a core body temperature less than 36°C. The Turkish Society of Anesthesiology and Reanimation [Türk Anesteziyoloji ve Reanimasyon Derneği (TARD)] published a “Guideline for the Prevention of the Unintended Perioperative Hypothermia” in 2013. This study aims to decrease the incidence of unintended UPH in our hospital using a protocol, which is prepared according to the recommendations in the Guideline for the prevention of unintended perioperative hypothermia. METHODS: A prospective quality improvement study was conducted with the protocol, which was prepared to decrease the incidence of unintended perioperative hypothermia in patients undergoing surgery. We measured and compared the perioperative hypothermia incidence before the implementation (November 24th, 2015 – January 15th, 2016) and after the implementation (April 6th, 2016 – July 21st, 2017). RESULTS: The incidence of unintended perioperative hypothermia was 35% and 23.8% in the pre-implementation and postimplementation sections, respectively, and the difference was statistically significant (p=0.002). CONCLUSION: The incidence of unintended perioperative hypothermia can be significantly decreased with the evidence-based implementations. Keywords: Patient safety; unintended perioperative hypothermia; warming.

INTRODUCTION Unintended Perioperative Hypothermia (UPH) is defined as a core body temperature less than 36°C (96.8°F) starting from the first hour before anesthesia until the end of the first 24 hours after anesthesia.[1] The reported incidence of hypothermia in the perioperative period is between 25% and 80%.[2] Today, as a result of UPH, the effects of the hypnotic anesthetic agents and neuromuscular blockers are prolonged, the need for blood transfusion increases depending on the increased blood loss, cardiac complications may develop, the postanesthetic recovery delays, the incidence of postoperative nausea and vomiting increases, the risk of surgical wound

infection increases, the duration of the hospitalization prolonges, and finally the cost increases.[3] Regarding the prevention of UPH, several guidelines were introduced in the past by different institutes like National Institute for Health and Care Excellence (NICE, UK), Canadian Association of General Surgeons, and Association of the Scientific Medical Societies in Germany [Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, (AMWF)] in different countries.[4–6] In our country, the Turkish Society of Anesthesiology and Reanimation (TARD) also published the “Guideline for the Prevention of the Unintended Perioperative Hypothermia” in 2013.[7]

Cite this article as: Şenkal S, Kara U. Guideline implementation and raising awareness for unintended perioperative hypothermia: Single-group “before and after” study. Ulus Travma Acil Cerrahi Derg 2020;26:719-727. Address for correspondence: Serkan Şenkal, M.D. Sağlık Bilimleri Üniversitesi, Gülhane Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, 06010 Etlik, Ankara, Turkey Tel: +90 312 - 304 59 24 E-mail: senkalserkan@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):719-727 DOI: 10.14744/tjtes.2020.55237 Submitted: 09.03.2020 Accepted: 22.05.2020 Online: 11.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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The TARD guideline has two major chapters titled “Definitions” and “Guideline for the Prevention and Treatment of UPH.” The first chapter “Definitions” contains the subtitles like the “Definition of the UPH”, “The Role of Anesthesia in the Development of Hypothermia”, “Stages, and Complications of UPH”, “Monitorization”, “Techniques used in the Prevention of Hypothermia”, and “Time to Start Warming up Patients”. “The recommendations to decrease the difference between the core and peripheral temperatures” and “Maintaining the core body temperature between 36°C (96.8°F) and 37°C (98.6°F)” are listed in the second main chapter.[7] In our clinic, we planned a study for the prevention of the UPH. The primary objective of our study was to investigate the change in the incidence of UPH by implementing a protocol that is prepared according to the recommendations in the “TARD Guideline for the prevention of UPH”. The secondary aims of the study were to find out the correlated risk factors and adverse effects of UPH if there were any.

MATERIALS AND METHODS This single-center, prospective study was conducted in line with the Helsinki Declaration in the central operating rooms area of the Gülhane Military Medical Academy between November 1st, 2015 and July 31st, 2016. Our study was approved by the Ethics Committee for Clinical Research at Gülhane Military Medical Academy (2015 KAEK/33- The Efficacy of a protocol prepared according to the TARD Guideline for Unintended Perioperative Hypothermia: Implementation Study). Patients, who were older than 18 years, scheduled for elective surgery by the departments of general surgery, urology, orthopedics, and thoracic surgery with an expected duration of surgery longer than 30 minutes, had ASA scores of I, II, and III; and accepted to participate with a verbal and written informed patient consent form, were included in our study. Patients, who had preoperative or postoperative obstacles for the body temperature measurement from the tympanic membrane, high fever related to the central nervous system, thermoregulation anomalies, active hypothyroidism/hyperthyroidism, infectious fever, a body temperature equal or higher than 38.5°C (101.3°F) in the last seven days, a body temperature less than 36°C (96.8°F) in the waiting room before anesthesia and patients pre-scheduled to active cooling or warming procedures as a part of the planned surgical treatment, were excluded from this study. To measure the incidence of UPH, which was the primary evaluation parameter, the body temperatures of patients, were measured from the tympanic membrane with an electronic thermometer of the same brand (Genius 2 Infrared Tympanic Electronic Thermometer/Covidien, Mansfield, United States of America). This device has a sensitivity of ±0.1°C.[8] Before starting this study, the devices were calibrated according to the user manual published by the manu720

facturer to minimize the measurement errors. The body temperatures of the patients were measured from the tympanic membranes bilaterally and several times following their referral to the post-anesthesia care unit and recorded. We chose the higher value from the measurements done in both ears to decrease the errors due to the interobserver variability. Our study consisted of three sequential periods (Fig. 1). In the first period, the condition before the protocol was evaluated. In this period, which we called the pre-implementation section, the data of 349 patients, who underwent perioperative thermal care and follow-up with the existing methods between 24.11.2015 and 15.01.2016, were recorded. Patients, who underwent surgery in the departments of general surgery, urology, orthopedics and traumatology, and thoracic surgery, were included in this study without randomization in order of arrival. During this period, the anesthesia clinic staff was not informed about the study details to obtain objective data related to the incidence of UPH. The second period of this study is the protocol development and implementation strategy period, which was carried out between 16.01.2016 and 15.02.2016. In this period: 1. Microsoft PowerPoint presentations related to the prevention of UPH were prepared. 2. Presentations related to the content of the TARD guideline were briefed to all occupational groups working in the anesthesia clinic (anesthesia technicians, nurses, physicians). 3. On-site applied training was given to demonstrate the proper use of different types of thermometers, equipment used for active and passive warming in the pre-anesthesia waiting room, operating rooms and postanesthesia care unit (PACU). 4. A clinical checklist manual “Prevention of the Unintended Perioperative Hypothermia Manual” based on the TARD guideline was prepared (Fig. 2). Copies of this manual were distributed to the pre-anesthesia waiting room, operating rooms, and postoperative-anesthesia care unit. In the third period between 06.04.2016 and 21.07.2016, which we called the postimplementation section, the data of

Postimplementation arm April 06, 2016 to July 21,2016 Implementation Phase

320 patients

Jan 16, 2016 to Feb 15, 2016

Preimplementation arm Nov 24, 2015 to Jan 15, 2016 349 patients

Figure 1. Study Figure 1. Study timeline

timeline.

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“PREVENTION OF UNINTENDED PERIOPERATIVE HYPOTHERMIA” MANUAL* PROCEDURE

EQUIPMENT / METHOD / ACTION PRE-OPERATİVE HOLDİNG AREA Tympanic thermometer

Body core temperature should be measured. For patients with a body temperature equal to or higher than 36°C: passive insulation Patients with a body temperature less than 36°C: actively warmed

Blanket, stockings, beret… Forced air warming devices

The patient should not be referred to the operating room if the body temperature is not equal to or higher than 36°C. OPERATING ROOM Body temperature should be monitored at the lower end of the esophagus

Bedside monitor, esophagus temperature probe

Ambient temperature above 21°C

Climate control center (Tel. No: 2875)

Only if active warming is started after the patients were covered with surgical drapes. The room temperature can be reduced to lower degrees, which is more suitable for the surgical team to work. If IV liquid, blood-blood derivative more than 1000mL Fluid warming device, operation table cover warmers; will be administered, temperature should be increased to 37°C. (aqueous or electrical systems), forced air warming devices High-risk patients should be actively warmed, even though the intervention will last less than 30 minutes. Temperature should be adjusted to the maximum level when using hot air blowing systems.

Forced air warming devices

Active warming should be stopped when the body temperature rises to or above 37°C. Patient irrigation fluids should be warmed to 38-40°C.

Warmed irrigation fluids and serum

Mechanical ventilation

Anest. circuit HME filter, Low-flow anesthesia POSTANESTHESIA CARE UNIT

Body temperature should be measured as soon as the patient arrives at the recovery unit. Measurements should be either continuous or repeated at 15-minute intervals. "Passive insulation" should be implemented, if the patient's body temperature is equal to or higher than 36°C in the recovery unit. In patients with a body temperature less than 36°C active warming should be implemented.

Tympanic thermometer Tympanic thermometer, Bedside monitor heat probe Blanket, stockings, beret… IV fluid warmers, Forced air warming devices

Patients with a body temperature equal to or higher than 36°C should be sent to the ward covered at least with one blanket. Patients should not be transferred to the ward until the body temperature rises above 36°C. 1. 2.

* The Turkish Anaesthesiology and Reanimation Society Guidelines for the prevention of inadvertent perioperative hypothermia. Turk J Anaesthesiol Reanim 2013 Oct;41(5):188-90.

Figure 2 “Prevention of Unintended Perioperative Hypothermia” Manual

Figure 2. “Prevention of Unintended Perioperative Hypothermia” Manual.

320 surgical patients were recorded to assess the efficacy of the implementation. During this period, patients, who were scheduled for surgery in the departments of general surgery, urology, orthopedics and traumatology, and thoracic surgery were included in this study without randomization in order of arrival. Data related to the age, gender, body mass index (BMI) of patients, and the name of the surgical department, type of surgery (endoscopic/non-endoscopic), anesthesia technique (only general anesthesia/general anesthesia and others/no general anesthesia component), ASA physical status, amount of the infused intraoperative intravenous fluids, blood or blood derivatives, duration of surgery, PACU complications (shivering, pain, nausea-vomiting, hypoxemia, hypertension, tachycardia, bradycardia) and duration of hospitalization in PACU were obtained from the anesthesia record forms. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

The primary objective of this study was to compare the UPH incidence between the pre-implementation and postimplementation sections. Classification of all participating patients in two groups as hypothermic patients and normothermic patients; comparison of the postoperative PACU complications between these two groups, and evaluation of the possible relationship between hypothermia and intraoperative variables were the secondary objectives.

Definitions “UPH” was defined as the core body temperature measured below 36°C (96.8°F) in patients who were just referred to the PACU. A measured core body temperature between 36°C (96.8°F) and 37°C (98.6°F) was defined as “normothermia”. The time between the admission to the operating room and admission to PACU was accepted as the “duration of 721

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the surgery”. In the PACU, a VAS score greater than 3 was considered as “pain”, fasciculations in one region of the face, neck or body was defined as “shivering”, the presence of one of nausea, gagging or vomiting was defined as “nausea-vomiting”, oxygen saturation less than 95% as “hypoxemia”, a heart rate higher than 100 beats/min as “tachycardia”, a heart rate less than 60 beats/min as “bradycardia” and systolic blood pressure higher than 140 mmHg as “hypertension”. In the PACU, the measurements were recorded every 10 minutes and two sequential measurements indicating the above-mentioned complications were defined as “complication present.” The duration between the arrival to the PACU and discharge from the PACU was defined as “PACU length of stay”.

Statistical Analysis The sample size analysis carried out before this study for the determination of the required number of patients for the inclusion in this study showed that 600 patients should be enrolled to achieve a difference with a power of 0.8 at a significance level of 0.05 for a 10% improvement in the unintended UPH incidence after the implementation. Regarding the descriptive statistics, mean and standard deviation were used for the continuous variables and frequency and percentage for the categorical variables. The distribution of the categorical variables in the groups was analyzed with Pearson’s Chi-Square test. The normal distribution was checked using the Kolmogorov-Smirnov test. The distribution of the variables that do not match parametric assumptions (age, BMI, and PACU length of stay) was investigated with the Mann-Whitney U test in both groups. The variables of the participating patients, who had undergone surgery in different clinics, were first investigated with the univariate logistic regression analysis if a correlation with UPH was considered. If the p-value belonging to the Wald statistics, which was obtained as a result of the univariate logistic regression, was less than 0.25 (p<0.25), the variables were included in the multivariate logistic regression analysis. The age, BMI, amount of intraoperative fluids and duration of surgery; continuous independent variables were analyzed with the Box-Tidwell approach and they were included in the logistic regression analysis as a continuous variable. The multicollinearity test for the accuracy or validation (sufficiency) of the model was assessed with the multivariate linear regression and the effective observations Cook’s distance, distant observations Leverage (observation distance) values and outlier observations were evaluated with the Pearson or deviation residues. All study data were analyzed with the IBM SPSS Statistics version 25 software package (IBM SPSS Inc., Chicago, IL). The accepted limit of significance was p<0.05.

RESULTS In this study, 669 patients were included and 411 (61.4%) 722

of these patients were males and 258 (38.6%) females. The mean age and BMI values were 47.54±18.82 (18–82) years, 26.65±5.01 kg/m2, respectively. The distribution and comparison of the pre- and postimplementation sections according to the demographic characteristics are shown in Table 1. There was no statistically significant difference between the groups. The distribution and comparison of the core body temperature on arrival to the PACU, which was the primary evaluation parameter, in the pre- and postimplementation sections are summarized in Table 2. The incidence and percentage of patients with a core body temperature less than 36°C (96.8°F) at PACU admission were significantly higher in the pre-implementation section (n=122; 35%) compared to the postimplementation section (n=76; 23.8%) (p=0.002). All participants were divided into two groups as hypothermic and normothermic patients. The distribution and comparison of the PACU complications between these groups are summarized in Table 3. The incidence of complications as shivering, pain, hypoxemia, hypertension and tachycardia was significantly higher in the hypothermia group (p<0.05). The PACU length of stay was also significantly longer in the hypothermia group (60.98±39.07 min.) compared to the normothermia group (48.75±27.42 min.) (p<0.05). Considering all participants, the mean volume of the intravenously administered fluids, the mean duration of surgery and the percentage of the intraoperative blood and blood derivative transfusion were 1316.89±898.11 (min: 500– max: 9500) milliliters, 139.22±80.45 minutes and 1.79%, respectively. These parameters were included in the logistic regression analysis related to hypothermia as a candidate variable. The independent variables as ASA implemented anesthesia technique and intraoperative blood and blood derivative transfusion with a p-value greater than 0.25 (p>0.25), which belongs to the Wald statistics obtained from the univariate logistic regression analysis, were not included in the multivariate logistic regression analysis carried out for the examination of the candidate variables related to hypothermia. The model fit was significant according to the Model Chi-Square (χ2(9)=45.462, p<0.001), Hosmer-Lemeshow goodness of fit test (χ2 (8)=11.811, p=0.160), percentile rank (70.1%), and Nagelkerke (R2=0.098) statistics. Seven candidate variables included in the model were investigated using the likelihood ratio test with the backward LR elimination method. The continuous independent variables as age, BMI, amount of intraoperative fluids, and duration of surgery were analyzed with the Box-Tidwell approach and they were included in the logistic regression analysis as a continuous variable. We determined that the clinical variables age, gender, BMI and the Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

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Table 1. Distribution of the pre- and postimplementation arms according to the perioperative characteristics

Pre-implementation (n=349)

Post-implementation (n=320)

χ2=2.642*, p=0.267

ASA physical status, (n, %)

ASA 1

n=196, 56.1%

n=182, 56.9%

ASA 2

n=136, 39.0%

n=130, 40.6%

ASA 3

n=17, 4.9%

n=8, 2.5%

Gender, (n, %)

Male

n=214, 61.3%

n=197, 61.6%

Female

n=135, 38.7%

n=123, 38.4%

Age (year), (mean±SD)

48.13±18.45

46.89±19.22

z=-0.806**, p=0.420

Body mass index (kg/m2), (n, %)

26.78±5.26

26.51±4.72

z=-0.398**, p=0.691

n=170, 48.7%

n=153, 47.8%

χ2=3.637*, p=0.303

χ2=0.004*, p=0.948

Surgical specialities (n, %)

General surgery

Urology

n=80, 22.9%

n=62, 19.4%

Orthopaedics and trauma

n=79, 22.6%

n=76, 23.8%

Thoracic surgery

n=20, 5.7%

n=29, 9.1%

Type of procedure, (n, %)

Endoscopic

n=121, 34.7%

n=115, 35.9%

Not endoscopic

n=228, 65.3%

n=205, 64.1%

General anesthesia only

n=237, 67.9%

n=228, 71.3%

No general anesthesia component

n=108, 30.9%

n=87, 27.2%

General anesthesia and others

n=4, 1.1%

n=5, 1.6%

χ2=0.117*, p=0.732

Type of anesthesia, (n, %)

χ2=1.292*, p=0.524

ASA: American Society of Anesthesiologists; SD: Standard deviation. *Pearson chi-square test statistic value; **Mann-Whitney U test statistical value.

Table 2. Distribution and comparison of the core body temperature on arrival to the PACU in the pre- and postimplementation arms

Pre-implementation Post-implementation (n=349) (n=320)

Body Temperature on Arrival to the PACU, (n, %) <36°C

n=122, 35.0%

n=76, 23.8%

36°C and above

n=227, 65.0%

n=244, 76.3%

χ2=10.062*, p=0.002**

Pearson chi-square test statistic value; **Statistically significant at level of 0.05. PACU: Postanesthesia care unit.

related surgery department had a significant correlation with the dependent variable perioperative hypothermia (p<0.05). The results of the multivariate logistic model created with the candidate variables are given in Table 4.

Regarding the gender (another independent variable), the probability of the perioperative hypothermia was 0.6 times lower in females compared to males (95% CI=0.421– 0.921).

The age was included in the model as a continuous variable and we found that the probability of perioperative hypothermia increased 9.8 times with a 10-year increase in the age (95% CI=0.972–0.991). In other words, the probability of perioperative hypothermia was directly proportional to the advanced age and this probability dropped with the decrease of the age.

BMI was included as a continuous variable in the model and it was found out that the probability of the perioperative hypothermia increased 1.04 times with the 1 point increase in BMI (95% CI=1.008–1.089), which means that high BMI values favor the presence of perioperative hypothermia, while a decrease in BMI value led to a decrease in the probability of perioperative hypothermia.

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Table 3. Distribution and comparison of the PACU complications in hypothermic and normothermic patients

Hypothermic patients (n=198)

Normothermic patients (n=471)

Shivering, (n, %)

Yes

n=41, 20.7%

n=17, 3.6%

n=157, 79.3%

n=454, 96.4%

χ2=51.466*, p=0.000***

Pain (n,%)

Yes

n=58, 29.3%

n=101, 21.4%

n=140, 70.7%

n=370, 78.6%

χ2=4.740*, p=0.029***

Nausea and vomiting, (n, %)

Yes

n=13, 6.6%

n=44, 9.3%

n=185, 93.4%

n=427, 90.7%

χ2=1.378*, p=0.240

Hypoxaemia, (n, %)

Yes

n=64, 32.3%

n=105, 22.3%

n=134, 67.7%

n=366, 77.7%

χ2=7.428*, p=0.006***

Hypertension, (n, %)

Yes

n=53, 26.8%

n=88, 18.7%

n=145, 73.2%

n=383, 81.3%

χ2=5.477*, p=0.019***

Tachycardia, (n, %)

Yes

n=27, 13.6%

n=34, 7.2%

n=171, 86.4%

n=437, 92.8%

χ2=6.928*, p=0.008***

Bradicardia, (n, %)

Yes

n=12, 6.1%

n=29, 6.2%

n=186, 93.9%

n=442, 93.8%

60.98±39.07

48.75±27.42

Length of stay in the PACU (min.), (mean±SD)

Pearson chi-square test statistic value; **Mann-Whitney U test statistical value; care unit.

χ2=0.002*, p=0.962 z=-4.232**, p=0.000***

Statistically significant at level of 0.05. SD: Standard deviation. PACU: Postanesthesia

***

There was also a statistically significant difference between the related surgery department and the risk of perioperative hypothermia (p=0.042). The probability of perioperative hypothermia was 1.78 times higher in patients undergoing orthopedic surgery compared to patients undergoing general surgery (95% CI=0.913–3.504). It was 0.97 times lower in patients undergoing urologic surgery compared to patients undergoing general surgery (95% CI=0.485–1.951) and it was 1.27 times higher in patients undergoing thoracic surgery compared to patients undergoing general surgery (95% CI=0.619–2.628).

this study, the incidence of UPH declined from 35% to 23.8% (p<0.005).

DISCUSSION

The incidence of UPH was 66% in a study conducted by Karalapillai et al.[11] In this study, the core body temperature was monitored after cardiac surgery in the intensive care unit for 24 hours. We did not include cardiac surgeries in our study and recorded only the core body temperature on arrival to the PACU. These factors may explain the conflicting results between these two studies.

We found in our study that the UPH incidence in surgery patients declined from 35% to 23.8% thanks to the implementation strategy that was developed according to the evidence-based recommendations in the “TARD Prevention of UPH Guideline”. However, in the 1st Patient Safety Campaign,[9] a core body temperature above 36°C (96.8°F) was targeted in 95% of patients, who were referred from the operation room. Even though this target was not achieved in 724

Yi et al.,[10] conducted a nationwide study in China and they reported an incidence rate of 44.3% for UPH. This study had a multicenter design, the core body temperature was measured every 15 minutes throughout the perioperative period, hypothermia was defined as a core body temperature less than 36°C (96.8°F) in any measurement, and a much wider spectrum of the surgical departments, including cardiovascular and peripheral vascular surgeries, was included.[10]

Aksu et al.[12] conducted a study in Turkey and reported an incidence of 45.7% for UPH. Like in our study, the incidence Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Şenkal et al. Guideline implementation and raising awareness for unintended perioperative hypothermia

Table 4. The results of the hypothermia-related candidate variables according to the logistic regression models Independent variable

S.E.

Wald

95% CI for Odds Ratio (OR)

Below OR Exp(B) Above Gender* (Reference male)

-.473 .200 5.620 .018 .421

.623

.921

Age

.019 .005 13.536 .000 .972

.982

.991

Body mass index

.046

1.048

1.089

.020

5.523

.019

1.008

Surgical specialities** (Reference general surgery)

8.205

.042

2.869

.090

Orthopaedics and trauma

.581

.343

.913

1.788

3.504

Urology

-.028 .355 .006 .937 .485

Thoracic surgery

.243 .369 .434 .510 .619 1.275 2.628

.972 1.951

Type of Procedure*** (Reference endoscopic)

-.400 .207 3.747 .053 .447

.670

1.005

Intraoperative IV Fluid

.000

2.502

.114

1.000

Total surgery time

-.002

.001

2.117

.146

.996

.998

1.001

CI: Confidence Interval. *Gender: reference male; **Surgical specialities: reference general surgery; ***Type of Procedure: reference endoscopic.

of UPH was determined with the core body temperatures measured on arrival to the PACU, but hypothermia was defined as a core body temperature less than 35°C (95.0°F). Sagiroglu et al.[13] conducted a study with 529 patients and reported an incidence of 63.3% for UPH. This high UPH incidence might be explained with inclusion of patients who had undergone only gynecological, obstetric, urological, and general surgeries. In Turkey, Duman et al.[14] conducted a study with 116 patients who had undergone orthopedic surgery and reported an incidence of 69.8% for UPH. In this study, the incidence was evaluated according to the core body temperatures measured in the first hour of surgery. This can be explanatory for the different results between our study and Duman’s study. As is seen in the literature, studies report different incidence rates for UPH in comparison to our study. This may be explained by the variability of methodologies, lack of a standard definition for the perioperative hypothermia, different cut-off points and measurement time for hypothermia, inclusion of different surgery types, and various kinds of equipment used in the prevention of UPH. The time between the end of the implementation stage and recording of the postimplementation data is relatively short (50 days) in our study. The evaluation of the behavioral change before a sufficiently long time passes after the intervention may not be appropriate for the observation of the efficacy of the intervention. However, another study conducted one year later in our department provided valuable information. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

In the study conducted by Eksert et al.[15] with 629 patients, the incidence of UPH was 22.1%. We believe that this study provided objective evidence for the success and reliability of the implementation given that this study was conducted just one year later than our implementation and reported a similar incidence rate. In the survey, which was conducted by Köksal et al.[16] with anesthetists in Turkey and published before the introduction of the TARD guideline, the investigators had foreseen the necessity of standardization regarding the concepts related to perioperative hypothermia and the prevention of UPH and recommended to TARD to prepare a guideline. In 2017, after the introduction of the TARD guideline, İnal et al.[17] surveyed with the anesthetists to evaluate their perioperative hypothermia management. They found that the TARD guideline was the most commonly referred guideline by the anesthetists for UPH. In our study, the implementation was built on the evidence-based recommendations of the TARD guideline. A similar study was conducted in Germany. In this multicenter study, which had comprised the Northern Germany hospitals, compliance with the German S3 guideline was investigated. In this study, the details of the implementation had been listed item by item and then the authors had checked whether the anesthetists had followed these items or not. Although at the end of the study, the authors found that the anesthetists had only partially followed the recommendations in the guideline, hypothermia had not been observed in any of the included 431 patients.[18] In our study, we did not itemize our implementations, but we used cotton blankets that 725

Şenkal et al. Guideline implementation and raising awareness for unintended perioperative hypothermia

provided passive isolation and active warming methods like devices blowing heated air, electrical surgery table warming pad, intravenous fluid warmer, and HME filters in anesthesia circuit in both pre-implementation and postimplementation sections. We hung the prevention of the UPH checklist manual (Fig. 2) on easily visible walls in the working areas. However, we received feedback from the staff that the clinical guideline was too detailed. We decided to shorten the text with simpler and clearer expressions and made it available in the pre-anesthesia room, operation rooms, and PACU. We added extra lines to the anesthesia record forms and to the monitorization part for the core body temperature follow-up and core body temperature monitorization. As a secondary outcome of our study, we found that, in the PACU, the rate of the complications as shivering, pain, hypoxemia, hypertension, and tachycardia was significantly higher in the hypothermia group compared to the normothermia group. These results were consistent with the current information in the literature.[19] We also evaluated correlated risk factors for UPH. In the TARD guideline, age over 70 was considered as a risk factor for the development of hypothermia.[7] In our study, the age was accepted as a continuous variable and we found out that the possibility of the hypothermia incidence increased with the advanced age. Lau et al. conducted a study with 18,758 patients and showed that the UPH incidence was higher in patients over 65 years.[20] In the study conducted by Flores-Maldonado et al., no correlation between gender and UPH incidence was found in 130 patients.[21] We determined that the probability of UPH was lower in females compared to males. We believe that this difference depended on that our study was conducted in a military hospital and the male: female ratio was 62%: 38% and the surgical interventions implemented in males are relatively more complicated. The relationship between BMI and perioperative hypothermia incidence is not fully elucidated yet. While Okue et al. showed that BMI did not affect the intraoperative body temperature,[22] Vinslow et al.[23] demonstrated that high BMI had a mild protective effect on UPH. We added BMI as a continuous variable to regression analysis and showed that high BMI values increased the probability of UPH. The conflicting results in the literature may indicate that BMI is not an independent risk factor for UPH incidence or cannot be considered as a protective factor and may provide significant results only together with parameters like the type and duration of surgery. We compared UPH incidence in different surgery clinics and found significant results. However, we believe that the results related to the surgical clinics were specific to our center and cannot be generalized. If we had classified surgeries as minor, moderate, and major, as universally accepted, the obtained 726

findings might probably have been evaluated as generalizable results. In our study, the first period was conducted in the autumn and winter months and the second period in the spring and summer months. Although we have some concerns about the effects of the seasonal differences on our results, we did not implement any adjustments. However, we recommend that patient sampling should be preferably done in the same season and seasonal temperatures in the UPH studies. Our study was a quality improvement study in a good purpose in light of the published guidelines. We recommend the consideration of international standards defined for such studies like the SQUIRE project by the investigators, which we did not consider.[24] The single-center, uncontrolled and semi-experimental design, the inclusion of only anesthesia staff and lack of separate itemization are the limitations of our study. UPH is not a perioperative problem concerning only the staff of the anesthesiology department. The staff of all related surgery departments should be informed about UPH and their awareness should be improved.

Conclusion Unintended perioperative hypothermia is a common complication and its incidence is still far away from the targeted level. Our primary recommendation is the standardization of the core body temperature monitorization in the perioperative period and the incidence of UPH and indirectly related perioperative complications can be significantly decreased with the implementation of the evidence-based recommendations (Fig. 2) like the “Guideline for the Prevention of the Unintended Perioperative Hypothermia” published by TARD. Suitable protocols should be established for the prevention and management of UPH in the operating rooms, and efforts should be made to improve the awareness and encourage behavioral changes. Ethics Committee Approval: This study was approved by the Ethics Committee for Clinical Research at Gülhane Military Medical Academy (2015/KAEK/33). Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.Ş.; Design: S.Ş.; Supervision: S.Ş.; Fundings: S.Ş., U.K.; Materials: S.Ş., U.K.; Data: S.Ş., U.K.; Analysis: U.K.; Literature search: S.Ş., U.K.; Writing: S.Ş., U.K.; Critical revision: S.Ş., U.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Sajid MS, Shakir AJ, Khatri K, Baig MK. The role of perioperative warming in surgery: a systematic review. Sao Paulo Med J 2009;127:231−7. 2. Moola S, Lockwood C. Effectiveness of strategies for the management

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3. 4.

10.

11.

12.

13.

and/or prevention of hypothermia within the adult perioperative environment. Int J Evid Based Healthc 2011;9:337−45. Frank SM, Tran KM, Fleisher LA, Elrahmany HK. Clinical importance of body temparature in the surgical patient. J Therm Biol 2000;25:151−5. National Institute for Health and Clinical Excellence. Hypothermia: Prevention and management in adults having surgery. Clinical Guideline 65, 2016. Available at: https://www.nice.org.uk/guidance/cg65/resources/hypothermia-prevention-and-management-in-adults-having-surgery-pdf-975569636293. Accessed November 20, 2019. Forbes SS, Eskicioglu C, Nathens AB, Fenech DS, Laflamme C, McLean RF, et al; Best Practice in General Surgery Committee, University of Toronto. Evidence-based guidelines for prevention of perioperative hypothermia. J Am Coll Surg 2009;209:492−503.e1. Torossian A, Bräuer A, Höcker J, Bein B, Wulf H, Horn EP. Preventing inadvertent perioperative hypothermia. Dtsch Arztebl Int 2015;112:166−72. The Turkish Anaesthesiology and Reanimation Society Guidelines for the prevention of inadvertent perioperative hypothermia. Turk J Anaesthesiol Reanim 2013;41:188−90. Lawson L, Bridges EJ, Ballou I, Eraker R, Greco S, Shively J, et al. Accuracy and precision of noninvasive temperature measurement in adult intensive care patients. Am J Crit Care 2007;16:485−96. Patient Safety First. The ‘How to’ Guide for Reducing Harm in Perioperative Care, 2009. Available at: http://www.odpskills.co.uk/pdf/patient_ safety.pdf. Accessed November 22, 2019. Yi J, Lei Y, Xu S, Si Y, Li S, Xia Z, et al. Intraoperative hypothermia and its clinical outcomes in patients undergoing general anesthesia: National study in China. PLoS One 2017;12: e0177221. Karalapillai D, Story D, Hart GK, Bailey M, Pilcher D, Cooper DJ, Bellomo R. Postoperative hypothermia and patient outcomes after elective cardiac surgery. Anaesthesia 2011;66:780−4. Aksu C, Kuş A, Gürkan Y, Solak M, Toker K. Survey on postoperative hypotermia incidence in operating theatres of Kocaeli University. Turk J Anaesth Reanim 2014;42:66−70. Sagiroglu G, Ozturk GA, Baysal A, Turan FN. Inadvertent Perioperative

Hypothermia and Important Risk Factors during Major Abdominal Surgeries. J Coll Physicians Surg Pak 2020;30:123−8. 14. Duman AY, Yılmaz E. Incidence of perioperative hypothermia in orthopaedic surgery and risk factors. Cukurova Med J 2016;41:687−94. 15. Eksert S, Sir E. Incidence of hypothermia and analgesic use in the postanesthesia care unit. Gulhane Med J 2019;61:69−72. 16. Köksal GM, Dikmen Y, Utku T, Ekici B, Erbabacan E, Alkan F, et al. Perioperative Temperature Monitoring and Patient Warming: A Survey Study. Turk J Anaesthesiol Reanim 2013;41:149−55. 17. İnal MA, Ural SG, Çakmak HŞ, Arslan M, Polat R. Approach to Perioperative Hypothermia by Anaesthesiology and Reanimation Specialist in Turkey: A Survey Investigation. Turk J Anaesthesiol Reanim 2017;45:139−45. 18. Gabriel P, Höcker J, Steinfath M, Kutschick KR, Lubinska J, Horn EP. Prevention of inadvertent perioperative hypothermia - Guideline compliance in German hospitals. Ger Med Sci 2019;17:Doc07. 19. Reynolds L, Beckmann J, Kurz A. Perioperative complications of hypothermia. Best Pract Res Clin Anaesthesiol 2008;22:645−57. 20. Lau LL, Hung CT, Chan CK, Chow B, Chui PT, Ho B, et al. Anaesthetic clinical indicators in public hospitals providing anaesthetic care in Hong Kong: prospective study. Hong Kong Med J 2001;7:251−60. 21. Flores-Maldonado A, Guzmán-Llanez Y, Castañeda-Zarate S, et al. Risk factors for mild intraoperative hypothermia. Arch Med Res 1997;28:587−90. 22. Okoué R, Calabrese D, Nzé P, Msika S, Keita H. Efficacy of ForcedAir Warming to Prevent Perioperative Hypothermia in Morbidly-Obese Versus Non-obese Patients. Obes Surg 2018;28:1955−9. 23. Winslow EH, Cooper SK, Haws DM, Balluck JP, Jones CM, Morse EC, et al. Unplanned perioperative hypothermia and agreement between oral, temporal artery, and bladder temperatures in adult major surgery patients. J Perianesth Nurs 2012;27:165−80. 24. Davidoff F, Batalden P, Stevens D, Ogrinc G, Mooney S; SQUIRE Development Group. Publication guidelines for quality improvement in health care: evolution of the SQUIRE project. Qual Saf Health Care 2008;17:i3−9.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

İstenmeyen perioperatif hipotermi için farkındalık oluşturmak ve kılavuz implementasyonu: Tek gruplu “önce ve sonra” çalışması Dr. Serkan Şenkal,1 Dr. Umut Kara2 1 2

Sağlık Bilimleri Üniversitesi, Gülhane Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Ankara Sağlık Bilimleri Üniversitesi, Gülhane Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, Ankara

AMAÇ: İstenmeyen perioperatif hipotermi vücut sıcaklığının 36°C’nin altına düşmesi olarak tanımlanır. Türk Anesteziyoloji ve Reanimasyon Derneği (TARD) 2013 yılında “İstenmeyen Perioperatif Hipoterminin Önlenmesi Rehberini” yayınladı. Amacımız rehber önerilerini içeren bir protokol oluşturmak ve hastanemizde perioperatif hipotermi insidansını azaltmaktır. GEREÇ VE YÖNTEM: Cerrahi geçiren hastalarda perioperatif hipotermi insidansını azaltmaya yönelik oluşturulan protokol ile ileriye yönelik bir kalite iyileştirme çalışması yaptık. Hastaların perioperatif hipotermi insidansını; implementasyondan önce (24 Kasım 2015–15 Ocak 2016) ve implementasyondan sonra (6 Nisan 2016–21 Temmuz 2017) ölçtük ve karşılaştırdık. BULGULAR: İstenmeyen perioperatif hipotermi (<36°C) insidansı preimplementasyon kolunda %35, postimplementasyon kolunda %23.8 olarak bulundu ve bu farkın istatistik olarak anlamlı olduğu görüldü (p=0.002). TARTIŞMA: Kanıta dayalı uygulamalar ile yapılan müdahaleler sonucunda istenmeyen perioperatif hipotermi insidansı belirgin olarak azaltılabilir. Anahtar sözcükler: Hasta güvenliği; ısıtma; istenmeyen perioperatif hipotermi. Ulus Travma Acil Cerrahi Derg 2020;26(5):719-727

doi: 10.14744/tjtes.2020.55237

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ORIGIN A L A R T IC L E

The concordance of optic nerve sheath diameter measurements with the clinical course in children with traumatic head injury Rasime Pelin Kavak, M.D.,1 Meltem Özdemir, M.D.,1 Nurcan Ertan, M.D.,1 Bahadır Külah, M.D.3

Nezih Kavak, M.D.,2

Department of Radiology, University of Health Sciences Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara-Turkey

Department of Emergency Medicine, University of Health Sciences Dışkapı Yıldırım Beyazıt Training and Research Hospital, Ankara-Turkey

Department of General Surgery, A Life Park International Academic Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: Intracranial pressure (ICP) monitoring is of profound importance concerning prognosis and treatment among children with traumatic brain injury (TBI). Measurements of the optic nerve sheath diameter (ONSD) are one of the methods recommended for ICP monitoring. In this study, we aimed to evaluate the correlation of ONSD change in brain computed tomography (CT) with pediatric Glasgow Coma Score (pGCS) in the follow-up of pediatric cases with TBI, and also to evaluate the usability of the ONSD, which is the indicator of ICP. METHODS: The data of 921 pediatric patients who were admitted to the emergency department with head injury between January 2016 and January 2018 were retrospectively evaluated in this study. Age, gender, trauma type, brain CT finding, pGCS, type of intracranial hemorrhage (ICH), and isolated skull fracture (ISF) were investigated. The patients were evaluated in three groups based on CT findings: (i) patients with parenchymal brain injury, (ii) patients with ISF, and (iii) patients with normal brain CT results. The measurements of ONSD were performed using CT. Whether the ONSD measurement results of the patients were compatible with the clinical data was investigated. RESULTS: The median age of the patients was 36 months (interquartile range [IQR] = 64) and 64.2% were male. The ONSD values and pGCSs of the patients with parenchymal injury were found to be significantly higher than patients with ISF and normal brain CT findings (p<0.05). The pGCSs showed a significant negative correlation with the first and second measurement results of ONSD (p<0.05). In groups undergoing control brain CT, ONSD levels in the second brain CT were found to be significantly high (p<0.05). CONCLUSION: In the clinical follow-up, ONSD measurements are reliable and significant parameters when evaluated with brain CT findings and pGCSs. We think that repeated ONSD measurements will be useful in determining possible adverse effects of secondary injury, as well as in determining the severity of the trauma during admission. Keywords: Intracranial pressure; optic nerve sheath diameter; traumatic brain injury.

INTRODUCTION Severe traumatic brain injury (TBI) is the leading cause of mortality and morbidity in children.[1] Pathophysiologic characteristics and management options are different from those in adults. These differences result from age-related structural

change, injury mechanisms related to the ability of the child and difficulty in neurologic evaluation of pediatric patients.[1–3] There are two mechanisms that cause TBI. The first cause is primary injuries resulting from direct trauma, and the second cause is secondary injuries due to metabolic causes,

Cite this article as: Kavak RP, Özdemir M, Kavak N, Ertan N, Külah B. The concordance of optic nerve sheath diameter measurements with the clinical course in children with traumatic head injury. Ulus Travma Acil Cerrahi Derg 2020;26:728-734. Address for correspondence: Rasime Pelin Kavak, M.D. Sağlık Bilimleri Üniversitesi Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Radyoloji Kliniği, Ankara, Turkey Tel: +90 312 - 596 20 00 E-mail: drrpelindemir6@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):728-734 DOI: 10.14744/tjtes.2020.13446 Submitted: 16.03.2020 Accepted: 11.07.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Kavak et al. The concordance of ONSD measurements with the clinical course in children with traumatic head injury

such as hypoxia, hypercapnia, hypotension, increased intracranial pressure (ICP) and hyperglycemia.[4] Although it is not possible to avoid primary injuries, secondary injuries can be prevented by minimizing metabolic causes. The increase in brain edema may lead to increased ICP, resulting in mortality. Increased ICP may cause secondary injuries by decreasing cerebral perfusion and cerebral blood flow. If no intervention is made, this will continue in a vicious circle until the patient dies. Therefore, monitoring of ICP and identification of any elevation are of vital importance.[5–7] The monitoring of ICP plays an important role in treatment in pediatric patients as in adults and predicts morbidity and mortality significantly.[8] Monitoring of ICP is a method that can be measured invasively under normal conditions, has complications, and requires technical equipment.[9,10] The measurement of optic nerve sheath diameter (ONSD) using different radiological imaging techniques has become a popular non-invasive method for monitoring ICP. There are studies reporting that computed tomography (CT), magnetic resonance imaging and ultrasonography (USG) can also be used for this purpose.[11–14] The ONSD diameter has been reported to increase if there is an increase in the ICP since the dura mater extends to surround the optic nerve, and the most suitable area for the measurement has been reported to be 3 mm behind the globe in particular.[7,9] Pediatric Glasgow Coma Score (pGCS) is a significant scoring system that can be used in the follow-up of patients with TBI and can guide the clinician. According to the current data, ICP monitoring is important in the management of treatment in cases with a pGCS of 8 or less.[5,8,12] We aimed to investigate the correlation between the ONSD change on brain CT used in the follow-up of pediatric patients with TBI and pGCS and the usability of ONSD, an indicator of ICP, in the follow-up of patients.

MATERIALS AND METHODS After ethical committee approval, medical records of 921 pediatric patients admitted to the emergency department of our hospital with complaints of traumatic head injury between 1 January 2016 and 1 January 2018 were retrospectively reviewed in this study. Age, gender, trauma type, brain CT finding, pGCS, type of intracranial hemorrhage (ICH) and isolated skull fracture (ISF) were analyzed. The patients were divided into three groups according to the CT findings such as parenchymal brain injury, ISF and normal CT finding. The medical records of pediatric patients with intracranial mass, head trauma-induced ocular or orbital injury, previous optic nerve trauma, and brain surgery were excluded from this study. The presence of artifacts obscure the visualization of the optic nerve on CT imagining was accepted as exclusion criteria. It was investigated whether there was a significant difference Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

between the first brain CT and control brain CT concerning ONSD width among patients undergoing control CT due to additional symptoms or changes in the clinical condition.

CT Protocol and Measurement of ONSD CT examinations were performed with a 64-detector row CT machine (GE Optima 660 SE 64 Detector 128-slice CT, General Electric Medical Systems, Milwaukee, WI). The standardized pediatric brain CT protocols were based on the following: effective dose level of 65–110 mAs, 110 kVp, 20 mm collimation, 5 mm thickness reconstruction at 5 mm intervals, 0.5 second rotation time. The CT protocol using 0.625 mm*32 row contiguous slices. 20 mm (32*0.625) detector coverage was used for all brain non-contrast acquisition. In addition, radiation-sensitive organs, such as gonads are routinely protected from radiation with shields. Suitable dose sedative was used in uncooperative pediatric patients if required. All ONSD measurements have been performed on the initial brain CT images obtained upon admission to the ED. Images demonstrated the maximum width of the optic nerve was chosen and the retrobulbar area was magnified five times. The ONSD was measured from one side of the optic nerve sheath to the other site 3 mm behind the posterior globe margin in a perpendicular vector in reference to the linear axis of the optic nerve (Fig. 1a-c). ONSD measurements were carried out using electronic calipers on the Extreme Picture Archiving and Communication System (ExtremePacs, Ankara, Turkey). The average of the right and left eye optic nerve sheath measurements was taken in millimeters (mm) as the mean ONSD value for the final analysis. All the measurements were made on images through the brain window using the same window settings for all patients. Two experienced radiologists (R.P.K and M.Ö.) examined the brain CT images and made the repeated ONSD measurements in a blinded manner for the clinical data of the patients.

Statistical Analysis Statistical analysis was performed using Statistical Package for the Social Sciences, Version 22.0 (SPSS Inc., Chicago, IL). Categorical data were analyzed by Chi-Square test. The distribu-

(b)

(c)

(a) Figure 1. Axial computed tomography section demonstrating the optic nerves (yellow arrows) (a). ONSD was measured 3 mm behind the insertion of the optic nerve into the globe, on a perpendicular line (red line), with reference to the linear axis of the optic nerve (yellow line) (b). Note the location where the optic nerve sheath diameter measurement was performed (red arrow) (c).

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Kavak et al. The concordance of ONSD measurements with the clinical course in children with traumatic head injury (a)

(b)

(c)

(d)

(e)

(f)

Figure 2. Axial computed tomography sections of a patient with isolated head trauma obtained at admission (a-d) and at 24th hour following the trauma (d-f). Note the development of subarachnoid hemorrhage (green arrows in d-f) and the noticeable increase in the optic nerve sheath diameter in the sections obtained 24th hour following the trauma (red arrowhead in e).

tion of the data was analyzed using the Kolmogorov-Smirnov test. Upon determining that quantitative data is non-parametric, a Mann-Whitney U test or Kruskal Wallis test was used to analyze the data with categorical variables. Quantitative (parametric) variables were presented as median and interquartile range (IQR) deviation, and qualitative (nonparametric) variables were expressed as observed numbers and percentages. The change between the ONSD on brain CT taken at the time of admission and ONSD on control brain CT was measured using the Paired Samples t-test. These data were expressed as mean and standard deviation. Spearmanâ&#x20AC;&#x2122;s rank correlation analysis was used to compare ONSD values and pGCS. P-values less than 0.05 were considered statistically significant.

findings (p<0.05). No difference was observed between the patients with ISF and patients with normal brain CT findings concerning pGCSs (p>0.05). The mortality rate was 5.8% in the present study, and it was significantly higher in patients with parenchymal injury (p<0.05) (Table 1).

RESULTS

DISCUSSION

The median age of the patients was 36 months (IQR=64) and 64.2% were male. The median age of patients with parenchymal injury and ISF was found to be significantly higher than patients with normal brain CT findings (p<0.05). The patients were most frequently admitted with fall and the frequency of parenchymal injury was significantly higher in these patients (p<0.05). The most common parenchymal injury was subarachnoid hemorrhage.

There are many studies in the literature showing that ONSD increases with the increased ICP in patients with TBI.[13,15] Control brain CT can also be performed if there is a clinical worsening or change during follow-up of patients with TBI, or in the follow-up of patients. In the present study, ONSD values on the control brain CTs have been examined and the relationship between impaired clinical status and ICP increase has been investigated. The relationship of the existing change with ICP increase has been evaluated and it has been investigated whether ONSD could be used in the prognosis of patients without additional examination. The ONSD has been observed to increase in control brain CTs in patients with impaired clinical status, regardless of the presence of parenchymal injury. A significant relationship has been found between this change and the pGCSs of the patients. In studies involving pediatric patients, it has been reported

The ONSD values of the patients with parenchymal injury were found to be significantly higher than those with ISF and normal CT findings (p<0.05). No difference was observed between the patients with ISF and those with normal brain CT findings in terms of the ONSD measurements (p>0.05). The pGCSs of the patients with parenchymal injury were found to be significantly lower than those with ISF and normal CT 730

The pGCSs showed a significant negative correlation with the first and second measurement results of ONSD (p<0.05) (Table 2). Control brain CT was observed to be performed in 755 (82%) of the cases. In groups undergoing control CT, ONSD levels in the second brain CT were found to be significantly high (p<0.05) (Table 3) (Fig. 2a-f).

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Table 1. Demographic and clinical characteristics of the groups

The causes of traumatic head injury

Brain parenchymal damage n (%)

Isolated skull fracture n (%)

Normal brain CT findings n (%)

Age (month), median (IQR)

48 (74)

24 (52)

12 (12)

<0.001a,b

Male/female (n)

350/121

113/81

128/128

<0.001

Trauma mechanism, n (%)

Fall

261 (55.4)

132 (68)

120 (46.9)

Motor vehicle accident

178 (37.8)

62 (32)

136 (53.1)

Others (e.g., gunshot wounds)

32 (6.8)

–

Type of parenchymal damage, n (%)

Subarachnoid hemorrhage

245 (27)

Subdural hemorrhage

120 (13)

Epidural hemorrhage

113 (12)

Cerebral contusion

105 (11)

Cerebral edema

74 (8)

1. ONSD (mm), median (IQR)

5.36 (1)

3.60 (1)

3.99 (1)

<0.001a,b

2. ONSD (mm), median (IQR)

5.36 (1)

3.60 (1)

4.00 (1)

<0.001a,b

pGCS, median (IQR)

12 (1)

15 (1)

<0.001a,b,c

Mortality, n (%)

53 (11)

None

<0.001

IQR: Interquartile range; CT: Computed tomography; ONSD: Optic nerve sheath diameter; mm: Millimeter; pGCS: Pediatric Glasgow Coma Score (a: for traumatic brain injury and, isolated skull fracture p<0.05; b: for traumatic brain injury and normal brain CT p<0.05; c: for an isolated skull fracture and normal brain CT p<0.05).

Table 2. Relationship between Pediatric Glasgow Coma Score and optic nerve sheath diameter values

Pediatric Glasgow Coma Score

r p

1. ONSD (mm)

-0.528* <0.001

2. ONSD (mm)

-0.476* <0.001

*: Corelation p<0.001; ONSD: Optic nerve sheath diameter.

that most of the patients are male and that the severity of trauma increases with the advancing age.[16,17] Ong et al.[18] have attributed this to high-risk behaviors that are common in male children. Compatible with the literature, we found that the number of male children with TBI was higher, the age of these patients was higher than others, and the incidence of TBI was higher in boys in the present study. This can be attributed to that boys play more aggressive games and are more prone to violence than girls. It may also be associated with the fact that sutures of young children are not closed or

Table 3. Optic nerve sheath diameter difference between two measurements of groups

1. ONSD

2. ONSD

Difference

Mean±SD Mean±SD Mean±SD

Parenchymal damage (+) (Alive) (n=449)

4.79±0.83

4.82±0.81

-0.028±0.068

<0.001

Parenchymal damage (+) (Exitus ) (n=46)

4.93±0.81

5.02±0.72

-0.08±0.12

<0.001

Subarachnoid hemorrhage (n=222)

4.77±0.86

4.79±0.85

-0.018±0.05

<0.001

Subdural hemorrhage (n=112)

4.75±0.81

4.79±0.79

-0.041±0.07

<0.001

Epidural hemorrhage (n=107)

4.98±0.76

5.02±0.74

-0.04±0.08

<0.001

Cerebral contusion (n=101)

4.69±0.84

4.74±0.82

-0.05±0.075

<0.001

Cerebral edema (n=68)

4.76±0.80

4.81±0.78

-0.048±0.069

<0.001

Isolated skull fracture (n=143)

3.71±0.52

3.75±0.51

-0.04±0.08

<0.001

Normal (n=155)

3.79±0.53

3.80±0.52

-0.02±0.06

<0.001

SD: Standard deviation; ONSD: Optic nerve sheath diameter; SD: Standard deviation.

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have been recently closed, or that they have more tolerance to trauma due to the relatively low ossification. Studies in the literature have reported that the cause of TBI in the pediatric population is fall and the incidence of traffic accidents increases with the advancing age.[16,17,19] In the present study, fall has been the most common cause of injury and the number of TBI and ISF cases developed as a result of a traffic accident has been the lowest. This may be due to children fall as a result of being careless while playing or when they were in a high-rise place. The clinician wants to rule out a possible TBI since other injuries, as well as head injury, are frequently observed in traffic accident cases. This may have caused the frequency of pathology to be low in brain CTs. In traumas caused by falls, the physical examination is clearer and more specific, and the trauma coming directly to the head may have increased the rate of ISF and TBI. Studies with the pediatric population have reported that skull fracture is the most common lesion and epidural hematoma is the most common complication of TBI.[16,17] Compatible with the literature, skull fracture ranks the first place concerning incidence in the present study. However, unlike the literature, subarachnoid hemorrhage has been the most common complication in TBI. This may be due to the trauma mechanism, severity of the trauma, and admission of patients with poor clinical status to tertiary hospitals like our hospital. Many studies have shown that ONSD measured on brain CT is associated with TBP-related ICP increase and has drawn attention to the high sensitivity and negative predictive value of ONSD.[9,20,21] There are also studies showing a correlation between the ONSD measured using USG or CT and ICP in pediatric patients.[13,22] In a study by Young et al.[23] involving pediatric patients, have reported that there is an increase in ONSD value in cases with TBI and that ONSD can be used in ICP monitoring. In the present study, the ONSD value of patients with TBI in the first and second measurements has been found to be higher than the patients with ISF or normal brain CT findings, compatible with the literature. We believe that this is associated with an increase in ICP caused by increased brain edema due to both primary and secondary injuries. The pGCS is an important clinical parameter in determining the clinical status of pediatric patients with a head injury.[2,6,24] Therefore, current guidelines recommend the use of pGCS in the follow-up of children with TBI.[25] Young et al.[23] have reported a significant relationship between pGCS and ONSD in their study involving pediatric patients. In a study by Yagar et al.[26] in which the ONSD measurement was performed using cranial CT in patients with a head injury, the ONSD value of children with a pGCS of 3 to 13 has been reported to be higher than those with a pGCS of 14 or 15. In the present study, the pGCSs of the patients with TBI have been found to be significantly lower than those with ISF and normal CT findings. We have further found that pGCS decreases as the ONSD value increases. We believe that this is due to that ONSD 732

increases as a result of deterioration in intracranial circulation because of the increased severity of TBI. As a contrary relationship, the patientâ&#x20AC;&#x2122;s clinical status is impaired and consciousness becomes deepen as the severity of TBI increases. We believe that a negative correlation has been found between pGCS and ONSD due to this contrary relationship. Specific symptoms of ICP increase may not always be seen in the pediatric patient group, which can lead to an overlook of ICP increase.[11] In TBI cases, secondary injuries, as well as brain damage caused by primary injury, may also cause brain edema and thus an increase in ICP, resulting in impaired clinical status.[6,27,28] In the literature, it has been reported that ONSD is an independent variable for morbidity and mortality, and mortality rates have been lower in patients who underwent ICP monitoring and required interventions.[29,30] To our knowledge, there is no study in which serial ONSD monitoring is performed in pediatric head trauma cases in the literature. However, in a study conducted by Thotakura et al.[31] in which ONSD was measured with an interval of 24â&#x20AC;&#x201C;48 hours in adult head trauma cases, it was reported that the clinical course was good in all patients in the group with a decrease in their ONSD values and that none of the patients in this group received surgical treatment. In the present study, a significant increase has been observed in the ONSD values of the patients (alive, died, with and without CT lesion) who had to undergo control brain CT due to any reason (clinical change, new symptom, or follow-up). We believe that ONSD values of the patients with parenchymal injury have increased due to the ICP, which increases due to the effect of the increase in the amount of bleeding on the mass and secondary injuries that develop over time. Although some patient groups have normal brain CT results or ISF, we believe that ONSD increases by the ICP that increases due to very small amounts of bleeding, axonal injuries, and secondary effects of trauma in these patient groups. It should be considered that the physician may have requested control brain CT since increased ICP in these patient groups may have led to new symptoms and changes in the clinical status. It is noteworthy that the most significant increase has been observed in patients with TBI and patients with a mortal clinical course. This has led to the emergence of the idea that patients with a significant increase in ONSD values have a more mortal clinical course and that it may guide the physician to change the treatment plan. We believe that this repeated measurement showing an increase in ONSD on a brain CT that has been already taken may guide the clinician in terms of follow-up and treatment. The greatest limitation of this study is that why the control brain CT is performed and whether there is a change in the control pGCS are not known due to its retrospective design. There were no comparable results of invasive ONSD measurement known as a gold standard.

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Kavak et al. The concordance of ONSD measurements with the clinical course in children with traumatic head injury

Conclusion The results of our study suggest that the evaluation of ICP using brain CT-based ONSD measurements is extremely helpful in predicting the severity of trauma on admission in patients with head trauma patients. Pathologic brain CT findings and pGSCs were compatible with the results of ONSD measurements. Increased ICP levels in repeated ONSD measurements are also meaningful in terms of early diagnosis of adverse outcomes due to secondary insult of traumatic brain injury. Brain CT-based ONSD measurements should be considered as a non-invasive and effective method in monitoring the increase of intracranial pressure in the emergency admissions, follow-up, and treatments of pediatric patients with head trauma. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: R.P.K., N.K., M.Ö.; Design: R.P.K., N.K., M.Ö.; Supervision: R.P.K.; Materials: R.P.K., N.K., N.E.; Data: R.P.K., N.K., M.Ö., N.E.; Analysis: B.K., N.K.; Literature search: R.P.K., B.K., M.Ö.; Writing: R.P.K., N.K.; Critical revision: R.P.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Lovett ME, O’Brien NF, Leonard JR. Children With Severe Traumatic Brain Injury, Intracranial Pressure, Cerebral Perfusion Pressure, What Does it Mean? A Review of the Literature. Pediatr Neurol 2019;94:3— 20. 2. Araki T, Yokota H, Morita A. Pediatric Traumatic Brain Injury: Characteristic Features, Diagnosis, and Management. Neurol Med Chir (Tokyo) 2017;57:82—93. 3. Bardes JM, Benjamin E, Escalante AA, Wu J, Demetriades D. Severe traumatic brain injuries in children: Does the type of trauma center matter?. J Pediatr Surg 2018;53:1523—5. 4. Dilmen ÖK, Akçıl EF, Tunalı Y. Intensive Care Treatment in Traumatic Brain Injury. Turk J Anaesthesiol Reanim 2015;43:1—6. 5. Hussain E. Traumatic Brain Injury in the Pediatric Intensive Care Unit. Pediatr Ann 2018;47:e274—9. 6. Vella MA, Crandall ML, Patel MB. Acute Management of Traumatic Brain Injury. Surg Clin North Am 2017;97:1015—30. 7. Robba C, Bacigaluppi S, Cardim D, Donnelly J, Bertuccio A, Czosnyka M. Non-invasive assessment of intracranial pressure. Acta Neurol Scand 2016;134:4—21. 8. Narayan V, Mohammed N, Savardekar AR, Patra DP, Notarianni C, Nanda A. Noninvasive Intracranial Pressure Monitoring for Severe Traumatic Brain Injury in Children: A Concise Update on Current Methods. World Neurosurg 2018;114:293—300. 9. Sekhon MS, Griesdale DE, Robba C, McGlashan N, Needham E, Walland K, et al. Optic nerve sheath diameter on computed tomography is correlated with simultaneously measured intracranial pressure in patients with severe traumatic brain injury. Intensive Care Med 2014;40:1267—74.

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10. Luerssen TG. Intracranial pressure: current status in monitoring and management. Semin Pediatr Neurol 1997;4:146—55. 11. Komut E, Kozacı N, Sönmez BM, Yılmaz F, Komut S, Yıldırım ZN, et al. Bedside sonographic measurement of optic nerve sheath diameter as a predictor of intracranial pressure in ED. Am J Emerg Med 2016;34:963—7. 12. Jenjitranant P, Tunlayadechanont P, Prachanukool T, Kaewlai R. Correlation between optic nerve sheath diameter measured on imaging with acute pathologies found on computed tomography of trauma patients. Eur J Radiol 2020;125:108875. 13. Kerscher SR, Schöni D, Hurth H, Neunhoeffer F, Haas-Lude K, Wolff M, et al. The relation of optic nerve sheath diameter (ONSD) and intracranial pressure (ICP) in pediatric neurosurgery practice - Part I: Correlations, age-dependency and cut-off values. Childs Nerv Syst 2020;36:99—106. 14. Khan MN, Shallwani H, Khan MU, Shamim MS. Noninvasive monitoring intracranial pressure - A review of available modalities. Surg Neurol Int 2017;8:51. 15. Munawar K, Khan MT, Hussain SW, Qadeer A, Shad ZS, Bano S, et al. Optic Nerve Sheath Diameter Correlation with Elevated Intracranial Pressure Determined via Ultrasound. Cureus 2019;11:e4145. 16. Işık HS, Gökyar A, Yıldız Ö, Bostancı U, Özdemir C. Pediatric head injuries, retrospective analysis of 851 patients: an epidemiological study. Turkish J Trauma & Emerg Surg 2011;17:166—72. 17. Ökten Aİ, Yalman M, Kaplanoğlu E, Gül B, Gezici AR, Sertel İ, et al. Pediatric head traumas. Turkish J Trauma & Emerg Surg 1996;2:94—9. 18. Ong AC, Low SG, Vasanwala FF. Childhood Injuries in Singapore: Can Local Physicians and the Healthcare System Do More to Confront This Public Health Concern?. Int J Environ Res Public Health 2016;13:718. 19. Langlois J, Rutland-Brown W, Thomas K. Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations, and Deaths 2002-2006. Atlanta, GA: Centers for Disease Control and Prevention; 2006. 20. Maas AI, Hukkelhoven CW, Marshall LF, Steyerberg EW. Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors. Neurosurgery 2005;57:1173—82. 21. Legrand A, Jeanjean P, Delanghe F, Peltier J, Lecat B, Dupont H. Estimation of optic nerve sheath diameter on an initial brain computed tomography scan can contribute prognostic information in traumatic brain injury patients. Crit Care 2013;17:R61. 22. Lin JJ, Chen AE, Lin EE, Hsia SH, Chiang MC, Lin KL. Point-of-care ultrasound of optic nerve sheath diameter to detect intracranial pressure in neurocritically ill children - A narrative review. Biomed J. 2020 Apr 23:S2319-4170(20)30032-9. doi: 10.1016/j.bj.2020.04.006. [Epub ahead of print]. 23. Young AM, Guilfoyle MR, Donnelly J, Scoffings D, Fernandes H, Garnett M, et al. Correlating optic nerve sheath diameter with opening intracranial pressure in pediatric traumatic brain injury. Pediatr Res 2017;81:443—7. 24. O’Brien NF, Maa T, Reuter-Rice K. Noninvasive screening for intracranial hypertension in children with acute, severe traumatic brain injury. J Neurosurg Pediatr 2015;16:420—5. 25. Kochanek PM, Tasker RC, Carney N, Totten AM, Adelson PD, Selden NR, et al. Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines. Pediatr Crit Care Med 2019;20:S1—82. 26. Yagar AB, Kozaci N, Avci M, Yildiz S, Karaman Y. Determination of op-

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Kavak et al. The concordance of ONSD measurements with the clinical course in children with traumatic head injury tic nerve sheath diameter variability with age in pediatric groups and comparison of increased intracranial pressure and optic nerve sheath diameter in pediatric patients with head trauma. Ann Med Res 2018;25:460—5. 27. Sönmez BM, Temel E, İşcanlı MD, Yılmaz F, Gülöksüz U, Parlak S, Uçkun ÖM. Is initial optic nerve sheath diameter prognostic of specific head injury in emergency departments? J Natl Med Assoc 2019;111:210—7. 28. Hon KL, Huang S, Poon WS, Cheung HM, Ip P, Zee B. Mortality And Morbidity of Severe Traumatic Brain Injuries; A Pediatric Intensive Care Unit Experience Over 15 Years. Bull Emerg Trauma 2019;7:256—62. 29. Karakitsos D, Soldatos T, Gouliamos A, Armaganidis A, Poularas J,

Kalogeromitros A, et al. Transorbital sonographic monitoring of optic nerve diameter in patients with severe brain injury. Transplant Proc 2006;38:3700—6. 30. Al Saiegh F, Philipp L, Mouchtouris N, Chalouhi N, Khanna O, Shah SO, et al. Comparison of Outcomes of Severe Traumatic Brain Injury in 36,929 Patients Treated with or without Intracranial Pressure Monitoring in a Mature Trauma System. World Neurosurg 2020;136:e535—41. 31. Thotakura AK, Marabathina NR, Danaboyina AR, Mareddy RR. Role of serial ultrasonic optic nerve sheath diameter monitoring in head injury. Neurochirurgie 2017;63:444—8.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Kafa travmalı çocuklarda optik sinir kılıf çapı ölçümlerinin klinik seyir ile uyumu Dr. Rasime Pelin Kavak,1 Dr. Meltem Özdemir,1 Dr. Nezih Kavak,2 Dr. Nurcan Ertan,1 Dr. Bahadır Külah3 1 2 3

Sağlık Bilimleri Üniversitesi Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Radyoloji Kliniği, Ankara Sağlık Bilimleri Üniversitesi Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, Ankara A Life Park Uluslararası Akademik Hastanesi, Genel Cerrahi Kliniği, Ankara

AMAÇ: Travmatik beyin hasarlı (TBH) çocuklarda kafa içi basıncının (KİB) takibi prognoz ve tedavi açısından önemlidir. Optik sinir kılıf çapı (OSKÇ) ölçümleri kafa içi basıncının monitorizasyonunda önerilen yöntemlerden birisidir. Bu çalışmada, TBH olan pediatrik olguların takibinde beyin bilgisayarlı tomografideki (BT) OSKÇ değişiminin pediatrik Glasgow Koma Skoru (pGKS) ile korelasyonunu değerlendirmeyi ve aynı zamanda KİB göstergesi olan OSKÇ’nin hasta takibinde kullanılabilirliğini değerlendirmeyi amaçladık. GEREÇ VE YÖNTEM: Ocak 2016–Ocak 2018 tarihleri arasında acil servise kafa travması ile başvuran 921 pediatrik hasta geriye dönük olarak değerlendirildi. Yaş, cinsiyet, travma tipi, beyin BT bulguları, pGKS, serebral hemoraji tipleri ve izole kafatası kırıkları (İKK) incelendi. Hastalar BT bulgularına dayalı; parankimal beyin hasarı, İKK ve normal beyin BT’si olanlar şeklinde üç grupta değerlendirildi. OSKÇ ölçümü BT ile yapıldı. Hastaların OSKÇ ölçüm sonuçlarının klinik verilerle uyumu karşılaştırıldı. BULGULAR: Çalışmamızda hastaların yaş ortancası 36 (IQR=64) ay olup, hastaların %64.2’si erkekti. Parankimal yaralanması hastaların OSKÇ’si ve pGKS’si, İKK olan ve normal beyin BT’si olan hastalardan anlamlı olarak yüksek saptandı (p<0.05). Çalışmamızda pGKS’nin birinci ve ikinci ölçüm OSKÇ değerleri arasında negatif yönlü anlamlı korelasyon verdiği saptandı (p<0.05). Çalışmamıza almış olduğumuz ve kontrol beyin BT’si çekilen gruplarda, ikinci beyin BT’de saptanan OSKÇ düzeyleri anlamlı olarak yüksek saptandı (p<0.05). TARTIŞMA: Beyin BT bulguları ve pGKS birlikte değerlendirildiğinde OSKÇ ölçümleri klinik takipte güvenilir ve anlamlı parametrelerdir. Tekrarlayan OSKÇ ölçümlerinin, ikincil yaralanmaların olası olumsuz etkilerini ve başvuru esnasında yaşanan travmanın şiddetini belirlemede faydalı olacağına inanıyoruz. Anahtar sözcükler: Kafa içi basınç; optik sinir kılıf çapı; travmatik beyin hasarı. Ulus Travma Acil Cerrahi Derg 2020;26(5):728-734

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doi: 10.14744/tjtes.2020.13446

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ORIGIN A L A R T IC L E

Relationship of mortality with neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume in patients undergoing acute abdominal surgery Şükran Merve Çolakoğlu, M.D.,1 Döndü Genç Moralar, M.D.,2 Büşra Tok Çekmecelioğlu, M.D.,3 Gülsüm Oya Hergünsel, M.D.2 1

Department of Anesthesia and Reanimation,University of Health Sciences, Gaziosmanpaşa Taksim Training and Research Hospital,

İstanbul-Turkey 2

Department of Anesthesia and Reanimation, University of Health Sciences, Bakırköy Dr. Sadi Konuk Training and Research Hospital,

İstanbul-Turkey 3

Department of Anesthesia and Reanimation, University of Health Sciences, Sultan Abdulhamid Han Training and Research Hospital,

İstanbul-Turkey

ABSTRACT BACKGROUND: Acute abdominal surgery has a high rate of mortality and morbidity, and intensive care is often needed in the postoperative period. In intensive care units, various scoring systems are used to determine prognosis and mortality but are not sufficient to predict mortality and prognosis. For this purpose, easily applicable, effective methods are being investigated. In this study, we aimed to investigate the relationship between mortality and blood parameters, such as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and mean platelet volume (MPV), in patients undergoing acute abdominal surgery. METHODS: This study included a total of 249 patients who underwent acute abdominal surgery. The patients were divided into two groups as survivors (n=126) and non-survivors (n=123). The patient data were retrospectively analysed. The NLR, PLR, and MPV values were compared between the groups. Data including age, sex, Acute Physiology and Chronic Health Evaluation II-IV scores (APACHEII-IV), Sequential Organ Failure Assessment scores (SOFA), Glasgow Coma Scale were assessed. RESULTS: The mortality rate was 49.4% in our study. There was no statistically significant difference in the NLR and PLR values between the groups. However, MPV was significantly higher in the non-survivors group (p<0.004). CONCLUSION: Our study results showed that MPV values were significantly higher in the non-survivors following acute abdominal surgery, and NLR and PLR were not associated with mortality. Keywords: Acute abdomen; intensive care unit; mean platelet volume; mortality; neutrophil/lymphocyte ratio; platelet/lymphocyte ratio.

INTRODUCTION Non-traumatic pathological events, which suddenly involve in any of the intra-abdominal organs and cause serious life-threatening conditions, are classified under the title of an acute abdomen.[1] Patients undergoing acute abdominal surgery often need intensive care in the postoperative period. In recent years, studies have increasingly addressed the optimal

use of the intensive care resources and correct prediction of the outcome in critically ill patients. Although the Acute Physiology and Chronic Health Evaluation (APACHE) II-IV and Sequential Organ Failure Assessment (SOFA) scores are widely used in the prediction of the mortality and morbidity, yielding satisfactory results, studies for the more easy-to-use tools to identify the risk of mortality and organ dysfunction are still going on.[2–4]

Cite this article as: Çolakoğlu ŞM, Genç Moralar D, Tok Çekmecelioğlu B, Hergünsel GO. Relationship of mortality with neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and mean platelet volume in patients undergoing acute abdominal surgery. Ulus Travma Acil Cerrahi Derg 2020;26:735-741 Address for correspondence: Döndü Genç Moralar, M.D. SBÜ, Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Kliniği, İstanbul, Turkey Tel: +90 212 - 414 71 71 E-mail: dondugencm@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):735-741 DOI: 10.14744/tjtes.2020.81783 Submitted: 21.05.2019 Accepted: 02.02.2020 Online: 11.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Çolakoğlu et al. Relationship of mortality with NLR, PLR, and MPV in patients undergoing acute abdominal surgery

Inflammation is a protective response to eliminate the body of the cause of cellular damage (e.g., microorganisms and toxins) and to remove the necrotic cells and tissues from the environment.[3] While the causes of the acute abdomen may independently initiate the inflammatory cascade, stress that arises from the therapeutic, surgical intervention may also induce the inflammatory process. The systemic inflammatory response is associated with the altered white blood cell levels in the peripheral blood, particularly with neutrophilia, which occurs concomitantly with relative lymphocytopenia.[4] The novel inflammation markers, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and mean platelet volume (MPV), are under investigation for their predictive value for prognosis and mortality in critically ill patients. These markers have become popular in recent years and considered as a suitable predictor of the inflammatory events with other inflammatory predictors. In the present study, we aimed to investigate the possible relationship between mortality and NLR, PLR, and MPV in patients who underwent acute abdominal surgery.

MATERIALS AND METHODS This study included patients who were hospitalized in the intensive care unit (ICU) of Bakirkoy Dr. Sadi Konuk Training and Research Hospital and underwent acute abdominal surgery between 12.04.2012 and 20.10.2017. The patient data were retrospectively analyzed. The study protocol was approved by the Clinical Trials Ethics Committee of Bakirkoy Dr. Sadi Konuk Training and Research Hospital (25.09.2017; No: 2017/287 2017-12-08). The study was conducted in accordance with the principles of the Declaration of Helsinki. A total of 300 patients were screened in our database. Exclusion criteria were as follows: being under 18 years of age, being hospitalized shorter than 24 hours, receiving immunosuppressive therapy, having hematological malignancies, neutropenia and multiple short-time hospitalizations in the ICUs. As a result, a total of 249 patients who met the inclusion criteria were enrolled. The patient data were obtained from the PROBEL hospital information management system (Probel Computer Software Hardware Industry and Trade Inc., Izmir, Turkey) and the bedside recording system used in our ICU (Metavision; EMRall-QlinICU, Imdsoft/Metavision 5.46.38, USA). The 28-day mortality follow-up was done with the PROBEL and Mortality Notification System (OBS). All patients were divided into two groups as survivors (Group I; n=126) and non-survivors (Group II; n=123). Parameters of the complete blood count (Sysmex XN3000 America, Inc ICU (Metavision; EMRall-QlinICU, Imdsoft/Metavision 5.46.38. 577 Aptakisic Road Lincolnshire, IL 60069, USA), biochemistry (Roche Cobas 8000 modular analyzer - Roche Diagnostics International Ltd. CH-6343 Rotkreuz, Switzer736

land) and arterial blood gases (Siemens RAPIDLab 1265AG Healthcare Sector Henkestrasse 127 91052 Erlangen, Germany) were evaluated during the ICU stay. In addition, hemoglobin (Hb), platelets, MPV, neutrophils, and lymphocytes were analyzed. The NLR and PLR values were calculated with the division of neutrophil count to the lymphocyte count and platelet count to the lymphocyte count, respectively. The albumin and lactate levels were also measured and the scores of APACHE II-IV, Sequential Organ Failure Assessment (SOFA) scores and Glasgow Coma Scale (GCS) were compared between the groups. The primary aim of this study was to investigate the relationship between NLR, PLR and MPV in patients undergoing acute abdominal surgery admitted to our intensive care unit. The secondary aim of our study was to compare the scoring systems used to predict mortality (APACHE II-IV, SOFA, GCS) and the relationship between parameters such as lactate, albumin, hemoglobin and mortality.

Statistical Analysis Statistical analysis was performed using the SPSS for Windows version 23.0 software package (IBM Corp., Armonk, NY, USA). Before this study, 95% power and 5% type 1 errors were predicted and the sample size was calculated as 180 patients, 90 patients in both groups. The descriptive data were expressed in mean, standard deviation (SD) for continuous variables and in number and percentage for categorical variables. The distribution of the variables was evaluated using the Kolmogorov-Smirnov test. The parametric and non-parametric tests were used to analyze normally and non-normally distributed variables, respectively. The Mann-Whitney U test was used to compare non-normal distribution, while the Student’s t-test was carried out to compare normal distribution between the groups. The relationship of the mortality with the blood parameters like NLR, PLR, and MPV in patients who underwent acute abdominal surgery logistic regression analysis was also carried out to examine the independent effect of each significant factor on the prediction of the mortality. The correlation analysis for continuous variables was performed using the Spearman’s correlation coefficient. A p-value of <0.05 was considered statistically significant. According to the results, the power of the study was calculated as 70.9%.

RESULTS Of a total of 249 patients included in this study, 132 (53%) were males and 117 (47%) were females. The mean age was 71.8±16.3 in females and 67.7±16.8 years in males (Table 1). A total of 126 patients (50.6%) were referred to the clinic, and 123 patients (49.4%) died. The mortality was 49.4% (Table 1). The mean age was higher in Group II than Group 1 (p=0.002). However, there was no significant correlation between sex and mortality (p=0.416) (Table 1). Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Çolakoğlu et al. Relationship of mortality with NLR, PLR, and MPV in patients undergoing acute abdominal surgery

Table 1. Demographic characteristics of the patient groups

Group I (n=126)

Age (mean±SD)

Group II (n=123)

Total

66.2±18.2

73.2±14.1

p 0.002*

Sex, n (%)

Female

56 (47.9)

61 (52.1)

117 (47)

Male

70 (53.0)

62 (47.0)

132 (53)

Total

126 (50.6)

123 (49.4)

249 (100)

416**

*Mann-Whitney U test, p<0.05 was considered statistically significant. **Chi-square test, p<0.05 was considered statistically significant. SD: Standard deviation.

Table 2. NLR, PLR, and MPV values of the patient groups

Group I

Neutrophil/Lymphocyte ratio Platelet/Lymphocyte ratio Mean platelet volume

Group II

Mean±SD Mean±SD 14.82±23.29

15.13±15.56

0.338

363.08±387.13

370.11±634.17

0.293

8.50±1.76

9.19±2.41

0.004

*Mann-Whitney U test, p<0.05 was considered statistically significant. NLR: Neutrophil/lymphocyte ratio; PLR: Platelet/lymphocyte ratio; MPV: Mean platelet volume; SD: Standard deviation.

Table 3. ROC analysis of the NLR, PLR, and MPV values

AUC p BTV Sensitivity* Specificity*

NLR 0.535 0.339 13.6136

41.46%

70.63%

PLR 0.539 0.296 172.3404

36.59%

78.57%

MPV 0.606 0.003 9.18

53.66%

70.63%

Sensitivity and specificity values at the highest point of the summed value of sensitivity and specificity in the ROC analysis. NLR: Neutrophil/ lymphocyte ratio; PLR: Platelet/lymphocyte ratio; MPV: Mean platelet volume; AUC: Area under the curve; BTV: Best threshold value; ROC: Receiver operating characteristic.

There was no statistically significant difference in the NLR and PLR values between the groups. However, the MPV values were significantly higher in Group II (p=0.004) (Table 2). The diagnostic value of the NLR and PLR was not statistically significant (Table 3). The cut-off value of MPV was 9.18 and area under the curve (AUC) value was 0.606 and considered a significant predictor for mortality (Table 3) (Fig. 1). In the survivor group, we found a weak but statistically significantly negative correlation between the NLR and albumin, Hb and platelets (r=-0.186, -0.218, -0.194; p<0.05) (Table 4). There was also a statistically significantly positive correlation between the PLR and platelets (r=0,220; p<0.05) (Table 4). We also found a weak but statistically significantly negative correlation between the MPV and albumin and platelets (r=0.182, -0.305; p<0.05) (Table 4). Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

There was a statistically significantly weak positive correlation between PLR and Platelet for the patients who died (r=0.313; p<0.05). There was a statistically significantly weak negative correlation between MPV and PLT (r-0.205; p<0.05) (Table 4). In Group II, APACHE II, APACHE IV, SOFA scores were significantly higher (p<0.001, p<0.001, p<0.001) (Table 5). There was not statistically significantly correlation between lactate levels, APACHE IV, SOFA, GCS score and NLR, PLR, MPV between the groups (Table 4).

DISCUSSION In the present study, we investigated the relationship between mortality and NLR, PLR, and MPV in patients who underwent acute abdominal surgery. Our study results showed that NLR and PLR were not correlated with mortality, while MPV was 737

Çolakoğlu et al. Relationship of mortality with NLR, PLR, and MPV in patients undergoing acute abdominal surgery

Table 4. Correlation analysis

Group I

Age

Group II

NLR PLR MPV NLR PLR MPV r

0.079 0.380 0.182 0.041 0.035 0.701 0.083 0.361 0.005 0.960 0.039 0.671

APACHE-II score -0.023 0.798 0.013 0.885 0.060 0.502 -0.047 0.605 -0.077 0.400 -0.022 0.808 APACHE-IV score -0.023 0.796 -0.011 0.904 -0.001 0.988 0.113 0.214 -0.082 0.368 0.130 0.152 SOFA score

-0.092 0.307 -0.004 0.968 0.030 0.741 0.049 0.590 -0.145 0.111 0.120 0.185

GCS score

-0.044 0.625 -0.170 0.057 0.145 0.106 0.145 0.110 0.102 0.263 -0.021 0.817

Lactate

0.006 0.946 -0.039 0.669 0.168 0.060 -0.069 0.446 -0.074 0.416 0.127 0.163

Albumin

-0.186 0.038 -0.133 0.139 -0.182 0.041 -0.041 0.656 0.029 0.752 -0.031 0.733

-0.218 0.015 -0.068 0.449 -0.061 0.495 -0.007 0.938 0.064 0.480 0.147 0.105

Platelets

-0.194 0.030 0.220 0.013 -0.305 0.001 -0.040 0.659 0.313 <0.001 -0.205 0.023

NLR: Neutrophil/lymphocyte ratio; PLR: Platelet/lymphocyte ratio; MPV: Mean platelet volume; ASA: American Society of Anesthesiologists; APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; GCS: Glasgow Coma Scale; Hb: Hemoglobin.

the NLR. However, we were unable to identify any significant threshold value in our study.

Table 5. Clinical scoring values by groups Group I

Group I

Mean±SD Mean±SD

APACHE-II score

19.8±7.8

26.6±7.9

<0.001*

APACHE-IV score

90.5±35.9

125.7±39.6

<0.001*

6.5±3.9

10.6±4.4

<0.001*

SOFA score

* Mann-Whitney U test, p<0.05 was considered statistically significant. SD: Standard deviation.

statistically significantly correlated with mortality. In clinical practice, various blood parameters have been used to predict prognosis and mortality in the intensive care setting. The NLR is the proportion of the neutrophil count, which reflects the severity of the inflammation, to the lymphocyte count, which is altered depending on the physiological stress. There are several studies in the literature using NLR as a marker in certain acute abdominal events, including mesenteric ischemia, peptic ulcer perforation, and acute cholecystitis, as a marker of lymph node metastasis in certain types of cancer and investigating its value in vascular events, such as aorta dissection and acute coronary syndrome, in rheumatic diseases, such as rheumatoid arthritis and ankylosing spondylitis, in the exacerbation of chronic obstructive lung disease, after acute tonsillitis and several infections such as deep neck infection.[5–10] In our study, we found no significant difference between the groups concerning the NLR values (for survivors: 14.82±23.39; for non-survivors: 15.13±15.56) (p=0.338). Although there are more than one threshold values in the literature, the AUC value was 0.535 in our ROC analysis of 738

Forget et al.[11] conducted a study to identify the lower and upper limits of NLR in healthy individuals and included participants between the ages of 12 and 66 years, who did not have any active disease, including malignancy and infectious diseases. The authors reported that the normal values of NLR were between 0.78 and 3.53. In another study conducted by Augène et al.[12] with patients with acute mesenteric ischemia, no statistically significant difference was found, even though patients with higher NLR tend to have higher mortality. 100

Sensitivity

20 NLO PLO MPV

0 0

100

100-Specificity

Figure 1. ROC analysis of NLR, PLR, and MPV values.

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Çolakoğlu et al. Relationship of mortality with NLR, PLR, and MPV in patients undergoing acute abdominal surgery

Mean platelet volume is an accurate measure of platelet size and reflects the reactivity of platelets. It is considered that it plays a key role in the activation of the thrombosis and platelets with the predisposition in the pathophysiology of inflammation.[13] Several studies have shown that changes in MPV have been observed during infection, sepsis, coronary artery disease, cerebrovascular diseases, arterial and venous thrombosis, and chronic inflammatory disorders.[14,15] In Beyazit et al.’s[16] study, the MPV values were prominently decreased in patients with acute pancreatitis, compared to the control group. In the aforementioned study, decreased MPV values were found to be associated with poor prognosis without any advantage over other inflammatory markers in predicting prognosis. However, in another study, the MPV values significantly increased in patients with complicated acute pancreatitis.[17] Kim et al.[18] showed that platelet count and MPV were higher in patients who died of severe sepsis and/or septic shock than those who survived the first 72 hours after admission. In a similar sepsis study, MPV was found to be significantly different between those who died and survived sepsis.[15] In our study, MPV values were higher in Group II than Group I (Group I: 8.50±1.76; Group II: 9.19±2.41), indicating statistical significance for mortality (p=0.004). The best threshold value of MPV for mortality was found to be 9.18, and the sensitivity, specificity, and AUC values were 53.66%, 70.63%, and 0.606, respectively. In the literature, the relationship between increased MPV and mortality was investigated in many disease groups and ICU patients. Although there is a significant relationship between comorbid diseases and MPV concerning mortality, there are studies showing that MPV value in intensive care patients is not associated with predicting mortality. In our study, we found a significant relationship between increased MPV and mortality. The platelet count is another hematological marker of inflammation, which has a predictive role in survival. It has been shown that MPV is an independent risk factor for poor survival in patients with pancreatic or colorectal cancer.[19,20] In another study involving 34 patients with acute mesenteric ischemia, it was found that PLR was significantly higher in patients who died compared to survivors (373.8–288.5, p=0.045).[21] Duman et al.[22] conducted a study on sepsis patients; however, they found no significant difference in the PLR values between the groups with and without mortality (p=0.336). In our study, similar to the study of Duman et al.,[22] we Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

found no statistically significant difference in the PLR values between the groups (Group I: 363.08±387.13; Group II: 370.11±634.17; p=0.293). The AUC value was 0.539 and a significant threshold value was unable to be identified. We also found that NLR and PLR could not be used as a predictor of mortality, although MPV could be used for this purpose. NLR and PLR are systemic inflammatory markers that may be affected by the comorbidities of patients.[23,24] In our study, we found that NLR and PLR were not usable in predicting mortality. In our study, blood samples were taken at the time of admission to the intensive care unit, not at the time of admission to the emergency department. We think that the follow-up, including the patient’s pre-operation, will be more meaningful. Furthermore, this study will be performed on more patients and this will increase the power of this study. In the ICUs, where the mortality is relatively high, albumin and Hb values are correlated with mortality. In another study, Jansen et al.[25] evaluated patients treated in the ICUs due to sepsis, hemorrhagic shock, and other conditions leading to low oxygen transportation and measured the arterial lactate levels at 12 and 24 h. A decline in the lactate levels at 24 h reduced mortality in the patients with sepsis. Furthermore, albumin levels can be used to predict the mortality risk. In our study, we found that the APACHE II-IV and SOFA scores were useful in the prediction of the mortality, which is consistent with the literature. All three scores were higher in the non-survivor patients, compared to the survivors. In the present study, the results of the scoring systems are consistent with the literature in patients who underwent acute abdominal surgery. Brinkman et al.[26] suggested that the APACHE IV was more reliable than APACHE II, considering the prediction of the mortality in the ICUs in the Netherlands. In addition, there are several studies using SOFA scores for the prediction of mortality. One of these studies, which is also consistent with our study findings, was conducted by Hwang SY et al.[27] The authors suggested that combined scoring systems could be used in the trauma patients. The first-day SOFA scores were significantly higher in the non-survivors, indicating that it may have a predictive value for the prolonged hospitalization durations. Nonetheless, there are some limitations to this study. First, the causes of the deaths were not recorded and classified. Second, our study has a single-center design with a small sample size. Third, the parameters were measured in the first blood samples taken after surgery, and a comparative study with serial measurements was unable to be carried out. Therefore, we believe that further large-scale, multi-center studies with serial measurements are needed to confirm our findings. 739

Çolakoğlu et al. Relationship of mortality with NLR, PLR, and MPV in patients undergoing acute abdominal surgery

Conclusion In conclusion, our study results demonstrated that NLR and PLR were not associated with mortality. On the other hand, MPV values were significantly higher in the non-survivors following acute abdominal surgery. Further studies are needed to gain a better understanding of the predictive role of these markers in this patient population. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Ş.M.Ç., D.G.M., B.T.Ç., G.O.H.; Design: Ş.M.Ç., D.G.M.; Supervision: D.G.M., G.O.H.; Fundings: Ş.M.Ç.; Materials: Ş.M.Ç., B.T.Ç.; Data: Ş.M.Ç., B.T.Ç.; Analysis: Ş.M.Ç., D.G.M., G.O.H.; Literature search: Ş.M.Ç., D.G.M., B.T.Ç., G.O.H.; Writing: Ş.M.Ç., D.G.M.; Critical revision: D.G.M. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Turan M, Şen M, Koyuncu A, Aydın C, Karadayı K, Canbay E. The Acute Abdomen with Recent Advances. Cumhurıyet University J Med School 2002;24:45−52. 2. Quach S, Hennessy DA, Faris P, Fong A, Quan H, Doig C. A comparison between the APACHE II and Charlson Index Score for predicting hospital mortality in critically ill patients. BMC Health Serv Res 2009;30:9:129. 3. Güç D. Inflammation. J Curr Med 1998;3:126−4. 4. Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001;102:5−14. 5. Aktimur R, Cetinkunar S, Yildirim K, Aktimur SH, Ugurlucan M, Ozlem N. Neutrophil-to-lymphocyte ratio as a diagnostic biomarker for the diagnosis of acute mesenteric ischemia. Eur J Trauma Emerg Surg 2016;42:363−8 6. Jung J, Park SY, Park SJ, Park J. Prognostic value of the neutrophil-to-lymphocyte ratio for overall and disease-free survival in patients with surgically treated esophageal squamous cell carcinoma. TumourBiol 2016;37:7149−54.

11. Forget P, Khalifa C, Defour JP, Latinne D, Van Pel MC, De Kock M. What is the normal value of the neutrophil-to-lymphocyte ratio?. BMC Res Notes 2017;10:12. 12. Augène E, Lareyre F, Chikande J, Guidi L, Ballaith A, Bossert JN, Pelletier Y, Caradu C, Hassen-Khodja R, Raffort J. Platelet to lymphocyte ratio as a predictive factor of 30-day mortality in patients with acute mesenteric ischemia. PLoS One 2019;14:e0219763. 13. Paraskevas F, Greer JP, Rodgers GM. Variations of leucocytes in disease. In: Wintrobe’s Clinical Hematology. Lee GR, Foerster J, Lukens J, editors. 10th edition. Baltimore: Lippincott Williams and Wilkins;1999.p.1836−61. 14. Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, et al. Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis. J Thromb Haemost 2010;8:148−56. 15. Azab B, Torbey E, Singh J, Akerman M, Khoueiry G, McGinn JT, et al. Mean platelet volume/platelet count ratio as a predictor of longterm mortality after non-ST-elevation myocardial infarction. Platelets 2011;22:557−66. 16. Beyazit Y, Sayilir A, Torun S, Suvak B, Yesil Y, Purnak T, et al. Mean platelet volume as an indicator of disease severity in patients with acute pancreatitis. Clin Res Hepatol Gastroenterol 2012;36:162−8. 17. Akbal E, Demirci S, Koçak E, Köklü S, Başar O, Tuna Y. Alterations of platelet function and coagulation parameters during acute pancreatitis. Blood Coagul Fibrinolysis 2013;24:243−6. 18. Kim CH, Kim SJ, Lee MJ, Kwon YE, Kim YL, Park KS, et al. An increase in mean platelet volume from baseline is associated with mortality in patients with severe sepsis or septic shock. PLoS One 2015;10:e0119437. 19. Smith RA, Bosonnet L, Raraty M, Sutton R, Neoptolemos JP, Campbell F, et al. Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma. Am J Surg 2009;197:466−72. 20. Kwon HC, Kim SH, Oh SY, Lee S, Lee JH, Choi HJ, et al. Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer. Biomarkers 2012;17:216−22. 21. Yılmaz EM, Cartı EB. Prognostic factors in acute mesenteric ischemia and evaluation with Mannheim Peritonitis Index and platelet-to-lymphocyte ratio. Ulus Travma Acil Cerrahi Derg 2017;23:301−5. 22. Duman A, Akoz A, Kapci M, Ture M, Orun S, Karaman K, Turkdogan KA. Prognostic value of neglected biomarker in sepsis patients with the old and new criteria: predictive role of lactate dehydrogenase. Am J Emerg Med 2016;34:2167−71. 23. Lin BD, Hottenga JJ, Abdellaoui A, Dolan CV, de Geus EJC, Kluft C, et al. Causes of variation in the neutrophil-lymphocyte and platelet-lymphocyte ratios: a twin-family study. Biomark Med 2016;10:1061−72.

7. Dirican N, Karakaya YA, Gunes S, Daloglu FT, Dirican A. Association of intra-tumoral tumour-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio is an independent prognostic factor in non-small cell lung cancer. Clin Respir J 2017;11:789−96.

24. Qin B, Ma N, Tang Q, Wei T, Yang M, Fu H, et al. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were useful markers in assessment of inflammatory response and disease activity in SLE patients. Mod Rheumatol 2016;26:372−6.

8. Zhou D, Wan Z, Fan Y, Zhou J, Yuan Z. A combination of the neutrophil-to-lymphocyte ratio and the GRACE risk score better predicts PCI outcomes in Chinese Han patients with acute coronary syndrome. Anatol J Cardiol 2015;15:995−1001.

25. Jansen TC, van Bommel J, Mulder PG, Lima AP, van der Hoven B, et al. Prognostic value of blood lactate levels: does the clinical diagnosis at admission matter? J Trauma 2009;66:377−85.

9. Tekeoğlu İ, Gürol G, Harman H, Karakeçe E, Çiftçi İH. Overlooked hematological markers of disease activity in rheumatoid arthritis. Int J Rheum Dis 2016;19:1078−82. 10. Sevim Y, Namdaroglu OB, Akpınar MY, Ertem AG. The diagnostic value of neutrophil lymphocyte ratio in acute appendicitis. Sakaryamj 2014;4:78−81.

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26. Brinkman S, Bakhshi-Raiez F, Abu-Hanna A, de Jonge E, Bosman RJ, Peelen L, et al. External validation of Acute Physiology and Chronic Health Evaluation IV in Dutch intensive care units and comparison with Acute Physiology and Chronic Health Evaluation II and Simplified Acute Physiology Score II. J Crit Care 2011;26:105.e11-105. e1.05E18. 27. Hwang SY, Lee JH, Lee YH, Hong CK, Sung AJ, Choi YC. Compari-

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Severity Score method for predicting the outcomes of intensive care unit trauma patients. Am J Emerg Med 2012;30:749−53.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut karın cerrahisi geçiren hastalarda, nötrofil-lenfosit oranı, trombosit-lenfosit oranı ve ortalama trombosit hacminin mortalite ile ilişkisi Dr. Şükran Merve Çolakoğlu,1 Dr. Döndü Genç Moralar,2 Dr. Büşra Tok Çekmecelioğlu,3 Dr. Gülsüm Oya Hergünsel2 Sağlık Bilimleri Üniversitesi, Gaziosmanpaşa Taksim Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Kliniği, İstanbul Sağlık Bilimleri Üniversitesi, Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Kliniği, İstanbul 3 Sağlık Bilimleri Üniversitesi, Sultan Abdulhamid Han Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Kliniği, İstanbul 1 2

AMAÇ: Akut karın cerrahisi sonrası yüksek oranda mortalite ve morbidite görülmekte, postoperatif dönemde sıklıkla yoğun bakım ihtiyacı olmaktadır. Yoğun bakım ünitelerinde, prognoz ve mortaliteyi belirlemek amacıyla çeşitli skorlama sistemleri kullanılmakta ancak mortalite ve prognozu öngörmede yeterli olmamaktadır. Bu amaçla kolay uygulanabilir, etkin yöntemler araştırılmaktadır. Biz bu çalışmada, akut karın cerrahisi geçiren hastalarda nötrofil-lenfosit oranı (NLO), trombosit-lenfosit oranı (TLO) ve ortalama trombosit hacmi (OTH) gibi kan parametrelerinin mortalite ile ilişkisini araştırmayı amaçladık. GEREÇ VE YÖNTEM: Bu çalışmaya, akut karın ameliyatı geçiren 249 hasta alındı. Hastalar sağ kalan (n=126) ve ölenler (n=123) olarak iki gruba ayrıldı. Hasta verileri retrospektif olarak incelendi. NLO, TLO ve OTH değerleri gruplar arasında karşılaştırıldı. Yaş, cinsiyet, Akut Fizyoloji ve Kronik Sağlık Değerlendirmesi II-IV skorları (APACHEII-IV), Sıralı Organ Yetmezliği Değerlendirme skorları (SOFA), Glasgow Koma Skalası gibi veriler değerlendirildi. BULGULAR: Çalışmamızda mortalite oranı %49.4 idi. NLO ve TLO değerlerinde gruplar arasında istatistiksel olarak anlamlı fark yoktu. Ancak, OTH ölenler grubunda anlamlı olarak yüksek bulundu (p<0.004). TARTIŞMA: Çalışma sonuçlarımız akut karın cerrahisi sonrası hayatını kaybedenlerde OTH değerlerinin anlamlı derecede yüksek olduğunu ve NLO ve TLO’nın mortalite ile ilişkili olmadığını göstermiştir. Anahtar sözcükler: Akut karın; bakım ünitesi; mortalite, nötrofil lenfosit oranı; ortalama trombosit hacmi; trombosit lenfosit oranı. Ulus Travma Acil Cerrahi Derg 2020;26(5):735-741

doi: 10.14744/tjtes.2020.81783

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ORIGIN A L A R T IC L E

Treatment of acute appendicitis: Urgent surgery or emergent surgery? Emre Bozkurt, M.D.,

Mustafa Fevzi Celayir, M.D.

Department of General Surgery, University Of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: The standard treatment of acute appendicitis, which is a rapidly progressive inflammatory disease, remains surgery. However, several studies have suggested antibiotics treatment for acute appendicitis, especially in centers where surgery at all hours is not possible. Therefore, in this study, we investigated the relationship between the preoperative waiting period and postoperative complications in patients who underwent interval surgery following conservative management during the same admission. METHODS: All patients who were diagnosed with uncomplicated acute appendicitis between October 2014 and February 2015 and underwent surgery at a single center were included in this retrospective study. Patients were divided into two groups based on the waiting period between the diagnosis and the time of surgery: group A (emergency, waiting period <10 h) and group B (urgency, waiting period ≥10 h). The demographic features, preoperative waiting period, antibiotics use, pathological diagnosis, postoperative complications, length of hospital stay, and readmission were compared between the two groups. RESULTS: This study comprised 160 patients, including 79 and 81 patients in groups A and B, respectively. The demographic features, comorbidities, and pathological diagnosis were comparable between the two groups. The average preoperative waiting period was significantly longer in group B than in group A. However, the mean length of hospital stay and the rate of postoperative complications, including infections at the surgical sites and intra-abdominal abscesses, were similar between the two groups. CONCLUSION: Our analyses revealed that there were no disadvantages associated with a longer preoperative waiting period in patients diagnosed with uncomplicated appendicitis. Keywords: Appendicitis; delayed appendectomy; medical therapy; uncomplicated appendicitis.

INTRODUCTION Acute appendicitis (AA) is the most common cause of acute abdomen,[1] for which standard therapy is surgery; the mortality rate of AA ranges between 0.07% and 0.7%.[2,3] The mechanism underlying AA includes abdominal wall necrosis following a decrease in blood and lymph flow after luminal obstruction, and the delayed diagnosis of AA leads to perforation. Although emergent surgical intervention is considered to prevent the progression of AA, the effects of emergent appendectomy on morbidity and mortality have been reported to have limited benefits based on accumulating evidence. In addition, recent reports regarding pediatric patients have indicated that surgical treatment can be safely postponed with

effective fluid and antibiotic therapy.[4–6] Therefore, the waiting period is considered to not contribute to increased morbidity in patients who have to wait for mandatory reasons. We, therefore, investigated whether AA in adult patients was a surgical emergency requiring immediate intervention and assessed the relationship between preoperative waiting time and postoperative complications.

MATERIALS AND METHODS This retrospective study included all the patients who were diagnosed with uncomplicated AA between October 2014 and February 2015 at the study institution. Ethics approv-

Cite this article as: Bozkurt E, Celayir MF. Treatment of acute appendicitis: Urgent surgery or emergent surgery?. Ulus Travma Acil Cerrahi Derg 2020;26:742-745. Address for correspondence: Emre Bozkurt, M.D. Sağlık Bilimleri Üniversitesi, Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 373 50 00 E-mail: dr.emrebozkurt@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):742-745 DOI: 10.14744/tjtes.2020.23236 Submitted: 05.12.2019 Accepted: 13.06.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Bozkurt et al. Treatment of acute appendicitis: Urgent surgery or emergent surgery?

al was not required for this retrospectively designed study (analysing of pre-existing data). This study was conducted in accordance with the 1964 Helsinki Declaration. Informed consent was obtained from all subjects, and all methods were carried out in accordance with the relevant guidelines and regulations. While the inclusion criteria were as follows: (1) age between 18-65 years, (2) no additional comorbidity, (3) patients with final pathological diagnosis as AA, the exclusion criteria were as follows: (1) age, <18 years or >66 years; (2) patients undergoing additional surgical procedures concomitantly with appendectomy; (3) pregnancy; (4) requirement for intensive care; and (5) patients with incidental, interval, and negative appendectomies. Demographical data, comorbidities, the time interval between the diagnosis and surgery, operation time, length of hospital stay, antibiotics use, analgesic requirement, pathological diagnosis, and readmission status were included. On the basis of our review of similar studies, the patients who fulfilled the inclusion and exclusion criteria were classified into the following two groups: group A comprising patients with a preoperative waiting time of <10 h (emergent appendectomy) and group B comprising patients with a preoperative waiting time of ≥10 h (urgent appendectomy). The patient characteristics were compared between the two groups. Antibiotic prophylaxis was performed with 1-g cefazolin sodium (Mustafa Nevzat, Istanbul, Turkey) within one h of the AA diagnosis in all patients. The results were analyzed using SPSS version 21.0 (IBM, Armonk, NY, USA). Continuous variables were expressed as

means ± standard deviation (SD) or medians (range) on the basis of data distribution, whereas categorical variables were presented as absolute values and percentages. Differences in continuous variables between the two groups were assessed using Student’s t-test for normally distributed variables and the Mann–Whitney U test for non-normally distributed variables. Differences in categorical variables were assessed using Fisher’s exact or chi-square tests. A P-value of less than 0.05 was considered to indicate statistical significance.

RESULTS A total of 160 patients diagnosed with AA between October 2014 and February 2015 and fulfilled the study criteria were included in the present study. Groups A and B included 79 and 81 patients, respectively, with F/M ratios of 23/56 and 27/54, respectively. The mean ages were 31.9±11.5 (range, 18–66) and 30.8±8.8 (range, 18–65) years in groups A and B, respectively (p=0.882). No significant difference was noted in the comorbidity rates between the two groups (p=0.339). In groups A and B, the mean preoperative waiting periods were 4.4±2.0 (range, 1–9) and 15.1 ± 4.3 (range, 10–32) h (p<0.001), and the mean operation times were 50.3±16.2 (range, 20–90) and 54.0±12.6 (range, 20–80) min (p=0.040), respectively. The mean length of hospital stay was 30.4±13.5 (range, 8–96) h in group A and 30.3±8.3 (range, 11–48) h in group B (p=0.391) (Table 1). Wound infections were observed in three patients (3.8%) in group A and in five patients (6.17%) in group B, which did not significantly differ between the two groups (p=0.720).

Table 1. Comparison of the surgical details between the two study groups

Group A

Group B

Mean±SD Min-Max Mean±SD Min-Max

Preoperative waiting period (h)

4.4±2.0

1–9

15.1±4.3

10–32

<0.001

Operation time (min)

50.3±16.2 20–90 54.0±12.6 20–80 0.040

Hospital stay (h)

30.4±13.5

8–96

30.3±8.3

11–48

0.391

SD: Standard deviation.

Table 2. Comparison of the postoperative features between the two study groups In-hospital SSIs

Group A

Group B

n (79) % n (81) % 3 3.8 5 6.2 0.720

Intra-abdominal abscess

– – 2 2.5 0.497

Antibiotic use

79 100 80 98.8 1.000

Narcotic analgesic requirement

8.9

11.1

0.343

SSI: Surgical site infection.

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Furthermore, the intra-abdominal abscesses, which were observed only in two patients in group B, did not significantly differ between the two groups (p=0.497). No significant differences were noted in the rates of antibiotic and analgesic use between the two groups (p=1.000 and 0.343, respectively) (Table 2). According to the pathological assessment, 75 (94.9%), three (3.8%), and one (1.3%) patient in group A received the definitive diagnoses of AA, lymphoid hyperplasia, and mucinous neoplasia, respectively. In group B, 78 (96.3%) and three (3.7%) patients were definitively diagnosed with AA and lymphoid hyperplasia, respectively, based on the pathological assessment. No significant difference was noted in the distribution of the definitive diagnoses between the two groups (p=0.837).

DISCUSSION Appendectomy is the most frequently performed emergency surgery by general surgeons.[7,8] Following diagnosis, patients are usually treated within a few hours for preventing the progression of inflammation. Studies have shown that AA can be treated without interval appendectomy, especially in patients with plastron appendicitis.[9–11] Antibiotic therapy has also been demonstrated to be successful without surgery in select cases of uncomplicated AA.[12,13] The ideal timing for surgery in patients who require surgery remains a focus of debate. Certain studies have suggested that the outcomes are better with emergent appendectomy than with delayed appendectomy.[13–17] In contrast to these studies suggesting that delayed surgery for appendicitis is associated with increased rates of postoperative complications, such as surgical site infections, other studies have reported no significant differences in the complication rates between early and late appendectomies.[4,18,19] Moreover, some studies have shown that fatigue and the lack of sleep adversely affect the clinical performance and cognitive skills of the surgeons during immediate appendectomies performed at night or at the end of long shifts in the operating room, leading to an increase in complication rates.[20,21] In the present study, we found that delaying the surgery for several reasons (fasting status of the patient and the order of urgency of waiting operations) following the diagnosis of AA in the emergency department was not associated with increased complication rates or increased length of hospital stay. One likely explanation for these findings is the initiation of treatment with antibiotics and fluid support in patients with a waiting period of more than 10 h, which may allow the control of inflammation. Accordingly, no significant differences were noted in the rates of postoperative surgical site infections or intra-abdominal abscesses between the patients treated with emergency surgery and patients treated with urgent surgery. However, Busch et al.[22] reported that an in-hospital delay of more than 12 h was associated with 744

increased rates of perforation and other complications. Furthermore, Teixeira et al.[13] reported that an in-hospital delay of more than six h led to an increased surgical site infection rate independently of other factors. Giraudo et al.[17] reported a significant increase in the complication rates between the delayed (≥24 h) and early (<24 h) appendectomy groups. However, two other retrospective studies reported that no significant differences were noted in the complication rates between the early (<12 h) and late (12–24 h) groups.[5,23] A meta-analysis found that delays over 48 h were associated with increased wound infection rates.[24] Patients with AA can wait for more than 10 h for surgery at our center, which is a high-volume trauma center with a 24-hour surgical team on duty. Patients with AA can be maintained with fluid resuscitation and intravenous antibiotic therapy, excluding patients with perforation, who are pregnant, and those exhibiting sepsis symptoms. No differences were noted in the patient outcomes, complications, and the length of hospital stay between the patients treated with emergency surgery and patients treated with urgent surgery. In conclusion, patients receiving antibiotic and fluid therapy, with the exclusion of high-risk patients, can be safely maintained for up to 24 h although AA requires surgery. These findings derived from retrospective data should be substantiated in prospective studies. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: E.B., M.F.C.; Design: E.B., M.F.C.; Supervision: E.B., M.F.C.; Fundings: E.B., M.F.C.; Materials: E.B., M.F.C.; Data: E.B., M.F.C.; Analysis: E.B., M.F.C.; Literature search: E.B., M.F.C.; Writing: E.B., M.F.C.; Critical revision: E.B., M.F.C. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Humes DJ, Simpson J. Acute appendicitis. BMJ 2006;333:530−4. 2. Blomqvist P, Ljung H, Nyrén O, Ekbom A. Appendectomy in Sweden 1989-1993 assessed by the Inpatient Registry. J Clin Epidemiol 1998;51:859−65. 3. Margenthaler JA, Longo WE, Virgo KS, Johnson FE, Oprian CA, Henderson WG, et al. Risk factors for adverse outcomes after the surgical treatment of appendicitis in adults. Ann Surg 2003;238:59−66. 4. Yardeni D, Hirschl RB, Drongowski RA, Teitelbaum DH, Geiger JD, Coran AG. Delayed versus immediate surgery in acute appendicitis: do we need to operate during the night?. J Pediatr Surg 2004;39:464−9. 5. Surana R, Quinn F, Puri P. Is it necessary to perform appendicectomy in the middle of the night in children?. BMJ 1993;306:1168. 6. Bachoo P, Mahomed AA, Ninan GK, Youngson GG. Acute appendicitis: the continuing role for active observation. Pediatr Surg Int 2001;17:125−8. 7. Pittman-Waller VA, Myers JG, Stewart RM, Dent DL, Page CP, Gray GA, et al. Appendicitis: why so complicated? Analysis of 5755 consecu-

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Bozkurt et al. Treatment of acute appendicitis: Urgent surgery or emergent surgery? tive appendectomies. Am Surg 2000;66:548−54. 8. Lee HJ, Park YH, Kim JI, Choi PW, Park JH, Heo TG, et al. Comparison of clinical outcomes and hospital cost between open appendectomy and laparoscopic appendectomy. J Korean Surg Soc 2011;81:321−5. 9. Andersson RE, Petzold MG. Nonsurgical treatment of appendiceal abscess or phlegmon: a systematic review and meta-analysis. Ann Surg 2007;246:741−8. 10. Lugo JZ, Avgerinos DV, Lefkowitz AJ, Seigerman ME, Zahir IS, Lo AY, et al. Can interval appendectomy be justified following conservative treatment of perforated acute appendicitis? J Surg Res 2010;164:91−4. 11. Kaya C, Demir U, Arısoy M, Okul Ş, Bostancı Ö, Köksal HM, et al. Does interval appendectomy necessary for the patients diagnosed as appendicular masses? SETB 2012;46:189−92. 12. Sakorafas GH, Mastoraki A, Lappas C, Sampanis D, Danias N, Smyrniotis V. Conservative treatment of acute appendicitis: heresy or an effective and acceptable alternative to surgery?. Eur J Gastroenterol Hepatol 2011;23:121−7. 13. Teixeira PG, Sivrikoz E, Inaba K, Talving P, Lam L, Demetriades D. Appendectomy timing: waiting until the next morning increases the risk of surgical site infections. Ann Surg 2012;256:538−43. 14. Udgiri N, Curras E, Kella VK, Nagpal K, Cosgrove J. Appendicitis, is it an emergency?. Am Surg 2011;77:898−901. 15. Ditillo MF, Dziura JD, Rabinovici R. Is it safe to delay appendectomy in adults with acute appendicitis?. Ann Surg 2006;244:656−60. 16. Earley AS, Pryor JP, Kim PK, Hedrick JH, Kurichi JE, Minogue AC,

et al. An acute care surgery model improves outcomes in patients with appendicitis. Ann Surg 2006;244:498−504. 17. Giraudo G, Baracchi F, Pellegrino L, Dal Corso HM, Borghi F. Prompt or delayed appendectomy? Influence of timing of surgery for acute appendicitis. Surg Today 2013;43:392−6. 18. Nagpal K, Udgiri N, Sharma N, Curras E, Cosgrove JM, Farkas DT. Delaying an appendectomy: is it safe? Am Surg 2012;78:897−900. 19. Stahlfeld K, Hower J, Homitsky S, Madden J. Is acute appendicitis a surgical emergency?. Am Surg 2007;73:626−30. 20. Eastridge BJ, Hamilton EC, O’Keefe GE, Rege RV, Valentine RJ, Jones DJ, et al. Effect of sleep deprivation on the performance of simulated laparoscopic surgical skill. Am J Surg 2003;186:169−74. 21. Kahol K, Leyba MJ, Deka M, Deka V, Mayes S, Smith M, et al. Effect of fatigue on psychomotor and cognitive skills. Am J Surg 2008;195:195−204. 22. Busch M, Gutzwiller FS, Aellig S, Kuettel R, Metzger U, Zingg U. In-hospital delay increases the risk of perforation in adults with appendicitis. World J Surg 2011;35:1626−33. 23. Abou-Nukta F, Bakhos C, Arroyo K, Koo Y, Martin J, Reinhold R, et al. Effects of delaying appendectomy for acute appendicitis for 12 to 24 hours. Arch Surg 2006;141:504−6; discussioin 506−7. 24. United Kingdom National Surgical Research Collaborative, Bhangu A. Safety of short, in-hospital delays before surgery for acute appendicitis: multicentre cohort study, systematic review, and meta-analysis. Ann Surg 2014;259:894−903.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut apandisit tedavisinde acil cerrahi veya gecikmiş cerrahinin yeri Dr. Emre Bozkurt, Dr. Mustafa Fevzi Celayir Sağlık Bilimleri Üniversitesi, Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul

AMAÇ: Akut apandisit, hızla ilerleyen bir iltihabi hastalık olup, standart tedavisi acil cerrahi girişimdir. Bununla birlikte, son zamanlarda bazı olgularda yarı elektif olarak apendektomi planlanabileceği konusunda görüşler belirtilmektedir. Bu çalışmamızdaki amacımız zorunlu nedenlere bağlı ameliyatın ertelendiği durumlarda ve komplike olmayan olgularda sıvı ve antibiyotik tedavisi altında güvenli olarak apendektomi uygulanabileceğini ortaya koymaktır. GEREÇ VE YÖNTEM: Çalışmamız Ekim 2014–Şubat 2015 tarihleri arasında akut apandisit ön tanısı ile apendektomi yapılmış 160 olguyu içermektedir. Hastalar, ameliyat öncesi bekleme süresi 10 saat altı ve üstü olacak şekilde iki gruba ayrıldı ve patoloji sonuçları, komplikasyon oranları ve hastanede kalış sürelerine göre karşılaştırıldı. BULGULAR: Çalışmaya 160 hasta alındı. Grup A’da 79, Grup B’de 81 hasta vardı. Hastaların demografik verileri, patoloji raporları ve komorbid durumları incelendiğinde istatistiksel anlamlı fark yoktu. Ortalama ameliyat öncesi bekleme süresi ve ameliyat süreleri karşılaştırıldığında gruplar arasında anlamlı fark saptandı. Hastaneden kalış süreleri, yara yeri enfeksiyonu ve karıniçi apse açısından her iki grup arasında anlamlı fark saptanmadı. TARTIŞMA: Komplike olmayan akut apandisit tanısı alan hastaların, acil serviste ameliyat öncesi uygun medikal tedavi ve gözlem altında geçirdiği bekleme süresinin, komplikasyon ve hastanede yatış süresi üzerine olumsuz etkisi yoktur. Anahtar sözcükler: Apandisit; gecikmiş apendektomi; komplike olmayan apandisit; medikal tedavi. Ulus Travma Acil Cerrahi Derg 2020;26(5):742-745

doi: 10.14744/tjtes.2020.23236

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ORIGIN A L A R T IC L E

Comparison of early and delayed diagnosis of mortality in ERCP perforations: A high-volume patient experience Ersin Borazan, M.D.,1

Buğra Tolga Konduk, M.D.2

Department of General Surgery, Gaziantep University Faculty of Medicine, Gaziantep-Turkey

Department of Gastroenterology, Gaziantep University Faculty of Medicine, Gaziantep-Turkey

ABSTRACT BACKGROUND: Although ERCP (Endoscopic retrograde cholangiopancreatography) perforation is a rare complication, it results in high morbidity and mortality. In this study, clinical evaluation was performed concerning the incidence, clinical data and time of diagnosis for ERCP perforations that were either surgically or medically treated. To reduce the ERCP perforations and related mortality, in this study, we aimed to reveal the clinical features and compare them with the literature. METHODS: In this clinical retrospective study, 51 perforations were detected in 8676 ERCP procedures performed in the past eight years in our hospital. We compared the two groups: early diagnosed patients [Group 1: n=40] and the delayed diagnosed patients [Group 2: n=11] concerning primary diagnosis, blood and biochemical tests before ERCP, perforation type, treatment method, clinical features, length of stay, and mortality. These groups were compared concerning stent placement, papillotomy choledochal dilatation and the number of ERCP procedures. RESULTS: The ERCP perforation rate in our hospital was 0.59%. The majority of patients who underwent ERCP procedures was due to the choledocholithiasis and periampullary tumors. The mean age was 62.78±17.13 (24–89 years old) and 56.9% of the patients (n=29) were women. Stapfer type II perforations (49%) were the most common type of perforation. However, 62.5% of the total mortality occurred in patients with type I perforation. The overall mortality rate was 13.72% (n=7). The duration of hospitalization (13.38±10.09 days) was higher in the patients who were treated surgically (n=24). Choledochal stents were utilized mostly in the medically treated patients (74.1%) (p=0.039). The patients in Group 1 were detected visually by the operator during the ERCP by leakage of contrast substance (13/40) or by abdominal tomography due to clinical suspicion. Patients in Group 2 had higher pre-ERCP leukocyte levels (p=0.044). The urgent surgery requirement in Group 2 was 72.7%, while the mortality rate was 36.4%. Significant mortality difference was observed between the early and late detection of perforations, indicating a higher rate in Group 2 (p=0.014). CONCLUSION: In the patients who were diagnosed early, fewer surgical interventions were required, except for the type I perforations. Type II perforations can often be safely treated non-surgically if there are no signs of acute abdomen and sepsis. Early diagnosis and treatment significantly reduce ERCP-related mortality. Keywords: Early diagnosis; endoscopic retrograde cholangiopancreatography; mortality; perforation; surgery.

INTRODUCTION Endoscopic retrograde cholangiopancreatography (ERCP), as an invasive procedure, has been often used in the diagnosis and treatment of pancreatic and biliary diseases. Although ERCP-associated perforation is a rare complication, it may result in high mortality. The use of ERCP for diagnostic pur-

poses has dramatically decreased with the increased usage of magnetic resonance cholangiopancreatography and endoscopic ultrasonography. According to the commonly used Stapfer classification, there are four types of ERCP perforations that have been identified. The anatomical localization of ERCP associated perforation

Cite this article as: Borazan E, Konduk BT. Comparison of early and delayed diagnosis of mortality in ERCP perforations: A high-volume patient experience. Ulus Travma Acil Cerrahi Derg 2020;26:746-753. Address for correspondence: Ersin Borazan, M.D. Gaziantep Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Gaziantep, Turkey Tel: +90 342 - 360 60 60 / 76322 E-mail: ersinborazan@gantep.edu.tr Ulus Travma Acil Cerrahi Derg 2020;26(5):746-753 DOI: 10.14744/tjtes.2020.61289 Submitted: 31.03.2020 Accepted: 30.05.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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determines whether the need for surgical intervention.[1] The most common type of the perforation is retroduodenal perforations which are seen in the range of 0.5 to 2.1% of all sphincterotomies during an ERCP procedure.[2] When performed by highly experienced endoscopists, the rate of perforation decreases below 0.5%.[3,4] Intraperitoneal duodenal perforations generally require surgical intervention, while other types of perforations may be treated with choledochal stenting in most of the cases and medical treatment. Although there have been many studies highlighting that the delay of diagnosis in ERCP perforation may result in critical clinical outcomes, there is no consensus on which terms the early and late diagnosis time is determined. Some studies reported that early diagnosis times cover the first 28 hours after the initiation of the ERCP procedure.[4â&#x20AC;&#x201C;6] However, there are not many studies focusing on a comparison of the outcomes between the early and late diagnosis times in ERCP perforations. This study aims to evaluate the patients who were treated surgically or medically following the diagnosis of ERCP perforation concerning their incidence, clinical features and time of diagnosis. To reduce ERCP perforations, the further aim was to reveal clinical data, compare it with the literature, and protect patients from the complications that may result in mortality.

MATERIALS AND METHODS This clinical retrospective study was conducted following the approval of the ethics committee with the number of 2019/381 on 02.10.2019. In this study, the medical records of 51 patients who were followed up and treated with ERCP perforation among all ERCP procedures (n=8676) between November 2010 and March 2018 were examined retrospectively from the hospital records. All ERCP perforations were divided into two groups according to the time of diagnosis: the patients with perforation noticed or suspected during ERCP, who were diagnosed and started to be treated within the first 24 hours, were classified as the early diagnosis group (Group 1) while the patients with the diagnosis of ERCP perforation after 24 hours were classified as the delayed diagnosis group (Group 2). In the early period, the diagnosis of perforation was either diagnosed radiologically by contrast leakage during the procedure, by visual detection of perforation during endoscopy, or by post-ERCP abdominal tomography if the endoscopist suspected a perforation during the procedure. The delayed diagnosis perforation was made with the abdominal tomography following either the abdominal pain exacerbated 24 hours after the procedure, fever or examination findings of the acute abdominal syndrome. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

After clinical and demographic characteristics of all cases were examined, ERCP perforations were classified according to the Stapfer classification system.[1] This classification was selected since it is the most frequently used and directs the anatomical localization of the perforation, the severity of the injury and the need for surgical interventions. The four types of perforations include Stapfer Type I perforation (acute perforation of the medial or lateral wall of the duodenum intraperitoneally before choledochal cannulation utilizing a lateral-view endoscope); Type II perforation (perforation of the peripapillary duodenum during sphincterotomy); Type III perforation (bile duct perforation with a guidewire, choledochal stenting or stone extraction,), and Type IV perforation (patients having air in retroperitoneum due to excessive insufflation). We compared the mortality in the early and delayed diagnosis groups concerning primary disease diagnoses, blood and biochemical tests before ERCP, perforation type, treatment method, clinical features and duration of hospitalization. In addition, during ERCP, papillary interventions were compared concerning stent placement, choledochal dilatation and the number of ERCP procedure attempts for a specific patient if needed more than once. We managed the medical and surgical surveillances of our perforation cases following the algorithm suggested by Miller et al.[7] In statistical analyses, the normal distribution of the data was tested using Kolmogorov Smirnov and Shapiro-Wilk. The test revealed that our data were not normally distributed (p<0.05). Therefore, the Mann-Whitney U test was used to compare all biochemical values in the groups. Chi-square analysis was used to analyze ERCP related procedures and clinical parameters in the groups. All statistical analyses were performed using SPSS 22.0 program, while p<0.05 was set as the significance level.

RESULTS Between November 2010 and March 2018, 8676 ERCP procedures were performed in the Gastroenterology Department of our Hospital. In this study, 51 ERCP perforations (0.59%) were followed up and treated in General Surgery and Gastroenterology Clinics during this period. The mean age of ERCP perforations was 62.78Âą17.13 (ranging from 24 to 89 years old) while 56.9% of the patients (n=29) were women. According to the Stapfer classification, type II perforations (49%) were the most commonly observed type of perforation in our patients. However, most of the mortality seen among all of the patients was due to type I perforations (62.5%). Concerning the clinical features of all patients (Table 1), the choledochal diameter was larger than 8 mm in 70.6% of the patients. Papillary sphincterotomy procedure was performed 747

Borazan et al. Comparison of early and delayed diagnosis of mortality in ERCP perforations: A high-volume patient experience

to 80.4%, while stenting was performed to 60.8% of the patients. Only 24 of ERCP perforations were surgically treated while conservative medical follow-up and treatment was applied to the other 27 patients. The hospitalization duration of the patients who were treated surgically (13.38±10.09 days) was significantly higher than that of the patients treated medically (4.19±2.86 days) (p=0.001). More choledochal stents were placed into the patients who were medically treated, compared to patients treated with surgery (74.1% vs. 45.8%, respectively) (p=0.039). Total mortality following the ERCP perforation was seen in only seven patients (13.72%). Choledocholithiasis and periampullary tumors were the majority of the primary diagnoses of the patients (Table 2). A percentage of 78.4% of ERCP perforations (n=40) were detected early period (Group 1). However, only 13 of 40 patients were detected using contrast agent leakage. The vast majority of the ERCP perforations were detected visually by the physician’s experience during the procedure or

by postoperative computerized abdominal tomography due to the possibility for ERCP perforation. On the other hand, 21.6% of the total patients were diagnosed with ERCP perforation in the late period (Group 2) (n=11). More clinical and biochemical comparisons of the groups are seen in Table 3. No statistically significant differences were observed among the Stapfer perforation types concerning the blood values before ERCP, biochemical values, time of diagnosis or duration of hospitalization (p>0.05). In 88.2% of all ERCP perforation patients (n=45), after applying sphincterotomy or choledochal stenting or stone extraction for primary disease, the perforation was noticed towards the end of the ERCP or after the procedure. In the other six patients, the perforation was detected early during ERCP without choledochal cannulation or sphincterotomy; therefore, the procedure was terminated. Since Stapfer type I perforation occurred in these patients, duodenal primary repair and peritoneal drainage surgery were performed for

Table 1. General, clinical and demographic features of the ERCP perforations

Patient (n=51)

Age

62.78±17.13

(24–89)

29/22

59.9%/40.1%

Type 1

31.4%

Gender (female/male) Stapfer perforation classification

Type 2

49.0%

Type 3

13.7%

Type 4

5.9%

Choledochal diameter (>8 mm)

70.6%

Papillotomy

41 80.4%

Choledochal stenting

60.8%

78.4%

Early detection of perforation (within 24 hours) Choledochal stone extraction with ERCP

22/27

Surgical treatment

47.06%

ERCP: Endoscopic retrograde cholangiopancreatography.

Table 2. The primary diagnosis of patients before ERCP procedure Diagnoses

Group 1 (Early diagnosis) n=40

Group 2 (Delayed diagnosis) n=11

Total

Choledocholithiasis

5 32

Periampullary tumor

Postoperative choledochal stricture

Klatskin tumor

A postoperative bile leak

Periampullary diverticulum, papillary adenoma

ERCP: Endoscopic retrograde cholangiopancreatography.

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Table 3. The comparisons between ERCP perforation groups

Group 1 (n=40)

Stapfer classification [Type I/II/III/IV] Surgical treatment

Group 2 (n=11)

p-values

11/22/6/1

5/3/1/2

0.108

16/40 (40%)

8/11 (72 7%)

0.054

Multiple ERCP procedure (2 or more procedures)

9/40

3/11

0.741

Choledochal diameter (>8 mm)

30/40

6/11

0.187

Choledochal cannulation

30/40

10/11

0.256

Choledochal stenting

26/40

5/11

0.240

Papillotomy

30/40

11/11 0.064

Contrast leak

12/40

1/11

0.159

7.43±6.28

12.55±13.60

0.713

32.28±33.98

71.94±72.47

0.270

Lenght of hospitalization (days) Pre-ERCP laboratory values

C-reactive protein (mg/L)

Leukocyte (103/μL)

8.77±3.87 12.31±5.73 0.044

Neutrophil (103/μL)

6.41±3.77 8.78±5.39 0.119

Lymphocytes (103/μL)

1.51±0.73 2.54±2.22 0.276

Total bilirubin (mg/dL)

5.68±5.67

7.14±8.49

0.991

Direct bilirubin (mg/dL)

4.26±5.18

4.50±5.81

0.963

Alkaline phosphatase (U/L)

300.33±228.70

325.64±340.12

0.590

Gamma Glutamyl Transferase (U/L)

380.05±366.13

439.55±481.63

0.837

Alanine transaminase (U/L)

136.34±157.56

191.00±261.69

0.360

Aspartate transaminase (U/L)

102.38±111.67

194.00±341.97

0.372

Amylase (U/L)

117.23±127.07

150.64±165.11

0.565

Albumin (g/L)

3.64±0.59

3.52±0.92

0.973

Mortality

3/40

4/11 0.014

ERCP: Endoscopic retrograde cholangiopancreatography.

them. When all perforations were evaluated together, we observed that surgical procedures, such as choledochotomy, stone extraction, and t-tube placement, were performed in 11 patients during the same hospitalization for their primary diseases. Types of Management Therapy Surgery

Medical

100 90 80

70 60 50

5 1

40 30 20 10 0

4 G1 Stapfer 1 G1 Stapfer 2

G1 Stapfer 3 G1 Stapfer 4 G2 Stapfer 1 G2 Stapfer 2 G2 Stapfer 3

G2 Stapfer 4

Figure 1. Frequency of the various types of management therapy according to the groups. G1: Group 1 (The early diagnosed patients); G2: Group 2 (The delayed diagnosed patients).

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Group 1 and 2 patients were compared concerning treatment by Stapfer injury type (Fig.1). Duodenal primary repair and peritoneal drainage surgery were performed for all patients in the Stapfer type I injury group. In Stapfer type II injury group, the rate of surgery in group 1 was 18.2%, and only one of these patients underwent duodenal primary repair. Cholecystectomy, choledochal t-tube application, and peritoneal drainage were performed for the other patients in this group. In the delayed diagnosed group, the rate of surgery was 66.6%. The surgical decisions were made in both patients due to acute abdominal and sepsis findings. In the Stapfer type III injury group, t-tube application and peritoneal drainage surgery were performed in one patient in each group while all patients were treated medically in the Stapfer type IV injury group. ERCP perforations were diagnosed in the patients with delayed diagnosis (Group 2) (n=11) using abdominal tomography following abdominal pain. The abdominal tomography revealed widespread free air densities in intraabdominal and/ or retroperitoneal, perirenal, periampullary regions. An urgent surgical treatment was required for 72.7% of patients in the group 2. In this group, ten patients received choledochal 749

Borazan et al. Comparison of early and delayed diagnosis of mortality in ERCP perforations: A high-volume patient experience

cannulation, five patients received choledochal stenting, and all had papillotomy. Anterior incision with a needle-tipped papillotomy was required in only one patient. Three patients who were followed-up medically without surgery were in the Stapfer II and Stapfer IV perforations. Among these three patients, one patient had already a stent from the previous ERCP session, and the other two were patients with choledochal stenting during the procedure.

the past eight years in our clinic. The findings of this study showed that the mortality rate of patients who diagnosed and were treated early was significantly lower compared to patients who were diagnosed late. Another finding was that surgical treatment was also higher in lately diagnosed patients. Moreover, the patients with Stapfer type II and III perforations that endoscopically had choledochal stenting had successful outcomes.

Four of the patients (36.4%) in the Group 2 had a mortal course. The causes of mortality were found to be related to septic shock in two patients, while postoperative myocardial infarction accompanied by septicemia and recurrent atrial fibrillation for other two patients. The characteristics of patients with late detection of ERCP perforation are shown in Table 4.

Similarly, in the examination of 14045 patients over 10 years, Bill et al.[4] reported that there was a lower incidence of systemic inflammatory response syndrome, less need for intensive care, and shorter hospital stay for patients whose ERCP perforation was detected during the ERCP procedure.[4] Although the mortality rate difference between the early and delayed diagnosis was not significant in all ERCP perforations, they showed that delayed diagnosis increased mortality in especially type I and type II perforations. Although it did not reach the level of statistically significance in our study, the duration of hospitalization was also shorter in the patients who were diagnosed early. In fact, this was due to the relatively extended length of required hospital stay for the patients who had to be treated surgically. It was also noteworthy that pre-ERCP leukocyte values were found to be high in patients who were delayed diagnosed perforation.

Compared to the group diagnosed early, leukocyte levels were found to be higher in patients whose ERCP perforation was detected after 24 hours of the procedure (p=0.044). Concerning mortality, a statistically significant difference was observed between the early and delayed diagnosis of ERCP perforation (p=0.014), clearly demonstrating that the mortality rate (7.5%) of patients diagnosed with ERCP perforation in the early period was lower.

DISCUSSION In this study, we examined 51 patients who had undergone ERCP procedures, which resulted in perforations, covering

According to the reported data in the literature, the early diagnosis incidence of ERCP perforation is above 70% in the experienced centers.[7] In a similar manner, the detection rate of ERCP perforation in the early period was 78.4% in our

Table 4. Demographic and clinical characteristics of the delayed diagnosis group (group 2) in ERCP perforations Age Gender Type Time Diagnosis Treatment Length of of to diagnosis type hospitalization perforations (days) (days) 49 Female 75 Male

Choledocholithiasis

Surgery

Choledocholithiasis

Surgery

Male

Pancreas tumor

Medical

Female

Hydatid cyst, cholangitis

Surgery

51 Male

Female

Periampullary diverticulum Choledocholithiasis Choledocholithiasis

Medical

Surgery

52 Male

Medical

Female

Benign stricture

Surgery

Male

III

Pancreas tumor

Surgery

24 Female

Choledocholithiasis

Surgery

Female

Klatskin tumor

Surgery

The cause of mortality

Exitus (Septic shock)

Exitus (Septicemia, Myocardial infarction) Exitus (Septic shock) Exitus (Septicemia, Atrial fibrillation)

ERCP: Endoscopic retrograde cholangiopancreatography.

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series. Since late diagnosis increased both the rate of surgery and mortality, the detection of the type of perforation during the procedure or in the early period offers a good opportunity for early medical intervention. Though the contrast agent extravasation, retroperitoneal air or intraperitoneal air may be seen in the detection of perforation, the amount of air does not indicate the severity of the perforation.[8] In our clinical experience, the attention of the endoscopist was significant in recognizing perforation early. Therefore, even suspicion of ERCP perforation was one of the indications for post-ERCP abdominal tomography, which helped us for an early diagnosis. Prevention of fluid leakage into the peritoneal area by correcting the gastrointestinal luminal continuity in the early period is imperative. Therefore, oral feeding was temporarily suspended for all patients who were diagnosed with a perforation in our clinic. Furthermore, nasogastric decompression, proton pump inhibitors, and appropriate antibiotherapy were administrated. Definitive treatment was also planned depending on the time of detection of localization and perforation. All patients with type I perforation were treated with the surgical repair since the current algorithms and general consensus suggest that the surgery is a more effective treatment option for type I perforations.[1,6] Endoscopic mucosal clipping techniques for type I perforation, which was noticed during the ERCP procedure, can be preferred in suitable patients. Interestingly, four of the seven deaths which developed after the ERCP perforation were in the type I perforation. This suggests that the duodenal injury may be controlled with a conventional forward-viewing-endoscope at the end of the ERCP procedure or all patients may be radiologically evaluated for free air under the diaphragm. In type II and type III perforations, clinical follow-up is recommended primarily for patients with choledochal stents while the surgical options should be considered in the case of acute abdominal signs or sepsis. Moreover, if contrast leakage is minimal in non-stented patients, it is a good choice to place

a stent in choledochus endoscopically or perform a percutaneous drainage accompanied by ultrasound. Along with such options, early definitive surgery for type II perforation may also be considered; however, the annual ERCP number and the level of evidence of the specified study are not high. [7] Since non-surgical interventional treatment methods are mostly available in the fully equipped tertiary centers in our country, the chance of success may be considered to be relatively high depending on the experience. On the other hand, the type IV perforations, which are rather not considered as a true perforation, are in the form of air transfer from the intestine to the retroperitoneum due to excessive air insufflation. Thus, they do not require any surgical treatment. In an abdominal CT scan taken 24 hours after the ERCP, in 29% of all cases, retroperitoneal air can be detected.[9] However, surgical exploration is almost never necessary, excluding the patients with acute abdominal signs, which cannot be ruled out from having an overlooked perforation despite all non-invasive diagnostic modalities. The patients with anatomical abnormalities around the sphincter and patients with a history of Billroth II diversion surgery are in the risk group and deserve excessive attention.[10,11] To reduce the possibility of a type I perforation occurrence, it is necessary to be aware of the predisposing factors[12] along with paying the highest attention to the manipulations with the side-viewing endoscope during an ERCP procedure. In the setting of a perforation, early diagnosis can very effectively reduce mortality.[13] For the patients who require surgery, sepsis and an unstable patient significantly impact the surgical procedure. Therefore, in addition to an effective repair, biliary and gastrointestinal diversion techniques may be preferred. According to an analytic-study which evaluated studies performed between 2000 and 2014, the incidence of perforation was as low as 0.39%,[14] while a sphincterotomy was associated with 41% of these perforations, which supports that the early diagnosis of a perforation (73%) during the same ERCP procedure, resulted in better outcomes. In the evaluation of

Table 5. ERCP-related perforations and mortality rates Study published by

Publication Study Number Perforation year of the duration of ERCP rate study (years) procedures

Stapfer Type I perforation number

Surgery rate

Mortality rate

Fatima[15]

2007

12427

76 (0.6%)

22 (28.9%)

5 (6.6%)

Morgan[16]

2009

12817

24 (0.2%)

10 (41.7%)

1 (4.2%)

Jin[5]

2013

22998

59 (0.26%)

18 (30.5%)

5 (8.4%)

Kodali[17]

2015

8264

12 (0.14%)

3 (25%)

Kumbhari

2016

3331

61 (1.83%)

9 (15%)

2 (3%)

Bill[4]

2018

14045

63 (0.46%)

9 (14.28%)

3 (4.76%)

The present study

2020

8676

51 (0.59%)

24 (47.06%)

7 (13.72%)

[6]

ERCP: Endoscopic retrograde cholangiopancreatography.

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these 18 separate studies in the review, it is clearly seen that the mortality was higher in the groups which required surgical treatment. In experienced centers with a high number of patients, the perforation rate is below 1%. When compared with high volume studies performed in the past 12 years (Table 5), we observed that our type 1 perforations were high. Thus, the number of surgical treatments was inevitably also high. We should also note that in our study the patients who were diagnosed lately led to this high number as an outcome. In the light of the latest available data, it is unlikely that ERCP perforations can completely be prevented. The majority of our patients with mortality were patients with underlying conditions, such as malignancy, chronic obstructive pulmonary disease (COPD) and atrial fibrillation. To reduce the mortality, it is significant to be careful in pre-ERCP risk groups and to diagnose all patients early to avoid the type I perforation. This study has some limitations. One of the limitations that would potentially affect the results is that the presence of a high number of patients with significant comorbidities may disrupt randomization due to the referral of patients to the department as a tertiary medical institution. Another potential limitation is that although we obtained the detailed data (diagnostic codes, patient files, ERCP reports and surgery notes) from the hospital database, there is a possibility that there may be patients whose diagnosis and follow-up are overlooked, especially when they are asymptomatic. Another limitation, if the number of patients were high in our study, the early diagnosis group would be sub-grouped as the patients who were diagnosed during ERCP and within the first 24 hours. Taking all into consideration, although our ERCP-related perforations were rare, the overall mortality was 13.72%. The patients who were diagnosed at an early stage required less surgery, with the exception of type I perforations. Type II perforations can often be safely treated non-operatively if there are no signs of an acute abdomen or sepsis. Finally, ERCP-related mortality is significantly reduced when early diagnosis and treatment can be made, especially during the first 24 hours of a perforation. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: E.B.; Design: E.B.; Supervision: E.B.; Materials: E.B., B.T.K.; Data: E.B., B.T.K.; Analysis: E.B.; Literature search: E.B.; Writing: E.B.; Critical revision: B.T.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

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REFERENCES 1. Stapfer M, Selby RR, Stain SC, Katkhouda N, Parekh D, Jabbour N, et al. Management of duodenal perforation after endoscopic retrograde cholangiopancreatography and sphincterotomy. Ann Surg 2000;232:191−8. 2. Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991;37:383−93. 3. Enns R, Eloubeidi MA, Mergener K, Jowell PS, Branch MS, Pappas TM, Baillie J. ERCP-related perforations: risk factors and management. Endoscopy 2002;34:293−8. 4. Bill JG, Smith Z, Brancheck J, Elsner J, Hobbs P, Lang GD, et al. The importance of early recognition in management of ERCP-related perforations. Surg Endosc 2018;32:4841−9. 5. Jin YJ, Jeong S, Kim JH, Hwang JC, Yoo BM, Moon JH, et al. Clinical course and proposed treatment strategy for ERCP-related duodenal perforation: a multicenter analysis. Endoscopy 2013;45:806−12. 6. Kumbhari V, Sinha A, Reddy A, Afghani E, Cotsalas D, Patel YA, et al. Algorithm for the management of ERCP-related perforations. Gastrointest Endosc 2016;83:934−43. 7. Miller R, Zbar A, Klein Y, Buyeviz V, Melzer E, Mosenkis BN, et al. Perforations following endoscopic retrograde cholangiopancreatography: a single institution experience and surgical recommendations. Am J Surg 2013;206:180−6. 8. Wu HM, Dixon E, May GR, Sutherland FR. Management of perforation after endoscopic retrograde cholangiopancreatography (ERCP): a population-based review. HPB (Oxford) 2006;8:393−9. 9. Genzlinger JL, McPhee MS, Fisher JK, Jacob KM, Helzberg JH. Significance of retroperitoneal air after endoscopic retrograde cholangiopancreatography with sphincterotomy. Am J Gastroenterol 1999;94:1267−70. 10. Avisse C, Flament JB, Delattre JF. Ampulla of Vater. Anatomic, embryologic, and surgical aspects. Surg Clin North Am 2000;80:201−12. 11. Vaira D, Dowsett JF, Hatfield AR, et al. Is duodenal diverticulum a risk factor for sphincterotomy?. Gut 1989;30:939−42. 12. Loperfido S, Angelini G, Benedetti G, Chilovi F, Costan F, De Berardinis F, et al. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc 1998;48:1−10. 13. Ercan M, Bostanci EB, Dalgic T, Karaman K, Ozogul YB, Ozer I, et al. Surgical outcome of patients with perforation after endoscopic retrograde cholangiopancreatography. J Laparoendosc Adv Surg Tech A 2012;22:371−7. 14. Vezakis A, Fragulidis G, Polydorou A. Endoscopic retrograde cholangiopancreatography-related perforations: Diagnosis and management. World J Gastrointest Endosc 2015;7:1135−41. 15. Fatima J, Baron TH, Topazian MD, Houghton SG, Iqbal CW, Ott BJ, et al. Pancreaticobiliary and duodenal perforations after periampullary endoscopic procedures: diagnosis and management. Arch Surg 2007;142:448-54; discussion 454−5. 16. Morgan KA, Fontenot BB, Ruddy JM, Mickey S, Adams DB. Endoscopic retrograde cholangiopancreatography gut perforations: when to wait! When to operate!. Am Surg 2009;75:477−84. 17. Kodali S, Mönkemüller K, Kim H, Ramesh J, Trevino J, Varadarajulu S, et al. ERCP-related perforations in the new millennium: A large tertiary referral center 10-year experience. United European Gastroenterol J 2015;3:25−30.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

ERCP perforasyonlarında erken ve gecikmiş tanının mortalite ile karşılaştırılması: Yüksek hacimli hasta deneyimi Dr. Ersin Borazan,1 Dr. Buğra Tolga Konduk2 1 2

Gaziantep Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Gaziantep Gaziantep Üniversitesi Tıp Fakültesi, Gastroenteroloji Bilim Dalı, Gaziantep

AMAÇ: Endoskopik retrograt kolanjiyopankreatografi (ERCP) perforasyonu nadir görülen, fakat mortalitesi yüksek seyredebilen bir komplikasyondur. Bu çalışmada, cerrahi veya tıbbi tedavi edilen ERCP perforasyonlarına insidans, klinik veriler ve tanı zamanına göre klinik değerlendirme yapıldı. ERCP perforasyonlarının azaltılabilmesi için klinik özelliklerinin ortaya konulması, literatür ile karşılaştırılması ve mortalitenin azaltılması hedeflendi. GEREÇ VE YÖNTEM: Bu klinik geriye dönük çalışmada 8 yılda yapılan tüm ERCP işlemleri (n=8676) içinde 51 perforasyon saptandı. Erken tanı konulan [Grup 1: 40], geç tanı konulan [Grup 2: 11] gruplar primer tanıları, ERCP öncesi kan ve biyokimyasal incelemeleri, perforasyon tipi, tedavi yöntemi, klinik özellikleri, yatış süresi, mortalite yönünden karşılaştırıldı. Ek olarak ERCP sırasında papillotomi, stent yerleştirilmesi, koledok dilatasyonu, ERCP işlemi sayısı yönünden karşılaştırıldı. BULGULAR: Hastanemizde ERCP perforasyonu oranı %0.59’du. Hastaların çoğunluğu koledokolitiazis ve periampuller tümörlerdi. Hastaların yaşı 62.78±17.13 (24–89); %56.9'u (n=29) kadındı. En sık stapfer tip II perforasyonlar (%49) görüldü. Ancak mortalitenin %62.5’i stapfer tip I’di. Toplam mortalite %13.72 (n=7) idi. Cerrahi tedavi edilen hastaların (n=24) yatış süresi (13.38±10.09 gün) daha fazla idi. Tıbbi tedavi edilenlere (%74.1) daha çok koledok stenti yerleştirilmişti (p=0.039). Grup 1, ERCP sırasında görsel olarak veya kontrast madde kaçağı (13/40) ile veya şüphe nedeniyle tomografi ile tespit edildi. Grup 2 hastaların Pre-ERCP lökosit seviyesi daha yüksekti (p=0.044). Acil cerrahi gereksinimi %72.7 ve mortalite %36.4 idi. Perforasyonunun erken ve geç farkedilmesi arasında mortalite açısından farklılık belirlendi (p=0.014). TARTIŞMA: Erken tanı konulanlarda, tip I perforasyonlar hariç, daha az cerrahi gereksinim olmuştur. Tip II perforasyonlar, akut karın ve sepsis bulguları yok ise, çoğunlukla non-operatif güvenli bir şekilde tedavi edilebilmektedir. Erken tanı ve tedavi mortaliteyi azaltmaktadır. Anahtar sözcükler: Erken tanı, Endoskopik retrograt kolanjiopankreatografi, Mortalite, Perforasyon, Cerrahi Ulus Travma Acil Cerrahi Derg 2020;26(5):746-753

doi: 10.14744/tjtes.2020.61289

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ORIGIN A L A R T IC L E

Sedoanalgesia modality during laser photocoagulation for retinopathy of prematurity: Intraoperative complications and early postoperative follow-up Sedat Saylan, M.D.,1 Ali Akdoğan, M.D.,1 Ahmet Beşir, M.D.,1 Mehmet Kola, M.D.,3

Şebnem Kader, M.D.,2 Yakup Aslan, M.D.2

Ersagun Tuğcugil, M.D.,1

Department of Anesthesiology, Karadeniz Technical University Faculty of Medicine, Trabzon-Turkey

Department of Neonatology, Karadeniz Technical University Faculty of Medicine, Trabzon-Turkey

Department of Ophtalmology, Karadeniz Technical University Faculty of Medicine, Trabzon-Turkey

ABSTRACT BACKGROUND: Laser photocoagulation (LPC) is a surgical procedure used in the treatment of premature retinopathy that may cause retinal detachment and blindness if not diagnosed and treated early. The anesthesia method used in LPC varies from sedoanalgesia to general anesthesia and airway management varies from spontaneous ventilation to endotracheal intubation. In this study, we aimed to evaluate the effectiveness of sedoanalgesia applications and this anesthesia procedure concerning intraoperative and postoperative complications by avoiding intubation and mechanical ventilation in premature infants with a fragile population. METHODS: This retrospective study included 89 patients who underwent laser photocoagulation under anesthesia for premature retinopathy. Patients’ demographic characteristics, preoperative risk factors, anesthesia technique, especially airway management, changes in ventilation status during surgery, intraoperative complications, postoperative complications, and intensive care follow-up, were recorded and analyzed statistically. RESULTS: Two of the 89 patients who underwent laser photocoagulation were excluded from this study because they were followed up intubated. The number of patients who received mask ventilation due to intraoperative complications was 12 (13.8%). The mean operation time was 36.2±10.1 minutes. In 86.2% (n=75) of the patients, the surgical procedure was completed with sedoanalgesia while maintaining spontaneous ventilation. CONCLUSION: Sedoanalgesia application during the surgical intervention of patients with Retinopathy of Prematurity (ROP) requiring early diagnosis and emergency treatment will minimize intraoperative and postoperative complications. We believe that sedoanalgesia as an anesthetic method can be applied as an effective alternative method while preserving spontaneous ventilation. Keywords: Laser photocoagulation; retinopathy of prematurity; sedoanalgesia.

INTRODUCTION Retinopathy of Prematurity (ROP) is a retinal disease that arises from abnormal proliferation of retinal vessels. ROP may cause retinal detachment and blindness if not detected early or left untreated. ROP is a major and preventable clinical problem worldwide leading to blindness in childhood.[1,2]

Epidemiological studies have identified prematurity and low birth weight as the most important risk factors for the development of ROP. Other identified risk factors include hyperoxia, hypoxia, mechanical ventilation, sepsis, intraventricular hemorrhage, blood transfusions, parenteral nutrition, pulmonary insufficiency and patent ductus arteriosus.[3,4]

Cite this article as: Saylan S, Akdoğan A, Kader Ş, Tuğcugil E, Beşir A, Kola M, et al. Sedoanalgesia modality during laser photocoagulation for retinopathy of prematurity: intraoperative complications and early postoperative follow-up. Ulus Travma Acil Cerrahi Derg 2020;26:754-759. Address for correspondence: Sedat Saylan, M.D. Karadeniz Teknik Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Trabzon, Turkey Tel: +90 462 - 377 50 00 E-mail: sedatsaylan@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(5):754-759 DOI: 10.14744/tjtes.2020.62378 Submitted: 23.10.2019 Accepted: 29.05.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Saylan et al. Sedoanalgesia modality during LPC for ROP: Intraoperative complications and early postoperative follow-up

Recent advances in neonatal care and the increase in neonatal intensive care units (NICUs) have decreased the mortality of the premature and low birth weight infants and increased the incidence of the ROP. Laser photocoagulation therapy (LPT) is a surgical procedure to prevent the progression of ROP to visual impairment or blindness.[5] The anesthesia method used in LPT varies from sedoanalgesia to general anesthesia, and airway management varies from spontaneous ventilation to endotracheal intubation.[6] The low birth weight of the newborns who will be treated for ROP, the presence of additional systemic diseases, and more frequent peroperative and postoperative complications make the anesthesia method and follow-up more important. The primary objective of this study was to evaluate the results of sedoanalgesia as an anesthesia protocol during laser photocoagulation in ROP. The secondary aim was to investigate the effects of anesthesia method on follow-up results and discharge in the neonatal intensive care unit concerning intraoperative and postoperative complications. The clinical data of these newborns were retrospectively analyzed to evaluate the effectiveness of the sedoanalgesia procedure to avoid intubation and mechanical ventilation.

MATERIALS AND METHODS Upon the approval of the local ethics committee of the state university, this study was started. This study included 89 cases that underwent laser photocoagulation under anesthesia for ROP between 2012 and 2017. Two of the patients were excluded from this study due to intubation and mechanical ventilation requirement. Patient files, anesthesia record forms, early postoperative and NICU follow-up procedures were evaluated retrospectively to evaluate the effectiveness of anesthesia procedure in our clinic. Five-point scale was used to evaluate the babies according to their birth week and birth weight, and infants were classified as follows: Birth week

0 <500 (abort)

Severe <28 weeks:

1 <750 g ILBW (incredibly low birth weight)

Medium 28–32 weeks: 2 1000–750 g ELBW (extremely low birth weight)

Light 32–36 weeks:

At the limits 37 weeks: 4 2500–1500 g LBW(low birth weight)

Preoperative anesthesia recommendations were followed and the evaluations and suggestions of the pediatric minor physicians were obtained. Transport of the patients from the neonatal intensive care unit to the operating room was performed using mechanical ventilator transport incubator, and heat-pulse, pulse-oximeter monitoring was performed by a pediatric physician. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Electrocardiogram (ECG), peripheral oxygen saturation, blood pressure and body temperature measurements were performed. Gender, gestational age, postconceptional age, birth weight, weight during treatment, laser photocoagulation week and preoperative risk factors (low birth weight, respiratory distress syndrome, bronchopulmonary dysplasia, oxygen therapy, CPAP, mechanical ventilation, apnea, sepsis and cardiac anomaly) were recorded. Anesthesia technique was examined especially for airway management, changes in ventilation status during surgery and intraoperative complications (bronchospasm, desaturation, apnea, convulsion and bradycardia), operation time and other drugs used. Patients admitted to the postoperative recovery unit were allowed to be transferred to the NICU when the Post-Anesthesia Recovery Scoring System (PARSS) score was 6 or higher.[7] All patients were transported postoperatively in an incubator and monitored by a pediatric physician. Postoperative follow-up was monitorized in the NICU for 24 hours. Postoperative complications (bronchospasm, desaturation, apnea, convulsion and bradycardia) were recorded.

Sedoanalgesia Procedure After noninvasive monitoring of the patients brought to the operating table under the incubator, midazolam 0.1 mg/kg and ketamine 1 mg/kg were administered intravenously to all patients for sedoanalgesia, and ketamine 0.25 mg/kg/h infusion was administered for maintenance. All babies were also administered atropine to minimize the salivation effect seen with ketamine and to decrease the oculocardiac reflex. The degree of sedation was monitored with a neonatal infant pain scale (NIPS). Surgical procedure was allowed when NIPS ≤1 and no response to eye speculum placement. In case of prolonged apnea or desaturation, patients were ventilated via a mask.

Statistical Methods

Birth weight

Immature <24 weeks:

3 1500–1000 g VLBW (very low birth weight)

In this study, 2.5% phenylephrine hydrochloride and 0.5% tropicamide were applied to all patients half an hour before the procedure for pupillary dilatation. In addition, 0.5% proparacaine hydrochloride drops were used for all the patients as local anesthesia five minutes before the operation.

The data were analyzed using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL) Version 23.0. Normal distribution of the numerical variables was evaluated with the Kolmogorov-Smirnov test. Descriptive statistics were made. Numerical variables were given as mean ± standard deviation (SD) and median (IQR: 25%–75%) and categorical variables as number (n) and percentage (%). Statistical significance level was taken as p<0.05.

RESULTS Demographic data, preoperative characteristics and risk factors of the patients are given in Table 1. The anesthesia man755

Saylan et al. Sedoanalgesia modality during LPC for ROP: Intraoperative complications and early postoperative follow-up

Table 1. Demographic data and preoperative characteristics

Table 2. Anesthesia management and intraoperative complications

Gender, n (%)

Male

43 (48.3)

Type of anesthesia, n (%)

Female

46 (51.7)

Sedoanalgesia (spontaneous breathing)

American Society of Anesthesiologists, n (%)

Sedoanalgesia (mask ventilation)

84 (94.4)

Operation time (min), mean±SD

III

5 (5.6)

Gestational age (week), (mean±SD) Birth weight (gr), (mean±SD) Postconceptional age (week), (mean±SD) Body weight (gr) [Median (IQR: 25%–75%)] Laser week (mean±SD) Multiple pregnancies, n (%)

27.94±2.95

75 (86.2) 12 (13.8) 36.24±10.19

Intraoperative complications, n (%)

Bronchospasm

1102.4±404.4

Desaturation

39.65±4.6

Apnea

3 (2.3) 12 (13.8) 8 (9.2)

2600 (2100–2875)

Convulsions

1 (1.1)

11.67±4.69

Bradycardia

10 (11.5)

15 (16.9)

Definition of baby by birth weight, n (%)

2 (2.2)

13 (14.6)

29 (32.6)

34 (38.2)

11 (12.4)

Definition of the baby by birth week, n (%)

4 (4.5)

51 (57.3)

23 (25.8)

9 (10.1)

1 (1.1)

Preoperative risk factors, n (%)

Low birth weight

87 (97.8)

Mechanical ventilation

52 (58.4)

Continuous positive airway pressure

36 (40.4)

Sepsis

25 (28.1)

Anemia, transfusion

24 (27.0)

O2 treatment

20 (22.5)

Respiratory distress syndrome

18 (20.2)

Cardiac anomaly

18 (20.2)

Epilepsy

10 (11.2)

Hypothyroidism

7 (7.9)

Bronchopulmonary dysplasia

6 (6.7)

Apnea

6 (6.7)

Intracranial bleeding

6 (6.7)

Phototherapy

3 (3.4)

Arterial blood gas abnormality

2 (2.2)

Hydrocephalus

2 (2.2)

Total parenteral nutrition

1 (1.1)

agement, mean operation time and intraoperative complications of the cases are shown in Table 2. 756

Table 3. Postoperative complications and intensive care follow-up (n=87)

n %

New antiepileptic therapy

Oxygen supply

2.3

In incubator

With Hood

2.3

Nasal-SIMV

3.6

Endotracheal-SIMV

4.6

Emerging respiratory failure and mv requirement

8.0

Respiratory stimulant (caffeine) requirement

4.6

Monitoring time in mechanical ventilator (days)

6.9

1.1

Two of the 89 patients who underwent laser photocoagulation were excluded from this study because they were followed up intubated. Eight of the 87 patients included in this study had apnea, three had bronchospasm, and one patient had convulsion during operation and these desaturated patients underwent mask ventilation (Fig. 1). Surgical procedure was completed smoothly in patients whose spontaneous respiration returned after mask ventilation and peripheral oxygen saturation was within normal limits. Ten patients had bradycardia and surgery was interrupted, and tactile stimulation and atropine were used to achieve normal heart rate in all patients. In 86.2% (n=75) of the patients, the surgical procedure was completed with sedoanalgesia while maintaining spontaneous ventilation. In the postoperative NICU follow-up, two patients developed convulsion and started antiepileptic treatment. The history of these patients included risk factors, such as low birth weight, respiratory distress syndrome and epilepsy. Sixteen patients who developed apnea and bronchospasm needed oxygen support, and seven of these patients received mechanical ventilaUlus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Saylan et al. Sedoanalgesia modality during LPC for ROP: Intraoperative complications and early postoperative follow-up

Laser photocoagulation (n=89) Intubated patients excluded from this study (n=2) Laser photocoagulation with sedoanalgesia (n=87) Mean operation time 36.2Âą10.1 minutes Patients undergoing mask ventilation as a result of intraoperative complications (13.8%) (n=12) Patients whose surgery was completed with sedoanalgesia (86.2%) (n=75)

Figure 1. Study flow diagram.

tion. Patients who had mechanical ventilation for a maximum of two days did not develop any problems during the subsequent follow-up (Table 3).

DISCUSSION ROP is a disease that needs early diagnosis and treatment.[8] Newborns and premature babies perceive pain and produce a stress response to painful stimuli.[9] In addition, the oculocardiac reflex is well developed in infants, and they are more susceptible to apnea attacks and bradycardia with increased cardiorespiratory instability.[10] Therefore, anesthesia support is required for ROP treatment with laser. However, there is still no consensus on the best anesthetic approach to use.[6] Previous studies have examined the use of topical anesthetics, general anesthetics, sedation and analgesia combinations during laser photocoagulation for ROP treatment. Haigh et al.[11] found that the incidence of cardiovascular and respiratory complications was significantly increased with the use of topical anesthesia, but the performance of the procedure under general anesthesia or sedation/analgesia was comparable. We applied sedoanalgesia to all of our patients, but at the same time, we used eye drops containing local anesthetics five minutes before the operation. Piersigili et al.[12] demonstrated that fentanyl analgesia and propofol sedation were effective in this short-term surgery and had no side effects, thus forming the basis of a randomized trial to evaluate propofol safety. They stated that their aim was to avoid intubation in the neonatal patient group, but they used a laryngeal mask for airway safety. Lyon et al.[13] stated that the use of ketamine sedation provides satisfactory conditions for the treatment of ROP, thus Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

preventing complications related to general anesthesia in infants with many medical problems. They recommended the use of ketamine and other sedative techniques in the treatment of the ROP. We used ketamine in our unit. Ketamine is a short-acting â&#x20AC;&#x2DC;dissociativeâ&#x20AC;&#x2122; anesthetic with a strong analgesic effect lasting longer than the anesthesia period, and this analgesic effect occurs even at subanesthetic doses.[14] Ketamine increases airway tone and thus maintains airway patency and respiratory function, and some studies suggest mild respiratory depression, but this has not been shown in other studies.[15] We use low doses of midazolam to prevent ketamine-induced dissociative effects. We also use atropine in our clinic to prevent the increase of ketamine-induced salivation and to alleviate the oculocardiac reflex. Ketamine is still the preferred drug in pediatric anesthesia because of its bronchodilator effect, protection of laryngeal, pharyngeal reflexes and minimal central respiratory effect. Meta-analysis of 32 studies on ketamine in sedoanalgesia demonstrated the incidence of apnea in 0.8% and laryngospasm in 0.3% of the patients.[16] In premature newborns, general anesthesia may be associated with a high risk of morbidity, especially when intraventricular hemorrhage, patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), history of mechanical ventilation or bronchopulmonary dysplasia (BPD) are present.[17] The presence of additional systemic diseases, as well as low birth weight, increases the risk in general anesthesia applications in premature infants. The use of invasive airway devices in this group of patients with a high rate of pulmonary disease in history paves the way for serious complications. Manipulation of the endotracheal tube may cause airway edema, bronchospasm, and laryngospasm in the postoperative period.[18] Ulgey et al. compared the effects of general anesthesia and sedoanalgesia on postoperative mechanical ventilation for ROP. They stated that the use of deep sedation in premature infants who underwent ROP surgery reduced the need for postoperative mechanical ventilation compared to general anesthesia.[19] Sixteen of our patients required postoperative oxygen supplementation, and only four of these patients underwent mechanical ventilation with endotracheal intubation. Invasive (4.6%) and noninvasive (3.6%) MV treatment was applied to seven patients who developed apnea and bronchospasm in the NICU. All of these patients had other preoperative risk factors, especially low birth weight. As a result, some infants who recently stopped care and mechanical ventilation required post-operative mechanical ventilation. Patients who received mechanical ventilation support for a maximum of two days were then discharged without any problems. Based on the available data, postoperative complications were not 757

Saylan et al. Sedoanalgesia modality during LPC for ROP: Intraoperative complications and early postoperative follow-up

associated with ketamine. The incidence of apnea in premature babies is 20–30% and the frequency of apnea after general anesthesia increases up to 30%. Especially low birth weight, low postconceptional age and endotracheal intubation increase the incidence of postoperative apnea.[20] Thus, sedoanalgesia with close monitorized follow-up will provide hemodynamic stability and surgical comfort while avoiding intubation.[21] Yavaşcaoğlu et al.[22] stated that monitoring babies in the first 24 hours in the intensive care unit provided appropriate care to reduce postoperative complications. We provide the NICU transportation of all our patients in a standard, monitorized incubator with appropriate temperature in the company of pediatric doctors. In addition, all our patients are followed up in the postoperative NICU for 24 hours. This study is limited to the anesthetic procedures applied in our hospital. The anesthetic approaches used in various centers in our country can be evaluated for the treatment of the ROP in future studies. In the light of these studies, a consensus can be established for the anesthesia method or methods used in the treatment of patients with ROP. In addition, this study does not compare sedoanalgesia with general anesthesia for patients with ROP. Therefore, it is not an alternative to general anesthesia. As a result, sedoanalgesia application during the surgical intervention of the patients with ROP requiring early diagnosis and emergency treatment will minimize intraoperative and postoperative complications. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.S.; Design: S.S., A.A., Ş.K.; Supervision: E.T., A.B., M.K., Y.A.; Materials: A.A., Ş.K.; Data: S.S., A.A., Ş.K.; Analysis: S.S., A.A; Literature search: S.S., Ş.K., M.K.; Writing: S.S.; Critical revision: E.T., A.B., M.K., Y.A. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Zin A, Gole GA. Retinopathy of prematurity-incidence today. Clin Perinatol 2013;40:185−200. 2. Gilbert C, Muhit M. Twenty years of childhood blindness: what have we learnt?. Community Eye Health 2008;21:46−7. 3. Owen LA, Morrison MA, Hoffman RO, Yoder BA, DeAngelis MM. Retinopathy of prematurity: A comprehensive risk analysis for prevention and prediction of disease. PLoS One 2017;12:e0171467. 4. Karna P, Muttineni J, Angell L, Karmaus W. Retinopathy of prematurity

758

and risk factors: a prospective cohort study. BMC Pediatr 2005;5:18. 5. Allegaert K, Van de Velde M, Casteels I, Naulaers G, Vanhole C, Devlieger H. Cryotherapy for threshold retinopathy: perioperative management in a single center. Am J Perinatol 2003;20:219−26. 6. Chen SD, Sundaram V, Wilkinson A, Patel CK. Variation in anaesthesia for the laser treatment of retinopathy of prematurity--a survey of ophthalmologists in the UK. Eye (Lond) 2007;21:1033−6. 7. Steward DJ. A simplified scoring system for the post-operative recovery room. Can Anaesth Soc J 1975;22:111−3. 8. Early Treatment For Retinopathy Of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch Ophthalmol 2003;121:1684−94. 9. Anand KJ, Hickey PR. Pain and its effects in the human neonate and fetus. N Engl J Med 1987;317:1321−9. 10. Clarke WN, Hodges E, Noel LP, Roberts D, Coneys M. The oculocardiac reflex during ophthalmoscopy in premature infants. Am J Ophthalmol 1985;99:649−51. 11. Haigh PM, Chiswick ML, O’Donoghue EP. Retinopathy of prematurity: systemic complications associated with different anaesthetic techniques at treatment. Br J Ophthalmol 1997;81:283−7. 12. Piersigilli F, Di Pede A, Catena G, Lozzi S, Auriti C, Bersani I et al. Propofol and fentanyl sedation for laser treatment of retinopathy of prematurity to avoid intubation. J Matern Fetal Neonatal Med 2019;32:517−21. 13. Lyon F, Dabbs T, O’Meara M. Ketamine sedation during the treatment of retinopathy of prematurity. Eye 2007;21:1−3. 14. White PF, Way WL, Trevor AJ. Ketamine--its pharmacology and therapeutic uses. Anesthesiology 1982;56:119−36. 15. Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth 1989;36:186−97. 16. Green SM, Roback MG, Krauss B, Brown L, McGlone RG, Agrawal D, et al; Emergency Department Ketamine Meta-Analysis Study Group. Predictors of airway and respiratory adverse events with ketamine sedation in the emergency department: an individual-patient data meta-analysis of 8,282 children. Ann Emerg Med 2009;54:158−68.e1-4. 17. Welborn LG, Greenspun JC. Anesthesia and apnea. Perioperative considerations in the former preterm infant. Pediatr Clin North Am 1994;41:181−98. 18. Demirel N, Bas AY, Kavurt S, Celik IH, Yucel H, Turkbay D, et al. Remifentanil analgesia during laser treatment for retinopathy of prematurity: a practical approach in neonatal intensive care unit. Am J Perinatol 2014;31:983–6. 19. Ulgey A, Güneş I, Bayram A, Aksu R, Biçer C, Uğur F, et al. Decreasing the need for mechanical ventilation after surgery for retinopathy of prematurity: sedoanalgesia vs. general anesthesia. Turk J Med Sci 2015;45:1292−9. 20. Shah VA, Yeo CL, Ling YL, Ho LY. Incidence, risk factors of retinopathy of prematurity among very low birth weight infants in Singapore. Ann Acad Med Singapore 2005;34:169−78. 21. Walther-Larsen S, Rasmussen LS. The former preterm infant and risk of post-operative apnoea: recommendations for management. Acta Anaesthesiol Scand 2006;50:888−93. 22. Yavaşcaoğlu B, Kaya FN, Özcan B, Yılmaz C, Töre G, Ata F, et al. The Practice of General Anesthesia for the Laser Therapy of Neonates with Retinopahty of Prematurity: A Retrospective Analysis. Uludağ Üniversitesi Tıp Fakültesi Derg 2007;33:65−9.

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Saylan et al. Sedoanalgesia modality during LPC for ROP: Intraoperative complications and early postoperative follow-up

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Prematüre retinopatisinde lazer fotokoagülasyon sırasında sedoanaljezi yöntemi: İntraoperatif komplikasyonlar ve erken postoperatif takip Dr. Sedat Saylan,1 Dr. Ali Akdoğan,1 Dr. Şebnem Kader,2 Dr. Ersagun Tuğcugil,1 Dr. Ahmet Beşir,1 Dr. Mehmet Kola,3 Dr. Yakup Aslan2 1 2 3

Karadeniz Teknik Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Trabzon Karadeniz Teknik Üniversitesi Tıp Fakültesi, Yenidoğan Bilim Dalı, Trabzon Karadeniz Teknik Üniversitesi Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı, Trabzon

AMAÇ: Erken teşhis ve tedavi edilmezse retinal dekolmana ve körlüğe neden olabilen prematüre retinopatisinin (PR) tedavisinde uygulanan laser fotokoagülasyon tedavisi (LFT) cerrahi bir prosedürdür. LFT’de uygulanan anestezi yöntemi sedo-analjeziden genel anesteziye, havayolu yönetimi spontan ventilasyondan endotrakeal entübasyona kadar değişkenlik göstermektedir. Bu çalışma ile kırılgan popülasyon olan prematüre bebeklerde entübasyon ve mekanik ventilasyondan kaçınarak sedoanaljezi uygulamalarımızın etkinliğini, bu anestezi yöntemini intraoperatif ve postoperatif komplikasyonlar açısından değerlendirmeyi amaçladık. GEREÇ VE YÖNTEM: Bu geriye dönük çalışma, PR nedeniyle anestezi altında lazer fotokoagülasyon uygulanmış 89 olguyu içermektedir. Hastaların demografik özellikleri, preoperatif risk faktörleri, anestezi tekniği, özellikle havayolu yönetimi, cerrahi süresince ventilasyon durumundaki değişiklikler, intraoperatif komplikasyonlar, postoperatif komplikasyonlar, yoğun bakım takip süreci kayedildi ve istatistiksel olarak analiz edildi. BULGULAR: Lazer fotokoagülasyon uygulanan 89 hastadan ikisi entübe halde takip edildiği için çalışma dışı bırakıldı. İntraoperatif komplikasyon gelişmesi sonucu maske ventilasyon uygulanan hasta sayısı 12 (%13.8) idi. Ortalama operasyon süresi 36.2±10.1 dakika idi. Hastaların %86.2’sinde (n=75) cerrahi işlem spontan ventilasyon korunarak sedoanaljezi ile tamamlanandı. TARTIŞMA: Erken tanı ve acil tedavi gerektiren PR hastalarının cerrahi müdahalesi sırasında sedoanaljezi uygulaması intraoperatif ve postoperatif komplikasyonları azaltabilir. Anestezi yöntemi olarak sedoanaljezi yaklaşımının spontan ventilasyonu koruyarak etkili bir alternatif yöntem olarak uygulanabileceği kanısındayız. Anahtar sözcükler: Lazer fotokoagülasyon; prematüre retinopatisi; sedoanaljezi. Ulus Travma Acil Cerrahi Derg 2020;26(5):754-759

doi: 10.14744/tjtes.2020.62378

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759

ORIGIN A L A R T IC L E

The role of C-reactive protein to lymphocyte ratio in the differentiation of acute and perforated appendicitis Serhat Koyuncu, M.D.,1

Okan İsmail, M.D.2

Department of Emergency Medicine, Tokat Gaziosmanpaşa University Faculty of Medicine, Tokat-Turkey

Department of General Surgery, Tokat Gaziosmanpaşa University Faculty of Medicine, Tokat-Turkey

ABSTRACT BACKGROUND: This study aimed to investigate the superiority of C-reactive protein (CRP) lymphocyte ratio (CLR) in acute appendicitis (AA) and perforated appendicitis (PA) compared to routine laboratory parameters in patients where radiological tests were insufficient to clarify the diagnosis. METHODS: In this cross-sectional and retrospective study, the patients were divided into two groups as PA and AA. Age, sex, length of hospital stay, leukocytes, neutrophil, lymphocyte, CRP, and CLR were recorded at the time of diagnosis. Regression analyses were performed for the parameters, which were found to be statistically significant in univariate analysis. RESULTS: One hundred thirty-one patients were included in this study (111 patients in the AA group, and 20 patients in the PA group). Age (p=0.03), gender (p<0.001), length of hospital stay (p<0.001), CRP (p<0.001), NLR (p=0.004) and CLR (p<0.001) were significantly different between both groups. However, only CLR was found as a significant risk factor in PA cases (p=0.016). The ROC analysis showed the highest AUC value in CLR (0.83). The cut-off value for predicting PA was found 0.45. CONCLUSION: This study provided that the CLR is an important parameter for the differentiation of AA and PA patients. Besides, it is a valuable predictor in the preoperative risk classification of these patients. Keywords: Acute appendicitis; C-reactive protein to lymphocyte ratio; perforation.

INTRODUCTION Acute appendicitis (AA) is one of the most common surgical diseases and causes of abdominal pain requiring acute surgery seen in emergency departments.[1,2] The rate of acute appendicitis is between 7.5 and 12.5/10000 throughout the world. The lifetime risk of an average individual is 7% and the complication rate is around 17–20 %. However, there are some reports of increased incidence of AA (22.71/10000) depending on the definition and detection method; the perforation rate is similar (2.9/10000).[3] Surgery provides recovery in the short-term in cases diagnosed with uncomplicated AA. However, delay in the diagnosis causes difficulties in complicated cases. Mortality risk is low in AA patients (0.3%) but increases when the patients have perforation (6%).[4,5]

The diagnosis of AA is easy and can be made by routine physical examination. Importantly, the diagnosis interval may increase in patients with retrocecal appendixes, children and elderly patients. Moreover, ovarian pathologies may lead to misdiagnosis, which subsequently leads to a delay in diagnosis. [2,6,7] Ultrasonography (USG) and computed tomography (CT) are frequently used techniques in the diagnosis of AA and PA. However, these techniques require special equipment and an experienced radiologist.[8,9] White blood cells (WBC) and C-reactive protein (CRP) are routinely-used laboratory parameters, which strengthen the diagnosis of AA. Although recent studies have assessed several parameters, such as NLR, PLR, MPV, PLT, and serum bilirubin, there is no definitive parameter that is used to differ-

Cite this article as: Koyuncu S, İsmail O. The role of C-reactive protein to lymphocyte ratio in the differentiation of acute and perforated appendicitis. Ulus Travma Acil Cerrahi Derg 2020;26:760-764. Address for correspondence: Serhat Koyuncu, M.D. Tokat Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Tokat, Turkey Tel: +90 356 - 212 95 00 E-mail: dr_serhats@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):760-764 DOI: 10.14744/tjtes.2020.47973 Submitted: 26.02.2020 Accepted: 07.06.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Koyuncu et al. The role of CRP to lymphocyte ratio in the differentiation of acute and perforated appendicitis

entiate AA and PA.[7,8,10] A few studies reported that these laboratory parameters are useful in the diagnosis of complicated appendicitis, but could not reach a satisfactory level. [11,12] The lack of a marker in this field raised an interest to look for new parameters. Recent studies performed with the inclusion of inflammatory parameters have shown that the ratio of lymphocyte and CRP (CLR) is more useful in demonstrating systemic inflammatory response, especially in malignancy patients. In the end, CLR was reported more sensitive and specific than other parameters.[13–16] Since appendicitis is characterized by increased inflammation, we aimed to investigate whether the CLR is a diagnostic parameter for the differentiation of AA and PA. We also aimed to test the inflammatory parameters if they could be a predictor in the preoperative risk classification of these patients.

MATERIALS AND METHODS This is a retrospective study and performed in a tertiary university Department of Emergency between June 2018 and January 2019. Central Provincial Health Directorate and Ethical Committee of University approved this study with number 20-KAEK-011. The data of the patients with the diagnosis of AA and PA were retrospectively collected from Central Provincial Health Database. We assessed the data related to appendicitis in all pathology reports from the central database of the hospitals and included the patients whose final diagnosis was AA and PA. We included the patients with age >18 years, pathologically diagnosed with AA and PA, and whose laboratory parameters included at least complete blood count (CBC) and CRP tests. Patients under 18 years of age, patients with a pathologic diagnosis other than appendicitis, and patients with a lack of laboratory parameters were excluded from this study. Age, gender, length of hospital stay, WBC, neutrophil, lymphocyte, and CRP were recorded from the database values at the time of diagnosis. SYSMEX XE2100 test and IMMAGE 800 Immunochemistry system were used to test CBC and CRP, respectively. Because this study was planned as a cross-sectional study, all patients admitted to the emergency department in a 6-month period with the diagnosis of AA were examined and their information was recorded in the computer system. Patients were divided into two groups as AA and PA and compared concerning WBC, NLR, CRP, and CLR, as well as their age, gender, and length of hospital stay. CLR was calculated as (CRP/lymphocyte)x100.

Statistical Analysis We presented parametric variables as mean and standard Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

deviations and non-parametric variables as median and interquartile intervals (lower and upper quarters). Kolmogorov-Smirnov test and a histogram analysis were used to determine whether continuous variables were normally distributed. We used logarithmic for the variables, not showing normal distribution. We assessed the homogeneity of the variances with Levene’s test. For categorical variables, we used the number of cases and percentages. We compared two independent parametric variable groups using Student’s t-test and applied the Mann-Whitney U test for non-parametric variables. ROC (receiver operating characteristic) curves were created to evaluate the presence of PA. We calculated the area under the curve of the ROC value (AUC) for the evaluation of perforation in AA. EasyROC (ver. 1.3) was used to compare the AUCs (WBC, CRP, NLR, and CLR) and perform the ROC curve analysis. In multivariate analysis, we examined independent predictors for predicting treatment outcome using logistic regression analysis. We used the Hosmer-Lemeshow test for model fit. Cases with a type-1 error level below 5% were considered statistically significant.

RESULTS We found that 348 patients were operated with AA during the 6-month period. One hundred and twenty-seven of them were <18 years of age. Pathological diagnosis indicated reactive lymphoid hyperplasia (RLA) in nine patients, neoplasia in five patients, and ovarian pathology in seven patients. Sixty-nine patients’ laboratory parameters did not include CRP as it had not been requested at the time of diagnosis. All these patients were excluded from this study. In the end, 131 patients were included in this study. One hundred eleven patients were diagnosed with AA and 20 were diagnosed with PA (Fig. 1). Seventy-two of the patients were male (55%). The mean age of all patients was 33 (24; 46). When the patients were assessed separately, the mean age of AA and PA patients were 32 (24; 43) and 44.5 (25; 70), respectively (p=0.03). The duration of hospital stay was three (3; 5) days in AA patients and five (4; 6.75) in PA patients (p<0.001). WBC, neutrophil, CRP, NLR, and CLR were compared between the AA and PA groups. In the PA group, CRP (7.9 vs. 0.6, p<0.001), CLR (0.55 vs. 0.04, p<0.001) and NLR (7.5 vs. 4.2, p=0.004) were significantly higher. However, no difference was shown in WBC (12700 vs. 13800, p=0.3) and neutrophil (9700 vs 11300, p=0.1) values between PA and AA cases (Table 1). ROC curve analysis showed the highest AUC value as 0.83 in CLR. On the other hand, the AUC values for NLR and CRP were 0.70 and 0.82, respectively (Fig. 2). CLR sensitivity was 0.700 (upper-upper limit; 0.457–0.881) and specificity was 0.96 (lower-upper limit; 0.91–0.99). The cut-off value for 761

Koyuncu et al. The role of CRP to lymphocyte ratio in the differentiation of acute and perforated appendicitis

Table 1. Demographic characteristics and laboratory parameters in the differentiation of PA and AA

Tuhe number of patients diagnosed with acute

appendicitis (n=348)

RLA (n=9)

Ovarian pathology (n=69)

Perforation (-)

Perforation (+)

Age

32 (24;43) (IQR)

44.5 (25;70) (IQR)

0.03

LOS*

3 (3;5) (IQR)

5 (4;6.75) (IQR)

<0.001

WBC

Neoplasia

12.76±4.2 13.83±3.9 0.3

Neutrophil 9.7±4.2

(n=5)

CRP

Deficiency of laboratory parameters(n=69)

Under 18 years of age (n=127)

11.3±3.8 0.1

0.6 (0.2;2.3)

7.9 (2.3;11.5)

<0.001

NLR

4.2 (2.6;6.7)

7.5 (4.8;9.8)

0.004

CLR

0.04 (0.009;0.1)

0.55 (0.16;0.7)

<0.001

Tables LOS: Length of stay; WBC: White blood cell; CRP: C-reactive protein; NLR: Neutrophil/lymphocyte ratio; CLR: (CRP/lymphocyte ratio)x100.

Acute appendicitis

Perforated

(n=111)

appendicitis (n=20)

Figure 1. Follow chart of acute appendicitis, RLA: Reactive lymphoid hyperplasia.

1.0

Sensitivity

0.8 0.6 0.4

Table 2. ROC curve analyses of CLR

Value Lower Upper

Sensitivity

0.700 0.457 0.881

Specificity

0.964 0.910 0.990

Positive Predictive Value

0.78

0.57

0.92

Negative Predictive Value

0.95

0.87

0.99

Positive Likelihood Ratio

19.4

7.2

Negative Likelihood Ratio

0.3

0.16

0.61

CLR: CRP/lymphocyte ratio. 0.2

CLR CRP NLR

0.0 0.0

0.2

0.4 0.6 1 - Specificity

0.8

1.0

Figure 2. ROC analysis in the evaluation of PA (CLR: (CRP/lymphocyte ratio)x100; CRP: C-reactive protein; NLR: neutrophil/lymphocyte ratio).

predicting PA was 0.45. ROC analysis with this cut-off value revealed that positive predictive value was 0.78 (lower-upper limit; 0.57–0.92), negative predictive value 0.95 (lower-upper limit; 0.87–0.99), Positive Likelihood Ratio 19.4 (lower-upper limit) 7.2–53), Negative Likelihood Ratio 0.31 (upper-lower limit; 0.16–0.61) (Table 2). This finding showed that CLR had a higher significance value than WBC, CRP and NLR in showing AA perforation. Age, CRP, NLR, and CLR were found significant in univariant analyses and further evaluated by multivariant analyses. In the end, CLR was found to be the only significant risk factor in PA cases (p=0.016) (Table 3).

DISCUSSION Here, we studied some biochemical markers from patient se762

Table 3. Statistical values of CLR in PA in the multivariate analysis

OR (95% CI)* p**

Age

1.05 (0.98–1.054)

0.365

CRP

0,91 (0.66–1.26)

0.578

NLR

1.14 (0.41–3.19)

0.407

CLR

1641,15 (4.09–658741.53)

0.016

CRP: C-reactive protein; NLR: Neutrophil/lymphocyte ratio; CLR: (CRP/ lymphocyte ratio)x100.

rum to reveal whether perforated appendicitis can be differentiated from acute appendicitis. To our knowledge, this is the first study in the literature investigating the efficacy of CLR in the differentiation of PA and AA. We found that CLR was significantly higher in patients with PA than patients with AA. We have also shown that it has a high sensitivity and specificity ratio compared to the other measured inflammatory parameters. We analyzed the demographic data of the patients: the median age was 32 (24;43, IQR) in and 44.5 (25;70, IQR) in the AA and PA groups, respectively. Although there was an age differUlus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Koyuncu et al. The role of CRP to lymphocyte ratio in the differentiation of acute and perforated appendicitis

ence between the groups, we do not think that it is clinically significant. The mean length of hospital stay was significantly lower in the AA group than in the PA group, as expected. Postoperative length of hospital stay has paramount importance concerning patient comfort and the costs of treatment. The length of hospital stay varies in the literature depending on several factors like whether the disease was complicated or the operation was performed laparoscopically or not.[17–19] The imaging techniques are valuable for the differentiation of AA and PA. In this regard, CT was regarded as a highly sensitive and specific examination method. Compared with CT, the, sensitivity and specificity of USG has been found lower than CT in several studies.[20–24] To increase the sensitivity of CT in perforated apendicitis, the appendix sphericity index was defined and subsequently shown that the consideration of this index was well correlated with prediction of perforation.[6] On the other hand, both USG and CT have higher sensitivity and specificity than other laboratory parameters. The sensitivity and specificity of USG decrease especially in cases of obesity, atypical appendix location, abdominal rigidity due to perforation, and incompatible in abdominal distension.[21,25] CT has also some disadvantages; regional availability varies, it cannot be used in pregnant women, and uses contrast materials.[8,9] In an attempt to search for simple and easily available biochemical indicators many reports have long been published. There have been several studies investigated the WBC, CRP, NLR, bilirubin, and PLR as the diagnostic parameters to differentiate between PA and AA. AUC value for WBC was 0.68, 0.84 for CRP, 0.72 for NLR, 0.62 for bilirubin and 0.65 for PLR.[1,8,26] Similarly, the sensitivity and specificity of CRP to differentiate between perforated and non-perforated cases were found to be 0.80 and 0.81, respectively.[1] Another study performed in 392 cases by Sevinç et al.[8] showed that the sensitivity of NLR was 0.78, the specificity was 0.41, the bilirubin sensitivity was 0.34, and the specificity was 0.8. In patients with acute appendicitis, the CRP value higher than 35 mg/dl had a positive likelihood ratio of 2.79 to differentiate between acute and perforated appendicitis cases.[27] CLR has recently been introduced as a new parameter to determine the prognosis of malignancy in some studies.[14–16] It is a simple calculation obtained by the ratio of CRP to lymphocyte. Both CRP elevation and decrease in peripheral blood lymphocyte in patients with malignancy have been associated with poor prognosis.[28] Several studies have shown that the relationship between CRP and lymphocyte plays a significant role in certain types of cancer. Preoperative screening of CRP, lymphocyte and various ratio analysis (CLR, LCR, CLS) were more sensitive in predicting survival and prognosis in many cancers, including colorectal, hepatocellular, and stomach in the postoperative period.[14–16] This provoked the thought that inflammation-induced elevation of CLR in malignancy patients might also be observed in inflammations, such as appendicitis. The results obtained in this study showed that CLR was more Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

accurate in differentiating AA and PA than other parameters, such as WBC, CRP, and NLR. In our study, although CRP alone was a good predictor of perforation, we found that CLR was more accurate in detecting perforation concerning sensitivity and specificity compared with other parameters in AA cases (AUC of CRP: 0.82 vs. AUC of CLR: 0.83 respectively). Therefore, we can propose CLR as a novel prognostic marker in differentiating acute appendicitis cases from perforations. The question of whether it can be used for other infectious conditions like cholecystitis awaits new studies. Although the current study has added novel information to the literature, it also has some limitations. This is a retrospective study which has inherent deficiencies like in other retrospective studies. Missing data, such as lack of CRP resulted in the exclusion of some patients from this study. However, the group without CRP data did not affect the current outcome. Secondly, the sample size was limited and there was a proportional difference between the two groups.

Conclusion In conclusion, this study suggests that CLR has a critical role in differentiating PA and AA. Since CLR is a ratio between CRP and lymphocyte, which are readily available in many hospitals, it can offer an alternative to sophisticated imaging modalities to differentiate acute appendicitis from perforated cases in resource-limited centers. Future prospective validation studies may shed further light on this subject. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.K.; Design: S.K.; Supervision: O.İ.; Fundings: S.K.; Materials: S.K.; Data: S.K.; Analysis: O.İ.; Literature search: O.İ.; Writing: S.K.; Critical revision: O.İ. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Shin DH, Cho YS, Cho GC, Ahn HC, Park SM, Lim SW, et al. Delta neutrophil index as an early predictor of acute appendicitis and acute complicated appendicitis in adults. World J Emerg Surg 2017;12:32. 2. Al-Abed YA, Alobaid N, Myint F. Diagnostic markers in acute appendicitis. Am J Surg 2015;209:1043−7. 3. Lee JH, Park YS, Choi JS. The epidemiology of appendicitis and appendectomy in South Korea: national registry data. J Epidemiol 2010;20:97−105. 4. Ditillo MF, Dziura JD, Rabinovici R. Is it safe to delay appendectomy in adults with acute appendicitis?. Ann Surg 2006;244:656−60. 5. Sand M, Bechara FG, Holland-Letz T, Sand D, Mehnert G, Mann B. Diagnostic value of hyperbilirubinemia as a predictive factor for appendiceal perforation in acute appendicitis. Am J Surg 2009;198:193−8. 6. Şirik M, İnan İ. Contribution of the appendix sphericity index in pre-

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Koyuncu et al. The role of CRP to lymphocyte ratio in the differentiation of acute and perforated appendicitis dicting perforated acute appendicitis. Ulusal Travma Acil Cerrahi Derg 2019;25:123−8. 7. Hajibandeh S, Hajibandeh S, Hobbs N, Mansour M. Neutrophil-to-lymphocyte ratio predicts acute appendicitis and distinguishes between complicated and uncomplicated appendicitis: A systematic review and meta-analysis. Am J Surg 2020;219:154−63. 8. Sevinç MM, Kınacı E, Çakar E, Bayrak S, Özakay A, Aren A, et al. Diagnostic value of basic laboratory parameters for simple and perforated acute appendicitis: an analysis of 3392 cases. Ulus Travma Acil Cerrahi Derg 2016;22:155−62. 9. Panagiotopoulou IG, Parashar D, Lin R, Antonowicz S, Wells AD, Bajwa FM, et al. The diagnostic value of white cell count, C-reactive protein and bilirubin in acute appendicitis and its complications. Ann R Coll Surg Engl 2013;95:215−21. 10. Jung SK, Rhee DY, Lee WJ, Woo SH, Seol SH, Kim DH, et al. Neutrophil-to-lymphocyte count ratio is associated with perforated appendicitis in elderly patients of emergency department. Aging Clin Exp Res 2017;29:529−36. 11. Kahramanca S, Ozgehan G, Seker D, Gökce EI, Seker G, Tunç G, et al. Neutrophil-to-lymphocyte ratio as a predictor of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2014;20:19−22. 12. Yazar FM, Bakacak M, Emre A, Urfalıoglu A, Serin S, Cengiz E, et al. Predictive role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for diagnosis of acute appendicitis during pregnancy. Kaohsiung J Med Sci 2015;31:591−6. 13. Okugawa Y, Toiyama Y, Yamamoto A, Shigemori T, Ide S, Kitajima T, et al. Lymphocyte-C-reactive Protein Ratio as Promising New Marker for Predicting Surgical and Oncological Outcomes in Colorectal Cancer. Ann Surg. 2019 Feb 16. doi: 10.1097/SLA.0000000000003239. [Epub ahead of print]. 14. Okugawa Y, Toiyama Y, Yamamoto A, Shigemori T, Ichikawa T, Yin C, et al. Lymphocyte-to-C-reactive protein ratio and score are clinically feasible nutrition-inflammation markers of outcome in patients with gastric cancer. Clinical Nutrition 2019;39:1209−17. 15. Nozoe T, Kono M, Kuma S, Tsujita E, Ohga T. New scoring system to create a prognostic criteria in colorectal carcinoma based on serum elevation of C-reactive protein and decrease in lymphocyte in peripheral blood. JMI 2019;66:264−8. 16. Liao M, Chen P, Liao Y, Li J, Yao W, Sun T, et al. Preoperative high-sensitivity C-reactive protein to lymphocyte ratio index plays a vital role in the prognosis of hepatocellular carcinoma after surgical resection. Onco

Targets Ther 2018;11:5591−600. 17. Holloway JJ, Lett LA, Kim DY, Saltzman DJ, Ferebee MB, Macqueen IT, et al. Investigating the effect of discordant clinical and pathological diagnoses of complicated appendicitis on clinical outcomes. The American J Surg 2020;219:71−4. 18. Yau, KK, Siu WT, Tank CN, Yang GC, Li MW. Laparoscopic versus open appendectomy for complicated appendicitis. J American College of Surg 2007;205:60−5. 19. Zhu JH, Li W, Yu K, Wu J, Ji Y, Wang JW. New strategy during complicated open appendectomy: convert open operation to laparoscopy. World J Gastroenterol 2014;20:10938−43. 20. Gaitini D, Beck-Razi N, Mor-Yosef D, Fischer D, Ben Itzhak O, Krausz MM, et al. Diagnosing acute appendicitis in adults: accuracy of color Doppler sonography and MDCT compared with surgery and clinical follow-up. AJR Am J Roentgenol 2008;190:1300−6. 21. Elghany E, Ali G. Multidetector row helical CT and US in diagnosing appendicitis. The Egyptian J Radiology and Nuclear Med 2011;42:139−45. 22. Karabulut N, Kiroglu Y, Herek D, Kocak TB, Erdur B. Feasibility of low-dose unenhanced multi-detector CT in patients with suspected acute appendicitis: comparison with sonography. Clin Imaging 2014;38:296−301. 23. Kim HY, Park JH, Lee YJ, Lee SS, Jeon JJ, Lee KH. Systematic Review and Meta-Analysis of CT Features for Differentiating Complicated and Uncomplicated Appendicitis. Radiology 2018;287:104−15. 24. Foley WD. CT Features for Complicated versus Uncomplicated Appendicitis: What Is the Evidence?. Radiology 2018;287:116−8. 25. Emil S, Mikhail P, Laberge JM, Flageole H, Nguyen LT, Shaw KS, et al. Clinical versus sonographic evaluation of acute appendicitis in children: a comparison of patient characteristics and outcomes. J Pediatr Surg 2001;36:780−3. 26. Beltran MA, Mendez PE, Barrera RE, Contreras MA, Wilson CS, Cortes VJ, et al. Is hyperbilirubinaemia in appendicitis a better predictor of perforation than C-reactive protein? - a prospective study. Indian J Surg 2009;71:265−72. 27. Özozan ÖV, Vural V. High C-reactive protein level as a predictor for appendiceal perforation. Ulusal Travma Acil Cerrahi Derg 2020;26:63−6. 28. Shibutani M, Maeda K, Nagahara H, Noda E, Ohtani H, Nishiguchi Y, et al. A high preoperative neutrophil-to-lymphocyte ratio is associated with poor survival in patients with colorectal cancer. Anticancer Res 2013;33:3291−4.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut ve perfore apandisit ayırımında C-reaktif protein lefosit oranının rolü Dr. Serhat Koyuncu,1 Dr. Okan İsmail2 1 2

Tokat Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Tokat Tokat Gaziosmanpaşa Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Tokat

AMAÇ: Bu çalışmada, CRP lenfosit oranının akut apandisit (AA) ve perfore apandisit (PA) ayrımında radyolojik tetkiklerin tanıyı netleştirmede yetersiz kaldığı vakalarda rutin kullanılan laboratuvar parametrelerine göre üstünlüğünü araştırmak amaçlanmıştır. GEREÇ VE YÖNTEM: Kesitsel ve ileriye yönelik olarak plananlanan bu çalışmada hastalar perfore ve non-perfore akut apandisit olarak iki gruba ayrıldı. Her iki gruptaki hastaların yaşı, cinsiyeti, yatış süresi, tanı anındaki lökosit, nötrofil, lenfosit, C reaktif protein (CRP), lenfosit oranı (CLR) değerleri kayıt altına alındı. Tek değişkenli analiz ile istatistiksel olarak anlamlı sonuçlar saptanan değerler arasında regresyon analizleri yapıldı. BULGULAR: Çalışmaya 131 hasta alındı (AA grubunda 111 hasta ve PA grubunda 20 hasta). Yaş (p=0.03), cinsiyet (p<0.001), hastanede kalış süresi (p<0.001), CRP (p<0.001), NLR (p=0.004), CLR (p<0.001) değerleri her iki grup arasında anlamlı olarak farklı tespit edildi. Ancak yapılan regresyon analizinde sadece CLR anlamlı bir risk faktörü olarak bulundu (p=0.016). ROC analizinde CLR’de en yüksek AUC değeri gösterildi (0.83). PA’nin kestirim değeri 0.45 olarak bulundu. TARTIŞMA: Bu çalışma CLR’nin AA ve PA hastalarının ayırımı için önemli bir parametre olduğunu gösterdi. Ayrıca, bu hastaların preoperatif risk sınıflandırmasında değerli bir belirleyicidir. Anahtar sözcükler: Akut apandisit; C-reaktif protein lenfosit oranı; perforasyon. Ulus Travma Acil Cerrahi Derg 2020;26(5):760-764

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ORIGIN A L A R T IC L E

Pediatric head traumas: A different perspective Soner Yaşar, M.D.,

Alparslan Kırık, M.D.,

Mehmet Ozan Durmaz, M.D.

Department of Neurosurgery, University of Health Sciences, Gülhane Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: We aim to present our series on pediatric head traumas and discuss our results with the current literature. METHODS: The data of children who underwent treatment for head trauma in our department between 2010 and 2019 were retrospectively reviewed. Their clinical condition at admission, radiological findings, treatment methods and outcomes were analyzed. RESULTS: Ninety children underwent treatment for head trauma, 60 of them were male and 30 were female. The mean age was 6.6 years. Linear skull fracture was seen 55 patients, while epidural hematoma in 15 patients. Twenty patients underwent surgical treatment, while 70 patients underwent conservative treatment. No patient died in our series, three patients underwent rehabilitation due to neurological deficits after discharge. CONCLUSION: Children were more prone to head trauma, but their mortality was less than the adults. Conservative treatment should be the first goal, but surgical management should be reserved for children with significant hematoma and declining neurological conditions. Keywords: Child; head trauma; outcome; surgery.

INTRODUCTION Head trauma is an important health issue in the population. Adults and children may be affected by head traumas. These injuries may cause different clinical and surgical conditions, ranging from mild to severe head traumas.[1] Although most of childhood head injuries are minor, many children die or develop permanent disabilities each year from head trauma.[2–4] The most common causes of head injuries in children are motor vehicle accidents, falls, assaults, bicycle accidents and sport traumas. Most serious head injuries in infants younger than one year old are related to child abuse or abusive head traumas.[5–7] Head injuries may cause many symptoms, depending on the type of injury, its severity and its location on the head. The child’s neurological symptoms may include: loss of consciousness, headache, dizziness, nausea and vomiting, difficulty walking, slurred speech, amnesia, seizure and hemiparesis or hemiplegia.[1,2,4,8,9]

Mild head traumas in children usually do not require any treatment other than close monitoring for at least 48 hours. Careful monitoring is very important in children with concussion and the child may need bed rest and to stay out of sports for a limited time period. In children with serious head traumas, management protocol depends on the type and severity of head injury, as well as on the location. Sometimes, the patient needs medical treatment in an intensive care unit, including antiedema, anticonvulsives, analgesics, and antibiotics if required.[1,4,10] The aim of medical treatment is to decrease the intracranial pressure, maintain the blood pressure and prevent seizures. Surgery may need for an epidural or subdural hematoma, or a depressed skull fracture, brain hemorrhage or contusion. The present study aims to present our series of 90 children who underwent treatment for head trauma. Their clinical presentation and treatment strategies are summarized and discussed with the current literature.

Cite this article as: Yaşar S, Kırık A, Durmaz MO. Pediatric head traumas: A different perspective. Ulus Travma Acil Cerrahi Derg 2020;26:765-768. Address for correspondence: Soner Yaşar, M.D. Sağlık Bilimleri Üniversitesi, Gülhane Tıp Fakültesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 304 53 44 E-mail: dr.soneryasar@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):765-768 DOI: 10.14744/tjtes.2020.24287 Submitted: 28.09.2019 Accepted: 19.01.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Yaşar et al. Pediatric head traumas: A different perspective

MATERIALS AND METHODS Ethical approval was obtained for this retrospective study. The data of pediatric patients (0–18 years) who were admitted and treated for head trauma in our department between 2010 and 2019 were retrospectively reviewed. Demographic, radiological, clinical and surgical features of the patients were analyzed. Computed tomography (CT) was used in all patients for diagnosis. Magnetic resonance imaging (MRI) was preferred in selected cases with diffuse axonal injury. Surgical treatment was administered in patients with acute epidural/ subdural hematoma causing intracranial hypertension, depressed skull fractures and open fractures. Other cases were treated conservatively.

RESULTS Ninety patients were treated in a 10 year period. Thirty patients were female and 60 were male. Mean age was 6.6 years (range 0 and 18 years). The causes of trauma were falls, car accidents, and sport injuries. The most common diagnosis was linear fracture in 55 cases (Fig. 1) and epidural hematoma in 15 patients (Fig. 2). Subdural hematoma was observed in six children and three of them underwent surgical treatment. Others were treated conservatively (Fig. 3). Depression fracture was observed in five cases (Fig. 4). After the diagnosis, surgical treatment was administered in 20 children, while conservative management was applied in 70 cases. There was no mortality in our series, while three patients were transferred to the rehabilitation unit for neurological deficits. Other patients were discharged without complication or deficit. The mean follow-up was 17 months (ranged 3–39 months).

Figure 2. Axial CT scan of a 12-years old male child with occipital fracture and acute epidural hematoma. He underwent emergent evacuation of the epidural hematoma.

Figure 1. Axial CT scan of a 2-years old male child with the left temporal linear fracture.

Figure 4. 3-D CT scan of a child with left frontal depression fracture reaching to the orbital roof.

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(a)

(b)

Figure 3. Axial CT scan of a 3-years-old child shows left parietal acute subdural hematoma (a). Three days later, subdural hematoma was spontaneously cleaned with the CSF (b).

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Yaşar et al. Pediatric head traumas: A different perspective

DISCUSSION We presented the results of 90 children who admitted to our department with head trauma. Most of them had skull fractures but surgical treatment was applied only in 70 patients. Conservative treatment was the most preferred method for children in our series. None of them died after treatment. Head trauma occurs commonly in childhood. Most children with head trauma are young and male. In addition, head trauma in children is usually minor and not associated with brain injury or long-term squeal. However, a small number of children who appear to be at low risk after minor head trauma may have a clinically important brain injury. In the USA, children younger than 14 years of age, traumatic brain injury (TBI) accounts for approximately 500,000 emergency department visits, 37,000 hospitalizations and over 2000 deaths annually.[11] In developed countries, TBI is the most common cause of death and disability in childhood.[12] In children, the major challenge for assessment of a mild head trauma is to determine those young children and infants who need a neuroradiological study. Today, CT scan is highly sensitive to identify an intracranial lesion that may require acute intervention.[7,13,14] MRI is not useful in the initial management of head trauma in children because of the longer duration of MRI than CT scan and it requires full cooperation of child. MRI can also miss out skull fractures which can be easily detected by CT scan. In our series, we used CT scans in all cases, but MRI was mainly preferred to detect diffuse axonal injury. Pediatric head trauma may be mild, moderate or severe. Mild trauma is generally associated with minor symptoms, such as a short loss of consciousness, disorientation or vomiting.[1] They usually have GCS scores of 13 to 15 which measured approximately 30 minutes after the injury. In comparison, patients with moderate trauma generally have an initial GCS scores between 9 and 12, whereas patients with severe trauma have GCS scores ≤8. Concussion can be defined as trauma-induced brain dysfunction without any structural injury on standard neuroradiology.[4] Brain injury may occur following a minor head trauma because rotational acceleration-deceleration of the head generates shearing forces that cause mechanical disruption of nerve fibers, resulting in diffuse axonal injury.[1,6,13] This condition can only be detected by MRI scan. Head trauma may produce hematoma in the child’s brain. These hematomas are epidural, subdural or intraparenchymal. Epidural hematomas typically arise from a direct blow resulting in a linear fracture that cross the branches of middle meningeal artery or dural venous sinuses, but may also occur without an associated fracture in a significant number of children. Early diagnosis and treatment is crucial for epidural hematoma.[15–17] Binder et al.[8] reviewed 41 pediatric patients with traumatic epidural hematoma and they concluded that age, severity of trauma and neurological status are the main Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

factors affecting the outcome of acute epidural hematoma in children. In our series, linear skull fracture was detected in 55 patients, while epidural hematoma in 15 patients, 13 of them underwent surgical treatment. None of them died after surgery. Gekat et al.[17] reviewed 56 cases of epidural and 38 cases of subdural hemorrhage and they showed that subdural hematoma is more common in young children and mostly the result of a suspected abuse in children under two years of age. Subdural hematomas may also be seen in children with head trauma. Sometimes, abusive traumas may present with subdural hematoma or hygroma. Subdural hematomas usually require surgery, but rapid spontaneous resolution may also occur.[18,19] In our series, subdural hematoma is less frequent and observed in six patients. There was no suspicion of abuse in our cases. Three of them underwent early surgical evacuation. One patient with acute subdural hematoma was improved within three days with conservative treatment. Abusive head trauma, also known as a shaken baby syndrome, is one of the most common subtypes of nonaccidental trauma and is a leading cause of traumatic brain injury in young children.[5] Understanding the common patterns of abusive head injury can help increase diagnostic accuracy both by increasing recognition of injuries with high specificity for AHT and by avoiding unwarranted concern in patients with concordant injury patterns and clinical history.[20] In our series, we not encountered any abusive head trauma. Astrand et al.[21] reported new evidence-based guidelines for the initial management of head trauma in the paediatric population and their guidelines to include criteria for selecting children for CT scans, in-hospital observation or early discharge, and suggestions for monitoring routines and discharge advice for children and guardians. This guideline separate mild head trauma patients into high-, medium- and low-risk categories, favouring observation for mild, low-risk patients as an attempt to reduce CT scans in children. The limitation of our study is the retrospective nature and a small number of patients. In addition, there was a statistical study for the comparison of our outcomes.

Conclusion Children have unique anatomic and physiologic properties, and head trauma is an important clinical condition in children. It should always be managed seriously and appropriate treatment methods should be applied. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.Y., A.K.; Design: S.Y.; Supervision: M.O.D.; Materials: S.Y.; Data: A.K.; Analysis: S.Y.; Literature search: S.Y., A.K.; Writing: A.K.; Critical revision: M.O.D. 767

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Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Araki T, Yokota H, Morita A. Pediatric Traumatic Brain Injury: Characteristic Features, Diagnosis, and Management. Neurol Med Chir (Tokyo) 2017;57:82−93. 2. Dubey V, Nau E, Sycip M. Altered Mental Status in Children After Traumatic Brain Injury. Pediatr Ann 2019;48:e192−6. 3. Lindholm EB, D’Cruz R, Fajardo R, Meckmongkol T, Ciullo S, Grewal H, et al. Admission of Pediatric Concussion Injury Patients: Is It Necessary? J Surg Res 2019;244:107−10. 4. Rotter J, Kamat D. Concussion in Children. Pediatr Ann 2019;48:e182−5. 5. Duhaime AC, Christian CW, Rorke LB, Zimmerman RA. Nonaccidental head injury in infants--the “shaken-baby syndrome”. N Engl J Med 1998;338:1822−9. 6. Hahn YS, McLone DG. Risk factors in the outcome of children with minor head injury. Pediatr Neurosurg 1993;19:135−42. 7. Greenberg JK, Jeffe DB, Carpenter CR, Yan Y, Pineda JA, Lumba-Brown A, et al. North American survey on the post-neuroimaging management of children with mild head injuries. J Neurosurg Pediatr 2018;23:227−35. 8. Binder H, Majdan M, Tiefenboeck TM, Fochtmann A, Michel M, Hajdu S, et al. Management and outcome of traumatic epidural hematoma in 41 infants and children from a single center. Orthop Traumatol Surg Res 2016t;102:769−74. 9. Rumalla K, Smith KA, Letchuman V, Gandham M, Kombathula R, Arnold PM. Nationwide incidence and risk factors for posttraumatic seizures in children with traumatic brain injury. J Neurosurg Pediatr 2018;22:684−93. 10. Zhang F, Huang L, Singichetti B, Li H, Sullivan L, Yang JG. Sex and age differences in hospitalised paediatric traumatic brain injuries. Pediatr Int.

2019 Jul 9. doi: 10.1111/ped.13946. [Epub ahead of print]. 11. Langlois JA, Rutland-Brown W, Thomas KE. Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations and Deaths. Atlanta: Centers for Disease Control and Prevention; 2004. 12. Luerssen TG, Klauber MR, Marshall LF. Outcome from head injury related to patient’s age. A longitudinal prospective study of adult and pediatric head injury. J Neurosurg 1988;68:409−16. 13. Smith A, Gruskin K, Monuteaux MC, Stack AM, Sundberg M, Yim R, et al. Reducing the cranial CT rate for pediatric minor head trauma at three community hospitals. Pediatr Qual Saf 2019;4:e147. 14. Weber CD, Lefering R, Weber MS, Bier G, Knobe M, Pishnamaz M, et al. Predictors for pediatric blunt cerebrovascular injury (BCVI): An international multicenter analysis. World J Surg 2019;43:2337−47. 15. Champagne PO, He KX, Mercier C, Weil AG, Crevier L. Conservative Management of Large Traumatic Supratentorial Epidural Hematoma in the Pediatric Population. Pediatr Neurosurg 2017;52:168−72. 16. Faheem M, Jaiswal M, Ojha BK, Chandra A, Singh SK, Srivastava C. Traumatic Pediatric Extradural Hematoma: An Institutional Study of 228 Patients in Tertiary Care Center. Pediatr Neurosurg 2019;54:237−44. 17. Gekat W, Binder S, Wetzel C, Rothschild MA, Banaschak S. SDH and EDH in children up to 18 years of age-a clinical collective in the view of forensic considerations. Int J Legal Med 2018;132:1719−27. 18. Nguyen VN, Wallace D, Ajmera S, Akinduro O, Smith LJ, Giles K, et al. Management of Subdural Hematohygromas in Abusive Head Trauma. Neurosurgery 2020;86:281−7. 19. Öğrenci A, Ekşi MŞ, Koban O, Karakuş M. Spontaneous rapid resolution of acute subdural hematoma in children. Childs Nerv Syst 2015;31:2239−43. 20. Wright JN. CNS Injuries in abusive head trauma. AJR Am J Roentgenol 2017;208:991−1001. 21. Astrand R, Rosenlund C, Undén J; Scandinavian Neurotrauma Committee (SNC). Scandinavian guidelines for initial management of minor and moderate head trauma in children. BMC Med 2016;14:33.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Pediyatrik kafa travmaları: Farklı bir bakış açısı Dr. Soner Yaşar, Dr. Alparslan Kırık, Dr. Mehmet Ozan Durmaz Sağlık Bilimleri Üniversitesi, Gülhane Tıp Fakültesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, Ankara

AMAÇ: Pediyatrik kafa travmaları çalışmamızı sunmak ve sonuçlarımızı güncel literatürle tartışmaktır. GEREÇ VE YÖNTEM: 2010 ve 2019 yılları arasında kliniğimizde kafa travması nedeniyle tedavi gören çocukların verileri geriye dönük olarak incelendi. Başvuru sırasındaki klinik durumu, radyolojik bulgular, tedavi yöntemleri ve sonuçları analiz edildi. BULGULAR: Doksan çocuk kafa travması nedeniyle tedavi edildi, bunların 60’ı erkek, 30’u kız idi. Yaş ortalaması 6.6 idi. Elli beş hastada lineer kafatası kırığı, 15 hastada epidural hematom görüldü. Yirmi hastaya cerrahi tedavi uygulandı, 70 hastaya konservatif tedavi uygulandı. Çalışmamızda hiçbir hasta kaybedilmedi, üç hastaya taburcu olduktan sonra nörolojik defisit nedeniyle fizik tedavi ve rehabilitasyon uygulandı. TARTIŞMA: Çocuklar kafa travmasına daha erişkinlere göre yatkındır, ancak mortalite yetişkinlerden daha azdır. Konservatif tedavi ilk hedef olmalı, ancak önemli boyutlarda hematomlu ve kötüleşen nörolojik tablosu olan çocuklar için cerrahi tedavi düşünülmelidir. Anahtar sözcükler: Cerrahi; çocuk; kafa travması; sonuç. Ulus Travma Acil Cerrahi Derg 2020;26(5):765-768

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doi: 10.14744/tjtes.2020.24287

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ORIGIN A L A R T IC L E

The value of inflammatory markers in diagnosing acute appendicitis in pregnant patients Ahmet Akbaş, M.D.,1 Zeliha Aydın Kasap, M.D.,2 Nadir Adnan Hacım, M.D.,1 Merve Tokoçin, M.D.,1 Yüksel Altınel, M.D.,1 Hakan Yiğitbaş, M.D.,1 Serhat Meriç, M.D.,1 Bakiye Okumuş, M.D.3 1

Department of General Surgery, University of Health Sciences, Bağcılar Training and Research Hospital, İstanbul-Turkey

Department Biostatistics and Medical Informatics, Karadeniz Technical University Faculty of Medicine, Trabzon-Turkey

Department of Obstetrics and Gynecology, İstinye University Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: Acute appendicitis (AA) is the most common extra-obstetric condition requiring surgery during pregnancy. AA diagnosis is made by laboratory tests along with anamnesis and physical examination findings. Due to the physiological and anatomical changes during the pregnancy, AA diagnosis is more challenging in pregnant women compared to non-pregnant patients. The present study evaluated the significance of white blood cell counts (WBC), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CAR) and lymphocyte-to-C-reactive protein ratio (LCR) to diagnose acute appendicitis during pregnancy. METHODS: Pregnant patients admitted to General Surgery Inpatient Clinic with AA pre-diagnosis in September 2015-December 2019 period were screened using International Statistical Classification of Diseases and Related Health Problems-10 (ICD-10) diagnosis code (K35= acute appendicitis, Z33= pregnancy), and AA patients were identified retrospectively. The patients were divided into two groups. The Group I included the patients who had appendectomy due to AA and had a suppurative appendicitis diagnosis based on the pathological evaluation. On the other hand, Group II had the patients admitted as an inpatient with AA pre-diagnosis, but discharged from the hospital with full recovery without operation. Group III, i.e., the control group, on the other hand, was constituted by 32 randomly and prospectively recruited healthy pregnant women who were willing to participate in the study and who had matching study criteria among the patients followed in Obstetrics and Gynecology outpatient clinic of our hospital. RESULTS: This study included 96 pregnant women with an average age of 29.20±4.47 years (32 healthy pregnant women, 32 pregnant women followed for acute abdominal observation and 32 pregnant women who underwent appendectomy). Of these patients, three cases who turned out not to have suppurative appendicitis (negative appendectomy) and two cases found to have perforated appendicitis based on intraoperative and histopathological evaluations were excluded from this study. The results showed that Group I patients had significantly higher WBC (p=0.001), CAR (p=0.001) and NLR (p=0.001), but significantly lower LCR values (p=0.001) compared to the Groups II and III. Besides, based on logistic regression analysis, it was revealed that higher WBC, CAR and NLR values and lower LCR values were independent variables that could be used for the diagnosis of AA in pregnant women. CONCLUSION: Considering WBC, NLR, CAR and LCR parameters in addition to medical history, physical examination and imaging techniques could help clinicians diagnose acute appendicitis in pregnant women. Keywords: Acute appendicitis; CRP albumin ratio; lymphocyte; neutrophil; pregnancy.

INTRODUCTION The most common cause of non-obstetric surgery during

pregnancy is acute appendicitis (AA), and its incidence rate is similar to that of non-pregnant patients.[1] The diagnosis of AA is made based on the patient’s anamnesis and physical

Cite this article as: Akbaş A, Aydın Kasap Z, Hacım NA, Tokoçin M, Altınel Y, Yiğitbaş H, et al. The value of inflammatory markers in diagnosing acute appendicitis in pregnant patients. Ulus Travma Acil Cerrahi Derg 2020;26:769-776. Address for correspondence: Ahmet Akbaş, M.D. Sağlık Bilimleri Üniversitesi, İstanbul Bagcılar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 440 40 00 E-mail: draakbas@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):769-776 DOI: 10.14744/tjtes.2020.03456 Submitted: 03.02.2020 Accepted: 23.07.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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examination findings accompanied by laboratory tests. Due to physiological and anatomical changes during pregnancy, the diagnosis of AA is more difficult than in non-pregnant patients. In addition, the lack of pathognomonic signs and findings, and poor predictive value of the relevant laboratory tests make the diagnosis of AA difficult in pregnant patients. [2] This could be life-threatening for the mother and fetus.[3]

Computed Tomography (CT) is restricted due to its ionizing radiation.[6] In the present study, we aimed to draw attention to the importance of using easily available, cost-effective inflammatory markers that could help physicians in the evaluation of patients with suspected acute appendicitis.

There is no specific laboratory parameter specific to AA diagnosis, but white blood cell count (WBC) and C-reactive protein (CRP) are commonly used for this purpose. However, physiological leukocytosis occurs during pregnancy, and WBC and CRP levels increase in the late weeks of gestation. [4,5] Therefore, the use of WBC and CRP parameters alone could be misleading in the diagnosis of AA during pregnancy.[6] Neutrophil white blood cells are a major part of the immune system. Mast cells, epithelial cells and neutrophils regulated by macrophages also play important roles in inflammatory events. The role of lymphocytes in the development of inflammation and infection is well-known.[7] There have been recent reports about using the ratios of these inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-C-reactive protein ratio (LCR), for early inflammation markers in AA diagnosis.[4,8]

After this study was approved by the ethical board of İstanbul Bağcılar Training and Research Hospital, pregnant patients admitted to General Surgery Inpatient Clinic of our hospital with AA pre-diagnosis in September 2015-December 2019 period were screened online in the hospital database system using International Statistical Classification of Diseases and Related Health Problems-10 (ICD-10) diagnosis code (K35= acute appendicitis, Z33= pregnancy), and AA patients were identified retrospectively. The patients were divided into two groups. The Group I included the patients who underwent appendectomy due to AA and had a suppurative appendicitis diagnosis based on pathological evaluation, while Group II had the patients who were admitted as an inpatient with AA pre-diagnosis, but discharged from the hospital with full recovery without being operated. Control group, i.e., the Group III, on the other hand, included 32 randomly and prospectively recruited healthy pregnant women who were willing to participate in the study and had matching study criteria among the patients monitored in Obstetrics and Gynecology outpatient clinic of our hospital. The individuals for whom laboratory parameters were not available, individuals who had hematological impairment, chronic liver or kidney disease, chronic obstructive pulmonary disease, asthma, any viral or bacterial infection, cancer or autoimmune disease, alcohol or tobacco use, individuals who were operated but did not have suppurative appendicitis based on histopathological findings (who had perforated appendicitis or negative appendectomy patients) and the patients with missing records were excluded.

AA causes the initiation of an inflammatory process secondary to bacterial infection in the body, resulting in the formation of an acute phase response by the body against the pathological agent. Proteins whose serum or plasma levels increase or decrease during this period are called acute phase proteins (APP). APP synthesis takes place in the liver due to cytokines released from tissue macrophages, and they nonspecifically reflect the presence and severity of inflammation. [9] The proteins whose synthesis increase depending upon AFY are referred to positive acute phase reactant while those whose synthesis decrease are termed negative acute phase reactant. The amount of CRP increases in the acute phase response secondary to inflammation in the organism, while the amount of albumin decreases.[10,11] CRP/albumin ratio (CAR) is a parameter that has been used recently, and there are not many studies about this parameter in the literature. Some studies indicated that elevated CAR values indicate the severity of infection-related inflammation.[11] Among them are the studies mentioning that high CAR values could be used as a marker to determine the severity of infection in acute exacerbations of Crohn’s disease.[10,12] Similarly, Goulart et al. [13] found that high CAR values could be used as a marker to determine surgical site infection during the postoperative period in patients operated due to colorectal cancer. Although ultrasonography (USG) is the most frequently used sonographic method in the diagnosis of AA, it may not meet the expectations due to anatomical changes observed during pregnancy. The use of Magnetic Resonance (MR) is limited since it is expensive, is not easily accessible and takes a long time for the examination. On the other hand, the use of 770

MATERIALS AND METHODS

Hemogram tests were performed on blood samples obtained from the venous system collected into ethylene diamine tetra acetic acid tubes. Blood samples for albumin and CRP were taken into serum tubes, with increased silica act clot activator, silicone-coated interior. As hemogram, albumin and CRP values, the assays performed within 24 hours of the patient’s initial application were used. In case of the multiple analyses, the first analysis was taken into account. The white blood cell, neutrophil and lymphocyte values were taken from hemograms. NLR value was calculated as the neutrophil/lymphocyte ratio, while LCR value was calculated as lymphocyte/CRP, and CAR was calculated as the CRP/albumin ratio. Hemogram testing parameters were measured using Abbott Cell-Dyn 3700 Hematology Analyzer, Abbott Diagnostics, USA, while biochemistry tests were carried out using Beckman Coulter AU 5800 Chemistry analyzer, USA; albumin was analyzed with brome Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

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cresol purple method, and CRP was studied as an immunoturbidimetric assay. The limits of the reference intervals were as follows: leukocyte counts (WBC): 4600–10200/μL, neutrophil: 2.0–6.9×10³/μL; lymphocyte: 0.6–3.4×10³/μL; CRP: 0-5 mg/l; albumin: 3.5–5.4 mg/l). All statistical analyses were performed using IBM SPSS Statistics 22.0 software. The Kolmogorov Smirnov test was used to determine the normality of the distribution, and the Levene test was used to determine the homogeneity of variances among the groups. ANOVA and Kruskal Wallis tests were used to compare the means of the variables. Bonferroni and Tamhane’s T2 tests were used as post hoc analysis. Receiver Operating Characteristic (ROC) curve and Area under the Curve (AUC) was calculated for diagnostic performance and to evaluate biomarkers’ ability for classifying disease status. The Likelihood Ratios and Youden Index were calculated with the help of sensitivity and specificity values in order to decide the most appropriate cut-off points using MS Excel software. A multinomial logistic regression test was used to define the cause-effect relationship of the categorical response variable with explanatory variables. Quantitative data were expressed as mean±standard deviation. Nonparametric test results were expressed as median (maximum-minimum). Data were analyzed at a 95% confidence interval, and statistical significance was set at p<0.05.

RESULTS This study included 96 pregnant patients with an average age of 29.20±4.47 years (32 healthy pregnant women, 32 pregnant women under acute abdominal observation and 32 pregnant women who underwent appendectomy). Of these patients, three cases that did not have suppurative appendicitis based on surgery and histopathological findings (negative

appendectomy) and two patients with perforated appendicitis were excluded from this study. There was no significant difference among the groups concerning mean age (p=0.190) and gestational week (p=0.235). In addition, it was found that Group I patients had a mean WBC value of 14.09±3.60 /mm3, a median CAR value of 10.93 (76.18–1.43), a median NLR value of 6.00 (11.04–1.39) and a median LCR value of 0.05 (0.004–0.356), while Group II and III had mean WBC values of 9.66±2.84 /mm3 and 10.68±2.32 /mm3, median CAR values of 2.13 (30.60–0.36) and 0.30 (2.13–0.04), median NLR values of 3.29 (6.91–0.97) and 3.69 (17.22 –0.75), and median LCR values of 0.23 (0.01–1.40) and 2,01 (0.38–11.50), respectively. Thus, Group I had significantly higher WBC, CAR and NLR (p<0.01) but significantly lower LCR values compared to Group II and III (p=0.01) (Table 1). Based on the multivariate logistic regression analysis, high WBC level (OR:1.45; 95% CI:1.16–1.81; p=0.001), high CAR level (OR:13.826; 95% CI:4.30–44.45; p=0.001), high NLR level (OR:1.34; 95% CI:1.01–1.78; p=0.046) and low LCR level (OR:0.001; 95% CI:3.642–0.001; p=0.001) were independent variables for AA diagnosis in pregnant patients (Table 2). In ROC curve analyses of these independent variables, AUC was above 0.600 for WBC, CAR, NLR and LCR (Fig. 1). When a cutoff value of >11.965/mm3 was used for WBC, the sensitivity was 77% and the specificity was 81% (accuracy rate 79%, AUC ± SE = 0.828±0.055 and p<0.001) for AA diagnosis. For CAR variable to predict AA diagnosis, the sensitivity was 96% and the specificity was 80% (accuracy rate 88%, AUC±SE = 0.917±0.028, p<0.001) using a cutoff value of >2.473. For NLR, the sensitivity was 68% and the specificity was 86% (accuracy rate 77%, AUC ± SE= 0.781±0.065

Table 1. Gestational age and hemogram parameters of the study groups Appendectomy (Group I) (n=27) Age*

Acute abdominal observation (Group II) (n=32)

Healthy pregnant women (Group III) (n=32)

27.45±4.76 29.44±6.385 30.19±4.782 0.190***

Gestational week 23.51±6.35 *

21.18±6.27

24.43±7.32 0.235***

WBC* (/mm3) 14.09±3.60 9.66±2.84

10.68±2.32 <0.01

(0.000***) CAR**

10.93 (76.18–1.43)

2.13 (30.60–0.36)

0.30 (2.13–0.04)

<0.01

(0.000****) NLR**

6 (11.04–1.39)

3.29 (6.91–0.97)

3.69 (17.22–0.75)

<0.01

(0.000****) LCR

0.05 (0.004–0.356)

0.23 (0.01–1.40)

2,01 (0.38–11.50)

<0.01

(0.000****) *Mean±standard deviation; **Median (max-min); ***One-way ANOVA test; **** Kruskal Wallis Test. CAR: CRP/Albumin ratio; WBC: White blood cell count; NLR: Neutrophil-to-lymphocyte ratio; LCR: Lymphocyte/CRP ratio.

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Table 2. Results of the multinomial logistic regression analysis of white blood cell count, neutrophil-to-lymphocyte ratio, CRP/ albumin ratio and lymphocyte-to-CRP ratio to determine independent predictors of acute appendicitis in pregnant women Independent variables

B±SE

Odds Ratio

95% CI

White blood cell count

0.37±0.11

<0.001

1.45

1.16–1.81

Neutrophil-to-lymphocyte ratio

0.29±0.145

0.046

1.34

1.01–1.78

Lymphocyte-to-CRP ratio

-1.07±0.27

<0.001

0.342

0.203–0.577

CRP/Albumin ratio

2.63±0.60

<0.001

13.826

4.30–44.45

p<0.001

Predicted (%) = 83

Dependent variable: groups Nagelkerke R2=0.808

Multinomial logistic regression. B: The set of coefficients estimated for the model; CI: Confidence interval; SE: Standard error; CRP: C-reactive protein.

Table 3. The results of ROC analysis Parameter

Cut-off values

Accuracy rate (%)

Sensitivity (%)

Specificity (%)

AUC ± SE

WBC

>11.965

0.79

0.77

0.81

0.828±0.055 <0.001

CAR

>2.473

0.88

0.96

0.80

0.917±0.028 <0.001

NLR

>5.025

0.77

0.68

0.86

0.781±0.065 <0.001

LCR

<0.127

0.81

0.73

0.89

0.895±0.033 <0.001

AUC: Area under the receiver operating characteristic curve; SE: Standard error; WBC: White blood cells. CAR: CRP/Albumin ratio; NLR: Neutrophil-to-lymphocyte ratio; LCR: Lymphocyte-to-CRP ratio.

and p<0.001) for the prediction of AA diagnosis when a cutoff value of >5.025 was used. When a cutoff value of <0.127 was used for LCR to predict AA diagnosis, the sensitivity was 73% and the specificity was 89% (accuracy rate 81%, AUC±SE = 0.895±0.033, p<0.001). Proposed cutoff values and performance characteristics for these variables were shown in Table 3. ROC Curve

1.0

Source of the Curve CAR WBC NLR LCR Reference Line

Sensitivity

0.8

0.6

0.4

0.2

0.0 0.0

0.2

0.4

0.6

0.8

1.0

1 - Specificity

Figure 1. Receiver operating characteristic (ROC) curve analyses of significant parameters for the diagnosis of acute appendicitis: CAR: CRP/Albumin ratio; WBC: White blood cell count; NLR: Neutrophil-to-lymphocyte ratio; LCR: Lymphocyte-to-CRP ratio.

772

DISCUSSION AA is among the most common causes of emergency surgery in pregnant patients. Physical examination and anamnesis are important in diagnosing AA. There are difficulties in AA diagnosis due to physiological and anatomical changes observed during pregnancy and due to the restrictions on the use of radiological methods. This increases the importance of using parameters involving acute phase reactants secondary to an inflammatory reaction in the body. In the present study, we found that inflammatory parameters, such as WBC, NLR, CAR, and LCR, could be considered to be statistically significant in AA diagnosis for pregnant patients. WBC is a highly cost-effective and easily accessible laboratory parameter that is widely used in the diagnosis of AA. Elevated WBC level is not a pathognomonic finding in patients with AA, but is used as an auxiliary parameter for AA diagnosis.[14] Elevated WBC levels in peripheral blood are used as an acute phase reactants secondary to inflammation.[15] Keskek et al.[15] and Panagiotopoulou et al.[16] reported that the WBC value of patients with AA was higher than the normal population. Yazar et al.,[4] on the other hand, found that the average WBC value was 10.762±1.513/mm3 in healthy pregnant women and 13.768±3.443/mm3 in patients undergoing an appendectomy. Yilmaz et al.[17] reported an average WBC value of 12.702±4.180/mm3 in pregnant women who were operated due to AA. In the present study, the average WBC value in healthy pregnant women was 10.680±2.32/ mm3, which was 14.090±3.60/mm3 in pregnant patients opUlus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

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erated due to AA. According to these results, WBC value was significantly higher in patients who were operated for AA compared to healthy pregnant women and pregnant women under acute abdominal observation (Table 1). Based on the multivariate logistic analysis (multinomial logistic regression), WBC was found to be an independent risk factor for the diagnosis of AA in pregnant patients (Table 2). Previous studies reported sensitivity levels of 73.0–97.8%, specificity levels of 52.0–55.7%, PPV levels of 42.0–91.3%, and NPV levels of 25.2–82.0% for WBC in AA diagnosis.[14] Such large sensitivity and specificity ranges could be due to the different cut-off values used in the diagnosis of AA. For example, Keskek et al. [15] reported a cut-off value of 10.500/mm3, while Körner et [18] al. mentioned a value of 12.300/mm3. Yazar et al.[4] calculated the sensitivity as 57.1% and specificity as 82.9% when they used a cut-off level of 13.880, while Çınar et al.[19] obtained a sensitivity level of 72.5% and a specificity level of 72.3% using a cut-off value of 10.300. Considering a cut-off value of >11.965/mm3, we calculated the sensitivity as 77%, specificity as 81% (Table 3). Based on these findings, elevated WBC level could be used by clinicians as a parameter to support physical examination and anamnesis findings for the diagnosis of AA in pregnant women. In AA cases, a characteristic shifting to the left is observed in hemogram due to neutrophilia and lymphopenia.[20,21] Markar et al.[22] and Yavuz et al.[23] reported that NLR had statistically higher diagnostic sensitivity for AA than WBC and CRP. Eren et al.,[21] on the other hand, reported that the NLR ratio was higher in patients with complicated appendicitis than in patients subjected to negative appendectomy. This finding was attributed to elevated neutrophilia severity secondary to increased inflammation level and a more evident decrease in lymphopenia.[22] In the present study, the median NLR value observed in patients undergoing appendectomy was 6.00 (1.39–11.04), which was 3.69 (0.75–17.22) in healthy pregnant women. According to these results, the NLR value was significantly higher in patients who were diagnosed with AA and who had appendectomy compared to healthy pregnant women and pregnant women under acute abdominal observation (Table 1). Based on multivariate logistic regression analysis using the data obtained in the present study (multinomial logistic regression), NLR was found to be an independent risk factor for the diagnosis of AA (Table 2). The most appropriate cut-off value for NLR was reported as >3.5 by Białas et al.[24] and as ≥4.5 by Eren et al.[21] Yavuz et al.[23] calculated a sensitivity level of 92.5% and a specificity level of 59.3% for NLR in geriatric patients, when they considered a cut-off value of 3.95. In all three studies, it was stated that the elevated NLR value was associated with complicated appendicitis. Yazar et al.[4] calculated that for AA diagnosis accuracy rate of NLR was 79.4% and AUC ± SE was 0.852±0.049 (p<0.001) when they used a cut-off value of >6.84. On the other hand, Çınar et al.[19] used a cut-off value of >5.50 and calculated the sensitivity as 90%, specificity as 89.4%, accuracy rate as 90.8% and AUC ± SE value as 0.920±0.034 for NLR Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

in AA diagnosis. In the present study, we used a cut-off value of >5.025 for NLR, and calculated sensitivity level as 68% and specificity level as 86% (Table 3). Similar to those reported by Yazar[4] and Çınar,[19] sensitivity and specificity values in the present study were also significant. Based on our findings, elevated NLR level could be used as a supportive parameter to physical examination and anamnesis findings for AA diagnosis in pregnant patients. Bacterial infections, trauma, malignant neoplasms, burns, tissue infarctions, immunological and inflammatory events and birth are stimuli that cause acute phase response in the body. The purpose of the acute phase response is to neutralize pathogens by isolating them, to reduce tissue damage to a minimum by limiting them, to prevent the generalization of the events, to start the repair, thereby allowing the host hemostatic mechanisms to restore the normal physiological function in a fast manner.[25] AA causes the initiation of an inflammatory process secondary to bacterial infection in the body, resulting in the formation of an acute phase response by organism against the pathogen. Regardless of the localized or generalized nature of the disease, the acute phase response is a general host reaction. Proteins whose serum or plasma levels change during this response are called acute phase proteins (AFP). Synthesis of AFP proteins occurs in the liver as a result of cytokines released from tissue macrophages, and these proteins reflect nonspecifically the presence and severity of inflammation.[26,27] Proteins whose synthesis increase due to AFY are called positive reactants, while those whose synthesis decrease is termed acute phase reactants. In acute phase response secondary to inflammation in the organism, the amount of CRP increases, whereas the amount of albumin decreases.[26] CRP is an acute phase reactant that starts to increase in the body within 8-12 hours due to the acute phase response caused by inflammation. Its increase is somewhat slower than that of WBC and reaches a maximum level within 24–48 hours.[28] CRP is an acute phase reactant used quite frequently in the diagnosis of AA, and its sensitivity ranges from 40.0 to 95.6%, and its specificity varies from 53 to 82%.[27] In many studies examining the relationship between AA and CRP, the CRP level was reported to be especially high in complex appendicitis cases, such as perforation and periapical abscess. [27,29] Using a CRP cut-off level of 20 mg/L, Ayrık et al.[14] reported a sensitivity level of 54.33% and a specificity level of 56.06% for CRP in AA cases. On the other hand, Yokoyama et al.[30] found a sensitivity level of 84.3% and specificity level of 75.8% using a cut-off value of 49.5 mg/L for CRP. Yang et al.[31] reported a CRP cut-off value of 24.1 mg/L for AA cases. There are publications reporting that CRP value increases while the albumin level decreases in the acute phase response secondary to inflammation in pregnant patients.[10,32] Fairclough[10] and Karasahin[11] reported that the combined use of decreased albumin and elevated CRP levels improved the accuracy rate in detecting the acute infection. Both studies 773

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reported that CAR elevation increased as parallel to the severity of the disease. There are reports showing that elevated CAR levels were associated with aggressive tumor behavior and poor prognosis in oncology patients.[33–35] Qin et al.[10] and Gibson et al.[12] reported that high CAR values reflected the severity of infection in the acute phase of inflammatory bowel disease. Both studies showed that elevated CAR values were associated with the extent and severity of the infection. Goulart[13] stated that increased CAR values could be used as an early marker to determine surgical site infection in cases operated due to colorectal cancer. In the present study, the median CAR value was 10.93 (1.43–76.18) in patients who underwent appendectomy, which was 0.30 (0.04–2.13) in healthy pregnant women. The CAR value was significantly higher in patients who underwent appendectomy after AA diagnosis compared to pregnant women who were under acute abdominal observation or healthy pregnant women (Table 1). Multivariate logistic regression analysis (multinomial logistic regression) in the present study indicated CAR as an independent predictor for AA diagnosis (Table 2). Goulart et al.[13] calculated sensitivity and specificity of CAR as 77.3% and 66.2%, respectively, for identifying the surgical site infection when they used a cut-off value of 43 for CAR. Karaşahin et al.[11] studied infection vulnerability in geriatric patients using a cut-off value of 1.70 for CAR, and they calculated the sensitivity as 74.3% and specificity 79.6% (p<0.001). In the present study, using a CAR cut-off value of >2.473 for AA diagnosis in pregnant patients, we determined the sensitivity and specificity of CAR values to be 96 and 80%, respectively (Table 3). In the study conducted by Goulart et al., high CAR values were because their study included oncology patients and that the measurements were made in the postoperative period. According to these findings, elevated CAR levels could help physicians in the diagnosis of AA in pregnant patients as an additional parameter to support physical examination and anamnesis. Lymphocytes are involved in immune system regulation and their number increases with inflammation.[36,37] Low lymphocyte number and high CRP level may indicate an infection in the body. Therefore, the combination of lymphocytes and CRP can be used as a biochemical marker to determine the severity of the infection. There are studies reporting that low lymphocyte count and elevated CRP level can be used as an infection marker in orthopedic prosthetic surgeries for an early onset of treatment for the infection.[38,39] Evaluating the data from 554 gastric cancer patients, Okugawa et al.[40] mentioned that low LCR values can be used as a marker to determine surgical site infection. Yazar et al.[4] and Çınar et al.[19] studied pregnant patients and reported that the number of lymphocytes was lower, but CRP was higher in the group of patients who had appendectomy compared to healthy pregnant women. In both studies, the number of lymphocytes decreased while the CRP value increased depending upon the severity of the infection. In the present study, the median LCR value was 0.05 (0.004–0.356) in patients who underwent 774

appendectomy due to AA and 2.01 (0.38–11.50) in healthy pregnant women. Decrease in the rate of lymphocytes and an increase in CRP value secondary to infection resulted in a negative correlation between these two parameters. Thus, LCR value was significantly lower in patients who underwent appendectomy after AA diagnosis compared to pregnant women under acute abdominal observation and healthy pregnant women (Table 1). Multivariate logistic analysis (multinomial logistic regression) in the present study revealed that LCR was an independent risk factor for the diagnosis of AA in pregnant women patients (Table 2). Using a cut-off value of <0.127, LCR could predict AA in pregnant women with an accuracy of 81%, a sensitivity of 73% and a specificity of 89% (Table 3). Based on these result, low LCR values could be used by clinicians as support data to physical examination and anamnesis for AA diagnosis in pregnant patients. Our study carries the limitations inherent in retrospective case studies. In addition, the scarcity of the patients who had appendectomy and exclusion of a small number of patients with complicated appendicitis from the study were the main limitations. Another limitation of this study is the lack of information between the blood withdrawal and the operation time since the inflammatory values may change with time.

Conclusion In pregnant patients with suspected AA, WBC, NLR, CAR and LCR could be used as support parameters to the findings from anamnesis, physical examination and imaging methods in the diagnosis. Such a practice could lower the maternal and fetal morbidity/mortality rates and negative laparotomy rates. Our results could contribute and provide valuable insights to limited literature associated with AA in pregnant women. Prospective studies with large cohorts in this area could be useful. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.A., M.T., B.O.; Design: A.A., N.A.H., B.O.; Supervision: A.A., Y.A., M.T.; Materials: A.A., B.O.; Data: M.T., B.O.; Analysis: Z.A.K., H.Y.; Literature search: Y.A., M.T., S.M., H.Y.; Writing: A.A., N.A.H.; Critical revision: S.M., H.Y. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Zhang Y, Zhao YY, Qiao J, Ye RH. Diagnosis of appendicitis during pregnancy and perinatal outcome in the late pregnancy. Chin Med J (Engl) 2009;122:521−4. 2. Wray CJ, Kao LS, Millas SG, Tsao K, Ko TC. Acute appendicitis: controversies in diagnosis and management. Curr Probl Surg 2013;50:54−86.

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Akbaş et al. The value of inflammatory markers in diagnosing acute appendicitis in pregnant patients 3. Yagci MA, Sezer A, Hatipoglu AR, Coskun I, Hoscoskun Z. Acute appendicitis in pregnancy. Dicle Tip Derg 2010;37:134−139. 4. Yazar FM, Bakacak M, Emre A, Urfalıoglu A, Serin S, Cengiz E, et al. Predictive role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for diagnosis of acute appendicitis during pregnancy. Kaohsiung J Med Sci 2015;31:591−6. 5. Abbassi-Ghanavati M, Greer LG, Cunningham FG. Pregnancy and laboratory studies: a reference table for clinicians. Obstet Gynecol 2009;114:1326−31. 6. Franca Neto AH, Amorim MM, Nóbrega BM. Acute appendicitis in pregnancy: literature review. Rev Assoc Med Bras (1992) 2015;61:170−7. 7. İlhan M, İlhan G, Gök AF, Bademler S, Verit Atmaca F, Ertekin C. Evaluation of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and red blood cell distribution width-platelet ratio as early predictor of acute pancreatitis in pregnancy. J Matern Fetal Neonatal Med 2016;29:1476−80. 8. Daldal E, Akbas A, Dasiran MF, Dagmura H, Bakir H, Okan I. Prognostic importance of neutrophil/lymphocyte and lymphocyte/crp ratio in cases with malignant bowel obstruction. Med Science 2019;8:927−30. 9. Sevgisunar NS, Şahinduran Ş. Hayvanlarda akut faz proteinleri, kullanım amaçları ve klinik önemi. MAKÜ Sag Bil Enst Derg 2014;2:50−72. 10. Qin G, Tu J, Liu L, Luo L, Wu J, Tao L, et al. Serum Albumin and C-Reactive Protein/Albumin Ratio Are Useful Biomarkers of Crohn’s Disease Activity. Med Sci Monit 2016;22:4393−400. 11. Karaşahin Ö, Tosun Taşar P, Timur Ö, Baydar Ö, Yıldırım F, Yıldız F, et al. Palyatif Bakım Alan Geriatrik Hastalarda Enfeksiyon Tanı ve Prognozunda Laboratuvar Belirteçlerin Değeri. Tepecik Eğit ve Araşt Hast Dergisi 2016;26:238−42. 12. Gibson DJ, Hartery K, Doherty J, Nolan J, Keegan D, Byrne K, et al. CRP/Albumin Ratio: An Early Predictor of Steroid Responsiveness in Acute Severe Ulcerative Colitis. J Clin Gastroenterol 2018;52:e48−52. 13. Goulart A, Ferreira C, Estrada A, Nogueira F, Martins S, Mesquita-Rodrigues A, et al. Early inflammatory biomarkers as predictive factors for freedom from infection after colorectal cancer surgery: a prospective cohort study. Surgical infections 2018;19:446−50. 14. Ayrık C, Karaaslan U, Dağ A, Bozkurt S, Toker İ, Demir F. Lökosit sayısı, yüzde nötrofil oranı ve C-reaktif protein konsantrasyonlarının “kesim değeri” düzeylerinde apandisit tanısındaki değerleri. Ulus Travma Acil Cerrahi Derg 2016;22:76−83. 15. Keskek M, Tez M, Yoldas O, Acar A, Akgul O, Gocmen E, Koc M. Receiver operating characteristic analysis of leukocyte counts in operations for suspected appendicitis. Am J Emerg Med 2008;26:769−72. 16. Panagiotopoulou IG, Parashar D, Lin R, Antonowicz S, Wells AD, Bajwa FM, Krijgsman B. The diagnostic value of white cell count, C-reactive protein and bilirubin in acute appendicitis and its complications. Ann R Coll Surg Engl 2013;95:215−21. 17. Yilmaz HG, Akgun Y, Bac B, Celik Y. Acute appendicitis in pregnancy— risk factors associated with principal outcomes: a case control study. Int J Surg 2007;5:192−7. 18. Körner H, Söndenaa K, Söreide JA. Perforated and non-perforated acute appendicitis—one disease or two entities? Eur J Surg 2001;167:525−30. 19. Çınar H, Aygün A, Derebey M, Tarım İA, Akalın Ç, Büyükakıncak S, et al. Significance of hemogram on diagnosis of acute appendicitis during pregnancy. Ulus Travma Acil Cerrahi Derg 2018;24:423−8. 20. Andersson RE. Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg 2004;91:28−37. 21. Eren T, Tombalak E, Burcu B, Özdemir İA, Leblebici M, Ziyade S, et al. Akut Apandisit Olgularında Nötrofil/Lenfosit Oranının Tanıda ve

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Hastalığın Şiddetini Belirlemedeki Prediktif Değeri. Dicle Tıp Derg 2016;43:279−84. 22. Markar S, Karthikesalingam A, Falzon A, Kan Y. The diagnostic value of neutrophil: lymphocyte ratio in adults with suspected acute appendicitis. Acta Chir Bel 2010;110:543−7. 23. Yavuz E, Erçetin C, Uysal E, Solak S, Biricik A, Yiğitbaş H, et al. Diagnostic Value of Neutrophil/Lymphocyte Ration in Geriatric Cases With Appendicitis. Turkish J Geriatrics 2014;17:345−9. 24. Białas M, Taran K, Gryszkiewicz M, Modzelewski B. Evaluation of neutrophil-lymphocyte ratio usefulness in the diagnosis of appendicitis. Wiad Lek 2006;59:601−6. 25. Uluğ M, Can-Uluğ N, Selek Ş. Akut brusellozlu hastalarda akut faz reaktanlarının düzeyi. Klimik Dergisi 2010;23:48−50. 26. Yaylı G. İnfeksiyon hastalıklarında C-reaktif protein, sedimantasyon ve lökositler. Ankem Derg 2005;19:80−4. 27. Soylu L, Aydin OU, Yıldız M. Diagnostic value of procalcitonin, C-reactive protein, and erythrocyte sedimentation rate for acute complicated appendicitis. J Clin Anal Medicine 2018;9:47−50. 28. Wu HP, Lin CY, Chang CF, Chang YJ, Huang CY. Predictive value of C-reactive protein at different cutoff levels in acute appendicitis. Am J Emerg Med 2005;23:449−53. 29. Shogilev DJ, Duus N, Odom SR, Shapiro NI. Diagnosing appendicitis: evidence-based review of the diagnostic approach in 2014. West J Emerg Med 2014;15:859−71. 30. Yokoyama S, Takifuji K, Hotta T, Matsuda K, Nasu T, Nakamori M, et al. C-Reactive protein is an independent surgical indication marker for appendicitis: a retrospective study. World J Emerg Surg 2009;4:36. 31. Yang HR, Wang YC, Chung PK, Chen WK, Jeng LB, Chen RJ. Laboratory tests in patients with acute appendicitis. ANZ J Surg 2006;76:71−4. 32. Beyazıt F, Pek E, Türkön H. Serum Ischemia-Modified Albumin Concentration and Ischemia-Modified Albumin/Albumin Ratio in Hyperemesis Gravidarum. Med Bull Haseki 2018;56:292−8. 33. Yu ST, Zhou Z, Cai Q, Liang F, Han P, Chen R, Huang XM. Prognostic value of the C-reactive protein/albumin ratio in patients with laryngeal squamous cell carcinoma. Onco Targets Ther 2017;10:879−84. 34. Liu Z, Jin K, Guo M, Long J, Liu L, Liu C, et al. Prognostic Value of the CRP/Alb Ratio, a Novel Inflammation-Based Score in Pancreatic Cancer. Ann Surg Oncol 2017;24:561−8. 35. Akbas A, Bakir H, Dasiran M, Dagmura H, Ozmen Z, Celtek NY, et al. Significance of Gastric Wall Thickening Detected in Abdominal CT Scan to Predict Gastric Malignancy. J Oncol 2019;2019. 36. Maurizi G, Della Guardia L, Maurizi A, Poloni A. Adipocytes properties and crosstalk with immune system in obesity-related inflammation. J Cell Physiol 2018;233:88−97. 37. Ustundag Y, Huysal K, Gecgel SK, Unal D. Relationship between C-reactive protein, systemic immune-inflammation index, and routine hemogram-related inflammatory markers in low-grade inflammation. Int J Med Bioch 2018;1:24−8. 38. Bekmez Ş, Çağlar Ö, Atilla B. Total kalça artroplastisi sonrası enfeksiyon. TOTBİD Derg 2013;12:268–75. 39. Smith T. Nutrition: its relationship to orthopedic infections. Orthop Clin North Am 1991;22:373−7. 40. Okugawa Y, Toiyama Y, Yamamoto A, Shigemori T, Ichikawa T, Yin C, et al. Lymphocyte-to-C-reactive protein ratio and score are clinically feasible nutrition-inflammation markers of outcome in patients with gastric cancer. Clin Nutr 2020 39:1209−17.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Gebe hastalarda enflamatuvar belirteçlerin akut apandisit tanısı koymadaki değeri Dr. Ahmet Akbaş,1 Dr. Zeliha Aydın Kasap,2 Dr. Nadir Adnan Hacım,1 Dr. Merve Tokoçin,1 Dr. Yüksel Altınel,1 Dr. Hakan Yigitbaş,1 Dr. Serhat Meriç1, Dr. Bakiye Okumuş3 1 2 3

Sağlık Bilimleri Üniversitesi, İstanbul Bagcılar Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Karadeniz Teknik Üniversitesi Tıp Fakültesi, Biyoistatistik ve Tip Bilişimi Anabilim Dalı, Trabzon İstinye Üniversitesi Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, İzmir

AMAÇ: Gebelik esnasında en sık obstetrik dışı cerrahi müdahaleye neden olan hastalık akut apandisittir (AA). AA tanısı laboratuvar testleri eşliğinde anamnez ve fizik muayene ile birlikte konulmaktadır. Gebelikte gözlenen fizyolojik ve anatomik değişiklikler nedeni ile AA tanısı gebe olmayan hastalara göre daha zordur. Bu çalışmada, hamilelik esnasında AA tanısında beyaz küre (WBC), nötrofil/lenfosit oranı (NLR), CRP/albümin oranı (CAR) ve lenfosit/CRP oranı (LCR) önemini araştırdık. GEREÇ VE YÖNTEM: Çalışmada, Eylül 2015–Aralık 2019 yıları arasında genel cerrahi kliniğinde AA ön tanısı ile yatışı yapılarak takibi yapılan gebe hastalar “International Statistical Classification of Diseases and Related Health Problems-10” (ICD-10) tanı kodu kullanılarak retrospektif olarak belirlendi. Hastalar iki gruba ayrılarak I. Gruba AA nedeni ile apendektomi uygulanan, patolojik değerlendirme sonucuna göre süpüratif apandisit tanısı konulan hastalar, II. Gruba AA ön tanısı ile yatırılan ve takiplerinde ameliyat edilmeden şifa ile taburcu edilen gebe hastalar dahil edildi. Kontrol grubuna (Grup III) ise hastanemiz kadın doğum polikliniğinde takibi yapılan çalışma kriterlerine uygun, rastgele seçilmiş, çalışmaya katılmayı kabul eden 32 sağlıklı gebe prospektif olarak belirlenerek dahil edildi. BULGULAR: Çalışmaya, yaş ortalaması 29.20±4.47 olan 96 gebe hasta (32 sağlıklı gebe, 32 akut batın müşahede ile takip edilen gebe, 32 apendektomi uygulanmış gebe) alındı. Bu hastalardan ameliyat ve histopatolojik bulgulara göre süpüratif apandisit olmayan üç olgu (negatif apendektomi) ile perfore apandisit tespit edilen iki olgu çalışma dışı bırakıldı. Yapılan değerlendirmelerde Grup I oluşturan hastaların WBC değeri (p=0.001), CAR değeri (p=0.001), NLR değeri (p=0.001) grup II ve III’den anlamlı düzeyde yüksek iken, LCR değerinin düşük olduğu gözlendi (p=0.001).Yapılan çok değişkenli lojistik regresyon analizine göre; WBC, CAR, NLR yüksekliği ile LCR düşüklüğü gebe hastalarda AA tanısında bağımsız değişken olduğu gözlendi. TARTIŞMA: Tıbbi öykü, fizik muayene ve görüntüleme tekniklerine ek olarak, gebe kadınlarda AA tanısı için WBC, NLR, CAR ve LCR değerlerinin göz önünde bulundurulması klinisyene karar vermede kolaylık sağlayabilir. Anahtar sözcükler: Akut apandisit; CRP albümin oranı; gebelik; lenfosit; nötrofil. Ulus Travma Acil Cerrahi Derg 2020;26(5):769-776

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doi: 10.14744/tjtes.2020.03456

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ORIGIN A L A R T IC L E

Factors affecting the mortality at patients with burns: Single centre results Ayetullah Temiz, M.D.,1 Ayşe Albayrak, M.D.,2 Rıfat Peksöz, M.D.,3 Esra Dışcı, M.D.,4 Ercan Korkut, M.D.,4 Yusuf Tanrıkulu, M.D.,5 Yavuz Albayrak, M.D.4 1

Department of General Surgery, Erzurum Regional Training and Research Hospital, Erzurum-Turkey

Department of Infectious Diseases, Atatürk University Faculty of Medicine, Erzurum-Turkey

Department of General Surgery, Malazgirt State Hospital, Muş-Turkey

Department of General Surgery, Atatürk University Faculty of Medicine, Erzurum-Turkey

Department of General Surgery, KTO Karatay University Faculty of Medicine, Konya-Turkey

ABSTRACT BACKGROUND: Burns are a primary cause of mortality along with the severe physical and psychological morbidities in patients and their families. Such kinds of injuries bring about considerable financial burdens due to the treatment processes and sequels. The present study aims to investigate the factors that affect the mortality of burns. METHODS: The archives files of the patients admitted because of burn injuries in our burn centre between September 2008 and December 2016 were examined in this study. Some of the lab values, such as age, sex, percentage of total burn surface area (TBSA), referral status, burning site, degree of burns, time of admission to hospital, aetiology of burning, blood and blood products collection, complete blood count, routine biochemistry, coagulation parameters, C-reactive protein (CRP), sedimentation rate, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were examined while evaluating the patients’ mortalities. RESULTS: A total of 133 patients were included in this study. The patient’s age (p=0.001), the degree of burns (p<0.001), surface area of burns (p<0.001), the time of hospital admission (p<0.001), burning aetiology (p=0.006), erythrocyte suspension, fresh frozen plasma, along with the administration of albumin transfusion (p<0.001), mean platelet volume (MPV) (p=0.028), NLR (p<0.001) and PLR (p<0.030) values were found to be associated with mortality in patients with burns. CONCLUSION: In this study, age, burn grade, TBSA, hospital admission time, burn aetiology, erythrocyte, fresh frozen plasma and albumin transfusion, MPV, NLR and PLR values were found to be associated with mortality in patients with burns. With this study, it is possible to produce the treatment guidelines to reduce mortality by taking these parameters into consideration, which were determined to be associated with mortality while evaluating the patients with burns. Keywords: Burn; mean platelet volume; neutrophil-to-lymphocyte ratio; platelet-to-lymphocyte ratio.

INTRODUCTION Burns are the fourth most common type of trauma worldwide, followed by traffic accidents, falls and interpersonal violence and are a major public health problem among all injuries.[1–3] Burns are a major cause of mortality along with severe physical and psychological morbidities in patients and their families. In addition, such kinds of injuries impose con-

siderable financial burdens due to treatment processes and sequels.[4,5] Every year, approximately 200,000 people around the world die of burn injuries.[3] Various fires, scalding agents, chemicals, electricity and radiation are seen as the causes of burning and all these agents cause burns of varying severity, thereby resulting in severe morbidity and mortality.[6] In general, the mortality risk factors for patients with burns are gender, age, total burn surface area (TBSA), presence of in-

Cite this article as: Temiz A, Albayrak A, Peksöz R, Dışcı E, Korkut E, Tanrıkulu Y, et al. Factors affecting the mortality at patients with burns: Single centre results. Ulus Travma Acil Cerrahi Derg 2020;26:777-783. Address for correspondence: Yavuz Albayrak, M.D. Atatürk Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Erzurum, Turkey Tel: +90 442 - 242 22 75 E-mail: yavuzalbayrakdr@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):777-783 DOI: 10.14744/tjtes.2020.37862 Submitted: 18.11.2019 Accepted: 02.02.2020 Online: 10.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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halation damage, co-morbid disease and other concomitant trauma.[7,8] With advances in intensive care and burn care, the survival outcomes of patients with severe burn injuries over the past ten years have improved significantly.[9]

MATERIALS AND METHODS This study received approval from the Ataturk University Faculty of Medicine clinical research Ethics committee (dated 13/03/2019 and numbered 02–01). Of the 301 patients with BSA of 15% and over who were referred to Erzurum Regional Training and Research Hospital Burn Center between September 2008 and December 2016 from other centres, 133 patients (whose full information could be obtained) were included in this study. The files of these patients were retrieved from the electronic archives and their data were retrospectively examined. The patients were divided into two groups as follows: survivors and the deceased patients. Some of the lab values, such as age, sex, percentage of TBSA, referral status, burning site, degree of burn, time to admission to hospital, aetiology of burning, blood and blood products collection, complete blood count, routine biochemistry, coagulation parameters, C-reactive protein (CRP), sedimentation rate, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were examined while evaluating the patients’ mortalities.

Statistical Analysis Statistical analyses were performed by employing SPSS 15.0 software (SPSS Inc., Chicago, IL, USA). The distribution of data was determined using the Kolmogorov–Smirnov test. Continuous variables were expressed as mean ± std. deviation, whereas categorical variables as frequency and percentage. Continuous variables were compared with the independent sample t-test or Mann–Whitney U test and categorical variables were compared using Pearson’s Chi-square test for two groups. A p-value of less than 0.05 was considered statistically significant.

RESULTS Of the admitted patients, 69 (52.7%) were males, and 64 (47.3%) were females. Of the deceased patients, eight (6.1%) patients were males and 16 (12.2%) patients were females. There was no statistically significant difference between the two groups (p=0.070). The mean ages of surviving patients and deceased patients were 15.17±18.23 and 33.04±26.64, respectively. There was a statistically significant difference between the two groups (p=0.001). According to the degree of burns, two of the surviving patients had first-degree burns, 66 patients had superficial second-degree burns, 12 patients had deep second-degree burns, 29 patients had third degree burns, whereas in the deceased patients, one patient had superficial second-degree burnseight patients had deep second-degree burns and 15 patients had third-degree burns. 778

There was a statistically significant difference between the two groups (p<0.001). The percentages of TBSA in surviving patients and deceased patients were 22.92±9.11 and 52.04±23.52, respectively. There was a statistically significant difference between the two groups (p=0.001). A total of five of the 96 patients with a TBSA ratio of 16%–30% were deceased patients, whereas 19 of the 37 patients with a TBSA ratio higher than 30% were deceased patients. Again, there was a statistically significant difference between the two groups (<0.001). Of the 114 patients admitted directly, six were deceased patients, whereas 18 of the 19 patients referred from another centre were deceased patients. There was a significant difference between the two groups (<0.001). According to the burn site, among the surviving patients, 91 patients were burned at home, two patients at work and 16 patients in an open area, whereas among the deceased patients, 19 patients were burned at home, one patient at work and four patients in an open area. There was no statistically significant difference between the two groups (p=0.752). Patients were divided into two groups as early and late arrivals according to the admission hours. Accordingly, patients who were admitted in the first four hours of the event were defined as early applicants; whereas, patients who were admitted four hours after the event were defined as late applicants. In total, four of 80 patients who applied early were deceased patients, whereas 20 of the 53 patients who were admitted late were deceased patients. There was a statistically significant difference between the two groups (p<0.001). The demographic characteristics of the patients are presented in Table 1. According to the aetiology of burning, the largest group of patients discharged with healing were 57 patients with hot water burns, 22 patients with flame burns, 12 patients with tandoori burns, nine patients with home electrical burns, four patients with milk burns, three patients with hot water burns, one patient with a lightning strike and one patient with sand contact burns. Concerning deceased patients, eight patients had hot water burns, 14 patients had flame burns and two patients had tandoori burns. There was a statistically significant difference between the two groups concerning aetiology of burn (p=0.006) (Table 2). Of the 76 patients receiving erythrocyte suspension, five patients were deceased patients, whereas 19 of 57 patients without erythrocyte suspension were deceased patients. There was a statistically significant difference between these two groups (p<0.001). Of the 65 patients receiving fresh frozen plasma, one patient was a deceased patient, whereas 23 out of the 68 patients were deceased patients. There was a statistically significant difference between these two groups Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Temiz et al. Factors affecting the mortality at patients with burns

Table 1. Comparison of the groups according to general demographic data Age

Alive Deceased (n=109) (n=24) 15.17±18.23 33.04±26.64

Table 3. Comparison of the groups according to blood and blood products transfusion status p

0.001

Alive Deceased (n=109) (n=24)

Erythrocyte suspension

Gender 0.070

transfusion

Male

Yes

Female

Burn percentage

22.92±9.11 52.04±23.52 <0.001

Burn percentage group

<0.001

Fresh frozen plasma transfusion

≤15%

Yes

16–30%

≥31%

Referral status

Direct admission

Referred

108 1

Albumin transfusion <0.001

Workplace

Open area

<0.001

Yes

<0.001

Burn location Home

<0.001

Burn grade

0.752

Table 4. Comparison of the groups according to laboratory findings

<0.001

Alive (n=109)

Deceased (n=24)

Superficial 1st degree

Haemoglobin

13.56±2.92 14.52±3.50 0.635

Superficial 2nd degree

WBC

18.66±10.27 22.50±11.20 0.116

Deep

Eosinophils

Deep+superficial

Platelet

2nd degree

MPV

Time elapsed for

<0.001

admission

Creatinine

2–4 hours

Sodium

0.006

8.07±1.24 0.028

29.60±12.71 30.84±17.98 0.956

7.63±2.36

147.92±70.21 184.12±117.35 0.234

Alive Deceased (n=109) (n=24)

402.95±181.80 344.20±171.65 0.169

BUN

≤4 hours

0.14±0.26 0.025

Glucose

Table 2. Comparison of the groups according to the aetiology of burning

0.66±0.99

0.59±0.77

1.47±3.35 0.001

135.50±13.52 138.46±6.35 0.254

Potassium

4.46±0.67

4.29±0.77 0.041

Calcium

8.95±1.01

7.42±1.20 <0.001

AST

59.30±83.86 58.16±29.75 0.081

ALT

33.12±41.27 30.04±24.01 0.146

Albumin

3.80±0.73

2.56±0.70 <0.001

INR

1.09±0.19

1.22±0.25

0.010

Sedimentation 15.04±22.51 8.62±17.60 0.001

Burning by hot water

Flame burn

CRP

Tandoori burn

NLR

6.34±12.13

12.96±9.70 <0.001

House electricity burn

PLR

52.77±94.30

46.56±31.34

Milk burn

Tea water burn

Lightning strike

Sand contact burn

(p<0.001). Of the 99 patients who underwent albumin transfusion, seven patients were deceased patients, whereas 17 Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

24.76±49.81 39.35±56.73 0.173 0.030

WBC: White blood cell; BUN: Blood urea nitrogen; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; INR: International normalized ratio; CRP: C-reactive protein; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio.

out of the 34 patients without transfusion were deceased patients. There was a statistically significant difference between these two groups (p<0.001) (Table 3). 779

Temiz et al. Factors affecting the mortality at patients with burns

When patients were evaluated according to laboratory values, there was a statistically significant difference between eosinophils, MPV, creatinine, potassium (K), calcium (Ca), albumin, international normalized ratio (İNR), sedimentation, NLR, PLR values between the survivors and deceased survivors or burns, whereas among the haemoglobin (Hg), white blood cell (WBC), platelets (PLT), glucose, blood urea nitrogen (BUN), sodium (Na), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and CRP values, there was no statistically significant difference between the two groups (Table 4).

DISCUSSION Skin is one of the most important organs of the body and the largest organ that covers our body. Heat regulation, the role of sensation, protection from the external environment and having immunologic functions increase the importance of the skin even more. As a result of burning injury, in addition to the loss of functions, a life-threatening situation may also arise.[8] Every year, millions of people in the world are affected by burns. Half of them consist of children, and one-fourth of these cases are of severe burns. Therefore, patients with burns should be treated as serious trauma patient.[10] Advanced age, large TBSA and the presence of inhalation injury are the factors affecting the mortality rate of patients with burns.[11–13] In addition, other factors, such as the presence of shock, the presence of sepsis and thrombocytopenia, have been reported to affect mortality rates during the admission.[14–17] In our study, the relationship between mortality in patients with burns and gender, age, degree of burn, burn percentage, aetiology, receiving erythrocyte suspension, receiving fresh frozen plasma, albumin, haemogram and biochemical values were evaluated.

Gender and Age The majority of the studies have reported that the female gender is a risk factor for mortality.[18–20] Zarei et al.[21] reported that the mortality rate was higher in men. In a study conducted by Brusselaers,[22] no statistically significant difference was reported between males and females concerning mortality. In our study, similar to Brusselaers’ study, no statistically significant difference was found between males and females concerning gender. In the burns literature, it has been reported that age plays a key role in the relationship with mortality, especially in children and elderly people.[23–25] Other studies examining the relationship between age and mortality have shown a marked increase in mortality in children younger than two years old as compared with those older than two years of age.[25] Another study reported that the mortality rate was highest in children.[26] A study conducted by Tiryaki et al.[27] on patients with electrical burns reported that elderly people were a large number of deceased ones in such cases. In our study, when we compared the survivors and deceased patients, we concluded that the deceased survivors of burns constitute the older group and this was consistent within the 780

literature. In our study, increased mortality was found with increased age.

Burn Degree Albayrak et al. reported that tandoori burns caused deeper burns as compared to other types of burns. Therefore, morbidity and mortality rates are reported to be higher in the cases of tandoori burns.[28] Zarei et al.[21] revealed that second- and third-degree burns were a risk factor in mortality rates. A study conducted by Kaya et al.[29] regarding the electrical burns reported that there was a significant increase in mortality in the third-degree burns group as compared to the first- and second-degree burns groups. Lip et al.[30] reported that the mortality rates in patients with full-thickness burns were higher than those in the patients with partial-thickness burns. In our study, we also concluded that the increase in mortality was parallel with the increase in the degree of burns.

Burn Percentage Some studies have reported that BSA is an independent risk factor in determining mortality.[24,31–33] In some studies, the BSA of the 70%–79%, 80%–89% and more than 90% of the burns were reported to have a mortality rate of 51.1%, 70.6% and 82.6%, respectively.[31,33,34] A study reported that a burn area of more than 20% was an important predictor factor in determining the mortality rate.[30] In a study, the mortality rate was found to be two-thirds higher in a burn patient group with TBSA between 21 and 30% than the burns patient group with TBSA between 11 and 20%.[35] Also, in our study, five of the 96 patients with burn percentage of 15 and 30% were deceased patients, whereas 19 of the 37 patients with burn percentage higher than 30% were deceased patients. Our results, too, were consistent with the literature.

Admission Time A study, which included 235 paediatric patients in our paediatric patient group, reported that two people were deceased, and two of these deceased patients were brought to hospital 24 hours after the incident of burning.[36] In this study, we found that mortality was significantly higher in the patient group who applied to our clinic after the four hours following the occurrence of the event. The late admission of patients with burns to the hospital causes a delay in both emergency fluid resuscitation and burn wound care treatment.[37,38] In addition, patients who do not apply to health institutions after burns generally use traditional treatment methods, and burn wound infections occur as a result of these incorrect treatments.[39,40] All of these are the causes of mortality in the patients admitted late to the hospital after the incident of burning.

Burning Aetiology Previously conducted studies reported that the most common cause of death in patients with burns was flame burns.[4,21,41–43] Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Temiz et al. Factors affecting the mortality at patients with burns

The pathogenesis of electrical burns has certain differences concerning the other types of burns (6). A study conducted on 964 patients in Iran by Aghazadeh et al.[44] reported that death arose from scalding with flame, chemicals and hot liquid, respectively. Al et al.[26] in reported that a total of 624 patients (76.5%) were scalded, of them, 192 patients (23.5%) had flame-induced burns, 18 patients (9.4%) had burns due to flames, 32 patients (5.1%) died due to scald burns and the effects of flame burns on mortality were statistically significant. In our study, the highest mortality rate arose from flame burns and, then, by the scald burns, which was consistent with the literature. It can be concluded that the most common cause of mortality in flame burns may be because flame burns lead to a larger BSA and cause deeper burns.

Administration of Erythrocyte Koljonen et al. found that the mortality of the patients with burns undergoing transfusion was five times higher than the mortality of the patients without transfusion.[45] Although some studies in the literature have reported a high mortality rate in patients undergoing transfusion, this relationship could not be found in most of the studies on this matter.[46â&#x20AC;&#x201C;50] In our study, we also concluded that the administration of erythrocyte suspension reduces mortality.

Administration of Fresh Frozen Plasma Lu et al.[49] reported that plasma transfusion is associated with mortality. Previous research works have claimed that transfusions can facilitate the formation of serious infections by suppressing the immune system, thereby increasing the mortality rate.[51,52] Fresh frozen plasma should be used in the event of severe bleeding or coagulopathy; however, it is recommended that early and aggressive plasma transfusion should be performed if burn wound excisions are performed in patients with severe coagulopathy.[53â&#x20AC;&#x201C;55] In our study, it was found that mortality was higher in the group without FFP administration.

Administration of the Albumin Melinyshyn et al. compared the two groups with and without routine albumin. In this study, some parameters, such as length of hospital stay, wound healing time and mortality, were compared and no difference was found between the two groups. It was also reported that the treatment costs were higher in the albumin-treated group. The results of this study concluded that the administration of albumin in patients with burns increased the cost of treatment and had no benefits.[56] A different study reported that albumin resuscitation might reduce fluid leakage and the negative effects of excessive fluid administration.[57] A sub-group evaluation performed in the Cochrane meta-analysis reported that the administration of albumin increased the mortality in patients with burns, whereas the results of Wilkes meta-analysis did not increase the mortality and had a neutral effect.[58,59] Another meta-analysis study reported that albumin was not Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

beneficial.[60] Our study concluded that the use of albumin reduces mortality. Although our results were consistent with a small portion of the literature, it was found to be incompatible with most of the research works in literature.

MPV MPV is used as an inflammatory marker in some diseases, such as sepsis, thrombosis, acute appendicitis and respiratory distress syndrome.[61,62] To date, we have not found a study examining MPV mortality in patients with burns. Our study showed that MPV levels were significantly higher in deceased patients than in survivors.

NLR NLR indicates the ratio of neutrophils and lymphocytes. NLR is shown as one of the new markers of systemic inflammation.[63] Fuss et al.[64] reported that NLR is significantly higher in patients with burns along with sepsis. In our study, we evaluated burn patients with sepsis, along with all the burn trauma patients. In conclusion, we found a higher rate of NLR in patients with the mortal course.

PLR Recently, PLR has been shown to be an important new marker of systemic inflammation, such as NLR.[65] To our knowledge, there was no study on PLR regarding the patients with burns. Our study is in contrast with many other studies on other pathologies in the literature; however, it is in parallel with the small number of studies, i.e., PLR was found to be lower in the group with deceased patients. Our study was conducted on 133 burn patients, and the factors, such as age, degree of burn, admission time, aetiology of burning, erythrocyte, FFP and albumin transfusion, MPV, NLR and PLR values of the patients were found to be associated with mortality in patients with burns. This study was limited to one centreâ&#x20AC;&#x2122;s experience. Even within one healthcare system, it remains difficult to match and carefully compare data, mostly because of different treatment approaches and selection of outcome parameters. Future studies can determine the factors that affect the mortality of burns and may ensure the development of treatment guidelines that will decrease the mortality of the patients with burns. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.T., Y.A.; Design: Y.A.; Supervision: Y.A.; Materials: A.T., R.P., E.D., E.K., Y.T.; Data: A.T., A.A., R.P., E.D., E.K., Y.T.; Analysis: Y.A., A.A.; Literature search: Y.A.; Writing: Y.A.; Critical revision: Y.A. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. 781

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REFERENCES 1. Forjuoh SN. Burns in low- and middle-income countries: a review of available literature on descriptive epidemiology, risk factors, treatment, and prevention. Burns 2006;32:529−37. 2. Peck MD, Kruger GE, van der Merwe AE, Godakumbura W, Ahuja RB. Burns and fires from non-electric domestic appliances in low and middle income countries Part I. The scope of the problem. Burns 2008;34:303−11. 3. Mathers C, Fat DM, Boerma JT. The global burden of disease: 2004 update. Geneva: World Health Organization; 2008. 4. Macedo JL, Santos JB. Predictive factors of mortality in burn patients. Rev Inst Med Trop Sao Paulo 2007;49:365−70. 5. Mashreky SR, Rahman A, Chowdhury SM, Giashuddin S, SvanstrOm L, Linnan M, et al. Epidemiology of childhood burn: yield of largest community based injury survey in Bangladesh. Burns 2008;34:856−62. 6. Bekerecioğlu M, Yüksel F, Peker F, Karacaoğlu E, Durak N, Kişlaoğlu E. “Tandir”: an old and well known cause of burn injury in the Middle East. Burns 1998;24:654−7. 7. Smith DL, Cairns BA, Ramadan F, Dalston JS, Fakhry SM, Rutledge R, et al. Effect of inhalation injury, burn size, and age on mortality: a study of 1447 consecutive burn patients. J Trauma 1994;37:655−9. 8. McGwin G Jr, George RL, Cross JM, Rue LW. Improving the ability to predict mortality among burn patients. Burns 2008;34:320−7. 9. Brusselaers N, Monstrey S, Snoeij T, Vandijck D, Lizy C, Hoste E, et al. Morbidity and mortality of bloodstream infections in patients with severe burn injury. Am J Crit Care 2010;19:e81−7. 10. Al B, Güloğlu MN, Okur H, Öztürk H, Kara İH, Aldemir M. Doğu ve Güneydoğu Anadolu bölgelerinde haşlanma ve alev yanıklarının epidemiyolojik özellikleri. Tıp Araştırma Derg 2005;3:14–21. 11. Seo DK, Kym D, Yim H, Yang HT, Cho YS, Kim JH, et al. Epidemiological trends and risk factors in major burns patients in South Korea: a 10-year experience. Burns 2015;41:181–18. 12. You K, Yang HT, Kym D, Yoon J, HaejunYim, Cho YS, et al. Inhalation injury in burn patients: establishing the link between diagnosis and prognosis. Burns 2014;40:1470−5. 13. Jeschke MG, Pinto R, Kraft R, Nathens AB, Finnerty CC, Gamelli RL, et al; Inflammation and the Host Response to Injury Collaborative Research Program. Morbidity and survival probability in burn patients in modern burn care. Crit Care Med 2015;43:808−15. 14. Herndon DN, Gore D, Cole M, Desai MH, Linares H, Abston S, et al. Determinants of mortality in pediatric patients with greater than 70% full-thickness total body surface area thermal injury treated by early total excision and grafting. J Trauma 1987;27:208−12. 15. Housinger TA, Brinlerhoff C, Warden GD. The relationship between platelet counts, sepsis, and survival in pediatric burn patients. Arch Surg 1993;128:65−7. 16. de Macedo JL, Rosa SC, Castro C. Sepsis in burned patients. Rev Soc Bras Med Trop 2003;36:647−52. 17. Merrell SW, Saffle JR, Sullivan JJ, Larsen CM, Warden GD. Increased survival after major thermal injury. A nine year review. Am J Surg 1987;154:623−7. 18. Gomez M, Wong DT, Stewart TE, Redelmeier DA, Fish JS. The FLAMES score accurately predicts mortality risk in burn patients. J Trauma 2008;65:636−45. 19. Muller MJ, Pegg SP, Rule MR. Determinants of death following burn injury. Br J Surg 2001;88:583−7. 20. O’Keefe GE, Hunt JL, Purdue GF. An evaluation of risk factors for mortality after burn trauma and the identification of gender-dependent differences in outcomes. J Am Coll Surg 2001;192:153−60. 21. Zarei MR, Dianat S, Eslami V, Harirchi I, Boddouhi N, Zandieh A, et al. Factors associated with mortality in adult hospitalized burn patients in

782

Tehran. Ulus Travma Acil Cerrahi Derg 2011;17:61−5. 22. Brusselaers N, Juhász I, Erdei I, Monstrey S, Blot S. Evaluation of mortality following severe burns injury in Hungary: external validation of a prediction model developed on Belgian burn data. Burns 2009;35:1009−14. 23. Ryan CM, Schoenfeld DA, Thorpe WP, Sheridan RL, Cassem EH, Tompkins RG. Objective estimates of the probability of death from burn injuries. N Engl J Med 1998;338:362−6. 24. Wolf SE, Rose JK, Desai MH, Mileski JP, Barrow RE, Herndon DN. Mortality determinants in massive pediatric burns. An analysis of 103 children with > or = 80% TBSA burns (> or = 70% full-thickness). Ann Surg 1997;225:554−569. 25. Bessey PQ, Arons RR, Dimaggio CJ, Yurt RW. The vulnerabilities of age: burns in children and older adults. Surgery 2006;140:705−17. 26. Al B, Yildirim C, Coban S, Aldemir M, Güloğlu C. Mortality factors in flame and scalds burns: Our experience in 816 patients. Ulus Travma Acil Cerrahi Derg 2009;15:599−606. 27. Haksal MC, Tiryaki C, Yazıcıoğlu MB, Güven M, Çiftci A, Esen O, et al. General characteristics of paint thinner burns: Single center experience. Ulus Travma Acil Cerrahi Derg 2017;23:51−5. 28. Lee KH, Hwang SJ, Kim SH, Lee SH, Yu DK, Hwang JH, et al. Comparison of mortality and morbidity in multiple versus singleton very low birth weight infants in a neonatal intensive care unit. J Korean Med Sci 2003;18:779−82. 29. Ay N, Alp V, Aliosmanoğlu İ, Sevük U, Kaya Ş, Dinç B. Factors affecting morbidity and mortality in traumatic colorectal injuries and reliability and validity of trauma scoring systems. World J Emerg Surg 2015;10:21. 30. Tan Chor Lip H, Tan JH, Thomas M, Imran FH, Azmah Tuan Mat TN. Survival analysis and mortality predictors of hospitalized severe burn victims in a Malaysian burns intensive care unit. Burns Trauma 2019;7:3. 31. Panjeshahin MR, Lari AR, Talei A, Shamsnia J, Alaghehbandan R. Epidemiology and mortality of burns in the South West of Iran. Burns 2001;27:219−26. 32. Kobayashi K, Ikeda H, Higuchi R, Nozaki M, Yamamoto Y, Urabe M, et al. Epidemiological and outcome characteristics of major burns in Tokyo. Burns 2005;31:S3−11. 33. Laloë V. Epidemiology and mortality of burns in a general hospital of Eastern Sri Lanka. Burns 2002;28:778−81. 34. Waller AE, Marshall SW, Langley JD. Adult thermal injuries in New Zealand resulting in death and hospitalization. Burns 1998;24:245−51. 35. Lionelli GT, Pickus EJ, Beckum OK, Decoursey RL, Korentager RA. A three decade analysis of factors affecting burn mortality in the elderly. Burns 2005;31:958−63. 36. Albayrak Y, Albayrak A, Yıldız A, Aylu B. Clinical and demographic features of pediatric burns in the eastern provinces of Turkey. Scand J Trauma Resusc Emerg Med 2011;19:6. 37. Carvajal HF. Fluid therapy for the acutely burned child. Compr Ther 1977;3:17−24. 38. Albertyn R, Bickler SW, Rode H. Paediatric burn injuries in Sub Saharan Africa--an overview. Burns. 2006;32:605−12. 39. Ndiritu S, Ngumi ZW, Nyaim O. Burns: the epidemiological pattern, risk and safety awareness at Kenyatta National Hospital, Nairobi. East Afr Med J 2006;83:455−60. 40. Okoro PE, Igwe PO, Ukachukwu AK. Childhood burns in south eastern Nigeria. Afr J Paediatr Surg 2009;6:24−7. 41. Meshulam-Derazon S, Nachumovsky S, Ad-El D, Sulkes J, Hauben DJ. Prediction of morbidity and mortality on admission to a burn unit. Plast Reconstr Surg 2006;118:116−20. 42. Tyson AF, Boschini LP, Kiser MM, Samuel JC, Mjuweni SN, Cairns BA, et al. Survival after burn in a sub-Saharan burn unit: challenges and opportunities. Burns 2013;39:1619−25. 43. Fazeli S, Karami-Matin R, Kakaei N, Pourghorban S, Safari-Faramani R, Safari-Faramani B. Predictive factors of mortality in burn patients. Trau-

Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Temiz et al. Factors affecting the mortality at patients with burns ma Mon 2014;19:e14480. 44. Mirza Aghazadeh A, Lotfi M, Ghahramanian A, Ahadi F. Lethal Area 50 in Patients with Burn Injuries in North West, Iran. J Caring Sci 2018;7:53−8. 45. Koljonen V, Tuimala J, Haglund C, Tukiainen E, Vuola J, Juvonen E, et al. The Use of Blood Products in Adult Patients with Burns. Scand J Surg 2016;105:178−85. 46. Palmieri TL, Caruso DM, Foster KN, Cairns BA, Peck MD, Gamelli RL, et al; American Burn Association Burn Multicenter Trials Group. Effect of blood transfusion on outcome after major burn injury: a multicenter study. Crit Care Med 2006;34:1602−7. 47. Boral L, Kowal-Vern A, Yogore M 3rd, Patel H, Latenser BA. Transfusions in burn patients with/without comorbidities. J Burn Care Res 2009;30:268−73. 48. Kwan P, Gomez M, Cartotto R. Safe and successful restriction of transfusion in burn patients. J Burn Care Res 2006;27:826−34. 49. Lu RP, Lin FC, Ortiz-Pujols SM, Adams SD, Whinna HC, Cairns BA, et al. Blood utilization in patients with burn injury and association with clinical outcomes (CME). Transfusion 2013;53:2212-21; quiz 2211. 50. Graves TA, Cioffi WG, Mason AD Jr, McManus WF, Pruitt BA Jr. Relationship of transfusion and infection in a burn population. J Trauma 1989;29:948−54. 51. Scornik JC, Meier-Kriesche HU. Blood transfusions in organ transplant patients: mechanisms of sensitization and implications for prevention. Am J Transplant 2011;11:1785−91. 52. Refaai MA, Blumberg N. Transfusion immunomodulation from a clinical perspective: An update. Expert Rev Hematol 2013;6:653–63. 53. Pham TN, Cancio LC, Gibran NS; American Burn Association. American Burn Association practice guidelines burn shock resuscitation. J Burn Care Res 2008;29:257−66. 54. Sherren PB, Hussey J, Martin R, Kundishora T, Parker M, Emerson B. Acute burn induced coagulopathy. Burns 2013;39:1157−61.

55. Palmieri TL, Greenhalgh DG, Sen S. Prospective comparison of packed red blood cell-to-fresh frozen plasma transfusion ratio of 4: 1 versus 1: 1 during acute massive burn excision. J Trauma Acute Care Surg 2013;74:76−83. 56. Melinyshyn A, Callum J, Jeschke MC, Cartotto R. Albumin supplementation for hypoalbuminemia following burns: unnecessary and costly!. J Burn Care Res 2013;34:8−17. 57. Hunter JE, Drew PJ, Potokar TS, Dickson W, Hemington-Gorse SJ. Albumin resuscitation in burns: a hybrid regime to mitigate fluid creep. Scars Burn Heal 2016;2:2059513116642083. 58. Albumin Reviewers (Alderson P, Bunn F, Li Wan Po A, Li L, Blackhall K, Roberts I, Schierhout G). Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev 2011;(10):CD001208. 59. Wilkes MM, Navickis RJ. Patient survival after human albumin administration. A meta-analysis of randomized, controlled trials. Ann Intern Med 2001;135:149−64. 60. Eljaiek R, Heylbroeck C, Dubois MJ. Albumin administration for fluid resuscitation in burn patients: A systematic review and meta-analysis. Burns 2017;43:17−24. 61. Albayrak Y, Albayrak A, Albayrak F, Yildirim R, Aylu B, Uyanik A, et al. Mean platelet volume: a new predictor in confirming acute appendicitis diagnosis. Clin Appl Thromb Hemost 2011;17:362−6. 62. Canpolat FE, Yurdakök M, Armangil D, Yiğit S. Mean platelet volume in neonatal respiratory distress syndrome. Pediatr Int 2009;51:314−6. 63. Zahorec R. Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 2001;102:5−14. 64. Fuss J, Voloboyeva A, Poliovyj V. Prognostic value of using neutrophil-lymphocyte ratio in patients with burn injury for the diagnosis of sepsis and bacteraemia. Pol Przegl Chir 2018;90:13−6. 65. Balta S, Demırkol S, Kucuk U. The platelet lymphocyte ratio may be useful inflammatory indicator in clinical practice. Hemodial Int 2013;17:668−9.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Yanıklı hastalarda mortaliteyi etkileyen faktörler: Tek merkez sonuçları Dr. Ayetullah Temiz,1 Dr. Ayşe Albayrak,2 Dr. Rıfat Peksöz,3 Dr. Esra Dışcı,4 Dr. Ercan Korkut,4 Dr. Yusuf Tanrıkulu,5 Dr. Yavuz Albayrak4 Erzurum Bölge Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Erzurum Atatürk Üniversitesi Tıp Fakültesi, Enfeksiyon Hastalıkları Anabilim Dalı, Erzurum 3 Malazgirt Devlet Hastanesi, Genel Cerrahi Kliniği, Muş 4 Atatürk Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Erzurum 5 KTO Karatay Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Konya 1 2

AMAÇ: Yanıklar, hasta ve ailelerine ciddi fiziksel ve psikolojik morbidite meydana getirmeleri yanında önemli bir mortalite nedenidir. Ayrıca bu tür yaralanmalar, tedavi süreçleri ve bıraktığı sekeller nedeniyle önemli mali yükler de getirmektedir. Bu çalışmada amaç, yanık mortalitesini etkileyen faktörleri belirlemektir. GEREÇ VE YÖNTEM: Yanık merkezimize Eylül 2008–Aralık 2016 yılları arasında yanık nedeni ile başvuran hastaların kayıtları incelendi. Hastaların mortaliteleri değerlendirilirken yaş, cinsiyet, yanık yüzey alanı yüzdesi, sevk durumu, yanma yeri, yanık derecesi, hastaneye başvuru için geçen süre, yanma etyolojisi, kan ve kan ürünleri alıp almaması, tam kan sayımı, rutin biyokimya, kuagülasyon parametreleri, C-reaktif protein (CRP), sedimentasyon hızı, nötrofil lenfosit oranı (NLR) ve trombosit-lenfosit oranı (PLR) gibi bazı laboratuvar değerleri incelendi. BULGULAR: Toplam 133 hasta çalışmaya dahil edildi. Hastanın yaşı (p=0.001), yanık derecesi (p<0.001), yanık yüzey alanı (p<0.001), hastaneye başvuru süresi (p<0.001), yanma etiyolojisi (p<0.001), eritrosit süspansiyonu, Taze Donmuş Plazma ve albümin transfüzyonu verilmesi (p<0.001), MPV (p<0.001), NLR (p<0.001) ve PLR (p<0.001) değerlerinin yanık hastalarında mortalite ile ilişkili olduğu tespit edildi. TARTIŞMA: Bu çalışmada, hastanın yaşı, yanık derecesi, yanık yüzey alanı, hastaneye başvuru süresi, yanma etiyolojisi, eritrosit, TDP ve albümin transfüzyonu, MPV, NLR ve PLR değerlerinin yanık hastalarında mortalite ile ilişkili olduğu tespit edildi. Yaptığımız bu çalışma ile yanık hastaları değerlendirilirken mortalite ile ilişkili tespit edilen bu parametreler göz önünde bulundurularak hastaların mortalitesini azaltacak tedavi rehberlerinin oluşturulması sağlanabilir. Anahtar sözcükler: Nötrofil lenfosit oranı; ortalama trombosit hacmi; trombosit-lenfosit oranı; yanık. Ulus Travma Acil Cerrahi Derg 2020;26(5):777-783

doi: 10.14744/tjtes.2020.37862

Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

783

ORIGIN A L A R T IC L E

The efficacy of continuous lumbar drainage in post-traumatic cerebrospinal fluid fistulas Alparslan Kırık, M.D.,

Soner Yaşar, M.D.

Department of Neurosurgery, Health Sciences University, Gülhane Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: This study aims to investigate the clinical outcomes of patients who underwent closed continuous lumbar drainage (CLD) for post-traumatic cerebrospinal fluid (CSF) fistula and to compare with those of non-traumatic patients. METHODS: The data of patients who were treated in the department of neurosurgery between January 2018 and December 2019 and underwent CLD were analyzed. The diagnosis, demographic characteristics, CSF results and clinical outcomes of these patients were evaluated. The outcomes of the patients with dura defect and CSF fistula due to trauma were compared with patients who underwent CLD for other diagnoses. RESULTS: In this study, 45 patients underwent CLD for 51 times. The mean age was 38.84 years, and 27 (60%) of the patients were male. Seven (15.55%) patients underwent CLD due to post-traumatic CSF fistula and 38 patients after tumor or malformation surgery. While five patients developed CSF fistula due to dura defect after gunshot injury, two patients developed CSF fistula secondary to motor vehicle accident. Staphylococcus Epidermidis was isolated in one patient among post-traumatic CSF fistula patients while Serratia Marcescens was isolated in patients with CSF fistula secondary to posterior fossa tumor surgery. While none of the seven patients died during the follow-up period in post-traumatic group, one of the 38 patients with CLD secondary to tumor surgery was lost due to sepsis in the follow-up period. CONCLUSION: CLD in post-traumatic CSF fistulas is a safe and effective treatment method. Especially in patients with gunshot wounds, CLD should be performed before revision surgery in the treatment of CSF fistula. Studies with different parameters are needed in larger trauma populations. Keywords: Cerebrospinal fluid fistula; continuous lumbar drainage; trauma; tumor.

INTRODUCTION Cerebrospinal fluid (CSF) fistula is a troublesome but a wellknown complication of post-traumatic skull fractures, skull base surgery, and spinal surgeries.[1,2] CSF may cause significant morbidity and mortality due to meningitis, as well as sepsis.[1,3] The treatment is mostly surgical repair of the site of CSF leakage. However, this is a challenging surgical procedure, especially in deeply located skull base dura defects. In patients with unidentified fistula site, diversion of CSF with closed continuous lumbar drainage (CLD) is the first choice of treatment and has been widely used.[1]

CLD systems are devices placed in the subarachnoid space from the lumbar region when there is a CSF fistula in anywhere of the central nervous system (CNS). The aims of the CLD are to remove the CSF with this drainage, to reduce the CSF pressure, and to close the CSF fistula site in the upper CNS.[1,4] Although CLD is used in patients of all ages and all types of diagnosis, it is commonly used in cases with rhinorrhea or otorrhea that occurs after surgery in the sellar region or after skull traumas. However, it may also occur following spinal traumas. Although the average CLD duration is seven days, the patient can stay for three to five days.[1,3–5]

Cite this article as: Kırık A, Yaşar S. The efficacy of continuous lumbar drainage in post-traumatic CSF fistulas. Ulus Travma Acil Cerrahi Derg 2020;26:784-788. Address for correspondence: Alparslan Kırık, M.D. SBÜ Gülhane Eğitim ve Araştırma Hastanesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, 06018 Etlik, Ankara, Turkey Tel: +90 312 - 304 53 07 E-mail: dr_alper@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):784-788 DOI: 10.14744/tjtes.2020.26446 Submitted: 09.03.2020 Accepted: 19.07.2020 Online: 15.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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The most significant complications are excessive CSF drainage and subdural effusion, occlusion and continuation of CSF fistula, pneumocephalus and infection (meningitis).[1,5,6] Headache and blindness may be observed after pneumocephalus and overdrainage. Rarely, the roots that form the cauda equina can also be damaged. Especially the infection has been reported between 3–5% and the most important risk factor for infection is the duration of drainage.[1,6] CSF culture, CSF protein and glucose values are the most significant parameters of infection. In this study, the data of patients who had a CLD system between 2018 and 2019 at the Gülhane Training and Research Hospital Neurosurgery Clinic was analyzed retrospectively. Patients’ ages, genders, diagnoses, CSF protein and glucose results, surgical methods, CSF culture results and treatment results of patients were examined.

MATERIALS AND METHODS This is a retrospective clinical study and the approval of the ethics committee of our institution was obtained for this study. The data of 45 patients who underwent CLD (Argifix® External lumbar drainage catheter, ArgiGroup, Ankara, Turkey) between 2018 and 2019 were retrospectively reviewed. The age, gender, cause of CSF fistula, culture results, and clinical outcomes were documented. CSF analysis was performed in all patients and CSF was obtained from the reservoir of the lumbar drainage. The radiological and neurological conditions of the patients were also analyzed. Computed tomography (CT) scan was obtained from all patients to rule out any pneumocephalus or CNS lesion before the CLD. Particular attention was paid for lumbar drainage, which was performed in post-traumatic CSF fistula cases. The CLD catheter was placed in the lumbar subarachnoid place with a Tuohy needle through the lumbar 4–5 interspinous space when the patient was in a lateral decubitus position (Argifix® External lumbar drainage catheter, ArgiGroup, Ankara, Turkey). The remaining part of the drainage kit coursed transversely across the back of the patient. The catheter insertion site was sutured and treated with povidone-iodine ointment. Steril drape was used to cover the entire external part of the CLD. The CSF was collected within the closed beg. The patients underwent an absolute bed rest after the insertion of CLD. The drainage rate was approximately 5–10 ml/hour or 150–250 ml/day. The system was left in place for 5–12 days (mean 8.3 days). CSF samples were obtained from the collection beg on the 3rd day of drainage for biochemical and microbiological analysis. CSF glucose and protein levels were measured, and CSF culture was performed. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

RESULTS A total of 51 CLD was inserted in 45 patients between 2018 and 2019. Among them, 27 (60%) were male and 18 were female with a mean age of 38.84 years (ranged between 13 and 72 years). The diagnosis was pituitary adenoma in 16 patients, craniopharyngioma in six patients, skull base meningioma in five patients, trauma in seven (15.5%) patients, Chiari malformation in four patients, posterior fossa tumor in five patients, and spinal tumor in three patients (Fig. 1). Trauma was the second common cause of CSF fistula after the pituitary adenoma and five of seven patients had gunshot injuries. Other two patients had blunt head injury secondary to the motor vehicle accidents. Four of five patients had cranial gunshot wounds, and one had a lumbar spinal gunshot wounds. These patients underwent debridement of the necrotic tissue and repair of dura mater before the CLD, but CSF leak persisted after surgery. Two patients with motor vehicle accidents also underwent craniotomy for a skull fracture and intracranial hematoma, but CSF leak occurred after the surgery despite the meticulous closure of the dura mater. Headache was the main complication and observed in 25 (55.5%) patients during the drainage. Pneumocephalus was detected in CT scan in three patients and the drainage was immediately stopped. Pneumocephalus was spontaneously disappeared after a few days (Fig. 2). The microorganism was isolated in two (3.92%) of 51 CSF samples obtained from all of CLD procedures. One of them was Staphylococcus Epidermidis and the other was Serratia Marcescens. Staphylococcus Epidermidis was isolated in case of right occipital trauma case secondary to the motor vehicle accident, and Serratia Marcescens was isolated in a CSF

Chiari (9%)

Trauma (15%)

Tumor (76%)

Figure 1. The distributions of patients based on the cause of CSF fistula.

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gical practice. The success rate of this system has been reported as 85–94% by different publications.[1,12–15] Fishman et al.[16] demonstrated that CLD is a highly effective technique to treat CSF leak following acoustic neuroma surgery. CLD may be used after post-traumatic CSF fistula or after anterior skull base operations that may pose a CSF leak risk. Routine CLD placement is intended to decrease CSF leaks and CNS complications.[5] In our series, 38 (84.4%) of 45 patients underwent CLD because of CSF fistula secondary to CNS tumor surgery and Chiari malformation. The most common tumor in our series was pituitary adenoma, followed by craniopharyngioma.

Figure 2. Axial CT scan of a patient who underwent CLD for posttraumatic CSF fistula and pneumocephalus in the lateral ventricles and post-traumatic encephalomalacia in the right occipital region are apparent.

fistula secondary to posterior fossa tumor surgery. Thus, the infection rate was 14.28% in CLD cases secondary to post-traumatic CSF fistula. In addition, the mean CSF glucose was 50.7 mg/dl, and the mean CSF protein was 146.14 mg/dl in post-traumatic CSF fistula cases (Table 1).

DISCUSSION Cranial and spinal traumas may cause CSF fistula secondary to dura mater defects.[7,8] Post-traumatic CSF fistulas are severe complications of gunshot wounds, which may cause significant mortality and morbidity.[9,10] They may usually present with rhinorrhea or otorrhea, but sometimes CSF leaks may observe at the wound site after the surgical repair of the head or spinal injuries. The first choice is to repair the dural defect by surgical procedure. However, CLD may also be used to decrease the CSF pressure, to allow healing to occur at the fistula site.[3,7,9] Ziyal et al.[3] presented their series of 48 patients with post-traumatic CSF fistula and they performed CLD between seven and 12 days in 17 (35.4%) cases that were unresponsive to bed rest and antibiotics. Vourc’h first introduced continuous spinal CSF drainage in 1963.[11] Since then, this method has been used in neurosur-

Açikbaş et al.[1] reported their experience with CLD in nine years and they performed CLD in 63 patients. Nine (14.28%) of them had post-traumatic CSF fistula, and they lost one patient due to hepatic failure and meningitis. They performed CLD for 5–10 days. They determined the duration of CLD based on the success of the system. Alagöz et al.[17] reported 22 patients with traumatic CSF fistula and they performed conservative treatment or CLD in all patients before the surgical repair of the dural defect. In our series, post-traumatic CSF fistula was the cause of CLD in 15.55% of our patients, and the mean duration of CLD was 8.3 days (ranged between five and 12 days). We used CLD after the surgical repair of trauma patients. In case of infection, we immediately removed the catheter. Silver- and antibiotic-impregnated catheters were previously recommended for infected hydrocephalus, but we did not use these catheters for CSF fistulas because these catheters were not commercially available for CLD cases.[18,19,20] Ren et al.[6] evaluated the efficacy of CLD in the treatment of post-craniotomy meningitis, and they found that intravenous antibiotic and steroid therapies combined with CLD may be an effective and safe treatment for post-craniotomy meningitis. They performed continuous drainage or episodical CSF drainage at 2–3 hour or 6-hour intervals, draining 300–350 ml CSF per day. This is the largest study in the literature, which was performed on 1062 patients over 16 years. In our study, the CSF drainage was 150–250 ml/day, and none of our patients had meningitis before the drainage. Ten of 45 patients had the previous craniotomy for trauma, tumor or Chiari malformation surgery. Twenty-five patients had transsphenoidal surgery before the CLD and high-flow CSF leak

Table 1. The demographic features and laboratory results of the patients with CLD Cause of CSF fistula

Number of patients

Mean age (years)

Male/ Female

Mean CSF glucose (mg/dl)

Mean CSF protein (mg/dl)

Positive CSF culture

Trauma

26.29 6/1

50.7

146.14

Tumor

42.18 18/16

36.43

102.23

Chiari malformation

38.23

86.46

3/1

CSF: Cerebrospinal fluid; CLD: Continuous lumbar drainage.

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was observed during surgery and then lumbar drainage was inserted just after the surgery. Recently, Hussein and Abdellatif reported their series of 20 patients who underwent CLD for CSF fistula. In this series, all patients showed successful cessation of CSF leakage at different durations of CLD. Minimal pneumocephalus and headache were the most common complications in this series and they concluded that CLD is simple, safe, and effective on the treatment of CSF fistulas.[4] We observed headache in 25 of 45 patients during CLD and pneumocephalus was seen in the CT scan in three patients. The CLD was stopped immediately in these patients. Vourc’h[11] and Açikbaş et al.[1] advised to avoid excessive CSF withdrawal because this may lead to headaches, nausea and vomiting. We also avoided draining more than 250 ml CSF a day because of the risk of overdrainage which may cause severe headache. We also did not leave in place the CLD for more than 12 days because of the risk of meningitis. We observed CSF infection in one of seven patients with post-traumatic CSF fistula and this case was treated using antibiotics. None of these seven patients died after CLD during the follow-up period.

Conclusion Continuous lumbar drainage is a safe, simple and effective treatment method in the treatment of post-traumatic CSF fistula. It should be the first choice if surgical repair is not feasible. More clinical studies with larger trauma populations are needed to elucidate the risk factors for CLD. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.K, S.Y.; Design: A.K.; Supervision: S.Y.; Materials: A.K.; Data: A.K.; Analysis: A.K.; Literature search: S.Y.; Writing: A.K.; Critical revision: S.Y. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Açikbaş SC, Akyüz M, Kazan S, Tuncer R. Complications of closed continuous lumbar drainage of cerebrospinal fluid. Acta Neurochir (Wien) 2002;144:475–80. 2. Izci Y, Kayali H, Daneyemez M, Koksel T, Cerrahoglu K. The clinical, radiological and surgical characteristics of supratentorial penetrating

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craniocerebral injuries: a retrospective clinical study. Tohoku J Exp Med 2003;201:39–46. 3. Ziyal IM, Kılınçoğlu BF, Şahin Y, Aydın Y. Evaluation of posttraumatic cerebrospinal fluid fistula. Ulus Travma Acil Cerrahi Derg 1999;5:86–9. 4. Hussein M, Abdellatif M. Continuous lumbar drainage for the prevention and management of perioperative cerebrospinal fluid leakage. Asian J Neurosurg 2019;14:473–8. 5. Ringel B, Carmel-Neiderman NN, Peri A, Ben Ner D, Safadi A, Abergel A, et al. Continuous lumbar drainage and the postoperative complication rate of open anterior skull base surgery. Laryngoscope 2018;128:2702–6. 6. Ren Y, Liu X, You C, Zhang Y, Du L, Hui X, et al. Efficacy of closed continuous lumbar drainage on the treatment of postcraniotomy meningitis: A retrospective analysis of 1062 cases. World Neurosurg 2017;106:925– 31. 7. Solmaz I, Kural C, Temiz C, Seçer HI, Düz B, Gönül E, et al. Traumatic brain injury due to gunshot wounds: a single institution’s experience with 442 consecutive patients. Turk Neurosurg 2009;19:216–23. 8. Izci Y, Tehli O. Cranial and spinal cord injuries in terror and war. Eur Arc Med Res 2017;33:21–39. 9. Izci Y, Kayali H, Daneyemez M, Koksel T. Comparison of clinical outcomes between anteroposterior and lateral penetrating craniocerebral gunshot wounds. Emerg Med J 2005;22:409–10. 10. Gönül E, Akbörü M, Izci Y, Timurkaynak E. Orbital foreign bodies after penetrating gunshot wounds: retrospective analysis of 22 cases and clinical review. Minim Invasive Neurosurg 1999;42:207–11. 11. Vourc’h G. Continuous cerebrospinal fluid drainage by indwelling spinal catheter. Br J Anaesth 1963;35:118–20. 12. Graf CJ, Gross CE, Beck DW. Complications of spinal drainage in the management of cerebrospinal fluid fistula. J Neurosurg 1981;54:392–5. 13. Kitchel SH, Eismont FJ, Green BA. Closed subarachnoid drainage for management of cerebrospinal fluid leakage after an operation on the spine. J Bone Joint Surg Am 1989;71:984–7. 14. Roland PS, Marple BF, Meyerhoff WL, Mickey B. Complications of lumbar spinal fluid drainage. Otolaryngol Head Neck Surg 1992;107:564–9. 15. Shapiro SA, Scully T. Closed continuous drainage of cerebrospinal fluid via a lumbar subarachnoid catheter for treatment or prevention of cranial/spinal cerebrospinal fluid fistula. Neurosurgery 1992;30:241–5. 16. Fishman AJ, Hoffman RA, Roland JT Jr, Lebowitz RA, Cohen NL. Cerebrospinal fluid drainage in the management of CSF leak following acoustic neuroma surgery. Laryngoscope 1996;106:1002–4. 17. Alagöz F, Dağlıoğlu E, Korkmaz M, Yıldırım AE, Uçkun ÖM, Divanlıoğlu D, et al. Surgical management of traumatic cerebrospinal fluid fistulas with associated lesions. Ulus Travma Acil Cerrahi Derg 2015;21:450–6. 18. Secer HI, Kural C, Kaplan M, Kilic A, Duz B, Gonul E, et al. Comparison of the efficacies of antibiotic-impregnated and silver-impregnated ventricular catheters on the prevention of infections. An in vitro laboratory study. Pediatr Neurosurg 2008;44:444–7. 19. Izci Y, Secer H, Akay C, Gonul E. Initial experience with silver-impregnated polyurethane ventricular catheter for shunting of cerebrospinal fluid in patients with infected hydrocephalus. Neurol Res 2009;31:234–7. 20. Baysallar M, Izci Y, Kilic A, Avci IY, Senses Z, Doganci L. A case of ventricular drainage infection with a rare pathogen in cerebrospinal fluid: vancomycin-resistant Enterococcus faecium. Microb Drug Resist 2006;12:59–62.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Posttravmatik beyin omurilik sıvısı fistüllerinde kontinü lomber drenajın etkinliği Dr. Alparslan Kırık, Dr. Soner Yaşar Sağlık Bilimleri Üniversitesi, Gülhane Eğitim ve Araştırma Hastanesi, Beyin ve Sinir Cerrahisi Anabilim Dalı, Ankara

AMAÇ: Kliniğimizde yatırılarak kontinü lomber drenaj (KLD) uygulanan posttravmatik beyin omurilik sıvısı (BOS) fistülü olan hastaların klinik sonuçlarını araştırmak ve bunu non-travmatik nedenlerle KLD uygulanan hastalarla karşılaştırmaktır. GEREÇ VE YÖNTEM: Ocak 2018–Aralık 2019 tarihleri arasında beyin ve sinir cerrahisi kliniğine yatırılan ve KLD takılan hastaların dosyası incelendi. Bu hastaların tanısı, demografik özellikleri, BOS sonuçları ve klinik sonuçları değerlendirildi. Travma nedeniyle dura defekti ve BOS fistülü olan hastaların sonuçları diğer sebeplerle BOS fistülü olan ve lomber drenaja alınan hastalarla karşılaştırıldı. BULGULAR: Toplam 45 hastaya 51 kez KLD uygulandı. Hastalardaki yaş ortalaması 38.84 yıl olup hastaların 27’si (%60) erkek idi. Yedi (%15.55) hastaya posttravmatik BOS fistülü nedeniyle, 38 hastaya ise tümör veya malformasyon cerrahisi sonrası KLD uygulandı. Beş hastada ateşli silah yaralanması (ASY) sonrası dura defektine bağlı BOS fistülü gelişmiş iken iki hastada trafik kazası sonrası BOS fistülü gözlenmiştir. Staphylococcus epidermidis posttravmatik BOS fistülü olan bir hastada, Serratia marcescens ise posterior fossa tümörüne sekonder BOS fistülü olan hastada üremiştir. Posttravmatik KLD uygulan yedi hastadan hiçbirisi takip sürecinde ölmemiş iken tümörlere bağlı KLD uygulan hastalarda bir tanesi takip sürecinde sepsisden dolayı kaybedilmiştir. TARTIŞMA: Posttravmatik BOS fistüllerinde KLD uygulaması güvenli ve etkili bir tedavi yöntemidir. Özellikle ateşli silah yaralanmalı hastalarda BOS fistülünün tedavisinde revizyon cerrahisi yapılmadan önce mutlaka KLD uygulanmalıdır. Daha geniş travma gruplarında daha farklı parametreler ile yapılacak çalışmalara ihtiyaç vardır. Anahtar sözcükler: Beyin omurilik sıvısı kaçağı; kontinü lomber drenaj; travma; tümör. Ulus Travma Acil Cerrahi Derg 2020;26(5):784-788

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ORIGIN A L A R T IC L E

Intraperitoneal rupture of the hydatid cyst disease: Single-center experience and literature review Cemalettin Koç, M.D., Sami Akbulut, M.D., Adem Tuncer, M.D., Sezai Yılmaz, M.D.

Tevfik Tolga Şahin, M.D.,

Department of General Surgery, İnönü University Faculty of Medicine, Malatya-Turkey

ABSTRACT BACKGROUND: The primary aim of this study was to present our experience in the intraperitoneal rupture of the hydatid cyst in the guidance of literature data. METHODS: Demographical, clinical, radiological and postoperative follow-up data of 29 patients who underwent surgical treatment in our institution with the diagnosis of intraperitoneal rupture of the hydatid cyst from January 2003 to July 2020 were analysed retrospectively in this study. RESULTS: Among the 29 patients with an age range of from 16 to 79 years (median= 39, IQR=25.5), 16 were male (55.2%), and 13 were female (44.8%). Intraperitoneal rupture of the hydatid cyst was spontaneous in 21 (72.4%), traumatic in seven (24.13%) (two of them were iatrogenic) and was due to shotgun in one patient. Vast majority of the patients were admitted to the emergency department in the first 24 hours after the onset of sign and symptoms. WBC varied from 8.600 to 30.900/mm3 (median=12.100, IQR=5.7). Ruptured cysts were localised in liver (n=25, 86.2%), in spleen (n=2, 6.89%) or in pelvis (n=2, 6.89%) and diameter varied from 40 to 200 mm (median=90, IQR=50). Among the cysts ruptured in liver, 19 (76%) of them were localised in the right lobe. Among the ruptured cysts of the liver, 20 (80%) of them underwent conservative surgery (e.g., partial pericystectomy), the remaining five patients (20%) underwent a radical surgical treatment (e.g., pericystectomy). A biliary orifice was diagnosed during surgical exploration in either cyst cavity or cut surface of the liver in 12 (48%) of the patients. Patients with a dilated common bile duct or a visible biliary duct orifice in cystic cavity underwent common bile duct exploration and T-tube drainage procedure (n=6, 24%). One patient died on postoperative day one, due to cardiopulmonary complications secondary to cyst rupture. All along the postopeartive follow-up of median 1416 days, seven (24.1%) patients were diagnosed for diseased recurrence. CONCLUSION: Intraperitoneal rupture of the hydatid cyst is a life-threatening complication of hydatid cyst disease, for which diagnosis without delay and timing of surgical treatment is essential. Anaphylactic shock require rapidly initiation of medical treatment against allergic reactions. Despite scolocidal agents, vesicular spread into peritoneal cavity accounts for the major risk factor for disease recurrence. Hence, abdominal cavity should be explored cautiously. Keywords: Acute abdomen; anaphylactic reactions; Hydatid cyst; rupture; perforation; recurrence

INTRODUCTION Echinococcus granulosus belong to Taenidae family and cystic echinococcosis, also known as hydatid cyst disease is a zoonotic disease which affects mainly the liver, lung, and various other tissues and organs. Cystic echinococcosis accounts for approximately 95% of hydatid diseases.[1,2] Following initial in-

vasion of an organ or tissue, hydatid cysts remain silent for a long time. Most of the hydatid cysts are diagnosed incidentally during an radiological evaluation performed for another indication.[3] However, some of the patients may present with abdominal pain, nausea, vomiting, jaundice depending on the dimension and localisation of hydatid cysts.[3] Internal rupture-perforation (cysto-biliary fistula, rupture into the

Cite this article as: Koç C, Akbulut S, Şahin TT, Tuncer A, Yılmaz S. Intraperitoneal rupture of the hydatid cyst disease: Single-center experience and literature review. Ulus Travma Acil Cerrahi Derg 2020;26:789-797. Address for correspondence: Sami Akbulut, M.D. İnönü Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Malatya, Turkey Tel: +90 422 - 341 06 60 E-mail: akbulutsami@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):789-797 DOI: 10.14744/tjtes.2020.32223 Submitted: 17.08.2020 Accepted: 06.09.2020 Online: 14.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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hollow viscus, broncho-biliary fistula, bronchopleural fistula, intrapericardial rupture, intrapleural rupture, intraperitoneal rupture), external rupture (cysto-cutaneous fistula), bacterial super-infection, anaphylactoid reaction, vasculary compression, biliary compression and neighboring organ compression are among hydatid cystic disease related complications. [4–6] Intraperitoneal rupture of the hydatid cyst is a rare and life-threatening complication of hydatid disease for which rapid diagnosis and treatment is essential to reduce mortality. [4,7,8] This study aims to present demographical, clinical and long-term follow-up results of 29 intraperitoneal rupture of the hydatid cyst cases in guidance of current literature.

MATERIALS AND METHODS Between January 2003 and July 2020, demographic, clinical and follow-up data of 29 patients who were admitted to Inonu University Faculty of Medicine Emergency Unit (n=28) and General Surgery Outpatient Clinic (n=1) with signs and symptoms of intraperitoneal rupture of the hydatid cyst were analyzed retrospectively. Some of the patients with intraperitoneal rupture of the hydatid cyst included in this study were previously published.[1,3,9] In this study, we aimed to present all of our published and unpublished cases as single-center experience. The following parameters were investigated for this study: age (year), sex (male, female), complaints/signs/symptoms (e.g., abdominal pain, nauseas and anaphylactic reactions) possible cause of cyst rupture (spontaneous, traumatic), history of hydatid cyst, history of anthelmintic treatment (e.g., albendazole), interval between the onset of symptoms and the admission to the hospital, diagnostic tools (abdominal computed tomography [CT], ultrasonography [US]), last white blood count (WBC) before the operation, ruptured cyst location (e.g., liver, spleen and pelvis), ruptured cyst diameter (mm), pre or postoperative serologic tests (anti-echinococcus IgG ELISA and IHA), surgical incision (e.g., midline, right subcostal and J-shaped), surgical approaches (e.g., conservative and radical surgery), presence of cysto-biliary communication, postoperative complications, recurrence, follow-up (day) and outcomes (alive, dead). Regardless of the type of surgical approach, all patients were treated using albendazole (Andazol; Biofarma, Istanbul, Turkey) at a dose of 10–15 mg/kg/day in the postoperative period. The type of surgical procedure, antiscolosidal agent, and the duration of the postoperative anthelmintic treatment varied depending on the experience of the surgical team. All patients except the patient who died in the postoperative day one were invited for periodic outpatient clinic control in the postoperative period. The surveillance protocol was as follows; patients were requested to come to outpatient clinic control every three months in the first year, every six months in the second year, and once a year afterwards. During the 790

controls, the abdominal US and serological tests were studied routinely. Abdominal CT was additionally performed to patients in whom there was a suspicion of recurrence.

Statistical Analysis Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) v25.0 (IBM Corp., Armonk, NY, USA). The continuous variables were expressed as median and Interquartile range (IQR). The categorical variables were reported as number and percentage. This retrospective study was approved by the Inonu University Institutional Review Board for Non-interventional Studies (Approval No:2020/1010).

RESULTS Among the 29 patients with an age range of from 16 to 79 years (median=39, IQR=25.5), 16 were male (55.2%) and 13 were female (44.8%). Age of females varied from 22 to 79 years (median=50, IQR=30), and the age of males varied from 16 to 59 years (median=33.5, IQR=24.5). Intraperitoneal rupture of the hydatid cyst was spontaneous in 21 (72.4%), traumatic in seven (24.13%) (two of them were iatrogenic) and was due to penetrating abdominal trauma (shotgun injury) in one patient. Traumatic perforation cases were due to falling from height (n=3), assault (n=2) and iatrogenic injury (n=2). Time from incident to admission into the emergency department was determined in 24 cases, which varied from one hour to 30 days. However, 17 patients were admitted in the first 24 hours. The US and CT (n=20), US (n=4) or CT (n=3) was the diagnostic tool in 27 of the patients, the remaining two patients were directly admitted to the operating theater (Fig. 1a–c). Upon admission to the emergency room, WBC varied from 8.600 to 30.900/mm3 (median=12.100, IQR=5.7). Major complaints and symptoms upon admission were abdominal pain, nausea/vomiting, fever, anaphylaxis, hypotension, urticaria and dyspnea in the decreasing order of frequency. Localization of perforated cysts were in liver (n=25, 86.2%), spleen (n=2, 6.89%) and pelvis (n=2, 6,89%). Localization of cysts perforated in liver were right lobe (n=19, 76%) or left lobe (n=6, 24%). Perforated cyst diameters varied from 40 to 200 mm (median=90, IQR=50). Preoperative or postoperative echinococcal ELISA or IHA results were achieved in 17 cases, among which 14 (82.3%) were seropositive.

Surgical Management Patients underwent surgical treatment due to emergent conditions, except one case who was admitted to the emergency department with non-specific symptoms and underwent elective surgical treatment. Midline (n=18), right subcostal (n=7), J-shaped (n=3) or laparoscopic trocar incisions (n=1) was used. Among the perforated cysts of the liver, 20 (80%) of them underwent conservative surgery (e.g., partial pericystectomy), the remaining five patients (20%) underwent a radical surgical treatment (e.g., pericystectomy). Following Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

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Figure 1. (a) Coronal section of the contrast-enhanced CT scan shows that one of the hydatid cysts localized in the right lobe of the liver is ruptured into the peritoneal cavity. (b) Coronal section of the contrast-enhanced CT scan shows that hydatid cyst rupture causing free fluid accumulation in the pelvic cavity. (c) Coronal section of the contrast-enhanced CT scan shows hydatid cyst rupture causing free fluid accumulation in the right paracolic gutter.

partial or total pericystectomy, a biliary orifice was diagnosed during surgical exploration (with either leakage test or visual inspection) inside the cyst cavity or on the cut surface of the liver in 12 (48%) of the cases. All visible bile duct orifices were sutured. Common bile duct exploration and t-tube insertion was performed to six (24%) patients with a dilated common bile duct or a wide bile duct orifice inside the cystic cavity. Partial cystectomy was performed to the pelvic cyst, considering adhesions to surrounding tissues. An iatrogenic injury due to dissection was diagnosed in a patient during splenectomy. Following chest-tube insertion, diaphragm was sutured primarily. A patient admitted with abdominal pain and dyspnea was diagnosed with cystic perforation located in the right liver lobe with right pleural effusion. Surgical exploration of this patient revealed empyema as a result of cystic perforation into the right hemithorax. Following drainage, chest-tube was inserted, and diaphragm was sutured primarily. All the patients included were treated with one of the NaCL (3%), Cetrimide-Chlorhexidine (1/30), Povidone-iodine (10%) or NaCL (0.9%) solution for cystic cavity and intraabdominal lavage.

Follow-Up Liver abscess (n=2), haemorrhage (n=1) and cardiopulmonary arrest (n=1) were events on postoperative course. Patients with liver abscess underwent percutaneous US-guided drainage, patient with haemorrhage underwent explorative laparotomy. Albendazole treatment with a dose of 10–15 mg/kg/day was administered to 28 patients postoperatively. Duration of anti-helminthic treatment varied from two to six months according to clinical status, disease recurrence and personal experience of the surgeon. During the postopeartive follow-up of median 1416 days (min-max=1–3456, IQR=1625), seven (24.1%) patients were diagnosed for disUlus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

eased recurrence. One of the patients died on postoperative first day due to cardiopulmonary complications of cyst perforation. Another patient died due to cardiopulmonary disease on postoperative day 60. Demographic and clinical characteristics of 29 patients with intraperitoneal hydatid cyst rupture are summarized in Table 1.

DISCUSSION Depending on the size, location, stage, relationship of the cyst with neighboring organs, 0.6–40% of patients with abdominal hydatid cyst disease may develop various complications, such as cystobiliary communication, superinfection, bronchobiliary fistula, intrapericardial rupture, intrapleural rupture, intraperitoneal rupture, Budd-Chiari syndrome, portal hypertension, gastric outlet obstruction, allergic reactions and rupture into the hollow viscus organs.[1,3,4,7,10,11] Current studies on complications of the hydatid cysts suggest that intraperitoneal rupture (1–16%) is the third most common complication of the disease following intrabiliary rupture (overall: 2–50%, occult: 10–37%, frank: 3–17%) and allergic reactions (1–25%).[1,3,7,12–15] We have summarized the results of the literature search on PubMed and Medline databases using the key words hydatid cyst, echinococcosis, rupture ve perforation in different combinations in Table 2. The current literature suggets that intraperitoneal rupture develops in 0.4–18.1% of the cases. In the second period of the present study (2009–2020), 11.2% of the patients who underwent abdominal hydatid cyst surgery were operated due to hydatid cyst rupture, which is consistent with the current literature. Intraperitoneal rupture of the hydatid cyst may develop as a result of trauma or spontaneously due to increased intracystic pressure. Occasionally, intraperitoneal rupture of the hydatid 791

Koç et al. Intraperitoneal rupture of the hydatid cyst disease

Table 1. Summary of the demographic and clinical characteristics of 29 patients with intraperitoneal hydatid cyst rupture Age Sex Cause of cyst Preoperative Diagnostic Preop Complaint/Sign/ perforation duration tools WBC Symptoms (hour)

Perforated Cyst cyst diameter location (mm)

Serology

Seg VI-VII

130

IHA (+)

Seg. IV–VI

110

Abdominal pain + Nausea

Seg VI-VII

140

Abdominal pain +

Seg VI

Abdominal pain

Seg VI

Abdominal pain+ Nausea/

Pelvis

Spontaneous

US+CT

18.000

Abdominal pain +

Trauma (Fall)

US+CT

12.000

Urticaria Abdominal pain

Nausea/Vomiting 20

Spontaneous

US+CT

11.800

Spontaneous

US+CT

12.400

Spontaneous

Trauma (Fall)

Laparotomy 11.400 US+ CT

10.700

Nausea + Blindness

Vomiting+ Urticaria 79

Spontaneous

9.200

Abdominal pain

Seg VI

Spontaneous

US+CT

19.900

Abdominal pain

Seg VI-VII

100

Shotgun

Laparotomy 13.000

Abdominal pain

Pelvis

100

Spontaneous

Abdominal pain +

Spleen

11.200

Nausea + Urticaria

Trauma (Fall)

US+CT

11.800

Abdominal pain

Seg VI

ELISA (+)

Trauma

US+CT

11.900

Abdominal pain

Seg VI-VII

ELISA (+)

US+CT

8.600

Abdominal pain +

Seg VI

ELISA (+)

Seg VIII

ELISA (+)

(percutaneous) 44

Spontaneous

US+CT

14.900

Hypotension + Anaphylaxis Abdominal pain + Fever + Urticaria

Spontaneous

12.500

Abdominal pain

Seg VI-VII

150

ELISA (+)

Spontaneous

13.100

Abdominal pain +

Seg V-VI

ELISA (+)

Abdominal pain

Seg III

100

ELISA (-)

Abdominal pain +

Spleen

ELISA (+) NA

Spontaneous

US+CT

12.100

Trauma

11.600

Spontaneous

US+CT

Cyanosis + Urticaria

Hypotension + Anaphylaxis

11.900

Abdominal pain

Seg II- III

140

Spontaneous

US+CT

16.700

Abdominal pain + Dyspnea

Seg VI-VII

200

ELISA (+)

Spontaneous

US+CT

10.300

Abdominal pain + Fever

Seg II- III

ELISA (+)

Trauma

US+CT

30.900

Abdominal pain + Fever

Seg II- III

110

ELISA (+)

Abdominal pain + Fever

Seg V-VIII

Abdominal pain +

Seg VI-VII

ELISA (+)

(percutaneous) 20

Spontaneous

120

US+CT

18.800

Spontaneous

168

US+CT

9.800

Hypotension + Anaphylaxis

Spontaneous

US+CT

11.000

Abdominal pain

Seg VII-VIII

160

ELISA (+)

Spontaneous

US+CT

20.100

Abdominal pain +

Seg III

ELISA (-)

Hypotension 67

Spontaneous

17.300

Abdominal pain

Seg VII-VIII

200

Trauma

US+CT

14.300

Abdominal pain +

Seg VI-VII

ELISA (+)

Seg II-VI

ELISA (-)

Nausea/Vomiting 40

Spontaneous

30 (day)

18.500

Abdominal pain +

Anaphylaxis

792

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Koç et al. Intraperitoneal rupture of the hydatid cyst disease

Table 1. Summary of the demographic and clinical characteristics of 29 patients with intraperitoneal hydatid cyst rupture (continue) Surgical approaches Intracavitary lavage Partial pericystectomy +

Cysto-biliary Postop Recurrence communication complication

Follow up (day)

Outcomes

NaCl (3%) + NaCL (0.9%)

Yes (Sutured)

Yes (CT)

2100

Alive

NaCl (3%) + NaCL (0.9%)

1200

Alive

Partial pericystectomy

Cetrimide–chlorhexidine (1/30)

840

Alive

Partial pericystectomy + T-tube

Cetrimide–chlorhexidine (1/30)

110

Alive

Drainage+ Omentopexy + T-tube Partial pericystectomy + Drainage+ Falciformopexy

Partial pericystectomy

NaCl (3%) + NaCL (0.9%)

780

Alive

Partial pericystectomy

Cetrimide–chlorhexidine (1/30)

900

Alive

Total pericystectomy + T-Tube

NaCl (3%) + NaCL (0.9%)

Yes (Sutured)

Cardiac arrest

Exitus

Partial pericystectomy + Drainage

NaCl (3%) + NaCL (0.9%)

Alive

Partial pericystectomy + Drainage

NaCl (3%) + NaCL (0.9%)

1680

Alive

Saline 1/10

1170

Alive

Partial pericystectomy + Omentopexy

NaCl (3%) + NaCL (0.9%)

Yes (Sutured)

1273

Alive

Pericystectomy+ Drainage +

NaCl (3%) + NaCL (0.9%)

Yes (Sutured)

457

Alive

NaCl (3%)

Liver abscess

Yes (US+CT)

3044

Alive

Cetrimide–chlorhexidine (1/30)

Yes (Sutured)

3357

Alive

Cetrimide–chlorhexidine (1/30)

Yes (Sutured)

3456

Alive

Partial pericystectomy + Drainage

Povidone-iodine (10%)

Yes (US+CT)

2603

Alive

Partial pericystectomy + Drainage

NaCl (3%)

2267

Alive

Splenectomy+ Retroperitoneal +

NaCl (3%)

Bleeding

1694

Alive

Partial pericystectomy+ Drainage

NaCl (3%)

Yes (Sutured)

Yes (US+CT)

1590

Alive

Partial pericystectomy+ Drainage

NaCl (3%)

Cardiac arrest

Exitus

NaCl (3%)

982

Alive

NaCl (3%)

Yes (US+CT)

1451

Alive

Povidone-iodine (10%)

Yes (Sutured)

573

Alive

Partial pericystectomy

Cholecystectomy Partial Cystectomy + Omentopexy + T-Tube Partial pericystectomy + Drainage + Cholecystectomy + T-tube Partial pericystectomy + Drainage + Cholecystectomy+Omentopexy

Retrovesical Cystectomy

(right pleural empyema-chest tube) Partial pericystectomy + Drainage+ Omentopexy Partial pericystectomy + Drainage + Omentopexy Pericystectomy + Drainage + Cholecystectomy Partial pericystectomy + Drainage

Cetrimide–chlorhexidine (1/30)

Yes (US+CT)

1639

Alive

Partial pericystectomy + Drainage

NaCl (3%)

Yes (Sutured)

1385

Alive

NaCl (3%) + NaCL (0.9%)

Yes (Sutured)

1416

Alive

NaCl (3%) + NaCL (0.9%)

Yes (Sutured)

3116

Alive

Cetrimide–chlorhexidine (1/30)

Yes (Sutured)

Yes (US+CT)

3125

Alive

NaCl (3%)

Liver abscess

1701

Alive

Partial pericystectomy + Drainage + Cholecystectomy + Omentopexy Pericystectomy + Drainage + Cholecystectomy Pericystectomy + Drainage + Cholecystectomy + T-tube Partial Cystectomy + Omentopexy

cyst may develop iatrogenically during elective abdominal surgery or after percutaneous radiological procedures, such as in the two patients, presented in this study. There are many studies showing that the rupture of the hydatid cysts may Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

develop due to trauma and contradicting studies that show it is more frequently a spontaneous perforation.[1,16–18] The factors that increase the risk of cystic rupture include early age, the diameter of the cyst (>10 cm) and superficial lo793

Koç et al. Intraperitoneal rupture of the hydatid cyst disease

Table 2. Brief literature review on intraperitoneal ruptured hydatid cyst First author’s References (Journal Information) Country surname Tatli Toumi Aghajanzadeh Kloppers Bozdag

Study period

Total case

Cyst perforation

Rate (%)

Dicle Medical J 2017; 44:251-6

Turkey

2012-2016

218

5.5

Eur J Trauma Emerg Surg. 2017;43:387-91

Tunisia

1990-2015

1350

0.9

Clin Surg. 2017; 2: 1820

Iran

2004-2015

352

1.1

S Afr J Surg. 2017;55:72

S. Africa

2012-2017

18.1

Dig Liver Dis. 2016;48:98-100

Turkey

2005-2015

Sakcak

J J Gastro Hepato. 2016. 3: 018

Turkey

1996-2013

756

2.1

Ozturk

J Surg Arts (Cer San D) 2016; 2: 61-6

Turkey

2008-2012

Symeonidis Mouaqit

Scand J Surg 2013;102:171-7

Greece

1980-2010

227

2.6

World J Emerg Surg. 2013;8:28

Morocco

2008-2012

306

4.6

Rami

Pan Afr Med J 2011;8:27

Morocco

2004-2008

Malik

World J Gastrointest Surg 2010;2:78-84

India

2004-2005

2.9

Akcan

World J Gastroenterol 2010;16:3040-8

Turkey

1990-2008

372

7.5

Unalp

Saudi Med J 2010;31:37-42

Turkey

2000-2009

368

5.7

Agayev

Hepatogastroenterology 2008;55:1373-9

Azerbaijan

484

1.2

Tekin

J Gastrointestin Liver Dis. 2008;17:33-7

Turkey

1985-2005

700

2.0

Akcan

World J Surg 2007;31:1284-91

Turkey

1990-2005

347

7.8

Ozturk

Am J Surg 2007;194:313-6

Turkey

1979-2004

653

3.1

Derici

World J Surg 2006;30:1879-83

Turkey

1988-2005

306

5.6

Presse Med 2004;33:378-84

Tunisia

1990-2000

970

1.8

Puia

Chirurgia (Bucur) 2004;99:541-4

Romania

1993-2002

160

3.8

Kurt

J Gastrointest Surg. 2003;7:635-41

Turkey

1995-2001

7.1

Larbi

Ann Chir 2002;127:487-8

Tunisia

1993-1999

302

5.0

Sozuer

Am J Trop Med Hyg. 2002;66:575-7

Turkey

242

8.7

Agayev

Khirurgiia (Mosk) 2001;:32-6

Azerbaijan

280

0.7

Gunay

J Trauma 1999; 46: 164-7

Turkey

1985-1997

Beyrouti

Karydakis

J Chir (Paris). 1994;131:363-70

Greece

1972-1992

421

1.0

Zhonghua Wai Ke Za Zhi. 1994;32:166-8

China

1954-1990

907

5.5

Bilge

HPB Surg. 1992;6:57-64

Turkey

1978-1990

226

0.4

Erguney

Ann Chir. 1991;45:584-9

Turkey

1979-1989

328

2.1

Pulatov

Klin Khir. 1990;6:12-4

Russia

Placer

Br J Surg. 1988;75:157

Spain

1965-1985

471

3.2

Eur Surg Res 1986;18:145-50

Greece

1964-1984

1310

0.5

Vestn Khir Im I I Grek. 1976;116:42-4

Russia

231

15.2

Chen

Androulakis Dedenko

calization.[1,7,18,19] Hydatid cysts are more frequently observed in younger people who are also more frequently involved in traumatic events. It is a common fact that intracystic pressure increases with increasing diameter. Once the intracystic pressure increases beyond 50 cm-H20, the risk of spontaneous rupture or rupture following minor trauma increases.[1,9,16,17] In superficial cysts, the free surface of the cysts is a risk factor for intraperitoneal rupture and fistulization to adjacent hollow organs and cavities.[1,3,5] The present surgery was performed in our department of surgery, and we did not include pre-adolescent patients. Thus, we can not comment on this 794

age group; however, the more than half of the patients in our study were ≤40 years which seems to support the age range of the complication stated in the literature.[3] The signs and symptoms of intraperitoneal rupture of the hydatid cyst depend on the underlying cause, the interval between onset of symptoms and admission to the emergency department and the medical history of the patient. The common symptoms of the intraperitoneal rupture of hydtid cyts are mild to severe abdominal pain, nausea, vomiting, urticaria and hemodynamic instability (hypotension and tachyUlus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Koç et al. Intraperitoneal rupture of the hydatid cyst disease

cardia) and dyspnea.[1,3,5] The cystic fluid is highly toxic and allergic. Thus, cystic fluid leakage to the peritoneal cavity, biliary system or systemic circulation can cause mild allergic reactions to severe anaphylactic shock depending on the amount of cyst fluid.[1,3,4] The review of the literature suggests that 16.7% to 25% of the cases develop minor allergic reactions, whereas 1–12.5% of the cases have life-threatening allergic reactions that require preoperative or intraoperative intervention, such as epinephrine, steroid and ventilatory support.[1,3,16,19] It should be kept in mind that 0.2–3.3% of the patients develop anaphylactic reactions during hydatid cyst surgery without obvious perforation.[20,21] Thus, allergic reactions can be encountered in any elective or emergency interventions for hydatid cysts and necessary precautions should be obtained. The authors of the present study have a consensus that any patients without prior antihelminthic therapy that will undergo hydatid cyst surgery should receive antihistaminic and 1 mg/kg corticosteroid during the anesthesia induction phase. In the diagnosis of intraperitoneal rupture of the hydatid cysts anamnesis, physical examination and radiological evaluation of the patients should be made alltogether. There is leukocytosis in most of the patients as presented in our study, but this is mainly due to peritoneal irritation rather than cyst rupture. There may be eosinophilia in certain patients. US is the first option for imaging due to the easy access and non-invasive nature of the technique. On the other hand, if the patients are hemodynamically stable, the best imaging modality that should be applied is the abdominal CT. CT can show the disruption of the cyst wall, reduction in the size of the cyst and intraabdominal rupture of the cyst as well as the exact localization of the cyst in the liver. The sensitivities of the US and CT are reported to be 85% and 100%, respectively.[5,7,9,19] The patients with confirmed intraperitoneal hydatid cyst rupture should be treated with an evaluation of the signs and symptoms. The hemodynamic stability of the patients should be achieved and the operation should be performed as soon as possible to reduce the morbidity and mortality of the patients. The primary goal of medical therapy, which includes antihistaminics, fluid resuscitation, corticosteroids and oxygen support, is to provide hemodynamic stability and prevent anaphylactic reactions in the patients. Depending on the experience of the surgical team, laparoscopic or open surgical approaches may be preferred in patients who are hemodynamically stable. On the other hand, the open surgical approach is more suitable for patients who are hemodynamically unstable. During emergency operations, complete evaluation of the abdominal cavity should be performed through a midline incision. However, the type of incision (e.g., right subcostal or J-shaped incision) can change according to the preference of the surgical team. The content of the cyst should be removed from the abdominal cavity as soon as possible and the peritoneal surface Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

should be irrigated with saline to minimalize the contact with content, which will reduce the severity of anaphylactic reactions. After this step the abdominal cavity and cavity of the cyst can be irrigated with certain scolicidal agents, such as hypertonic saline (3–10–15–30%), silver nitrate (0.5%), cetrimide (0.5%), chlorhexidine (0.05%), cetrimide + chlorhexidine (1.5%+0.15%=10% Savlon), hydrogen peroxide (1.5–3%), povidone-iodine (10% betadine), ethyl alcohol (70–95%) and formalin (2%) according to the preference and experience of the surgical team.[3,6,7,18,19] Each scolicidal solution has a different duration of action. We usually prefer hypertonic saline and cetrimide+chlorhexidine and we irrigate the abdominal cavity twice with 10 minutes interval and we wait for 10 to 15 minutes as we apply the fluid to the abdominal and cystic cavities.[1,3,9] We believe that we remove all the factors that cause allergic reactions. The cystic cavity should be evaluated as all these procedures are performed. This will enable the surgeon to see the cystic cavity thoroughly and any bile leakage can be determined. The ruptured cystic cavity can be evaluated directly for any cystobiliary communication, and in suspected cases, transcystic or transcholedochal saline can be injected to perform bile leakage test.[22,23] Bile duct orifices in cyst cavities should be sutured. If the bile orifices are wide or there is a high output biliary fistula, than common bile duct exploration and T-tube drainage should be performed. However, since the intracystic pressure is higher than the intrabiliary pressure, the exploration of the cavity may not yiled any bile leakage and biliary fistula may develop in the early postoperative period. Drainage of the cystic cavity enables early diagnosis and control of the biliary fistula. In patients with postoperative bile leakage, early ERCP (sphincterotmy±stenting) may be an effective diagnostic and therapeutic option. In the present study, 12 (48%) patients had cystobiliary communication; however, only four underwent common bile duct exploration+ T-tube drainage. Besides, two patients underwent common bile duct exploration and T-tube drainage due to the presence of cystic content in the biliary ducts and presence of dilatation in the bile ducts. Only one patient underwent postoperative ERCP due to biliary fistula, and in this patient biliary fistula was determined in the first operation. In splenic cyst ruptures, spleen preserving procedures should be selected to preserve the immunologic function of the spleen.[1,6,24] Recurrence due to missed daughter vesicles is prevented by starting the antihelminthic therapy as soon as possible after the operation. There is no generally accepted protocol for the dose and duration of antihelminthic therapy (continuous or cyclic). Although there are controversial data in the literature, it is suggested that antihelminthic therapy should be continued for one to 12 months after the operation.[1,3,5,16,25] In the present study, we started antihelminthic therapy for 2–6 months after the operation to all the patients (except the patients who died on the postoperative first day). 795

Koç et al. Intraperitoneal rupture of the hydatid cyst disease

Current literature suggests that morbidity and mortality due to operation performed for intraperitoneal rupture of the hydatid cysts are 10–63% and 0–23.5%, respectively.[1,3,7,18,19] The postoperative recurrence rates vary between 0 to 28.6%. [1,3,7,18,19] US, echinococcus IgG ELISA or IHA can be performed for the postoperative surveillance of these patients. In patients who are suspected of having a recurrence should be evaluated further by CT. The patients are evaluated every three months for the first year and every six months for the second year and annually thereafter. In the present study, 24.1% of the patients developed recurrence. We do not have the data of all the cases with hydatid cysts and therefore we cannot perform an evidence-based evaluation of the results. However, the high recurrence rate in the present study can be due to variation in the surgical team, non-satisfactory exploration of the cystic cavity, inability to remove the daughter cyst from the abdominal cavity, absence of definitive scolicidal agent for irrigation and absence of definitive albendazole treatment scheme. In conclusion, intraperitoneal, intrapericardial or intrapleural rupture is a rare but fatal complication of the hydatid cysts. In endemic areas, the presence of abdominal pain, urticaria and anaphylactic reactions should raise the suspicion of rupture of hydatid cyst. The timing of medical and surgical therapy is a significant factor that affects the morbidity and mortality of the patients. A thorough evaluation of the abdominal cavity is vital for the reduction of the recurrence in patients who are urgently operated for ruptured hydatid cysts. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: S.A., C.K.; Design: S.A., A.T., C.K.; Supervision: S.A., S.Y.; Fundings: C.K., S.A., A.T., T.T.S.; Materials: C.K., A.T.; Analysis: T.T.S., S.A.; Writing: S.A., C.K.; Critical revision: S.A., S.Y. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Akbulut S, Ozdemir F. Intraperitoneal rupture of the hydatid cyst: Four case reports and literature review. World J Hepatol 2019;11:318–29. 2. Akbulut S, Demircan F, Sogutcu N. Hydatid cyst disease of the thyroid gland: report of two cases. Int Surg 2015;100:643–7. 3. Yilmaz M, Akbulut S, Kahraman A, Yilmaz S. Liver hydatid cyst rupture into the peritoneal cavity after abdominal trauma: case report and literature review. Int Surg 2012;97:239–44. 4. Akbulut S. Parietal complication of the hydatid disease: Comprehensive literature review. Medicine (Baltimore) 2018;97:e10671. 5. Toumi O, Noomen F, Salem R, Rabeh H, Jabra SB, Korbi I, et al. In-

796

traperitoneal rupture of hydatid cysts. Eur J Trauma Emerg Surg 2017;43:387–91. 6. Belli S, Akbulut S, Erbay G, Koçer NE. Spontaneous giant splenic hydatid cyst rupture causing fatal anaphylactic shock: a case report and brief literature review. Turk J Gastroenterol 2014;25:88–91. 7. Mouaqit O, Hibatallah A, Oussaden A, Maazaz K, Taleb KA. Acute intraperitoneal rupture of hydatid cysts: a surgical experience with 14 cases. World J Emerg Surg 2013;8:28. 8. Velitchkov NG, Losanoff JE, Kjossev KT, Mironov MB. Life-threatening traumatic rupture of a liver hydatid cyst. Eur J Emerg Med 2001;8:225– 8. 9. Dirican A, Yilmaz M, Unal B, Tatli F, Piskin T, Kayaalp C. Ruptured Hydatid Cysts into the Peritoneum: A Case Series. Eur J Trauma Emerg Surg 2010;36:375–9. 10. Mehta V, Singh A, Sood A. An Unusual Cause of Gastric Outlet Obstruction. Gastroenterology 2017;152:e1–4. 11. Kabiri EH, El Maslout A, Benosman A. Thoracic rupture of hepatic hydatidosis (123 cases). Ann Thorac Surg 2001;72:1883–6. 12. Atli M, Kama NA, Yuksek YN, Doganay M, Gozalan U, Kologlu M, et al. Intrabiliary rupture of a hepatic hydatid cyst: associated clinical factors and proper management. Arch Surg 2001;136:1249–55. 13. Yildirgan MI, Başoğlu M, Atamanalp SS, Aydinli B, Balik AA, Celebi F, et al. Intrabiliary rupture in liver hydatid cysts: results of 20 years’ experience. Acta Chir Belg 2003;103:621–5. 14. Ramia JM, Figueras J, De la Plaza R, García-Parreño J. Cysto-biliary communication in liver hydatidosis. Langenbecks Arch Surg 2012;397:881– 7. 15. Akkapulu N, Aytac HO, Arer IM, Kus M, Yabanoglu H. Incidence and risk factors of biliary fistulation from a hepatic hydatid cyst in clinically asymptomatic patients. Trop Doct 2018;48:20–4. 16. Unalp HR, Yilmaz Y, Durak E, Kamer E, Tarcan E. Rupture of liver hydatid cysts into the peritoneal cavity. A challenge in endemic regions. Saudi Med J 2010;31:37–42. 17. Erel S, Kilicoglu B, Kismet K, Gollu A, Akkus MA. Peritoneal hydatid cyst perforation: a rare cause of emergency abdominal surgeries. Adv Ther 2008;25:943–50. 18. Tinsley B, Abbara A, Kadaba R, Sheth H, Sandhu G. Spontaneous intraperitoneal rupture of a hepatic hydatid cyst with subsequent anaphylaxis: a case report. Case Reports Hepatol 2013;2013:320418. 19. Akcan A, Akyildiz H, Artis T, Ozturk A, Deneme MA, Ok E, et al. Peritoneal perforation of liver hydatid cysts: clinical presentation, predisposing factors, and surgical outcome. World J Surg 2007;31:1284–91. 20. Davarci I, Tuzcu K, Karcioglu M, Yetim I, Aydogan A, Turhanoglu S. Anaesthetic Management of Anaphylactic Shock Caused by Nonruptured Hydatid Cyst of the Liver. West Indian Med J 2014;63:545–7. 21. Khanna P, Garg R, Pawar D. Intraoperative anaphylaxis caused by a hepatic hydatid cyst. Singapore Med J 2011;52:e18–9. 22. Kayaalp C. Intraoperative diagnosis of cystobiliary communications of hydatid liver cysts. Clinics (Sao Paulo) 2012;67:515. 23. Kayaalp C, Aydin C, Olmez A, Isik S, Yilmaz S. Leakage tests reduce the frequency of biliary fistulas following hydatid liver cyst surgery. Clinics (Sao Paulo) 2011;66:421–4. 24. Ran B, Shao Y, Yimiti Y, Aji T, Shayiding P, Jiang T, et al. Spleen-preserving surgery is effective for the treatment of spleen cystic echinococcosis. Int J Infect Dis 2014;29:181–3. 25. Sozuer E, Akyuz M, Akbulut S. Open surgery for hepatic hydatid disease. Int Surg 2014;99:764–9.

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Koç et al. Intraperitoneal rupture of the hydatid cyst disease

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Hidatik kist hastalığının periton içine rüptürü: Tek merkez deneyimi ve literatür analizi Dr. Cemalettin Koç, Dr. Sami Akbulut, Dr. Tevfik Tolga Şahin, Dr. Adem Tuncer, Dr. Sezai Yılmaz İnönü Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Malatya

AMAÇ: Bu çalışmanın amacı, intraperitoneal hidatik kist rüptürü gelişen hastalarla ilgili merkezimizin deneyimlerini literatür verileri ışığında sunmaktır. GEREÇ VE YÖNTEM: Ocak 2003 ile Temmuz 2020 tarihleri arasında kliniğimiz tarafından intraperitoneal hidatik kist rüptürü sebebiyle ameliyat edilen 29 hastanın demografik, klinik, radyolojik ve ameliyat sonrası takip verileri geriye dönük olarak incelendi. BULGULAR: Yaşları 16 ile 79 yıl (median=39, IQR=25.5) arasında değişen 29 hastanın 16’sı (%55.2) erkek ve 13’ü kadın idi. Hastaların 21’inde (%72.4) spontan, yedisinde travmatik (iyatrojenik=2) ve birinde ateşli silah yaralanmasına bağlı hidatik kist rüptürü gelişti. Hastaların çoğu semptom ve bulguların başlamasından sonraki ilk 24 saat içinde acil servise başvurmuştu. WBC sayıları 8.600 ile 30.900/mm3 (median=12.100, IQR=5.7) arasında değişmekteydi. Rüptüre kistlerin 25’i (%86.2) karaciğer, ikisi dalak ve geriye kalan ikisi pelvisteydi. Karaciğerde rüptüre olan kistlerin 19’u (%76) sağ lobtaydı. Rüptüre kistlerin çapları 40 mm ile 200 mm (median=90, IQR=50) arasında değişmekteydi. Karaciğer yerleşimli rüptüre kistlerin 20’sine (%80) konservatif cerrahi (parsiyel perisistektomi) işlem uygulanırken geriye kalan beş (%20) hastaya radikal cerrahi (perisistektomi) işlem uygulandı. Cerrahi işlem sırasında karaciğer yerleşimli rüptüre kistlerin 12’sinde (%48) kist kavitesinde veya karaciğer kesi yüzeyinde safra orifisi tespit edildi. Koledok çapı geniş olan veya kist kavitesinde geniş safra orifisi olan altı (%24) hastaya koledok eksplorasyonu ve t-tube drenaj işlemi uygulandı. Bir hasta kist rüptürüne ikincil kardiyopulmoner komplikasyonlar sebebiyle ameliyat sonrası birinci günde kaybedildi. Ameliyat sonrası median 1416 günlük takipte yedi (%24.1) hastada nüks gelişti. TARTIŞMA: Intraperitoneal rüptür hidatik kist hastalığının hayatı tehdit eden bir komplikasyonudur. Hızlı tanı ve cerrahi tedavinin zamanlaması hayatidir. Anaflaktik komplikasyon gelişen hastalarda allerjik reaksiyonlara yönelik tıbbi tedaviye olabildiğince hızlıca başlanmalıdır. Her ne kadar skolosidal ajanlar kullanılsa bile rüptür sonucunda periton boşluğuna dökülen kız veziküller daha sonra nüks gelişmesi için en önemli risk faktörüdür. Bu yüzden tüm karın boşluğu itina ile kontrol edilmelidir. Anahtar sözcükler: Akut karın; anaflaktik reaksiyonlar; hidatik kist; nüks; perforasyon; rüptür. Ulus Travma Acil Cerrahi Derg 2020;26(5):789-797

doi: 10.14744/tjtes.2020.32223

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ORIGIN A L A R T IC L E

The mid-term effects on quality of life and foot functions following pilon fracture Yüksel Uğur Yaradılmış, M.D.,1 Mustafa Caner Okkaoğlu, M.D.,1 Alparslan Kılıç, M.D.,1 Bahtiyar Haberal, M.D.,2 İsmail Demirkale, M.D.,1 Murat Altay, M.D.1 1

Department of Orthopaedics and Traumatology, University of Health Sciences Keçiören Training and Research Center, Ankara-Turkey

Department of Orthopaedics and Traumatology, Başkent University Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: Although pilon fractures are uncommon, they are of importance to orthopaedic surgeons because of the difficulty of treatment. Poor outcomes and high complication rates are seen despite various surgical methods. This study aims to examine the changes affecting the quality of life and foot functions in patients applied with open reduction and internal fixation (ORIF) for a pilon fracture. METHODS: In this study, a total of 45 patients treated with ORIF for a pilon fracture in our clinic between January 2010 and December 2016 were evaluated with AOFAS and SF-12 in a total of 10 categories according to demographic data, fracture classification and surgical technique. In addition to functional values, patient records were examined regarding complications, including infection, soft-tissue defect, malalignment, non-union, arthrosis and Sudeck atrophy. In patients with AOFAS <85 and low SF-12 scores, variables were examined and the relationship with complications was evaluated. RESULTS: The mean follow-up period was 3.7 years (range 2 to 7). The AOFAS value was determined to fall to <85 when the Ruedi Allgower classification increased (p=0.010), when AO classification increased (p=0.020), when there was a concomitant lateral malleolar fracture (p=0.028), and when the status was non-anatomic according to the Ovadia Bell criteria (p=0.031). The SF-12 PCS value was observed to decrease when the Ruedi Allgower classification increased (p=0.018) and when the status was non-anatomic according to the Ovadia Bell criteria (p=0.012). A correlation was determined between the SF-12 PCS and the AOFAS values (p=0.000). CONCLUSION: The reasons for the failure of ORIF in tibia pilon fractures were found to be Ruedi 3 classification, concomitant lateral malleolar fracture, and non-anatomic surgical reduction. Failure in foot functions has a direct effect on quality of life in both the short and mid term. Keywords: Arthrosis; infection; open reduction; pilon fracture; quality of life.

INTRODUCTION Pilon fractures are fractures of the distal tibia joint surface involving the metaphysis. Some authors have described them as including a 5 cm section of the distal tibia.[1] Pilon fractures constitute approximately 1% of all lower extremity fractures and 5%–10% of all tibia fractures.[2] Most pilon fractures occur as a result of a turning or twisting mechanism at varying degrees following axial loading. Although these fractures are seen infrequently, they are labelled as difficult-to-treat frac-

tures as they are seen as multi-fragmented articular fractures in a weight-bearing joint.[3,4] The aim of treatment is to obtain anatomic restoration of the joint, appropriate alignment, stable internal fixation and early mobilization.[5,6] Therefore, conservative treatment methods are not currently recommended for these fractures. Open reduction and internal fixation (ORIF), twostage surgery and external fixation methods are used in surgical treatment. Although surgery is the gold standard

Cite this article as: Yaradılmış YU, Okkaoğlu MC, Kılıç A, Haberal B, Demirkale İ, Altay M. The mid-term effects on quality of life and foot functions following pilon fracture. Ulus Travma Acil Cerrahi Derg 2020;26:798-804. Address for correspondence: Yüksel Uğur Yaradılmış, M.D. Sağlık Bilimleri Üniversitesi, Keçiören Eğitim ve Araştırma Hastanesi Ortopedi ve Travmatoloji Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 356 90 00 E-mail: ugur_yaradilmis@outlook.com Ulus Travma Acil Cerrahi Derg 2020;26(5):798-804 DOI: 10.14744/tjtes.2020.85601 Submitted: 26.11.2019 Accepted: 13.05.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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treatment, low foot function scores and high complication rates may be seen.[7] Another problem encountered in these fractures is low quality of life due to inability to undertake daily tasks and a late return to work.[8,9] Although this study is short-term and presents different surgical techniques, it may be able to provide some ideas for these deficiencies. It is necessary to know the complications of pilon fractures affecting long-term foot functions and quality of life and the effects of these to be able to predict them and take precautions. In this study, an examination was carried out of mid-term foot functions, quality of life and complications occurring in patients applied with ORIF for pilon fractures. This study aims to investigate the variables affecting foot functions and quality of life in patients applied with ORIF for pilon fracture and to investigate the relationships with complications.

MATERIALS AND METHODS A retrospective cohort study examination was carried out with 55 patients who were operated on because of pilon fractures in our clinic between January 2010 and December 2016 (Fig. 1). Patients treated with ORIF and followed up for at least two years were included in this study. A total of 10 (18.2%) patients were excluded from this study: two (3.6%) patients because external circular fixation was used, two (3.6%) patients because adjunct foot fractures were treated, and six (10.9%) patients because of incomplete data. The patients

Pilon fracture (n=55)

External sirculer fixation (n=2)

were grouped according to age, gender, osteoporosis, preoperative waiting time, postoperative follow-up time, Ruedi Allgower classification, AO classification, concomitant lateral malleolar fracture, Ovadia Bell criteria,[10] plate placement evaluation and statistical distribution. The 45 (81.8%) patients treated with ORIF were evaluated with AOFAS and SF-12 according to a total of 10 categories according to demographic data, fracture classification and surgical technique.[11–14] Foot scoring of the patient was made with AOFAS and quality of life was evaluated with the SF-12. The AOFAS values were grouped in four groups as >85, 85-70, 70-50 and <50. Apart from the functional values, a record was made for each patient of complications, including infection, soft-tissue defects, malalignment, non-union, arthrosis and Sudeck atrophy.

Preoperative Evaluation In the Emergency Department, a splint was applied to the patients, correcting malalignment and providing joint compatibility. Preoperatively, a cold compress, non-steroid anti-inflammatory drugs (NSAID) and antibiotic treatment were applied. Soft tissue was carefully evaluated preoperatively with checks made within the splint three times a day. In cases with a positive “wrinkle test” and the healing of hemorrhagic bullae, surgery was planned with three surgeons’ approval. In two of the current series of patients, skeletal traction was applied from the calcaneus as stability was not obtained with the splint (Fig. 2).

Surgical Technique Each patient was positioned supine on a radiolucent operating table. A medial or lateral incision was planned according to the fracture wound. In cases with a lateral malleolar fracture, lateral malleolar reduction and fixation were applied first. The joint surface restoration was performed first, then metaphyseal diaphyseal bone reduction. Full joint reduction and <5˚ coronal sagittal, alignment were accepted. When applying medial or lateral plating, an additional fragment-specific screw was applied when necessary (Fig. 3). Soft tissue layers were sutured appropriately.

Open reduction internal fixation (n=53)

With talus fracture (n=2)

Unavailable data (n=6)

Included patients (n=45)

Figure 1. Follow up diagram.

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Figure 2. Skeletal traction for instability and follow up soft tissue.

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Yaradılmış et al. The mid-term effects on quality of life and foot functions following pilon fracture (a)

Table 1. Demografic data of the patients Age , n (%)

44.7 (18–77)

<50

28 (62.2)

>50

17 (37.8)

Gender, n (%) (b)

Male

29 (64.4%)

Female

16 (35.6%)

3.7 (1–7)

Follow up (year), n (%)

Figure 3. Case example of medial plate fixation (a) and lateral plate fixation (b).

<4 year

>4 year

26 (57.7) 19 (42.3)

4.5 (1–16)

Preoperatice day, n (%)

<7 day

31 (68.8)

Follow-up

>7 day

14 (31.2)

Soft tissue follow-up was made daily postoperatively, and when it was assured, the patient was discharged. A splint was applied for two weeks for soft tissue healing. At the end of the second week, after removal of the splint, joint range of movement exercises were started together with Vitamin C therapy. Partial weight-bearing was permitted at six weeks postoperatively and full weight-bearing at eight weeks.

Ruedi allgower, n (%)

Ruedi1

15 (33.3)

Ruedi2

18 (40)

Ruedi3

12 (26.7)

5 (11.1)

11 (24.4)

6 (13.3)

5 (11.1)

7 (15.6)

Our study was ethically approved by the Ethical Committee of our hospital and also the University of Health Sciences Keçiören Health Practice and Research Center.

7 (15.6)

Anatomic

29 (64.4)

Statistical Analysis

Good

8 (17.7)

Moderate

7 (15.5)

Poor

1 (2.2)

Ethical Approval

Data obtained in the study were analyzed statistically with SPSS vn 22 software and examined in a 95% confidence interval. Qualitative data were stated as frequency distribution and quantitative data as mean, minimum and maximum values. The relationships between AOFAS and variables were analyzed using the Chi-square test. To determine differences in SFC-12 PCS (physical) variables, the analysis was applied using ANOVA tests as normal distribution was shown. As the SF-12 MCS (mental) points did not show normal distribution, analyses were applied with the Mann-Whitney and Kruskal Wallis tests. Statistical significance was defined at the 5% (p≤0.05) level.

RESULTS The cohort consisted of 29 (64.4%) males and 16 (35.6%) female with a mean age of 44.7 years (range 18–77 years). The mean follow-up period was 3.7 years (range 2 to 7). The time from trauma to surgery was mean 4.5 days (range 1 to 16). A preoperative wait of < 7 days was determined in 70.5% of cases and ≥7 days in 29.5%. Patient data are shown with frequencies and percentages in Table 1. 800

Ovadia Bells Criteria, n (%)

Lateral malleol fracture, n (%)

Yes

25 (55.5)

20 (44.5)

Plate fixation, n (%)

Medial

35 (77.7)

Lateral

10 (33.3)

AOFAS*, n (%)

>85

70–85

17 (37.7)

18 (40)

70–50

8 (17.7)

50–30

2 (4.4)

SF12-PCS (Physical)

47.6 (24.2–56.5)

SF12-MCS (Mental)

59.4 (39.9–65.0)

When patients were grouped acording to AOFAS, 40% of patients were evaluated as excellent, 37.7% as good, 17.7% as fair and 4.4% as poor. The SF-12 PCS (physical score) was Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

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mean 47.6 (range, 24.2–56.5) and the SF-12 MCS (mental) was mean 59.4 (range, 39.9–65.0).

spect of SF-12 values (p=0.041). Arthodesis was not requested as treatment in any of the patients with arthrosis (Table 3).

The AOFAS value was determined to fall to <85 when the Ruedi Allgower classification increased (p=0.010), when AO classification increased (BC1, BC2, BC3) (p=0.020), when there was a concomitant lateral malleolar fracture (p=0.028), and when the status was non-anatomic according to the Ovadia Bell criteria (p=0.031) (Table 2).

Table 3. Analyse of the relationship between SF12-PCS and variables

Arthrosis was observed in 11 patients (24%) and in these 11, a significant difference was observed from other patients in re-

Gender

Table 2. Analysis of the relationship between AOFAS and variables

AOFAS

>85

Age, n (%) <50

10 (37)

17 (63)

>50

7 (41.2)

10 (58.8)

0.784

Gender, n (%)

Male

8 (28.6)

20 (71.4)

Female

9 (56.3)

7 (43.8)

0.068

<4 year

12 (46.2)

14 (53.8)

>4 year

5 (29.4)

12 (70.6)

0.436

<7 day

13 (41.9)

18 (58.1)

>7 day

4 (33.3)

8 (66.7)

<50

48.08±6.59

>50

46.82±9.04

Male

47.15±6.22

Female

48.42±9.65

0.640

<4 year

47.5±8.51

>4 year

47.78±6.35

0.907

<7 day

48.52±6.71

>7 day

45.46±9.41

0.229

Ruedi Allgower Ruedi1

51.59±5.16

Ruedi2

46.89±7.01

Ruedi3

43.68±8.82

0.018*

Yes

49.63±6.01

46±8.43

0.119

Ovadia Bells Criteria

Preoperative day, n (%)

0.593

Age

Intact fibula

Follow up (year), n (%)

Preoperaative time (day)

<85

SF12-PCS (Physical)

Follow up (year)

0.437

Anatomic

49.81±6.45

41.43±9.75

Good

Moderate/poor

Ruedi allgower, n (%)

0.012*

45.78±5.3

Plate fixatio

Ruedi1

10 (66.7)

5 (33.3)

0.010*

Medial

47.95±6.94

Ruedi2

6 (33.3)

12 (66.7)

Lateral

47.58±6.78

Ruedi3

1 (9.1)

10 (90.9)

B1-C1

50.84±5.45

AO clasification, n (%)

0.765

AO clasification

B1-C1

7 (70)

3 (30)

0.020*

B2-C2

47.22±6.86

B2-C2

6 (33.3)

12 (66.7)

B3-C3

43.47±8.47

B3-C3

1 (8.3)

11 (91.7)

AOFAS

Intact fibula, n (%)

11 (57.9)

8 (42.1)

Yes

6 (25)

18 (75)

0.028

Ovadia Bells Criteria, n (%)

>85

53.94±3.83

70-85

46.82±4.42

38.75±6.96

<70

0.059

0.000*

Infection

Anatomic

15 (51.7)

14 (48.3)

Other

2 (13.3)

13 (86.7)

0.031*

Plate fixation, n (%)

Superfisial/deep

40.20±4.29

49.26±7.23

0.002*

Artrosis

Medial

15 (42.9)

20 (57.1)

Lateral

2 (25)

6 (75)

0.304

*p<0.05. AOFS: American Orthopedic Foot and Ankle Society.

Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Yes

43.92±6.56 48.79±7.53

0.041*

*p<0.05. AOFS: American Orthopedic Foot and Ankle Society.

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Yaradılmış et al. The mid-term effects on quality of life and foot functions following pilon fracture

Infection was observed in eight patients (17%), all of whom sustained the fracture in high-energy trauma (Ruedi 2: n=2, Ruedi 3: n=6). Patients with superficial infection were treated with oral antibiotics and for those with deep infection, the implant was removed and debridement was treated. Delayed union was observed in one of the patients with deep infection. Arthrosis developed in three patients with superficial infection and in one with deep infection. A significant difference was determined between the patients with infection and the other patients regarding the long-term scores (p=0.002). Sudeck’s atrophy was observed in four patients (9%), of whom three patients had C3 fractures and one patient had a C2 fracture. Treatment was applied with a physical therapy program. Malalignment was observed in five patients (11%), all of whom had a concomitant lateral malleolar fracture. Full union of the fractures was obtained at a high rate (95.5%). In two patients with delayed union, one patient had a B2 fracture with deep infection and the other patient had a C1 fracture with superficial infection.

DISCUSSION Pilon fractures are always accepted as problematic fractures by orthopaedic surgeons because they are injuries of large dimensions with damage to the cartilage joint surface and soft tissue oedema.[15] High complication rates are seen, which may include skin necrosis and infection in the early period, and non-union and arthrosis in the long-term.[16–19] However, they are infrequently seen fractures constituting approximately 1% of all lower extremity fracture.[2] In the current study, the severity of the injury was determined as Ruedi 1 in 33.3%, Ruedi 2 in 40.0% and Ruedi 3 in 26.7%. There were seen to be similar rates of low-energy and high-energy traumas. The time from trauma to surgery was mean 4.5 days (range, 1–16 days) and this period was seen to be prolonged in cases evaluated as Ruedi 3. The approach of early surgery before soft tissue swelling has formed has been abandoned as some studies have reported worse results from surgery performed in the first five days.[20] This period varies according to the severity of the injury. When the soft tissue status has been ensured, surgery should be applied. Successful operations with ORIF came to prominence with a study by Rüedi and Allgöwer[21] in 1969, which reported 74% success in 84 patients treated with ORIF. Anatomic reduction according to AO rules and early mobilization were applied. The weakest point of that study was that the majority of patients had low-energy skiing injuries. In a second series by the same team, the majority of cases arose from by high-energy 802

injuries (traffic accidents). The same level of success could not be achieved with a good result obtained in 69%. Other studies conducted according to the mechanism of injury have reported that the success rate has fallen to 50%.[22] When the patients in the current study were grouped acording to AOFAS, 40% of the patients were evaluated as excellent, 37.7% as good, 17.7% as fair and 4.4% as poor. Rubio-Suarez et al.[19] treated 90 patients with ORIF and reported 30.5% as excellent results (>85 AOFAS), 46.7% as good, 13.1% as fair and 9.7% as poor. In that study, Rubio-Suarez et al.[19] examined complications and emphasized the risk of medial plating. When the patients with AOFAS <85 (60%) were examined in the current study, they were seen to be those with Ruedi type 3 (p=0.010) and AO type C injuries (p=0.020), those with lateral malleolar fractures (p=0.028) and those who were non-anatomic according to Ovadia Bell criteria (p=0.031). No difference was seen regarding age, gender, preoperative waiting time, follow-up period, and plate placement. Infection and arthrosis were determined to decrease AOFAS values. Ilizarov fixation was applied to two patients because of both metaphyseal and tibial defect, and these cases were excluded from this study. Single-stage ORIF was applied to the pilon fractures externally. Rather than two-stage surgery the cases were transferred to the ward with a splint. In two patients (4.4%) where stability could not be achieved with a splint, skeletal traction was applied from the calcaneus and they were followed up in the ward. When the single-stage ORIF of the current study was compared with literature, the results of single-stage were found to be the same as those for two-stage.[23] In a similar study that compared three methods, low AOFAS scores were obtained with external fixators.[24] However, the use of external fixators in more severe injuries could explain the worse results of external fixators in these studies. In a comparison of limited ORIF and external fixation with ORIF, no shortfall was found in the limited approach.[25] In Ruedi Allgower type 1 and type 2 injuries, results have been shown to be better irrespective of the treatment, and treatment problems have not yet been resolved in Ruedi type 3 injuries.[26] In the light of these data, the effects of classic ORIF treatment were examined in the current study rather than the surgical methods. The SF-12 PCS value in the current study was found to be mean 47.6 (range, 24.2–56.5), which was lower than the SF-12 value of the Turkish population in general. However, the SF12 MCS value of mean 59.4 (range, 39.9–65.0) was observed to be similar to that of the general population. When the SF12 PCS was examined, the most significant relationship was seen to be in parallel with the AOFAS values (p=0.000). Cutillas-Ybarra et al.[9] examined short-term quality of life with the SF36 and reported that patients were affected both physically and psychosocially compared to the general population. In Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Yaradılmış et al. The mid-term effects on quality of life and foot functions following pilon fracture

the current study, foot function in the long-term was found to have no mental effect (SF-12 MCS evaluation). The SF-12 PCS was seen to be most affected by foot functions. In a similar study in Australia of a 12-month examination of pilon fractures, lower SF-12 PCS values were obtained.[8] A concomitant lateral malleolar fracture was observed to reduce the functional results in the current study (p=0.028). In a study by Liangjun et al.,[27] higher functional results were obtained in pilon fractures with an intact lateral malleolus. Medial plate placement has been said to be associated with skin necrosis, more severe arthrosis and non-union.7 In the current study, flap was applied to one patient with medial plate placement. In addition, of the eight patients who developed infection, there was observed to be medial plate osteosynthesis in seven patients. However, no difference was determined regarding arthrosis and non-union. Although there was no statistically significant difference, there was observed to be more arthrosis in cases with lateral plate placement (lateral plate osteosynthesis 44.4%, medial plate osteosynthesis 20%). In a study by Rubio-Suarez et al.,[19] ORIF complications were examined in a series of 137 patients. Skin necrosis was determined in 15%, non-union in 16%, arthrosis in 13% and infection in 8%. In the current study, infection was observed at the rate of 17.7%. In two (4%) patients with deep infection, the implant was removed and debridement was performed, and the only risk factor was determined to be Ruedi classification (p=0.044). As the severity of the wound increases, care must be taken in respect of infection. Delayed union was seen in two (4.4%) patients. The two patients with non-union were also determined to have infection (1 superficial, 1 deep). Arthrosis was observed in 11 (24.4%) patients of the current study. In Ruedi type 3, AO type C injuries, patients with concomitant lateral malleolar fracture (p=0.028) and those with non-anatomic fixation according to Ovadia Bell (p=0.031), arthrosis was observed at a statistically signifcantly higher rate. Patients with arthrosis were seen to have lower AOFAS and SF-12 scores. Arthrodesis was not requested for any of these patients. Similarly, Bonar et al.[28] reported that arthodesis was not required in patients with reduction and malalignment.

Conclusion The results of this study demonstrated that the reasons for ORIF failure in tibia pilon fractures were Ruedi 3, lateral malleolar fracture, and non-anatomic reduction. Failure in foot functions has a direct effect on the quality of life in both the short and mid-term. Ethics Committee Approval: Approved by the local ethics committee. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Y.U.Y; Design: Y.U.Y., B.H.; Supervision: Y.U.Y, B.H.; Fundings: Y.U.Y., A.K.; Materials: Y.U.Y., A.K.; Data: Y.U.Y., A.K.; Analysis: Y.U.Y., İ.D; Literature search: Y.U.Y., M.C.O; Writing: Y.U.Y., M.C.O.; Critical revision: Y.U.Y., M.A. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Tornetta P 3rd, Weiner L, Bergman M, Watnik N, Steuer J, Kelley M, et al. Pilon fractures: treatment with combined internal and external fixation. J Orthop Trauma 1993;7:489−96. 2. Bourne RB, Rorabeck CH, Macnab J. Intra-articular fractures of the distal tibia: the pilon fracture. J Trauma 1983;23:591−6. 3. Chowdhry M, Porter K. The pilon fracture. Trauma 2010;12:89−103. 4. Calhoun JH, Li F, Ledbetter BR, Viegas SF. A comprehensive study of pressure distribution in the ankle joint with inversion and eversion. Foot Ankle Int 1994;15:125−33. 5. Borrelli J Jr, Ellis E. Pilon fractures: assessment and treatment. Orthop Clin North Am 2002;33:231−x. 6. Rüedi T. Fractures of the lower end of the tibia into the ankle joint: results 9 years after open reduction and internal fixation. Injury 1973;5:130−4. 7. Carbonell-Escobar R, Rubio-Suarez JC, Ibarzabal-Gil A, Rodriguez-Merchan EC. Analysis of the variables affecting outcome in fractures of the tibial pilon treated by open reduction and internal fixation. J Clin Orthop Trauma 2017;8:332−8. 8. Bonato LJ, Edwards ER, Gosling CM, Hau R, Hofstee DJ, Shuen A, et al. Patient reported health related quality of life early outcomes at 12 months after surgically managed tibial plafond fracture. Injury 2017;48:946−53. 9. Cutillas-Ybarra MB, Lizaur-Utrilla A, Lopez-Prats FA. Prognostic factors of health-related quality of life in patients after tibial plafond fracture. A pilot study. Injury 2015;46:2253−7. 10. Ovadia DN, Beals RK. Fractures of the tibial plafond. J Bone Joint Surg Am 1986;68:543−51. 11. Kitaoka HB, Alexander IJ, Adelaar RS, Nunley JA, Myerson MS, Sanders M. Clinical rating systems for the ankle-hindfoot, midfoot, hallux, and lesser toes. Foot Ankle Int 1994;15:349−53. 12. Ibrahim T, Beiri A, Azzabi M, Best AJ, Taylor GJ, Menon DK. Reliability and validity of the subjective component of the American Orthopaedic Foot and Ankle Society clinical rating scales. J Foot Ankle Surg 2007;46:65−74. 13. Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care 1996;34:220−33. 14. Orthotolkit. SF-12 – OrthoToolKit. Available at: http://orthotoolkit. com/sf-12. 15. Mast JW, Spiegel PG, Pappas JN. Fractures of the tibial pilon. Clin Orthop Relat Res 1988;230:68−82. 16. McFerran MA, Smith SW, Boulas HJ, Schwartz HS. Complications encountered in the treatment of pilon fractures. J Orthop Trauma 1992;6:195−200. 17. D’Alleyrand JC, Manson TT, Dancy L, Castillo RC, Bertumen JB, Meskey T, et al. Is time to flap coverage of open tibial fractures an independent predictor of flap-related complications?. J Orthop Trauma 2014;28:288−93.

803

Yaradılmış et al. The mid-term effects on quality of life and foot functions following pilon fracture 18. Lomax A, Singh A, N Jane M, C Senthil K. Complications and early results after operative fixation of 68 pilon fractures of the distal tibia. Scott Med J 2015;60:79−84. 19. Rubio-Suarez JC, Carbonell-Escobar R, Rodriguez-Merchan EC, Ibarzabal-Gil A, Gil-Garay E. Fractures of the tibial pilon treated by open reduction and internal fixation (locking compression plateless invasive stabilising system): Complications and sequelae. Injury 2018;49:S60−4. 20. Trumble TE, Benirschke SK, Vedder NB. Use of radial forearm flaps to treat complications of closed pilon fractures. J Orthop Trauma 1992;6:358−65. 21. Rüedi TP, Allgöwer M. The operative treatment of intra-articular fractures of the lower end of the tibia. Clin Orthop Relat Res 1979;(138):105−10. 22. Kellam JF, Waddell JP. Fractures of the distal tibial metaphysis with intra-articular extension--the distal tibial explosion fracture. J Trauma 1979;19:593−601. 23. Minator Sajjadi M, Ebrahimpour A, Okhovatpour MA, Karimi A, Zandi R, Sharifzadeh A. The Outcomes of Pilon Fracture Treatment: Prima-

ry Open Reduction and Internal Fixation Versus Two-stage Approach. Arch Bone Jt Surg 2018;6:412−9. 24. Biz C, Angelini A, Zamperetti M, Marzotto F, Sperotto SP, Carniel D, et al. Medium-Long-Term Radiographic and Clinical Outcomes after Surgical Treatment of Intra-Articular Tibial Pilon Fractures by Three Different Techniques. Biomed Res Int 2018;2018:6054021. 25. Zhang SB, Zhang YB, Wang SH, Zhang H, Liu P, Zhang W, et al. Clinical efficacy and safety of limited internal fixation combined with external fixation for Pilon fracture: A systematic review and meta-analysis. Chin J Traumatol 2017;20:94−8. 26. Kemal Aktuğlu, Nadir Özkayın. Surgical modalities in tibial pilon fractures TOTBİD Derg 2013;12:142−52. 27. Liangjun J, Qiang Z, Hang L, Zhijun P. Injury mechanism, fracture characteristics and clinical treatment of pilon fracture with intact fibula-A retrospective study of 23 pilon fractures. J Clin Orthop Trauma 2017;8:S9−15. 28. Bonar SK, Marsh JL. Tibial Plafond Fractures: Changing Principles of Treatment. J Am Acad Orthop Surg 1994;2:297−305.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Pilon kırıkları sonrası ayak fonksiyonları ve hayat kalitesinde orta dönem etkenler Dr. Yüksel Uğur Yaradılmış,1 Dr. Mustafa Caner Okkaoğlu,1 Dr. Alparslan Kılıç,1 Dr. Bahtiyar Haberal,2 Dr. İsmail Demirkale,1 Dr. Murat Altay1 1 2

Sağlık Bilimleri Üniversitesi, Keçiören Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Anabilim Dalı, Ankara Başkent Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Ankara

AMAÇ: Pilon kırıkları az görülmesine rağmen tedavisi zor olması nedeniyle ortopedik cerrahlar tarafından önemsenmiştir. Değişen cerrahi yöntemlere rağmen kötü sonuç ve yüksek komplikasyonlar görülmektedir. Bu çalışmanın amacı, pilon kırığı nedeniyle açık redüksiyon ve iç fiksasyon (ORIF) yaptığımız hastalarda ayak fonksiyonları ve hayat kalitesini etkileyen değişkenleri incelemek ve komplikasyonlarla ilişkilendirmek. GEREÇ VE YÖNTEM: Kliniğimizde Ocak 2010–Aralık 2016 tarihleri arasında, pilon kırığı nedeniyle ORIF uygulanan 45 hasta demografik verileri, kırık sınıflaması ve cerrahi tekniğe göre toplam 10 kategoriye göre AOFAS ve SF-12 ile değerlendirildi. Hastalar fonksiyonel değerler haricinde komplikasyonlar olarak enfeksiyon, yumuşak doku defekti, dizilim bozukluğu, kaynamama, artroz ve Sudeck atrofisi açısından da hastaların kayıtları incelendi. AOFAS 85 altı olan ve düşük SF12 olan hastaların değişkenleri incelendi ve komplikasyonlarla ilişkisi değerlendirildi. BULGULAR: Ortalama takip süresi 3.7 yıl olup (2–7 yıl). AOFAS değerlerine bakıldığında, Ruedi-Allgower sınıflaması arttığında (p=0.010), AO sınıflaması arttığında (p=0.020), eşlik eden lateral malleol kırığında (p=0.028) ve Ovadia-Bell kriterleri’ne göre non-anatomik olması durumunda (p=0.031) AOFAS değerleri 85’in altına düşmektedir. SF-12 PCS değerlerine bakıldığında, Ruedi-Allgower sınıflaması arttığında (p=0.018), OvadiaBell kriterleri’ne göre non-anatomik olması durumunda (p=0.012) SF-12 PCS değerlerinde düşme gözlendi. SF-12 PCS ile AOFAS değerlerinde korelasyon gözlendi (p=0.000). TARTIŞMA: Tibia pilon kırıklarında ORIF ile başarısızlık nedeni Ruedi 3, lateral malleol kırığı, cerrahi anatomik olmayan redüksiyon olarak bulundu. Ayak fonksiyonlarındaki başarısızlık hem erken dönem hem de orta dönemde hayat kalitesini doğrudan etkilemektedir. Anahtar sözcükler: Açık cerrahi; artroz, enfeksiyon; hayat kalitesi; pilon kırıkları. Ulus Travma Acil Cerrahi Derg 2020;26(5):798-804

804

doi: 10.14744/tjtes.2020.85601

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ORIGIN A L A R T IC L E

Management of thoracolumbar injury classification and severity score of 4 (TLICS=4) thoracolumbar vertebra fractures: Surgery versus conservative treatment Evren Karaali, M.D.,1 Osman Çiloğlu, M.D.,1 Altuğ Duramaz, M.D.,2 Aslıhan Kuşvuran Özkan, M.D.,3 Timur Ekiz, M.D.4 1

Department of Orthopedics and Traumatology, Adana City Hospital, Adana-Turkey

Department of Orthopedics and Traumatology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul-Turkey

Department of Physical and Rehabilitation Medicine, Özülkü Medical Center, Adana-Turkey

Department of Physical Therapy and Rehabilitation, İstanbul Gedik University Faculty of Health Sciences, İstanbul-Turkey

ABSTRACT BACKGROUND: This study aims to compare clinical and radiographic outcomes of surgical treatment and conservative treatment with bracing in neurologically intact patients with score 4 of TLICS thoracolumbar vertebra fractures. METHODS: Patients with traumatic thoracolumbar junction fractures (T11-L2), the score of TLICS 4, and minimum 24-month follow-up were included in this study. Patients were divided into surgery and bracing groups. The groups were compared concerning clinical and demographical features, local kyphotic angles (LKA), vertebra height loss percentage (VHL), Oswestry Disability Index (ODI), Visual Analog Scale (VAS) and time to return to work. RESULTS: There were 74 patients (71 males, 3 females) in the surgery group and 76 patients (58 males, 18 females) in the bracing group. Although the surgery group showed better improvement in VAS scores within six months postoperatively, no significant difference was observed at the 24th-month evaluation (p<0.001 and p=0.270, respectively). ODI, LKA and VHL were significantly lower in the surgery group (p<0.001, p<0.001 and p<0.001, respectively). In addition, return to work was significantly earlier in the surgery group (p<0.001). CONCLUSION: The findings obtained in this study suggest that the surgical treatment for TLICS 4 patients with thoracolumbar fractures has better clinical and radiographic outcomes than the bracing. Moreover, returning time to the work of patients is shortened with surgical treatment. The surgical treatment seems to be the first and the appropriate choice in the management of TLICS 4 thoracolumbar vertebral fractures. Keywords: Clinical and radiological outcomes; spinal bracing; surgical treatment; thoracolumbar fractures; TLICS.

INTRODUCTION Acute fractures of the thoracolumbar spine can be managed either nonoperatively or surgically according to the type of fracture and clinic status of the patients (e.g., fracture morphology, neurological deficits, and ligamentous integrity).[1] Using an easy, accurate, and injury classification system is crucial to guide surgeons in decision making on which treatment

is more suitable for better clinical outcomes. In this context, although there is no unique universally accepted classification by surgeons, the Thoracolumbar Injury Classification and Severity score (TLICS) has been widely used among surgeons. [1,2] There is almost no debate on the surgical treatment of severe fractures with posterior ligamentous complex (PLC) disruption and neurological injury as a score of more than 4 in TLICS. Conservative approach is recommended for the

Cite this article as: Karaali E, Çiloğlu O, Duramaz A, Kuşvuran Özkan A, Ekiz T. Management of thoracolumbar injury classification and severity score of 4 (TLICS=4) thoracolumbar vertebra fractures: Surgery versus conservative treatment. Ulus Travma Acil Cerrahi Derg 2020;26:805-810. Address for correspondence: Altuğ Duramaz, M.D. Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul, Turkey Tel: +90 212 - 414 71 71 E-mail: altug.duramaz@yahoo.com Ulus Travma Acil Cerrahi Derg 2020;26(5):805-810 DOI: 10.14744/tjtes.2020.30524 Submitted: 16.09.2019 Accepted: 28.03.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Karaali et al. Management of TLICS=4 thoracolumbar vertebra fractures

scores of less than 4 in minor traumas. However, as for the treatment of TLICS score 4 vertebra fractures, treatment may be surgical or conservative depending on patient variables and choice of the surgeon.[3] The outcomes of operative and non-operative treatments in TLICS 4 thoracolumbar vertebra fractures are conflicting.[4–6] From this point of view, there is a need for further studies comparing clinical outcomes of surgical and non-surgical methods for TLICS 4 vertebra fractures. Therefore, the present study aims to determine whether surgery or initial conservative treatment with bracing has a better clinical outcome in neurologically intact patients with intermediate severity thoracolumbar junction traumatic fractures classified TLICS 4. The present study hypothesized that clinical and radiological outcomes would be better in the surgical group within six months, but that there would be no difference between the groups after two years of follow-up.

MATERIALS AND METHODS Study Design and Patients This study was conducted as a single-center, comparative, and retrospective cohort study. The patients who had been followed-up in our center due to the TLICS 4 vertebra fracture between 2013 to 2017 were reviewed retrospectively, after approval of the local ethics committee (IRB protocol ID: 2017/04-10). Inclusion criteria were traumatic thoracolumbar junction fractures (compression and burst) between T11 –L2, the only score of TLICS 4, without any neurologic deficit, age at ≥18 years, without previous surgery, within 24 hours of presentation and a minimum six months of the follow-up period. Exclusion criteria were: patients with a follow-up period of fewer than six months, pregnancy, having pathologic or osteoporotic fractures, previous history of spine surgery, and any missing data regarding the fracture.

Treatment Methods Conservative treatment protocol comprised horizontal bed rest depending on pain, a standardized rehabilitation program to train trunk musculature, and compliance to wearing thoracolumbar orthosis for at least three months. Short-segment posterior stabilization and instrumentation were performed to all the patients who underwent surgery and they did not wear thoracolumbar orthosis neither postoperatively nor after discharged. Also, a rehabilitation program was given to strengthen the trunk muscles.

Data Collection and Radiographic Evaluation Demographical data, such as age, gender, level of injury, AO fracture type and etiology of the trauma, were gathered. All patients had images of plain radiographs, computed tomography, magnetic resonance imaging at presentation, and two plain radiographs at every follow-up visit. Angular measurements were performed on lateral spine radiographs at the 806

first admission, third month, sixth month and 24th month. Local kyphosis (LKA) was measured as the angle from the superior end-plate to the inferior end-plate. The anterior and posterior vertebral body heights of the injured segment were measured. Normalized vertebral body height loss (VHL) was calculated as a percentage of the height loss normalized to the average of the vertebral bodies above and below the injured segment.[7] Radiographic measurements were made by the same senior spinal surgeons who followed the patients.

Outcome Measures The primary functional outcome measure was the Oswestry Disability Index (ODI). The ODI is a functional, disease-specific instrument comprising 10 questions on limitations in activities of daily living, caused by low back pain. Each question is scored 0 to 5. The ODI score is multiplied by two to acquire the percentage. The total score ranges from 0 (best health state) to 100 (worst health state). The index was validated for the Turkish population.[8] Secondary outcome measures included back pain Visual Analog Scale (VAS) score and time to return to work. Records of VAS score for back pain at pre-treatment, third month, sixth month and 24th month were collected and compared between the groups. VAS is a well-known, validated instrument to let patients score their daily pain. We used a 0 to 10 scale as scored; 0=no pain and 10=unbearable pain.[9] Time to return to work was determined from self-reported at the last follow-up time.

Statistical Analyses The IBM Statistical Package for the Social Sciences 20.0 (SPSS) was used to analyze the data. After checking the normal distribution with Kolmogorov Smirnov test and histogram graphics, the descriptive data were given as mean, standard deviation, number or percentage. Between-group comparisons of numeric data were administered using the Student’s t-test. Repeated evaluations were compared using the Repeated Measures. The Chi-Square test was used to compare categorical data between the groups. A p-value of 0.05 was set as the significance level. In the calculation of post hoc sample size (Power and Precision, Version 2.0; Biostat, Englewood, NJ, USA), the power of the study with 0.05 alpha value was found over 80%. The standard effect size for quantitative data was set at 1.37% and the power of this study was 99%.

RESULTS Demographic characteristics of the patients are presented in Table 1. There was no significant difference between the groups concerning mean age, level of injury, AO fracture type and extra-vertebral fracture (p>0.05). However, the number of male patients, duration of hospitalization, and fall from the height were significantly higher in the surgery group Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Karaali et al. Management of TLICS=4 thoracolumbar vertebra fractures

Table 1. Demographic features of the patients in both groups

Surgery

Brace

Age (years), mean±SD

49.64±18.5

49.49±20.6

0.963

Hospitalization (days), mean±SD

3.18±1.74

1.50±0.6

<0.001

71 (95.9)

58 (76.3)

0.001

3 (4.1)

18 (23.7)

Gender, n (%)

Male

Female

Level of injury, n (%)

T11

9 (12.2)

5 (6.6)

T12

23 (31.1)

20 (26.3)

21 (28.4)

32 (42.1)

21 (28.4)

19 (25.0)

0.295

AO classification, n (%)

24 (32.4)

21 (27.6)

21 (28.4)

23 (30.2)

18 (24.3)

19 (25.0)

11 (14.9)

13 (17.2)

0.896

Trauma mechanism, n (%)

Fall from height

53 (71.6)

25 (32.9)

Simple fall

10 (13.5)

22 (28.9)

In-car accident

8 (10.8)

15 (19.7)

Pedestrian accident

3 (4.1)

14 (18.3)

17 (23.0)

20 (26.3)

Extra-vertebral fracture, n (%)

<0.001

0.635

Statistically significant p values marked as bold. SD: Standard deviation.

(p<0.001, p<0.001 and p<0.001, respectively). No significant difference was observed between the groups concerningpre-treatment VAS values (p=0.709). Although the surgery group showed better improvement in VAS scores within the six months postoperatively, no significant difference was observed at the 24th-month evaluation (Fig. 1). The 24th month ODI, LKA and VHL values were significantly lower in the surgery group (Table 2). Also, the time to return to work was statistically significant in the surgery group (p<0.001). When compared with the pre-treatment values, it was noteworthy

VAS Score

9 8 7 6 5

p=0.709

p<0.001

3 2 1 0

Surgery Bracing

p=0.270

Preoperative

3rd month

6th month

24th month

8.29 8.36

3.54 4.35

1.66 2.89

0.54 0.67

Figure 1. Preoperative and postoperative Visual Analog Scale (VAS) values of the groups.

Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

that the third-, sixth- and 24th- month VHL increased in the brace group (p<0.001).

DISCUSSION There are four important findings that were obtained in the current study. First, the surgery group had significantly better functional outcomes within the six-month follow-up. Second, the surgery group showed better improvement in VAS scores at the 3rd- and 6th-month postoperatively, but not the 24th-month. Third, the 3rd-, 6th, and 24th-month LKA and VHL values were significantly lower in the surgery group. Lastly, the return to work was significantly earlier in the surgery group. TLICS has been suggested as a reliable classification for guidance in the treatment of acute thoracolumbar spinal trauma.[10] However, the TLICS has no clear recommendation for guiding surgeons for the treatment of patients with a score of TLICS 4.[2] This ambiguity arises from indeterminate imaging findings as to the integrity of PLC, whether disrupted or intact. Two systematic reviews about the treatment of patients in traumatic thoracolumbar fractures without neurological deficits have demonstrated that there is a lack of evidence providing a reliable answer to whether operative or conservative treatment is more effective.[6,11] Therefore, the present study compared the clinical and ra807

Karaali et al. Management of TLICS=4 thoracolumbar vertebra fractures

Table 2. Comparison of clinical and radiological outcomes of the patients in both groups

Surgery (n=74)

Mean±SD

Conservative (n=76)

Mean±SD

Clinical evaluation

ODI score

VAS score

19.89±9.9

29.9±6.9

<0.001

Pre-treatment

8.29±1.3

8.36±1.1

3rd month

3.54±1.1

4.35±1.0

<0.001

6th month

1.66±0.9

2.89±0.9

<0.001

24th month

0.54±0.6

0.67±0.7

0.270

104.79±20.6

142.21±18.5

<0.001

Return to work (days)

0.709

Radiological evaluation

LKA (O)

Pre-treatment

31.58±4.6

32.89±5.6

3 month

28.6±7.9

33.81±4.8

0.020

6th month

26.2±6.9

34.5±2.6

0.004

24th month

20.56±10.77

38.17±6.0

<0.001

0.123

Vertebra height loss (%)

Pre-treatment

60.24±8.6

58.46±9.2

<0.001

3rd month

21.98±5.3

59.72±4.9

<0.001

6 month

21.43±8.3

61.27±7.1

<0.001

24th month

20.21±3.2

67.61±8.7

<0.001

ODI: Oswestry disability index; VAS: Visual Analog Scale; LKA: Local kyphosis angle; SD: Standard deviation. Statistically significant p values marked as bold.

diological outcomes of non-operative treatment and surgery in TLICS 4 patients. The studies compared the surgical versus conservative treatment in TLICS 4 vertebra fractures in the literature have conflicting results. Siebenga et al.[12] found better clinical and radiological outcomes in patients with AO type A fractures and treated surgically than conservatively after mean 4.3 years follow-up. Mohamadi et al.[3] suggested using surgical treatment rather than conservative treatment due to significantly lower pain scores and shorter time to return to work in TLICS 4 fractures. Similar to our results, Shen et al.[13] reported better improvement in pain scores for the surgical treatment compared to conservative treatment at an intermediate follow-up time; however, there was no difference at the latest follow-up. On the other hand, there is a conspicuous study highlighting the conservative treatment as a safe approach in TLICS 4 patients (n=20) compared with TLICS ≤3 patients (n=38) treated conservatively.[14] This study demonstrated that conservative treatment for TLICS 4 thoracolumbar fractures could be safely applied and the conservative treatment of cases scoring TLICS 4 is equally effective to those scoring ≤3. Furthermore, Nataraj et al.[15] found no significant difference in terms of ODI, VAS score and time to return to work in another study comparing 808

surgically- and conservatively- treated patients during sixmonth follow-up. Compared with the previous studies, the sample size was relatively larger and the mean follow-up period was relatively longer in the present study. According to our results, time to return to work was significantly shorter in the surgery group compared with the bracing group and the surgery group showed better improvement in terms of ODI and VAS score. Although a better improvement was found at the 3rd- and the 6th-month in VAS scores, the results were similar inthe 24th-month. Another important issue that needs to be underscored in the treatment of stable vertebra fractures without neurological deficit is the kyphotic angle because the vertebral column becomes unstable as the kyphotic angle increases.[1,7,16] In this context, the integrity of PLC has a critical role.[7,17] Surgical treatment is indicated in case of persistent back pain and progressive kyphosis during the follow-up of relevant patients.[16] In the current study, the surgery group had significantly lower LKA and VHL at the 3rd-, 6th- and 24th-month. Also, LKA and VHL in the surgical group tended to decrease towards the postoperative 24th-month, while the brace group tended to increase. The orthosis allows preventing gross trunk movements rather than preventing intervertebral movement, but reminds and helps the patient to keep the trunk in an upUlus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Karaali et al. Management of TLICS=4 thoracolumbar vertebra fractures

right position.[1] However, there has been a debate about the effectiveness of bracing in stable fractures.[18] Bailey et al.[19] concluded that using the brace in burst fractures with neurologically stable patients did not affect the outcome regarding pain control and function. In the current paper, similarly to Bailey’s study, complete and incomplete burst fractures with neurologically stable patients did not show the differences regarding the clinical outcomes. Shamji et al.[20] compared bracing with no-bracing groups in their randomized controlled trial whereby there was no difference regarding the VHL, kyphotic progression or clinical outcomes during the sixth months of the follow-up period. In the present study, a significant increase in kyphotic deformity in the bracing group at 3rd-, 6th- and 24th-month was observed. This progression of kyphotic deformity may be due to indeterminate PLC injury and/or inadequate trunk stability due to the failure of the brace treatment. There are some limitations to the present study. The retrospective design and no randomization are the main limitations. Although the follow-up period (at least 24 months) is acceptable compared with the previous studies, it could be longer. Differences regarding the gender between the groups are another limitation. This could be attributed to that male patients might have consented to surgery more easily. However, a more homogenous group would be noteworthy.

Conclusion The present study demonstrated that the surgical treatment for TLICS 4 patients with thoracolumbar fractures had better clinical and radiographic outcomes compared with the bracing at the 3rd-, 6th- and 24th-month postoperatively. Although there was a better improvement in VAS pain scores in the surgery group within six months postoperatively, the groups showed similar results at the 24th-month evaluation. Moreover, it was shown that returning time to work of patients is shortened with surgery. As a result, our results suggest surgical treatment as the first and the appropriate choice in the management of TLICS 4 thoracolumbar vertebral fractures. Ethics Committee Approval: All procedures performed in studies involving human participants were following the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: E.K., O.Ç.; Design: E.K., A.D.; Supervision: O.Ç., A.K.Ö.; Fundings: O.Ç., T.E.; Materials: E.K., O.Ç.; Data: E.K., A.K.Ö., T.E.; Analysis: T.Ö., A.D.; Literature search: E.K., A.D., O.Ç.; Writing: E.K.; Critical revision: A.D., E.K. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

REFERENCES 1. Joaquim AF, Patel AA, Schroeder GD, Vaccaro AR. A simplified treatment algorithm for treating thoracic and lumbar spine trauma. J Spinal Cord Med 2019;42:416−22. 2. Schroeder GD, Harrop JS, Vaccaro AR. Thoracolumbar Trauma Classification. Neurosurg Clin N Am 2017;28:23−9. 3. Mohamadi A, Googanian A, Ahmadi A, Kamali A. Comparison of surgical or nonsurgical treatment outcomes in patients with thoracolumbar fracture with Score 4 of TLICS: A randomized, single-blind, and single-central clinical trial. Medicine (Baltimore) 2018;97:e9842. 4. Dodwad SN, Dodwad SJ, Wisneski R, Khan SN. Retrospective Analysis of Thoracolumbar Junction Injuries Using the Thoracolumbar Injury Severity and Classification Score, American Spinal Injury Association Class, Injury Severity Score, Age, Sex, and Length of Hospitalization. J Spinal Disord Tech 2015;28:E410−6. 5. Joaquim AF, Ghizoni E, Tedeschi H, Batista UC, Patel AA. Clinical results of patients with thoracolumbar spine trauma treated according to the Thoracolumbar Injury Classification and Severity Score. J Neurosurg Spine 2014;20:562−7. 6. van der Roer N, de Lange ES, Bakker FC, de Vet HC, van Tulder MW. Management of traumatic thoracolumbar fractures: a systematic review of the literature. Eur Spine J 2005;14:527−34. 7. Radcliff K, Su BW, Kepler CK, Rubin T, Shimer AL, Rihn JA, et al. Correlation of posterior ligamentous complex injury and neurological injury to loss of vertebral body height, kyphosis, and canal compromise. Spine (Phila Pa 1976) 2012;37:1142−50. 8. Yakut E, Düger T, Oksüz C, Yörükan S, Ureten K, Turan D, et al. Validation of the Turkish version of the Oswestry Disability Index for patients with low back pain. Spine (Phila Pa 1976) 2004;29:581−5; discussion: 585. 9. Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain 1983;17:45−56. 10. Joaquim AF, de Almeida Bastos DC, Jorge Torres HH, Patel AA. Thoracolumbar Injury Classification and Injury Severity Score System: A Literature Review of Its Safety. Global Spine J 2016;6:80−5. 11. Thomas KC, Bailey CS, Dvorak MF, Kwon B, Fisher C. Comparison of operative and nonoperative treatment for thoracolumbar burst fractures in patients without neurological deficit: a systematic review. J Neurosurg Spine 2006;4:351−8. 12. Siebenga J, Leferink VJ, Segers MJ, Elzinga MJ, Bakker FC, Haarman HJ, et al. Treatment of traumatic thoracolumbar spine fractures: a multicenter prospective randomized study of operative versus nonsurgical treatment. Spine (Phila Pa 1976) 2006;31:2881−90. 13. Shen WJ, Liu TJ, Shen YS. Nonoperative treatment versus posterior fixation for thoracolumbar junction burst fractures without neurologic deficit. Spine (Phila Pa 1976) 2001;26:1038−45. 14. Pneumaticos SG, Karampinas PK, Triantafilopoulos G, Koufos S, Polyzois V, Vlamis J. Evaluation of TLICS for thoracolumbar fractures. Eur Spine J 2016;25:1123−7. 15. Nataraj A, Jack AS, Ihsanullah I, Nomani S, Kortbeek F, Fox R. Outcomes in Thoracolumbar Burst Fractures With a Thoracolumbar Injury Classification Score (TLICS) of 4 Treated With Surgery Versus Initial Conservative Management. Clin Spine Surg 2018;31:E317−21. 16. Hitchon PW, Abode-Iyamah K, Dahdaleh NS, Shaffrey C, Noeller J, He W, et al. Nonoperative Management in Neurologically Intact Thoracolumbar Burst Fractures: Clinical and Radiographic Outcomes. Spine (Phila Pa 1976) 2016;41:483−9. 17. Khurana B, Sheehan SE, Sodickson A, Bono CM, Harris MB. Traumatic

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Karaali et al. Management of TLICS=4 thoracolumbar vertebra fractures thoracolumbar spine injuries: what the spine surgeon wants to know. Radiographics 2013;33:2031−46. 18. Joaquim AF, Patel AA. Thoracolumbar spine trauma: Evaluation and surgical decision-making. J Craniovertebr Junction Spine 2013;4:3−9. 19. Bailey CS, Dvorak MF, Thomas KC, Boyd MC, Paquett S, Kwon BK, et al. Comparison of thoracolumbosacral orthosis and no orthosis for

the treatment of thoracolumbar burst fractures: interim analysis of a multicenter randomized clinical equivalence trial. J Neurosurg Spine 2009;11:295−303. 20. Shamji MF, Roffey DM, Young DK, Reindl R, Wai EK. A pilot evaluation of the role of bracing in stable thoracolumbar burst fractures without neurological deficit. J Spinal Disord Tech 2014;27:370−5.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Torakolomber yaralanma sınıflaması ve ciddiyet skoru 4 (TLICS = 4) olan torakolomber vertebra kırıklarının yönetimi: Cerrahi mi, konservatif tedavi mi? Dr. Evren Karaali,1 Dr. Osman Çiloğlu,1 Dr. Altuğ Duramaz,2 Dr. Aslıhan Kuşvuran Özkan,3 Dr. Timur Ekiz4 Adana Şehir Hastanesi, Ortopedi ve Travmatoloji Kliniği, Adana Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul Özülkü Tıp Merkezi, Fizik Tedavi ve Rehabilitasyon Kliniği, Adana 4 İstanbul Gedik Üniversitesi Sağlık Bilimleri Fakültesi, Fizik Tedavi ve Rehabilitasyon Anabilim Dalı, İstanbul 1 2 3

AMAÇ: Torakolomber yaralanma sınıflaması ve ciddiyet skoru 4 (TLICS = 4) olan nörolojik intakt torakolomber vertebra kırıklı hastalarda cerrahi tedavi ve korse tedavisinin klinik ve radyografik sonuçlarının karşılaştırılması amaçlandı. GEREÇ VE YÖNTEM: Travmatik torakolomber kırık (T11-L2), TLICS 4 skoru ve en az 24 ay takip edilen hastalar alındı. Hastalar cerrahi ve korse gruplarına ayrıldı. Gruplar klinik ve demografik özellikler, lokal kifoz açıları (LKA), vertebra yükseklik kaybı yüzdesi (VYK), Oswestry Engellilik İndeksi (ODI), Visual Analog Skala (VAS) ve işe geri dönme süresi açısından karşılaştırıldı. BULGULAR: Cerrahi grubunda 74 hasta (71 erkek, 3 kadın), korse grubunda 76 hasta (58 erkek, 18 kadın) vardı. Cerrahi grupta ameliyat sonrası ilk altı ay içinde VAS skorlarında daha iyi olsa da 24. ayda gruplar arasında anlamlı bir fark gözlenmedi (sırasıyla, p<0.001 ve p=0.270). ODI, LKA ve VYK cerrahi grubunda anlamlı olarak düşüktü (sırasıyla, p<0.001, p<0.001 ve p<0.001). İşe geri dönüş süresi ameliyat grubunda anlamlı olarak daha kısa idi (p<0.001). TARTIŞMA: Torakolomber kırıkları olan nörolojik olarak intakt TLICS 4 hastaların cerrahi tedavisinin, korseye göre daha iyi klinik ve radyografik sonuçları olduğunu saptandı. Ayrıca, hastaların işe dönüş sürelerinin cerrahi tedavi ile kısaltıldığı gösterildi. TLICS 4 torakolomber vertebral kırıkların tedavisinde cerrahi tedavi ilk ve uygun seçenek olarak görünmektedir. Anahtar sözcükler: Cerrahi tedavi, klinik ve radyolojik sonuçlar; spinal korse; TLICS; torakolomber kırıklar. Ulus Travma Acil Cerrahi Derg 2020;26(5):805-810

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ORIGIN A L A R T IC L E

Comparison of functional outcomes in patients fixed with dynamic hip screw and proximal femur nail-anti-rotation in A1 and A2 type intertrochanteric femur fractures Hüseyin Fatih Sevinç, M.D.,1 Meriç Çırpar, M.D.,2 İbrahim Deniz Canbeyli, M.D.,2 Bülent Dağlar, M.D.,3 Birhan Oktaş, M.D.,2 Serhat Durusoy, M.D.4 1

Department of Orthopedics and Traumatology, Nevşehir State Hospital, Nevşehir-Turkey

Department of Orthopedics and Traumatology, Kırıkkale University Faculty of Medicine, Kırıkkale-Turkey

Department of Orthopedics and Traumatology, Güven Hospital, Ankara-Turkey

Department of Orthopedics and Traumatology, Bozok University Faculty of Medicine, Yozgat-Turkey

ABSTRACT BACKGROUND: We aimed to compare clinical and functional outcomes between patients treated with Dynamic hip screw (DHS) and Proximal Femoral Nail-Antirotation (PFN-A) implants. METHODS: This study included 122 patients (66 men [54.1%] and 56 women [45.9%]) who underwent surgery with DHS and PFN-A for an intertrochanteric femur fracture and had at least 12 months follow-up. Reduction assessment, femoral neck-shaft angle and tip-apex distance measurements were performed in early postoperative radiographs. On control visits in months 1, 3, 6 and 12, range of motion, thigh or hip pain, and Trendelenburg positivity were assessed in clinical examination and reduction assessment, femoral neck-shaft angle and tip-apex distance measurements were performed on radiographs after the union. Patients were assessed using Hip Harris Score after the union. RESULTS: Regardless of implant type used, mean tip-apex distance measured at the immediate postoperative period was 27.6 in patients with implant failure, whereas 21.6 in patients without, indicating a significant difference. Again, mean femoral neck-shaft angle measured at the immediate postoperative period was 123 degree in patients with implant failure, whereas 130 degree in those without, indicating a significant difference. It was found that the femoral neck-shaft angle was <128 degree in all patients with implant failure whereas it was >128 degree in 94% of patients without implant failure at immediate postoperative period. CONCLUSION: The findings regarding femur neck-shaft angle at the immediate postoperative period was <128 degree in all patients with implant failure and that it was ≥128 degree in 94% of patients without implant failure emphasize the importance of anatomic restoration in femur neck-shaft angle during surgery. The finding that mean tip-apex distance was 27.6 mm in patients with implant failure and 21.6 mm in patients without implant failure indicates that the technique is as important as implant type selected for treatment success of the implantation. Keywords: Dynamic hip screw; femoral neck-shaft angle; intertrochanteric femur fractures; proximal femoral nail anti-rotation; tip-apex distance.

INTRODUCTION In the treatment of intertrochanteric femur fractures, which often occur in elder individuals, the aim is to return to daily

activities as before the fracture and to prevent complications that arise from immobilization by ensuring mobilization as soon as possible.[1] There is a consensus that the primary aim is to ensure early mobilization by providing stable fixation.[2]

Cite this article as: Sevinç HF, Çırpar M, Canbeyli İB, Dağlar B, Oktaş B, Durusoy S. Comparison of functional outcomes in patients fixed with dynamic hip screw and proximal femur nail-anti-rotation in A1 and A2 type intertrochanteric femur fractures. Ulus Travma Acil Cerrahi Derg 2020;26:811-817. Address for correspondence: Hüseyin Fatih Sevinç, M.D. Nevşehir Devlet Hastanesi, Ortopedi ve Travmatoloji Kliniği, Nevşehir, Turkey Tel: +90 384 - 228 50 50 E-mail: drhfatihsevinc@gmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):811-817 DOI: 10.14744/tjtes.2020.39888 Submitted: 01.11.2019 Accepted: 02.02.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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However, there is an ongoing debate on the selection of the implant type to be used for fixation. Dynamic hip screw (DHS) is considered as the gold standard in the treatment of stable intertrochanteric femur fractures. [3,4] The rate of implant problems is 1% in stable intertrochanteric femur fractures, whereas the rate reaches up to 20% in unstable intertrochanteric femur fractures treated by DHS. [5,6] Despite the success of lag plate-screw implants, failure in unstable fractures has led to an increased interest in proximal femur nails (PFN).[7] Theoretically, PFNs have many biomechanical advantages when compared to lag screws. Despite their advantages, their rate of complications is higher than lag screws.[8] There are new-generation nails designed to reduce complication rates. As a result, PFNs are increasingly used in the treatment of both stable and unstable intertrochanteric femur fractures. In a study conducted by Anglen and Weinstein, it was found that the rate of PFN use reached from 3% in 1999 to 67% in 2006.[9] However, many studies showed that there was no significant difference between DHS and PFN-antirotation (PFN-A) used in the treatment of low-energy (A1 and A2) intertrochanteric fractures concerning radiological and clinical parameters, operation time, scopy time, mean blood loss, length of hospital stay and functional outcomes. [4,10–12] In several series, excellent outcomes were achieved with DHS used for fixation in intertrochanteric fracture.[13,14] In this study, we aimed to compare clinical and functional outcomes between patients treated with DHS and PFN-A implants. This study was approved by the Institutional Ethics Committee numbered 04/01-23.02.1015. All patients gave written informed consent before their participation.

MATERIALS AND METHODS This study included 122 patients (66 men [54.1%] and 56 women [45.9%]) who underwent surgery with DHS and

(a)

(b)

PFN-A for an intertrochanteric femur fracture and had at least 12 months follow-up. Patients who had undergone surgery with a proximal femoral plate and bipolar hip arthroplasty for intertrochanteric fracture of the femur and patients who did not voluntarily participate in follow-ups and did not willingly participate in this study were excluded. As the use of DHS in the treatment of A3 type femur intertrochanteric fractures resulted in high complication rates, A3 type fractures were excluded from this study. This study was conducted in the outpatient setting at a tertiary-level care center in three surgeons’ practice (Figs. 1, 2). Bilateral anteroposterior and lateral hip radiographs, anteroposterior femur radiographs including the hip on the involved side, and hip radiographs in internal rotation were taken at presentation for all patients. Fractures were classified according to the Müller AO classification system. Patients were operated on by three surgeons who had 10 years of experience as a specialist in orthopaedics and traumatology. Implant selection was made according to our clinical protocol, which considered fracture and patients’ characteristics. No randomization was used for implant selection. All patients were treated on the elective basis as soon as conditions are satisfied. Radiolucent standard operating table was used according to surgeons’ preference. All patients were positioned supine with a bump under the ipsilateral buttock when the standard table was used. Perfect anteroposterior and lateral images were obtained before patient preparation. Standard operative techniques were utilized according to implant chosen. The postoperative regime was the same for all patients, which includes immediate weight-bearing according to patients’ tolerance. Reduction assessment, femoral neck-shaft angle and tip-apex distance measurements were performed in early postoperative radiographs. On control visits in months 1, 3, 6 and 12, range of motion, thigh or hip pain and Trendelenburg positivity

(c)

Figure 1. (a) Anteroposterior radiograph of a 56 years old man with an A1 type intertrochanteric femur fracture. (b) Postoperative anteroposterior radiograph of the fracture treated with DHS. (c) Postoperative lateral radiograph of the fracture treated with DHS.

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(a)

(b)

(c)

Figure 2. (a) Anteroposterior radiograph of an 83 years old man with an A2 type intertrochanteric femur fracture. (b) Postoperative anteroposterior radiograph of the fracture treated with PFN-A. (c) Postoperative lateral radiograph of the fracture treated with PFN-A.

were assessed in clinical examination and reduction assessment, femoral neck-shaft angle and tip-apex distance measurements were performed on radiographs after the union. Patients were assessed using Hip Harris Score after the union. Statistical analyses were carried out using the SPSS version 17.0 software package. Descriptive statistics (mean, standard deviation) were used to analyze the data. Quantitative data with normal distribution were compared using Student’s t-test, and those with skewed distribution were compared using the Mann-Whitney U test. To assess relationships, Pearson’s correlation analysis was used for parametric variables and Spearman’s correlation analysis was used for non-parametric variables.

RESULTS When the mechanism of injury was considered, it was found that fractures developed as a result of fall at home in 109 (89.3%), fall at outdoors in eight (6.6%), in-vehicle traffic accident in three (2.5%) and out-of-vehicle traffic accident in two patients (1.6%). No significant difference was detected concerning implant type according to the mechanism of injury (p=0.370). Patient characteristics in the DHS and PFN-A groups are shown in Table 1. Patient characteristics in the both A1 groups are shown in Table 2. Patient characteristics in the both A2 groups are shown in Table 3.

Table 1. Patients characteristics in both groups Variable

DHS (n=66)

PFNA (n=56)

Age (years)

77.1 (35–92)

78.9 (50–105)

0.370

39/27

27/29

0.230

Sex (male/female)

AO, n (%)

0.001

48 (72.7)

16 (28.6)

18 (27.3)

40 (71.4)

39/27

27/29

0.986

Side (right/left) Singh Index

2.81

2.78

0.755

Implant failure (n=13) (10.7%), n (%)

2 (3.0)

11 (19.6)

0.003

Mean TAD immediate postoperative

21.3

23.5

0.009

Mean TAD after the union

20.4

18.9

0.281

Mean NSA immediate postoperative

132.2

126.2

0.001

130

124

0.001

Mean NSA after the union Harris Trendelenburg, n (%)

80.5 4 (6.1)

66.5 0.001 25 (44.6)

0.001

DHS: Dynamic hip screw; PFNA: Proximal femoral nail-antirotation; TAD: Tip apex distance; NSA: Neck shaft angle.

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Table 2. Patients characteristics in both A1 groups Variable Implant failure (n=2) (3.1%) Mean TAD immediate postoperative

DHS (n=66)

PFNA (n=16)

2 (12.5%)

0.013

20.9

22.1

0.377

Mean TAD after the union

20.5

19.5

0.281

Mean NCA immediate postoperative

132.5

127.7

0.001

Mean NSA after the union

130.8

126

0.001

Harris Trendelenburg

72.5 0.004

2 (4.2%)

5 (31.3%)

0.003

DHS: Dynamic hip screw; PFNA: Proximal femoral nail-antirotation; TAD: Tip apex distance; NSA: Neck shaft angle.

Table 3. Patients characteristics in both A2 groups Variable Implant failure (n=11) (19%) Mean TAD immediate postoperative

DHS (n=18)

PFNA (n=40)

2 (11.1%)

9 (22.5%)

0.306

22.1

0.138

Mean TAD after the union

20.1

18.7

0.566

Mean NCA immediate postoperative

131.3

125.7

0.001

Mean NSA after the union

127.7

123.2

0.016

Harris

71.1

64.2 0.270

Trendelenburg

2 (11.1%)

20 (50%)

0.005

DHS: Dynamic hip screw; PFNA: Proximal femoral nail-antirotation; TAD: Tip apex distance; NSA: Neck shaft angle.

When early mobilization was assessed, 66 patients (100%) treated with DHS were mobilized at the first postoperative day by weight-bearing as tolerated, while 51 (91.1%) treated with PFN-A were mobilized at the first postoperative day by weight-bearing as tolerated. Four patients (7.1%) were mobilized by partial weight-bearing, and no weight-bearing was allowed in one patient (1.8%). A significant difference was detected between the groups concerning the postoperative first day early mobilization (p=0.046). When complications were considered, complications were observed in eight patients who underwent DHS (12.1%) and in 12 (21.4%) who underwent PFN-A, indicating a significant difference (p=0.065). In DHS patients, complications included a loosening of compression screw in six patients and implant failure in two patients. In PFN-A patients, complications included intraoperative fracture in one patient and implant failure in 11. Regardless of the implant type, mean tip-apex distance measured at the immediate postoperative period was 27.6 in patients with implant failure and 21.6 in patients without, indicating a significant difference (p=0.001). Again, mean femoral neck-shaft angle measured at the immediate postoperative period was 123 degrees in patients with implant failure and 814

130 degrees in those without, indicating a significant difference (p=0.001). It was found that the femoral neck-shaft angle was <128 degrees in all patients with implant failure and >128 degrees in 94% of patients without implant failure at the immediate postoperative period.

DISCUSSION DHS is the choice of the implant in stable fractures, while the intramedullary nail is preferred in instable fractures due to its effectiveness. However, there is no consensus on the choice of the implant in unstable fractures.[15] We should note that given that DHS systems are inadequate for instable fractures, there is a growing interest in intramedullary nails. While DHS is the choice of the implant in stable fractures, the preference of surgeons has shifted to PFN-A due to its potential biomechanical advantages in theory.[15] In a multicenter meta-analysis, including 3279 patients, it was concluded that intramedullary nails had no superiority over the dynamic hip screw in both stable and instable trochanteric fractures.[16] In many studies, dynamic hip screws have been considered as the gold standard in the treatment of stable intertrochanteric femur fractures.[8,15,17] When our cases were assessed according to the MĂźller AO classification, it was seen that we mainly used DHS in A1 fractures and PFN-A in A2 fractures. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Sevinç et al. Comparison of functional outcomes in patients fixed with DHS and PFN-A in A1 and A2 type intertrochanteric femur fractures

At the immediate postoperative period, a significant difference was detected between patients with and without implant failure regarding femoral neck-shaft angle, which is used to investigate whether the reduction is achieved in varus-valgus position in clinical practice. The finding that the femur neck-shaft angle at the immediate postoperative period was <128 degrees in all patients with implant failure, and that it was ≥128 degrees in 94% of those without implant failure emphasizes the importance of anatomic restoration in femur neck-shaft angle during surgery. These data are inconsistent with the study of Davis et al.,[18] who reported that the femur-shaft angle did not affect the loosening rate. Şahin et al.[19] found the mean femur-shaft angle as 136.7 degrees in patients treated for instable intertrochanteric femur fracture, and authors observed that femur-shaft angle decreased from 125 degrees to 118 in a case with the loosening of the helical screw. In a study by Ertürer et al.,[20] the mean femur-shaft angle was found to be 125.5 degrees in patients treated with profine nail for the intertrochanteric femur fracture. The femur-shaft angle is approximately 125 degrees in individuals aged >75 years.[21] Based on our data, we think that femur-shaft angle <128 degrees is not acceptable at the immediate postoperative period as it increases complications. Lag screws are used for fixation in DHS and PFN-A fixation systems for intertrochanteric femur fractures, which is sent to the femur head via femur neck over the implant system. The tip-apex distance is the best marker for implant survival and outcome, which was first defined by Baumgaertner et al.[5,22] Tip-apex distance is directly correlated to implant failure. Baumgaertner et al.[5,22] suggested that implant failure is less likely when the tip-apex distance is below 25 mm and that it is the most important parameter, although not the only one, to predict treatment success. In our study, regardless of implant type, a significant difference was detected between patients with and without implant failure in terms of immediate postoperative tip-apex distance. In consistent with the literature, the finding that mean tip-apex distance was 27.6 mm in patients with implant failure and 21.6 mm in those without indicates that the technique is as important as implant type for the success of implantation. In A2 fractures, no significant difference was found in tip-apex distance measured at the immediate postoperative period and after the union between DHS and PFN-A groups. However, the presence of a significant difference in femur-shaft angel favoring DHS at immediate postoperative period and after the union and better clinical outcomes in DHS patients indicates that the DHS system can maintain long-term stability even in displaced fractures. When clinical outcomes and complications were assessed in our study, complication rates for A1 and A2 fractures were lower in the DHS group when compared to the PFN-A group, and complications were considered as minor in the Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

DHS group. When the groups were compared regarding Hip Harris Score, it was found that Hip Harris Score was higher in A2 fractures undergoing DHS. We think that the difference occurred as PFN-A was mainly preferred in A2 fractures, in which stable reduction can be challenging. In many studies comparing DHS and gamma nail, it was shown that there was no significant difference in terms of complications and clinical and functional outcomes.[23–27] However, Xu et al.[28] reported that PFN-A was associated with lower complication rates than DHS. Again, Kristek et al.[29] reported lower complications in patients undergoing PFN-A. Thus, these advantages in the selection of the implant system can explain the tendency to choose intramedullary nails. In the literature, there are studies reporting that walking ability at the postoperative period was recovered more rapidly with intramedullary nails when compared to DHS and that intramedullary nails provided better restoration of hip anatomy. In our study, the finding of less Trendelenburg and significantly higher Hip Harris Score in DHS patients is inconsistent with the literature. In many studies, it was reported that walking ability was recovered more rapidly in PFN-A patients than DHS patients.[29,30] Another difference in our study was the finding that DHS patients could be mobilized earlier with weight-bearing as tolerated. We think that the differences in recovery of walking ability, presence of Trendelenburg and tolerance to weight-bearing can be attributed to injury in the hip abductor mechanism for optimal positioning of the intramedullary nail. In conclusion, based on our findings, we think that fracture type and stability, and regardless of the system used, tip-apex distance are the most important factors in the selection of the implant system for fixation. We believe that DHS when implemented by a proper technique, will provide better results in A1 and A2 fractures (if a stable reduction is possible) regarding union, functional outcomes and complication rates. However, further studies with larger samples are needed to use these findings as a guide in clinical practice.

Conclusion We think that both DHS and PFN-A implant systems can be selected in A1 intertrochanteric femur fractures and that both systems can ensure union without implant failure in such fractures. However, DHS should be the first choice in A1 fractures as the femur-shaft angle is better after DHS treatment, resulting in more convenience functional activity. Both DHS and PFN-A can be selected in A2 intertrochanteric femur fractures; however, DHS can be preferred in A2 fractures, where stable reduction can be achieved since PFN-A is associated with higher rates of Trendelenburg presence, complication and implant failure, and Hip Harris Score is lower after union. PFN-A should be the choice of the implant in A2 intertrochanteric femur fractures, but DHS can provide successful clinical outcomes in selected patients if a proper 815

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reduction is provided and implantation techniques are followed meticulously. We think that femur neck-shaft angle <128 degrees should not be accepted during surgery since it is associated with increased complication rates. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: H.F.S., B.D., M.Ç.; Design: H.F.S., B.D., M.Ç.; Supervision: H.F.S., B.D., M.Ç.; Fundings: H.F.S., B.D., M.Ç.; Materials: H.F.S., B.D., M.Ç., B.O., S.D.; Data: H.F.S., B.D., M.Ç., İ.D.C., B.O., S.D.; Analysis: H.F.S., B.D., M.Ç., S.D.; Literature search: H.F.S., B.D., M.Ç., İ.D.C., B.O., S.D.; Writing: H.F.S., M.Ç., B.D., S.D.; Critical revision: H.F.S., B.D., S.D. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Koval KJ, Chen AL, Aharonoff GB, Egol KA, Zuckerman JD. Clinical pathway for hip fractures in the elderly: the Hospital for Joint Diseases experience. Clin Orthop Relat Res 2004;425:72–81. 2. Siegmeth AW, Gurusamy K, Parker MJ. Delay to surgery prolongs hospital stay in patients with fractures of the proximal femur. J Bone Joint Surg Br 2005;87:112–36. 3. Dodds SD, Baumgaertner MR. The sliding hip screw. Curr Opin Orthop 2004;15:12−7. 4. Baumgaertner MR, Curtin SL, Lindskog DM. Intramedullary versus extramedullary fixation for the treatment of intertrochanteric hip fractures. Clin Orthop Relat Res 1998;348:87−94. 5. Baumgaertner MR, Curtin SL, Lindskog DM, Keggi JM. The value of the tip-apex distance in predicting failure of fixation of peritrochanteric fractures of the hip. J Bone Joint Surg Am 1995;77:1058−64. 6. Hardy DC, Descamps PY, Krallis P, Fabeck L, Smets P, Bertens CL, et al. Use of an intramedullary hip-screw compared with a compression hip-screw with a plate for intertrochanteric femoral fractures. A prospective, randomized study of one hundred patients. J Bone Joint Surg Am 1998;80:618−30. 7. Kenzora JE, McCarthy RE, Lowell JD, Sledge CB. Hip fracture mortality. Relation to age, treatment, preoperative illness, time of surgery, and complications. Clin Orthop Relat Res 1984;186:45−56. 8. Parker MJ, Handoll HH. Gamma and other cephalocondylic intramedullary nails versus extramedullary implants for extracapsular hip fractures in adults. Cochrane Database Syst Rev 2008;3:CD000093. 9. Anglen JO, Weinstein JN; American Board of Orthopaedic Surgery Research Committee. Nail or plate fixation of intertrochanteric hip fractures: changing pattern of practice. A review of the American Board of Orthopaedic Surgery Database. J Bone Joint Surg Am 2008;90:700−7. 10. Bellabarba C, Herscovici D Jr, Ricci WM. Percutaneous treatment of peritrochanteric fractures using the Gamma nail. Clin Orthop Relat Res 2000;375:30−42. 11. Saudan M, Lübbeke A, Sadowski C, Riand N, Stern R, Hoffmeyer P. Pertrochanteric fractures: is there an advantage to an intramedullary nail?: a randomized, prospective study of 206 patients comparing the dynamic

816

hip screw and proximal femoral nail. J Orthop Trauma 2002;16:386−93. 12. Papasimos S, Koutsojannis CM, Panagopoulos A, Megas P, Lambiris E. A randomised comparison of AMBI, TGN and PFN for treatment of unstable trochanteric fractures. Arch Orthop Trauma Surg 2005;125:462−8. 13. Kyle RF, Gustilo RB, Premer RF. Analysis of six hundred and twenty-two intertrochanteric hip fractures. J Bone Joint Surg Am 1979;61:216−21. 14. Zuckerman JD. Hip fracture. N Engl J Med 1996;334:1519−25. 15. Browner B, Levine A, Jüpiter J, Trafton P, Krettek C. Skeletal Trauma. 2 Vol. WB Saunders Company, 1996. 16. Jones HW, Johnston P, Parker M. Are short femoral nails superior to the sliding hip screw? A meta-analysis of 24 studies involving 3,279 fractures. Int Orthop 2006;30:69−78. 17. Larsson S. Treatment of osteoporotic fractures. Scand J Surg 2002;91:140−6. 18. Davis TR, Sher JL, Horsman A, Simpson M, Porter BB, Checketts RG. Intertrochanteric femoral fractures. Mechanical failure after internal fixation. J Bone Joint Surg Br 1990;72:26−31. 19. Şahin S, Ertürer E, Oztürk I, Toker S, Seçkin F, Akman S. Stabil olmayan intertrokanterik femur kırıklarının tedavisinde proksimal femoral çivi antirotasyon osteosentezinin radyografik ve fonksiyonel sonuçları Acta Orthop Traumatol Turc 2010;44:127−34. 20. Ertürer E, Sönmez M, Sarı S, Seçkin F, Kara A, Öztürk İ. Yaşlı hastalarda intertrokanterik kalça kırıklarında Profin® çivisi ile intramedüller osteosentez. Acta Orthop Traumatol Turc 2012;46:107−12. 21. Boyd HB, Anderson LD. Management of Unstable Trochanteric Fractures. Surg Gynecol Obstet 1961;112:633−8. 22. Baumgaertner MR, Solberg BD. Awareness of tip-apex distance reduces failure of fixation of trochanteric fractures of the hip. J Bone Joint Surg Br 1997;79:969−71. 23. Ahrengart L, Törnkvist H, Fornander P, Thorngren KG, Pasanen L, Wahlström P, et al. A randomized study of the compression hip screw and Gamma nail in 426 fractures. Clin Orthop Relat Res 2002;401:209−22. 24. Barton TM, Gleeson R, Topliss C, Greenwood R, Harries WJ, Chesser TJ. A comparison of the long gamma nail with the sliding hip screw for the treatment of AO/OTA 31-A2 fractures of the proximal part of the femur: a prospective randomized trial. J Bone Joint Surg Am 2010;92:792−8. 25. Habernek H, Wallner T, Aschauer E, Schmid L. Comparison of ender nails, dynamic hip screws, and Gamma nails in the treatment of peritrochanteric femoral fractures. Orthopedics 2000;23:121−7. 26. Jaworski JM, Gaździk TS, Kaleta M, Dec J, Godula R. Treatment of trochanteric fractures of the femur: DHS or Gamma nail? - own experience. Ortop Traumatol Rehabil 2003;5:53−9. 27. Utrilla AL, Reig JS, Muñoz FM, Tufanisco CB. Trochanteric gamma nail and compression hip screw for trochanteric fractures: a randomized, prospective, comparative study in 210 elderly patients with a new design of the gamma nail. J Orthop Trauma 2005;19:229−33. 28. Xu YZ, Geng DC, Mao HQ, Zhu XS, Yang HL. A comparison of the proximal femoral nail antirotation device and dynamic hip screw in the treatment of unstable pertrochanteric fracture. J Int Med Res 2010;38:1266−75. 29. Kristek D, Lovrić I, Kristek J, Biljan M, Kristek G, Sakić K. The proximal femoral nail antirotation (PFNA) in the treatment of proximal femoral fractures. Coll Antropol 2010;34:937−40. 30. Pajarinen J, Lindahl J, Michelsson O, Savolainen V, Hirvensalo E. Pertrochanteric femoral fractures treated with a dynamic hip screw or a proximal femoral nail. A randomised study comparing post-operative rehabilitation. J Bone Joint Surg Br 2005;87:76−81.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

A1 ve A2 tipi femur intertrokanterik kırıklarında kayan kalça vidası ve proksimal femur çivisi-antirotasyon ile tespit sonrası hastaların fonksiyonel sonuçlarının karşılaştırılması Dr. Hüseyin Fatih Sevinç,1 Dr. Meriç Çırpar,2 Dr. İbrahim Deniz Canbeyli,2 Dr. Bülent Dağlar,3 Dr. Birhan Oktaş,2 Dr. Serhat Durusoy4 Nevşehir Devlet Hastanesi, Ortopedi ve Travmatoloji Kliniği, Nevşehir Kırıkkale Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Kırıkkale Güven Hastanesi, Ortopedi ve Travmatoloji Kliniği, Ankara 4 Bozok Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Yozgat 1 2 3

AMAÇ: Dinamik hip screw (DHS) ve proksimal femoral çivi-antirotasyonu (PFN-A) implantları ile tedavi edilen hastaların klinik ve fonksiyonel sonuçlarını karşılaştırmayı amaçladık. GEREÇ VE YÖNTEM: Çalışmaya Kırıkkale Üniversitesi Tıp Fakültesi Ortopedi ve Travmatoloji Anabilim Dalı’nda femur intertrokanterik kırığı nedeniyle DHS ve PFN-A kullanılarak ameliyat edilen, en az 12 ay takibi olan 66’sı erkek, 56’sı kadın olan toplam 122 hasta alındı. Hastaların erken postoperatif grafilerinde kırığın redüksiyonu değerlendirilmesi, boyun cisim açısı ve tip apeks mesafesi ölçümleri yapıldı. Postoperatif 1. ay, 3. ay, 6. ay, 12. ay yapılan takiplerinde kalça eklem hareket açıklığı, uyluk-kalça ağrısı, Trendelenburg pozitifliği bakıldı ve takiplerdeki ve kaynama sonrası çekilen grafilerinde redüksiyon, fiksasyon kaybı, boyun cisim açısı ve tip apeks mesafesi ölçümleri yapıldı. Hastalar kaynama sonrası dönemde Kalça Harris Skoru ile değerlendirildi. BULGULAR: Kullanılan implanttan bağımsız olarak implant yetmezliği görülen grupta erken postoperatif ölçülen tip apeks mesafesi ortalaması 27.6 iken implant yetmezliği görülmeyen grupta 21,6 idi ve istatistiksel olarak anlamlı bir fark saptandı. Kullanılan implanttan bağımsız olarak implant yetersizliği görülen grupta erken postoperatif ölçülen boyun cisim açısı ortalaması 123 iken implant yetersizliği görülmeyen grupta 130 idi ve istatistiksel olarak anlamlı bir fark saptandı. İmplant yetersizliği görülen hastaların tümünde erken postoperatif ölçülen boyun cisim açısının 128 derecenin altında olduğu saptandı. İmplant yetersizliği görülmeyen hastaların %94’ünün erken postoperatif ölçülen boyun cisim açısının 128 derecenin üstünde olduğu saptandı. TARTIŞMA: İmplant yetersizliği olan hastaların tümünde erken postoperatif boyun cisim açısının 128° altında olması ve implant yetersizliği görülmeyen hastaların %94’ünde erken postoperatif boyun cisim açısının 128° ve üzerinde olması cerrahi sırasında bu açının anatomik şekilde restore edilmesinin önemini ortaya çıkarmaktadır. İmplant yetersizliği görülen grupta TAD’nin ortalama 27.5 mm ve implant yetersizliği görülmeyen grupta ortalama 21.7 olması, bu sistemlerin implantasyonunda tedavi başarısı açısından tekniğin en az seçilen implant türü kadar önemli olduğunu göstermektedir. Anahtar sözcükler: Dinamik kalça vidası; femur boyun cisim açısı; femur intertrokanterik kırık; proksimal femoral çivi antirotasyon; tip apeks mesafesi. Ulus Travma Acil Cerrahi Derg 2020;26(5):811-817

doi: 10.14744/tjtes.2020.39888

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ORIGIN A L A R T IC L E

Injury mechanisms of ankle fractures with dislocation and analysis of differences on functional outcome Yüksel Uğur Yaradılmış, M.D.,1 Caner Öğük, M.D.,2 Mustafa Caner Okkaoğlu, M.D.,2 Ahmet Ateş, M.D.,2 İsmail Demirkale, M.D.,2 Murat Altay, M.D.2 1

Department of Orthopaedics and Traumatology, Çankırı State Hospital, Çankırı-Turkey

Department of Orthopaedics and Traumatology, University of Health Sciences, Keçiören Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: In the existing classifications, no importance is given to dislocations accompanying ankle fractures. The present study aims to investigate differences in injury mechanisms of ankle fractures with concomitant dislocation injury in respect of functional outcomes and complications. METHODS: A retrospective evaluation was carried out of 285 patients who underwent surgery in our clinic for an ankle fracture between January 2012 and December 2018. A comparison was made of functional scores and complications between the patients with ankle fracture with dislocation (AF-D group) and patients with ankle fracture without dislocation (AF-WD). The correlation of dislocation with current classifications (Lauge-Hansen and Danis-Weber) and the effects on functional outcomes were also evaluated. In addition to functional scores, a record was also made for each patient of infection during follow-up, soft-tissue defect, malalignment, non-union, arthrosis and Reflex Sympathetic Dystrophy Syndrome (RSD). RESULTS: The mean age of the patients was 44.7±12.04 years (range, 18-72 years) and the mean follow-up period was 3.2 years. Ankle fracture with dislocation was observed in 88 (30.8%). Similar functional results were determined in the AF-WD and AF-D groups with mean AOFAS 84.05±10.5, and 80.33±9.47, respectively (p=0.379), and mean VAS scores of 1±0.5 and 1.23±0.48, respectively (p=0.117). When the AOFAS values of the dislocation function results were evaluated according to the Lauge-Hansen and Danis-Weber subgroups, no significant difference was observed (p=0.562, 0.723). Arthrosis was seen in two of the AF-WD group and seven of the AF-D group (p=0.004). RSD was determined in two of the AF-WD group and in 10 of the AF-D group (p=0.000). From a medico-legal perspective, patients should be informed about arthrosis, and RSD is another significant problem encountered in this patient group. CONCLUSION: Although dislocation accompanying ankle fracture was not seen to worsen functional results, arthrosis and RSD were determined more often in these patients. Keywords: Ankle fracture; AOFAS; arthrosis; complications; dislocation; functional results; unstable fracture.

INTRODUCTION Ankle fractures (AF) constitute approximately 10% of all fractures.[1] The most common mechanism of injury is rotational forces or falls at the same level.[2] While stable fractures can be treated conservatively, unstable fractures require surgical treatment.[3] Unstable ankle fractures include lateral malleolar fractures with talar displacement, >3 mm displacement

in the lateral malleolus, bimalleolar fractures and trimalleolar fractures. Although good functional results are obtained after surgical treatment, comorbidities (diabetes mellitus) and age (osteoporosis) are at the forefront of risk factors for poor functional results.[4–6] In patients with ankle fracture with dislocation, bigger soft-tissue damage, cartilage damage or talus lesions are an-

Cite this article as: Yaradılmış YU, Öğük C, Okkaoğlu MC, Ateş A, Demirkale İ, Altay M. Injury mechanisms of ankle fractures with dislocation and analysis of differences on functional outcome. Ulus Travma Acil Cerrahi Derg 2020;26:818-825. Address for correspondence: Yüksel Uğur Yaradılmış, M.D. Çankırı Devlet Hastanesi, Ortopedi ve Travmatoloji Kliniği, Çankırı, Turkey Tel: +90 376 - 213 27 27 E-mail: ugur_yaradilmis@outlook.com Ulus Travma Acil Cerrahi Derg 2020;26(5):818-825 DOI: 10.14744/tjtes.2020.57034 Submitted: 20.06.2019 Accepted: 19.01.2020 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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ticipated and poorer functional results can be expected associated with these lesions. Just as soft-tissue trauma may cause infection or wound site problems, cartilage and talus lesions can be a reason for early post-traumatic arthrosis in the long-term. Cartilage tissues, soft-tissue and a robust ligament structure, which is important in ankle stability, can be best evaluated with magnetic resonance imaging (MRI), but the direct effects on functional results are not known. While some studies have reported that ankle fracture with dislocation in SER4 (supination-external rotation) and PER4 (pronation-external rotation) injuries could be a factor for poor functional results, there has been no evaluation of arthrosis.[7–9] The Lauge-Hansen and Danis-Weber classifications are often used in ankle fractures. In the Lauge-Hansen classification, fractures are classified according to the injury mechanism and the position of the foot at the time of the injury (supination-pronation) and the forces affecting the foot at that time (abduction, adduction, eversion).[10] In the Danis-Weber classification, fractures are classified according to the level of the fracture in the fibula.[11] Dislocations accompanying the fractures are not mentioned in either classification. To our knowledge, there is no information in the literature about the orientation of the dislocation deformity, frequency, relationship with fractures or correlations with existing classifications. The present study aims to investigate differences in injury mechanisms of ankle fractures with concomitant dislocation injury in respect of functional outcomes and complications. This study also aimed to investigate differences in respect to the correlation of functional outcomes of ankle fractures with dislocations with current classifications.

MATERIALS AND METHODS A retrospective evaluation was made of 322 patients who underwent surgery in our clinic for an ankle fracture between January 2012 and December 2018. A total of 37 patients were excluded from this study because of multi-trauma (n=2), open fracture (n=3), exitus (n=2), the anatomic reduction could not be achieved (n=10) and data could not be obtained (n=20). Thus, the evaluation was carried out on a total of 285 patients who were aged 18-72 years, did not have a pilon fracture and had at least a 1-year follow-up period. Age, gender, affected side and accompanying dislocations were recorded. Surgery performed according to the following indications: Any talar displacement, displaced isolated medial or lateral fracture, displaced bimalleolar fracture posterior malleolus fracture higher than >%25 or >2 mm step-off. A fracture-dislocation was diagnosed when radiographs demonstrated no apposition of the tibia and talus on either the anteroposterior or lateral view. In patients with ankle fractures with dislocation, the relationship of the orientation of the dislocation with the fracture was noted. The Lauge-Hansen and Danis-Weber classifications were applied Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

and the relationships with the dislocations were determined. The patients were grouped as ankle fracture with dislocation (AF-D) and ankle fracture without dislocation (AF-WD), and the functional scores and complications were compared between these groups. The correlation between the classification systems (Lauge-Hansen and Danis-Weber) and the functional results was evaluated. In addition to the functional results, a record was made for all patients in both the AF-D and AFWD groups of infection during follow-up, soft-tissue defect, malalignment, non-union, arthrosis and Reflex Sympathetic Dystrophy Syndrome (RSD).

Preoperative Evaluation AF-D patients were applied with a reduction in the Emergency Department and were immobilised with a short-leg splint. Daily soft-tissue evaluation for surgery was carried out with the wrinkle test. In the wound site evaluation, the reduction was carefully checked and the short-leg splint application was continued under the supervision of an orthopaedic and traumatology doctor. Surgical planning was done by evaluating ligament injuries on x-ray of the tibiofibular clear space, syndesmosis with tibiofibular coverage, medial gap (>6 mm) and deltoid injury.

Surgical Technique The patient was positioned supine on a radiolucent operating table. Lateral and medial malleolar fractures were determined. First, osteosynthesis was applied with lateral malleolar plate screw (tubular 1/3 or anatomic plate), followed by fixation with medial malleolar cannulated screw (3.5 or 4.5 screw). For patients with a positive modified cotton test in the syndesmosis examination, syndesmosis fixation was applied with a 3.5 screw and plate using three or four cortexes according to the surgeon’s preference. Fractures bigger than 25% of the joint or with posterior malleolar fracture displacement were fixated. The deltoid injury was evaluated with the stress graph after syndesmosis fixation. During the operation, the reduction was evaluated as fibula length and intra-articular step-off <2 mm.

Follow-up For soft-tissue healing, s short-leg splint was applied to patients for two weeks, after which it was removed and joint movements were started. In patients with deltoid ligament injury, the splint was continued for four weeks. Weight-bearing was permitted after six weeks for patients applied with syndesmosis fixation and after four weeks for those where it was not applied. Partial weight-bearing was achieved in all patients at a maximum of six weeks postoperatively and full weight-bearing at eight weeks. Non-union was evaluated as pain in the fracture line at six months postoperatively and non-visualisation of the union in three cortices. Arthrosis was diagnosed with the visualisation of sclerosis and loss of joint 819

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space on the direct radiograph and was classified according to the Takakura Classification system.[12] RDS was diagnosed according to the Vieldman diagnostic criteria.[13]

Ethical Approval Informed consents were taken routinely before surgery in our clinic. All of the study procedures met the ethical standards of the institutional and national research committees and all of the tenets of the 1964 Helsinki declaration. Written informed consent was obtained from all the participants. Approval for this study was granted by the Ethics Committee of Keçiören SUAM Hospital.

Statistical Analysis Data obtained in the study were analyzed statistically using SPSS vn 22 software. Qualitative variables were stated as number (n) and percentage (%) and quantitative variables

as mean, minimum and maximum values. The conformity of the data to normal distribution was assessed using the Kolmogorov-Smirnov test, and normal distribution was not observed. The AF-D and AF-WD groups were compared statistically using the Mann-Whitney U test. Complications in the groups were compared using the Chi-square test. The Kruskal Wallis test was applied to evaluations of more than one group according to the Lauge-Hansen and Danis-Weber classifications. For subgroups of SER, PER, Weber B and C, evaluations were made again with paired ANOVA. A value of p<0.05 was accepted as statistically significant.

RESULTS The total of 285 patients comprised 155 males and 130 females (M/F: 1.2/1) with a mean age of 44.7±12.04 years were included in this study. The mean follow-up period was 3.2 years (range, 1–7 years). The patient data are shown in Table 1.

Table 1. Demographic data of the patients

Ankle fracture without dislocation (AF-WD)

Patients, n (%) Age

Ankle fracture with dislocation (AF-D)

197 (69.2)

88 (30.8)

40.1 (20–68)

54.7 (21–72)

Total n (%)

44.7±12.04

Gender

Male

107

155 (45.6)

Female

130 (54.4)

Side

Right

143 (50.1)

Left

100

142 (49.9)

27.6 (24–38)

28.4 (23–37)

27.8±4.54

Body mass index

Lauge-Hansen, n (%) Supination-external rotation

155

52 (25.1)

Pronation-external rotation

22 (41)

Pronation-adduction

13 (76)

Supination-adduction

1 (5)

0.010

Danis-Weber, n (%) A

155

52 (25.1)

35 (58.3)

AOFAS (final score)

84.05±10.5

80.33±9.47

0.379

Visual Analog Score

1±0.5

1.23±0.48

0.117

Sudeckatrofi, n (%)

2 (1)

10 (11)

0.000

Artrosis, n (%)

2 (1)

7 (8)

0.004

2 (1)

1 (1)

0.680

1 (0.5)

1 (1)

0.580

1 (0.5)

2 (2)

0.112

64.1 (30–70)

72.1 (40–96)

0.260

Infection, n (%) Soft tissue, n (%) Nonunion, n (%) Surgery time (minute/patients)

1 (5) 0.090

AOFAS: American Orthopaedic Foot&Ankle Society.

820

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The fractures were isolated malleolar in 115 patients (113 lateral, 8 medial), bimalleolar in 98, and trimalleolar in 72. According to the Lauge-Hansen classification, the injuries were observed to be 207 SER, 43 PER, 17 PAD and 18 SAD. According to the Danis-Weber classification, the injuries were 60 type C, 207 type B and 18 type A. Of the 285 patients with an ankle fracture, ankle fracture with dislocation was observed in 88 (30.8%). In all the patients with dislocation, the dislocation was observed in the

(a)

(b)

coronal plane. The lateral dislocation was observed in SAD injury in one patient, and medial dislocation in 87. No isolated sagittal dislocation was observed. Of the patients with dislocation in the coronal plane, dislocation was observed in the sagittal plane in 37. The dislocations in the sagittal plane were observed in the anterior. All of the anterior dislocations were posterior malleolar fractures. Dislocations were observed in 22 PER, 13 PAD, 52 SER and one SAD injuries. Examples of ankle fractures with dislocation with the classification subtypes are shown in Figures 1, 2, 3 and 4.

(c)

Figure 1. Ankle fracture with dislocation for Weber A or SAD: (a) preoperative grafy, (b) preoperative graphy after reduction, (c) postoperative grafy on the 6th month.

(a)

(b)

Figure 2. Ankle fracture with dislocation for Weber B or SER: (a) preoperative grafy, (b) postoperative grafy on the 6th month.

(a)

(b)

(c)

Figure 3. Ankle fracture with dislocation for Weber C or PER: (a) preoperative grafy, (b) preoperative grafy after reduction, (c) postoperative grafy on the 6th month.

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(a)

(b)

(c)

Figure 4. Ankle fracture with dislocation for Weber C or PAD: (a) preoperative grafy, (b) preoperative grafy after reduction, (c) postoperative grafy on the 6th month.

The American Orthopedic Foot Ankle Society (AOFAS) values of the AF-WD and AF-D groups were determined as mean 84.05±10.5, and 80.33±9.47, respectively (p=0.379), and the mean Visual Analog Scale (VAS) scores were 1±0.5 and 1.23±0.48, respectively (p=0.117). No difference was determined between the dislocation functional results in the AOFAS values and the Lauge-Hansen and Danis-Weber subgroups (p=0.562, p=0.723). The effects on the results of the frequently seen subgroups of dislocation (SER, PER, Weber, B and C) were evaluated separately and similar results were observed (Table 2). When the 28 patients with AOFAS <70 were examined, 10 patients were in the AF-D group and 18 in the AF-WD group, and no correlation was determined between dislocation and low AOFAS (p=0.728). A significant correlation was determined between AOFAS <70 and age (56.7±10.14 years) and diabetes (n=10, 35%). Complications were examined of soft-tissue defect, infection, non-union, arthrosis and RSD. Arthrosis was determined in

two (1%) of the AF-WD group and seven (8%) of the AF-D group (p=0.004). The patients with arthrosis were classified as Stage 1 and Stage 2 according to the Takakura classification system. RSD was determined in two (1%) of the AF-WD group and in 10 (11%) of the AF-D group (p=0.000). Superficial infection developed in two (1%) patients with AF-WD and one (1%) AF-D (p=0.680). All these infections recovered with oral antibiotics with no requirement for debridement and implant removal. The soft-tissue defect was seen in one (0.5%) patient in the AF-WD group and one (1%) patient in the AFWD group (p=0.580), which were treated with debridement and dressing with no requirement for graft or flap (Table 1).

DISCUSSION Although successful results are obtained at a high rate in the surgical treatment of unstable ankle fractures, there is still a patient group with low functional results. In a prospective follow-up study of 230 ankle fractures, Egol et al.[14] reported high AOFAS values in 90% of the patients, and that in the 10% with low AOFAS values, factors of age >40 years, female gender, ASA score ≥2 and diabetes were found to affect poor

Table 2. Comparison of the final AOFAS

Ankle fracture without dislocation (AF-WD)

Ankle fracture with dislocation (AF-D)

Total n (%)

Lauge-Hansen 0.562

Supination-external rotation

83.61±11.2

80.12±10.2

0.881

Pronation-external rotation

85.25±6.92

80.8±8.45

0.829

Pronation-adduction

84±6.92

84±3.46

1.00

Supination-adduction

84.72±9.82

0.000

Danis-Weber 0.723 A

84.72±9.82

83.61±11.2

80.72±10.2

0.789

0.000

84.22±7.17

80.84±7.82

0.948

AOFAS

<70

>70

18 (9%) 181

10 (11%)

0.723

AOFAS: American Orthopaedic Foot&Ankle Society.

822

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Yaradılmış et al. Injury mechanisms of ankle fractures with dislocation and analysis of differences on functional outcome

functional results. Özkan et al.[15] stated that good results in ankle fractures were obtained with anatomic restoration, provision of fibula length and functional syndesmosis. In another study that examined poor results in trimalleolar fractures, advanced age, high ASA score, high BMI, and fractures with dislocation were observed to be factors for poor functional results.[16] Dislocation formed in ankle fractures suggests that the severity of the trauma continued and together with the dislocation, soft tissues are damaged more and there is an increased risk of cartilage injury. There are very few studies in the literature that have examined concomitant injuries in ankle fracture with dislocation. In the current study of patients with an ankle fracture, the injuries, functional results and complications were examined in patients with ankle fractures with dislocation. The most significant finding of the study was that dislocation accompanying ankle fracture did not affect the functional results. However, arthrosis and RSD were observed more in patients with ankle fractures with dislocation. In this study, first, an examination was conducted on the relationship between the orientation of AFD injuries and the current classifications. The dislocation was determined in 30.8% of the ankle fractures in this study. In all the AFD patients, the dislocation was observed in the coronal plane (98% medial plane) and dislocation was observed in the sagittal plane (97% anterior) in 37 (42%) patients. While no isolated sagittal dislocation was observed, 34 (93%) of the sagittal dislocations were posterior malleolar fracture. Although this subject has not been discussed in the literature, dislocations were usually observed to be medial, except in one SAD injury with lateral dislocation in the coronal plane. With the exception of this one patient, sagittal dislocations were observed to be anterior and 93% of the anterior dislocations were posterior malleolar fractures. Ankle fractures are known to be most often SER injuries (55-60%), followed by PER (20%), and then, PAD and SAD injuries at lower rates.[17] The relationship of the dislocation with which injuries is not known. Tantigate et al.[18] examined the data of 118 patients and accompanying dislocation was observed in 28%. The correlation between dislocation and Lauge-Hansen and Danis-Weber types has not been investigated in the literature. In the present study, according to the Lauge-Hansen (dislocations determined in SER 25%, PER 41%, PAD 76%, SAD 5%) and the Danis-Weber (C 58%, B 25%, A 5%) classifications, dislocations were observed more in Weber C and Lauge-Hansen PAD or PER subgroups (p=0.90, p=0.010, respectively). This statistical significance can be explained by a large number of patients, that dislocation was seen in SAD injury and there was a high number of cases with dislocation in PAD injury. In the study by Tangigate et al. about 118 ankle fractures with dislocation, it was reported that dislocations were observed Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

statistically more in elderly, female and diabetic patients. When the AOFAS scores were evaluated of 62 patients (18 with dislocation) with more than one year of follow-up, it was reported that with the exception of the pain score, no difference was observed in the functional scores. In the present study, similar functional results were obtained in the 197 AF-WD patients and the 88 AF-D patients with mean AOFAS scores of 84.05±10.5 and 80.33±9.47, respectively (p=0.379). In the VAS evaluation, similar pain values were observed; AF-D group 1±0.5 and AF-WD group 1.23±0.48 (p=0.117). When the 28 (10%) patients with AOFAS <70 were examined, 9% of the AF-WD group had this value and 11% of the AF-D group (p=0.723). While no relationship was determined between patients with dislocation and patients with low AOFAS score, a significant difference was determined in respect of age and diabetes in patients with low AOFAS score. In the present study, patients with open fractures were not included, and there was no requirement for external fixator in any of the patients. Follow-up was applied with daily dressings and checking of the reduction, and when the wrinkle test was positive, open reduction and internal fixation were applied. In addition to arthrosis and RDS as frequent complications, non-union, malunion, soft-tissue problems and wound site infections may also be seen. Patients most at risk of complications are obese, osteoporotic and diabetic patients.[19] Post-traumatic arthrosis can be observed in ankle fractures at not insubstantial rates, such as 14%.[19] When a good anatomic relationship cannot be established between the distal tibia and fibula, the tibiotalar joint biomechanics are impaired and post-traumatic arthrosis may develop.[20] In a study of 57183 patients by SooHoo et al.,[21] the poor union of fractures, talocrural instability and the severity of the fracture (trimalleolar fracture, open fracture) were observed as risk factors for post-traumatic arthrosis. However, in the same study, the need for fusion surgery because of arthrosis was seen to be 1%. In the present study, while arthrosis was seen in 3.2% of patients, it was observed at 8% in the dislocation group. The patients observed with arthrosis did not wish to have fusion surgery, which was thought to be because the arthrosis was at an early stage (Takakura Stage 1, 2). There are high rates (23%) of plate irritation findings in ankle fracture and implant removal may be required.[22] Despite this high rate of plate irritation complaints, infection and wound site problems are seen at low rates.[21] However, in the current AFD patients with high soft-tissue damage, no increase was observed in the rates of soft-tissue problems and infection. In literature, it has been reported that infection and soft-tissue problems can be observed at the rate of 1%. Non-union was observed in four patients (1.4%). In two of them, PRP was applied in the 6th month and union was determined in the 9th month. In 1 diabetic patient, revision surgery was applied in the second month because of implant failure, 823

Yaradılmış et al. Injury mechanisms of ankle fractures with dislocation and analysis of differences on functional outcome

and the union was determined in the 7th month. Revision surgery with autograft and plate osteosynthesis was applied to one patient in the 12th month. Reflex Sympathetic Dystrophy Syndrome (RSD) is often seen following an extremely painful injury. In the present study, RSD was determined in 11% of the patients with dislocation, which was a statistically significantly higher rate than in the patients without dislocation (p=0.000). It should be kept in mind for AFD patients that in recent years there has been an increasing trend for the use of Vitamin C to prevent RSD[23] and this could perhaps be recommended routinely to these patients postoperatively. In this study, evaluating the mechanism of injury of ankle fractures with dislocation and determining the relationships with current classifications, the results are strengthened by the number of patients included. A limitation of this study can be said to be the retrospective design. Evaluation of the bone injuries with CT could have provided a better evaluation of the bony structures. In addition, ligament injuries were not evaluated with MRI but with preoperative direct radiographs and physical examination findings. MRI evaluations of the dislocations, together with ligament injuries, could have increased the value of this study. However, the investigation of the relationship between dislocations and MRI findings has arisen as a subject for further studies.

Conclusion Although dislocation accompanying ankle fracture was not seen to worsen functional results in the mid-term, arthrosis and RSD were determined more often in these patients. From a medico-legal perspective, patients should be informed about arthrosis and RSD, and the necessary precautions should be taken to prevent RSD in cases with ankle fractures with dislocation. Ethics Committee Approval: Approved by the local ethics committee. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: Y.U.Y; Design: Y.U.Y., M.C.O.; Supervision: Y.U.Y., M.C.O.; Fundings: Y.U.Y., C.Ö.; Materials: Y.U.Y., C.Ö.; Data: Y.U.Y., C.Ö.; Analysis: Y.U.Y., İ.D.; Literature search: Y.U.Y., A.A.; Writing: Y.U.Y., A.A.; Critical revision: Y.U.Y., M.A. Conflict of Interest: None declared. Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Schepers T, De Vries MR, Van Lieshout EM, Van der Elst M. The timing of ankle fracture surgery and the effect on infectious complications; a case series and systematic review of the literature. Int Orthop 2013;37:489−94.

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2. Thur CK, Edgren G, Jansson KÅ, Wretenberg P. Epidemiology of adult ankle fractures in Sweden between 1987 and 2004: a population-based study of 91,410 Swedish inpatients. Acta Orthop 2012;83:276−81. 3. Sanders D. Fractures of the ankle and tibial plafond. In: Lieberman JR, editor. AAOS comprehensive orthopaedic reviev 5th ed. New York: American Academy of Orthopaedic Surgeons; 2009.p.659−76. 4. Nilsson GM, Jonsson K, Ekdahl CS, Eneroth M. Unsatisfactory outcome following surgical intervention of ankle fractures. Foot Ankle Surg 2005;11:11–6. 5. Ribeiro de Ávila V, Bento T, Gomes W, Leitão J, Fortuna de Sousa N. Functional Outcomes and Quality of Life After Ankle Fracture Surgically Treated: A Systematic Review. J Sport Rehabil 2018;27:274−83. 6. Dean DM, Ho BS, Lin A, Fuchs D, Ochenjele G, Merk B, et al. Predictors of Patient-Reported Function and Pain Outcomes in Operative Ankle Fractures. Foot Ankle Int 2017;38:496−501. 7. Sculco PK, Lazaro LE, Little MM, Berkes MB, Warner SJ, Helfet DL, et al. Dislocation is a risk factor for poor outcome after supination external rotation type ankle fractures. Arch Orthop Trauma Surg 2016;136:9−15. 8. Warner SJ, Schottel PC, Hinds RM, Helfet DL, Lorich DG. Fracture-Dislocations Demonstrate Poorer Postoperative Functional Outcomes Among Pronation External Rotation IV Ankle Fractures. Foot Ankle Int 2015;36:641−7. 9. Hak DJ, Egol KA, Gardner MJ, Haskell A. The “not so simple” ankle fracture: avoiding problems and pitfalls to improve patient outcomes. Instr Course Lect 2011;60:73−88. 10. Lauge-Hansen N. Fractures of the ankle. II. Combined experimental-surgical and experimental-roentgenologic investigations. Arch Surg 1950;60:957−85. 11. Weber BG. Die Verletzungen des oberen Sprunggelenkes, 2nd edition. Berne, Switzerland: Verlag Hans Huber;1972. 12. Takakura Y, Tanaka Y, Kumai T, Tamai S. Low tibial osteotomy for osteoarthritis of the ankle. Results of a new operation in 18 patients. J Bone Joint Surg Br 1995;77:50−4. 13. Veldman PHJM, Reynen JAM, Arnzt JE, Goris RJA. Sign and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet 1993;34:1012−6. 14. Egol KA, Tejwani NC, Walsh MG, Capla EL, Koval KJ. Predictors of short-term functional outcome following ankle fracture surgery. J Bone Joint Surg Am 2006;88:974−9. 15. Özkan Y, Öztürk A, Özdemir R, Atıcı T, Özbölük S. The results of surgical management of ankle fractures. Ulus Travma Acil Cerrahi Derg 2005;11:329−35. 16. Testa G, Ganci M, Amico M, Papotto G, Giardina SMC, Sessa G, et al. Negative prognostic factors in surgical treatment for trimalleolar fractures. Eur J Orthop Surg Traumatol 2019;29:1325−30. 17. Jensen SL, Andresen BK, Mencke S, Nielsen PT. Epidemiology of ankle fractures. A prospective population-based study of 212 cases in Aalborg, Denmark. Acta Orthop Scand 1998;69:48−50. 18. Tantigate D, Vosseller JT, Greisberg J, Ascherman B, Kirschenbaum J, Freibott C, et al. Functional outcomes after fracture-dislocation of the ankles. Foot & Ankle Orthopaedics 2017;2:247. 19. Irgıt K, Gökçen HB. Ayak bileği kırıkları sonrası görülen komplikasyonlar. TOTBİD Dergisi 2016;15:214−21. 20. Ramsey PL, Hamilton W. Changes in tibiotalar area of contact caused by lateral talar shift. J Bone Joint Surg Am 1976;58:356−7. 21. SooHoo NF, Krenek L, Eagan MJ, Gurbani B, Ko CY, Zingmond DS. Complication rates following open reduction and internal fixation of ankle fractures. J Bone Joint Surg Am 2009;91:1042−9.

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Yaradılmış et al. Injury mechanisms of ankle fractures with dislocation and analysis of differences on functional outcome 22. Brown OL, Dirschl DR, Obremskey WT. Incidence of hardware-related pain and its effect on functional outcomes after open reduction and internal fixation of ankle fractures. J Orthop Trauma 2001;15:271–4.

23. Zollinger PE, Tuinebreijer WE, Kreis RW, Breederveld RS. Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomised trial. Lancet 1999;354:2025−8.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Ayak bileği kırıklarına eşlik eden çıkıkların yaralanma mekanizmaları ve fonksiyonel sonuçlarındaki farklılıkların incelenmesi Dr. Yüksel Uğur Yaradılmış,1 Dr. Caner Öğük,2 Dr. Mustafa Caner Okkaoğlu,2 Dr. Ahmet Ateş,2 Dr. İsmail Demirkale,2 Dr. Murat Altay2 1 2

Çankırı Devlet Hastanesi, Ortopedi ve Travmatoloji Kliniği, Çankırı Keçiören Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, Ankara

AMAÇ: Mevcut sınıflandırmalarda ve literatürde çıkığın eşlik ettiği ayak bileği kırıklarına ayrıca önem verilmemiştir. Çalışmamızda, ayak bileği kırıklarına eşlik eden çıkıklardaki yaralanma mekanizması, fonksiyonel sonuçlar ve komplikasyonlar açısından farklılıkları belirlemeyi amaçladık. GEREÇ VE YÖNTEM: Kliniğimizde Ocak 2012–Aralık 2018 tarihleri arasında, ayak bileği kırığı nedeniyle ameliyat edilen 285 hasta geriye dönük olarak incelendi. Kırıklara eşik eden çıkıklar kaydedildi. Çıkığın eşlik ettiği ayak bileği kırıkları (AF-D) ile çıkığın eşlik etmediği ayak bileği kırıkları (AFWD) arasında fonksiyonel skorlar ve komplikasyonlar karşılaştırıldı. Mevcut sınıflamalar (Lauge-Hansen ve Danis-Weber sınıflamaları) ile çıkığın birlikteliği ve fonksiyonel sonuçlara etkisi de değerlendirildi. Hastalar fonksiyonel değerler haricinde takiplerdeki enfeksiyon, yumuşak doku defekti, dizilim bozukluğu, kaynamama, artroz ve Refleks Sempatik Distrofi Sendromu (RSD) açısından da incelendi. BULGULAR: Hastaların yaş ortalaması 44.7±12.04 (18–72), takip süresi 3.2 yıl idi. Hastaların 88’inde (%30.8) ayak bileği kırıkları çıkıkla birlikte gözlendi. Çıkık hastalarının hepsinde koronal planda çıkık gözlenirken, 37’sinde sagital planda da anteriora çıkık gözlendi. AF-WD ve AF-D gruplarında sırasıyla AOFAS 84.05±10.5, 80.33±9.47 (p=0.379), VAS değerlendirmesi ise 1±0.5, 1.23±0.48 (p=0.117) olmak üzere benzer fonksiyonel sonuçlar gözlendi. AOFAS değerleri Lauge-Hangene ve Danis-Webere göre değerlendirildiğinde altgruplar arası fark gözlenmedi (p=0.562, 0.723). AF-WD grubunda 2, AF-D grubunda 7 artroz gözlendi (p=0.004). AF-WD grubunda 2, AF-D grubunda 10 hastada RSD gözlendi (p=0.000). TARTIŞMA: Ayak bileği kırığına eşlik eden çıkıkların, fonksiyonel skorlarda kötüleşmeye neden olmadığı gözlenmekle birlikte artroz ve RSD bu hastalarda daha sık bulundu. Mediko legal açıdan artroz hakkında hastaların bilgilendirilmesi gerekmekte ve RSD de bu hastalarda önemli bir sorun olarak karşımıza çıkmaktadır. Anahtar sözcükler: AOFAS; artroz; ayak bileği kırıkları; çıkık; fonksiyonel sonuçlar; instabil kırık; komplikasyon. Ulus Travma Acil Cerrahi Derg 2020;26(5):818-825

doi: 10.14744/tjtes.2020.57034

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CA S E R EP O RT

Tension gastrothorax secondary to trauma in the emergency room: A case report Abdullah Algın, M.D.,1 Mehmet Özgür Erdoğan, M.D.,2 Mehmet Sarıaydın, M.D.,3 Korkut Bozan, M.D.,4 Serdar Özdemir, M.D.,1 İbrahim İnan, M.D.5 1

Department of Emergency, University of Health Sciences, Ümraniye Training and Research Hospital, İstanbul-Turkey

Department of Emergency Medicine, Bahçeşehir University Faculty of Medicine, İstanbul-Turkey

Department of Internal Medicine, Adıyaman University Faculty of Medicine, Adıyaman-Turkey

Department of Emergency Medicine, Göztepe Medicalpark Hospital, İstanbul-Turkey

Department of Radiology, Biruni University Faculty of Medicine, İstanbul-Turkey

ABSTRACT In tension gastrothorax, the abdominal contents are displaced into the thorax, leading to a mediastinal shift that arises from the pressure placed on the intrathoracic region. This condition is often due to a congenital or acquired (secondary to surgery) diaphragmatic defect and is rarely seen secondary to trauma. A 40-year-old man presented to the emergency department after an in-vehicle traffic accident. He had no active complaint other than mild chest pain. On auscultation, breath sounds were audible in the left lung base and bowel sounds were heard. Computed tomography of the thorax revealed left-sided diaphragmatic hernia. The jugular vein was distended, and the patient became desaturated in the emergency room. Nasogastric decompression was performed, and the saturation improved. The patient underwent open surgery. Traumatic tension gastrothorax should be considered in the differential diagnosis of acute-onset severe respiratory failure. It can be diagnosed by rapid clinical and radiological evaluation. Keywords: Case report; diaphragmatic rupture; tension gastrothorax.

INTRODUCTION Trauma-related deaths are common worldwide and the fifth most frequent cause of death in the United States.[1] Among these fatal cases, traumas of the thorax rank third.[2] A significant number of trauma-related deaths occur in the pre-hospital setting, and most patients who reach the hospital die in the emergency department.[3] A rare cause of thoracic trauma–related mortality is tension gastrothorax, defined as the herniation of the abdominal organs into the chest cavity from a ruptured diaphragm secondary to trauma.[4] In patients with chest pain secondary to trauma, the preliminary diagnosis is guided primarily by the clinical symptoms

and physical examination findings, which may include Charcot fractures, tension pneumothorax, and solid organ injury. In patients requiring urgent care, in addition to first-line imaging modalities, the procedures needed to achieve presumptive diagnoses depend on the symptoms. Acute gastrothorax is post-traumatic in origin in approximately 15% of all cases of gastrothorax, but it is often overlooked because of its rarity. In trauma patients, it may result from a diaphragmatic defect.[4] In this paper, we discuss a case in which a patient presented with chest pain after trauma to the thorax and developed traumatic gastrothorax. By discussing this rare traumatic complication, including the challenges faced in the emergency setting, our aim is to contribute to

Cite this article as: Algın A, Erdoğan MÖ, Sarıaydın M, Bozan K, Özdemir S, İnan İ. Tension gastrothorax secondary to trauma in the emergency room: A case report. Ulus Travma Acil Cerrahi Derg 2020;26:826-828. Address for correspondence: Abdullah Algın, M.D. Sağlık Bilimleri Üniversitesi, Ümraniye Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İstanbul, Turkey Tel: +90 216 - 632 18 18 E-mail: dralgin@hotmail.com Ulus Travma Acil Cerrahi Derg 2020;26(5):826-828 DOI: 10.14744/tjtes.2019.94694 Submitted: 17.04.2019 Accepted: 18.10.2019 Online: 09.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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the management of acute gastrothorax, as the condition may lead to acute hemodynamic impairment.

CASE REPORT A 40-year-old man presented to the outpatient clinic of the emergency service following an in-vehicle traffic accident. While driving, he lost control of the car and crashed into concrete barriers. The front wall of his chest hit the steering wheel upon impact. He complained of mild chest pain on the left side. His Glasgow Coma Scale score was 15. His blood pressure was 100/60 mm/Hg, his pulse was 113/min, his respiratory rate was 27/min, and his finger saturation was 88% on the pulse oximeter. He was mildly anxious. There was no evidence of mild hyperemia on the skin. His medical history included the use of amlodipine as an anti-hypertensive agent and a home nebulizer for chronic obstructive pulmonary disease, secondary to which he had developed finger clubbing. In the systemic examination, breath sounds were audible in the upper lobe, but not in the lower lobe, of the left lung, and bowel sounds were heard with unclear dullness on percussion. Physical examination revealed crepitus on the right side of the thorax. The patient’s bed was cordoned off based on suspicion of gastrothorax. His arterial blood gas showed non-compensatory type 1 respiratory failure with normal base deficit levels. He had stable vital signs. Computed tomography (CT) of the thorax revealed a large volume of intra-abdominal air in the left hemithorax and a left-sided diaphragmatic hernia, causing a mediastinal shift. Pneumothorax was present on the right side (Fig. 1). Acute traumatic gastrothorax was considered. A chest tube was placed for the pneumothorax on the right. The patient’s

oxygen level indicated desaturation and his jugular vein was distended 30 min after chest tube insertion. Breath sounds were audible in the right, but not the left, lung. Based on suspicion of gastrothorax and the presence of a minimal shift, nasogastric decompression was performed, which improved his oxygen saturation. An emergency thoracotomy was then undertaken. Two-thirds of the abdomen and bowel segments were observed to have shifted to the thoracic region, secondary to an 11-cm diaphragm rupture. The possibility of solid organ injury and intestinal perforation was investigated. No pathology was detected, and the herniated abdominal organs in the thoracic cavity were reduced to the abdominal cavity. The diaphragm was sutured with non-absorbable material. After two days in the intensive care unit and seven days in an emergency service room, the patient was discharged without any problem. Written consent from the patient and approval from the hospital for the presentation of this case report were obtained.

DISCUSSION In tension gastrothorax, the abdominal contents are displaced into the thorax, leading to a mediastinal shift caused by the pressure placed on the intrathoracic region.[5] Most cases are congenital or develop due to a diaphragmatic defect secondary to surgery. Congenital diaphragmatic hernia (CDH) occurs in one in 2,500–4,000 live births. The majority of cases are diagnosed at birth or shortly thereafter in infants with respiratory distress.[6,7] However, in approximately 10% of patients with CDH, symptoms develop at a later time.[8,9] Gastrothorax secondary to trauma is very rare, and only 0.8–1.6% of blunt abdominal traumas causes diaphragmatic injuries.[10] Diaphragmatic rupture has clinical effects on the circulation and respiration. Displacement of the abdominal organs into the thoracic area results in the displacement of the mediastinum. The clinical signs include hemodynamic impairment secondary to the reduction of venous return to the heart and respiratory symptoms, such as shortness of breath and tachypnea, indicative of tension pneumothorax due to the restriction of pulmonary expansion. In the supine position, the diaphragm provides all of the tidal volumes. Hemidiaphragm losses decrease pulmonary function by 25–50%. This effect explains the development of cyanosis shortly after our patient’s arrival at the emergency department. The absence of breath sounds in the basal left lung and the presence of audible bowel sounds led us to consider the diagnosis of traumatic tension gastrothorax.

Figure 1. Transverse thorax CT section in the lung window demonstrates pneumothorax (arrowheads) and increased density in the right lung due to pulmonary parenchymal contusion. Subcutaneous emphysema under the skin and between muscular structures in the right thoracic wall is demonstrated (arrows). The structure in the left hemithorax containing air-fluid levels (asterisks) is herniated stomach and it causes minimal mediastinal shift to the right.

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Grimes[11] defined three phases characterizing the clinical severity of diaphragmatic rupture: acute, latent, and obstructive. The acute phase refers to polytrauma, specifically multiple intra-abdominal and chest traumas. The latent phase is characterized by the diaphragmatic rupture in the absence of hernia. In the obstructive phase, the diaphragmatic hernia causes 827

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obstruction and the patient develops distension and strangulation. Our patient initially presented with acute-phase diaphragmatic rupture, and signs indicating gastrothorax became evident somewhat later. Gastrothorax can be diagnosed by thoracic CT in a patient with an elevated hemidiaphragm seen on an X-ray. The patient, in this case, was diagnosed based on the CT findings. Tension gastrothorax is treated surgically by the primary repair of the diaphragmatic rupture. In dyspneic patients, nasogastric tube insertion may be the first choice for the immediate decompression of tension gastrothorax. An awareness of the risk factors and clinical presentation of tension gastrothorax can help to quickly and successfully manage this life-threatening clinical situation. In conclusion, although traumatic tension gastrothorax is rare, it should be considered in the differential diagnosis of acute-onset severe respiratory failure. Traumatic tension gastrothorax can be diagnosed by rapid clinical and radiological evaluation. Abdominal decompression will correct the associated hemodynamic impairment. Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed. Authorship Contributions: Concept: A.A.; Design: A.A.; Supervision: M.Ö.E.; Fundings: K.B.; Materials: K.B.; Data: K.B.; Analysis: İ.İ.; Literature search: A.A., M.S.; Writing: A.A.; Critical revision: S.Ö., M.S. Conflict of Interest: None declared.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Centers for Disease Control and Prevention. Web-based Injury Statistics Query and Reporting System (WISQARS). 2010. http://www.cdc.gov/ injury/wisqars/index.html. Accessed April 10, 2010. 2. Regel G, Lobenhoffer P, Grotz M, Pape HC, Lehmann U, Tscherne H. Treatment results of patients with multiple trauma: an analysis of 3406 cases treated between 1972 and 1991 at a German Level I Trauma Center. J Trauma 1995;38:70−8. 3. Davis JH, Pruitt JH, Pruitt Jr BA. History In: Mattox KL, Feliciano DV, Moore EE, editors. Trauma. 4th edition. New York: McGraw Hill; 2000.p.3−19. 4. Nishijima D, Zehbtachi S, Austin RB. Acute posttraumatic tension gastrothorax mimicking acute tension pneumothorax. Am J Emerg Med 2007;25:734.e5−6. 5. Ordog GJ, Wasserberger J, Balasubramaniam S. Tension gastrothorax complicating post-traumatic rupture of the diaphragm. Am J Emerg Med 1984;2:219−21. 6. Fuller G, Cacala S, Oosthuizen G. Tension gastrothorax-colothorax secondary to traumatic diaphragmatic hernia. Pediatr Emerg Care 2010;26:299−301. 7. Langham MR Jr, Kays DW, Ledbetter DJ, Frentzen B, Sanford LL, Richards DS. Congenital diaphragmatic hernia. Epidemiology and outcome. Clin Perinatol 1996;23:671−88. 8. Nitecki S, Bar-Maor JA. Late presentation of Bochdalek hernia: our experience and review of the literature. Isr J Med Sci 1992;28:711−4. 9. Coren ME, Rosenthal M, Bush A. Congenital diaphragmatic hernia misdiagnosed as tension pneumothorax. Pediatr Pulmonol 1997;24:119−21. 10. Ala-Kulju K, Verkkala K, Ketonen P, Harjola PT. Traumatic rupture of the right hemidiaphragm. Scand J Thorac Cardiovasc Surg 1986;20:109−14. 11. Grimes OF. Traumatic injuries of the diaphragm. Diaphragmatic hernia. Am J Surg 1974;128:175−81.

OLGU SUNUMU - ÖZET

Acil serviste travmaya sekonder tansiyon gastrotoraks: Bir olgu sunumu Dr. Abdullah Algın,1 Dr. Mehmet Özgür Erdoğan,2 Dr. Mehmet Sarıaydın,3 Dr. Korkut Bozan,4 Dr. Serdar Özdemir,1 Dr. İbrahim İnan5 Sağlık Bilimleri Üniversitesi, Ümraniye Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İstanbul Bahçeşehir Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, İstanbul Adıyaman Üniversitesi Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, Adıyaman 4 Göztepe Medikalpark Hastanesi, Acil Tıp Kliniği, İstanbul 5 Biruni Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, İstanbul 1 2 3

Tansiyon gastrotoraks, abdominal içeriğin toraksa yer değiştirmesi ve intratorasik bölgeye uygulanan baskı sonucu mediastinal kayma ile seyreden klinik bir durumdur. Genellikle doğuştan veya edinilmiş (cerrahiye sekonder) diyafragma defekti nedeniyle olup, nadiren travmaya sekonder görülür. Kırk yaşında erkek hasta, araç içi trafik kazası sonrası acil servise başvurdu. Hafif göğüs ağrısı dışında aktif bir şikayeti yoktu. Oskültasyonda sol akciğer tabanında solunum sesleri ile birlikte bağırsak sesleri duyuldu. Çekilen bilgisayarlı toraks tomografisinde sol taraflı diyafragma hernisi izlendi. Kısa süre sonra desatürasyon ve juguler venöz dolgunluk gelişen hastaya nazogastrik dekompresyon uygulandı. Ardından açık cerrahi girişim amaçlı ameliyata alındı. Akut başlangıçlı ciddi solunum yetersizliğinin ayırıcı tanısında travmatik tansiyon gastrotoraks düşünülmelidir. Hızlı klinik ve radyolojik değerlendirme ile tanı konulabilir. Anahtar sözcükler: Diyafragma rüptürü; olgu sunumu; tansiyon gastrotoraks. Ulus Travma Acil Cerrahi Derg 2020;26(5):826-828

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Hemorrhagic adrenal myelolipoma after trauma to left adrenal gland: A case report Tse-Hao Chen, M.D.,1

Pei Fang Lai, M.D.,2

Yung-Hsiang Hsu, M.D.3

Division of Medical Education, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231-Taiwan

Department of Emergency Medicine, Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970-Taiwan

Department of Pathology, Buddhist Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970-Taiwan

ABSTRACT Myelolipomas are rare benign tumors comprised of mature adipose tissue and hematopoietic elements. Adrenal myelolipomas associated with traumatic adrenal injury are relatively rare and less common on the left due to the limited size and well-protected position of the gland. A 59-year-old female admitted to the emergency department with intermittent left flank pain radiating to the left abdomen after falling from the bed six hours earlier. Her vital signs were stable, and she had tenderness over the left flank area and left abdomen. Her initial hemoglobin level was 12.9 g/dL. Bedside focused assessment with sonography for trauma revealed unclear left kidney margins. Contrast abdominal computed tomography (CT) revealed a space-occupying mass, 11.6×10.4×8.8 cm in dimension, in the left suprarenal region with active bleeding in the lower pole. Angiography did not reveal any active contrast medium extravasation. The CT-guided biopsy, was well performed concomitantly with angiography. Pathological assessment of the biopsy specimen revealed the presence of mostly adipose tissue with few erythrocytes and leukocytes. She was diagnosed with adrenal myelolipoma and admitted to the urology ward for left adrenalectomy with tumor resection.Traumatic adrenal injury, an unusual presentation of adrenal myelolipoma incidentally found in less than 5% of all abdominal blunt injuries, should be considered in cases of bleeding with trauma to the flank for prompt treatment. Keywords: Adrenal emergency; adrenal myelolipoma; case report; incidentaloma; traumatic adrenal injury.

INTRODUCTION The majority of myelolipomas, rare benign tumors comprised mainly of mature adipose tissue and hematopoietic elements, originate from the adrenal gland, although other sites of involvement include retroperitoneum, thorax, and pelvis.[1,2] Adrenal myelolipoma is an incidentaloma typically discovered during routine radiological studies or autopsy. [2] The overall incidence of adrenal myelolipoma is approximately 0.05%–0.2%.[3,4] While most adrenal incidentalomas are nonfunctioning adenomas, tumor-like pheochromocytomas or aldosterone-producing adenomas were also reported.

[4] Importantly, the incidence of adrenal myelolipomas have increased to 15% of all adrenal incidentalomas with advances in and convenience of computed tomography (CT) and magnetic resonance imaging (MRI).[5,6]

Due to their limited size and well-protected position, traumatic injury to the adrenal glands is relatively rare, with the right side affected more frequently.[7,8] The left adrenal gland is spared because of the surrounding organs, whereas the right adrenal gland, which can be compressed by the liver and the vertebral bodies, is more prone to injury.[9] Typically, patients with traumatic injury to the adrenal gland present with non-

Cite this article as: Chen TH, Lai PF, Hsu YH. Hemorrhagic adrenal myelolipoma after trauma to left adrenal gland: A case report. Ulus Travma Acil Cerrahi Derg 2020;26:829-832. Address for correspondence: Pei Fang Lai, M.D. Department of Emergency Medicine, Buddhist Tzu Chi General Hospital, No. 707, Section 3, Chung-Yang Road, Hualien 970, Taiwan. 970 Hualien, Taiwan Tel: 86638561825 E-mail: lpf2826@tzuchi.com.tw Ulus Travma Acil Cerrahi Derg 2020;26(5):829-832 DOI: 10.14744/tjtes.2019.99457 Submitted: 22.11.2018 Accepted: 06.09.2019 Online: 15.09.2020 Copyright 2020 Turkish Association of Trauma and Emergency Surgery

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Chen et al. Hemorrhagic adrenal myelolipoma after trauma to left adrenal gland

specific symptoms, whereas some patients may present with major trauma and nearby organ damage. We herein report an uncommon case of traumatic hemorrhage of the left adrenal myelolipoma presenting to the emergency department.

CASE REPORT A 59-year-old female presented to the emergency department with intermittent left flank pain radiating to the left abdomen after falling from the bed six hours earlier. She had a ten-year history of hypertension treated with amlodipine (5 mg/day) and had no history of surgery. The patient first went to a local clinic for pain, which was not resolved. Physical examination on admission revealed tenderness over the left flank area and left abdomen. Her blood pressure was 130/92 mmHg with a heart rate of 87 beats per minute. Laboratory test results were as follows: hemoglobin, 12.9 g/dL; hematocrit, 39.2%; blood urea nitrogen, 15 mg/dL; creatinine, 0.6 mg/dL; sodium, 141 mmol/L; and potassium, 3.6 mmol/L. Her platelet count, prothrombin time, and activated partial thromboplastin time were normal. Bedside focused assessment with sonography for trauma revealed unclear left kidney margins. Contrast abdominal CT due to suspicious left kidney rupture revealed a space-occupying mass, 11.6×10.4×8.8 cm in dimensions, in the left suprarenal region with active bleeding in the lower pole. The left kidney was encased almost entirely by dense material collection (Fig. 1). The liver and spleen were unremarkable. Angiography by a radiologist did not reveal active extravasation, and the renal vein was patent (Fig. 2). The CT-guided biopsy was well performed concomitantly with angiography.

Figure 2. Aortogram and renal angiograms were performed by inserted a 5-Fr angiosheath through the left renal artery. Downward displacement of the left kidney without active contrast medium extravasation was found. Patency of left renal veins was also noted.

Figure 3. Microscopically, it consisted mostly of adipose tissue with few erythrocytes and leukocytes compatible with adrenal myelolipoma.

Pathological assessment of the biopsy specimen revealed the presence of mostly adipose tissue with few erythrocytes and leukocytes, and the mass was diagnosed as adrenal myelolipoma (Fig. 3). The patient was admitted and underwent left adrenalectomy with tumor resection under the laparotomy method. The procedure was uneventful, and she recovered without sequelae. Patient’s consent was obtained for this study.

DISCUSSION Figure 1. A mass, 11.6×10.4×8.8 cm in dimensions, in the left suprarenal region. The mass exhibited diffuse soft tissue density composed of macroscopic fat tissue and hematopoietic elements. The dense collection of material in the lower pole of the mass encasing the left kidney was also observed.

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To our knowledge, the current case of hemorrhage from a massive adrenal myelolipoma due to trauma to the left side is a unique presentation illustrating the relationship between traumatic adrenal injury and adrenal myelolipoma. Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Chen et al. Hemorrhagic adrenal myelolipoma after trauma to left adrenal gland

Myelolipoma is a usually small, nonfunctioning benign tumor with nonspecific symptoms, although cases with myelolipomas of up to 35 cm in diameter were reported.[3,6] Most adrenal myelolipomas are unilateral and on the right side.[6,10] The etiology of myelolipoma remains unclear; however, Zorgdrager et al.[10] suggested that previous high-energy trauma might be a factor. Most patients are asymptomatic, and few experience abdominal discomfort or flank pain.[6,11] However, lethal cases with hemorrhagic shock that arises from giant myelolipomas were described.[3,9,12] Traumatic adrenal injury is rare, comprising less than 5% of all traumatic injuries.[7,13] A study reported that the most common mechanism of traumatic adrenal injury was road traffic accidents (66%), followed by falling from height (23.4%), as in the case of the current patient.[14] Bedside focused assessment with sonography for trauma was utilized in the current case. Active bleeding, albeit echogenic, can be observed as a homogeneous or heterogeneous mass.[7,11] Contrast abdominal CT remains the gold standard for myelolipoma diagnosis.[11,15] The most frequent presentation of traumatic adrenal injury is an oval hematoma encasing the adrenal gland.[7,14,16] Intraparenchymal hematomas and bulky adrenal glands with or without extravasation were also reported.[14] In the current case, extravasation observed by contrast CT was accompanied by a decrease in hemoglobin. However, there were no active bleeding sites by angiography. Several potential events might explain the clinical course. First, angiography might not have detected the contrast extravasation due to venous damage. Second, the large, space-occupying hematoma might have twisted after formation, which would hinder the observation of extravasation by angiography; extravasation due to traumatic adrenal injury was not detected by angiography in 76% of the cases.[13] There are three treatment options for adrenal myelolipomas: surgical intervention, adrenal artery embolization, and conservative medical treatment.[7] Surgery should be considered for symptomatic cases and tumors larger than 7 cm.[6,11] Laparoscopic adrenalectomy was conducted increasingly over the years. Giant adrenal myelolipoma with size up to 14 cm was also reported to be suitable for laparoscopy interventions.[17] Because of its encapsulated structure, conversion from laparoscopic adrenalectomy to open method was unusual. Comparing to open adrenalectomy, laparoscopic adrenalectomy was reported to have less blood loss, shorter hospital stays, sooner recovery and less surgical pain.[18] However, this patient had a large left adrenal myelolipoma with bleeding and hematoma encased left kidney. The laparoscopic method was no recommended at that time. Embolization, a safe approach to stop bleeding, was reported to achieve hemostasis and avoid subsequent adrenalectomy. [19] However, most patients with myelolipoma are treated conservatively.[4–6,10,16] Ulus Travma Acil Cerrahi Derg, September 2020, Vol. 26, No. 5

Traumatic adrenal injury is an unusual presentation of adrenal myelolipoma. Although it is incidentally found in less than 5% of all abdominal blunt injuries, adrenal myelolipoma should be considered in patients presenting with bleeding and a history of trauma to the flank to provide the necessary prompt treatment. Informed Consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images. Peer-review: Internally peer-reviewed.

REFERENCES 1. Hakim A, Rozeik C. Adrenal and extra-adrenal myelolipomas - a comparative case report. J Radiol Case Rep 2014;8:1−12. 2. Schaeffer EM, Kavoussi LR. Adrenal myelolipoma. J Urol 2005;173:1760. 3. Kumar S, Jayant K, Prasad S, Agrawal S, Parma KM, Roat R, et al. Rare adrenal gland emergencies: a case series of giant myelolipoma presenting with massive hemorrhage and abscess. Nephrourol Mon 2015;7:e22671. 4. Kerkhofs TM, Roumen RM, Demeyere TB, van der Linden AN, Haak HR. Adrenal tumors with unexpected outcome: a review of the literature. Int J Endocrinol 2015;2015:710514. 5. Shenoy VG, Thota A, Shankar R, Desai MG. Adrenal myelolipoma: Controversies in its management. Indian J Urol 2015;31:94−101. 6. Ramirez M, Misra S. Adrenal myelolipoma: To operate or not? A case report and review of the literature. Int J Surg Case Rep 2014;5:494−6. 7. Aysegul K, Kahraman B, Ozdemir ZM, Görmeli CA, editors. Traumatic adrenal hematoma: clinical and imaging findings. ECR 2016 / C-0193. Austria Center Vienna: European Congress of Radiology; 2016. 8. To’o KJ, Duddalwar VA. Imaging of traumatic adrenal injury. Emerg Radiol 2012;19:499−503. 9. Chernyak V, Patlas MN, Menias CO, Soto JA, Kielar AZ, Rozenblit AM, et al. Traumatic and non-traumatic adrenal emergencies. Emerg Radiol 2015;22:697−704. 10. Zorgdrager M, Pol R, van Hemel B, van Ginkel R. Giant adrenal myelolipoma: when trauma and oncology collide. BMJ Case Rep 2014;2014:bcr2014204023. 11. Daneshmand S, Quek ML. Adrenal myelolipoma: diagnosis and management. Urol J 2006;3:71−4. 12. Fowler AM, Burda JF, Kim SK. Adrenal artery embolization: anatomy, indications, and technical considerations. AJR Am J Roentgenol 2013;201:190−201. 13. Liao CH, Lin KJ, Fu CY, Wang SY, Yang SJ, Ouyang CH. Adrenal gland trauma: is extravasation an absolute indication for intervention?. World J Surg 2015;39:1312−9. 14. Panda A, Kumar A, Gamanagatti S, Bhalla AS, Sharma R, Kumar S, et al. Are traumatic bilateral adrenal injuries associated with higher morbidity and mortality?-A prospective observational study. J Trauma Manag Outcomes 2015;9:6. 15. Mayo-Smith WW, Boland GW, Noto RB, Lee MJ. State-of-the-art adrenal imaging. Radiographics 2001;21:995−1012. 16. Karwacka IM, Obołończyk Ł, Sworczak K. Adrenal hemorrhage: A single center experience and literature review. Adv Clin Exp Med 2018;27:681−7. 17. Maestroni U, Ziglioli F, Dinale F, Ferretti S, Frattini A, Cortellini P. Is laparoscopy contraindicated in giant adrenal masses?. Surg Laparosc Endosc Percutan Tech 2010;20:288−90. 18. Thompson GB, Grant CS, van Heerden JA, Schlinkert RT, Young WF Jr, Farley DR, et al. Laparoscopic versus open posterior adrenalectomy: a

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taneous hemorrhagic adrenal myelolipoma with variant adrenal arteries. J Vasc Interv Radiol 2015;26:1086−8.

OLGU SUNUMU - ÖZET

Sol adrenal bezde travma sonrası hemorajik adrenal miyelolipom: Olgu sunumu Dr. Tse-Hao Chen,1 Dr. Pei Fang Lai,2 Dr. Yung-Hsiang Hsu3 1 2 3

Taipei Tzu Chi Hastanesi, Budist Tzu Chi Tıp Vakfı, Tıp Eğitimi Bölümü, Yeni Taipei 231-Tayvan Budist Tzu Chi Genel Hastanesi, Budist Tzu Chi Tıp Vakfı, Acil Tıp Departmanı, Hualien 970-Tayvan Budist Tzu Chi Genel Hastanesi, Budist Tzu Chi Tıp Vakfı, Patoloji Bölümü, Hualien 970-Tayvan

Miyelolipomlar, matür yağ dokusu ve hematopoetik elementlerden oluşan nadir iyi huylu tümörlerdir. Travmatik adrenal yaralanma ile ilişkili adrenal miyelolipomlar, bezin sınırlı boyutu ve iyi korunan pozisyonu nedeniyle sol tarafta nispeten nadirdir ve daha az yaygındır. Elli dokuz yaşında kadın hasta, altı saat önce yataktan düştükten sonra sol karın bölgesine yayılan aralıklı sol yan ağrısı şikayeti ile acil servise başvurdu. Vital bulguları stabildi ve sol yan bölgede ve sol karın bölgesinde hassasiyeti mevcuttu. Başlangıç hemoglobin düzeyi 12.9 g/dL idi. Travma için ultrason ile yatak başı değerlendirmede sol böbrek sınırları belirsiz olarak saptandı. Kontrastlı abdominal bilgisayarlı tomografide (BT) sol suprarenal bölgede 11.6×10.4×8.8 cm boyutunda yer kaplayıcı bir kitle ile birlikte alt polde aktif kanama saptandı. Anjiyografide herhangi bir aktif kontrast madde ekstravazasyonu saptanmadı. Anjiyografi ile eş zamanlı olarak BT eşliğinde biyopsi başarılı bir şekilde gerçekleştirildi. Biyopsi örneğinin patolojik değerlendirmesi, az sayıda eritrosit ve lökosit içeren çoğunlukla yağ dokusunun varlığını ortaya koymuştur. Hastaya adrenal miyelolipom tanısı konuldu ve tümör rezeksiyonu ile sol adrenalektomi için üroloji servisine yatırıldı. Tüm künt abdominal yaralanmaların %5’inden azında tesadüfen bulunan adrenal miyelolipomun olağandışı bir sunumu olan travmatik adrenal yaralanma, karın travmasına bağlı kanama olgularında acil tedavi için dikkate alınmalıdır. Anahtar sözcükler: Adrenal acil; adrenal myelolipom; insidentaloma; olgu sunumu; travmatik adrenal yaralanma. Ulus Travma Acil Cerrahi Derg 2020;26(5):829-832

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