TJTES 2019-3 by KAREPUBLISHING

ISSN 1306 - 696X

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

Volume 25 | Number 3 | May 2019

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TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi Editor-in-Chief Recep Güloğlu Editors Kaya Sarıbeyoğlu M. Mahir Özmen Hakan Yanar Former Editors Ömer Türel, Cemalettin Ertekin, Korhan Taviloğlu 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, Halil Ateş Ortopedics and Traumatology Mahmut Nedim Doral, Mehmet Can Ünlü Plastic and Reconstructive Surgery Ufuk Emekli, Figen Özgür Pediatric Surgery Aydın Yagmurlu, Ebru Yeşildağ Thoracic Surgery Alper Toker, Akif Turna Urology Ali Atan, Öner Şanlı Vascular Surgery Cüneyt Köksoy, Mehmet Kurtoğlu

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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)

Kaya Sarıbeyoğlu M. Mahir Özmen Hakan Yanar Ali Fuat Kaan Gök Osman Şimşek Orhan Alimoğlu Mehmet Eryılmaz

CORRESPONDENCE İLETİŞİM Ulusal Travma ve Acil Cerrahi Derneği Şehremini Mah., Köprülü Mehmet Paşa Sok. Dadaşoğlu Apt., No: 25/1, 34104 Şehremini, İstanbul, Turkey

Tel: +90 212 - 588 62 46 Fax (Faks): +90 212 - 586 18 04 e-mail (e-posta): travma@travma.org.tr Web: www.travma.org.tr

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)

Kaya Sarıbeyoğlu Kaya Sarıbeyoğlu 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), Index Copernicus, DOAJ, EBSCO, and Turkish Medical Index (Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, 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 • Redaction (Redaksiyon): Erman Aytaç • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): May (Mayıs) 2019 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

KARE P U B L I S H I N G

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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.

tion, called “Upload Your Files”.

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 0.473 (JCR 2016). It is cited as ‘Ulus Travma Acil Cerrahi Derg’ in PubMed.

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.

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. 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. Open Access Policy: Full text access is free. There is no charge for publication or 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, 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. 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” sec-

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.

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. 2016 Journal Citation Report IF puanımız 0.473 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. 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 25

Number - Sayı 3 May - Mayıs 2019

Contents - İçindekiler ix-x Editorial - Editörden

Deneysel Çalışma - Experimental Experimental Studies - DeneyselStudy Çalışma 205-212 The role of heparin-binding protein in the diagnosis of acute mesenteric ischemia Akut mezenter iskemi tanısında heparin-bağlayıcı proteinin rolü Koçak S, Acar T, Ertekin B, Güven M, Dündar ZD 213-221 Effects of dapagliflozin in experimental sepsis model in rats Dapagliflozin’in sıçanlarda deneysel sepsis modeli üzerine etkileri Kıngır ZB, Özdemir Kumral ZN, Çam ME, Çilingir ÖT, Şekerler T, Ercan F, Bingöl Özakpınar Ö, Özsavcı D, Sancar M, Okuyan B

Original Articles - Orijinal Çalışma 222-228 Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in identifying complicated appendicitis in the pediatric emergency department Pediatrik acil serviste komplike apandisitin belirlenmesinde nötrofil-lenfosit oranı ve trombosit-lenfosit oranının rolü Çelik B, Nalçacıoğlu H, Özçatal M, Altuner Torun Y 229-237 Role of Alvarado score and biological indicators of C-reactive protein, procalicitonin and neopterin in diagnosis of acute appendicitis Akut apandisit tanısında Alvarado skorlaması, C-reaktif protein, prokalsitonin ve neopterin biyolojik belirteçlerin yeri Dal F, Çiçek Y, Pekmezci S, Kocazeybek B, Bahartokman H, Konukoğlu D, Şimşek O, Taner Z, Sirekbasan S, Uludağ SS 238-246 Use of angiographic embolization in trauma-induced pediatric abdominal solid organ injuries Anjiyografik embolizasyonun çocuklarda künt karın travmasına bağlı solid organ yaralanmasında kullanımı Gürünlüoğlu K, Ceran C, Yıldırım İO, Kutlu R, Saraç K, Yıldız T, Bayrakçı E, Taşçı A, Arslan AK, Demircan M 247-252 SAPS III or APACHE IV: Which score to choose for acute trauma patients in intensive care unit? Yoğun bakımdaki akut travma hastalarında hangi skoru seçmeliyiz: SAPS III mü APACHE IV mü? Korkmaz Toker M, Gülleroğlu A, Karabay AG, Biçer İG, Demiraran Y 253-258 Acute biliary pancreatitis during pregnancy and in the post-delivery period Gebelikte ve doğum sonrası dönemde akut biliyer pankreatit Hot S, Eğin S, Gökçek B, Yeşiltaş M, Karakaş DÖ 259-267 The correlation between Injury Severity Score, vital signs, and hemogram values on mortality in firearm injuries Ateşli silah yaralanması olgularında mortalite üzerine yaralanma şiddeti skoru (ISS), yaşamsal skorlar ve hemogram değerleri arasındaki korelasyonun etkisi Turan Ö, Eryılmaz M, Albuz Ö 268-280 Etiology, management, and survival of acute mechanical bowel obstruction: Five-year results of a training and research hospital in Turkey Mekanik bağırsak tıkanıklığının etiyoloji, yönetimi ve sağkalımı: Türkiye’deki bir eğitim ve araştırma hastanesinin beş yıllık sonuçları Karakaş DÖ, Yeşiltaş M, Gökçek M, Eğin S, Hot S Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

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TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 25

Number - Sayı 3 May - Mayıs 2019

Contents - İçindekiler 281-286 Extension-block pinning to treat bony mallet finger: Is a transfixation pin necessary? Kemiksel çekiç parmak tedavisi için ekstansiyon blok pinleme: Transfiksasyon pini gerekli mi? Çapkın S, Büyük AF, Sürücü B, Bakan ÖM, Atlıhan D 287-292 Outcomes of salvage total hip arthroplasty after failed osteosynthesis for collum femoris fractures Femur boyun kırıklarında osteosentez sonrası gelişen komplikasyonların tedavisinde total kalça protezi uygulamalarının sonuçları Akgül T, Birişik F, Polat G, Şen C, Kılıçoğlu Öİ 293-297 Finite element analysis of the effect of intramedullary nail compression amount on fracture union in distal tibial diaphyseal fractures Tibia distal diafiz kırıklarında intramedüller çivi kompresyon miktarının kırık kaynaması üzerine etkisinin sonlu eleman analizli değerlendirilmesi Turhan S 298-302 23-gauge transconjunctival vitrectomy for posterior segment intraocular foreign bodies Göz içi arka segment yabancı cisimlerinin yönetiminde 23-gauge transkonjonktival vitrektomi Özdamar Erol Y, Tekin K, Yılmazbaş P

Case Reports - Olgu Sunumu 303-306 Prehospital emergency thoracotomy performed by helicopter emergency medical service team: A case report Helikopter acil tıbbi servis ekibi tarafından yapılan hastane öncesi acil torakotomi: Bir olgu sunumu Darocha T, Kosiński S, Serednicki W, Derkowski T, Podsiadło P, Szpor J, Sanak T, Gałązkowski R 307-310 Strangulated inguinal hernia accompanied by paratesticular leiomyosarcoma Strangüle inguinal herniye eşlik eden paratestiküler leiomiyosarkom Ağca B, İşcan Y, Aydın T, Şahin A, Memişoğlu K 311-315 A rare case of fatal venous and cerebral air embolism Nadir görülen ölümcül venöz ve serebral hava embolisi Petekkaya S, Celbis O, Öner BS, Turhan Ö, Yener Z

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Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

EXPERIMENTAL STUDY

The role of heparin-binding protein in the diagnosis of acute mesenteric ischemia Sedat Koçak, M.D.,1 Merve Güven, M.D.,1

Tarık Acar, M.D.,2 Birsen Ertekin, M.D.,2 Zerrin Defne Dündar, M.D.1

Department of Emergency, Necmettin Erbakan University Meram Faculty of Medicine, Konya-Turkey

Department of Emergency, Beyhekim State Hospital, Konya-Turkey

ABSTRACT BACKGROUND: Acute mesenteric ischemia (AMI) is associated with a high mortality rate, yet diagnostic difficulties persist. Although many biomarkers have been investigated for diagnostic purposes, as well as imaging methods, a sufficiently specific and sensitive marker has not been identified. This research was designed to examine whether heparin-binding protein (HBP), which has a role in the early phase of inflammation, could be useful in the diagnosis of AMI. METHODS: Serum samples obtained from a previously performed rabbit model of AMI were used in the study. HBP, C-reactive protein (CRP) and interleukin 6 (IL-6) levels were measured in blood samples obtained at baseline and 1, 3, and 6 hours from subjects that were separated into 3 groups: control, sham, and ischemia. The change in each marker over time and comparisons of the groups were evaluated statistically. RESULTS: A significant difference was not detected at the first hour in any of the studied markers. At the third hour, the CRP and IL-6 levels in the ischemia group indicated a significant increase in comparison with the control and sham groups (p<0.001). The HBP values showed a significant increase at the sixth hour in the ischemia group in comparison with the others (p<0.001). CONCLUSION: The HBP level demonstrated a slower increase in a rabbit model of AMI compared with CRP and IL-6. However, it still has the potential to become an early diagnostic biomarker. Diagnostic sensitivity and specificity should be evaluated in further clinical trials. Keywords: Acute mesenteric ischemia; biomarker; heparin-binding protein.

INTRODUCTION Mesenteric ischemia (MI) is less commonly observed in emergency units compared with other causes of abdominal pathology, but should be diagnosed quickly due to its high mortality risk. The most important step in the management of the disease is the diagnosis. Despite advanced radiological and surgical techniques, acute mesenteric ischemia (AMI) is still a disease with high mortality rate.[1–4] Prognosis is significantly improved by the reinstatement of the blood flow within the first 6 hours of ischemia, and particularly embolism-related ischemia. The prognosis is wors-

ens as the duration of intestinal ischemia is prolonged. New diagnostic methods have been investigated in order to provide early diagnosis and to thereby reduce mortality. The use of serum markers in the diagnosis of AMI is quite limited. Although many plasma markers have been investigated, no generally accepted specific marker has yet been defined.[5] In a review of 20 studies that included 18 different biochemical markers, the current markers were defined as not satisfactory. However, some new markers could contribute to diagnostic improvement.[6] Heparin-binding protein (HBP), also known as azurocidin or CAP37, is a protein that is stored in the azurophilic granules

Cite this article as: Koçak S, Acar T, Ertekin B, Güven M, Dündar ZD. The role of heparin-binding protein in the diagnosis of acute mesenteric ischemia. Ulus Travma Acil Cerrahi Derg 2019;25:205-212. Address for correspondence: Birsen Ertekin, M.D. Beyhekim Devlet Hastanesi, Acil Servis Klinği, Selçuklu, Konya, Turkey. Tel: +90 332 - 224 30 00 E-mail: biceacil@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):205-212 DOI: 10.5505/tjtes.2018.49139 Submitted: 21.08.2017 Accepted: 26.07.2018 Online: 17.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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of the neutrophils. Its potential role in infectious diseases has long been known and many studies have been conducted on the subject. In a recent study, HBP was demonstrated to be the only component of neutrophils that provokes increased permeability in in-vitro endothelial cell monolayers and invivo vascular endothelium.[7] HBP also has proinflammatory chemotactic effects against monocytes and T cells. HBP is easily mobilized within neutrophils, and this process or other functions of HBP appear to be important in early inflammation processes.[8] Clinical studies suggest HBP could be predictive in the progress of organ dysfunction, sepsis, and septic shock in patients admitted to emergency units with suspected infections and in intensive care patients.[9,10] Bacterial translocation develops in AMI, which in turn, initiates the inflammatory process. Inflammatory markers, including biomarkers, have been widely studied in AMI due to the inflammation accompanied by ischemia. The aim of this study was to analyze the blood level of HBP in AMI, which has not been studied before, and to evaluate its diagnostic potential compared with current markers. HBP may be a beneficial molecule in the early diagnosis of AMI since it has a role in the early stage of inflammation. In the present study, an experimental rabbit model of AMI was constructed and HBP, C-reactive protein (CRP) and interleukin 6 (IL-6) levels were measured at specific intervals. The change in the level of these biomarkers over time and their relationship to each other were compared statistically, and their roles in the diagnosis of AMI were evaluated.

MATERIALS AND METHODS No new animal experiment was performed in the study. The serum samples obtained by Acar et al.[11] were used for the present research. That study was approved by the Laboratory Animals Ethical Committee of Necmettin Erbakan University Experimental Medicine Research and Practice Center on January 20, 2012 (reg. no 2012-01) and conducted at Necmettin Erbakan University Experimental Medicine Research and Practice Center in May 2012. The present study was approved by the same committee on April 17, 2013 (reg. no 2013-073). The methods applied in the original study are described in detail in the published report. As a summary:

Experimental Protocol The study included 27 adult male and female New Zealand rabbits weighing 2500 to 3000 g. All of the animals had the same environment and nutritional conditions. Prior to the experimental study, food was withheld for 12 hours and only water was provided. The animals were classified into 3 groups: a control group of 7 rabbits, a sham group of 10 rabbits, and an ischemia group of 10 rabbits. Control group (Group I): A dose of 50 mg/kg ketamine and 15 mg/kg xylazine was administered via the intramuscular route through the hind leg, and following attainment of anes206

thesia, vascular access at the dorsal ear vein of the animals was used to obtain blood samples and perform an infusion with a 22-G intravascular catheter. Blood samples of 5 mL were collected in Vacutainer gel tubes (Becton Dickinson and Co., Franklin Lakes, NJ, USA) at baseline and the first, third, and sixth hours for biochemical analysis. Following each sampling, 5 mL of 0.9% physiological saline was infused through the same catheter. Sham group (Group II): The same procedure was applied to the rabbits in this group as in the control group. Following blood sampling for the baseline value, the abdominal region of the animals was shaved and cleaned with 10% povidone iodine. A laparotomy was performed via a midline incision, and when the peritoneum was accessed, the abdominal wall and peritoneum were closed using 2/0 silk sutures. Blood samples were collected at the first, third, and sixth hours for biochemical evaluation. Following each sampling, 5 mL of 0.9% physiological saline was infused through the same catheter, as in the control group. Ischemia group (Group III): The same preparation that was described for the rabbits in the sham group was used in the ischemia group. Following blood sampling for the baseline value, a laparotomy was performed via midline incision, and the superior mesenteric artery was found and ligated. The peritoneum and abdominal wall were closed using 2/0 silk. Blood samples were collected at the postoperative first, third, and sixth hours for biochemical analysis. Following each sampling, 5 mL of 0.9% physiological saline was infused through the same catheter. At the end of the 6-hour ischemia period, the rabbits were sacrificed with a high dose of ketamine.

Storage of the Samples The 5 mL blood samples collected in Vacutainer gel tubes were held for 30 minutes for coagulation, and centrifuged at 3000 rpm for 10 minutes. The serum samples were pipetted in Eppendorf tubes (Eppendorf AG, Hamburg, Germany) and kept at -80Â°C until biochemical analysis.

Evaluation of the Samples Biochemical Analysis Enzyme-linked immunosorbent assay (ELISA) tests and ready-to-use commercial kits were used for all 3 markers. The Sunred Rabbit Heparin Binding Protein (HBP) ELISA Kit (Lot No: 201090291; Shanghai Sunred Biological Technology Co., Ltd, Shanghai, China) was used for the measurement of serum HBP levels, the Scientific Research Special Eastbiopharm Rabbit CRP ELISA kit (Lot No: 20121024; Hangzhou Eastbiopharm Co. Ltd., Hangzhou, China) was used for the measurement of CRP levels, and the Cusabio Rabbit Interleukin-6 (IL-6) ELISA kit (Lot No: I4061791; Cusabio Biotech Co., Ltd, Wuhan, China) was used for measurement of IL-6 levels. Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Koçak et al. The role of HBP in the diagnosis of AMI

Statistical Analysis Data were recorded on prepared forms. SPSS for Windows, Version 16.0 (SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. Variance analysis with a post hoc Tukey test was used to examine the measurements between groups. A Bonferroni-corrected paired T-test was used to determine the difference between measurements. Non-normally distributed ordinary variables were analyzed using the Friedman test. A Bonferroni-corrected Mann-Whitney U test was used to determine the difference between measurements. A p value of <0.05 was accepted as statistically significant. The results were presented in tables and graphs.

RESULTS One of the rabbits in the ischemia group died at the first hour and therefore it was excluded. The study was completed with 26 rabbits.

Biochemical Markers CRP The mean CRP level measured from the blood samples collected at baseline and the first, third and sixth hours in each group and the comparisons are illustrated in Table 1. The initial values were somewhat lower in the sham group than in the control group (p<0.007). No significant difference was detected between groups in the levels at the first hour (p>0.05). The CRP levels measured at the third and sixth

hours revealed no significant difference between the sham and control groups (p=0.994 and p=0.932, respectively), whereas a significant increase was observed in the ischemia group compared with both the control and sham groups (p=0.0001 and p=0.0001, respectively). The change in CRP level over time is presented in Fig. 1. A progressive increase in the CRP level is notable in the sham group and particularly in the ischemia group.

IL–6 The mean IL-6 level measured from the blood samples collected at baseline and the first, third, and sixth hours in each group and the comparisons are demonstrated in Table 2. No significant difference was detected between the groups with regard to the levels at baseline and the first hour (p>0.05). The IL-6 levels measured at the third and sixth hours revealed no significant difference between the sham and control groups (p=0.882 and p=0.775, respectively), whereas a significant increase was observed in the ischemia group compared with both the control (p=0.005 and p=0.0001, respectively) and sham groups (p=0.0008 and p=0.0001, respectively) at both the third and sixth hours. The change in IL-6 level over time is presented in Fig. 2. The increase in IL-6 level in the ischemia group is notable.

HBP The mean HBP level measured from the blood samples collected at baseline and the first, third, and sixth hours in each

Table 1. Comparison of CRP values in the groups at baseline, 1, 3, and 6 hours

CRP

Mean

95% CI

Control Sham Ischemia C0 Control 7 0.42 0.04 Sham

–

10 0.35 0.05 0.007

LL–UL

0.007 0.112 0.386–0.462 –

0.390 0.315–0.383

Ischemia 9 0.37 0.05 0.112 0.390

–

0.342–0.411

Total

–

0.357–0.400

26 0.38 0.05

C1 Control 7 0.49 0.10 Sham

– –

10 0.39 0.02 0.075

–

0.075 0.879 0.368–0.609 –

0.150 0.361–0.422

Ischemia 9 0.47 0.08 0.879 0.150

–

0.408–0.527

Total

–

0.407–0.481

26 0.44 0.09

C3 Control 7 0.42 0.06 Sham

– –

10 0.42 0.03 0.994

–

0.994 <0.001 0.367–0.469 –

<0.001 0.398–0.444

Ischemia 9 0.52 0.05 <0.001 <0.001

–

0.484–0.567

Total

–

0.429–0.484

26 0.45 0.07

C6 Control 7 0.44 0.07 Sham

– –

10 0.45 0.04 0.932

–

0.932 <0.001 0.374–0.506 –

<0.001 0.423–0.475

Ischemia 9 0.62 0.05 <0.001 <0.001

–

0.586–0.658

Total

–

0.466–0.546

26 0.50 0.10

–

CI: Confidence interval; CRP: C-reactive protein; LL: Lower limit; SD: Standard deviation; UL: Upper limit.

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Koçak et al. The role of HBP in the diagnosis of AMI

Table 2. Comparison of IL-6 values in the groups at baseline, 1, 3, and 6 hours

IL-6

Mean

95% CI

Control Sham Ischemia LL–UL 10 Control 7 9.26 3.10 Sham

–

0.729 0.988 6.390–12.124

10 7.78 2.73 0.729

–

0.597 5.829–9.733

Ischemia 9 9.55 5.37 0.988 0.597

– 5.423–13.674

Total

– 7.232–10.348

26 8.79 3.86

–

I1 Control 7 10.17 3.78

–

Sham

Ischemia 9 13.22 5.44 0.360

Total

–

0.999 0.360 6.679–13.664

10 10.10 3.52 0.999 26 11.20 4.43

–

I3 Control 7 7.91 3.93

–

Sham

Ischemia 9 24.28 14.73 0.005

Total

–

9.044–17.407

–

9.413–12.989

0.882 0.005 4.276–11.553

10 10.10 4.18 0.882 26 14.42 11.56

–

I6 Control 7 7.68 4.66

–

0.280 7.584–12.617

0.280

–

0.008 7.110–13.093

0.008

–

12.963–35.601

–

9.751–19.092

0.775 <0.001 3.376–11.996

Sham

Ischemia 9 33.10 13.91 <0.001 <0.001

10 10.65 3.37 0.775

–

22.413–43.795

Total

–

11.847–23.402

26 17.62 14.30

–

<0.001 8.242–13.057

–

CI: Confidence interval; IL-6: Interleukin 6; LL: Lower limit; SD: Standard deviation; UL: Upper limit.

Table 3. Comparison of HBP values in the groups at baseline, 1, 3, and 6 hours

HBP

Mean

95% CI

Control Sham Ischemia LL–UL H0 Control 7 6.22 2.58 Sham

–

0.696 0.397 3.834–8.612

10 5.35 1.46 0.696

–

0.072 4.309–6.394

Ischemia 9 7.66 2.45 0.397 0.072 Total

–

5.779–9.548

26 6.38 2.31

5.455–7.317

H1 Control 7 5.13 1.90 Sham

–

0.414 0.617 3.383–6.888

10 3.90 2.38 0.414

–

0.059 2.194–5.601

Ischemia 9 6.46 2.56 0.617 0.058 Total

–

4.496–8.431

26 4.91 2.99

3.704–6.123

H3 Control 7 6.30 2.79 Sham

–

0.959 0.345 3.718–8.881

10 6.64 2.14 0.959

–

0.427 5.111–8.170

Ischemia 9 8.10 2.68 0.345 0.427 Total

H6 Control 7 5.13 1.33 Sham

– 6.047–10.159

26 7.05 2.54 –

0.592 0.012 3.900–6.360

10 4.08 1.34 0.592

–

<0.001 3.122–5.043

Ischemia 9 8.54 3.15 0.012 <0.001 Total

6.031–8.079

– 6.115–10.964

26 5.91 2.87

4.747–7.068

CI: Confidence interval; HBP: Heparin-binding protein; LL: Lower limit; SD: Standard deviation; UL: Upper limit.

group and the comparisons are provided in Table 3. No significant difference was detected between groups in the levels at baseline or the first and third hours (p>0.05). A significant 208

increase was observed in the HBP level of the ischemia group compared with both the control and sham groups at the sixth hour (p=0.0012 and p=0.0001, respectively). The change in Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

KoĂ§ak et al. The role of HBP in the diagnosis of AMI

HBP level over time is presented in Fig. 3. The increase in HBP level over time was less significant compared with the increase in CRP and IL-6 levels.

0.7

CRP (mcg/mL)

0.6 0.5

DISCUSSION

0.4 0.3 0.2 0.1 0

Control

0.42

0.49

0.42

0.44

Sham

0.35

0.39

0.42

0.45

Ischemia

0.37

0.47

0.52

0.62

Hours

Figure 1. Time course of serum C-reactive protein levels in the control, sham, and ischemia groups.

IL-6 (pg/mL)

30 25 20 15 10 5 0

Control

9.26

10.17

7.91

7.68

Sham

7.78

10.10

10.65

Ischemia

9.55

13.22

24.28

33.10

Hours

Figure 2. Time course of serum interleukin 6 levels in the control, sham, and ischemia groups.

9 8 HBP (ng/mL)

7 6 5 4 3 2 1 0

Control

6.22

5.13

6.30

5.13

Sham

5.35

3.90

6.64

4.08

Ischemia

7.66

6.46

8.10

8.54

Hours

Figure 3. Time course of serum heparin-binding protein levels in the control, sham, and ischemia groups.

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The clinical findings of AMI arise from impaired perfusion, systemic inflammatory responses due to impaired microcirculation, and reperfusion damage.[12] At the cellular stage, ischemia leads to mitochondrial dysfunction, impaired ion transport, and intracellular acidosis. Alterations in membrane permeability and the secretion of free radicals and disintegrating enzymes result in cell death and necrosis.[12,13] Many cells within the ischemic tissue, such as neutrophils, endothelial cells, monocytes, and platelets are activated. Many proinflammatory substances, including tumor necrosis factor (TNF), interleukins, platelet activating factor, and leukotrienes are secreted. As a result, the damage is related to leukocyte adhesion, platelet aggregation, and impaired nitric oxide production.[14] It has long been known that ischemia leads to bacterial translocation due to changes in vascular permeability within a short time.[15,16] In this study, we investigated the possibility that HBP, which has been demonstrated to have antibacterial effects as well as effects on both inflammation and vascular permeability, could be a beneficial marker for early diagnosis of AMI. The animals in the ischemia group were found to have significantly higher HBP levels at the sixth hour of ischemia compared with those in the sham and control groups. HBP is a member of the serin protease family.[17] Although it has no enzymatic activity, it is a multi-functional protein. It accumulates and activates monocytes, induces T cells, starts detachment of endothelial cells and fibroblasts and the homotypic accumulation of these cells. Furthermore, endocytosis of HBP into monocytes increases the production of lipopolysaccharide-derived TNF-Îą.[8] Other studies have suggested that internalized HBP protects endothelial cells against apoptosis.[18] HBP has been shown to play a specific role in mediating the change in vascular permeability that is stimulated by chemoattractant-induced polymorphonuclear leukocyte activation.[7] The localization of HBP duplicates within azurophilic granules and secreted vesicles indicates a possible role of the protein in neutrophils. The HBP localized in azurophilic granules is in close contact with internalized bacteria after the azurophil granules are fused with the phagosome. Again, the HBP secreted from the secretory vesicles has been reported to have important functions during early stages of inflammation. Unfortunately, in more than 20 studies conducted of biomarkers, no ideal biomarker with a high sensitivity and specificity has been detected for the diagnosis of AMI. The serum phosphate level is one of the biochemical parameters researched for diagnostic value in AMI. In a study conducted on 20 rabbits, the serum phosphate levels were shown to increase 209

KoĂ§ak et al. The role of HBP in the diagnosis of AMI

in AMI.[19] Feretis et al.[20] demonstrated significantly higher serum phosphate levels in 18 patients with acute intestinal infarction compared with 24 patients without intestinal ischemia. In an intestinal ischemia study conducted on dogs, a significant increase in the phosphate level was observed in the fourth hour of ischemia. However, the authors noted that this had no benefit in early diagnosis, and that the increase in phosphate level was meaningful following the development of irreversible necrosis within the intestines.[21] Leo et al.[22] found in a study of 23 AMI patients that serum phosphate levels had no diagnostic or prognostic value. Another marker used in AMI is amylase. It has been reported that amylase levels were found to be higher than normal in 27 of 52 patients diagnosed with AMI.[23] In a study that included patients with acute abdomen on admission and who were diagnosed with AMI that amylase was 25% specific and 63% sensitive.[24] In another study, the amylase levels of the patients with AMI were observed to be high starting at the third hour.[25] Amylase has been demonstrated to increase in many disorders included in the etiology of acute abdomen. Its single usage in AMI is controversial, however, and should be confirmed with other parameters. Alone, the sensitivity and specificity are low. In the experimental study conducted by Kurt et al.,[26] the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of D-dimer in AMI were found to be 88.8%, 90%, 88.8%, and 100%, respectively, and they concluded that D-dimer may be beneficial in the early diagnosis of AMI. In another experimental AMI study, procalcitonin (PCT) was demonstrated to significantly increase in blood starting in the first hour of ischemia.[27] In a study investigating the PCT level in intestinal strangulation, PCT levels were higher than normal in the group with strangulation. PCT levels were observed to increase at the 30th and 60th minutes of the study, and a significant increase was detected in the 120th minute.[28] In a series that included 7 patients with AMI, the ischemia-modified albumin (IMA) level were observed to be significantly higher than that of healthy controls.[29] In another clinical study, the IMA level was measured in 26 patients, 12 of whom were diagnosed to have intestinal ischemia, and the IMA level was significantly elevated. High IMA levels were reported to have 100% sensitivity and 100% specificity in the diagnosis of intestinal ischemia.[30] In a study conducted on rabbits, the IMA level was found to significantly increase with additional ischemia time.[31] In a study of 61 patients with acute abdominal pain, serum intestinal fatty acid binding protein (IFABP) levels were significantly higher in cases with ischemic bowel disease.[32] In another study, true positivity was detected for high IFABP in 7 patients with intestinal ischemia, whereas false positivity was detected in 10.[33] Another study examined 21 patients with 210

strangulated intestinal obstruction, 3 of whom had intestinal necrosis. The serum IFABP level was high in all of the patients with intestinal necrosis.[34] A meta-analysis determined that the sensitivity and specificity of the serum IFABP level in the diagnosis of intestinal ischemia was 72% (51â&#x20AC;&#x201C;88%) and 73% (62â&#x20AC;&#x201C;83%), respectively.[6] In the study conducted by Dundar et al.,[35] no significant difference was detected between the serum IFABP level in control, sham, and ischemia groups. Furthermore, no significant difference was observed at the initial, first, third, and sixth hours of ischemia in the ischemia group. A literature search revealed no study on the diagnostic or prognostic value of HBP on patients with AMI. The number of clinical studies on HBP is limited. Considering its effect on vascular permeability, studies investigating whether it could be a marker of acute respiratory or circulatory failure in serious infections and sepsis have become important. Chew et al.[36] investigated the HBP level in 53 patients with septic and non-septic shock in the emergency unit, The HBP level was significantly higher among patients with shock compared with that of healthy or control patients with an infection (such as urinary infection, pneumonia, gastroenteritis), whereas no difference was observed between patients with septic and non-septic shock. Research performed by Linder et al.[9] investigating the predictive value of HBP in the progression to circulatory failure or septic shock in patients with a suspected infection or sepsis, the HBP level in patients with serious sepsis or septic shock was significantly higher compared with that of patients with non-serious sepsis. PCT, white blood cell count (WBC), CRP, IL-6, and lactate values were used for comparison in predicting the progression to serious sepsis and septic shock and were found to be lower than that of HBP. The sensitivity, specificity, NPD, PPD and receiver operating characteristic (ROC) curve values of HBP were higher than those of other markers. In another study, Linder et al.,[10] investigated 759 patients admitted to emergency units with a suspected infection. In all, 674 were diagnosed with various infections, and among that group, 487 had no organ dysfunction at admission. During the study period (72 hours), 141 of the 487 developed organ dysfunction. The authors reported that blood samples were collected for measurement of HBP, WBC, PCT, CRP and lactate on admission and within 12 to 24 hours after admission and compared for their predictive value for serious sepsis and organ dysfunction. HBP was superior to the other markers in patients with organ failure both on admission and during the study in terms of sensitivity, specificity, NPD, PPD, and ROC values. HBP was reported to increase hours before organ dysfunction (median: 10.5 hours) and to have a higher odds ratio (OR: 20.5) for indicating progression to organ dysfunction in comparison with the other markers. In another study investigating the relationship between reduced oxygenation and circulatory failure and the HBP level in intensive care patients, the HBP level on admission was Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Koçak et al. The role of HBP in the diagnosis of AMI

found to be related to respiratory and circulatory failure and 30-day mortality.[37]

other markers should be considered as factors to increase the specificity and sensitivity.

In an experimental study using CRP as a marker in intestinal ischemia, CRP was found to be more elevated in rats with bacterial translocation.[38] CRP concentrations were also observed to increase parallel with the severity of tissue damage or inflammation in acute intensive infection.[39] In an AMI model study conducted on pigs, the increase in total microflora and bacterial translocation was determined to be consistent with the increase in CRP.[40] Willetts et al.[41] reported high CRP levels in children with acute endotoxinemia with acute invagination, and the finding was correlated to the severity of the disease. Studies of IL-6 have revealed that systemic secretion of TNF-α and IL-6 was related to septic shock and mortal outcomes. It has been reported in a study that TNF-α and IL–6 levels continuously increased following intestinal ischemia, and that these cytokines were secreted from Kuppfer cells.[42] The increase in blood levels of IL-6 in AMI is valuable in demonstrating the early stage onset of systemic response and evaluating the clinical situation of the patients, rather than diagnosing the disease. Another experimental study that compared hemorrhagic shock and intestinal ischemia, no correlation was observed between bacterial translocation and blood levels of cytokines, and IL–6 levels were demonstrated to peak in the third hour after superior mesenteric artery occlusion.[43] In our study, the significant increases in both the CRP and IL-6 levels in the ischemia group were also observed in the third hour, which was earlier than the increase in HBP. However, it should be considered that both CRP and IL-6 are highly non-specific markers and are elevated in many ischemic and inflammatory conditions. Therefore, it is important to note the diagnostic sensitivity and specificity in addition to the ability to be detected in blood at early stages, because the markers studied so far have not been found to be sufficiently sensitive and specific. Since our study was an animal study and included a limited sample, the specificity and sensitivity tests would not produce acceptable statistical results.

Conflict of interest: None declared.

Conclusion This study investigated whether or not HBP, which has been known to have antibacterial effects as well as effects on the early stages of inflammation and vascular permeability, was a beneficial marker in the early diagnosis of acute mesenteric ischemia. Furthermore, the HBP level was compared to the levels of IL-6, which is an important cytokine in inflammatory conditions, and CRP, which is an acute phase reactant induced by IL-6. Although detected later than IL-6 and CRP, a significant increase in the HBP level in the ischemia group in the sixth hour has demonstrated that it could be a potential biomarker in the diagnosis of AMI. However, in order to define the specificity and sensitivity of HBP for AMI, and to determine a cutoff value, clinical studies with larger sample sizes are needed. Combination studies conducted with Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

REFERENCES 1. Yasuhara H. Acute mesenteric ischemia: the challenge of gastroenterology. Surg Today 2005;35:185–95. 2. Ujiki M, Kibbe MR. Mesenteric ischemia. Perspect Vasc Surg Endovasc Ther 2005;17:309–18. 3. Oldenburg WA, Lau LL, Rodenberg TJ, Edmonds HJ, Burger CD. Acute mesenteric ischemia: a clinical review. Arch Intern Med 2004;164:1054– 62. 4. Chang JB, Stein TA. Mesenteric ischemia: acute and chronic. Ann Vasc Surg 2003;17:323–8. 5. Acosta S, Nilsson TK, Björck M. D-dimer testing in patients with suspected acute thromboembolicocclusion of the superior mesenteric artery. Br J Surg 2004;91:991–4. 6. Evennett NJ, Petrov MS, Mittal A, Windsor JA. Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia. World J Surg 2009;33:1374–83. 7. Gautam N, Olofsson AM, Herwald H, Iversen LF, Lundgren-Akerlund E, Hedqvist P, et al. Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked alteration of vascular permeability. Nat Med 2001;7:1123–7. 8. Tapper H, Karlsson A, Mörgelin M, Flodgaard H, Herwald H. Secretion of heparin-binding protein from human neutrophils is determined by its localization in azurophilic granules and secretory vesicles. Blood 2002;99:1785–93. 9. Linder A, Christensson B, Herwald H, Björck L, Akesson P. Heparinbinding protein: an early marker of circulatory failure in sepsis. Clin Infect Dis 2009;49:1044–50. 10. Linder A, Arnold R, Boyd JH, Zindovic M, Zindovic I, Lange A, et al. Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department. Crit Care Med 2015;43:2378–86. 11. Acar T, Koçak S, Cander B, Ergin M, Dikmetaş C. Liporotein-associated phospholipase-A2 can be a diagnostic marker inthe early stage diagnosis of acute mesenteric ischemia. Turk J Med Sci 2016;46:120–5. 12. Abboud B, Daher R, Boujaoude J. Acute mesenteric ischemia after cardio-pulmonary bypass surgery. World J Gastroenterol 2008;14:5361–70. 13. Cerqueira NF, Hussni CA, Yoshida WB. Pathophysiology of mesenteric ischemia/reperfusion: a review. Acta Cir Bras 2005;20:336–43. 14. Harward TR, Brooks DL, Flynn TC, Seeger JM. Multiple organ dysfunction after mesenteric artery revascularization. J Vasc Surg 1993;18:459– 67. 15. Necefli A, Dolay K, Arikan Y, Guloglu R, Karayay S, Halici E, et al. The effect of ceftriaxone on bacterial translocation in mesenteric ischemia. Ulus Travma Acil Cerrahi Derg 1999;5:7–10. 16. Deitch EA. Bacterial translocation or lymphatic drainage of toxic products from the gut: what is important in human beings? Surgery 2002;131:241–4. 17. Pereira HA. CAP37, a neutrophil-derived multifunctional inflammatory mediator. J Leukoc Biol 1995;57:805–12. 18. Olofsson AM, Vestberg M, Herwald H, Rygaard J, David G, Arfors KE, et al. Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis. J Clin Invest 1999;104:885–94. 19. Uncu H, Uncu G, İlçöl Y, Aker Y. Diagnosis of intestinal ischemia by measurement of serum phosphate and enzyme changes and the effectiveness of vitamin E treatment. Turk J Gastroenterol 1999;10:272–5. 20. Feretis CB, Koborozos BA, Vyssoulis GP, Manouras AJ, Apostolidis NS,

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Koçak et al. The role of HBP in the diagnosis of AMI Golematis BC. Serum phosphate levels in acute bowel ischemia. An aid to early diagnosis. Am Surg 1985;51:242–4. 21. Lores ME, Cañizares O, Rosselló PJ. The significance of elevation of serum phosphate levels in experimental intestinal ischemia. Surg Gynecol Obstet 1981;152:593–6. 22. Leo PJ, Simonian HG. The role of serum phosphate level and acute ischemic bowel disease. Am J Emerg Med 1996;14:377–9. 23. Wilson C, Gupta R, Gilmour DG, Imrie CW. Acute superior mesenteric ischaemia. Br J Surg 1987;74:279–81. 24. Delaney CP, O’Neill S, Manning F, Fitzpatrick JM, Gorey TF. Plasma concentrations of glutathione S-transferase isoenzyme are raised in patients with intestinal ischaemia. Br J Surg 1999;86:1349–53. 25. Aslan A,Temiz M, Semerci E, Özkan OV. Acute Mesenteric Ischemia: Clinical Experience. Eurasian J Emerg Med 2009;8:28–32. 26. Kurt Y, Akin ML, Demirbas S, Uluutku AH, Gulderen M, Avsar K, et al. D-dimer in the early diagnosis of acute mesenteric ischemia secondary to arterial occlusion in rats. Eur Surg Res 2005;37:216–9. 27. Karabulut K, Gül M, Dündar ZD, Cander B, Kurban S, Toy H. Diagnostic and prognostic value of procalcitonin and phosphorus in acute mesenteric ischemia. Ulus Travma Acil Cerrahi Derg 2011;17:193–8. 28. Papaziogas B, Anthimidis G, Koutelidakis I, Atmatzidis S, Atmatzidis K. Predictive value of procalcitonin for the diagnosis of bowelstrangulation. World J Surg 2008;32:1566–7. 29. Gunduz A, Turedi S, Mentese A, Karahan SC, Hos G, Tatli O, et al. Ischemia-modified albumin in the diagnosis of acute mesenteric ischemia: a preliminary study. Am J Emerg Med 2008;26:202–5. 30. Polk JD, Rael LT, Craun ML, Mains CW, Davis-Merritt D, Bar-Or D. Clinical utility of the cobalt-albumin binding assay in the diagnosis of intestinal ischemia. J Trauma 2008;64:42–5. 31. Dundar ZD, Cander B, Gul M, Karabulut KU, Girisgin S. Serum ischemia-modified albumin levels in an experimental acute mesenteric ischemia model. Acad Emerg Med 2010;17:1233–8. 32. Kanda T, Fujii H, Tani T, Murakami H, Suda T, Sakai Y, et al. Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans. Gastroenterology 1996;110:339–43.

33. Lieberman JM, Sacchettini J, Marks C, Marks WH. Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia. Surgery 1997;121:335–42. 34. Cronk DR, Houseworth TP, Cuadrado DG, Herbert GS, McNutt PM, Azarow KS. Intestinal fatty acid binding protein (I-FABP) for the detection of strangulated mechanical small bowel obstruction. Curr Surg 2006;63:322–5. 35. Dundar ZD, Cander B, Gul M, Karabulut KU, Kocak S, Girisgin S, et al. Serum intestinal fatty acid binding protein and phosphate levels in the diagnosis of acute intestinal ischemia: an experimental study in rabbits. J Emerg Med 2012;42:741–7. 36. Chew MS, Linder A, Santen S, Ersson A, Herwald H, Thorlacius H. Increased plasma levels of heparin-binding protein in patients with shock: a prospective, cohort study. Inflamm Res 2012;61:375–9. 37. Tydén J, Herwald H, Sjöberg F, Johansson J. Increased Plasma Levels of Heparin-Binding Protein on Admission to Intensive Care Are Associated with Respiratory and Circulatory Failure. PLoS One 2016;11:e0152035. 38. Cevikel MH, Ozgün H, Boylu S, Demirkiran AE, Aydin N, Sari C, et al. C-reactive protein may be a marker of bacterial translocation in experimental intestinal obstruction. ANZ J Surg 2004;74:900–4. 39. Johnson HL, Chiou CC, Cho CT. Applications of acute phase reactants in infectious diseases. J Microbiol Immunol Infect 1999;32:73–82. 40. Meddah AT, Leke L, Romond MB, Grenier E, Cordonnier C, Risbourg B, et al. The effects of mesenteric ischemia on ileal colonization, intestinal integrity, and bacterial translocation in newborn piglets. Pediatr Surg Int 2001;17:515–20. 41. Willetts IE, Kite P, Barclay GR, Banks RE, Rumley A, Allgar V, et al. Endotoxin, cytokines and lipid peroxides in children with intussusception. Br J Surg 2001;88:878–83. 42. Towfigh S, Heisler T, Rigberg DA, Hines OJ, Chu J, McFadden DW, et al. Intestinal ischemia and the gut-liver axis: an in vitro model. J Surg Res 2000;88:160–4. 43. Grotz MR, Ding J, Guo W, Huang Q, Deitch EA. Comparison of plasma cytokine levels in rats subjected to superior mesenteric artery occlusion or hemorrhagic shock. Shock 1995;3:362–8.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut mezenter iskemi tanısında heparin-bağlayıcı proteinin rolü Dr. Sedat Koçak,1 Dr. Tarık Acar,2 Dr. Birsen Ertekin,2 Dr. Merve Güven,1 Dr. Zerrin Defne Dündar1 1 2

Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Acil Tıp Anabilim Dalı, Konya Beyhekim Devlet Hastanesi, Acil Servis Kliniği, Konya

AMAÇ: Akut mezenterik iskemi (AMİ), acil servislere sık başvuru nedenlerinden biri değildir. Ancak tanısal zorluklar ve bununla ilişkili yüksek mortalite düzeyleri sürmektedir. Görüntüleme yöntemleri yanı sıra birçok biyokimyasal belirteç tanısal amaçlı araştırılmış olmasına rağmen yeterince özgül ve duyarlı bir belirteç ortaya konamamıştır. Bu çalışmada, enflamasyonun erken safhasında rol oynadığı belirlenen heparin-bağlayıcı proteinin (HBP) AMİ tanısında yararlı olup olamayacağı araştırıldı. GEREÇ VE YÖNTEM: Çalışmada daha önce yapılmış, AMİ’nin bir tavşan modelinden elde edilmiş serum örnekleri kullanıldı. Kontrol, sham ve iskemi grubu olmak üzere üç gruba ayrılan deneklerden 0., 1., 3. ve 6. saatlerde elde edilen kan örneklerinde HBP, C-reaktif protein (CRP) ve interlökin-6 (IL-6) düzeyleri ölçüldü. Herbir belirtecin zamanla değişimi ve biribirleriyle karşılaştırılması istatistiksel olarak değerlendirildi. BULGULAR: Çalışılan belirteçlerin hiçbirinde 1. saatte gruplar arasında anlamlı bir fark belirlenmedi. Üçüncü saatten itibaren iskemi grubunda CRP ve IL-6 düzeyleri, kontrol ve sham gruplarına göre anlamlı yükselme göstermiştir (p<0.001). HBP değerleri ise 6. saatten itibaren iskemi grubunda diğerlerine göre anlamlı yükselme gösterdi (p<0.001). TARTIŞMA: Heparin-bağlayıcı protein düzeyleri, AMİ’nin tavşan modelinde CRP ve IL-6’ya göre daha geç yükselme gösterdi. Ancak yine de bir erken tanı belirteci olma potansiyel taşımaktadır. Yapılacak klinik çalışmalarla tanısal sensitivite ve spesifisitesinin değerlendirilmesi gerekmektedir. Anahtar sözcükler: Akut mezenter iskemi; biyobelirteç; heparin-bağlayıcı protein. Ulus Travma Acil Cerrahi Derg 2019;25(3):205-212

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EXPERIMENTAL STUDY

Effects of dapagliflozin in experimental sepsis model in rats Zehra Betül Kıngır, M.Sc.,1 Zarife Nigar Özdemir Kumral, Ph.D.,2 Muhammet Emin Çam, Ph.D.,3 Özlem Tuğçe Çilingir, Ph.D.,4 Turgut Şekerler, M.Sc.,5 Feriha Ercan, Ph.D.,4 Özlem Bingöl Özakpınar, Ph.D.,5 Derya Özsavcı, Ph.D.,5 Mesut Sancar, Ph.D.,1 Betül Okuyan, Ph.D.1 1

Department of Clinical Pharmacy, Marmara University Faculty of Pharmacy, İstanbul-Turkey

Department of Physiology, Marmara University Faculty of Medicine, İstanbul-Turkey

Department of Pharmacology, Marmara University Faculty of Pharmacy, İstanbul-Turkey

Department of Histology and Embryology, Marmara University Faculty of Medicine, İstanbul-Turkey

Department of Biochemistry, Marmara University Faculty of Pharmacy, İstanbul-Turkey

ABSTRACT BACKGROUND: The aim of this study was to evaluate the possible protective effects of dapagliflozin in an experimental sepsis model in rats. METHODS: Saline (1 mL/kg, p.o.) or dapagliflozin (10 mg/kg, p.o.) was administered to Sprague-Dawley rats for 5 days prior to the surgical procedures. Under anesthesia, sepsis was induced by cecal ligation puncture, while sham control groups underwent laparotomy only. Blood urea nitrogen, creatinine, and glucose levels were measured in serum samples and the levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor alpha, interleukin 1 beta, caspase 8, and caspase 9 were determined in tissue samples (kidney, liver, and lung). Histological evaluation was also performed. RESULTS: The administration of dapagliflozin in a sepsis model reduced oxidative stress (MDA), increased antioxidant levels (GSH), and reduced inflammation (MPO) in the kidney (p<0.05). Dapagliflozin also decreased oxidative stress (MDA) in lung tissue and decreased inflammation (MPO) in lung and liver tissue (p<0.05). Caspase 8 and 9 levels in kidney, lung, and liver tissue were increased (p<0.05) in the dapagliflozin group compared with the sepsis group. According to the histopathological results, sepsis was moderately improved in renal tissue and slightly attenuated in lung and liver tissue with the administration of dapagliflozin. CONCLUSION: Dapagliflozin had a preventive effect on sepsis-induced kidney damage, but the protective effect was mild in lung and liver tissue in the present study. Keywords: Apoptosis; dapagliflozin; inflammation; oxidative stress; sepsis.

INTRODUCTION Sepsis is defined as serious clinical syndrome which occurs as a consequence of an impaired inflammation response against infection characterized by an abnormal physiological, biological, and biochemical process.[1] According to a retrospective analysis of international databases, the global incidence rate between 1995 and 2015 was 437 out of 100,000 for sepsis and 270 out of 100,000 for severe sepsis.[2] During the management of sepsis, organ failure must be carefully evaluated because it is well established that damage to the

pulmonary system, coagulation mechanism, central nervous system, gastrointestinal system, and renal failure are common problems that can increase mortality.[3] Acute renal damage associated with sepsis and the deleterious effects of organic waste, such as uremic toxins, cause oxidative stress, inflammation, and insulin resistance, and these consequences also affect morbidity and mortality in sepsis.[4] Cecal ligation and puncture (CLP) is a well-designed, easy, and inexpensive polymicrobial septic shock model in experimental animals that also conforms to the human sepsis model.[5–7]

Cite this article as: Kıngır ZB, Özdemir Kumral ZN, Çam ME, Çilingir ÖT, Şekerler T, Ercan F, et al. Effects of dapagliflozin in experimental sepsis model in rats. Ulus Travma Acil Cerrahi Derg 2019;25:213-221. Address for correspondence: Betül Okuyan, Ph.D. Marmara Üniversitesi Eczacılık Fakültesi, Klinik Eczacılık Anabilim Dalı, İstanbul, Turkey. Tel: +90 216 - 414 05 45 E-mail: betulokuyan@yahoo.com Ulus Travma Acil Cerrahi Derg 2019;25(3):213-221 DOI: 10.5505/tjtes.2018.82826 Submitted: 03.04.2018 Accepted: 18.09.2018 Online: 20.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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In many studies, sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as dapagliflozin, have been observed to have antioxidant effects by increasing antioxidant enzymes and reducing oxidative stress markers. Furthermore SGLT2 inhibitors have been reported to reduce inflammatory markers, suppress apoptosis in the cell and have a potential effect on cell healing.[8–12]

were injected with saline.[9,14,15,17] On day 5, sepsis was induced using the CLP model and 24 hours later the rats were sacrificed. There were 4 female rats (250–300 g) and 4 male rats (300–350 g) in each group. Serum and tissue (kidney, lung, liver) samples were obtained and preserved (-80°C or 10% buffered formalin) in order to be used for further biochemical and histological analysis (Fig. 1).

A literature review revealed that dapagliflozin, a new antidiabetic agent, has not been investigated for its effects on oxidative stress, inflammation, and apoptosis in an experimental sepsis model. Therefore, the objective of this study was to investigate the antioxidant, anti-inflammatory, and antiapoptotic effects of dapagliflozin in rats in a cecal binding and puncture sepsis model.

Biochemical Analyses Measurement of Serum Blood Urea Nitrogen, Creatinine, and Glucose

MATERIALS AND METHODS Experimental Animals Sprague-Dawley rats (250–350 g) of both sexes supplied by the Experimental Animal Implementation and Research Center of Marmara University were housed in relative humidity (65–70%) and a temperature-controlled room (22±2°C) with standardized light/dark (12-hour) cycles. The rats were fed with standard rat pellets and had free access to water. This study protocol was approved by Marmara University Animal Experiments Local Ethical Committee (Ethical approval number and date: 115.2016.mar; 12.12.2016).

Experimental Design The experimental sepsis model was developed using a CLP procedure. It has been established that the cecum contains a high concentration of Gram-positive and Gram-negative bacteria. This polymicrobial content spreads to the peritoneum in the CLP model and causes sepsis. The rats were randomly divided into a sham or a CLP group, each of which included subjects of both sexes. Anesthesia was provided with a combination of ketamine 100 mg/kg and xylazine 10 mg/kg. After the midline laparotomy, the cecum was gently pulled out and ligated above the ileocecal valve to maintain bowel passage, 3 perforations were made on the antimesenteric side with a 21-gauge needle, and feces expression was allowed. The sham-operated control group (n=16) underwent a laparotomy without ligature or punctures and the abdomen was closed appropriately. Data obtained from previous studies indicate that CLP-induced sepsis mortality occurs in the first 3 days.[13] The rats were decapitated 24 hours after the operation.[5,6] The survival rate of the experimental animals was recorded throughout the process.[14–16] Four days before the CLP surgery, saline (n=8) or dapagliflozin (n=8; 10 mg/kg, 10 mL/kg; Forxiga, AstraZeneca, Cambridge, UK) was administered to the subjects in the sham and dapagliflozin groups. Orogastric gavage was performed in the dapagliflozin-treated CLP group and the sham-operated rats 214

The serum blood urea nitrogen (BUN), creatinine, and glucose levels were determined using an auto analyzer according to the manufacturer’s instructions (Cobas Integra 400 plus; Roche Diagnostics GmbH, Risch-Rotkreuz, Switzerland).

Measurement of Malondialdehyde and Glutathione The level of malondialdehyde (MDA), a byproduct of lipid peroxidation, was measured based on thiobarbituric acid reactive substance formation in kidney, lung, and liver tissues. [18] Tissue samples were homogenized in 10% trichloroacetic acid solution using 10-fold dilutions. The homogenized tissue samples were then centrifuged at 2000 g for 15 minutes at 4°C; the supernatant was removed and re-centrifuged at 41,400 g for 8 minutes. The upper organic liquid layer was separated and was measured with a spectrophotometer (Epoch; BioTek Instruments, Inc., Winooski, VT, USA) at 532 nm. Thiobarbituric acid reactive substance formation was measured[19] and the lipid peroxidation measurement was provided in terms of MDA equivalents using an extinction coefficient of 1.56×105 M−1 cm−1 and expressed as nmoL MDA/g tissue. GSH levels were measured in kidney, lung, and liver tissues according to the method developed by Beutler[20] using a modification of the Ellman procedure. The experimental principle is to measure the colored product resulting from the reaction of the sulphydryl groups with 5-5 ‘dithiobis 1-2

Saline-treated sham group Dapagliflozin (10 mg/kg) - treated sham group

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Figure 1. Schematic representation of the experimental design.

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nitrobenzoic acid in the spectrophotometer at 412 nm. The results were expressed as µmol GSH/g tissue.

Measurement of Myeloperoxidase Activity Myeloperoxidase (MPO) is a member of the peroxidase family. MPO activity in the lysates of kidney, lung, and liver tissues was assessed using a commercial enzyme-linked immunosorbent assay (ELISA) kit (Catalog No: LS-F4305, Lot No: 103692; LifeSpan BioSciences, Inc., Seattle, WA, USA). The results were measured as U/g tissue.

Measurement of Interleukin 1 Beta and Tumor Necrosis Factor-Alpha Interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured in all tissues (kidney, lung, liver) with commercial ELISA kits (Catalog No: BMS630, Lot No: 143373023; eBio-science, Inc., San Diego, CA, USA; Catalog No: KRC3011, Lot No: 1818268a; Thermo Fisher Scientific, Inc., Waltham, MA, USA, respec-tively). The results were measured as ng/mL.

Measurement of Tissue Caspase 8 and Caspase 9 The kidney, lung, and liver lysates were analyzed to determine caspase 8 and 9 levels with a commercial kit (Catalog No: APT171, Lot No: 2829013; Cat. No: APT173, Lot No: 2841705, respectively; MilliporeSigma, Burlington, MA, USA). The p-nitroaniline absorbance in non-apoptotic specimens and apoptotic specimens was compared and the caspase 8 and 9 activity was calculated as fold increase.

Histological Evaluation The samples obtained from kidney, liver, and lung tissues were fixed in 10% neutral buffered formalin for 48 hours and then examined with routine histological processing. Approximately 4 µm-thick paraffin sections were stained with hematoxylin and eosin. Periodic acid-Schiff staining was applied to assess the basal membrane and proximal tubules of kidney samples. The sections were examined and photographed using a light

1.0

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Statistical analysis was performed using GraphPad Prism 5.0 (GraphPad Software, Inc. La Jolla, CA, USA). All data are expressed as mean±SEM. Relationships within groups were measured using one-way analysis of variance followed by Tukey’s post hoc test. P<0.05 was considered statistically significant. The odds ratio (OR) was calculated based on a chisquare test for survival rate.

RESULTS Survival Rate The 24-hour survival rate was 75% (6/8 rats) in the salinetreated CLP group, whereas the survival rate was 100% for the other groups. There was no statistically significant difference in survival between the dapagliflozin-treated CLP group and the saline-treated CLP group (OR: 0.75, 95% conﬁdence interval [CI]: 0.50–1.12; p>0.05).

Blood Urea Nitrogen, Creatinine and Glucose Levels The CLP surgery groups developed kidney dysfunction and had higher plasma BUN (p<0.01) and creatinine (p<0.01– 0.001) levels in comparison with the saline-treated sham group (Fig. 2). The glucose level was significantly higher in the dapagliflozintreated sham group compared with the saline-treated sham group (p<0.05). A significant decrease was observed in the saline-treated CLP group when it was compared with the saline-treated sham group (p<0.01) (Fig. 2c).

(b) Saline Dapagliflozin

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microscope (BX51; Olympus Corp., Tokyo, Japan) attached to a digital camera (DP72; Olympus Corp., Tokyo, Japan). Histologists evaluated the glomerular structure and Bowman’s capsule, proximal and distal tubules, interstitial bleeding, and vascular congestion in kidney tissue; damaged hepatocytes with vacuoles and pyknotic nuclei, sinusoidal congestion, and increase of activated Kupffer cells in liver tissue; and alveolar morphology, interstitial bleeding, and vascular congestion in lung tissue.

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Figure 2. The level of blood urea nitrogen (BUN) and creatinine was increased, and the blood glucose level was decreased in the cecal ligation and puncture (CLP) groups, but dapagliflozin use did not demonstrate a change in the level of these parameters. (a) Serum BUN level after dapagliflozin treatment. (b) Serum creatinine level after dapagliflozin treatment. (c) Body glucose level after dapagliflozin treatment. The data are presented as the mean±SEM. One-way analysis of variance and post hoc Tukey-Kramer multiple comparison tests were used. *p<0.05, **p<0.01, ***p<0.001 vs saline-treated sham group. Each group consisted of 6–8 samples.

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The MDA level in all tissues was significantly elevated in the saline-treated CLP group when compared with the salinetreated sham group (p<0.05–0.01; Fig. 3). The MDA level in the dapagliflozin-treated CLP group was significantly lower in all tissues than that of the saline-treated CLP group (p<0.05– 0.01; Fig. 3). Interestingly, the MDA level in the dapagliflozintreated sham group was significantly higher in kidney tissue than that of the saline-treated sham group (p<0.05) (Fig. 3a). The GSH level was significantly lower in the kidney and hepatic tissue of the saline-treated CLP group when compared with the saline-treated sham group (p<0.050–001; Fig. 3b and f ), while an increase in GSH in kidney tissue was observed with administration of dapagliflozin (p<0.001, Fig. 3).

Myeloperoxidase, Tumor Necrosis Factor Alpha, and Interleukin 1 Beta Levels MPO activity was found to be significantly high in all of the tissue samples of the saline-treated CLP group when compared with the saline-treated sham group (p<0.01–0.001; Fig. 4). CLP-induced elevation in MPO activity were only significantly decreased in renal tissue in the dapagliflozin-treatment group (p<0.05; Fig. 4). TNF-α and IL-1β levels demonstrated a statistically significant increase in the saline-treated CLP group when compared with the saline-treated sham group in lung and liver tissues (p<0.05–0.001). Administration of dapagliflozin significantly Kidney **

30 *

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Regular morphology of the interstitial space, Bowman’s space and glomeruli, proximal and distal tubules were seen in kidney tissues obtained from the saline-treated sham and dapagliflozin-treated sham groups (Fig. 6a, b). In the saline-treated CLP group, interstitial bleeding, glomerular congestion, significant dilation of Bowman’s space, and tubular degeneration were observed (Fig. 6c). Regression in the dilation of Bowman’s space, tubular degeneration, moderate glomerular congestion, mild interstitial bleeding, and vascular congestion were observed in the dapagliflozin-treated CLP group (Fig. 6d). Regular parenchyma morphology was also seen in liver tissue collected from the saline and dapagliflozin treated sham groups (Fig. 7a, b). In the saline-treated CLP group, significant sinusoidal congestion, degenerated hepatocytes, and an increased number of activated Kupffer cells were observed

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In the saline-treated CLP group, caspase-8 and 9 activity in kidney, lung, and liver tissues was significantly greater when compared with the saline-treated sham group (p<0.01– 0.001; Fig. 5). Dapagliflozin administration did not alleviate CLP-induced apoptosis and there was a significant increase (p<0.001) in caspase-8 activity in kidney tissue samples when compared with the saline-treated CLP group.

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diminished these alterations in the saline-treated CLP group (p<0.01–0.001; Fig. 4).

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Figure 3. Dapagliflozin reduced the level of malondialdehyde (MDA) in kidney, lung and liver tissue, and increased the level of glutathione (GSH) in kidney tissue. (a) Kidney MDA level after dapagliflozin treatment. (b) Kidney GSH level after dapagliflozin treatment. (c) Lung MDA level after dapagliflozin treatment. (d) Lung GSH level after dapagliflozin treatment. (e) Liver MDA level after dapagliflozin treatment. (f) Liver GSH level after dapagliflozin treatment. The data are presented as the mean±SEM. One-way analysis of variance and post hoc Tukey-Kramer multiple comparison tests were used. *p<0.05, **p<0.01, ***p<0.001 vs saline-treated sham group. Each group consisted of 6–8 samples.

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Figure 4. Dapagliflozin reduced the level of myeloperoxidase (MPO) only in kidney tissue, and decreased the level of tumor necrosis factor alpha (TNF-α) in lung and liver tissue and the level of interleukin 1beta (IL-1β) in liver tissue. (a) Kidney MPO level after dapagliflozin treatment. (b) Kidney TNF-α level after dapagliflozin treatment. (c) Kidney IL-1β level after dapagliflozin treatment. (d) Lung MPO level after dapagliflozin treatment. (e) Lung TNF-α level after dapagliflozin treatment. (f) Lung IL-1β level after dapagliflozin treatment. (g) Liver MPO level after dapagliflozin treatment. (h) Liver TNF-α level after dapagliflozin treatment. (i) Liver IL-1β level after dapagliflozin treatment. The data are presented as the mean±SEM. One-way analysis of variance and post hoc Tukey-Kramer multiple comparison tests were used. *p<0.05, **p<0.01, ***p<0.001 vs saline-treated sham group. Each group consisted of 6–8 samples.

(Fig. 7c). Sinusoidal congestion, and degenerated hepatocytes and activated Kupffer cells were reduced in the dapagliflozintreated CLP group (Fig. 7d). Regular parenchyma morphology was viewed in lung tissue obtained from the saline-treated sham and dapagliflozin-treated sham groups (Fig. 8a, b). Severe interstitial bleed-ing and vascular congestion, cellular debris in the alveolar lu-men, and degenerated alveolar structures were observed in the salinetreated CLP group (Fig. 8c). Moderate interstitial bleeding and vascular congestion, partial degeneration of alveolar structures, cellular debris in the lumen of a number of alveoli, and in some regions, alveoli with regular morphology were seen in the dapagliflozin-treated CLP group (Fig. 8d).

DISCUSSION Dapagliflozin reduced oxidative stress (MDA) and inflammaUlus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

tion (MPO), but conversely, increased the level of antioxidants (GSH) in the kidney. Recovery of histological features of renal injury was demonstrated. In addition, dapagliflozin treatment decreased oxidative stress (MDA) and inflammation (TNF-α) in lung tissue. A slight recovery in the histological features of lung injury was noted. Additionally, dapagliflozin treatment lowered inflammation (TNF-α, IL-1β), but there was only a limited decrease in the level of oxidative stress in the liver. A slight recovery in the histological features of liver injury was observed. Immune system function declines with diabetes mellitus. This altered immune response can lead to the progression toward sepsis through the growth of microorganisms. In experimental animal models and diabetic human studies, deficiencies in immunoreactivity have been shown to increase susceptibility to sepsis and other infections. In patients with Type 1 diabetes, 217

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Figure 5. Dapagliflozin increased the level of caspase 8 only in kidney tissue. No changes were observed in the level of caspase 9. (a) Kidney caspase 8 level after dapagliflozin treatment. (b) Kidney caspase 9 level after dapagliflozin treatment. (c) Lung caspase 8 level after dapagliflozin treatment. (d) Lung caspase 9 level after dapagliflozin treatment. (e) Liver caspase 8 level after dapagliflozin treatment. (f) Liver caspase 9 level after dapagliflozin treatment. The data are presented as the mean±SEM. One-way analysis of variance and post hoc Tukey-Kramer multiple comparison tests were used. *p<0.05, **p<0.01, ***p<0.001 vs saline-treated sham group. Each group consisted of 6–8 samples. (a)

(b)

(c)

(d)

Figure 6. Representative photomicrographs of kidney tissue in the experimental groups. Regular kidney morphology in saline-treated sham control (a) and dapagliflozin-treated sham control (b) groups. Interstitial bleeding (arrowhead) and glomerular congestion, dilation of Bowman’s space (*), degenerated tubules (arrow) seen in saline-treated cecal ligation and puncture (CLP) group (c) and Bowman’s capsule with regular morphology (*), mild glomerular congestion (*, upper inset), vascular congestion (arrowhead), and a few damaged tubules (arrow) in the dapagliflozin-treated CLP group (d). H&E staining, A and B insets, C and D below insets: PAS staining, scale bars: 50 µm (x20), inset: 20 µm (x40). (a)

(b)

(c)

(d)

Figure 7. Representative photomicrographs of liver tissue in the experimental groups. Regular liver parenchyma in saline-treated sham control (a) and dapagliflozin-treated sham control (b) groups with severe sinusoidal dilation and congestion (*), numerous damaged hepatocytes (arrow) and activated Kupffer cells (arrowhead), and in the saline-treated cecal ligation and puncture (CLP) group (c), mild sinusoidal congestion (*), a few damaged hepatocytes (arrow), and activated Kupffer cells (arrowhead) in the dapagliflozin-treated CLP group (d). H&E staining, scale bar: 20 µm (x40).

neutrophil function (chemotaxis, phagocytosis, and cell death), reactive oxygen species production, bacteremia, and sepsis may occur as a result of the impairment in bacterial control 218

at the infection site. The prognosis of patients with sepsis is more pronounced in patients with type 2 diabetes compared with type 1 diabetes. The mortality rate is significantly high in Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Kıngır et al. Effects of dapagliflozin in experimental sepsis model in rats (a)

(b)

(c)

(d)

Figure 8. Representative photomicrographs of lung tissue in the experimental groups. Lung parenchyma with regular morphology in the saline-treated sham (a) and dapagliflozin-treated sham (b) groups and severe interstitial bleeding (*) and vascular congestion, degeneration in alveolar structure (arrow) in the saline-treated cecal ligation and puncture (CLP) group (c) with mild interstitial bleeding (*) and vascular congestion, partly degeneration of alveolar structure (arrow), and regular alveolar morphology (arrow, inset) in the dapagliflozintreated CLP group in some places (d). H&E staining, scale bars: 50 µm (x20).

sepsis patients and sepsis can be a common consequence in diabetic patients. Therefore, new treatments are needed.[21] Dapagliflozin, a new drug used in the treatment of diabetes, is an inhibitor of SGLT2.[9] A review of the literature did not reveal any studies of dapagliflozin and sepsis as yet. However, consistent with the results of the present study, it has been reported that dapagliflozin (10 mg/kg/day) decreased BUN and creatinin levels in a renal ischemic reperfusion model in rats and had a protective effect on renal tubular cells.[9] In addition, it has been shown that dapagliflozin reduced apoptotic cell death by inducing hypoxia inducible factor 1 in ischemic renal tissue and ischemic tubular cell cultures and decreasing Bax/BcL2 ratio and terminal dUTP nick-end labeling-positive cells.[9] Depending on the characteristics of a critical illness (sepsis, burns, etc.), acute hyperglycemia and insulin resistance can develop even if there is no history of diabetes mellitus in the patient. This condition has been assessed as a stress response. The development of this response may involve the release of inflammatory cytokines such as TNF-α and IL-6; an increase in stress hormones, such as cortisol; and the use of drugs such as corticosteroids. In the case of sepsis or septic shock, hyperglycemia occurs at an early stage and hypoglycemia has a late stage development.[22,23] In our study, the decrease in blood glucose levels in the sepsis group when compared with the control suggests late-stage sepsis. In a study of mice using a sepsis model (CLP), it was demonstrated that blood glucose levels decreased in the sepsis group and that the glucose levels increased in the group given pioglitazone, which is also an anti-diabetic agent.[24] In our study, there was a decrease in blood glucose levels in the CLP group, consistent with other research available in the literature.[23–27] In the present study, although glucose levels were significantly increased in the dapagliflozin-treated sham group, there was no significant change in the glucose levels of the dapagliflozin-treated CLP group. Therefore, the positive findings of the current study do not suggest that dapagliflozin makes a strong contribution to glucose control. In CLP studies performed on rats, serum TNF-α, IL-6, BUN, and creatinine levels were higher in the sepsis group compared with the control group. Increases in MDA and MPO Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

values, a decrease in GSH values, and an increase in apoptosis were observed in the kidney, and histological examination showed renal tissue damage.[28–34] Similar findings were obtained in the sepsis model applied in our study. It was determined that there was no significant difference in the serum creatinine value between the groups, but a significant increase was noted in the CLP group after 72 hours. In addition, oxidative stress parameters and apoptotic (caspase 3) values were greater in the CLP group compared with the controls and more tissue damage was determined in the kidney and lung tissue in the histological examination.[35] Serum BUN and creatinine values in our study were consistent with the findings of sepsis (CLP method) in the literature.[8,35] In another study, TNF-α, IL-1β, IL-6, MDA, and MPO levels of lung tissue were greater in the sepsis group compared with the control group. GSH levels were lower.[28,36–40] In the histopathological evaluation, severe tissue damage was reported.[38] These results are also consistent with the findings we obtained in our sepsis model. It has also been reported that there were increases in the levels of caspase 3 and Bax/BcL 2 in the lungs.[40] The MDA level in liver tissue was elevated, whereas the GSH level decreased in the sepsis group compared with the controls.[31,39] These results are consistent with our sepsis model. In another study, rats were evaluated 24 hours after CLP, and when the sepsis group was compared with the control group, the MDA level was significantly higher in the liver tissue, but there was no increase in the kidney or lung tissues. MPO values increased in the lung; however, there was no significant difference in the liver or kidney tissues. In the same study, plasma cytokines (TNF-α, IL-1β, etc.), BUN, and creatinine levels were greater in the CLP group, and there was no significant decline in glucose levels.[25] Other research indicated that there was an increase in kidney MPO values as well as MDA values in kidney and liver tissue, but there was no significant different in liver MPO level.[41] The effect of long-term use of dapagliflozin on glucose homeostasis and diabetic nephropathy has previously been investigated. Dapagliflozin has improved hyperglycemia and albuminuria, depending on the dose (0.1–1.0 mg/kg), and reduced macrophage infiltration, gene expression of inflammatory cytokines, and oxidative stress in diabetic mice. There was 219

Kıngır et al. Effects of dapagliflozin in experimental sepsis model in rats

no significant difference in BUN or serum creatinine levels.[8] These results are consistent with those of our study. Other researchers found that dapagliflozin reduced oxidative stress and apoptosis induced by high glucose in type 1 diabetic mice, alleviated diabetic nephropathy, and reduced macrophage infiltration.[42] In another study, the effect of SGLT inhibition on polycystic kidney dysfunction was investigated in rats. Dapagliflozin (10 mg/kg) was found to unexpectedly cause an increase in cyst volume with albuminuria, hyperfiltration, and polycystic kidney failure in rats.[43] Additional studies should be conducted to develop new alternatives for prophylactic treatment of sepsis and to investigate the different effects of this new medicine, dapagliflozin. The results of our study suggest that diabetic patients using dapagliflozin may also benefit from the effect on oxidative stress. As a result, the findings of this study highlighted a possible protective effect of dapagliflozin in renal damage. Dapagliflozin also slightly alleviated lung and liver injury.

Acknowledgement This work was supported by Marmara University Scientific Research Projects Committee (SAG-C-YLP-090217-0040), İstanbul, Turkey. Conflict of interest: None declared.

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11. Thomson SC, Rieg T, Miracle C, Mansoury H, Whaley J, Vallon V, et al. Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat. Am J Physiol Regul Integr Comp Physiol 2012;302:R75–83. 12. Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, et al. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol 2013;715:246–55. 13. Craciun FL, Schuller ER, Remick DG. Early enhanced local neutrophil recruitment in peritonitis-induced sepsis improves bacterial clearance and survival. J Immunol 2010;185:6930–8. 14. Shafaroodi H, Hassanipour M, Mousavi Z, Rahimi N, Dehpour AR. The Effects of Sub-Chronic Treatment with Pioglitazone on the Septic Mice Mortality in the Model of Cecal Ligation and Puncture: Involvement of Nitric Oxide Pathway. Acta Med Iran 2015;53:608–16. 15. Tsujimura Y, Matsutani T, Matsuda A, Kutsukake M, Uchida E, Sasajima K, et al. Effects of pioglitazone on survival and omental adipocyte function in mice with sepsis induced by cecal ligation and puncture. J Surg Res 2011;171:e215–21. 16. Gao M, Jiang Y, Xiao X, Peng Y, Xiao X, Yang M. Protective effect of pioglitazone on sepsis-induced intestinal injury in a rodent model. J Surg Res 2015;195:550–8. 17. Rodriguez D, Kapoor S, Edenhofer I, Segerer S, Riwanto M, Kipar A, et al. Inhibition of Sodium-Glucose Cotransporter 2 with Dapagliflozin in Han: SPRD Rats with Polycystic Kidney Disease. Kidney Blood Press Res 2015;40:638–47. 18. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8. 19. Casini AF, Ferrali M, Pompella A, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzeneintoxicated mice. Am J Pathol 1986;123:520–31. 20. Beutler S. Glutathione in red blood cell metabolism. In: Beutler E, editor. A manual of biochemical methods. 2nd ed. New York: Grune and Stratton; 1975. p. 112–14. 21. Trevelin SC, Carlos D, Beretta M, da Silva JS, Cunha FQ. Diabetes Mellitus and Sepsis: A Challenging Association. Shock 2017;47:276–87. 22. Ürkmez S. Sepsiste Kan Şekeri Kontrolü. İÜ Cerrahpaşa Tıp Fakültesi Sürekli Tıp Eğitimi Etkinlikleri: Güncel Bilgiler Işığında Sepsis Sempozyum Dizisi. 2006;51:89–97. 23. Ferreira FBD, Dos Santos C, Bruxel MA, Nunes EA, Spiller F, Rafacho A. Glucose homeostasis in two degrees of sepsis lethality induced by caecum ligation and puncture in mice. Int J Exp Pathol 2017;98:329–40. 24. Kaplan J, Nowell M, Chima R, Zingarelli B. Pioglitazone reduces inflammation through inhibition of NF-κB in polymicrobial sepsis. Innate Immun 2014;20:519–28. 25. Ahmad A, Druzhyna N, Szabo C. Delayed Treatment with Sodium Hydrosulfide Improves Regional Blood Flow and Alleviates Cecal Ligation and Puncture (CLP)-Induced Septic Shock. Shock 2016;46:183–93. 26. Heuer JG, Bailey DL, Sharma GR, Zhang T, Ding C, Ford A, et al. Cecal ligation and puncture with total parenteral nutrition: a clinically relevant model of the metabolic, hormonal, and inflammatory dysfunction associated with critical illness. J Surg Res 2004;121:178–86. 27. Yamashita H, Ishikawa M, Inoue T, Usami M, Usami Y, Kotani J. Interleukin-18 Reduces Blood Glucose and Modulates PlasmaCorticosterone in a Septic Mouse Model. Shock 2017;47:455–462. 28. Cadirci E, Halici Z, Odabasoglu F, Albayrak A, Karakus E, Unal D, et al. Sildenafil treatment attenuates lung and kidney injury due to overproduction of oxidant activity in a rat model of sepsis: a biochemical and histopathological study. Clin Exp Immunol 2011;166:374–84. 29. Wang A, Xiao Z, Zhou L, Zhang J, Li X, He Q. The protective effect of atractylenolide I on systemic inflammation in the mouse model of sepsis created by cecal ligation and puncture. Pharm Biol 2016;54:146–50.

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Kıngır et al. Effects of dapagliflozin in experimental sepsis model in rats 30. Xu L, Nagata N, Nagashimada M, Zhuge F, Ni Y, Chen G, et al. SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice. EBioMedicine 2017;20:137– 49. 31. Aydın S, Şahin TT, Bacanlı M, Taner G, Başaran AA, Aydın M, et al. Resveratrol Protects Sepsis-Induced Oxidative DNA Damage in Liver and Kidney of Rats. Balkan Med J 2016;33:594–601. 32. Yu C, Li P, Qi D, Wang L, Qu HL, Zhang YJ, et al. Osthole protects sepsis-induced acute kidney injury via down-regulating NF-κB signal pathway. Oncotarget 2017;8:4796–813. 33. Başol N, Erbaş O, Çavuşoğlu T, Meral A, Ateş U. Beneficial effects of agomelatine in experimental model of sepsis-related acute kidney injury. Ulus Travma Acil Cerrahi Derg 2016;22:121–6. 34. Zhao WY, Zhang L, Sui MX, Zhu YH, Zeng L. Protective effects of sirtuin 3 in a murine model of sepsis-inducedacute kidney injury. Sci Rep 2016;6:33201. 35. Sung PH, Chang CL, Tsai TH, Chang LT, Leu S, Chen YL, et al. Apoptotic adipose-derived mesenchymal stem cell therapy protectsagainst lung and kidney injury in sepsis syndrome caused by cecalligation puncture in rats. Stem Cell Res Ther 2013;4:155. 36. Chen HH, Chang CL, Lin KC, Sung PH, Chai HT, Zhen YY, et al. Melatonin augments apoptotic adipose-derived mesenchymal stem cell treatment against sepsis-induced acute lung injury. Am J Transl Res 2014;6:439–58.

37. Zolali E, Asgharian P, Hamishehkar H, Kouhsoltani M, Khodaii H, Hamishehkar H. Effects of gamma oryzanol on factors of oxidative stress and sepsis-induced lung injury in experimental animal model. Iran J Basic Med Sci 2015;18:1257–63. 38. Zong Y, Zhang H. Amentoflavone prevents sepsis-associated acute lung injury through Nrf2-GCLc-mediated upregulation of glutathione. Acta Biochim Pol 2017;64:93–8. 39. Aliomrani M, Sepand MR, Mirzaei HR, Kazemi AR, Nekonam S, Sabzevari O. Effects of phloretin on oxidative and inflammatory reaction in ratmodel of cecal ligation and puncture induced sepsis. Daru 2016;24:15. 40. Ge L, Hu Q, Shi M, Yang H, Zhu G. Design and discovery of novel thiazole derivatives as potential MMP inhibitors to protect against acute lung injury in sepsis rats via attenuation of inflammation and apoptotic oxidative stress. Rsc Advances 2017;7:32909–22. 41. Aksoy AN, Toker A, Celık M, Aksoy M, Halıcı Z, Aksoy H. The effect of progesterone on systemic inflammation and oxidative stress in the rat model of sepsis. Indian J Pharmacol 2014;46:622–6. 42. Hatanaka T, Ogawa D, Tachibana H, Eguchi J, Inoue T, Yamada H, et al. Inhibition of SGLT2 alleviates diabetic nephropathy by suppressinghigh glucose-induced oxidative stress in type 1 diabetic mice. Pharmacol Res Perspect 2016;4:e00239. 43. Kapoor S, Rodriguez D, Riwanto M, Edenhofer I, Segerer S, Mitchell K, et al. Effect of Sodium-Glucose Cotransport Inhibition on Polycystic Kidney Disease Progression in PCK Rats. PLoS One 2015;10:e0125603.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Dapagliflozin’in sıçanlarda deneysel sepsis modeli üzerine etkileri Zehra Betül Kıngır,1 Dr. Zarife Nigar Özdemir-Kumral,2 Dr. Muhammet Emin Çam,3 Dr. Özlem Tuğçe Çilingir,4 Turgut Şekerler,5 Dr. Feriha Ercan,4 Dr. Özlem Bingol-Özakpınar,5 Dr. Derya Özsavcı,5 Dr. Mesut Sancar,1 Dr. Betül Okuyan1 Marmara Üniversitesi Eczacılık Fakültesi, Klinik Eczacılık Anabilim Dalı, İstanbul Marmara Üniversitesi Tıp Fakültesi, Fizyoloji Anabilim Dalı, İstanbul 3 Marmara Üniversitesi Eczacılık Fakültesi, Farmakoloji Anabilim Dalı, İstanbul 4 Marmara Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, İstanbul 5 Marmara Üniversitesi Eczacılık Fakültesi, Biyokimya Anabilim Dalı, İstanbul 1 2

AMAÇ: Bu çalışmada, sıçanlarda dapagiflozinin deneysel sepsis modeli üzerindeki olası koruyucu etkilerinin değerlendirilmesi amaçlandı. GEREÇ VE YÖNTEM: Sprague-Dawley sıçanlara cerrahi operasyonların 5 gün öncesinde serum fizyolojik (1 mL/kg, p.o.) veya dapagliflozin (10 mg/kg, p.o.) verilmeye başlandı. Sepsis, anestezi altında, çekal ligasyon ve perforasyon modeli ile oluşturulurken, sham kontrol gruplarına sadece laparotomi yapıldı. Serumda BUN, kreatinin ve glukoz düzeyleri; dokularda (böbrek, karaciğer ve akciğer) ise MDA, GSH, MPO, TNF-α, IL-1β, kaspaz 8 ve kaspaz 9 düzeyleri belirlendi. Bu dokularda histolojik değerlendirme de yapıldı. BULGULAR: Sepsiste dapagliflozin uygulaması, böbrek dokularında oksidatif stresi (MDA) azalttı, antioksidan düzeyleri (GSH) arttırdı ve enflamasyonu (MPO) azalttı (p<0.05). Sepsiste dapagliflozin uygulaması akciğer dokularında oksidatif stresi (MDA) azalttı, akciğer ve karaciğer dokularında ise enflamasyonu (MPO) azalttı (p<0.05). Ayrıca, böbrek, akciğer ve karaciğer dokularında kaspaz 8 ve 9 düzeylerini arttırdı (p<0.05). Histopatolojik sonuçlara göre, dapagliflozin uygulaması böbrek dokularında orta derece; akciğer ve karaciğer dokularında ise hafif iyileştirdi. TARTIŞMA: Bu çalışmada, dapagliflozinin deneysel sepsis modelinde böbrek hasarını önleyici etkisinin olduğu gösterilmesine rağmen akciğer ve karaciğer dokuları üzerine hafif koruyucu etkisi olduğu bulunmuştur. Anahtar sözcükler: Apoptoz; dapagliflozin; enflamasyon; oksidatif stres; sepsis. Ulus Travma Acil Cerrahi Derg 2019;25(3):213-221

doi: 10.5505/tjtes.2018.82826

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ORIGIN A L A R T IC L E

Role of neutrophil-to-lymphocyte ratio and plateletto-lymphocyte ratio in identifying complicated appendicitis in the pediatric emergency department Binnaz Çelik, M.D.,1 Hülya Nalçacıoğlu, M.D.,2 Yasemin Altuner Torun, M.D.4

Mustafa Özçatal, M.D.,3

Department of Pediatrics, Kayseri Training and Research Hospital, Kayseri-Turkey

Department of Pediatric Nephrology, Kayseri Training and Research Hospital, Kayseri-Turkey

Department of Pediatric Surgery, Kayseri Training and Research Hospital, Kayseri-Turkey

Department of Pediatric Hematology-Oncology, Kayseri Training and Research Hospital, Kayseri-Turkey

ABSTRACT BACKGROUND: The objective of this research was to evaluate the potential clinical utility of baseline hematological parameters measured on admission as adjuncts in the identification of complicated and uncomplicated appendicitis in children. METHODS: The records of a total of 334 pediatric patients who underwent curative surgery for acute appendicitis (AA) between 2015 and 2016 were retrospectively investigated. The patients were categorized as complicated or uncomplicated appendicitis based on the histopathological reports. The clinical features and baseline hematological parameters of leukocyte count, neutrophil percentage, thrombocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), red cell distribution width (RDW), and platelet distribution width (PDW) of the groups were compared. RESULTS: Complicated AA was determined in 36 (10.8%) patients. The white blood cell count (WBC) (p<.001), neutrophil percentage (p<.001), NLR (p<.001), and PLR (p=.004) were higher in the complicated appendicitis group compared with the uncomplicated group, while the RDW, MPV, and PDW levels were uninformative. Analysis of receiver operating characteristic curves yielded the cut off values of 14.870 cell/mm3 for WBC (area under the curve [AUC]: 0.675; sensitivity: 86.1%; specificity: 41.6%), 10.4 for NLR (AUC: 0.717; sensitivity: 61.1%; specificity: 73.2%), and 284 for PLR (AUC: 0.647; sensitivity: 42%; specificity: 86%) were found to be the best predictive values for the determination of complicated acute appendicitis. CONCLUSION: The present study demonstrated that AA patients with higher NLR and PLR levels might be more likely to develop a complication. The NLR and PLR values combined with a physical examination, imaging studies, and other laboratory tests may help clinicians to identify high-risk AA patients in the emergency department. Keywords: Acute appendicitis; complicated; neutrophil-to-lymphocyte ratio; pediatrics; platelet-to-lymphocyte ratio.

INTRODUCTION Acute appendicitis (AA) is a common surgical disease which occurs in almost all age groups, and especially in childhood. A clinical history and physical examination remain the basis of the diagnosis. Other diagnostic tools, such as inflammatory markers and imaging studies, including ultrasonography (US)

and computed tomography (CT), are of significant help in the diagnostic process.[1] Despite the development of diagnostic advances, approximately 30% of patients, in particular children under the age of 5 years, are revealed to have perforation at diagnosis, and 28% to 57% of older children present with missed and de-

Cite this article as: Çelik B, Nalçacıoğlu H, Özçatal M, Altuner Torun Y. Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in identifying complicated appendicitis in the pediatric emergency department. Ulus Travma Acil Cerrahi Derg 2019;25:222-228. Address for correspondence: Binnaz Çelik, M.D. Kayseri Eğitim ve Araştırma Hastanesi, Pediatri Kliniği, Kayseri, Turkey. Tel: +90 352 - 336 88 84 E-mail: btekatli2003@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):222-228 DOI: 10.5505/tjtes.2018.06709 Submitted: 04.04.2018 Accepted: 22.10.2018 Online: 15.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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layed diagnosis.[2,3] An initial misdiagnosis can be the result of nonspecific presenting symptoms or a difficult physical examination due to an anxious or distressed child. Another challenge is the variability in appendicular location, such as a hidden or retrocecal appendicitis, which may not exhibit enough peritoneal signs to support the diagnosis of AA.[3,4] Delay in the diagnosis and surgery for AA may lead to complications associated with perforation, gangrene, and intraabdominal abscess formation.[3,5] Optimal treatment depends on early diagnosis followed by rapid intervention. A number of inflammatory markers have long been proposed as a tool to support the clinical data in the decisionmaking process to determine AA.[6,7] The most studied and used in clinical practice include the measurement of white blood cell count (WBC), absolute neutrophil count, and C-reactive protein.[8–18] Recently, other potential markers of appendicitis have been evaluated and reported as potential predictors. such as procalcitonin,[10] bilirubin,[19] calprotectin,[20] interlekin-6,[21] and fibrinogen.[22,23] However, these tests require special equipment and may not be available in some hospitals. The complete blood count (CBC) is the most frequently used and easily found baseline hematological parameter in clinical laboratories. The parameters of leukocyte count, neutrophil percentage, thrombocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-tolymphocyte ratio (PLR), mean platelet volume (MPV), red cell distribution width (RDW), and platelet distribution width (PDW) have been studied for use in the diagnosis and prediction of complicated AA.[24–31] However, their role in the diagnosis of appendicitis has yielded diverse and controversial results.[5–10,32] Therefore, the aim of this study was to assess the potential use of basic laboratory parameters of the CBC: leukocyte count, neutrophil percentage, thrombocyte count, NLR, PLR, MPV, RDW, and PDW, in the diagnosis of AA and determining complicated appendicitis on admission in pediatric patients.

MATERIALS AND METHODS The medical records of 334 pediatric patients at a single institution who underwent appendectomy between January 2015 and December 2016 and had histopathological findings consistent with AA were retrospectively analyzed. The preoperative clinical diagnosis was AA in all patients. For each patient, the age; sex; presenting symptoms; laboratory values of WBC, neutrophil percentage, thrombocyte count, NLR, PLR, MPV, RDW, and PDW; abdominal US (appendiceal diameter); contrast-enhanced CT; and pathological findings were investigated. The CBC was measured at admission with an automated hematology analyzer (LH 780 analyzer; Beckman Coulter, Inc., Brea, CA, USA). The markers recorded were WBC, Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

neutrophils, lymphocytes, platelets, RDW, MPV, and PDW. The NLR and PLR were calculated using the neutrophil, platelet, and lymphocyte counts as part of the routine preoperative workup. The normal WBC value was accepted as 4.5–11×103/mm3. The pathological diagnosis of AA was based on intraoperative findings combined with a macroscopic and histological examination of the resected appendix. Patients were classified into 2 groups according to the intraoperative findings and pathology reports: complicated (gangrenous, perforated, or abcess) and uncomplicated AA (suppurative appendicitis). The patients included in this study had a pathological confirmation of acute appendicitis. This study was approved by the Clinical Research Ethics Committee of Kayseri Research and Training Hospital (12.06.2017/05).

Statistical Analysis Analyses were performed using SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA). The compatibility of variables were investigated using the Shapiro-Wilks test. The characteristics of patients were expressed using descriptive statistics. Parameters compatible with normal distribution were described as mean±SD, and parameters that did not fit normal distribution were described with the median and distribution (lower-upper limit). The comparisons of proportions were performed with a chi-square test. For comparisons between the uncomplicated and the complicated groups, an independent samples t-test was used for the parameters with normal distribution and the Mann-Whitney U test was used for the parameters with non-normal distribution. A summary receiver operating characteristic (sROC) curve was utilized to characterize and compare the accuracy of the hematological ratios. An sROC curve is a graphical representation of sensitivity (x-axis) plotted against 1 – specificity (y-axis). The area under the curve (AUC) represented the accuracy of the marker in distinguishing between complicated and uncomplicated AA. Cut-off values were calculated for each biomarker using Youden’s index. Sensitivity and specificity with 95% confidence intervals and the likelihood ratio (LR) were also calculated. P<0.05 was considered to be statistically significant.

RESULTS A total of 334 patients underwent an appendectomy at the institution during the study period. The median age of the study group was 11 years (range: 3–16 years). In all, 210 (62.9%) were male and 124 (37.1%) were female. Non-complicated appendicitis was found in 298 (89.2%) patients while 36 (10.8 %) patients had complicated appendicitis. No significant differences were found between the uncomplicated and complicated group in terms of age or gender (p=0.091, p=0.219, respectively). 223

Çelik et al. Role of NLR and PLR in identifying complicated appendicitis in the pediatric emergency department

Table 1. Baseline clinical characteristics of the study cohort Variables

Pathologically confirmed appendicitis

Study population (n=334)

Uncomplicated (n=298, %)

Complicated (n=36, %)

Age (years)

11 (3–16)

10 (3–16)

0.091

Gender, male, n ( %)

210 (62.9)

184 (61.7)

26 (72.2)

0.219

10 (3)

8 (2.7)

2 (5.6)

0.271

Clinical findings, n (%)

Fever

Abdominal pain

333 (99.7)

298 (100)

35 (97.2)

0.004

Vomiting

186 (55.7)

160 (53.7)

26 (72.2)

0.013

Diarrhea

23 (6.9)

20 (6.7)

3 (8.3)

0.639

Baseline laboratory findings, n (%)

Leukocyte count (cell/mm3)

Neutrophils (%)

16.511±4864

Thrombocyte count (cell/mm ) 299.500

82 (43–95) 3

(156.000–552.000)

16.170±4805

19.330±4472 <0.001

81 (43–95)

85 (66–93)

298.000

(156.000–552.000)

<0.001

309.000 0.610

(167.000–532.000)

NLR

7.4 (0.85–56.8)

6.9 (0.85–56.8)

12.7 (3.19–30)

<0.001

PLR

161.7 (26.39–870)

156.2 (26.4–870)

234 (68–629)

0.004

RDW

13.3 (11.3–17.8)

13.7 (11.9–16)

MPV

PDW

9.49±1.08

9.47±1.074

9.66±1.141

0.207 0.304

15.4 (8–17.80)

15.4 (8–17.8)

15.5 (8.7–17.7)

0.161

25 (7.5)

20 (6.7)

5 (13.9)

<0.001

Individual US findings (appendiceal diameter), n (%)

Appendix not visualized

<6 mm

13 (3.9)

11 (3.7)

2 (5.6)

6–8 mm

139 (41.6)

136 (45.6)

3 (8.3)

>8 mm

137 (41)

128 (43)

9 (25)

Perforated

16 (4.8)

3 (1)

13 (36.1)

Abscess

4 (1.2)

0 (0)

4 (11.1)

Individual CT findings, n (%)

Appendicitis

Perforation/abscess

11 (3)

9 (3)

2 (5.6)

1/1

0 (0)s

1 (2.8)/1 (2.8)

0.070

Data are presented as mean±SD or as median with range. P<0.05 was considered significant. MPV: Mean platelet volume; NLR: Neutrophil-to-lymphocyte ratio; PDW: Platelet distribution volume; PLR: Platelet-to-lymphocyte ratio; RDW: Red cell distribution volume.

The most frequently observed symptoms were abdominal pain (99.7%) and vomiting (55.7%). These findings were significantly different in the complicated group compared with the uncomplicated group (p=0.004, p=0.013, respectively). The laboratory results of the study group and comparisons between the 2 groups are shown in Table 1. There was a significant difference in the WBC, neutrophil percentage, NLR, and PLR results between the complicated group and the uncomplicated group. The mean WBC count in the complicated group was 19.330±4472 cell/mm3, and it was significantly higher than that of the uncomplicated AA group (p<0.001). The median neutrophil percentage, NLR, 224

and PLR in the complicated AA group was 85%, 12,7 and 234, respectively and these values were significantly higher in the complicated AA group (p<0.00, p<0.001, p=0.004, respectively). Figure 1 illustrates the distribution of the parameters in the complicated and uncomplicated AA groups. There was no significant difference between the complicated and uncomplicated AA groups in the median thrombocyte count, RDW, MPV, or PDW (p=0.610, p=0.207, p=0.304, p=0.161, respectively). Based on the US findings, a total of 309 (92.5%) patients had a visualized appendix. The most frequent appendix diameter was 6–8 mm (139 patients, 41.6%), followed by a diameter Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Çelik et al. Role of NLR and PLR in identifying complicated appendicitis in the pediatric emergency department

Table 2. Receiver operating characteristic curve results of hematological indices for discrimination of complicated from uncomplicated appendicitis Predictors

Complicated and uncomplicated acute appendicitis

AUC

Cutoff

Sensitivity (95% CI)

Specificity (95% CI)

LR+

LR-

Leukocyte count (cell/mm3)

0.675

0.001

14.870

86.1 (71–95.3)

41.6 (36–47.4)

1.48

0.33

Neutrophil %

0.678

<0.001

97.2 (85.5–99.9)

32.2 (27–38)

1.43

0.09

NLR

0.717

<0.001

10.4

61.1 (44–77)

73.2 (68–78)

2.28

0.53

PLR

0.647

0.004

284

42 (26–60)

86 (81–89)

2.89

0.68

AUC: Area under the curve; LR+: Likelihood ratio positive; LR-: Likelihood ratio negative; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio.

of >8 mm (137 patients, 41%). Perforated appendicitis was seen in 16 (4.8 %) patients, 13 of whom were in complicated group. All 4 (1.2%) patients with an abscess were in the complicated group. These findings represented a significant difference between the complicated group and the uncomplicated group (p<0.001). Abdominal CT was performed for 13 patients with a diagnosis of perforation, and CT revealed an abcess in 1 patient (Table 1).

80 70 40

5000

Neutrophil %

15000

Leukocyte

25000

An sROC curve was employed to evaluate the accuracy of hematological indices in distinguishing between complicated and uncomplicated AA. The AUC reflects marker accuracy

and p values reflect statistical significance for the given population. Curves representing each hematological index were plotted and compared. WBC (AUC: 0.675; p=0.001), neutrophil percentage (AUC: 0.678; p<0.001), NLR (AUC: 0.717; p<0.001), and PLR (AUC: 0.647; p=0.004) were the most accurate markers in distinguishing the 2 groups (complicated vs. uncomplicated; Table 2, Fig. 2). Utilizing WBC >14.87 cell/ mm3 as a predictor of complicated AA, the cutoff point had a sensitivity of 86.1% and a specificity of 41.6%. A neutrophil percentage of >76% had a sensitivity of 97.2% and a specificity of 32.2% for determining complicated AA. Utilizing a NLR >10.4 as a predictor of complicated AA, the cutoff point

Complicated AA

Uncomplicated AA

Complicated AA

Uncomplicated AA

Complicated AA

800 600 400 200 0

platelets to lymphocyte ratio

Neutrophil-to-lymphocyte ratio 10 20 30 40 50

Uncomplicated AA

Complicated AA

Figure 1. Distiribution graph of the hematologic indices (leukocyte, neutrophil percentage, NLR, PLR) in complicated and uncomplicated AA. AA: Acute appendicitis; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio.

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In this study, the focus was to determine the predictive significance for complicated AA of markers of inﬂammation in the CBC. WBC, neutrophil percentage, thrombocyte count, NLR, PLR, MPV, RDW, PDW were assessed. To best of our knowledge, this is the first study to utilize CBC parameters with the intent of evaluating the ability to diﬀerentiate complicated AA from uncomplicated AA in the pediatric age group. We found that admission values of WBC, neutrophil percentage, NLR, and PLR were all significantly increased in patients with complicated appendicitis compared with patients suffering from uncomplicated AA.

ROC curve

1.0

Sensitivity

0.8

0.6

0.4 Source of the Curve Leukocyte count Neutrophils (%) NLR PLR Reference Line

0.2

0.0 0.0

0.2

0.4 0.6 1 - Specificity

0.8

1.0

Figure 2. ROC curves for leukocyte, neutrophil percentage, NLR, and PLR to discriminate complicated appendicitis from uncomplicated appendicitis. NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; ROC: Receiver operating characteristic.

had a sensitivity of 61.1% and a specificity of 73.2%. A cutoff value of 284 for the PLR had a sensitivity of 86% and a specificity of only 41% (Table 2, Fig. 2). The test performance of the PLR was maximal (LR+ of 2.89), while for the neutrophil percentage, WBC count, and NLR, it provided a LR of 1.43, 1.48, and 2.28, respectively (Table 2).

DISCUSSION AA is the one of the most common childhood surgical emergencies of the abdomen. Severe phlegmonous or gangrenous appendiceal inflammation can easily lead to peritonitis if perforation occurs.[1–3,6,7] Therefore, correct evaluation of the severity and discrimination between uncomplicated and complicated appendicitis provides valuable information to surgeons. Non-operative management with antibiotics alone may be an option for patients with uncomplicated appendicitis; however, surgery is still the first choice for complicated AA, and especially gangrenous appendicitis. Early detection of cases of complicated appendicitis and timely therapeutic intervention can reduce the risks of postoperative complications, such as intra-abdominal abscess or life-threatening peritonitis, which are more common when the appendix is perforated.[1–3,5,13,25,33] Understanding whether a child is experiencing simple or complicated appendicitis is still a diagnostic challenge for the clinician. Although a thorough assessment of clinical symptoms, use of a scoring system, and imaging methods are important in the general diagnosis of appendicitis, these evaluations provide only some hints in establishing the severity of appendicitis.[7,12,15,32,33] 226

Previous studies have revealed conflicting and varying information of traditional biomarkers such as the WBC count in the diagnosis of AA.[6,10] An increase in WBC concentration has been reported as the earliest sign of appendiceal inflammation. Part of the difficulty in drawing exact conclusions from the studies is that there is wide variability in the WBC concentration sensitivity, specificity, LR, and accuracy.[10] A WBC cutoff of greater than 10–12,000 cell/mm3 yielded a range of sensitivity between 65% and 85% and a specificity between 32% and 82%.[6,10–18] A 2003 meta-analysis of 14 studies (3382 patients) likely gives a representative approximation of the true sensitivity and specificity of a WBC >10,000 cell/mm3 measured at 83% and 67%, respectively, with a positive and negative LR of 2.52 and 0.26.6 Our findings are supported by prior research that found a sensitivity and specificity of the WBC count of 86.1% and 41.6%, respectively, and an AUC of 0.675. However, the presence of a WBC count >14,870 cell/ mm3 provided a LR of 1.48, which has limited clinical significance. The limited utility of a WBC concentration should not be surprising, as appendicitis is a dynamic, changing process, for which variations in levels might be assumed. The neutrophil percentage >75% was a discriminator of AA, but had limited clinical significance due to a sensitivity of 66% to 87% and a specificitiy of 33% to 84%.[6,12,15,17] Again, the LR was not high enough to significantly change the probability of appendicitis. Similar to previous reports, our study found that a neutrophil percentage >76% had a total sensitivity of 97.2% and a specificity 32.2%. Here, the LR was 1.43. Systemic inflammatory response can also cause neutrophilia and lymphocytopenia, resulting in an increase in the NLR and PLR, a sign of inflammation in AA.[24,25,33,34] It has also been reported that changes in platelet indices are involved in inflammatory processes.[35] The NLR and PLR are a simple, non-invasive, and cost-effective inflammatory markers, which can easily be calculated from the blood count in the emergency department. However, the role of these parameters in AA has only been investigated in a few studies.[24,25,33,34,36–38] A study conducted by Yazici et al.[24] showed that a NLR over 3.5 in a pediatric patient group had maximum sensitivity and more sensitivity than the WBC count. Another study by Ishizuka et al.[25] revealed that an NLR >8 had a significant association with gangrenous appendicitis in patients undergoing appendectomy. Markar et al.[36] assessed 1117 pediatric Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Çelik et al. Role of NLR and PLR in identifying complicated appendicitis in the pediatric emergency department

patients who underwent appendectomy and determined that the NLR appeared to be of greater diagnostic accuracy than the total WBC count. In our study, significant differences were not detected between the complicated and uncomplicated AA patients in the platelet count, MPV, or PDW, wheares a higher NLR and PLR were reported in complicated AA patients. The NLR had a higher AUC value than the other diagnostic factors, and an NLR cutoff of 10.4 demonstrated acceptable specificity and sensitivity. We found that NLR had a better AUC (0.717) compared with PLR (AUC: 0.647), neutrophil percentage (AUC: 0.678) or WBC (AUC: 0.675) for predicting complicated/severe appendicitis and a reasonable sensitivity and specificity. This suggests that NLR is a superior marker of acute phase response inflammatory processes. We think that these findings may be particularly important when clinical fndings and WBC are not adequate to safely distinguish complicated AA from uncomplicated AA. However, we concluded that the diagnostic value of these parameters alone was low and the positive or negative LR of NLR and PLR were unacceptably poor for use as a stand-alone rule-in or rule-out tool. There are limitations to this study, beginning with the retrospective design. In addition, the data were only collected for a 1-year period, which may not show the real potential of NLR and PLR in the discrimination of complicated AA in pediatric patients. In all, 36 complicated AA patients were included in the study with 298 uncomplicated AA patients, which may affect the statistical significance determined. We attempted to limit selection bias by including only patients who had histological evidence of appendicitis. Finally, we did not ask or record when the pain began, so we could not consider the effect of time on the parameters studied. Compared with other studies in this area, because of the large sample size we had a large amount of patient data. In conclusion, our study revealed that high NLR and PLR levels might help identify those who are more likely to develop complications in patients with AA. Moreover, these parameters are not expensive to measure, are easily available, and the short time required for analysis is valuable in the emergency department. We recommend that clinicians use the NLR and PLR values combined with the results of a physical examination, imaging studies, and other laboratory tests to help identify high-risk AA patients in the emergency department. Conflict of interest: None declared.

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31. Boshnak N, Boshnaq M, Elgohary H. Evaluation of Platelet Indices and Red Cell Distribution Width as NewBiomarkers for the Diagnosis of Acute Appendicitis. J Invest Surg 2018;31:121–9. 32. Mollitt DL, Mitchum D, Tepas JJ 3rd. Pediatric appendicitis: efficacy of laboratory and radiologic evaluation. South Med J 1988;81:1477–9. 33. Zani A, Teague WJ, Clarke SA, Haddad MJ, Khurana S, Tsang T, et al. Can common serum biomarkers predict complicated appendicitis in children? Pediatr Surg Int 2017;33:799–805. 34. 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. [Article in English, Slovak] 35. Smith TL, Weyrich AS. Platelets as central mediators of systemic inflammatory responses. Thromb Res 2011;127:391–4. 36. Markar SR, Karthikesalingam A, Falzon A, Kan Y. The diagnostic value of neutrophil: lymphocyte ratio in adults with suspected acute appendicitis. Acta Chir Belg 2010;110:543–7. 37. 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. 38. 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.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Pediatrik acil serviste komplike apandisitin belirlenmesinde nötrofil-lenfosit oranı ve trombosit-lenfosit oranının rolü Dr. Binnaz Çelik,1 Dr. Hülya Nalçacıoğlu,2 Dr. Mustafa Özçatal,3 Dr. Yasemin Altuner Torun4 Kayseri Eğitim ve Araştırma Hastanesi, Pediatri Kliniği, Kayseri Kayseri Eğitim ve Araştırma Hastanesi, Çocuk Nefroloji Kliniği, Kayseri 3 Kayseri Eğitim ve Araştırma Hastanesi, Çocuk Cerrahi Kliniği, Kayseri 4 Kayseri Eğitim ve Araştırma Hastanesi, Çocuk Hematoloji-Onkoloji Kliniği, Kayseri 1 2

AMAÇ: Çocuklarda komplike ve komplike olmayan apandisitin saptanmasında yardımcı olarak başlangıç hematolojik parametrelerin olası klinik faydalarını değerlendirmek amaçlandı. GEREÇ VE YÖNTEM: 2015’ten 2016’ya kadar akut apandisit için küratif cerrahi geçiren 334 pediatrik hasta geriye dönük olarak incelendi. Hastalar histopatolojik raporlara dayanarak komplike veya komplike olmayan apandisit olarak sınıflandırıldı. Klinik bulgular ve temel hematolojik parametrelerden lökosit sayısı, nötrofil yüzdesi, trombosit sayısı, nötrofil-lenfosit oranı (NLR), trombosit-lenfosit oranı (PLR), ortalama trombosit hacmi, kırmızı hücre dağılım genişliği, trombosit dağılım genişliği gruplar arasında karşılaştırıldı. BULGULAR: Komplike akut apandisit 36 (%10.8) hastada bulundu. Komplike apandisitte WBC (p<0.001), nötrofil yüzdesi (p<0.001), NLR (p<0.001), PLR (p=.004) komplike olmayan gruba göre daha yüksek iken, RDW, MPV, PDW düzeyleri anlamlı fark bulunmadı. ROC eğrilerinin analizi, WBC için 14.870 hücre/mm3 (eğri altındaki alan [AUC], 0.675; duyarlılık, %86.1; özgüllük, %41.6), NLR için 10.4 (AUC, 0.717; duyarlılık, %61.1, özgüllük, %73.2), PLR için 284 (AUC, 0.647; duyarlılık, %42; özgüllük, %86) komplike akut apandisitin belirlenmesinde en iyi kestirim değerler olarak bulundu. TARTIŞMA: Bu çalışma, daha yüksek NLR ve PLR düzeylerine sahip akut apandisitli hastalarda komplikasyon gelişme olasılığının daha yüksek olabileceğini göstermiştir. Klinisyenlerin acil servisteki yüksek riskli akut apandisit hastalarını tespit etmelerine yardımcı olmak için fizik muayene, görüntüleme çalışmaları ve diğer laboratuvar testleri ile birlikte NLR ve PLR kullanılmasını öneririz. Anahtar sözcükler: Akut apandisit; komplike; nötrofil-lenfosit oranı; pediatri; platelet-lenfosit oranı. Ulus Travma Acil Cerrahi Derg 2019;25(3):222-228

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ORIGIN A L A R T IC L E

Role of Alvarado score and biological indicators of C-reactive protein, procalicitonin and neopterin in diagnosis of acute appendicitis Fatih Dal, M.D.,1 Yusuf Çiçek, M.D.,2 Salih Pekmezci, M.D.,2 Bekir Kocazeybek, M.D.,3 Hrisi Bahar Tokman, M.D.,3 Dildar Konukoğlu, M.D.,4 Osman Şimşek, M.D.,2 Zeynep Taner, M.D.,3 Serhat Sirekbasan, M.D.,3 Server Sezgin Uludağ, M.D.2 1

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

Department of General Surgery, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

Department of Medical Microbioloji, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul-Turkey

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

ABSTRACT BACKGROUND: The determination of a definitive preoperative diagnosis of acute appendicitis (AA) remains a challenge; however, delays in diagnosis increase complication rates. The aim of this study was to investigate the contribution of the Alvarado score (AS) alone and the AS combined with the use of the biological indicators of C-reactive protein (CRP), procalcitonin (PCT) and neopterin (NP) in the diagnosis. METHODS: Serum was collected from 100 patients who were admitted to the general surgery clinic of Istanbul University, Cerrahpasa Medical Faculty between March 4, 2014 and July 29, 2015 with the pre-diagnosis of AA and who agreed to take part in the study. The serum samples were stored at -70°C. The patients were divided into 2 groups: AA-positive (n=60) and AA-negative (n=40). The AA positive group was divided into subgroups of complicated (n=11), uncomplicated AA (n=49) and the AS, CRP, PCT, NP levels were compared. RESULTS: The study population consisted of 45 men (45%) and 55 women (55%), with a mean age of 32.8±13.7 years (range: 18–92 years). There was no significant difference between the groups in age and gender. There were 24 patients with an AS ≤4 (3 had surgery), 35 patients with an AS of 5–7 (22 had surgery), and 41 patients with an AS of 8–10 (38 had surgery). Three of the 63 patients who underwent surgery were diagnosed with a normal appendix. The serum CRP, PCT, and NP measures were found to be inadequate to make an AA diagnosis alone, these values increased the sensitivity and specificity of the AS. The biological indicators were also significant in differentiating between the complicated and uncomplicated AA groups (p<0.05). CONCLUSION: Although the AS is useful, additional testing and clinical approaches are valuable to inform the diagnostic procedure. When considered alone, serum CRP, PCT and NP values are insufficient for a diagnosis of AA. However, they increased the diagnostic value of the AS and can be helpful in distinguishing complicated AA cases. Keywords: Acute appendicitis; Alvarado score; C-reactive protein; neopterin; procalcitonin.

INTRODUCTION Acute appendicitis (AA) is one of the most common causes of acute abdomen requiring surgical intervention. Approxi-

mately 30% of patients present with atypical clinical symptoms.[1] Anamnesis, physical examination, laboratory tests, imaging methods, and scoring systems are used to make a diagnosis of AA.[2,3] The Alvarado score (AS) is the most

Cite this article as: Dal F, Çiçek Y, Pekmezci S, Kocazeybek B, Bahartokman H, Konukoğlu D, et al. Role of Alvarado score and biological indicators of C-reactive protein, procalicitonin and neopterin in diagnosis of acute appendicitis. Ulus Travma Acil Cerrahi Derg 2019;25:229-237. Address for correspondence: Fatih Dal, M.D. Sağlık Bilimleri Üniversitesi, İstanbul Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 588 44 00 E-mail: fatihdal07@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):229-237 DOI: 10.5505/tjtes.2018.57362 Submitted: 23.06.2018 Accepted: 22.10.2018 Online: 15.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

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Dal et al. Role of AS and biological indicators of CRP, PCT and NP in diagnosis of AA

commonly used scoring system for the diagnosis of appendicitis. The components of the Alvarado score are migration of pain, anorexia, nausea-vomiting, right lower quadrant tenderness (RLQT), rebound, temperature ≥37.3°C, leukocytosis, and increased neutrophilia. RLQT and leukocytosis score 2 points, while other parameters score 1 point.[1–3] In many studies, it has been recommended that patients with an AS ≤4 be discharged, those with an AS of 5–7 be monitored for 24 hours, and patients with an AS of 8–10 undergo surgery.[3–6] Fever, white blood cell (WBC) count, sedimentation rate, Creactive protein (CRP) level, and procalcitonin (PCT) level are reliable parameters used in the diagnosis of acute bacterial infections. The serum level of PCT concentration changes with the inflammatory reaction, and an operative intervention and antibiotherapy can reduce the PCT level.[7–9] Transplantation, which is associated with cellular immunity activity, is known to increase serum neopterin (NP) in some clinical scenarios, such as viral diseases.[10] Despite current advanced methods, it is still challenging to make a certain AA diagnosis.[3] The objective of this study was to investigate the contribution of the AS and the biomarkers of CRP, PCT and NP when used alone or together to diagnose AA.

MATERIALS AND METHODS This study was conducted with the approval of the Istanbul University Cerrahpaşa Medical Faculty Ethics Committee (no. 88931902/262 dated 21.01.2014). The study included a total of 100 patients who presented at the emergency service of the general surgery department between March 4, 2014 and July 29, 2015 with suspected AA and who gave written consent for inclusion in the study. The criteria for the study were age over 18 years and the presence of complaints for more than 12 hours. Patients who were pregnant, younger than 18 years of age, those who had chronic renal failure, chronic viral disease, autoimmune disease or did not give consent to participate were excluded from the study. Medical care and monitoring was provided to the patients by an independent physician who was associated with the study. Patients who did not undergo surgery were monitored for 24-hours. Patient data, including AS, age, gender, CRP level and the duration of abdominal pain, were recorded on admission. To assess the PCT and NP, serum samples were collected from all of the patients and stored at -70 °C. Fluid samples were collected at the start of the surgeryafter irrigation of the periappendiceal area with 10 cc of normal saline. A culture test was also performed. Patients who were monitored in the ward for 24-hours after the first examination and discharged due to the regression of complaints were clinically regarded as AA-negative. 230

Those who were assessed to have a normal appendix according to the pathology evaluation and discharged after observation were classified as AA-negative, whereas patients determined to have appendicitis in the histopathological examination were classified as AA-positive. Patients with histopathologically determined AA were divided into subcategories of uncomplicated AA (phlegmonous appendicitis) and complicated (gangrene or perforated appendicitis) AA cases (Fig. 1). At the end of the study, PCT was evaluated using the Brahms PCT sensitive Kryptor kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA) with a 50 μL sample volume at the Istanbul University Cerrahpaşa Medical Faculty biochemistry laboratory and NP was assessed using the DRG Neopterin 96-test (DRG International, Inc., Springfield Township, NJ, USA) at the microbiology laboratory. The thresholds of 5 mg/L, 0.5 ng/mL, and 10 nmol/L were used to determine the sensitivity of CRP, PCT, and NP. Patients with an AS of >7 were regarded as AA-positive, while those with an AS of ≤7 were considered AA-negative. Mean, SD, median, minimum, maximum, frequency, and ratio values were used in the descriptive statistics of study data. Distribution of the variables was measured using the Kolmogorov Smirnov test. The Mann-Whitney U test was used for the analysis of quantitative data. The effect and cut-off values were determined with a receiver operating characteristic curve. A kappa test was used to evaluate compliance. All of the analyses were conducted using SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA).

RESULTS A total of 100 patients who were admitted to the general surgery department and provided consent for the study were included in the study. Sixty-three (63%) patients had laparoscopic surgery due to AA, whereas 37 (37%) patients were discharged after 24 hours of follow-up and classified as AA-negative. Patients who were operated on with the prediagnosis of AA were divided into 3 subgroups according to their pathology results: 1) complicated AA (Atypical A.A) group, consisting of 11 patients (11%) with perforated or gangrenous appendicitis, 2) uncomplicated AA group, comprising 49 (49%) patients with phlegmonous appendicitis, and 3) AA-negative group, consisting of 3 (3%) patients whose pathological examination demonstrated a normal appendix. In terms of clinical and pathological findings, 40 (40%) of 100 patients were classified as AA-negative, while the remaining 60 patients (60%) were AA-positive (Fig. 1, Table 1). In this study group, 45 (45%) patients were men and 55 (55%) were women, and the mean age was 32.8±13.7 years (range: 18–92 years) (Table 1). The 60 patients clinically and histopathologically diagnosed with AA included 31 (52%) female and 29 (48%) male patients with an averUlus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Dal et al. Role of AS and biological indicators of CRP, PCT and NP in diagnosis of AA

Table 1. Average and distribution of demographic and variable data of the study population

100 patients

Discharged from the emergency department, other pathology 37 patients

Age

Surgery patients: 63

Min-Max Median Mean±SD n 18–92

32.8±13.7

Patients

Female

Male Histopathologically AA negative patients: 3

Histopathologically noncomplicated AA patients: 49

Histopathologically complicated AA patients: 11

55 55.0 45 45.0

Abdominal pain (hours)

12–720 24 49.4±78.6

Clinic+histopathology

Atypical AA

11 11.0

Phlegmonous Clinical and histopathologically negative AA patients: 40

AA+AA Histopathologically positive AA patients: 60

Figure 1. Distribution of patients.

age age of 32.3±12.8 years. The mean duration of abdominal pain was 38.6±36.4 hours. In the, group classified clinically and histopathologically as AA-negative, there were 24 (60%) female and 16 (40%) male patients. The mean age was 33.6±14.8 years and the average duration of abdominal pain was 65.5±115 hours in the AA-negative group. There was no statistically significant (p>0.05) difference between the AAnegative and AA-positive patients in age, gender, or duration of abdominal pain (Table 2). There were 6 (55%) male and 5 (45%) female patients in the complicated AA group, and the average age of the patients was 41±18.2 years. The uncomplicated AA group consisted of 23 (47%) men and 26 (53%) women, and the mean age was 30.3±10.5 years. No significant difference was detected between the 2 groups regarding gender distribution (p>0.05). However, the patients in the uncomplicated AA group were significantly younger than the complicated AA patients (p<0.05). It was estimated that the mean length of abdominal pain was 71.1±65.2 hours for the complicated AA patients while it was 31.6±21.2 hours for the non-complicated AA cases. In other words, the duration of abdominal pain was significantly shorter among the non-complicated patients compared with the complicated patients (Table 4). There were 24 patients with an AS of ≤4 and 21 were discharged after 24 hours of follow-up while 3 patients underwent surgery and were confirmed to have AA by the histopathology test. Of the 35 patients with an AS of 5–7, 22 had surgery, while 13 were discharged after 24 hours of follow-up. Among the patients who underwent surgery, 3 had a normal appendix and 19 patients were diagnosed with AA in the histopathology examination. Of 41 AS 8–10 patients, 38 had surgery and all were diagnosed with AA Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

48 48.0

Negative appendectomy

3 3.0

38 38.0

Other pathologies

Acute appendicitis

(-)

(+)

Alvarado score

2.0–10.0

7.0

40 40.0

60 60.0

6.5±2.2

Alvarado score ≤4

24 24.0

5–7

35 35.0

41 41.0

59 59.0

41 41.0

8–10

Alvarado score 8–10

CRP (mg/L)

0.2–333.0

16.5

42.8±65.6

CRP (mg/L) ≤5

32 32.0

68 68.0

NP (nmol/L)

1.5–33.3

3.0

4.6±4.9

NP (nmol/L)

≤10

>10

PCT (ng/mL)

0.0–9.0

0.1

91 91.0 9 9.0

0.4±1.3

PCT (ng/mL) ≤0.5

>0.5

93 93.0 7 7.0

AA: Acute appendicitis; CRP: C-reactive protein; NP: Neopterin; PCT: Procalcitonin; Min: Minimum; Max: Maximum; SD: Standard deviation.

through histopathology. However, additional tests demonstrated that 3 patients did not have AA, and they were discharged after 24 hours of monitoring. The average AS was 4.7±1.7 in the AA-negative group (n=40) and 7.7±1.5 in patients who had histopathologically positive AA (n=60) (Tables 1–3). 231

Dal et al. Role of AS and biological indicators of CRP, PCT and NP in diagnosis of AA

Table 2. Comparison of acute appendicitis positive and negative groups in terms of age, gender, and abdominal pain

Acute appendicitis (-)

Age (years)

Acute appendicitis (+)

Mean±SD

Med (Min-Max)

Mean±SD

Med (Min-Max)

33.6±14.8

29 (18–92)

32.3±12.8

30 (18–85)

0.952

Patients, n (%)

Female

Male

Abdominal pain (hours)

24 (60)

31 (52)

16 (40)

29 (48)

65.5±115.0

33 (12–720)

38.6±36.4

0.412

24 (12–192)

0.062

Mann-Whitney U Test / Chi-square test. Min: Minimum; Max: Maximum; SD: Standard deviation.

Table 3. Comparison of variable data of acute appendicitis positive and negative groups

Acute appendicitis (-)

Acute appendicitis

Mean±SD

Acute appendicitis (+)

Med (Min-Max)

Mean±SD

Med (Min-Max)

4.7±1.7

4.0 (2.0–8.0)

7.7±1.5

8.0 (4.0–10.0)

0.000

22.4±32.6

10.5 (0.2–129.0)

56.4±77.7

29.2 (0.4–333.0)

0.008

Neopterin (nmol/L)

4.3±5.2

2.8 (1.7–33.3)

4.8±4.7

3.3 (1.5–29.1)

0.107

Procalcitonin (ng/mL)

0.1±0.1

0.0 (0.0–0.5)

0.6±1.6

0.1 (0.0–9.0)

0.000

C-reactive protein (mg/L)

Mann-Whitney U Test / Chi-square test. Min: Minimum; Max: Maximum; SD: Standard deviation.

Table 4. Comparison of complicated and uncomplicated acute appendicitis groups

Age

Histopathologically acute appendicitis positive group Complicated acute appendicitis

Uncomplicated acute appendicitis

Mean±SD

Med (Min-Max)

Mean±SD

Med (Min-Max)

41.0±18.2

39 (22–85)

30.3±10.5

28.5 (18–61)

0.032

Patients, n (%)

Female

5 (45)

Male

6 (55)

Abdominal pain time Alvarado score C-reactive protein (mg/L)

26 (53)

23 (47)

0.692

71.1±65.2

48 (17–192)

31.6±21.2

24 (12–96)

0.034

8.2±1.4

8 (6–10)

7.6±1.6

8 (4–10)

0.403

110.4±98.4

107 (5–330)

44.4±68.5

21.6 (0–333)

0.005

Neopterin (nmol/L)

6.3±5.1

3.83 (3–16.59)

4.5±4.6

3.14 (2–29.1115)

0.049

Procalcitonin (ng/mL)

1.1±1.9

0.2 (0–6.227)

0.5±1.6

0.07 (0–8.974)

0.001

E. coli culture positivity of peri-appendicular sample, n (%)

E. coli (-)

6 (54.5)

36 (75.0)

E. coli (+)

5 (45.5)

12 (25.0)

0.177

Mann-Whitney U Test / Chi-square test. Min: Minimum; Max: Maximum; SD: Standard deviation.

The mean CRP level was 42.8±65.6 mg/L (range: 0.2–333 mg/L) for the study group (n=100). In all, 68 (68%) patients had a CRP of >5 mg/L, and 32 (32%) patients had a CRP of ≤5 mg/L (Table 1). The mean CRP value was significantly 232

higher in the AA-positive group than in the AA-negative group (22.4±32.6 mg/L and 56.4±77.7 mg/L, respectively; p<0.05) (Table 3). The mean CRP level in the uncomplicated and complicated AA groups was 44.4±68.5 mg/L and Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Dal et al. Role of AS and biological indicators of CRP, PCT and NP in diagnosis of AA

Table 5. Reference cutoff values and ROC curve results for Alvarado scoring, C-reactive protein, neopterin, and procalcitonin

Area under the curve

Confidence interval

Lower limit

Upper limit

Alvarado scoring

0.902

0.842

0.961

0.000

Alvarado scoring cutoff value: 8

0.779

0.687

0.871

0.000

C-reactive protein (mg/L)

0.657

0.550

0.765

0.008

C-reactive protein cutoff value: 5

0.588

0.472

0.703

0.140

Neopterin (nmol/L)

0.595

0.479

0.712

0.107

Neopterin cutoff value: 10

0.513

0.397

0.628

0.833

Procalcitonin (ng/mL)

0.718

0.613

0.822

0.000

Procalcitonin cutoff value: 0.5

0.558

0.445

0.671

0.325

Table 6. Sensitivity and specificity of Alvarado scoring, C reactive protein, neopterin, and procalcitonin in diagnosis of acute appendicitis

AA (-)

AA (+)

Sensitivity (%)

PPV (%)

Specificity (%)

NPV (%)

Kappa

≤7 37 22 63 93 93 63 0.517 0.000

>8 3 38

CRP (mg/L) ≤5 17 15 75 66 43 53 0.181 0.066

>5 23 45

NP (nmol/L)

≤10

>10 3 6

PCT (ng/mL)

≤0.5

54 53

10 12

67 100

93 100

41 43

0.021 0.096

0.669 0.025

>0.5 0 7 ∨ AS CRP (-) 17 6 90 70 43 74 0.350 0.000 AS∨NP

(+) 23 54

AS∨PCT

(+) 6 39

(-) 34 21 65 87 85 62 0.471 0.000 (-) 37 21 65 93 93 64 0.535 0.000

(+) 3 39 ∨ ∨ AS CRP NP (-) 17 6 90 70 43 74 0.350 0.000 (+) 23 54 ∨ ∨ AS CRP PCT (-) 17 6 90 70 43 74 0.350 0.000 (+) 23 54 ∨ ∨ AS PCT NP (-) 34 21 65 87 85 62 0.471 0.000 (+) 6 39 ∨ ∨ ∨ AS CRP NP PCT (-) 17 6 90 69 41 74 0.350 0.000

(+) 24 54

Kappa compliance test. AA: Acute appendicitis; PPV: Positive predictive value; NPV: Negative predictive value; AS: Alvarado score; CRP: C-reactive protein; NP: Neopterin; PCT: Procalcitonin.

110.4±98.4 mg/L, respectively. That is, the mean CRP was significantly higher in the complicated AA group (p<0.05) (Table 4). The mean NP value was 4.6±4.9 nmol/mL (range: 1.5–33.3 nmol/L); 9 (9%) patients had an NP of >10 nmol/L and 91 (91%) had an NP of ≤10 nmol/L (Table 1). The mean NP of Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

the AA-negative group was 4.3±5.2 nmol/L and that of AApositive group was 4.8±4.7 nmol/L. No significant difference was observed between the 2 groups (p>0.05) (Table 3). It was determined that the mean NP was 4.5±4.6 nmol/L in the uncomplicated AA group and 6.3±5.1 nmol/L in the complicated AA group. The mean NP value of the complicated AA group was significantly higher (p<0.05) (Table 4). 233

Dal et al. Role of AS and biological indicators of CRP, PCT and NP in diagnosis of AA

The mean PCT value of the study patients was 0.4±1.3 ng/ mL (range: 0–9 ng/mL). In all, 7 (7%) patients had a PCT of >0.5 ng/mL and 93 (93%) had a PCT of ≤0.5 ng/mL (Table 1). The mean PCT of the AA-positive group was significantly higher than that of the AA-negative group (0.6±1.6 ng/mL and 0.1±0.1 ng/mL, respectively; p<0.05) (Table 3). The mean PCT was 0.5±1.6 ng/mL in the uncomplicated AA group and 1.1±1.9 ng/mL in the complicated AA group. The complicated AA group had a significantly higher PCT (p<0.05) (Table 4). The AS cutoff score of 8 was significant (p<0.05) in differentiating AA-negative and AA-positive patients; however, the cutoff values for CRP, NP, and PCT were insignificant (p>0.05) (Table 5). The AA-positive and AA-negative patients: C-reactive protein, procalcitonin, and neopterin, were evaluated separately and in the context of the AS. The AS [mean: 0.902 (range: 0.842–0.961); p<0.05] and the AS cutoff value of 8 [mean: 0.779 (range: 0.687–0.871; p<0.05] were seen to be effective (Table 5). The AS was found to have a sensitivity of 63%, a specificity of 93%, a positive predictive value of 93% and a negative predictive value of 63%. The biological indicators of CRP, PCT, and NP were ineffective alone (p>0.05), but significantly influenced the sensitivity, specificity, positive predictive value, and negative predictive value of the AS when considered together (Table 6).

DISCUSSION Anamnesis and physical examination are the basic tools used in the diagnosis of AA. Typical signs and symptoms of AA were first reported by Heber Fitz in 1886.[11] In cases of AA, the goal is to make a timely and correct diagnosis before the development of complications and to decrease the incidence of negative appendectomy. A number of methods have been suggested for this purpose. The AS, which was introduced in 1986, is widely used in clinical practice since it is easy, noninvasive, reproducible, and inexpensive.[4,6,12,13] Since its introduction, the AS has been the focus of interest for many researchers. Douglas et al.[14] did not perform surgical treatment in patients with an AS of ≤4. Winn et al.[15] discharged 12 AS ≤4 patients after observation. When 2 of these 4 patients presented again, they performed surgery, but did not detect appendicitis. Winn et al.[15] suggested that surgical intervention is not necessary for AS ≤4 patients. Alvarado et al.[4] reported that 80% of negative appendectomy patients had an AS of <6. They also argued that the use of the AS system can increase the reliability of diagnosis, especially in patients with different clinical conditions. Khan et al.[16] discharged 17 AS ≤4 patients. However, when 3 of these patients re-applied for treatment, researchers calculated the AS at 7, and therefore performed surgery. Many studies in the literature suggest that patients with an AS of ≤4 be discharged; however, there are studies reporting on 234

surgical treatment for AS ≤4 patients. Yildirim et al.[5] performed a surgical intervention for 14 of 18 patients with an AS of ≤4 and observed AA in 13 of those patients. In their study of 313 cases, Yüksel et al.[6] performed surgery for 23 of 60 AS ≤4 patients. Of the 60 patients, 7 were discharged after monitoring. Yüksel et al.[6] noted that if patients with an AS of ≤4 are discharged without clinical follow-up, some AA cases may go unnoticed. Although there is no consensus in the literature on a clinical approach for AS ≤4 patients, the relevant research shows that such patients are generally discharged. In our study, there were 24 patients with an AS of ≤4; of those, 21 patients were discharged and 3 were operated on. It is possible to encounter AA in AS ≤4 patients. AA was identified in the histopathological examination of these 3 surgical patients. The AS ≤4 patients suspected of AA should be observed for 24-hours. During that 24 hour follow-up period, the AS should be repeated and additional tests should be performed. If patients are to be discharged, they should be given appropriate guidance. In the literature, there are distinct clinical approaches toward patients with an AS 5–7. Winn et al.[15] treated 49 of 52 patients with an AS of 5–7 with antibiotics. Twenty seven patients re-applied to the clinic and 10 underwent surgery. Khan et al.[16] reported that they discharged 22 of 31 AS 5–7 patients after a 24-hour follow-up period, but performed surgery for the other 9 patients. AA was confirmed in 6 of the 9 surgical patients. Yildirim et al.[5] performed surgery for 62 of 70 patients with an AS of 5–7 and found a normal appendix in 3 patients. In a study of 55 AS 5–7 patients, Memon et al.[13] reported that 50 patients were found to have AA and 5 patients had a normal appendix, and the authors underlined the importance of clinical experience in forming the diagnosis. Moreover, Yüksel et al.[6] diagnosed 60 AA cases among 79 patients with an AS of 5–7. In the conclusion of that study, Yüksel et al.[6] recommended that AS 5–7 patients should be assessed with consideration for the clinical findings, additional imaging methods should be employed in suspect cases, and decision making should include repeating the AS a few times at intervals. Uzunköy et al.[17] stated that abdominal ultrasound with high sensitivity and specificity is an easy-to-use, repeatable, inexpensive, and non-invasive radiological examination alternative for additional testing in suspected cases of AA. Although there is no definitive clinical approach for AS 5–7 patients in the literature, conducting a 24-hour follow-up and performing additional examinations is the commonly accepted method when there is a suspicion of AA. In the present study, 22 of the 35 AS 5–7 patients underwent a surgical intervention, and 13 patients were discharged after being monitored for 24-hours. Among the patients who underwent surgery, 3 patients turned out to be AA-negative. However, AA was present in the remaining 19 patients. We believe that AS 5–7 patients with suspected AA should be subjected to a 24-hour monitoring period, during which the Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Dal et al. Role of AS and biological indicators of CRP, PCT and NP in diagnosis of AA

AS should be repeated and additional diagnostic tests should be performed as needed. When it comes to patients with an AS of 8–10, Winn et al.[15] operated on 52 of their 57 patients and detected AA in 47 patients. Khan et al.[16] found AA in 45 of 52 AS 8–10 patients, while the appendix was normal in 7 patients. Yildirim et al.[5] performed surgery on 51 of 55 patients with an AS of 8–10 and found AA in 50 of the operated patients. Memon et al.[13] operated on 41 AS 8–10 patients and detected AA in all cases. In the study conducted by Yüksel et al.[6] a total of 110 patients with an AS of 8–10 had surgery and 97 of them were diagnosed with AA. In the literature, all of the researchers have recommended surgical intervention for AS 8–10 patients. In our study, 38 of 41 patients with an AS of 8–10 were operated on and all were diagnosed with AA through histopathological examination. In our opinion, surgery is recommended for patients with an AS of 8–10. There are several biological markers that register an increase in the serum level during inflammatory reactions, the most known of which are CRP, PCT and NP. CRP values are commonly used in the diagnosis decision-making of patients with suspected AA.[18] Albu et al.[19] found that 56 patients being monitored with the pre-diagnosis of AA had a serum CRP level of more than 2.5 mg/L and reported that CRP had 100% sensitivity, 84.6% specificity, 86.6% positive predictive value, and 100% negative predictive value. They argued that surgery can be postponed if the CRP level is below 2.5 mg/L. In a study conducted by Kaya et al.[7] with 78 patients, the CRP level increased in line with the severity of appendiceal inflammation, but such an increase in CRP was found to be ineffective in making a surgical intervention decision in AA cases. Peltola[8] and Mikaelsson[20] reported the positivity rate (10 mg/L and 12 mg/L) of CRP in cases with suspected AA to be 72% and 47%, respectively. Some researchers argue that the CRP value is more useful than other indicators in predicting complicated appendicitis.[18] Yang et al.[21] analyzed 897 patients undergoing surgery due to suspected AA and found the mean CRP level to be 24.1 mg/L in inflammatory appendicitis cases and 96.8 mg/L in perforated appendicitis cases. Yildirim et al.[22] indicated in an analysis of 85 patients who were operated on with a pre-diagnosis of AA that the mean CRP of non-complicated cases was 68.4±63.5 mg/L and that the mean of complicated cases was 135.9±53.8 mg/L. In a study of 231 patients, Pruekprasert et al.[23] found the sensitivity and specificity of CRP to be 62% and 56%, respectively, when it is used along with the AS in the diagnosis of AA. They concluded that CRP measures may have a diagnostic value in forming the clinical diagnosis when considered together with the AS. Wu et al.[24] analyzed 214 patients in their study and demonstrated that the AS is more effective than PCT or CRP values, but using PCT and CRP along with the AS may improve diagnostic success. Mengücük et al.[9] reported in their study that included 100 patients that histopathoUlus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

logical findings of focal appendicitis, suppurative appendicitis, and perforated appendicitis had significantly higher PCT levels, and that patients with focal appendicitis, suppurative appendicitis, perforated appendicitis, abscess, or localized peritonitis had statistically significantly higher serum levels of CRP compared with patients discharged after follow-up. In the same study, Mengücük et al. demonstrated that the serum NP level was significant in patients histopathologically diagnosed with focal appendicitis, whereas it was not significant in plastron or perforated appendicitis cases. As a result of the study, Mengücük et al. argued that as the sensitivity and specificity of serum PCT, CRP, NP levels are low, they are not adequate (whether alone or used together) for diagnosis of AA. However, PCT, CRP, and NP can be regarded as clinical parameters to support the anamnesis and physical examination findings of patients. In this study, we respectively evaluated the reference values of inflammatory indicators suggested to be effective in differentiating AA-positive and AA-negative patients and observed that the cutoff value of 8 for the AS was significantly effective (p<0.05). The AS had a sensitivity of 63%, a specificity of 93%, a positive predictive value of 93%, and a negative predictive value of 63%. When we investigated the use of positive reference values of the indicators (AS >7, CRP >5 mg/L, PCT >0.5 ng/ mL, NP >10 nmol/L) in differentiating the AA-positive and AA-negative patients, we observed that the serum levels of CRP, PCT, and NP were ineffective, while the AS was effective (Tables 3, 5, 6). The use of inflammatory indicators with the AS influences the sensitivity, specificity, positive predictive value, and negative predictive value of the AS. The highest sensitivity (90%) was obtained when the combinations of AS∨CRP, AS∨CRP∨NP, AS∨CRP∨PCT, and AS∨CRP∨NP∨PCT were used. The highest specificity (93%) was observed with the combination of AS∨PCT (Table 6). This study indicated that if a surgery decision is to be made for a patient with suspected AA considering the reference values, the AS itself is effective; however, the CRP, PCT, and NP values are not effective when used alone. On the other hand, these indicators impact the sensitivity and specificity of the AS in the diagnosis of AA. When the complicated and uncomplicated AA groups were compared with regard to the mean inflammatory indicators, the complicated AA group showed significantly higher results than the non-complicated AA group (p<0.05) (Table 4). We believe that after the AA diagnosis has been established, the serum levels of CRP, PCT, and NP can be effective in differentiating complicated and uncomplicated AA patients.

Conclusion In conclusion, AA is one of the common causes of acute abdomen in all age groups. Delays in diagnosis can elevate the rate of complications, which may result in increased morbidity and mortality. AA may be seen in patients with an AS of ≤4. Suspected patients with an AS of ≤4 and all patients with AS 5–7 should be followed-up for 24 hours with repeated 235

Dal et al. Role of AS and biological indicators of CRP, PCT and NP in diagnosis of AA

AS evaluations and additional tests, if necessary. Surgery is important for AS 8-10 patients. Although the AS is a well-designed scoring system, additional diagnostic tests and clinical approaches are also needed in the diagnosis of AA. Serum levels of CRP, PCT, and NP alone are not adequate for an AA diagnosis; however, they are important indicators that increase the diagnostic value of the AS. The serum levels of CRP, PCT, and NP are also useful in distinguishing complicated and uncomplicated AA cases.

Acknowledgment The authors would like to thank the Istanbul University Scientific Research Projects Unit. Conflict of interest: None declared.

REFERENCES 1. Behzatoğlu B, Hatipoğlu E, Bayramoğlu S, Yılmaz G, Yirik G, Cimili T. Comparison of ultrasonographic and computed tomographic findings in the diagnosis of acute apendicitis. Med J Bakirkoy 2006;2;22–4. 2. Doğan S, Bulut AŞ, Karamürsel BS. A rare differential diagnosis of acute appendicitis: Appendiceal endometriosis. Turk J Surg 2012;28;159–61. 3. Lowry SF, Hong JJ. Appendicitis and appendiceal abscess In: Fischer JE, editor. Mastery of surgery. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 1430–43. 4. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557–64. 5. Yildirim E, Karagülle E, Kirbaş I, Türk E, Hasdoğan B, Tekşam M, et al. Alvarado scores and pain onset in relation to multislice CT findings in acute appendicitis. Diagn Interv Radiol 2008;14:14–8. 6. Yüksel Y, Dinç B, Yüksel D, Dinç SE, Mesci A. How reliable is the Alvarado score in acute appendicitis? Ulus Travma Acil Cerrahi Derg 2014;20:12–8. 7. Kaya B, Sana B, Eris C, Karabulut K, Bat O, Kutanis R. The diagnostic value of D-dimer, procalcitonin and CRP in acute appendicitis. Int J Med Sci 2012;9:909–15. 8. Peltola H, Ahlqvist J, Rapola J, Räsänen J, Louhimo I, Saarinen M, et al. C-reactive protein compared with white blood cell count and erythrocyte sedimentation rate in the diagnosis of acute appendicitis in children. Acta Chir Scand 1986;152:55–8. 9. Mengücük ME, Ayten R, Bülbüller N, Gödekmerdan A, Başbuğ M, Mungan İ. Role of C-reactive Protein, Procalsitonin and Neopterin in the Diagnosis of Acute Appendicitis. Fırat Tıp Dergisi 2010;15:40–3.

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10. Fuchs D, Weiss G, Reibnegger G, Wachter H. The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases. Crit Rev Clin Lab Sci 1992;29:307– 41. 11. Phoprom J, Trivej T. The Modified Alvarado Score Versus the Alvarado Score for the Diagnosis of Acute Appendicitis. Thai J Surg 2005;26:69– 72. 12. Menteş Ö, Eryılmaz M, Yiğit T, Taşcı S, Balkan M, Kozak O, et al. Retrospectively analysis of appendectomies which performed elderly cases. [Article in Turkish] EAJEM 2008;7:36–41. 13. Memon AA, Vohra LM, Khalig T, Lehri AA. Diagnostic Accururacy of Alvarado Score in the Diagnosis of Acute Appendicitis. Pak J Med Sci 2009;25:118–21. 14. Douglas CD, Macpherson NE, Davidson PM, Gani JS. Randomised controlled trial of ultrasonography in diagnosis of acute appendicitis, incorporating the Alvarado score. BMJ 2000;321:919–22. 15. Winn RD, Laura S, Douglas C, Davidson P, Gani JS. Protocol-based approach to suspected appendicitis, incorporating the Alvarado score and outpatient antibiotics. ANZ J Surg 2004;74:324–9. 16. Khan I, ur Rehman A. Application of alvarado scoring system in diagnosis of acute appendicitis. J Ayub Med Coll Abbottabad 2005;17:41–4. 17. Uzunköy A, Akıncı ÖF, Coşkun A, Karamanoğlu M, Erdoğan M. The role ultrasonographic investigation in the diadnosis of akut Appendicitis. Ulus Travma Acil Cerrahi Derg 1998;4:202–5. 18. 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. 19. Albu E, Miller BM, Choi Y, Lakhanpal S, Murthy RN, Gerst PH. Diagnostic value of C-reactive protein in acute appendicitis. Dis Colon Rectum 1994;37:49–51. 20. Mikaelsson C, Arnbjörnsson E. The value of C-reactive protein (CRP) determinations in patients with suspected acute appendicitis. Ann Chir Gynaecol 1984;73:281–4. 21. 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. 22. Yildirim O, Solak C, Koçer B, Unal B, Karabeyoğlu M, Bozkurt B, et al. The role of serum inflammatory markers in acute appendicitis and their success in preventing negative laparotomy. J Invest Surg 2006;19:345–52. 23. Pruekprasert P, Maipang T, Geater A, Apakupakul N, Ksuntigij P. Accuracy in diagnosis of acute appendicitis by comparing serum C-reactive protein measurements, Alvarado score and clinical impression of surgeons. J Med Assoc Thai 2004;87:296–303. 24. Wu JY, Chen HC, Lee SH, Chan RC, Lee CC, Chang SS. Diagnostic role of procalcitonin in patients with suspected appendicitis. World J Surg 2012;36:1744–9.

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Dal et al. Role of AS and biological indicators of CRP, PCT and NP in diagnosis of AA

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut apandisit tanısında Alvarado skorlaması, C-reaktif protein, prokalsitonin ve neopterin biyolojik belirteçlerin yeri Dr. Fatih Dal,1 Dr. Yusuf Çiçek,2 Dr. Salih Pekmezci,2 Dr. Bekir Kocazeybek,3 Dr. Hrisi Bahar Tokman,3 Dr. Dildar Konukoğlu,4 Dr. Osman Şimşek,2 Dr. Zeynep Taner,3 Dr. Serhat Sirekbasan,3 Dr. Server Sezgin Uludağ2 Sağlık Bilimleri Üniversitesi, İstanbul Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul İstanbul Üniversitesi-Cerrahpaşa, Cerrahpaşa Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul İstanbul Üniversitesi-Cerrahpaşa, Cerrahpaşa Tıp Fakültesi, Tıbbi Mikrobiyoloji Anabilim Dalı, İstanbul 4 İstanbul Üniversitesi-Cerrahpaşa, Cerrahpaşa Tıp Fakültesi, Tıbbi Biyokimya Anabilim Dalı, İstanbul 1 2 3

AMAÇ: Akut apandisit (AA), günümüzde hala kesin tanısını koymak mümkün değildir. Tanıdaki gecikmeler, komplikasyon oranlarını artırmaktadır. Alvarado skorlaması (AS) ve biyolojik belirteçlerin (C-reaktif protein [CRP], prokalsitonin [PCT], neopterin [NP]) tek ve AS ile birlikte kullanılmalarının tanıya olan katkılarının araştırılması amaçlandı. GEREÇ VE YÖNTEM: İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Genel Cerrahi Kliniği’ne, 04.03.2014–29.07.2015 tarihleri arasında, AA ön tanısıyla, gönüllü 100 hastadan, yatış öncesi serumları alınarak -70 derecede saklandı. Hastalar, AA pozitif (n=60), negatif (n=40) gruplandı. AA pozitif grup; komplike (n=11), nonkomplike (n=49) olarak gruplandırılarak, AS, CRP, PCT ve NP değerleri karşılaştırıldı. BULGULAR: Çalışmaya alınan hastaların; 45’i erkek (%45), 55’i kadın (%55),yaş ortalamaları 32.8±13.7 18–92) yıl idi. Gruplar arasında, yaş, cinsiyet açısından anlamlı fark yoktu. AS dağılımı; AS ≤4 (n=24) üçü, AS 5–7 (no: 35) 22’si, AS 8–10 (no: 41) 38’i ameliyat edildi. Ameliyat edilen 63 hastanın üçünde normal apendiks saptandı. AA pozitif ve negatif grupların, serum CRP, PCT, NP değerlerinin tanıda yetersiz olduğu ancak AS’nin sensivite ve duyarlılığını artırdığı görüldü. Biyolojik belirteçlerin ortalaması karşılaştırıldığında; komplike AA grup ayrımında anlamlıydı (p<0.05). TARTIŞMA: Alvarado skorlaması, iyi bir skorlama olmasına karşın, ek inceleme ve klinik yaklaşımlara ihtiyaç vardır. Serum CRP, PCT ve NP değerleri, tek başlarına, AA tanısında yetersizdir. Ancak AS’nin değerini arttırmakta ve komplike AA olgularını ayırmada yararlıdır. Anahtar sözcükler: Akut apandisit; Alvarado skorlaması; C-reaktif protein; neopterin; prokalsitonin. Ulus Travma Acil Cerrahi Derg 2019;25(3):229-237

doi: 10.5505/tjtes.2018.57362

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ORIGIN A L A R T IC L E

Use of angiographic embolization in trauma-induced pediatric abdominal solid organ injuries Kubilay Gürünlüoğlu, M.D.,1 Canan Ceran, M.D.,1 İsmail Okan Yıldırım, M.D.,2 Ramazan Kutlu, M.D.,2 Kaya Saraç, M.D.,2 Turan Yıldız, M.D.,1 Ercan Bayrakçı, M.D.,1 Aytaç Taşçı, M.D.,1 Ahmet Kadir Arslan, M.D.,3 Mehmet Demircan, M.D.1 1

Department of Pediatric Surgery, İnönü University Faculty of Medicine, Turgut Özal Medical Center, Malatya-Turkey

Department of Radiolgy, İnönü University Faculty of Medicine Turgut Özal Medical Center, Malatya-Turkey

Department of Biostatistics and Medical Informatic, İnönü University Faculty of Medicine, Malatya-Turkey

ABSTRACT BACKGROUND: Knowledge of the utility of angiographic embolization (AE) in pediatric cases of blunt abdominal solid organ trauma injuries is limited. The current study is an examination of AE as an effective and reliable method to control bleeding in patients with persistent bleeding due to blunt trauma-induced abdominal solid organ injury. METHODS: This was a retrospective examination of patients <17 years of age who had experienced blunt abdominal solid organ injury and who presented at a single institution within 4 years. A statistical analysis of the data was performed. RESULTS: The mean length of intensive care unit stay was 4 days for those who underwent embolization (n=11), and the mean length of hospital stay was 12 days. The average pre-AE blood loss, as measured by the decrease in hematocrit (%) from admission to embolization, was −7.33±5.3% (p<0.001). The average post-AE blood loss, as measured by the change in hematocrit 72 hours post AE, was 2±0.97% (p>0.05). All of the patients were discharged with a full recovery. CONCLUSION: AE was a safe and effective method to control solid organ hemorrhage in pediatric patients with blunt abdominal injuries. Keywords: Angiographic; children; embolization; solid organ injury.

INTRODUCTION Injuries are the leading cause of death in all age groups worldwide,[1] and active hemorrhage is the most common cause of death among trauma patients.[2] Abdominal trauma is an important source of mortality and morbidity in children.[3] About 90% of childhood injuries are blunt trauma injuries, and the most common forms are head and limb trauma.[4] Abdominal trauma represents 8% of all childhood blunt trauma cases, and the liver, spleen, and kidney are the primary organs affected. [4] The spleen is the most frequently injured intra-abdominal organ in cases of blunt trauma.[5] Isolated upper abdominal injuries can lead to liver, spleen, and pancreas injuries.[5] Mul-

tisystem trauma often occurs in injuries caused by events such as traffic accidents or falling from a significant height.[5] Since the mid-1990s, angiographic embolization (AE) has been widely used in hemodynamically unstable adult patients with blunt abdominal solid organ injuries that involve the liver, spleen, or kidney.[6,7] Although AE can be successfully performed in such patients, precise knowledge of the utility in children with blunt trauma-induced abdominal solid organ injuries is limited.[3,8,9] The present study describes the effective and reliable use of AE at a single center to control hemorrhage in hemodynam-

Cite this article as: Gürünlüoğlu K, Ceran C, Yıldırım İO, Kutlu R, Saraç K, Yıldız T, et al. Use of angiographic embolization in trauma-induced pediatric abdominal solid organ injuries. Ulus Travma Acil Cerrahi Derg 2019;25:238-246. Address for correspondence: Kubilay Gürünlüoğlu, M.D. İnönü Üniversitesi Tıp Fakültesi Turgut Özal Tıp Merkezi, Çocuk Cerrahisi Anabilim Dalı, 44315 Battalgazi, Malatya, Turkey. Tel: +90 422 - 341 06 60 / 3404 E-mail: kgurunluoglu@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):238-246 DOI: 10.5505/tjtes.2018.00056 Submitted: 27.01.2018 Accepted: 23.10.2018 Online: 14.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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ically unstable patients with an ongoing hemorrhage due to blunt trauma-induced abdominal solid organ injury.

MATERIALS AND METHODS The records of pediatric patients <17 years of age who presented at a single level 1 trauma center between 2014 and 2018 with a blunt abdominal solid organ injury were reviewed retrospectively. Any existing childhood injuries of the abdominal organs were identified, as well as the severity score of the injury and any evidence of continued bleeding due to the injury. The success and complication rate of an AE procedure was analyzed, including the duration of stay in the hospital and the intensive care unit (ICU), as well as the need for additional blood transfusion. Abdominal injuries were identified with an intravenous contrast-enhanced abdominal computed tomography (CT) scan. It was then graded according to the American Trauma Surgery Association’s organ injury score. Non-operative management was the first treatment approach for all of the patients. Ongoing hemorrhage was identified by a decrease in the hematocrit percentage observed in serial laboratory measurements. All of the patients who underwent AE received a blood transfusion before the procedure. AE was performed in patients with continued unstable hemodynamics despite the transfusion. Sedation or general anesthesia was provided in the radiology unit to all of the patients treated with AE. In all cases, arterial access was obtained for all procedures via the right common femoral artery using the Seldinger technique with ultrasound. First, a diagnostic arteriogram was performed with a suitable catheter. If the arteriography indicated vascular injury, a pseudoaneurysm formation, or contrast extravasation, the patient was prepared for an AE procedure. A special catheter suitable for this procedure was used. Once the injured vessel was detected, the blood flow in this artery was then embolized and stopped. In some cases, embolic agents (microparticles and metal coils) were used in combination to provide maximum hemostasis in the injured artery. In patients with pseudoaneurysms, the input and output vessels were angiographically embolized to prevent reperfusion. To optimize perfusion in the injured organ, only the distal part of the damaged artery was embolized.

Statistical Analysis Comparison of Independent Groups (AE/Non-AE) The data were summarized as mean±SD, median (range), and counts (percentages). The Kolmogorov–Smirnov or Shapiro–Wilk test was used to determine whether the quantitative data exhibited a normal distribution at the group level. An independent sample t-test was conducted to determine whether there was a significant difference between Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

independent groups that confirmed the parametric test hypotheses. The Mann–Whitney U test was used to determine whether there was a significant difference between independent groups that contradicted the parametric hypotheses. Pearson’s chi-square test was used in cases where the independent variable was qualitative. A p value of <0.05 was considered significant.

Comparison of Dependent Groups The data were summarized using median values (range). The normality of the data distribution was tested with the Shapiro–Wilk test. Friedman’s test was used to determine whether there was a significant difference between dependent groups that contradicted the parametric hypotheses. Multiple comparisons were performed using the Bonferronicorrected Wilcoxon signed-rank test after applying Friedman’s test. A p value of <0.05 was considered significant. Hemorrhage and hematocrit-thrombocyte stabilization parameters were evaluated using Friedman’s test (two-sided; p<0.05 significance). After performing Friedman’s test for paired comparisons, the Wilcoxon signed-rank test with the Bonferroni correction was applied. No significant difference was observed between the 72-hour post-AE and immediately post-AE hematocrit levels, suggesting controlled hemorrhage. Similarly, no significant difference was observed between the 72-hour and immediately post-AE thrombocyte counts, again suggesting a controlled hemorrhage. All of the patient data were compared based on a Mann-Whitney U test or independent sample t-test two-sided; p<0.05 was considered significant) in the AE group (n=11) and the nonAE group (n=72). IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA) was used to perform the statistical analysis. Approval for the present study was obtained from the Inonu University Scientific Research and Publication Ethics Committee (No. 2018/2-13).

RESULTS Patient Data A total of 83 patients were treated for abdominal solid orTable 1. Patient demographics Angiographic embolization Age (years) Gender Transfusion

n=11 11.7±4.8 (1–16) 7 male (63%), 4 female (37%) 11 patients (100%)

Complications

Major

1 patient (9%)

Minor

3 patiens (27%)

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Table 2. Comparison of AE and Non-AE group length of care

Table 4. Embolized organ injuries

Mean

Patient Injured organs and grade

Embolized organ

Grade IV left kidney

Kidney IV

Grade IVleft kidney

Kidney IV

Grade IV right kidney, grade IV right

adrenal, severe TBI

Kidney IV

Grade IV right kidney

Kidney IV

Grade IV spleen

Spleen IV

Grade IV spleen

Spleen IV

Grade IV liver, right lung contusion

Liver IV

Grade V left kidney

Kidney V

Grade IV left kidney

Kidney IV

Grade IV spleen, grade I liver, ileal

mesenteric defect

Spleen IV

Grade V left kidney

Kidney V

AE Non-AE p (n=11) (n=72)

Length of intensive care unit stay (days)

4 (2–15)

2 (2–10)

<0.001

Length of hospital stay (days)

12 (7–28)

5.5 (4–30)

<0.001

AE: Angiographic embolization.

Table 3. Injury grade comparison of AE and Non AE groups

Groups Non-AE

Total

Grade, n (%)

31 (43)

0 (0)

31 (43)

29 (40.2)

0 (0)

29 (40.2)

III

12 (16.8)

0 (0)

12 (16.8)

0 (0)

9 (81.9)

0 (0)

2 (18.1)

72 (86.7)

11 (13.3)

83 (100)

Total, n (%)

<0.001

Mean injury grade: 4.18±0.30. TBI: Traumatic brain injury.

AE is presented in Table 1. The injury mechanism was a fall (>6 feet) in 5 cases, a motor vehicle accident in 5 cases, and 1 instance of assault.

AE: Angiographic embolization.

gan injuries between July 2014 and December 2017. Of these patients, 41 were splenic injuries, 27 were liver injuries, and 15 were renal injuries. In all, 72 patients were successfully managed non-operatively and no additional treatment was provided. Eleven patients with abdominal solid organ injury underwent AE due to ongoing hemorrhage-induced hemodynamic instability. A laparotomy was also performed for 1 patient who underwent AE due to an ileal mesenteric defect induced by a fall; resection and anastomosis was performed. Demographic information on the patients who underwent

(a)

(b)

The mean age of the patients who underwent AE (n=11) was 11.7±4.8 years (range: 1–16 years). The mean length of ICU stay was 4 days (range: 2–15 days), and the mean length of hospital stay was 12 days (range: 7–28 days). The mean organ injury grade was 4.18±0.40. The mean age of the patients who did not undergo AE (n=72) was 9.1±3.8 years. The mean length of ICU stay for these patients was 2 days (range: 2–10 days), the mean length of hospital stay was 5.5 days (range: 4–30 days) (Table 2) and the mean organ injury grade was 1.73±0.75 (Table 3). Table 4 demonstrates that the solid organ injuries were significantly more severe in the patients who underwent AE (p<0.001). The ICU duration

(c)

Figure 1. (a) Three-dimensional shaded surface display computed tomography angiographic image shows active contrast extravasation of contrast material (hemorrhage) from the right hepatic artery (arrows). (b) Non-selective celiac angiographic image demonstrating active hemorrhage from the right hepatic arterial branches (arrows). (c) Cessation of active extravasation and patency of remaining hepatic arterial branches seen in a control angiographic image obtained after coil embolization of anterior sectorial branches of the right hepatic artery (white arrows) and gel-foam embolization of posterior sectorial branches of the right hepatic artery (black arrows).

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of stay (p<0.001) and hospital stay (p<0.001) were longer in these cases.

(a)

(b)

Angiographic Embolization Data Single-organ AE was performed for 11 children: The group included 1 case of liver injury (grade IV) (Fig. 1), 7 patients with renal injury (5 grade IV, 2 grade V) (Fig. 2–8), and 3 splenic injuries (grade IV ) (Fig. 9–11). There were 3 patients with multiple solid organ injuries. Each of these underwent embolization in a single organ. In patients treated with AE, the mean organ injury grade was 4.18±0.30 (Table 4). AE was performed within 72 hours after admission (range: 1–72 hours). General anesthesia was administered in 3 cases. After the procedure, the mean time spent in the ICU was 22 hours.

Figure 2. (a) Selective renal artery angiography revealing active extravasation. (b) Successful angiographic embolization of a grade IV renal injury.

Hemorrhage Data

(a)

(b)

The mean blood volume measured in the hematocrit before

(b)

Figure 3. (a) Selective renal artery angiography illustrating active extravasation. (b) Successful angiographic embolization of a grade IV renal injury.

Figure 6. (a) Selective renal artery angiography shows transection with pseudoaneurysm formation of renal artery (arrow). (b) Successful angiographic embolization of transection with pseudoaneurysm formation of renal artery (arrows).

(a)

(b)

Figure 4. (a) Selective renal artery angiography indicating active extravasation. (b) Successful angiographic embolization of a grade IV renal injury.

(a)

(b)

Figure 5. (a) Selective renal artery angiography demonstrating active extravasation. (b) Successful angiographic embolization of a grade IV renal injury.

Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

(b)

Figure 7. (a) Selective renal artery angiography shows active extravasation. (b) Successful angiographic embolization of a grade IV renal injury (arrows).

(a)

(b)

Figure 8. (a) Selective renal artery angiography illustrating transection with pseudoaneurysm formation of renal artery (arrow). (b) Successful angiographic embolization of transection with pseudoaneurysm formation of renal artery (arrows).

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Gürünlüoğlu et al. Use of AE in trauma-induced pediatric abdominal solid organ injuries

(a)

(b)

(c)

Figure 9. (a) Selective splenic artery angiography shows active extravasation and pooling of contrast material in the splenic parenchyma (arrows). (b) Non-selective celiac angiographic image demonstrates successful embolization of splenic artery distal to the pancreatic branches (black arrow) with detachable coils (white arrows). (c) Control computed tomography image illustrates coils (black arrow) and remaining superior pole of spleen (white arrow).

the AE procedure was 37.33±5.3% (p<0.001). The decrease in the thrombocyte count measured between admittance and AE was −129.8±64.6 X103/mm3 (p<0.001). The data on the change in hematocrit level are presented in Figure 12. The decision to perform AE was based on the hematocrit level; however, the thrombocyte count was also significant in the decision. The mean post-AE blood loss, as measured by the change in hematocrit level between that recorded at the time of the AE and 72 hours post AE, was 2±0.97% (p>0.05). The change in thrombocyte count between that observed immediately post AE and 72 hours later was 33.6±22.8 X103/mm3 (p<0.05). The data on the change in thrombocyte level are presented in Figure 13. A blood transfusion was performed prior to AE in all patients (15 mL/kg red blood cells per patient). Twelve hours after the AE, 1 patient underwent another blood transfusion (15 mL/kg red blood cells) due to ongoing hemorrhage, and this patient was re-embolized. All of the patients were discharged with a full recovery. No deaths were observed.

Complications No complications developed during the AE in any of the study patients. A minor complication of pleural effusion subsequently developed in 3 patients, requiring external drainage. Thoracic catheters were installed in 5 patients a mean of 7.7 242

(a)

(b)

(c)

Figure 10. (a) Selective splenic artery angiographic image reveals active hemorrhage from superior and inferior splenic branches (arrow). (b) Control selective splenic angiographic image obtained after embolization of actively bleeding splenic branches with polyvinyl alcohol particles demonstrates embolization of distal branches (black arrows) and preservation of superior polar splenic arterial branches (white arrows). (c) Control coronal computed tomography image illustrates preserved perfused superior pole of spleen (white arrows) and remaining avascular spleen parenchyma (black arrow).

(a)

(b)

Figure 11. (a) Selective splenic artery angiographic image shows injury to the inferior splenic artery branches (arrow). (b) Successful angiographic embolization of the inferior splenic artery branches (arrow).

days after the pleural drainage. A major complication developed in 1 patient who experienced ongoing hemorrhage, and a second AE was performed on the same organ. A laparotomy was performed due to findings observed on the upright direct abdominal radiographs taken due to ongoing abdominal pain before the AE and the presence of acute abdomen sympUlus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

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40 35 Hematocrit

30 25 20 15 10 5 0

Admission

Pre-AE

Post-AE

Post-AE 72 Discharge

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10 Patient 11 Median

Time (Intervetion)

Thrombocyte

100 50 0

Admission

Pre-AE

Post-AE

Post-AE 72 Discharge

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient 10 Patient 11 Median

Time (Intervetion)

Figure 13. Hemorrhage control with angiographic embolization (AE). Serial thrombocyte counts were determined before and after AE. Before AE, the patients showed significantly decreased thrombocyte counts (−129.8±64.6 X103/mm3; p<0.001). After AE, the thrombocyte counts stabilized (33.6±22.8 X103/mm3; p=NS). No significant decrease in thrombocyte count (%) was observed at 72 hours post AE.

toms (albeit unrelated to AE). A mesenteric defect developed in a 10-cm ileac segment as the result of a fall, which led to ischemia unrelated to AE. Resection of the ischemic segment and anastomosis was performed. Feeding per oral was initiated after 5 days.

Non-operative Success The non-operative management success rate was 100% for the spleen (n=38), liver (n=26), and kidney (n=8). All of the patients were hemodynamically stable and there was no patient mortality. The mean hematocrit percentage was significantly lower in the AE group compared with the non-AE group (Table 5, Fig. 14). Although the decision to perform AE was based on the change in hematocrit level, it was noted that the mean thrombocyte value was significantly lower in the AE group (Table 6, Fig. 15). The mean hospital and ICU unit stays were significantly longer for patients who underwent AE than Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Variable

Groups

AE non-AE (n=11) (n=72)

Mean±SD Mean±SD

Hematocrit %

28.97±2.16

35.95±3.30

<0.001

AE: Angiographic embolization; SD: Standard deviation.

Figure 12. Hemorrhage control with angiographic embolization (AE). Serial hematocrit measurements were taken to assess the extent of hemorrhage before and after AE. Before AE, the patients experienced significant hemorrhage (−7.33±5.3%; p<0.001). After AE, the patients’ hematocrit levels stabilized (2±0.97%; p=NS). No significant decrease in the hematocrit level (%) was observed at 72 hours post AE. 450 400 350 300 250 200 150

Table 5. Hematocrit comparison of AE and Non-AE groups

Table 6. Thrombocyte comparison of AE and Non-AE groups Variable

Groups

AE non-AE (n=11) (n=72) Mean±SD Mean±SD

Thrombocyte 201.03±68.01 281±60.28

<0.001

×109/L AE: Angiographic embolization; SD: Standard deviation.

those in the non-AE group. This was likely due to the fact that the organ injuries were significantly more severe in the AE group than in the non-AE group (Table 2, Figs. 16 and 17).

DISCUSSION Non-operative management of significant abdominal injuries represents standard care for pediatric patients. More than 95% of isolated abdominal solid organ injuries are successfully managed without surgery.[10,11] However, in cases where emergency surgical intervention is required, removal of the damaged organ is often necessary, which can increase both morbidity and mortality.[12,13] AE has been used as an adjunct to non-operative management, although its role in pediatric cases has not been defined.[14–16] A detailed literature review revealed that although AE is effective for treating solid organ injuries due to blunt abdominal trauma in adults, only a few studies have examined its use in children.[3,17–20] Skattum et al.[17] reported that AE increased the rate of splenic preservation from 90% to 98% during nonoperative management of splenic injuries. Gross et al.[20] performed embolization on 15 patients with a splenic injury over a 10-year period and reported that the spleen was preserved in 93% of cases. Kiankhooy et al.[3] successfully treated 7 children with blunt abdominal trauma via AE. Two of these patients had hepatic injuries, 2 others splenic injuries, and 3 had renal injuries. The AE procedure was performed an average of 11 hours after admission. Fenton et al.[21] performed an angiography on 29 children with blunt abdominal trauma, 11 of whom subsequently underwent an embolization procedure. 243

Gürünlüoğlu et al. Use of AE in trauma-induced pediatric abdominal solid organ injuries

45 40

Hematocrit

35 30 25 20 15 10 5 0

Groups

Non-AE

Figure 14. Mean hematocrit level of the angiographic embolization (AE) and non-AE groups. 400 350 Thrombocyte

300 250 200 150 100 50 0

Groups

Non-AE

Figure 15. Mean thrombocyte level of the angiographic embolization (AE) and non-AE groups.

Simple boxplot of length of intensive care unit stay by groups

Length of intensive care unit stay (day)

In the abovementioned studies, the decision to perform AE was based on a reduction in the hematocrit level in serial blood samples taken from patients with ongoing hemorrhage. [3,17–21] This suggests that AE should be performed when a contrast blush sign is present on a CT scan. Bansal et al.[22] identified a contrast blush on a CT scan in 47 children with blunt splenic injuries and successfully applied non-operative management without AE. Van der Vlies et al.[23] also reported successful non-operative management without AE in 9 blunt splenic trauma patients with contrast blush findings. Zamora et al.[24] reported that AE was performed for patients with high-grade (IV–V) injuries. In the present study, the decision to perform AE was based on a progressive decrease in the hematocrit level in serial blood samples of hemodynamically unstable patients with high-grade (IV–V) injuries. Although there are no studies demonstrating a correlation between hemodynamic instability and an ongoing decrease in the number of thrombocytes, we found a significant decrease in the thrombocyte count in the 11 patients who underwent AE.

15.00

*3 *

26 25

10.00

*54 31

*78 *60

5.00

.00

Non-AE

The literature includes reports of AE performed for highgrade (IV–V) injuries in pediatric patients with blunt abdominal trauma; however, it is unclear which organ injuries require AE most frequently. Kiankhooy et al.[3] reported that 3 of 7 patients who underwent AE had kidney injuries, 2 had spleen injuries, and 2 had liver injuries. Fenton et al.[21] performed angiography on 29 patients and embolization in 11 cases with splenic hemorrhage. In the present study, 7 of 11 patients with blunt abdominal injury who underwent AE due to ongoing bleeding had kidney injuries, 2 had splenic injuries, and 2 had liver injuries. The number of kidney injuries is noteworthy because 15 of 83 patients who presented with trauma suffered a kidney injury and 7 ultimately underwent AE. Kidney injuries constitute 8% to 12% of all cases of children with blunt abdominal injuries.[25] Children’s kidneys are larger than those of adults, less guarded, and more susceptible to blunt trauma injury.[3] In the present study it was also considered that the cause of kidney injury and ongoing hemorrhage might also have been related to urine in the kidney.

Groups

Figure 16. Length of intensive care unit stay (days) in the angiographic embolization (AE) and non-AE groups.

Length or hospital stay (day)

Simple boxplot of length of hospital stay by groups

30.00

20.00

*31

*13 *60 *14

78 18

10.00

.00

Non-AE Groups

Figure 17. Length of hospital stay (days).

244

Although post-embolization transient hypertension has been reported in patients with a kidney injury who underwent AE,[3] hypertension was not observed in the patients who underwent AE in the current study. The success of AE in the treatment of splenic injuries after blunt abdominal injury is good.[3] This is probably because the trabecular distribution of splenic vessels allows for targeted embolization while maintaining blood flow to uninjured areas of the organ.[3] Sclafani et al.[26] demonstrated that the spleen maintains reticuloendothelial function after AE. Several studies have proposed the use of AE in splenic trauma cases; however, this approach has not been standardized in adult patients.[27] Capecci et al.[27] reported that AE was used in 19% of splenic trauma cases in centers routinely performing a standard splenectomy, while the rate was 24% in centers for which Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

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standard splenectomy was non-routine. In the present study, 2 patients underwent AE due to blunt splenic injuries, and no complications were encountered after AE or discharge.

inal solid organ injuries due to blunt trauma if an intervention is required due to ongoing bleeding. Conflict of interest: None declared.

In pediatric blunt solid organ injuries, the second most frequently injured solid organ is the liver.[28] Vane et al.[28] reported that non-operative management produced better results in blunt liver injuries than operative treatment. It has also been reported that AE may be successful in blunt liver injuries because the blood supply to the liver is provided by the portal vein and hepatic artery, which prevents ischemia. Ohtsuka et al.[29] reported that hemorrhaging stopped 2 hours after AE and Kiankhooy reported that hemorrhaging was brought under control within 3 hours.[3] AE was successful in stopping the hemorrhage after 3 hours in the 2 cases presented in this study. Liver blood flow was normal in 2 patients on a CT scan during the follow-up examination conducted 6 months after discharge. AE has certain advantages in the case of solid organ injury, depending on the operative intervention.[8] Surgical operation in the case of persistent hemorrhage in a solid organ injury due to blunt abdominal trauma often results in surgical removal of the injured organ.[8] The mortality rate of operative intervention is quite high, reported to be between 10% and 65%.[8] AE intervention maintains organ function, but the organ remains subject to the effects of the traumatic injury.[3] Some studies have reported complications, such as pleural effusion and transient hypertension, during the post-AE period in pediatric patients; however, ongoing hemorrhage has not been reported.[3] In the present study, a patient with grade IV kidney injury experienced hemodynamic instability 24 hours after the first angiography with a hemorrhage located in a region that did not display any indication of hemorrhage during the angiography. Pleural effusion developed in 3 patients who underwent AE due to blunt kidney injuries, and drainage was performed. The AE technique can present some difficulties in the pediatric population.[30,31] These include locating the femoral artery for vascular cannulation and reaching the outermost end to stop the bleeding.[30] There were no significant problems in the current group of patients. Based on the present results, we conclude that AE can be used effectively and safely in pediatric cases of blunt abdominal injury, even on children as young as 1 year of age. An ongoing low hematocrit level is the gold standard marker informing the decision to intervene, and a low thrombocyte count was also a significant indicator of those who would later require intervention. Although the kidneys are the least frequently injured organs among cases of blunt abdominal solid organ injury, the majority of the children who underwent AE in the present study had a kidney injury. We strongly recommend the use of AE for pediatric patients with abdomUlus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

REFERENCES 1. Papakostidis C, Kanakaris N, Dimitriou R, Giannoudis PV. The role of arterial embolization in controlling pelvic fracture haemorrhage: a systematic review of the literature. Eur J Radiol 2012;81:897–904. 2. Ierardi AM, Duka E, Lucchina N, Floridi C, De Martino A, Donat D, et al. The role of interventional radiology in abdominopelvic trauma. Br J Radiol 2016;89:20150866. 3. Kiankhooy A, Sartorelli KH, Vane DW, Bhave AD. Angiographic embolization is safe and effective therapy for blunt abdominal solid organ injury in children. J Trauma 2010;68:526–31. 4. Moore EE, Shackford SR, Pachter HL, McAninch JW, Browner BD, Champion HR, et al.Organ injury scaling: spleen, liver, and kidney. J Trauma 1989;29:1664–6. 5. Gaines BA. Intra-abdominal solid organ injury in children: diagnosis and treatment. J Trauma 2009;67:S135–9. 6. Davis KA, Fabian TC, Croce MA, Gavant ML, Flick PA, Minard G, et al. Improved success in nonoperative management of blunt splenic injuries: embolization of splenic artery pseudoaneurysms. J Trauma 1998;44:1008–13. 7. Dent D, Alsabrook G, Erickson BA, Myers J, Wholey M, Stewart R, et al. Blunt splenic injuries: high nonoperative management rate can be achieved with selective embolization. J Trauma 2004;56:1063–7. 8. Peitzman AB, Richardson JD. Surgical treatment of injuries to the solid abdominal organs: a 50-year perspective from the Journal of Trauma. J Trauma 2010;69:1011–21. 9. Ong CC, Toh L, Lo RH, Yap TL, Narasimhan K. Primary hepatic artery embolization in pediatric blunt hepatic trauma. J Pediatr Surg 2012;47:2316–20. 10. Notrica DM. Pediatric blunt abdominal trauma: current management. Curr Opin Crit Care 2015;21:531–7. 11. Wisner DH1, Kuppermann N, Cooper A, Menaker J, Ehrlich P, Kooistra J, et al. Management of children with solid organ injuries after blunt torso trauma. J Trauma Acute Care Surg 2015;79:206–14. 12. Cloutier DR, Baird TB, Gormley P, McCarten KM, Bussey JG, Luks FI. Pediatric splenic injuries with a contrast blush: successful nonoperative management without angiography and embolization. J Pediatr Surg 2004;39:969–71. 13. Potoka DA, Schall LC, Ford HR. Risk factors for splenectomy in children with blunt splenic trauma. J Pediatr Surg 2002;37:294–9. 14. Puapong D, Brown CV, Katz M, Kasotakis G, Applebaum H, Salim A, et al. Angiography and the pediatric trauma patient: a 10-year review. J Pediatr Surg 2006;41:1859–63. 15. Haan JM, Biffl W, Knudson MM, Davis KA, Oka T, Majercik S, et al. Splenic embolization revisited: a multicenter review. J Trauma 2004;56:542–7. 16. Hagiwara A, Murata A, Matsuda T, Matsuda H, Shimazaki S. The efficacy and limitations of transarterial embolization for severe hepatic injury. J Trauma 2002;52:1091–6. 17. Skattum J, Gaarder C, Naess PA. Splenic artery embolisation in children and adolescents--an 8 year experience. Injury 2014;45:160–3. 18. Vo NJ, Althoen M, Hippe DS, Prabhu SJ, Valji K, Padia SA. Pediatric abdominal and pelvic trauma: safety and efficacy of arterial embolization.

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25. Halachmi S, Chait P, Hodapp J, Bgli DG, McLorie GA, Khoury AE, et al. Renal pseudoaneurysm after blunt renal trauma in a pediatric patient: management by angiographic embolization. Urology 2003;61:224. 26. Sclafani SJ, Shaftan GW, Scalea TM, Patterson LA, Kohl L, Kantor A, et al. Nonoperative salvage of computed tomography-diagnosed splenic injuries: utilization of angiography for triage and embolization for hemostasis. J Trauma 1995;39:818–25. 27. Capecci LM, Jeremitsky E, Smith RS, Philp F. Trauma centers with higher rates of angiography have a lesser incidence of splenectomy in the management of blunt splenic injury. Surgery 2015;158:1020–4. 28. Vane DW, Keller MS, Sartorelli KH, Miceli AP. Pediatric trauma: current concepts and treatment. J Intensive Care Med 2002;17:230–49.

22. Bansal S, Karrer FM, Hansen K, Partrick DA. Contrast blush in pediatric blunt splenic trauma does not warrant the routine use of angiography and embolization. Am J Surg 2015;210:345–50.

29. Ohtsuka Y, Iwasaki K, Okazumi S, Yoshida H, Matsunaga T, Kouchi K, et al. Management of blunt hepatic injury in children: usefulness of emergency transcatheter arterial embolization. Pediatr Surg Int 2003;19:29–34.

23. van der Vlies CH, Saltzherr TP, Wilde JC, van Delden OM, de Haan RJ, Goslings JC. The failure rate of nonoperative management in children with splenic or liver injury with contrast blush on computed tomography: a systematic review. J Pediatr Surg 2010;45:1044–9.

30. Singh A, Kumar A, Kumar P, Kumar S, Gamanagatti S. “Beyond saving lives”: Current perspectives of interventional radiology in trauma. World J Radiol 2017;9:155–177.

24. Zamora I, Tepas JJ 3rd, Kerwin AJ, Pieper P, Bhullar IS. They are not just little adults: angioembolization improves salvage of high grade IV-V blunt splenic injuries in adults but not in pediatric patients. Am Surg 2012;78:904–6.

31. Siddik-Sayyid SM, Aouad MT, Ibrahim MH, Taha SK, Nawfal MF, Tfaili YJ, et al. Femoral arterial cannulation performed by residents: a comparison between ultrasound-guided and palpation technique in infants and children undergoing cardiac surgery. Paediatr Anaesth 2016;26:823–30.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Anjiyografik embolizasyonun çocuklarda künt karın travmasına bağlı solid organ yaralanmasında kullanımı Dr. Kubilay Gürünlüoğlu,1 Dr. Canan Ceran,1 Dr. İsmail Okan Yıldırım,2 Dr. Ramazan Kutlu,2 Dr. Kaya Saraç,2 Dr. Turan Yıldız,1 Dr. Ercan Bayrakçı,1 Dr. Aytaç Taşçı,1 Dr. Ahmet Kadir Arslan,3 Dr. Mehmet Demircan1 1 2 3

İnönü Üniversitesi Tıp Fakültesi Turgut Özal Tıp Merkezi, Çocuk Cerrahisi Anabilim Dalı, Malatya İnönü Üniversitesi Tıp Fakültesi Turgut Özal Tıp Merkezi, Radyoloji Anabilim Dalı, Malatya İnönü Üniversitesi Tıp Fakültesi, Bioistatistik ve Tıp Bilişimi Anabilim Dalı, Malatya

AMAÇ: Anjiyografik embolizasyon (AE) çocuklarda künt karın travmasına bağlı solid organ yaralanmalarında sınırlı olarak kullanılmaktadır. Bu çalışmada, künt travmaya bağlı karındaki solid organ hasarına bağlı kanamalı hastalarda kanamayı kontrol etmek için AE’yi etkin ve güvenilir bir yöntem olarak kullanma deneyimimizi sunuyoruz. GEREÇ VE YÖNTEM: Çalışmamız da künt karın solid organ yaralanması geçirmiş ve son dört yıl içinde kliniğimize başvuran 17 yaş altı hastaları geriye dönük olarak araştırıldı. Veriler istatistiksel olarak analiz edildi. BULGULAR: Embolizasyon yapılan hastaların (AE) (n=11) yoğun bakım ünitesinde (YBÜ) kalış süresi ortalama dört gün olup ortalama hastanede kalış süresi 12 gündü. Ortalama hasta organ yaralanma derecesi 4.18±0.40 idi. Ameliyatsız tedavi uygulanan (embolizasyonsuz) (n=72) yaş ortalaması 9.1±3.8 yıl idi. YBÜ’de ortalama kalış süresi iki gündü (dağılım, 2–10 gün) ve ortalama hastanede kalış süresi 5.5 gündü (dağılım, 4–30 gün). Hastaların ortalama organ yaralanma derecesi 1.73±0.75 idi. AE gerektiren hastalarda solid organ hasarı daha ciddi derecede yüksekti (p<0.001). Bu nedenle yoğun bakım ünitelerinde (p<0.001) ve hastanede kalış süresi uzundu (p<0.001). Hematokritteki düşüş ortalama -7.33±5.3 (p<0.001) idi. AE sonrası hematokrit değişikliği (%) ile AE sonrası 72 saatlik ortalama AE sonrası kan kaybı 2±0.97 (p>0.05) idi. Tüm hastalar şifa ile taburcu edildi. TARTIŞMA: Anjiyografik embolizasyon, künt karın travmasına bağlı solid organ yaralanması olan çocuk hastalarda kanama kontrolü için etkili ve güvenilir bir yöntem olarak kullanılabilir. Anahtar sözcükler: Anjiyografik embolizasyon; çocuk; solid organ yaralanması. Ulus Travma Acil Cerrahi Derg 2019;25(3):238-246

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doi: 10.5505/tjtes.2018.00056

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ORIGIN A L A R T IC L E

SAPS III or APACHE IV: Which score to choose for acute trauma patients in intensive care unit? Melike Korkmaz Toker, M.D.,1 Aykan Gülleroğlu, M.D.,2 İlhan Güney Biçer, M.D.,4 Yavuz Demiraran, M.D.5

Ayşe Gül Karabay, M.D.,3

Department of Anesthesiology and Reanimation, Muğla Sıtkı Koçman University Training and Research Hospital, Muğla-Turkey

Department of Anesthesiology and Intensive Care Unit, Başkent University Ankara Hospital, Ankara-Turkey

Department of Anesthesiology, Ota-Jine Med Private Hospital, İstanbul-Turkey

Department of Anesthesiology and Reanimation, Osmaniye State Hospital, Osmaniye-Turkey

Department of Anesthesiology and Reanimation, Medipol University Faculty of Medicine, İstanbul-Turkey

ABSTRACT BACKGROUND: The aim of the present study was to evaluate the effectiveness of the Simplified Acute Physiology Score (SAPS) III and the Acute Physiology and Chronic Health Evaluation (APACHE) IV in the prediction of in-hospital mortality in surviving multitrauma patients. METHODS: This study was conducted in the 13-bed intensive care unit (ICU) of a tertiary hospital. A retrospective review of multitrauma patients whose care was managed in the ICU was performed. Data collection included details of age, gender, ICU admission, and outcome. APACHE IV and SAPS III scores, as well as the predicted mortality rate (PMR), were calculated using web-based calculators. RESULTS: Of the 90 patients 20% (n=18) were female and 80% (n=72) were male. The overall mortality rate was 25.6%. The mean APACHE IV, Acute Physiology Score (APS) and SAPS III score was 69.27±34.51, 66.42±33.72, and 26.36±27.14, respectively. The mean PMR according to the APACHE IV and the SAPS III was 26.36±27.14 and 17.07±24.88, respectively. The area under the curve result of receiver operating characteristic curve analysis was 0.87 for the APACHE IV and 0.93 for the SAPS III. CONCLUSION: The performance of the SAPS III was more sensitive and discriminative than the APACHE IV scoring system for multi-trauma ICU patients. Keywords: Acute Physiology and Chronic Health Evaluation IV; intensive care unit; mortality; scoring systems; Simplified Acute Physiology Score III; trauma.

INTRODUCTION Trauma is one of the world’s leading causes of death and disability.[1] The in-hospital mortality rate of trauma patients in Europe ranges between 15% and 17%.[2] Following the initial, immediate care provided in the emergency department or operating theater, patients with severe trauma need a close evaluation to determine treatment and further management in the intensive care unit (ICU). Management in the ICU includes predicting survival using severity scores. The estimation of mortality in trauma patients is important in order to

determine and address factors that prolong hospitalization. According to the data of the German Trauma Annual Registry Report System, the average duration of stay in the ICU after severe trauma was 8 days.[3] A number of scoring systems have been developed for critically ill patients. These include the. Acute Physiology and Chronic Health Evaluation (APACHE) score and the Simplified Acute Physiology Score (SAPS) models, which are widely used to assess the severity of illness and perform outcome predictions in critically ill patients.

Cite this article as: Korkmaz Toker M, Gülleroğlu A, Karabay AG, Biçer İG, Demiraran Y. SAPS III or APACHE IV: Which score to choose for acute trauma patients in intensive care unit?. Ulus Travma Acil Cerrahi Derg 2019;25:247-252. Address for correspondence: Melike Korkmaz Toker, M.D. Muğla Sıtkı Koçman Üniversitesi Eğitim ve Araştırma Hast., Anesteziyoloji ve Reanimasyon Anabilim Dalı, Muğla, Turkey Tel: +90 252 - 214 13 23 E-mail: meltoker@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):247-252 DOI: 10.5505/tjtes.2018.22866 Submitted: 29.01.2018 Accepted: 19.11.2018 Online: 14.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Korkmaz Toker et al. SAPS III or APACHE IV: Which score to choose for acute trauma patients in intensive care unit?

The APACHE-IV, the most recent version, is calculated based on 129 variables derived within the first 24 hours of ICU admission, and was developed based on 110,588 patients admitted to more than 104 ICUs across the US.[4] The SAPS III was created in 2005 using a database of 16,784 patients from 303 ICUs in 35 countries.[5] Several studies have compared the different outcomes of prediction scoring systems.[6,7] The latest ICU scoring systems, the SAPS III and the APACHE IV are powerful and have benefited from multiple revisions.[5] Although they were determined using several groups of ICU patients, these models have never been designed specifically for multi-trauma patients. Patients with traumatic injuries are typically evaluated with the commonly used scoring systems.[8] Initial arrival trauma scoring systems, such as the Injury Severity Score, the New Injury Severity Score, the Revised Trauma Score, and the Trauma Revised Injury Severity Score have been studied. [9–11] Orhon et al.[10] remarked upon the difficulty of determining an adequate prognosis with only anatomical and physiological injury scores. Nonetheless, the application of severity scoring systems to trauma patients facilitates the evaluation of likely clinical outcomes and the effectiveness of care in multi-trauma patients in the ICU. Both the APACHE and the SAPS tools are logistic regression models that include physiological and laboratory parameters. To our knowledge, no study has been conducted to evaluate the accuracy of the APACHE-IV and the SAPS III to predict in-hospital mortality in multi-trauma patients in Turkey. The objective of this study was to evaluate and compare the mortality assessment in multi-trauma patients in the ICU predicted by the APACHE IV and the SAPS III scoring systems.

MATERIALS AND METHODS Approval for this retrospective cohort research was granted by Istanbul Kanuni Sultan Suleyman Training and Research Hospital Clinical Research Ethical Committee. This study was conducted at the 13 bed ICU at Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Turkey. The retrospective data of multi-trauma patients treated in the ICU between 2013 and 2015 were reviewed. Data collection included patient age, gender, ICU length of stay, and ICU admission and outcome. The APACHE IV, Acute Physiology Score (APS), and SAPS III scores and predicted mortality rate (PMR) were calculated using web-based calculators: http://intensivecarenetwork.com/ Calculators/Files/APACHE4.html and http://intensivecarenetwork.com/Calculators/Files/SAPS3.html. Patients younger than 18 years of age, readmissions to the ICU, burn patients, and patients with insufficient data were excluded from this study.

analysis. The descriptive data of the study were specified as mean, SD, median, frequency, rate, minimum, and maximum. Mean tests were compared using an independent t-test if the data distribution was normal or the nonparametric MannWhitney U test if the data were not distributed normally. Spearman’s correlation analysis was performed to evaluate inter-parameter relationships. Diagnostic screening tests (sensitivity, specificity, positive predictive value, negative predictive value) and receiver operating characteristic (ROC) curve analysis were used to determine the cutoff for the parameters. The p values of <0.01 and <0.05 were considered statistically significant. Sample size was calculated based on data from a pilot group of 15 trauma patients. These patients were not included in the main study. In this pilot study, the mean PMR of patients was 29±22.6 according to the APACHE IV and 23±26.8 according to the SAPS III. Data from 80 patients were required to determine a significant difference with a one-sided type I error (α) of 0.1 and a power (1−β) of 0.7. An additional 10 patients were added to compensate for dropouts; a total of 90 patients were enrolled.

RESULTS The study was conducted with 90 multi-trauma patients who were admitted to the ICU between January 2013 and February 2015. Of the 90 patients, 20% (n=18) were female and 80% (n=72) were male. The mean patient age was 38.83±18.67 years. The overall mortality rate was 25.6% (n=23). In all, 63.3% (n=57) of the patients were transferred to general surgery or neurosurgery wards after ICU treatment and 11.1% (n=10) were referred to other hospitals (Table 1). Ten patients referred to other hospitals were subsequently followed up and included in the analysis. All of the patients who were referred survived. The mean APACHE IV, APS, and SAPS III scores, calculated within 24 hours of admission to the ICU, were 69.27±34.51, Table 1. Characteristics of the study group on admission and during follow-up

n % Min-Max Mean±SD

Age (years)

18–92 38.83±18.67

Gender Female

18 20.0

Male

72 80.0

Patient outcome Exitus

23 25.6

Discharge to ward

57 63.3

Statistical Analysis

Referred to another hospital 10 11.1

NCSS 2007 and PASS 2008 statistical software (NCSS, LLC, Kaysville, UT, USA) were used to perform the statistical

Min: Minimum; Max: Maximum; SD: Standard deviation.

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Table 2. Distribution of APACHE IV, APS, and SAPS III scores

Min-Max Mean±SD

APACHE IV

21–173

69.27±34.51

APS

21–173

66.42±33.72

SAPS III PMR according to APACHE IV

13–92

42.18±19.96

0.70–94.10

26.36±27.14

0–86

17.07±24.88

PMR according to SAPS

APACHE: Acute Physiology and Chronic Health Evaluation; APS: Acute Physiology Score; PMR: Predicted mortality rate; SAPS: Simplified Acute Physiology Score.; Min: Minimum; Max: Maximum; SD: Standard deviation.

66.42±33.72, and 26.36±27.14, respectively. The mean PMR according to the APACHE IV and SAPS III was 26.36±27.14 and 17.07±24.88, respectively (Table 2). The APACHE IV, APS, and SAPS III scores were significantly different with respect to patient outcome (p<0.01). The PMR according to the APACHE IV and SAPS III was statistically significant (p<0.01) (Table 3). Analysis of the APACHE IV scores according to mortality revealed a statistically significant difference (p<0.01). The SAPS III mortality scores were also statistically significant (p<0.01) (Table 4).

Table 3. APACHE IV, APS, and SAPS III scores according to patient outcome and PMR

Exitus (n=23)

Discharge (n=57)

Referral (n=10)

106.09±38.55

51.04±15.83

88.50±24.60

21–99 (52)

52–133 (92)

APACHE IV

Mean±SD

Min–Max (Median)

47–173 (109)

APS

Mean±SD

100.83±38.66 48.75±15.35 88.00±24.64 <0.01**

Min–Max (Median)

45–173 (101)

21–99 (49)

52–133 (89.50)

SAPS III

Mean±SD

65.87±17.54

30.30±8.98

55.40±12.75

Min–Max (Median)

36–92 (61)

13–49 (30)

33–73 (54)

APACHE IV PMR

Mean±SD

58.22±28.37

11.37±11.18

38.50±18.93

8.4–94.1 (67.5)

0.7–48.0 (6.9)

10.9–66.1 (39.8)

45.48±29.64

3.25±3.90

30.50±20.18

4–86 (38)

0–16 (2)

3–62 (24)

Min–Max (Median)

SAPS III PMR

Mean±SD

Min–Max (Median)

<0.01**

<0.01** <0.01** <0.01**

aKruskal-Wallis test. **P<0.01. APACHE: Acute Physiology and Chronic Health Evaluation; APS: Acute Physiology Score; PMR: Predicted mortality rate; SAPS: Simplified Acute Physiology Score.; Min: Minimum; Max: Maximum; SD: Standard deviation.

Table 4. APACHE IV and SAPS III scores according to mortality

No mortality (n=67)

Mortality (n=23)

Mean±SD (Median)

Acute Physiology and Chronic Health Evaluation IV

56.63±21.82 (55.00)

106.09±38.55 (109.00)

<0.01**

Simplified Acute Physiology Score III

34.05±13.11 (33.00)

65.87±17.54 (61.00)

<0.01**

Mann-Whitney U Test. **P<0.01. APACHE: Acute Physiology and Chronic Health Evaluation; SAPS: Simplified Acute Physiology Score; SD: Standard deviation.

Table 5. Diagnostic scanning tests and ROC curve results for PMR

Diagnostic scan

ROC curve

Cut-off Sensitivity Specificity Positive predictive Negative predictive Area 95% confidence value value interval APACHE IV

69.57

91.04

72.73

89.71

0.870

0.782–0.959

<0.01**

SAPS III

91.30

80.60

61.76

96.43

0.933

0.882–0.984

<0.01**

APACHE: Acute Physiology and Chronic Health Evaluation; ROC: Receiver operating characteristic; SAPS: Simplified Acute Physiology Score. PMR: Predicted mortality rate.

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ROC analysis and diagnostic scanning tests were used to calculate cutoff points for the APACHE IV and SAPS III prediction of mortality. The data obtained for the APACHE IV were a cutoff value of 95, with a sensitivity of 69.57%, specificity of 91.04%, positive predictive value of 72.73, and negative predictive value 89.71. The cutoff point for the SAPS III score and mortality was 45, with a sensitivity of 91.30%, specificity of 80.60%, positive predictive value of 61.76, and a negative predictive value of 96.43 (Table 5). The area under ROC Curve 1.0

Sensitivity

0.6

0.4

0.2

0.0 0.0

0.2

0.4 0.6 1 - Specificity

0.8

1.0

Figure 1. ROC curve graph for APACHE IV score and mortality. APACHE: Acute Physiology and Chronic Health Evaluation; ROC: Receiver operating characteristic. ROC Curve 1.0

The results of this study demonstrated that the performance of the SAPS III was more sensitive and discriminative than the APACHE IV score when we evaluated the accuracy of these prediction models for surviving multi-trauma patients in the ICU. Both scoring systems were sufficiently accurate to determine the ICU mortality of trauma patients.

In data from Californian ICUs,[7] and Dutch ICUs[13] the overall discrimination of the APACHE IV model was significantly better than the discrimination of the customized SAPS II model. In contrast to the 24-hour time interval used for the SAPS II model, the SAPS III measures the severity of disease based on data recorded within the first hour after admission. [5] The SAPS III score has been shown to exhibit good discrimination, calibration, and goodness of fit.[14] Based on a review of the literature,[7,15] we decided to evaluate the results of the SAPS III against the APACHE IV. Discrimination is a critical element in the assessment of the reliability of severity scoring systems. It is typically quantified using the AUC.[16] The discrimination of a prognostic model is considered good if the AUC is >0.8, moderate if the AUC is between 0.6 and 0.8, and poor if the AUC is <0.6.[17] Our results for the discrimination of the SAPS III were consistent with previous external validation studies (earlier AUC results: 0.82â&#x20AC;&#x201C;0.93).[13,18,19] Our findings were also supported by the results of an external validation study in which APACHE IV models proved to have good overall discrimination and accuracy in Dutch ICUs (AUC: 0.87; Brier score: 0.10).[13]

0.8

Sensitivity

DISCUSSION

The APACHE II was developed 3 decades ago, in 1985, and became the most commonly used scoring system in ICUs.[4] The advances in quality of care and the emergence of new treatment modalities since then have been immense and have significantly decreased the mortality rate in ICUs, making the older scoring systems more and more inaccurate.[12] The APACHE IV model has been found to have excellent discrimination and calibration in a USA population.[4] Parajuli et al.[12] found that the discrimination of the APACHE IV was better than the APACHE II model. Given the improvements in the APACHE scoring system, we decided to use the APACHE IV instead of the APACHE II in these multi-trauma patients.

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 graph for SAPS III score and mortality. ROC: Receiver operating characteristic; SAPS: Simplified Acute Physiology Score.

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the curve (AUC) recorded in the ROC curve graph for the APACHE IV and the SAPS III was 87% and 93.3%, respectively (Fig. 1 and Fig. 2).

Nassar et al.[19] researched the performance of the APACHE IV, the SAPS III and the Mortality Probability Model in Brazilian ICUs. They reported an AUC of 0.883 for the APACHE IV, while it was 0.855 for the SAPS III. The results of this study were not exactly consistent with our research; however, Nassar et al. used study groups with low-risk patient Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Korkmaz Toker et al. SAPS III or APACHE IV: Which score to choose for acute trauma patients in intensive care unit?

populations due to the absence of intermediate ICU facilities, and differences in the study population, regional variability in end-of-life decisions, and temporal bias, that is, the interval between the development of the prognostic models and study enrollment, may explain some variations. The observed mortality rate in the present study was 25.6%, and the mortality rate of each prognostic model studied was 26.36±27.14 for the APACHE IV and 17.7±24 for the SAPS III. All of the prognostic models we were used in our study, were produced a near-complete mortality estimate. accurate Our results suggest that the SAPS III scoring system was more sensitive to in-hospital mortality prediction than the APACHE IV for surviving trauma patients. The SAPS III admission score was based on records from within the first hour of acceptance of trauma patients to the ICU.[5] Half of the estimated power of earlier versions of the SAPS score is generated by compiling patient data from prior to admission to the ICU. A score recorded after the first 24 hours following ICU admission may in large part reflect the standard of care, rather than actual clinical status. Likely as a result of this advantage, we found the SAPS III score to be more sensitive than the APACHE IV. Ayazoglu et al.[20] conducted an APACHE IV validation study on a segment of the Turkish population and reported that the APACHE IV scoring system was successful in predicting mortality and evaluating the efficacy of treatment in a cardiovascular-thoracic surgery ICU. Geyik et al.[21] compared the mortality rate of ICU patients according to the APACHE II and IV scores and found that the APACHE II was superior in predicting mortality. This result may have been a reflection of the consistency of the patient groups in their study. To our knowledge, the present study is the first to compare the APACHE IV and the SAPS III using a Turkish population of trauma patients. Our study has potential limitations. The first is associated with the retrospective design. Another is that the study was conducted at a single ICU. Due to institutionally related differences in the management of trauma, the assessment of prognostic models from a single institution limits the ability to generalize our results to other ICUs. In conclusion, the results of our research demonstrated that the discrimination of both the APACHE IV and the SAPS III indicated that they were good tools for the evaluation of trauma patients treated in our ICU. The SAPS III had greater discriminatory power and sensitivity than the APACHE IV in predicting the mortality of multi-trauma patients in the ICU. It is recommended that further studies be performed to validate the SAPS III scoring system in varied ICUs that mostly deal with trauma. Conflict of interest: None declared. Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

REFERENCES 1. Curry N, Hopewell S, Dorée C, Hyde C, Brohi K, Stanworth S. The acute management of trauma hemorrhage: a systematic review of randomized controlled trials. Crit Care 2011;15:R92. 2. Böhmer AB, Just KS, Lefering R, Paffrath T, Bouillon B, Joppich R, et al. Factors influencing lengths of stay in the intensive care unit for survivingtrauma patients: a retrospective analysis of 30,157 cases. Crit Care 2014;18:R143. 3. Lefering R, Nienaber U, Paffrath T. TraumaRegister DGU® of the German Trauma Society. Notf Rett Med 2013;16:269–73. 4. Zimmerman JE, Kramer AA, McNair DS, Malila FM. Acute Physiology and Chronic Health Evaluation (APACHE) IV: hospital mortality assessment for today’s critically ill patients. Crit Care Med 2006;34:1297– 310. 5. Vincent JL, Moreno R. Clinical review: scoring systems in the critically ill. Crit Care 2010;14:207. 6. Livingston BM, MacKirdy FN, Howie JC, Jones R, Norrie JD. Assessment of the performance of five intensive care scoring models within a large Scottish database. Crit Care Med 2000;28:1820–7. 7. Kuzniewicz MW, Vasilevskis EE, Lane R, Dean ML, Trivedi NG, Rennie DJ, et al. Variation in ICU risk-adjusted mortality: impact of methods of assessment and potential confounders. Chest 2008;133:1319–27. 8. Moon SH, Kim JW, Byun JH, Kim SH, Choi JY, Jang IS, et al. The thorax trauma severity score and the trauma and injury severity score: Do they predict in-hospital mortality in patients with severe thoracic trauma?: A retrospective cohort study. Medicine (Baltimore) 2017;96:e8317. 9. Honarmand A, Safavi M. The new Injury Severity Score: a more accurate predictor of need ventilator and time ventilated in trauma patients than the Injury Severity Score. Ulus Travma Acil Cerrahi Derg 2008;14:110–7. 10. Orhon R, Eren SH, Karadayı S, Korkmaz I, Coşkun A, Eren M, et al. Comparison of trauma scores for predicting mortality and morbidity on trauma patients. Ulus Travma Acil Cerrahi Derg 2014;20:258–64. 11. Schluter PJ, Cameron CM, Davey TM, Civil I, Orchard J, Dansey R, et al. Using Trauma Injury Severity Score (TRISS) variables to predict length of hospital stay following trauma in New Zealand. N Z Med J 2009;122:65–78. 12. Parajuli BD, Shrestha GS, Pradhan B, Amatya R. Comparison of acute physiology and chronic health evaluation II and acute physiology and chronic health evaluation IV to predict intensive care unit mortality. Indian J Crit Care Med 2015;19:87–91. 13. 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 ChronicHealth Evaluation II and Simplified Acute Physiology Score II. J Crit Care 2011;26:105.e11–8. 14. Moreno RP, Metnitz PG, Almeida E, Jordan B, Bauer P, Campos RA, et al. SAPS 3--From evaluation of the patient to evaluation of the intensive care unit. Part 2: Development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med 2005;31:1345–55. 15. Khwannimit B, Bhurayanontachai R. The performance and customization of SAPS 3 admission score in a Thaimedical intensive care unit. Intensive Care Med 2010;36:342–6. 16. Frederickson TA, Renner CH, Swegle JR, Sahr SM. The cumulative effect of multiple critical care protocols on length of stay in a geriatric trauma population. J Intensive Care Med 2013;28:58–66. 17. Hernandez AM, Palo JE. Performance of the SAPS 3 admission score as a predictor of ICU mortality in a Philippine private tertiary medical center intensive care unit. J Intensive Care 2014;2:29.

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20. Ayazoglu AT, Candan A, Ozkaynak I EI. Investigation of the effectiveness of the APACHE IV Model for the evaluation of prognosis in the intensive care unit patients. New J Med 2012;29:100–4.

19. Nassar AP Jr, Mocelin AO, Nunes AL, Giannini FP, Brauer L, Andrade FM, et al. Caution when using prognostic models: a prospective comparison of 3 recentprognostic models. J Crit Care 2012;27:423.e1–7.

21. Geyik FD, Altun GT, Citak N, Ayazoglu TA. A comparison of APACHE II and APACHE IV scoring systems in patients admitted to an Intensive Care Unit. [Turkish]. Journal of Anesthesia 2013;21:182–6.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Yoğun bakımdaki akut travma hastalarında hangi skoru seçmeliyiz: SAPS III mü, APACHE IV mü? Dr. Melike Korkmaz Toker,1 Dr. Aykan Gülleroğlu,2 Dr. Ayşe Gül Karabay,3 Dr. İlhan Güney Biçer,4 Dr. Yavuz Demiraran5 Muğla Sıtkı Koçman Üniversitesi Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Muğla Başkent Üniversitesi Ankara Hastanesi, Anesteziyoloji ve Yoğun Bakım Anabilim Dalı, Ankara Ota-Jine Med Hastanesi, Anesteziyoloji Kliniği, İstanbul 4 Osmaniye Devlet Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, Osmaniye 5 Medipol Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reaniamasyon Anabilim Dalı, İstanbul 1 2 3

AMAÇ: Çalışmanın amacı, hayatta kalan çoklu travma hastalarında basitleştirilmiş akut fizyoloji skoru (SAPS) III ve akut fizyoloji ve kronik sağlık değerlendirmesi (APACHE) IV’ün mortaliteyi öngörmedeki etkinliğini değerlendirmektir. GEREÇ VE YÖNTEM: Bu çalışma üçüncü basamak bir hastanenin 13 yataklı yoğun bakım ünitesinde (YBÜ) gerçekleştirildi. YBÜ’de tedavi edilen çoklu travma hastalarının geriye dönük bir incelemesi yapıldı. Toplanan veriler yaş, cinsiyet, yoğun bakım kabul ve yoğun bakımdaki sonuçları içeriyordu. APACHE IV, SAPS III ve öngörülen mortalite oranı web tabanlı bir hesap makinasıyla hesaplandı. BULGULAR: Doksan hastanın %20’si (n=18) kadın, %80’i (n=72) erkekti. Genel mortalite oranı %25.6 idi. APACHE IV, APS ve SAPS III puan ortalamaları 69.27±34.51, 66.42±33.72 ve 26.36±27.14 bulundu. APACHE IV ve SAPS III’e göre ortalama öngörülen mortalite oranı 26.36±27.14 ve 17.07±24.88 idi. Eğrinin altındaki alan (EAA) sırasıyla APACHE IV ve SAPS III için 0.87, 0.93 idi. TARTIŞMA: Çoklu travmalı yoğun bakım hasta grubunda, SAPS III’ün performansı APACHE IV skoruna göre daha hassas ve ayırt edicidir. Anahtar sözcükler: Akut fizyoloji ve kronik sağlık değerlendirmesi IV; basitleştirilmiş akut fizyoloji skoru III; mortalite; skorlama sistemleri; travma; yoğun bakım ünitesi. Ulus Travma Acil Cerrahi Derg 2019;25(3):247-252

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doi: 10.5505/tjtes.2018.22866

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ORIGIN A L A R T IC L E

Acute biliary pancreatitis during pregnancy and in the post-delivery period Semih Hot, M.D., Seracettin Eğin, M.D., Berk Gökçek, M.D., Metin Yeşiltaş, M.D., Dursun Özgür Karakaş, M.D. Department of General Surgery, University of Health Science İstanbul Okmeydanı Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: Acute pancreatitis has an incidence of approximately 1 in 1000 to 5000 pregnancies, and is most often seen in the third trimester or the postpartum period. The most common cause of pregnancy-related acute pancreatitis is cholelithiasis, which accounts for more than 65% of cases. The aim of this study was to present a detailed analysis of 4 years of experience with cases of acute biliary pancreatitis related to pregnancy from a single center. METHODS: The medical records of 55 consecutive patients who were hospitalized in the emergency surgery clinic for acute biliary pancreatitis related to pregnancy between January 1, 2014 and January 1, 2018 were examined in this single-center, retrospective study. RESULTS: Fifty-five patients with acute biliary pancreatitis related to pregnancy were included in the study. Of the 55 women, 13 (24%) were in the pregnant group, 28 (51%) in the postpartum (6 weeks) group, and 14 (25%) were in the 1-year (6 weeks-1 year) group. There was no statistically significant difference between the 3 groups. The most appropriate treatment for each patient was targeted. Six (10%) patients had recurrent acute pancreatitis. There was no maternal or fetal mortality or morbidity. CONCLUSION: Acute biliary pancreatitis related to pregnancy is not limited to pregnant women, and the incidence of these cases was greater than expected. Acute biliary pancreatitis related to pregnancy can be successfully managed with conservative treatment because it usually has a mild to moderate clinical course. However, the surgeon should keep an early cholecystectomy in mind for patients other than those in the first trimester. Keywords: Acute pancreatitis; management; pregnancy; prognosis.

INTRODUCTION The physiological changes that usually occur during pregnancy may change the process, symptoms, and signs of many diseases. It also affects the accuracy and reliability of many diagnostic tests. While early diagnosis of diseases becomes more challenging, the results and prognosis can also worsen. Also, serious emergency surgical conditions, such as acute pancreatitis (AP), are difficult to diagnose during pregnancy and in the postpartum period. The symptoms may be misleading and considered normal in pregnancy.[1] Also, pregnancy is an exclusion criterion in some AP studies.[2]

The incidence rate of pregnancy-related biliary colic, acute cholecystitis, acute biliary pancreatitis, or acute cholangitis is between 0.05% and 8%.[1] AP usually occurs with an incidence of approximately one in 1000–5000 pregnancies, particularly in the third trimester or the postpartum period.[1,3,4] During pregnancy, changes in the bile composition and gall bladder mobility lead to the formation of gall bladder stones. [5] Cholelithiasis is the most common cause of pregnancy-related AP, which accounts for more than 65% of cases.[6] A gallstone passing through the ampulla of Vater leads to AP.

Cite this article as: Hot S, Eğin S, Gökçek B, Yeşiltaş M, Karakaş DÖ. Acute biliary pancreatitis during pregnancy and in the post-delivery period. Ulus Travma Acil Cerrahi Derg 2019;25:253-258. Address for correspondence: Semih Hot, M.D. İstanbul Okmeydanı Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 221 77 77 / 5260 E-mail: semihhot@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):253-258 DOI: 10.14744/tjtes.2019.03846 Submitted: 27.02.2019 Accepted: 27.03.2019 Online: 15.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Hot et al. Acute biliary pancreatitis during pregnancy and in the post-delivery period

If AP is not correctly diagnosed and treated, it can lead to pancreatic necrosis, abscess, and multiple organ dysfunction and subsequently maternal and fetal morbidity and mortality. [7–9] Despite the issues, there are no guidelines currently available for AP diagnosis and management in pregnant women. In addition, a gallstone disease (acute cholecystitis, choledocholithiasis, cholangitis, or gallstone pancreatitis) is the most common cause of maternal hospitalization in the first year after delivery.[10] Particularly, acute biliary pancreatitis related to pregnancy (ABPP) has a relatively high recurrence rate of 70% in pregnant women compared to the general population (20–30%).[2,6] For the management of ABPP, the physician should consider maternal and fetal risks associated with irradiation using endoscopic retrograde cholangiopancreatography (ERCP), imaging methods, medical treatment, general anesthesia, and surgery. Laparoscopic cholecystectomy (LC) reduces the morbidity of surgical treatment in ABPP patients. In this study, medical data, management, and outcomes of women with ABPP were examined.

MATERIALS AND METHODS Study Ethics The clinical study protocol was approved by the Institutional Ethics Committee of University of Health Sciences, Okmeydanı Training and Researh Hospital. The study was performed according to the principles of the Helsinki Declaration. All the patients were routinely informed about the procedures and provided their written informed consent (no: 09.01.2018/806).

Study Design In this single center retrospective study, medical records of the patients who were hospitalized in the Emergency Surgery Clinic for ABPP between January 1, 2014, and January 1, 2018 were examined. The patients were divided into three groups: (1) pregnancy; (2) postpartum; and (3) the first year after delivery. Patients with non-biliary AP and those with acute cholecystitis, choledocholithiasis, or acute cholangitis were excluded from the study. Pregnancy was grouped as the first (0–13 weeks), second (14–26), and third (27–40 weeks) trimesters. Infants who were born before the end of week 37 were considered premature, while a pregnancy was considered full term at 40 weeks. For an AP diagnosis, at least two of the following three criteria were stipulated: (1) acute abdominal pain; (2) serum lipase activity (or amylase activity) at least three-fold greater than the upper limit of the normal reference range; and (3) radiological AP findings. The ABPP severity was determine using the 0- and 48 h Ranson scores. Abdominal ultrasonography (USG) was performed on all patients by radiologists. Magnetic resonance cholangiopancreatography (MRCP) was performed in patients with high bilirubin levels or in those who had abnormal biliary channel signs detected in USG. 254

ERCP was performed in patients with the evidence of stones in the common bile duct (CBD). The following parameters were reviewed: the patient’s age, pregnancy trimester, AP severity, risk factors such as hormonal therapy, in vitro fertilization (IVF) procedure, multiparity, obesity and diabetes mellitus, imaging modalities, results of biochemical tests, treatment methods, length of hospital stay (LOS), and maternal or fetal morbidity and mortality. The medical data from maternal and fetal obstetric evaluations that were performed on a monthly basis by the gynecologist were reviewed. The infant’s height and weight at birth, gestational week, and physical examination findings were evaluated. The mainstay of management in ABPP patients consisted of conservative treatment in the first trimester, LC in the second trimester; conservative treatment or endoscopic sphincterotomy (ES) via ERCP in the third trimester, and LC in the postpartum period in our clinic. The follow-up of the patients was continued until the first year after delivery.

Statistical Analysis The data analysis was carried out using the Statistical Package for Social Sciences (SPSS®) software, version 15.0 (IBM® Corp., Armonk, NY, USA). All values were expressed as mean ± standard deviation or number (percentage). The data were compared between subgroups using ANOVA (SPSS software, version 15). A p value of <0.05 was considered statistically significant.

RESULTS In total, 55 patients with ABPP were included the study, of which 13 (24%) were in the pregnant group, 28 (51%) in the postpartum (6 weeks) group, and 14 (25%) in the 1 year (6 weeks–1 year) group. During the same 4-year period, 15,229 deliveries were reported at our center. The incidence of ABPP was one case per 1171 pregnancies during pregnancy, and if the total patients in the three groups were considered, the incidence of ABPP was calculated as one case per 277 pregnancies. Overall, 86% of the patients in the 1 year group had ABPP within the first 6 months after birth. Epigastric pain was the main complaint in all patients and 43 (78%) patients had nausea and vomiting. All the patients had high serum lipase and amylase activity (at least three-fold greater than the upper limit of the normal reference range) and biliary pathology detected in abdominal USG. Seven of 13 pregnant patients were in the third trimester and five were in the second trimester. There was only one woman in the first trimester. The mean age of the patients was 28.93±6.3 (range, 18–45) years, with no significant difference between the pregnancy, postpartum, and the first-year groups (31.8±6.2, 28.1±6.5, and 27.9±5.6 days, respectively, p>0.05). Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Hot et al. Acute biliary pancreatitis during pregnancy and in the post-delivery period

Table 1. Characteristics of the patients with ABPP Groups

Pregnant

Postpartum

One year

Total

Patients, n (%)

13 (24)

28 (51)

14 (25)

55 (100)

Maternal age, years (Mean±SD)

31.8±6.2

28.1±6.5

27.9±5.6

28.93±6.3

Multiparity, n (%)

13 (100)

18 (64)

8 (57)

39 (71)

Parity (Mean±SD)

3.5±2.2 1.9±1.1 2.1±1.1 2.4±1.6

Ranson score (Mean±SD)

0.3±0.5

0.6±0.9

0.9±0.9

0.62±0.8

Recurrence, n (%)

3 (23)

3 (10)

–

6 (11)

Length of the hospital stay, days (Mean±SD)

5.0±1.0

4.5±1.3

4.5±0.9

4.6±1.1

ABPP: Acute biliary pancreatitis related to pregnancy; SD: Standard deviation.

When all patients were considered, 39 (71%) women were multiparous and two had undergone IVF treatment for pregnancy. Other risk factors in the total patients with ABPP included morbid obesity (n=2), preeclampsia (n=2), diabetes mellitus (n=2), multiple (twin) pregnancies (n=1), and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (n=1). When the patients were evaluated according to the Ranson system, they usually had mild pancreatitis. Thirty-one (56%) patients had a Ranson score level (RSL) of 0, 15 (27%) patients had 1, eight (15%) patients had 2, and one (2%) patient had 3. No significant differences were found between the groups in terms of age, multiparity, parity, and RSL. The characteristics of patients with ABPP are presented in Table 1. However, pregnant women with ABPP were older, and more number of parities but lower mean RSL than women with ABPP in the postpartum and 1-year groups was observed. The mean RSL was 0.62±0.8 (3–9) days with no significant differences between the three groups (pregnancy, 0.3±0.5l; postpartum, 0.6±0.9, and first year after delivery, 0.9±0.9, p>0.05). The mean LOS was 4.6±1.1 (range, 3–9) days with no significant differences between the pregnancy, postpartum, and the 1-year groups (5.0±1.0, 4.5±1.3, and 4.5±0.9 days, respectively, p>0.05). A total of six (10%) patients (three in the pregnant group and three in the postpartum group had recurrent ABPP. LC was used for three pregnant women in their second trimesters. ES via ERCP was applied to four women in their third trimesters. Two of these patients had had previous cholecystectomies, and three patients had recurrent ABPP. Eight patients in the pregnant group underwent planned LC in the first 6 months after birth. Only a 44-year-old female in the postpartum group had acute necrotizing pancreatitis. There were stones in the CBD, as detected in the MRCP imaging. This patient underwent percutaneous drainage, and stones were removed by standard techniques using ERCP. A 36 year-old multiparous (three children) patient with preeclampsia and Class II HELLP synUlus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

drome had ABPP in the postpartum period. This patient underwent conservative treatment and ES via ERCP followed by LC. LC was performed in 21 (75%) of the 28 patients in the postpartum group and 11 (78.5%) of the 14 patients in the 1-year group. ES via ERCP and LC were performed in three patients with recurrent ABPP in the postpartum group. There were no postoperative or post-ERCP procedural complications. Of the 13 patients who were pregnant, 10 (77%) had normal vaginal delivery and three (27%) had cesarean delivery. There was no fetal or maternal mortality. Seven (54%) patients with ABPP in the pregnant group had high risk pregnancies because of advanced age (>35 years, n=4), morbid obesity (n=1), twin pregnancy (n=1), and preeclampsia (n=1). Eleven patients had full-term births, while two patients had premature labor. One of them was a 45-year-old woman who was morbidly obese and multiparous (six children and one abortion) and the other was a 25-year-old multiparous woman (three children) with preeclampsia.

DISCUSSION Studies have shown that the use of oral contraceptives and multiparity increase the risk of biliary stasis and therefore leads to gallstones formation.[11,12] The gallbladder motility disorder continues for about 1 year after delivery. The frequency of pregnancy and multiparity are the major risk factors for cholesterol gallstones. As the number of pregnancies increased, gallstone-related diseases also increased.[11,13] In this study, multiparity was detected in most of the patients (71%). Furthermore, all patients in the pregnant group were multiparous. ABPP has a high likelihood of recurrence. However, it is possible to prevent the recurrence by the early diagnosis and optimal treatment. For this reason, the etiology should be prioritized in the management of ABPP patients.[8,14] In the present study, six (10%) patients had recurrent ABPP. Five patients with recurrent ABPP were multiparous, and a primiparous patient had undergone IVF to induce pregnancy. 255

Hot et al. Acute biliary pancreatitis during pregnancy and in the post-delivery period

USG is a highly reliable modality with approximately 100% sensitivity and specificity to diagnose gallbladder diseases in pregnant women.[15] Therefore, USG is the first-referenced imaging method to elucidate the etiology of biliary pancreatitis and confirm it in patients whose diagnosis was compatible with pancreatitis based on the clinical signs and laboratory parameters. In the present study, USG proved to be reliable once again by detecting biliary pathology in all patients. Abdominal computed tomography (CT) is the most commonly used imaging modality to determine the severity of AP. However, it is not recommended in all trimesters, particularly to prevent the fetus from being exposed to radiation.[8] A CT scan was used for only one patient with an increase in the 48-h Ranson score to level 3. A 27-year-old postpartum patient who had single peripancreatic fluid collection seen in the CT scan underwent LC. The effects of non-contrast MRCP on the fetus during pregnancy are unknown. However, it is not recommended to use this method in the first trimester. Data in the fetal safety are limited during this period. The administration of gadolinium during pregnancy is controversial, and the physician should be aware of the fact that it is not used unless absolutely necessary.[16,17] However, MRCP is useful for detecting gallstones in the CBD, while CT and USG modalities have low sensitivities in this regard.[18] ERCP is used for diagnostic and therapeutic purposes. This method is particularly useful for detecting the presence of small gallstones in the CBD. In addition, many studies have reported that ERCP and ES can be safely performed in pregnant women.[19] In the present study, ES via ERCP were successfully carried out in 13 (24%) patients without any complications. The Ranson criteria comprise one of the oldest scoring systems for assessing the severity and mortality of AP. However, it is still used safely today.[20,21] While the criteria with 11 parameters are used to score acute alcoholic pancreatitis, the modified Ranson criteria with 10 parameters are used to score acute biliary pancreatitis. In the present study, the AP severity was evaluated according to the Ranson scoring system, and most of the patients had mild ABPP. The absence of mortality and morbidity in the patients supported the accuracy of the Ranson scoring system. Hospitalization, supportive treatment, intravenous fluid therapy, and nutritional supplements such as probiotics, glutamine, omega-3 fatty acids, and vitamins are preferred for the initial ABPP management. Most patients recovered well with the appropriate treatment and support.[22] In addition, the components of conservative treatment include pain control and antibiotic therapy (depending on the clinical picture). Antibiotic therapy is recommended when there is a biliary infection or infected necrotizing pancreatitis accompanied by ABPP.[23] However, the management was difficult in patients with comorbid factors, such as morbid obesity, diabetes mellitus, 256

preeclampsia, and HELLP syndrome. These patients should be managed by a multidisciplinary team with experienced surgeons working at high-volume centers. There was no significant difference in the maternal mortality when conservative and surgical treatments were compared, but fetal mortality was significantly higher in patients who did not rapidly benefit from the supportive treatment.[24] ERCP and ES, biliary stent placement, or cholecystectomy should be performed in patients who do not respond quickly to supportive therapy and in those with acute cholangitis during follow-up. To avoid recurrences and reduce costs, cholecystectomy can be performed in patients with mild ABPP who recover during the hospital stay.[25] Cholecystectomy may be performed safely, focusing on pregnant patientsâ&#x20AC;&#x2122; changing anatomy and not harming the fetus, although this technique can be challenging in pregnant patients, particularly in the last weeks of the third trimester.[26] Undoubtedly, the surgical treatment by experienced surgeons working at high-volume centers is associated with less maternal and fetal complications compared to the surgical treatment by less experienced surgeons.[27] LC is the gold standard for gallbladder-associated surgical treatment and should also be preferred in pregnant women.[28] Although LC seems to be a reliable surgical treatment in pregnancy, it is ideally performed in the second trimester because the uterus is not very large and the organogenesis has been achieved in the fetus. LC may be advised as soon as possible, without maternal and fetal morbidity.[6] The best choice in the treatment of ABPP can be summarized as follows: (1) conservative treatment and planned LC in the second trimester for patients in the first trimester; (2) LC for patients in the second trimester; and (3) and conservative treatment or ES via ERCP and early postpartum planned LC for patients in the third trimester.[6] Hypertension, the essential sign of preeclampsia, is common in patients with the HELLP syndrome. Thrombocytopenia is one of the criteria for the HELLP syndrome and is common in preeclampsia. Hypertension and thrombocytopenia may occur after the twentieth week of pregnancy. Pregnant women with preeclampsia or the HELLP syndrome may have high levels of liver enzymes.[29] HELLP syndrome may cause placental abruption, uterine rupture, intra-amniotic infections, and pulmonary and cerebral edema.[30] There are microvascular abnormalities in preeclampsia. If the splanchnic circulation is affected, preeclampsia can cause the HELLP syndrome, AP, and cholecystitis. In the present study, ABPP was observed in a 36-year-old woman with preeclampsia and class II HELLP syndrome in the postpartum period. Initially, the patient underwent conservative treatment. Later, ES via ERCP and LC were performed. In the present study, 10% (n=6) of the conservatively treated patients were accepted for recurrent ABPP and re-hospitalized. It is unpredictable to determine when and how severe ABPP can be in case of relapses; therefore, cholecystectomy should be performed at the earliest. The incidence of ABPP Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Hot et al. Acute biliary pancreatitis during pregnancy and in the post-delivery period

during pregnancy was calculated as one case per 1171 pregnancies. However, when ABPP cases observed during the first year after delivery were added to the total number, the incidence of ABPP was determined as one case per 277 pregnancies. Considering that the physiological changes during pregnancy are normalized within 1 year after delivery, this study showed that the incidence of ABPP cases was actually higher than that originally presumed. This awareness was accepted as the novelty of our research. There are certain limitations to the present study. The first limitation was the retrospective nature of this study. The results of the retrospective study are limited to change existing practices in the management of diseases. However, this limitation could be ignored because the medical records were evaluated very cautiously. In addition, such a study is difficult to perform prospectively due to ethical concerns related to very close maternal and fetal follow up. Another limitation of the present study was the small size of patients used for analysis, a reflection of the low incidence of ABPP. In conclusion, ABPP remains a difficult clinical problem today to overcome with a comparatively limited evidence base. ABPP does not only include pregnant women, but the incidence of these cases is actually higher than expected. ABPP can be successfully managed with conservative treatment because it usually has a mild to moderate clinical course. However, the surgeon should consider early cholecystectomy in patients except in the first trimester. ES via ERCP should be performed if necessary. In addition, patients with high risks for maternal and fetal mortality and morbidity should be managed by a multidisciplinary team consisting of an obstetrician, radiologist, gastroenterologist, and experienced surgeons working at high-volume centers Conflict of interest: None declared.

REFERENCES 1. Hernandez A, Petrov MS, Brooks DC, Banks PA, Ashley SW, Tavakkolizadeh A. Acute pancreatitis and pregnancy: a 10-year single center experience. J Gastrointest Surg 2007;11:1623–7. 2. Aziret M, Ercan M, Toka B, Parlak E, Karaman K. Risk factors for morbidity in walled-off pancreatic necrosis and performance of continuous postoperative lavage: A single-center experience. Ulus Travma Acil Cerrahi Derg 2018;24:488–96. 3. Mador BD, Nathens AB, Xiong W, Panton ONM, Hameed SM. Timing of cholecystectomy following endoscopic sphincterotomy: a populationbased study. Surg Endosc 2017;31:2977–85. 4. Eddy JJ, Gideonsen MD, Song JY, Grobman WA, O’Halloran P. Pancreatitis in pregnancy. Obstet Gynecol 2008;112:1075–81. 5. de Bari O, Wang HH, Portincasa P, Liu M, Wang DQ. The deletion of the estrogen receptor α gene reduces susceptibility to estrogen-induced cholesterol cholelithiasis in female mice. Biochim Biophys Acta 2015;1852:2161–9. 6. Ducarme G, Maire F, Chatel P, Luton D, Hammel P. Acute pancreatitis during pregnancy: a review. J Perinatol 2014;34:87–94.

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7. Howden JK, Baillie J. Preoperative versus postoperative endoscopic retrograde cholangiopancreatography in mild to moderate pancreatitis: a prospective randomized trial. Gastrointest Endosc 2001;53:834–6. 8. Pitchumoni CS, Yegneswaran B. Acute pancreatitis in pregnancy. World J Gastroenterol 2009;15:5641–6. 9. Tang M, Xu JM, Song SS, Mei Q, Zhang LJ. What may cause fetus loss from acute pancreatitis in pregnancy: Analysis of 54 cases. Medicine (Baltimore) 2018;97:e9755. 10. Ko CW, Beresford SA, Schulte SJ, Matsumoto AM, Lee SP. Incidence, natural history, and risk factors for biliary sludge and stones during pregnancy. Hepatology 2005;41:359–65. 11. Wang HH, Liu M, Clegg DJ, Portincasa P, Wang DQ. New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation. Biochim Biophys Acta 2009;1791:1037–47. 12. Ansari-Moghaddam A, Khorram A, Miri-Bonjar M, Mohammadi M, Ansari H. The Prevalence and Risk Factors of Gallstone Among Adults in South-East of Iran: A Population-Based Study. Glob J Health Sci 2015;8:60–7. 13. Everhart JE, Khare M, Hill M, Maurer KR. Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology 1999;117:632–9. 14. Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006;101:2379–400. 15. Gilo NB, Amini D, Landy HJ. Appendicitis and cholecystitis in pregnancy. Clin Obstet Gynecol 2009;52:586–96. 16. Chen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol 2008;112:333–40. 17. Kanal E, Barkovich AJ, Bell C, Borgstede JP, Bradley WG Jr, Froelich JW, et al; ACR Blue Ribbon Panel on MR Safety. ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol 2007;188:1447–74. 18. Scheiman JM, Carlos RC, Barnett JL, Elta GH, Nostrant TT, Chey WD, et al. Can endoscopic ultrasound or magnetic resonance cholangiopancreatography replace ERCP in patients with suspected biliary disease? A prospective trial and cost analysis. Am J Gastroenterol 2001;96:2900–4. 19. Cappell MS, Stavropoulos SN, Friedel D. Systematic review of safety and efficacy of therapeutic endoscopic-retrograde-cholangiopancreatography during pregnancy including studies of radiation-free therapeutic endoscopic-retrograde-cholangiopancreatography. World J Gastrointest Endosc 2018;10:308–321. 20. Ruan GJ, Mukherjee S. Ranson Criteria. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018-2019 Jan 19. 21. Kılıç MÖ, Çelik C, Yüksel C, Yıldız BD, Tez M. Correlation between Ranson score and red cell distribution width in acute pancreatitis. Ulus Travma Acil Cerrahi Derg 2017;23:112–6. 22. Lu EJ, Curet MJ, El-Sayed YY, Kirkwood KS. Medical versus surgical management of biliary tract disease in pregnancy. Am J Surg 2004;188:755–9. 23. Villatoro E, Bassi C, Larvin M. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev 2006;(4):CD002941. 24. Date RS, Kaushal M, Ramesh A. A review of the management of gallstone disease and its complications in pregnancy. Am J Surg 2008;196:599– 608. 25. Juo YY, Khrucharoen U, Sanaiha Y, Seo YJ, Dutson E, Benharash P. Cumulative Financial Burden of Readmissions for Biliary Pancreatitis in Pregnant Women. Obstet Gynecol 2018;132:415–22.

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http://www.sages.org/publications/guidelines/guidelines-for-diagnosistreatment-and-use-of-laparoscopy-for-surgical-problems-duringpregnancy/. Accessed Apr 10, 2019. 29. Upadya M, Rao ST. Hypertensive disorders in pregnancy. Indian J Anaesth 2018;62:675–81. 30. Rao D, Chaudhari NK, Moore RM, Jim B. HELLP syndrome: a diagnostic conundrum with severe complications. BMJ Case Rep 2016;2016. pii: bcr2016216802.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Gebelikte ve doğum sonrası dönemde akut biliyer pankreatit Dr. Semih Hot, Dr. Seracettin Eğin, Dr. Berk Gökçek, Dr. Metin Yeşiltaş, Dr. Dursun Özgür Karakaş Sağlık Bilimleri Üniversitesi, İstanbul Okmeydanı Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul

AMAÇ: Akut pankreatit, özellikle üçüncü trimesterde veya doğum sonrası dönemde, 1000–5000 gebelikte yaklaşık bir oranında görülür. Gebeliğe bağlı akut pankreatitin en yaygın nedeni, olguların %65’inden fazlasını oluşturan kolelitiazistir. Bu çalışma, gebeliğe bağlı akut biliyer pankreatit olgularında tek bir merkezin dört yıllık deneyiminin detaylı bir analizini sunmayı amaçlamıştır. GEREÇ VE YÖNTEM: Bu tek merkez geriye dönük çalışmada, acil cerrahi kliniğinde 1 Ocak 2014–1 Ocak 2018 tarihleri arasında gebeliğe bağlı akut biliyer pankreatit nedeniyle hastaneye yatırılan 55 ardışık hastanın tıbbi kayıtları incelendi. BULGULAR: Çalışmaya gebeliğe bağlı akut biliyer pankreatitli elli beş hasta dahil edildi. Elli beş kadından 13’ü (%24) hamile, 28’i (%51) doğum sonrası (altı hafta), 14’ü (%25) bir yıl (6 hafta–1) grubuydu. Üç grup arasında istatistik olarak anlamlı fark yoktu. Her hasta için en uygun tedavi hedef alındı. Altı hastada (%10) tekrarlayan akut pankreatit vardı. Anne veya fetal mortalite ve morbidite yoktu. TARTIŞMA: Gebeliğe bağlı akut biliyer pankreatit sadece hamile kadınları içermez ve bu olguların görülme sıklığı beklenenden daha yüksektir. Gebeliğe bağlı akut biliyer pankreatit konservatif tedavi ile başarılı bir şekilde tedavi edilebilir, çünkü genellikle hafif-orta şiddette bir klinik ile seyreder. Ancak, cerrah ilk trimester dışındaki hastalar için erken kolesistektomiyi akılda tutmalıdır. Anahtar sözcükler: Akut pankreatit; gebelik; prognoz; yönetim. Ulus Travma Acil Cerrahi Derg 2019;25(3):253-258

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doi: 10.14744/tjtes.2019.03846

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ORIGIN A L A R T IC L E

The correlation between Injury Severity Score, vital signs, and hemogram values on mortality in firearm injuries Özcan Turan, M.D.,1

Mehmet Eryılmaz, M.D.,2

Özgür Albuz, M.D.3

Department of Emergency Medicine, Prof. Dr. Necmi Ayanoğlu Silivri State Hospital, İstanbul-Turkey

Department of Emergency Medicine, Health Sciences University, Gülhane Training and Research Hospital, Ankara-Turkey

Department of General Surgery, Keçiören Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: Several scoring systems have been and continue to be developed in numerous countries with the goal of quickly and accurately assessing the severity of trauma injuries. The aim of this study was to identify factors that help to determine the gravity of damage and to minimize it, in order to reduce mortality and morbidity. It is important that the criteria set for the determination of the severity of trauma are objective, measurable, and comparable. This study was an assessment of the contribution of vital signs, hemogram values, and trauma severity scores recorded at initial admission in the prediction of mortality in patients with firearm trauma wounds. METHODS: This was a retrospective cohort study. Patients with gunshot injuries who were admitted to the emergency department (ED) of a single facility between December 2015 and March 2016 were included in the study. Statistical software was used to perform bivariate analyses using a t-test or the Mann-Whitney U test for continuous variables, depending on the distribution of variables, and logistic regression analysis was utilized to determine independent predictors of mortality after ED admission. A p value of <0.05 was considered statistically significant. RESULTS: A total of 418 patients were included. A statistically significant difference was found between the white blood cell count, respiratory rate, Glasgow Coma Scale score, Abbreviated Injury Scale score, and the Injury Severity Score (ISS) of the patients who survived and those who died (p<0.05). The analysis also indicated that a systolic blood pressure below 90 mmHg and a heart rate above 100 beats/minute were independent variables in terms of the expectation of mortality. CONCLUSION: The objective assessment of the ISS at admission to the ED is an important element in the calculation of hemoglobin requirements, mortality, and morbidity. Keywords: Firearm injury; hemogram; Injury Severity Score; mortality; vital values.

INTRODUCTION Trauma injury, defined as the structural tissue damage resulting from the transfer of kinetic, thermal, or chemical energy to tissues in more than one body area or system, is one of the most serious problems currently confronting society, and represents significant economic, social, and health costs.[1] Despite advancements, trauma continues to be the leading cause of death in people younger than 40 years of age, and is fourth in people over 45 years of age. Trauma accounts for

50% of deaths under the age of 14, 80% of deaths in the 15 to 24 age group, and 65% of deaths in the 25 to 40 age group. It has been established that 50% of these deaths occur in the first few minutes, 30% in the early period (the first 3 hours), and 20% in the late period (after the first 3–4 days).[2–4] One definition of multiple trauma is an injury that affects at least 2 of the 4 regions of the human body: the head and neck, the chest, the abdomen, and the extremities; or injuries to 2 of the major systems (head/chest/abdomen); or a major system and 2 major extremities (femur/humerus).[5]

Cite this article as: Turan Ö, Eryılmaz M, Albuz Ö. The correlation between Injury Severity Score, vital signs, and hemogram values on mortality in firearm injuries. Ulus Travma Acil Cerrahi Derg 2019;25:259-267. Address for correspondence: Özgür Albuz, M.D. Keçiören Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Keçiören, 06350 Ankara, Turkey. Tel: +90 312 - 356 90 00 E-mail: oalbuz@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):259-267 DOI: 10.5505/tjtes.2018.68338 Submitted: 27.05.2018 Accepted: 01.11.2018 Online: 15.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Turan et al. The correlation between ISS, vital signs, and hemogram values on mortality in firearm injuries

In Turkey and globally, traffic accidents are the leading cause of trauma.[6] In England, the total annual economic loss due to major trauma has been estimated to be between 3.3 and 3.7 billion pounds.[7,8] Among the causes of trauma, warfare injuries are very different from most cases encountered in daily life. The quantity of tissue damage and contamination typically seen in warfare injuries is unlike that seen in the ordinary trauma practice.[9,10] Procedures such as laparoscopy, radioscopic embolization, and intramedullary nailing are not a problem for today’s surgeons, but it is of no use to know these techniques when faced with a patient with abdominal injury due to a land mine or a patient with a complex hip injury that is the result of an automatic weapon.[9,11] The most common cause of death following trauma in military operations is hemorrhage.[12] Hemorrhagic deaths account for approximately 30% of overall traumatic deaths and 50% in battle environments.[8] The most important factor affecting mortality in major injuries is time, and this has been described as the “golden hour” rule. This concept originated with emergency health services, which developed rapidly in civilian life, and the importance of this concept is well established in blunt trauma cases.[12] Experience gained in war conditions in the past and in the present have revealed the accuracy of the “golden hour” concept. In the race to achieve an adequate intervention in time, triage has a unique importance. In triage care, the critical point is to quickly and correctly determine the necessary medical attention necessary according to a score of the patient’s injuries. Adequate triage in severe traumatic events is one of the key points for trauma care.[13] Severe injuries and risk of death can be determined by assessing physiological parameters in the majority of trauma patients.[14] The triage system applied to major trauma patients is a cornerstone for the care process of these patients.[13] Patients at risk can be identified in the early period following trauma-related injury using physiological data associated with mortality. Accurate evaluation of mortality and morbidity factors and continuous development of the triage system is at the core of major trauma research. Various scoring systems are used in traumatic injury outcome prediction and triage system research.[15] In this study, the aim was to examine and report the effectiveness of physiological parameters and trauma scores of major trauma patients in predicting mortality and morbidity.

MATERIALS AND METHODS Patients This study was designed as a retrospective, single-center, clinical trial. It was evaluated and approved at the fifth session of the Gülhane Training and Research Hospital ethics 260

committee on April 5, 2016 (protocol no: 206). Emergency department (ED) data from this tertiary care facility, where 150,000 adult patients are admitted annually, from the period between December 1, 2015 and March 31, 2016 were reviewed and analyzed. Patients over 18 years of age admitted to the ED with a gunshot injury, with or without intervention, were included. The data regarding primary measures, trauma scores, vital findings, and hemogram values were extracted from the archives. Patients with any of these data lacking were excluded from the study. In addition, patients whose diagnoses were entered into the system with the International Classification of Diseases (ICD) code for a gunshot injury, but who were not recently injured and those who applied with a posttraumatic stress pre-diagnosis were also excluded from the study.

Methods Patients with a direct referral from the field to the ED with a gunshot injury, and patients who were referred to the ED following a primary intervention at another hospital were included in the study. Patient information was obtained through a retrospective screening of the hospital data system using the ICD code for gunshot injury and by screening emergency service patient files. The sociodemographic data of the patients were obtained from the hospital data system. Patient files were then extracted from the archive and the vital signs of the patients at the time of admission to the emergency room and the hemogram results in the computer system were recorded. Data regarding any required blood transfusion, how many units were administered, and what kind of blood product was transfused, were also retrieved from the hospital data system. Mortality statistics related to the relevant injury were also determined through the hospital data system and the national death registration system. The Injury Severity Score (ISS) was calculated by summing the squares of the severity of the injuries in the 3 most seriously injured anatomical regions. For patients referred from other hospitals, ISS values were calculated and recorded using the examination findings obtained from the patient epicrises.

Collection of Data and Statistical Methods Frequency and percentage were used to describe sociodemographic data. Normal distribution of the data was tested using the Kolmogorov-Smirnov test. Mean, SD, minimum, and maximum values were used for the data with normal distribution, and median, interquartile range, minimum, and maximum values were used for data with non-normal distribution. When the groups were divided according to mortality status, a t-test was used for continuous variables with normal distribution, the Mann-Whitney U test was used for continuous variables with non-normal distribution, and a chi-square test was used for categorical variables to determine the intergroup differences. Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Turan et al. The correlation between ISS, vital signs, and hemogram values on mortality in firearm injuries

The effect of multiple variables on mortality was assessed using logistic regression analysis. SPSS Statistics for Windows, Version 17.0 (SPSS Inc., Chicago, IL, USA) was used to perform the statistical analysis. A p value <0.05 was considered statistically significant. The primary measurement criteria of the trauma score, physiological parameters and hemogram values, and the effect of primary criteria on mortality were evaluated. Sociodemographic data, such as age, gender, etc., and the injured areas, were secondary criteria.

systolic blood pressure (BP), heart rate, fever, Glasgow Coma Scale (GCS) score, Abbreviated Injury Scale (AIS), ISS, laboratory results, and the number of days of hospitalization for all of the patients are provided in Table 1.

RESULTS

When the distribution of the location of the injuries was examined, the most frequently seen was the extremities, followed by the head and neck, and the thorax, respectively. The distribution of injured areas is given in Figure 1.

A total of 418 patients were included in the study, and all of the patients were male. The mean age of the study participants was 30.17Âą7.36 years (min-max: 20â&#x20AC;&#x201C;51 years). The Table 1. Distribution of demographic data of all of the study patients n Min. Max. Mean 1.50

41.10

12.1330

White blood cell

418

Hemoglobin

418 3.00 18.10 12.7672 2.39049

4.50057

Hematocrit

418 10.80 56.20 38.8117 7.04521

SBP

418 61.00 152.00 119.4952 15.79716

Heart rate

418 52.00 128.00 87.0694 15.30466

Fever

418 35.80 38.80 36.8392 .49819

Respiratory rate

418 10.00

GCS

418 3.00 15.00 12.9019 2.74276

AIS

418 1.00 7.00 3.0579 1.21242

ISS

418 1.00 75.00 12.4522 13.73346

28.00

16.2416

418

1.00

Age (years)

418 20.00

177.00 18.0981 19.52131 51.00

30.1746

The orthopedic clinic was the most frequent clinic of admission, followed by the plastic and reconstructive surgery clinic. The distribution of the patients according to the clinic of hospitalization can be seen in Table 2.

4.17098

Hospitalization period (days)

The distribution of the organ- or limb-threatening pathologies revealed fractures in 198 patients as the most common, followed by penetrating eye injuries that represent a risk to visual function in 50 patients, hearing pathology that is a risk to hearing function in 17 patients, and intracranial hemorrhage that may be life-threatening in 17 patients (Fig. 2).

7.36318

Min.: Minimum; Max.: Maximum; SD: Standard deviation; SBP: Systolic blood pressure; GCS: Glasgow Coma Scale; AIS: Abbreviated Injury Score; ISS: Injury Severity Scores.

Table 2. The distribution of the patients according to the clinic in which they were hospitalized

n %

Intensive care

9.1

General surgery

8.1

Orthopedics

149 35.6

Plastic surgery

15.8

Brain surgery

7.4

Chest surgery

6.2

Ophthalmology

36 8.6

Other (ear nose throat, urology, cardiovascular)

Total

418 100.0

250

Number of patients

The distribution of injuries according to the mechanism of trauma was 48.6% (n=203) homemade explosives (HMEs) and 51.4% (n=215) gunshot injuries. Of 418 cases, 18 (4.3%) resulted in mortality.

223

200 150

149

100 44

50 0

Head and neck

Thorax

Abdomen

Pelvis

Extremity

Figure 1. The distribution of the injured areas.

50 198

Loss of or decrease in hearing Intracranial hemorrhage Penetrating eye injury Bone fracture

9.1 Figure 2. Distribution of patients with additional pathologies.

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Turan et al. The correlation between ISS, vital signs, and hemogram values on mortality in firearm injuries

During follow-up, 119 (28.5%) patients were administered blood or blood products. The blood transfusion distribution according to mortality is given in Table 3. When the injury mechanisms were evaluated according to mortality, it was observed that the rate was highest among those with HME injuries (Table 4). The GCS results were grouped as GCS <9, GCS 9–12, and GCS >12. The distribution of patients was evaluated accordTable 3. The distribution of mortality according to blood transfusion use n %

Mortality is absent

Transfusion (–)

282

70.5

Transfusion (+)

118

29.5

Total

400

100.0

94.4

Mortality is present

Transfusion (–)

Transfusion (+)

5.6

Total

100.0

Table 4. The distribution of mortality by injury mechanism Mortality

Frequency %

Mortality (–) Bullet

208

52.0

Handmade explosives

192 48.0

Total

400

100.0

Mortality (+) Bullet

Handmade explosives

11 61.1

Total

GCS score

Frequency

3.3

9–12

24.0

>12

291

72.8

Total

400 100.0

Mortality (+)

Total GCS: Glasgow Coma Scale.

262

9–12

94.4

5.6

18 100.0

An ISS of 16 or more or an ISS of 20 or more was not significant as independent variable for mortality with a 95% confidence interval (p<0.001). The mortality rate was determined to be 6.49 times (min-max: 1.02–41.25 times) greater in patients with a systolic BP of less than 90 mmHg (p<0.048), ROC Curve

1.0

100.0

Table 5. The distribution of mortality according to GCS group

Mortality (–)

Based on the current literature, the cutoff point used in logistic regression analysis for systolic BP was 90 mmHg and below. The cutoff values used for the ISS were 16 and 20, 8 mg/dL was used for the Hb measure, and 12 or less and 20 or more were applied to the respiratory rate.

38.9

Mortality

Comparisons of mortality in terms of sociodemographic parameters, physiological parameters, laboratory results, and trauma scores yielded a statistically significant difference in white blood cell count (WBC) (p<0.001), respiratory rate (p<0.001), GCS (p<0.001), AIS (p<0.001), and ISS (p<0.001) parameters. No statistically significant difference was found between the groups in terms of age (p=0.867), hemoglobin (Hb) (p=0.088), hematocrit (Hct) (p=0.167), systolic blood pressure (BP) (p=0.542), heart rate (HR) (p=0.052), fever (p=0.386), or number of days in hospital (p=0.052) (Table 6). Receiver operating characteristic (ROC) analysis was performed to estimate the mortality of patients using the data of age, systolic BP, HR, respiratory rate, Hb, Hct, WBC, GCS, AIS, and ISS values. The highest area under the curve (AUC) values were the ISS (AUC: 0.993) and the AIS (AUC: 0.978). The ROC curves according to the parameters studied are illustrated in Figure 3 and the AUC values are given in Table 7.

Source of the Curve

Age SBP PR HR HB WBC HCT GCS AIS ISS Reference Line

0.8

Sensitivity

Mortality

ing to mortality and it was detected that 94.4% of the patients who died had a GCS <9, while 5.6% of the fatalities had a GCS of 9–12. It is noteworthy that there was no case of mortality with a GCS of >12. The mortality distribution by GCS score is provided in Table 5.

0.6

0.4 0.2

0.0 0.0

0.2

0.4 0.6 1 - Specificity

0.8

1.0

Figure 3. ROC curves for mortality estimation using physiological criteria, laboratory results, and trauma scores. AIS: Abbreviated Injury Scale; Hb: Hemoglobin; Hct: Hematocrit; ISS: Injury Severity Score; HR: Heart rate; ROC: Receiver operating characteristic; RR: Respiratory rate; SBP: Systolic blood pressure; WBC: White blood cell.

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Turan et al. The correlation between ISS, vital signs, and hemogram values on mortality in firearm injuries

Table 6. Trauma scores and physiological parameters according to survival

Minimum

Maximum

Mean

Standard deviation

400

1.50

41.10

11.8153

4.05113

Survival

White blood cell

Hemoglobin

400

3.00

18.10

12.8095

2.38408

Hematocrit

400

10.80

53.30

38.9138

6.99868

Systolic blood pressure

400

61.00

152.00

119.3950

16.06297

Heart rate

400

61.00

128.00

86.9400

15.13039

Fever

400

35.80

38.80

36.8348

.48539

400

10.00

26.00

16.0450

4.07117

Respiratory rate

Glasgow Coma Scale

400

3.00

15.00

13.3075

1.95512

Abbreviated Injury Score

400

1.00

7.00

2.9305

1.07425

Injury Severity Scores

400

1.00

75.00

10.1725

7.67333

Hospitalization period (days)

400

1.00

177.00

18.4900

19.76072

Age (years)

400

20.00

51.00

30.1875

7.38062

7.70

32.00

19.1944

7.51551

8.50

17.30

11.8278

2.40681

Non-survival

White blood cell

Hemoglobin Hematocrit

26.70

56.20

36.5444

7.88679

Systolic blood pressure

100.00

130.00

121.7222

7.74449

Heart rate

52.00

116.00

89.9444

19.06173

36.00

38.40

36.9389

Fever

.73974

Respiratory rate

14.00

28.00

20.6111

4.07487

Glasgow Coma Scale

3.00

11.00

3.8889

2.21993

Abbreviated Injury Score

5.00

6.00

5.8889

.32338

Injury Severity Scores

25.00

75.00

63.1111

20.12283

Hospitalization period (days)

1.00

41.00

9.3889

9.94182

Age (years)

21.00

44.00

29.8889

7.16108

Table 7. Area under the curve values for mortality estimation using physiological criteria, laboratory results, and trauma scores Test result variables

Area

Standard deviation

Asymptotic Sig.b

Age (years)

.492

.072

.913

Asymptotic 95% confidence interval Lower limit

Upper limit

.351

.634

Systolic blood pressure

.497

.040

.962

.418

.576

Heart rate

.554

.080

.441

.397

.711

Respiratory rate

.792

.044

.000

.706

Hemoglobin

.367 .068

White blood cell

.795

Hematocrit

.382 .073

.069

.878

.057 .234

.501

.000

.929

.660

.090 .240

.524

Glasgow Coma Scale

.012

.008

.000

.027

Abbreviated Injury Score

.978

.007

.000

.964

.992

Injury Severity Scores

.993

.004

.000

.984

1.000

and increased by 0.11 times (min-max: 0.023â&#x20AC;&#x201C;0.56 times) (p<0.008) in tachycardic patients with a heart rate of 100/ Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

minute or more. The parameters of a respiratory rate below 12 or above 20 breaths per minute and an Hb value below 263

Turan et al. The correlation between ISS, vital signs, and hemogram values on mortality in firearm injuries

Table 8. Multivariable logistic regression analysis of primary criteria

S.E.

Wald

Sig.

Exp (B)

Systolic blood pressure <90 Respiratory rate

1.870

.944

3.926

.048

6.488

95% Confidence interval (B) Lower limit

Upper limit

1.020

41.251

.223

.729

.093

.760

1.249

.299

5.217

Heart rate

-2.183

.820

7.083

.008

.113

.023

.563

Hemoglobin <8 mg/dL

-19.068

11236.146

.000

.999

.000

–

Injury Severity Scores <20

21.181

2066.608

.000

.992

1.581

.000

–

Constant

-21.036 2066.608 .000 1 .992 .000

8 mg/dL were not significant as an independent variable for mortality (Table 8).

DISCUSSION This study was designed to examine the predictive efficacy of vital sign findings, WBC, Hb, and trauma scores on the mortality of 418 patients presenting after gunshot injuries in order to better predict mortality. In the group of patients with a high WBC, respiratory rate, AIS and ISS values, and a low Hb and low GCS, the AUC was high for the AIS and ISS, and a systolic BP below 90 mmHg and a heart rate higher than 100/ minute were found to be independent variables for mortality. Trauma is more common at younger ages, and as has been shown in studies, there is a strong relationship with factors such as age, sex, and the area of injury. Other studies have reported a similar gender ratio among trauma patients: Régnier et al.[16] found a distribution of 71.5% male and 28.5% female, and Odom et al.[17] reported 67.2% male and 32.8% female. In studies evaluating patients according to age, the mean age of survival and death reported by Régnier et al. was 37±15 years and 45±18 years, respectively, Odom et al. reported a mean of 48.20±22.1 years and 67.89±21.1 years. Callaway et al.[18] found that in a group aged more than 65 years, the mean was 80±8.3 years and 81±8.1 years, while it was 38±14 years and 42±14 years in the group with an age below 65 years, Molina et al.[19] determined in their study

Figure 4. Hemopneumothorax and multiple costal fractures seen on chest X-ray. (Clinic l archive image of GATA Emergency Medicine AD).

264

that the average age of patients who committed suicide by gunshot was 46.7 years, while the mean age of gunshot homicide victims was 34.3 years, and the ratio of females to males was 1/5 for all nonaccidental handgun death s. In our study, all of the patients were male. This was due to the fact that the vast majority of the patients included in the study were military and police officers working in operational units and that our hospital is a high-ranking military hospital. The mean age of survival and death in our study was 29.8±7.1 years and 30.18±7.3 years of age. This young age distribution of the patients was consistent with other studies. The age difference between the patients who survived and those who died was not statistically significant, likely as a result the small number of deaths, the mechanism of trauma, and the fact that all of the patients studied were young adults. Mortality in gunshot injuries is most often related to the location of the injury and the number of injured organs. The death rate due to gunshot injury has been reported to be between 12% and 18% in the literature. In isolated chest or abdominal injuries, the reported mortality is 17%, while for abdominal injuries accompanied by brain or lung injuries, mortality has been reported at 80% and death usually occurs on the first day (Fig. 4).[20–22] Sheffy et al.[20] reported that gunshot injuries were most frequently associated with lower extremity injuries (42%), followed by head and neck injuries (39%) and thoracic injuries (23.5%), when evaluated according to the localization. Otte et al.[23] found that 69.6% of patients with multiple trauma had head trauma, 69.2% had chest injuries, 51.9% had abdominal injuries, and 33.1% had other injuries. In our study, the mortality rate was determined to be 4.3%, which is lower than the rates seen in the literature. We believe that the low mortality rate was associated with the fact that the great majority of patients were referred from other hospitals, and the losses seen in the first 24 hours were likely to have occurred at these hospitals or at the incident scene. The evaluation of the injury area revealed similar results in our study to those previously reported: the most commonly seen injured area was the extremities. Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Turan et al. The correlation between ISS, vital signs, and hemogram values on mortality in firearm injuries

Findlay et al.[24] studied 774 patients who were admitted to the intensive care unit with multiple traumas, and they found that patients had a duration of stay of between 1 and 68 days, with a median stay of 2 days. In a study of 4651 patients, Render et al.[25] determined that the average length of stay of patients in hospital was 3.1 days. In our study, the mean duration of stay in hospital was 18.09 days (min-max: 1–177 days) and this long duration of stay was thought to be due to the injury mechanism of the patients included in the study, the different forms of trauma, the clinical treatment duration of the patients in our hospital, and the fact that the clinical treatment duration was not limited to intensive care, but also included subsequent treatment in the clinic and physical therapy. Several studies have evaluated the effects of vital findings on mortality in trauma patients. In studies performed by Jo et al.[15] and Régnier et al.,[16] a low BP was associated with mortality, and as the heart rate increased, the BP increased. [15,16] In a study of patients with head trauma conducted by Butcher et al.,[26] the prognosis was better in cases where the systolic BP was between 90 and 120 mmHg than in patients with lower or higher levels. They reported that the result was worse in cases in which both oxygen deficiency and low BP were seen than in cases in which only 1 of these parameters appeared. [26] There was no statistically significant difference in patient mortality according to the systolic BP or heart rate in our study; however, mortality was 6.49 times greater (p<0.048) in patients with a systolic BP of less than 90 mmHg at admission to the emergency service. We think that the small difference in the systolic BP and heart rate between the surviving and non-surviving patients in our study, as seen in the published literature, was mostly due to the fact that the vast majority of patients were brought to our hospital after receiving fluid resuscitation, blood transfusions, and damage control surgery. In addition to intensive care scoring systems, various trauma scoring systems are used in the evaluation of patients with multiple trauma. Developed by Jennett and Teasdale,[2] the GCS is used to assess cerebral dysfunction, particularly neurological condition, and is often applied in cases of multiple trauma associated with head trauma. The GCS can reliably assesses the degree of consciousness and coma in patients with craniocerebral injury. The GCS scoring system can provide quick, detailed information, is simple to evaluate, does not require additional examination, and is therefore frequently used. The benefits are fewer in severely hypotensive, tachycardic patients with hemorrhage. Nonetheless, in 2 studies conducted by Teasdale and Jennet[27] and Cho and Wang,[28] the GCS was reported to have a high accuracy rate of 81.9% and 92%, respectively, in predicting mortality in patients with head trauma. It has been recommended that the GCS be used in combination with other scoring tools in multitrauma cases.[28] Teoh et al.[29] studied 1390 patients who were treated in intensive care units and followed up for 4 years, and found a significant relationship between the GCS score and mortality. Mpe et al.[30] conducted a retrospective Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

study and found that the mortality rate was high in trauma patients, the prognosis of patients with a GCS value of 4 and below at admission to the intensive care unit was poor, and that very few patients with low GCS values were able to fully recover.[30] In the present study, the mean GCS of patients who died was low; 17 of the 18 cases of mortality had a GCS below 9. No deaths were seen in patients with a GCS >12. Our results were consistent with the literature. The ISS is an anatomical trauma score used to assess the severity of injury and was developed primarily for blunt trauma. The value scored is between 3–75 and is directly proportional to mortality. Mortality increases as the score increases. It is considered severe trauma if the score is above 15. If the ISS is above 25, mortality is seen in 20% to 30% of patients under 50 years of age and in 40% to 50% of patients above 50 years of age. When all age groups are considered, mortality is 30% to 40%. The ISS has some limitations. A disadvantage of the system is that it relies on the AIS scoring, and therefore ignorance of other organ injuries in either another other system or the same system due to the reliance on the 3 systems where only the most serious injury is present in patients with multiple system injuries will increase ISS error. Another weakness is that the severity of all system injuries are considered equal, which may cause a head injury, in particular, to not be given sufficient significance with respect to mortality. It is also inadequate in differentiating patients with the same score but different hemodynamic status. Simmons et al.[31] reported that the mean ISS value of military service members receiving a massive transfusion before and after a change in guidelines was 24 and 25. Eastridge et al.[32] found that 28.6% of the patients in the field before reaching a hospital had an ISS value of 25 or less, 61.2% had between 25 and 50, and 10.2% had an ISS over 50.[32] A low GCS (especially <5), low Revised Trauma Score (RTS), and a high ISS (especially >16) has been reported to be associated with high mortality in clinical trials examining the GCS, ISS, and RTS.[33–35] In our study, the mean ISS was 63.11 in patients who did not survive and 10.17 in patients who survived. The ISS values were found to be significantly higher in patients who died, which is in accordance with the literature. The ISS had the highest value in our assessment of the prediction of mortality, with an AUC value of 0.993. Despite limitations, the ISS was found to be a useful tool and may be especially valuable in cases of severe trauma.

Conclusion In this study we evaluated the effects of vital findings, laboratory results, and trauma scores on mortality in emergency patients admitted after gunshot injuries, and found that the WBC, respiratory rate, GCS, AIS, and ISS values differed significantly between the patients who survived and those who did not. A systolic BP value below 90 mmHg and a heart rate above 100/minute were found to be independent variables for mortality. In addition, the AIS and ISS trauma scores were significantly successful in the prediction of mortality. As a re265

Turan et al. The correlation between ISS, vital signs, and hemogram values on mortality in firearm injuries

sult, systolic BP and heart rate, and the AIS and ISS will be helpful during the evaluation of patients with gunshot injuries during triage before admission to the hospital, transportation from the field and treatment at the appropriate trauma center, admission to the emergency service, and the evaluation of additional treatment and the prediction of the mortality. Conflict of interest: None declared.

REFERENCES 1. Salehi O, Tabibzadeh Dezfuli SA, Namazi SS, Dehghan Khalili M, Saeedi M. A New Injury Severity Score for Predicting the Length of Hospital Stay in Multiple Trauma Patients. Trauma Mon 2016;21:e20349. 2. Glen J, Constanti M, Brohi K; Guideline Development Group. Assessment and initial management of major trauma: summary of NICE guidance. BMJ 2016;353:i3051. 3. Holst JA, Perman SM, Capp R, Haukoos JS, Ginde AA. Undertriage of Trauma-Related Deaths in U.S. Emergency Departments. West J Emerg Med 2016;17:315–23. 4. Johnson G. Trauma Triage and Trauma System Performance. West J Emerg Med 2016;17:331–2. 5. Joubert C, Dulou R, Delmas JM, Desse N, Fouet M, Dagain A. Military neurosurgery in operation: experience in the French role-3 medicaltreatment facility of Kabul. Acta Neurochir (Wien) 2016;158:1453–63. 6. Wang SY, Li YH, Chi GB, Xiao SY, Ozanne-Smith J, Stevenson M, et al. Injury-related fatalities in China: an under-recognised public-health problem. Lancet 2008;372:1765–73. 7. Holcomb JB. The 2004 Fitts Lecture: current perspective on combat casualty care. J Trauma 2005;59:990–1002. 8. Potenza BM, Hoyt DB, Coimbra R, Fortlage D, Holbrook T, Hollingsworth-Fridlund P; Trauma Research and Education Foundation. The epidemiology of serious and fatal injury in San Diego County over an 11-year period. J Trauma 2004;56:68–75. 9. Giannou C, Baldan M. Savaş Cerrahisi. Cilt 1. ICRC. Available at: file:///Users/batti/Downloads/savas-cerrahisi-war-surgery.pdf 10. Butler FK Jr, Holcomb JB, Giebner SD, McSwain NE, Bagian J. Tactical combat casualty care 2007: evolving concepts and battlefield experience. Mil Med 2007;172:1–19. 11. Adams BD, Cuniowski PA, Muck A, De Lorenzo RA. Registry of emergency airways arriving at combat hospitals. J Trauma 2008;64:1548–54. 12. Gofrit ON, Leibovici D, Shapira SC, Shemer J, Stein M, Michaelson M. The trimodal death distribution of trauma victims: military experience from the Lebanon War. Mil Med 1997;162:24–6. 13. Bouzat P, Broux C, Ageron FX, Thony F, Arvieux C, Tonetti J, et al. Trauma network for severely injured patients. Ann Fr Anesth Reanim 2013;32:531–4. 14. Joosse P, Soedarmo S, Luitse JS, Ponsen KJ. Trauma outcome analysis of a Jakarta University Hospital using the TRISS method: validation and limitation in comparison with the major trauma outcome study. Trauma and Injury Severity Score. J Trauma 2001;51:134–40. 15. Jo S, Lee JB, Jin YH, Jeong T, Yoon J, Choi SJ, et al. Comparison of the trauma and injury severity score and modified early warning score with rapid lactate level (the ViEWS-L score) in blunt trauma patients. Eur J Emerg Med 2014;21:199–205. 16. Régnier MA, Raux M, Le Manach Y, Asencio Y, Gaillard J, Devilliers C, et al. Prognostic significance of blood lactate and lactate clearance in trauma patients. Anesthesiology 2012;117:1276–88. 17. Odom SR, Howell MD, Silva GS, Nielsen VM, Gupta A, Shapiro NI,

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et al. Lactate clearance as a predictor of mortality in trauma patients. J Trauma Acute Care Surg 2013;74:999–1004. 18. Callaway DW, Shapiro NI, Donnino MW, Baker C, Rosen CL. Serum lactate and base deficit as predictors of mortality in normotensive elderly blunt trauma patients. J Trauma 2009;66:1040–4. 19. Molina DK, DiMaio VJ, Cave R. Handgun wounds: a review of range and location as pertaining to manner of death. Am J Forensic Med Pathol 2013;34:342–7. 20. Sheffy N, Mintz Y, Rivkind AI, Shapira SC. Terror-related injuries: a comparison of gunshot wounds versus secondary-fragments-induced injuries from explosives. J Am Coll Surg 2006;203:297–303. 21. Peleg K, Aharonson-Daniel L, Stein M, Michaelson M, Kluger Y, Simon D, et al. Gunshot and explosion injuries: characteristics, outcomes, and implications for care of terror-related injuries in Israel. Ann Surg 2004;239:311–8. 22. Köksal O, Ozdemir F, Bulut M, Aydin S, Almacioğlu ML, Ozgüç H. Comparison of trauma scoring systems for predicting mortality in firearm injuries. Ulus Travma Acil Cerrahi Derg 2009;15:559–64. 23. Otte D, Pohlemann T, Wiese B, Krettek C. [Changes in the injury pattern of polytraumatized patients over the last 30years]. Unfallchirurg 2003;106:448–55. [Article in German] 24. Findlay JY, Plenderleith JL, Schroeder DR. Influence of social deprivation on intensive care outcome. Intensive Care Med 2000;26:929–33. 25. Render ML, Welsh DE, Kollef M, Lott JH 3rd, Hui S, Weinberger M, et al. Automated computerized intensive care unit severity of illness measure in the Department of Veterans Affairs: preliminary results. SISVistA Investigators. Scrutiny of ICU Severity Veterans Health Sysyems Technology Architecture. Crit Care Med 2000;28:3540–6. 26. Butcher I, Maas AI, Lu J, Marmarou A, Murray GD, Mushkudiani NA, et al. Prognostic value of admission blood pressure in traumatic brain injury: results from the IMPACT study. J Neurotrauma 2007;24:294–302. 27. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2:81–4. 28. Cho DY, Wang YC. Comparison of the APACHE III, APACHE II and Glasgow Coma Scale in acute head injury for prediction of mortality and functional outcome. Intensive Care Med 1997;23:77–84. 29. Teoh LS, Gowardman JR, Larsen PD, Green R, Galletly DC. Glasgow Coma Scale: variation in mortality among permutations of specific total scores. Intensive Care Med 2000;26:157–61. 30. Mpe MJ MK, Mzileni MO. The outcome of neuro-trauma. A 1 year retrospective study in an intensive care unit. Critical Care Med 2001;5:115. 31. Simmons JW, White CE, Eastridge BJ, Mace JE, Wade CE, Blackbourne LH. Impact of policy change on US Army combat transfusion practices. J Trauma 2010;69:S75–80. 32. Eastridge BJ, Mabry RL, Seguin P, Cantrell J, Tops T, Uribe P, et al. Death on the battlefield (2001-2011): implications for the future of combat casualty care. J Trauma Acute Care Surg 2012;73:S431–7. 33. Eryılmaz M, Tezel O, Taş H, Arzıman I, Oğünç GI, Kaldırım U, et al. The relationship between Injury Severity Scores and transfusion requirements of 108 consecutive cases injured with high kinetic energy weapons: a tertiary center end-mode mortality analysis. Ulus Travma Acil Cerrahi Derg 2014;20:39–44. [Article in Turkish] 34. Martins RS, Siqueira MG, Santos MT, Zanon-Collange N, Moraes OJ. Prognostic factors and treatment of penetrating gunshot wounds to the head. Surg Neurol 2003;60:98–104. 35. Finley CJ, Hemenway D, Clifton J, Brown DR, Simons RK, Hameed SM. The demographics of significant firearm injury in Canadian trauma centres and the associated predictors of inhospital mortality. Can J Surg 2008;51:197–203.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Ateşli silah yaralanması olgularında mortalite üzerine yaralanma şiddeti skoru (ISS), yaşamsal skorlar ve hemogram değerleri arasındaki korelasyonun etkisi Dr. Özcan Turan,1 Dr. Mehmet Eryılmaz,2 Dr. Özgür Albuz3 1 2 3

Prof. Dr. Necmi Ayanoğlu Devlet Hastanesi, Acil Servis Kliniği, İstanbul Sağlık Bilmleri Üniversitesi, Gülhane Eğitim ve Araştırma Hastanesi, Acil Tıp Anabilim Dalı, Ankara Keçiören Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara

AMAÇ: Birçok ülkede kişilerin maruz kaldığı travmanın şiddeti ve ortaya çıkan hasarı değerlendirmek için bazı skorlama sistemleri geliştirilmiş ve geliştirilmeye devam etmektedir. Burada amaç hastanın hasar oranlarını en iyi biçimde belirleyerek mortalite ve morbiditeye etki eden faktörleri saptayarak bunları en aza indirgemeye çalışmaktır. Travmanın ağırlığının tespiti için ortaya konulan kriterlerin ölçülebilir ve karşılaştırılabilir objektif kriterler olması önemlidir. Bu amaçla anatomik ve fizyolojik birçok puanlama sistemleri oluşturulmuştur. Bu araştırmada acil servise ilk kabul anındaki vital skorların, hemogram değerlerinin ve yaralanma şiddeti skorunun (ISS) mortaliteyi öngörmeye katkısını ortaya koymaktır. GEREÇ VE YÖNTEM: Bu çalışma geriye dönük kohort çalışması olarak tasarlandı. Aralık 2015–Mart 2016 tarihleri arasında acil servisimize başvuran ateşli silah yaralanması olan hastalar çalışmaya alındı. Değişkenlerin dağılımı açısından sürekli değişkenler için t-testi veya Mann-Withney U-testi kullanılarak ikili değişkenler analiz edildi. Acil servise kayıttan sonra bağımsız mortalite belirleyicilerini belirlemek için lojistik regresyon ve istatistiksel analiz için SPSS17.0 programı kullanıldı. P<0.05 değeri istatistiksel olarak anlamlı kabul edildi. BULGULAR: Toplam 418 hasta alındı. Sağ kalan ve ölen hastalar arasında beyaz kan hücresi (WBC), solunum hızı, Glasgow Koma Skalası (GCS), Kısaltılmış Yaralanma Skoru (AIS) ve ISS arasında istatistiksel olarak anlamlı bir fark bulundu (p<0.05). Sistolik kan basıncının 90 mmHg’nin altında ve kalp atım hızının 100 atım/dk üzerinde olmasının mortalite açısından bağımsız değişkenler olduğu belirlendi. TARTIŞMA: Acil servise kabul anındaki ISS’nin objektif değerlendirmesi, hemoglobin gereksinimi, mortalite ve morbiditeyi öngörmek için önemli bir unsurdur. Anahtar sözcükler: Ateşli silah yaralanması; hemogram ve yaşamsal değerler; mortalite; yaralanma şiddeti skoru. Ulus Travma Acil Cerrahi Derg 2019;25(3):259-267

doi: 10.5505/tjtes.2018.68338

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ORIGIN A L A R T IC L E

Etiology, management, and survival of acute mechanical bowel obstruction: Five-year results of a training and research hospital in Turkey Dursun Özgür Karakaş, M.D., Metin Yeşiltaş, M.D., Seracettin Eğin, M.D., Semih Hot, M.D.

Berk Gökçek, M.D.,

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

ABSTRACT BACKGROUND: Acute mechanical bowel obstruction (AMBO) is still a major surgical problem for emergency departments. The aim of this study was to evaluate AMBO in terms of etiology, management, and survival. METHODS: Data of the age, sex, etiology, management, and survival of patients who were hospitalized for bowel obstruction between January 2014 and December 2018 were evaluated retrospectively. Adhesions, tumors, hernias and peritoneal carcinomatosis were evaluated in detail. RESULTS: A total of 735 patients were included in the study. The obstruction was located in the small bowel (AMSBO) in 60% and in the large bowel (AMLBO) in 40%. The mean patient age was 59.9±16.02 years and 52.9% of the patients were male. Adhesion, tumor, and hernia were the most common etiologies of the overall AMBO group (43.3%, 26.2%, and 6%, respectively). The most common etiology for AMSBO was an adhesion (69.3%), while it was a tumor for AMLBO cases (61.6%). The most common management of AMBO patients was a conservative approach (53.2%; adhesions: 76.7%). Surgical palliation was performed in 24.9% (peritoneal carcinomatosis: 65.7%), and resection was performed in 21.9% (volvulus: 61.9%). The mortality rate in the group was 8.6%. The most common etiology was colorectal surgery (51.4%) for adhesions, colorectal cancer (93.8%) for tumors, and incisional hernia (47.7%) in cases of hernia-related AMBO. CONCLUSION: Adhesions, tumors, and hernias are the most common etiologies of AMBO. The incidence of femoral/inguinal hernia have decreased while that of incisional hernia has increased, and it was further observed that peritoneal carcinomatosis has now become as common as hernia as a cause. Keywords: Adhesion; acute colonic pseudo-obstruction; bowel obstruction; hernia; paralytic ileus; tumor.

INTRODUCTION Acute mechanical bowel obstruction (AMBO) is still one of the major surgical problems encountered in emergency departments. AMBO constitutes 3% of all emergency admissions and 15% of acute abdominal pain cases. AMBO is an important cause of mortality as well as costs, as it may involve a long hospital stay, readmissions, and reoperations.[1] AMBO is described as local blockage of intestinal content transit for reasons that may be intramural (e.g., invagination, bezoar,

gallstone, etc.), mural (e.g., cancer, inflammation, congenital cause, etc.), or extramural (e.g., hernia, adhesion, etc.). AMBO is described as small (AMSBO) or large (AMLBO) according to the level of the bowel obstruction, and complete or incomplete obstruction according to the discharge of gas.[2] AMBO is observed in the small bowel in 75% to 80% of cases and in the large bowel in 20% to 25%.[3] The etiology of AMBO varies according to considerations such as age, development of the country of occurrence, and the level of the obstruc-

Cite this article as: Karakaş DÖ, Yeşiltaş M, Gökçek M, Eğin S, Hot S. Etiology, management, and survival of acute mechanical bowel obstruction: Five-year results of a training and research hospital in Turkey. Ulus Travma Acil Cerrahi Derg 2019;25:268-280. Address for correspondence: Dursun Özgür Karakaş, M.D. Okmeydanı Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 314 55 55 E-mail: drdok1978@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):268-280 DOI: 10.14744/tjtes.2019.44834 Submitted: 23.01.2019 Accepted: 03.05.2019 Online: 15.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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tion in the bowel. A hernia is still a common cause of AMBO in developing countries, while postoperative adhesions are the most common cause in developed countries as a result of the increase in surgical procedures. Postoperative adhesions have been reported to be the most common cause of small bowel obstruction and colorectal cancers have similarly been described as the most common cause of large bowel obstruction.[4] Peritoneal adhesions occurred in 93% of patients after abdominopelvic surgery; however, only 5% were symptomatic. Colorectal operations, gynecological surgery, and appendectomy are the most common primary surgery sources of peritoneal adhesions. The frequency of obstruction due to hernia has decreased with increased application of elective surgery. Tumors located distal to the splenic flexure are the most frequent cause of tumoral obstruction. Volvulus is another common reason for large bowel obstruction encountered in developing or eastern countries.[5] Conservative management is commonly used for an adhesive obstruction; however, resection is typically used for tumoral obstructions. Sometimes surgical palliation can be performed for passage continuity. Enteroclysis or endoscopic stent implementation is an alternative nonsurgical treatment for uncomplicated obstructions.[2,3] The AMBO mortality rate has been reported to be between 1.5% and 11.5% in the literature. Age, etiology, bowel necrosis, and comorbidities are risk factors for mortality and morbidity and considerations in management.[6,7] The aim of this study was to evaluate the etiology, management, and survival of AMBO patients based on the records of 5 years at a training and research hospital in Turkey.

MATERIALS AND METHODS After receiving institutional approval from the ethics committee of Okmeydanı Training and Research Hospital (08.01.2019/ 1088), the records of patients who hospitalized due to ileus and/or acute bowel obstruction between January 2014 and December 2018 were evaluated retrospectively. Patients diagnosed with mechanical bowel obstruction, Ogilvie syndrome (acute colonic pseudo-obstruction [ACPO]), paralytic ileus (PI), or suspicion of a primary tumor ileus (SPTI), which may be clinically and/or radiologically compatible but excluded by colonoscopy, were included in the study. Age, sex, etiology, management, and survival were evaluated for all-type AMBO, AMSBO, and AMLBO. The approach to management of AMBO may be conservative, or surgical palliation or resection, with herniorrhaphy ± mesh for hernia cases. Records of death during hospitalization were used to determine survival data. Adhesions were categorized as primary benign or malignant, and details of primary surgery, management, and survival were analyzed. Primary adhesion surgery included upper gasUlus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

trointestinal system (GIS) surgery, colorectal surgery, hepaticopancreaticobiliary surgery, appendectomy, gynecological surgery, urological surgery, laparotomy, and hernia surgery. Tumors were evaluated according to the location, patient sex, pathology, management, and survival. The location and characterization of the tumor was classified as small bowel, cecum, right colon, hepatic flexure, transverse colon, splenic flexure, left colon, sigmoid colon, rectosigmoid, rectum, recurrence, or non-gastrointestinal tumor. The pathology of tumors was assessed as none (no surgical pathology because of non-resection management), adenocarcinoma, mucinous carcinoma, invasion of other cancer, lymphoma/neuroendocrine tumor (NET), or benign. Hernias were evaluated by type, primary surgery, management, and survival. Hernias were divided according to type and side. Primary surgery for incisional hernia consisted of GIS, gynecological, or hernia surgery. Peritoneal carcinomatosis (PC) as a primary malignancy was categorized as upper GIS, colorectal, hepaticopancreaticobiliary, gynecological, urological, breast, or of unknown origin. The statistical analysis was performed with SPSS for Windows, Version 16.0 (SPSS Inc., Chicago, IL, USA). A onesample T-test was used for age (mean±SD). The variables of males, females, etiology, management, and survival were evaluated as a percentage.

RESULTS A total of 735 (9.2% of all hospitalizations) patients were included in the study. In all, 443 (60%) patients had AMSBO, 292 (40%) patients had AMLBO. The mean age was 59.9±16.02 years for the overall AMBO group, 56.77±16.37 years for AMSBO, and 64.36±14.48 years for AMLBO. Total AMBO statistics revealed that ACPO patients were the oldest group, with a mean age of 74.92±12.17 years, and diverticulitis was the most common etiology in the youngest group at 34.20±23.43 years. In this study group, 52.9% of the patients were male, 47.1% were female. The percentage of female patients was greater in the hernia group (75%), while male patients were the majority in the SPTI group (78.8%). The overall mortality rate was 8.6%. Tumor (39.7%) was the most common reason for mortality, and adhesions and PC were the next most common reason for mortality (22.2% and 12.7%, respectively). AMBO analysis indicated that adhesion was the most common etiological factor (43.3%). Tumors and hernias were the other etiological factors seen most frequently (26.2% and 6%, respectively). The most common management approach for AMBO was conservative management (53.2%). Surgical palliation was performed in 24.9% and surgical resection was performed in 21.9% of patients. Conservative management was pursued for most cases of adhesion (76.7%), while sur269

Karakaş et al. Etiology, management, and survival of AMBO

gical palliation was performed for PC (65.7%), and surgical resection was performed for volvulus (61.9%) (Table 1). In AMSBO patients, adhesion was the most common etiological factor (69.3%). Hernia and PC were the other etiological factors most often observed (9.5% and 4.7%, respectively).

The most common approach for AMSBO was conservative management (69%). Surgical palliation was performed in 23% and surgical resection was performed in 8%. Conservative management was most often used for adhesions (79.4%), surgical palliation for bezoar (81.8%), and surgical resection for diverticulitis (Meckel’s) (100%) (Table 2).

Table 1. Distribution of etiology for AMBO Etiology Age, years (Mean±SD)

Sex

Treatment

Survival

Total

M F Conservative Palliation Resection Yes No

Adhesion

56.30±16.33 154 164

244

20 304 14 318 43.3

Tumor

62.94±13.61 115 77

105 167 25 192 26.2

Hernia

62.14±15.31 11 33

12 41 3 44 6

Peritoneal carcinomatosis 58.34±12.11 15 23

2 30 8 38 5.2 0 32 1 33 4.5

Suspicion of primary tumor ileus

66.48±13.83 26 7

Inflammatory bowel disease

54.67±18.95

Volvulus

70.81±17.25 15 6

13 17 4 21 2.9

Paralytic ileus

62.86±15.37 8 6

0 13 1 14 1.9

pseudo-obstruction

74.92±12.17 6 6

Bezoar

57.91±16.80 6 5

0 11 0 11 1.5

3.2

Acute colonic

8 4 12 1.6

Gastric outlet obstruction

55.25±21.37

Diverticulitis

34.20±23.43 4 1

3 5 0 5 0.7

1.1

Other

66.14±15.31 10 5

2 14 1 15 1.9

Total

59.9±16.02 389 346

384

189

162 672 63 735 100

AMBO: Acute mechanical bowel obstruction; M: Male; F: Female; SD: Standard deviation.

Table 2. Distribution of etiology for AMSBO Etiology Age, years (Mean±SD)

Sex

Treatment

Survival

Total

M F Conservative Palliation Resection Yes No

Adhesion

56.18±16.54 157 150

244

15 296 11 307 69.3

Hernia

62.19±15.41 10 32

10 39 3 42 9.5

Peritoneal carcinomatosis 56.48±11.60 4 17

0 17 4 21 4.7

Inflammatory bowel disease

52.00±15.17

Paralytic ileus

62.86±15.37 8 6

0 13 1 14 3.2

Tumor

58.00±12.30

Bezoar

57.91±16.80 6 5

0 11 0 11 2.5

Gastric outlet obstruction

55.25±21.38

8 7 5

7 5 3

14 8 7

1 4 1

15 12 8

3.4 2.7 1.8

Diverticulitis

19.00±2.65 3 0

3 3 0 3 0.7

Other

61.50±16.24

Total

56.77±16.37 214 229

299

108

2.2

36 417 26 443 100

AMSBO: Acute mechanical bowel obstruction; M: Male; F: Female; SD: Standard deviation.

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For AMLBO patients, a tumor was the most common etiological factor (61.6%). SPTI and volvulus were the other etiological factors most often seen (11.3% and 7.2%, respectively). The management approach for AMLBO most often applied was surgical resection (43.5%). Surgical palliation was performed in 28.8% and conservative management in 27.8%. Surgical resection was performed most for tumors (56.1%), surgical palliation was performed for PC (76.5%), and conservative management was applied for SPTI (100%) (Table 3). The distribution of adhesion data is shown in Table 4. The

mean age was 56.30±16.33 years. In all, 154 (48.4%) patients were male and 164 (51.6%) patients were female. Among this group, 54.4% underwent surgery for malignant disease. The most common primary malignancy was colorectal cancer (51.4%). Conservative management was pursued for 76.7%, surgical palliation was performed for 17%, and surgical resection was performed for 6.3%. Magnetic resonance enteroclysis was performed in 6.3% and surgical adhesiolysis in 10.4%. The most common primary operation was colorectal surgery (29.5%), followed by gynecological (23.2%) and upper

Table 3. Distribution of etiology for AMLBO Etiology Age, years (Mean±SD)

Sex

Tumor

Treatment

Survival

Total

M F Conservative Palliation Resection Yes No

63.27±13.67 108 72

101

159 21 180 61.6

Suspicion of primary tumor ileus

66.48±13.83 26 7 33

0 0 32 1 33 11.3

Volvulus

70.81±17.26 15 6

17 4 21 7.2

Peritoneal carsinomatosis

60.65±12.70

5.8

Acute colonic pseudo-obstruction

74.92±12.18 6 6 7

3 2 8 4 12 4.1

Adhesion

59.64±12.82 4 7 0

5 6 8 3 11 3.8

Inflammatory bowel disease

59.11±24.38

Diverticulitis

57.00±21.21 1 1 2

0 0 2 0 2 0.7

Ischemic colitis

74.00±2.83 1 1 2

0 0 2 0 2 0.7

Hernia

61.00±18.38 1 1 0

0 2 2 0 2 0.7

3.1

Other

74.00±9.85 3 0 3

0 0 3 0 3 1

Total

64.36±14.48 182 110

127

255 37

292 100

Survival

Total (%)

AMLBO: Acute mechanical bowel obstruction; M: Male; F: Female; SD: Standard deviation.

Table 4. Evaluation of AMBO due to adhesions Primary surgery

Sex

Malignant/Benign

Treatment

F Malignant Benign Conservative Adhesiolysis Palliation Resection Yes

Colorectal surgery

94 (29.5)

Gynecological surgery

74 (23.2)

Upper GIS surgery

60 (18.9)

Appendectomy

25 (7.9)

Laparotomy

24 (7.5)

Urological surgery

15 (4.7)

Hernia surgery

14 (4.4)

Hepatopancreato biliary surgery Total

155 163

12 (3.9)

173

145

244

304

318

AMBO: Acute mechanical bowel obstruction; GIS: Gastrointestinal system; M: Male; F: Female.

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272

4 192

GIS (18.9%) surgery. The mortality rate was 4.4% (n=14); 50% of these occurred following colorectal surgery.

The distribution of tumor locations is illustrated in Table 5. The mean age of those with a tumor was 62.94±13.61 years. In this group, 115 (59.9%) patients were male and 77 (40.1%) patients were female. Surgical resection was performed in 54.7%, surgical palliation in 33.3%, and 12% were managed conservatively. The pathology was reported as 42.7% none, 47.4% adenocarcinoma, 2.6% mucinous carcinoma, 3.1% invasion, 2.6% lymphoma/ NET, and 1/6% benign pathology. The mortality rate was 13% (n=25). The most common location of the tumor was the sigmoid colon (n=42, 21.9%), followed by the rectum (n=36, 18.7%) and the rectosigmoid (n=23, 12%). Tumors located distal to the sigmoid colon comprised 52.6% and tumors distal to the splenic flexure represented 71.3%. One patient underwent a total proctocolectomy with ileoanal anastomosis due to attenuated familial adenomatous polyposis.

AMBO: Acute mechanical bowel obstruction; NET: Neuroendocrine tumor; GIS: Gastrointestinal system.

23 12 18 18 42 Total

4 11 16 3

2 167

2 25 1

3 1

0 5 3 3 1 4 1 No

31 20 11 15 17 38 3 9 14 3

1 2 2 0

Survival Yes

0 3

0 5 0

0 0 0 0

0 0 0 0 1 0 1 0 Benign

Lymphoma/NET 2 1 0 0

2 0

0 5

0 6 1

0 0 0 0

2 2 0 1

2 1 0 0

0 0 0 0

0 1 0 0

Mucinous

Invasion

0 0

0 91

3 82 3

1 1 3

31 0 9

5 5 10 3

7 10 11 32

1 7 3 2

Adeno carcinoma 0 2 12 1

Pathology None

1 105

3 64 4

0 1 5

28 0 8

4 3 6 4

0 1 2 1

3 5 11 1

Palliation

Resection

13 13 33

0 23

2 77 3

0 0 2

12 7 6 19 4

0 2 5 2

Female

Treatment Conservative 1 5 3 1

1 2 3

15 0

2 115 1 1 21 11 11 12 23 8 4 9 11 1 Male Sex

Small Cecum Right Hepatic Transverse Splenic Left Sigmoid Rectosigmoid Rectum Total Recurrence Non GIS Total bowel colon flexure colon flexure colon colon colorectal tumors Location of tumor

Table 5. Evaluation of AMBO due to tumor and tumor locations

Karakaş et al. Etiology, management, and survival of AMBO

The hernia distribution is shown in Table 6. The mean patient age was 62.14±15.31 years. There were 11 (25%) male patients and 33 (75%) were female. In all, 25% of the patients were managed conservatively; herniorrhaphy±mesh was performed in 47.7% and surgical resection was performed in 27.3%. The most common type of hernia observed in the group was an incisional hernia (47.7%), followed by an inguinal hernia (18.2%), and an umbilical hernia (11.4%). In 75% (n=6) of those with an inguinal hernia and in 66% (n=2) of those with a femoral hernia, the hernia was located on the right side. The most common reason for an incisional hernia was GIS surgery (57.1%), followed by hernia surgery (23.8%) and gynecological surgery (19.1%). The mortality rate in this group was 6.8% (n=3) and all were patients with an incisional hernia. PC was the fourth most common cause of AMBO: 43.6% (n=17) occurred as a result of colorectal cancers, 30.8% (n=12) from gynecological cancers, and the remainder were of upper GIS, hepaticopancreaticobiliary, breast, urological, or unknown cancer origin. In all, 26.3% of the patients were managed conservatively, surgical palliation was performed in 65.8%, and surgical resection in 7.9%. The mortality rate was 21% (n=8) (Table 7). The incidence of inflammatory bowel disease was determined to be 3.2% in the total AMBO group: 3.4% in those with AMSBO and 3.1% in the AMLBO patients. Conservative management was Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

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Table 6. Evaluation of AMBO due to hernia Type

Sex

Treatment

Primary surgery

Survival

M F Conservative Herniorrhaphy± Resection None GIS Gynecological Hernia Yes Mesh Incisional

3 18

Inguinal R:6 6 2 2

0 12

Total

1 8 0 0 0 8 0 8

L:2

Umbilical 0 5 2

0 5 0 0 0 5 0 5

Diaphragmatic 1 4 2

1 3 1 0 1 5 0 5

Femoral R:2 0 3 0

0 3 0 0 0 3 0 3

L:1

Internal 1 1 0

2 0 1 1 0 2 0 2

Total

11 33

19 14

AMBO: Acute mechanical bowel obstruction; GIS: Gastrointestinal system; M: Male; F: Female.

Table 7. Evaluation of AMBO due to peritoneal carcinomatosis Primary malignancy

Sex

Treatment

Survival

Total

Male Female Conservative Palliation Resection Alive Exitus

Upper GIS

1 2

0 3 0 3

Colorectal

11 6

3 13 4 17

Hepatopancreato biliary 1 1

0 2 0 2

Gynecological

0 12

0 10 2 12

Urological

1 0

0 0 1 1

Breast

0 2

0 1 1 2

Unknown origin

1 0

0 1 0 1

Total

15 23

3 30 8 38

AMBO: Acute mechanical bowel obstruction; GIS: Gastrointestinal system.

applied in 79.2% of patients and surgery was performed in 20.8% (12.5% palliation, 8.3% resection). Mortality was 4.2% (n=1; small bowel obstruction) in this group. The AMBO incidence of colonic volvulus was 2.9% and 7.2% were AMLBO cases. The mean patient age was 70.81±17.25 years and the male/female proportion was 2.5:1 (15/6). In this group, 61.9% (n=13) underwent a Hartmann procedure or resection and anastomosis, 9.5% (n=2) a surgical detorsion and 28.6% a colonoscopic decompression. The mortality rate was 19% (n=4). The total incidence of bezoars was 1.5%. Of those, 18.2% were managed conservatively and 81.8% were treated surgically (27.2% milking, 54.6% enterotomy). No mortality occurred among the bezoar patients in the study. The incidence of gastric outlet obstruction (GOO) was 1.1%. Palliation was the most common management approach, apUlus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

plied to 87.5%, while gastrojejunostomy was performed for 12.5% (n=1). The mortality rate was 12.5% (n=1). Diverticulitis was determined in the AMBO group in 0.7% (n=5): 40% were AMLBO patients and 60% were AMSBO (Meckel’s diverticulitis). All of the large bowel diverticulitis cases were managed conservatively; however, a diverticulectomy was performed for those with small bowel diverticulitis (Meckel’s). No mortality was seen in the diverticulitis patients. In this study group, 33 (4.5%) patients were hospitalized for SPTI evaluation. The mean age was 66.48±13.83 years. All of the patients were managed conservatively and underwent a colonoscopy for further evaluation. A total of 3% (n=1) died due to comorbidities. The incidence of PI was 1.9% in the AMBO group. Concomitant malignancy was found in 1 patient, neurological disorders in 2 patients, and chronic renal failure in 6 patients. All of 273

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the patients were managed conservatively. The mortality rate was 7.1% (n=1). The ACPO incidence was found to be 1.6% overall. Concomitant neurological disorders were found in 6 patients, cardiac disorders in 9 patients, and a psychiatric disorder in 1 patient. In this group, 58.3% were treated conservatively with neostigmine and an enema. An ostomy was performed in 25% (n=3) and resection in 16.7% (n=2). The rate of mortality was 25% (n=3); 1 patient died due to aspiration and 2 patients died after surgery. The incidence of rare etiological factors was 1.9%. These were development post endoscopic retrograde cholangiopancreatography, globe vesicale, ischemic colitis, cecal intramural hematoma, splenic infarct, ileocolic fistula, rectal ulcer, mesenteric ischemia, gallstone ileus, cocoon, and tuberculosis peritonitis. A total of 80% of the patients were managed conservatively, surgical palliation was performed for 6.7%, and surgical resection was performed for 13.3%. The mortality rate was 6.7% (n=1) (gallstone ileus).

DISCUSSION AMBO was an important surgical problem in the past, is still a problem today, and will continue to be one in the future. Hernia and volvulus remain important causes of obstruction; however, adhesions are the most common reason for AMBO. The incidence of AMBO as a result of a tumor or PC has also increased with the prolongation of human life and the advances of development. Pędziwiatr et al.[8] reported a mean age of 38.5 years in AMBO patients before the 20th century, while more recently, it has increased to 63.9 years. Markogiannakis et al.[3] found a mean age of 63.8±1.3 years. Akcakaya et al.[5] reported a mean age of tumoral patients of 58±13 years and 49±20 years among non-tumoral patients. In the present study, the mean of age was 59.9±16.02 years in the total AMBO group, while it was 56.77±16.37 years in patients with AMSBO and 64.36±14.48 years in those with AMLBO. The most common cause of AMLBO was a tumor (61.6%). Consistent with the literature, the mean age of those with large bowel obstruction was greater than those with small bowel obstruction. The proportion of males has been greater than that of females in some studies (51.8% to 74%),[5,9,10] but in other research the female proportion was greater (60%).[3,8] Pędziwiatr et al.[8] noted that the female proportion increased from 47.8% to 60.2% over time. Akcakaya et al. reported that the male proportion was greater in both the tumoral and non-tumoral groups.[3] We determined a male/female ratio of 389/346 (52.9%/47.1%) in AMBO cases: 214/229 (48.3%/51.7%) in the AMSBO group and 182/110 (62.3%/37.7%) in the AMLBO group. There was a larger proportion of female patients in the AMSBO (non-tumoral) group. 274

AMBO has been observed in the small bowel in approximately 75% to 80% of cases in the literature, and 20% to 25% in the large bowel.[3] In our study, the incidence of AMBO was 60% in the small bowel and 40% in the large bowel. The difference in this ratio may be due to the fact that those patients with acute small bowel obstruction, especially due to adhesions, for whom intestinal passage could be provided without requiring hospitalization, were not included in the study. The most common causes of AMBO are adhesions, tumors, and hernias in Europe and the USA (60–68.4%, 15.4–20%, 10–14.8%, respectively).[3,11] In the last 50 years, the incidence of strangulated hernia has decreased from 55.8% to 26.5%, while tumors increased from 6.3% to 22.2% and adhesions remained statistically unchanged.[8] Volvulus and intussusception were reported to be the most common causes of AMBO in Ethiopia,[12] and hernia remained the most common cause of intestinal obstruction in Sudan in some research.[13] The etiology of AMBO has varied over time and according to geographic region in Turkey. External hernias have been cited as the most common cause of AMBO (37.9–45%), followed by volvulus, tumors, and adhesions (28.6%, 27%, 35.1%, respectively).[14–18] The most common etiology of AMBO as well as AMSBO in the literature is peritoneal adhesions. Adhesions reportedly occurred in 63% to 97% of all abdominopelvic surgery patients, but only 5% were symptomatic. Pelvic pain, infertility, and mechanical bowel obstruction are frequent complications of adhesions.[19,20] Parker et al.[21] described a risk of readmission after duodenum and jejunum surgery of 1.8%, ileum surgery 7.7% (10.6% ileostomy, 7% ileal resection), colon surgery 5%, rectal surgery 5.2% (15.4% total proctocolectomy, 8.8% total colectomy), and appendectomy 0.9% (The Surgical and Clinical Adhesions Research [SCAR-3] study). The rate of abdominal reoperation required due to adhesion was 30% to 41%, and increased to 65% to 75% in the small bowel. Surgery in the transverse mesocolon has also caused obstructive adhesions.[22] Ten Broek et al.[23] reviewed the incidence of adhesive small bowel obstruction according to the type of operation. They found that pediatric surgery had the highest incidence rate at 4.2%, followed by gastrointestinal surgery at 3.2%, hepatopancreaticobiliary surgery at 2.2%, gynecological surgery at 2.1%, urological surgery at 1.5%, upper gastrointestinal surgery at 1.2%, and abdominal wall surgery at 0.5%. The incidence after laparotomy was reported as 3.8% and 2.7% after laparoscopy. Barmparas et al.[24] reviewed post-laparotomy adhesive small bowel obstruction. They reported that the most common cause of AMSBO was open adnexal surgery at 23.9%, ileal pouch anastomosis at 19.3%, followed by open total abdominal hysterectomy at 15.6%, and open colectomy at 9.5%. The incidence rate for an open appendectomy was 1.4% vs 1.3% for a laparoscopic appendectomy, but the rate for a laparoscopic cholecystectomy vs. an open cholecystectomy decreased from 0.2% to 7.1%. In our study, the incidence of adhesions was 69.3% for AMSBO and Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

KarakaĹ&#x; et al. Etiology, management, and survival of AMBO

43.3% for AMBO. The most common cause of adhesions was colorectal surgery (29.5%), followed by gynecological surgery (23.2%) and upper GIS surgery (18.9%). Adhesive AMBO can be managed conservatively or surgically. The literature records conservative treatment of adhesive AMBO in 20% to 73% of cases.[25] Fluid resuscitation, electrolyte balancing, and nasogastric decompression are the initial treatments recommended for adhesive AMBO; however, while this initial treatment succeeds in some 80% of cases of partial obstruction, the rate is 40% for complete obstruction.[26] Water-soluble oral contrast agents have been used for conservative management of adhesive AMBO. Oral contrast agents reduced the need for surgery (20% vs 29% in controls) and the therapeutic effects were evident after 24 hours.[27] Operative management of adhesive AMBO initially requires exploration with either an open or laparoscopic approach. According to the etiology and/or patient comorbidities, adhesiolysis, or resection with or without anastomosis and palliation (bypass or ostomy) can be performed. A laparoscopic operation has some advantages, such as less pain, less bleeding, fewer surgical site infections, fewer adhesions, and a shorter hospital stay. However laparoscopic adhesiolysis requires experience, and has an increased bowel injury risk of 6.3% to 26.9% and may delay a diagnosis of perforation.[28] The mortality rate of adhesive AMBO has decreased from 5.29% to 3.77% with timely operative management, but there is still a higher mortality risk than with conservative management.[29,30] In the present study, 76.7% of adhesive AMBO cases were managed conservatively and only 23.3% underwent surgery. In all, 44.6% (n=33) of the surgical group had adhesiolysis and 15% (n=5) of the adhesiolysis procedures were performed laparoscopically. Surgical palliation (ileostomy, colostomy, or bypass) was performed (28.4%) somewhat more than resection (27%). The mortality rate of all adhesive AMBO patients in this study was 4.4% (n=14/318), while it was 71.4% (n=10) among those who underwent surgical resection or palliation. Tumors are the second most common cause of AMBO. Primary or metastatic tumors may obstruct the gastrointestinal passage. Colorectal and ovarian cancers are the most frequent types of tumoral AMBO. The incidence of tumoral AMBO overall is 3%. The reported incidence of colorectal cancer varies from 10% to 28% and ovarian cancer varies from 5.5% to 51%. The most frequently seen extra-peritoneal malignancies are breast cancer, lung cancer, and melanoma.[31,32] Small bowel tumors are a very rare condition (1â&#x20AC;&#x201C;1.6% of gastrointestinal tract tumors) and 53% of these tumors present with AMSBO.[33] The sigmoid colon is the most common site of AMLBO. Research has indicated that 59.4% of tumors are seen distal to the splenic flexure and 34.6% of tumors are observed in the left colon and the sigmoid.[34,35] The main treatment of tumoral AMBO is surgery for palliation or resection. Conservative management can be performed for patients with a partial obstruction in preparation for surgery or with neoadUlus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

juvant oncological treatment. Stents can be used for palliation or in preparation for surgery, but some complications have been recorded, such as stent migration (11%), perforation (4.5%), and re-obstruction (12%).[36] The pathology of tumors has been reported in the literature as 81.9% non-mucinous and 18.1% mucinous in cases of advanced-stage, obstructive, colorectal tumors.[37] One study reported a mortality rate of 14% after surgery in tumoral AMBO.[34] Our data revealed that among all the AMBO cases, 26.2% were tumoral. In all, 94% of the tumors arose from the large bowel, 2% the small bowel, 2% were recurrent, and 2% were non-gastrointestinal. Of the tumors in this study, 62% were distal to the splenic flexure and 31.2% were located in the left colon or the sigmoid. The incidence of tumoral AMBO and colorectal tumor in this study was greater than that seen in the literature, while the incidence of ovarian tumor was less. Conservative management was applied for 12%, patients with a partial obstruction before elective surgery or prior to pathological diagnosis. Another 54.7% underwent a resection procedure, such as anterior resection, left or right hemicolectomy, etc., and 33.3% received palliative care, such as an ileostomy or colostomy, for advanced tumors or frozen abdomen. Our experience with colonic stent placement was limited and was applied in only a few cases of tumoral AMBO. The pathology reports were 2% mucinous and 47.4% adenocarcinoma; 47.2% had no pathology due to palliation of tumoral obstructions. A smaller percentage of mucinous pathology than seen in the literature may be related to patients without pathology. The mortality rate was 13%, which is consistent with the literature. Hernia is still an important cause of AMBO in developing countries. The incidence has decreased from 30% to 15% in developed nations, in part, as a result of elective hernia surgery. Inguinal hernia is the most common type, with a proportion of 75%, and there is a 29% incidence of strangulation. The incidence of strangulation of umbilical hernia has been reported at 60%, incisional hernia at 50%, and femoral hernia at 46%. Internal, parastomal, and diaphragmatic hernias are other types of hernias that can lead to AMBO. Incisional hernia can occur after abdominal surgery in 2% to 50% of cases. Herniorrhaphy with or without mesh and bowel resection, and with or without anastomosis is the first treatment choice for hernia due to bowel strangulation, ischemia, or necrosis. [1,38] In our study, the incidence of hernia leading to AMBO was 6%, which is less than that seen in the literature. The most common type of strangulated hernia was an incisional hernia (47.7%), which is also contrary to literature reports. Diaphragmatic hernia (11.4%) was an important cause of AMBO in this study. Herniorrhaphy, with or without mesh, was the most common treatment (47.7%) and bowel resection was performed in 66.6% of cases of incisional hernia. The mortality rate was 6.8% and all of these were cases of operated incisional hernia. PC has been described as the peritoneal locoregional spread of tumoral cells. Epithelial ovarian cancer, colorectal cancer, 275

Karakaş et al. Etiology, management, and survival of AMBO

gastric cancer, and pancreatic cancer are the most common causes of PC. The incidence of AMBO as a result of PC has been reported as 8% to 14%. Some 75% of epithelial ovarian cancer cases are diagnosed at an advanced stage (PC). The reported PC incidence of colorectal cancer is 4% to 19%, while for gastric cancer it is 53% to 60%, and for pancreatic cancer it is 68.5%; however, obstruction occurred most often in cases of colorectal cancer (19.7% vs 0.07%, 10.3% respectively). AMBO due to PC may be treated with conservative management or surgery. Resection or palliation (ostomy or bypass) are the surgical choices. The overall mortality has been reported as 21%.[39–41] In our study, the incidence of AMBO due to PC was 5.2%, which is less than that reported in the literature. Colorectal cancer was the most common etiology of AMBO due to PC with 44.7%, followed by gynecological (ovarian) cancer with 31.6%, and gastric cancer with 2.5%. Palliation surgery was the most common treatment at 65.8% and resection was performed in only 7.9%. The overall mortality rate was 26.%, which is greater than that reported in the literature. A total of 62.5% of mortality was seen after palliation surgery. Inflammatory bowel disease (IBD) is another etiological factor of AMBO, and particularly Crohn’s disease. The occurrence of obstruction and the need for surgery is greater in the small bowel (35–54%) than the large bowel (5–17%). The inflammatory process, abscess, stricture, and the development of cancer are potential causes of obstruction of the bowel. The incidence of IBD has been reported as 0.7% for AMBO and 7% for AMSBO. The inflammatory process or an abscess are initially treated conservatively (medical or percutaneous drainage). Stricture or tumors are managed surgically. A surgical intervention is performed to achieve palliation or resection of a strictured bowel. The standardized mortality rate for Crohn’s disease has been reported as 1.2% and 0.8% for ulcerative colitis. The mortality rate has been decreased by performing surgery for severe complications or cancer development.[42,43] In the present study, the incidence of IBD was 3.2% for the overall AMBO group, 3.4% for AMSBO, and 3.1% for AMLBO. This is a greater rate for the AMBO group than seen in the literature, while less for AMSBO. In all, 79.2% of patients were managed conservatively and surgery was performed only in cases of Crohn’s disease (20.8%) (12.5% palliation, 8.3% resection). The mortality rate was as 4.2% (n=1; small bowel obstruction). Colonic volvulus (sigmoid colon) is another potential etiology of AMLBO. Colonic volvulus is endemic in Africa, South America, Russia, Eastern Europe, the Middle East, India, and Brazil. The incidence has been reported as 13% to 42%. North America, Western Europe, and Australia have a low incidence rate (5%). The incidence has been reported as 80.2% in the eastern region of Turkey and 38.8% in the western portion of the country. The proportion of males was greater than that of females (4:1). Endemic volvulus is seen in the fourth decade of life, whereas it is more typically observed in 276

the seventh decade in western countries. The management of colonic volvulus varies according to status: uncomplicated cases may be managed conservatively (colonoscopic decompression), while complicated cases (perforation, necrosis) generally require surgical intervention (Hartman procedure or resection anastomosis). The mortality rate of colonic volvulus has been reported as 9.44%.[44–46] The incidence of colonic volvulus in our study was 2.9% for the AMBO group and 7.2% among the AMLBO patients, which is less than rates reported in the national and international literature. The mean age was 70.81±17.25 years and the male/female proportion was 2.5:1 (15/6), which is similar to that reported in western countries. A Hartmann procedure or resection and anastomosis was performed for 61.9% (n=13), surgical detorsion was performed for 9.5% (n=2), and colonoscopic decompression for 28.6%. The mortality rate was 19% (n=4), which is greater than that cited in the literature. The incidence of bezoar leading to AMBO has been reported as 4%. Some 65% had an anamnesis of previous surgery, especially gastric surgery. Bezoars are initially managed conservatively with bowel rest and hydration, including the intake of acidic fluids such as pineapple juice. Surgical intervention can include milking the colon, enterostomy, or bowel resection and anastomosis. The mortality rate has been reported as 4%.[47,48] Our data revealed an AMBO incidence of bezoars of 1.5%. In all, 18.2 of the patients had a history of gastric surgery. Conservative management was applied for 18.2% of the bezoar patients, and 81.8% underwent surgery (27.2% milking, 54.6% enterotomy). A bezoar that was the result of an impacted stool could be milked to the colon, but seed formations required an enterotomy. No mortality was seen in our bezoar patients. The incidence, history of gastric surgery, and mortality rate was less than that reported in the literature. GOO is the consequence of a blockage preventing gastric emptying, often due to gastric, duodenal, or pancreatic disease. Palliative management, such as endoscopic stent replacement, can be as effective as surgery (bypass). The mortality rate of palliative management has been reported as 3.9%, while it is 2% to 36% in cases of surgical intervention. [49] In a recent study, the incidence of GOO was determined to be 1.1%. Palliation was the most common management approach, applied to 87.5%, and a gastrojejunostomy (primary breast cancer) was performed for 12.5%. The mortality rate was 12.5% (n=1; inoperable pancreas cancer). Diverticulitis has been reported to develop in 10% to 25% of cases as a result of diverticular disease and 15% to 20% of diverticulitis cases may include the complication of obstruction. Among patients with colonic diverticulitis, the incidence of obstruction has been reported as 2.3%. Two-thirds of cases of diverticulitis obstruction of the large bowel are managed surgically and 50% are managed with resection, with or without anastomosis. The mortality rate has been reported as 2.6%.[50] Meckel’s diverticulum is the most frequently seen Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

Emergent Surgery (Palliative or Curative)

Yes

-IBD -Ischemic Colitis

*Perforation *Peritonitis *Ischemia

Conservative

-Diverticulitis

Conservative

*Persistent Obstruction >72 hours *NG volume >500 mL at 72 hours *Peritonitis or Ischemia: *Aggravation of pain *CRP >75 mg/dL *Wbc >10,000/m3 *>500 mL free intraperitoneal fluid[56]

Partial Obstruction

-Strangulated Hernia

Emergent Surgery (Palliative or Curative)

Yes

Complete Obstruction

*Oral-IV Contrast Abdominal CT *Gastroscopy (Gastric Outlet Syndrome or Bezoar) *MR Enterography/ Enterocylisis

-Evaluation The Other Etiology

Small Bowel

Emergent Surgery

Contrast in Colon 24-36 hours after

-Water-soluble Oral Contrast Intake -Serial Plain Abdominal Radiography

-Adhesions?

*Perforation *Peritonitis *Strangulation *Ischemia

-Colonic PseudoObstruction

Conservative

Non-Mechanical

-Paralytic Ileus

*History (Previous Surgery, Cancer or Systemic Disease) *Physical Examination (Bowel Movement Sound, Distention, Rigidity, Rebound Tenderness, Rectal Examination) *Nasogastric Tube (Decompression, Bilous or Colonic Content, Follow-up) *Laboratory Tests (Inflammatory, Metabolic, Organ Functions and Ischemia Parameters) *Plain Abdominal Radiography

Figure 1. Algorithm for the diagnostic and therapeutic approach to AMBO. (AMBO: Acute mechanical bowel obstruction; CRP: C-reactive protein; CT: Computed tomography; IBD: Inflammatory bowel disease; IV: Intravenous; MR: Magnetic Resonance; NG: Nasogastric; WBC: White Blood Cell).

*Palliation *Detortion

-Primary Tumor Ileus -Volvulus

Rectoscopy or Colonoscopy

*Oral-IV-Rectal Contrast Abdominal CT

Large Bowel

Mechanical

Bowel Obstruction

Symptoms and Signs of Bowel Obstruction

KarakaĹ&#x; et al. Etiology, management, and survival of AMBO

277

Karakaş et al. Etiology, management, and survival of AMBO

gastrointestinal tract congenital anomaly in these patients, with a 2% incidence. Meckel’s diverticulum has 4% to 6% risk of complication over a lifetime, and intestinal obstruction is the most common in adults. The management of Meckel’s diverticulitis with complications is usually a diverticulectomy or bowel resection.[51] In our study, the incidence of diverticulitis in the AMBO group was 0.7% (n=5). Of those, 40% occurred in the large bowel, and 60% in the small bowel (Meckel’s diverticulitis). A diverticulectomy was performed for all of the small bowel diverticulitis (Meckel’s) patients. No mortality was seen in the diverticulitis patient group. Colorectal cancer is the second most common cancer in the world. Age >50 years, a family history of the disease, anemia, and changes in defecation habits are some risk factors associated with colorectal cancers. AMBO can be a reason for hospital admission for patients with colorectal cancers. Contrast-enhanced computed tomography (CT) results are important in the differential diagnosis and making a final diagnosis. Increased colonic mucosal thickness observed on CT can be a sign of colon pathologies. It has been reported that the lesions revealed by a colonoscopy were 35.7% tumoral and 13.9% benign in these patients.[52,53] In our study, 33 (45%) patients were hospitalized for further evaluation of SPTI. The mean age was 66.48±13.83 years, and they were in the risk group. Symptoms and findings of AMBO, such as non-discharge of gas or stool, vomiting, air-fluid levels observed on plain radiography, and obstruction signs seen on an oral-intravenous contrast abdominal CT were among the reasons for suspicion of a tumoral ileus. Patients for whom a tumoral ileus was excluded by colonoscopy were admitted to a follow-up program and discharged. PI and ACPO were the non-mechanical types of bowel obstruction, and the differential diagnosis is important when considering treatment. PI or adynamic ileus is defined as a non-mechanical reason for a decrease in peristalsis that affects intestinal contents. The most common type of PI is postoperative ileus, which occurs particularly after abdominal surgery. Prolonged surgery and some mediators have been described as important causes of postoperative ileus. Additionally, critical illness, metabolic instability, neurological disorders, and more may be other causes of PI. Supportive treatment, such as cessation of oral intake, fluid and electrolyte replacement, chewing gum, and antibiotics are the basic elements of treatment for PI. Cisapride, neostigmine, and peripheral opiate antagonists are some of the drugs used to treat PI.[54] In our study, PI was found in 1.9% of the AMBO group. The cause of PI was metabolic in all cases and the most common disorder was chronic renal failure, seen in 6 patients, 1 of whom died (mortality rate: 7.1%). ACPO is described as non-mechanical or non-inflammatory acute dilatation of a partial segment or the total colon and 278

rectum. Pelvic surgery, trauma, orthopedic surgery, and acute cardiac events are the most common reasons for ACPO. Conservative treatment includes nasogastric, and/or rectal decompression, and fluid and electrolyte replacement. Neostigmine, cisapride, gastrografin, and polyethylene glycol can be used as pharmacologic treatment. Colonoscopic decompression and surgery (resection or ostomy) can be performed when conservative or pharmacological treatment is ineffective or in complicated cases. The mortality rate has been reported to be 14% to 30% in non-operated patients and 30% to 50% in patients who undergo surgery.[55] Our data indicated that the incidence of ACPO was 1.6% in the overall AMBO group. Concomitant neurological disorders were found in 6 patients, cardiac disorders in 9 patients, and psychiatric disorders in 1 patient. In all, 58.3% were treated conservatively with neostigmine and enema. An ostomy was performed in 25% (n=w3) and resection was performed in 16.7% (n=2). The mortality rate was 25% (n=3): 1 patient died due to aspiration, and 2 patients died after surgery. Our algorithm for a diagnostic and therapeutic approach to AMBO is provided in Fig 1. In conclusion, AMBO remains important as it is the reason for 9.2% of all hospitalization to the emergency surgery department. Adhesions are still the most common cause of AMBO, and the incidence has increased. Conservative management of adhesions increases with the experience of the emergency department team. Strategies to prevent adhesions are important and the first responsibility in this regard falls on surgeons with respect to selecting a minimally invasive surgical intervention and minimizing scar tissue. Tumors are the second most common cause of AMBO now that the incidence of hernias has been reduced. Tumors must usually be managed with surgical resection to provide passage, and the mortality rate is higher in this group. Now that screening for colorectal cancers is becoming more routine for patients >50 years of age, it will be diagnosed before obstruction of the intestinal passage more often. The incidence of inguinal or femoral hernia has decreased due to elective surgery; however, the number of incisional hernia cases has increased. The incidence of peritoneal carcinomatosis has also grown, and it is as frequent as hernia as an etiology of AMBO. Rare etiological factors must also be kept in mind in the differential diagnoses of AMBO, PI, and ACPO. Conflict of interest: None declared.

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D. The incidence and risk factors of post-laparotomy adhesive small bowel obstruction. J Gastrointest Surg 2010;14:1619–28. 25. Fevang BT, Jensen D, Svanes K, Viste A. Early operation or conservative management of patients with small bowel obstruction? Eur J Surg 2002;168:475–81. 26. Köstenbauer J, Truskett PG. Current management of adhesive small bowel obstruction. ANZ J Surg 2018;88:1117–22. 27. Zielinski MD, Bannon MP. Current management of small bowel obstruction. Adv Surg 2011;45:1–29. 28. Ten Broek RPG, Krielen P, Di Saverio S, Coccolini F, Biffl WL, Ansaloni L, et al. Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2017 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group. World J Emerg Surg 2018;13:24. 29. Matsushima K, Sabour A, Park C, Strumwasser A, Inaba K, Demetriades D. Management of adhesive small bowel obstruction: A distinct paradigm shift in the United States. J Trauma Acute Care Surg 2019;86:383– 91. 30. Hajibandeh S, Hajibandeh S, Panda N, Khan RMA, Bandyopadhyay SK, Dalmia S, et al. Operative versus non-operative management of adhesive small bowel obstruction: A systematic review and meta-analysis. Int J Surg 2017;45:58–66. 31. Ripamonti CI, Easson AM, Gerdes H. Management of malignant bowel obstruction. Eur J Cancer 2008;44:1105–15. 32. Lynch B, Sarazine J. A guide to understanding malignant bowel obstruction. Int J Palliat Nurs 2006;12:164–6, 168–71. 33. Turan M, Karadayi K, Duman M, Ozer H, Arici S, Yildirir C, et al. Small bowel tumors in emergency surgery. Ulus Travma Acil Cerrahi Derg 2010;16:327–33. 34. Biondo S, Parés D, Frago R, Martí-Ragué J, Kreisler E, De Oca J, et al. Large bowel obstruction: predictive factors for postoperative mortality. Dis Colon Rectum 2004;47:1889–97. 35. Pisano M, Zorcolo L, Merli C, Cimbanassi S, Poiasina E, Ceresoli M, et al. 2017 WSES guidelines on colon and rectal cancer emergencies: obstruction and perforation. World J Emerg Surg 2018;13:36. 36. Dolan EA. Malignant bowel obstruction: a review of current treatment strategies. Am J Hosp Palliat Care 2011;28:576–82. 37. Winner M, Mooney SJ, Hershman DL, Feingold DL, Allendorf JD, Wright JD, et al. Incidence and predictors of bowel obstruction in elderly patients with stage IV colon cancer: a population-based cohort study. JAMA Surg 2013;148:715–22. 38. Hayden GE, Sprouse KL. Bowel obstruction and hernia. Emerg Med Clin North Am 2011;29:319–45, ix. 39. Baratti D, Kusamura S, Guaglio M, Deraco M. Peritoneal metastases: challenges for the surgeon. Minerva Chir 2015;70:195–215. 40. Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer 2000;88:358–63. 41. Shariat-Madar B, Jayakrishnan TT, Gamblin TC, Turaga KK. Surgical management of bowel obstruction in patients with peritoneal carcinomatosis. J Surg Oncol 2014;110:666–9. 42. Marrero F, Qadeer MA, Lashner BA. Severe complications of inflammatory bowel disease. Med Clin North Am 2008;92:671–86, ix. 43. Berg DF, Bahadursingh AM, Kaminski DL, Longo WE. Acute surgical emergencies in inflammatory bowel disease. Am J Surg 2002;184:45–51. 44. Perrot L, Fohlen A, Alves A, Lubrano J. J Visc Surg 2016;153:183–92. Management of the colonic volvulus in 2016. 45. Halabi WJ, Jafari MD, Kang CY, Nguyen VQ, Carmichael JC, Mills S, et al. Colonic volvulus in the United States: trends, outcomes, and predictors of mortality. Ann Surg 2014;259:293–301. 46. Gürleyik G, Kotan C, Dulundu E, Oztürk E, Sönmez R, Sağlam

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requiring hospitalization. Dig Surg 2007;24:471–6. 51. Marwah S, Singla P, Marwah N, Gupta S, Singh VP. Ileal stricture following Meckel’s diverticulitis: a rare cause of intestinal obstruction. Clin J Gastroenterol 2016;9:118–23. 52. Read TE, Kodner IJ. Colorectal cancer: risk factors and recommendations for early detection. Am Fam Physician 1999;59:3083–92. 53. Chandrapalan S, Tahir F, Kimani P, Sinha R, Arasaradnam R. Systematic review and meta-analysis: does colonic mural thickening on CT correlate with endoscopic findings at colonoscopy? Frontline Gastroenterol 2018;9:278–84. 54. Batke M, Cappell MS. Adynamic ileus and acute colonic pseudo-obstruction. Med Clin North Am 2008;92:649–70, ix. 55. Pereira P, Djeudji F, Leduc P, Fanget F, Barth X. Ogilvie’s syndrome-acute colonic pseudo-obstruction. J Visc Surg 2015;152:99–105.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Mekanik bağırsak tıkanıklığının etiyoloji, yönetimi ve sağkalımı: Türkiye’deki bir eğitim ve araştırma hastanesinin beş yıllık sonuçları Dr. Dursun Özgür Karakaş, Dr. Metin Yeşiltaş, Dr. Berk Gökçek, Dr. Seracettin Eğin, Dr. Semih Hot Okmeydanı Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul

AMAÇ: Akut mekanik bağırsak tıkanıklığı (AMBT) acil servisler için halen ciddi bir cerrahi problemdir. AMBT’nin etiyoloji, yönetimi ve sağ kalımı açısından değerlendirmeyi amaçlamaktayız. GEREÇ VE YÖNTEM: Ocak 2014 ile Aralık 2018 tarihleri arasında bağırsak tıkanıklığı için yatırılmış hastalar geriye dönük incelendi. Yaş, cinsiyet, etiyoloji, yönetim ve sağ kalım AMBT açısından geriye dönük değerlendirildi. Adezyonlar, tümörler, herniler ve peritoneal karsinomatoza daha detaylı değerlendirildi. BULGULAR: Çalışmaya 735 hasta dâhil edildi. %60’ı ince bağırsak %40’ı kalın bağırsak tıkanıklığıydı. Yaş ortalaması 59.9±16.02 yıldı. %52.9’u erkek, %47.1’i kadındı. AMBT’nin en sık nedeni adezyonlar, tümörler ve hernilerdi (sırasıyla, %43.3, %26.2 ve %6). İnce bağırsak için en sık neden adezyon (%69.3), kalın bağırsaklar için ise tümörlerdi (%61.6). AMBT’nin en sık yönetimi konservatif yaklaşımdı (%53.2), cerrahi palyasyon %24.9 ve rezeksiyon %21.9 oranında uygulanmıştı. Konservatif yaklaşım en sık adezyonlarda (%76.7), cerrahi palyasyon peritoneal karsinomatozada (%65.7), ve rezeksiyon ise volvulusta (%61.9) uygulanmıştı. Mortalite oranı %8.6 bulundu. Adezyon için kolorektal cerrahi (%51.4), tümör için splenik fleksura distal (%71.3) yerleşimli kolorektal kanserler (%93.8) ve herniler için ise sıklıkla gastrointestinal cerrahi (%57.1) sonrası gelişen insizyonel herni (%47.7) en sık nedenlerdi. TARTIŞMA: Adezyon, tümör ve herniler AMBT’nin sırasıyla en sık nedenleridir. En sık yönetim şekli konservatif yaklaşımdır ve çoğunlukla adezyonlar için uygulanır. Femoral ve inguinal herni sıklığı azalırken insizyonel herni sıklığı artmakta, peritoneal karsinomatoza son yıllarda herni kadar sık gözlenmektedir. Anahtar sözcükler: Adezyon; akut kolonik psödo obstrüksiyon; bağırsak tıkanıklığı; fıtık; paralitik ileus; tümör. Ulus Travma Acil Cerrahi Derg 2019;25(3):268-280

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ORIGIN A L A R T IC L E

Extension-block pinning to treat bony mallet finger: Is a transfixation pin necessary? Sercan Çapkın, M.D.,1 Abdul Fettah Büyük, M.D.,2 Özgür Mert Bakan,4 M.D., Doğan Atlıhan, M.D.3

Serkan Sürücü, M.D.,3

Department of Orthopaedics and Traumatology, Division of Hand Surgery, Uludağ University Faculty of Medicine, Bursa-Turkey

Department of Orthopaedics and Traumatology, Baltalimanı Bone Diseases Training and Research Hospital, İstanbul-Turkey

Department of Orthopaedics and Traumatology, Haseki Training and Research Hospital, İstanbul-Turkey

Department of Orthopaedics and Traumatology, Ege University Faculty of Medicine, İzmir-Turkey

ABSTRACT BACKGROUND: Extension-block pinning is a popular treatment for mallet fractures, but it is associated with several pitfalls. Of note, transfixation Kirschner wires used to fix the distal interphalangeal (DIP) joint may cause iatrogenic nail bed injury, bone fragment rotation, chondral damage, or osteoarthritis. The objective of this study was to determine whether a transfixation pin was necessary for extension-block pinning in the treatment of bony mallet fracture. METHODS: Patients were treated with a pin-orthosis extension-block technique if they had been diagnosed with a type IVB mallet fracture according to Doyle’s classification. Radiological outcomes were evaluated based on postoperative X-ray results, and functional outcomes were evaluated using Crawford’s criteria. RESULTS: Thirteen patients (9 males and 4 females) with a mean age of 26 years were included. The mean time between the injury and surgery was 3.3 days, and the mean follow-up period was 8.2 months (range: 4–12 months). Radiographic bone union was achieved in all patients within an average of 5.1 weeks (range: 5–6 weeks). At the final follow-up, the DIP joint had an average degree of flexion of 76.1° (range: 65°–80°) and an average extension deficit of 3.84° (range: 0°–15°). According to Crawford’s criteria, 8 patients had excellent results, 4 patients had good results, and 1 patient had a fair result. No patient reported pain at the final follow-up. CONCLUSION: Satisfactory clinical and radiological outcomes were obtained with the pin-orthosis extension-block technique. Future prospective and randomized studies are justified to confirm the efficacy of this technique. Keywords: Bony mallet finger; extension-block pinning; pin-orthosis; transfixation pin.

INTRODUCTION A mallet fracture involves damage to the terminal extensor mechanism caused by bony avulsion of the distal phalanx base. Such fractures typically result from forced flexion of the extended distal interphalangeal (DIP) joint.[1] Although several treatment options have been reported, from conservative to surgical management, the optimal treatment continues to be a subject of debate.[2–5] However, surgery is usually advocated when the dorsal fragment involves more than one-third of the

articular surface or when there is volar subluxation.[6–8] The main surgical options are Kirschner (K)-wire fixation,[9] tension band wiring,[7] micro screws,[10] pull-out wire fixation,[11] hook plate,[12] small external fixator,[2] or extension-block fixation.[8,13–16] The extension-block pinning technique reported by Ishiguro et al.[13] is among the most popular treatment methods for mallet fractures, but is associated with several potential problems. Transfixation K-wires used to fix the DIP joint may cause iatrogenic nail bed injury, bone fragment rotation, chondral damage, or osteoarthritis. Furthermore, the

Cite this article as: Çapkın S, Büyük AF, Sürücü B, Bakan ÖM, Atlıhan D. Extension-block pinning to treat bony mallet finger: Is a transfixation pin necessary?. Ulus Travma Acil Cerrahi Derg 2019;25:281-286. Address for correspondence: Sercan Çapkın, M.D. Uludağ Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, El Cerrahisi Bilim Dalı, Bursa 16059, Turkey. Tel: +90 224 - 295 00 00 E-mail: sercancapkn@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):281-286 DOI: 10.5505/tjtes.2018.59951 Submitted: 22.05.2018 Accepted: 30.10.2018 Online: 02.11.2018 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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Çapkın et al. Extension-block pinning to treat bony mallet finger: Is a transfixation pin necessary? Table 1. Doyle classification Type characteristics I

Closed injury±avulsion fracture

II Open injury (laceration at or around distal interphalangeal joint) III Open injury+deep soft tissue abrasion involving loss of skin and

extendor tendon substance

Approval for this prospective study was granted by Haseki Training and Research Hospital Ethics Committee (date: 31.05.2017, approval no: 497), and all of the participating patients provided written, informed consent before enrollment. The only inclusion criterion was for the patient to have a Doyle type IVB mallet fracture (Table 1).[1]

MATERIALS AND METHODS

IV A: Growth plate fracture (pediatric)

Surgical Technique

B: Fracture fragment involving 20%–50% of articular surface (adult)

C: Fracture fragment involving >50% of articular surface (adult)

All of the procedures were performed by a single surgeon, using an image intensifier under digital block anesthesia without a tourniquet. Under lateral-view fluoroscopy, the DIP joint was then held in maximum flexion, and a 1.2-mm K-wire was inserted just behind the fragment into the dorsal rim of the articular surface of the middle phalangeal head. Insertion was at an angle of approximately 40° to 45° relative to the longitudinal axis. The fracture was then reduced with the DIP

need for prolonged immobilization may cause flexion contracture of the DIP joint. Presently described is a simple and minimally invasive pin-orthosis extension-block technique for the management of mallet fractures.

(a)

(b)

(c)

(d)

(e)

(f)

Figure 1. A 28-year-old male with a mallet fracture of the right little finger. (a) Preoperative lateral X-ray of a type IVB mallet fracture. (b) A 1.2-mm Kirschner wire was inserted just behind the fragment into the dorsal rim of the articular surface of the middle phalangeal head, at an angle of approximately 40°–45° relative to its longitudinal axis, and an aluminum orthotic device was applied. (c) Postoperative lateral view with fluoroscopy. (d-f) Clinical appearance after applying the aluminum orthotic device.

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joint in traction and slight extension, and the K-wire was cut to between 0.5 and 1 cm above the skin. Wound dressing was accomplished with sterile strips (Steri-Strip; The 3M Co., Maplewood, MN, USA). After appropriate reduction was achieved, an aluminum splint was applied to the volar side, keeping the finger in the reduced position and allowing the metacarpophalangeal joint to have free movement. The operation was terminated after obtaining a satisfactory lateral fluoroscopy image in the splinted position (Fig. 1a-f).

Table 2. Crawford criteria for the assessment of mallet

Postoperative Management

Full flexion

No pain

The patients were discharged on the day of surgery and requested to return for weekly review by the surgeon who performed the surgery. Dressing was managed by holding the DIP joint in extension so as not to disrupt the fracture reduction. After 4 weeks, the K-wire was removed, and the orthosis was left in place for another week. If union was not complete at this time, the orthosis was retained until the end of the sixth week. Lateral and posteroanterior plain radiographs were taken immediately after fixation and weekly (Fig. 2). Active range of motion exercises were initiated immediately after removal of the aluminum orthosis.

Evaluation Clinical and radiographic evaluations were conducted in all cases. Fracture union was defined as the X-ray presence of bridging trabeculae and a radiolucent line at the fracture gap and the clinical absence of tenderness at the fracture site. Complications and progress with bony union were evaluated with clinical examinations and weekly radiographs. The active range of motion and extension lag of the DIP joint was measured with a goniometer. Full flexion was considered to be achieved when the angle of the injured side reached that of the opposite side at follow-up. Functional outcomes were evaluated using Crawford’s criteria (Table 2).[17]

(a)

(b)

finger outcome Grade Excellent Good

Fair Poor

Characteristics of DIP joint Full extension Full flexion No pain Extension deficit 0º–10º

Extension deficit 10º–25º Any flexion loss No pain Extension deficit >25º Persistent pain

DIP: Distal interphalangeal.

RESULTS Thirteen patients (9 males and 4 females) with a mean age of 26 years (range: 17–36 years) were treated with the current technique (Table 3). Eight fractures were of the right hand and 5 were of the left hand, with the ring finger being most commonly affected (6 cases), followed by the little finger (4 cases), middle finger (2 cases) and index finger (1 case). The causes of injury were a fall (7 cases), sports injury (3 cases), work accident (2 cases) and a fight (1 case). The mean time between the injury and surgery was 3.3 days. The mean follow-up period was 8.2 months (range: 4–12 months), with all K-wires removed after 4 weeks. However, union was incomplete after 5 weeks in 2 patients, so the orthoses were retained until the end of week 6 in these cases, meaning that overall the orthotic splints were used for an a mean of 5.1 weeks. Radiographic bone union was achieved by either week 5 or 6 (mean of 5.1). At the final follow-up, the DIP had an average flexion of 76.1° (range: 65°–80°) and an average extension deficit of 3.84° (range: 0°–15°). According to Crawford’s criteria, 8 patients had excellent results, 4 patients had good results, and 1 patient had a fair result. No patient reported pain at the final follow-up. There were no complications, such a comminution of the fracture fragment, nail deformity, volar subluxation, or dislocation or DIP joint osteoarthritis. Two cases developed superficial infection, and 1 case developed skin necrosis; all were treated with oral antibiotics and wound care, as needed.

DISCUSSION Figure 2. (a) Early postoperative lateral X-ray view. (b) Lateral X-ray view after week 6, before the aluminum orthotic splint was removed.

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There is no optimal treatment for mallet finger injuries; there are a range of potential treatments that are considered appropriate.[14] Ishiguro et al.[13] first described extension-block pin283

Çapkın et al. Extension-block pinning to treat bony mallet finger: Is a transfixation pin necessary?

Table 3. Summary of patient data Patient no

Age Sex Affected finger Cause (years)

20 Male

33 Male Right-index

28 Male Right-little

Male

Right-little

Sport injury

Female

Left-little

Sport injury

23 Male Left-middle Female

Left-little

Time from injury to surgery (days)

29 Male Right-ring

17 Male

Female

Right-ring Left-ring Right-middle

Follow-up period (months)

Fall

Fall Work accident Fall Fight Sport injury

27 Female Right-ring

Fall

31 Male Right-ring

Fall

Male

Left-ring

ning as a simple and reliable method, and it has since become one of the most popular methods of treating mallet finger, with later modifications.[15–21] Most of these resulting techniques involve some use of K-wire fixation across the DIP joint, despite awareness that it is difficult to insert a temporary transfixation pin through the DIP joint. Potential disadvantages associated with repeated attempts at insertion include articular cartilage damage that can lead to secondary osteoarthritis, especially if more than one attempt at pin insertion is needed,[8] and iatrogenic nail bed injury. However, the presently described method did not require that a transfixation pin be inserted through the joint, which should reasonably be expected to decrease the risk of secondary arthritis. Indeed, we observed no arthritic change or nail deformity in any case during the 8.2-month mean follow-up period. Early union has previously been reported in 5 to 7 weeks with extension-block fixation,[13,15,16] and the results of this study compared favorably. Miura[2] described a modified version of the extension-block fixation method that was designed to achieve accurate reduction and stable fixation by controlling dorsal rotation of the fragment with an external fixator. Twelve acute mallet fractures were treated with this method and not only were all united after an average of 5±1 weeks, but there were no arthritic changes after an average follow-up of 4 months. However, that design required a bulky fixator and a DIP joint splint for an average of 6 weeks. It also required increased surgical time, increased radiation exposure, and a second surgical procedure to remove the fixator. We achieved comparable results with a less invasive method, albeit with the disadvantage that treatment success was closely related to patient compliance. Miranda et al.[22] described a simple technique to improve intraoperative bony mallet reduction and avoid complications, 284

Work accident

such as articular cartilage damage, nail bed damage, and dorsal skin necrosis. They used a blunt needle as a joystick to reduce the bony fragment of a stab incision. After reduction was achieved, a dorsal splint was applied holding the DIP joint in 15° to 30° extension. They achieved and maintained satisfactory reduction, and reported their technique as a less-invasive management option for bony mallet injures. Criticism of this technique focused on the difficulty of maintaining the reduction of the unstable fragment with the dorsal splint alone due to the extensor tendon pulling on the bony fragment. [23] In the present study, only an extension-block K-wire was used to reduce and maintain reduction. Once the appropriate reduction was achieved, an aluminum splint was applied to the volar side instead of using transfixation wire. Karslıoğlu et al.[24] emphasized that rotation of the mallet fragment can prevent appropriate fracture reduction and may result in extension lag, incongruity of the articular surface, premature osteoarthritis, or stiffness. They described a percutaneous derotation technique utilizing needle-tip reduction during surgery for type IIb and IIIc patients according to the Wehbe and Schneider classification.[25] They found that derotation of type II (25% rotation) and III (50% rotation) mallet pieces with closed reduction was simple, effective, and could prevent surgical failure.[24] The transfixation K-wire was used as in the original extension-block technique. The technique presented in the current study was not used in the presence of rotational deformity. Patients who have rotational deformity may benefit from direct reduction techniques and more rigid fixation. Closed reduction by extension-block K-wire fixation is a relative contraindication in bony mallet fractures older than 5 weeks. Reduction may not be achieved due to scar tissue that Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

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prevents closed reduction in these fractures.[13] Open reduction to restore the congruity of the articular surface is usually indicated in such cases.[14] Pegoli et al.[8] used percutaneous curettage with an Ishiguro extension-block K-wire to treat mallet fracture cases older than 5 weeks. All of the patients in this study were treated in the early period, with the latest presentation at 10 days after trauma. Our indications for the pin-orthosis extension-block technique include acute bony mallet injuries in compliant patients who are well-motivated for splint use. Because the fracture fragment is indirectly reduced, anatomical reduction may not be achieved if rotation of the fracture fragment is present. Fractures that involve more than 50% of the articular surface may be difficult to reduce with the presently described technique, and even if reduction is achieved, this reduction may not be protected without rigid fixation. Therefore, patients with Doyle type IVC mallet fractures and fractures with irreducible subluxation of the distal phalanx formed the exclusion criteria for this study. Patients with open injuries were also excluded. This study has several limitations. Of note, we only included a small sample that was limited to patients with Doyle type IVB mallet fractures. Further research will be essential to assess the efficacy of this approach with fracture fragments that involve more than 50% of the articular surface (e.g., Doyle type IVC). Finally, the follow-up period may have been too short to observe long-term adverse outcomes.

Conclusion In conclusion, our modified technique reduces the risks of iatrogenic chondral injury, joint degeneration, and nail bed injury, as well as fracture displacement due to interposition of the K-wire used for transfixation. Clinically, it also reduces the duration of surgery and radiation exposure. The pin-orthosis extension-block technique may, therefore, be a useful alternative method for the treatment of mallet fractures, benefitting from being less invasive and easy to apply, and without damaging key anatomical structures. Conflict of interest: None declared.

REFERENCES 1. Doyle J. Extensor tendons: acute injuries. In: Green DP, Hotchkiss RN, Pederson WC, editors. Operative hand surgery. 4th ed. Churchill Livingstone: Philadelphia; 1999. p. 1950–70. 2. Miura T. Extension block pinning using a small external fixator for mallet finger fractures. J Hand Surg Am 2013;38:2348–52. 3. Wada T, Oda T. Mallet fingers with bone avulsion and DIP joint subluxation. J Hand Surg Eur Vol 2015;40:8–15. 4. Kim JK, Kim DJ. The risk factors associated with subluxation of the distal interphalangeal joint in mallet fracture. J Hand Surg Eur Vol

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2015;40:63–7. 5. Yoon JO, Baek H, Kim JK. The Outcomes of Extension Block Pinning and Nonsurgical Management for Mallet Fracture. J Hand Surg Am 2017;42:387.e1–387.e7. 6. Hamas RS, Horrell ED, Pierret GP. Treatment of mallet finger due to intra-articular fracture of the distal phalanx. J Hand Surg Am 1978;3:361– 3. 7. Damron TA, Engber WD. Surgical treatment of mallet finger fractures by tension band technique. Clin Orthop Relat Res 1994;133–40. 8. Pegoli L, Toh S, Arai K, Fukuda A, Nishikawa S, Vallejo IG. The Ishiguro extension block technique for the treatment of mallet finger fracture: indications and clinical results. J Hand Surg Br 2003;28:15–7. 9. Lubahn JD. Mallet finger fractures: a comparison of open and closed technique. J Hand Surg Am 1989;14:394–6. 10. Kronlage SC, Faust D. Open reduction and screw fixation of mallet fractures. J Hand Surg Br 2004;29:135–8. 11. Zhang X, Meng H, Shao X, Wen S, Zhu H, Mi X. Pull-out wire fixation for acute mallet finger fractures with k-wire stabilization of the distal interphalangeal joint. J Hand Surg Am 2010;35:1864–9. 12. Teoh LC, Lee JY. Mallet fractures: a novel approach to internal fixation using a hook plate. J Hand Surg Eur Vol 2007;32:24–30. 13. Ishiguro T, Itoh Y, Yabe Y, Hashizume N. Extension block with Kirschner wire for fracture dislocation of the distal interphalangeal joint. Tech Hand Up Extrem Surg 1997;1:95–102. 14. Lin JS, Samora JB. Surgical and Nonsurgical Management of Mallet Finger: A SystematicReview. J Hand Surg Am 2018;43:146–163.e2. 15. Hofmeister EP, Mazurek MT, Shin AY, Bishop AT. Extension block pinning for large mallet fractures. J Hand Surg Am 2003;28:453–9. 16. Lee YH, Kim JY, Chung MS, Baek GH, Gong HS, Lee SK. Two extension block Kirschner wire technique for mallet finger fractures. J Bone Joint Surg Br 2009;91:1478–81. 17. Inoue G. Closed reduction of mallet fractures using extension-block Kirschner wire. J Orthop Trauma 1992;6:413–5. 18. Crawford GP. The molded polythene splint for mallet finger deformities. J Hand Surg Am 1984;9:231–7. 19. Yoon HK, Kim BM, Rah SK. Modified extension block technique for large mallet fracture. J Korean Soc Surg Hand 2005;10:227–33. 20. Lee SK, Kim KJ, Yang DS, Moon KH, Choy WS. Modified extensionblock K-wire fixation technique for the treatment of bony mallet finger. Orthopedics 2010;33:728. 21. Chung DW, Lee JH. Anatomic reduction of mallet fractures using extension block and additional intrafocal pinning techniques. Clin Orthop Surg 2012;4:72–6. 22. Miranda BH, Murugesan L, Grobbelaar AO, Jemec B. PBNR: Percutaneous Blunt Needle Reduction of Bony Mallet Injuries. Tech Hand Up Extrem Surg 2015;19:81–3. 23. Karslioglu B, Tekin AC, Tasatan E. Percutaneous Blunt Needle Reduction (PBNR) Needs Stable Fixation. Tech Hand Up Extrem Surg 2018;22:35–6. 24. Karslıoğlu B, Uzun M, Tetik C, Tasatan E, Tekin AC, Buyukkurt CD. Derotation of the mallet piece: A crucial point in mallet fracture surgery. Hand Surg Rehabil 2018 Jun 6. doi: 10.1016/j.hansur.2018.03.004. [Epub ahead of print] 25. Wehbé MA, Schneider LH. Mallet fractures. J Bone Joint Surg Am 1984;66:658–69.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Kemiksel çekiç parmak tedavisi için ekstansiyon blok pinleme: Transfiksasyon pini gerekli mi? Dr. Sercan Çapkın,1 Dr. Abdul Fettah Büyük,2 Dr. Serkan Sürücü,3 Dr. Özgür Mert Bakan,4 Dr. Doğan Atlıhan3 Uludağ Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, El Cerrahisi Bilim Dalı, Bursa Baltalimanı Kemik Hastalıkları Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul Haseki Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul 4 Ege Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Kliniği, İzmir 1 2 3

AMAÇ: Kemiksel çekiç parmak yaralanmalarının tedavisinde popüler bir tedavi yöntemi olan ekstansiyon blok pinleme yönteminde kullanılan transfiksasyon pininin gerekliliğini araştırmak. GEREÇ VE YÖNTEM: Doyle sınıflamasına göre tip 4B çekiç parmak yaralanması olan hastalar tariflediğimiz pin-ortez ekstansiyon blok yöntemi ile tedavi edildi. Radyolojik sonuçlar ameliyat sonrası çekilen röntgenlerle, fonksiyonel sonuçlar Crawford kriterlerine göre değerlendirildi. BULGULAR: Yaş ortalaması 26 olan 13 hasta (9 erkek, 4 kadın) çalışmaya dahil edildi. Yaralanma ile cerrahi arasında geçen ortalama süre 3.3 gün, ortalama takip 8.2 ay (dağılım, 4–12 ay) dı. Tüm hastalarda ortalama 5.1 haftada (dağılım, 5–6 hafta) radyolojik kemik kaynaması elde edildi. Son kontrollerde ortalam aktif distal interfalangeal eklem fleksiyonu 76.1° (dağılım, 65°–80°) ve ortalama ekstansiyon kaybı 3.84° (dağılım, 0°–15°) di. Crawford kriterlerine göre, sekiz hastada mükemmel sonuç, dört hastada iyi sonuç, bir hastada kötü sonuç elde edildi. Son kontrollerde hiç bir hastada ağrı yoktu. TARTIŞMA: Kullandığımız pin-ortez ekstansiyon blok tekniğinde tatmin edici klinik ve radyolojik sonuçlar elde ettik. Randomize kontrollü ve ileriye yönelik çalışmalar ile tekniğin etkinliği teyit edilecektir. Anahtar sözcükler: Ekstansiyon-blok pinleme; kemik çekiç parmak; pin-ortez. Ulus Travma Acil Cerrahi Derg 2019;25(3):281-286

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ORIGIN A L A R T IC L E

Outcomes of salvage total hip arthroplasty after failed osteosynthesis for collum femoris fractures Turgut Akgül, M.D.,1 Fevzi Birişik, M.D.,2 Gökhan Polat, M.D.,1 Cengiz Şen, M.D.,1 Önder İsmet Kılıçoğlu, M.D.1 1

Department of Orthopedics and Traumatology, İstanbul University İstanbul Faculty of Medicine, İstanbul-Turkey

Department of Orthopedics and Traumatology, İstanbul Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: This study is an investigation of the outcomes of salvage total hip arthroplasty (THA) to treat collum femoris fractures that resulted in complications or failure after osteosynthesis. METHODS: Twenty patients (6 male, 14 female; mean age: 56.7 years) who underwent salvage total hip arthroplasty (THA) between 1988 and 2012 due to failure developing after closed reposition and osteosynthesis in the treatment of collum femoris fractures were included in the study. The type of osteosynthesis, and the length of time until failure and before THA application after collum femoris fracture were recorded. Cementless acetabular and femoral components were used in all of the patients. Complications were defined as those occurring during and after surgery. The clinical results were assessed with the Harris Hip Score (HHS) and the presence of loosening was assessed with radiological evaluation in follow-up. RESULTS: The mean length of the follow-up period was 59.4 months (range: 15–178 months). The collum femoris fractures of the 20 patients were classified as: 5 Garden type II, 13 type III, 2 type IV, and 3 Pauwels type I, 8 type II, and 9 type III. Cannulated screws were used in 13 patients (65%) and dynamic hip screw (DHS) fixation was used in 7 patients (35%). Complications observed after osteosynthesis were nonunion in 4 cases (20%), malunion in 2 (10%), avascular necrosis in 10 (50%), and implant failure in 4 (20%). A mean of 9.66 months (range: 3–54 months) elapsed before osteosynthesis failure and the mean length of time until THA was 31.6±51.7 months. There was no statistically significant difference between cannulated screw and DHS fixation in the development of complications (p=0.084). Early dislocation (5%), periprosthetic fracture (5%) and acetabular protrusion (5%) were recorded as complications. A revision was made upon determination of loosening in the 10th year in the patient who developed early dislocation. While the mean HHS was 54.05±8.22 before THA, it was evaluated to be 86.45±8.73 at the last follow-up, which was a statistically significant difference (p<0.0001). CONCLUSION: The study findings demonstrated that THA applied with suitable surgical technique is a safe and successful method that may be used after failed osteosynthesis in cases of collum femoris fracture. Keywords: Hip arthroplasty; hip fracture; osteosynthesis.

INTRODUCTION Osteosynthesis is recommended as the first treatment of choice in the early period of collum femoris fracture treatment. There is some divergence of opinion about treatment options in patients of advanced age, especially in cases of displaced collum femoris fracture.[1–3] Although some authors

recommend total hip arthroplasty (THA), stating that there is high rate of failure after osteosynthesis, the traditionally accepted view is to use the osteosynthesis technique in patients over 65 years of age.[2] Osteosynthesis treatment includes open and closed reposition surgical options in combination with cannulated screw or dynamic hip screw (DHS) application. Independent of the option, the failure rate of osteosyn-

Cite this article as: Akgül T, Birişik F, Polat G, Şen C, Kılıçoğlu Öİ. Outcomes of salvage total hip arthroplasty after failed osteosynthesis for collum femoris fractures. Ulus Travma Acil Cerrahi Derg 2019;25:287-292. Address for correspondence: Turgut Akgül, M.D. İstanbul Üniversitesi İstanbul Tıp fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, İstanbul, Turkey. Tel: +90 212 - 414 20 00 E-mail: doktorturgut@yahoo.com Ulus Travma Acil Cerrahi Derg 2019;25(3):287-292 DOI: 10.5505/tjtes.2018.55506 Submitted: 16.04.2018 Accepted: 06.09.2018 Online: 16.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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thesis in advanced age is reported to be 22.6%.[4] THA is a salvage therapy in the treatment of failure developing after osteosynthesis. There is no consensus in the literature about the success or complications of hip arthroplasty performed as salvage therapy. While some authors report poor clinical outcomes and high complication rates, others report successful clinical outcomes and low complication rates.[5,6] This study was an evaluation of the clinical and radiological outcomes of THA applications performed as salvage therapy in the treatment of problems occurring related to osteosynthesis for collum femoris fractures.

MATERIALS AND METHODS Twenty patients who underwent THA between 1988 and 2012 due to the development of failure after closed reposition and osteosynthesis following a collum femoris fracture were included in the study. Patients with union occurring after closed reposition but coxarthrosis developing in the late period were not included in the study. Nonunion, avascular necrosis, and implant failure were considered to be preoperative osteosynthesis failures. Femoral stem with cement procedures and hemiarthroplasty cases were excluded from the study. The mean age of the patients included in the study was 56.75±12.15 years. The collum femoris fractures were classified according to the Garden and Pauwels systems and the surgical implant was performed with cannulated screw or DHS fixation. After removal of osteosynthesis materials in the lateral decubitus position with a lateral approach as the standard method, the anterior capsule and labrum were partially resected to achieve standard exposure. The acetabular component was press fit and an acetabular screw was added for extra stability. The femoral component was press fit without cement. A highly cross-linked polyethylene acetabular insert was used in the last 14 cases that were operated on after 2006. A 28mm metal cobalt chrome femoral head was used in all of the patients. Patients with a cemented femoral component were excluded from this study to create a homogenous series.

The patients were allowed to walk with tolerated weightbearing within 48 hours after the surgery. Full weight-bearing was initiated at 6 weeks after surgery. The HHS was used in the clinical assessment of the patients. Complications that developed after surgery and their treatments were determined. IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA) was used to perform the statistical analysis. A t-test was used for intergroup comparisons of quantitative data and a chi-square test for intergroup comparisons of qualitative data. Post-hoc power analysis was performed by using G*power version 3.1.7 (Faul, F. et al., Heinrich-HeineUniversität Düsseldorf, Düsseldorf, Germany). The comparison of preoperative and postoperative HHS values had a level of α=0.05, power 100% (1-β=1.00), and impact magnitude (d) of 6.50 (cannulated screw) and 3.69 (DHS).

RESULTS Twenty hips of 6 male and 14 female patients were included in the study. The development of a complication after osteosynthesis occurred at a mean of 9.66 months (range: 3–54 months) and THA was performed at a mean 31.6±51.7 months (range: 5–240 months) after osteosynthesis surgery (Table 1). The mean duration of the follow-up period of the patients included in the study was 59.4±52.4 months (range: 15–178 months). Five patients were classified as type II, 13 patients as type III, and 2 patients as type IV according to the Garden classification system, and 3 patients were considered to be type I, 8 patients type II, and 9 patients type III according to the Pauwel classification system. The mechanism of the fracture was a simple fall for 11 patients, 7 patients had a fall from a height, and 2 patients were involved in traffic accidents. Osteosynthesis applied due to a collum femoris fracture was performed on a traction table using 3 cannulated screws in 13 patients (65%) (Fig. 1a, b) and DHS in 7 patients (35%) after closed reposition. Complications developing after osteosynthesis were nonunion in 4 patients, malunion in 2 patients, symptomatic avascular necrosis in 10 patients, and implant failure in 4 patients (Table 1).

The length of time between the fracture and osteosynthesis as well as between the osteosynthesis and the application of salvage THA was recorded. The presence of >3 mm or >2° change in position of the femoral component observed on X-ray, or the presence of >2° or ≥2 mm change in position of the acetabular component and presence of pain were considered to indicate loosening.[7]

Femoral components used for THA as prosthesis options were inserted into the femur without cement (Fig. 1c). An acetabular component with screw fixation was used in 18 of the patients and a porous-coated acetabular component without screw fixation was used in 2 patients. The diameter of the implants inserted into the acetabulum was between 46 and 54 mm. Anterolateral entry was used in all patients, with a standard lateral approach.

Enoxaparin was administered at a dose of 0.4 cc subcutaneously as prophylaxis for deep-vein thrombosis and the patients were discharged with directions for the use of 300 mg oral acetylsalicylic acid. The use of a cephalosporin antibiotic initiated for prophylaxis before surgery was maintained for 48 hours and then discontinued.

Due to excessive reaming in 1 patient during preparation of a line-to-line presplit of the acetabular component, the medial acetabular wall was breached. It was not possible to press fit the acetabular component or to use only cement. This problem was resolved with an acetabular reconstruction cage and an acetabular liner with cement. Dislocation was seen in 1

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Osteosynthesis- THA time (months)

F.E.

M.O

N.Y

Cannulated screws

Avascular necrosis

240 157

102

Postoperative

fissure

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Cannulated screws

İmplant failure

7 24

Cannulated screws

1 DHS

THA: Total hip arthroplasty; HHS: Haris hip score; F: Female; M: Male; L: Lift; R: Right.

S.Ş 73 F R 2 2

DHS

S.U

R DHS

N.T 61 M L 2 2

Malunion

Implant failure

Avascular necrosis

H.D

B.A 60 F L 3 2 Cannulated screws Nonunion

A.S. 52 F L 3 3 Cannulated screws Nonunion

E.D.

Avascular necrosis

DHS

M.K. 40 F R 3 1

Implant failure

7 26

Cannulated screws

Nonunion Avascular necrosis

DHS

Cannulated screws

DHS

S.S. 78 F L 3 2

Z.U. 55 F R 3 2

H.C.

Avascular necrosis

V.Ç. 52 M L 3 3 Cannulated screws Malunion

F.A.

DHS

Cannulated screws

S.K. 67 M L 3 3

R.İ

178

118

102

dislocation

D.A.

Loosening

No 64

No 28 56 83 No

28 55 89 No

28 59 94 No

28 56 92 No

28 47 83 No

28 46 73 No

28 41 65 No

28 55 92 No

28 41 89 No

84 Femoral 28 47 78 No

THA Complication Femoral Preop Control follow-up head HHS HHS (months)

C.A. 63 F L 4 2 Cannulated screws Nonunıon

Patient Age Sex Side Garden Pauwels Osteosynthesis Osteosynthesis material failure

Table 1. Patient demographic data and clinical and radiological results

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(a)

(b)

(c)

(d)

Figure 1. (a) A 63-year-old female referred for pain in the right hip. (a) Preoperative pelvis anteroposterior (AP) and (b) hip AP X-ray revealing failed osteosynthesis with cannulated screws. (c) Early postoperative X-ray. (d) Control X-ray demonstrating enough union.

patient in the early period and treated with open reduction and femoral component revision. The femoral component was malpositioned and the abductor tension was loose. The position of the femoral component was adjusted with a lateralized component. Debridement was performed and a second surgery was performed for this patient due to a superficial surgical site infection in the early period. Loosening of the arthroplasty was encountered at the 10th year follow-up of the patient. Deep infection was not encountered in any of the patients. Due to the occurrence of a nondisplaced fracture during the insertion of the femoral component in 1 patient during the surgery, osteosynthesis was provided with a surgical cable. Final follow-up radiological evaluations were conducted in all but 2 cases; the patients had died due to diseases not related to the THA surgery (Fig. 1d). Those 2 patients had 84 months and 8 months of radiological follow-up. Revision was performed in 1 patient (5%) after loosening. Radiological loosening and corrosion of polyethylene components was not observed in any of the other patients. The mean HHS assessment performed in the clinical evaluation of the patients before the salvage THA was 54.05±8.22, and the mean value recorded in the last follow-up visit was 86.45±8.73, which demonstrated a statistically significant difference (p<0.0001).

DISCUSSION Ordinarily, the first treatment of choice in a collum femoris fracture is osteosynthesis.[1,8] In a meta-analysis regarding displaced collum femoris fractures, the failure rate of correction within the first 2 years was reported to be 26% to 30%.[9] Parker et al.[10] reported that the failure rate in cases of osteosynthesis was high and secondary surgeries were required. Failure can be treated with the application of salvage THA. [5,11] Some authors suggest performing THA in the first instance due to the failure rate of osteosynthesis, especially in patients over 70 years of age with a displaced collum femoris fracture.[1] McKinley et al.[5] compared the results of THA performed in the early period after a collum femoris fracture and the 290

results of THA performed as salvage treatment, and they reported higher complication rates and a low survival rate in the patients who underwent a salvage procedure after an opere collum femoris fracture. In a comparative study performed by Oztürkmen et al.,[12] the authors found a higher rate of failure in salvage THA cases compared with primary THA cases. The authors reported a higher complication rate with salvage THA after failure of osteosynthesis performed following proximal femur fractures, but the cases with a collum femoris fracture were not evaluated separately.[13,14] Archibeck et al.[15] reported that THA used to treat failure after osteosynthesis for a collum femoris fracture had a successful and acceptable complication rate. Mortazavi et al.[16] found that among THA cases, collum femoris fractures had a more successful course with a lower complication rate compared with intertrochanteric fractures. However, both successful and unsuccessful results have been published in the literature. [5,6] Said et al.[17] reported a study which included eight patients with salvage THA. In this study, six patients had achieved good functional outcome and pain-free gait and the other two patients had unsatisfactory result. Archibeck et al.[15] reported a mean HHS of 82 at the last follow-up in salvage THA cases. The mean HHS was determined to be 86.45±8.73 in the follow-up of the cases included in our study. The clinical success rate in our study was higher than that of similar studies. A complication rate of 15% was determined in the present study. Mortazavi et al.,[16] Archibeck et al.,[15] Mehlhoff et al.,[18] McKinley et al.,[5] and Oztürkmen et al.[12] reported complications related to orthopedics at a rate of 10%, 12%, 15%, 18%, and 60%, respectively. Complications that may develop after salvage THA include early dislocation, periprosthetic fracture, and infection developing during surgery. The rate reported for early dislocation in the literature ranges between 0% and 20%. While McKinley et al.[5] and Oztürkmen et al.[12] reported early dislocation at a rate of 20%, Mortazavi et al.,[16] Lombardi et al.[19] and Mehlhoff et al.[18] reported early dislocation at a rate of 0% with salvage THA performed after collum femoris fracture. In the study performed by Mortazavi et al.,[16] they found that most of the dislocation cases in the literature were cases of Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

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surgery with the posterolateral incision technique and this could be a risk factor for early dislocation. A lateral approach was used in our study, and we observed early dislocation at a rate of 5%, which was less than the rate reported in much of the literature. The rate of infection developing in salvage THA performed after collum femoris fracture is between 1.2% and 12% in the literature.[12,14–16] In our study, no instance of prosthesis infection in the early or late period was encountered. The rate of infection developing after primary salvage THA performed following collum femoris fracture has been reported to be 2.9%.[12] Furthermore, there was no case of periprosthetic fracture impairing the stability of the prosthesis. The subtrochanteric region was passed over sufficiently with the primary prosthesis and cannulated screw and short DHS fixation were used. In 1 patient (5%), nondisplaced fracture developed at the upper level of the screw entrance while a larger size prosthesis measured during surgery with a template was being placed but uneventful improvement was seen after fixation with a cable. Fractures developing during surgery occur generally at the level of implant entry in the lateral cortex in cases of arthroplasty performed after peritrochanteric fracture. Protective cable application is recommended to prevent fractures occurring during surgery.[15] While DeHaan et al.[14] determined a risk for periprosthetic fracture of 9%, the rate has been reported to be 2.5% in the application of salvage THA after a collum femoris fracture. Oztürkmen et al.[12] reported a higher rate of 14.7%, while Archibeck et al.[15] found a rate of 4%. There are not enough data in the literature to adequately define a high complication rate after salvage THA for a failed proximal femoris fracture. Franzén et al.[20] noted greater risk in patients over 70 years of age, but noted that the complication rate was similar to that of primary THA for treatment of a collum femoris fracture. Recently, Tetsunaga et al.[21] presented their research comparing the results of THA after failed pertrochanteric and collum femoris fractures, and they observed that THA after a failed collum femoris fracture had a lower complication rate. Abductor muscle insufficiency, trochanteric malunion, and the lack of restoration of vertical and lateral offset associated with dislocation are potential reasons for complications after salvage hip arthroplasty.[15,18–21] Weaknesses of our study are the retrospective design and small sample size. A different feature of our study from others is that the mean age is >65 years in the literature, while the mean age of the patients in our group was 57 years. While osteosynthesis is the first treatment of choice after a collum femoris fracture, arthroplasty options are current methods of treatment in the event of failure. In our study, Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

we obtained highly successful clinical results after cementless THA performed after collum femoris fractures with a low complication rate. THA performed with a suitable surgical technique is a safe and successful method of treatment after failed osteosynthesis in cases of a collum femoris fracture. Conflict of interest: None declared.

REFERENCES 1. Palm H, Krasheninnikoff M, Holck K, Lemser T, Foss NB, Jacobsen S, et al. A new algorithm for hip fracture surgery. Reoperation rate reduced from 18 % to 12 % in 2,000 consecutive patients followed for 1 year. Acta Orthop 2012;83:26–30. 2. Raaymakers EL. Fractures of the femoral neck: a review and personal statement. Acta Chir Orthop Traumatol Cech 2006;73:45–59. 3. Knobe M, Siebert CH. Hip fractures in the elderly : Osteosynthesis versus joint replacement. [Article in German]. Orthopade 2014;43:314–24. 4. Gjertsen JE, Vinje T, Engesaeter LB, Lie SA, Havelin LI, Furnes O, et al. Internal screw fixation compared with bipolar hemiarthroplasty for treatment of displaced femoral neck fractures in elderly patients. J Bone Joint Surg Am 2010;92:619–28. 5. McKinley JC, Robinson CM. Treatment of displaced intracapsular hip fractures with total hip arthroplasty: comparison of primary arthroplasty with early salvage arthroplasty after failed internal fixation. J Bone Joint Surg Am 2002;84-A:2010–5. 6. Hammad A, Abdel-Aal A, Said HG, Bakr H. Total hip arthroplasty following failure of dynamic hip screw fixation of fractures of the proximal femur. Acta Orthop Belg 2008;74:788–92. 7. Martell JM, Pierson RH 3rd, Jacobs JJ, Rosenberg AG, Maley M, Galante JO. Primary total hip reconstruction with a titanium fiber-coated prosthesis inserted without cement. J Bone Joint Surg Am 1993;75:554–71. 8. Nikolopoulos KE, Papadakis SA, Kateros KT, Themistocleous GS, Vlamis JA, Papagelopoulos PJ, et al. Long-term outcome of patients with avascular necrosis, after internal fixation of femoral neck fractures. Injury 2003;34:525–8. 9. Lu-Yao GL, Keller RB, Littenberg B, Wennberg JE. Outcomes after displaced fractures of the femoral neck. A meta-analysis of one hundred and six published reports. J Bone Joint Surg Am 1994;76:15–25. 10. Parker MJ, Gurusamy K. Internal fixation versus arthroplasty for intracapsular proximal femoral fractures in adults. Cochrane Database Syst Rev 2006;(4):CD001708. 11. Tabsh I, Waddell JP, Morton J. Total hip arthroplasty for complications of proximal femoral fractures. J Orthop Trauma 1997;11:166–9. 12. Oztürkmen Y, Karamehmetoğlu M, Azboy I, Açikgöz I, Caniklioğlu M. Comparison of primary arthroplasty with early salvage arthroplasty after failed internal fixation for displaced femoral neck fractures in elderly patients. [Article in Turkish]. Acta Orthop Traumatol Turc 2006;40:291– 300. 13. Srivastav S, Mittal V, Agarwal S. Total hip arthroplasty following failed fixation of proximal hip fractures. Indian J Orthop 2008;42:279–86. 14. DeHaan AM, Groat T, Priddy M, Ellis TJ, Duwelius PJ, Friess DM, et al. Salvage hip arthroplasty after failed fixation of proximal femur fractures. J Arthroplasty 2013;28:855–9. 15. Archibeck MJ, Carothers JT, Tripuraneni KR, White RE Jr. Total hip arthroplasty after failed internal fixation of proximal femoral fractures. J Arthroplasty 2013;28:168–71. 16. Mortazavi SM, R Greenky M, Bican O, Kane P, Parvizi J, Hozack WJ. Total hip arthroplasty after prior surgical treatment of hip fracture is it

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Akgül et al. Outcomes of salvage total hip arthroplasty after failed osteosynthesis for collum femoris fractures always challenging? J Arthroplasty 2012;27:31–6. 17. Said GZ, Farouk O, El-Sayed A, Said HG. Salvage of failed dynamic hip screw fixation of intertrochanteric fractures. Injury 2006;37:194–202. 18. Mehlhoff T, Landon GC, Tullos HS. Total hip arthroplasty following failed internal fixation of hip fractures. Clin Orthop Relat Res 1991;(269):32–7. 19. Lombardi AV Jr, Skeels MD, Berend KR. Total hip arthroplasty after

failed hip fractures: a challenging act. Orthopedics 2007;30:752–3. 20. Franzén H, Nilsson LT, Strömqvist B, Johnsson R, Herrlin K. Secondary total hip replacement after fractures of the femoral neck. J Bone Joint Surg Br 1990;72:784–7. 21. Tetsunaga T, Fujiwara K, Endo H, Noda T, Tetsunaga T, Sato T, et al. Total hip arthroplasty after failed treatment of proximal femur fracture. Arch Orthop Trauma Surg 2017;137:417–24.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Femur boyun kırıklarında osteosentez sonrası gelişen komplikasyonların tedavisinde total kalça protezi uygulamalarının sonuçları Dr. Turgut Akgül,1 Dr. Fevzi Birişik,2 Dr. Gökhan Polat,1 Dr. Cengiz Şen,1 Dr. Önder İsmet Kılıçoğlu1 1 2

İstanbul Üniversitesi İstanbul Tıp fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, İstanbul İstanbul Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul

AMAÇ: Bu çalışmada osteosentez sonrası komplikasyon gelişmiş veya başarısız olunmuş kollum femoris kırıklarının, kurtarıcı total kalça artroplastisi (TKA) ile tedavisinin sonuçları araştırıldı. GEREÇ VE YÖNTEM: 1988 ile 2012 yılları arası kollum femoris kırığı tedavisinde kapalı repozisyon ve osteosentez sonrası başarısızlık gelişen ve kurtarıcı TKA yapılan 20 hasta (6 erkek, 14 kadın; ortalama yaş: 56.7) çalışmaya alındı. Kollum femoris kırıkları sonrası osteosentez şekli, başarısızlık gelişme süresi ve TKA uygulama süreleri kaydedildi. Hastalara sementsiz femoral ve asetabuler komponent kullanıldı. Komplikasyonlar operasyon esnası ve sonrası olarak belirlendi. Son kontrolde Haris kalça skorlaması ile klinik sonuçlar ve çekilen grafiler ile gevşeme varlığı değerlendirildi. BULGULAR: Hastaların takip süreleri ortalama 59.4 (dağılım, 15–178) ay idi. TKA uygulanan 20 hastanın kollum femoris kırıklarının sınıflaması osteosentez sonrasında komplikasyonlar kaynamama 4 (%25), malunion 2 (%10), avasküler nekroz 9 (%45), implant yetersizliği 4 (%20) idi. Komplikasyonlar gelişmesinde kanüle vida ve DHS arasında istatistiksel anlamlı farklılık bulunmamakta idi (p=0.084). Komplikasyon olarak erken dislokasyon (%5), protez çevresi kırık (%5) ve asetabuler protrüzyon (%5) saptandı. Erken dislokasyon gelişen hastada 10. yılda gevşeme saptanması üzerine revizyon yapıldı. TKA öncesi HHS 54.05 iken son kontrolde 86.45 olarak değerlendirildi ve istatistiksel olarak aralarında anlamlı bir fark saptandı (p<0.0001). TARTIŞMA: Çalışma bulgularımız, kollum femoris kırıklarında başarısız osteosentez sonrası TKA uygun cerrahi teknik ile başarılı ve güvenli bir yöntem olduğunu göstermektedir. Anahtar sözcükler: Femur boyun kırığı; kalça protezi; osteosentez. Ulus Travma Acil Cerrahi Derg 2019;25(3):287-292

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doi: 10.5505/tjtes.2018.55506

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ORIGIN A L A R T IC L E

Finite element analysis of the effect of intramedullary nail compression amount on fracture union in distal tibial diaphyseal fractures Sadullah Turhan, M.D. Department of Orthopedics and Traumatology, University of Health Sciences Antalya Training and Research Hospital, Antalya-Turkey

ABSTRACT BACKGROUND: The objective of this study was to investigate the relationship between the stress values on the fracture surface and union periods seen in cases of different compression amounts used to manage distal tibial diaphyseal fractures treated with intramedullary nailing (IMN). METHODS: Ninety-five patients (mean age: 33.99±10.65 years; male: n=78, female: n=17) with tibial shaft fracture were included in the study. The patients were divided into 3 groups: No compression was used in Group 1 (33 patients), and dynamic compressive fixation was performed with IMN in Group 2 (1 mm, 32 patients) and Group 3 (1.5 mm, 30 patients). A finite element study was performed for Group 2 and Group 3. RESULTS: The average time to achieve radiological union was 16.08±2.02, 13.54±1.52, and 12.56±1.73 weeks in Groups 1, 2, and 3, respectively. Comparatively, the union period in the non-compression group was significantly longer (p<0.001). The functional results were evaluated as excellent in 28 (85%) patients and good-medium in 5 (15%) in Group 1, excellent in 27 (92%) and good-medium in 5 (8%) in Group 2, and excellent in 26 (92%) and good-medium in 4 (8%) in Group 3. CONCLUSION: IMN is a highly effective treatment method for tibial shaft fracture. Keywords: Compression; fracture union; intramedullary nail; nonunion; tibia distal diaphyseal fracture.

INTRODUCTION Distal tibial diaphysis fractures constitute 10% of all tibial fractures.[1] The objectives of surgical treatment are to protect the sagittal and coronal alignments, arrange bone length and rotation, and provide early range of motion of the knee and ankle.[2] Serious soft tissue injuries, malunion, nonunion, and infection frequently accompany these fractures.[3] Intramedullary nailing (IMN) is a widely used treatment method for tibial fractures, and it provides a functional result that is superior to conservative treatments.[4,5] It provides adequate mechanical stability with better fracture alignment.[6] Interlocked nails may be inserted with or without reaming or compression, and there are static, dynamic, and dynamic

compression alternatives. The decision to use reaming in IMD remains controversial.[7] Using active compression on the fracture line accelerates the fracture union process.[8,9] The present study is an assessment of the effect of different compression methods on the fracture union period in INM patients. In addition, the stress values on the fracture surface according to the compression amount applied were examined in a finite element study.

MATERIALS AND METHODS The data of 95 patients who had a tibial shaft fracture (mean age: 33.99±10.65 years; male: n=78, female: n=17) between

Cite this article as: Turhan S. Finite element analysis of the effect of intramedullary nail compression amount on fracture union in distal tibial diaphyseal fractures. Ulus Travma Acil Cerrahi Derg 2019;25:293-297. Address for correspondence: Sadullah Turhan, M.D. Antalya Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, Antalya, Turkey Tel: +90 242 - 249 44 00 E-mail: sturhan@dr.com Ulus Travma Acil Cerrahi Derg 2019;25(3):293-297 DOI: 10.14744/tjtes.2019.86613 Submitted: 11.09.2018 Accepted: 27.03.2019 Online: 15.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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2006 and 2016 were retrospectively examined. In this study, only patients with closed fractures that were classified as 43-A1, 43-A2, and 43-A3 in accordance with the AO classification were included; those with other diseases were excluded. The study patients were divided into 3 groups: Group 1 comprised 33 non-compression patients, Group 2 was made up of 32 patients for whom 1 mm of compression was applied, and 30 patients who had 1.5 mm of compression applied were included in Group 3. In Group 1, static interlocked nailing was used without compression after reaming. In Group 2 and 3, dynamic compression interlocking was performed after reaming and insertion of the intramedullary compression nail. Notably, none of the patients required postoperative splinting or bracing. All of the patients wore an anti-embolism stocking for 4 weeks. Low molecular weight heparin was used for a period of 4 weeks, and 1 g intravenous cefazolin sodium was administered 3 times within a period of 24 hours after the procedure. X-ray images of the patients captured following the surgery and during follow-up were evaluated according to the criteria of the radiographic union score for tibial fractures, and functional results were evaluated in accordance with the Johner–Wrush criteria. A finite element study was performed to examine the 1-mm and 1.5-mm compression applied in Groups 2 and 3, respectively. One-way analysis of variance (ANOVA), Fisher’s exact test, Pearson’s chi-squared test, Mann-Whitney U test, and Student’s t-test were used to statistically evaluate the data. This study was approved by Antalya Training and Research Hospital ethical committee of clinical research approval was obtained for the study. Ethical protocol number of the research is 2018-132 and informed consent was obtained from all participants included in the study.

Statistical Analysis Descriptive statistics were presented as mean±SD, median (min-max), and n (%) values, as appropriate. Fisher’s exact test and Pearson’s chi-squared analysis were performed for categorical variables. Student’s t-test was used for comparison of 2 groups, and one-way ANOVA was used for the comparison of the 3 groups with normal distribution. The Mann-Whitney U-test was used to assess quantitative variables with non-normal distribution. The statistical analysis was performed using IBM SPSS Statistics for Windows, Version 21.0 (IBM Corp., Armonk, NY, USA). A p value <0.05 was considered statistically significant.

Finite Element Analysis Nonlinear analysis was performed using 3-dimensional (3D) finite element stress analysis. A computer equipped with Intel Xeon R CPU (Intel Corp., Santa Clara, CA, USA), 3.30 GHz microprocessor, 500 GB hard disk, 14 GB RAM, and Windows 7 Ultimate Version Service Pack 1 operating system (Microsoft Corp., Redmond, WA, USA), a 3D scanning device with Activity 880 (Smart Optics, Sensortechnik GmbH, Bochum, Germany) optical scanner (Fig. 1), Rhinoceros 4.0 3D modeling software (Robert McNeel & Associates, Seattle, WA. USA) and VRMesh Studio (VirtualGrid Inc., Bellevue City, WA, USA), and ALGOR FEMPRO (ALGOR, Inc., Pittsburgh, PA, USA) analysis programs were used to create a 3D network structure and homogeneous conditions based on 3D solid model and finite elements stress analysis. To perform the analysis, the models were transferred to the ALGOR FEMPRO software in .stl format after they were cre-

Surgical Technique All patients were in the supine position when the fracture line was accessed. The patellar tendon was longitudinally accessed in all cases via a transtendinous approach. Reaming was performed using a superior entry from the proximal tibia following the reduction. A nail of appropriate length and diameter was inserted in the apex position such that the tibial plateau was lower than the level of the anterior side. Distal interlocking was first performed with 2 interlocking screws, followed by the proximal dynamic hole with a single screw in Groups 2 and 3. The distal interlocking was performed using the technique described by Aldemir et al.,[8] but without fluoroscopy. The application of 1-mm and 1.5-mm compression was performed by rotating the screw 1 or 1.5 turns, respectively, enabling the interlocking screw to pass through the dynamic hole and engage with the nail. All of the compression screws were applied in the proximal end. The compression screws were statically locked in Group 1. Finally, the apex screw was inserted and the procedure was completed. 294

Figure 1. Activity 880 (Smart Optics, Sensortechnik GmbH, Bochum, Germany) optical scanner.

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Turhan. Finite element analysis of the effect of IMN compression amount on fracture union in distal tibial diaphyseal fractures

Table 1. Comparison of time to bony union in the study groups

Time to bony union

Mean±SD Non-compression

16.08±2.02 0.001*

1-mm compression

13.54±1.52

1.5-mm compression

12.56±1.73

Two materials were used in the analyses. The first was the cortical bone material, which has the mechanical properties of an elasticity modulus of 20 GPa, a Poisson’s ratio of 0.15, and a density of 1650 kg/m3. The mechanical properties of the titanium screws used were an elasticity modulus of 96 GPa, a Poisson’s ratio of 0.36, and a density of 4620 kg/m3. Positive values in the analysis results indicated tensile stress and negative values indicated compression stress.

RESULTS

*P<0.001.

ated geometrically using the VRMesh software. The .stl format is universally applicable to 3D modeling programs; there is no information loss during transfer between programs. However, it is necessary to identify the bone structure components. The material values (elasticity module and Poisson’s ratio) identifying the physical properties were fed into each structure of the models.

Union was achieved in all of the study patients. The union periods are shown in Table 1. The mean time to radiological union was 16.08±2.02 weeks in Group 1, 13.54±1.52 weeks in Group 2, and 12.56±1.73 weeks in Group 3. The union period for the non-compression group was statistically significantly longer than that of the other 2 groups (p<0.001). No statistically significant difference was found between the 1-mm and 1.5-mm compression groups (Fig. 2 and 3). The functional results were evaluated as excellent in 28 (85%) patients and good-medium in 5 (15%) in Group 1, excellent in 27 (92%) and good-medium in 5 (8%) in Group 2, and excellent in 26 (92%) and good-medium in 4 (8%) in Group 3. Anterior knee pain was observed in only 5 patients. No instance of infection, compartment syndrome, or thromboembolism was observed in any of the patients. The finite element study revealed that the average stress value was

(a)

(b)

Figure 2. (a) Preoperative radiographs of a 38-year-old male patient with right distal diaphyseal tibia fracture extending to the metaphysis resulting from a fall. (b) Radiographs of the patient in the first year of follow-up after intramedullary nailing with 1.0-mm compression.

Figure 4. Stress on the fracture surface when the screw is inserted at 1.0 mm.

(a)

(b)

Figure 3. (a) Preoperative radiographs of a 32-year-old female patient with right distal diaphyseal tibia fracture extending to the metaphysis resulting from a fall. (b) Radiographs of the patient in the first year of follow-up after intramedullary nailing with 1.5-mm compression.

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Figure 5. Stresses on the fracture surface when the screw is inserted at 1.5 mm.

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26.22 MPa in the 1-mm compression group and 45.2 MPa in the 1.5-mm group.

DISCUSSION Intramedullary interlocking compression nails can reduce the length of the fracture union period in patients with tibial fracture.[9] In our study, the union period was much shorter in Groups 2 and 3 (compression) when compared with that of Group 1 (non-compression). No statistically significant difference was found between Groups 2 and 3 in terms of the length of the union period. Therefore, we believe that greater compression is not required in tibial shaft fracture types AO A2, A3, and B2. Högel et al.[10] compared the strength value of compression screws and bone fixation screws used in diaphyseal tibial fractures. They reported a mean postoperative compression load of 1852 N (range: 362–4325 N) that was 980 N (range: 188– 2550 N) 4 weeks later. Högel et al. did not mention stress value on the fracture surface in their study. We performed a finite element study with the hypothesis that the stress value on the fracture surface would be useful. In our study, the pressure distribution in the tibial fracture region was calculated according to the amount of compression applied (1 or 1.5 mm). The axial strength mentioned in Högel et al.’s work and the overloads that resulted from the bending moment that this strength created in the fracture section had an effect on this distribution. In an experimental study conducted by Baki et al.[11] using rabbits, they demonstrated the effects of different compression levels on fracture union. They applied 0.5-mm and 1-mm compression to the fracture surface and subsequently conducted finite element studies. They reported stress values of 34.5 MPa in the 0.5-mm compression group and 88 MPa in the 1-mm compression group. In addition, they found that the union was histologically better and was achieved sooner in the 34.5 MPa group. Our finite element study revealed that the average stress value was 26.22 MPa in the 1-mm compression group and 45.2 MPa in the 1.5-mm compression group (Fig. 4 and 5). The axial load and tensile values were determined when they were subjected to linearly varying deforming powers due to the inclined structure of the tibia (e.g., 26.22 MPa in 1-mm compression and 45.2 MPa in 1.5-mm compression). The tensile value of the fracture in certain anatomical regions represents a nonlinear relationship due to the anatomical curve in the femur (e.g., 34.5 MPa in 0.5-mm compression and 88 MPa in 1-mm compression). An average stress value of 50 MPa was measured with 1-mm compression in humeral shaft fractures.[12] Therefore, the stress values obtained in a finite element study with the same degree of compression applied to the humerus, femur, and tibia varied due to the different anatomical curves and fracture surface 296

fields of the bones. The compression required to create stress values between 34 MPa and 88 MPa were found to be ideal, which was consistent with the results of the experimental study of Baki et al. and with our clinical results. We believe that the MPa parameter showing surface stress tension is more important than mm and Newton parameters indicating compression. While some authors have suggested the use of the backstroke technique, Mückley et al.[13] reported that compression was a superior means of attaining initial stability. The backstroke technique had not been used in any of the patients whose reduction was completed. A number of authors have mentioned anterior knee pain occurring at different ratios in their patients after IMN in tibial shaft fractures.[14,15] We found anterior knee pain in only 5 (7%) patients. All of these were cases in which the nail was at a higher level; the pain findings were independent from the application of compression. Infection was not seen in any of our cases. To the best of our knowledge, this is the first study in humans to examine both the compression and fracture surface stress values in the treatment of tibial shaft fracture. Limitations of this study include the retrospective design and the fact that we were only able to examine tibial distal end fractures. Further study of proximal fractures is required due to the surface difference.

Conclusion The use of interlocking compression nails in AO A2, A3, and B2 tibia distal end fractures substantially shortens the fracture union period. There was no statistically significant difference in terms of the union period between a 1-mm compression group and a 1.5-mm group. We believe the stress value that occurred on the fracture surface is an important loading parameter in compression. Conflict of interest: None declared.

REFERENCES 1. Augat P, Hoegel F, Stephan D, Hoffmann S, Buehren V. Biomechanical effects of angular stable locking in intramedullary nails for the fixation of distal tibia fractures. Proc Inst Mech Eng H 2016;230:1016–23. 2. Moongilpatti Sengodan M, Vaidyanathan S, Karunanandaganapathy S, Subbiah Subramanian S, Rajamani SG. Distal tibial metaphyseal fractures: does blocking screw extend the indication of intramedullary nailing? SRN Orthop 2014;2014:542623. 3. Kline AJ, Gruen GS, Pape HC, Tarkin IS, Irrgang JJ, Wukich DK. Early complications following the operative treatment of pilon fractures with and without diabetes. Foot Ankle Int 2009;30:1042–7. 4. Yasuda T, Obara S, Hayashi J, Arai M, Sato K. Semiextended approach for intramedullary nailing via a patellar eversion technique for tibial-shaft

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Turhan. Finite element analysis of the effect of IMN compression amount on fracture union in distal tibial diaphyseal fractures fractures: Evaluation of the patellofemoral joint. Injury 2017;48:1264–8. 5. Petrisor BA, Bhandari M, Schemitsch E. Tibia and fibulae fractures. In: Bucholz RW, Heckman JD, Court-Brown CM, Tornetta P, editors. Rockwood and Green’s Fractures in Adults. 7th ed. Lippincot, Williams and Wilkins; 2010. p. 1880–2. 6. Mukherjee S, Arambam MS, Waikhom S, Santosha, Masatwar PV, Maske RG. Interlocking Nailing Versus Plating in Tibial Shaft Fractures in Adults: A Comparative Study. J Clin Diagn Res 2017;11:RC08–RC13. 7. Bhandari M, Guyatt G, Tornetta P 3rd, Schemitsch EH, Swiontkowski M, Sanders D, et al; Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures Investigators. Randomized trial of reamed and unreamed intramedullary nailing of tibial shaft fractures. J Bone Joint Surg Am 2008;90:2567–78. 8. Aldemir C, Doğan A, İnci F, Sertkaya Ö, Duygun F. Distal locking techniques without fluoroscopy in intramedullar nailing. Eklem Hastalik Cerrahisi 2014;25:64–9. [Article in Turkish] 9. Karaarslan AA, Acar N, Aycan H, Sesli E. The functional results of tibial shaft fractures treated with intramedullary nail compressed by proximal tube. Strategies Trauma Limb Reconstr 2016;11:25–9.

10. Högel F, Gerber C, Bühren V, Augat P. Reamed intramedullary nailing of diaphyseal tibial fractures: comparison of compression and non-compression nailing. Eur J Trauma Emerg Surg 2013;39:73–7. 11. Baki ME, Aldemir C, Duygun F, Doğan A, Kerimoğlu G. Comparison of non-compression and compression interlocking intramedullary nailing in rabbit femoral shaft osteotomy model. Eklem Hastalik Cerrahisi 2017;28:7–12. 12. Duygun F, Aldemir C. Is locked compressive intramedullary nailing for adult humerus shaft fractures advantageous? Eklem Hastalik Cerrahisi 2017;28:80–6. 13. Mückley T, Diefenbeck M, Sorkin AT, Beimel C, Goebel M, Bühren V. Results of the T2 humeral nailing system with special focus on compression interlocking. Injury 2008;39:299–305. 14. Song SY, Chang HG, Byun JC, Kim TY. Anterior knee pain after tibial intramedullary nailing using a medial paratendinous approach. J Orthop Trauma 2012;26:172–7. 15. Darabos N, Bajs ID, Rutić Z, Darabos A, Poljak D, Dobsa J. Nail position has an influence on anterior knee pain after tibial intramedullary nailing. Coll Antropol 2011;35:873–7.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Tibia distal diafiz kırıklarında intramedüller çivi kompresyon miktarının kırık kaynaması üzerine etkisinin sonlu eleman analizli değerlendirilmesi Dr. Sadullah Turhan Sağlık Bilimleri Üniversitesi Antalya Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, Antalya

AMAÇ: Intramedüller çivi (IMN) uygulanan tibia distal diafiz kırığı olgularında farklı kompresyon miktarlarının kırık yüzeyindeki stres değerleri ve kaynama süreleri arasındaki ilişkiyi araştırmak. GEREÇ VE YÖNTEM: 2006–2016 yılları arasında tibia cisim kırığı olan 95 hasta çalışmaya alındı. AO sınıflamasına göre 43-A1, 43-A2, 43-A3, Gustillo-Anderson sınıflamasına göre kapalı kırık olan hastalar çalışmaya alındı. Yetmiş sekiz hasta erkek, 17 hasta kadın olup ortalama yaş 33.99 (SS± 10.65) idi. Hastalar üç gruba ayrıldı. Grup 1’de (33 hasta) kompresyon yapılmadı. Grup 2’de (32 hasta) ve 3 (30 hasta) IMN ile dinamik kompressif tespit yapıldı. Kompresyon miktarı Grup 2’de 1 mm, Grup 3’de 1.5 mm olarak uygulandı. Hastaların ameliyat sonrası ve takiplerinde çekilen röntgen grafileri Rust kriterlerine göre, fonksiyonel sonuçlar ise Johner-Wrush kriterlerine göre değerlendirildi. Ayrıca Grup 2 ve 3’de uygulanan 1 mm ve 1.5 mm kompresyon ile ilgili sonlu eleman çalışması yapıldı. İstatistiksel olarak tek yönlü Anova, Fisher kesin testi, Pearson ki-kare, Mann-Whitney U-test ve Student t-testleri kullanıldı. BULGULAR: Bütün hastalarda kaynama elde edildi. Radyolojik kaynama Grup 1’de ortalama 16.08 (SS±2.02) hafta, Grup 2’de 13.54 (SS±1.52) hafta ve Grup 3’de 12.56 (SS±1.73) haftada sağlandığı görüldü. Kompresyon uygulanmayan grupta kaynama süresi, kompresyon uygulanan diğer gruplara göre anlamlı düzeyde uzundu (p<0.001). Fonksiyonel sonuçlar Grup 1’de 28 (%85) hasta mükemmel, beş (%15) hasta iyi-orta, Grup 2’de 27 (%92) hasta mükemmel, beş (%8) hasta iyi-orta, Grup 3’de 26 (%92) hasta mükemmel, dört (%8) hasta iyi-orta olarak değerlendirildi. Toplam beş hastada diz önü ağrısı mevcuttu. Hiçbir hastada enfeksiyon görülmedi. TARTIŞMA: Kilitli kompressif çiviler tibia cisim kırıklarında oldukça etkin bir tedavi yöntemidir. Çivi üzerinden uygulanan kompresyon kaynama süresini belirgin şekilde kısaltmaktadır. Anahtar sözcükler: İntramedüller çivi; kırık kaynaması; kompresyon; nonunion; tibia distal uç kırığı. Ulus Travma Acil Cerrahi Derg 2019;25(3):293-297

doi: 10.14744/tjtes.2019.86613

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ORIGIN A L A R T IC L E

23-gauge transconjunctival vitrectomy for posterior segment intraocular foreign bodies Yasemin Özdamar Erol, M.D.,

Kemal Tekin, M.D.,

Pelin Yılmazbaş, M.D.

Department of Ophthalmology, Ulucanlar Eye Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: This study is a report of the outcomes of 23-gauge (G) transconjunctival vitrectomy (TV) performed to treat a posterior segment intraocular foreign body (IOFB). METHODS: The data of 14 eyes of 14 patients who underwent 23-G TV for the removal of a posterior segment IOFB were reviewed in this study. Surgery was initiated with a 23-G system in each case and the posterior segment IOFB was removed through the enlarged sclerotomy site. All of the patients were male. The mean age of the patients was 36.6±11.0 years. RESULTS: The foreign body (FB) was located in the vitreous in 11 eyes and in the retina in 3 eyes. Before the 23-G TV, complicated cataract was detected in 6 eyes, vitreous hemorrhage was detected in 5 eyes, and retinal detachment was detected in 1 eye. The size of the FB ranged from 3 mm to 7 mm; 12 of the FBs were metallic and 2 were glass. Silicone oil was used as a tamponade agent in 5 eyes and gas tamponade (C3F8) was used in 4 eyes. The mean follow-up time was 8.15±2.9 months. At the last examination, of the 14 eyes included in the study, the visual acuity (VA) was 0.1 or better in 10 eyes and less than 0.1 in 4 eyes because 2 eyes had perimacular scar, 1 eye had massive sub-epiretinal membrane and 1 eye had retinal re-detachment. CONCLUSION: 23-G TV is seen as an effective and minimally invasive technique to remove posterior segment IOFBs. Keywords: Intraocular foreign body; retina; transconjunctival vitrectomy; vitreous.

INTRODUCTION Posterior segment intraocular foreign bodies (IOFBs) are one of the most common causes of vision loss. IOFBs may lead to devastating consequences, including toxic effects, chronic inflammation, development of fibrocellular proliferation, detachment of the retina and retinal traction, endophthalmitis, or phthisis bulbi. The main goals of treating posterior segment IOFBs are to remove the FB, retain globe integrity, and provide better anatomic and visual outcomes. Fundamental advances in microsurgical and vitreoretinal techniques have enabled direct visualization and controlled removal of posterior segment IOFBs, resulting in fewer complications and improved postoperative results.[1–3] Recently, sutureless vitrectomy systems have been developed for expanding surgical indications and have been used more frequently in compli-

cated vitreoretinal diseases.[4–7] Sutureless systems can minimize surgically induced trauma to the conjunctiva and sclerotomy sites; therefore, they improve operative efficiency and hasten postoperative recovery. Also, diminished conjunctival scarring may result in higher success rates for future conjunctival-scleral surgical procedures.[8–11] The aim of this study was to reveal the outcomes of 23-gauge (G) transconjunctival vitrectomies (TV) performed for the management of posterior segment IOFBs.

MATERIALS AND METHODS This clinical, retrospective, descriptive study was performed at the retina unit of an Eye Training and Research Hospital from June 2015 to October 2016. The study included 14 eyes

Cite this article as: Özdamar Erol Y, Tekin K, Yılmazbaş P. 23-gauge transconjunctival vitrectomy for posterior segment intraocular foreign bodies. Ulus Travma Acil Cerrahi Derg 2019;25:298-302. Address for correspondence: Yasemin Özdamar Erol, M.D. Ulucanlar Göz Eğitim ve Araştırma Hastanesi, Göz Hastalıkları Kliniği, Ankara, Turkey. Tel: +90 312 - 359 10 20 E-mail: yasemin_oz@yahoo.com Ulus Travma Acil Cerrahi Derg 2019;25(3):298-302 DOI: 10.5505/tjtes.2018.44763 Submitted: 15.03.2017 Accepted: 10.09.2018 Online: 23.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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that underwent 23-G TV for the removal of a posterior segment IOFB. the study protocol was approved by the Ankara Numune Training and Research Hospital ethics committe. All of the patients provided written, informed consent prior to the surgery. In this study, all of the IOFBs were located in the posterior segment of the eye. Pars plana vitrectomy was performed in all cases, and additional surgical approaches were applied in some eyes. Examination details, vitreoretinal surgical techniques, and complications were evaluated. All of the eyes had a complete preoperative ophthalmic examination, including testing of best-corrected visual acuity (VA) with Snellen charts, measurement of intraocular pressure, and biomicroscopic anterior segment and dilated fundus examination. B-scan ultrasonography and/or computed tomography of the orbita were performed in all eyes in which visualization of the posterior segment was not achieved.

Surgical Methods Patients were operated on under retrobulbar lidocaine anesthesia. A sclerotomy was performed with the one-step method using 23-G trocars in the inferotemporal, superotemporal, and superonasal quadrants, and the vitrectomy was carried out using 23-G surgical instruments. After a core vitrectomy, the posterior hyaloid was removed in all of the patients with the aid of triamcinolone acetonide, and the vitreous base was cleaned. To protect the posterior pole, 1 mL to 2 mL perfluorocarbon liquid was injected, and after the location of the IOFB was determined, one of the superior microcannulas was removed. Then this sclerotomy was enlarged with a 20-G microvitreoretinal (MVR) blade to facilitate removal of the IOFB. All of the IOFBs were removed from the enlarged sclerotomy site using IOFB forceps. The infusion pressure was also increased to maintain intraocular pressure and/or the enlarged sclerotomy was partially closed with 6-0 vicryl sutures. No external or internal magnet was used. Cryoapplication, endolaser photocoagulation, or both were applied around the site of impact of the IOFB or the possible retinal damage. Silicone oil (5000 centistoke [cs] or 1000 cs) or gas tamponade (C3F8) was used if needed. The enlarged scleral and conjunctival wounds were closed using vicryl suture (6-0), and the entry site 23-G cannulas were removed from the other sclerotomies. Surgery was completed after no wound leakage occurred at the sclerotomy site. Scleral buckling was not performed in any of the study cases. Combined cataract surgery (phacoemulsification or lens aspiration) with vitrectomy was performed when there was a significant opacity of the lens or if needed for another reason, and then an intraocular lens was inserted into the capsular bag or the posterior chamber. Postoperative follow-up examinations were performed weekly in the first month and monthly in the following months. The silicone oil was removed after a 6-month follow-up period. Visual acuity, intraocular pressure, findings about the anterior segment and the fundus, and complications were recorded for each patient. Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

RESULTS All of the study patients were male. The mean age of the patients was 36.6±11.0 years (range: 18–55 years). The composition of the IOFB was metallic in 12 eyes and glass in 2 eyes. The interval between the time of injury and IOFB removal ranged from 5 to 30 days. The IOFB was found to be in the vitreous in 11 eyes (78.6%) and embedded in the retina in 3 eyes (21.4%). All of the eyes were phakic. Associated ophthalmic findings were cataract formation (6 eyes, 42.9%), vitreous hemorrhage (5 eyes, 35.7%), and retinal detachment (1 eye, 7.14%). One of the superior sclerotomy sites was enlarged to remove the IOFB; at the beginning of the operation, this opening was enlarged through the conjunctiva and sclera together using a 20-G MVR blade. It turned out that passing the vitreoretinal instruments through the widened site was more difficult as a result of conjunctival chemosis. In subsequent operations, after a minimal conjunctival opening was created, the scleral opening was enlarged using a 20-G MVR blade. IOFBs were successfully removed from the enlarged sclerotomy site in all eyes. Endolaser photocoagulation, at a minimum of 3 sequences surrounding the site of impact of the IOFB, was applied to the eyes that had retinal injuries. A silicone oil tamponade (5000 or 1000 cs) was used in 5 eyes, and C3F8 gas tamponade was used in 4 eyes. The size of the FB ranged from 3 mm to 7 mm. In 9 eyes, a pars plana vitrectomy was combined with cataract surgery. Adequate capsular support was observed in 6 eyes and an intraocular lens was implanted. No case of hypotony, endophthalmitis, or unsealed sclerotomy was observed in this study. The silicone oil was removed from the eye after a 6-month follow-up period. The mean follow-up time was 8.15±2.9 months (range: 3 to 15 months). Preoperative VA ranged from light perception to counting fingers in 11 eyes (78.6%) and 0.1 to 0.4 in 3 eyes (21.4%). After the follow-up period, the VA was 0.1 LogMAR and better in 10 eyes (71.4%) and 0.1 or less in 4 eyes (28.6%) due to a perimacular scar in 2 eyes, massive sub-epiretinal membrane in 1 eye, and retinal re-detachment in 1 eye. After silicone oil removal, recurrent retinal detachment was detected in 1 eye. Re-operation with silicone oil was performed and the retina attached during the 3-month followup period. The descriptive features and ocular findings are shown in Table 1.

DISCUSSION Dramatic advances in vitreoretinal surgical instruments and techniques have enabled ophthalmologists to perform sutureless self-sealing sclerotomies for pars plana vitrectomy. Initially, 25-G transconjunctival sutureless vitrectomy (TSV) 299

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Table 1. Demographic features and ocular and surgical findings of the patients who underwent 23-gauge transconjunctival vitrectomy for removal of posterior segment intraocular foreign bodies No Gender Age Preop-intraop findings

Surgical approaches

Follow-up Visual acuity Final retinal (months) findings

1 Male 24

IOFB+VH

PPV+C3F8

2 Male 32

IOFB

PPV

3 Male 46 IOFB+C+RT 4 Male 50

IOFB+RT

PPV+CS+SO

PPV+C3F8

Preop VA

Final VA

CF 20/200 NRD 20/200 20/25 CF

NRD

HM RRD+Reop

20/200 20/50

NRD

5 Male 18

IOFB+C

PPV+CS+IOL

20/30

NRD

6 Male 23

IOFB+C

PPV+CS+IOL

20/20

NRD

20/25

NRD

7 Male 33

IOFB+C

PPV+CS+IOL

8 Male 37

IOFB+VH

PPV+CS+SO

9 Male 40

IOFB+VH

PPV+CS+SO+IOL

20/25

NRD

10 Male 47

IOFB+C

PPV+CS+IOL

20/30

NRD

PPV+CS+SO

MS+NRD

11 Male 55 IOFB+C+VH+RD 12

Male

IOFB+VH

PPV+ CS+IOL+C3F8

Male

IOFB

PPV+ C3F8

Male

IOFB

PPV+ SO

CF MS+NRD

20/200

20/50

NRD

20/30

NRD

C:Cataract; CF: Counting fingers; CS: Cataract surgery; HM: Hand motion; Intraop: Intraoperative; IOFB: Intraocular foreign body; IOL: Intraocular lens; M: Male; MS: Macular scar; NRD: No retinal detachment; PPV: Pars plana vitrectomy; Preop: Preoperative; Reop: Re-operation; RM: Retinal membrane; RT: Retinal tear; RRD: Recurrent retinal detachment; SO: Silicone oil; VA: Visual acuity; VH: Vitreous hemorrhage.

systems became available, and later 23-G systems were described for vitreoretinal surgery.[8,9] While TSV had been performed previously for the management of simple vitreoretinal disease, it has been used recently in more complex surgical cases, such as retinal detachment with proliferative vitreoretinopathy, tractional retinal detachment, proliferative diabetic retinopathy, and removal of retained lens fragments and IOFBs.[4–7] Specifically, smaller surgical incisions have advantages, including not requiring sutures, reduced operation time, faster wound healing, diminished conjunctival scarring, less postoperative inflammation, and more rapid patient recuperation.[8–11] In some cases, combinations of 23-G, 25-G, and 20-G systems have been used to simplify the surgical procedures and take advantage of each system.[4,12] This study focused on revealing the outcomes of 23-G TV for the management of posterior segment IOFBs. The optimal vitreoretinal surgical technique for extraction depends on the size, the composition, and the location of an IOFB.[1–3] Numerous studies have been conducted concerning the removal of posterior segment IOFBs using 20-G conventional vitreoretinal surgical methods and external or internal magnetic extraction.[13–17] Recently, several studies have reported sutureless vitrectomy techniques for the management of posterior segment IOFBs. Kiss and Vavvas[4] performed 25-G TSV for the removal of retained lens fragments and IOFBs. In their study, 25-G TSV was performed on 5 eyes for the removal of a posterior segment IOFB. They reported 300

that an expanded sclerotomy site was used to remove posterior segment IOFBs. Removal of an irregularly shaped or large IOFB from a 23-G sclerotomy site and grasping these IOFBs with 23-G forceps can be quite difficult. In the present study, 1 of the superior sclerotomy sites was enlarged using a 20-G MVR blade, and the IOFB was removed successfully in all cases. Long-acting internal tamponades have been used in eyes with a posterior segment IOFB and secondary complications. They limit retinal detachment and provide direct sealing of chorioretinal injuries.[1,3,4,14,15] In TSV, gas tamponade or silicone oil has been commonly used.[5–8] Kiss and Vavvas[4] reported that 2 of the 5 eyes with an IOFB had retinal detachment, and they performed surgery with silicone oil. They concluded that 25-G TSV was a safe and efficient approach for these cases. In the present study, silicone oil or gas tamponade (C3F8) was used as a long-acting endotamponade in the eyes with possible retinal injuries or tears and retinal detachment. Despite these advantages of TSV, numerous studies have reported some drawbacks, such as hypotony and a possible increased rate of endophthalmitis due to unsutured sclerotomies. The increased rate of endophthalmitis after sutureless vitrectomy has been described in numerous studies. Scott et al.[18] found that endophthalmitis occurred at a rate of 0.84% (1 in every 119 cases) in 25-G TSV and 0.03% (1 in every 3,188 cases) in 20-G TSV. In recent studies, decreasing Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

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rates of postoperative endophthalmitis have been reported after TSV. Parolini et al.[19] reported that the incidence of endophthalmitis was 0.03% in the 20-G group (3078 eyes), but no endophthalmitis cases were reported in the 23-G group (943 eyes). The development of postoperative hypotony has been reported in numerous studies. Hypotony is usually seen in the early postoperative period and is generally self-limiting, though it occasionally persists and requires an additional surgical method or placement of a suture.[10,20,21] In the current study, no postoperative hypotony or endophthalmitis was noted. In this study, favorable results were obtained in the management of posterior segment IOFBs with 23-G TV. A 23-G sclerotomy was preferred to reduce surgically induced trauma to the sclerotomy site and hasten postoperative recovery in suitable eyes. It can be suggested that 23-G vitreoretinal surgery is an effective procedure in suitable eyes for the management of posterior segment IOFBs and associated complications. The small study sample of the present study is a limitation. In conclusion, advanced vitreoretinal surgical techniques can save traumatized eyes with posterior segment IOFBs. TV reduces the surgical trauma and hastens postoperative recovery. Thus, 23-G TV is a safe and effective means of performing vitreoretinal surgery and can be effectively used to manage most cases with posterior segment IOFBs.

Disclosure The authors report no conflicts of interest and have no proprietary interest in any of the materials mentioned in this article. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of interest: None declared.

REFERENCES 1. McCabe CM, Mieler WF, Postel EA. Surgical Management of Intraocular Foreign Bodies. In: Alfaro III DV, Liggett PE, editor. Vitreoretinal Surgery of the Injured Eye. Philadelphia: Lippincott-Raven Publishers; 1999. p. 257–71. 2. Khani SC, Mukai S. Posterior segment intraocular foreign bodies. Int Ophthalmol Clin 1995;35:151–61. 3. Charles S, Katz A, Wood B. Vitreous Microsurgery. 3rd ed. Philadelphia: Lippincott Williams and Wilkins; 2002. p. 195–209.

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4. Kiss S, Vavvas D. 25-gauge transconjunctival sutureless pars plana vitrectomy for the removal of retained lens fragments and intraocular foreign bodies. Retina 2008;28:1346–51. 5. Oliveira LB, Reis PA. Silicone oil tamponade in 23-gauge transconjunctival sutureless vitrectomy. Retina 2007;27:1054–8. 6. Erakgun T, Egrilmez S. Surgical outcomes of transconjunctival sutureless 23-gauge vitrectomy with silicone oil injection. Indian J Ophthalmol 2009;57:105–9. 7. Shah CP, Ho AC, Regillo CD, Fineman MS, Vander JF, Brown GC. Short-term outcomes of 25-gauge vitrectomy with silicone oil for repair of complicated retinal detachment. Retina 2008;28:723–8. 8. Eckardt C. Transconjunctival sutureless 23-gauge vitrectomy. Retina 2005;25:208–11. 9. Fujii GY, De Juan E Jr, Humayun MS, Chang TS, Pieramici DJ, Barnes A, et al. Initial experience using the transconjunctival sutureless vitrectomy system for vitreoretinal surgery. Ophthalmology 2002;109:1814– 20. 10. Chen E. 25-Gauge transconjunctival sutureless vitrectomy. Curr Opin Ophthalmol 2007;18:188–93. 11. Spirn MJ. Comparison of 25, 23 and 20-gauge vitrectomy. Curr Opin Ophthalmol 2009;20:195–9. 12. Hubschman JP, Gonzales CR, Bourla DH, Gupta A, Schwartz SD. Combined 25- and 23-gauge surgery: a new sutureless vitrectomy technique. Ophthalmic Surg Lasers Imaging 2007;38:345–8. 13. Soheilian M, Feghi M, Yazdani S, Anisian A, Ahmadieh H, Dehghan MH, et al. Surgical management of non-metallic and non-magnetic metallic intraocular foreign bodies. Ophthalmic Surg Lasers Imaging 2005;36:189–96. 14. Wickham L, Xing W, Bunce C, Sullivan P. Outcomes of surgery for posterior segment intraocular foreign bodies--a retrospective review of 17 years of clinical experience. Graefes Arch Clin Exp Ophthalmol 2006;244:1620–6. 15. Demircan N, Soylu M, Yagmur M, Akkaya H, Ozcan AA, Varinli I. Pars plana vitrectomy in ocular injury with intraocular foreign body. J Trauma 2005;59:1216–8. 16. Coleman DJ, Lucas BC, Rondeau MJ, Chang S. Management of intraocular foreign bodies. Ophthalmology 1987;94:1647–53. 17. De Souza S, Howcroft MJ. Management of posterior segment intraocular foreign bodies: 14 years’ experience. Can J Ophthalmol 1999;34:23–9. 18. Scott IU, Flynn HW Jr, Dev S, Shaikh S, Mittra RA, Arevalo JF, et al. Endophthalmitis after 25-gauge and 20-gauge pars plana vitrectomy: incidence and outcomes. Retina 2008;28:138–42. 19. Parolini B, Romanelli F, Prigione G, Pertile G. Incidence of endophthalmitis in a large series of 23-gauge and 20-gauge transconjunctival pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol 2009;247:895–8. 20. Woo SJ, Park KH, Hwang JM, Kim JH, Yu YS, Chung H. Risk factors associated with sclerotomy leakage and postoperative hypotony after 23-gauge transconjunctival sutureless vitrectomy. Retina 2009;29:456–63. 21. Batman C, Ozdamar Y, Aslan O, Sonmez K, Mutevelli S, Zilelioglu G. Tissue glue in sutureless vitreoretinal surgery for the treatment of wound leakage. Ophthalmic Surg Lasers Imaging 2008;39:100–6.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Göz içi arka segment yabancı cisimlerinin yönetiminde 23-gauge transkonjonktival vitrektomi Dr. Yasemin Özdamar Erol, Dr. Kemal Tekin, Dr. Pelin Yılmazbaş Ulucanlar Göz Eğitim ve Araştırma Hastanesi, Göz Hastalıkları Kliniği, Ankara

AMAÇ: Göz içi arka segment yabancı cisimlerinin (GİASYC) yönetiminde 23-gauge (G) transkonjonktival vitrektomi (TV) sonuçlarının bildirilmesi amaçlanmıştır. GEREÇ VE YÖNTEM: Bu çalışmada GİASYC nedeniyle 23-G TV uygulanan 14 hastanın 14 gözü incelendi. Tüm olgularda cerrahiye 23-G sistem kullanılarak başlandı ve GİASYC’ler genişletilmiş sklerotomilerden çıkartıldı. Çalışmadaki tüm olgular erkek olup, ortalama yaş 36.6±11.0 yıldı. BULGULAR: Yabancı cisim 11 olguda vitreus içerisindeyken, üç olguda retina içindeydi. 23-G TV cerrahisi öncesinde, altı hastada komplike katarakt, beş hastada vitreus içi kanama ve bir olguda retina dekolmanı tespit edildi. On ikisi metalik ve ikisi cam tipinde olan yabancı cisimlerin boyutları 3 mm ile 7 mm arasında değişmekteydi. Cerrahi tamponat olarak, beş olguda silikon yağı kullanılırken dört olguda gaz tamponat (C3F8) kullanıldı. Cerrahi sonrası ortalama takip süresi 8.15±2.9 aydı. Son muayenede, çalışmaya dahil edilen 14 gözün 10’unda görme keskinliği (GK) 0.1 veya üzerindeyken, dört gözde 0.1’in altındaydı ki bunlardan ikisinde perimaküler skar, birinde yoğun sub-epiretinal membran ve birinde nüks retina dekolmanı mevcuttu. TARTIŞMA: Göz içi arka segment yabancı cisimlerinin çıkarılmasında 23-G TV etkin ve minimal invaziv bir yöntem olarak görünmektedir. Anahtar sözcükler: Göz içi yabancı cisim; retina; transkonjonktival vitrektomi; vitreus. Ulus Travma Acil Cerrahi Derg 2019;25(3):298-302

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CA S E R EP O RT

Prehospital emergency thoracotomy performed by helicopter emergency medical service team: A case report Tomasz Darocha, M.D., PhD,1 Sylweriusz Kosiński, M.D., PhD,2 Wojciech Serednicki, M.D., PhD,3 Tomasz Derkowski, M.D.,4 Paweł Podsiadło, M.D., PhD,4 Jan Szpor, M.D.,3 Tomasz Sanak, EMT-P, PhD,5 Robert Gałązkowski, Ass. Prof.6 1

Department of Anesthesiology and Intensive Care, Medical University of Silesia, Katowice-Poland

Department of Anesthesiology and Intensive Care, Pulmonary Hospital, Zakopane-Poland

Department of Anesthesiology and Intensive Care, Trauma Center, University Hospital, Krakow-Poland

Polish Medical Air Rescue, Warsaw-Poland

Department of Disaster Medicine and Emergency Care, Jagiellonian University Medical College, Krakow-Poland

Department of Emergency Medical Services, Medical University of Warsaw, Warsaw-Poland

ABSTRACT Emergency thoracotomy can be a life-saving procedure in critically injured patients who present with chest injuries. Currently, the indications for an on-the-scene thoracotomy are penetrating trauma of the chest or upper abdomen with cardiac arrest that has occurred in the presence of an emergency team or within 10 minutes prior to their arrival. The indications for an emergency thoracotomy in blunt chest trauma are less clearly defined. In the present case, a helicopter emergency medical service (HEMS) team performed an emergency thoracotomy at the scene.To the best of our knowledge, it is the first description of such a procedure in Poland. A 41-yearold male was crushed in a tractor accident.Though all available measures were taken, a sudden cardiac arrest occurred.The HEMS team performed an emergency thoracotomy at the scene as an integral part of prehospital cardiopulmonary arrest management.The patient survived, and was later discharged from the hospital in good physical condition. No neurological deficit was identified (cerebral performance category 1). The patient returned to his previous activities with no complications or deficits. The presence of a fully trained crew allows for the performance of a potentially critical on-the-scene emergency thoracotomy. In a well-selected group of patients with blunt thoracic injury, a prehospital emergency thoracotomy may be a significant and life-saving procedure. Keywords: Emergency treatment; prehospital critical care; thoracotomy.

INTRODUCTION Helicopter emergency medical service (HEMS) has 2 important assets: it quickly delivers highly qualified medical aid to the site, and has the advantage of reducing transport time to the destination facility. Due to a large catchment area and precisely defined dispatch criteria, HEMS crews are more likely to be involved with

critical trauma patients. In addition, they are more capable of making decisions under the pressure of time, as well as performing high-risk, invasive medical procedures on site. One of these rarely performed, life-saving procedures is prehospital emergency thoracotomy (PET). Only a few air ambulance services in the world have introduced a systematic procedure regarding PET.[1,2] The indications for the procedure are penetrating trauma of the chest or upper abdomen with circulatory arrest that has occurred in the presence of

Cite this article as: Darocha T, Kosiński S, Serednicki W, Derkowski T, Podsiadło P, Szpor J, et al. Prehospital emergency thoracotomy performed by helicopter emergency medical service team: A case report. Ulus Travma Acil Cerrahi Derg 2019;25:303-306. Address for correspondence: Tomasz Sanak, EMT-P, PhD. Kopernika 19 31-501 Krakow, Poland. Tel: +48 504 445 152 E-mail: sanaktomek@gmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):303-306 DOI: 10.5505/tjtes.2018.50284 Submitted: 30.05.2018 Accepted: 23.10.2018 Online: 17.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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emergency team or up to 10 minutes before their arrival. [3,4] An emergency thoracotomy in cases of blunt trauma may be associated with higher mortality, as the indications for its performance are less clearly defined.[1,2,5] Presently described is the case of a patient with a crush injury to the chest in which the HEMS team performed an emergency thoracotomy at the scene. To the best of our knowledge, it is the first description of such a procedure in Poland.

CASE REPORT A 41-year-old male was crushed in a tractor accident. As the local air ambulance helicopter was involved with another mission, the dispatch center sent the nearest paramedic-staffed ambulance, which arrived on site after about 30 minutes. Following extrication and initial management, the patient was moved to a temporary landing site at a local stadium. Upon the arrival of the HEMS team, approximately 80 minutes after the accident (08:11 pm), the patient was positioned in the left lateral recumbent position, clearly suffering, breathing spontaneously, and required supplementary oxygen therapy (15 l/ minute) through a face mask. During the initial examination by a HEMS doctor, the patient was conscious (Glasgow Coma Scale 12), and was found to be under the influence of alcohol. The patient was markedly dyspneic with a respiratory rate of about 30/minute and an oxygen saturation (SpO2) level of 81%. There was bleeding from the mouth as a result of bilateral open mandible fracture. Subcutaneous emphysema developed and progressed rapidly on the face and the trunk, while chest palpation revealed bilateral instability of the chest wall with multiple ribs fractures. The abdominal wall was pain-free on palpation. The outline of the extremities was normal and the pelvis was stable. No other external bleeding was observed, both jugular veins were distended, the heart rate (HR) was 135/minute, and the noninvasive blood pressure (NIBP) was 109/40 mmHg. Once intravenous (IV) access was obtained (17G), 25 mg of IV ketamine was administered, followed by 500 mL of crystalloids. The patient was rotated to a supine position, and 2 intravenous cannulas were placed into both thoracic cavities in the second intercostal space: an angiocath 14G × 83 mm in the midclavicular line on the right side, due to subcutaneous emphysema, and a standard 14G on the left. Air flow was obtained from both cannulas under pressure. Due to a quickly deteriorating state of consciousness, worsening subcutaneous emphysema, and aggravating respiratory failure despite pleural decompression, the patient was intubated with a 9.0-mm tube to a depth of 22 cm. The initial end-tidal carbon dioxide (EtCO2) of 30 mmHg decreased rapidly in line with the deterioration of cardio-respiratory function. Pulseless electrical activity (PEA) was observed at 08:23 pm and manual chest compressions were started. A chest drain (28F) was inserted into the left pleural cavity with continued cardio-pulmonary resuscitation followed by 100 mL of bloody discharge. As the 304

HEMS team was equipped with only a single thoracic drainage set, a 6.0-mm cuffed endotracheal tube was inserted through the single incision and manual tissue dilation into the right pleural cavity was initiated. Owing to the suspicion of cardiac tamponade (persisting PEA with progressive deformation of QRS complexes, significant distention of jugular veins), a substernal incision was attempted. Due to the patient’s marked obesity, as well as the subcutaneous emphysema, the attempt to reach the pericardiac sac failed. In this situation, considering the ineffectiveness of the chest compressions (multiple rib fractures with chest wall instability, low EtCO2 values, and the widening of QRS complexes), the team decided to perform an emergency thoracotomy. The incision of the left 5th intercostal space, used to introduce the drain, was widened to a length of about 20 cm. After manual retraction of the ribs and ruling out cardiac tamponade, the treating physician began direct compressions of the heart. After 4 minutes, ventricular fibrillation (VF) was observed and an external biphasic defibrillation with a 200 J of energy was performed. After another minute of cardiac compressions, the return of spontaneous circulation (ROSC) was seen, with a palpable carotid artery pulse. The total time of circulatory arrest was about 10 minutes. The HR was 130/minute, NIBP: 113/82 mmHg (mean 90), SpO2: 90%, and EtCO2: 28 mmHg after ROSC. All tubes and cannulas, as well as the thoracotomy itself were fixed with sterile dressings, and the patient was covered with thermo-insulating material. Due to emerging hypotension, a continuous infusion of norepinephrine was initiated at a dose of 0.25 µg/kg/minute. The transport to the trauma center in Cracow took 34 minutes. The parameters on admission were HR: 130/minute, NIBP: 78/50 mmHg, SpO2: 97%, and a slow but pronounced pupillary reaction to light. After performing an imaging examination and laboratory tests, both the thoracotomy and chest drainage were managed surgically. A chest computed tomography scan revealed bilateral pneumothorax and hydrothorax, pneumomediastinum, subcutaneous emphysema, massive contusion of both lungs with numerous sites of tissue tearing, and multi-

Figure 1. A chest computed tomography scan of the injuries.

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level, bilateral fractures of the ribs (Fig. 1). The patient was extubated on the 17th day. Chest tubes were removed on the 22nd day. No neurological deficits were identified (cerebral performance category 1). On the 31st day, the patient was discharged from the intensive care unit for further treatment in the rehabilitation ward. Having completed the rehabilitation program, the patient returned home free of any neurological deficits and returned to his previous activities. At 1-year follow-up, his general condition was in line with the state before the accident.

DISCUSSION Although the first PET was probably performed in 1902,[6,7] the first reported case was published in 1994.[8] Both cases occurred in the United States, and both patients survived and recovered fully. However, it was in other countries, such as Great Britain, Japan, Australia, Holland, Austria, and Spain, where PET became recognized as part of the algorithm used for severe trauma patients.[2,4,9–11] In recent years, there has been an increase in the number of case reports and case series of patients for whom PET was performed, with both penetrating and blunt injuries.[1,2,11–15] The presented case is probably the first example of an effective prehospital emergency thoracotomy performed on-scene in Poland. Emergency thoracotomy performed in a hospital setting by qualified personnel is a commonly recognized procedure, which greatly increases the survival rate in patients after a major penetrating trauma with simultaneous or immediate cardiac arrest.[16] There is still, however, a lot of controversy around both the ethical as well as practical and procedural issues concerning conditions, indications, and the timing and selection of candidates for this procedure. In particular, there are concerns regarding the indications to perform PET in patients with blunt trauma. Conventional resuscitation procedures have proven to be less effective in patients with cardiac arrest in trauma.[17–19] A recently published comparative analysis of groups of patients subjected to either external chest compressions or direct heart compressions after blunt injury revealed that both the 24-hour and definitive (on discharge) survival rate was lower in the PET group. An attempt to identify subgroups of patients in which an emergency thoracotomy was performed in an emergency unit that would increase chances of survival was unsuccessful. However, this analysis did not take into account a range of important factors, such as time intervals between emergency actions or the precise mechanism of injury.[19] The survival rate of patients after PET was performed in the emergency department due to blunt injury to the chest has been reported to be 1.4% to 12.9%,[20,21] compared with a rate of 8.8% to 41.6% of those with penetrating injuries. [20,21] The interesting fact is that an analysis of HEMS data in Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

London (where the PET procedure was introduced in 1993) revealed that of 27 patients with blunt injuries who had PET performed on site, 2 (7.4%) survived, including 1 presenting no signs of life on the team’s arrival.[1] The explanation for these surprisingly good treatment results, may be the active approach, decision time, and efficiency of the medical team. Indeed, the importance of the time factor has been confirmed by Matsumoto et al.[2] In that group of 95 patients with blunt injuries treated by PET, the probability of survival was significantly higher in the subgroup in which the PET had been performed by doctors at the scene compared with PET performed in the emergency department. Furthermore, the study carried out by Athanasiou et al.[1] suggests that patients with signs of life on arrival represents the target group most likely to benefit from PET. The teams most experienced in performing PET are currently HEMS teams.[2,15] The knowledge, equipment, and high skill level of HEMS personnel, combined with their professional flexibility and task organization make them especially predisposed to act in a “stay and play” manner. The safe and effective performance of PET requires a high degree of surgical training. Thus, the suggestion of introducing such a procedure to the HEMS in Norway was criticized by the Norwegian Surgical Association.[5] However, considering other invasive procedures performed on site (such as emergency cricothyrotomy and thoracostomy), it is not simply the extent of tissue damage that determines the ethical issue of one or another procedure in a situation when other techniques fail.[5] Nonetheless, it is beyond doubt that the degree of complexity of PET requires appropriate preparation of the whole team based on merit. This can only be achieved with both regular theoretical and practical training. We hope that the case presented above will stimulate discussion concerning PET, and will induce further discussion regarding introducing nationwide services and the possible training of medical personnel in performing this life-saving procedure. Conflict of interest: None declared.

REFERENCES 1. Athanasiou T, Krasopoulos G, Nambiar P, Coats T, Petrou M, Magee P, et al. Emergency thoracotomy in the pre-hospital setting: a procedure requiring clarification. Eur J Cardiothorac Surg 2004;26:377–86. 2. Matsumoto H, Mashiko K, Hara Y, Kutsukata N, Sakamoto Y, Takei K, et al. Role of resuscitative emergency field thoracotomy in the Japanese helicopter emergency medical service system. Resuscitation 2009;80:1270–4. 3. Coats TJ, Keogh S, Clark H, Neal M. Prehospital resuscitative thoracotomy for cardiac arrest after penetrating trauma: rationale and case series. J Trauma 2001;50:670–3. 4. Lockey DJ, Lyon RM, Davies GE. Development of a simple algorithm to guide the effective management of traumatic cardiac arrest. Resuscitation 2013;84:738–42.

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Darocha et al. Prehospital emergency thoracotomy performed by helicopter emergency medical service team 5. Ottestad W, Bredmose PB, Berve PO, Stave H, Farstad G, Wik L, et al. Prehospital thoracotomy for traumatic cardiac arrest. Tidsskr Nor Laegeforen 2016;136:1964–5. [Article in English, Norwegian] 6. Stephenson LW, Rodengen JL. State of the Heart: The Practical Guide to Your Heart and Heart Surgery. Ft. Lauderdale, FL: Write Stuff Enterprises; 1999. p. 18. 7. http://trauma.org/index.php/main/article/361/ website 16.07.2017 8. Wall MJ Jr, Pepe PE, Mattox KL. Successful roadside resuscitative thoracotomy: case report and literature review. J Trauma 1994;36:131–4. 9. Sherren PB, Reid C, Habig K, Burns BJ. Algorithm for the resuscitation of traumatic cardiac arrest patients in a physician-staffed helicopter emergency medical service. Crit Care 2013;17:308. 10. Chalkias A, Xanthos T. Should prehospital resuscitative thoracotomy be incorporated in advanced life support after traumatic cardiac arrest? Eur J Trauma Emerg Surg 2014;40:395–7. 11. Van Vledder MG, Van Waes OJF, Kooij FO, Peters JH, Van Lieshout EMM, Verhofstad MHJ. Out of hospital thoracotomy for cardiac arrest after penetrating thoracictrauma. Injury 2017;48:1865–9. 12. Keogh SP, Wilson AW. Survival following pre-hospital arrest with onscene thoracotomy for a stabbed heart. Injury 1996;27:525–7. 13. Silfvast T. Prehospital thoracotomy for cardiac arrest due to perforating chest wounds: case reports of two Patients. Prehosp Disaster Med 1997;12:S21. 14. Corral E, Silva J, Suárez RM, Nuñez J, Cuesta C. A successful emergency

thoracotomy performed in the field. Resuscitation 2007;75:530–3. 15. Davies GE, Lockey DJ. Thirteen survivors of prehospital thoracotomy for penetrating trauma: a prehospital physician-performed resuscitation procedure that can yield good results. J Trauma 2011;70:E75–8. 16. Working Group, Ad Hoc Subcommittee on Outcomes, American College of Surgeons. Committee on Trauma. Practice management guidelines for emergency department thoracotomy. Working Group, Ad Hoc Subcommittee on Outcomes, American College of Surgeons-Committee on Trauma. J Am Coll Surg 2001;193:303–9. 17. Lockey D, Crewdson K, Davies G. Traumatic cardiac arrest: who are the survivors? Ann Emerg Med 2006;48:240–4. 18. Luna GK, Pavlin EG, Kirkman T, Copass MK, Rice CL. Hemodynamic effects of external cardiac massage in trauma shock. J Trauma 1989;29:1430–3. 19. Endo A, Shiraishi A, Otomo Y, Tomita M, Matsui H, Murata K. Openchest versus closed-chest cardiopulmonary resuscitation in blunttrauma: analysis of a nationwide trauma registry. Crit Care 2017;21:169. 20. Rhee PM, Acosta J, Bridgeman A, Wang D, Jordan M, Rich N. Survival after emergency department thoracotomy: review of published data from the past 25 years. J Am Coll Surg 2000;190:288–98. 21. Narvestad JK, Meskinfamfard M, Søreide K. Emergency resuscitative thoracotomy performed in European civilian trauma patients with blunt or penetrating injuries: a systematic review. Eur J Trauma Emerg Surg 2016;42:677–85.

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Helikopter acil tıbbi servis ekibi tarafından yapılan hastane öncesi acil torakotomi: Bir olgu sunumu Dr. Tomasz Darocha,1 Dr. Sylweriusz Kosiński,2 Dr. Wojciech Serednicki,3 Dr. Tomasz Derkowski,4 Dr. Paweł Podsiadło,4 Dr. Jan Szpor,3 Dr. Tomasz Sanak,5 Dr. Robert Gałązkowski6 Anestezi ve Yoğun Bakım Anabilim Dalı, Silezya Tıp Üniversitesi, Katowice-Polonya Akciğer Hastanesi, Anesteziyoloji ve Yoğun Bakım Bölümü, Zakopane-Polonya 3 Anesteziyoloji ve Yoğun Bakımın Bölümü, Travma Merkezi, Üniversite Hastanesi, Krakow-Polonya 4 Polis Medikal Hava Kurtarma, Varşova-Polonya 5 Afet Tıbbı ve Acil Bakım Anabilim Dalı, Jagiellonian Üniversitesi Tıp Fakültesi, Krakow-Polonya 6 Acil Tıbbi Servis, Varşova Tıp Üniversitesi, Varşova-Polonya 1 2

Göğüs yaralanmaları ile başvuran kritik hastalarda acil torakotomi hayat kurtarıcı bir işlem olabilir. Halen, olay yerinde uygulanan torakotomi için endikasyonlar acil ekip varlığında veya gelmeden 10 dakika önce meydana gelen kalp durması nedeniyle göğsün veya karnın üst bölümünün penetran yaralanmasıdır. Künt göğüs travmasında acil torakotomi için endikasyonlar daha düşük netlikte tanımlanmıştır. Bu olguda bir helikopter acil tıbbi servis ekibi olay yerinde acil torakotomi gerçekleştirmiştir. Bildiğimiz kadarıyla, Polonya’da böyle bir müdahale ilk kez tarif edilmektedir. Kırk bir yaşındaki bir erkek, kazaen traktör altında kalarak ezilmiştir. Tüm mevcut önlemler alınmış olmasına rağmen, yaralının kalbi aniden durmuş. Helikopter acil müdahale ekibi hastane öncesi kardiyopulmoner arest tedavisinin ayrılmaz bir bileşeni olarak olay yerinde acilen torakotomi gerçekleştirmiştir. Hasta hayatta kalmış ve daha sonra hastaneden iyi bir fiziksel durumda taburcu edilmiştir. Serebral performans kategorisi 1’e göre nörolojik defisit saptanmamıştır. Hasta önceki aktivitelerine herhangi bir komplikasyon veya defisit olmaksızın geri dönmüştür. Tamamen eğitimli bir ekibin varlığı, olay yerinde potansiyel olarak kritik acil durumda torakotomi yapılmasına olanak sağlar. Künt toraks yaralanması olan iyi seçilmiş bir hasta grubunda, hastane öncesi acil torakotomi önemli ve hayat kurtarıcı bir işlem olabilir. Anahtar sözcükler: Acil tedavi; hastane öncesi kritik bakım; torakotomi. Ulus Travma Acil Cerrahi Derg 2019;25(3):303-306

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CA S E R EP O RT

Strangulated inguinal hernia accompanied by paratesticular leiomyosarcoma Birol Ağca, M.D.,1 Yalın İşcan, M.D.,1 Timuçin Aydın, M.D.,1 Aytaç Şahin, M.D.,2 Kemal Memişoğlu, M.D.1 Department of General Surgery, University of Health Sciences, İstanbul Fatih Sultan Mehmet Training and Research Hospital, İstanbul-Turkey

1 2

Department of Urology, University of Health Sciences, İstanbul Fatih Sultan Mehmet Training and Research Hospital, İstanbul-Turkey

ABSTRACT Sarcomas that arise from the spermatic cord constitute 2.1% of soft tissue sarcomas and are observed at a rate of 1% to 2% in the genitourinary system. A 74-year-old patient presented at the emergency department with complaints of groin pain and swelling persisting for 3 days. On physical examination, a firm mass that was approximately 5x5 cm in size and could not be reduced was observed at the right inguinal area as well as a right inguinal hernia. Computed tomography revealed a large hernia sac in the right inguinal area and a mass that was 77x55 mm in size within the hernial sac. A radical orchiectomy and hernia repair were performed. A diagnosis of leiomyosarcoma was made based on the pathological evaluation of the mass. At the 7-month postoperative follow-up, no local relapse or distant metastasis was found. To conclude, although paratesticular leiomyosarcoma is rare, it should be kept in mind as one of the possible diagnoses for older patients presenting with an inguinal mass. Keywords: Inguinal hernia; leiomyosarcoma; paratesticular tumor.

INTRODUCTION

CASE REPORT

Sarcomas constitute less than 1% of all malignant tumors, and less than 3% to 5% of these arise from the genitourinary system, particularly from the paratesticular region. The paratesticular region consists of the spermatic cord, testicular tunics, epididymis, and the vestigial remnants. Tumors in this region contain multiple structures that are of embryologically different origins and show different characteristics, and while 70% of them are benign, 30% of these tumors are malignant in nature. Paratesticular leiomyosarcomas account for 1% to 2% of the tumors that stem from the genitourinary system.[1] Tumors that arise from the spermatic cord structure may be observed with inguinal hernia and this condition is often detected during surgery.[2]

A 74-year-old patient presented at the emergency department with the complaints of groin pain that had been persisting for 3 months, and a solid swelling in the groin present for the last 3 days. There was no urinary system symptom or history of trauma, but the physical examination revealed a mass extending from the right inguinal canal to the scrotum and a right indirect hernia. The lump, which was thought to be strangulated, could not be reduced. Routine biochemical and hematological test results were within the normal range. Lower abdominal and pelvic computed tomography (CT) scans with contrast were performed and revealed a large right-side inguinal hernia that did not contain bowel loops and a structure that occupied 77x50 mm of space within the sac (Fig. 1a). Concurrent ultrasonography (US) revealed a mass located at the mid inguinal canal that was hypoechoic with lobulated borders, approximately 60x65 mm in size, along with a 2 cm opening observed

A case of strangulated indirect inguinal hernia and a mass originating from the spermatic cord that required radical orchiectomy is presented.

Cite this article as: Ağca B, İşcan Y, Aydın T, Şahin A, Memişoğlu K. Strangulated inguinal hernia accompanied by paratesticular leiomyosarcoma. Ulus Travma Acil Cerrahi Derg 2019;25:307-310. Address for correspondence: Birol Ağca, M.D. İstanbul Fatih Sultan Mehmet Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey. Tel: +90 216 - 578 30 00 E-mail: birolagca@yahoo.com Ulus Travma Acil Cerrahi Derg 2019;25(3):307-310 DOI: 10.5505/tjtes.2018.68709 Submitted: 11.01.2018 Accepted: 24.10.2018 Online: 25.10.2018 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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(a)

(b)

Figure 1. (a) Hernia in right inguinal region and a mass of 77x50 mm within the hernia sac. (b) Sarcoma located in right spermatic cord and enlarged testis.

in the transverse fascia. It was found that intestinal loops had herniated through this opening. Surgery was performed with a preliminary diagnosis of strangulated hernia. Bassiniâ&#x20AC;&#x2122;s incision was performed. Upon inguinal exploration, a right-sided strangulated indirect inguinal hernia and a mass lesion that was thought to have arisen from the spermatic cord was observed adjacent to the hernia sac (Fig. 1b). It was observed that the right spermatic cord was thickened and the right testis was approximately more than 3 times larger than the left testis. A

perioperative urology consultation was conducted. The mass was observed to have originated from the paratesticular region and extended to the right scrotum, with cord ligation at the inguinal ring level. A radical orchiectomy was performed. The small bowel loops inside the hernia were seen to be healthy and were reduced back to the abdomen, and an indirect hernia repair was performed using the tension-free mesh repair method. The patient was discharged uneventfully on the second postoperative day.

(a)

(b)

(c)

(d)

Figure 2. (a) Spindle-cell tumor proliferation with smooth bundles, (b) mitotic figures observed in some goblet cells, (c) no CD34 staining outside the vessels, (d) desmin positivity.

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The pathological examination of the specimen determined paratesticular leiomyosarcoma that had originated from the spermatic cord. The radical orchiectomy material macroscopically comprised a specimen that was 8x6x6 cm in size with 11x4 cm of spermatic cord on it. In the specimen section, a regularly structured testis with an intact capsule, which was 6x5 cm in size, was detected. In the spermatic cord, a tumoral mass with irregular borders, which was approximately 2 cm from the surgical margin and 6x7 cm in size, was observed. Within the serial sections that were obtained, a tumoral proliferation of fusiform mesenchymal cells was determined. Cellular atypia, atypical mitotic figures, and increased focal cellularity were observed in the tumoral proliferation. In addition, during the immunohistochemical evaluation, vimentin/SMA/HHF-35 was found to be strongly and diffusely positive, CD34 was positive in vascular structures, CD 117 was weakly positive, and Ki-67 proliferation was low. When morphological and immunohistochemical features were evaluated together, a diagnosis of leiomyosarcoma was made (Fig. 2a-d). No residual mass, lymph nodes, or distant metastasis were found in radiological evaluations aimed at detecting metastasis after the pathological diagnosis. The case was discussed at the surgical oncology meeting and a decision was made to pursue conservative follow-up. At the 7-month postoperative follow-up, no local recurrence or systemic disease was observed.

DISCUSSION Paratesticular leiomyosarcoma is a malignancy that arises from the spermatic cord, scrotum, or epididymis, and constitutes approximately 10% of all sarcomas.[3] Sarcomas account for 90% of the paratesticular tumors with malignant characteristics and are mostly of mesenchymal origin.[1,4] Spermatic cord leiomyosarcomas differ from scrotal leiomyomas, which are encountered more frequently in the 6th and 7th decades of life, as in our case.[5] Patients mainly present to polyclinics with a mass that may be painful or painless.[6] Our patient presented at the polyclinic with complaints of groin pain, which had been present for 3 months and a swelling that he had noticed 3 days previously. In such cases, tumor markers and imaging tests should be ordered in addition to performing a physical examination. Since a definitive diagnosis can be made with pathological evaluation, a differential diagnosis from lipomas of the cord and inguinal hernia should be made carefully. [2] In a study conducted by Cardenosa et al.,[7] it was suggested that a definitive preoperative diagnosis is quite hard to reach. In our case, although the hernia had been detected prior to surgery, a conclusive diagnosis was made with the pathological evaluation of the mass encountered in the spermatic cord. Sarcomas are usually spotted on US as solid and extensive, hyperechoic, extratesticular masses. However, the sonographic appearance of these tumors is variable and not speUlus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

cific. CT and/or magnetic resonance imaging is more specific in terms of diagnosis.[8] Even so, with the evaluation of a CT scan in our case, a clear diagnosis regarding the content of the mass could not be made and US only displayed the hernia sac and the position of the bowel loops. All of these findings show that the role of preoperative methods is limited when reaching a definitive diagnosis, and that benign leiomyoma; fibrous mesothelioma; various benign fibrous tumors; pseudotumors, including fibromatous, inguinoscrotal hernia; testicular malignancy; and other rare tumors are also possibilities that must be kept in mind in the differential diagnosis.[9] In a study of 24 cases with primary paratesticular leiomyosarcoma, the tumor location was reported as follows: 11 in the testicular tunica, 10 in the spermatic cord, 1 in the scrotal subcutis, 1 in the dartos muscle, and 1 in the epididymis.[9] It was also reported in another study that the spermatic cord was the most frequent location, at a rate of 90%.[4] In our case, the tumor location was the spermatic cord. Smooth muscle actin, muscle-specific actin, and desmin expression have been observed in most of leiomyosarcomas in the pathological evaluation, while in some cases, CD117, myogenin, Ki-67, S-100 protein, and cytokeratin expression have been reported in immunohistochemical staining as well. [4] Smooth muscle vimentin, CD34, CD117 and Ki-67 were found to be positive in our case. Since paratesticular sarcomas are seen rarely, there is no clinical consensus regarding the treatment. Despite this fact, radical orchiectomy and high ligation of the spermatic cord is the approach most often adopted. The tumorâ&#x20AC;&#x2122;s tendency to expand to the surrounding tissues is a factor that complicates the complete excision of the tumor.[4] In our case, with radical orchiectomy, the tumor was excised completely with a 2-cm surgical margin. Post orchiectomy, the local recurrence rate in the groin and the scrotal area has been reported to be 27%.[10,11] Local adjuvant radiotherapy and/or surgical intervention after orchiectomy appears to reduce the risk of local recurrence.[4] There is still no clear evidence with regard to adjuvant chemotherapy in the treatment of paratesticular leiomyosarcoma. Nonetheless, doxorubicin-based adjuvant chemotherapy has been shown to be beneficial for local and distant metastases.[12] In conclusion, although paratesticular leiomyosarcomas are seen quite rarely in surgical practice, it is a differential diagnostic possibility that must be kept in mind, particularly in male patients in the 6th and the 7th decades, when a mass is detected in the groin area and strangulated inguinal hernia is observed. Conflict of interest: None declared. 309

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REFERENCES 1. Erdemir F, Atılgan D, Parlaktaş BS, Markoç F, Fırat F. Paratesticular Leiomyosarcoma: A Case Report and Review of the Literature. J Clin Anal Med 2012;3:227–30. 2. Krones CJ, Junge K, Conze J, Peiper C, Schumpelick V. Leiomyosarcoma of the hernial sac in inguinal hernia. [Article in German]. Chirurg 2002;73:283–6. 3. Galosi AB, Scarpelli M, Mazzucchelli R, Lopez-Beltran A, Giustini L, Cheng L, et al. Adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of spermatic cord leiomyosarcoma. Diagn Pathol 2014;9:90. 4. Khoubehi B, Mishra V, Ali M, Motiwala H, Karim O. Adult paratesticular tumours. BJU Int 2002;90:707–15. 5. Dangle P, Basavaraj DR, Bhattarai S, Paul AB, Biyani CS. Leiomyosarcoma of the spermatic cord: case report and literature review. Can Urol Assoc J 2007;1:55–8. 6. Montgomery E, Fisher C. Paratesticular liposarcoma: a clinicopathologic

study. Am J Surg Pathol 2003;27:40–7. 7. Cardenosa G, Papanicolaou N, Fung CY, Tung GA, Yoder IC, Althausen AF, et al. Spermatic cord sarcomas: sonographic and CT features. Urol Radiol 1990;12:163–7. 8. Frates MC, Benson CB, DiSalvo DN, Brown DL, Laing FC, Doubilet PM. Solid extratesticular masses evaluated with sonography: pathologic correlation. Radiology 1997;204:43–6. 9. Fisher C, Goldblum JR, Epstein JI, Montgomery E. Leiomyosarcoma of the paratesticular region: a clinicopathologic study. Am J Surg Pathol 2001;25:1143–9. 10. Fagundes MA, Zietman AL, Althausen AF, Coen JJ, Shipley WU. The management of spermatic cord sarcoma. Cancer 1996;77:1873–6. 11. Dotan ZA, Tal R, Golijanin D, Snyder ME, Antonescu C, Brennan MF, et al. Adult genitourinary sarcoma: the 25-year Memorial Sloan-Ketteringexperience. J Urol 2006;176:2033–8. 12. Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet 1997;350:1647–54.

OLGU SUNUMU - ÖZET

Strangüle inguinal herniye eşlik eden paratestiküler leiomiyosarkom Dr. Birol Ağca,1 Dr. Yalın İşcan,1 Dr. Timuçin Aydın,1 Dr. Aytaç Şahin,2 Dr. Kemal Memişoğlu1 1 2

Sağlık Bilimleri Üniversitesi, İstanbul Fatih Sultan Mehmet Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Sağlık Bilimleri Üniversitesi, İstanbul Fatih Sultan Mehmet Eğitim ve Araştırma Hastanesi, Üroloji Kliniği, İstanbul

Spermatik kord kaynaklı sarkomlar yumuşak doku sarkomlarının %2.1 ve genitoüriner sistemde ise %1–2 oranlarında görülen nadir malignitedir. Yetmiş dört yaşında erkek hasta son üç gündür süren kasık ağrısı ve şişlik şikâyeti ile acil polikliniğimize başvurdu. Fizik muayenede sağ inguinal bölgede yaklaşık 5x5 cm boyutlarında sert redükte edilemeyen kitle ve sağ inguinal herni tespit edildi. Bilgisayarlı tomografide sağ inguinal bölgede büyük bir herni kesesi ve içerisinde 77x55 mm ölçülerinde kitle saptanan hastaya radikal orşiektomi ve herni onarımı yapıldı. Kitlenin patolojik değerlendirmesinde paratestiküler leiomyosarkom tanısı konuldu. Ameliyat sonrası yedinci ayda lokal nüks veya uzak metastaz izlenmedi. Sonuç olarak paratestiküler leiomyosarkomlar nadir görülmelerine rağmen özellikle inguinal kitle ile başvuran ileri yaştaki hasta grubunda akılda tutulması gereken bir durumdur. Anahtar sözcükler: Kasık fıtığı; leiomyosarkom; paratestiküler tümör. Ulus Travma Acil Cerrahi Derg 2019;25(3):307-310

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CA S E R EP O RT

A rare case of fatal venous and cerebral air embolism Semih Petekkaya, M.D.,1 Osman Celbis, M.D.,2 Ömer Turan, M.D.,4 Zeynep Yener, M.D.5

Bedirhan Sezer Öner, M.D.,3

Department of Forensic Medicine, Çanakkale Onsekiz Mart University Faculty of Medicine, Bolu-Turkey

Department of Forensic Medicine, İnönü University Faculty of Medicine, Malatya-Turkey

Department of Forensic Medicine, Amasya University Faculty of Medicine, Amasya-Turkey

Department of Forensic Medicine, İstanbul Medeniyet University Faculty of Medicine, İstanbul-Turkey

Council of Forensic Medicine, Yalova Branch Office, Yalova-Turkey

ABSTRACT A venous air embolism can occur as a result of circumstances that include blunt head or chest trauma, thoracentesis, arterial catheterization, neurosurgery, cardiac surgery, and Caisson disease. The formation of a venous air embolism requires an air source, interaction between the air source and the vessel, and a pressure gradient supporting air migration into the vessel. Air enters through the impaired venous structure and travels to the right side of the heart and the pulmonary arteries, and depending on the amount of air, may occasionally be fatal. This report is the description of the case of a 3-year-old child who developed a fatal venous and cerebral embolism during neurosurgery for the treatment of skull fractures with epidural and subdural bleeding due to blunt head and chest trauma resulting from a television falling on her.The pathophysiology of death and notes regarding the medico-legal autopsy procedure in such cases are discussed. Meticulous autopsy techniques must be used to determine the presence of an air embolism in cases of blunt trauma, especially in patients with blunt trauma to the head who die during neurosurgery, and possible future malpractice claims should be kept in mind. Keywords: Craniotomy complications; frothy blood; medicolegal autopsy; venous air embolism.

INTRODUCTION A venous air embolism is a rare, but potentially fatal, condition that can occur as a result of blunt head and chest trauma, thoracentesis, arterial catheterization, and especially during neurosurgical and cardiac surgery or cases of Caisson disease. [1–4] A venous air embolism is also known as a pulmonary air embolism. Three conditions are required for the formation of a venous air embolism: the presence of an air source, interaction between the air source and a vessel, and a pressure gradient supporting air migration to the vessel.[2,5] Air enters through a damaged vein wall and travels to the right side of the heart and the pulmonary arteries. The transition of at least 75 cm³ to 200–300 cm³ of air into the circulation is nec-

essary for the development of a fatal venous air embolism.[6,7] Low-volume venous air emboli occurring after minor intravenous interventions may reach the pulmonary circulation via the right atrium and the right ventricle, but they are generally asymptomatic. A large quantity of air entering the venous circulation, however, can cause death as a result of cardiovascular system blockage.[8] In invasive surgical interventions, such as an adult cardiac bypass operation, the incidence of massive air embolism varies between 0.003% and 0.007%, and various complications occur in half of the affected patients.[9] According to DiMaio,[6] air embolism occurs in 21% to 29% of all craniotomies and 40% of all occipital craniotomies, though

Cite this article as: Petekkaya S, Celbis O, Öner BS, Turhan Ö, Yener Z. A rare case of fatal venous and cerebral air embolism. Ulus Travma Acil Cerrahi Derg 2019;25:311-315. Address for correspondence: Zeynep Yener, M.D. İsmet Paşa Mah., Hakim Saadettin Berki Cad., Yalova Adliyesi, 5. Kat (Adli Tıp Şube Müdürlüğü) Yalova, Turkey. Tel: +90 226 - 814 29 68 / 176 E-mail: drzeynepyener@hotmail.com Ulus Travma Acil Cerrahi Derg 2019;25(3):311-315 DOI: 10.5505/tjtes.2018.58201 Submitted: 13.04.2018 Accepted: 22.10.2018 Online: 16.05.2019 Copyright 2019 Turkish Association of Trauma and Emergency Surgery

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it is rarely fatal. A venous air embolism may be seen in open cranial fractures resulting from blunt head trauma, especially if the fracture is displaced and multisegmental.[5]

hematoma in the same region. A follow-up CT revealed increased bleeding and an urgent operation to drain the subdural-epidural hematomas was performed.

Presently described is the case of a rare, fatal venous and cerebral air embolism that occurred during a neurosurgical operation on a 3-year-old girl who had blunt chest and head trauma as a result of a television falling upon her. Points to be considered in the medico-legal autopsy of such cases, and the pathophysiology and treatment of venous air embolism are discussed.

She was placed on the operating table and her head was deviated to the left side for the neurosurgical operation. A fracture line initiating from the right temporal bone leading to the mastoid and occipital bone was observed. Bleeding from the posterior part of the fracture line was detected and this area was closed with bone wax and antihemorrhagic agents. A temporoparietooccipital craniotomy was performed by creating a burr hole in the occipital bone. Underneath the craniotomy defect, 2 cm of hemorrhagic fluid consistent with an epidural hematoma was observed and removed. When the dura was opened, additional hemorrhagic fluid compatible with an acute subdural hematoma was also removed. The brain pulsation was not clear. A sudden decrease in the end tidal carbon dioxide volume occurred. The patient was turned upside down. A drain was placed in the epidural space and suturing was performed. Upon the development of cardiac arrest following the suturing, cardiopulmonary resuscitation was performed; however, she didnâ&#x20AC;&#x2122;t respond to resuscitation and was declared dead.

CASE REPORT An unconscious 3-year-old girl was brought to the emergency department of a university hospital. A CRT television set had fallen on her while she was playing with the TV unit at her grandfatherâ&#x20AC;&#x2122;s house. On initial examination, her general condition was poor; she was unconscious and had a parietal cephalohematoma. The initial cranial computerized tomography (CT) scan showed displaced fractures in the right temporoparietooccipital bones and acute subdural-epidural

(a)

(c)

(b)

(d)

Figure 1. (a) The sternum was opened in a manner sufficient to preserve the upper third inside the chest. (b) Air bubbles in the heart. (c) A few air bubbles in the cerebral vessels. (d) Fractures in both orbital roofs, and the right temporal and occipital bones.

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Approximately 8 hours after her death, an autopsy was conducted to determine the cause of death. The medico-legal autopsy determined that the patient was a 12 kg, 91 cm, female child, and that livor mortis and rigor mortis were present. No putrefaction sign or gas formation due to putrefaction was detected. A 22-cm, C-shaped, sutured surgical wound was noted on the temporoparietooccipital region, as well as left periorbital ecchymosis and needle marks on various regions of the body. In order to determine any presence of an air embolism, the thoracic cavity was opened in such a way as to preserve the upper one-third of the sternum inside the chest (Fig. 1a). The vessels of the thoracic inlet were preserved. The pericardium was opened and the inside was filled with water. The presence of air was investigated by puncturing the right ventricle with a scalpel. It was observed that there was a dense pocket of air bubbles (Fig. 1b). The main vessels of the heart were observed in the normal anatomical locations. There was frothy blood inside the heart. The foramen ovale was closed. Regions of petechial bleeding over the surface as well as parenchymal bleeding were observed in both lungs in cross-sections. An 8.5x5 cm-sized bone defect was observed on the right temporoparietooccipital region. Epidural bleeding was observed in the bilateral temporal and occipital regions. The brain had an edematous appearance. A few air bubbles were observed in the cerebral vessels (Fig. 1c). Subarachnoid bleeding in the lower part of the left frontal region and hemorrhagic infarct regions in the thalamus was observed. There were linear fractures in both orbital roofs, and in the right temporal and occipital bones (Fig. 1d). Subarachnoid bleeding in the frontal lobe and fresh bleeding foci on the dura mater, as well as bleeding foci in both lungs were reported in the histopathological examination. No lethal or fatal toxic substances were detected in the toxicological examination. The conclusion was that the childâ&#x20AC;&#x2122;s death occurred due to an air embolism.

DISCUSSION A fatal embolism is a rare diagnosis in childhood medico-legal autopsies. Nonetheless, childhood traumas and medical interventions, such as surgery, vascular catheterization, and ventilation, may result in the transition of air into the arterial or venous circulation.[10] The surgical procedures most frequently related to an air embolism are neurosurgical and cardiac surgery, epidural interventions, and umbilical venous catheterization.[11] In our case, venous and cerebral air embolism occurred during a neurosurgical operation after blunt head trauma, which is the most common cause of air embolism. In the postmortem period, a venous air embolism is diagnosed by the presence of air in either the vessel lumen or the chambers of the heart.[5] A cerebral air embolism is diagnosed based on the presence of air bubbles in the cerebral vascular system in autopsy. In order to diagnose a venous air embolism in suspected cases, the manubrium and upper ribs are preserved in order not to damage the main vessels, and Ulus Travma Acil Cerrahi Derg, May 2019, Vol. 25, No. 3

the remaining parts of the sternum and ribs are dissected carefully. The pericardium is punctured and filled with water. The right and left ventricles are penetrated underwater and the presence of air bubbles is assessed.[2,12â&#x20AC;&#x201C;14] This technique can lead to false positive results in decaying corpses due to the gas formation related to putrefaction.[13] In our case, the upper one-third of the sternum was preserved in order not to damage the main vessels. Afterwards, the pericardial sac was punctured and filled with water, and when the right ventricle was penetrated using a bistoury, an air bubble flow was observed. A diagnosis of venous air embolism was made. This technique is consistent with the literature and the accuracy of the diagnosis was increased by not creating an artifact, which may cause false positivity. Due to the absence of signs of decay in the body, false positivity as a result of decay-related gases was excluded. Venous air embolism occurs most frequently during a neurosurgical operation in the context of a posterior fossa craniotomy performed in the sitting position as a result of the gradient created due to gravity. The incidence has been reported to be 76%, though the rate of a fatal embolism is lower. Air enters through the venous sinuses during surgery and travels to the right side of the heart.[15,16] Most vessels have thin walls, and when injured, the vessel lumen collapses due to external pressure exceeding the internal pressure. Thus, air transition and embolism are prevented. The dural sinuses have more rigid walls and preserve their luminal space even after injury.[5] Our case had a displaced linear fracture in the bilateral orbital roofs, the right temporal bone, and occipital bones. Linear and displaced fracture lines, especially in the occipital region, cause tears and bleeding in the dural sinuses in this region. A craniotomy was performed in the side-lying position. An air embolism is less frequent in this position compared with the sitting position. In spite of blood and a blood clot being removed during the surgery, the injured dural sinuses retained sufficient rigid structure and negative air pressure to allow for an air embolism leading to subsequent death. The pathophysiological effect of venous air embolism is correlated with the air volume that has accumulated in the right ventricle. Clinical findings may vary from focal neurological deficits to seizures, coma, loss of consciousness and diffuse encephalopathy in living cases.[4] An air embolism can also cause severe cardiovascular and respiratory dysfunction. A major embolism could lead to sudden cardiovascular collapse through complete output obstruction of the right ventricle, a decrease in pulmonary venous input, sudden right heart failure, a decrease in left ventricular preload, or a decrease in cardiac output.[1,12,14,15] Right ventricular activity turns air and blood into frothy blood.[6,11] During surgery, a sudden decrease in the end tidal CO2 volume and arterial oxygen saturation are important markers of an air embolism.[15] In our case, a sudden decrease in the end tidal CO2 volume was considered a sign of a potential air embolism, thus the body was upside-down and cutaneous-subcutaneous suturing 313

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was performed in order to prevent more air from entering the circulation; however, sudden cardiac collapse occurred. The medico-legal autopsy revealed frothy blood due to right ventricular activity and an air embolism inside the heart, as expected. Clinical findings occur in living cases due to the amount of air entering the vein, the localization, and the air velocity. The findings may vary from focal neurological deficit to death, although asymptomatic cases may also be seen.[17] An air or gas embolism can cause mechanical blockage of a vessel lumen with irritation and vascular endothelial damage. [18] Mechanical occlusion in a cerebral venous air embolism does not cause sudden arterial ischemia, but its interrelationship with the endothelium triggers neutrophil aggregation with beta2-integrin adhesion, and worsening venous stasis can potentially cause infarction. An ischemia-reperfusion mechanism to manage the inflammatory process further increases the damage.[19,20] Treatment of an air embolism involves the delivery of emergency oxygen. The increased partial oxygen pressure will accelerate the absorption of gas and the air embolism will decrease in size.[21,22] Hyperbaric oxygen therapy (HBOT) has been used to reduce the volume of intravascular gas bubbles in patients with a neurological deficit, though the clinical effects are still controversial.[20,23–26] HBOT has 2 primary effects. First, increased atmospheric pressure will affect gas bubbles mechanically and their volume will decrease inversely with pressure. In addition, increased pressure helps the passage of gas and oxygen through the tissues and venous blood for elimination through the lungs. The second effect is significantly increased partial oxygen pressure.[22,27] Satisfactory results were obtained after HBOT therapy was administered within the first 7 hours of a cerebral air embolism developing following cranial surgery.[28] If air enters the arterial circulation directly through the pulmonary veins, even small amounts (0.5–1 mL) of air can be fatal.[20,29] If the foramen ovale is closed, air transition from the venous to the arterial system may result either from pulmonary arteriovenous malformations or a physiological pulmonary shunt. A 1.5–3 mL/kg air volume could also lead to over exceeding the filtration capacity of the lungs, thus resulting in embolism.[1] Since the foramen ovale was closed in our case, a cerebral air embolism seems to have resulted from air transition to the arterial circulation from the lungs via the physiological shunts. The presence of a hemorrhagic infarct region in the thalamus, which requires more oxygen, as well as cerebral edema support our diagnosis. However, air can be an artifact in cerebral vessels when the skull is opened. In such cases, a cerebral air embolism diagnosis should be made after a detailed investigation of diagnosis-supporting signs. Damage can be minimized by early diagnosis and treatment of air emboli, which have a high rate of mortality and morbidity. It should be considered that death may be due to air embolism in patients with blunt trauma findings, particularly to the head, who die during a neurosurgical operation. Precise medico-legal autopsy techniques that are sufficient to 314

diagnose air embolization should be used to determine the presence of an air embolism, particularly given the possibility of a malpractice claim. Conflict of interest: None declared.

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Petekkaya et al. A rare case of fatal venous and cerebral air embolism 24. Mirski MA, Lele AV, Fitzsimmons L, Toung TJ. Diagnosis and treatment of vascular air embolism. Anesthesiology 2007;106:164–77. 25. van Hulst RA, Klein J, Lachmann B. Gas embolism: pathophysiology and treatment. Clin Physiol Funct Imaging 2003;23:237–46. 26. Blanc P, Boussuges A, Henriette K, Sainty JM, Deleflie M. Iatrogenic cerebral air embolism: importance of an early hyperbaricoxygenation. Intensive Care Med 2002;28:559–63. 27. Berlot G, Rinaldi A, Moscheni M, Ferluga M, Rossini P. Uncommon occurences of air embolism: Description of cases and review of the litera-

ture. Hindawi Case Reports in Critical Care 2018;1–7. 28. Lundborg M, Helseth E, Josefsen R, Braathen M, Skogen K, Ramm-Pettersen J. Hyperbaric oxygen therapy or air embolus in the cerebral venous sinuses after intracranial surgery: a case report. Acta Neurochirurgica 2018;160:1401–5. 29. Yadav S, Jain S, Aggarwal P, Gupta R. Systemic arterial air embolism: positive pressure ventilation can be fatal in a patient with blunt trauma. BMJ Case Rep 2013 Feb 15 [E-pub ahead of print], doi: 10.1136/bcr2012-008343.

OLGU SUNUMU - ÖZET

Nadir görülen ölümcül venöz ve serebral hava embolisi Dr. Semih Petekkaya,1 Dr. Osman Celbis,2 Dr. Bedirhan Sezer Öner,3 Dr. Ömer Turan,4 Dr. Zeynep Yener5 Çanakkale Onsekiz Mart Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, Çanakkale İnönü Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, Malatya Amasya Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, Amasya 4 İstanbul Medeniyet Üniversites Tıp Fakültesi, Adli Tıp Anabilim Dalı, İstanbul 5 Adli Tıp Kurumu, Yalova Şubesi, Yalova 1 2 3

Venöz hava embolisi kafa ve göğüs bölgelerine künt travma maruziyeti, torasentez, arteryel kateterizasyon gibi girişimler, vurgun hastalığı, kardiyak ve nöroşirürji cerrahi operasyonları sonrası ender olarak gelişebilmekte, gelişmesi halinde ise kardiyovasküler sistemde blokaj meydana getirerek ölüme yol açabilmektedir. Düşük miktarlardaki venöz hava embolileri sıklıkla asemptomatik olup, venöz hava embolisinin ölümcül olabilmesi için 75 cm3 ile 200–300 cm3 arasında hacme sahip havanın dolaşıma geçmesi gerekmektedir. Zedelenmiş sistemik ven yapısının içine giren hava dolaşım sisteminde önce sağ atriyuma sonra sırası ile sağ ventrikül ve pulmoner artere ulaşmaktadır. Çalışmamızda üzerine televizyon düşmesi sonucu künt göğüs ve kafa travması geçiren, yapılan incelemelerde kafatası kemiklerinde deplase kırıklar ve akut subdural-epidural hematom saptanması üzerine operasyona alınan, ancak operasyon sırasında ani kardiyak arrest gelişmesi üzerine öldüğü bildirilen üç yaşındaki kız çocuğu olgusu sunuldu. Küçük çocuğun yapılan medikolegal otopsisinde saptanan venöz ve serebral hava embolisi ile birlikte diğer otopsi bulguları sunularak, bu tür olgularda medikolegal otopsi uygulamasında dikkat edilmesi gereken noktaların ve gelişen ölümün patofizyolojisinin tartışılması amaçlanmaktadır. Anahtar sözcükler: köpüklü kan; kraniotomi koplikasyonları; medikolegal otopsi; nöroşirurji; venöz hava embolisi. Ulus Travma Acil Cerrahi Derg 2019;25(3):311-315

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