Travma 2017 / 2 by KAREPUBLISHING

ISSN 1306 - 696X

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

Volume 23 | Number 2 | March 2017

www.tjtes.org

TURKISH JOURNAL of TRAUMA & EMERGENCY SURGERY Ulusal Travma ve Acil Cerrahi Dergisi Editor-in-Chief Recep Güloğlu Editors Kaya Sarıbeyoğlu (Managing Editor) 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

www.tjtes.org

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

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

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) Amblem Correspondence address (Yazışma adresi) Tel Fax (Faks)

Kaya Sarıbeyoğlu Kaya Sarıbeyoğlu M. Mahir Özmen 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): March (Mart) 2017 • 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

www.tjtes.org

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

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 2008 in Index Copernicus. Our impact factor in SCI-E indexed journals is 0.5. 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 may be submitted in Turkish or 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, 2001 yılından itibaren Index Medicus ve Medline’da, 2005 yılından itibaren Excerpta Medica / EMBASE indekslerinde, 2007 yılından itibaren Science Citation Index-Expanded (SCI-E) ile Journal Citation Reports / Science Edition uluslararası indekslerinde ve 2008 yılından itibaren Index Copernicus indeksinde yer almaktadır. 2015 yılında SCI-E kapsamında İmpakt faktörümüz 0,5 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 Türkçe ve İngilizce yazılmış makaleler yayınlanabilir. 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 kişiler-

den 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 23

Number - Sayı 2 March - Mart 2017

Contents - İçindekiler Deneysel Çalışma - Experimental Experimental Studies - DeneyselStudy Çalışma 85-90 The effect of 2 different surgical methods on intracompartmental pressure value in tibial shaft fracture: An experimental study in a rabbit model Tibia cisim kırıklarında iki farklı cerrahi yöntemin kompartman basıncı üzerine etkisi: Tavşan modelinde deneysel bir çalışma Ertürk C, Altay MA, Altay N, Öztürk İA, Baykara İ, Sert C, Işıkan UE 91-99 A comparison of the effects of platelet-rich plasma and demineralized bone matrix on critical bone defects: An experimental study on rats Sıçan segmenter kemik defekti modelinde trombositten zenginleştirilmiş plazmanın ve demineralize kemik matriksinin kırık iyileşmesi üzerine etkisinin karşılaştırılması Turhan E, Akça MK, Bayar A, Songür M, Keser S, Doral MN 100-106 Effect of N-acetylcysteine on neutrophil functions during experimental acute pancreatitis Deneysel akut pankreatitte nötrofil fonksiyonları üzerine N-asetilsistein’in etkisi Atayoğlu K, Gürleyik G, Demirel G, Özkara S

Original Articles - Orijinal Çalışma 107-111 Importance of diagnostic laparoscopy in the assessment of the diaphragm after left thoracoabdominal stab wound: A prospective cohort study Sol torakoabdominal bölge delici kesici alet yaralanması olan hastalarda diafragmanın değerlendirilmesinde diagnostik laparoskopinin önemi: İleriye yönelik kohort çalışması Yücel M, Özpek A, Tolan HK, Başak F, Baş G, Ünal E, Alimoğlu O 112-116 Correlation between Ranson score and red cell distribution width in acute pancreatitis Akut pankreatitte Ranson skoru ile eritrosit dağılım hacmi (RDW) arasındaki korelasyon Kılıç MÖ, Çelik C, Yüksel C, Yıldız BD, Tez M 117-121 Evaluation of forearm arterial repairs: Functional outcomes related to arterial repair Önkol damar onarımlarının değerlendirilmesi: Arter onarımı ile ilişkili fonksiyonel sonuçlar Keleş MK, Şimşek T, Polat V, Yosma E, Demir A 122-127 Approach to inguinal hernia in high-risk geriatric patients: Should it be elective or emergent? Yüksek riskli geriatrik hastalarda inguinal hernilere yaklaşım: Elektif mi, acil mi olmalıdır? Işıl RG, Yazıcı P, Demir U, Kaya C, Bostancı Ö, İdiz UO, Işıl CT, Demircioğlu MK, Mihmanlı M 128-133 Primary small intestinal non-Hodgkin lymphoma diagnosed after emergency surgery Acil cerrahi sonrası tanı alan primer ince barsak non-Hodgkin lenfomaları Avcı T, Yabanoğlu H, Arer İM, Koçer NE, Çalışkan K, Börcek P, Ekici Y 134-138 How to avoid negative appendectomies: Can US achieve this? Negatif apendektomilerden kaçınmanın yolu: Ultrasonografi bunu başarabilir mi? Kartal K, Yazıcı P, Ünlü TM, Uludağ M, Mihmanlı M 139-143 Can we make an early ‘do not resuscitate’ decision in severe burn patients? Ciddi yanık hastalarında erken “do not resuscitate=resüsite etme” talimatı verilebilir mi? Yüce Y, Acar HA, Erkal KH, Tuncay E

Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

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TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 23

Number - Sayı 2 March - Mart 2017

Contents - İçindekiler

144-149 Minimal invasive fixation of distal tibial fractures does not result in rotational malalignment: A report of 24 cases with CT imaging Distal tibia kiriklarinin minimal invaziv tespiti rotasyonel deformiteye neden olmaz: Yirmi dört hastanın bilgisayarlı tomografi incelemesi Sönmez MM, Gülabi D, Uğurlar M, Uzun M, Sarban S, Şeker A 150-155 Repair of comminuted fracture of the lower patellar pole Patella distal ucu parçalı kırığının onarımı Massoud EIE 156-162 The geriatric polytrauma: Risk profile and prognostic factors Geriatrik politravma: Risk profili ve prognoz faktörleri Rupprecht H, Heppner HJ, Wohlfart K, Türkoglu A

Case Series - Olgu Serisi 163-166 Variations in otological presentation of lightning strike victims: Clinical report of 3 patients Yıldırım düşmesine bağlı oluşan farklı otolaringolojik tablolar: Üç hastaya ait klinik rapor Kılıç E, Genç H, Aydın Ü, Aşık B, Satar B

Case Case Reports Reports -- Olgu Olgu Sunumu Sunumu 167-169 An excellent anatomical and visual recovery after surgical repair of an open eye injury with poor baseline prognostic factors Kötü başlangıç prognostik faktörlere sahip açık göz yaralanmasında cerrahisi sonrası mükemmel anatomik ve görsel iyileşme Yazgan S, Ayar O, Akdemir O, Koban Y 170-172 Behçet’s disease-related superior vena cava syndrome and bleeding downhill varices: A rare complication Behçet hastalığı ile ilişkili süperior vena kava sendromu ve kanayan downhill varisler: Nadir bir komplikasyon Yaşar B, Kılıçoğlu G

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EXPERIMENTAL STUDY

The effect of 2 different surgical methods on intracompartmental pressure value in tibial shaft fracture: An experimental study in a rabbit model Cemil Ertürk, M.D.,1* Mehmet Akif Altay, M.D.,1 Nuray Altay, M.D.,2 İbrahim Avşin Öztürk, M.D.,1 İslam Baykara, M.D.,1 Cemil Sert, M.D.,3 Uğur Erdem Işıkan, M.D.1 1

Department of Orthopedics and Traumatology, Harran University Faculty of Medicine, Şanlıurfa-Turkey

Department of Anesthesiology and Reanimation, Harran University Faculty of Medicine, Şanlıurfa-Turkey

Department of Biophysics, Harran University Faculty of Medicine, Şanlıurfa-Turkey

ABSTRACT BACKGROUND: Intracompartmental pressure (ICP) monitoring is a widely used modality, particularly after intramedullary nailing of tibial shaft fractures. It was hypothesized that ICP value in fracture fixed with Ilizarov circular fixator (ICF) might be lower than in fracture fixed with intramedullary pin (IMP). The present study is a comparison of ICP value in tibial fractures in a rabbit model fixed with ICF and IMP. METHODS: Twenty male New Zealand White rabbits were randomly divided into 2 groups of equal size: ICF group (Group 1) and IMP group (Group 2). Under anesthesia, half of proximal part of the right tibia of all rabbits was fractured. Tibial fractures were fixed with ICF in Group 1 and IMP in Group 2. ICP values were monitored at 6-hour intervals for 48 hours. RESULTS: There was statistically significant difference in ICP value between groups (p<0.001). While there was statistically significant increase in ICP values 24 hours post surgery, there was statistically significant decrease during second 24 hours following surgery. Most importantly, ICP values of ICF group were significantly lower than those of IMP group at 30, 36, and 42 hours post surgery (p<0.05). CONCLUSION: At 24th hour after fixation, ICP values measured in ICF group were lower compared with those of IMP group. These results indicate that use of ICF in tibial fractures provides additional decompression in the anterior compartment. In light of these findings, ICF may be preferable for treatment of tibial fractures with high risk for compartment syndrome. Keywords: Acute compartment syndrome; Ilizarov external fixator; intracompartmental pressure monitoring; intramedullary pin fixation; tibial fractures.

INTRODUCTION Acute compartment syndrome (ACS) is a common and well-recognized complication after tibial bone fracture.[1–6] Development of ACS may be related to treatment modalYazarın şimdiki kurumu: İstanbul Sağlık Bilimleri Üniversitesi Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi, İstanbul.

Address for correspondence: Cemil Ertürk, M.D. İstanbul Sağlık Bilimleri Üniversitesi Kanuni Sultan Süleyman Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Anabilim Dalı, Küçükçekmece, İstanbul, Turkey Tel: +90 212 - 404 15 00 E-mail: erturkc@yahoo.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

ity employed or nature of tibial fracture. Diagnosis of ACS is difficult and is often achieved using combination of clinical findings and measurements of intracompartmental pressure (ICP).[3] There are numerous surgical methods for treatment of tibia shaft fracture, such as intramedullary nailing or pinning (IMP), external fixation, open reduction, and internal fixation (plating).[7–9] Although intramedullary nailing is considered optimal method of treatment for closed tibial shaft fracture, external fixation may be indicated for patients with unstable closed fracture or fracture complicated by compartment syndrome. [5] Tensioned-wire external fixators, especially Ilizarov circular fixator (ICF), have been used most frequently for segmental fractures and diaphyseal fractures with periarticular extension.[5,10] Intramedullary nailing is suitable method to achieve acceptable alignment and rigid fixation of tibial diaphyseal fractures.[11] Nail can be inserted percutaneously, causing 85

Ertürk et al. The effect of 2 different surgical methods on intracompartmental pressure value in tibial shaft fracture

minimal morbidity and without disrupting the fracture hematoma. ICF also provides opportunity for closed reduction and repositioning of bone fragments, and causes minimal disruption of soft tissues in region of fracture with preservation of blood supply.[5,12,13] Both methods are suitable for early use and weight-bearing on the limbs, and neither compromises bone biology. ACS after intramedullary reamed or unreamed nailing of tibial diaphyseal fracture has been reported in several studies.[9,14–19] According to these articles, ACS can develop as complication of closed intramedullary nailing secondary to traction, manipulation, or reaming. In addition, it was reported in a recent study that ACS can also develop in pediatric tibial shaft fracture treated with flexible IMP.[20] Clinical observation has demonstrated that edema in tibial shaft fracture dissolves day after treatment with ICF; however there is no study investigating ICP measurements after application of ICF for tibial shaft fracture. ICP monitoring after IMP in such fracture has been well documented. Data suggested hypothesis that ICP values in tibial fracture fixed with ICF might be lower than those in fracture fixed with IMP. The aim of the present study was to evaluate ICP values of these 2 commonly used surgical methods (ICF and IMP) in treatment of tibia shaft fracture in rabbit model.

MATERIALS AND METHODS Total of 20 6-month-old, male New Zealand White rabbits weighing 2.5 to 3.0 kg each were used for the present study. Approval was granted by the Harran University animal research ethics committee and study was performed according to guidelines of the Association for Assessment and Accreditation of Laboratory Animal Care.

Fracture Injury Procedure and Surgery Technique Before initiating injury-inducing procedure, each rabbit was anesthetized with intramuscular injection of combination 5 mg/kg xylazine hydrochloride and 50 mg/kg ketamine hydrochloride administered by an anesthesiologist as previously described.[21] In addition, 20 mg/kg/day cefazolin sodium was administered prior to surgery and maintained until 48th hour after injury. Animals were randomly selected and divided into ICF group (Group 1; n=10) and IMP group (Group 2; n=10). After shaving appropriate area, half of proximal part of the right tibia of each rabbit was exposed and tibial bone fracture was performed using custom-made device to create injury similar to standard injury pattern as described in our previous study (Fig. 1a, b).[22] This method creates uniform type of fracture in all subjects with 2.5-kg weight released free-fall from height of 30 cm. In Group 1, after closed reduction of the fractured tibia, pre-constructed ICF was applied to the right tibia. Circular external frame composed of 2 5/8 C rings 40 to 45 mm in diameter was fixed to metaphysis of the tibia proximal to fracture site and diaphysis distal 86

(a)

(b)

Figure 1. (a) Placement of right tibia on the apparatus. (b) Diagrammatic representation of the fracture.

to fracture site as previously described.[23] Frame was fixed to the tibia with 2 K-wires 1 mm in diameter inserted at 45° to 60° angle to one another. Tension was applied to wires at force of 30 to 35 N (Fig. 2). In Group 2, the fractured tibias were fixed with single 2-mm K-wire at intramedullary location in closed fashion with stab incision at level of tibial tuberosity. Upper end of K-wire was cut to appropriate length and buried. Intramuscular injection of tramadol (1 mg/kg) was administered for post-procedure pain relief. All animals were kept in separate cages under standard environmental conditions with free access to water and food. Rabbits were maintained in the above-mentioned care conditions and followed-up for 6 weeks to allow for adequate fracture healing before being released to farm environment.

Measurement of Compartmental Pressure Side-ported needle was connected to ICP monitoring system (Stryker Intra-Compartmental Pressure Monitor; Stryker Corp., Kalamazoo, MI, USA), which consists of recording box, switch, numerical display, single-use pre-filled syringe of physiological saline, and pressure transmitter. ICP monitoring of

Figure 2. Circular external fixator applied to the fractured tibia.

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ErtĂźrk et al. The effect of 2 different surgical methods on intracompartmental pressure value in tibial shaft fracture

(a)

(b)

Intercompartmental pressure (mmHg)

*; p<0.05 intergroup difference

Figure 3. (a) Roentgenogram of fracture just after application of circular external fixator (black arrow). (b) Roentgenogram of fracture just after application of intramedullary pin fixation (black arrow).

anterior tibial compartments of affected tibias was initiated immediately before and after injury, and was performed at 6-hour intervals until 48th hour post injury.

Radiological Analysis Anteroposterior radiographs of affected tibias were taken with 52 kV tube voltage and 4.10 mA tube current just before and after fixation (Fig. 3a, b) as well as at the end of the 6-week follow-up period to confirm fracture position and adequate healing. All radiographs were evaluated by a radiologist.

Statistical Analysis Statistical analyses were performed using SPSS software (version 20; IBM Corp., Armonk, NY, USA). Continuous variables were expressed as medianÂąinterquartile range. MannWhitney U test was used to compare groups. Continuous

Group 1 Group 2

0 BF

12 18 24 30 Time after fracture (hrs)

Figure 4. Intracompartmental pressure profiles of rabbits in Groups 1 and 2.

variables were compared using repeated measurement of variance analysis and post hoc Bonferroni test within each group. Two-tailed p value of <0.05 was considered to indicate statistical significance.

RESULTS All rabbits showed good general health without any sign of discomfort and completed the study uneventfully. They were capable of partial weight-bearing following initial post-injury period. ICP monitoring results for experimental groups are summarized in Table 1. ICP profiles of groups during follow-up

Table 1. Median intracompartmental pressure values of each group at each time point Time after fracture (h)

Median intracompartmental pressure in mmHg (Interquartile range)

Group 1 (Fixed circular external fixator)

Group 2 (Fixed intramedullary pin)

Before fracture

4.0 (3.0)

4.5 (2.7)

0.631

Just after fracture

10.5 (4.0)

11.0 (4.7)

0.481

6 h after fracture

25.0 (5.7)

26.0 (9.2)

0.739

12 h after fracture

30.0 (12.0)

25.0 (8.0)

0.481

18 h after fracture

38.0 (5.2)

36.0 (8.7)

0.315

24 h after fracture

46.5 (7.0)

51.0 (9.5)

0.280

30 h after fracture

36.5 (7.0)

43.0 (6.2)

0.023

36 h after fracture

28.0 (10.5)

36.0 (11.0)

0.029

42 h after fracture

21.5 (8.5)

31.0 (12.5)

0.043

48 h after fracture

19.0 (7.2)

24.5 (9.0)

0.075

*Mann-Whitney U test.

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ErtĂźrk et al. The effect of 2 different surgical methods on intracompartmental pressure value in tibial shaft fracture

period are displayed in Figure 4. There was statistically significant difference in ICP values between groups (p<0.001). In both groups, measured ICP values at postoperative 24th hour revealed statistically significant increase. There was also statistically significant decrease in ICP values during second 24 hours post surgery in both groups. Most importantly, ICP values of ICF group were significantly lower compared with values obtained in IMP group at postoperative 30th, 36th, and 42nd hours (p<0.05). Radiological analyses revealed healing of proximal tibial fractures with similar physiological alignment pattern in all 20 animals during initial postoperative period, and all fractures were determined to be completely healed within 6 weeks.

DISCUSSION Most important finding of the present study is that ICP values of ICF group were significantly lower than those of IMP group at 30th, 36th, and 42nd postoperative hour. In both groups, measured ICP values at postoperative 24th hour were found to be significantly increased. There was also statistically significant decrease in ICP during second 24 hours post surgery in both groups. To our knowledge, this is the first study comparing ICP profiles of tibial fractures with same injury pattern using 2 different fixation methods. In both groups, significant increase in ICP was observed within first 24-hour postoperative period. ACS is associated with insufficient microcirculation at the extremity. Pathogenetic mechanisms underlying this inadequate microcirculation are linked to increased pressure within non-elastic soft tissue compartment enclosed by fascia and bone.[3,5,11] Therefore, ICP may be elevated due to increase in contents of compartment (e.g., as result of bleeding or edema) following fracture of the tibia. Furthermore, traction and manipulation associated with external fixation and tibial nailing during surgery may increase ICP. It has been reported that ICP increases as consequence of further tissue damage related to manipulation and longitudinal traction that occurs during tibial nailing procedure.[3,14] Similar mechanism has been demonstrated in patients after placement of spanning external fixators. Longitudinal traction has been shown to increase ICP in highenergy plateau fractures.[24] In the present study, we observed gradual decrease in ICP after 24 hours in both groups. This decrease may be attributed to resolution of edema and reperfusion of the compartment in fixed tibial fracture.[15,16] In our previous study, we found similar results: ICP values of rabbits who underwent open and closed tibial fractures significantly decreased during second postoperative 24-hour period.[22] In our opinion, the most valuable result of the present study is significant decrease in ICP at postoperative 30th, 36th, and 42nd hours in ICF group in comparison with IMP group. For transosseous fixation, K-wires are key components of Ilizarov 88

device. K-wires can be considered slender beams that are subjected to transverse loading after being pretensioned axially and fixed to a support. K-wires are passed through the skin, and sometimes the muscles, multidirectionally to connect external fixator to the bone.[12,13,25,26] Ilizarov external fixation produces trampoline effect because of highly tensioned wires supported circumferentially.[5] Dynamic cleavage may occur due to trampoline effect of K-wires in all intercompartmental spaces (subcutaneous, fascial, muscular, and periosteal tissue). We think that drop in ICP may be due to increased serous drainage through pin tract during early postoperative period. K-wires passing through the skin make up the pin tract, and they act as openings (similar to a pop-up window) from the bone, muscle, and tissue compartments to the outside environment. In normal physiological tissue, the skin has typical tonus and elasticity, which means that it does not permit drainage through the skin.[12,27] Immediately after bone fracture, combination of hematoma, edema, and extravasation of extracellular fluid occur at injury site.[11] During this period, swelling and edema are observed in the injured soft tissue compartment. In addition, the skin becomes edematous and non-elastic in nature. Thus, percutaneous drainage via K-wires from tissue compartment to the outside may be result of the skin losing its elasticity. This drainage of extravasated fluid may be similar to subcutaneous fasciotomy. Furthermore, K-wires are not passed through just 1 compartment; they pass through almost all compartments. In this regard, serous drainage may be considered advantageous in reducing ICP. Therefore, Ilizarov circular fixation may provide additional decompression in all compartment of the lower leg. Pin site must be kept clean to avoid infection of pin tract. Pin tract infection may cause loosening of the pin, which requires pin removal.[28] In previous studies, increases in ICP have been noted with application of spanning external fixator.[24,29] However, only 2 or 3 unilateral percutaneous Schanz pins were used for spanning of external fixators. Therefore, effect of drainage through Schanz pins can be ignored in the case of spanning external fixator. Although we did not encounter any drainage or hematoma on the edge of the K-wires during ICP application or within the first 24 hours of follow-up, with increased swelling and hematoma, drainage began to appear in second 24-hour period. We believe that lower ICP values of ICF group in second 24 hours were result of this change. In this study, the fractured tibias in Group 2 were fixated with a 2-mm K-wire at intramedullary location in closed fashion. This method may be similar to flexible intramedullary nailing of long bone fractures. In recent studies,[20,30] flexible intramedullary nailing of long bone fractures has been shown to have high risk for development of ACS in pediatric population. The reason may be soft-tissue trauma caused by multiple attempts to reduce the fracture and pass the nail. The present study has several limitations. First of all, numUlus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Ertürk et al. The effect of 2 different surgical methods on intracompartmental pressure value in tibial shaft fracture

ber of animals used to determine effects of fracture on ICP profile was limited. Second, we used 2-mm K-wire as an intramedullary nail, rather than locking intramedullary nail, and IMP used has weaker stabilizing force on fractured bone fragments. Therefore, IMP was unlike modern intramedullary nails, which have additional locking holes that provide torsional stability to fracture. However, we did not have the opportunity to apply the implant type used in human tibia. Third, at middle region of tibia, tibia and fibula become fused in rabbits, and fracture was created at a site that is atypical for human fractures. Accordingly, clinical study that involves similar type of fracture with larger cohort will be needed to evaluate ICP values of fractures fixed with ICF versus IMP. Clinical message of the current study is that ICF can be considered a surgical alternative to minimize serious risk of compartment syndrome in cases such as large hematoma with multiple fractures, extensive soft tissue damage and skin edema, or when patient cannot adapt to elevation. ICF can be definitive treatment option in such kind of complicated fracture. It is generally accepted that IMN is optimal choice for simple fracture. Furthermore, process of removal of ICF is less invasive than for IMN. Possible pin tract infection is more tolerable problem compared with detrimental risk of compartment syndrome.

Conclusion ICP values of fractures fixed with ICF were lower than those of fractures fixed with IMP at the first postoperative 24 hours. These results indicate that ICF in tibial fracture provides additional decompression in the anterior compartment. This decrease in ICP may be related to serous drainage from the compartment to outside of the body via the Kwires in postoperative period. Therefore, ICF technique may be preferable for tibial fractures with risk for compartment syndrome. Since animal models may not completely reflect clinical course in humans, our results should be compared with the existing literature.

Acknowledgments This project was funded by the Harran University Scientific Research Coordination Committee (2011/2/1143). Animal research ethics committee approval number: B.30.2.H RU.0.05.07.00/270-2010/41. The authors declare that they have no relevant financial involvement with any commercial organization with direct financial interest in the subject or materials discussed in this manuscript. Conflict of interest: None declared.

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26. Zamani AR, Oyadiji SO. Analytical modelling of Kirschner wires in Ilizarov circular external fixator as pretensioned slender beams. J R Soc Interface 2009;6:243–56. 27. Barnea Y, Gur E, Amir A, Leshem D, Zaretski A, Miller E, et al. Delayed primary closure of fasciotomy wounds with Wisebands, a skin- and soft tissue-stretch device. Injury 2006;37:561–6. 28. Ertürk C, Çağman B, Altay MA, Işıkan UE. The use of Ender nail in intertrochanteric fractures supported with external fixation. Ulus Travma Acil Cerrahi Derg 2011;17:407–12. 29. Stark E, Stucken C, Trainer G, Tornetta P 3rd. Compartment syndrome in Schatzker type VI plateau fractures and medial condylar fracturedislocations treated with temporary external fixation. J Orthop Trauma 2009;23:502–6. 30. Blackman AJ, Wall LB, Keeler KA, Schoenecker PL, Luhmann SJ, O’Donnell JC, et al. Acute compartment syndrome after intramedullary nailing of isolated radius and ulna fractures in children. J Pediatr Orthop 2014;34:50–4.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Tibia cisim kırıklarında iki farklı cerrahi yöntemin kompartman basıncı üzerine etkisi: Tavşan modelinde deneysel bir çalışma Dr. Cemil Ertürk,1* Dr. Mehmet Akif Altay,1 Dr. Nuray Altay,2 Dr. İbrahim Avşin Öztürk,1 Dr. İslam Baykara,1 Dr. Cemil Sert,3 Dr. Uğur Erdem Işıkan1 1 2 3

Harran Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Şanlıurfa Harran Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Şanlıurfa Harran Üniversitesi Tıp Fakültesi, Biyofizik Anabilim Dalı, Şanlıurfa

AMAÇ: Kompartman içi basınç (KİB) monitarizasyonu özellikle tibia cisim kırıklarının intramedüller çivilemesinden sonra sıkça kullanılan bir izlem yöntemidir. İlizarov sirküler fiksatör (İCF) ile tespit yapılan tibia kırıklarındaki KİB değerlerinin intramedüller telleme (İMT) ile yapılanlardan daha düşük olabileceği öngörüldü. Bu çalışmada, İCF ve İMT ile tespit yapılan tibia kırıklarında KİB değerleri karşılaştırıldı. GEREÇ VE YÖNTEM: Yirmi Yeni Zelenda Beyaz tavşanları rastgele İCF (Grup 1) ve İMT (Grup 2) olmak üzere iki gruba ayrıldılar. Anestezi altında tavşanların sağ tibialarının üst yarısında kırık oluşturuldu. Tibia kırıkları Grup 1’de İCF, Grup 2’de İMT ile tespit edildi. Kompartman içi basınç değerleri 48 saat boyunca altışar saat arayla ölçüldü. BULGULAR: Kompartman içi basınç değerlerinde her iki grup içinde önemli farklar vardı (p<0.001). Ayrıca, her iki grupta KİB değerleri ameliyat sonra ilk 24 saatte önemli derecede artarken, ikinci 24 saatte azalmıştı. En önemlisi de, İCF grupta KİB değerleri İMT gruptakine göre, 30, 36 ve 42. saatlarda önemli derecede düşüktü (p<0.05). TARTIŞMA: Tespitten 24 saat sonra, İCF grubundaki KİB değerleri İMT’ye göre daha düşüktü. Bu sonuçlar tibia kırıklarında İCF kullanımının ön kompartmanda ek dekompresyon sağladığını göstermektedir. Bu bulguların ışığında, İCF uygulaması kompartman sendromu riski taşıyan yüksek riskli tibia kırıkların tedavisinde tercih edilebilir. Anahtar sözcükler: Akut kompartman sendromu; Ilizarov eksternal fiksatör; intramedüller çivi tespiti; kompartman içi basınç monitarizasyonu; tibia kırıkları. Ulus Travma Acil Cerrahi Derg 2017;23(2):85–90

doi: 10.5505/tjtes.2016.82177

Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

EXPERIMENTAL STUDY

A comparison of the effects of platelet-rich plasma and demineralized bone matrix on critical bone defects: An experimental study on rats Egemen Turhan, M.D.,1 Mustafa Kemal Akça, M.D.,2 Ahmet Bayar, M.D.,3 Murat Songür, M.D.,3 Selçuk Keser, M.D.,3 Mahmut Nedim Doral, M.D.1 1

Department of Orthopedics and Traumatology, Hacettepe University Faculty of Medicine, Ankara-Turkey

Department of Orthopedics and Traumatology, Bandırma Government Hospital, Balıkesir-Turkey

Department of Orthopedics and Traumatology, Bülent Ecevit Faculty of Medicine, Zonguldak-Turkey

ABSTRACT BACKGROUND: Delayed union of fractured bone is one of the main problems of orthopedics and traumatology practice. It was hypothesized that the beneficial effects of allogeneic platelet-rich plasma (PRP) would be valuable in the treatment of segmental bone defects. This study is a comparison of the effects of demineralized bone matrix (DBM) and PRP in a segmental bone defect model. METHODS: Total of 48 Wistar albino rats were separated into 4 groups. Segmental bone defect was created at right radius diaphysis in all specimens using dorsal approach. Four additional rats were used as PRP source. Intracardiac blood was withdrawn before the operation for preparation of allogeneic PRP. Group 1 (n=12) served as control group and defects were left untreated. Group 2 (n=12), was PRP group, and received grafting with PRP. Group 3 (n=12) was PRP+DBM combination group, and was treated with grafting and mixture of DBM and PRP. In Group 4 (n=12), defect area was grafted with DBM only. At the end of 10th week, rats were sacrificed, forearms were dissected, and defect areas were examined with radiological and histopathological parameters. RESULTS: Radiological evaluation revealed that ossification was best in PRP group, followed by DBM group. According to results of histopathological studies, union quality was better than control group in all treatment groups (Groups 2, 3, and 4), and was best in PRP group (p<0.05). Results were also better in PRP group when examined in terms of cortex development and remodeling (p<0.05). When examined in terms of new osteogenesis, results were comparable in Groups 2, 3, and 4, but all were better than control group. CONCLUSION: It was concluded that PRP and DBM have comparable effect on recovery of defective bones, but there is no synergistic effect when used together. We believe that PRP can be a cost-effective, readily available alternative to DBM with minimal morbidity. Keywords: Demineralized bone matrix; platelet-rich plasma; segmental bone defect.

INTRODUCTION Bone defects caused by infection, tumor, high-energy trauma, metabolic disease or massive osteolysis due to prosthesis loosening still remain a major clinical concern. Unfortunately,

Address for correspondence: Egemen Turhan, M.D. Hacettepe Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, 06100 Ankara, Turkey Tel: +90 312 - 305 12 09 E-mail: dregementurhan@yahoo.com Qucik Response Code

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the self-repair capacity of the critically defected bone is extremely limited and this condition generally requires bone grafting for mechanical and biological enhancement. Osteoinductivity, osteoconductivity, and osteogenesis are desired properties of an optimal bone graft substitute. Autogenous bone grafts (ABG) have these features and are currently considered the “gold standard”.[1–3] ABG also have advantages of being easy to harvest, economical, and non-immune. However, use of ABG has some limitations such as donor side morbidity, limited reserve, and weak mechanical properties. Allografts or xenografts have unique osteoconductive properties and rarely cause disease transmission. As a result of these limitations, synthetic bone graft substitutes are being investigated. Osteoconductive agents such as ceramics, polymers, trabecular metals, and bioactive glass have been employed to provide mechanical support for vascular and bone ingrowth.[4,5] Osteoinductive growth factors, autogenic bone 91

Turhan et al. A comparison of the effects of platelet-rich plasma and demineralized bone matrix on critical bone defects

marrow and mesenchymal root cells promote osteogenesis while demineralized bone matrix (DBM) and platelet-rich plasma (PRP) induce formation of progenitor cells from surrounding tissues. However, each of these substitutes has its own significant limitations and none of them meets full expectations to serve as bone substitute in instance of bone defect.[6] Both PRP and DBM are osteoinductive substitutes that have been proven to yield satisfactory results for fracture healing. [1–3,7–14] A number of growth and differentiation factors are liberated, including platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), insulin-like growth factor-1 (IGF-1), hepatocyte growth factor, platelet factor-4, fibroblast growth factor (FGF), trombospondin-1, osteonectin, and fibronectin via activation of platelets.[15] These factors play an imperative role in intracellular signaling pathways, initiating the production of ultimate proteins essential for cellular proliferation, matrix formation, osteoid production, and the collagen synthesis involved in fracture healing.[16–22] DBM is an organic collagen matrix that includes various types of bone morphogenetic proteins (BMP), which are responsible for its osteoinductive properties. This BMP-rich matrix modulates the differentiation of progenitor cells into osteoprogenitor cells, which are responsible for bone and cartilage formation.[23,24] PRP can be prepared easily with 2-step centrifugation of autogenous blood, and DBM can be obtained commercially. Positive impacts of PRP and DBM alone and in combination with other substitutes are well documented, but no assessment has been made as yet of a combination of PRP and DBM on healing of long bone defects. Based on these findings, the present study evaluated the impact of individual and combined applications of PRP and DBM on fracture healing of critical bone defects. It was hypothesized that allogeneic PRP would have beneficial effect on treatment of segmental bone defects, comparable to DBM. Possibility of agonistic or additive osteoinductive effects of DBM and PRP combination was also investigated.

MATERIALS AND METHODS Animals and Surgical Procedure This experimental study was conducted at Bülent Ecevit University (Zonguldak, Turkey) animal research laboratories, after receiving the approval of the ethics committee for animal research (1564-2599-2011/21). Forty-eight, 9-month-old, male, inbred Wistar albino rats with an average weight of 350 g were used in this study. Twelve rats of similar age and weight were used for PRP preparation. Prior to surgical creation of bone defects, all animals were allowed to acclimate to the laboratory environment for a period of 10 days. All rats were kept in plastic cages with access to food and water ad libidum and screened for common disease. Rats were 92

maintained at 22°C±-2°C environmental temperature in 12 hours light and 12 hours darkness cycle. None of the rats had been subjected to any experiments prior to this study. The rats were randomly divided into 4 groups: 1. Control group (n=12) 2. PRP group (n=12) 3. PRP+DBM group (n=12) 4. DBM group (n=12) Twenty-four hour before surgical procedure, the animals were fasted. A single dose of Iespor (cephazoline sodium, 20 mg/kg; Ibrahim Ethem Ulugay İlaç Sanayi Türk A.Ş., İstanbul, Turkey) was administered to all animals preoperatively. All rats were anesthetized with 50 mg/kg of ketamine hydrochloride (Ketalar; Pfizer Inc., NY, NY, USA), injected intraperitoneally, prior to surgery.[25] Anesthesia was monitored and maintained by a veterinarian during all phases of surgical procedure. Rats were placed in right decubitus and left forearm was shaved. Bone defect of approximately 10-mm (twice the radius of radii) was created in midshaft of the radius with a sharp rib bone knife. Osteotomy site was then irrigated with 0.9% saline, but no attempt was made to resect the periosteum around osteotomy site as this had been retracted with the overlying muscles. Osteotomy site was treated following the protocol for each group. As only the radius had been osteotomized, no fixation was employed, and the animals were able to use both extremities effectively.[26–28] Bone defects in Group 3 (DBM) and Group 4 (DBM+PRP) were filled with approximately 0.3 cc injectable DBM (Ultra DBM Matrix; TissueNet, Inc., Orlando, FL, USA). Immediately after surgery, while rats were still under anesthesia, roentgenograms of the limbs were taken. Fifteen mg/kg of tramadol (Ultramex, Adeka İlaç Kimyasal Ürünler Sanayi ve Ticaret A.Ş., Istanbul, Turkey) was used for postoperative analgesia. Rats were then put into separate cages with no restriction of activities. Parizi et al. proposed that if PRP was injected intraoperatively during the surgical operation, inflammatory agents could destroy the injected PRP and render it potentially ineffective in later stages of healing. [29] Therefore 1 mL of allogeneic PRP was injected percutaneously into bone defects in Group 2 and Group 3 on postoperative third day.

Allogeneic PRP Preparation Four rats per 12 experimental animals (12 exsanguination animals total) were anesthetized with 50 mg/kg of ketamine hydrochloride (Ketalar; Pfizer Inc., NY, NY, USA), injected intraperitoneally, prior to blood collection via intracardiac aspiration after sternotomy. Sterile disposable monovette system (blood collection tubes) and compatible centrifuge machine (Nüve NF 1000R, Nüve Sanayi Malzemeleri Imalat ve Ticaret A.Ş., Ankara, Turkey) was used to prepare PRP. Blood was transferred into blue Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

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capped monovette containing 3.2% sodium citrate (0.5 mL), approximately 30 minutes before injection. Monovette was centrifuged at 1800 rpm for 10 minutes.[16,19] After first centrifugation, 2 layers were clearly visible in monovette. Upper yellow layer consisted of platelet-rich and platelet-poor plasma, while lower red layer consisted of erythrocytes and leukocytes, as has previously been documented.[30] Lower red layer has been reported to be rich in platelets that recently entered the circulation.[31,32] Total plasma consisting of complete upper yellow layer and top 1 to 2 mm of lower red layer was transferred to sterile monovette. After second centrifugation at 4000 rpm for 7 minutes, approximately 0.7 mm at the bottom of the monovette was platelet-rich plasma and upper portion was mostly platelet-poor plasma.[30] Supernatant platelet-poor plasma was collected and removed by pipette. Remaining platelet-rich plasma was then carefully transferred into application injector.

Radiological Analysis After 10 weeks of healing, rats were sacrificed and upper extremities were removed from the corpus in order to obtain optimal anterior-posterior X-ray images. Two orthopedic surgeons who were blinded to group assignments but informed about evaluation method performed radiological assessments. These 2 surgeons were not involved in the present study. Results were scored using the grading scale described by Cook et al. (Table 1).[33]

Histological and Histomorphometrical Analysis Whole specimens were initially fixed in 10% formaldehyde for 2 weeks. During subsequent 2 weeks, samples were placed in 10% ethylenediaminetetraacetic acid solution for decalcification process. Samples were than embedded in paraffin blocks and 5 µm-thick sections were cut through long axis from fractured zone and stained with hematoxylin and eosin for routine light microscope analysis.[34] Pathologist who was blinded to groups and experimental procedure evaluated the specimens with 14-point histological grading scale described by Salkeld et al. (Table 2) to determine quali-

ty of union, appearance and quality of cortical and cancellous bone remodeling, and degree of bone graft incorporation and remodeling.[35]

Statistical Analysis Statistical analysis was performed in the Department of Biostatistics at Bülent Ecevit University Faculty of Medicine using SPSS software, version 18.0 (Customer number: 114094, 2012; SPSS, Inc., Chicago, IL, USA). Descriptive statistics included median (minimum and maximum) values. KruskalWallis analysis of variance was used to compare the groups in terms of radiological and histopathological results. After performing Kruskal-Wallis analysis of variance, Wilcoxon test was performed with Bonferroni correction for paired comparison of groups. Results were expressed within a 95% confidence interval. Significance was defined as p<0.05.

RESULTS One rat from control group did not wake from anesthesia, so total of 47 completed the experiment without major wound or other complication. These 47 rats were sacrificed for radiological and histological assessments.

Radiological Findings Table 3 summarizes radiological evaluation results. In radiological assessment of healing, there were significant differences between control group and PRP group, and PRP group and PRP+DBM combination group, in favor of PRP group (p=0.007). There was no significant difference between control group and PRP+DBM combination group (p=0.354). No obvious cortical bridging was denoted in either control or PRP+DBM groups. There was significant difference between control group and DBM group (p<0.001). There was also significant difference between DBM group and PRP+DBM combination group. PRP group achieved higher scores in radiological assessment. Radiological data also indicated that control group and PRP/DBM combination group displayed similar level of radiological healing (Figure 1a–d).

Table 1. Radiographic grading scale for the degree of healing[33] Description Score No change from immediate postoperative appearance

A slight increase in radiodensity distinguishable from the graft  Recognizable increase in radiodensity, bridging of one cortex with new-bone formation to the graft

Bridging of at least one cortex with material of nonuniform radiodensity, early incorporation of the graft suggested by obscurity of graft borders

Defect bridged on both medial and lateral sides with bone of uniform radiodensity, cut ends of the cortex still visible, graft and new bone not easy to differentiate

Same as grade 3, with at least one of four cortices obscured by new bone

Defect bridged by uniform new bone, cut ends of cortex no longer distinguishable, graft no longer visible

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Table 2. Histological grading scale for the degree of healing[35] Criteria Description

Score

Quality of union

No sign of fibrous or other union

Fibrous union

Fibrocartilaginous union or cartilage union

Mineralizing cartilage and bone union

Bone union

Cortex development and

No cortex formed

remodeling

Formation of new bone along exterior borders

Recognizable formation of both the outer cortex border and the medullary space

Cortices formed but incomplete bridging

Complete formation of cortices with bridging of defect

Bone-graft incorporation and new bone formation No new bone, all or most of graft Visible Graft material present, no incorporation, and no new-bone formation

Graft present, some incorporation with new bone formation, and small

amount of new bone

Graft present, some incorporation with new bone formation, and moderate

amount of new bone

Decreasing graft, increasing new bone

Graft present, some incorporation with new-bone formation continuous

with host bone, and early remodeling changes in new bone

Decreased amount of graft (compared with grade 3), good graft

incorporation, and ample new bone

3 4

Less amount of graft still visible (compared with grade 4), good incorporation

of graft and new bone with host and ample new bone

No graft visible, extensive new bone

Difficult to differentiate graft from new bone, excellent incorporation, and

advanced remodeling of new bone with graft and host

Histopathological Findings Histopathological evaluation was based on the following parameters: 1) quality of union, 2) cortical development and remodeling, and 3) new bone formation.

(a)

(b)

There was a significant difference between control group and PRP group in terms of quality of union (p<0.001). Endochondral ossification in defect site was most clearly seen in PRP group. There was significant difference between control group

(c)

(d)

Figure 1. Radiological samples of the groups (a) Control group - No change from immediate postoperative appearance. (b) PRP group - Defect bridged by uniform new bone, cut ends of cortex no longer distinguishable. (c) PRP/DBM group - Recognizable increase in radiodensity, bridging of cortex with new-bone formation to the graft. (d) DBM group - Defect bridged on both medial and lateral sides with bone of uniform radiodensity, cut end of distal cortex still visible.

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Table 3. Radiological assessment scoring of the experiment groups according to Cook criteria Cook Score

Group 1 Control (n=11)

Group 2 PRP (n=12)

Group 3 PRP+DBM (n=12)

Group 4 DBM (n=12)

Minimum 0 2 2 2 Maximum 4 6 5 6 Median 2 4 2 3 PRP: Platelet-rich plasma; DBM: Demineralized bone matrix.

Table 4. Histopathological evaluation results according to Salkeld scoring method Criteria

Control PRP PRP+DBM DBM

Quality of union

Median

Minimum 1 2

Maximum 2 4

Cortex development and remodeling

Median

Minimum 0 1

Maximum 2 4

New bone formation

Median

Minimum 1 1

Maximum 2 4

3 2.5

PRP: Platelet-rich plasma; DBM: Demineralized bone matrix.

and PRP+DBM combination group, while no difference was found between PRP group and DBM group (p=768). There was significant difference between control group and DBM group (p<0.001): fibrous union was greatest in control group. There was no significant difference between PRP group and PRP+DBM combination group (p=0.456). Although Salkeld scores were slightly higher in PRP+DBM combination group, there was no statistically significant difference between combination group and DBM group (p=0.874). Significant difference was found between PRP group and PRP+DBM group in terms of cortical development and remodeling that favored PRP group (p<0.001). There was also statistically significant difference between the PRP+DBM combination group and DBM group, with greater healing seen in DBM group (p=0.010). In addition, there was significant difference found between control group and PRP group (p<0.001). There was no significant difference between control group and PRP+DBM group (p=0.624). Cortex development remodeling was significantly superior in DBM group than control group (p<0.001). No significant difference was determined between PRP group and DBM group (p=0.323). In terms of new bone formation, rats in control group had significantly lower scores compared with PRP, PRP+DBM combination, and DBM groups (p=0.334), and there was no significant difference between the experiment groups Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

(p=0.063). Summary of histopathological findings is provided in Table 4. Significant microscopic findings of the groups are provided in Figure 2aâ&#x20AC;&#x201C;d.

DISCUSSION Segmental bone defects continue to be a major problem in the practice of orthopedics and traumatology. There is still no universally accepted treatment standard for this problem. The current therapies are disputable in terms of morbidity and cost/benefit ratio, and it is obvious that new approaches are required. The present study evaluated effects of PRP application to healing of segmental bone defects, what we consider to be a new approach in the treatment of segmental bone defects. This research demonstrated that PRP is as efficient as DBM based on radiological and histopathological evidence of healing in segmental bone defects; however, same effects were not observed with the combined use of PRP and DBM. For many years, researchers working with bone tissue have been investigating methods and bone grafts that would accelerate fracture healing and promote rapid recovery of bone defects or that could be used in the reconstruction of larger defects to achieve union and filling of the defect with fewer complications. Although there was success in these studies, 95

Turhan et al. A comparison of the effects of platelet-rich plasma and demineralized bone matrix on critical bone defects

(a)

(b)

(c)

(d)

Figure 2. (a) Control group - Arrow indicates bone defect region filled with fibrous tissue (H&E; original magnification x40). (b) PRP group - The defect site in PRP group filled with cartilaginous tissue (black arrow) (H&E; original magnification x40). High power view of the inset reveals periosteal new bone, bridging, and cortex development (H&E; original magnification x100). (c) PRP/DBM group - The osteotomy site filled with fibrocartilaginous tissue without cortex formation (black arrow) (H&E; original magnification x40). (d) DBM group - The osteotomy site filled with cartilaginous tissue with minimal new bone formation (black arrow) (H&E; original magnification x40).

these methods are not commonly used in clinical practice.[1,2,4– 6] It was realized that bone metabolism is regulated through various chemical and metabolic pathways, and that certain peptides (growth factors) are released from platelets, macrophages, and fibroblasts during the union of fractures. These proteins are known to organize delicate processes such as proliferation, differentiation, migration, and resorption in the healing of fractures. Studies have focused on the production of these growth factors with recent advances in recombinant gene technology. The main focus of these studies has been BMPs from the TGF family, and TGF-β, PDGF, VEGF, FGF, and IGF have been shown to have favorable effects on bone healing. Experimental studies have demonstrated the favorable effects of these molecules on bone healing; however, these substances have not been introduced into clinical practice due to high costs of recombinant gene technology.[36–38] Many growth factors including PDGF, VEGF, TGF β1-2, and FGF are deposited in the granules of circulating platelets, and these substances are released in response to various stimulations.[39] In light of these data, the present study aimed to 96

extract these growth factors by centrifugation of allogeneic venous blood in order to reduce the costs. PRP suspension prepared from venous blood contains many growth factors as well as fibrinogen, and application to fracture site allows direct activity to occur. Experimental studies with PRP are required before the introduction of PRP into clinical practice due to the fact that available studies either lack control groups or they are insufficient. Among these limited studies, Marx et al. compared autologous bone graft alone with autologous bone graft plus PRP application and noted an increase in bone formation and bone density, which they attributed to PDGF and TGF-β.[18,40– 42] Anitua et al. injected PRP into empty cavity after tooth extraction and reported an increase in both epithelialization and bone density.[9] Aghaloo and Butterfield study of bone grafts and PRP application failed to show superiority of PRP; however, there are also studies showing accelerated advancement of bone tissue when PRP is used with the grafts used in dentistry for osteointegration, and there are also reports on successful outcomes in maxillary arthroplasty.[8,32,43] Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

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PRP has been used together with autograft and hydroxyapatite in patients undergoing lumbar spinal fusion, and both favorable and unfavorable outcomes have been reported.[44,45] Siebrecht et al. showed that PRP increased tissue ingrowth and ossification inside porous hydroxyapatite, and they also reported increased tensile strength and callus of Achilles tendon of rats after PRP application.[42] Use of plasma-rich plasma was recommended in arthroscopic surgery after demonstration of favorable effects on ligaments.[36] Nagata et al. compared autograft and autograft-PRP combination after creating critically large calvarial bone defect in rabbits, and they noted significantly faster ossification at 4 weeks in the autograft-PRP group; however, outcomes at 12 weeks were similar in the 2 groups.[45] Cheng et al. evaluated outcomes of PRP, autograft, and PRP-bone marrow-derived stromal cell mixture on critically large calvarial bone defect in rabbits, and reported minimum repair in PRP group and significantly higher new bone formation in bone marrow-derived stromal cell plus PRP group.[46] Gumieiro et al. compared PRP and control groups using monocortical defect model in irradiated rat tibia and reported statistically significant outcomes in terms of ossification.[47] In the present study we also questioned the possibility of agonistic effects of DBM and PRP on fracture healing. DBM was selected for its osteoinductive effects based on BMPs, while PRP lacks these proteins. Our study revealed that both PRP and DBM had favorable effects on fracture healing when applied separately, but combination of these methods did not provide additional benefits. This finding was also supported by a study conducted by Ranly et al. on athymic rats in which DBM embedded in gastrocnemius muscle was combined with PRP that was and was not activated by thrombin, and ossification was evaluated at days 14, 28, and 56 after application.[48] Combination of PRP and DBM did not display any additional benefits to condrogenesis over DBM alone at day 14; however, the combination was associated with induction of osteogenesis and higher production of new bone islets and new bone formation at days 28 and 56. On the other hand, thrombin-activated PRP had inhibitor effect on DBM and inhibited both condrogenesis and osteogenesis. In our study, PRP was kept in citrated tubes after preparation and activated with citrate. In a study conducted by BoHan et al., combination of DBM and PRP was implanted in muscle tissue to examine ectopic bone formation within the connective tissue. PRP produces different responses in different tissue. Their study evaluated the fracture healing process when PRP was used alone and in combination with DBM.They concluded that PRP significantly increased in vivo DBM osteoinductivity only when used without thrombin activation.[49] In the present study we demonstrated that citrate-activated PRP can also inhibit osteoinductive effect of DBM. In another study by Ranly et al. in immunosuppressed rats, Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

implants prepared with DBM and various doses of PRP were inserted into leg muscles of rats, and they evaluated osteoinduction, new bone and cartilage formation, and if PRP and implanted DBM played a modulator role in osteoinduction by dissecting the tissue at days 14, 28, and 56.[50] The examination at day 14 showed that amount of cartilage decreased with increasing PRP doses, and in addition, dissection performed at days 28 and 56 showed that PRP delayed new bone formation and resorption of the graft in a dose-dependent manner. In their study, both PRP and DBM were found to be effective in the healing of fractures; however, combined use of these substances did not have additional benefit over single use. This study evaluated new bone formation inside muscle tissue and not new bone formation in the fracture line. PRP results are different in each model, and exogenous PRP applied to the fracture line may accelerate the healing of fracture together with other osteogenic proteins. PRP applied in the present study was released from implants in the early inflammatory phase of osteoinduction in the soft tissue, whereas later application of PRP to the fracture site induces PRP production from the osteoblasts as if it were a paracrine factor. Due to technical difficulties the dose of PRP was not adjusted in our study, and the response to the healing of segmental defect was evaluated after application of PRP to the bone defect One of the limitations of our study was that dose standardization for PRP and DBM was not possible due to technical drawbacks. This study evaluated 2 phases, namely the initial and final phases, and interim phases were not evaluated. In addition, biomechanical studies regarded as optimal for evaluating the healing of fractures were not appropriate in rat bone defect model and therefore could not be performed. In this study, withdrawal of autologous blood from each rat for PRP preparation was not feasible because of the risk of sample loss due to blood collection, and therefore, PRP was prepared from blood withdrawn from 4 other rats though intracardiac route at the beginning of the study and allogeneic PRP was used. Burhoe and Moore demonstrated that there are subgroups of blood in rats, although there is no blood type; however, this was not taken into consideration due to the fact that these subgroups do not exhibit immunogenicity against each other.[51,52]

Conclusion Radiological and histological assessment in this study revealed similar results for PRP and DBM, and the combination of these 2 did not provide additional benefits. As an autologous product, absence of any risk for the transmission of infection, absence of allergic reactions, easy preparation in the operating room, and lack of additional costs can be regarded as advantages of PRP over commercial DBM products. The present study was an experimental animal study, and our literature search revealed that this was the first study to eval97

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uate use of PRP and DBM combination in bone tissue. PRP is currently used in muscle-tendon injuries and similar studies can guide future prospects for the use of PRP to accelerate healing in segmental bone defects. This research demonstrated that PRP is as efficient as DBM in the treatment of segmental bone defects, and similar results in in vivo tests and biomechanical studies may lead to the introduction of PRP therapy to clinical practice in the treatment of segmental bone defects. Conflict of interest: None declared.

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bone-healing and repair. J Bone Joint Surg Am 2008;90 Suppl 1:85–91. 17. Pape HC, Evans A, Kobbe P. Autologous bone graft: properties and techniques. J Orthop Trauma 2010;24 Suppl 1:36–40. 18. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:638–46. 19. Anitua E, Sánchez M, Orive G, Andía I. Shedding light in the controversial terminology for platelet rich products. J Biomed Mater Res A 2009;90:1262–3. 20. Dohan Ehrenfest DM, Bielecki T, Del Corso M, Inchingolo F, Sammartino G. Shedding light in the controversial terminology for platelet-rich products: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), plateletleukocyte gel (PLG), preparation rich in growth factors (PRGF), classification and commercialism. J Biomed Mater Res A 2010;95:1280–2. 21. Mora R, Pedrotti L, Battista Galli G. Failure of Union. Nonunion of the long bones: diagnosis and treatment with compression: distraction techniques. Springer, Italy 2006. 22. Marsell R, Einhorn TA. Emerging bone healing therapies. J Orthop Trauma 2010;24 Suppl 1:4–8. 23. Urist MR, Silverman BF, Büring K, Dubuc FL, Rosenberg JM. The bone induction principle. Clin Orthop Relat Res 1967;53:243–83. 24. Jones CB. Biological basis of fracture healing. J Orthop Trauma 2005;19(10 Suppl):1–3. 25. Wixson SK, Smiler KL Anesthesia and analgesia in rodents. In: Kohn DF, Wixson SK, White WJ, Benson GJ (eds) Anesthesia and analgesia in laboratory animals. Academic, San Diego 1998. p. 173–84. 26. Alper G, Bernick S, Yazdi M, Nimni ME. Osteogenesis in bone defects in rats: the effects of hydroxyapatite and demineralized bone matrix. Am J Med Sci 1989;298:371–6. 27. Ozturk AM, Cila E, Kanatli U, Isik I, Senkoylu A, Uzunok D, et al. Treatment of segmental bone defects in rats by the stimulation of bone marrow osteo-progenitor cells with prostaglandin E2. Int Orthop 2005;29:73–7. 28. Oztürk A, Yetkin H, Memis L, Cila E, Bolukbasi S, Gemalmaz C. Demineralized bone matrix and hydroxyapatite/tri-calcium phosphate mixture for bone healing in rats. Int Orthop 2006;30:147–52. 29. Parizi AM, Oryan A, Shafiei-Sarvestani Z, Bigham AS. Human platelet rich plasma plus Persian Gulf coral effects on experimental bone healing in rabbit model: radiological, histological, macroscopical and biomechanical evaluation. J Mater Sci Mater Med 2012;23:473–83. 30. Özdemir B, Kurtiş B, Tüter G, Sengüven B, Tokman B, Pınar-Özdemir S, et al. Double-application of platelet-rich plasma on bone healing in rabbits. Med Oral Patol Oral Cir Bucal 2012;17:171–7. 31. Lekovic V, Camargo PM, Weinlaender M, Vasilic N, Kenney EB. Comparison of platelet-rich plasma, bovine porous bone mineral, and guided tissue regeneration versus platelet-rich plasma and bovine porous bone mineral in the treatment of intrabony defects: a reentry study. J Periodontol 2002;73:198–205. 32. Camargo PM, Lekovic V, Weinlaender M, Vasilic N, Madzarevic M, Kenney EB. Platelet-rich plasma and bovine porous bone mineral combined with guided tissue regeneration in the treatment of intrabony defects in humans. J Periodontal Res 2002;37:300–6. 33. Cook SD, Baffes GC, Wolfe MW, Sampath TK, Rueger DC. Recombinant human bone morphogenetic protein-7 induces healing in a canine long-bone segmental defect model. Clin Orthop Relat Res 1994;301:302–12. 34. Gruber HE, Stasky AA. Histologic study in orthopaedic animal research. In: An YH, Friedman RJ (eds) Animal models in orthopaedic research. CRC Press, Boca Raton, 1999. p. 115–37. 35. Salkeld SL, Patron LP, Barrack RL, Cook SD. The effect of osteogenic protein-1 on the healing of segmental bone defects treated with autograft or allograft bone. J Bone Joint Surg Am 2001;83:803–16.

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Turhan et al. A comparison of the effects of platelet-rich plasma and demineralized bone matrix on critical bone defects 36. Boden SD. Bioactive factors for bone tissue engineering. Clin Orthop Relat Res 1999;(367 Suppl):84–94. 37. Khan SN, Bostrom MP, Lane JM. Bone growth factors. Orthop Clin North Am 2000;31:375–88. 38. Mathes SJ: Repair and grafting of bone. In: Plastic surgery. 2nd ed. Saundes Elsevier Inc, Philadelphia 2006;639–718. 39. Malhotra A, Pelletier MH, Yu Y, Walsh WR. Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes. Arch Orthop Trauma Surg 2013;133:153–65. 40. Thor A, Franke-Stenport V, Johansson CB, Rasmusson L. Early bone formation in human bone grafts treated with platelet-rich plasma: preliminary histomorphometric results. Int J Oral Maxillofac Surg 2007;36:1164–71. 41. Castro FP Jr. Role of activated growth factors in lumbar spinal fusions. J Spinal Disord Tech 2004;17:380–4. 42. Siebrecht MA, De Rooij PP, Arm DM, Olsson ML, Aspenberg P. Platelet concentrate increases bone ingrowth into porous hydroxyapatite. Orthopedics 2002;25:169–72. 43. Butterfield KJ, Bennett J, Gronowicz G, Adams D. Effect of platelet-rich plasma with autogenous bone graft for maxillary sinus augmentation in a rabbit model. J Oral Maxillofac Surg 2005;63:370–6. 44. Kevy SV, Jacobson MS. Comparison of methods for point of care preparation of autologous platelet gel. J Extra Corpor Technol 2004;36:28–35. 45. Nagata MJ, Melo LG, Messora MR, Bomfim SR, Fucini SE, Garcia VG,

et al. Effect of platelet-rich plasma on bone healing of autogenous bone grafts in critical-size defects. J Clin Periodontol 2009;36:775–83. 46. Cheng X, Lei D, Mao T, Yang S, Chen F, Wu W. Repair of critical bone defects with injectable platelet rich plasma/bone marrow-derived stromal cells composite: experimental study in rabbits Ulus Travma Acil Cerrahi Derg 2008;14:87–95. 47. Gumieiro EH, Abrahão M, Jahn RS, Segretto H, Alves MT, Nannmark U, et al. Platelet-rich plasma in bone repair of irradiated tibiae of Wistar rats. Acta Cir Bras 2010;25:257–63. 48. Ranly DM, McMillan J, Keller T, Lohmann CH, Meunch T, Cochran DL, et al. Platelet-derived growth factor inhibits demineralized bone matrix-induced intramuscular cartilage and bone formation. A study of immunocompromised mice. J Bone Joint Surg Am. 2005;87:2052–64. 49. Han B, Woodell-May J, Ponticiello M, Yang Z, Nimni M. The effect of thrombin activation of platelet-rich plasma on demineralized bone matrix osteoinductivity. J Bone Joint Surg Am 2009;91:1459–70. 50. Ranly DM, Lohmann CH, Andreacchio D, Boyan BD, Schwartz Z. Platelet-rich plasma inhibits demineralized bone matrix-induced bone formation in nude mice. J Bone Joint Surg Am 2007;89:139–47. 51. Burhoe SO. Blood Groups of the Rat (Rattus Norvegicus) and Their Inheritance. Proc Natl Acad Sci U S A 1947;33:102–9. 52. Moore DM. Hematology of rat (Rattus norvegicus). In: Feldman BF, Zinkl JG, Jain NC, editors. Schalm’s Veterinary Hematology. Lippincott Williams&Wilkins; 2000. p. 1210.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sıçan segmenter kemik defekti modelinde trombositten zenginleştirilmiş plazmanın ve demineralize kemik matriksinin kırık iyileşmesi üzerine etkisinin karşılaştırılması Dr. Egemen Turhan,1 Dr. Mustafa Kemal Akça,2 Dr. Ahmet Bayar,3 Dr. Murat Songür,3 Dr. Selçuk Keser,3 Dr. Mahmut Nedim Doral1 Hacettepe Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Ankara Bandırma Devlet Hastanesi, Ortopedi ve Travmatoloji Kliniği, Balıkesir 3 Bülent Ecevit Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Zonguldak 1 2

AMAÇ: Kırık iyileşmesinin gecikmesi ortopedi ve travmatoloji kliniğinin başlıca sorunlarından biridir ve özellikle defektif kemiklerde iyileşme gecikmesi veya kaynamama görülmektedir. Bu çalışmamızda defektif kemik dokunun iyileşmesinde ticari bir ürün olan ve klinik pratikte greft olarak sıkça kullanılan demineralize kemik matriks (DBM) ve kandan üretilen ve birçok büyüme faktörü içeren trombositten zengin plazmanın (TZP) defektif kırık modelinde kırık iyileşmesi üzerine etkileri incelendi. GEREÇ VE YÖNTEM: Kırk sekiz adet Albino-Wistar tipi sıçan 12’li gruplar halinde dört gruba ayrıldı ve sağ önkollarında dorsal insizyon ile radiuslarına ulaşılarak radiuslarında diafizden kemik çapının iki katı kadar defektif kemik modeli oluşturuldu. Dört adet sıçan ise işlem öncesi sakrifiye edilerek intrakardiak kanları alındı ve uygun santrifüj işlemleri sonrasında TZP hazırlandı. İlk grup kontrol grubu olarak ayrıldı ve kostatom ile oluşturulan kemik defekti olduğu gibi bırakılarak primer kapatıldı. İkinci grupta defekt alanı TZP ile greftlendi ve primer kapatıldı. Üçüncü grupta defektif alan TZP+DKM kombinasyonu ile greftlenirken son grupta defekt alanı DKM ile greftlendi ve primer kapatıldı. İşlem sonrası onuncu haftada sıçanlar yüksek doz anestezik madde ile sakrifiye edilerek sağ önkolları diseke edildi, defekt alanı radyolojik ve histopatolojik parametreler ile incelendi. BULGULAR: Radyolojik olarak incelendiğinde TZP grubunda ve daha sonrada DKM grubunda kemikleşmenin daha iyi olduğu gözlendi. Histopatolojik inceleme sonucunda ise kaynama kalitesi açısından kontrol grubuna göre diğer grupların iyi olduğu fakat TZP grubunda kaynama kalitesinin diğer çalışma gruplarına göre daha iyi olduğu görüldü. Korteks gelişimi ve yeniden şekillenme açısından incelendiğinde TZP grunbunda sonuçların daha iyi olduğu ve yeni kemik oluşumu açısından değerlendirildiğinde ise de TZP, TZP-DKM ve DKM gruplarının kontrol grubuna göre daha iyi olduğu gözlendi. TARTIŞMA: Çalışmamız TZP’nin defektif kemik iyileşmesi üzerine olumlu etkilerini gösteren in vitro şartlarda yapılmış bir hayvan deneyidir. Bu bulgular eşliğinde değerlendirldiğinde defektif kemik iyileşmesinde TZP ve DKM’nin etkisinin aynı olduğu fakat birlikte kullanımında birbirlerinin etkilerini arttırmadığı kanaatine varılmıştır. Trombositten zengin plazmanın otolog kandan ve ameliyathane şartlarında dahi üretebiliyor olması, ek bir maliyet ve ek morbiditeye neden olmaması nedeniyle ticari bir ürün olan DKM’nin bir alternatifi olabileceğini düşünmekteyiz. Anahtar sözcükler: Demineralize kemik matriks, plazma, segmenter kemik defekti; trombosit. Ulus Travma Acil Cerrahi Derg 2017;23(2):91–99

doi: 10.5505/tjtes.2016.68249

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EXPERIMENTAL STUDY

Effect of N-acetylcysteine on neutrophil functions during experimental acute pancreatitis Kemal Atayoğlu, M.D.,1 Günay Gürleyik, M.D.,1 Gülderen Demirel, M.D.,2 Selvinaz Özkara, M.D.3 1

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

Department of Immunology, Yeditepe University Faculty of Medicine, İstanbul-Turkey

Department of Pathology Laboratory, Haydarpaşa Numune Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: Systemic inflammatory responses and extrapancreatic vital organ impairment are mediated by activated neutrophil functions and products, such as oxygen-derived free radicals, in patients with acute pancreatitis (AP). The present study is an examination of effects of an antioxidant, N-acetylcysteine (NAC), on local and systemic histopathological changes and neutrophil functions during AP. METHODS: This experimental study was performed on 24 Wistar albino rats equally divided into 3 groups: Group 1 comprised sham laparotomy, Group 2 had AP induced with taurocholate infusion, and Group 3 consisted of AP with NAC treatment. Histopathological features in pancreas, kidney, and lung tissues were examined for local and systemic changes during AP. Neutrophil functions were evaluated using flow cytometry. RESULTS: Serum levels of pancreatic enzymes were elevated, and histopathological parameters showed acinar cell damage and pancreatic tissue necrosis in the 2 groups with AP. Severe histopathological changes were found in pulmonary and renal tissues, and flow cytometry results indicated defective neutrophil functions in the group with AP alone. NAC treatment significantly ameliorated phagocytosis, chemotaxis, and opsonization of neutrophils (p<0.05). NAC treatment also ameliorated systemic changes in pulmonary and renal tissue damage in all microscopic parameters (p<0.05). CONCLUSION: Uncontrolled and defective neutrophil functions could provoke severe systemic inflammatory responses. In addition to local inflammation and necrosis, severe systemic responses and histopathological changes in extrapancreatic vital organs occur during AP. Treatment with antioxidant NAC significantly reverses detrimental systemic responses in extrapancreatic vital organs by significantly ameliorating neutrophil functions despite ongoing AP. Keywords: Flow cytometry; leucocytes; pancreatitis; systemic inflammatory response.

INTRODUCTION Acute pancreatitis (AP) is an acute inflammatory condition that is thought to be due to activation of enzymes in pancreatic acinar cells, with inflammation spreading into surrounding tissues. It is mediated by proinflammatory factors released from acinar cells and leucocytes infiltrating in glandular tissue.

Address for correspondence: Günay Gürleyik, M.D. Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 216 - 542 32 32 E-mail: ggurleyik@yahoo.com Qucik Response Code

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Previous reports have suggested that pathogenesis of AP is associated with oxidative stress.[1–3] Activation of circulating leucocytes and their subsequent interaction with endothelial vascular cells results in local, initial oxidative stress and production of inflammatory mediators within the pancreas, leading to cell damage.[4] Sanfey et al.[5] designed an experimental model in which capillary injury developing due to increased permeability was reported to be commonly observed phase in pathogenesis of AP. Oxygen-derived free radicals (OFR) were shown to have been predominating determinants of this stage. Many studies have been conducted to investigate role of oxidative stress in different experimental models of AP. OFR production overwhelms cellular antioxidant defense systems, and thus, oxidative stress develops. This leads to disturbances in cellular homeostasis because these OFR can cause biochemical and functional alterations at different cellular levels.[4,6] Local pancreatic inflammation and necrosis triggers activation of neutrophils that produce and secrete cytokines, and OFRs create systemic inflammatory responses. Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Atayoğlu et al. Effect of N-acetylcysteine on neutrophil functions during experimental acute pancreatitis

An end result of this systemic response may be vital organ dysfunction and failure.

First aim of the present study was to investigate effects of NAC in the course of experimental AP. In addition, pathway for pathogenesis via neutrophil functions was examined based on histopathological changes in the pancreas.

biliopancreatic duct (BPD). In Groups 2 and 3, the duodenal wall was punctured at anti-mesenteric side with 24-G catheter (Introcan-W; B. Braun Medical, Inc., Bethlehem, PA, USA), and catheter was advanced into the common BPD. Leakage of sodium taurocholate was prevented by temporary ligature of the proximal bile duct with 4/0 silk (Mersilk; Ethicon, Inc., Somerville, NJ, USA), while the distal bile duct was occluded with microvessel clip. Sodium taurocholate 5% (0.15 mg/kg; Sigma-Aldrich, Corp., St. Louis, MO, USA) was infused into the common BPD via catheter. After infusion, microvessel clip, injection needle, and silk ligature were removed, reconstituting physiological flow of bile. Puncture site at the duodenal wall was closed with 5/0 Prolene suture (Ethicon, Inc., Somerville, NJ, USA), and the abdomen was closed with 3/0 silk.

MATERIALS AND METHODS

Sample Collection and Laboratory Analyses

All experiments were performed in accordance with the National Institutes of Health guidelines for the care and handling of animals. This study was approved by the animal ethics commitee of Haydarpaşa Numune Training and Research Hospital.

After 72 hours, rats were anesthetized with sodium pentobarbital. Blood samples were collected by cardiac puncture. All animals were sacrificed with excessive anesthesia, and the pancreas, lungs and kidneys were excised for histopathological examination.

N-acetylcysteine (NAC) is well-known free radical scavenger capable of stimulating glutathione synthesis. It has been investigated as an antioxidant compound in various experimental studies.[7,8] Various antioxidants have no useful effects in taurocholate-induced pancreatitis, but NAC was found to be beneficial. Therefore, OFR formation may be an important factor in taurocholate-induced pancreatitis.[9]

Twenty-four female Wistar albino rats (250–300 g) were used in this study. The animals were housed in metabolic cages with free access to standard food and water at controlled temperature with 12-hour light-dark cycles during entire study, beginning 1 week prior to experimental stage.

Experimental Groups A total of 24 rats were randomly divided into 3 groups. Group 1 [(G1); n=8; sham group]: Only laparotomy was performed. One mL 0.9% saline was intraperitoneally injected at postoperative days 1 and 2. Group 2 [(G2); n=8; pancreatitis group]: Pancreatitis was induced by sodium taurocholate infusion. One mL 0.9% saline was intraperitoneally injected at postoperative days 1 and 2. Group 3 [(G3); n=8; pancreatitis and NAC treatment group]: Pancreatitis was induced by sodium taurocholate infusion, and 200 mg/kg NAC (Asist 300 mg, 10%; Bilim Pharmaceuticals, Istanbul, Turkey) in 1 mL 0.9% saline was intraperitoneally injected at postoperative days 1 and 2.

Operative Procedure According to previous experimental studies,[10] AP was induced by retrograde infusion of sodium taurocholate into the common bile duct with surgical techniques. Anesthesia was induced via intraperitoneal injection of 50 mg/kg of ketamine hydrochloride (Ketalar; Pfizer, Inc., NY, NY, USA) and 10 mg xylazine hydrochloride (2%, 20 mg/mL; Alfasan International B.V., Woerden, The Netherlands). All groups underwent median laparotomy to manipulate the duodenum and common Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Biochemical Analyses Serum amylase and lipase levels were measured using automated analyzer.

Histopathological Evaluation Samples of pancreatic, pulmonary, and renal tissue were collected for histopathological examination. Relevant specimens were fixed in 10% formalin solution. Formalin-fixed tissues were embedded in paraffin, and 3 to 5 µm sections were cut and stained with hematoxylin and eosin to be evaluated by light microscopy. Injury in the pancreas was scored by recording number of lobes affected according to several criteria, including edema, hemorrhage, leucocyte infiltration, acinar necrosis, peripancreatic fat necrosis, fibrosis, and acinar vacuolization. Injury in the lungs was scored with respect to intraalveolar hemorrhage, parenchymatous congestion, edema, and inflammation. Injury in the kidneys was scored for interstitial hemorrhage, vacuolization in tubular epithelium, and epithelial necrosis. Each criterion was graded on scale of 0 to 3.

Neutrophil Function Evaluation In assessment of neutrophil functions, phagocytosis, oxidative burst, opsonization, and chemotaxis tests were evaluated using flow cytometry. Dihydrorhodamine 123 (DHR 123) dye (Invitrogen; Thermo Fisher Scientific, Inc., Waltham, MA USA) was used to measure mitochondrial responses to different stimulants: Escherichia coli for phagocytosis, C3b for opsonization, N-Formylmethionyl-leucyl-phenylalanine for chemotaxis, and phorbol 12-myristate 13-acetate for oxidative burst. Neutrophils were obtained by layering 1:1 saline-diluted whole blood onto Ficoll (Sigma-Aldrich Corp., 101

Atayoğlu et al. Effect of N-acetylcysteine on neutrophil functions during experimental acute pancreatitis

Figure 1. Microscopic image. Histopathology of the pancreas from Group 2 (pancreatitis) revealing inflammatory cell infiltration creating significant acinar and fat necrosis (hematoxylin and eosin stain x40).

Figure 2. Microscopic image. Histopathology of the pancreas from Group 3 (pancreatitis and N-acetylcysteine treatment) revealing peripancreatic area of fat necrosis (hematoxylin and eosin stain x100).

St. Louis, MO, USA) and left at room temperature for 40 minutes for density separation by gravity. Upper 500 µL was collected, and each group of samples was run in parallel with healthy rat sample as control. After stimulants were added to granulocytes, measurements of fluorescence were completed at 0 and 20 minutes using BD FACSCalibur flow cytometer (BD BioSciences, Inc., San Jose, CA, USA). Daily calibration and quality control of the system was performed with BD CaliBrite beads (BD BioSciences, Inc., San Jose, CA, USA). Forward scatter/side scatter gram was used for identification and gating of granulocytes and FL1 (green fluorescence) histogram was used to observe fluorescence changes. For each tube, 2500 granulocytes were counted. Index value for each test was obtained by dividing test sample mean fluorescence channel value by control sample.

ware, version 15.0 (IBM, Corp., Armonk, NY, USA). Comparison of mean values of groups for statistical analysis as well as histopathological scores was performed using Kruskal-Wallis test, whereas dual comparisons were performed using MannWhitney U test. Value of p<0.05 was considered statistically significant.

Statistical Methods All statistical measurements were performed using SPSS soft-

RESULTS Biochemical Findings Serum amylase and lipase levels were significantly higher in both AP groups (G2 and G3) compared with sham group (G1). These levels were significantly lower in NAC-treated group (G3) than group with AP alone (G2).

Local (Pancreatic) Histopathological Changes Polymorphonuclear leucocyte (PNL) infiltration was elevated in both pancreatitis groups. NAC treatment slightly, but not

Table 1. Results of histopathological analysis of pancreatic tissue in study groups Pathology

Group 1 (G1)

Group 2 (G2)

Group 3 (G3)

Control

Acute pancreatitis

Acute pancreatitis+NAC

Means1 G1

Grade

0 1 2 3 0 1 2 3 0 1 2 3

Edema

7 1 – – – 3 2 3 – 5 3 – 0.13 2* 1.38*

Hemorrhage

4 4 – – – 4 1 3 – 3 4 1 0.50 1.88 1.5

Leukocyte infiltration

8 – – – – 4 4 – – 5 3 – 0 1.5 1.38

Acinar necrosis

8 – – – – – 4 4 – 2 3 3 0 2.5 2.13

Peripancreatic fat necrosis 8 – – – – 2 4 2 – 2 4 2 0

Fibrosis

8 – – – – 7 1 – 1 4 3 – 0 1.13 1.25

Acinar vacuolization

8 – – – – – 6 2 – 3 2 3 0 2.25 2

Comparison between G2 and G3 results: No changes was significant (p>0.05) except edema (*p<0.05). NAC: N-acetylcysteine.

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significantly, reduced leucocyte infiltration. Significant acinar and fat necrosis was histopathologically observed in AP groups (Figure 1). Fat necrosis was not reduced with NAC treatment (Figure 2). All microscopic findings were slightly, but not significantly, reduced by NAC treatment (p>0.05). Edema was the only microscopic finding for which NAC treatment provided significant reduction (Table 1).

Systemic Histopathological Changes Significant detrimental histological changes were found in

pulmonary tissue of animals with AP compared with sham group. NAC treatment significantly decreased damage, such as congestion, edema, inflammation, and intra-alveolar hemorrhage, in the pulmonary tissue, compared with group with AP alone (Table 2). Significant detrimental changes were also observed in renal tissue of animals with AP compared with sham group. NAC treatment significantly ameliorated renal histology compared with group with AP alone (Table 3).

Table 2. Results of histopathological analysis of pulmonary tissue in study groups

Group 1 (G1)

Group 2 (G2)

Group 3 (G3)

Control

Acute pancreatitis

Acute pancreatitis+NAC

Pathology

Means1 G1

G2* G3*

Grade

0 1 2 3 0 1 2 3 0 1 2 3

Congestion

3 4 1 – – 2 4 2 – 6 2 – 0.75 2 1.25

Edema

7 1 – – – 3 4 1 2 6 – – 0.13 1.75 0.75

Inflammation

4 4 – – – 2 4 2 – 5 3 – 0.50 2 1.38

Intra-alveolar hemorrhage 5 3 – – – 1 3 4 – 4 4 – 0.38 2.38 1.50 Comparison between G2 and G3 results: All changes were significant (*p<0.05). NAC: N-acetylcysteine.

Table 3. Results of histopathological analysis of renal tissue in study groups

Group 1 (G1)

Group 2 (G2)

Group 3 (G3)

Control

Acute pancreatitis

Acute pancreatitis+NAC

Pathology

Means1 G1

G2* G3*

Grade

0 1 2 3 0 1 2 3 0 1 2 3

Interstitial hemorrhage

6 2 – – – 3 4 1 3 4 1 – 0.25 1.75 0.75

Vacuolization in tubular epithelium

4 4 – – – – 7 1 2 4 2 – 0.50 2.13 1.0

Necrosis in tubular epithelium

6 2 – – – 1 6 1 1 4 3 – 0.25 2 1.25

Comparison between G2 and G3 results: All changes were significant (*p<0.05). NAC: N-acetylcysteine.

Table 4. Mean values of neutrophil function tests in acute pancreatitis Function

Group 1 (G1)

Group 2 (G2)

Group 3 (G3)

Statistical analysis

Sham

Acute pancreatitis

Acute pancreatitis + NAC

P (G2 vs G3)

Mean±SD Mean±SD

Mean±SD

Phagocytosis 2.0±0.28 1.39±0.18

2.06±0.18

0.001

Chemotaxis 2.13±0.40 1.33±0.22

1.84±0.15

0.002

Opsonization 2.1±0.28 1.47±0.17

1.94±0.35

0.003

Oxidative burst

1.47±0.09

0.313

1.78±0.51

1.38±0.15

SD: Standard deviation; NAC: N-acetylcysteine.

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Flow Cytometry of Neutrophil Activity Flow cytometry results revealed that all tested neutrophil functions were significantly affected in group with AP alone (G2) compared with sham group (G1). In AP group with NAC treatment (G3), phagocytosis, chemotaxis, and opsonization of PNL were significantly improved with NAC treatment (p<0.05). After NAC treatment, only oxidative burst was not changed significantly among neutrophil functions (Table 4).

DISCUSSION Severity of AP depends on extent of systemic inflammatory response, as well as cytokines and chemokines, which play critical roles in the activation and migration of inflammatory cells. It is generally believed that pancreatitis begins with intrapancreatic activation of digestive enzyme zymogens, acinar cell injury, and activation of transcription factors.[1,2] Active enzymes in pancreatic acinar cells create inflammation, spreading into the pancreatic tissues. Our results of serum level of pancreatic amylase and lipase indicated that AP was induced by taurocholate infusion. Our histopathological findings confirmed cellular damage due to detrimental enzymatic activity in the pancreatic tissue. In addition, we found that NAC treatment mildly ameliorated edema and hemorrhage in tissues. Histopathological examination confirmed slight reduction of acinar necrosis with NAC treatment. NAC provides effective protection against pancreatic and vital organ damage and extrapancreatic complications during severe AP.[11,12] NAC improves pancreatic microvascular perfusion and alleviates severity of AP.[13] Histopathological results of vital organs, the lungs and kidneys, indicated systemic deteriorating effects of AP. Although AP is local inflammatory process in pancreatic tissue, systemic responses increase severity of the pathological condition. Results in NAC-treated group revealed that NAC ameliorated systemic effects of the disease. Seo et al.[3] recently reported that antioxidant NAC attenuates cellular responses and reduces cell death. Flow cytometry indicated that PNL activity was ameliorated by NAC treatment in rats with experimental AP. Neutrophils play central role in producing cellular immune response. They are the first phagocytic cells to appear at site of inflammation. Neutrophil activation, subsequent phagocytosis, and release of oxygen radicals play crucial role in host defense. Defects in neutrophil function cause increased incidence of sepsis and multiorgan failure.[14] Experimental and clinical studies have shown that oxidative stress and leucocyte infiltration play important roles in AP. Reactive oxygen species (ROS) produced within the pancreas by acinar cells and infiltrating leucocytes trigger activation of signaling pathways regulating the gene expression of inflammatory mediators and increased production of cytokines and chemokines, which induce the progression of local pancreatic inflammation to systemic inflammatory reaction and remote organ damage.[3–6] In our study, ameliorating the action of NAC on PNL activity was confirmed with chemotaxis, phagocytosis, and opsonization of PNL mea104

sured with flow cytometry. Therefore, we can conclude that NAC reduced systemic responses via pathways for neutrophil action during AP process. In addition to pancreatic cellular damage and necrosis, systemic inflammatory responses significantly affect clinical outcomes of AP cases. We found that main neutrophil functions, such as phagocytosis, chemotaxis, and opsonization, were impaired by AP. These effects could increase production of ROS and provoke severe inflammatory responses. We can hypothesize that some antioxidants reverse effects of OFR and palliate local and systemic complications during AP. Santos et al.[15] recently reported that NAC prevents inflammatory responses induced by various detrimental biochemical materials. NAC reduces pancreatic oxidative stress and inhibits signaling pathways involved in generation of inflammation.[16] The outcome of a patient is mostly dependent on systemic complications of AP. NAC-induced antioxidant effects could be helpful to lessen local and systemic alterations of AP.[3,11–13] In our study, results of flow cytometry indicated detrimental neutrophil functions during AP. These functions were recovered with NAC treatment despite ongoing pancreatitis. Yagci et al.[8] found that leucocyte infiltration and production of lipid peroxidation were lower in NAC-treated group. Due to direct scavenging effects of NAC on ROS, higher remaining nitric oxide may have been beneficial to regulation of microcirculation in the pancreatic tissue in NAC-treated group. Improvement in pancreatic microvascular perfusion with NAC treatment alleviates severity of AP.[13] In some clinical studies, NAC has been used for AP, post-endoscopic retrograde cholangiopancreatogram pancreatitis, and chronic pancreatitis. They have reported that NAC decreases severity of AP.[9,17] Severity of systemic responses and vital organs impairment are main determinants of prognosis during AP. Neutrophil functions, such as phagocytosis, chemotaxis and opsonization, could increase production of ROS and cytokines and provoke severe changes. Recent publications have studied effects of some chemicals on systemic responses to experimental pancreatitis by way of neutrophil function. They reported that reduction of neutrophil accumulation, depletion of neutrophils, and inhibited infiltrations of macrophages and neutrophils improved systemic events during experimental AP.[18–20] Therefore, chemicals that improve neutrophil functions may reduce detrimental systemic effects of AP. Gender of animals may affect systemic and local inflammatory response. In the literature, majority of studies used male rats,[3,4,6,7,13,14,19] some both male and female rats without sex discrimination,[12] and finally some studies used only female rats.[21,22] In this study, we used female rats. We believe that using animals of same gender provided homogeneity of the study in terms of inflammatory response. Based on results of present and previous studies, we can comment that whatever the gender of experimental animals, NAC treatment alleviates systemic response to experimental AP. Based on results of current study, we concluded that NAC Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Atayoğlu et al. Effect of N-acetylcysteine on neutrophil functions during experimental acute pancreatitis

treatment cannot prevent spreading active enzymes into pancreatic tissue. Although mild improvement was observed in NAC-treated group, cellular damage and tissue necrosis occurred despite NAC treatment. In addition to local inflammation and necrosis, severity of systemic inflammatory responses and extrapancreatic vital organ impairment are main determinants of prognosis of patients with AP. Cytokines, PNL products, and OFRs are effective against severity of systemic events. Uncontrolled and defective neutrophil functions, such as phagocytosis, chemotaxis, and opsonization, could increase production of ROS and cytokines and provoke severe inflammatory responses. Therefore, effects of antioxidants that reverse (or ameliorate) PNL functions may have beneficial effects on systemic changes during AP. Based on our findings, we observed that neutrophil functions were recovered by NAC treatment despite ongoing AP. This effect may prevent systemic responses and extrapancreatic damages. We concluded that NAC treatment strengthens functions of neutrophils, which play important role in enhancement of host immune responses during AP, and reduces extrapancreatic tissue damage. Conflict of interest: None declared.

REFERENCES 1. Weber CK, Adler G. From acinar cell damage to systemic inflammatory response: current concepts in pancreatitis. Pancreatology 2001;1:356– 62. 2. Frossard JL, Pastor CM. Experimental acute pancreatitis: new insights into the pathophysiology. Front Biosci 2002;7:275–87. 3. Seo JB, Gowda GA, Koh DS. Apoptotic damage of pancreatic ductal epithelia by alcohol and its rescue by an antioxidant. PLoS One 2013;8:81893. 4. Czakó L, Takács T, Varga IS, Tiszlavicz L, Hai DQ, Hegyi P, et al. Involvement of oxygen-derived free radicals in L-arginine-induced acute pancreatitis. Dig Dis Sci 1998;43:1770–7. 5. Sanfey H, Bulkley GB, Cameron JL. The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis. Ann Surg 1984;200:405– 13. 6. Czakó L, Takács T, Varga IS, Tiszlavicz L, Hai DQ, Hegyi P, et al. Oxidative stress in distant organs and the effects of allopurinol during experimental acute pancreatitis. Int J Pancreatol 2000;27:209–16. 7. Sevillano S, de la Mano AM, Manso MA, Orfao A, De Dios I. N-acetylcysteine prevents intra-acinar oxygen free radical production in pancre-

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atic duct obstruction-induced acute pancreatitis. Biochim Biophys Acta 2003;1639:177–84. 8. Yagci G, Gul H, Simsek A, Buyukdogan V, Onguru O, Zeybek N, et al. Beneficial effects of N-acetylcysteine on sodium taurocholate-induced pancreatitis in rats. J Gastroenterol 2004;39:268–76. 9. Mohseni Salehi Monfared SS, Vahidi H, Abdolghaffari AH, Nikfar S, Abdollahi M. Antioxidant therapy in the management of acute, chronic and post-ERCP pancreatitis: a systematic review. World J Gastroenterol 2009;15:4481–90. 10. Wittel UA, Wiech T, Chakraborty S, Boss B, Lauch R, Batra SK, et al. Taurocholate-induced pancreatitis: a model of severe necrotizing pancreatitis in mice. Pancreas 2008;36(2):9–21. 11. Gürleyik G, Zahidullahoğlu Cirpici O, Aktekin A, Sağlam A. The value of Ranson and APACHE II scoring systems, and serum levels of interleukin-6 and C-reactive protein in the early diagnosis of the severity of acute pancreatitis. Ulus Travma Acil Cerrahi Derg 2004;10:83–8. 12. Chen F, Zhou YJ. Hepatic effect of NAC on sevear acute pancteatise of rats. Asian Pac J Trop Med 2014;7:141–3. 13. Manso MA, Ramudo L, De Dios I. Extrapancreatic organ impairment during acute pancreatitis induced by bile-pancreatic duct obstruction. Effect of N-acetylcysteine. Int J Exp Pathol 2007;88:343–9. 14. Du BQ, Yang YM, Chen YH, Liu XB, Mai G. N-acetylcysteine improves pancreatic microcirculation and alleviates the severity of acute necrotizing pancreatitis. Gut Liver 2013;7:357–62. 15. Hazeldine J, Hampson P, Lord JM. The impact of trauma on neutrophil function. Injury 2014;45:1824–33. 16. Santos CL, Bobermin LD, Souza DG, Bellaver B, Bellaver G, Arús BA, et al. Lipoic acid and N-acetylcysteine prevent ammonia-induced inflammatory response in C6 astroglial cells: The putative role of ERK and HO1 signaling pathways. Toxicol In Vitro 2015;29:1350–7. 17. Ramudo L, Manso MA. N-acetylcysteine in acute pancreatitis. World J Gastrointest Pharmacol Ther 2010;1:21–6. 18. Kim DG, Bae GS, Choi SB, Jo IJ, Shin JY, Lee SK, et al. Guggulsterone attenuates cerulein-induced acute pancreatitis via inhibition of ERK and JNK activation. Int Immunopharmacol 2015;26:194–202. 19. Fakhari S, Abdolmohammadi K, Panahi Y, Nikkhoo B, Peirmohammadi H, Rahmani MR, et al. Glycyrrhizin attenuates tissue injury and reduces neutrophil accumulation in experimental acute pancreatitis. Int J Clin Exp Pathol 2013;7:101–9. 20. Chen G, Xu F, Li J, Lu S. Depletion of neutrophils protects against L-arginine-induced acute pancreatitis in mice. Cell Physiol Biochem 2015;35:2111–20. 21. Zhang KJ, Zhang DL, Jiao XL, Dong C. Effect of phospholipase A2 silencing on acute experimental pancreatitis. Eur Rev Med Pharmacol Sci 2013;17:3279–84. 22. Yin G, Hu G, Wan R, Yu G, Cang X, Ni J, et al. Role of bone marrow mesenchymal stem cells in L-arg-induced acute pancreatitis: effects and possible mechanisms. Int J Clin Exp Pathol 2015;8:4457–68.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Deneysel akut pankreatitte nötrofil fonksiyonları üzerine N-asetilsistein’in etkisi Dr. Kemal Atayoğlu,1 Dr. Günay Gürleyik,1 Dr. Gülderen Demirel,2 Dr. Selvinaz Özkara3 1 2 3

Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Yeditepe Üniversitesi Tıp Fakültesi, İmmünoloji Bilim Dalı, İstanbul Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Patoloji Laboratuvarı, İstanbul

AMAÇ: Akut pankreatitli (AP) olgulardaki sistemik enflamatuvar cevap ve pankreas dışı vital organ bozuklukları aktive olmuş nötrofillerin fonksiyonları ve ürünleri olan serbest oksijen radikalleri aracılığıyla oluşur. Çalışmamızda, deneysel AP süresince sistemik histopatolojik değişiklikler ve nötrofil fonksiyonları üzerinde antioksidan N-asetilsistein’in (NAC) etkilerinin araştırılması amaçlandı. GEREÇ VE YÖNTEM: Bu deneysel çalışma eşit olarak üç gruba ayrılmış 24 Wistar-albino sıçan üzerinde gerçekleştirildi. Grup 1: Yalnız laparotomi grubu, grup 2: Taurokolat infüzyonu ile oluşturulan AP grubu, grup 3: NAC tedavisi yapılan AP grubu. Lokal ve sistemik etkiler için böbrek, akciğer ve pankreas dokusundaki histopatolojik değişiklikler araştırıldı. Nötrofil fonksiyonları flow sitometri yöntemiyle belirlendi. BULGULAR: Her iki AP grubunda pankreas enzimlerinin serum seviyeleri yüksek bulundu. Histopatolojik bulgularda asiner hücre hasarı ve pankreas doku nekrozu vardı. Eş zamanlı olarak renal ve pulmoner dokuda ciddi histopatolojik değişiklikler gözlendi. Flow sitometri bulguları, tedavisiz AP grubunda bozulan nötrofil fonksiyonlarını göstermekteydi. Akut pankreatitli deneklerde NAC tedavisi nötrofillerin fagositoz, kemotaksis ve opsonizasyon işlevlerini anlamlı olarak iyileştirdi (p<0.05). Aynı zamanda NAC tedavisiyle pulmoner ve renal dokudaki hasarların, bütün mikroskobik parametreler için anlamlı olarak düzeldiği gözlendi (p<0.05). TARTIŞMA: Deneysel AP süresince, bozulan nötrofil fonksiyonları ciddi sistemik enflamatuvar cevapları uyarabilir. Lokal enflamasyon ve nekroza ek olarak pankreas dışı vital organlarda ciddi sistemik cevap ve histopatolojik değişiklikler oluşur. Antioksidan NAC tedavisi, pankreas dışı vital organlardaki zararlı sistemik cevapları, nötrofil fonksiyonlarını anlamlı ölçüde iyileştirerek geri döndürmektedir. Anahtar sözcükler: Flow sitometri; lökosit; pankreatit; sistemik enflamatuvar cevap. Ulus Travma Acil Cerrahi Derg 2017;23(2):100–106

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doi: 10.5505/tjtes.2016.59844

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ORIGIN A L A R T IC L E

Importance of diagnostic laparoscopy in the assessment of the diaphragm after left thoracoabdominal stab wound: A prospective cohort study Metin Yücel, M.D.,1 Adnan Özpek, M.D.,1 Hüseyin Kerem Tolan, M.D.,1 Fatih Başak, M.D.,1 Gürhan Baş, M.D.,2 Ethem Ünal, M.D.,1 Orhan Alimoğlu, M.D.2 1

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

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

ABSTRACT BACKGROUND: Stab wounds in the left thoracoabdominal region may cause diaphragmatic injury. The aim of the present study was to determine incidence of diaphragmatic injury and role of diagnostic laparoscopy in detection of injury in patients with left thoracoabdominal stab wound. METHODS: Total of 81 patients (75 male, 6 female; mean age 27.5±9.8 years; range 14 to 60 years) who presented with left thoracoabdominal stab wound between April 2009 and September 2014 were evaluated. Laparotomy was performed on patients who had hemodynamic instability, signs of peritonitis, or organ evisceration. Remaining patients were followed conservatively. After 48 hours, diagnostic laparoscopy was performed on patients without laparotomy indication to examine the left diaphragm for injury. Follow-up and treatment findings were prospectively evaluated. RESULTS: Thirteen patients underwent laparotomy while diagnostic laparoscopy was performed on remaining 68 patients. Left diaphragmatic injury was observed in 19 patients (23.5%) in the study group. Four injuries were diagnosed by laparotomy and 15 were diagnosed by laparoscopy. Presence of hemopneumothorax did not yield difference in incidence of diaphragmatic injury (p=0.131). No significant difference was detected in terms of diaphragmatic injury with respect to entry site of stab wound in the thoracoabdominal region (p=0.929). CONCLUSION: It is important to evaluate the diaphragm in left thoracoabdominal stab injuries, and diagnostic laparoscopy is still the safest and most feasible method. Keywords: Diagnostic laparoscopy; diaphragm injury; left thoracoabdominal stab injury.

INTRODUCTION Thoracoabdominal injuries may result in diaphragmatic injury, in addition to intraabdominal and intrathoracic injuries. Diaphragm injury is observed in 10% to 50% of left thoracoabdominal stab injuries. Early diagnosis of diaphragm injury is difficult based on physical examination and imaging modalities, unless obvious signs and symptoms are present.[1–8] Delay in Address for correspondence: Metin Yücel, M.D. Ümraniye Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ümraniye, İstanbul, Turkey Tel: +90 216 - 632 18 18 E-mail: drmetin69@mynet.com Qucik Response Code

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diagnosis and treatment may lead to diaphragmatic hernia, due to pressure difference between the 2 cavities, a condition that may cause morbidity or even death.[2,9,10] In patients who undergo laparotomy due to hemodynamic instability or peritonitis, it may be easy to evaluate the diaphragm. However, such an evaluation may be challenging in asymptomatic patients who are followed conservatively. Patients must be examined to rule out diaphragm injury. Laparoscopy is efficient technique to diagnose and treat diaphragm injury at early stage. The aim of this study was to evaluate role of laparoscopy in detecting diaphragmatic injury in patients with left thoracoabdominal stab wounds and assess incidence of diaphragmatic injuries.

MATERIALS AND METHODS This study was performed in general surgery clinic with the permission of the Ümraniye Training and Research Hospital 107

Yücel et al. Importance of diagnostic laparoscopy in the assessment of the diaphragm after left thoracoabdominal stab wound

ethics committee (21.04.2009–4749/261). Patients who were admitted to emergency department with left thoracoabdominal stab wound between April 2009 and September 2014 were evaluated prospectively. Thoracoabdominal region was defined as the area between the sternum, the fourth intercostal space, and the arcus costa anteriorly, and as the area between the vertebra, the inferior margin of the scapula and the last costal margin posteriorly. Region was divided into 3 subgroups: anterior (between the sternum and the anterior axillary line), lateral (between the anterior and posterior axillary lines) and posterior (between the posterior axillary line and the sternum). After initial evaluation and efficient resuscitation, patients who were hemodynamically unstable or showing signs of peritonitis were taken for emergency laparotomy. Remaining patients were followed conservatively according to an algorithm (Fig. 1). Hemodynamic instability was determined with hypovolemia finding, such as systolic blood pressure below 90 mmHg; tachycardia; dry, pale or cold skin; or signs of fatigue and dehydration after sufficient fluid resuscitation. Diagnosis of peritonitis was made based on physical examination findings, such as rigidity and/or rebound in the abdomen and severe pain in other regions of the abdomen far from the stab wound. Conservative treatment constituted hospitalization of the patient and close follow-up for 48 hours. In addition to performing physical examination, hemogram, as well as chest and abdominal X-rays were obtained. Patients who did not require emergency surgery 48 hours after being admitted were offered option of undergoing diagnostic laparoscopy to evaluate the left diaphragm, even though they did not have symptoms. For those who provided consent, laparoscopy was performed under general anesthesia with single port inserted

Hemodynamicinstability Peritonitis symptoms Organ evisceration No

Laparotomy

Diagnostic laparoscopy (For evaluation of diaphragm)

Patient data were collected prospectively and recorded in digital database. SPSS Statistics 22 program (IBM Corp., Armonk, NY, USA) was used to analyze the data. Normally distributed continuous variables were expressed as mean±SD. Categorical variables were expressed as frequencies and percentages. Fisher’s exact test, chi-square test, and FisherFreeman-Halton exact test were used to compare continuous parametric variables. P value <.05 was considered to be statistically significant.

RESULTS Total of 104 patients were hospitalized with left thoracoabdominal stab wound during study period. Twenty-three patients who declined diagnostic laparoscopy were excluded. In all, 81 patients were included in the study; 75 patients (92.6%) were male and 6 patients (7.4%) were female with mean age in cohort of 27.5±9.8 years (range: 14–60 years). Thirteen patients underwent therapeutic laparotomy due to hemodynamic instability or findings of peritonitis. Left diaphragm injury was found in 4 (30.8%) laparotomy patients. In addition to diaphragmatic injury, there was splenic injury in 1 patient and multiple small bowel injuries in another. There was no associated pathology in the remaining 2 patients.

(a)

(b)

Fail

Laparotomy

Figure 1. Algorithm used for left thoracoabdominal stab injury.

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Statistical Analyses

Four diaphragmatic injuries were in the central region and

Observation (48 hours) Successful

When hemopneumothorax was detected on chest X-ray, diagnostic laparoscopy was followed by tube thoracostomy. Tubes were removed after expansion of the lungs and termination of drainage. This study was fully compliant with the Strengthening the Reporting of Observational Studies in Epidemiology criteria.[11]

Diagnostic laparoscopy was performed on the remaining 68 patients. Left diaphragm injury was observed in 15 (22.1%) of these patients; no additional pathology was detected (Table 1). Procedure of 2 patients with diaphragm injury was converted to laparotomy due to technical difficulties. Remaining patients with diaphragm injuries were treated laparoscopically (Fig. 2).

Left thoracoabdominal stab injury

Yes

using open approach above the umbilicus. Additional ports were added if needed.

Figure 2. Omental tissue in diaphragmatic defect (a), and polipropylene suture repair (b).

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Yücel et al. Importance of diagnostic laparoscopy in the assessment of the diaphragm after left thoracoabdominal stab wound

remaining 15 injuries were in the periphery. Average size of defect was 2 cm (range: 1–3 cm) and separate 2/0 polypropylene sutures were used to repair diaphragmatic defect. Relationship between entry site of the stab in the left thoracoabdominal region and presence of diaphragmatic injury was examined. Left diaphragmatic injury was detected in 10 of 45 patients (22.2%) who had anterior area injuries, in 7 of 27 patients (25.9%) who had lateral area injuries, and in 2 of 9 patients (22.2%) who had posterior area injuries. No significant difference was found related to location of stab entry (p=0.929; Table 2). Seven of the 19 patients (36.8%) who had hemopneumothorax, and 12 of the 62 patients (19.4%) who did not have hemopneumothorax had left diaphragm injuries. There was Table 1. Rate of diaphragmatic injury in left thoracoabdominal stab wound

Diaphragmatic injury

n %

Total

19 23.5

Laparotomy

4 30.8

Diagnostic laparoscopy

22.1

Table 2. Diaphragmatic injury according to left thoracoabdominal area subgroup

Diaphragmatic injury

Yes No

n % n %

Anterior 10 22.2 35 77.8 Lateral

7 25.9 20 74.1

Posterior 2 22.2 7 77.8 p 0.929 Fisher Freeman Halton exact test.

Table 3. Diaphragmatic injury according to chest X-ray findings

Diaphragmatic injury Yes No n % n %

Hemopneumothorax 7 36.8 12 63.2 Normal

12 19.4 50 80.6

p 0.131 Fisher’s exact test.

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no statistically significant difference between patients with or without hemopneumothorax in terms of diaphragmatic injury (p=0.131; Table 3). Four of the patients who underwent emergent laparotomy due to hemodynamic instability died; however, patient deaths were not related to diaphragm injury. Mortality rate was 4.9%. Average 42-month (range: 6–79 months) follow-up revealed no morbidity, recurrence or complications.

DISCUSSION In the past, laparotomy was performed routinely in cases with penetrating abdominal stab injuries to minimize risk of missing potential intraabdominal pathologies. With the guidance of clinical research, it has been demonstrated that unnecessary laparotomy rate was high, as well as morbidity and mortality. Therefore, routine laparotomy has largely been abandoned and more selective conservative treatments have been adopted.[12–16] Selective conservative approach consists of immediate surgery for patients with hemodynamic instability or peritonitis, while remaining patients are followed conservatively and discharged from the hospital 48 hours after admission if no need for surgical intervention is observed. The situation is different for thoracoabdominal region stab wounds. In early stage, diaphragm injury may not demonstrate any clinical signs or symptoms. Presence of the liver on right side under the diaphragm may reduce risk of developing herniation in right diaphragm injuries but risk of herniation is high in left diaphragm injuries. Diaphragm injuries caused by left thoracoabdominal stab wound can be small and asymptomatic in early hours after the injury. Wound in the diaphragm may enlarge over time and lead to herniation of intraabdominal organs into the thoracic cavity, causing mortality in up to 48% of cases.[2,8–10,17,18] Early diagnosis and treatment is essential. Use of laparoscopy in trauma patients was first described by Adamthwaite.[19] Application of procedure has become widespread over time, and high sensitivity and specificity have contributed to it becoming preferred method to diagnose and treat diaphragmatic injuries.[8,19,20] Majority of routine laparotomies performed to evaluate the diaphragm in left thoracoabdominal stab injuries may be unnecessary and result in a high rates of morbidity and mortality.[14,15,21–23] Diagnostic laparoscopy is minimally invasive procedure that offers advantage of early detection and treatment of diaphragmatic injuries.[4,6–8,17,21,24,25] Diaphragm injury rates have been reported in range of 10% to 50% in several studies that investigated left thoracoabdominal stab injuries using diagnostic laparoscopy. [1–5,8,22,26,27] In the present study, diaphragm injury rate was 23.5% in all patients and 22.1% in patients who underwent diagnostic laparoscopy. 109

Yücel et al. Importance of diagnostic laparoscopy in the assessment of the diaphragm after left thoracoabdominal stab wound

Early diagnosis of diaphragm injuries in left thoracoabdominal stab injuries is challenging based on physical examination, chest X-ray, ultrasonography, and tomography.[1,2,5,28,29] Signs and symptoms may not be enough for diagnosis. In a study performed by Powell et al., 68% of patients with diaphragm injuries had normal chest X-ray.[30] Mjoli et al. reported that 10 of 26 patients (38.5%) who had abnormal radiological findings on plain chest radiography had diaphragmatic injury, and 12 of 28 patients (42.9%) with normal chest radiography had diaphragmatic injury.[8] Similar results have been reported in other studies.[1,3,5] In our study, 36.8% of patients with diagnosis of hemopneumothorax had diaphragmatic injury, and 19.4% of patients with normal chest X-ray had diaphragm injury. In light of these findings, we can assume that presence of hemopneumothorax is not determining factor for diaphragm injury. In a study conducted by Bagheri et al., stab wounds at the eighth intercostal space were found to be most responsible for diaphragm injuries in comparison of left thoracoabdominal injuries by area subgroup.[31] Mjoli et al. found site of injury to thoracoabdominal area was anterior in 11 cases (20%), lateral in 23 (41.8%), and posterior in 20 (36.4%); anterior penetrating wounds had highest incidence of diaphragmatic injury. [8] Anterior region was most common site of stab wound in our population; however, we found no significant difference between subgroups in terms of incidence of diaphragm injury. In contrast to studies reporting high morbidity and mortality in cases of diaphragm injury that were overlooked early on, other experimental studies have demonstrated spontaneous healing of injured diaphragm in time without any treatment. In a study performed by Shatney et al., diaphragm injury model was created in 16 pigs. Spontaneous healing was observed in 15 of the pigs (93.75%) in 6 weeks.[32] However, data are insufficient and there have been no studies indicating spontaneous healing of the diaphragm in humans. Early evaluation of the diaphragm for injury after left thoracoabdominal stab wound continues to be important at the present time. Limitation of this study was size of study group. Therefore, larger future studies examining impact of routine diagnostic laparoscopy are needed to clarify this issue.

Conclusion Shortly after left thoracoabdominal stab wound, patients with diaphragm injury may be asymptomatic. Physical examination and imaging modalities may not be adequate as result of low sensitivity and specificity for diagnosing diaphragm injury. Patients who do not require laparotomy should be informed about possible latent diaphragm injury. Diagnostic laparoscopy is safe and efficient method to evaluate the diaphragm for any injury and should be presented as an option before the patient is discharged. Well-conducted, randomized, controlled studies are needed to further investigate stab wounds. 110

Funding

The authors declare that this study was not funded by any company or person.

Informed Consent Informed consent was obtained from all patients. Conflict of interest: None declared.

REFERENCES 1. Murray JA, Demetriades D, Cornwell EE 3rd, Asensio JA, Velmahos G, Belzberg H, et al. Penetrating left thoracoabdominal trauma: the incidence and clinical presentation of diaphragm injuries. J Trauma 1997;43:624–6. 2. Reber PU, Schmied B, Seiler CA, Baer HU, Patel AG, Büchler MW. Missed diaphragmatic injuries and their long-term sequelae. J Trauma 1998;44:183–8. 3. Leppäniemi A, Haapiainen R. Occult diaphragmatic injuries caused by stab wounds. J Trauma 2003;55:646–50. 4. Shaw JM, Navsaria PH, Nicol AJ. Laparoscopy-assisted repair of diaphragm injuries. World J Surg 2003;27:671–4. 5. Friese RS, Coln CE, Gentilello LM. Laparoscopy is sufficient to exclude occult diaphragm injury after penetrating abdominal trauma. J Trauma 2005;58:789–92. 6. Zantut LF, Ivatury RR, Smith RS, Kawahara NT, Porter JM, Fry WR, et al. Diagnostic and therapeutic laparoscopy for penetrating abdominal trauma: a multicenter experience. J Trauma 1997;42:825–31. 7. Fabian TC, Croce MA, Stewart RM, Pritchard FE, Minard G, Kudsk KA. A prospective analysis of diagnostic laparoscopy in trauma. Ann Surg 1993;217:557–65. 8. Mjoli M, Oosthuizen G, Clarke D, Madiba T. Laparoscopy in the diagnosis and repair of diaphragmatic injuries in left-sided penetrating thoracoabdominal trauma: laparoscopy in trauma. Surg Endosc 2015;29:747–52. 9. Madden MR, Paull DE, Finkelstein JL, Goodwin CW, Marzulli V, Yurt RW, et al. Occult diaphragmatic injury from stab wounds to the lower chest and abdomen. J Trauma 1989;29:292–8. 10. Degiannis E, Levy RD, Sofianos C, Potokar T, Florizoone MG, Saadia R. Diaphragmatic herniation after penetrating trauma. Br J Surg 1996;83:88–91. 11. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int. J. Surg 2014;12:1495–9. 12. Inaba K, Demetriades D. The nonoperative management of penetrating abdominal trauma. Adv Surg 2007;41:51–62. 13. Schmelzer TM, Mostafa G, Gunter OL Jr, Norton HJ, Sing RF. Evaluation of selective treatment of penetrating abdominal trauma. J Surg Educ 2008;65:340–5. 14. Ohene-Yeboah M, Dakubo JC, Boakye F, Naeeder SB. Penetrating abdominal injuries in adults seen at two teaching hospitals in ghana. Ghana Med J 2010;44:103–8. 15. Como JJ, Bokhari F, Chiu WC, Duane TM, Holevar MR, Tandoh MA, et al. Practice management guidelines for selective nonoperative management of penetrating abdominal trauma. J Trauma 2010;68:721–33. 16. Jansen JO, Inaba K, Rizoli SB, Boffard KD, Demetriades D. Selective non-operative management of penetrating abdominal injury in Great Britain and Ireland: survey of practice. Injury 2012;43:1799–804.

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Yücel et al. Importance of diagnostic laparoscopy in the assessment of the diaphragm after left thoracoabdominal stab wound 17. Hallfeldt KK, Trupka AW, Erhard J, Waldner H, Schweiberer L. Emergency laparoscopy for abdominal stab wounds. Surg Endosc 1998;12:907–10.

26. McQuay N Jr, Britt LD. Laparoscopy in the evaluation of penetrating thoracoabdominal trauma. Am Surg 2003;69:788–91.

18. Okan I, Baş G, Ziyade S, Alimoğlu O, Eryılmaz R, Güzey D, et al. Delayed presentation of posttraumatic diaphragmatic hernia. Ulus Travma Acil Cerrahi Derg 2011;17:435–9.

27. Yucel T, Gonullu D, Matur R, Akinci H, Ozkan SG, Kuroglu E, et al. Laparoscopic management of left thoracoabdominal stab wounds: a prospective study. Surg Laparosc Endosc Percutan Tech 2010;20:42–5.

19. Adamthwaite DN. Traumatic diaphragmatic hernia: a new indication for laparoscopy. Br J Surg 1984;71:315.

28. Nau T, Seitz H, Mousavi M, Vecsei V. The diagnostic dilemma of traumatic rupture of the diaphragm. Surg Endosc 2001;15:992–6.

20. Ertekin C, Onaran Y, Güloğlu R, Günay K, Taviloğlu K. The use of laparoscopy as a primary diagnostic and therapeutic method in penetrating wounds of lower thoracal region. Surg Laparosc Endosc 1998;8:26–9.

29. Mahajna A, Mitkal S, Bahuth H, Krausz MM. Diagnostic laparoscopy for penetrating injuries in the thoracoabdominal region. Surg Endosc 2004;18:1485–7.

21. Simon RJ, Rabin J, Kuhls D. Impact of increased use of laparoscopy on negative laparotomy rates after penetrating trauma. J Trauma 2002;53:297–302.

30. Powell BS, Magnotti LJ, Schroeppel TJ, Finnell CW, Savage SA, Fischer PE, et al. Diagnostic laparoscopy for the evaluation of occult diaphragmatic injury following penetrating thoracoabdominal trauma. Injury 2008;39:530–4.

22. Berg RJ, Karamanos E, Inaba K, Okoye O, Teixeira PG, Demetriades D. The persistent diagnostic challenge of thoracoabdominal stab wounds. J Trauma Acute Care Surg 2014;76:418–23. 23. Keen G. Chest injuries. Ann R Coil Surg Engl 1974;54:124–31. 24. Cherry RA, Eachempati SR, Hydo LJ, Barie PS. The role of laparoscopy in penetrating abdominal stab wounds. Surg Laparosc Endosc Percutan Tech 2005;15:14–7. 25. Chol YB, Lim KS. Therapeutic laparoscopy for abdominal trauma. Surg

Endosc 2003;17:421–7.

31. Bagheri R, Tavassoli A, Sadrizadeh A, Mashhadi MR, Shahri F, Shojaeian R. The role of thoracoscopy for the diagnosis of hidden diaphragmatic injuries in penetrating thoracoabdominal trauma. Interact Cardiovasc Thorac Surg 2009;9:195–8. 32. Shatney CH, Sensaki K, Morgan L. The natural history of stab wounds of the diaphragm: implications for a new management scheme for patients with penetrating thoracoabdominal trauma. Am Surg 2003;69:508–13.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Sol torakoabdominal bölge delici kesici alet yaralanması olan hastalarda diafragmanın değerlendirilmesinde tanısal laparoskopinin önemi: İleriye yönelik kohort çalışması Dr. Metin Yücel,1 Dr. Adnan Özpek,1 Dr. Hüseyin Kerem Tolan,1 Dr. Fatih Başak,1 Dr. Gürhan Baş,2 Dr. Ethem Ünal,1 Dr. Orhan Alimoğlu2 1 2

Ümraniye Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Medeniyet Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul, Türkiye

AMAÇ: Sol torakoabdominal bölge delici kesici alet yaralanmaları potansiyel olarak diafragma yaralanmasına neden olabilir. Bu çalışmanın amacı, sol torakaoabdominal bölge delici kesici alet yaralanması olan hastalarda diafragma yaralanmasının insidansını belirlemek ve laparoskopinin diafragma yaralanmasını tespit etmedeki rolünü değerlendirmek idi. GEREÇ VE YÖNTEM: Nisan 2009 ve Eylül 2014 tarihleri arasında sol torakoabdominal bölge delici kesici alet yaralanması nedeniyle kliniğimize başvuran 81 hasta (75 erkek, 6 kadın; yaş ortalaması 27.5±9.8 yıl; dağılım 14–60) çalışmaya dahil edildi. Hemodinamik instabil, peritonit bulguları ve organ eviserasyonu olan hastalara laparotomi yapılırken, diğer hastalar selektif konservatif olarak takip edildi. Laparotomi endikasyonu olmayan ve semptomsuz seyreden hastalara 48 saatlik gözlem sonunda sol diafragmayı değerlendirmek için tanısal laparoskopi uygulandı. Takip ve tedavi sonuçları ileriye yönelik olarak değerlendirildi. BULGULAR: On üç hastaya laparotomi, kalan 68 hastaya tanısal laparoskopi uygulandı. Laparotomi yapılan hastaların dördünde, tanısal laparoskopi yapılan hastaların ise 15’inde olmak üzere toplam 19 hastada (%23.5) sol diafragmada yaralanma tespit edildi. Hemopnömotoraks olan ve olmayan hasta grupları arasında diafragma yaralanmasının insidansında fark saptanmadı (p=0.131). Diafragmatik yaralanma açısından sol torakoabdominal bölgede delici kesici aletin giriş yerleri arasında istatistiksel fark saptanmadı (p=0.929). TARTIŞMA: Sol torakoabdominal bölge delici kesici alet yaralanmalarında diafragma değerlendirilmelidir. Tanısal laparoskopi, günümüzde hala bu amaçla kullanılan en güvenli yöntemdir. Anahtar sözcükler: Diafragma yaralanması; sol torakoabdominal delici kesici alet yaralanması; tanısal laparoskopi. Ulus Travma Acil Cerrahi Derg 2017;23(2):107–111

doi: 10.5505/tjtes.2016.91043

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Correlation between Ranson score and red cell distribution width in acute pancreatitis Murat Özgür Kılıç, M.D., Canbert Çelik, M.D., Cemil Yüksel, M.D., Barış Doğu Yıldız, M.D., Mesut Tez, M.D. Department of General Surgery, Numune Training and Research Hospital, Ankara-Turkey

ABSTRACT BACKGROUND: Ranson’s criteria are widely used to evaluate severity of acute pancreatitis (AP). Red blood cell distribution width (RDW) has been demonstrated to be useful marker to predict mortality in these patients. The aim of the present study was to investigate correlation between Ranson score and RDW in patients with AP. METHODS: Total of 202 patients with AP were included in the study. Patients were classified as mild or severe AP, based on presence of organ failure for more than 48 hours and/or local complications. RESULTS: Forty patients (19.8%) were diagnosed as severe AP. High sensitivity and specificity values were obtained from receiver operating characteristic curve for initial RDW and Ranson score in predicting severe AP. Ranson ≥4 was selected cut-off value for Ranson score and 14% was limit for RDW. RDW at time of admission was correlated with 48-hour Ranson score (r=0.22; p<0.002). However, at day 0, there was no correlation between RDW and 0-hour Ranson score (r=0.07; p=0.600). CONCLUSION: Although there is no single, ideal method to assess severity of AP, RDW level at admission can be helpful in earlier prediction of AP severity, especially in first-line centers, taking into consideration disadvantages of multifactorial scoring systems. Keywords: Acute pancreatitis; Ranson score; red cell distribution width.

INTRODUCTION Acute pancreatitis (AP) is an acute inflammatory disease, and is one of the most frequent gastrointestinal causes of hospital admission. Prognosis of AP depends on its severity, which can be classified as mild or severe, according to latest revised Atlanta Classification. Majority of patients have mild, self-limited disease; however, approximately 20% of patients have severe form. Early assessment of severity is fundamental. Several single and multiparameter predictors to evaluate severity of the disease have been described. Ranson criteria are widely used in clinical practice worldwide, but this scoring system has limitation that evaluation cannot be completed Address for correspondence: Murat Özgür Kılıç, M.D. Ankara Numune Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Talatpaşa Bulvarı, No: 44, 06230 Ankara, Turkey Tel: +90 312 - 508 40 00 E-mail: murat05ozgur@hotmail.com Qucik Response Code

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until 48 hours following admission, which may lead to missing an early therapeutic window and increased mortality. Complete blood count (CBC) is a laboratory test frequently used in clinical practice, and comprises white blood cell, red blood cell, and platelet counts, and their morphological indices, such as red blood cell distribution width (RDW). RDW measures size variability of erythrocytes. It is used to differentiate etiology of anemia, and in a previous study, RDW was demonstrated to be useful marker for predicting mortality in AP patients.[1,2] The present study is investigation of correlation between RDW and Ranson score in group of AP patients.

MATERIALS AND METHODS Patients A total of 202 patients with AP treated between January 2012 and December 2014 were included in the study. AP was diagnosed with typical physical examination findings associated with plasma amylase level ≥3 times upper limit of normal level and radiological verification of disease with ultrasonography and/or abdominal tomography. AP was classified as mild or severe based on presence of organ failure for more than Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Kılıç et al. Correlation between Ranson score and red cell distribution width in acute pancreatitis

Demographic, radiographic, and laboratory data were collected from patient records for retrospective study. Ranson score was calculated using data recorded in first 24 hours and 48 hours after admission.

15.00 Red cell distribution width

48 hours and/or local complications, according to Atlanta criteria.[3] Organ failure included shock (systolic blood pressure <90 mmHg), pulmonary insufficiency (arterial partial pressure of oxygen <60 mmHg at room air or need for mechanical ventilation), or renal failure (serum creatinine level >2 mg/dL after rehydration or hemodialysis).

14.00 13.00

12.00

11.00

Statistical Analysis Statistical analyses were performed using SPSS software, version 17.0 (IBM Corp., Armonk, NY, USA). Normality of data distribution was assessed with Kolmogorov-Smirnov or Shapiro-Wilk test. All values are expressed as median (interquartile range), mean±standard deviation or count (percentage), unless otherwise specified. Comparisons were made using (1) chi-square test or Fisher’s exact test for categorical data, (2) unpaired or paired Student’s t-test for continuous normally distributed variables, and (3) Mann-Whitney U-test for continuous non-normally distributed variables. Correlations of RDW with Ranson score were assessed with Spearman’s correlation coefficient.

RESULTS Mean age at presentation was 59.2 years, and 91 patients (45%) were males. Most frequent AP etiology was biliary, seen in 146 patients (72.3%). Forty patients (19.8%) were diagnosed as having severe AP (organ failure with local complications). Median length of hospital stay was 6 days (range: 3–11 days). Clinical characteristics and outcomes of all patients are summarized in Table 1. Median RDW was 14.25% in severe AP group, while patients

.00

1.00

2.00

3.00 4.00 Ranson 48 h

5.00

6.00

Figure 1. Correlation between RDW (at day 0) and 48-hour Ranson score (r=0.22; p<0.002). RDW: Red blood cell distribution width.

with mild AP had median RDW of 13.6%. Difference between these 2 groups was statistically significant (p=0.004). Receiver operating characteristic (ROC) curve for initial RDW predicting severe AP yielded area under curve (AUC) of 0.648 (95% CI, 0.55–0.74). Median Ranson scores were 4 (range: 3–5) and 1 (range: 1–2) for severe AP patients and mild AP patients, respectively. ROC curve for Ranson score predicting severe AP yielded AUC of 0.625 (95% CI, 0.49–0.77). On basis of highest sensitivity and specificity values generated from ROC curve, ≥4 was selected as cut-off value for Ranson score and 14% was used as RDW limit. RDW at time of admission (day 0) was correlated with 48hour Ranson score (r=0.22; p<0.002) (Figure 1). At day 0 there was no correlation between RDW and 0-hour Ranson score (r=0.07; p=0.6).

Table 1. Demographic and clinical characteristics of the patients with acute pancreatitis Characteristics Mean age (min–max)

Total (n=202)

Patients with mild acute pancreatitis (n=162)

Patients with severe acute pancreatitis (n=40)

59.2 (17–90)

56.9 (17–90)

69.1 (22–90)

Gender, n (%)

Male

91 (45)

78 (85.7)

13 (75.7)

Female

111 (55)

84 (14.3)

27 (23.4)

Etiology, n (%)

Biliary

156 (72.3)

126 (77.3)

30 (75)

Non-biliary

46 (27.7)

36 (22.3)

10 (25)

Median hospital stay Median red cell distribution width Median Ranson score

6 days (3–11)

6 days (4–9)

9 days (3–16)

13.8 (12.9–14.7)

13.6 (12.8–14.5)

14.25 (13.6–15.5)

1 (1–2)

4 (3–5)

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Median RDW was found to be significantly higher in Ranson score ≥4 patients than Ranson <4 patients (14.2% [range: 13.6–15.2%] vs 13.8% [range: 12.9–14.6%]; p=0.046).

DISCUSSION Initial assessment of severity is one of the most important issues in the management of AP. Approximately 15% to 20% of patients with AP develop severe disease, which complicates the clinical course and often causes organ failure.[1] Identifying severity of disease within 24 to 48 hours after admission is essential for planning initial treatment. Our results indicated that RDW level at admission was significantly different between patients with mild or severe AP and was correlated with Ranson’s score. Ranson’s criteria were the first widely used severity scoring system, described by John Ranson in 1970s, and included basic laboratory data and clinical variables obtained within 48 hours after hospital admission.[4] Since sensitivity of this score was found to be between 40% and 80%, especially among biliary etiology group,[5–8] Ranson group developed a modified index.[9] It is still the most common scoring system used to evaluate severity of AP, due to its simplicity. Papachristou et al.[10] compared predictive accuracy of multiparameter score determined by AUC, and found that Ranson score was the only score with AUC >0.9. However, primary disadvantage of this scoring system is need for 48 hours to elapse in order to complete evaluation. Single prognostic serum markers are widely accepted in clinical use to determine AP severity. Hemoconcentration is acknowledged to be important factor in development of severe AP. Therefore, it could be assumed that hematocrit level on admission could be novel predictor of severity of the disease. Some studies have indicated that hematocrit level over 50% is sign of severity.[11] Other studies carried out in this field have demonstrated hematocrit level over 44% is associated with complications in AP.[12,13] However, whether changes in hematocrit level during follow-up could be used to assess severity is still unknown. Recent studies have reported that elevated hematocrit level on admission or within first 24 hours is satisfactory single prognostic variable when compared with Ranson criteria and Acute Physiology and Chronic Health Evaluation (APACHE) II system for predicting severity of AP.[11,12,14,15]

cholangitis and pneumonia, ruled out.[17–20] Sensitivity and positive predictive value of serum CRP level in patients with severe AP have been reported to be 83% to 90% and 75% to 86%, respectively, with remarkable increase from onset of AP through first 72 hours.[19] However, CRP level on admission is poor predictor of severity of the disease as result of increased hepatic synthesis due to inflammation-induced cytokine release, and has initial accuracy similar to that of APACHE II score.[7] Interleukin 6 (IL-6) is major mediator of CRP and is released primarily by macrophages. Value measured at admission has sensitivity and specificity of between 69% to 100% and 70% to 86%, respectively, in distinguishing between severe and mild pancreatitis.[21] IL-6 rises with beginning of symptoms and peaks on third day. As it has short plasma half-life, degradation during course of disease can be used as indicator of progression. IL-8 is a neutrophil-activating cytokine, and can be used as early predictor of severity and complications of AP.[21] Variety of results (sensitivity: 72–100%, specificity: 75–81%) have been reported for prediction of infected necrosis in AP.[22,23] Despite high prediction rates, however, it still has limited use in daily clinical practice. IL-10 is a well-known anti-inflammatory cytokine. Though 1 study reported sensitivity of 67% and specificity of 100% with IL-10 for prediction of severity on first day of AP,[24] other studies have stated less reliable results compared with IL-6 and IL-8.[19] Tumor necrosis factor alpha (TNF-α), which is produced primarily by macrophages, is a cytokine that stimulates acute phase reaction. Many clinicians have investigated its role in predicting severity of AP.[25,26] Unfortunately, outcomes of these studies are not very promising. As result of its rapid clearance, TNF-α is less useful than other cytokines in prediction of severity.

Creatinine and blood urea nitrogen (BUN) levels are easily measured, and they are routine, inexpensive tests that serve as indicator of acute renal failure. In one study, sensitivity and specificity of BUN elevation to predict severity of AP were determined to be 79% and 70%, respectively.[16]

Serum procalcitonin level is known as reliable marker of infection and sepsis.[27] It has 94% sensitivity and 91% specificity rates for detection of infected necrosis in AP.[22] In a review, procalcitonin and relationship to infected necrosis was reported to have overall sensitivity of 80% and specificity of 91%.[28] In an article published in 2006, parallel results were obtained for procalcitonin level over 0.5 ng/mL.[29] Procalcitonin could be recognized as an indicator of infected necrosis, which is one of the major complications that can advance in the progress of AP. However, procalcitonin level is not preferred laboratory data in daily use, which is main handicap of this marker.

C-reactive protein (CRP) is broadly recognized as indicator of severity 48 hours after disease onset with value greater than 150 mg/dL and other causes of inflammation, such as

Urinary trypsinogen activation peptide (uTAP) is liberated during activation of trypsinogen to trypsin and has been used in recent years to predict severity of AP. According to 1992

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Atlanta criteria, uTAP is rapid test that is reliable in prediction of severity of AP.[30] Several studies have demonstrated significant correlation between uTAP level and severity of disease. In a study published in 1997, level of uTAP greater than 10 ng/mL at admission was found to be predictor of severity with sensitivity and specificity rates of 100% and 85%, respectively.[31] Other subsequent studies revealed different sensitivity (58–100%) and specificity (65.8–77%) rates for different uTAP cut-off levels.[32–34] Meta-analysis determined sensitivity and specificity for uTAP >35 nmol/L of 71% and 75%, respectively (AUC=0.83).[34] Value of uTAP is that it provides useful information about severity at admission, but as it is not widely used in many hospitals, benefit is still limited. RDW reflects systemic inflammation, and is a remarkable prognostic marker to determine risk of mortality in wide range of clinical manifestations.[35–38] Şenol et al.[39] demonstrated in their study that increased RDW value at admission was independent predictor of mortality in patients with AP. In this study, high RDW level, i.e., >14.8%, at onset of disease displayed more distinct correlation with non-survival than novel prognostic markers in the literature used to predict mortality. In conclusion, analysis of CBC panel can provide valuable information, especially for patients with AP. RDW is routine part of CBC. RDW level at admission is helpful to make earlier prediction of severity of AP, especially at first-line centers, considering the disadvantages of multifactorial scoring systems. However, there is no single ideal method to assess severity of the disease. Institutional facilities influence method used for prognostic assessment of AP. Large, multicenter cohort studies are needed.

Financial Support Authors declare that they received no financial support for this study. Conflict of interest: None declared.

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5. Khanna AK, Meher S, Prakash S, Tiwary SK, Singh U, Srivastava A, et al. Comparison of Ranson, Glasgow, MOSS, SIRS, BISAP, APACHEII, CTSI Scores, IL-6, CRP, and Procalcitonin in Predicting Severity, Organ Failure, Pancreatic Necrosis, and Mortality in Acute Pancreatitis. HPB Surg 2013;2013:367581. 6. Chatzicostas C, Roussomoustakaki M, Vlachonikolis IG, Notas G, Mouzas I, Samonakis D, et al. Comparison of Ranson, APACHE II and APACHE III scoring systems in acute pancreatitis. Pancreas 2002;25:331–5. 7. Taylor SL, Morgan DL, Denson KD, Lane MM, Pennington LR. A comparison of the Ranson, Glasgow, and APACHE II scoring systems to a multiple organ system score in predicting patient outcome in pancreatitis. Am J Surg 2005;189:219–22. 8. Wilson C, Heath DI, Imrie CW. Prediction of outcome in acute pancreatitis: a comparative study of APACHE II, clinical assessment and multiple factor scoring systems. Br J Surg 1990;77:1260–4. 9. Ranson JH. The timing of biliary surgery in acute pancreatitis. Ann Surg 1979;189:654–63. 10. Papachristou GI, Muddana V, Yadav D, O’Connell M, Sanders MK, Slivka A, et al. Comparison of BISAP, Ranson’s, APACHE-II, and CTSI scores in predicting organ failure, complications, and mortality in acute pancreatitis. Am J Gastroenterol 2010;105:435–42. 11. Gan SI, Romagnuolo J. Admission hematocrit: a simple, useful and early predictor of severe pancreatitis. Dig Dis Sci 2004;49:1946–52. 12. Brown A, Orav J, Banks PA. Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis. Pancreas 2000;20:367–72. 13. Sun B, Li HL, Gao Y, Xu J, Jiang HC. Factors predisposing to severe acute pancreatitis: evaluation and prevention. World J Gastroenterol 2003;9:1102–5. 14. Baillargeon JD, Orav J, Ramagopal V, Tenner SM, Banks PA. Hemoconcentration as an early risk factor for necrotizing pancreatitis. Am J Gastroenterol 1998;93:2130–4. 15. Corfield AP, Cooper MJ, Williamson RC, Mayer AD, McMahon MJ, Dickson AP, et al. Prediction of severity in acute pancreatitis: prospective comparison of three prognostic indices. Lancet 1985;2:403–7. 16. Fan ST, Lai EC, Mok FP, Lo CM, Zheng SS, Wong J. Prediction of the severity of acute pancreatitis. Am J Surg 1993;166:262–8. 17. Uhl W, Büchler M, Malfertheiner P, Martini M, Beger HG. PMN-elastase in comparison with CRP, antiproteases, and LDH as indicators of necrosis in human acute pancreatitis. Pancreas 1991;6:253–9. 18. Al-Bahrani AZ, Ammori BJ. Clinical laboratory assessment of acute pancreatitis. Clin Chim Acta 2005;362:26–48. 19. Imamura T, Tanaka S, Yoshida H, Kitamura K, Ikegami A, Takahashi A, et al. Significance of measurement of high-sensitivity C-reactive protein in acute pancreatitis. J Gastroenterol 2002;37:935–8. 20. Schütte K, Malfertheiner P. Markers for predicting severity and progression of acute pancreatitis. Best Pract Res Clin Gastroenterol 2008;22:75– 90. 21. Pezzilli R, Billi P, Miniero R, Fiocchi M, Cappelletti O, Morselli-Labate AM, et al. Serum interleukin-6, interleukin-8, and beta 2-microglobulin in early assessment of severity of acute pancreatitis. Comparison with serum C-reactive protein. Dig Dis Sci 1995;40:2341–8. 22. Rau B, Steinbach G, Gansauge F, Mayer JM, Grünert A, Beger HG. The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis. Gut 1997;41:832–40. 23. Stoelben E, Nagel M, Ockert D, Quintel M, Scheibenbogen C, Klein B, et al. Clinical significance of cytokines Il-6, Il-8 and C-reactive protein in serum of patients with acute pancreatitis. [Article in German] Chirurg 1996;67:1231–6.

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Kılıç et al. Correlation between Ranson score and red cell distribution width in acute pancreatitis 24. Chen CC, Wang SS, Lu RH, Chang FY, Lee SD. Serum interleukin 10 and interleukin 11 in patients with acute pancreatitis. Gut 1999;45:895–9. 25. Papachristou GI. Prediction of severe acute pancreatitis: current knowledge and novel insights. World J Gastroenterol 2008;14:6273–5. 26. Novovic S, Andersen AM, Ersbøll AK, Nielsen OH, Jorgensen LN, Hansen MB. Proinflammatory cytokines in alcohol or gallstone induced acute pancreatitis. A prospective study. JOP 2009;10:256–62. 27. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341:515–8. 28. Mofidi R, Suttie SA, Patil PV, Ogston S, Parks RW. The value of procalcitonin at predicting the severity of acute pancreatitis and development of infected pancreatic necrosis: systematic review. Surgery 2009;146:72–81. 29. Bülbüller N, Doğru O, Ayten R, Akbulut H, Ilhan YS, Cetinkaya Z. Procalcitonin is a predictive marker for severe acute pancreatitis. Ulus Travma Acil Cerrahi Derg 2006;12:115–20. 30. Bradley EL. A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch Surg 1993;128:586–90. 31. Tenner S, Fernandez-del Castillo C, Warshaw A, Steinberg W, HermonTaylor J, Valenzuela JE, et al. Urinary trypsinogen activation peptide (TAP) predicts severity in patients with acute pancreatitis. Int J Pancreatol 1997;21:105–10. 32. Neoptolemos JP, Kemppainen EA, Mayer JM, Fitzpatrick JM, Raraty MG, Slavin J, et al. Early prediction of severity in acute pancreatitis

by urinary trypsinogen activation peptide: a multicentre study. Lancet 2000;355:1955–60. 33. Khan Z, Vlodov J, Horovitz J, Jose RM, Iswara K, Smotkin J, et al. Urinary trypsinogen activation peptide is more accurate than hematocrit in determining severity in patients with acute pancreatitis: a prospective study. Am J Gastroenterol 2002;97:1973–7. 34. Huang QL, Qian ZX, Li H. A comparative study of the urinary trypsinogen-2, trypsinogen activation peptide, and the computed tomography severity index as early predictors of the severity of acute pancreatitis. Hepatogastroenterology 2010;57:1295–9. 35. Ku NS, Kim HW, Oh HJ, Kim YC, Kim MH, Song JE, et al. Red blood cell distribution width is an independent predictor of mortality in patients with gram-negative bacteremia. Shock 2012;38:123–7. 36. Patel KV, Semba RD, Ferrucci L, Newman AB, Fried LP, Wallace RB, et al. Red cell distribution width and mortality in older adults: a metaanalysis. J Gerontol A Biol Sci Med Sci 2010;65:258–65. 37. Kim CH, Park JT, Kim EJ, Han JH, Han JS, Choi JY, et al. An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. Crit Care 2013;17:R282. 38. Hunziker S, Celi LA, Lee J, Howell MD. Red cell distribution width improves the simplified acute physiology score for risk prediction in unselected critically ill patients. Crit Care 2012;16:R89. 39. Şenol K, Saylam B, Kocaay F, Tez M. Red cell distribution width as a predictor of mortality in acute pancreatitis. Am J Emerg Med 2013;31:687– 9.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Akut pankreatitte Ranson skoru ile eritrosit dağılım hacmi arasındaki korelasyon Dr. Murat Özgür Kılıç, Dr. Canbert Çelik, Dr. Cemil Yüksel, Dr. Barış Doğu Yıldız, Dr. Mesut Tez Numune Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara

AMAÇ: Ranson kriterleri akut pankreatit (AP) şiddetini değerlendirmek için yaygın olarak kullanılır. Eritrosit dağılım genişliği (RDW) de bu gibi hastalarda mortaliteyi öngörmede yararlı bir belirteç olarak gösterilmiştir. Amaç, AP hastalarında Ranson skoru ile RDW arasındaki ilişkiyi araştırmaktır. GEREÇ VE YÖNTEM: Toplam 202 AP hastası çalışmaya alındı. Hastalar, 48 saatten uzun süren organ yetersizliği ve/veya lokal komplikasyon varlığına bağlı olarak, hafif ve şiddetli AP olarak sınıflandırıldı. BULGULAR: Kırk hastaya (%19.8) şiddetli AP tanısı kondu. Şiddetli AP’nin belirlenmesinde, başlangıç RDW ve Ranson skorları için hesaplanan ROC eğrisinde yüksek duyarlılık ve özgüllük değerleri elde edildi. Ranson skoru için 4’ten büyük değerler, RDW için %14 değeri cutoff değerler olarak belirlendi. Başvuru anındaki RDW değerinin 48. saat Ranson skoru ile korele olduğu saptandı (r=0.22, p<0.002). Ancak, 0. günde, RDW ile 0. saat Ranson skoru arasında korelasyon yoktu (r=0.07, p=0.600). TARTIŞMA: Akut pankreatit şiddetini değerlendirmede tek bir ideal yöntem olmasa da, başvuru anındaki RDW seviyesi, birden çoklu skorlama sistemlerinin dezavantajları dikkate alındığında, özellikle birinci basamak sağlık merkezlerinde, AP şiddetinin erken tahmininde yararlı olabilir. Anahtar sözcükler: Akut pankreatit; eritrosit dağılım hacmi; Ranson skoru. Ulus Travma Acil Cerrahi Derg 2017;23(2):112–116

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ORIGIN A L A R T IC L E

Evaluation of forearm arterial repairs: Functional outcomes related to arterial repair Musa Kemal Keleş, M.D.,1 Tekin Şimşek, M.D.,2 Veysel Polat, M.D.,3 Engin Yosma, M.D.,2 Ahmet Demir, M.D.2 1

Department of Plastic, Reconstructive and Aesthetic Surgery, Dışkapı Yildirim Beyazıt Training and Research Hospital, Ankara-Turkey

Department of Plastic Surgery, Ondokuz Mayıs University Faculty of Medicine, Samsun-Turkey

Department of Radiology, Ondokuz Mayıs University Faculty of Medicine, Samsun-Turkey

ABSTRACT BACKGROUND: There are few studies of single forearm arterial injury repair that compare long-term results of intact and obliterated forearm arterial repair. Aim of the present study was to compare long-term results of forearm arterial repair using Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score and color Doppler ultrasound (CDUS). METHODS: Records of 166 consecutive patients with forearm arterial injury were reviewed, and 30 patients with same injury (ulnar artery, ulnar nerve, and tendon injuries at flexor zone V) were called back for CDUS and QuickDASH scoring. Patients evaluated with CDUS were divided into 2 groups according to results: patent vessels (Group 1) and obliterated vessels (Group 2), and statistical analysis was performed to compare QuickDASH scores of groups. RESULTS: Difference in QuickDASH scores was statistically significant: Group 1 had lower score (24.27) than Group 2 (36.34), indicating better outcome in patients with patent vessels. CONCLUSION: Vascular repair that achieved vessel patency led to better functional outcome with lower QuickDASH score and less cold intolerance. Keywords: Cold intolerance; forearm injury; functional outcome; nerve injury; vascular injury.

INTRODUCTION Arterial injuries at the forearm level form a relatively small number of total injuries in the upper extremities. Stab wounds and injuries caused by broken glass constitute primary causes of this type of injury.[1] Arterial bleeding along axis of the wound, pulselessness distal to the injury, and positive Allen test are sufficient to diagnose problem. However, color Doppler ultrasonography (CDUS) can be used to confirm diagnosis.[2] Angiography, which is an invasive test that can be performed to diagnose arterial problems, is impractical method for diagnosing acute trauma in patients.[3] Careful Address for correspondence: Musa Kemal Keleş, M.D. Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi Plastik, Rekonstrüktif ve Estetik Cerrahi Kliniği, 06110 Ankara, Turkey Tel: +90 312 - 596 20 00 E-mail: mukeke@gmail.com Qucik Response Code

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exploration of wound edges and visual identification of the 2 ends of the transected vessels can confirm diagnosis. Tendon, nerve, muscle, and even bone injuries frequently accompany arterial injuries. Although functional recovery directly depends on severity of accompanying injuries, decreased arterial flow can also negatively affect wound healing and functional recovery.[1] Twenty years ago, occlusion after vessel repair was frequent, and ligature of arteries in patients who had well-perfused hand was reliable method.[1] However, present widespread use of surgical loupes and improvements in technical facilities have raised success rate of surgical repair by almost 100%.[4] Although isolated vessel injuries of the forearm are a problem frequently encountered by plastic surgeons, long-term data in the literature concerning this type of injury are quite limited. Most of them fall under the heading of “total upper extremity injuries.” The aim of this study was to analyze demographic data and evaluate functional outcome of procedures on hands in patients with at least 6 months of follow-up. Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score was used for this evaluation. QuickDASH is a self-report ques117

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tionnaire designed to measure physical function and symptoms in people with any of several musculoskeletal disorders of the upper limb.

MATERIALS AND METHODS Review of 166 consecutive cases of repair of vessel injury in the forearm region performed between October 2006 and August 2014 was conducted. Emergency operation was performed within 5 days of injury. Before surgery, informed consent was obtained from all patients. All operations were performed by experienced plastic surgeons or hand surgeons. All anastomosis was performed under microscopic magnification with interrupted 9–0 Prolene suture (Ethicon, Inc., Cornelia, GA, USA). Use of Fogarty catheter (Edwards Lifesciences Corp., Irvine, CA, USA) was avoided, as doing so may damage the endothelium. Postoperatively, anastomosis was examined for patency with hand-held Doppler US. Only painkillers and antibiotics were administered in postoperative period. Patient demographic details, etiology, accompanying injuries, cold intolerance, and QuickDASH scores were documented. Evaluation of arterial flow was performed in 30 patients who had both ulnar artery and ulnar nerve injury with accompanying tendon injury at level of the wrist that had been repaired at least 6 months prior. CDUS were performed using Aplio XG SSA-790A (Toshiba Medical Systems Corp., Otawara, Japan) device, which employs 12 MHz linear probe. US filtering and gain were adjusted to provide greatest level of detail without artifacts. Doppler insonation angle was set to less than 60 degrees during velocity measurement. Flow parameters, such as diameter of the injured and contralateral ulnar artery and peak systolic maximum velocity (Vmax) of both arteries, were measured in each patient. Following CDUS, patients were divided into 2 groups: non-obliterated artery group (Group 1) and obliterated artery group (Group 2). Distal blood flow of non-obliterated arteries and contralateral arterial blood flow at the same level were also evaluated, and data obtained from QuickDASH scores of Groups 1 and 2 were compared. All data were statistically analyzed with SPSS 20 software (IBM Corp., Armonk, NY, USA) using non-parametric MannWhitney U and chi-square tests. P<0.05 was adopted to represent statistically significant difference.

RESULTS

73 patients formed largest group. Thirty-seven patients had more than 1 nerve injury (ulnar, median, radial). Whereas 155 (93.37%) vessels were repaired directly, 11 (6.63%) necessitated vein grafting. Most patients had right forearm injury (105 patients), and most injuries were located in one-third distal part of the forearm (143 patients). Only 2 patients received concomitant fasciotomy. No amputation was performed. Demographic results are summarized in Table 1.

Color Doppler Results Of 30 patients evaluated, Group 1 comprised 23 patients who had patent artery at least 6 months after the operation and Group 2 was made up of 7 patients who had obliterated arteries. Seven of 30 arteries were occluded, including 5 vein grafts and 2 primary repairs. Mean patency rate of 76.66% Table 1. Demographic data of the patients n % Patients (Total)

166

Gender Male

144 86.74

Female

22 13.25

Age (years)

30±14.66 (1–76)

Traumatic event Laceration

Blunt trauma

162 97.59 4

2.4

Repaired artery Radial

38 22.89

Ulnar

114 68.67

Both

7.83

0.6

Brachial

total

179

Coexisting nerve/bone injury

Ulnar nerve

43.97

Median nerve

9.63

Radial nerve

9.03

Both nerves

22.28

No nerve

14.45

Bone

0.6

Patient Demographics

Affected arm

Total of 144 male and 22 female patients with mean age of 30 years (range: 1–76 years) were included in the study. Repair of 179 arteries were conducted in 166 patients. Most frequent mechanisms of injury included laceration from stabbing, glass, circular saw, or grinder (162 cases). Majority of repaired arteries consisted of isolated ulnar artery injury with accompanying nerve and tendon injuries (114 vessels). Among accompanying lesions, isolated ulnar nerve injury in

Right

112

67.46

Left

31.92

Bilateral

0.6

118

Mean±SD (Range)

Surgical procedure

End-to-end anastomosis

168

93.85

Vein graft

6.14

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was established. Two of 7 patients in whom obliterated anastomosis was detected displayed collateral circulation. Mean Vmax at distal part of anastomosis site was 42.19 cm/s and mean luminal diameter was 1.85 mm in Group 1. There was no statistically significant difference between mean flow rate of contralateral ulnar arteries (45.23 cm/s) and distal part of anastomosis site (42.19 cm/s) (p=0.35>0.05).

QuickDASH Score and Cold Intolerance Results Average QuickDASH score was 24.27±11.50 in Group 1 and 36.34±7.89 in Group 2. Difference in average QuickDASH Table 2. Summary of QuickDASH scores, cold intolerance, and color Doppler ultrasound results Patients

QuickDASH score

Cold intolerance

Vessel patency on CDUS

11.3 No Patent

31.8 No Patent

27.2 Yes Occluded

31.8 No Patent

31.8 No Occluded

11.3 No Patent

29.5 Yes Patent

53.2 No Patent

15.9 Yes Patent

10 40.9 No Patent 11 13.6 No Patent 12 18.1 Yes Patent 13 29.5 No Patent 14 31.8 No Patent 15 31.8 Yes Occluded 16 11.3 No Patent 17 29.5 No Patent 18 15.9 Yes Patent 19

31.8 No Occluded

20 31.8 No Patent 21 15.9 No Patent 22 40.9 No Patent 23 40.9 Yes Occluded 24 40.9 No Patent 25 13.6 No Patent 26 13.6 No Patent 27

Yes

Occluded

28 18.1 No Patent 29

40.9 No Occluded

30 18.1 No Patent QuickDASH: Quick Disabilities of the Arm, Shoulder and Hand; CDUS: Color Doppler ultrasound.

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score was found to be statistically significant (p=0.014<0.05). Four patients in Group 1 (17.4%) reported cold intolerance and 4 patients in Group 2 (57.1%) reported experiencing cold intolerance. Difference in cold intolerance ratio was statistically significant (p=0.04<0.05). Results are summarized in Table 2.

DISCUSSION Centers that serve military and civilian populations provide different data on age and sex distribution, etiological factors, and most commonly injured vessels of patients suffering from wrist injury. Nonetheless, it occurs more often among males, especially those in their twenties.[4] In present series, sex and age distribution of wrist injury patients was similar to previous reports. Ballard1 reported that broken glass was leading mechanism of laceration injury and that most commonly observed accompanying injury was damage to the median nerve. Laceration caused by broken glass, especially those caused by punching, emerged as most frequent in our series, as well. Fasciotomy associated with vascular injury in the forearm region has been reported at rate of 26.92% to 48% in the literature.[5,6] In the present study, incidence of fasciotomy was lower (3.6%) due to non-blunt trauma. When primary vascular repairs are not feasible, repair using autologous or prosthetic grafts should be pursued. Use of prosthetic grafts remains controversial.[7–9] They have been preferred for large forearm vessels.[9] In our clinic, we preferred to use size-matched vein grafts harvested from the lower extremities. Graft usage ratio in this series was determined to be 11%. CDUS is noninvasive, rapid, and accurate technique to evaluate results of vascular repair, flow value, and flow characteristics.[10] In previous studies, patency rate reported has been between 0% and 100%, depending on both use of graft and magnification tools.[10,11] In addition, different methods have been used to evaluate patency.[10–12] In our study, CDUS, which has several advantages, was used.[10] Patency, flow rate, and collateral vascular development were evaluated using CDUS. Patency rate of 76.66% was found in present study; however, patency ratio reflected only small number of results, obtained from 30 patients with ulnar artery and ulnar nerve injury at level of the wrist, and 5 of these patients needed vein graft for arterial repair. Debate continues as to whether repair of injured artery in well-perfused hand is clinically beneficial. Johnson suggested that in absence of an acute hand ischemia, ligation of the injured artery is safe and economical approach in radial or ulnar artery injuries.[4] Sitzmann also suggested that injuries to the radial or ulnar arteries alone can be treated using ligation without adverse sequelae.[13] Lee et al. performed arterial ligation for extensive, contaminated injuries that 119

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did not display hand ischemia.[3] They also advocated ligation when it was felt arterial repair would jeopardize the patient’s well-being.[3] Ballard et al.[1] treated almost half of their patients with single forearm arterial injuries using ligation; they compared results with patients who underwent repair, and declared that both treatment modalities led to same outcome. In cases where both arteries are transected, at least the ulnar artery should be repaired; however, if the palmar arch is not intact, both arteries must be reconstructed.[13,14] Presence of incomplete arch in 20% of the population increases risk of ischemic changes in hands.[13,14] McCready recommended supplying sufficient amount of blood to repair vascular damage to isolated arterial injury in an extremity, and repair of the ulnar artery, which is larger, in presence of damage to both arteries.[9] However, in recent studies, vessel repair has been demonstrated to have better results. Basetto has suggested that anastomosis is always preferable to ligation due to more substantial loss of bone mass, muscle mass, and strength in patients who underwent arterial ligation.[15] The literature indicates that most prominent factor in prognosis of arterial injury in the forearm is presence of accompanying nerve damage; ratio has been estimated to be as high as 58%.[1] Ratio was determined to be 85% in our series. As Douglas reports, Tsai found 87% of functional results ranged from adequate to excellent after ulnar nerve repair with concomitant patent ulnar artery repair, compared to 33% for thrombosed arterial repair.[10] Leclerq has also argued that when associated artery repair remained patent, ulnar nerve repair produced superior outcome.[16] Johnson has argued that cold insensitivity or neuropathic symptoms result from nerve damage.[4] To differentiate symptoms arising from nerve and artery injuries, we re-tested patients who only had ulnar artery and ulnar nerve injury at level of the wrist to evaluate functional healing using QuickDASH score to identify subgroup with standard injury. Doppler US was used to determine vascular patency. All of the patients had undergone surgery at least 6 months prior and all had concomitant flexor carpi ulnaris, flexor digitorum superficialis, or flexor digitorum profundus tendon injury. Statistically significant difference between QuickDASH scores of Group 1 and Group 2 was found, indicating superior functional healing in non-obliterated group. We believe that better results obtained after nerve repair were related to superior repair technique as well as presence of excellent vascular bed. In a previous study, researchers demonstrated that significant delay occurred in constitution of normal blood flow after cold stress testing following radial forearm flap.[17] This correlation indicates that cold intolerance might depend on blood supply. Johnson reported that cold-sensitivity, weakness, and paresthesia were independent of patency of damaged arteries and that conditions occurred in patients who had suffered 120

only nerve and/or tendon injury.[4] We found statistically significant difference between patent and thrombosed artery groups with respect to cold intolerance. This finding may indicate that cold intolerance depends on diminished blood flow as much as nerve injury. Vascular repair that achieved vessel patency yielded better functional outcome with lower QuickDASH score and less cold intolerance. Cold intolerance appears to be related to decreased blood supply as much as nerve dysfunction. Conflict of interest: None declared.

REFERENCES 1. Ballard JL, Bunt TJ, Malone JM. Management of small artery vascular trauma. Am J Surg 1992;164:316–9. 2. Noaman HH. Management and functional outcomes of combined injuries of flexor tendons, nerves, and vessels at the wrist. Microsurgery 2007;27:536–43. 3. Lee RE, Obeid FN, Horst HM, Bivins BA. Acute penetrating arterial injuries of the forearm. Ligation or repair? Am Surg 1985;51:318–24. 4. Johnson M, Ford M, Johansen K. Radial or ulnar artery laceration. Repair or ligate? Arch Surg 1993;128:971–5. 5. Prichayudh S, Verananvattna A, Sriussadaporn S, Sriussadaporn S, Kritayakirana K, Pak-art R, et al. Management of upper extremity vascular injury: outcome related to the Mangled Extremity Severity Score. World J Surg 2009;33:857–63. 6. Wali MA. Upper limb vascular trauma in the Asir region of Saudi Arabia. Ann Thorac Cardiovasc Surg 2002;8:298–301. 7. Feliciano DV, Mattox KL, Graham JM, Bitondo CG. Five-year experience with PTFE grafts in vascular wounds. J Trauma 1985;25:71–82. 8. Rich NM, Hughes CW. The fate of prosthetic material used to repair vascular injuries in contaminated wounds. J Trauma 1972;12:459–67. 9. McCready RA. Upper-extremity vascular injuries. Surg Clin North Am 1988;68:725–40. 10. Rothkopf DM, Chu B, Gonzalez F, Borah G, Ashmead D 4th, Dunn R. Radial and ulnar artery repairs: assessing patency rates with color Doppler ultrasonographic imaging. J Hand Surg Am 1993;18:626–8. 11. Boswick J. Injuries of the radial and ulnar arteries. In Proceedings of the American Society for Surgery of the Hand. J Bone Joint Surg 1967;49:582. 12. Stricker SJ, Burkhalter WE, Ouellette AE. Single-vessel forearm arterial repairs. Patency rates using nuclear angiography. Orthopedics 1989;12:963–5. 13. Sitzmann JV, Ernst CB. Management of arm arterial injuries. Surgery 1984;96:895–901. 14. Hunt CA, Kingsley JR. Vascular injuries of the upper extremity. South Med J 2000;93:466–8. 15. Bassetto F, Zucchetto M, Vindigni V, Scomparin MA, Corbetti F, Perissinotto E, et al. Traumatic musculoskeletal changes in forearm and hand after emergency vascular anastomosis or ligation. J Reconstr Microsurg 2010;26:441–7. 16. Leclercq DC, Carlier AJ, Khuc T, Depierreux L, Lejeune GN. Improvement in the results in sixty-four ulnar nerve sections associated with arterial repair. J Hand Surg Am 1985;10:997–9. 17. Kleinman WB, O’Connell SJ. Effects of the fasciocutaneous radial forearm flap on vascularity of the hand. J Hand Surg Am 1993;18:953–8.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Önkol damar onarımlarının değerlendirilmesi: Arter onarımı ile ilişkili fonksiyonel sonuçlar Dr. Musa Kemal Keleş,1 Dr. Tekin Şimşek,2 Dr. Veysel Polat,3 Dr. Engin Yosma,2 Dr. Ahmet Demir2 1 2 3

Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi Plastik, Rekonstrüktif ve Estetik Cerrahi Kliniği, Ankara Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Plastik Cerrahi Anabilim Dalı, Samsun Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, Samsun

AMAÇ: Tek damar yaralanması sonrası önkol damar onarımlarında, çalışan ve tıkalı arter onarımlarının geç dönem sonuçlarını karşılaştıran az sayıda çalışma vardır. Bu çalışmadaki amacımız önkol damar onarımlarının geç dönem sonuçlarını QuickDASH skoru ve renkli Doppler ultrason ile karşılaştırmaktı. GEREÇ VE YÖNTEM: Yüz altmış altı ön kol arter yaralanması olan hastalar tarandı. Aynı yaralanması olan 30 hasta (ulnar arter, ulnar sinir ve fleksör zon beş tendon yaralanması) renkli Doppler ve QuickDASH skorlaması için geri çağrıldılar. BULGULAR: Hastalar renkli Doppler sonuçlarına göre iki gruba ayrıldılar; çalışan damarı olanlar (grup 1) ve tıkalı damarı olanlar (grup 2). Bu iki grubun QuickDASH skorları arasında istatistiksel analiz yapıldı. Aradaki fark istatistiksel olarak anlamlıydı. Grup 1’de (24.27) grup 2’ye (36.34) göre daha düşük QuickDASH skoru vardı. Bu çalışan damarı olan hastalarda daha iyi sonuç alındığını göstermekteydi. TARTIŞMA: Sonuç olarak, vasküler onarım yapılan hastalarda daha iyi fonksiyonel sonuç alınabilmektedir. Anahtar sözcükler: Fonksiyonel sonuçlar; önkol yaralanması; sinir yaralanması; soğuk intoleransı; vasküler yaralanma. Ulus Travma Acil Cerrahi Derg 2017;23(2):117–121

doi: 10.5505/tjtes.2016.36080

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ORIGIN A L A R T IC L E

Approach to inguinal hernia in high-risk geriatric patients: Should it be elective or emergent? Rıza Gürhan Işıl, M.D.,1 Pınar Yazıcı, M.D.,1 Uygar Demir, M.D.,1 Cemal Kaya, M.D.,1 Özgür Bostancı, M.D.,1 Ufuk Oğuz İdiz, M.D.,1 Canan Tülay Işıl, M.D.,2 Mahmut Kaan Demircioğlu, M.D.,1 Mehmet Mihmanlı, M.D.1 1

Department of General Surgery, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul-Turkey

Department of Anesthesia and Reanimation, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: Elderly patients are more prone to have inguinal hernia due to weakened abdominal musculature. However, surgical repair of inguinal hernia (SRIH) may not be performed or may be delayed due to greater risk in presence of comorbidities. Present study is investigation of outcome of elective and emergency SRIH in geriatric patients. METHODS: Records of total of 384 high-risk (American Society of Anesthesiology classification III-IV) patients aged >65 years who underwent SRIH between January 2010 and December 2014 were reviewed. Patients were divided into 2 groups according to procedure type: elective (Group EL) or emergency (Group EM). Demographic features and surgical and postoperative period data of 2 groups were recorded and compared. RESULTS: Demographic data were similar, but number of ASA IV patients was greater in Group EM. Frequency of intestinal resection was significantly greater in emergency surgery group (1% vs 21%; p<0.01). Length of hospital stay (1.3 days vs 7.9 days; p<0.01) and intensive care unit stay (0.17 days vs 4.04 days; p<0.01) were also greater in Group EM. Morbidity (1% vs 24%; p<0.01) and mortality (0.3% vs 11%; p<0.01) were also significantly higher in Group EM compared to elective SRIH group. CONCLUSION: Emergency inguinal hernia surgery is associated with significantly higher morbidity and mortality compared with elective SRIH in high-risk geriatric patients. Elective hernia repair in these patients should be considered to reduce risk of need for intestinal resection as well as length of hospital stay. Keywords: Emergency surgery; geriatric; high risk; incarceration; inguinal hernia.

INTRODUCTION Improvement in global healthcare delivery has led to increase in aging population worldwide. An estimated 6 million people were older than 65 years of age in our country as of 2014.[1] Presence of co-morbid conditions in the elderly is known to be associated with high risk of surgical morbidity and mortality. In the absence of symptoms, surgical treatment is usually not performed or is delayed due to risk of morbidity. ConseAddress for correspondence: Rıza Gürhan Işıl, M.D. Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul, Turkey Tel: +90 212 - 373 50 00 E-mail: gurhanisil@hotmail.com Qucik Response Code

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quently, incidence of emergency surgeries among this patient population has increased significantly in recent years. Prevalence of inguinal hernia in the elderly is higher than in young people. One reason for this is progressive weakening of collagen tissue of the abdominal wall with age.[2] Recent guidelines issued by the European Hernia Association recommend watchful waiting in asymptomatic patients and patients with mild symptoms or co-morbid conditions.[3] Higher risk of morbidity is associated with emergency surgical repair of inguinal hernia (SRIH).[4,5] This study is an investigation of outcomes of elective and emergency SRIH in high-risk patients (American Society of Anesthesiologists [ASA] score >III).

MATERIALS AND METHODS The present study is retrospective analysis of 1824 elderly patients (age >65 years) who underwent elective or emerUlus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Işıl et al. Approach to inguinal hernia in high-risk geriatric patients

gency inguinal hernia repair at hospital between January 2010 and December 2014. In all, 1697 patients had SRIH under elective conditions, while 127 underwent emergency SRIH. Of total, 384 had ASA score greater than III and were considered high-risk patients. Study included only high-risk patients, who were then divided into 2 groups according to procedure performed: elective SRIH (Group EL, n=312) and emergency SRIH (Group EM, n=72). Medical records were examined to extract clinical, laboratory, and postoperative data on all study participants. Collected data included demographic characteristics, co-morbid conditions, ASA score (>III), operative procedure, duration of hospital/intensive

care unit (ICU) stay, and pre and postoperative morbidity parameters. All data were recorded in institutionally approved database and analyzed using SPSS software, version 15.0 (IBM Corp., Armonk, NY, USA). Kolmogorov-Smirnov test was used to test for normal distribution of parameters. Continuous variables are expressed as mean±SD and categorical variables as reported as numbers and percentages. Student’s t-test and Mann-Whitney U test were used in comparison of means of continuous variables, and chi-square and Fisher’s exact tests were used to evaluate differences in proportions. Statistical significance was accepted at p value of <0.05.

Table 1. Demographic features, perioperative data, postoperative complications, and co-morbidities

Group elective (n=312) n

Age

Mean±SD 77.1±7.6

Group emergency (n=72)

Min.-Max.

65–100

Mean±SD

Min.-Max.

77.3±7.7

65–99

0.935

Sex Female

39 13 12 7 0.348

Male

273 88

60 83

ASA III

269 86 18 5 <0.001*

43 14

50 9

310

Operation

Hernia repair (mesh)

Hernia repair+bowel resection

<0.001*

Result Discharge Exitus

311 100 63 87 <0.001* 1

Complication Yes No Anastomosis leakage

3 1 20 8 <0.001* 309 99

52 72

1 0 3 4

Hematoma

0 0 6 7

Scrotal edema

1 0 0 0

Wound infection

Hospital stay

1.3±1.0

1–14

7.9±12.3

2–82

<0.001*

Intensive care unit stay Yes

38 12 71 99 <0.001*

274

Co-morbidity

Type 2 diabetes mellitus

0.054

End stage renal disease

0.620

COPD

310 99 65 90 <0.001*

308

Coronary heart disease

<0.001*

ASA: American Society of Anesthesiologists; COPD: Chronic obstructive pulmonary disease; SD: Standard deviation; Min.: Minimum; Max.: Maximum. * p<0.05 is statistically significant. Independent samples t-test / Mann-Whitney U test / Chi-square test (Fischer’s exact test).

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RESULTS Demographic and clinical characteristics of both groups are provided in Table 1. Groups were comparable in terms of age and gender. There were more patients with ASA IV status in Group EM than Group EL (61% vs 14%; p=0.000). Incidence of cardiac and respiratory disease was also greater in Group EM than Group EL. Most often, general anesthesia was used in Group EM (95%), whereas only 8 patients (2.5%) underwent surgery with general anesthesia in Group EL (p<0.01). Significantly more patients in Group EM had concomitant bowel resection compared to Group EL (3% vs 1%; p<0.05), while incidence of laparotomy was only 3% in Group EM.

Emergency patients also stayed longer in the ICU (0.17±0.8 days vs 4.04±10.7 days; p<0.01) and hospital (1.3±1 days vs 7.9±12.2 days; p<0.01). Furthermore, they had greater incidence of postoperative morbidity (1% vs 24%; p<0.001) and mortality (0.3% vs 11%; p<0.001). Significant factors found in univariate analysis to predict postoperative complications were ASA score, end-stage renal disease (ESRD), and length of ICU/hospital stay. Multivariate analysis of these factors revealed ESRD and length of ICU/ hospital stay as independent predictors (p<0.05) of postoperative complications (Table 2). Four factors: ASA score, comorbid conditions (ESRD), length of ICU/hospital stay, and

Table 2. Morbidity Morbidity

Univariate model 95% CI

Multivariate model

95% CI

Age

1.01 1.07–0.96 0.730

Gender

1.02 3.57–0.29 0.972

American Society of Anesthesiologists score

7.99

3.57–3.53

Type 2 diabetes

2.59

0.28–7.40

0.076

End-stage renal disease

13.4

0.28–63.91

0.001* 22.3 3.2–156 0.002*

Chronically obstructive pulmonary disease

0.50

0.28–4.17

0.521

Coronary heart disease

0.31

0.28–0.98

0.051

Spinal/general anesthesia

11.4

71.7–1.80

0.010*

Inguinal incision/laparotomy

26.9

170.4–4.25

<0.001*

Intensive care unit stay

1.27

3.57–1.10

<0.001* 1.72 1.31–2.25 <0.001*

Hospital stay

1.41

3.57–1.24

<0.001* 1.99 2.59–1.54 <0.001*

<0.001*

CI: Confidence interval; OR: Odds ratio. *p<0.05 is statistically significant. Independent samples t-test / Mann-Whitney U test / Chi-square test (Fischer’s exact test).

Table 3. Mortality Morbidity

Univariate model

Multivariate model

95% CI

Age

1.0

0.9–1.1

0.483

Gender

0.6

0.1–2.9

0.530

American Society of Anesthesiologists score

17.1

4.6–63.9

<0.001* 13.8 2.4–80.9 0.004*

Type 2 diabetes

9.7

35.1–2.7

0.001*

End-stage renal disease

39.6

100<–7.4

<0.001* 36.8 2.8–489 0.006*

Chronically obstructive pulmonary disease

26.3

5.4–127.0

<0.001*

Coronary heart disease

0.2

0.6–0.0

0.009*

Spinal/general anesthesia

5–211

<0.001* 14.7 1.2–188.0 0.039*

Inguinal incision/laparotomy

249

24–2569

<0.001* 132.4 10.4–1694 <0.001*

Intensive care unit stay

1.4

1.2–1.6

<0.001*

Hospital stay

1.1

1.0–1.2

0.004*

Postoperative complications

0.1

0.0–0.3

<0.001*

ICU: intensive care unit; OR: Odds ratio. *p<0.05 is statistically significant. Independent samples t-test / Mann-Whitney U test / Chi-square test (Fischer’s exact test).

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postoperative complications predicted mortality in univariate analysis, while ASA score, incision type, anesthesia type, and ESRD were determined to be independent predictors of mortality in multivariate analysis (Table 3). In all, 10 patients died; mean±SD age was 82.7±4.5 years. Nine of these patients were in Group EM and only 1 belonged to Group EL. ASA score was IV in 9 of these patients and V in the remaining patient. Reasons for death were postoperative myocardial infarction (MI) in Group EL, and sepsis (n=1), postoperative MI (n=2), or respiratory complications (n=6) in Group EM patients.

DISCUSSION Study results indicate that there is higher risk of morbidity and mortality associated with emergency SRIH in geriatric patients with high ASA score. Moreover, these patients are more likely to have higher risk of incarcerated or strangulated hernia and thus undergo small bowel resection. These factors can lead to longer ICU and hospital stay among this group of patients. Surgery as treatment option in the elderly has been topic of interest for most clinicians over the past few decades. The reason for this widespread concern is effect of improved global healthcare, which has led to an aging population.[6] Among common surgical procedures worldwide, SRIH is one of the most frequently performed, especially in males older than 50 years of age. Incidence of inguinal hernia increases with progressive weakening of collagen tissue.[7,8] Surgical repair of herniated tissue is best known treatment option; however, with presence of co-morbid conditions that may occur with old age, treating elderly patients who present with hernia can be challenging. Previous studies have described safety and efficacy of SRIH among elderly patients. Nevertheless, higher risk of complications associated with SRIH and longer hospital stay have been reported in the elderly patient population compared with younger patients.[9] For this reason, in patients with appreciable risk factors, most surgeons resort to delay of elective surgery due to asymptomatic nature of inguinal hernia. Statement by the Inguinal Hernia: Conservative or Operative Approach Trialists’ Collaboration indicated that life expectancy for elderly male inguinal hernia patients associated with watchful waiting and with surgery differ very little. In cases of asymptomatic or mildly symptomatic patients, there seems to be no difference in pain relief between watchful waiting and operation.[10] Furthermore, in 2013 study conducted by Amato et al.,[11] authors reported that high-risk (ASA III-IV) elderly patients could undergo SRIH without limitations (existing co-morbidities). They demonstrated that high ASA score and comorbidities had no effect on operative success in elderly patients. Although consensus regarding timing of surgical intervention for asymptomatic elderly patients with comorbidities hasn’t been reached yet, need for in-depth risk-benefit analysis Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

involving both patients and surgeons cannot be denied. At our center, patients and their families are usually involved in making final decision about surgical treatment after patients complete their preoperative anesthesia and operative risk evaluation. Previous studies have proven that high risk of morbidity or mortality among the elderly is not associated with old age alone, but with presence of underlying co-morbid conditions.[4,12,13] Abete et al.[14] recently reported that with effective preoperative anesthesia and risk assessment evaluation, better postoperative outcomes can be achieved. In another study, by Gunnarsson et al.,[15] patients aged over 75 years who underwent elective inguinal hernia repair had promising post-operative outcomes. The authors concluded that SRIH in elderly population is worthwhile and highly appreciated by patients.[16] Compared to young patients, elderly patients are more likely to experience complicated inguinal hernia (incarceration or strangulation).[17] Compared to elderly patients, time from diagnosis to inguinal hernia repair is usually shorter in young patients, which might explain lower incidence of complicated inguinal hernia. Other reasons for choosing conservative methods over surgical treatment may include presence of co-morbid conditions.[12] About 90% of the patients who had emergency SRIH in our study had chronic obstructive pulmonary disease, 9% had chronic heart disease, 15% had type 2 diabetes, and 2% had end-stage renal disease. In elective SRIH group, 99% of the patients had chronic obstructive pulmonary disease, 99% had chronic heart disease, 9% had type 2 diabetes, and 2% had end-stage renal disease. These results seem to be confusing; however, 61% of emergency surgery group were ASA IV classification and 5% were ASA V. In elective surgery group, 86% were ASA III and 14% were ASA IV. This indicates that patients who underwent elective SRIH had co-morbidities that did not affect their routine life or limit quality of life. In contrast, the patients who underwent emergency SRIH had severe comorbidities that affected daily life, leading to increased perioperative morbidity and mortality rates. Previous studies have suggested reduction of incarcerated hernia in elderly patients; however, long-term follow-up studies later described reduction as temporary treatment option due to high incidence of re-incarceration.[18] Therefore, post-reduction repair in shortest possible time under elective conditions should be recommended as permanent solution. In this group of patients, emergency SRIH is reported to be associated with high risk of morbidity and mortality due to need for laparotomy and small bowel resection.[19–21] In patients who present with history of incarceration for more than 6 hours, resection is usually performed, which increases risk of mortality by 20 times.[21,22] Kulah et al.[23] demonstrated that risk of strangulation and small bowel resection is signifi125

Işıl et al. Approach to inguinal hernia in high-risk geriatric patients

cantly increased in patients with more than 48 hours between onset of symptoms and presentation. Intestinal complications are 4 times likely to occur in femoral hernia compared with inguinal hernia.[21] In our study, which included only elderly patients with high ASA score, incidence of small bowel resection was higher in patients who had emergency SRIH (21%) compared with those who underwent elective repair. Incidence of laparotomy was 5.5% in Group ER. Factors affecting morbidity were small bowel resection, low albumin level, and associated wound infection. Low albumin level is known to be responsible for longer ICU/hospital stay.[12] In our study, ICU/hospital stay and ESRD were found to be predictors of morbidity, and ASA score of IV or higher, ESRD, incision type, and anesthesia type were determined to be independent predictors of mortality. Postoperative complications were significantly associated with longer ICU/hospital stay. We could not determine value of low albumin, since albumin level is not part of routine biochemical work-up at our hospital in emergency setting.

Conflict of interest: None declared.

REFERENCES 1. http://www.tuik.gov.tr/PreIstatistikTablo.do?istab_id=945, at: December 31, 2015.

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2. Kulaçoğlu H, Polat A, Moran M, Gök R, Coşkun F. Electıve ınguınal hernıa repaır ın the elderly. Turk Geriatri Derg 2000;3:64–8. 3. Miserez M, Peeters E, Aufenacker T, Bouillot JL, Campanelli G, Conze J, et al. Update with level 1 studies of the European Hernia Society guidelines on the treatment of inguinal hernia in adult patients. Hernia 2014;18:151–63. 4. Malik AM, Khan A, Talpur KA, Laghari AA. Factors influencing morbidity and mortality in elderly population undergoing inguinal hernia surgery. J Pak Med Assoc 2010;60:45–7. 5. Mansouri M, Ekjam S, Hudairi A, Sannussi OI, Fakheri A. Emergency abdominal surgery in Libyan elderly patients. Sci Med J 2005;17:57–65. 6. Turrentine FE, Wang H, Simpson VB, Jones RS. Surgical risk factors, morbidity, and mortality in elderly patients. J Am Coll Surg 2006;203:865–77. 7. Zenilman ME. Surgery in the elderly. Curr Probl Surg 1998;35:99–179.

Primatesta et al.[16] reported emergency SRIH rate of only 9% in their analysis of over 30 000 SRIH cases in which 91% of the patients were male and there was mean age of 58 years. Mortality was significantly associated with emergency SRIH. Similar study by Martínez-Serrano et al.[24] that included patients over age of 70 years who underwent emergency abdominal hernia repair documented mortality rate of 4.5%. Mortality rate in our patient group was 11%. Higher rate than reported previously may be associated with higher ASA scores and greater age. Mean age of all patients in our study who died was 82 years, and 9 of the 10 patients had ASA score of IV while remaining patient had ASA score of V. Expected mortality in patients with ASA score of IV ranges between 7.8% and 23%, and that of patients with ASA score of V is between 9.4% and 51%. Although 11% mortality appears high in comparison with previous reports, it is far below expected mortality considering high ASA scores of our patients. Some studies have determined that small bowel resection was not predictive factor for mortality, but those patients did have higher rate of wound infections and longer hospital stay. [22,25] In present study, ASA score of IV, underlying co-morbid condition, specifically ESRD, and postoperative complications were among factors that predicted mortality. In conclusion, emergency SRIH is associated with high risk of mortality and morbidity in elderly patients with higher ASA classification. Small bowel resection may be required and length of hospital stay may be prolonged. As supported by findings from our study, we suggest elective SRIH be performed in geriatric patients with high ASA score after appropriate preoperative anesthesia assessment and surgical risk evaluation.

Acknowledgement There is no acknowledgement to declare. 126

8. Demir U, Mihmanli M, Coskun H, Dilege E, Kalyoncu A, Altinli E, et al. Comparison of prosthetic materials in incisional hernia repair. Surg Today 2005;35:223–7. 9. Pavlidis TE, Symeonidis NG, Rafailidis SF, Psarras K, Ballas KD, Baltatzis ME, et al. Tension-free by mesh-plug technique for inguinal hernia repair in elderly patients. Scand J Surg 2010;99:137–41. 10. INCA Trialists Collaboration. Operation compared with watchful waiting in elderly male inguinal hernia patients: a review and data analysis. J Am Coll Surg 2011;212:251–9. 11. Amato B, Compagna R, Fappiano F, Rossi R, Bianco T, Danzi M, et al. Day-surgery inguinal hernia repair in the elderly: single centre experience. BMC Surgery 2013;13:28. 12. Dunne JR, Malone DL, Tracy JK, Napolitano LM. Abdominal wall hernias: risk factors for infection and resource utilization. J Surg Res 2003;111:78–84. 13. Williams JS, Hale HW. The advisability of inguinal herniorrhaphy in the elderly. Surg Gynecol Obstet 1966;122:100–4. 14. Abete P, Cherubini A, Di Bari M, Vigorito C, Viviani G, Marchionni N, et al. Does comprehensive geriatric assessment improve the estimate of surgical risk in elderly patients? An Italian multicenter observational study. Am J Surg 2016;211:76–83. 15. Gunnarsson U, Degerman M, Davidsson A, Heuman R. Is elective hernia repair worthwhile in old patients? Eur J Surg 1999;165:326–32. 16. Primatesta P, Goldacre MJ. Inguinal hernia repair: incidence of elective and emergency surgery, readmission and mortality. Int J Epidemiol 1996;25:835–9. 17. Rutkow IM, Robbins AW. Classification systems and groin hernias. Surg Clin North Am 1998;78:1117–27. 18. Nehme AE. Groin hernias in elderly patients. Management and prognosis. Am J Surg 1983;146:257–60. 19. Kekeç Y, Alparslan A, Demirtaş S, Ezici H, Altınay R. The Effects of Strangulation on Morbidity and Mortality in Irreductible Hernias. Ulus Cerrahi Derg 1993;9:128–31. 20. Rai S, Chandra SS, Smile SR. A study of the risk of strangulation and obstruction in groin hernias. Aust N Z J Surg 1998;68:650–4. 21. Nilsson H, Stylianidis G, Haapamäki M, Nilsson E, Nordin P. Mortality after groin hernia surgery. Ann Surg 2007;245:656–60.

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Işıl et al. Approach to inguinal hernia in high-risk geriatric patients 22. Kurt N, Oncel M, Ozkan Z, Bingul S. Risk and outcome of bowel resection in patients with incarcerated groin hernias: retrospective study. World J Surg 2003;27:741–3. 23. Kulah B, Duzgun AP, Moran M, Kulacoglu IH, Ozmen MM, Coskun F. Emergency hernia repairs in elderly patients. Am J Surg 2001;182:455–9. 24. Martínez-Serrano MA, Pereira JA, Sancho JJ, López-Cano M, Bom-

buy E, Hidalgo J. Risk of death after emergency repair of abdominal wall hernias. Still waiting for improvement. Langenbecks Arch Surg 2010;395:551–6. 25. Alvarez JA, Baldonedo RF, Bear IG, Solís JA, Alvarez P, Jorge JI. Incarcerated groin hernias in adults: presentation and outcome. Hernia 2004;8:121–6.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Yüksek riskli geriatrik hastalarda inguinal hernilere yaklaşım: Elektif mi, acil mi olmalıdır? Dr. Rıza Gürhan Işıl,1 Dr. Pınar Yazıcı,1 Dr. Uygar Demir,1 Dr. Cemal Kaya,1 Dr. Özgür Bostancı,1 Dr. Ufuk Oğuz İdiz,1 Dr. Canan Tülay Işıl,2 Dr. Mahmut Kaan Demircioğlu,1 Dr. Mehmet Mihmanlı1 1 2

Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Kliniği, İstanbul

AMAÇ: İlerleyen yaşla birlikte inguinal herni insidansı artmaktadır. Bu hasta grubunda komorbiditelerin de artması inguinal herniye yaklaşımda cerrahiyi arka plana atmakta ve acil girişim oranlarını artırmaktadır. Bu çalışmada, inguinal herni nedeniyle ameliyat edilen yüksek riskli geriatrik hastalarda elektif ve acil yaklaşım sonuçlarını karşılaştırmalı olarak incelemeyi amaçladık. GEREÇ VE YÖNTEM: Ocak 2010 ve Aralık 2014 tarihleri arasında kliniğimizde inguinal bölge fıtıkları nedeni ile ameliyat edilen geriatrik (≥65 yaş) hastalar arasından yüksek riskli (ASA III ve üzeri) 384 hastanın dosyası geriye dönük olarak incelendi. Bu hastalar elektif (n=312) ve acil (n=72) operasyon olarak iki grupta incelendi. Tüm hastaların demografik özellikleri, ASA skoru, operasyon prosedürleri (insizyon şekli, ek prosedürler, anestezi tipi), yoğun bakım ve hastanede kalış süreleri, morbidite ve mortalite parametreleri kaydedildi. BULGULAR: Demografik özellikler Grup 2’de anlamlı yüksek ASA IV oranı hariç benzerdi. Bağırsak rezeksiyonu riski %1 ve karşı %21 olarak Grup 2’de anlamlı yüksek izlendi. Hastanede (1.3 güne 7.9 gün, sırasıyla, p<0.01) ve yoğun bakımda kalış süreleri de Grup 2’de anlamlı uzun bulundu. Ameliyat sonrası morbidite (%1’e karşı %24, p<0.01) ve mortalite (%0.3’e karşı %11, p<0.01) Grup 2’de anlamlı yüksek saptandı. Ameliyat sonrası komplikasyon üzerine etki gösteren bağımsız parametreler arasında böbrek yetersizliği, yoğun bakım ve hastanede kalış süreleri bulunurken; mortalite üzerine etkiyen bağımsız faktörler arasında ASA skoru, böbrek yetersizliği, insizyon şekli (laparotomi) ve anestezi türü (genel anestezi) saptandı. TARTIŞMA: Elektif inguinal herni ile karşılaştırıldığında, ASA skoru yüksek yaşlı hastalarda acil olarak uygulanan inguinal herni operasyonları daha yüksek morbidite ve mortalite ile seyretmektedir. Daha sık bağırsak rezeksiyon ihtiyacı ve anlamlı uzun hastanede kalış sürelerini de dikkate alarak inguinal herni tanısı alan yüksek riskli yaşlı hastalarda da elektif operasyon uygulanmasını öneriyoruz. Anahtar sözcükler: Acil operasyon; geriatrik; inkarserasyon; inguinal herni; yüksek riskli. Ulus Travma Acil Cerrahi Derg 2017;23(2):122–127

doi: 10.5505/tjtes.2016.36932

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ORIGIN A L A R T IC L E

Primary small intestinal non-Hodgkin lymphoma diagnosed after emergency surgery Tevfik Avcı, M.D.,1 Hakan Yabanoğlu, M.D.,2 İlker Murat Arer, M.D.,2 Nazım Emrah Koçer, M.D.,3 Kenan Çalışkan, M.D.,2 Pelin Börcek, M.D.,4 Yahya Ekici, M.D.1 1

Department of General Surgery, Başkent University Faculty of Medicine, Ankara-Turkey

Department of General Surgery, Başkent University Faculty of Medicine, Adana Training and Research Center, Adana-Turkey

Department of Pathology, Başkent University Faculty of Medicine, Adana Training and Research Center, Adana-Turkey

Department of Pathology, Başkent University Faculty of Medicine, Ankara-Turkey

ABSTRACT BACKGROUND: The aim of this study was to investigate clinical manifestation, diagnosis, treatment, and prognosis of patients with primary gastrointestinal non-Hodgkin lymphoma (PGI NHL), whose initial presentation was bowel obstruction or perforation. METHODS: Data of patients who underwent surgical intervention due to radiological evidence of perforation or intestinal obstruction and were subsequently diagnosed with intestinal lymphoma at Baskent University hospitals between January 2007 and November 2014 were examined retrospectively. Medical records, clinical history, symptoms, pathological reports, and treatment modalities were analyzed. RESULTS: Study population comprised 17 patients (8 male, 9 female) with PGI NHL and mean age of 52±20.2 years. Symptoms reported by the patients were abdominal pain, nausea, vomiting, weight loss, and loss of appetite. All 17 patients underwent surgical treatment; 12 also received postoperative chemotherapy. Most common pathological subtype was diffuse large B-cell lymphoma (70.5%). Mean follow-up time was 26 months (range: 1–69 months) and 5-year survival rate was 64.3%. CONCLUSION: Initial presentation of PGI NHL may be obstruction with or without perforation; clinicians and surgeons should keep this in mind while assessing patient with bowel obstruction, and particularly patient in fifth decade of life. Keywords: Emergency treatment; general surgery; ileus, intestinal perforation; lymphoma; small intestine.

INTRODUCTION Primary gastrointestinal non-Hodgkin lymphoma (PGI NHL) is most common type of extranodal lymphoma (30% to 50% of all extranodal lymphomas). PGI NHL is most often seen in the stomach, followed by the colon and small intestine. [1] Diffuse large B-cell lymphoma is most common pathological subtype of PGI NHL. Diagnosis of PGI NHL may be missed due to its unspecific clinical manifestation. Differential diagnosis of PGI NHL from other types of gastrointesAddress for correspondence: Tevfik Avcı, M.D. Başkent Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Ankara, Turkey Tel: +90 312 - 203 68 68 E-mail: tevfikavci@yahoo.com Qucik Response Code

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tinal (GI) tumors may not be possible. It has been reported that approximately 20% of all small bowel malignancies are newly diagnosed NHL.[2] Most frequently seen symptom of GI lymphoma is abdominal pain; however, signs and symptoms are generally nonspecific. “B symptoms,” such as fever, weight loss, and night sweats, are not common in nonsystemic disease, and are seen in fewer than 12% of patients. [3] Some 30% to 50% of patients are admitted to hospital with acute abdominal pain, and 25% of these have GI perforation.[4] Obstruction and perforation are uncommon and life-threatening complications of lymphoma that can occur either at diagnosis or during the treatment course. Occurrence of obstruction or perforation increases mortality rate as result of circumstances such as sepsis, multi-organ failure, prolonged hospitalization, impaired wound healing, and delay of chemotherapy. The present study retrospectively summarized outcome of 17 patients who underwent emergency surgical intervention for intestinal perforation or obstruction due to intestinal NHL and were diagnosed with intestinal NHL after surgery. Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Avcı et al. Primary small intestinal non-Hodgkin lymphoma diagnosed after emergency surgery

MATERIALS AND METHODS

(a)

Records of patients who underwent surgical intervention following radiological evidence of perforation or intestinal obstruction and were diagnosed with intestinal lymphoma after the surgery at Baskent University Faculty of Medicine, Ankara; Baskent University Adana Training and Research Hospital; and Baskent University İzmir Zübeyde Hanım Training and Research Hospital between January 2007 and November 2014 were examined retrospectively. Data of medical records, clinical history, symptoms, preoperative investigations, pathology reports, and details of management were analyzed. This study was approved by Baskent University institutional review board and supported by Baskent University research fund (KA14/143).

(b)

(c)

Statistical Analyses Statistical analyses of the data were performed using SPSS software, version 11.5 (IBM Corp., Armonk, NY, USA) Descriptive statistics for continuous and discrete numeric variables were expressed as mean±standard deviation or median (minimum-maximum) values and categorical variables as number of cases (%). Annual cumulative survival rate, median survival time, and 95% confidence interval were calculated using Kaplan-Meier survival analysis.

RESULTS At time of initial diagnosis of lymphoma, the patients were between 25 and 82 years of age, with median age for the group of 52 years. Of 17 patients, 9 were female and 8 were male. The patients presented with complaints of abdominal pain, nausea and/or vomiting, loss of appetite, and weight loss; most common symptom was abdominal pain. Physical examinations revealed abdominal tenderness and muscular rigidity. Contrast-enhanced computed tomography (CT) of the abdomen was performed on all patients for intestinal obstruction due to intraabdominal and/or intestinal mass. In 11 patients, only ileus was seen, whereas in 4 patients, free fluid in the pelvis and pneumoperitoneum within the peritoneal cavity, which were compatible with perforation, were detected. In 1 patient, invagination was observed in CT scans. Tumor localization was jejunum in 8 patients and ileum in 9 patients (Figure 1a–c). All obstruction and perforation events were initial presentation of intestinal lymphoma. There was no history of lymphoma in any of the patients; Patient 5 had history of acute lymphocytic leukemia, Patient 6 had history of renal-cell carcinoma, and Patient 17 had history of coeliac disease (Table 3). Clinical characteristics, clinical symptoms (or signs), clinical features, and outcome of the 17 patients with intestinal obstruction or perforation are summarized in Table 1, Table 2, and Table 3.

Figure 1. (a) A 25-year-old man presented with weight loss and loss of appetite. Oral and intravenous contrast-enhanced axial computed tomography image obtained from upper abdominal level demonstrates obstruction of the jejunum (open arrow) and extreme dilatation of proximal jejunal loops (arrows). Histopathology diagnosis was diffuse large B-cell lymphoma; (b) A 40-yearold man presented with nausea and vomiting. Coronal (b) and sagittal oblique (c) images reveal thickening of the small bowel wall at jejunal level (arrows in B and double arrows in (c) and mild dilatation of proximal loops. Histopathology diagnosis was T-cell lymphoma.

Table 1. Clinical characteristics of patients Variables Age (years; median)

Total (n=17)

52 (25–82)

Gender, n (%)

Male

8 (47)

Female

9 (53)

Symptoms, n (%)

Nausea and/or vomiting

5 (29.4)

Loss of appetite

3 (17.6)

Abdominal pain

14 (82.3)

Weight loss

2 (11.7)

Computed tomography, n (%)

Ileus

13 (76.4)

Intestinal mass

5 (29.4)

Intraabdominal mass

6 (35.2)

Intraabdominal multiple lymph nodes

3 (17.6)

Perforation

4 (23.5)

Invagination

1 (5.8)

Site of disease, n (%)

Ileum

9 (53)

Jejunum

8 (47)

Resection of affected segment and end-to-end anastomosis Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

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Avcı et al. Primary small intestinal non-Hodgkin lymphoma diagnosed after emergency surgery

(a)

Table 2. Clinical symptoms or signs of patients Variables

(b)

Total (n=17)

Size (cm; median)

5 (1–13)

Histological subtype, n (%)

Diffuse large B cell lymphoma

12 (70.5)

Mucosa-associated lymphoid tissue lymphoma

2 (11.7)

Anaplastic T-cell lymphoma

1 (5.8)

Peripheral T-cell lymphoma

1 (5.8)

Enteropathy type T-cell lymphoma

1 (5.8)

Clinical stage, n (%)

5 (29.4)

III

7 (41.1)

–

Chemotherapy after surgery, n (%)

12 (70.5)

4 (23.5)

Metastasis

Lung

1 (5.8)

Liver

1 (5.8)

Intraabdominal

4 (23.5)

Death, n (%)

5 (29.4)

Figure 2. (a) Infiltration of medium to large neoplastic lymphocytes beneath the colonic glands, (b) Ulceration and Candida hyphae and spots on the surface (A: HE x100; B: HE x100).

tistically significant correlation between tumor stage and survival rate, which was 75% in patients with stage I-II, and 83.3% in patients with stage III (p=0.784). Despite achieving remission, 4 of these patients relapsed within median disease-free period of 31.5 months (range: 19-46 months). In all 4, relapse occurred in distant lymph node location with or without extranodal involvement. Two of the 7 patients who

Table 3. Clinical features and outcomes of patients

was performed on all patients. Surgical specimens were sent toPatients pathology for examination (Figure b; Figure 3a,findings b; and Medical history Site of 2a, Radiological Histological subtype Stage Results Follow-up disease (months) Figure 4). PGI NHL was frequently encountered as single lesion with size of 5.5±3.3 cm (range: 1–13 cm). Final patho1 – Perforation MALToma IIIE Death – logical diagnosis was intestinalJejunum NHL with subtypes of diffuse 2 B-cell lymphoma – Diffuse large Bcell lymphoma IIIE Remission 8 large in 12Jejunum patients, mucosa Ileus –associated lymphoid tissue lymphoma (MALToma) in 2 patients, T-cell 3 – Jejunum Ileus, Intraabdominal mass Peripheral T-cell lymphoma IE Metastasis 21 anaplastic lymphoma peripheral T-cell lymphoma 4 – in 1 patient, Jejunum Ileus, Intraabdominal mass Diffuse large B-cell lymphoma IE Metastasis 19 in 1 patient, and enteropathy type T-cell lymphoma in 1 pa5 Acute Ileum Ileus, Intraabdominal mass Diffuse large B-cell lymphoma IIE Death – tient. As pathological diagnosis was PGI NHL, further exami lymphocytic nations were conducted for tumor grading, which resulted in 5 leukemia patients with stage I, 5 patients with stage II, and 7 patients 6 stage III Renal-cell Jejunum Ileus, mass Diffuse large B-cell lymphoma IIIE Remission 9 with tumor. In all, 12 patients hadIntraabdominal chemotherapy with cyclophosphamide, hydroxydaunorubicin, vincristine, carcinoma and regimen after Ileus, the surgery. 7 prednisone (CHOP) – Jejunum Intraabdominal mass Diffuse large B-cell lymphoma IIIE Death – 8

–

Ileum

Perforation

After treatment, the patients were followed-up for 5-year 9 – Perforation period (at 6 months, and 1, 2,Ileum and 5 years). Three patients 10 had diffuse – Ileus,died Intraabdominal mass who large B-cellJejunum lymphoma in the first 11 – Ileum Ileus, Intraabdominal mass month due to postoperative complications, 1 patient who had lymphoma afterIntraabdominal 4 months, and 12 diffuse large B-cell – Ileum diedIleus, mass 113 patient who had– T-cell lymphoma died after 5.5 years. The Ileum Ileus, Intraabdominal mass 5-year cumulative survival rate was 78.6% (Figure 5). When 14 – Jejunum Perforation 5-year survival rate was assessed according to subtype, no 15 – Ileum Invagination statistically significant difference was found between patients 16 B-cell and T-cell – lymphoma Ileum Ileus, Intraabdominal mass with (p=0.391); 5-year survival 17 was 83.3% Coeliac disease Ileum with Ileus, B-cell Intraabdominal mass rate and 50% in patients and T-cell lymphoma, respectively. Furthermore, there was no staMALToma: Mucosa –associated lymphoid tissue lymphoma.

130

Diffuse large B-cell lymphoma

IIE

Remission

Anaplastic T-cell lymphoma

IIE

Death

–

Diffuse large B-cell lymphoma

IIIE

Metastasis

MALToma

IIE

Remission

Diffuse large B-cell lymphoma

IIIE

Metastasis

Diffuse large B-cell lymphoma

Remission

Diffuse large B-cell lymphoma

IIIE

Remission

Diffuse large B-cell lymphoma

Remission

Diffuse large B-cell lymphoma

IIE

Death

Peripheral T-cell lymphoma

IIIE

Remission

Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Avcı et al. Primary small intestinal non-Hodgkin lymphoma diagnosed after emergency surgery

(a)

(b)

1.0

Cumulative survival (%)

0.0

Figure 3. (a) Necrosis and (b) periserosal adipose tissue infiltration (A: HE x100; B: HE x100).

Time (months)

Figure 5. Kaplan-Meier survival curves for 14 cases of primary gastrointestinal non-Hodgkin lymphoma.

ate area. PubMed search using “lymphoma, small intestine, emergency treatment, general surgery, ileus, intestinal perforation” also yielded no results.

Figure 4. Immunohistochemical stain indicating strong, diffuse CD3 positivity in the neoplastic lymphocytes (CD3 x200).

had stage III tumor died, as well as 3 of the 10 patients who had stage I-II tumor.

DISCUSSION The gastrointestinal tract is the most common site of extranodal NHL. However, primary small bowel lymphoma, which is second most common small bowel neoplasm after adenocarcinoma, is relatively rare.[3,4] It has been reported that approximately 20% of all small bowel malignancies are newly diagnosed NHL.[2] Some 30% to 50% of patients are admitted to hospital with acute abdomen and 25% of them have GI perforation.[4] Research of 7-year period at 3 different centers yielded only 17 patients who underwent surgical intervention with radiological evidence of perforation or intestinal obstruction and were diagnosed with intestinal lymphoma after surgery. Although there are many publications about small intestine lymphoma, PubMed search with keywords “lymphoma, small intestine, ileus” returned only 28 articles, most of which were case reports. None was related to Turkey or the immediUlus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Particularly in patients over 50 years of age, primary small bowel NHL should be considered in differential diagnosis of patients with small bowel obstruction in addition to causes of intestinal obstruction such as hernia, adhesions, and bezoars. In our study, median age of the patients with PGI NHL was 52 years (range: 25–82 years). Incidence of PGI NHL was higher in women than in men (male:female ratio: 8:9), which was not consistent with previous studies.[5,6] This is likely due to small number of patients included in present study. In recent research, associations between intestinal lymphoma and immunosuppression after transplantation, inflammatory bowel disease, or human immunodeficiency virus infection have been found.[7–9] Medical history of our patients was insignificant, except for coeliac disease in Patient 17. Patient 5 had history of acute lymphoblastic leukemia (ALL) and Patient 6 had history of renal cell carcinoma (RCC). To our knowledge, there are no data available regarding correlation between these 2 diseases and intestinal lymphoma. Further studies could be conducted to investigate potential associations between intestinal lymphoma and ALL or intestinal lymphoma and RCC. Primary small bowel NHL has wide range of clinical presentations, including nonspecific abdominal pain, ileus, weight loss, and perforation.[10,11] Clinical manifestations in our patients were: nausea and/or vomiting in 5 (29.4%) patients; loss of appetite in 3 (17.6%) patients; abdominal pain in 14 (82.3%) patients; and weight loss in 2 (11.7%) patients. These ratios were similar to those seen in previous studies. As reported in earlier studies, free intestinal perforation due 131

Avcı et al. Primary small intestinal non-Hodgkin lymphoma diagnosed after emergency surgery

to NHL may occur spontaneously or after chemotherapy. [12,13] In our study, initial presentation was obstruction due to mass, which caused ileus in 13 patients and perforation in 4 patients. PGI NHL was frequently encountered as single lesion with size of 5.5±3.3 cm (range: 1–13 cm). Most primary intestinal lymphomas are of B-cell origin,[14,15] and our data confirmed this: 14 (82.3%) of masses were of B-cell origin, while 3 (17.6%) were of T-cell origin. In the present study, ileum was more common primary tumor site than jejunum, with proportion of 53% and 47%, respectively. Although difference between tumor locations was not statistically significant, it is consistent with results of previous studies indicating ileum was most common site.[16] There is a lack of evidence to guide postoperative management of emergency presentations of intestinal NHL with respect to effect on overall prognosis and optimal timing of postoperative chemotherapy. Chemotherapy with CHOP regimen has been shown to be as effective as other chemotherapy regimes. For stage I–II intestinal NHL, surgical resection and postoperative chemotherapy seems to be preferred treatment choice and has 5-year survival rate of 50% to 67%. In stages III–IV, ideal treatment is less clear.[17–19] Three of our patients died in the first month due to postoperative complications, 1 patient died after 4 months, and 1 patient died after 5.5 years. Total of 12 patients received CHOP regimen after initial surgery. Our cumulative survival rate results were also different from those reported in the literature. It has been reported that patients at early stage (stage I-II) and patients with B-cell lymphoma have higher cumulative survival rate. [17,18] However, our data demonstrated no statistical difference in survival rate between B-cell and T-cell lymphoma, or between early stages and stage III. We propose that this contradiction may also be explained by small number of patients used here, and that if the patient number increases, results may be similar to previous studies. In conclusion, our data demonstrated that primary small bowel B-cell lymphoma is more common than T-cell lymphoma. Initial presentation of the disease may be obstruction with or without perforation. Therefore, clinicians and surgeons should keep this in mind when assessing patient with bowel obstruction, and particularly patient in fifth decade of life.

Acknowledgments This study did not receive any specific funding or grants. Conflict of interest: None declared.

REFERENCES 1. Gou HF, Zang J, Jiang M, Yang Y, Cao D, Chen XC. Clinical prognostic analysis of 116 patients with primary intestinal non-Hodgkin lymphoma. Med Oncol 2012;29:227–34.

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2. Koch P, del Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W, et al. Primary gastrointestinal non-Hodgkin’s lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92. J Clin Oncol 2001;19:3861–73. 3. Yoon SS, Coit DG, Portlock CS, Karpeh MS. The diminishing role of surgery in the treatment of gastric lymphoma. Ann Surg 2004;240:28– 37. 4. Koniaris LG, Drugas G, Katzman PJ, Salloum R. Management of gastrointestinal lymphoma. J Am Coll Surg 2003;197:127–41. 5. Hwang HS, Yoon DH, Suh C, Park CS, Huh J. Intestinal diffuse large Bcell lymphoma: an evaluation of different staging systems. J Korean Med Sci 2014;29:53–60. 6. Radić-Kristo D, Planinc-Peraica A, Ostojić S, Vrhovac R, KardumSkelin I, Jaksić B. Primary gastrointestinal non-Hodgkin lymphoma in adults: clinicopathologic and survival characteristics. Coll Antropol 2010;34:413–7. 7. Howdle PD, Jalal PK, Holmes GK, Houlston RS. Primary small-bowel malignancy in the UK and its association with coeliac disease. QJM 2003;96:345–53. 8. Lee J, Kim WS, Kim K, Ko YH, Kim JJ, Kim YH, et al. Intestinal lymphoma: exploration of the prognostic factors and the optimal treatment. Leuk Lymphoma 2004;45:339–44. 9. Berney T, Delis S, Kato T, Nishida S, Mittal NK, Madariaga J, et al. Successful treatment of posttransplant lymphoproliferative disease with prolonged rituximab treatment in intestinal transplant recipients. Transplantation 2002;74:1000–6. 10. Hall CH Jr, Shamma M. Primary intestinal lymphoma complicating Crohn’s disease. J Clin Gastroenterol 2003;36:332–6. 11. Aydin I, Başkent A, Celik G, Aren A, Eren MZ, et al. A case of primary intestinal lymphoma associated with intestinal perforation. Ulus Travma Derg 2001;7:74–6. 12. Yokota T, Yamada Y, Murakami Y, Yasuda M, Kunii Y, Yamauchi H, et al. Abdominal crisis caused by perforation of ileal lymphoma. Am J Emerg Med 2002;20:136–7. 13. Ara C, Coban S, Kayaalp C, Yilmaz S, Kirimlioglu V. Spontaneous intestinal perforation due to non-Hodgkin’s lymphoma: evaluation of eight cases. Dig Dis Sci 2007;52:1752–6. 14. Huang Q, Chang KL, Gaal K, Arber DA. Primary effusion lymphoma with subsequent development of a small bowel mass in an HIV-seropositive patient: a case report and literature review. Am J Surg Pathol 2002;26:1363–7. 15. Chim CS, Loong F, Leung AY, Tsang J, Ooi GC. Primary follicular lymphoma of the small intestine. Leuk Lymphoma 2004;45:1463–6. 16. Yin L, Chen CQ, Peng CH, Chen GM, Zhou HJ, Han BS, et al. Primary small-bowel non-Hodgkin’s lymphoma: a study of clinical features, pathology, management and prognosis. J Int Med Res 2007;35:406–15. 17. d’Amore F, Christensen BE, Brincker H, Pedersen NT, Thorling K, Hastrup J, et al. Clinicopathological features and prognostic factors in extranodal non-Hodgkin lymphomas. Danish LYFO Study Group. Eur J Cancer 1991;27:1201–8. 18. Amer MH, el-Akkad S. Gastrointestinal lymphoma in adults: clinical features and management of 300 cases. Gastroenterology 1994;106:846– 58. 19. Abbott S, Nikolousis E, Badger I. Intestinal lymphoma--a review of the management of emergency presentations to the general surgeon. Int J Colorectal Dis 2015;30:151–7.

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Avcı et al. Primary small intestinal non-Hodgkin lymphoma diagnosed after emergency surgery

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Acil cerrahi sonrası tanı alan primer ince bağırsak non-Hodgkin lenfomaları Dr. Tevfik Avcı,1 Dr. Hakan Yabanoğlu,2 Dr. İlker Murat Arer,2 Dr. Nazım Emrah Koçer,3 Dr. Kenan Çalışkan,2 Dr. Pelin Börcek,4 Dr. Yahya Ekici1 Başkent Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Ankara Başkent Üniversitesi Adana Uygulama ve Araştırma Merkezi, Genel Cerrahi Anabilim Dalı, Adana Başkent Üniversitesi Adana Uygulama ve Araştırma Merkezi, Patoloji Anabilim Dalı, Adana 4 Başkent Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, Ankara 1 2 3

AMAÇ: Bizim bu çalışmamızda amacımız, hastaneye obstrüksiyon veya perforasyon bulgularıyla başvuran ve ameliyat sonrası primer intestinal nonHodgkin lenfoma tanısı alan hastaların klinik bulgularını, tanı, tedavi ve prognozlarını incelemektir. GEREÇ VE YÖNTEM: Başkent Üniversitesi Tıp Fakültesi Hastanesi Genel Cerrahi Anabilim Dalı’nda, Ocak 2007–Kasım 2014 yılları arasında, radyolojik olarak obstrüksiyon veya perforasyon varlığı kanıtlanmış ve ameliyata alındıktan sonra non-Hodgkin lenfoma tanısı alan hastaların özgeçmişleri, başvuru anındaki semptomları, patoloji raporları ve cerrahi tedavi sonrası takipleri geriye dönük olarak incelendi. BULGULAR: Çalışmamıza dahil edilen primer intestinal non-Hodgkin lenfoma tanısı alan 17 hastanın ortalama yaşı 52±20.2, erkek: kadın oranı 8.9 idi. Hastaların başvuru anındaki semptomları; karın ağrısı, bulantı-kusma, kilo kaybı ve iştahsızlıktı. Tüm hastalar cerrahi olarak tedavi edildi ve 12 hastaya ameliyat sonrası dönemde kemoterapi uygulandı. En sık rastlanan patolojik alt tip diffüz B-hücreli lenfoma idi (%70.5). Hastaların takip süresi 26 (dağılım, 1–69) ay, sağkalım oranı %64.3 idi. TARTIŞMA: Primer intestinal non-Hodgkin lenfoma hastalığının ilk prezentasyonu, hastalarda gelişen intestinal obstrüksiyon ve/veya perforasyon olabileceği için, özellikle 50. dekatta bağırsak obstrüksiyonu ile gelen hasta değerlendirilirken non-Hodgkin lenfoma akılda bulundurulmalıdır. Anahtar sözcükler: Acil cerrahi; genel cerrahi; ileus; ince bağırsak; intestinal perforasyon; lenfoma. Ulus Travma Acil Cerrahi Derg 2017;23(2):128–133

doi: 10.5505/tjtes.2016.02359

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ORIGIN A L A R T IC L E

How to avoid negative appendectomies: Can US achieve this? Kinyas Kartal, M.D., Pınar Yazıcı, M.D., Taner Mehmet Ünlü, M.D., Mehmet Uludağ, M.D., Mehmet Mihmanlı, M.D. Department of General Surgery, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: Clinical diagnosis of acute appendicitis is based primarily on symptoms and physical findings. However, diagnosis of appendicitis is not always straightforward. The aim of this study was to demonstrate the diagnostic effectiveness of ultrasonography (US) in these cases in combination with white blood cell count (WBC) and C-reactive protein (CRP) level. METHODS: Retrospective analysis of data collected on 470 consecutive patients who underwent appendectomy at the same institution between January 2014 and January 2016 was conducted. Data included demographic features, preoperative WBC and CRP levels, and US measurement of diameter of appendix. Patients were divided into 3 groups: lymphoid hyperplasia (LH), non-complicated acute appendicitis (NCAA), and complicated acute appendicitis (CAA), according to postoperative histopathological examination results. RESULTS: There were 331 male and 139 female patients with mean age of 32.29±11.44 years included in the study. Mean WBC level was 12.31103/μL (±4.47 103/μL), 13.3 103/μL (±3.87 103/μL) and 14.08 103/μL (±4.11 103/μL) in LH, NCAA, and CAA groups, respectively (p=0.016). Mean CRP level was 14.2±19 mg/L, 36.9±59 mg/L, and 40.8±66 mg/L in LH, NCAA, and CAA groups, respectively (p=0.008). Mean outer diameter of the vermiform appendix on US was 4.8 mm (±3.9 mm), 6.9 mm (±4.08 mm) and 7.6 mm (±3.92 mm) in LH, NCAA, and CAA groups, respectively (p<0.01). When all variables were compared with each other, there were statistically significant differences in US findings according to group. CONCLUSION: WBC count and CRP level were higher in patients with acute appendicitis, but these findings alone were insufficient for definitive diagnosis. US findings were effectual both in diagnosis and demonstration of severe inflammation. US should be combined with laboratory tests and used as standard initial imaging in diagnostic pathway of patients with clinically suspected appendicitis. The authors of this study believe that this diagnostic pathway will reduce negative appendectomy rate. Keywords: Acute appendicitis; C-reactive protein; negative appendectomy; ultrasonography; white blood cell count.

INTRODUCTION Worldwide, appendicitis is most common cause of acute abdominal pain involving surgical intervention.[1] Clinical diagnosis of acute appendicitis is based primarily on symptoms and physical findings. However, diagnosis of appendicitis is not always straightforward. Authors of large prospective studies have reported removal rate in negative appendectomy of beAddress for correspondence: Kinyas Kartal, M.D. Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi, 4. Kat, C Blok, Genel Cerrahi Kliniği, 34371 Şişli, İstanbul, Turkey Tel: +90 212 - 373 50 00 E-mail: drkinyaskartal@gmail.com Qucik Response Code

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tween 22% and 30%.[2–5] There has been continuous search for complementary diagnostic methods to limit number of negative appendectomies without delaying the diagnostic process or increasing rate of complication due to perforation. Convenient medical history combined with clinical examination to elicit common physical signs associated with localized peritonitis is usually enough to make diagnosis of acute appendicitis. Diagnosis is usually supported by the presence of elevated level of inflammatory markers white blood cell count (WBC) and C-reactive protein (CRP), and use of imaging techniques, such as ultrasonography (US) and computed tomography (CT). However, several studies have demonstrated that individually they are neither sufficient nor suitably specific for the diagnosis of acute appendicitis.[6] Aim of the present study was to illustrate diagnostic effectiveness of US in the diagnosis of acute appendicitis when combined with WBC and CRP levels. Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Kartal et al. How to avoid negative appendectomies

MATERIALS AND METHODS Retrospective analysis of data related to all consecutive patients who underwent appendectomy at our institution during 2-year period (from January 2014 to January 2016) was conducted. All data, including patient demographic features; laboratory tests, including WBC and CRP levels; US outer diameter measurement of the vermiform appendix; and histopathology results, were obtained from hospital computerized record system. All patients were evaluated in 3 groups according to histopathological examination: (1) lymphoid hyperplasia (LH), which was considered negative appendectomy; (2) noncomplicated acute appendicitis (NCAA), those with only basic inflammatory changes; and (3) complicated acute appendicitis (CAA) in presence of necrosis, gangrene, or perforation. The study protocol was approved by the ethics and research committee of Sisli Hamidiye Etfal Training and Research Hospital. Appendectomy was performed conventionally or laparoscopically. Leukocytosis was defined as WBC greater than 10.3 103/μL, and CRP was considered elevated if the level was more than 5 mg/L. Outer diameter of the vermiform appendix as measured with US of >6 mm was considered positive for acute appendicitis. US assessments were performed with Toshiba Aplio 300 device (Toshiba Medical Systems Corp., Otawara, Japan) with 3.5-MHz transducer. Patient variables were analyzed using NCSS 2007 statistical software (NCSS, LLC, Kaysville, UT, USA). Continuous variables were expressed as mean and standard deviation or range and median. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of WBC, CRP, and US findings were calculated separately or in combination for all patients. One-way analysis of variance test was used to analyze difference between means of variables between patient groups. Dunn’s multiple comparison test was

used in comparison of subgroups. -P values were calculated using the chi-square statistic. Results were considered statistically significant when -p value was ≤0.05.

RESULTS Between January 2014 and January 2016, 513 appendectomies were performed at the same institution. Total of 43 patients were not included in the study after applying exclusion criteria (16 patients’ pathology reports could not obtained, 15 patients’ US reports could not obtained, 6 patients declined surgery and were admitted to another hospital, results of 4 patients were considered histologically malignant, 1 patient underwent elective surgery with indication of interval appendectomy, and 1 patient’s blood test results could not obtained). In all, 470 patients were included in the study; 331(70.42%) were men and 139 (29.58%) were women. Mean age of the patients was 32.29±11.44 years (range: 17 to 82 years). There were no statistically significant differences in terms of age, average age, or gender between LH, NCAA, and CAA groups (p=0.318, p=0.555, and p=0.224, respectively). There were 39 patients (8.3%) with negative appendectomy (LH group), of whom 24 were men and 15 were women. Number of patients with NCAA was 195, of whom 133 were men and 62 were women. CAA group numbered 236, of whom 174 were men and 62 were women (Table 1). Mean WBC level was 12.31 103/μL (±4.47 103/μL), 13.3 103/ μL (±3.87 103/μL), and 14.08 103/μL (±4.11 103/μL) in LH, NCAA, and CAA groups, respectively. There was a significant difference between groups (p=0.016). Mean CRP level was 14.27 mg/L (±19.38 mg/L), 36.93 mg/L (±59.44 mg/L) and 40.84 mg/L (±66.68 mg/L) in LH, NCAA, and CAA groups, respectively. A significant difference between groups was found (p=0.008). Mean CRP level of LH group was determined to be significantly lower than that of

Table 1. Demographic data of patient groups Mean age, Mean±SD

Lymphoid hyperplasia (n=39)

Non-complicated acute appendicitis (n=195)

Complicated acute appendicitis (n=236)

-p

31.13±9.75

31.57±10.39

33.07±12.47

0.318 0.555

Age groups, n (%)

17–30

24 (61.54)

103 (52.82)

120 (50.85)

30–45

13 (33.33)

66 (33.85)

80 (33.90)

45–60

1 (2.56)

22 (11.28)

26 (11.02)

>60

1 (2.56)

4 (2.05)

10 (4.24)

Gender, n (%)

Men

24 (61.54)

133 (68.21)

174 (73.73)

Women

15 (38.46)

62 (31.79)

62 (26.27)

0.204

SD: Standard deviation.

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NCAA and CAA groups (p=0.012, p=0.002, respectively). There were no statistically significant differences between NCAA and CAA groups in terms of CRP level (p=0.364). Mean outer diameter of the vermiform appendix on US was 4.86 mm (±3.93 mm), 6.98 mm (±4.08 mm) and 7.63 mm (±3.92 mm) in LH, NCAA, and CAA groups, respectively. There was a significant difference between groups (p=0.0001). Mean outer diameter of the vermiform appendix in LH group was significantly smaller than that of NCAA and CAA groups (p=0.002 and p=0.001, respectively). Outer appendix diameter was smaller in NCAA group when compared with CAA group, and difference was statistically significant (p=0.009) (Table 2).

When all variables were compared with each other, US findings revealed statistically significant differences between 3 groups. WBC count was only statistically significant in separation of LH and CAA groups. CRP was statistically significant in differentiation of LH group from NCAA and CAA groups. The only statistically significant difference between NCAA and CAA were outer appendiceal diameter measured by US (Table 3). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and logistic regression values for data were calculated and statistical comparison was performed between groups (Table 4, 5).

Table 2. Results of white blood cell, C-reactive protein, and ultrasonography findings with -p values Lymphoid hyperplasia Non-complicated acute Complicated acute appendicitis appendicitis

Mean±SD Mean±SD Mean±SD

White blood cell (103/μL) 12.31±4.47 C-reactive protein (mg/L)

13.3±3.87

14.08±4.11 0.016

14.27±19.38

36.93±59.44

40.84±66.68

0.008

4.86±3.93

6.98±4.08

7.63±3.92

0.0001

Ultrasonography (mm) SD: Standard deviation.

Table 3. Comparison of white blood cell, C-reactive protein, and ultrasonography findings in all groups Dunn’s multiple comparison test

White blood cell

C-reactive protein

Ultrasonography

Lymphoid hyperplasia/Non-complicated acute appendicitis

0.340

0.012

0.002

Lymphoid hyperplasia/Complicated acute appendicitis

0.031

0.002

0.0001

Non-complicated acute appendicitis/Complicated acute appendicitis

0.117

0.364

0.009

Table 4. Overall performance values of white blood cell, C-reactive protein, and ultrasonography findings for patients with non-complicated acute appendicitis compared with lymphoid hyperplasia group Cut-off Sensitivity Specificity

Positive predictive value

Negative predictive value

Logistic reggression (+)

White blood cell (103/uL) >11.6

69.23

53.85

88.2

25.9

1.50

C-reactive protein (mg/L)

>1.52

84.62

38.46

87.3

33.3

1.37

Ultrasonography (mm)

>7.2

59.49

71.79

91.3

26.2

2.11

Table 5. Overall performance values of white blood cell, C-reactive protein, and ultrasonography findings for patients with complicated acute appendicitis compared with lymphoid hyperplasia group Cut-off Sensitivity Specificity White blood cell (103/μL) >15.43

38.56

89.74

Positive predictive value

Negative predictive value

Logistic reggression (+)

95.8

19.4

3.76

C-reactive protein (mg/L)

>1.52

86.02

38.46

89.4

31.2

1.40

Ultrasonography (mm)

>7.2

68.22

71.79

93.6

27.2

2.42

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DISCUSSION Over the past century, diagnosis of acute appendicitis has been based on medical history, physical examination findings, and to a lesser extent, laboratory results.[7] However, diagnosis of appendicitis usually cannot be evaluated only based on these examinations.[8] Multiple scoring systems, such as the Alvarado and modified Alvarado scoring systems, have been used to improve the accuracy of diagnosis of acute appendicitis.[9–11] These scoring systems have proven successful in Western countries; however, when applied in different environments, such as the Middle East and Asia, sensitivity and specificity levels achieved have been very low.[12,13] Most common laboratory tests used in the diagnosis of appendicitis are WBC and CRP. Many studies have confirmed accuracy and effectiveness of these tests.[14–16] Nevertheless, none of these tests is sufficient or suitably specific to decrease negative appendectomy rate by itself. In the present study, WBC level had a directly proportional relationship to severity of inflammation in all groups. Mean WBC level was statistically significant between 3 groups. However, when subgroup analysis was performed using Dunn’s multiple comparison test, there was no significant difference between NCAA and CAA groups. Therefore, WBC count alone was not helpful to differentiate NCAA from CAA. Rafiq et al.[17] evaluated 408 patients with acute appendicitis and reported similar results. In our study, specificity and sensitivity of WBC count were 89.74% and 38.56%, respectively, with a cut-off value of WBC count >15.43 103/μL. While there was a statistically significant relationship between total WBC and acute appendicitis, this relationship is not believed to be clinically useful on its own. Likewise, Cardall et al.[18] also reported insufficient specificity and sensitivity rates for WBC count in the diagnosis of acute appendicitis. Although there was a statistical difference in mean CRP level between all groups, it was similar between NCAA and CAA groups. Therefore, CRP may be useful to differentiate LH from acute appendicitis, but not useful to determine the severity of inflammation. On the contrary, Amalesh et al.[19] noted that neither elevated nor normal CRP level was helpful in the diagnosis of acute appendicitis. This result may be due to the pediatric patient population of their study. Appendix diameter of >6 mm is usually considered positive for acute appendicitis.[20] In this study, diameter measurement was significantly smaller in LH group compared with other 2 groups. US was useful to differentiate LH from NCAA and CAA. Also, US was helpful to determine inflamed appendix and surrounding tissue, as well as free intra-abdominal fluid. Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Poortman et al.[21] suggested an algorithm for the diagnosis of acute appendicitis and performed a comparative analysis of the accuracy of US and CT. They noted the importance of US as an initial imaging technique in the diagnosis of acute appendicitis to avoid negative appendectomy and recommended CT only in patients with negative or inconclusive US findings. In the present study, negative appendectomy rate (8.29%) was lower when compared with current literature. This can be attributed to the routine use of US in the diagnosis of acute appendicitis at our clinic.

Conclusion Elevated WBC count and CRP level are associated with acute appendicitis, but US findings are more effectual both in the diagnosis and demonstration of severe inflammation. The US should be used as standard initial imaging test in the diagnosis of acute appendicitis. Conflict of interest: None declared.

REFERENCES 1. Graffeo CS, Counselman FL. Appendicitis. Emerg Med Clin North Am 1996;14:653–71. 2. de Dombal FT, Leaper DJ, Staniland JR, McCann AP, Horrocks JC. Computer-aided diagnosis of acute abdominal pain. Br Med J 1972;2:9– 13. 3. Deutsch AA, Shani N, Reiss R. Are some some appendectomies unnecessary? An analysis of 319 white appendices. J R Coll Surg Edinb 1983;28:35–40. 4. Simmen HP, Decurtins M, Rotzer A, Duff C, Brütsch HP, Largiadèr F. Emergency room patients with abdominal pain unrelated to trauma: prospective analysis in a surgical university hospital. Hepatogastroenterology 1991;38:279–82. 5. Rao PM, Rhea JT, Novelline RA. Helical CT of appendicitis and diverticulitis. Radiol Clin North Am 1999;37:895–910. 6. Emmanuel A, Murchan P, Wilson I, Balfe P. The value of hyperbilirubinaemia in the diagnosis of acute appendicitis. Ann R Coll Surg Engl 2011;93:213–7. 7. Andersson RE. Meta-analysis of the clinical and laboratory diagnosis of appendicitis. Br J Surg 2004;91:28–37. 8. Fan Z, Pan J, Zhang Y, Wang Z, Zhu M, Yang B, et al. Mean Platelet Volume and Platelet Distribution Width as Markers in the Diagnosis of Acute Gangrenous Appendicitis. Dis Markers 2015. 9. Alvarado A. A practical score for the early diagnosis of acute appendicitis. Ann Emerg Med 1986;15:557–64. 10. Kalan M, Talbot D, Cunliffe WJ, Rich AJ. Evaluation of the modified Alvarado score in the diagnosis of acute appendicitis: a prospective study. Ann R Coll Surg Engl 1994;76:418–9. 11. Konan A, Hayran M, Kılıç YA, Karakoç D, Kaynaroğlu V. Scoring systems in the diagnosis of acute appendicitis in the elderly. Ulus Travma Acil Cerrahi Derg 2011;17:396–400. 12. Al-Hashemy AM, Seleem MI. Appraisal of the modified Alvarado Score for acute appendicits in adults. Saudi Med J 2004;25:1229–31. 13. Khan I, ur Rehman A. Application of alvarado scoring system in diagnosis of acute appendicitis. J Ayub Med Coll Abbottabad 2005;17:41–4. 14. Xharra S, Gashi-Luci L, Xharra K, Veselaj F, Bicaj B, Sada F, et al. Cor-

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18. Cardall T, Glasser J, Guss DA. Clinical value of the total white blood cell count and temperature in the evaluation of patients with suspected appendicitis. Acad Emerg Med 2004;11:1021–7.

15. Asfar S, Safar H, Khoursheed M, Dashti H, al-Bader A. Would measurement of C-reactive protein reduce the rate of negative exploration for acute appendicitis? J R Coll Surg Edinb 2000;45:21–4.

19. Amalesh T, Shankar M, Shankar R. CRP in acute appendicitis—is it a necessary investigation? International journal of surgery 2004;2:88–9.

16. Erkasap S, Ates E, Ustuner Z, Sahin A, Yilmaz S, Yasar B, et al. Diagnostic value of interleukin-6 and C-reactive protein in acute appendicitis. Swiss Surg 2000;6:169–72. 17. Rafiq MS, Khan MM, Khan A, Ahmad B. Total leukocyte and neutrophil count as preventive tools in reducing negative appendectomies. Ulus Travma Acil Cerrahi Derg 2015;21:102–6.

20. Rettenbacher T, Hollerweger A, Macheiner P, Rettenbacher L, Tomaselli F, Schneider B, et al. Outer diameter of the vermiform appendix as a sign of acute appendicitis: evaluation at US. Radiology 2001;218:757–62. 21. Poortman P, Oostvogel HJ, Bosma E, Lohle PN, Cuesta MA, de Langede Klerk ES, et al. Improving diagnosis of acute appendicitis: results of a diagnostic pathway with standard use of ultrasonography followed by selective use of CT. J Am Coll Surg 2009;208:434–41.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Negatif apendektomilerden kaçınmanın yolu: Ultrasonografi bunu başarabilir mi? Dr. Kinyas Kartal, Dr. Pınar Yazıcı, Dr. Taner Mehmet Ünlü, Dr. Mehmet Uludağ, Dr. Mehmet Mihmanlı Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, İstanbul

AMAÇ: Akut apandist tanısı, genellikle semptomlar ve fizik muayene bulguları ile konulabilmektedir. Fakat, apandist tanısını kesinleştirmek her zaman kolay olmamaktadır. Bu çalışmada, akut apandist tanısında ultrasonografinin (USG), beyaz kan hücresi (WBC) ve C-reaktif protein (CRP) bulgularıyla birlikte kullanımının apandist tanısındaki yerini göstermeyi amaçladık. GEREÇ VE YÖNTEM: Ocak 2014–Ocak 2016 arasında, merkezimizde akut apandist tanısı ile ameliyat olan 470 hastanın bilgileri geriye dönük olarak tarandı. Hastaların patoloji sonuçları, CRP ve WBC düzeyleri ve USG sonuçları istatistiksel olarak karşılaştırıldı. Hastalar patoloji sonuçlarına göre, lenfoid hiperplazi (LH), komplike olmayan akut apandist (KOAA) ve komplike akut apandist (KAA) olarak üç grubu ayrıldı. BULGULAR: Üç yüz otuz bir erkek 139 kadın hastanın ortalama yaşı 32.29±11.44 olarak saptandı. Ortalama WBC düzeyi, LH grubunda 12.31 103/ uL (±4.47), KOAA grubunda 13.3 103/uL (±3.87) iken KAA grubunda 14.08 103/uL (±4.11) olarak saptandı (p=0.016). Ortalama CRP düzeyi LH grubunda 14.27 mg/L (±19.38) iken, KOAA grubunda 36.93 mg/L (±59.44) ve KAA grubunda 40.84 mg/L (±66.68) olarak saptandı (p=0.008). Sonografik olarak ölçülen ortalama apendiks çapı LH grubunda 4.86 (±3.93) iken, KOAA grubunda 6.98 mm (±4.08) ve KAA grubunda 7.63 mm (±3.92) olarak saptandı (p=0.0001). Tüm değişkenler altgruplar arasında analiz edildiğinde USG bulgularının tüm gruplar arasında da anlamlı farka sahip olduğu gözlemlendi. TARTIŞMA: Akut apandisit tanısı alan hastaların WBC ve CRP değerlerinin istatistiksel olarak anlamlı oranda yüksek olduğu fakat bu bulgunun kesin tanı için yeterli olmadığı gözlendi. Ultrasonografi bulgularının hem enflamasyonun şiddetini belirlemede hem de apandist tanısı konulmasında etkin olduğu görüldü. Ultrasonografinin akut apandist şüphesi bulunan hastalarda laboratuvar testleri ile kombine edilerek standart görüntüleme incelemesi olarak uygulanması gerektiğini düşünmekteyiz. Bu tanı sisteminin negatif apendektomi oranını azaltacağına inanmaktayız. Anahtar sözcükler: Akut apandisit; C-reaktif protein; lökositoz; negatif apendektomi; ultrasonografi. Ulus Travma Acil Cerrahi Derg 2017;23(2):134–138

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doi: 10.5505/tjtes.2016.79328

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ORIGIN A L A R T IC L E

Can we make an early ‘do not resuscitate’ decision in severe burn patients? Yücel Yüce, M.D.,1 Hakan Ahmet Acar, M.D.,2 Kutlu Hakan Erkal, M.D.,1 Erhan Tuncay, M.D.2 1

Department of Anaesthesiology and Reanimation, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul-Turkey

Department of Burn Treatment Center and General Surgery, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: The present study was conducted to examine topic of issuing early do-not-resuscitate (DNR) order at first diagnosis of patients with severe burn injuries in light of current law in Turkey and the medical literature. DNR requires withholding cardiopulmonary resuscitation in event of respiratory or cardiac arrest and allowing natural death to occur. It is frequently enacted for terminal cancer patients and elderly patients with irreversible neurological disorders. METHODS: Between January 2009 and December 2014, 29 patients (3.44%) with very severe burns were admitted to burn unit. Average total burn surface area (TBSA) was 94.24% (range: 85–100%), and in 10 patients, TBSA was 100%. Additional inhalation burns were present in 26 of the patients (89.65%). All of the patients died, despite every medical intervention. Mean survival was 4.75 days (range: 1–24 days). Total of 17 patients died within 72 hours. Lethal dose 50 (% TBSA at which certain group has 50% chance of survival) rate of our burn center is 62%. Baux indices were used for prognostic evaluation of the patients; mean total Baux score of the patients was 154.13 (range: 117–183). RESULTS: It is well known that numerous problems may be encountered during triage of severely burned patients in Turkey. These patients are referred to burn centers and are frequently transferred via air ambulance between cities, and even countries. They are intubated and mechanical ventilation is initiated at burn center. Many interventions are performed to treat these patients, such as escharotomy, fasciotomy, tangential or fascial excision, central venous catheterization and tracheostomy, or hemodialysis. Yet despite such interventions, these patients die, typically within 48 to 96 hours. Integrity of the body is often lost as result of aggressive intervention with no real benefit, and there are also economic costs to hospital related to use of materials, bed occupancy, and distribution of workforce. For these reasons, as well as patient comfort, early do-not-resuscitate or do-not-intubate protocol for these patients is suggested. Resources could then be directed to other patients with high expectancy of life and patients with burns that are beyond treatment can experience more comfortable end of life. CONCLUSION: At present in Turkey, it is not possible to give DNR order for patient with severe burns that are incompatible with survival due to legal interdiction. This subject should be discussed at high-level meetings with participation of doctors, legal experts, economists, and theologians. Keywords: Do not intubate order; do not resuscitate order; severe burns.

INTRODUCTION Cardiopulmonary resuscitation (CPR) is routine intervention when patient experiences cardiac or respiratory arrest. Address for correspondence: Yücel Yüce, M.D. Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, İstanbul, Turkey Tel: +90 216 - 458 30 00 E-mail: dryyuce@gmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

When administered outside hospital circumstances, airway management is initially performed. Next, for recovery of circulation, chest compressions are used. Chest compression to ventilation ratio of 30:2 should be provided. If the patient is in a hospital, more advanced treatment modalities are added to intervention, such as endotracheal intubation and cardiac defibrillation for rhythm recovery. Drugs such as adrenaline, atropine, and sodium bicarbonate may be administered via intravenous cannula.[1] Most important goal of CPR is prevention of clinical death. [2] However, use of CPR is frequently insufficient to achieve this objective. Study performed with 12 266 patients from 139

Yüce et al. Can we make an early ‘do not resuscitate’ decision in severe burn patients?

Table 1. Total burn surface area distribution of the patients Total burn surface area (%) Number of patients

85–89

90–94

95–99

100

Table 2. Age distribution of the patients Age

<10 11–20 21–30 31–40 41–50 51–60 >60

Number of patients 1 3 8 5 7 2 3

between 1960 and 1980 reported that 39% of the patients survived the procedure and 17% of the patients survived until discharge from hospital.[2] Do-not-resuscitate (DNR) order requires withholding CPR in event of respiratory or cardiac arrest and allowing natural death to occur. It was first introduced to medical literature in 1976.[3] It is frequently implemented for terminal cancer patients and elderly patients with irreversible neurological disorders. This decision is usually ordered by patient’s relatives. In small number of cases, the patient can provide informed consent regarding DNR order. Decision can only be considered if accepted by doctors and ethical committees of the hospital.[3] In severely burned patient, third-degree burns encompass nearly all of the skin. Inhalation injury may also be present. In early hours, spontaneous ventilation may be observed in these patients and they may be conscious, but with time, clinical situation becomes severe. Despite implementing all of the most recent medical interventions, injuries are irreversible and the patients are lost. Serious burn injuries constitute significant cause of morbidity and mortality.[4] Although apparent improvements in overall survival in burn injuries have been achieved, mortality in patients with severe burn injuries admitted to intensive care remains high.[4] The present study examined early DNR order for severe burn patients with analysis of the literature and current law in our country.

MATERIALS AND METHODS Medical records of 841 patients admitted to regional burn center between January 1, 2009 and December 31, 2014 were analyzed retrospectively. The Kartal Dr. Lütfi Kırdar Education and Research Hospital Wound Care and Burn Center was established in Istanbul, Turkey in late 2008. Main hospital was opened in 1987 as dedicated trauma hospital to meet needs in the area as result of industrial growth and increase in population. It is second largest state hospital in Turkey with 706 hospital beds, and 140

burn center is the largest and best equipped in the country. It has 6 intensive care unit (ICU) beds, 16 burn service beds, and 2 separate operating rooms, all housed in single building. Helicopter landing site on premises accepts patients from every region of Turkey, as well as from neighboring countries. Multidisciplinary team consisting of general surgeons, plastic surgeons, anesthetists, infectious disease specialists, pediatric surgeons, physiotherapists, psychologists, dieticians, and burn nurses work in the center according to American Burn Association (ABA) guidelines. All data for this study were obtained from medical records of the hospital. Age and gender of the patients, total burn surface area (TBSA), burn degree, duration of hospital stay, type and total count of surgical interventions, mortality rate, venue of burn incident, and ICU requirements were recorded.

RESULTS Between January 2009 and December 2014, 29 patients (3.44%) with very severe burns were admitted. Average TBSA was 94.24% (range: 85–100%), and in 10 patients, TBSA was 100% (Table 1, Figure 1). In addition, 24 patients (82.75%) had inhalation burns (Figure 2). In all, 6 patients were female and 23 were male. Mean age was 35.27 years (range: 7–66 years) (Table 2). Three patients were Syrian and had been transferred to center by air ambulance from Syria, where burn injuries occurred (Figure 1). Another 16 patients had been transferred from surrounding districts of Istanbul. Majority of burns (n=24; 82.75%) were flame burns. Three cases were electrical burns and 2 were scald burns (Table 3). All of the patients died, despite every medical intervention. Mean survival was 4.75 days (range: 1–24 days). Total of 17 patients died within 72 hours. LD50 (% TBSA at which certain group has 50% chance of survival) rate of our burn cenTable 3. Types of burn in the patients Type of burn Number of patients

Flame

Electrical

Scald

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Yüce et al. Can we make an early ‘do not resuscitate’ decision in severe burn patients?

Figure 1. A patient transferred to our burn center by air ambulance with full-thickness burns and 100% total body surface area involvement.

Figure 3. A patient with echarotomy performed on trunk as well as upper and lower extremities.

Figure 2. A patient with inhalation burn. Soot is aspirated with endotracheal tube.

Figure 4. Another patient with echarotomy performed on trunk and upper and lower extremities.

ter is 62%. Baux indices were used for prognostic evaluation of the patients; mean total Baux score of the patients was 154.13 (range: 117–183).

was calculated for every patient in study and mean total Baux score was 154.13 (range: 117–183).

DISCUSSION Several difficulties may be experienced in triage of severely burned patients in Turkey. Patients are referred to burn centers and may be transferred via air ambulance between cities, and even countries. Intubation of the patients may be performed either at the scene before transfer or at burn center. Upon arrival to burn center, mechanical ventilation is initiated. Many interventions are performed to treat these patients, such as escharotomy, fasciotomy, central venous catheterizations and tracheostomy, or hemodialysis (Figure 3, 4). But despite such interventions, these patients die, typically within 48 to 96 hours. Integrity of the body is often lost as result of aggressive intervention with no real benefit, and there are also economic costs related to use of materials, bed occupancy, and distribution of workforce. Total Baux score Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Original Baux score[5] is sum of the patient’s age and percentage of TBSA involvement; it is often quoted as estimated percentage risk of death.[6] Osler et al.[7] evaluated Baux score in 39 888 patients from the National Burn Registry of the USA and added inhalation injury as scoring component, creating revised Baux score. The Belgian Outcome in Burn Injury score[8] uses revised Baux score variables in different statistical model, which was derived from study of 5246 Belgian patients. The Abbreviated Burn Severity Index[9] utilizes gender and presence of any full-thickness burn in addition to the above variables. Studies in the literature have reported that revised Baux score and updated Charlson comorbidity index are independently associated with mortality in intensive care burn patients, and that total Baux score >140 is not compatible with life.[7] 141

Yüce et al. Can we make an early ‘do not resuscitate’ decision in severe burn patients?

Wilton et al. performed retrospective review at the United States Army Institute of Surgical Research burn intensive care unit (BICU). Charts from January 1, 2000 through August 31, 2009 were analyzed for the study. Data were collected from adult burn patients who experienced in-hospital cardiac arrest and CPR, either in BICU or burn unit operating room. It was found that CPR was effective in burn patients, and that those who survive are likely to have good neurological outcomes. However, prolonged CPR time is unlikely to result in return of spontaneous circulation and may be considered futile. Furthermore, those who experience multiple episodes of cardiac arrest are unlikely to survive to discharge. Multiple instances of cardiac arrest and prolonged CPR time can be observed in severely burned patients.[10] When results of these studies are considered, one must think about solution for these patients with severe burns. DNR order for these patients can provide patient with smoother, more natural death and opportunity for time with relatives, as well as avoiding aforementioned economic costs to hospital. In study of O’Mara et al., retrospective evaluation was conducted of all deaths that occurred in pediatric burn unit over 7-year period. Of 29 deaths (total admissions: 1261; 2.3% death rate), 12 were patients with DNR status. Active withdrawal of support occurred in 15 cases: 10 patients with DNR order, 5 without. Of the 12 patients with DNR status, only 5 had order indicating no CPR, no vasopressor, and no cardioversion was to be used. Mean time from activation of DNR protocol until death was 22.9±49.6 hours (median: 2.75 hours). Patients without DNR order in place before death had more CPR attempts (0.8-0.6 vs 0.3-0.6; p<.05). At time of death, few patients with DNR order were receiving vasopressor (2 patients) or underwent CPR (1 patient). Of the 17 patients without DNR order, 12 underwent resuscitative efforts: CPR, vasopressor, or cardioversion. No resuscitative efforts were undertaken for 4 children, 2 of whom had DNR order. In this study, authors found that further evaluation of indications, timing, and implementation of DNR order for children with severe burns was warranted.[11] This study is an example of use of DNR order with burn patients and can give an idea about DNR order for other severely burned patients. In our country, a committee makes decision regarding brain death. We propose similar committee organization for DNR decision in cases of severely burned patients. In case of brain death, aim is preservation of organ functions, but goal for severely burned patients will be aggressive pain treatment for comfort of the patient, rather than organ preservation. Similar to brain death evaluation commission, team consisting of emergency care, general surgery, plastic and reconstructive surgery, pediatrics and pediatric surgery, anesthesiology and reanimation, internal medicine, and chest disease specialists could evaluate severity and survivability of burn injury. 142

Information about clinical status of the patient could be given to relatives and they could provide informed consent not to transfer patient to burn center for further treatment. Hospital directors, judicial authorities, and ministry of health would also be informed. Main goal of ICU in case of brain death is to protect organs so that they may be transplanted, rather than to protect the brain. However, in severely burned patients it should be just the opposite: Rather than the whole body, it is proposed that in these cases, support be given to the patient’s brain. We will try to keep the patient conscious and free from pain to give them an opportunity to meet with relatives for as long as possible. Proper fluid resuscitation and oxygen support will be provided alongside effective pain treatment and sedation for anxiety. No intervention disturbing integrity of the body will be performed, and when respiratory or circulatory arrest occurs, CPR will not be performed. We found no such example in the literature. Hammond et al. report indicated that DNR order should be guided by experience of the center.[12] This is useful, but it is opinion of the authors that decision should also be unanimous. Once goals of treatment have been agreed upon, decisions about end-of-life care of individual patient are to be made. Conditions of care should be mutual decision with the understanding of the healthcare team that additional intervention has become inappropriate given goals decided upon. It is important to realize and remember that even when these conditions are met, there is still a duty to provide care for the patient. DNR order is not equivalent to a do-not-care order.[13] National laws and ethics committee rules must define profile of patients for whom this decision process will apply. In Turkey, 2012 Ministry of Health treatment algorithm for burn injuries noted importance of appropriate transfer of burn patient. It specified that burn patients are to be transferred from accident site to healthcare center, or from one healthcare center to another more experienced or betterequipped facility. In the guidelines it is noted that first point to be determined before transfer of patient is probability the patient will survive and likelihood of new threat to patient’s life occurring during transport. Immediate transfer to healthcare facility is specified for patient with probability of survival. Transfer is not priority for patients who have low probability of survival or severe cardiopulmonary instability, according to the treatment algorithm.[14] However, there is currently no related article of law in Turkey pertaining to this situation. Turkish Criminal Code maintains that one may be held responsible for death of a person when there is failure to perform a work-related responsibility. From this point of view, it can be inferred that a doctor may be charged with not performing duty to do all possible to save the life of a patient if DNR protocol is followed. Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Yüce et al. Can we make an early ‘do not resuscitate’ decision in severe burn patients?

Conclusion In Turkey, legal interdiction currently prevents DNR order for a patient with severe burns that are not compatible with survival. This subject should be discussed at high-level meetings with participation of doctors, legal experts, economists, and theologians. Once consensus has been reached, practice can be implemented in burn intensive care units. We offer DNR procedure, but legal circumstances must be addressed in our country prior to application. Such a protocol will offer patients with unsurvivable burn injuries a more comfortable end of life, prevent disturbing integrity of the body, avoid economic costs associated with intervention, and allow hospital resources to be directed to other patients with high expectancy of life. Conflict of interest: None declared.

REFERENCES 1. Basturk E. An appraisal of do-not-resuscıtate (dnr) orders. T Klin J Med Ethics Law and History 2003;11:12–21. 2. Guidelines for the Appropriate Use of Do-Not-Resuscitate Orders. JAMA 1991;265:1868–71. 3. Jesus JE, Allen MB, Michael GE, Donnino MW, Grossman SA, Hale CP, et al. Preferences for resuscitation and intubation among patients with do-not-resuscitate/do-not-intubate orders. Mayo Clin Proc 2013;88(7):658–65.

4. Heng JS, Clancy O, Atkins J, Leon-Villapalos J, Williams AJ, Keays R, et al. Revised Baux Score and updated Charlson comorbidity index are independently associated with mortality in burns intensive care patients. Burns 2015;41:1420–7. 5. Baux S. Contribution a l’etude du traitement local des brulures thermiques etendues. These 1961. 6. Sheppard NN, Hemington-Gorse S, Shelley OP, Philp B, Dziewulski P. Prognostic scoring systems in burns: a review. Burns 2011;37:1288–95. 7. Osler T, Glance LG, Hosmer DW. Simplified estimates of the probability of death after burn injuries: extending and updating the baux score. J Trauma 2010;68:690–7. 8. Belgian Outcome in Burn Injury Study Group. Development and validation of a model for prediction of mortality in patients with acute burn injury. Br J Surg 2009;96:111–7. 9. Tobiasen J, Hiebert JM, Edlich RF. The abbreviated burn severity index. Ann Emerg Med 1982;11:260–2. 10. Wilton JC, Hardin MO, Ritchie JD, Chung KK, Aden JK, Cancio LC, et al. Outcomes after cardiac arrest in an adult burn center. Burns 2013;39:1541–6. 11. O’Mara MS, Chapyak D, Greenhalgh DG, Palmieri TL. End of life in the pediatric burn patient. J Burn Care Res 2006;27:803–8. 12. Hammond J, Ward CG. Decision not to treat: “do not resuscitate” order for the burn patient in the acute setting. Crit Care Med 1989;17:136–8. 13. Hettiaratchy S, Dziewulski P. ABC of burns. Introduction. BMJ 2004;328:1366–8. 14. Yastı AÇ, Şenel E, Saydam M, Özok G, Çoruh A, Yorgancı K. Guideline and treatment algorithm for burn injuries. Ulus Travma Acil Cerrahi Derg 2015;21:79–89.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Ciddi yanık hastalarında erken “do not resuscitate-resüsite etme” talimatı verilebilir mi? Dr. Yücel Yüce,1 Dr. Hakan Ahmet Acar,2 Dr. Kutlu Hakan Erkal,1 Dr. Erhan Tuncay2 1 2

Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Anesteziyoloji ve Reanimasyon Kliniği, İstanbul Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Yanık Tedavi Merkezi ve Genel Cerrahi Kliniği, İstanbul

AMAÇ: Ülkemizdeki ciddi yanık hastalarında erken “resüsite etmeme=DNR” kararı verilip verilemeyeceği sorusuna literatür ve ülkemizin yasal mevzuatını inceleyerek cevap aramaya çalıştık. GEREÇ VE YÖNTEM: DNR terimi bir hastada solunumsal ya da dolaşım arresti meydana geldiğinde yapılan kardiyopulmoner resüsitasyon uygulamasının durdurulmasını ifade eder. Tıp literatürüne ilk olarak 1976 yılında girmiştir. Sıklıkla son dönem kanser hastalarında ve geri dönüşümsüz nörolojik hastalıkları olan hastalarda uygulanır. BULGULAR: Ocak 2009 ile Aralık 2014 tarihleri arasında yanık merkezimize 29 çok ciddi yanık hastası kabul edildi (%3.44). Ortalama toplam yanık yüzey alanı (TBSA) %94.24 (dağılım, %85–%100) idi ve 10 hastada TBSA oranı %100 dü. Yirmi altı hastada ilave inhalasyon yanığı mevcuttu (%89.65). Hastaların tümü bütün tıbbi girişimlere rağmen kaybedildi. Ortalama sağ kalım süresi 4.75 gündü (dağılım, 1–24). On yedi hasta ilk 72 saat içinde kaybedildi. Yanık merkezimizin LD50 oranı %62’dir. Prognostik değerlendirme için hastaların Total Baux indeksleri hesaplandı. Ortalama Total Baux İndeksi 154.13’tü (dağılım, 117–183). TARTIŞMA: Türkiye’de ciddi yanık hastalarının triyajında çeşitli sorunlarla karşılaşabileceğimiz bir bilinen faktördür. Bu hastalar yanık merkezlerine yönlendirilir ve hava ambulansları vasıtasıyla şehirler arasında ve hatta ülkeler arasında nakledilirler. Yanık merkezlerinde entübe edilip mekanik ventilasyon başlanır. Bu hastaları monitörize etmek ve tedavi etmek için birçok girişim uygulanır. Eskarotomiler, fasiyotomiler, tanjansiyel ya da fasiyel eskaratomiler, santral venöz kateterizasyonlar, trakeostomiler ve hemodiyaliz uygulamaları bu hastalarda gerçekleştirilir. Ancak tüm bu girişimlere rağmen 48–96 saatlik takip sırasında bu hastalar kaybedilirler. Bu durum da ekipman kullanımı, yatak işgali ve iş gücü kaybı gibi ekonomik kayıplara neden olmaktadır. Gerçekte hiçbir fayda sağlamayan çok çeşitli girişimlerle hastaların vücut bütünlüğü daha da bozulmaktadır. Bu nedenle, bu hastalarda alınabilecek bir erken DNR kararı ya da entübe etmeme kararı ile ekipman kullanımı, yatak işgali ve iş gücü kaybı gibi ekonomik kayıplar azalacaktır ve bu kaynaklar daha yüksek yaşam beklentisi olan diğer hastalar için efektif olarak kullanılabilir. Ayrıca yaşamla bağdaşmayacak kadar ciddi yanığı olan hastalar da daha huzurlu ve rahat bir şekilde hayatlarını sonlandırabileceklerdir. Türkiye’de yasal kısıtlamalar nedeniyle ciddi yanık hastalarında bir DNR kararı almak mümkün değildir. Bu konu doktorların, hukukçuların, ekonomistlerin, ilahiyatçıların katılacağı büyük toplantılarda tartışılmalıdır. Anahtar sözcükler: Ciddi yanıklar; entübe etme kararı; resüsite etme kararı. Ulus Travma Acil Cerrahi Derg 2017;23(2):139–143 doi: 10.5505/tjtes.2016.71508

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ORIGIN A L A R T IC L E

Minimal invasive fixation of distal tibial fractures does not result in rotational malalignment: A report of 24 cases with CT imaging Mehmet Mesut Sönmez, M.D.,1 Deniz Gülabi, M.D.,2 Meriç Uğurlar, M.D.,1 Metin Uzun, M.D.,4 Sezgin Sarban, M.D.,5 Ali Şeker, M.D.3 1

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

Department of Orthopedics and Traumatology, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul-Turkey

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

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

Department of Orthopedics and Traumatology, International Hospital, İstanbul-Turkey

ABSTRACT BACKGROUND: Tibial torsion is rotation of the proximal versus the distal articular axis in the transverse plane. This study used computed tomography (CT) to examine rotational malalignment in the crus following use of minimally invasive plate osteosynthesis (MIPO) technique in distal tibial fractures and evaluated effect of rotational difference on clinical outcomes and VAS scores. METHODS: Analysis of 24 patients who were operated on for closed distal tibial fracture with MIPO technique between 2010 and 2012 was conducted. Malrotation was defined as rotational difference >10°. Operated knees were evaluated with 0.5-mm, fine-cut, 3-dimensional CT scan performed in cooperation with radiology department. Side-to-side difference in tibial torsion angle >10° was considered significant degree of malrotation. All patients were assessed clinically (visual analogue scale [VAS] and American Orthopaedic Foot and Ankle Society [AOFAS] scores) and radiologically at final visit. RESULTS: Mean follow-up period was 20.00±9.46 months (range: 18-51 months). Mean VAS score was 2.58±0.83 (range: 1–4) and mean AOFAS score was 87.50±4.05 (range: 78–93). Mean tibial rotation angle was 31.54±6.00° (range: 18–45°) on healthy side and 32.00±6.24° (range: 10–43°) on the operated side. No statistically significant difference was determined (p>0.05). CONCLUSION: Use of intraoperative fluoroscopy, cable technique, and uninjured extremity as reference, can reduce incidence of rotational malalignment of distal tibial fractures treated with MIPO. Keywords: CT; distal tibia fractures; malrotation; MIPO.

INTRODUCTION Since the popularization of biological fixation, minimally invasive percutaneous plating is now used more frequently. Favorable outcomes, including shorter healing time and lower reoperation rates have been reported in the literature.[1,2] Address for correspondence: Deniz Gülabi, M.D. Maltepe Başıbüyük Mah., Emek Cad., Tepe İnşaat Narcity Konutları, G4: 30, İstanbul, Turkey Tel: +90 216 - 441 39 00 / 1450 E-mail: dgulabi@yahoo.com Qucik Response Code

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Achievement of optimal position using indirect reduction methods is technically difficult and may result in lower extremity malalignment. This displacement can lead to adverse effects in adjacent joints and articular cartilage, causing earlier development of arthrosis.[3,4] Tibial torsion is rotation of the proximal versus the distal articular axis in the transverse plane. Suero et al.[5] found that malrotation of the distal tibia led to abnormal load distribution in the ankle joint. Considerable concern exists that malalignment of healed distal tibial fracture may result in post-traumatic arthritis of the ankle. As the location of the deformity approaches the ankle, malalignment results in maldistribution of articular surface pressures, which may then predispose a patient to premature osteoarthritis.[6,7] It is well known that as osteoarthritis progresses, there will be reduction in ability of the patient to participate in physical and social activities. Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Sönmez et al. Minimal invasive fixation of distal tibial fractures does not result in rotational malalignment

Using computed tomography (CT), this study examined rotational malalignment in the crus following use of minimally invasive plate osteosynthesis (MIPO) technique in distal tibial fractures, and evaluated effect of rotational difference on clinical outcomes and visual analogue scale (VAS) scores.

bilized on 2 crutches. Weight-bearing was permitted when callus formation was observed on radiographs at follow-up examinations. All patients were evaluated clinically and radiologically at final visit. VAS and American Orthopaedic Foot and Ankle Society (AOFAS) scores were recorded.

MATERIALS AND METHODS

Assessment of Radiographs

Analysis of 30 patients who were operated on for closed distal tibial fracture with the MIPO technique between 2010 and 2012 was conducted. Chart notes were studied for demographic details, mechanism of injury, and type of fracture. All preoperative X-rays were reviewed and classified using the AO/OTA Classification of Fractures and Dislocations. Inclusion criteria were unilateral distal tibial closed fractures. Exclusion criteria were fixation or revision of previous fixation in the ipsilateral or the contralateral femur or tibia, disagreement in CT imaging, multiple fractures, 2-stage surgery, and pregnant females. Two patients who had multiple fractures, 3 patients with 2-stage surgery, and 1 patient with disagreement in CT imaging were excluded; thus, 24 patients were included in this study for evaluation. The patients were 11 (45.8%) males and 13 (54.2%) females with mean age of 33.67±10.72 years (range: 19 to 55 years). Mechanism of injury was fall from height in 11 (45.8%) patients, and motor vehicle accident in 13 (54.2%) patients. Fractures were classified according to the AO/OTA classification system. All procedures followed were in accordance with the Helsinki Declaration of 1975, as revised in 2008. Approval for the study was granted by the ethics committee on human experimentation (institutional and national). Informed consent agreement was obtained from all patients for inclusion in the study.

Surgical Technique All operations were performed within 2 days of the injury. All patients were operated on by a single surgeon. All cases were managed under regional anesthesia. Uninjured lower extremity in all patients was prepared for comparison. Image intensifier with C-arm was used in all cases to provide fluoroscopic guidance. Longitudinal traction was applied along the foot by a junior orthopedic surgeon. Rotational alignment was achieved by aligning the anterior superior iliac spine, patella, and second ray of the foot using the cable technique. In 8 patients with concomitant tibial and fibular fractures, fibular fixation was performed initially. For fractures with intraarticular components, after fixation of articular fragments with minimal dissection, “J”-shaped medial incision 3 cm in length was made. Distal medial tibial plate (DePuy Synthes Companies, Zuchwil, Switzerland) was used for fracture fixation. Plate was advanced from incision submuscularly and only swab incisions were made for screw placements. Quality of reduction was verified with fluoroscopy and rotational alignment was checked clinically (Fig. 1a, b). Patients were moUlus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

All measurements were calculated by independent radiographic reviewer who was blinded to the study. Observer assessed all radiographs twice at an interval of 1 week, and mean of the 2 values was accepted as rotation degree of each tibia. Reviewer had ample time to evaluate the radiographs, as no time limit was imposed on review. Measurements were taken using PACS System (Novard Corp., American Fork, UT, USA). Internal rotation deformity was assigned negative value and external rotation was given positive value. Rotational difference >10° was defined as malrotation. Operated knees were evaluated with 0.5-mm, fine-cut, 3-dimensional CT scans (Aquilion 64; Toshiba Medical Systems Corp., Otawara, Japan) in cooperation with radiology department. Patients were scanned in supine position with adjustable supports to prevent movement of lower extremities. Scanning included multiple 5-mm cuts at the proximal tibia and distal tibia. Axial plane images were used. Proximally, reference line was the tangent to the posterior tibial ridges at level just superior to the fibular head. Tibial torsion angle was calculated using difference between angles of the proximal and transmalleolar axis just proximal to the tibial plafond with horizontal reference line (Fig. 1c). Side-to side difference in tibial torsion angle >10° was considered significant degree of malrotation. Normal value for adults quoted in the literature is 30° to 40° of external rotation, with range of ±10°.[8,9]

Statistical Methodology Statistical analyses were performed using NCSS 2007 (NCSS, LLC, Kaysville, UT, USA) software. Descriptive statistical methods were used (mean, SD, frequency, percentage, minimum, maximum) were used to evaluate study data. Paired samples t-test was used to compare group of variables that demonstrated normal distribution. Pearson correlation analysis and Spearman correlation analysis were used to analyze relationships between variables. Statistical significance was determined at p<0.05.

RESULTS Intraobserver reliability was calculated as 0.92. Mean followup period was 20.00±9.46 months (range: 18–51 months). Mean body mass index of the patients was 22.04±1.55 kg/ m2 (range: 20-25 kg/m2). Mean time to union was 15.42±1.67 weeks (range: 13–19 weeks). Mean VAS score was 2.58±0.83 (range: 1–4) and mean AOFAS score was 87.50±4.05 (range: 78–93). (Table 1). AO fracture type was 42A1 in 3 cases (12.5%), 42A3 in 1 145

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(a)

(c)

(b)

Figure 1. (a) Preoperative radiographs of a 41-year-old patient with distal tibial fracture accompanied by fibular fracture. Tibial fracture extends to the ankle joint. (b) Early postoperative radiographs of the same patient. Intraarticular fragments were fixed with minimal soft tissue dissection. (c) Measurement of tibial torsion.

(4.2%), 42B1in 3 (12.5%), 42B2 in 2 (8.3%), 42B3 in 6 (25%), 42C1 in 2 (8.3%), 42C2 in 1 (4.2%), 43A1 in 1 (4.2%), 43A3 in 4 (16.7%) and 43C2 in 1 (4.2%). Tibial rotation angle was determined as mean 31.54±6.00° (range: 18–45°) on healthy side and mean 32.00±6.24° (range: 10–43°) on operated side.

No statistically significant difference was found between healthy side and operated side with respect to rotation angle (p>0.05) (Table 2). No statistically significant relationship was determined between VAS and AOFAS scores and difference between operated side rotation angle and healthy side rotation angle (p>0.05) (Table 3). In 1 patient, implants were removed due to soft tissue irritation 1 year after surgery.

Table 1. Distribution of descriptive characteristics

Minimum–Maximum Mean±SD

Gender

Male

45.8

Female

54.2

Age (years)

19–55

33.67±10.72

Body mass index (kg/m )

20–25

22.04±1.55

Follow-up period (months)

18–51

20.00±9.46

Time to union (weeks)

13–19

15.42±1.67

Visual analogue scale score

1–4

2.58±0.83

American Orthopaedic Foot and Ankle Society

78–93

87.50±4.05

SD: Standard deviation.

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Table 2. Tibial rotation angle

Tibia rotation angle (degrees)

Minimum-Maximum Mean±SD

Healthy side

18–45

31.54±6.00

Operated side

10–43

32.00±6.24

Difference (Operated–Healthy)

-12–18

0.46±7.44

p 0.766

SD: Standard deviation. *Paired samples t-test.

Table 3. Relationship between TRA and VAS and AOFAS scores

TRA difference (operated–healthy)

r p

VAS

AOFAS

-0.199 0.350

-0.138 0.521

Spearman correlation coefficient. Pearson correlation coefficient. TRA: Tibia rotation angles; VAS: Visual analogue scale; AOFAS: American Orthopaedic Foot and Ankle Society.

DISCUSSION This study has demonstrated that rotational profile of the distal tibia can be observed accurately with standard postoperative CT scans, even when standard intraoperative fluoroscopy was used to reduce malrotation of distal tibial fractures treated with MIPO technique. CT scanning has become the gold standard for assessment of limb rotational alignment. [8–11] Test is accurate and has good inter- and intra-observer reliability and repeatability.[12] The present study had good intraobserver reliability, as recommended in the literature. The results of this study confirmed that using intraoperative fluoroscopy, cable technique, and uninjured extremity as a reference can decrease incidence of rotational malalignment of distal tibial fractures treated with MIPO. With the popularity of biological fixation, MIPO is now being used more frequently at trauma centers. MIPO with indirect fracture reduction can lead to higher rates of limb malalignment.[13–15] Rotational deformity in the lower extremity has been shown to influence articular cartilage shearing and development of joint arthrosis, leading to clinically relevant degenerative changes.[3,4,16,17] Quality of reduction and limb alignment with use of MIPO technique has not been well documented. The few studies that have documented post-reduction limb rotation following MIPO cite incidence of malrotation >10° in 0% to 9% of limbs based on clinical examination and side-to-side comparison with the uninjured extremity.[18–22] In the present study, there were no cases with tibial malrotation compared with uninjured side. This was Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

considered to be related to accurate use of intraoperative fluoroscopy and the experience of the surgical team, who were certified in trauma. In the present study, the uninjured limb was prepared to assess rotation profile of the extremity. Inclusion of the uninjured limb in surgical preparation has been recommended to benefit reduction assessment, and previous studies that have used CT scans to examine uninjured lower limbs for rotation have reported average side-to-side difference in rotation of only 3° to 4°.[11] Tornetta has described technique of using distal femoral traction pin and fluoroscopy of both normal and injured extremities to better judge rotation for femoral shaft fractures.[23] In the current study, there was no statistically significant difference between injured and uninjured extremities with respect to rotational alignment (p=0.766). Preparing the uninjured limb as reference for normal rotation and intraoperative cable technique with guidance of fluoroscopy were considered to be beneficial in judging rotation of the injured extremity. However, no convenient and reliable method of assessing intraoperative lower limb rotation has been developed and used consistently. This is an area for further research. One study concluded that fibular plate fixation increased initial rotational stability of distal third tibia and fibula shaft fractures compared with intramedullary nailing of the tibia alone.[24] Prasad et al. stated that average rotation at the ankle was less, with 7.67° of external rotation in group with fibula fixed, compared with 10.68° of external rotation in group with non-fixed fibula (p=0.01).[25] In the current study, only 3 fibulae were stabilized with open reduction internal fixation technique. There was no statistically significant difference between these 3 cases and non-fixed fibula fractures (p>0.05). However, strength of recommendation is low due to small sample size in each group. Prospective randomized studies could be designed to evaluate difference in rotational malalignment of both groups (fixed and non-fixed fibula). Soft tissue coverage is weak in the distal tibia metaphyseal region and in the distal diaphysis. Various studies have reported on postoperative wound healing and infection risk in this area. Guo et al. reported wound problems at rate of 147

Sönmez et al. Minimal invasive fixation of distal tibial fractures does not result in rotational malalignment

14.6%[26] and Lau et al. reported late stage infection following MIPO at 15%.[27] In the current study, implant was removed in 1 patient (3.3%) due to implant irritation.

Limitations of the Study Primary limitations of this study were small number of cases and short duration of follow-up. Studies with larger patient population may demonstrate real extent of malalignment after such surgery. In addition, long-term follow-up results may reveal useful results regarding such deformities. In conclusion, the best method to avoid malrotation during MIPO technique is comparison with the opposite leg and use of intraoperative fluoroscopy and cable technique. It may be appropriate to prepare the normal leg for comparison. Malrotation is best identified by clinical inspection and best quantified by limited CT scan. Conflict of interest: None declared.

REFERENCES 1. Hazarika S, Chakravarthy J, Cooper J. Minimally invasive locking plate osteosynthesis for fractures of the distal tibia--results in 20 patients. Injury 2006;37:877–87. 2. Ronga M, Longo UG, Maffulli N. Minimally invasive locked plating of distal tibia fractures is safe and effective. Clin Orthop Relat Res 2010;468:975–82. 3. Gugenheim JJ, Probe RA, Brinker MR. The effects of femoral shaft malrotation on lower extremity anatomy. J Orthop Trauma 2004;18:658–64. 4. Netz P, Olsson E, Ringertz H, Stark A. Functional restitution after lower leg fractures. A long-term follow-up. Arch Orthop Trauma Surg 1991;110:238–41. 5. Suero EM, Hawi N, Westphal R, Sabbagh Y, Citak M, Wahl FM, et al. The effect of distal tibial rotation during high tibial osteotomy on the contact pressures in the knee and ankle joints. Knee Surg Sports Traumatol Arthrosc 2015 Mar 6. 6. Richmond J, Colleran K, Borens O, Kloen P, Helfet DL. Nonunions of the distal tibia treated by reamed intramedullary nailing. J Orthop Trauma 2004;18:603–10. 7. van der Schoot DK, Den Outer AJ, Bode PJ, Obermann WR, van Vugt AB. Degenerative changes at the knee and ankle related to malunion of tibial fractures. 15-year follow-up of 88 patients. J Bone Joint Surg Br 1996;78:722–5. 8. Jakob RP, Haertel M, Stüssi E. Tibial torsion calculated by computerised tomography and compared to other methods of measurement. J Bone Joint Surg Br 1980;62:238–42. 9. Jend H, Heller M, Dallek M, Schoettle H. Measurement of tibial torsion by computer tomography. Acta Radiol 1981;22:271–5. 10. Murphy SB, Simon SR, Kijewski PK, Wilkinson RH, Griscom NT. Femoral anteversion. J Bone Joint Surg Am 1987;69:1169–76.

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11. Strecker W, Keppler P, Gebhard F, Kinzl L. Length and torsion of the lower limb. J Bone Joint Surg Br 1997;79:1019–23. 12. Puloski S, Romano C, Buckley R, Powell J. Rotational malalignment of the tibia following reamed intramedullary nail fixation. J Orthop Trauma 2004;18:397–402. 13. Neer CS, Grantham SA, Shelton ML. Supracondylar fracture of the adult femur. A study of one hundred and ten cases. J Bone Joint Surg Am 1967;49:591–613. 14. Schatzker J, Home G, Waddell J. The Toronto experience with the supracondylar fracture of the femur, 1966-72. Injury 1974;6:113–28. 15. Williams J, Gibbons M, Trundle H, Murray D, Worlock P. Complications of nailing in closed tibial fractures. J Orthop Trauma 1995;9:476– 81. 16. Kettelkamp DB, Hillberry BM, Murrish DE, Heck DA. Degenerative arthritis of the knee secondary to fracture malunion. Clin Orthop Relat Res 1988;234:159–69. 17. van der Schoot DK, Den Outer AJ, Bode PJ, Obermann WR, van Vugt AB. Degenerative changes at the knee and ankle related to malunion of tibial fractures. 15-year follow-up of 88 patients. J Bone Joint Surg Br 1996;78:722–5. 18. Cole PA, Zlowodzki M, Kregor PJ. Treatment of proximal tibia fractures using the less invasive stabilization system: surgical experience and early clinical results in 77 fractures. J Orthop Trauma 2004;18:528–35. 19. Kregor PJ, Stannard JA, Zlowodzki M, Cole PA. Treatment of distal femur fractures using the less invasive stabilization system: surgical experience and early clinical results in 103 fractures. J Orthop Trauma 2004;18:509–20. 20. Ricci WM, Rudzki JR, Borrelli J Jr. Treatment of complex proximal tibia fractures with the less invasive skeletal stabilization system. J Orthop Trauma 2004;18:521–7. 21. Stannard JP, Wilson TC, Volgas DA, Alonso JE. The less invasive stabilization system in the treatment of complex fractures of the tibial plateau: short-term results. J Orthop Trauma 2004;18:552–8. 22. Weight M, Collinge C. Early results of the less invasive stabilization system for mechanically unstable fractures of the distal femur (AO/OTA types A2, A3, C2, and C3). J Orthop Trauma 2004;18:503–8. 23. Tornetta P, Ritz G, Kantor A. Femoral torsion after interlocked nailing of unstable femoral fractures. J Trauma 1995;38:213–9. 24. Morrison KM, Ebraheim NA, Southworth SR, Sabin JJ, Jackson WT. Plating of the fibula. Its potential value as an adjunct to external fixation of the tibia. Clin Orthop Relat Res 1991;266:209–13. 25. Prasad M, Yadav S, Sud A, Arora NC, Kumar N, Singh S. Assessment of the role of fibular fixation in distal-third tibia-fibula fractures and its significance in decreasing malrotation and malalignment. Injury 2013;44:1885–91. 26. Guo JJ, Tang N, Yang HL, Tang TS. A prospective, randomised trial comparing closed intramedullary nailing with percutaneous plating in the treatment of distal metaphyseal fractures of the tibia. J Bone Joint Surg Br 2010;92:984–8. 27. Lau TW, Leung F, Chan CF, Chow SP. Wound complication of minimally invasive plate osteosynthesis in distal tibia fractures. Int Orthop 2008;32:697–703.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Distal tibia kırıklarının minimal invaziv tespiti rotasyonel deformiteye neden olmaz: Yirmi dört hastanın bilgisayarlı tomografi incelemesi Dr. Mehmet Mesut Sönmez,1 Dr. Deniz Gülabi,2 Dr. Meriç Uğurlar,1 Dr. Metin Uzun,4 Dr. Sezgin Sarban,5 Dr. Ali Şeker3 Şişli Etfal Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul Kartal Dr. Lütfi Kırdar Eğitim ve Araştırma Hastanesi, Ortopedi ve Travmatoloji Kliniği, İstanbul 3 Medipol Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, İstanbul 4 Acıbadem Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, İstanbul 5 International Hospital, Ortopedi ve Travmatoloji Kliniği, İstanbul 1 2

AMAÇ: Tibial rotasyon prosimal eklemin transvers planda distal ekleme göre rotasyonda olmasıdır. Bu çalışmanın amacı minimal invaziv plaklama yöntemi (MİPO) ile tedavi edilen distal tibia kırıklarında, malrotasyonun bilgisayarlı tomografi (BT) ile tespit edilimesi, rotasyonel farkın klinik sonuçlar ve Vizüel Analog Skala (VAS) skoru üzerine etkisini araştırmaktı. GEREÇ VE YÖNTEM: 2010–2012 yılları arasında kapalı distal tibia kırığı nedeniyle MİPO yöntemiyle ameliyat edilen 24 hasta çalışmaya dahil edildi. On dereceden fazla rotasyon farkı malrotasyon olarak kabul edildi. Ameliyat edilen bacak 0.5 mm aralıklarla alınan üç boyutlu BT kesitleriyle radyoloji bölümü tarafından değerlendirildi. İki alt ekstremite arasındaki 10 dereceden fazla fark malrotasyon olarak kabul edildi. Tüm hastalar son takiplerinde klinik (VAS ve Amerikan Ortopedi Ayak ve Ayak Bileği Topluluğu [AOFAS]) ve radyolojik olarak değerlendirildi. BULGULAR: Ortalama takip süresi 20.00±9.46 aydı (dağılım, 18–51 ay). Ortalama VAS skoru 2.58±0.83 (dağılım, 1–4) ve ortalama AOFAS skoru 87.50±4.05 (dağılım, 78–93) idi. Ortalama tibia rotasyon açısı sağlam tarafta 31.54°±6.00° (dağılım, 18°–45°) ve ameliyatlı tarafta ise 32.00°±6.24° (dağılım, 10°–43°) idi. İstatiksel olarak anlamlı fark saptanmadı (p>0.05). TARTIŞMA: Minimal invaziv plaklama yöntemiyle distal tibia kırıklarının tedavi edilmesinde ameliyat sırasında skopi kullanılması, kablo tekniğinin ve sağlam tarafın referans olarak kullanılma yöntemi rotasyonel dizilim sorununu azaltacağı kanaatindeyiz. Anahtar sözcükler: BT; distal tibia kırığı; malrotasyon; MİPO. Ulus Travma Acil Cerrahi Derg 2017;23(2):144–149

doi: 10.5505/tjtes.2016.59153

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Repair of comminuted fracture of the lower patellar pole Elsayed Ibraheem Elsayed Massoud, M.D. Department of Orthopaedic, Sohag Teaching Hospital, General Organization for Teaching Hospitals and Institutes, Egypt

ABSTRACT BACKGROUND: Comminuted fracture of the lower patellar pole has characteristics of both patellar fracture and avulsion of the patellar tendon. Therefore, components of both injury types should be considered during treatment. None of the traditional techniques has proven sufficient alone. Currently described is technique that incorporates principles of osteosynthesis as well as repair of the patellar tendon. METHODS: Total of 23 patients with comminuted fracture of the lower patellar pole were treated surgically and prospectively followed for 24 months. RESULTS: All patients returned to pre-injury level of activities of daily living at average of fourth postoperative month. Average score on scale described by Böstman et al. was 28.1 points. All fractures united within average of 10 weeks. Patellar height was preserved. Only 4 patients, all post-menopausal, demonstrated increase in degenerative changes in patellofemoral joint. CONCLUSION: Successful osteosynthesis of the comminuted lower patellar pole using the present technique reduces potential need for partial patellectomy, and preserves original length of the extensor mechanism. Present technique allows for immediate full weight-bearing and early, extensive rehabilitation program. Keywords: Extensor mechanism; fractured patella; inferior pole of the patella; patellar tendon; patellectomy.

INTRODUCTION Progress in understanding mechanical function of extensor mechanism has rendered preservation of patellar dimensions mandatory.[1] Retention of the fractured lower patellar pole signifies restoration of length of the extensor mechanism; however, no accepted technique has yet emerged. Of the widely used techniques, modified AO tension band wiring requires large fragments suitable for fixation with Kirschner wire (Fig. 1). Circumferential wiring allows for separation of fracture fragments due to soft tissue between wire and bone.[2] Furthermore, it may strangle blood vessels in their peripatellar course.[3] Separate vertical wiring technique was first introduced by Yang and Byun, and several modifications have been made;[4–6] however, complications have been reported. Basket plate was designed for osteosynthesis of the lower patellar Address for correspondence: Elsayed Ibraheem Elsayed Massoud, M.D. Nile St Sohag 00 Sohag, Egypt Tel: +2 0934790632 E-mail: elsayedmassoud@hotmail.com Qucik Response Code

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pole and has also been modified,[7,8] but it failed to incorporate tiny fragments and to maintain patellar height simultaneously. In comminuted fracture of the lower patellar pole, bundles of the patellar tendon are denuded of bony attachment. Therefore, this injury should be treated according to considerations of osteosynthesis as well as repair of the patellar tendons. Biomechanical study indicated that Magnusson wiring technique, in which wire loop is in direct contact with bone, allowed for better fixation of patellar fracture.[2] In the same context, present author used transpatellar absorbable suture to reattach avulsed patellar tendon.[9] It was hypothesized that combination of both Magnuson and Massoud techniques could reduce drawbacks of other traditional techniques for repair of comminuted lower patellar pole. In this study, nature of comminuted fracture of the lower patellar pole is examined, and combination technique for repair is presented with analysis of results.

MATERIALS AND METHODS During period from April 2007 to April 2013, 23 patients who agreed to participate in prospective study were identified and managed for comminuted fracture of the lower patellar pole (Table 1). The Sohag Teaching Hospital ethics committee approved the study. Most of the patients were female (78%); mean age at time of operation was 53.4 years (range: Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Massoud. Repair of comminuted fracture of the lower patellar pole

(a)

(b)

(c)

Figure 1. (a) Preoperative lateral radiograph of the right knee of 39-year-old male shows fracture of the lower patellar pole. Patient was treated with modified AO tension band wiring; (b) Slippage of Kirschner wires was observed and presently described technique was applied; (c) Lateral radiograph taken 4 weeks postoperatively shows migration of wire loop to below main fracture line.

17â&#x20AC;&#x201C;73 years). They presented with recent history of trauma and inability to bear weight. Physical signs, such as swelling and infrequently, skin bruises, were observed. Tenderness, inability to elevate straight leg, and high proximal patellar pole compared with contralateral side were detected. Radiographic examination revealed comminuted fracture of lower pole of the patella. Common comorbidities were hepatitis C virus infection (HCV) in 52% of the patients, diabetes mellitus in 30%, and cerebral palsy in 2 young adults (Table 1).

Operative Technique Under spinal anesthesia and with tourniquet applied, patella

(a)

(b)

was exposed through midline longitudinal incision extending from the upper patellar pole to point proximal to tibial tuberosity. Drill bit 3.2 mm in size was used to create 2 longitudinal tunnels between site of fracture and the upper patellar pole (Fig. 2a). Interwoven #2 Vicryl sutures (Ethicon, Inc., Somerville, NJ, USA) were placed at proximal end of the patellar tendon just distal to osteotendinous junction and suture remnants were left in place. Interwoven sutures joined separated bundles of the patellar tendon to bundles still attached to bone fragments, converting them into integral units (Fig. 2a, b). Next, malleable stainless steel wire of 1 mm diameter was passed distally through mid-substance of a corner of

(c)

Figure 2. Drawing illustrates steps of repair of comminuted fracture of the lower patellar pole; (a) Interwoven absorbable sutures joining denuded bundles of the patellar tendon that attached to the bone fragments; (b) Cerclage wire passed through the patellar tendon, then with the Vicryl thread through transpatellar tunnels to upper patellar pole; (c) Final appearance after tying wire and thread.

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Table 1. Pre and postoperative details of patients with comminuted lower patellar pole Patient no

Preoperative data

Postoperative outcome

Clinical outcome

Age Sex Side Comorbidity Böstman et al. scale (years)

Radiographic outcome Time to A/B P-F joint union ratio (compared to (weeks) preoperative)

Points Rating

55 Female Left

HCV

Excellent

0.80

Similar

60 Female Right

HCV

Excellent

0.87

Similar

40 Female Left

Excellent

0.90

Similar

45 Female Left Irrelevant

Excellent

0.85

Similar

0.80

Similar

65 Female Right

HCV

Excellent

0.84

Similar

17 Male Right

Excellent

0.92

Similar

55 Female Right Irrelevant

Excellent

0.92

Similar

68 Female Left

Good

0.82

Dissimilar

63 Female Left Irrelevant

Excellent

0.90

Similar

53 Female Left

HCV

Excellent

0.90

Similar

72 Female Left

HCV

Good

0.76

Dissimilar

66 Female Left

Excellent

0.80

Similar

74 Female Left Irrelevant

Excellent

0.74

Similar

52 Male Left

Excellent

0.84

Similar

21 Male Left

Excellent

0.88

Similar

41 Female Left Irrelevant

Excellent

0.88

Similar

44 Female Right

Excellent

0.82

Similar

73 Female Left Irrelevant

Excellent

0.76

Female

Left

HCV, DM

Good

0.70

Male

Right

HCV, DM

Excellent

0.92

65 Female Left

0.82

0.80

Male

Female

Left

HCV, DM

HCV

HCV HCV, DM

25 28

Good

Good Excellent

Similar Dissimilar Similar Dissimilar Similar

A/B ratio: Blackburne-Peel A/B ratio; CP: Cerebral palsy; DM: Diabetes mellitus; HCV= Hepatitis C virus infection; P-F joint: Patellofemoral joint.

the lower patellar pole to emerge just distal to Vicryl suture and was interwoven through the patellar tendon to emerge through other corner, as in Kessler’s suture (Fig. 2b). Wire and thread were passed through tunnels to upper pole and tied while knee was extended (Fig. 2c). Stability of repair was tested with full flexion of knee. Excessive tightening of wire loop was avoided to nullify compression of comminuted fracture. Retinacular tears were repaired using #1 Vicryl suture, wound was closed, and Robert Jones bandage was applied for 2 weeks.[10]

Postoperative Care Immediately after surgery, isometric quadriceps exercises were instituted and walking with full weight-bearing was allowed. At postoperative 2 weeks, bandage was removed and program of straight leg raise and active flexion exercises was 152

initiated. At end of eighth week after surgery, vigorous program of straight leg raise with weights and active flexion exercises was implemented. Rehabilitation program continued until full range of knee motion and thigh girth compared with contralateral side was restored. Follow-up examinations were carried out every other week for 12 weeks and then again at 4, 6, and 12 months postoperatively. After first year, patients were examined twice per year. Outcome was assessed with clinical and radiographic data at 24 months.

Outcome Measures Function of the knee was evaluated using clinical grading scale of Böstman et al.[11] Evaluation involved completion of questionnaire regarding pain, work, assistance with walking, Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Massoud. Repair of comminuted fracture of the lower patellar pole

giving way, and stair climbing (maximum score: 18 points). Clinical evaluation included measurement of range of knee movement, thigh atrophy, and knee effusion (maximum score: 12 points). Overall score was rated excellent (30–28 points), good (27–20 points), or unsatisfactory (<20 points).[11] Radiographs were examined for assessment of fracture healing, for patellofemoral degenerative changes compared with preoperative radiograph, and assessment of patellar height using Blackburne-Peel A/B ratio.[12] Patella alta was diagnosed when A/B ratio was >1.06. Patella baja was diagnosed when A/B ratio was <0.54. Patella alta, patella baja, and increase in degenerative changes in the patellofemoral joint were considered unsatisfactory results.[9] Fracture was defined as healed if fracture line was obliterated or bridged. Time to union was estimated from date of surgery to date of fracture healing. Nonunion was defined as progressive widening of fracture line with or without wire fragmentation. Proximal migration of wire loop to fracture line and displacement of distal pole were considered technical failure. Migration of wire through substance of distal pole without widening of fracture line was not considered complication (Fig. 3b).

RESULTS At final follow-up, 18 patients were free of pain. However, 5 patients reported occasional pain with knee flexion or prolonged walking. Causes of pain were irritation of wire knot in suprapatellar area in 2 patients (Fig. 1c, 3b), and degenerative osteoarthritis in the patellofemoral joint in 3 patients. Pain in these patients persisted even after wire removal, and radiography revealed degenerative changes in patellofemoral joint. All patients returned to preoperative level of activities of daily living at average of 4 postoperative months. Patients who worked at home or outdoors before injury returned to work. Three patients reported knee sometimes giving way and dif-

(a)

(b)

ficulties with stair climbing. All patients had active full knee extension with >120 degree active knee flexion. Atrophy of thigh (range: 15–25 mm) was observed in 6 patients. According to clinical grading scale of Böstman et al.,[11] 18 patients were classified as excellent and 5 as good (Table 1). Mean Böstman et al. score was 28.1 points (range: 21–30 points).

Radiographic Results All fractures united within average of 10 weeks (range: 8–16 weeks). Using Blackburne-Peel A/B ratio,[12] patellar height averaged 0.84 (range: 0.70–0.92). There was no report of patella alta or patella baja. Final outcome radiographs demonstrated similarity to preoperative patellofemoral joint in 19 patients. Four postmenopausal female patients had dissimilarity in form indicating increased degenerative changes (Table 1). Overall radiographic outcome was satisfactory in 19 patients and unsatisfactory in 4 patients. Proximal migration of wire loop through the lower patellar pole but distal to the main fracture line was seen in 1 patient at fourth postoperative week (Fig. 1c). At final followup, fracture had healed, patella had preserved normal height, no further migration was observed, and the patient reported excellent result. Break of wire loop was observed in all patients during second year of follow-up period (Fig. 3b). By end of the second year, all wires had been removed.

DISCUSSION Comminuted fracture of the lower patellar pole presents special situation. Definition of this injury determines appropriate technique for repair. However, traditional techniques have drawbacks and limitations. Improvement of nature of this injury through conversion of the bundles attached to the comminuted bone and the denuded bundles of the patellar tendon to integral units seems an attractive option. Comminuted fracture of the lower patellar pole has been described as avulsion fracture.[8] This means that injury has characteristics of fracture and avulsion of the patellar tendon. Absorbable interwoven sutures through the patellar tendon have been used to tie fragments together.[5,8] In presently described technique, sutures were used to bind denuded tendon bundles to bundles that had bony attachments as well as to bring osteotendinous structure to its bed in main fragment. However, validity of absorbable suture for osteosynthesis was not tested widely. Therefore, Magnusson wire was also used for osteosynthesis (Fig. 2).

Figure 3. (a) Preoperative lateral radiograph of the left knee of 45-year-old female shows comminuted fracture of the lower patellar pole; (b) Lateral radiograph taken 1 year postoperatively shows healed fracture, preserved patellar height, and broken wire loop.

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Forces that act at fracture site are either three-points bending with knee flexion or distraction force in extension.[2,13] Carpenter et al. reported that wiring does not resist displacement at fracture site while knee is extended.[13] However, Weber et al. reported that Magnusson wiring rigidly 153

Massoud. Repair of comminuted fracture of the lower patellar pole

fixes fracture fragments through arc of motion of 90° flexion through 10°, but from 10° to 0° there was minimal separation of fracture fragments.[2] Even so, wide insertion of patellar retinaculum,[14] widely distributes tensile stress of extensor mechanism as well. Thus, Weber et al. considered repair of the retinaculum to be most important stabilizing factor in less rigid repairs.[2] Given minimum separation has occurred, Kenwright et al. reported in study of bone healing that small gaps and moderate axial interfragmentary movement are widely accepted as enhancing fracture healing.[15] Furthermore, it has been found that strength of implant has special importance, particularly in non-cooperative patients. Rigid implant causes additional destruction of bone fragments and/or laceration of the patellar tendon, which renders restoration of patellar length and height almost impossible. Conversely, less rigid implant allows for implant failure before damage to bone or tendon; therefore, making re-osteosynthesis practicable.[7] Separate vertical wiring technique has been used for fixation of the lower patellar pole. However, first reports were that technique was not suitable for comminuted fractures in which some bundles of the patellar tendon were separated from bony attachments. Furthermore, holding power of technique was not strong enough and failed to include small fragments. [4] Song et al. suggested augmentation with cerclage wire.[5] However, circumferential wiring has previously mentioned mechanical limitations and biological drawbacks.[2,3] Although Kim et al. used 3 cannulated screws in proximal fragments to avoid anterior migration of wire, anterior displacement of the lower pole was reported.[6] Basket plate is more advanced technique, and design seems suitable for osteosynthesis of lower pole fracture. However, Krkovic et al. noticed difficulties in retaining position of plate and preservation of patellar height when the longitudinal screws were placed in apex of the patella. Therefore, they suggested placement of screws outside insertion of the patellar tendon.[7] To our knowledge, this modification has not yet been tested clinically. Kastelec and Veselko used absorbable interwoven sutures through the patellar tendon to avoid slippage of fragment between the hooks that push fibers of the patellar tendon apart. Even with this modification, they reported shortening of the patellar tendon in 1 of 11 patients in study.[8] Immediate postoperative mobilization and early full weightbearing are among advantages of osteosynthesis. However, with use of separate vertical wiring technique, Kim et al. adopted long leg cast immobilization for 4 weeks and allowed full weight-bearing from eighth postoperative week.[6] Song et al. used immobilization with brace for 1 month and allowed partial weight-bearing as of second week.[5] Yang and Byun used brace and allowed partial weight-bearing at postoperative first month.[4] Osteosynthesis using basket plate allows for full weight-bearing at sixth postoperative week.[8] With present technique, full weight-bearing was encouraged immediately after surgery. Robert Jones bandage[10] was removed at end of second week. 154

Average Böstman clinical score for patients who underwent separate vertical wiring was 29.5 points in study conducted by Yang and Byun,[4] 28.7 points in Kim et al. study,[6] and 28.1 points in Song et al. study.[5] With presently described technique, which was primarily concerned with comminuted fracture, mean Böstman score was excellent 28.1 points. In the present study, 4 postmenopausal female patients demonstrated advancement of degenerative changes in patellofemoral joint. It is notable that most of study patients are females (78%) and common comorbidity was HCV (52%); both of which are associated with reduced bone mineral density.[16] These factors likely contributed to incidence of injury as well as results. Suboptimal vitamin D level is associated with incidence of knee osteoarthritis in postmenopausal females.[17] Moreover, low vitamin D level influences structural progression of osteoarthritis, in addition to association with muscle weakness and increased pain.[18] Present study is limited by lack of control group. Given rarity of this injury, it would require multicenter, randomized, controlled trial to compare relative merits of presently described technique with other methods.

Conclusion Present study addressed characteristics of comminuted fracture of lower pole of the patella and described technique to manage components of injury separately. Successful osteosynthesis of severe comminution using present technique reduces potential need for partial patellectomy and preserves original length of extensor mechanism. Excellent results obtained open the way for immediate full weight-bearing and early, extensive rehabilitation program.

Acknowledgement I would like to thank my daughter Sara Elsayed Ibraheem Massoud, because she has hand-painted the drawing that illustrates steps of repair of the comminuted fracture of the lower patellar pole. Conflict of interest: None declared.

REFERENCES 1. Massoud EIE. Fractured patella in children: Preservation of the patellar dimensions. Dicle Med J 2012;39:467–73. 2. Weber MJ, Janecki CJ, McLeod P, Nelson CL, Thompson JA. Efficacy of various forms of fixation of transverse fractures of the patella. J Bone Joint Surg Am 1980;62:215–20. 3. Scapinelli R. Blood supply of the human patella. Its relation to ischaemic necrosis after fracture. J Bone Joint Surg Br 1967;49:563–70. 4. Yang KH, Byun YS. Separate vertical wiring for the fixation of comminuted fractures of the inferior pole of the patella. J Bone Joint Surg Br 2003;85:1155–60. 5. Song HK, Yoo JH, Byun YS, Yang KH. Separate vertical wiring for the fixation of comminuted fractures of the inferior pole of the patella. Yonsei

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Massoud. Repair of comminuted fracture of the lower patellar pole Med J 2014;55:785–91. 6. Kim YM, Yang JY, Kim KC, Kang C, Joo YB, Lee WY, et al. Separate Vertical Wirings for the Extra-articular Fractures of the Distal Pole of the Patella. Knee Surg Relat Res 2011;23:220–6. 7. Krkovic M, Bombac D, Balazic M, Kosel F, Hribernik M, Senekovic V, et al. Modified pre-curved patellar basket plate, reconstruction of the proper length and position of the patellar ligament--a biomechanical analysis. Knee 2007;14:188–93. 8. Kastelec M, Veselko M. Inferior patellar pole avulsion fractures: osteosynthesis compared with pole resection. J Bone Joint Surg Am 2004;86:696– 701. 9. Massoud EI. Repair of fresh patellar tendon rupture: tension regulation at the suture line. Int Orthop 2010;34:1153–8. 10. Brodell JD, Axon DL, Evarts CM. The Robert Jones bandage. J Bone Joint Surg Br 1986;68:776–9. 11. Böstman O, Kiviluoto O, Nirhamo J. Comminuted displaced fractures of the patella. Injury 1981;13:196–202. 12. Blackburne JS, Peel TE. A new method of measuring patellar height. J Bone Joint Surg Br 1977;59:241–2.

13. Carpenter JE, Kasman RA, Patel N, Lee ML, Goldstein SA. Biomechanical evaluation of current patella fracture fixation techniques. J Orthop Trauma 1997;11:351–6. 14. Starok M, Lenchik L, Trudell D, Resnick D. Normal patellar retinaculum: MR and sonographic imaging with cadaveric correlation. AJR Am J Roentgenol 1997;168:1493–9. 15. Kenwright J, Richardson JB, Cunningham JL, White SH, Goodship AE, Adams MA, et al. Axial movement and tibial fractures. A controlled randomised trial of treatment. J Bone Joint Surg Br. 1991;73:654–9. 16. Lo Re V 3rd, Volk J, Newcomb CW, Yang YX, Freeman CP, Hennessy S, et al. Risk of hip fracture associated with hepatitis C virus infection and hepatitis C/human immunodeficiency virus coinfection. Hepatology 2012;56:1688–98. 17. Abu el Maaty MA, Hanafi RS, El Badawy S, Gad MZ. Association of suboptimal 25-hydroxyvitamin D levels with knee osteoarthritis incidence in post-menopausal Egyptian women. Rheumatol Int 2013;33:2903–7. 18. Felson DT, Niu J, Clancy M, Aliabadi P, Sack B, Guermazi A, et al. Low levels of vitamin D and worsening of knee osteoarthritis: results of two longitudinal studies. Arthritis Rheum 2007;56:129–36.

ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Patella distal ucu parçalı kırığının onarımı Dr. Elsayed Ibraheem Elsayed Massoud Sohag Eğitim Hastanesi, Ortopedi Bölümü, Eğitim Hastaneleri ve Enstitüleri, Mısır

AMAÇ: Patella distal ucunun parçalı kırığı hem patella kırığı hem de patella tendonu avülsiyonunun karakteristik özelliklerini taşır. Bu nedenle travmanın her iki bileşeni de tedavi sırasında düşünülmelidir. Ancak geleneksel tekniklerin herhangi biri mahzurları olmaksızın ayrı ayrı işe yaramaz. Osteosentez ve patella tendonunun eş zamanlı onarımını göz önüne alan bir teknik varsayımladık. GEREÇ VE YÖNTEM: Patella distal ucu parçalıkırığı olan 23 hasta cerrahi yöntemle tedavi edilmiş ve ileriye yönelik olarak 24 ay izlenmiştir. BULGULAR: Hastaların tümü ortalama ameliyat sonrası dördüncü ayda travma öncesi günlük aktivite düzeyine geri döndü. Böstman ve ark. skorlamasına göre hastalar ortalama 28,1 puan aldı. Kırıkların hepsi ortalama 10 haftada kaynadı. Patella yüksekliği muhafaza edilmişti, ancak dört hastada patellofemoral eklemde dejeneratif değişikliklerde artış görüldü. TARTIŞMA: Bu tekniği kullanarak patella distal uç parçalı kırığında osteosentezin başarısı parsiyel patellektomi olma ihtimalini azaltmakta, böylece ekstensör mekanizmanın fizyolojik uzunlluğu korunmaktadır. Bu teknik hemen tam olarak ağırlık taşımaya ve erken dönemde yoğun rehabilitasyon programının uygulanmasına yol açar. Anahtar sözcükler: Alt pol; ekstensör mekanizma; kırık; patella; patella tendonu; patellektomi. Ulus Travma Acil Cerrahi Derg 2017;23(2):150–155

doi: 10.5505/tjtes.2016.46402

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The geriatric polytrauma: Risk profile and prognostic factors Holger Rupprecht, M.D.,1 Hans Jürgen Heppner, M.D.,2 Kristina Wohlfart, M.D.,1 Alp Türkoglu, M.D.1 1

Department of General and Visceral Surgery, Klinikum Fürth, Fürth-Germany

Department of Geriatrics, University of Witten/Herdecke, Schwelm-Germany

ABSTRACT BACKGROUND: In the German population, the percentage of elderly patients is increasing, and consequently there are more elderly patients among trauma cases, and particularly cases of polytrauma. The aim of this study was to present clinical results and a risk profile for geriatric polytrauma patients. METHODS: Review of 140 geriatric (over 65 years of age) polytrauma patients who received prehospital treatment was performed. Severity of trauma was retrospectively assessed with Hannover Polytrauma Score (HPTS). Age, hemoglobin (Hb) level, systolic blood pressure (BP), Glasgow Coma Scale (GCS) score, timing of and necessity for intubation were analyzed in relation to mortality and in comparison with younger patients. RESULTS: Geriatric polytrauma patients (n=140) had overall mortality rate of 65%, whereas younger patients (n=1468) had mortality rate of 15.9%. Despite equivalent severity of injury (HPTS less age points) in geriatric and non-geriatric groups, mortality rate was 4 times higher in geriatric group. Major blood loss with Hb <8 g/dL was revealed to be 3 times more fatal than moderate or minor blood loss (Hb ≥8 g/dL). GCS score <12 corresponded to double mortality rate (39% vs 83%). CONCLUSION: Age by itself is significant risk factor and predictor of increased mortality in polytrauma patients. Additional risk factors include very low GCS score and systolic BP <80 mm Hg, for instance, as potential clinical indicators of massive bleeding and traumatic brain injury. Such parameters demand early and rapid treatment at prehospital stage and on admission. Keywords: Geriatric polytrauma; Glasgow Coma Scale; Hannover Polytrauma Score; polytrauma.

INTRODUCTION Percentage of elderly patients in the German population continues to grow. Consequently, there are more elderly patients among all trauma cases, especially as the elderly are more active now than former generations were.[1,2] Elderly polytrauma patients constitute special case due to reduced compensatory mechanisms and resources. In the present study, data of 140 trauma patients with minimum age of 65 years were analyzed. Severity of trauma was assessed using the Hannover Polytrauma Score (HPTS), as Address for correspondence: Holger Rupprecht, M.D. Chirurgische Klinik 1, Klinikum Fürth, Jakob-Henle-Straße 1, 90766 Fürth, Germany 90766 Fürth - Germany Tel: 004991175801201 E-mail: holger.rupprecht@klinikum-fuerth.de Qucik Response Code

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this score includes age as an additional criterion that influences outcome.

MATERIALS AND METHODS The study included 1608 polytrauma patients who underwent prehospital emergency treatment in Franconia, Germany. All patients were treated by single emergency department. Patients were divided into 2 groups: polytrauma patients below 65 years of age, and those 65 and over (geriatric patients). HPTS, Glasgow Coma Scale (GCS) score, hemoglobin (Hb) level at admission, score on shock index described by Allgöwer and Buri, and pupil status at trauma location were analyzed in order to determine severity of polytrauma.

RESULTS Of 1608 polytrauma patients, 140 (8.7%) were 65 years of age or older. HPTS score, used to assess severity of trauma, quantifies injuries in 5 anatomical regions (skull, thorax, abdomen, extremities, and pelvis) and adds point value for different age groups. HPTS accounts for multiple injuries in single Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Rupprecht et al. The geriatric polytrauma

anatomical region, which is a significant advantage over other scoring systems. Expected mortality rate increases with higher score values (Table 1).

observed that score values were nearly identical between geriatric group and younger group (<65 years). This shows crucial influence of old age on prognosis.

Geriatric trauma patients had mean score of 41.1 and overall mortality rate of 65%, whereas younger patients had score of 27.4 and mortality rate of 15.9%. This is 4-fold higher mortality in elderly patients. Table 2 demonstrates HTPS in 5 subgroups without age points. Severity of injury was comparable in all geriatric subgroups, as well as comparable to younger group (HPTS of 27.4).

Blood loss prior to admission also had noticeable effect on outcome (Table 3). Mortality on day of admission was below 10% if there was no significant blood loss (Hb ≥12g/ dL). Minor blood loss (Hb 8–11.9 g/dL) resulted in mortality rate twice as high, and two-thirds of the patients with major bleeding (Hb <8 g/dL) died on day of injury.

More than half of the patients (52.9%) were between 65 and 74 years old (Groups 1 and 2). Mean HPTS score was only slightly higher than that of younger group (39.9 vs 32.9). Groups 3 and 4 (75–84 years) represented 40% of all trauma patients. This population had significantly (p<0.001) higher HPTS score (47.2 vs 35.9), as well as higher mortality than Groups 1 and 2 (61.8% vs 36.4%). Only 8% of polytraumatized patients (Group 5) were 85 years of age or older. Ten of 11 died as result of injuries (90.9% mortality). When age points were subtracted from HPTS score, it was Table 1. TTrauma severity/Hannover Polytrauma Score/ expected mortality Severity

Score value

Expected lethality

Grade I

0–11

<10%

Grade II

12–30

<25%

Grade III

31–49

<50

Grade IV

>49

75%

Influence of blood loss on prognosis was also demonstrated in subgroup of patients with abdominal trauma. Abdominal trauma is most common reason for massive bleeding and hypovolemic shock. Mortality rate increased to 27% in the 633 of 1608 patients with intraabdominal bleeding source, in contrast to 16% in remaining 974 trauma patients without abdominal injury. This increase in mortality can be directly explained by correlating HPTS scores. Patients with intraabdominal bleeding had mean score of 35, while those without intraabdominal bleeding had score of 25. In geriatric group, overall mortality rate of 60% was observed in cases of intraabdominal bleeding, compared with 36% among those without abdominal injury. Extent of blood loss correlated with injury severity (Table 4). Patients with Hb <8 g/dL had mean HPTS of 35; patients with Hb >12 g/dL had mean HPTS of 18. Another striking relationship was seen between blood loss and GCS score. Massive bleeding (Hb ≤8 g/dL) correlated with low mean GCS score of 6.3, in contrast to GCS score of 11.2 among those with Hb >12 g/dL (Table 5). It was concluded that GCS, which primarily classifies severity of trau-

Table 2. Age group / HPTS / lethality Groups Age HPTS

HPTS – age points

Hospital lethality

Table 4. Hemoglobin / HPTS / HPTS + age points Hemoglobin (g/dL)

Group 1

65–69

33.7

25.7

35.9%

≤8.0

Group 2

70–74

38.1

25.1

37.1%

8.1–9.9

Group 3

75–79

47.3

26.2

66.7%

10.0–11.9

Group 4

80–84

47.4

26.4

56.0%

≥12

Group 5

>85

45.2

24.4

90.9%

HPTS: Hannoverian Polytrauma Score.

HPTS (HPTS + age points) 35 (51)

28 (43)

25 (40)

18 (33)

HPTS: Hannoverian Polytrauma Score.

Table 5. Hemoglobin / Glasgow Coma Scale Table 3. Hemoglobin / lethality Hemoglobin (g/dL)

Hemoglobin (g/dL) Lethality (%)

Glasgow Coma Scale points

≤8 6.3

<8 g/dL

62.5%

8.1–9.9 9.2

8–11.9 g/dL

22.0%

10.0–11.9 10.3

≥12 g/dL

9.7%

≥12 11.2

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and primary or secondary unconsciousness in only 26% of the patients with normal pupil reaction.

Table 6. Glasgow Coma Scale / Lethality rate Glasgow Coma Scale points 3–7

Lethality (%)

Necessity for urgent intubation proved to be important risk factor. Majority of patients (41.2%) had to be intubated at site of injury, and that group had worst outcomes, with mortality rate of 83%. It was also determined that group had lowest GCS score (mean: 5.8). Patients who did not require intubation or ventilation had mean GCS score of 14.3 and mortality rate of 37.1% (Table 8). Survival rate decreased with earlier necessity to intubate.

82.6

8–12 84.6 13–15 39.3

Table 7. Hemoglobin / Shockindex (SI) Hemoglobin (g/dL) Shockindex

≤8

8.1–9.9

10.9–11.9

≥12

1.14

0.87

0.68

matic brain injury (TBI), can also indicate severity of reduced cerebral perfusion caused by hypovolemia. GCS score below 12 was associated with mortality rate twice as high (39% vs 83%), which clearly indicates influence of GCS score on prognosis (Table 6). Shock index introduced by Allgöwer and Buri, defined as heart rate divided by systolic blood pressure (BP) and used to grade severity of shock, proved to be less reliable predictor. In the present study, only patients with Hb <8 g/dL demonstrated pathological shock index score (Table 7). Assessment of pupil status provided relevant information about outcome. Trauma patients with pupils of equal size or normal pupil reaction were found to have mortality rate of 43.6%, whereas patients with pathological pupil reactions (dilated pupils, pupils of unequal size) had higher mortality (87.2%). Of 16 patients with bilaterally small pupils, only 1 survived (93.8% mortality). Patients with pathological pupil reaction frequently had decreased level of consciousness. Only 15% had normal orientation and 70% had primary or secondary loss of consciousness. In contrast, normal orientation was observed in 50%

Decision to intubate urgently was influenced by severity of trauma, as in case of lung contusion, for example. Patients requiring intubation had 7-point higher HPTS with age factor excluded (Table 9). Total of 7% of all trauma patients died in resuscitation area. This group had worst injury score (HPTS: 58.8; HPTS-age factor: 42.1), lowest GCS score (6.7), and lowest Hg level (6.6 g/ dL), as well as lowest systolic BP (68.8 mmHg). Of the 32.6% of patients who required emergent operation, 59.5% died. Those patients had mean HPTS of 45.6 and HPTS-age factor of 31.0, GCS score of 9.4, Hg level of 9.8 g/ dL, and systolic BP of 106 mmHg. In this context, systolic BP on admission is of particular importance. Four-fold higher mortality rate was detected in all polytrauma cases (n=1608), including geriatric polytrauma cases, when BP was below 80 mmHg upon arrival to hospital. Most common injuries were to head and brain (76%), followed by thoracic trauma (66%), and fractures of upper (45%) and lower extremities (53%). Abdominal and pelvic injuries each occurred in 28%, and spinal column injuries in 16%. Abdominal trauma as sole injury had very poor prognosis. This type of injury was observed twice as often in patients who exited (35.3% vs 19.6%). As mentioned previously, mor-

Table 8. Time of intubation / lethality / Glasgow Coma Scale Lethality Glasgow Coma Scale

Trauma site

During transport

In hospital

No intubation

83.0%

75.0%

64.5%

37.1%

5.8

6.5

12.2

14.3

Table 9. Time of intubation / severity of injury

Trauma site

During transport

In hospital

No intubation

Hannoverian Polytrauma Score

43.0

44.1

48.7

32.7

Hannoverian Polytrauma Score-age factor

27.1

26.9

31.9

19.8

158

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Rupprecht et al. The geriatric polytrauma

Table 10. Thoracic injuries / lethality (%) Heart 100 Major thoracic vessels

100

Hematothorax 60.9 Pneumohematothorax 55.6 Parenchyma of the lung

55.0

Ribfracture 47.9 Pneumothorax 33.3

tality rate of 60% was detected in cases of intraabdominal bleeding with another concurrent injury, in contrast to only 36% in cases without abdominal bleeding. Another high-risk injury proved to be pelvic fracture. Massive bleeding caused by this injury occurred nearly twice as often in patients who died (31.8% vs 21.7%). This additional injury led to dramatic increase in mortality in the geriatric subgroup (78%) compared to 24% in the non-geriatric patients (≤64 years). Additional injury to the head and brain, or TBI, or to the thorax resulted in especially unfavorable outcome. Total of 80% of the patients who died on day of injury had concomitant injury of the head and brain or the thorax. Overall mortality rate was 82.4% with TBI and 65.9% with thoracic injury. In all, 106 patients (76.4% of the geriatric patients) suffered from 152 single injuries of the head and brain. In case of grade I TBI (concussion), mortality was 25%. However, mortality increased significantly in grade III TBI: Basal skull fracture had mortality rate of 47.4% and calvarial fracture had mortality rate of 64.3%. In event of intracerebral bleeding, mortality was above 70%. In the present study, 92 trauma patients had total of 144 thoracic injuries (Table 10). High in-hospital mortality rate of 60.9% in case of hematothorax is notable. All patients with either rupture of the heart (n=2) or major thoracic vessels (n=5) died instantly. Approximately 30% of our geriatric patients survived their extensive injuries in the long run. During follow-up period (mean: 9.3 years), 16 patients (11.4%) died of non-injuryrelated causes. Remaining 25 patients were without major health problems at time of data collection (only 2 were in need of professional care).

DISCUSSION Polytrauma poses special challenge at all ages due to imminent life-threatening circumstances and limited therapeutic window. Reduced physiological reserves as well as primarily reduced organ function demonstrate why increased demand in trauma (for example, elevated endogenous vasopressor level in case of shock) often cannot be met sufficiently in elUlus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

derly patients.[3–16] This pathophysiological restriction is demonstrated in increased mortality with greater age.[5,8,9,12,17–27] In the present study, 4 times greater mortality was determined in the geriatric group compared with the younger patient group (65% vs 15.9%). Direct correlation has been noted between increase in mortality and greater injury level in several publications.[14,22,26,28–32] Our data confirm correlation, revealing significantly increased mortality rate corresponding to elevated injury score: Patients older than 75 years of age had highest HPTS and highest mortality rate. We conclude that age alone constitutes substantial risk factor. Removal of age factor from total HPTS in all groups revealed nearly identical score values. HPTS was approximately 25 points in all groups (Table 1). Result highlights fact that geriatric trauma patients need rapid and appropriate prehospital evaluation and initiation of therapy in order to prevent fatal course of events.[3,9,14,33–39] Hypovolemic shock plays central role in bad outcome and increased mortality rate[8,9,12,20,25,28,40–43] as seen in our patients with massive bleeding. It was determined that additional intraabdominal bleeding doubles mortality rate (Table 2, 9). Necessity for blood transfusion in case of massive bleeding reveals hypovolemic shock as crucial factor in increased mortality.[32,44] Mortality was 25% when <20 blood units were transfused, and 56% if >20 blood units were necessary for hemodynamic stabilization. In the event of massive transfusion, coagulopathy and derangement of acid-base homeostasis are often seen. Simultaneous hypothermia amplifies coagulopathy and leads to ongoing bleeding[3,28,40,44] Pathological blood coagulation parameters measured on admission lead to increased mortality in all polytrauma cases compared with those who have normal coagulation parameters (25.7% vs 6.5% mortality rate). In geriatric polytraumatized patients we generally assume preexisting arteriosclerosis with consequently limited vascular tonus and reduced cardiac reserves, which can lead to rapid cardiovascular decompensation if hypovolemia develops.[3,5,6,18,20,21,33–36,38,39,45,46] Volume resuscitation as soon as possible should raise systolic BP to at least 80 mmHg. In case of concomitant head and brain injury, systolic BP should even be at least 120 mmHg in order to maintain adequate cerebral perfusion and to prevent secondary brain injury.[3,9,28,43] Systolic BP is important preclinical parameter, especially for managing volume resuscitation. If necessary, hyperosmotic solutions (e.g., HyperHaes 250 ml; Fresenius Kabi Deutschland GmbH, Bad Homburg v.d.H., Germany) should be used to raise BP rapidly in event of hemodynamic instability. If systolic BP was below 80 mmHg on admission, 4-fold increase in mortality was seen compared with trauma patients with systolic BP above 80 mmHg. 159

Rupprecht et al. The geriatric polytrauma

Unfortunately, shock is often noticed too late or underestimated because obvious signs of shock (e.g., tachycardia and/ or low BP) may be delayed.[27] Beta blockers, for example, suppress reflex tachycardia, and normal BP level may in fact be pathological for patient with untreated hypertension. Negative chronotropic effect of beta blockers leads to impaired cardiac output and may therefore be especially harmful.[12] The often-quoted shock index did not prove to be reliable predictor in our study (Table 6). In order to prevent diagnostic pitfalls, we recommend use of capillary refill time (pathological if >2 seconds) and GCS. GCS is of major prognostic relevance (Table 5), especially in relation to head and brain injuries.[3,8,15,16,23,25,29,32,35,42–44,47–49] Additionally, it allows for reproducible preclinic evaluation to determine necessity of intubation. It also provides evidence on possible volume deficit, which can lead to reduced cerebral perfusion and consequently to impaired or loss of consciousness (Table 4). Our data as well as other studies indicate that head and brain injuries and thoracic traumata are major risk factors,[3,9,13,18,50,26–28,40] and co-occurrence leads to exponential increase in mortality. Already limited pulmonary reserves[3,5,6,9,23] may be further reduced by trauma. For example, lung contusion may rapidly lead to hypoventilation and hypoxia, and can cause secondary brain injury. Therefore, liberal indication for intubation and ventilation with 100% oxygen is recommended.[3,20,33,35] Sufficient anesthesia achieves best possible management of pain. As pain stimulates release of shock mediators, anesthesia can also suppress shock mediator-induced cardiovascular depression. Early intubation was significant risk factor,[12,18,43] but primarily indicates that this group was most injured and had highest cerebral impairment (Table 8), thus requiring urgent intubation. Chest tubes (≥28-French) should be inserted early to establish adequate ventilation of the lung by draining hematoor pneumothorax. Pelvic fractures considerably reduce survival rates in polytraumatized patients.[3,51–55] In our study, mortality rate was 78% in geriatric group with pelvic fracture compared with 24% in younger group (≤64 years) with pelvic fracture. In this case, immediate prehospital procedures are necessary. For instance, applying pelvic belt, circumferential wrapping of the pelvis, or vacuum mattress, all of which help reduce bleeding from fractured bones. Another measure, often disregarded, is to preserve body temperature with warmed intravenous fluid therapy, warm interior of ambulance, or warm blankets, for example. This is of great pathophysiological importance, as hypothermia leads to coagulopathy and consequently to progressive bleeding (“deadly triad”). 160

In the elderly, limited physiological mechanisms of compensation necessitate close monitoring in prehospital stage with electrocardiogram, pulsoxymetry, and pupil reaction, and in hospital with advanced monitoring, such as invasive blood pressure and pulse contour cardiac output monitoring.[3,36,12,56] These measures are the only way to recognize life-threatening changes and intervene in time to prevent acute decompensation. Only a trauma center with appropriate modalities (resuscitation area, blood bank, blood recovery system, etc.) and experienced surgical team is able to keep high mortality within limits.[6,12,14,29,36,38,57]

Conclusion With aid of HPTS, we were able to generate risk profile for geriatric polytrauma patients that will enable statement on prognosis even at prehospital stage. Traumatized patients with systolic BP level <80 mmHg are at high risk, as are those with very low GCS score. GCS score is not only pathologically low in event of head and brain injury, but may also decrease due to cerebral hypoperfusion due to massive bleeding. Age by itself is significant risk factor; however, this should not encourage “therapeutic lethargy.” Quite the contrary, early and aggressive treatment for shock is called for, as physiological reserves in the elderly are reduced.[4,20,37–39,46] After all, nearly 30% of our geriatric polytrauma patients survived their injuries without major physical problems, with the exception of 2 who required professional care. Conflict of interest: None declared.

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ORİJİNAL ÇALIŞMA - ÖZET OLGU SUNUMU

Geriatrik politravma: Risk profili ve prognoz faktörleri Dr. Holger Rupprecht,1 Dr. Hans Jürgen Heppner,2 Dr. Kristina Wohlfart,1 Dr. Alp Türkoglu1 1 2

Klinikum Fürth Eğitim ve Araştırma Hastanesi, Genel ve Visseral Cerrahi, Fürth-Almanya Witten/Herdecke Üniversitesi, Geriatri Anabilim Dalı, Schwelm-Almanya

AMAÇ: Alman nüfusunda yaşlı hastaların oranı giderek artmaktadır. Bu sonuçla, travma ve özellikle politravma olgularındaki yaşlı hastaların oranı da artmaktadır. Bu çalışmamızın amacı, klinik bulgularımızı sunmak ve bu konuda geriatrik politravma olgularına bir risk profili oluşturmaktır. GEREÇ VE YÖNTEM: Hastane öncesi acil girişimde bulunulan 140 geriatrik politravma olgusunu kapsayan bir çalıma yürütüldü. Travmanın şiddeti Hanover Politravma skoruna (HPTS’ye) uyularak geçmişe yönelik olmak üzere değerlendirildi. Yaş, hemoglobin, sistolik kan basıncı, Glasgow Koma Skoru, entübasyona girişim zamanı ve endikasyonu mortalite ve genç hastalarla karşılaştırmalı olarak analiz edildi. BULGULAR: Geriatrik politravma olgularının (n=140) mortalite yüzdesi %65 olarak bulunurken, genç politravma hastalarındaki (n=1468) mortalite oranı sadece yüzde 15.9 olarak tespit edildi. İki gruptaki travma şiddeti yaklaşık olarak aynı olmasına rağmen (HPTS – yaş puanları), geriatrik hastalarda mortalite dört kat daha fazla idi. Bunun yanı sıra, ağır kan kaybı (hemoglobin <8 g/dL), orta derece ve hafif kan kaybına (hemoglobin ≥8 g/ dL) oranla da dört kat daha fazla mortalite bulundu. On ikinin altındaki bir Glasgow Koma Skoru ise bu değerin üzerindeki olgulara kıyasla iki kat daha fazla mortalite göstermekteydi (%39’a %83). TARTIŞMA: Politravma hastalarında, hasta yaşının, kendi başına anlamlı olan bir risk faktörü olduğu ve mortalite artışını önceden gösterdiği tespit edilmiştir. Buna ek olarak düşük Glasgow Koma Skoru; şiddetli kan kaybında klinik bir bulgu olan 60 mmHg’nin altındaki sistolik kan basıncı ve beyin travması, diğer risk önemli faktörlerindendir. Bu faktörler, hastane öncesi ve hastane acilinde, erken ve en kısa sürede tedaviyi gerektirmektedir. Anahtar sözcükler: Geriatrik politravma; Glasgow Koma Skoru; Hanover Politravma Skoru; politravma. Ulus Travma Acil Cerrahi Derg 2017;23(2):156–162

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CA S E SERI ES

Variations in otological presentation of lightning strike victims: Clinical report of 3 patients Erbil Kılıç, M.D.,1 Hakan Genç, M.D.,2 Ümit Aydın, M.D.,3 Burak Aşık, M.D.,4 Bülent Satar, M.D.3 Department of Otolaryngology, Head and Neck Surgery, Gülhane Military Medicine Academy, Haydarpaşa Training Hospital, İstanbul-Turkey

1 2

Department of Otolaryngology, Head and Neck Surgery Department, Isparta Military Hospital, Isparta-Turkey

Department of Otolaryngology, Head and Neck Surgery Gülhane Military Medicine Academy, Ankara-Turkey

Department of Otolaryngology, Head and Neck Surgery, Şırnak Military Hospital, Şırnak-Turkey

ABSTRACT Lightning strike can cause fatal or nonfatal injuries. Some nonfatal injuries are associated with otological symptoms and findings. Conductive hearing loss due to rupture of the tympanic membrane is the most common audiovestibular lesion of lightning strike. Various forms of sensorineural hearing loss and dizziness have also been reported. Presently described are 3 cases of lightning strike injury. First patient had mid-frequency hearing loss in right ear and high frequency sensorineural hearing loss in left ear. Second patient had high frequency sensorineural hearing loss in left ear, and the third had peripheral facial palsy with perilymphatic fistula on same side. This is the first documented case of mid-frequency hearing loss occurring after lightning strike. Keywords: High frequency hearing loss; lightning strike; mid-frequency hearing loss; perilymphatic fistula; peripheral facial nerve palsy.

INTRODUCTION

CASE REPORT

An array of clinical symptoms, most of which are nonfatal, can be produced by lightning strike. Audiovestibular involvement is infrequently reported. Tympanic membrane rupture is most common otological injury (50–70%) and transient vertigo is most common documented vestibular symptom caused by lightning strike.[1,2] Avulsion of the mastoid bone, burns to the external auditory canal, tinnitus, basilar skull fracture, ossicular disruption, perilymphatic fistula, cholesteatoma, and peripheral facial nerve palsy have also been reported following lightning strike.[2–4] Presently described are 2 cases of hearing loss and 1 case of peripheral facial palsy with perilymphatic fistula after lightning strike. To our knowledge, the first patient is the first documented case of mid-frequency hearing loss after lightning strike and the third patient is the first documented case of facial palsy with perilymphatic fistula occurring at the same time.

Case 1

Address for correspondence: Erbil Kılıç, M.D. GATA Haydarpaşa Eğitim Hastanesi, KBB Kliniği, İstanbul, Turkey Tel: +90 216 - 542 20 20 / 4354 E-mail: kilic_erbil@yahoo.com Qucik Response Code

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A 31-year-old male was referred to our hospital following witnessed lightning strike that occurred while patient was sitting on the ground in wooded area during thunderstorm. According to witness statement, victim was sitting under tree struck by lightning. The patient lost consciousness for almost 30 minutes. When he regained consciousness in the ambulance, he was confused and had amnesia of event. On arrival at emergency department (2 hours after the incident), the patient was still confused. First- and second-degree burns were found covering his back, gluteal region, and neck. Second-degree burns were mostly located on gluteal region and back (13 bullous lesions). Linear skin lesions of first-degree burns were noted on back of neck and right side of occipital region. After confusion receded, patient began to suffer from dizziness, hearing loss in right ear, and tinnitus in left ear. Otological examination revealed mild hemotympanum of right ear with bilateral intact tympanic membranes. Although the patient experienced dizziness, vestibular examination was normal. Pure tone audiometry test with audiometer (MA 53; Maico Diagnostic GmbH, Berlin, Germany) of the right ear indicated mid-frequency hearing loss threshold of 60 dB at 1000 Hz, 50 dB at 2000 Hz, and 30 dB at 4000 Hz. Bone conduction thresholds showed similar pattern. Pure tone audiometry 163

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test of the left ear revealed high frequency sensorineural hearing loss (30 dB at 2000 Hz, 60 dB at 4000 Hz, and 55 dB at 8000 Hz) (Figure 1a). Soft tissue density/effusion in the right tympanic cavity was visible on temporal bone computed tomography (CT) (Brilliance CT 64-slice; Philips Healthcare N.V., Best, The Netherlands). Cranial magnetic resonance imaging (MRI) was normal. The patient declined hyperbaric oxygen therapy and received intravenous (IV) methylprednisolone 1mg/kg (Prednol; Mustafa Nevzat Ilaç Sanayii A.S., Istanbul, Turkey), piracetam IV (Nootropil; UCB, S.A., Brussels, Belgium) and vitamin B complex IV (Bemiks 5; Zentiva, N.V., Prague, Czech Republic) for a week. Despite medication, however, audiometry testing revealed no change in right ear and only partial improvement (20 dB at 2000 Hz, 40 dB at 4000 Hz, and 50 dB at 8000 Hz) in left ear (Figure 1b). Conservative management was preferred for mild hemotympanum on right side, and 1-week follow up resulted in complete resolution of hemotympanum. After cessation of 1-week IV medication, intratympanic dexamethasone was administered to both ears once a day for 3 days. At conclusion of this treatment, high frequency hearing loss on the left side was recovered. Audiometry revealed threshold of 50 dB at 2000 Hz on the right; however, other frequencies were within normal limits (Figure 1c).

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A 21-year-old male was referred to hospital following lightning strike. According to the patient, lightning struck tree that was 9 to 10 meters away from him. After loud noise, he noted tinnitus and left-side hearing loss a few seconds later and he was referred to local infirmary within an hour. He received single dose of methylprednisolone 1mg/kg intravenously. Patient reported feeling some improvement in hearing loss following medication, but the patient presented to our department again the next day. Ear examination demonstrated bilateral intact and healthy tympanic membranes. Pure tone audiometry test performed 1 day after the incident revealed high frequency sensorineural hearing loss (40 dB at 4000 Hz and 50 dB at 8000 Hz) in the left ear (Figure 2a). The patient received methylprednisolone 1mg/kg IV, piracetam IV, and vitamin B complex IV for 1 day at hospital. Audiometry next day demonstrated normal hearing with resolution of all symptoms (Figure 2b).

Case 3 A 25-year-old male was admitted to the hospital 15 days after lightning strike. According to referral letter from local otolaryngologist, who had seen the patient in first few hours after the incident, the patient lost consciousness for 5 hours. After regaining consciousness, the patient began to suffer from dizziness and hearing loss in his left ear. Spontaneous left–beating horizontal nystagmus, left-sided grade 4 peripheral facial palsy, mild hyperemia in left ear drum, and skin lesions of second-degree burns located on neck and gluteal region were observed on physical examination (Figure 3a). On admission, physical examination demonstrated left-sided grade 3 peripheral facial palsy (Figures 3b-d), normal ear drums, and no spontaneous nystagmus; however, the patient still suffered from dizziness and left-sided hearing loss. Pure

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Figure 1. (Case 1) (a) Pure tone audiometry performed few hours after lightening strike. (b) Pure tone audiometry performed after initial medical treatment. (c) Pure tone audiometry performed after intratympanic dexamethasone treatment.

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Figure 5. (Case 3) Repair of perilymphatic leak with perichondrium of tragal cartilage. Black dashed line: perichondrium of tragal cartilage, short black line: left stapedial tendon, white dashed line: the incus, white arrow: the chorda tympani.

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DISCUSSION Figure 3. (Case 3) (a) Second-degree burns on the back and gluteal region. (b) Weak facial function on the left side of the forehead. (c) Slightly weak eyelid closure on the left. (d) Weak movement of the left corner of mouth.

tone audiogram revealed mixed hearing loss (with small gap) in the left ear (Figure 4a). Fistula test yielded positive response, especially with positive pressure. Temporal CT and MRI revealed no pathological finding. Methylprednisolone 1mg/kg was administered for 1 week and exploratory tympanotomy was performed with tentative diagnosis of left-sided perilymphatic fistula. During exploration of the middle ear, perilymphatic leak from posterior leg of the stapes was observed and repaired with tragal cartilage perichondrium (Figure 5). One month later, low and high frequency hearing loss remained (Figure 4b). Facial function improved to normal level in 2 months.

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Figure 4. (Case 3) (a) Pure tone audiometry before surgery. (b) Pure tone audiometry after exploratory tympanotomy and repair of perilymphatic leak.

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Worldwide, it is estimated that there are some 8 million flashes of lightning per day. Electrical potential of lightning bolt is approximately 20 million volts with temperature exceeding 20 000°C. Current flow of lightning strike varies from 100 to 110.000 amperes.[1,5,6] Since central audiovestibular system is extremely vulnerable to effects of lightning, all parts of hearing apparatus may be affected.[1,5,6] Tympanic membrane rupture is most frequent otological damage caused by lightning strike.[1,2] Dizziness, avulsion of the mastoid bone, burns to the external auditory canal, tinnitus, basilar skull fracture, ossicular disruption, peripheral facial nerve palsy, and deposit of squamous epithelium on the promontory are other reported clinical outcomes of lightning strike.[2,3,7] Middle ear and mastoid effusion, degeneration of stria vascularis and organ of Corti, total rupture of Reissner’s membrane, microfractures in otic capsule, and edema of facial nerve were also revealed in autopsy studies.[8] Mechanisms of otological injuries caused by lightning strike remain controversial. Cylindrical shock wave transmission from external auditory canal to inner ear, which has enough force to rupture tympanic membrane and to cause ossicular disruption, is considered to be mechanism of otological injuries. High frequency hearing loss without middle ear or tympanic membrane lesions can be explained by acoustic effects of lightning.[3,9] However, there are cases with intact middle and external ear developing sensorineural hearing loss, facial nerve palsy, ossicular disruption, and dizziness that cannot be explained by any of those mechanisms.[6,8,10] Lightning bolt may directly damage inner ear, which has no bony structure in medial part, and may cause temporary occlusion of internal auditory artery. These are alternative theories to explain neural damage with intact middle and external ear.[11] Use of earphones or telephone during thunderstorm has also been reported as possible risk factor for such ear injury.[3] Sound of strike, which causes acute acoustic trauma, can be described as unexpected and of short duration but high inten165

Kılıç et al. Variations in otological presentation of lightning strike victims

sity. A few cases of high frequency hearing loss after lightning strike have been reported.[12] High frequency hearing loss in left ear of our patients was considered to be caused by acute acoustic trauma. High frequency hearing loss of third patient persisting after surgery can also be explained by acoustic effects of lightning. Mid-frequency sensorineural hearing loss (cookie bite hearing loss or “U” shaped hearing loss) is uncommon. Most of these cases have hereditary or idiopathic etiology. A few cases of vestibular schwannoma have been reported as reason for mid-frequency hearing loss. To the best of our knowledge, the first patient described in this report is first documented case of mid-frequency hearing loss after lightning strike. Low frequency hearing loss of third patient might be accounted for by slightly hindered motion of the stapes footplate due to sealing oval window with the perichondrium of tragal cartilage. Little is known about mechanism of facial paralysis after lightning strike. Temporal bone fractures may cause facial paralysis. High temperature and electrical potential of lightning bolt can cause facial nerve edema. Finally, excessive stimulation may cause fatigue in facial nerve function. Relatively quick recovery of facial function in Case 3 would seem to support fatigue theory as result of excessive stimulation of lightning. Perilymphatic fistula likely resulted from exposure to excessive noise of lightning.

Conclusion Severity of injury caused by lightning depends on amount of current carried and its derivative, charge transferred, and energy transferred. Distance between the victim and point of lightning strike is also important. Lightning can cause different clinical symptoms and organ injuries, some of which can be fatal. During evaluation of victims of lightning strike in emergency department, comprehensive otological examination must be performed to avoid delay in detection of audiovestibular injuries.

Pathophysiology of audiovestibular damage following lightning strike is still unclear. Some theories and risk factors have been proposed as sources of otological injuries; however, none is yet sufficient to explain all clinical presentations. Written, informed consent was obtained from the patients described in this report.

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

REFERENCES 1. Browne BJ, Gaasch WR. Electrical injuries and lightning. Emerg Med Clin North Am 1992;10:211–29. 2. Ogren FP, Edmunds AL. Neuro-otologic findings in the lightning-injured patient. Semin Neurol 1995;15:256–62. 3. Offiah C, Heran M, Graeb D. Lightning strike: a rare cause of bilateral ossicular disruption. AJNR Am J Neuroradiol 2007;28:974–5. 4. Scalzitti NJ, Pfannenstiel TJ. A lightning strike causing a cholesteatoma: a unique form of otologic blast injury. Otol Neurotol 2014;35:298–300. 5. Cooper MA. Electrical and lightning injuries. J Emerg Med 1985;2:379– 88. 6. Wright JW Jr, Silk KL. Acoustic and vestibular defects in lightning survivors. Laryngoscope 1974;84:1378–87. 7. Seaman RW, Newell RC. Another etiology of middle ear cholesteatoma. Arch Otolaryngol 1971;94:440–2. 8. Bergstrom L, Neblett LW, Sando I, Hemenway WG, Harrison GD. The lightning-damaged ear. Arch Otolaryngol 1974;100:117–21. 9. Mora-Magaña I, Collado-Corona MA, Toral-Martiñòn R, Cano A. Acoustic trauma caused by lightning. Int J Pediatr Otorhinolaryngol 1996;35:59–69. 10. Fidan V, Fidan T, Saracoglu KT. Lightning strike: a rare cause of incudostapedial disruption with intact membrane. Pediatr Emerg Care 2012;28:213–4. 11. Ilan O, Syed MI, Weinreb I, Rutka JA. Re: Inner ear damage following electric current and lightning injury: a literature review. Eur Arch Otorhinolaryngol 2015;272:3083–4. 12. Angerer F, Hoppe U, Schick B. Lightning strike to a vehicle causing acute acoustic trauma. HNO 2009;57:1081–3.

OLGU SERİSİ - ÖZET

Yıldırım düşmesine bağlı oluşan farklı otolaringolojik tablolar: Üç hastaya ait klinik rapor Dr. Erbil Kılıç,1 Dr. Hakan Genç,2 Dr. Ümit Aydın,3 Dr. Burak Aşık,4 Dr. Bülent Satar3 Gülhane Askeri Tıp Akademisi Haydarpaşa Eğitim Hastanesi, Kulak Burun Boğaz, Baş ve Boyun Cerrahisi Servisi, İstanbul Isparta Asker Hastanesi, Kulak Burun Boğaz, Baş ve Boyun Cerrahisi Servisi, Isparta Gülhane Askeri Tıp Akademisi, Kulak Burun Boğaz, Baş ve Boyun Cerrahisi Anabilim Dalı, Ankara 4 Şırnak Asker Hastanesi, Kulak Burun Boğaz, Baş ve Boyun Cerrahisi Servisi, Şırnak 1 2 3

Yıldırım düşmesi, ölümcül veya morbit yaralanmalara sebep olabilir. Bu morbit yaralanmaların bir kısmı otolaringolojik semptom ve bulgularla birliktedir. Yıldırım düşmesine bağlı yaralanmalarda en sık görülen odyovestibüler lezyon; timpanik membran rüptürüne bağlı iletim tipi işitme kaybıdır. Ayrıca çeşitli tiplerde sensörinöral işitme kaybı ve dizines da görülebilir. Bu yazıda, yıldırım düşmesine bağlı otolaringolojik lezyonu olan üç hastanın klinik tablosu sunuldu. İlk hastanın sağ kulağında orta-frekans işitme kaybı varken sol kulağında yüksek frekans sensörinöral işitme kaybı vardı. İkinci hastanın sağ kulağında sadece yüksek frekans sensörinöral işitme kaybı vardı. Üçüncü hastada ise, yıldırım çarpması sonrası, periferik fasiyal paralizi ve aynı tarafta perilenf fistülü tespit edildi. Yıldırım çarpması sonrasında bir kulağında orta-frekans işitme kaybı oluşan hastamız, yıldırım çarpması sonrası orta-frekans sensörinöral işitme kaybı meydana gelen literatürde bildirilmiş ilk hastadır. Anahtar sözcükler: Orta-frekans işitme kaybı, periferik fasiyal paralizi; perilenf fistülü; yıldırım çarpması; yüksek frekans işitme kaybı. Ulus Travma Acil Cerrahi Derg 2017;23(2):163–166

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CA S E R EP O RT

An excellent anatomical and visual recovery after surgical repair of an open eye injury with poor baseline prognostic factors Serpil Yazgan, M.D.,1 Orhan Ayar, M.D.,1 Orçun Akdemir, M.D.,1 Yaran Koban, M.D.2 1

Department of Ophthalmology, Bülent Ecevit University Faculty of Medicine, Zonguldak-Turkey

Department of Ophthalmology, Kafkas University Faculty of Medicine, Kars-Turkey

ABSTRACT Presently described is case of a 42-year-old woman with eye injury that was result of gunshot fired by a man at a wedding celebration. Bullet penetrated inferior quadrant of nasal sclera of left eye 7–12 mm behind limbus. Choroid and vitreous were prolapsed around bullet. Hemorrhage, vitreous prolapse and lens subluxation were present in anterior chamber. Presenting visual acuity (VA) was hand motion. Bullet 14x5 mm in size was carefully extracted from the eye. Fifteen days later, argon laser photocoagulation was performed on retina in area of bullet entry point. VA was 20/25 (Snellen) at final visit. In this case, although foreign body was large, area of penetration was Zone III, and initial VA was poor, early and appropriate surgical repair achieved integrity of the globe and good vision prognosis. Keywords: Bullet; intraocular foreign body; ocular trauma.

INTRODUCTION Open-globe injuries are one of the main causes of enduring visual impairment and blindness. Estimated incidence rate is 3.5 per 100,000 persons per year worldwide.[1] Birmingham Eye Trauma Terminology classifies ocular lesions caused by intraocular foreign body (IOFB) separately from other openglobe injuries due to different properties and prognosis.[2] Eye injuries accompanied by IOFB involvement of posterior segment and laceration occurring in Zone III are poor prognostic factors.[3,4] However, in recent studies these criteria have become controversial.[5] High quality images from orbital computerized tomography (CT) can visualize localization of inorganic IOFB, and success of trauma surgery is increased with early surgical intervention.

CASE REPORT A 42-year-old woman presented at emergency clinic with complaint of decreased vision in the left eye as result of gunAddress for correspondence: Yaran Koban, M.D. Kafkas Üniversitesi Tıp Fakültesi Hastanesi, Göz Hastaklıkları Anabilim Dalı, 36000 Kars, Turkey Tel: +90 474 - 225 21 06 E-mail: yarankoban@yahoo.com.au Qucik Response Code

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shot that occurred 1 hour before our examination. After a man fired a gun to celebrate a wedding, the bullet ricocheted off a wall and struck the woman in the left eye. Bullet had penetrated inferior nasal sclera of the left eye 7–12 mm behind limbus (Zone III) at level of 7 o’clock. One end of bullet was in the vitreous cavity and the other was lodged in the left inferior eyelid. At site of entry to globe, choroid and vitreous were prolapsed (Figure 1a, b). Patient visual acuity (VA) was hand motion. In anterior chamber, hemorrhage and vitreous prolapse were present. Lens was clear and subluxated, and red reflex of the fundus was absent. Oral nutrition was halted, and tetanus prophylaxis and intravenous 1 gr sefazolin sodium were administered to the patient. Orbital computed tomography (CT) was performed and localization of IOFB in the eye was identified (Figure 2a). Surgery was performed 6 hours after injury occurred under general anesthesia. After sterile conditions were obtained, the eye was covered with sterile eye drape. Conjunctiva was widely excised. Medial rectus muscle was accessed and limits of scleral laceration were identified. The part of the bullet buried in the lower eyelid was released with small, careful incisions. Bullet was slowly and patiently extracted from the sclera without applying too much traction. Size of the bullet was 14x5 mm (Figure 1b). Prolapsed vitreous and choroid around scleral entry site were gently cut with scissors. After making certain that no vitreous was trapped, sclera and conjunctiva were sutured with 8–0 vicryl suture. Postoperatively, topical prednisolone acetate 1% 8x1, moxifloxacin 0.5% 8x1, cyclopentolate hydrochloride 1.5% 3x1, oral ciprofloxacin 750 mg 2x1, and methylprednisolone 64 mg were administered. Oral 167

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ciprofloxacin was discontinued after 1 week. Topical and oral steroid therapies were tapered back to zero in 4 weeks and 2 weeks, respectively. Topical cycloplegic and moxifloxacin therapies were halted in 3 weeks. In postoperative second week, vitreous hemorrhage decreased and argon laser photocoagulation was performed on inferior nasal retina around site of bullet entry. In postoperative follow-up period, fibrinoid reaction and hemorrhage in anterior chamber was

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resorbed, vitreous in the pupillary interspace disappeared, and lens returned to its normal location. Posterior synechia developed at 7 oâ&#x20AC;&#x2122;clock position (Figures 3a, b). One week after surgery, VA was 20/100 in the left eye and at postoperative 1 month had improved to 20/25. Excellent globe integrity was achieved despite magnitude of the injury. (Figures 2b, 3a, b). During regular follow-up for 1 year there was no change in VA or ocular findings. At first year follow-up, VA

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Figure 1. (a) Careful removal of the bullet. (b) Illustration of size of the bullet removed.

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Figure 2. (a) Preoperative CT image indicating large metallic intraocular foreign body in the left eye. (b) Postoperative CT image illustrating integrity of the left eye globe.

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Figure 3. (a) Healed site of scleral and conjunctival wound at bullet entry point. (b) Posterior synechia occurred at 7 oâ&#x20AC;&#x2122;clock position and lens returned to its normal position. Clear anterior chamber is seen following resorption of vitreous and hemorrhage.

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was 20/25 and intraocular pressure was 11 mmHg. There was no change in anterior segment findings. Fundus examination revealed laser spots in inferonasal area of the retina while remainder of the retina was normal.

score. All efforts should be made for appropriate and early surgical intervention in these situations because final VA in a traumatized patient cannot be estimated without information about macular anatomy and function.

DISCUSSION

Acknowledgements

In many of the studies that have tried to determine prognostic factors of eye injuries, authors have stated that prognosis is poor for posterior segment traumas with IOFB, especially depending on the size of the IOFB.[3,4] Valmaggia et al.[5] studied location of retinal lesion, initial VA, ocular trauma score,[6] and area of the eye where IOFB penetration occurred as prognostic factors, and found that macular lesion is mostly associated with low final best corrected visual acuity (BCVA). In the present case, bullet was lodged in the sclera, positioned such that half of the object was in the vitreous cavity and the other half outside the sclera in the lower eyelid. Although it was large, bullet did not hit the eye with full impact, indicating that bullet entered the eye at relatively slower speed. This milder impact probably helped to preserve macula from deep trauma, which in turn, affected final VA achieved. In contrast to many studies,[7] Valmaggia et al. stated that initial VA is not the most reliable predictive factor for final BCVA. Similarly, in this case, in spite of bad prognostic factors such as initial bad VA, large metallic IOFB (14x5 mm) and penetration located in Zone III, final VA of the patient was 20/25. This excellent anatomical and visual recovery may also be result of early medical treatment and surgical repair. Guidance of orbital CT in determining location of IOFB, gentle movements during surgery with little vitreous traction, no vitreous or choroid tissue loss, and unaffected macular anatomy and function may have also contributed to the result. Trauma score is a guide for the surgeon to estimate surgical success. However, it is not logical to abandon traumatized eyes with high trauma

This case report was not supported by any company. None of the authors has financial or proprietary interests in any material mentioned. These data have not previously been published. Conflict of interest: None declared.

REFERENCES 1. Négrel AD, Thylefors B. The global impact of eye injuries. Ophthalmic Epidemiol 1998;5:143–69. 2. Kuhn F, Morris R, Witherspoon CD. Birmingham Eye Trauma Terminology (BETT): terminology and classification of mechanical eye injuries. Ophthalmol Clin North Am 2002;15:139–43. 3. Zhang Y, Zhang M, Jiang C, Qiu HY. Intraocular foreign bodies in china: clinical characteristics, prognostic factors, and visual outcomes in 1,421 eyes. Am J Ophthalmol 2011;152:66–73. 4. Ehlers JP, Kunimoto DY, Ittoop S, Maguire JI, Ho AC, Regillo CD. Metallic intraocular foreign bodies: characteristics, interventions, and prognostic factors for visual outcome and globe survival. Am J Ophthalmol 2008;146:427–33. 5. Valmaggia C, Baty F, Lang C, Helbig H. Ocular injuries with a metallic foreign body in the posterior segment as a result of hammering: the visual outcome and prognostic factors. Retina 2014;34:1116–22. 6. Kuhn F, Maisiak R, Mann L, Mester V, Morris R, Witherspoon CD. The Ocular Trauma Score (OTS). Ophthalmol Clin North Am 2002;15:163–5. 7. Greven CM, Engelbrecht NE, Slusher MM, Nagy SS. Intraocular foreign bodies: management, prognostic factors, and visual outcomes. Ophthalmology 2000;107:608–12.

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Kötü başlangıç prognostik faktörlere sahip açık göz yaralanmasında cerrahisi sonrası mükemmel anatomik ve görsel iyileşme Dr. Serpil Yazgan,1 Dr. Orhan Ayar,1 Dr. Orçun Akdemir,1 Dr. Yaran Koban2 1 2

Bülent Ecevit Üniversitesi Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı, Zonguldak Kafkas Üniversitesi Tıp Fakültesi, Göz Hastalıkları Anabilim Dalı, Kars

Bu yazıda, düğün töreni sırasında ateşlenen mermi ile göz yaralanması oluşan 42 yaşındaki kadın hasta sunuldu. Mermi çekirdeği, sol göz nazal skleranın alt kadranında, limbusun 7–12 milimetre arkasını delmişti. Koroid ve vitreus çekirdeğin etrafına prolabeydi. Ön kamarada kanama, vitreus prolapsusu ve lens subluksasyonu mevcuttu. Başvuru anındaki görme keskinliği el hareketi seviyesindeydi. 14x5 mm büyüklüğündeki mermi çekirdeği gözden dikkatlice çıkarıldı. On beş gün sonra, giriş alanı çevresindeki retinaya argon lazer fotokoagülasyon uygulandı. Hastanın son ziyaretindeki görme keskinliği 20/25 (Snellen) idi. Bu olguda, yabancı cisim büyük, penetrasyon alanı zon 3’de ve başlangıç görme keskinliği kötü olmasına rağmen, erken ve uygun cerrahi onarım göz küresinin bütünlüğü ve iyi görme prognozu sağlamıştır. Anahtar sözcükler: İntraoküler yabancı cisim; mermi çekirdeği; oküler travma. Ulus Travma Acil Cerrahi Derg 2017;23(2):167–169

doi: 10.5505/tjtes.2016.23790

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CA S E R EP O RT

Behçet’s disease-related superior vena cava syndrome and bleeding downhill varices: A rare complication Bülent Yaşar, M.D.,1* Gamze Kılıçoğlu, M.D.2 1

Department of Gastroenterology and Hepatology, Çamlıca Erdem Hospital, İstanbul-Turkey

Department of Radiology, Haydarpaşa Numune Training and Research Hospital, İstanbul-Turkey

ABSTRACT Obstruction of the superior vena cava (SVC) due to any cause results in development of venous collaterals in the upper part of the esophagus, known as “downhill” varices. Although rare, bleeding can be life-threatening. Presently described is case of Behçet’s diseaserelated SVC occlusion in a patient who presented with gastrointestinal bleeding from upper esophageal varices. Keywords: Behçet’s disease; downhill varices; superior vena cava syndrome.

INTRODUCTION The most common esophageal varices are located in the distal part of the esophagus and are almost always associated with portal hypertension. This type is called “uphill,” due to upward direction of blood flow. Upper esophageal varices are less common than distal uphill type, and referred to as “downhill” varices (DEV). These varices are mostly associated with superior vena cava (SVC) obstruction secondary to mass effects of tumor or venous thrombosis. Increased blood flow into esophageal veins has been considered etiology of DEV in rare cases. Presently described is case of bleeding from downhill varices caused by SVC occlusion in a patient with history of Behçet’s disease.

CASE REPORT A 40-year-old male was admitted to hospital with suddenonset hematemesis. He seemed pale and vital signs revealed Yazarın şimdiki kurumu: Başkent Üniversitesi İstanbul Uygulama ve Araştırma Merkezi

Address for correspondence: Bülent Yaşar, M.D. Başkent Üniversitesi İstanbul Uygulama ve Araştırma Merkezi, İstanbul, Turkey Tel: +90 216 - 554 15 00 E-mail: drbyasar@yahoo.com Qucik Response Code

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slightly low blood pressure (100/70 mmHg blood pressure with heart rate of 92 bpm). Rectal examination revealed solid black stool, but no other abnormalities were present on physical examination. Laboratory values on admission showed anemia (9.0 g/dL hemoglobin (normal: 12.5–16 g/dL) and 29.8% hematocrit (normal: 37–47%) with normal platelet count and coagulation parameters. Medical history included diagnosis of Behçet’s disease in 1995. In 1996, the patient had intracranial hemorrhage due to prolonged prothrombin time as result of uncontrolled use of Coumadin (Bristol-Myers Squibb Co., New York, NY, USA). After recovery, Coumadin was exchanged for acetylsalicylic acid. Treatment regimen since then had been immunosuppressive (azathioprine 100 mg/day) and antiaggregant (acetylsalicylic acid 100 mg/day). After transfusion of a unit of red blood cells and attaining hemodynamic stabilization, esophagogastroduodenoscopy was performed with initial diagnosis of peptic ulcer bleeding due to acetylsalicylic acid use. Endoscopic examination revealed grade II esophageal varices in upper part of the esophagus, although neither active bleeding nor stigmata of recent bleeding were noted (Fig. 1). Distal esophagus, stomach, and duodenum were entirely normal and no peptic ulcer was detected. Most likely diagnosis was bleeding from downhill varices. As there was no active bleeding, the patient was managed conservatively. Contrast-enhanced computed tomography scan of the chest was performed to determine etiology of varices and it showed marked stenosis of the SVC and collateral veins on the chest wall (Fig. 2). The patient’s general condition and hemoglobin levels remained stable and he was discharged a few days later. Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

Yaşar et al. Behçet’s disease-related superior vena cava syndrome and bleeding downhill varices

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Figure 1. (a, b) Esophagogastroduodenoscopy revealing “downhill” varices in the upper part of the esophagus.

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Figure 2. Contrast-enhanced computed tomography of the chest. (a) The obvious occlusion of the superior vena cava (SVC) (yellow arrow), with dilated azygos vein (grey arrow), and collateral veins on the chest wall (white arrow). (b) Coronal reformatted images indicating tight SVC occlusion (arrow) and (c) subcutaneous collateral veins on the chest and abdominal walls.

DISCUSSION Behçet’s disease (BD) is a chronic multisystemic vasculitis of unknown origin, first described by Turkish dermatologist Hulusi Behçet in 1937.[1] It is characterized by recurrent oral and genital ulcerations, as well as inflammation of the eyes. Many other mucocutaneous, musculoskeletal, cardiovascular, gastrointestinal, and neurological systems can be affected. Vasculitis affects both arterial and venous systems, and involves all sizes of vessels, although arteritis is less frequent. [2] Involvement of great veins, such as SVC, is well-defined but rare complication, occurring in less than 2% of patients with BD.[3] When SVC obstruction occurs, blood from the head, neck, and upper extremities cannot directly reach the right atrium. One of the venous collaterals through which blood flows to bypass the obstruction is deep esophageal veins, resulting in proximal esophageal varices.[4] Due to retrograde blood flow, they are also known as DEV. This type of varices is rare, and has much lower risk of bleeding than classic (uphill) distal varices (9%). DEV are mostly due to SVC syndrome, which may be related to various etiological factors. Mass effect of malignancy is predominant (95%); DEV secondary to SVC in a patient with BD is very rare. Pubmed Ulus Travma Acil Cerrahi Derg, March 2017, Vol. 23, No. 2

search revealed only 7 reported cases. As the data are so limited, there is no consensus on treatment of such DEV; however, underlying cause of obstruction should be treated. As in many forms of vasculitis, immunosuppressive agents are primary therapy in BD with major venous involvement. Anticoagulant or antiaggregant therapy is controversial, as thrombus is adhered to vessel wall and embolism is rare.[5] However, these therapies may facilitate bleeding in case of varices. This case demonstrates that DEV could be possible etiology of gastrointestinal bleeding in a patient with BD; therefore, upper esophagus should be evaluated carefully in such patients. Conflict of interest: None declared.

REFERENCES 1. Behcet H. Über rezidivierende, aphtöse, durch ein Virus verursachte Geschwüre im Mund, am Auge an den Genitalien. Dermatol. Wschr 1937;105:1152–7. 2. Bahar S, Coban O, Gürvit IH, Akman-Demir G, Gökyiğit A. Spontaneous dissection of the extracranial vertebral artery with spinal subarachnoid haemorrhage in a patient with Behçet’s disease. Neuroradiology 1993;35:352–4.

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Yaşar et al. Behçet’s disease-related superior vena cava syndrome and bleeding downhill varices 3. Hanta I, Ucar G, Kuleci S, Ozbek S, Kocabas A. Superior vena cava syndrome: a rare clinical manifestation of Behcet’s disease. Clin Rheumatol 2005;24:314–5. 4. Yasar B, Abut E. A case of mediastinal fibrosis due to radiotherapy and ‘downhill’ esophageal varices: a rare cause of upper gastrointestinal bleed-

ing. Clin J Gastroenterol 2015;8:73–6. 5. Ennaifer R, B’chir Hamzaoui S, Larbi T, Romdhane H, Abdallah M, Bel Hadj N, et al. Downhill oesophageal variceal bleeding: A rare complication in Behçet’s disease-related superior vena cava syndrome. Arab J Gastroenterol 2015;16:36–8.

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Behçet hastalığı ile ilişkili süperior vena kava sendromu ve kanayan downhill varisler: Nadir bir komplikasyon Dr. Bülent Yaşar,1 Dr. Gamze Kılıçoğlu2 1 2

Çamlıca Erdem Hastanesi, Gastroenteroloji ve Hepatoloji Kliniği, İstanbul Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Radyoloji Kliniği, İstanbul

Süperior vena kava’nın herhangi bir nedenle tıkanması, yemek borusunun üst kısmında venöz genişlemeler ile sonuçlanır ve bunlar “downhill-aşağı yönlü” varisler olarak adlandırılır. Nadir olmasına rağmen, kanamaları hayatı tehdit edici olabilir. Bu yazıda, Behçet hastalığı’na bağlı süperior vena kava tıkanıklığı sonucu gelişen ve kanayan üst yemek borusu varisli bir olgu sunuldu. Anahtar sözcükler: Behçet hastalığı; downhill varisler; süperior vena kava sendromu. Ulus Travma Acil Cerrahi Derg 2017;23(2):170–172

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doi: 10.5505/tjtes.2016.92145

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