Travma 2014 5 by KAREPUBLISHING

ISSN 1306 - 696X

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

Volume 20 | Number 5 | September 2014

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) Hakan Yanar M. Mahir Özmen 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 (Başkan Yardımcısı) Secretary General (Genel Sekreter) Treasurer (Sayman) Members (Yönetim Kurulu Üyeleri)

Recep Güloğlu Kaya Sarıbeyoğlu M. Mahir Özmen Ali Fuat Kaan Gök Hakan Teoman Yanar Gürhan Çelik Osman Şimşek

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 - 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)

Recep Güloğlu Recep Güloğlu 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

Annual subscription rates: 75.- (USD) Abonelik: 2014 yılı abone bedeli (Ulusal Travma ve Acil Cerrahi Derneği’ne bağış olarak) 75.- YTL’dir. Hesap No: Türkiye İş Bankası, İstanbul Tıp Fakültesi Şubesi 1200 - 3141069 no’lu hesabına yatırılıp makbuz dernek adresine posta veya faks yolu ile iletilmelidir. 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, and Turkish Medical Index (Index Medicus, Medline; EMBASE, Excerpta Medica; Science Citation Index-Expanded (SCI-E), Index Copernicus, DOAJ 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): Corinne Can • Redaction (Redaksiyon): Erman Aytaç • Online Manuscript & Web Management (Online Dergi & Web): LookUs • Press (Baskı): Yıldırım Matbaacılık • Press date (Basım tarihi): September (Eylül) 2014 • This publication is printed on paper that meets the international standard ISO 9706: 1994 (Bu dergide kullanılan kağıt ISO 9706: 1994 standardına uygundur.)

KARE 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. For the five-year term of 2001-2006, 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. 2001-2006 yılları arasındaki 5 yıllık dönemde SCI-E kapsamındaki dergilerdeki 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 20

Number - Sayı 5 September - Eylül 2014

Contents - İçindekiler

Experimental Study- Experimental - Deneysel Çalışma Deneysel Çalışma Study 311-318 Surgical treatment of achilles tendon ruptures: the comparison of open and percutaneous methods in a rabbit model Aşil tendon rüptürlerinin cerrahi tedavisi: Açık ve kapalı yöntemlerin tavşan modeli üzerinde karşılaştırılması Yılmaz G, Doral MN, Turhan E, Dönmez G, Atay AÖ, Kaya D 319-327 The effects of sildenafil in liver and kidney injury in a rat model of severe scald burn: a biochemical and histopathological study Sildenafilin ağır haşlama yanığı oluşturulan sıçan modelinde karaciğer ve böbrek hasarı üzerine etkisi: Biyokimyasal ve histopatolojik çalışma Gökakın AK, Atabey M, Deveci K, Sancakdar E, Tuzcu M, Duger C, Topcu O 328-332 Thymoquinone attenuates trauma induced spinal cord damage in an animal model Timokinon deneysel spinal kord yaralanmalı sıçanlarda spinal kord hasarını azaltır Üstün N, Aras M, Ozgur T, Bayraktar HS, Sefil F, Ozden R, Yagiz AE

Original Articles- Original - Klinik Çalışma Klinik Çalışma Articles 333-337 Fournier’s gangrene: Review of 120 patients and predictors of mortality Fournier gangreni: 120 olgunun değerlendirmesi ve mortalite prediktörleri Yılmazlar T, Işık Ö, Öztürk E, Özer A, Gülcü B, Ercan İ 338-342 A series of civilian fatalities during the war in Syria Suriye’deki savaş esnasında meydana gelen sivil ölümler Çelikel A, Karaarslan B, Demirkıran DS, Zeren C, Arslan MM 343-352 The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis: a single-center prospective study Sekonder peritonitte prokalsitonin, CRP ve tiroit hormonlarının prognostik değeri; ileriye yönelik çalışma Akcay I, Okoh AK, Yalav O, Eray IC, Rencuzogullari A, Dalci K, Elkan H, Alparslan AH 353-358 Features of the traffic accidents happened in the province of Aydın between 2005 and 2011 2005-2011 yıllarında Aydın ilindeki trafik kazalarının özellikleri Dirlik M, Bostancıoğlu BÇ, Elbek T, Korkmaz B, Çallak Kallem F, Gün B 359-365 Evaluation of liver injury in a tertiary hospital: a retrospective study Üçüncü basamak hastanede karaciğer travmalarının değerlendirilmesi: Geriye dönük bir çalışma Bilgiç İ, Gelecek S, Akgün AE, Özmen MM 366-370 Comparison of early surgery (unroofing-curettage) and elective surgery (Karydakis flap technique) in pilonidal sinus abscess cases Pilonidal sinüs apse olgularında erken cerrahi (unroofıng-küretaj) ile elektif cerrahinin (Karydakis flep tekniği) karşılaştırılması Kanat BH, Bozan MB, Yazar FM, Yur M, Erol F, Özkan Z, Emir S, Urfalıoğlu A Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

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TURKISH JOURNAL OF TRAUMA & EMERGENCY SURGERY ULUSAL TRAVMA VE ACİL CERRAHİ DERGİSİ Vol. - Cilt 20

Number - Sayı 5 September - Eylül 2014

Contents - İçindekiler 281-285 A practice report of bladder injuries due to gunshot wounds in Syrian refugees Suriyeli mültecilerde ateşli silah yaralanmalarından dolayı mesane yaralanmalarındaki tecrübelerimiz Inci M, Karakuş A, Rifaioglu MM, Yengil E, Atçi N, Akin Ö, Tuzcu K, Kiper A, Demirbaş O, Şahan M 376-381 Multi-detector angio-CT and the use of D-dimer for the diagnosis of acute mesenteric ischemia in geriatric patients Geriatrik hastalarda akut mezenterik iskemi tanısında multidedektör anjiyo BT ve D-dimer kullanımı Gün B, Yolcu S, Değerli V, Elçin G, Tomruk Ö, Erdur B, Parlak İ

OlguReports Sunumu- -Olgu CaseSunumu Reports Case 382-384 A shocking craniofacial penetrating injury by a steel bar Çelik parmaklık üstüne düşme sonucu oluşan şok edici kraniyofasiyal penetran travma Chen PY, Yao SF, Dai AX, Chen HJ, Wang KW 385-388 Partial penectomy after debridement of a Fournier’s gangrene progressing with an isolated penile necrosis Fournier gangreni debridmanı sonrası devam eden izole penis nekrozunda parsiyel penektomi Akbulut F, Kucuktopcu O, Sonmezay E, Simsek A, Ozgor F, Gurbuz ZG 389-391 The journey of gastric phytobezoar followed by tomography Gastrik bezoarın tomografik yolculuğu Olgun DÇ, Kayadibi Y, Şimşek O, Karaduman Z 392-394 Successful treatment of a hepatic abscess formed secondary to fish bone penetration by laparoscopic removal of the foreign body: report of a case Balık kılçığı penetrasyonuna bağlı oluşmuş karaciğer apsesinin laparoskopik olarak başarılı tedavisi: Olgu sunumu Koşar MN, Oruk İ, Yazıcıoğlu MB, Erol Ç, Çabuk B

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EXPERIMENTAL STUDY

Surgical treatment of achilles tendon ruptures: the comparison of open and percutaneous methods in a rabbit model Güney Yılmaz, M.D.,1 Mahmut Nedim Doral, M.D.,2 Egemen Turhan, M.D.,2 Gürhan Dönmez, M.D.,2 Ahmet Özgür Atay, M.D.,2 Defne Kaya, M.D.3 1

Department of Orthopaedics and Traumatology, Selcuk University Faculty of Medicine, Konya;

Department of Orthopaedics and Traumatology, Hacettepe University Faculty of Medicine, Ankara;

Department of Sports Medicine, Hacettepe University Faculty of Medicine, Ankara

ABSTRACT BACKGROUND: This study was intended to investigate the healing properties of open and percutaneous techniques in a rabbit model and compare histological, electron microscopical, and biomechanical findings of the healed tendon between the groups. METHODS: Twenty-six rabbits were randomly assigned to two groups of thirteen rabbits each. Percutaneous tenotomy of the Achilles tendon (AT) was applied through a stab incision on the right side 1.5 cm above the calcaneal insertion in all animals. Using the same Bunnell suture, the first group was repaired with the open and the second group was repaired with the percutaneous method. ATs were harvested at the end of eight weeks for biomechanical and histological evaluation. RESULTS: When the sections were evaluated for fibrillar density under electron microscopy, it was noted that fibrils were more abundant in the percutaneous repair group. The tendon scores in the percutaneous group were less than the open group indicating closer histological morphology to normal. The difference was not significant (p=0.065). The mean force to rupture the tendon was 143.7± 9.5 N in percutaneous group and 139.2±8.2 N in the open group. The difference was not significant (p=0.33). CONCLUSION: Percutaneous techniques provide as good clinical results as the open techniques do. The healing tendon shows better findings in histological and electron microscopical level with percutaneous technique. Key words: Achilles tendon; open repair; percutaneous repair.

INTRODUCTION The incidence of Achilles tendon (AT) rupture is around eighteen per 100.000 people and it is more common in men aged 30 to 50 years.[1] Although AT is the strongest tendon, it is most frequently ruptured.[2-4] Autoimmune conditions, mechanical abnormalities of the foot, corticosteroid therapy, fluoroquinolone antibiotics, and exercise-induced hyperthermia are causative factors for AT ruptures.[5-9] Ruptured tenAddress for correspondence: Güney Yılmaz, M.D. Selçuk Üniversitesi Tıp Fakültesi Hastanesi, Ortopedi ve Travmatoloji Anabilim Dalı, Selçuklu, Konya, Turkey Tel: +90 332 - 241 50 00 E-mail: aflguney@hotmail.com Qucik Response Code

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dons have more histological abnormalities than unruptured ones.[10,11] The treatment of AT ruptures includes conservative and surgical methods.[12] Conservative treatments include fixed-angle casting or dynamic bracing;[13-16] however, their complications including pressure sores, fungal skin infections, and blisters reduce patient compliance with the treatment. Moreover, conservative treatments are associated with high re-rupture rates and prolonged recovery time.[17] Surgical treatments such as open and mini-open/percutaneous techniques enable early rehabilitation and faster return to pre-injury activity level.[18-21] Open techniques ensure accurate appositioning of the tendon ends, and thus, more stable suture fixation. However, the paratenon supplying blood to the tendon is disturbed.[18] The skin incision passes through poorly vascularized area on the posterior part of the distal calf causing morbidity such as dehiscence of the skin edges and delayed healing.[22,23] 311

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Percutaneous repair of the AT preserves the tendon sheaths and the blood supply around the AT enabling early rehabilitation.[24-27] However, percutaneous techniques have higher rerupture rates and sural nerve complications. In a meta-analysis; however, open and percutaneous repair have not differed significantly in terms of re-rupture and sural nerve injury.[28-30] Studies of in vivo histological and biomechanical comparison of open and percutaneous techniques are limited. This study aimed to investigate the healing properties of open and percutaneous techniques in a rabbit model and compare histological, electron microscopic, and biomechanical findings of the healed tendon of both groups.

MATERIALS AND METHODS Animals Three-month-old skeletally mature New Zealand white rabbits (n=26, 3.5±0.5 kg, University of Ankara, Animal Laboratory, Ankara, Turkey) were housed in cages and exposed to a diurnal light cycle. Animals were fed regularly with commercially available rabbit food. The right hind legs were used for the study and the left legs were preserved as control group. The temperature was kept between 23° and 25 °C. The Eth-

(a)

(c)

ics Committee for Experiment on Animals of Hacettepe University in Ankara, Turkey approved all procedures done in this study.

Experimental Design Twenty-six rabbits were randomly assigned to two groups of thirteen rabbits each. A percutaneous tenotomy of the AT was applied through a stab incision on the right side approximately 1.5 cm above the calcaneal insertion in all animals. Using the same suture technique, the first group was repaired with the open and the second group was repaired with the percutaneous technique. All animals participated in this study were followed by a veterinarian in the pre-operative period. The animals were sacrificed and the ATs were harvested at the end of eight weeks for biomechanical and histological evaluation.

Surgical Procedure All surgical procedures were performed in a fully-equipped operation theatre inside the animal laboratory unit by the first and the senior authors (GY, MND). The animals were anesthetized after overnight fasting with a combination of Rompun® (Xylazine, 2 mg/kg, Bayer, Germany) and Ketalar® (Ketamin HCL, 5

(b)

(d)

Figure 1. (a) Percutaneous Achilles tenotomy through a stab incision. (b) Suture technique used in both groups. (c) Open and (d) percutaneous repairs used in animals, respectively.

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Y脹lmaz et al. Surgical treatment of achilles tendon ruptures

mg/kg, Pfizer-USA) as a bolus injection. Pental Sodyum速 (Penthotal sodium, 10-15 mg/kg/h. Ibrahim Ethem Ulugay, Istanbul, Turkey) was used for maintenance of the anaesthesia as a continuous intravenous infusion. A single dose of Lespor速 (Cephazoline sodium, 20 mg/kg, Ibrahim Ethem Ulugay, Istanbul, Turkey) was applied to all animals preoperatively. The animals were laid prone and the posterior parts of their legs were shaved. The surgical field was washed with povidone-iodine and subsequently covered with sterile drapes. A percutaneous tenotomy of the AT was applied through a stab incision on the right side approximately 1.5 cm above the calcaneal insertion in all animals (Fig. 1a). The stab incisions were kept as small as possible in order not to disturb the paratenon. Later, using the same suture technique (Fig. 1b) the first group was repaired with the open and the second group was repaired with the percutaneous technique. In the open group, the tendon ends were exposed after the stab incision was elongated proximally and distally. In the percutaneous group, the repair was achieved with the same suture technique through four (two proximal and two distal) stab incisions manually controlling the apposition of the tendon ends (Figs. 1c, d). The AT repair was carried out by Vicryl速 (3.0, Polyglactin 910, Ethicon, USA) sutures. Left sided ATs were used as control groups. The operated legs were kept in long leg splints for three weeks with the ankle in 30 degrees of plantar flexion and the animals were left free in their cages. The animals were sacrificed at

(a)

(b)

(d)

(e)

the end of eight weeks and the ATs were harvested. The harvested tendons, then, underwent biomechanical, histological and electron microscopic examination.

Electron Microscopy Examination

Six tendons from each group were used for histological and electron microscopic examination. Tendon pieces obtained from the healing region (4 mm in length and 2 mm in diameter) were held in 2.5% glutaraldehyde for 24 hours, washed with phosphate buffer, and fixed with osmium tetroxide. Afterwards, 10% formaldehyde was applied to the samples for an hour and the samples were dehydrated in an environment with increasing alcohol concentration. The samples were washed with propylene oxide and were embedded in epoxy resin containing environment. 60 nm thick sections were obtained from the samples and were stained with uranyl acetate and lead on copper plates.[31] These sections were examined under transmission electron microscopy (Joel JEM 1200 EX, Japon) with 20.000 magnification for collagen fibril density. At the beginning of the study, our aim was to measure the collagen fibril diameters with the help of electron microscopy in the control, percutaneous, and the open groups. However, the transverse sections of the tendon samples obtained from the healing regions in the open and percutaneous groups showed significant disorganized patterns of the collagen fibrils, preventing the measurement of the collagen fibrils.

(c)

Figure 2. Electron microscopic sections in Control (a), Open (b) and Percutaneous (c) Groups, respectively (x20.000). The collagen fibrils in the open and the percutaneous groups were disorganized unlike the control tendon. The percutaneous group noted to have more abundant collagen fibrils than the open group. Light microscopy, hematoxylin eosin staining sections in Percutaneous (a) and Open (b) Groups (x40). Increased waviness and detachment between collagen bundles can be seen in the Open Group.

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Table 1. Results of histological scoring for each group

Number of tendons for each score

Percutaneous group Open group n=6 n=6 Scores 0 1 2 3 0 1 2 3

Fibril structure 4 1 1 4 2 Fibril arrangement 2 3 1 3 3 Roundness of cell nuclei

Geographic heterogenity of cell density

Vascularity

5 1 5 1

Collagen staining 4 2 2 3 1

Light Microscopy Evaluation Tendon pieces obtained from the healing region (4 mm in length and 2 mm in diameter) were fixed in formalin solution buffered with 10% phosphate, dehydrated using a graded alcohol series, and embedded in paraffin blocks. Sections in 5 μm thickness were obtained and stained with hematoxylin eosin. A standard grading system proposed by Movin et al.[32] was used for histological examination under light microscopy (Zeiss, Carl Zeiss, Oberkochen, Germany). Being a four grade scoring system used to examine tendon structure, 0 represents normal structure; 1 mild deterioration from normal; 2 moderate deterioration; and 3 severe deterioration. Collagen fibril structure, fibril organization, roundness of the cell nucleuses, geographic heterogeneity of cell density, vascularity and collagen staining were examined and scored using this system. Higher scores represent more abnormal tendon structures.

Biomechanical Evaluation

Biomechanical testing was achieved in the Biomechanical Laboratories of the Middle East Technical University. Fourteen dissected ATs were mounted with special clamping jaws on the testing device (Lloyd, LS500, England) on each ends and the pull-out test was applied with a speed of 10 mm/min.[33] The maximum rupture loads needed in Newton (N) were recorded for the control and the study groups.

Statistical Analysis

Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS) version 12.0. The Student-t and Mann Whitney-U tests were used to investigate differences between the mean force to rupture the tendons and histological scoring. Significance level was p<0.05.

RESULTS Electron Microscopy In all transverse sections obtained from the healed region of both groups, the collagen fibrils were noted to have disorga314

nized arrangement. This was thought to be due to immaturity of the healed region where the collagen fibrils were not able to organize in parallel arrangement. When the sections were evaluated in terms of fibril density, it was noted that fibrils were more abundant in percutaneous repair group (Figs. 2a-c).

Light Microscopy Examination of the fibril arrangement and structure revealed that the tendons in percutaneous group have more organized fibrillar structure and less waviness which is an indirect sign of tendon maturity. The sections obtained from percutaneous group showed less detachment between parallel collagen bundles (Figs. 2d, e) and it was noted that the bundles were more closely attached to each other. The arrangement of the collagen bundles in the percutaneous group resembled more like the control sections than the open group did. The open group had more polymorphonuclear cells causing a higher score in cell roundness which is an indirect sign of ongoing inflammation and healing. With respect to vascularity, both groups had mild vascularity without a significant difference. Geographic heterogeneity of cell density and collagen staining quality was similar in both groups. Overall, the tendon scores in the percutaneous group was less than the open group indicating closer histological morphology to normal; however, the difference was not significant (Table 1) (p=0.065).

Biomechanical Evaluation

The mean force to rupture the tendon in percutaneous group was measured 143.7± 9.5 N (132-159) and 191.1±9.7 N (184205) for the opposite control sides (Table 2). There was a significant difference between the percutaneous and the control groups (p<0.001). The mean force to rupture the tendon in open group was measured 139.2±8.2 N (126-152) and 196.4±8.2 N (185-210) for the opposite control sides. There was a significant difference between the open and the control groups (p<0.001). Although the force needed to rupture the tendons were higher in the percutaneous group than in the open group, the difference was not statistically significant Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

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Table 2. Maximum force needed to rupture the tendons in each group and percentages with respect to control sides

Percutaneous group P (n)

Pc (n)

Open group %

O (n)

Oc (n)

1 146 184 79 126 198 63 2 132 175 75 152 210 72 3 136 185 73 145 195 74 4 156 200 78 132 188 70 5 138 189 73 144 204 71 6 143 195 73 135 192 70 7 159 205 77 138 185 74 Mean±SD 143.7± 9.5 191.1±9.7 74.9±2.8 139.2±8.2 196.4±8.2 70.6±3.5 P: Percutaneous; Pc: Percutaneous control; O: Open; Oc: Open control; N: Newton; SD: Standard deviation.

(p=0.33). The maximum force to rupture was also calculated as the percentage of the corresponding control side. The measurements revealed higher percentages in percutaneous group with a significant difference (74.9%±2.8% [73-79] in percutaneous group; 70.6%±3,5% [63-74] in open group [p=0.02]).

DISCUSSION The open and percutaneous AT repair techniques in a rabbit model were compared for histological, electron microscopical and biomechanical findings for the first time in the present study. The most important findings of the present study were more mature histological tendon structure and presence of more abundant collagen fibrils in the percutaneous group. In addition, when the mean force to rupture the tendons were calculated as the percentage of the control sides, the percutaneous group had better outcomes. It is well known that as the healing progresses in the rupture area the tendon gets more mature and the histology resembles more like a normal tendon. The parallelism of the collagen fibrils increases; the angulations and the detachments around collagen bundles decreases; vascularity and cellular infiltration by polymorphonuclear and mononuclear cells decreases.[34] With the histological scoring system, it was aimed to identify whether one of the treatment groups would resemble the normal tendon structure more than the other. It was assumed that the healing would take place faster in the percutaneous group since the paratenon and all the vascularity around the tendon was protected. Although there was no statistically significant difference between the groups, the results showed better tendon scores in the percutaneous group. The mechanical strength of a collagen fibril is related to intramolecular bonding in its triple-helix structure and to its actual diameter.[31] Collagen type III which has a smaller diameter than collagen type II is more abundant in tendons with deUlus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

generation and in healing process.[35] Collagen fibril diameter increases as the tendons get more mature with more collagen type II; however, collagen fibrils were noted to have disorganized arrangement due to immaturity of the healing region. With regard to fibrillar density, fibrils were more abundant in the percutaneous repair group. Percutaneous group had more potential to produce fibrils with the paratenon and mesenchymal cells that were preserved and more numbers of collagen fibrils were noted in the healing area. How the collagen fibril abundance would affect the final outcome is unknown. The healing process around the repair site starts with inflammatory response. Petrou et al. showed that the inflammatory response around the healing region consists mainly of lymphocytes and fewer eosinophils, neutrophils and giant cells causing a heterogeneity in the cell types. Although a direct comparison of our results with this study is impossible due to lack of quantitative data, our results show similar cell heterogeneity both in percutaneous and open groups.[36] In another rabbit study comparing the effect of nicotine and saline on tendon healing, the investigators showed separation, slight waviness and loss of parallel arrangement of collagen fibers in the saline group which is similar to our open repair group. On the other hand, the percutaneous group in our study showed better collagen arrangement and less detachment between collagen bundles.[37] The vascularization was substantially increased in both the saline and nicotine group in the same study, which is a well-accepted healing process similar to our findings in both the percutaneous and open group. The goals of the treatment in AT ruptures are early return to pre-injury function level, minimization of morbidity, and prevention of complications. Although there are controversies in the treatment of fresh AT ruptures, surgical treatments are recommended in young and middle-aged active patients.[12,17,20,38,39] Conservative treatments are dispensed due to complications related to skin, high re-rupture rates, tendon elongation and 315

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long recovery period.[17] With the non-operative treatment, the tendon ends stay apart and gap forms between the two stumps leading to tendon elongation and muscle weakening. Open technique is associated with lower risk of re-rupture, provides faster rehabilitation and return to pre-injury activity level compared to non-operative treatment.[12] However, it is associated with infection, problems with incision (dehiscence, delayed healing), scar adhesions and longer hospital stay.[23] Percutaneous treatment aimed to reduce complications related to open surgery and lower the re-rupture rates associated with conservative treatment. Percutaneous treatment includes application of internal splint/sutures through the stab incisions around the rupture and protects paratenon and vascularity of the tendon with a theoretical benefit of increased healing potential. The technique is successful in terms of decreasing infection rates, preventing incision related complications and decreasing hospital costs but criticized for having high rates of sural nerve problems and not achieving optimum tendon stump apposition.[40] Percutaneous AT repair technique is minimally invasive and the exposure of the rupture site is unnecessary, having good functional results, less complications (wound-healing, infection), less scarring, and faster recovery than open surgery.[20] Percutaneous technique has been modified in different ways and sural nerve injury has reduced. Majewski et al.[41] have reported no sural nerve injury with the percutaneous repair after exposing the nerve through a small lateral incision. Webb et al.[42] have moved the lateral incisions more towards the midline staying away from the nerve and reported no nerve injury in twenty-seven patients. Doral et al.[20] have reported endoscopy assisted percutaneous suturing of the AT under local anaesthesia in sixty-two patients, 95% of whom returned to their previous sportive activities. They have concluded that the percutaneous technique allows early rehabilitation, provides cosmetic wound appearance and endoscopic control would provide precise apposition of the tendon stumps. These studies show that it is possible to overcome the drawbacks of the percutaneous technique by modifying the original method. In a study using no external support after endoscopy-assisted AT repair and immediate rehabilitation, there has been no significant difference in both ankle muscle strength and lower extremity functional level between the endoscopy-assisted repairs and the unaffected sides.[43] In a meta-analysis of randomized controlled trials comparing conventional open method with minimally invasive/percutaneous approaches for the repair of AT ruptures, no difference was reported in re-ruptures, sural nerve injury, deep infection or adhesions.[30] Superficial wound infection was significantly higher in the open group. Patients were nearly three times more likely to report a good or excellent outcome following minimal invasive/percutaneous repair compared to open surgery.[30] In another meta-analysis, the pooled rate of rerupture for open and percutaneous treatments were 4.3% and 2.1%, respectively.[39] The complication rate (excluding re-ruptures) in the open group was 26.1% versus 8.3% in the percutaneous group. In a randomized prospective study, 316

no difference was reported in isokinetic evaluation of peak torque and total work in plantar and dorsal flexion.[44] The current available data on open and percutaneous treatment of fresh AT ruptures reveal that both techniques have similar clinical and functional results.[43,44] On the other hand, complications related to surgical site have been reported more commonly in the open procedures. Additionally, the present study showed that percutaneous technique had advantages over open technique as noted in histological scoring, electron microscopic findings and biomechanical testing in an animal model. There were limitations in the present study. The tendon rupture was not a closed injury. A small stab incision was used to produce a tendon rupture, but the paratenon injury was kept minimum. The tendons used had no pre-existing structural tendon problem; however, in clinical settings, AT ruptures usually occur in tendons with existing degeneration or tendinosis. Therefore, the results may be different in abnormal tendons.

Conclusion Comparison of percutaneous/mini-invasive and open surgical treatment of fresh AT rupture in an animal model revealed similar results in biomechanical testing. On the other hand, histologic examination showed that percutaneous/mini-invasive methods may be more advantageous in terms of tendon healing and maturation. However, it should be kept in mind that animal studies cannot be extrapolated directly to human beings. Conflict of interest: None declared.

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Yılmaz et al. Surgical treatment of achilles tendon ruptures mechanism for tendon degeneration. J Biomech 1994;27:899-905. 10. Mc Master PE. Tendon and muscle ruptures. Clinical and experimental studies on the causes and location of subcutaneous ruptures. J Bone Joint Surg 1933;15:705-22. 11. Tallon C, Maffulli N, Ewen SW. Ruptured Achilles tendons are significantly more degenerated than tendinopathic tendons. Med Sci Sports Exerc 2001;33:1983-90. 12. Cetti R, Christensen SE, Ejsted R, Jensen NM, Jorgensen U. Operative versus nonoperative treatment of Achilles tendon rupture. A prospective randomized study and review of the literature. Am J Sports Med 1993;21:791-9. 13. Neumayer F, Mouhsine E, Arlettaz Y, Gremion G, Wettstein M, Crevoisier X. A new conservative-dynamic treatment for the acute ruptured Achilles tendon. Arch Orthop Trauma Surg 2010;130:363-8. 14. Costa ML, MacMillan K, Halliday D, Chester R, Shepstone L, Robinson AH, et al. Randomised controlled trials of immediate weight-bearing mobilisation for rupture of the tendo Achillis. J Bone Joint Surg Br 2006;88:69-77. 15. McComis GP, Nawoczenski DA, DeHaven KE. Functional bracing for rupture of the Achilles tendon. Clinical results and analysis of groundreaction forces and temporal data. J Bone Joint Surg Am 1997;79:1799808. 16. Roberts CP, Palmer S, Vince A, Deliss LJ. Dynamised cast management of Achilles tendon ruptures. Injury 2001;32:423-6. 17. Metz R, Verleisdonk EJ, van der Heijden GJ, Clevers GJ, Hammacher ER, Verhofstad MH, et al. Acute Achilles tendon rupture: minimally invasive surgery versus nonoperative treatment with immediate full weightbearing-a randomized controlled trial. Am J Sports Med 2008;36:1688-94. 18. Schmidt-Rohlfing B, Graf J, Schneider U, Niethard FU. The blood supply of the Achilles tendon. Int Orthop 1992;16:29-31. 19. Olsson N, Silbernagel KG, Eriksson BI, Sansone M, Brorsson A, Nilsson-Helander K, et al. Stable surgical repair with accelerated rehabilitation versus nonsurgical treatment for acute Achilles tendon ruptures: a randomized controlled study. Am J Sports Med 2013;41:2867-76. 20. Doral MN, Bozkurt M, Turhan E, Ayvaz M, Atay OA, Uzümcügil A, et al. Percutaneous suturing of the ruptured Achilles tendon with endoscopic control. Arch Orthop Trauma Surg 2009;129:1093-101. 21. Nilsson-Helander K, Silbernagel KG, Thomeé R, Faxén E, Olsson N, Eriksson BI, et al. Acute achilles tendon rupture: a randomized, controlled study comparing surgical and nonsurgical treatments using validated outcome measures. Am J Sports Med 2010;38:2186-93. 22. Haertsch PA. The blood supply to the skin of the leg: a post-mortem investigation. Br J Plast Surg 1981;34:470-77. 23. Saxena A, Maffulli N, Nguyen A, Li A. Wound complications from surgeries pertaining to the Achilles tendon: an analysis of 219 surgeries. J Am Podiatr Med Assoc 2008;98:95-101. 24. Ma GW, Griffith TG. Percutaneous repair of acute closed ruptured achilles tendon: a new technique. Clin Orthop Relat Res 1977;128:247-55. 25. Bradley JP, Tibone JE. Percutaneous and open surgical repairs of Achilles tendon ruptures. A comparative study. Am J Sports Med 1990;18:188-95. 26. Mandelbaum BR, Myerson MS, Forster R. Achilles tendon ruptures. A new method of repair, early range of motion, and functional rehabilitation. Am J Sports Med 1995;23:392-5. 27. Motta P, Errichiello C, Pontini I. Achilles tendon rupture. A new tech-

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nique for easy surgical repair and immediate movement of the ankle and foot. Am J Sports Med 1997;25:172-6. 28. Webb JM, Bannister GC. Percutaneous repair of the ruptured tendo Achillis. J Bone Joint Surg Br 1999;81:877-80. 29. Carmont MR, Maffulli N. Modified percutaneous repair of ruptured Achilles tendon. Knee Surg Sports Traumatol Arthrosc 2008;16:199-203. 30. McMahon SE, Smith TO, Hing CB. A meta-analysis of randomised controlled trials comparing conventional to minimally invasive approaches for repair of an Achilles tendon rupture. Foot Ankle Surg 2011;17:211-7. 31. Järvinen TA, Järvinen TL, Kannus P, Józsa L, Järvinen M. Collagen fibres of the spontaneously ruptured human tendons display decreased thickness and crimp angle. J Orthop Res 2004;22:1303-9. 32. Movin T, Gad A, Reinholt FP, Rolf C. Tendon pathology in long-standing achillodynia. Biopsy findings in 40 patients. Acta Orthop Scand 1997;68:170-5. 33. Ilhami K, Gokhan M, Ulukan I, Eray BM, Levent A, Ciğdem T. Biomechanical and histologic comparison of Achilles tendon ruptures reinforced with intratendinous and peritendinous plantaris tendon grafts in rabbits: an experimental study. Arch Orthop Trauma Surg 2004;124:608-13. 34. Woo SL, Hildebrand K, Watanabe N, Fenwick JA, Papageorgiou CD, Wang JH. Tissue engineering of ligament and tendon healing. Clin Orthop Relat Res 1999;(367 Suppl):312-23. 35. Maffulli N, Ewen SW, Waterston SW, Reaper J, Barrass V. Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing. Am J Sports Med 2000;28:499-505. 36. Petrou CG, Karachalios TS, Khaldi L, Karantanas AH, Lyritis GP. Calcitonin effect on Achilles tendon healing. An experimental study on rabbits. J Musculoskelet Neuronal Interact 2009;9:147-54. 37. Duygulu F, Karaoğlu S, Zeybek ND, Kaymaz FF, Güneş T. The effect of subcutaneously injected nicotine on achilles tendon healing in rabbits. Knee Surg Sports Traumatol Arthrosc 2006;14:756-61. 38. Winter E, Weise K, Weller S, Ambacher T. Surgical repair of Achilles tendon rupture. Comparison of surgical with conservative treatment. Arch Orthop Trauma Surg 1998;117:364-7. 39. Khan RJ, Fick D, Keogh A, Crawford J, Brammar T, Parker M. Treatment of acute achilles tendon ruptures. A meta-analysis of randomized, controlled trials. J Bone Joint Surg Am 2005;87:2202-10. 40. Klein W, Lang DM, Saleh M. The use of the Ma-Griffith technique for percutaneous repair of fresh ruptured tendo Achillis. Chir Organi Mov 1991;76:223-8. 41. Majewski M, Rohrbach M, Czaja S, Ochsner P. Avoiding sural nerve injuries during percutaneous Achilles tendon repair. Am J Sports Med 2006;34:793-8. 42. Webb JM, Bannister GC. Percutaneous repair of the ruptured tendo Achillis. J Bone Joint Surg Br 1999;81:877-80. 43. Gigante A, Moschini A, Verdenelli A, Del Torto M, Ulisse S, de Palma L. Open versus percutaneous repair in the treatment of acute Achilles tendon rupture: a randomized prospective study. Knee Surg Sports Traumatol Arthrosc 2008;16:204-9. 44. Cretnik A, Kosanovic M, Smrkolj V. Percutaneous versus open repair of the ruptured Achilles tendon: a comparative study. Am J Sports Med 2005;33:1369-79.

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DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Aşil tendon rüptürlerinin cerrahi tedavisi: Açık ve kapalı yöntemlerin tavşan modeli üzerinde karşılaştırılması Dr. Güney Yılmaz,1 Dr. Mahmut Nedim Doral,2 Dr. Egemen Turhan,2 Dr. Gürhan Dönmez,2 Dr. Ahmet Özgür Atay,2 Dr. Defne Kaya3 Selçuk Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Konya; Hacettepe Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Konya; 3 Hacettepe Üniversitesi Tıp Fakültesi, Spor Hekimliği Anabilim Dalı, Ankara 1 2

AMAÇ: Tavşan aşil tendon (AT) rüptürü modeli üzerinde açık ve perkütan yöntemlerin iyileşme özelliklerini araştırmak ve iki grup arasında histoljik, elektron mikroskopik ve biyomekanik bulguları karşılaştırmak. GEREÇ VE YÖNTEM: Yirmi altı adet tavşan her grupta 13 denek olacak şekilde rastlantısal olarak iki gruba ayrıldı. Tüm hayvanların sağ taraflarında AT’nin kalkaneusa yapışma bölgesinin 1.5 cm proksimalinde küçük bir insizyondan perkütan aşil tenotomisi uygulandı. Bunnel tarzı dikiş kullanılarak birinci grup açık yöntemle ikinci grup ise perkütan yöntem ile tedavi edildi. Sekiz hafta sonunda tendonlar biyemekanik ve histolojik değerlendirme amacıyla çıkartıldı. Tendonlar, fibriler yoğunluk için elektron mikroskobisiyle ve tendon iyileşme skorlaması için ise ışık mikroskopisi ile değerlendirildi. BULGULAR: Kesitler elektron mikroskopisi ile fibriler yoğunluk için değerlendirildiğinde perkütan grupta daha yoğun fibril yapısının olduğu görüldü. Tendon iyileşme skorları perkütan grupta daha düşük olmakla birlikte gruplar arasında anlamlı fark bulunmadı (p=0.065). Ortalama tendon kopma kuvvetleri perkütan grupta 143.7±9.5 Newton (N), açık grupta 139.2±8.2 N olarak ölçüldü. Aradaki fark anlamlı değildi (p=0.33). TARTIŞMA: Aşil tendon rüptürlerinde perkütan teknik en az açık teknik kadar iyi sonuçlar elde edilmesini sağlayabilir. Perkütan yöntemde tendon iyileşme dokusu daha iyi histolojik ve elektron mikroskopik bulgular gösterir. İki grup arasında erken dönemde biyomekanik olarak fark yoktur. Tendon iyileşmesine yardımcı olacak ve perkütan yöntemle beraber uygulanacak yeni yöntemlerin geliştirilmesi gelecek çalışmaların konusu olmalıdır. Anahtar sözcükler: Açık tamir; aşil tendonu; perkütan tamir. Ulus Travma Acil Cerrahi Derg 2014;20(5):311-318

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EXPERIMENTAL STUDY

The effects of sildenafil in liver and kidney injury in a rat model of severe scald burn: a biochemical and histopathological study Ali Kağan Gökakın, M.D.,1 Mustafa Atabey, M.D.,1 Koksal Deveci, M.D.,2 Enver Sancakdar, M.D.,2 Mehmet Tuzcu, M.D.,3 Cevdet Duger, M.D.,4 Omer Topcu, M.D.1 1

Department of General Surgery, Cumhuriyet University Faculty of Medicine, Sivas;

Department of Biochemistry, Cumhuriyet University Faculty of Medicine, Sivas;

Department of Pathology, Cumhuriyet University Faculty of Veterinary, Sivas;

Department of Anesthesiology, Cumhuriyet University Faculty of Medicine, Sivas

ABSTRACT BACKGROUND: Severe burn induces systemic inflammation and reactive oxygen species leading to lipid peroxidation which may play role in remote organs injury. Sildenafil is a selective and potent inhibitor of cyclic guanosine monophosphate specific phosphodiesterase-5. Sildenafil reduces oxidative stress and inflammation in distant organs. The aim of the present study was to evaluate the effects of different dosages of sildenafil in remote organs injury. METHODS: A total of thirty-two rats were randomly divided into four equal groups. The groups were designated as follows: Sham, Control, 10, and T20 mg/kg sildenafil treatment groups. Levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), VEGF receptor (Flt-1), activities of glutathione peroxidase (Gpx), levels of total antioxidative capacity (TAC), and total oxidant status (TOS) were measured in both tissues and serum, and a semi-quantitative scoring system was used for the evaluation of histopathological findings. RESULTS: Sildenafil increased levels of Gpx, and Flt-1, and decreased MDA and VEGF levels in tissues. Sildenafil also increased serum levels of TAC and Flt-1 and decreased TOS, OSI, and VEGF. CONCLUSION: Sildenafil decreased inflammation scores in remote organs in histopathological evaluation. It has protective effects in severe burn-related remote organ injuries by decreasing oxidative stress and inflammation. Key words: Remote organ injury; scald burn; sildenafil.

INTRODUCTION Burn is a posttraumatic inflammatory disease accompanied by both local and distant effects leading to intense inflammation, tissue damage, and infection.[1] Although a considerable progress in the management of burns has been achieved, systemic inflammatory response syndrome (SIRS), sepsis, and multiple Address for correspondence: Ali Kağan Gökakın, M.D. Cumhuriyet Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, 58140 Sivas, Turkey Tel: +90 346 - 341 2135 E-mail: dralihan20@hotmail.com Qucik Response Code

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organ failure (MOF) still continue to be leading causes of mortality and morbidity in severe burn patients.[1-4] The response to the initial burn is often associated with secondary damage to vital organs such as lung, liver, and kidneys, which are distant from the injured site.[4-9] The pathophysiological mechanism of such remote organ injury in severe burn remains unclear. However, animal models and clinical trials of burn injury implicate that reactive oxygen species (ROS) and reactive nitrogen species (RNS) mediated by elevated proinflammatory mediators released from both the gut and the burn site can act as causative agents in the development of distant organ injury.[1,9-14] The proinflammatory effects of ROS and RNS include endothelial damage, neutrophil reinforcement, cytokine release, and mitochondrial injury. Thus, remote organ injury following severe burn appears to be mediated by ROS and RNS via the formation of oxidative and nitrosative stress as a consequence of inflammatory response.[1,9,15,16] Inflammation has 319

Gökakın et al. The effects of sildenafil in liver and kidney injury in a rat model of severe scald burn

been defined as a process induced by injury that normally leads to healing and is an essential component of physiological and /or pathological angiogenesis in most organs. Inflammatory cells surrounding the microvasculature can have a profound effect on promoting new vessel growth via vascular endothelial growth factor (VEGF) and VEGF receptors such as VEGF Receptor-1 (Flt-1).[17-19] However, the roles of VEGF and VEGF decoy receptor Flt-1 in pathophysiological events, such as oxidative and nitrosative damage secondary to inflammation, are still in the area of active research.[17,19-24] Effects of different agents on oxidative damage due to severe burn injury were evaluated in remote organs such as the lung, liver, gut and kidney in previous studies.[4,9,25-28] Sildenafil is known as a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase-5 (PDE-5). PDE-5 catalyzes the hydrolysis of cGMP. Inhibition of PDE-5 causes increased concentration of cGMP and cyclic adenosine monophosphate (cAMP). The cyclic nucleotides cAMP and cGMP are second messengers playing major roles in various cellular processes, such as inflammation.[29] Sildenafil induces endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) generating nitric oxide (NO). Thus, sildenafil has a relaxant effect on smooth muscle cells of the arterioles and via NO dependent mechanism and may induce blocking of VEGF activity by a neutralized antibody against VEGF receptors as well as augment angiogenesis.[23] However, most of these effects appear to be dosage dependent due to the levels of generated NO.[20] Moreover, the beneficial effects of sildenafil have been shown in the balance of oxidation and antioxidation via decreasing oxidative and nitrosative stress in inflammatory events.[9,23,30-34] However, there is no study in the literature focusing on the effects of sildenafil in remote organ injury induced by severe burn except our previous study focusing on acute lung injury. [9] The purpose of the present study was to evaluate the effects of different dosages of sildenafil in distant organs, such as liver and kidneys, due to severe scald burn injury in rats.

MATERIALS AND METHODS The research was conducted in accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication no. 85-23, revised 1996) and approval has been received from the Institutional Animal Ethics Committee at Cumhuriyet University.

Animals A total of thirty-two adult female Wistar Albino rats weighing between 200-250 g were included in the study. Animals were provided by the Experimental Animals Center, Cumhuriyet University, Sivas, Turkey. The animals were fed ad libitum with standard diet and water throughout the experiment. All animals were housed separately and kept under standard condi320

tions of room temperature (22-24 °C) and a 12 h light/12 h dark cycle.

Burn Procedure Animals were anesthetized with (i.p.) xylazine (5 mg/kg) and ketamine (30 mg/kg) during the scalding and burn procedure, and 1 mg/kg morphine was administered intra-muscular just before immersing each of them to the boiling water. The dorsal surfaces of the rats were shaved closely, and the rats were secured in a constructed template device. The surface area of the skin on the dorsal surface exposed through the template device was immersed in 98 °C water for 12 s. All test animals were quickly dried after each exposure to avoid additional injury. With the use of this technique, full-thickness dermal burns comprising 30% of the total body surface area (TBSA) were obtained.[25]

Chemicals All the chemicals used in the experiments were purchased from Sigma Chemical Co. (Munich, Germany) except for Sildenafil which was obtained from Pfizer (Istanbul, Turkey).

Experimental Design Animals were randomly divided into four equal groups as follows: Group S (no burn, no medication), Group C (scald control) was administrated per orally (p.o) 2 ml 0.09% NaCl, Group T10 (Treatment with sildenafil 10 mg/kg): 10 mg/kg p.o sildenafil, and Group T20 (Treatment with sildenafil 20 mg/kg): 20 mg/kg p.o. sildenafil just after the scald burn. All animals were administered 4 ml/100 g body weight of lactated Ringer’s solution subcutaneously just after the burn injury for fluid resuscitation according to parkland formula. Later, all animals were located in their own cages and let free to reach food and water. The reason for the selection of 10 and 20 mg/kg doses of oral sildenafil was that 10 mg/kg/day of sildenafil would result approximately in the same plasma concentration as 50 mg in humans.[35] These doses are very common for rats and our first aim was to determine whether it was protective in burn induced organ damage, as well as how the dose affected protection. All animals were sacrificed at the 24th hour after the scald burn via an overdose of a general anesthetic (thiopental sodium, 50 mg/ kg). Blood samples of the animals were collected in tubes for biochemical analysis, and liver and kidneys were harvested from all rats and washed in ice cold saline. Half of the tissues were transferred to the biochemistry laboratory to be kept at -80°C for biochemical analyses and the other half were fixed in 10% formalin solution for histopathological analysis. Levels of malondialdehyde (MDA), VEGF, Flt-1, the activities of glutathione peroxidase (Gpx), levels of total antioxidative capacity (TAC), and total oxidant status (TOS) were measured in both tissue and serum. Oxidative stress index (OSI) was also calculated in tissue and serum. Additionally, ratios Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

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of VEGF/Flt-1 in tissue and serum were calculated. A semiquantitative scoring system was used for the evaluation of histopathological findings which was used in our previous study[9] (Table 1).

Biochemical Investigation of the Tissues In order to prepare the tissue homogenates, tissues were ground with liquid nitrogen in a mortar. The ground tissues (0.5 g each) were then treated by 1 ml of homogenization buffer per 100 mg of tissue. The mixtures were homogenized on ice using an Ultra-Turrax Homogenizer for 15 min. The homogenates were filtered and centrifuged, using a refrigerated centrifuge at 10,000 x g for 15 min at 4°C. Supernatants and assay samples were collected according to the kit booklet protocol. All assays were performed at room temperature in duplicate.

Measurement of TOS, TAC, and OSI TOS and TAC levels were measured using a spectrophotometric kit (Rel Assay Diagnostics, Gaziantep, Turkey,).[38,39] Levels of TOS and TAC were assayed in an autoanalyzer (Beckman Coulter LX 20, Inc., Fullerton, CA, USA). Results of serum levels were expressed as millimolar Trolox (Rel Assay Diagnostics) equivalent per liter (L). TOS and TAC levels in the tissue supernatants were normalized against protein (mmol Trolox Equiv/g). The ratio of TOS to TAC was accepted as the OSI.

Histopathological Evaluation of the Specimens

Measurement of MDA, Gpx, VEGF, and Flt-1

Tissue samples were fixed in 10% buffered formalin for two days. Later each liver and kidney tissue samples were processed routinely and embedded in paraffin. After embedding, 5-µm thick sections were taken from the tissue blocks and stained with hematoxylin and eosin (HE). Light microscope (X260) was used for histopathologic examination. The degree of the inflammation and destruction were scored for each group (Table 1). A pathologist unaware of the group assignment analyzed samples. A mean score for each of the variables was then calculated. A total histopathological score (maximum 14) was derived from the sum of the mean scores of the four variables. All the samples were reviewed by the same pathologist to achieve correct score and mean value of each group was used for statistical analysis.

All analyses were made for each parameter according to the protocols of each kit manufacturer’s requirements.

Statistical Analysis

Biochemical Investigation of the Serum Blood was collected without using an anticoagulant, and then was allowed to clot for 30 min at 25°C. Afterwards, blood samples were centrifuged at 2,000 x g for 15 min at 4°C, and serum layers were pipetted off without disturbing the white buffy layers. Subsequently, serums were stored on ice and samples were frozen at -80°C.

As an index of lipid peroxidation and free radical generation, MDA content in the tissue supernatant and serum was measured by the MDA-586 method using a Bioxytech MDA-586 assay kit (Oxis Research, Oregon, USA).[36] Protein concentration was determined by the Beckman Protein Assay on a Synchron® l x 20 analyzer (Beckman Coulter, 95942 Villepointe–Roissy-CDG, France) using BSA as a standard. MDA levels in the tissue supernatant were normalized against protein (pmol/g). Gpx was measured as a marker of enzymatic defense against ROS. Gpx activity in tissues and blood were measured spectrophotometrically using Cayman’s standard glutathione (GSH) assay kit (Cayman Chemical Company, Ann Arbor, MI, USA).[37] Gpx activity in tissue supernatant was normalized against protein (nmol/min/g). VEGF and Flt-1 were measured in both serum and tissues in order to identify the effects of sildenafil in vascular permeability as well as angiogenesis and inflammation. Concentrations of VEGF and Flt-1 were measured using two ELISA kits (RayBiotech. Inc., Norcross, GA, USA and Cusabio Biotech Co., Wuhan, Hubei Province, China). Values were calculated and converted to picograms per gram for tissues (pg/g), and picograms per milliliter for serum (pg/ml ).[21,22] Ratios of VEGF/Flt-1 in tissues and serum were calculated in order to evaluate the local and systemic effects of sildenafil in the NO – VEGF/Flt-1 relationship and assess the correlation between histopathologic findings and VEGF/Flt-1 ratios. Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Statistical analysis was performed with the Statistical Package for the Social Sciences for Windows (SPSS version 15.0, Chicago, IL, USA). All values were expressed as mean ± standard deviation (SD). Comparison of variables between the groups was performed with Kruskal-Wallis test and Mann-Whitney Table 1. Scoring of inflammation and destruction in organs Organ

Pathological Lesions

Score

Liver Hyperemia

Cloudy swelling of hepatocytes

Vacuolar degeneration

Mononuclear cell infiltration

Necrosis in hepatocytes (1-3 hepatocytes)

Necrosis in hepatocytes (>3 hepatocytes)

Hemorrhage

Kidney Hyperemia

Expansion of glomerular space

Mesangial cell hyperplasia in glomeruli

Degeneration of tubular epithelium

Mononuclear cell infiltration

Tubular epithelial necrosis

Hemorrhage

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U-test. Significance between histopathological scorings was determined with the chi-square test and Fisher’s exact test. A correlation analysis (Speerman test) was used to assess the relationship between histopathological scorings and VEGF/ Flt-1 ratios. A value of p<0.05 was considered as statistically significant.

RESULTS During the experimental period, only one death was observed in Group C and was seen in the first 12 h. There was no statistically significant difference in mortality between groups.

Levels of MDA, Gpx, VEGF, Flt-1, TAC, TOS and OSI in Liver Tissues Liver tissue levels of MDA, Gpx, VEGF, Flt-1, TAC, TOS and OSI were exhibited in Table 2. The lowest MDA levels were detected in Group S and Group T10 (1.15±0.95 and 1.08±0.37 pmol/g /tissue, respectively). Significant differences were found between Group S and Group C (p=0.002), and between Group C and Group T10 (p=0,009). The highest increase was detected in Group T10 (9.52±1.48 nmol/min/g/tissue) in terms of Gpx levels and this increase

rate was statistically different when compared to Group C (p=0.04) and Group T20 (p=0.017); however, no difference was detected between Group T10 and Group S. There was a significant increase in VEGF levels in Group T10 when compared to Group S (0.003), Group C (0.018), and Group T20 (0.001). Interestingly enough, VEGF levels were lower in Group T20 than in Group C, but this increase was not statistically significant (p=0.179). A trend of increase was found in Flt-1 levels in treatment groups, but there was only a significant difference between Group C and Group T20 (p=0.001). TAC levels were detected significantly higher in Group S than in Group C (0.001), Group T10 (0.002), and Group T20 (0.002). Also, TAC levels were statistically higher in Group T10 than in Group C (p=0.009). There was no difference between the four groups in terms of TOS levels. OSI levels were detected in significantly lower levels in Group T10 (p=0.008) than in Group C.

Levels of MDA, Gpx, VEGF, Flt-1, TAC, TOS, and OSI in Kidney Tissues Kidney tissue levels of MDA, Gpx, VEGF, Flt-1, TAC, TOS,

Table 2. Tissue levels of MDA, Gpx, VEGF, Flt-1, TAC, TOS and OSI in liver Groups MDA Gpx VEGF Flt-1 TAC TOS OSI (pmol/g/ (nmol/min/g/ (pg/g) (pg/g) (mmol Trolox (mmol Trolox (Arbitrary tissue) tissue) Equiv/g) Equiv/g) Units) Group S

1.08±0.37b 10.97±1.38b,d 6.94±1.41c 24.03±1.32 4.70±0.86b,c,d 10.06±1.47 2.17±0.31b

Group C

3.93±0.92a,c 3.06±0.73a,c 7.81±0.83c 21.30±1.65d 2.14±0.28a,c 15.31±1.41 8.06±1.55a,c

Group S10

1.15±0.95b 9.52±1.48b,d 10.62±0.45a,b,d 26.03±1.70 3.51±0.13a,b 11.61±1.33 3.30±0.41b

Group S20

2.53±0.12

4.61±0.99a,c 6.40±0.10c 31.07±0.53b 2.90±0.25a 13.42±1.68 4.90±0.71

Results are means±SD of two measurements. MDA: Malondialdehyde; Gpx: Glutathione peroxidase; VEGF: Vascular endothelial growth factor; Flt-1: VEGF receptor; TAC: Total antioxidative capacity; TOS: Total oxidant status, OSI: Oxidative stress index. a: Significantly different when compared to Group S; b: Significantly different when compared to Group C. c: Significantly different when compared to Group S10; d: Significantly different when compared to Group S20. Comparison of variables between the groups was performed with Kruscal-Wallis test and Mann-Whitney U test.

Table 3. Tissue levels of MDA, Gpx, VEGF, Flt-1, TAC, TOS, and OSI in kidney Groups MDA Gpx VEGF Flt-1 TAC TOS OSI (pmol/g/ (nmol/min/g/ (pg/g) (pg/g) (mmol Trolox (mmol Trolox (Arbitrary tissue) tissue) Equiv/g) Equiv/g) Units) Group S

1.09±0.16b,d 8.44±1.69b 8.96±1.63b 19.18±1.67c 4.01±0.15 7.66±0.84 1.91±0.74

Group C

3.12±0.31a,c,d 1.68±0.53a,c,d 13.06±0.69a,c,d 22.44±2.09c 2.50±0.20 17.84±4.02d 7.31±1.85

Group S10

1.26±0.11b,d 6.73±1.33b 10.22±0.90b 30.76±2.17a,b,d 3.37±0.42

Group S20

2.36±0.35a,b,c

5.87±0.71b

9.45±0.21b

23.60±0.88c

2.83±0.30

9.67±1.52 3.08±0.47 8.41±1.07b 3.73±1.12

Results are means±SD of two measurements. MDA: Malondialdehyde; Gpx: Glutathione peroxidase; VEGF: Vascular endothelial growth factor; Flt-1: VEGF receptor; TAC: Total antioxidative capacity; TOS: Total oxidant status, OSI: Oxidative stress index. a: Significantly different when compared to Group S; b: Significantly different when compared to Group C; c: Significantly different when compared to Group S10. d: Significantly different when compared to Group S20. Comparison of variables between the groups was performed with Kruscal-Wallis test and Mann-Whitney U test.

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and OSI were exhibited in Table 3. The lowest MDA levels were detected in Group S (1.09±0.16) and in Group T10 (1.26±0.11 pmol/g /tissue). There was a statistically significant difference between Group C and T10 and T20 Groups (p=0.001 and p=0.034); whereas a similar significant difference was detected between T10 and T20 Groups (p=0.001).

but no difference was found between Group C and Group T20.

The highest increase was detected in group T10 (6.733±1.33 nmol/min/g/tissue) in terms of Gpx levels and this increase rate in Group T10 was statistically different when compared to Group C (p=0.006); also, Gpx levels were significantly higher in Group T20 (p=0.018) than in Group C; however, no difference was detected between Group T10 and Group T20.

Levels of MDA, VEGF, Flt-1, Gpx, TAC, TOS, and OSI in Serum

There were significant decreases in VEGF levels in Group T10 (p=0.026) and Group T20 (p=0.003) compared to Group C; however, no statistical difference was found between Groups T10 and T20. Flt-1 levels were significantly higher in Group T10 than in Group C (p=0.013), and Group T20 (p=0.022),

There were no differences between the groups in terms of TAC, TOS and OSI levels except only in Group T20 whose TOS levels were detected lower than in Group C (p=0.028).

Levels of MDA, Gpx, VEGF, Flt-1, VEGF/Flt-1, TAC, TOS, and OSI in serum were shown in Table 4. MDA levels were the lowest in Groups S (1,27±0,24) and T10 (1,54±0,39) and it was significant when compared to Group C (p=0,001). There were no differences between Groups T10 and T20. Gpx levels were significantly higher in Group T10 when compared to Group C (p=0.001) and Group T20 (p=0.004). There were no differences between groups in terms of VEGF and Flt-1 levels. However, the Flt-1/VEGF ratios were sig-

Table 4. Levels of MDA, Gpx, VEGF, Flt-1, TAC, TOS, and OSI in serum Groups

MDA Gpx VEGF Flt-1 Flt-1/VEGF TAC TOS OSI (pmol/g/ (nmol/min/g/ (pg/g) (pg/g) (pg/l) (mmol Trolox (mmol Trolox (Arbitrary tissue) tissue) Equiv/g) Equiv/g) Units)

Group S

1.28±0.24b,d 7.13±4.44 21.72±14.25 8.21±4.90 0.31±0.40c 1.34±0.16b 18.97±9.5b,c 1.55±0.77

Group C

2.49±0.46a,c,d 3.29±1.99c 19.43±12.54 7.18±1.30 0.53±0.72c 0.99±0.10a,c 21.56±8.50a,c 1.49±0.60c

Group S10

1.56±0.39b 8.63±1.63b,d 34.30±11.22 9.34±2.21 1.39±0.60a,b,d 1.21±0.13b,d 13.12±5.50a,b 1.09±0.45b,d

Group S20

2.00±0.24a,b 4.29±1.78c 17.46±8.60 6.70±1.86c 0.57±0.47 1.08±0.17c 17.89±8.03 1.72±0.55c

Results are means±SD of two measurements. MDA: Malondialdehyde; Gpx: Glutathione peroxidase; VEGF: Vascular endothelial growth factor; Flt-1: VEGF receptor; TAC: Total antioxidative capacity; TOS: Total oxidant status; OSI: Oxidative stress index. a: Significantly different when compared to Group S; b: Significantly different when compared to Group C. c: Significantly different when compared to Group S10; d: Significantly different when compared to Group S20. Comparison of variables between the groups was performed with Kruscal-Wallis test and Mann-Whitney U test.

Table 5. Total scores of pathologic lesions in liver and kidney Rats

Histopathological scores in livers Group C

Group S10

Group S20

Histopathological scores in kidneys Group C

Group S10

Group S20

1 9 8 9 7 4 6 2 11 9 9 9 6 8 3 9 7 8 7 4 4 4 10 7 9 10 4 4 5 11 7 8 11 6 4 6 8 9 7 7 6 4 7 9 7 9 8 4 6 8 X 7 9 X 4 6 Mean±SD

9.57±0.42a 7.62±0.32b 8.50±0.26 8.57±0.57a 4.75±0.36b 5.25±0.52b

X: dead at the 12th hour. Significance between histopathological scorings was determined with the chi-square test and Fisher’s exact test. a: Value of control group for statistical analyses; b: Significantly different when compared to Group C according to the Chi-square test (p<0.05).

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(a)

(b)

(c)

Figure 1. (a-c) Findings of the liver in Group C (H&E. Bar=15 µm). Black Arrow: Degeneration and necrosis of hepatocytes. White Arrows: Mononuclear cell infiltration.

nificantly higher in Group T10 (p=0.25) than in Groups C (p=0.025) and T20 (p=0.029). Levels of TAC were higher in Group T10 than in Groups C (p=0.001) and T20 (p=0.004). TOS levels decreased significantly in Group T10 compared to Groups C (p=0.001) and T20 (p=0.002). OSI levels decreased significantly in Group T10 compared to Groups C (p=0.001) and T20 (p=0.001).

Histopathological Findings Histopathological scores in livers and kidneys were shown in (Table 5). Histopathological scores of the liver was found statistically lower in Group T10 (p=0.006) compared to group C (Fig. 1), and this score was also lower in Group T20 when compared to Group C; however, it was not statistically significant. Histopathological scores of the kidneys were significantly lower in Group T10 compared to Groups C (p=0.001) and T20 (p=0.003); whereas no difference was detected between Groups T10 and T20 (Fig. 2).

(a)

(b)

The Correlation of VEGF, Flt-1, and VEGF/Flt-1 Ratios in Tissue and Serum With Histopathological Findings The correlation between the liver, kidney and serum values of VEGF, Flt-1, and VEGF/Flt-1 ratios and histopathological scores of the organs were shown in Table 6. There was a negative correlation between pathological scores and Flt-1 levels in the liver (r=-0.522). This correlation was statistically significant (p=0.011). There were positive correlations between pathological scores and VEGF levels (r=0.477), VEGF/ Flt-1(r=0.529) ratios in kidneys. These correlations were statistically significant (p=0.009), (p=0.021). There was no statically significant correlation between pathological scores in remote organs and serum levels of VEGF, Flt-1, and VEGF/ Flt-1 ratios.

DISCUSSION Severe burn induces toxic mediators such as ROS and RNS leading to lipid peroxidation, which may have a pivotal role

(c)

Figure 2. (a-c) Findings of the kidney. Yellow arrows: Hyperemia in glomeruli and mesenchymal cell hyperplasia. (H&E. Bar=15 µm). Yellow arrows in B: Degeneration of tubular epithelium. Black Arrow: Necrosis of tubular epithelium. (H&E. Bar=30 µm).

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Table 6. The correlation of VEGF, Flt-1 levels and VEGF/Flt-1 ratios in tissues and serum with histopathological findings* Parameters

Pathological scores in liver¥

Liver

VEGF

Flt-1 r=-0.522#

r=0.099

p=0.011§

VEGF/Flt-1

p=0.159

Pathological scores in kidney¥

p=0.654

r=0.303

Kidney VEGF r=0.477# p=0.021§

Flt-1

VEGF/Flt-1 r=0.529# p=0.009§

r=-0.214 p=0.328

Serum

VEGF

r=-0.046 p=0.833 r=-0.137 p=0.533

Flt-1

r=-0.311 p=0.149 r=-0.289 p=0.181

VEGF/Flt-1 r=-0.164 p=0.454 r=-0.201 p=0.358

*: A correlation analysis (Speerman test) was used to assess the relationship between histopathological scorings and VEGF/Flt-1 ratio; ¥: There was a strong positive correlation between serum of histopathological scores of liver and kidneys (r=0.788 and p=0.001); #: Strong correlation; §: p<0.05 (statistically significant); VEGF: Vascular endothelial growth factor; Flt-1: VEGF receptor.

in remote organ injury such as that in the liver and kidneys. [16,40] MDA is an end product of lipid peroxidation and known as a good indicator of cell destruction due to oxidative and nitrosative damage.[1]

shows either increased oxidant production or a decreased antioxidant capacity in cells characterized by the release of free radicals, resulting in cellular degeneration which reflects TOS vs TAC ratio.[38,45]

VEGF is a mediator of angiogenesis and may also have a role in inflammation;[21,41] moreover, NO and VEGF may interact to promote angiogenesis.[42] However, the results showed that a high concentration of NO donors downregulates VEGF expression in endothelial cells.[43] On the other hand, previous studies show endogenous NO enhances VEGF synthesis.[23,43,44] NO is known as an inducer of VEGF synthesis under normoxia. However, why NO shows conflicting effects on VEGF is still unclear. An optimal amount of NO may upregulate the VEGF in limited cell lines while an excessive amount of NO inhibits the VEGF expression through an unidentified pathway. [20] All this information reveals that VEGF governs the controlled and regulated phenomenon of angiogenesis, whereas it may also have a role in inflammation dependent remote organ injury. Additionally, Flt-1 is known as a VEGF decoy receptor, serving to spatially control VEGF signaling and formation of angiogenic sprouts and in addition to its negative regulatory role in vascular development, Flt-1 is important in mounting an inflammatory response and inflammation-associated angiogenesis (denoted ‘pathological angiogenesis’) through recruitment of bone marrow- derived myelomonocytic cells followed by deposition of angiogenic growth factors.[22]

In the present study, we specified that sildenafil may have protective effects against severe burn- induced remote organ injury decreasing oxidative and nitrosative stress, as confirmed by biochemical assays and histopathological analysis in both tissues and serum. Our findings fairly presented that treatment with sildenafil increased Gpx and TAC, and decreased MDA, TOS, and OSI. Another important result of our study was that sildenafil had beneficial effects on decreasing the inflammation scores in tissues. Additionally, the 10 mg/kg sildenafil group had the lowest inflammation scores in both liver and kidneys, in our study. However, no additional benefit was pointed out when the dosage increased to 20 mg/kg. The effects of sildenafil treatment on VEGF and Flt-1 in tissue levels appear to be dependent upon dosage and organ. On the other hand, sildenafil treatment appears to be effective on VEGF serum levels through Flt-1. As in previous studies,[17,20,23] sildenafil showed conflicting effects in VEGF values in tissues in our study and these effects may be due to the amount of NO produced by sildenafil. However, not measuring the levels of NO can be accepted as a limitation of this trial.

Increase of Gpx enzyme activities following burn related injury protects tissues from the effects of free radicals and lipid peroxidation.[44] TOS and TAC parameters instead of individual oxidant and antioxidant compounds such as MDA, Gpx, and Cat acting in combination with each other may reflect the total effect of oxidant and antioxidant balance in tissues and serum levels. The definition of oxidative stress index (OSI) Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Cadirci et al.[32] reported effects of sildenafil (10 and 20 mg/ kg/p.o.) in remote organs, including the lung and kidneys, in a rat model of sepsis. They observed a significant decrease in oxidative stress and inflammation degree by evaluating similar biochemical parameters and histopathological scores, like ours, in the sildenafil-treated groups compared to the control group. However, unlike us, they evaluated the oxidant/antioxidant parameters in only tissue levels, whereas we evaluated them in both tissues and serum. Similarly, Uzun et al.[34] 325

Gökakın et al. The effects of sildenafil in liver and kidney injury in a rat model of severe scald burn

demonstrated that sildenafil administration (10 mg/kg/p.o.) in ischemic colonic anastomoses increased GSH levels and promoted healing of anastomosis. Additionally, Iseri et al.[33] found that sildenafil treatment (5 mg/kg/p.o.) decreased MDA and increased GSH levels in tissues and improved the healing of colonic inflammation in rats. Also, in a different trial, Karakoyun et al.[31] concluded in rat experimentally induced colitis that sildenafil treatment (25 mg/kg/p.o.) decreased MDA and increased GSH levels in colonic tissues and might have a beneficial effect in colitis treatment. Additionally, Zhang et al.[23] used sildenafil treatment (2 mg/kg/p.o.) in a rat model of brain ischemia and found out that sildenafil promoted angiogenesis via VEGF. These results supported the findings of the present study and demonstrated positive effects of different dosages of sildenafil treatment on different tissue injuries due to oxidative and nitrosative stress. In our review of the literature, we were not able to find any previous experimental study using TAC, TOS, and OSI levels to evaluate the oxidative stress in both tissues and serum except our previous study.[9] In our study, while TAC levels in liver tissues were found to be higher, TOS and OSI levels were found to be lower in treatment groups. A similar trend was found in the kidneys, but was not statistically significant. This situation may be accepted as additional evidence for the beneficial effects of sildenafil in tissue levels. Sildenafil seems to have dose dependent positive effects only on TAC levels in terms of serum levels. Positive effects of sildenafil administration in histopathological evaluations in inflammatory events have been demonstrated in a number of previous studies.[23,30-34,46,47] Histopathological evaluations of those studies also demonstrated the positive effects of various dosages of sildenafil administration (range 2±25 mg/kg) in decreased inflammation scores. In conclusion, our findings reveal that sildenafil may have a protective effect in scald burn- related remote organ injury by decreasing oxidative and nitrosative stress, as well as inflammation. In addition, the dosage of 10 mg/kg appears better than 20 mg/kg.

Disclosure The authors declare that they have no competing interests as defined by this journal, or other interests that might be perceived to influence the results and discussion reported in this paper.

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35. Walker DK, Ackland MJ, James GC, Muirhead GJ, Rance DJ, Wastall P, et al. Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog and man. Xenobiotica 1999;29:297-310. 36. Stevenson JM, Gamelli RL, Shankar R. A mouse model of burn wounding and sepsis. Methods Mol Med 2003;78:95-105. 37. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158-69. 38. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103-11. 39. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112-9. 40. Demling RH, Lalonde C. Systemic lipid peroxidation and inflammation induced by thermal injury persists into the post-resuscitation period. J Trauma 1990;30:69-74. 41. Scaldaferri F1, Vetrano S, Sans M, Arena V, Straface G, Stigliano E, et al. VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis. Gastroenterology 2009;136:585-95.e5. 42. Jozkowicz A, Cooke JP, Guevara I, Huk I, Funovics P, Pachinger O, et al. Genetic augmentation of nitric oxide synthase increases the vascular generation of VEGF. Cardiovasc Res 2001;51:773-83. 43. Dulak J, Józkowicz A, Ratajska A, Szuba A, Cooke JP, Dembińska-Kieć A. Vascular endothelial growth factor is efficiently synthesized in spite of low transfection efficiency of pSG5VEGF plasmids in vascular smooth muscle cells. Vasc Med 2000;5:33-40. 44. Lubos E, Loscalzo J, Handy DE. Glutathione peroxidase-1 in health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 2011;15:1957-97. 45. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004;37:277-85. 46. Hemnes AR, Zaiman A, Champion HC. PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation. Am J Physiol Lung Cell Mol Physiol 2008;294:L24-33. 47. Yildirim A, Ersoy Y, Ercan F, Atukeren P, Gumustas K, Uslu U, et al. Phosphodiesterase-5 inhibition by sildenafil citrate in a rat model of bleomycin-induced lung fibrosis. Pulm Pharmacol Ther 2010;23:215-21.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Sildenafilin ağır haşlama yanığı oluşturulan sıçan modelinde karaciğer ve böbrek hasarı üzerine etkisi: Biyokimyasal ve histopatolojik çalışma Dr. Ali Kağan Gökakın,1 Dr. Mustafa Atabey,1 Dr. Koksal Deveci,2 Dr. Enver Sancakdar,2 Dr. Mehmet Tuzcu,3 Dr. Cevdet Duger,4 Dr. Omer Topcu1 Cumhuriyet Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Sivas; Cumhuriyet Üniversitesi Tıp Fakültesi, Biokimya Anabilim Dalı, Sivas; Cumhuriyet Üniversitesi Veteriner Fakültesi, Patoloji Anabilim Dalı, Sivas; 4 Cumhuriyet Üniversitesi Tıp Fakültesi, Anesteziyoloji Anabilim Dalı, Sivas 1 2 3

AMAÇ: Ağır yanıklar sistemik enflamasyonu ve reaktif oksijen radikallerinin oluşumunu artırarak lipid peroksidasyonuna öncülük eder ve bu da uzak organ hasarında rol oynayabilir. Sildenafil selektif ve potent bir cyclic guanosine monofosfat ve spesifik bir fosfodiesteraz-5 inhibitörüdür. Sildenafil uzak organlarda enflamasyonu ve oksidatif stresi azaltır. Bu çalışmada, sildenafilin farklı dozlarda uzak organ hasarı üzerine olan etkisi araştırıldı. GEREÇ VE YÖNTEM: Otuz iki sıçan dört eşit gruba randomize şekilde ayrıldı. Sırasıyla; Sham, kontrol, 10 ve 20 mg/kg sildenafil tedavi grubu olarak adlandırıldı. Doku ve serumda malondialdehit (MDA), vasküler endotelyal büyüme faktörü (VEGF), VEGF reseptör (Flt-1), glutatyon peroksidaz aktivitesi (Gpx), total antioksidan kapasite (TAC) ve total oksidan durum (TOS) seviyeleri ölçüldü. Histopatolojik bulguların değerlendirilmesinde semi kantitatif skorlama sistemi kullanıldı. BULGULAR: Sildenafilin dokuda Gpx ve Flt değerlerini artırırken, MDA ve VEGF değerlerini azalttığı görüldü. Sildenafilin TAC ve Flt-1 serum seviyelerini artırdığı tespit edilse de TOS, OSI ve VEGF seviyelerini azalttığı görüldü. TARTIŞMA: Sildenafil histopatolojik incelemede uzak organ emflamasyon skorunu azaltır. Sildenafil ağır haşlama yanığına bağlı uzak organ hasarında oksidatif stres ve emflamasyonu azaltarak koruyucu etkiye sahiptir. Anahtar sözcükler: Haşlama yanığı; sildenafil; uzak organ hasarı. Ulus Travma Acil Cerrahi Derg 2014;20(5):319-327

doi: 10.5505/tjtes.2014.39586

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EXPERIMENTAL STUDY

Thymoquinone attenuates trauma induced spinal cord damage in an animal model Nilgün Üstün, M.D.,1 Mustafa Aras, M.D.,2 Tumay Ozgur, M.D.,3 Hamdullah Suphi Bayraktar, M.D.,4 Fatih Sefil, M.D.,5 Raif Ozden, M.D.,6 Abdullah Erman Yagiz, M.D.1 1

Department of Physical Medicine and Rehabilitation, Mustafa Kemal University Faculty of Medicine, Hatay;

Department of Neurosurgery, Mustafa Kemal University Faculty of Medicine, Hatay;

Department of Pathology, Mustafa Kemal University Faculty of Medicine, Hatay;

Department of Clinical Sciences, Mustafa Kemal University Faculty of Veterinary, Hatay;

Department of Physiology, Mustafa Kemal University Faculty of Medicine, Hatay;

Department of Orthopaedics and Traumatology, Mustafa Kemal University Faculty of Medicine, Hatay

ABSTRACT BACKGROUND: Spinal cord injury (SCI) is one of the most devastating conditions leading to neurological impairment and disabilities. The aim of the study was to investigate the potential neuroprotective effect of thymoquinone (TQ) histopathologically in an experimental model of traumatic spinal cord injury (SCI). METHODS: Twenty-four male Wistar albino rats were randomly divided into 4 groups: control group; SCI group; SCI-induced and 10 mg/kg/day TQ administered group; SCI-induced and 30 mg/kg/day TQ administered group. TQ was given as intraperitoneal for three days prior to injury and four days following injury. Spinal cord segment between T8 and T10 were taken for histopathologic examination. Hemorrhage, spongiosis and liquefactive necrosis were analyzed semiquantatively for histopathological changes. RESULTS: Administration of TQ at a dose of 10 mg/kg did not cause any significant change on the histological features of neuronal degeneration as compared to the SCI group (p=0.269); however, 30 mg/kg TQ significantly decreased the histological features of spinal cord damage below that of the SCI group (p=0.011). CONCLUSION: Data from this study suggest that TQ supplementation attenuates trauma induced spinal cord damage. Thus, TQ needs to be taken into consideration, for it may have a neuroprotective effect in trauma induced spinal cord damage. Key words: Experimental spinal cord injury; thymoquinone; histologic examination.

INTRODUCTION Spinal cord injury (SCI) is one of the most devastating conditions leading to neurological impairment and disabilities.[1] In SCIs, primary injury occurs after mechanical damage to neuronal and vascular tissues at the time of trauma. Just after mechanical injury, secondary injury occurs by the reduction of spinal cord microvascular circulation and the deleterious Address for correspondence: Nilgün Üstün, M.D. Mustafa Kemal Üniversitesi Tıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı, Hatay, Turkey Tel: +90 326 - 229 10 00 E-mail: drnustun@yahoo.com.tr Qucik Response Code

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biochemical effects of reactive oxygen species generation, cell membrane lipid peroxidation and inflammation.[2,3] Therefore, agents with antioxidant and anti-inflammatory properties are proposed to be useful in trauma induced spinal cord damage.[4] None of the clinically available anti-oxidant therapies has produced any clinically satisfactory intervention in trauma induced SCI due to its complexity.[5] Therefore, there is still a significant need for effective and safer agents for the treatment of spinal cord injury. Thymoquinone (TQ), the main active constituent of Nigella saliva seeds, is reported to have strong free radical scavenger and antioxidant[6-9] and anti-inflammatory[10,11] properties in different animal tissue models. To the best of our knowledge, the neuroprotective effect of TQ in SCI has not been investigated. Therefore, this study was designed to investigate the potential protective effect of TQ in a model of traumatic SCI. Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Yılmaz et al. Thymoquinone attenuates trauma induced spinal cord damage in an animal model

MATERIALS AND METHODS Animals Twenty-four adult male Wistar albino rats, weighing 300-350 g, were obtained from Mustafa Kemal University Laboratory of Experimental Animals. The animals were fed with a standard rat chaw and allowed access to water. All rats were kept in an air-conditioned room with 12-hour light and dark cycles, where the temperature (22 ± 2ºC) and relative humidity (65– 70%) were kept constant. All experimental protocols were approved by the Animal Care and Use Committee of Mustafa Kemal University, School of Veterinary Medicine.

Chemical TQ (2 isopropyl-5-methyl-1.4-benzoquinone) was obtained from Sigma Chemical Co. (St. Louis, Missouri, USA) and dissolved in saline and heated at 60-80°C.

Experimental Design Rats were randomly assigned into four groups of six rats each: One group served as controls where the rats received sham injury (laminectomy). Second group served as the SCI group that underwent SCI after laminectomy. Third group under-

went SCI and was given intraperitoneal administration of TQ aqueous solution at 10 mg/kg/day dose level for three days prior to and four days after SCI. Fourth group underwent SCI and was given intraperitoneal administration of TQ aqueous solution at 30 mg/kg/day dose level for three days prior to and four days after SCI.

Induction of SCI The animals were anesthetized with intraperitoneal injection of 75 mg/kg ketamine (Ketalar, Eczacıbaşı, Istanbul, Turkey) and 10 mg/kg xylazine (Rompun, Bayer, Istanbul, Turkey). Anesthetized rats were positioned in a prone position. Their dorsal regions were shaved and cleaned with povidone-iodine. Under sterile conditions, following T6-T12 midline skin incision and paravertebral muscle dissection, spinous processes and laminar arcs of T8-T10 were removed. The dura was left intact. A well characterized weight-drop technique was performed for spinal cord trauma.[12] The animals were subjected to an impact of 100 g/cm (10 g weight from 10 cm height) to the dorsal surface of the spinal cord. The force was applied via a stainless steel rod (3 mm diameter tip) rounded at the surface. The rod was dropped vertically through a 10 cm guide tube positioned perpendicular to the center of the spinal cord. Afterwards, the

(a)

(b)

(c)

(d)

Figure 1. Light photomicrographs of the rats’ spinal cord tissue sections (H&E, x 200). Sham-operated control group with preserved morphology (a). Spinal trauma group; hemorrhage (h), severe vacuolic degeneration (v), liquefactive necrosis (ln) and inflammatory infiltrate (i) (b). Degenerative changes remain with low doses of thymoquinone (TQ) (c). Improved spinal cord morphology with high doses of TQ (d).

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Yılmaz et al. Thymoquinone attenuates trauma induced spinal cord damage in an animal model

muscles and the incision were sutured. Rats in the sham injury group underwent a similar surgical procedure as other groups; however, no spinal cord trauma was performed. A week after SCI induction, rats were sacrificed using an overdose of pentobarbital (200 mg/kg) and the same part of the injured spinal cord tissue samples were excised. The sample of the spinal cord tissue was stored in 10% buffered formaldehyde solution for histologic examination.

Histologic Analysis For histological examination, all tissue samples were fixed at 10% buffered formaldehyde solution for 24 hours and processed according to routine light microscopic tissue processing technique. Formalin-fixed paraffin-embedded tissue sections (5 µm) were stained with hematoxylin and eosin (H&E) and examined by an Olympus DP20 camera attachedOlympus CX41 photomicroscope. To prevent inter-individual bias, all tissues were evaluated by the same pathologist (T.O.) who was uninformed of the groups and test materials. Hemorrhage, spongiosis and liquefactive necrosis were analyzed for histopathological changes. For histopathologic evaluation, a semi-quantitative grading system modified by Malinovsky et al.[13] was used on all specimens as following: No abnormal cells and change (grade 0), mild hemorrhage, spongiosis (grade 1), moderate hemorrhage and spongiosis with liquefactive necrosis (grade 2), severe hemorrhage and spongiosis with glial cell proliferation and liquefactive necrosis (grade 3).

Statistical Analysis Statistical analyses were performed using SPSS software package program (SPSS Inc., Chicago, IL, USA), version 13.0 for Windows. Kruskal-Wallis variance test was used to compare differences among groups. When analysis of variance showed significance, Mann-Whitney U-test was applied to determine the difference. Data were expressed as mean± SD. Values of p˂0.05 were accepted as statistically significant.

RESULTS Light microscopic examination of the spinal cord tissue sections revealed a normal histological structure in the shamoperated control group (Fig. 1a). Histological examination of the spinal cord tissue sections of the SCI group showed moderate to severe hemorrhage, necrosis, inflammatory infiltrate and fibrosis (Fig. 1b). A statistically significant difference was found among the groups (p=0.001). Neuronal degeneration in the SCI group was significant compared to the shamoperated control group (p=0.003, Table 1). Administration of TQ at a dose of 10 mg/kg for three days prior to and four days after SCI did not cause any significant change on histological features of neuronal degeneration as compared to the SCI group (p=269, Table 1; Fig. 1c). However, 30 mg/kg TQ significantly decreased the histological features of the spinal cord damage below that of the SCI group (p=0.011, Table 1; Fig. 1d). 330

Table 1. Histopathologic evaluation scores of the groups Rat

Control

SCI

SCI+TQ10 SCI+TQ30

0 2 2 1

0 3 2 1

0 3 3 2

0 3 2 1

0 2 3 1

0 3 2 1

Mean±SD 0.00±0.00 2.66±0.51 2.33±0.57 1.20±0.44 p 0.003a 0.269b 0.011c TQ: Thymoquinone; SCI: Spinal cord injured untreated group; SCI+TQ10: 10 mg/kg TQ treated spinal cord injured group; SCI+TQ30: 30 mg/kg TQ treated spinal cord injured group; histopathologic grading scores: 0, no abnormal cells and change; 1, mild hemorrhage, spongiosis; 2, moderate hemorrhage and spongiosis with liquefactive necrosis; 3, severe hemorrhage and spongiosis with glial cell proliferation and liquefactive necrosis. ap, compared with C group group; bp and cp, compared with SCI group.

DISCUSSION This study was initiated to investigate whether TQ supplementation could reduce trauma induced spinal cord damage. The results of the present study demonstrated that treatment with 30 mg/kg TQ for three days prior to and four days after trauma had protective effects on trauma induced spinal cord damage. This was shown by marked decrease in the histopathological damage scores of the injured spinal cord tissues. This neuroprotective effect of TQ could be explained on the basis of its antioxidant[6-9] and anti-inflammatory effects.[10,11] To the best of our knowledge, this is the first report evaluating the neuroprotective effects of TQ on trauma induced SCI. Reactive oxygen species are continuously produced during normal physiologic events and removed by antioxidant defense mechanism.[14] The imbalance between reactive oxygen species and antioxidant defense mechanisms leads to lipid peroxidation and oxidative damage in the lipid bilayers surrounding both the cell itself and membrane-bound organelles. [15] Recent studies have demonstrated that increase in reactive oxygen species and the decrease in the antioxidant defense mechanisms is a major contributor to the pathogenesis of trauma induced spinal cord damage.[16,17] A variety of known antioxidants and anti-inflammatory agents have shown protective effects on traumatic SCI in experimental models and clinical trials.[18-24] Toklu et al.[18] have found that alpha-lipoic acid reduces oxidative stress on traumatic SCI. Sahin et al.[19] have shown significant protective effects of curcumin on traumatic spinal cord tissues against oxidative damage. Karalija et al.[20] have demonstrated better pathological findings by Nacetyl-cysteine and acetyl-L-carnitine in the early treatment of traumatic SCI by using quantitative immunohistochemistry and western blotting for neuronal and glial cell markers, and indicated a therapeutic potential for NAC and ALC in the Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Yılmaz et al. Thymoquinone attenuates trauma induced spinal cord damage in an animal model

early treatment of traumatic SCI. Cemil B et al.[21] have put forward better pathological findings by aged garlic extract in the traumatic SCI against oxidative damage. Erşahın et al.[22] have reported that ghrelin could reduce SCI-induced oxidative stress and exert anti-inflammatory effects in the spinal cord following trauma. In the present study, histological examination of trauma induced spinal cord tissue sections revealed moderate to severe hemorrhage, necrosis, inflammatory infiltrate and fibrosis. TQ at a dose of 10 mg/kg for three days prior to and four days after trauma did not cause any significant reduction in the histopathologic damage scores as compared to the spinal cord injured untreated group, while TQ at dose of 30 mg/kg for three days prior to and four days after trauma significantly reduced the histopathologic damage scores below that of the spinal cord injured untreated group. These results are consistent with the data[25] demonstrating that TQ significantly decreased lipid peroxidation and increased the antioxidant levels in a model of hepatic ischemia reperfusion injury in a dose dependent manner. Neuroprotective effect of TQ in the present study could be due to its free radical scavenging effect that could protect cell membranes against trauma-induced lipid peroxidation. It has been reported that TQ has strong antioxidant potentials through scavenging ability of different free radicals, especially superoxide scavenging activity that prevents oxidative injury in several tissues with the ability to inhibit lipid peroxidation and to preserve cell integrity.[15,26] In an injured cord, overactivation of inflammatory response is also a contributor to the trauma induced spinal cord damage. [27] Marked neuroprotective effect with TQ in this study could also be explained by anti-inflammatory effect of TQ in addition to its antioxidant effects. TQ is reported to possess antiinflammatory effects by inhibition of eicosanoid generation. [10,11,26,28] The use of TQ has shown to have anti-inflammatory effects in several inflammatory diseases, including experimental allergic encephalomyelitis,[29] colitis,[30] arthritis,[31] and bacterial prostatitis.[32] One limitation of this study was the lack of measurement of antioxidant enzyme activities and the degree of membrane lipid peroxidation in the injured spinal cord tissue. The other limitation of this study was the lack of motor testing of the animals. Although SCI results in motor dysfunction in various degrees among animals, these deficits were not unique for each animal. Therefore, motor tests are not reliable to evaluate the effects of trauma on spinal cord tissue. In conclusion, data from this study suggest that TQ supplementation attenuates trauma induced spinal cord damage. Studies with presence of measurement of oxidant/antioxidant status and motor testing of the animals are needed to make inferences that are more reliable. Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Conflict of interest: None declared.

REFERENCES 1. Wu B, Ren X. Promoting axonal myelination for improving neurological recovery in spinal cord injury. J Neurotrauma 2009;26:1847-56. 2. Dumont RJ, Okonkwo DO, Verma S, Hurlbert RJ, Boulos PT, Ellegala DB, et al. Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol 2001;24:254-64. 3. Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars) 2011;71:281-99. 4. Slemmer JE, Shacka JJ, Sweeney MI, Weber JT. Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr Med Chem 2008;15:404-14. 5. Bains M, Hall ED. Antioxidant therapies in traumatic brain and spinal cord injury. Biochim Biophys Acta 2012;1822:675-84. 6. Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH. Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 2003;26:87-98. 7. Kruk I, Michalska T, Lichszteld K, Kładna A, Aboul-Enein HY. The effect of thymol and its derivatives on reactions generating reactive oxygen species. Chemosphere 2000;41:1059-64. 8. Mansour MA, Nagi MN, El-Khatib AS, Al-Bekairi AM. Effects of thymoquinone on antioxidant enzyme activities, lipid peroxidation and DTdiaphorase in different tissues of mice: a possible mechanism of action. Cell Biochem Funct 2002;20:143-51. 9. Nagi MN, Mansour MA. Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection. Pharmacol Res 2000;41:283-9. 10. Al-Ghamdi MS. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 2001;76:45-8. 11. Houghton PJ, Zarka R, de las Heras B, Hoult JR. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med 1995;61:33-6. 12. Allen AR. Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column. A preliminary report. JAMA 1911;57:878-80. 13. Malinovsky JM, Cozian A, Lepage JY, Mussini JM, Pinaud M, Souron R. Ketamine and midazolam neurotoxicity in the rabbit. Anesthesiology 1991;75:91-7. 14. Duffy S, So A, Murphy TH. Activation of endogenous antioxidant defenses in neuronal cells prevents free radical-mediated damage. J Neurochem 1998;71:69-77. 15. Dal-Pizzol F, Klamt F, Benfato MS, Bernard EA, Moreira JC. Retinol supplementation induces oxidative stress and modulates antioxidant enzyme activities in rat sertoli cells. Free Radic Res 2001;34:395-404. 16. Hamann K, Durkes A, Ouyang H, Uchida K, Pond A, Shi R. Critical role of acrolein in secondary injury following ex vivo spinal cord trauma. J Neurochem 2008;107:712-21. 17. Seligman ML, Flamm ES, Goldstein BD, Poser RG, Demopoulos HB, Ransohoff J. Spectrofluorescent detection of malonaldehyde as a measure of lipid free radical damage in response to ethanol potentiation of spinal cord trauma. Lipids 1977;12:945-50. 18. Toklu HZ, Hakan T, Celik H, Biber N, Erzik C, Ogunc AV, et al. Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats. J Spinal Cord Med 2010;33:401-9. 19. Sahin Kavaklı H, Koca C, Alıcı O. Antioxidant effects of curcumin in spinal cord injury in rats. Ulus Travma Acil Cerrahi Derg 2011;17:148.

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Yılmaz et al. Thymoquinone attenuates trauma induced spinal cord damage in an animal model 20. Karalija A, Novikova LN, Kingham PJ, Wiberg M, Novikov LN. Neuroprotective effects of N-acetyl-cysteine and acetyl-L-carnitine after spinal cord injury in adult rats. PLoS One 2012;7:e41086. 21. Cemil B, Gökce EC, Erdamar H, Karabörk A, Onur O, Heper Okcu A, et al. Effects of the aged garlic extract on spinal cord injury model in rat. Ulus Travma Acil Cerrahi Derg 2012;18:463-8. 22. Erşahın M, Toklu HZ, Erzık C, Akakin D, Tetık S, Sener G, et al. Ghrelin alleviates spinal cord injury in rats via its anti-inflammatory effects. Turk Neurosurg 2011;21:599-605. 23. Hall ED. Antioxidant therapies for acute spinal cord injury. Neurotherapeutics 2011;8:152-67. 24. Jia Z, Zhu H, Li J, Wang X, Misra H, Li Y. Oxidative stress in spinal cord injury and antioxidant-based intervention. Spinal Cord 2012;50:264-74. 25. Abd El-Ghany RM, Sharaf NM, Kassem LA, Mahran LG, Heikal OA. Thymoquinone triggers anti-apoptotic signaling targeting death ligand and apoptotic regulators in a model of hepatic ischemia reperfusion injury. Drug Discov Ther 2009;3:296-306. 26. El-Dakhakhny M, Madi NJ, Lembert N, Ammon HP. Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from rats. J Ethnopharmacol

2002;81:161-4. 27. Fehlings MG, Nguyen DH. Immunoglobulin G: a potential treatment to attenuate neuroinflammation following spinal cord injury. J Clin Immunol 2010;30 Suppl 1:109-12. 28. Marsik P, Kokoska L, Landa P, Nepovim A, Soudek P, Vanek T. In vitro inhibitory effects of thymol and quinones of Nigella sativa seeds on cyclooxygenase-1- and -2-catalyzed prostaglandin E2 biosyntheses. Planta Med 2005;71:739-42. 29. Mohamed A, Shoker A, Bendjelloul F, Mare A, Alzrigh M, Benghuzzi H, et al. Improvement of experimental allergic encephalomyelitis (EAE) by thymoquinone; an oxidative stress inhibitor. Biomed Sci Instrum 2003;39:440-5. 30. Mahgoub AA. Thymoquinone protects against experimental colitis in rats. Toxicol Lett 2003;143:133-43. 31. Tekeoglu I, Dogan A, Ediz L, Budancamanak M, Demirel A. Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models. Phytother Res 2007;21:895-7. 32. Inci M, Davarci M, Inci M, Motor S, Yalcinkaya FR, Nacar E, et al. Antiinflammatory and antioxidant activity of thymoquinone in a rat model of acute bacterial prostatitis. Hum Exp Toxicol 2013;32:354-61.

DENEYSEL ÇALIŞMA - ÖZET OLGU SUNUMU

Timokinon deneysel spinal kord yaralanmalı sıçanlarda spinal kord hasarını azaltır Dr. Nilgün Üstün,1 Dr. Mustafa Aras,2 Dr. Tumay Ozgur,3 Dr. Hamdullah Suphi Bayraktar,4 Dr. Fatih Sefil,5 Dr. Raif Ozden,6 Dr. Abdullah Erman Yagiz1 Mustafa Kemal Üniversitesi Tıp Fakültesi, Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı, Hatay; Mustafa Kemal Üniversitesi Tıp Fakültesi, Beyin Cerrahisi Anabilim Dalı, Hatay; 3 Mustafa Kemal Üniversitesi Tıp Fakültesi, Patoloji Anabilim Dalı, Hatay; 4 Mustafa Kemal Üniversitesi Veterinerlik Fakültesi, Klinik Bilimler Anabilim Dalı, Hatay; 5 Mustafa Kemal Üniversitesi Tıp Fakültesi, Fizyoloji Anabilim Dalı, Hatay; 6 Mustafa Kemal Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Anabilim Dalı, Hatay 1 2

AMAÇ: Spinal kord yaralanması (SKY) nörolojik bozukluk ve özürlülüğe yol açan en yıkıcı hastalık durumlarından biridir. Bu çalışmanın amacı deneysel SKY’lı sıçanlarda timokinonun (TQ) nöroprotektif etkilerinin histopatolojik olarak araştırılmasıdır. GEREÇ VE YÖNTEM: Yirmi dört adet erkek Wistar albino sıçan dört gruba ayrıldı: Kontrol grubu; SKY grubu; SKY ve 10 mg/kg/gün TQ verilen grup; SKY ve 30 mg/kg/gün TQ verilen grup. TQ intraperitoneal günde tek doz yaralanmadan 3 gün önce ve yaralanmayı takiben 4 gün olarak verildi. T8-T10 spinal segmentleri histopatolojik inceleme için alındı. Segmentler histopatolojik olarak hemoraji, spongioz ve likefaksiyon nekrozu açısından semikantitatif olarak analiz edildi. BULGULAR: 10 mg/kg/gün TQ verilen SKY grubun spinal kord segmentlerinin histopatoljik incelemesinde anlamlı nöronal iyileşme saptanmazken (p=0.269), 30 mg/kg/gün TQ verilen SKY grubunda anlamlı düzeyde nöronal iyileşme saptandı (p=0.011). TARTIŞMA: Bu çalışmadan elde edilen sonuçlar TQ takviyesinin travmaya bağlı spinal kord hasarını azalttığını göstermektedir. Bu nedenle TQ travmatik SKY’da, nöroprotektif etkileri olabileceği için, dikkate alınmalıdır. Anahtar sözcükler: Deneysel spinal kord yaralanması; histolojik inceleme; timokinon. Ulus Travma Acil Cerrahi Derg 2014;20(5):328-332

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doi: 10.5505/tjtes.2014.05021

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ORIGIN A L A R T IC L E

Fournier’s gangrene: Review of 120 patients and predictors of mortality Tuncay Yılmazlar, M.D.,1 Özgen Işık, M.D.,1 Ersin Öztürk, M.D.,1 Ali Özer, M.D.,1 Barış Gülcü, M.D.,1 İlker Ercan, M.D.2 1

Department of General Surgery, Uludag University Faculty of Medicine, Bursa;

Department of Biostatistics, Uludag University Faculty of Medicine, Bursa

ABSTRACT BACKGROUND: Fournier’s gangrene (FG) is a devastating and potentially fatal disease requiring prompt and aggressive debridement. In this study, it was aimed to assess the predictors of mortality in a large cohort. METHODS: Prospectively maintained data of patients with FG were analyzed. Demographic data, duration of symptoms, Uludag Fournier’s Gangrene Severity Index (UFGSI) scores, co-morbidities [particularly diabetes mellitus (DM)], etiologies, number of debridement, stoma requirements, length of intensive care unit and hospital stay, and morbidity and mortality rates were reviewed. Multivariate analysis was performed in order to determine factors affecting mortality. RESULTS: 120 patients (81 males) were included in the study. Median age was 58 (22-85) years. UFGSI score was median 9 (1-30). DM was present in 69 (57.5%) patients. Etiology of FG was perianal in fifty-nine, urogenital in 52, and skin in 9 patients. Median debridement count was 3 (1-12). Thirty-one patients required stoma. Forty-eight patients were admitted to intensive care unit and 25 patients required mechanical ventilation. Overall mortality rate was 20.8%. Multivariate analysis revealed UFGSI as the only predictor of mortality (p=0.001). Mortality rate was 13.64 times higher for patients with a UFGSI score of 9 or higher. CONCLUSION: Fournier’s gangrene is a mortal disease requiring emergency surgery. UFGSI is an efficient predictor of mortality for patients with FG. Key words: Fournier’s gangrene; mortality; severity score.

INTRODUCTION Fournier’s gangrene (FG) is progressive and, if inadequately treated, mortal, necrotizing fasciitis of perineal, perianal, and genital region requiring emergency surgery.[1-3] These infections are typically polymicrobial, with both aerobic and anaerobic organisms present in the majority of cases.[3,4] In spite of the widely varying microorganisms in the etiology, its treatment is unique for all cases including emergency removal of the devitalized tissues, adequate resuscitation, and intravenous (iv) administration of wide-spectrum antibiotics.[1-7]

Address for correspondence: Tuncay Yılmazlar, M.D. Uludağ Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Görükle Kampüsü, 16059 Bursa, Turkey Tel: +90 224 - 295 20 40 E-mail: tunyil@uludag.edu.tr Qucik Response Code

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FG affects both males and females regardless of age. Underlying colorectal or urological diseases and diabetes mellitus (DM) are common among patients with FG.[3] However, mortality of FG varies from 3 to 45%, even if it is well managed.[3,8-11] Factors affecting the outcomes are patient, disease, and surgeon related.[2] There are several scoring systems for predicting the risk of mortality of FG. Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system is a commonly used method for predicting outcomes of critically ill patients with necrotizing soft tissue infection (NSTI).[12] Another well-defined method, which is also disease specific, is Fournier’s Gangrene Severity Index (FGSI).[13] Uludag Fournier’s Gangrene Severity Index (UFGSI) is a novel scoring system established by our department previously.[2] In this study, it was aimed to present the largest single institute serial of FG and determine the risk factors associated with mortality.

MATERIALS AND METHODS Data of the patients who underwent emergency debridement for FG between 1996 and 2012 were extracted from the pro333

Yılmazlar et al. Fournier’s gangrene: Review of 120 patients and predictors of mortality

spectively maintained departmental FG database. Only adult patients admitted or referred to our department and diagnosed with FG were included in the study. FG is defined as NSTI of perianal, perineal and genital region. All patients underwent at least one radical debridement of affected devitalized tissues within 12 hours after admission. Iv. third-generation cephalosporin and metronidazole antibiotherapy was started at the emergency room and continued. Empiric antibiotherapy was changed according to the results of the microbiological analysis of the removed tissue samples in the first debridement, if necessary. Conventional wound dressings were changed daily and wound exploration was performed in the operating room every 48 hours until healthy granulation tissue was formed in the wound. Vacuum assisted closure (VAC; Kinetic Concepts, Inc., San Antonio, TX) in wound management of FG patients have been widely used by us for the last five years. Dressings were changed, and wound exploration was performed every 72 hours in the operating room for patients whose wounds were managed with VAC therapy. Patients underwent additional debridements, if necessary, during their wound explorations. Debridements continued until the removal of all necrotic tissues and the establishment of healthy granulation tissue in the wound. Patients with severe sepsis, requiring vasopressors or mechanical ventilation support were treated in the intensive care unit (ICU). Patients who were not stable enough to transfer from the ICU were debrided at the bedside. Skin defects, which were not convenient for staged tertiary closure, were reconstructed with split thickness skin graft (STSG). Patient demographics, duration of symptoms, co-morbidities, presence of DM, etiology of NSTI, direct admission or referral from peripheral centers, APACHE II score, FGSI score, UFGSI score, debridement counts, anesthesia type (general or regional), stoma requirement, microbiological analysis results, need of mechanical ventilation, wound closure type, length of hospital and ICU stay were recorded. Descriptive statistical methods were employed to evaluate clinical characteristics, management, and outcome. Data presented as median and ranges. Multivariate logistic regression analysis was performed to determine independent risk factors associated with mortality. Statistical Package for Social Sciences (SPSS) ver. 16.0 was used for performing statistical analysis.

RESULTS One hundred and twenty patients (81 males), with a median age of 58 (range, 22-85) were included in the study. Ninety-five of the 120 patients survived and the mortality rate was 20.8%. Twelve of the non-survivors were female. Most common cause of death was the multi-organ failure due to septic shock in fourteen patients. Pneumonia (n=5), cardio334

genic shock (n=4) and end-stage carcinoma (n=2) were other mortality causes. Median duration of symptoms (from the onset of the symptoms to arrival at our hospital) was median seven days (1-40). Mortality rate was 27% among patients with symptom duration longer than seven days. Forty patients (33%) were admitted primarily to our emergency department while others (67%) were referred from peripheral centers. Sixty-nine patients had DM and 31 patients had no other co-morbidities. While the etiology of FG was anorectal diseases in fifty-nine patients (49.2%), other sources were urogenital diseases (43.3%) and skin infections (7.5%). No microorganisms were isolated in ten patients. The most common pathogen was E. Coli in seventy-four patients. Enterococci, Streptococci, Staphylococci, Klebsiella, Pseudomonas and Proteus were other microorganisms isolated in wound cultures, consecutively. None of the three patients with fungi survived. Microbiological analysis results of thirty-six patients could not be documented. Anaerobic culture could not be performed in our hospital because of technical difficulties. Wound management was performed with VAC therapy in forty-two patients. Median debridement count was three (1-12). Majority of the debridements were performed under spinoepidural anesthesia; however, twenty-seven patients (22.5%) required general anesthesia. Fecal diversion with a temporary colostomy was established in thirty-one patients (25.8%). Forty-eight patients were treated in the intensive care unit (ICU) with a median of eight days (1-40) length of stay. Twenty-five patients developed respiratory failure requiring mechanical ventilation. Mechanical ventilation treatment need was seven days (1-25). Mortality rate for patients requiring mechanical ventilation support was 68%. Wounds of seventy-five patients were suitable for staged tertiary closure. On the other hand, the wounds of forty-five patients were reconstructed with split thickness skin graft (STSG). Length of hospital stay was 14.5 days (2-65) for all patients. Median UFGSI score was 9 (1-30) for all patients. Twentythree of 63 patients (36.5%) with a UFGSI score ≥9 did not survive. Median APACHE II and FGSI scores were 9 (0-31) and 5 (0-23) respectively. In logistic regression analysis, only UFGSI score ≥9 was detected as a significant predictor of mortality (p=0.001, OR: 13.64, CI: 2.874-64.802). Logistic regression analysis results are shown in Table 1.

DISCUSSION In spite of the developing medical technology and experience, FG is still a fatal disease. A mortality rate of 20.8% was Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Yılmazlar et al. Fournier’s gangrene: Review of 120 patients and predictors of mortality

Table 1. Logistic regression analysis results for mortality predictors of Fournier’s gangrene Factors

P value

Odd’s Ratio

95% Confidence Interval

Lower Upper Gender

0.45 1.53 0.502 4.683

Symptom duration

0.13

0.43 1.55 0.521 4.623

1.09

0.976

1.215

Etiology Anorectal 0.79 1.18 0.353 3.963 Urogenital 0.84 0.84 0.154 4.591 Skin-based Stoma Debridement count UFGSI§ score ≥9

>0.99

Not estimated

–

0.42 1.68 0.478 5.921 0.89

1.02

0.789

1.316

0.001*

13.64

2.874

64.802

¶ Diabetes Mellitus, § Uludag Fournier’s gangrene severity index.

detected in our tertiary and experienced center. Accurate estimation of the risk of mortality can help patients and their physicians to manage treatment process and expectations. There are several methods of mortality prediction including APACHE II score and FGSI which are commonly used traditional scoring systems. On the other hand, UFGSI is a novel and powerful predictor of mortality associated with FG.[2] Impact of gender on the mortality risk has been previously investigated in several studies. Female pelvic anatomy has been claimed to be better for drainage of secretions through the vagina.[14] According to this theory, it has been thought that FG is more frequent in the male gender. On the other hand, Czymek et al. reported that female gender was a risk factor for increased mortality. Mortality rate was 50% for female patients while it was 7.7% for male patients in their study. They suggested that female pelvic anatomy was a disadvantage related with rapid dissemination of the disease.[15] In our serial, mortality rate for female patients was 30.8% compared to 16% in male patients. Although the mortality rate was double for female patients, female gender was not detected as a risk factor for mortality (p=0.454). Early diagnosis was reported to be associated with better outcomes in FG.[1,16-18] A study including 379 patients identified from a nationwide database has suggested that early surgical treatment within two days after admission reduces mortality of FG.[17] Also, the interval time between the onset of symptoms and initial debridement has been reported to be a major predictor of mortality.[18] Symptom duration was median seven days (1-40) in our study. Mortality rate was 27% for patients with symptom duration higher than seven days. A lower mortality rate (18%) was detected in patients with symptom duration of seven days or fewer. However, we failed to determine symptom duration as a risk factor (p=0.126). Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

More than half of all patients (57.5%), and 68% of non-survivors had DM in our serial. There are several studies showing DM as a risk factor for patients with FG.[1,3,6,7] Nevertheless, there are also some studies where DM has been reported as one of the most frequent comorbidities in patients with FG although not influencing outcomes.[8-11,16,19] Although it was the most common co-morbidity among all patients, DM was not determined as a risk factor for mortality (p=0.429). The most common origin of the FG was anorectal diseases (49.2%) in our study, followed by urogenital diseases and skin infections. Since it is not always possible to determine the exact origin of the disease, FG may be treated by general surgeons and urologists, as well. There are two previous studies from general surgery departments reporting perianal abscess as the most common etiological factor.[10,16] As a general surgery department, we have also observed anorectal-originated cases more frequently. However, a significant impact of etiology on the mortality rate has not been detected. Fecal diversion was needed in thirty-one patients (25.8%), and median debridement count was three (1-12) in the present study. We previously reported a 41% fecal diversion rate in 2010 and fecal diversion was established to be related with higher costs and morbidity rates.[20] In our current practice, we apply enemas routinely before changing the VAC dressings and change VAC dressings every 72 hours. VAC therapy offers fewer dressing changes, less pain, and similar costs comparing to conventional wound dressings in the management of FG patients.[21] Therefore, wounds can be kept clean, be healed rapidly, and diversion requirement and debridement count can be reduced. Reduced fecal diversion rate in the present study comparing to our previous study is associated with increased utilization of VAC therapy, well-management of cases, and increased experience. However, both fecal di335

Yılmazlar et al. Fournier’s gangrene: Review of 120 patients and predictors of mortality

version requirement and debridement count were not shown as a risk factor for mortality.

110 cases for aetiology, predisposing conditions, microorganisms, and modalities for coverage of necrosed scrotum with bare testes. N Z Med J 2008;121:46-56.

FGSI is a scoring system first described by Laor et al. in 1995. [13] It is a physiological and metabolic status based scoring system. There are several studies validating the accuracy of FGSI and determining it as a predictor of mortality.[16,22] We first described UFGSI in 2010 as a novel scoring system that can be used for predicting mortality in patients with FG. Determined threshold score for UFGSI was 9. It is a powerful scoring system combining age and disease dissemination with FGSI score and has a sensitivity of 94% and specificity of 81%.[2]

6. Yanar H, Taviloglu K, Ertekin C, Guloglu R, Zorba U, Cabioglu N, et al. Fournier’s gangrene: risk factors and strategies for management. World J Surg 2006;30:1750-4.

There is a recent study comparing FGSI, UFGSI, age-adjusted Charlson Comorbidity Index (ACCI) and Surgical APGAR (sAPGAR) scoring systems for FG.[23] Although all four scoring systems have been claimed to be useful for mortality prediction, it has been suggested that scores can be easily calculated using ACCI and sAPGAR. Nevertheless, the highest sensitivity rate (85%) was detected for UFGSI comparing to other scoring systems despite the low patient volume of the study. In this study, UFGSI was determined as a mortality predictor in multivariate analysis (p=0.001). Patients with a UFGSI score ≥9 were 13.64 times likely to develop mortality. Although risk factors affecting mortality in Fournier’s Gangrene were assessed from prospectively collected data of the largest single center cohort, there may be a selection bias since our hospital is a tertiary referral center. However, large sample size gives this research its clinical value. To the best of our knowledge, this is the largest single center serial reported in the literature. We also had the opportunity of validating the UFGSI scoring system in this large cohort. Depending on this scoring system, we can say that patients with wide disease dissemination and older than 60 years of age are in a high-risk group. Since mortality is the major problem for this devastating disease, extra attention is required for the management of the patients in high-risk group. Conflict of interest: None declared.

REFERENCES 1. Aridogan IA, Izol V, Abat D, Karsli O, Bayazit Y, Satar N. Epidemiological characteristics of Fournier’s gangrene: a report of 71 patients. Urol Int 2012;89:457-61. 2. Yilmazlar T, Ozturk E, Ozguc H, Ercan I, Vuruskan H, Oktay B. Fournier’s gangrene: an analysis of 80 patients and a novel scoring system. Tech Coloproctol 2010;14:217-23. 3. Eke N. Fournier’s gangrene: a review of 1726 cases. Br J Surg 2000;87:718-28. 4. Bjurlin MA, O’Grady T, Kim DY, Divakaruni N, Drago A, Blumetti J, et al. Causative pathogens, antibiotic sensitivity, resistance patterns, and severity in a contemporary series of Fournier’s gangrene. Urology 2013;81:752-8. 5. Bhatnagar AM, Mohite PN, Suthar M. Fournier’s gangrene: a review of

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7. Martinschek A, Evers B, Lampl L, Gerngroß H, Schmidt R, Sparwasser C. Prognostic aspects, survival rate, and predisposing risk factors in patients with Fournier’s gangrene and necrotizing soft tissue infections: evaluation of clinical outcome of 55 patients. Urol Int 2012;89:173-9. 8. Erol B, Tuncel A, Hanci V, Tokgoz H, Yildiz A, Akduman B, et al. Fournier’s gangrene: overview of prognostic factors and definition of new prognostic parameter. Urology 2010;75:1193-8. 9. Ruiz-Tovar J, Córdoba L, Devesa JM. Prognostic factors in Fournier gangrene. Asian J Surg. 2012;35:37-41. 10. Ersoz F, Sari S, Arikan S, Altiok M, Bektas H, Adas G, et al. Factors affecting mortality in Fournier’s gangrene: experience with fifty-two patients. Singapore Med J 2012;53:537-40. 11. Benjelloun el B, Souiki T, Yakla N, Ousadden A, Mazaz K, Louchi A, et al. Fournier’s gangrene: our experience with 50 patients and analysis of factors affecting mortality. World J Emerg Surg 2013;8:13. 12. Yilmazlar T, Ozturk E, Alsoy A, Ozguc H. Necrotizing soft tissue infections: APACHE II score, dissemination, and survival. World J Surg 2007;31:1858-62. 13. Laor E, Palmer LS, Tolia BM, Reid RE, Winter HI. Outcome prediction in patients with Fournier’s gangrene. J Urol 1995;154:89-92. 14. Gürdal M, Yücebas E, Tekin A, Beysel M, Aslan R, Sengör F. Predisposing factors and treatment outcome in Fournier’s gangrene. Analysis of 28 cases. Urol Int 2003;70:286-90. 15. Czymek R, Frank P, Limmer S, Schmidt A, Jungbluth T, Roblick U, et al. Fournier’s gangrene: is the female gender a risk factor? Langenbecks Arch Surg 2010;395:173-80. 16. Kabay S, Yucel M, Yaylak F, Algin MC, Hacioglu A, Kabay B, et al. The clinical features of Fournier’s gangrene and the predictivity of the Fournier’s Gangrene Severity Index on the outcomes. Int Urol Nephrol 2008;40:997-1004. 17. Sugihara T, Yasunaga H, Horiguchi H, Fujimura T, Ohe K, Matsuda S, et al. Impact of surgical intervention timing on the case fatality rate for Fournier’s gangrene: an analysis of 379 cases. BJU Int 2012;110(11 Pt C):E1096-100. 18. Korkut M, Içöz G, Dayangaç M, Akgün E, Yeniay L, Erdoğan O, et al. Outcome analysis in patients with Fournier’s gangrene: report of 45 cases. Dis Colon Rectum 2003;46:649-52. 19. Sorensen MD, Krieger JN, Rivara FP, Klein MB, Wessells H. Fournier’s gangrene: management and mortality predictors in a population based study. J Urol 2009;182:2742-7. 20. Ozturk E, Sonmez Y, Yilmazlar T. What are the indications for a stoma in Fournier’s gangrene? Colorectal Dis 2011;13:1044-7. 21. Ozturk E, Ozguc H, Yilmazlar T. The use of vacuum assisted closure therapy in the management of Fournier’s gangrene. Am J Surg 2009;197:660-5. 22. Ersay A, Yilmaz G, Akgun Y, Celik Y. Factors affecting mortality of Fournier’s gangrene: review of 70 patients. ANZ J Surg 2007;77:43-8. 23. Roghmann F, von Bodman C, Löppenberg B, Hinkel A, Palisaar J, Noldus J. Is there a need for the Fournier’s gangrene severity index? Comparison of scoring systems for outcome prediction in patients with Fournier’s gangrene. BJU Int 2012;110:1359-65.

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Yılmazlar et al. Fournier’s gangrene: Review of 120 patients and predictors of mortality

KLİNİK ÇALIŞMA - ÖZET OLGU SUNUMU

Fournier gangreni: 120 olgunun değerlendirmesi ve mortalite prediktörleri Dr. Tuncay Yılmazlar,1 Dr. Özgen Işık,1 Dr. Ersin Öztürk,1 Dr. Ali Özer,1 Dr. Barış Gülcü,1 Dr. İlker Ercan2 1 2

Uludağ Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Bursa; Uludağ Üniversitesi Tıp Fakültesi, Biyoistatistik Anabilim Dalı, Bursa

AMAÇ: Fournier gangreni (FG) acil ve agresif debridman gerektiren, yıkıcı ve potansiyel ölümcül bir hastalıktır. Bu çalışmanın amacı FG için mortalite prediktörlerini geniş bir kohortta araştırmaktır. GEREÇ VE YÖNTEM: Fournier gangreni hastalarının ileriye yönelik olarak kaydedilmiş verileri derlendi. Demografik veriler, semptom süresi, Uludağ Fournier Gangreni Şiddet Skoru (UFGSI), yandaş hastalıklar [özellikle diabetes mellitus (DM)], etiyoloji, debridman sayısı, stoma gereksinimi, yoğun bakım ve hastane yatış süresi, morbidite ve mortalite oranları değerlendirildi. Multivaryans analiz ile mortaliteye etkili faktörler belirlendi. BULGULAR: Median yaşı 58 (22-85) olan 120 hasta (81 erkek) çalışmaya alındı. Median UFGSI skoru 9’du (1-30). Altmış dokuz hastada (%57.5) DM vardı. FG 59 hastada perianal, 52 hastada ürogenital ve 9 hastada cilt kaynaklıydı. Median debridman sayısı 3’tü (1-12) ve 31 hastada stoma açıldı, 48 hasta yoğun bakımda takip edilirken 25 hastada mekanik ventilasyon desteği gerekti. Toplam mortalite oranı %20.8’di. Multivaryans analizde UFGSI tek mortalite prediktörü olarak saptandı (p=0.001). UFGSI 9 veya daha yüksek olan hastalarda mortalite oranı 13.64 kez daha sıktı. TARTIŞMA: Fournier gangreni acil cerrahi gerektiren ölümcül bir hastalıktır. UFGSI FG hastalarında mortalitenin etkin bir prediktörüdür. Anahtar sözcükler: Fournier gangreni; mortalite; şiddet skoru. Ulus Travma Acil Cerr Derg 2014;20(5):333-337

doi: 10.5505/tjtes.2014.06870

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ORIGIN A L A R T IC L E

A series of civilian fatalities during the war in Syria Adnan Çelikel, M.D.,1 Bekir Karaarslan, M.D.,2 Dua Sümeyra Demirkıran, M.D.,1 Cem Zeren, M.D.,1 Muhammet Mustafa Arslan, M.D.1 1

Department of Forensic Medicine, Mustafa Kemal University Faculty of Medicine, Hatay;

Department of Forensic Medicine, Gaziantep University Faculty of Medicine, Gaziantep

ABSTRACT BACKGROUND: A considerable number of deaths due to firearm injuries have occurred during wars all over the world. In this study, it is aimed to evaluate demographic characteristics and injury properties of cases died during civil war in Syria. METHODS: The postmortem examination and autopsy reports of 321 forensic deaths occurred between January and December 2012 were analyzed, retrospectively. Of the 321 forensic deaths,186 cases were injured and died in the civil war in Syria and, therefore, included in the scope of the study. Four cases died by natural causes or traffic accidents were excluded. RESULTS: Cases were most commonly (n=73, 39.2%) aged between 21 and 30 years, and 21.5% (n=40) of cases aged under 20 years. Of females, 68.8% (n=11) were children and young adults under 20 years of age. An overwhelming majority of deaths (n=125, 67.2%) were caused by explosive and shrapnel injuries, followed by (n=49, 26.3%) gunshot injuries related deaths. CONCLUSION: This study indicated that a significant proportion of those who died after being injured in the Syrian war were children, women and elderly people. The nature and localization of the observed injuries indicated open attacks by military forces regardless of targets being civilians and human rights violations. Key words: Autopsy; civilian deaths; Syrian war.

INTRODUCTION People are widely exposed to adverse effects of wars worldwide. During wars, besides deaths of soldiers, high rates of civilian deaths have been reported. Injuries and deaths of soldiers and civilians were seen during the uprising in Syria in Arab Spring. Additionally, due to civil war, considerable social and medical problems were caused by migration to neighboring countries as refugees.[1,2] Individuals injured in the civil war in Syria were mostly transferred to Hatay, a neighboring city of Turkey, for treatment. Among these, those who died were included in the scope of this study. Cases of deaths caused by injuries in the civil war

Address for correspondence: Adnan Çelikel, M.D. Mustafa Kemal Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, Hatay, Turkey Tel: +90 326 - 229 10 00 E-mail: celikeladnan@yahoo.co.uk Qucik Response Code

338

in Syria were evaluated in terms of demographic characteristics and features. Data collected was statistically analyzed and discussed in light of the related literature.

MATERIALS AND METHODS The records of Hatay Public Prosecutor’s Office were used. The postmortem examination and autopsy reports of 321 forensic deaths occurred between January and December 2012 were analyzed, retrospectively. Of the 321 forensic deaths, 186 deaths caused by injuries in the civil war in Syria were included in the scope of the study. Four cases that migrated to Turkey because of war and died by natural causes or traffic accidents were excluded from the study. Although sufficient information on the occupations of the cases could not be obtained, it was evaluated in accordance with the statements of their relatives. These cases were evaluated in terms of age, gender, injured body parts, and types of injury. Cases were assessed by two independent physicians using AIS (abbreviated injury scale) and ISS (Injury Severity Score). Data collected was statistically analyzed using SPSS (Statistical Package for Social Sciences) for Windows13.0. Distribution between the ISS values and injury sites was evaluated by one way ANOVA test and a p value of <0.05 was considered as statistically significant. Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Çelikel et al. A series of civilian fatalities during the war in Syria

of building collapse, fall from height and being thrown onto wreckage and etc. during explosions. Observed injuries were gunshot wounds, explosive and shrapnel injuries, burns and blunt traumatic injuries.

RESULTS Among the cases, 91.4% (n=170) were male and 8.6% (n=16) were female. Ages of males ranged between 2 and 89 years, while ages of females ranged between 1 and 60 years. Mean age of males and females were 32 and 18 years, respectively (Table 1). Regarding age groups, a great number of cases (n=73, 39.2%) aged between 21 and 30 years. Among all, 21.5% (n=40) of cases aged under 20 years. Interestingly, 68.8% (n=11) of females were under 20 years of age. An overwhelming majority of deaths (n=125, 67.2%) were caused by explosive and shrapnel injuries, followed by (n=49, 26.3%) gunshot injuries related deaths. Among the remaining cases, twelve (6.5%) were caused by blunt force traumas as a result

Eighteen out of 186 cases (9.7%) were dead on admission to the hospital. Eighty-three out of 186 cases (44.6%) died within the first 24 hours after arrival to the hospital. On the other hand, the rest (n=85, 45.7%) died during treatment within 2-120 days due to complications of primary injuries. A great number of cases (n=101, 54.3%) suffered from multiple regional injuries, followed by head and neck (n=45, 24.2%) injuries (Table 2). In vast majority of cases, the cause of death

Table 1. General properties of cases

% Minimum Maximum

Mean

Age (years) Men

170 91.4

85.00

31.8±14.6

Women

16 8.6

60.00

18.2±17.3

All cases

186

30.6±15.3

Injury Severity Score

186

43.0±21.5

Duration of treatment (days)

186

120

5.4±11.1

Table 2. Distribution of injured body parts Body part

Head and Neck

24.2

Chest, Abdomen and Back

15.3

Extremities

12 6.3

Multiple parts

101

Total

186 100

54.3

Table 3. Distribution of causes of death Cause of death

Brain hemorrhage and brain damage

37.6

Vascular damage and exsanguinations

22.6

Internal organ damage and internal hemorrhage

16.2

Internal organ damage and complications

11.8

Brain hemorrhage and internal hemorrhage

8.1

Bone fracture and complications

2.2

Spinal fractures and respiratory paralysis

0.5

Burns and complications

0.5

Brain damage and complications (meningitis)

0.5

Total

186

100

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Ă&#x2021;elikel et al. A series of civilian fatalities during the war in Syria

Table 4. Comparison of injury regions according to ISS

Body regions

Mean

Std. Deviation

ISS Head-Neck

45 44.8889 25.01383

0.001

Multiple region

101

0.001

Chest-Abdomen 28 31.0357 17.50023

0.001

Extremity

0.001

47.2178

20.17355

12 29.3333 11.22767

*p<0.05; ISS: Injury Severity Score.

was traumatic brain injury and hemorrhage, followed by exsanguinations due to damage of vessels and/or internal organs (Table 3) (Figure 1).

AIS scores were â&#x2030;Ľ4 in all cases. AIS scores were 5 in 54.8% (n=102), while 6 in 27.4% of cases. There was a statistically significant difference between ISS scores regarding injured

(a)

(b)

(c)

(d)

(e)

(f)

Figure 1. (a) Injury due to blunt trauma. (b) Injury due to explosion. (c-f) Shrapnel injury.

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body parts, which was most significant in cases of head and neck injuries (Table 4) (Figure 1).

DISCUSSION 18.6% of deaths caused by firearm injuries all over the world have reportedly occurred during wars. War related injuries and deaths demonstrate different characteristics compared to civilian traumas. Civilian traumas are mostly blunt force traumas while war related traumas are mostly responsible for penetrated injuries caused by firearms and explosives (shrapnel, bullets, etc.). Injuries caused by pieces of shrapnel have been reported to be more fatal compared to injuries by bullets.[3-6] Similar to the literature, in the presented series an overwhelming majority of deaths were (n=125, 67.2%) caused by shrapnel injuries due to explosions. A study dealing with injured body parts during wars revealed that injury rates for different body parts were quite close. Head, neck, chest, and abdominal injuries were reported to be more fatal compared to injuries involving extremities. Most war related deaths have been reported to occur instantaneously at the incident scene or within the first 30 minutes after admission to a hospital.[7] Another study interested in fatalities during the war in Croatia showed that injuries mostly involved muscle and soft tissue, followed by bony tissue, abdominal and thoracic regions.[6] Studies concerning injuries caused by bombings presented that head and neck injuries were responsible for high morbidity and mortality.[8-13] In our study, injuries involving multiple body parts took the first place, followed by injuries involving the head and neck region. AIS scores were ≥ 4 in all cases. ISS scores were most significantly increased in cases of head and neck injuries. Similarly, in our series, the most common cause of death was head and neck injuries. High ratio of head and neck injuries, and injuries involving multiple body parts are thought to be the results of bombing attacks (air strikes, tank and mortar attacks, hand grenade explosions, and etc.). Previously conducted studies showed that civilians were the ones mostly affected and human rights were violated during wars all over the world. During Croatian war, it was reported that out of 23% civilian deaths, 5.8% were children and 27.9% were females.[6] Similarly, among injured individuals in Palestine, 9% were women and 12% were children under 14 years of age.[5] Dramatically, during the Gulf war, civilian injuries comprised 34%.[14] In accordance with the literature, among the fatalities presented in this study, women constituted 8.6%, children and young adults under 20 years of age constituted 21.6%, and individuals aged over 50 years constituted 10.8%. The subjects in this study included patients injured during Syrian war and died in our city. In the presented series, injuries were induced by gunshot wounds, explosive and shrapnel injuries, and burns and blunt traumatic injuries. Interestingly, shrapnel injuries involved extensive tissue damUlus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

age characterized with dirtiness and burned irregular edges. Bone fractures, brain and internal organ damages caused by small shrapnel pieces indicated high-energy impact. In addition, we believe that lack of a timely and professional first aid increased death risks. Forensic autopsies were carried out to find out the mechanism, cause and manner of death, and to determine time of death, characteristics and severity of wounds, and factors contributing to death. Owing to its judicial nature, performing detailed forensic autopsies on bodies in the course of war is of high importance in terms of documenting the characteristics of injuries. This study indicated that a significant proportion of those who injured and died in the Syrian war were children, women and elderly people. However, since cases exposed to more severe and fatal wounds died in the battlefield, the rate of civilian deaths is estimated to be much higher than presently reported. The nature and localization of the observed injuries suggested that these deaths might have been caused by air strikes indicating open attacks by military forces without discriminating civilians and opposition forces. Furthermore, obtained results are strongly indicative of significant human rights violations during the uprising and civil war in Syria. Conflict of interest: None declared.

REFERENCES 1. Coupland RM, Meddings DR. Mortality associated with use of weapons in armed conflicts, wartime atrocities, and civilian mass shootings: literature review. BMJ 1999;319:407-10. 2. Zeren C, Arslan MM, Aydoğan A, Özkalıpçı Ö, Karakuş A. Firearm injuries documented among Syrian refugees in Antakya Turkey. British Journal of Arts and Social Sciences 2012;5:1-5. 3. Rogov M. Pathological evaluation of trauma in fatal casualties of the Lebanon War, 1982. Isr J Med Sci 1984;20:369-71. 4. Bellamy RF. The medical effects of conventional weapons. World J Surg 1992;16:888-92. 5. Helweg-Larsen K, Abdel-Jabbar Al-Qadi AH, Al-Jabriri J, BrønnumHansen H. Systematic medical data collection of intentional injuries during armed conflicts: a pilot study conducted in West Bank, Palestine. Scand J Public Health 2004;32:17-23. 6. Hebrang A, Henigsberg N, Golem AZ, Vidjak V, Brnić Z, Hrabac P. Care of military and civilian casualties during the war in Croatia. [Article in Croatian] Acta Med Croatica 2006;60:301-7. [Abstract] 7. Scope A, Farkash U, Lynn M, Abargel A, Eldad A. Mortality epidemiology in low-intensity warfare: Israel Defense Forces’ experience. Injury 2001;32:1-3. 8. Peev MP, Naraghi L, Chang Y, Demoya M, Fagenholz P, Yeh D, et al. Real-time sample entropy predicts life-saving interventions after the Boston Marathon bombing. J Crit Care 2013;28:1109.e1-4. 9. Emile H, Hashmonai D. Victims of the Palestinian uprising (Intifada): a retrospective review of 220 cases. J Emerg Med 1998;16:389-94. 10. Frykberg ER, Tepas JJ 3rd. Terrorist bombings. Lessons learned from Belfast to Beirut. Ann Surg 1988;208:569-76. 11. Scott BA, Fletcher JR, Pulliam MW, Harris RD. The Beirut terrorist

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Çelikel et al. A series of civilian fatalities during the war in Syria bombing. Neurosurgery 1986;18:107-10. 12. Frykberg ER, Tepas JJ 3rd, Alexander RH. The 1983 Beirut Airport terrorist bombing. Injury patterns and implications for disaster management. Am Surg 1989;55:134-41. 13. Hadden WA, Rutherford WH, Merrett JD. The injuries of terrorist

bombing: a study of 1532 consecutive patients. Br J Surg 1978;65:52531. 14. Hinsley DE, Rosell PA, Rowlands TK, Clasper JC. Penetrating missile injuries during asymmetric warfare in the 2003 Gulf conflict. Br J Surg 2005;92:637-42.

KLİNİK ÇALIŞMA - ÖZET OLGU SUNUMU

Suriye’deki savaş esnasında meydana gelen sivil ölümler Dr. Adnan Çelikel,1 Dr. Bekir Karaarslan,2 Dr. Dua Sümeyra Demirkıran,1 Dr. Cem Zeren,1 Dr. Muhammet Mustafa Arslan1 1 2

Mustafa Kemal Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, Hatay; Gaziantep Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, Gaziantep

AMAÇ: Tüm dünyada ateşli silah yaralanmaları nedeniyle meydana gelen ölümlerin önemli bir kısmını savaş esnasında meydana gelmektedir. Bu çalışmada Suriye’deki iç savaş nedeniyle ölen olguların demografik özellikleri ve yaralanma niteliklerinin değerlendirilmesi amaçlandı. GEREÇ VE YÖNTEM: Hatay merkezde 2012 Ocak-Aralık ayları arasında meydana gelen 321 adli ölüm olgusunun ölü muayene ve otopsi tutanakları geriye dönük olarak incelendi. Suriye’de meydana gelen çatışmalar esnasında yaralanarak ölen 186 olgu çalışma kapsamına alındı. Doğal hastalık veya trafik kazası sonucu ölen dört olgu çalışma dışı bırakıldı. BULGULAR: Olgular en sık olguların 21-30 yaş aralığında olduğu (n=73, %39.2), 20 yaş altındaki olgu oranının %21.5 (n=40) olduğu belirlendi. Kadın olguların %68.8 (n=11) oranında 20 yaş altı çocuk ve ergenler olduğu görüldü. Olguların %67.2 (n=125) oranında bombalama ve şarapnel etkisi ile %26.3’ünün ateşli silah mermi çekirdeği yaralanması sonucu öldüğü belirlendi. TARTIŞMA: Sonuç olarak savaşta yaralanarak ölenlerin önemli bir bölümünün çocuk, kadın ve yaşlı kişiler olduğu görüldü. Yaralanma nitelik ve özellikleri silahsız sivillerin gözetilmeksizin yapılan saldırılar nedeniyle önemli insan hakları ihlalleri meydana gelmektedir. Anahtar sözcükler: Otopsi; sivil ölümler; Suriye savaşı. Ulus Travma Acil Cerrahi Derg 2014;20(5):338-342

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doi: 10.5505/tjtes.2014.71173

Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

ORIGIN A L A R T IC L E

The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis: a single-center prospective study Idris Akcay, M.D.,1 Alexis K. Okoh, M.D.,2 Orcun Yalav, M.D.,3 Ismail C. Eray, M.D.,3 Ahmet Rencuzogullari, M.D.,3 Kubilay Dalci, M.D.,3 Hasan Elkan, M.D.,4 Ali H. Alparslan, M.D.3 1

Department of General Surgery, Dr. Yaşar Eryılmaz Doğubeyazıt State Hospital, Ağrı;

Department of General Surgery, Ankara University Faculty of Medicine, Ankara;

Department of General Surgery, Çukurova University Faculty of Medicine, Adana;

Department of General Surgery, Balıklıgöl State Hospital, Şanlıurfa

ABSTRACT BACKGROUND: Infections and sepsis remain the leading cause of morbidity and mortality in secondary peritonitis. Clinicians are still challenged with the task of finding an early and reliable diagnosis of septic complications. The role of inflammatory markers (Procalcitonin (PCT), C-reactive Protein (CRP) and thyroid hormones in determining the severity of secondary peritonitis was evaluated in this study. METHODS: On the preoperative and first, third, fifth, seventh, and fourteenth postoperative days, PCT, CRP, and thyroid hormone concentrations were measured in serum taken from eighty-four consecutive patients who were operated on for secondary peritonitis between January 2008 and January 2010. All data was entered and analyzed using the Statistical Package for Social Sciences, version 15.0 and clinical parameters were compared using the student’s t-test. RESULTS: For the groups diagnosed with perforated viscus, PCT concentrations were significantly low in contrast to high thyroid hormone levels in patients who developed postoperative complications or died when compared to patients whose postoperative course was uneventful or discharged. The PCT concentration significantly correlated with the CRP concentration and WBC count. CONCLUSION: In the absence of postoperative complications, PCT is a better predictor of outcome than CRP in secondary peritonitis. Our study showed that a low thyroid hormone level can serve as an important prognostic parameter of disease severity in secondary peritonitis. Key words: C-reactive protein; procalcitonin; secondary peritonitis; thyroid hormone.

INTRODUCTION Secondary peritonitis, a condition caused by the spread of bacteria and contents of intraabdominal organs into the peritoneal cavity, is one of the most important causes of abdominal sepsis carrying a higher risk of mortality and morbidity

Address for correspondence: Ahmet Rencuzogullari, M.D. Çukurova Üniversitesi Tıp Fakultesi, Genel Cerrahi Anabilim Dalı, 01130 Adana, Turkey. Tel: +90 322 - 338 60 60 E-mail: rncz1980@gmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

in surgical intensive care units.[1] Mortality in secondary bacterial peritonitis is reported to be over 60% and known to correlate with the severity of the disease usually accessed by scoring systems such as the APACHE II/III and Mannheim Peritonitis Index (MPI).[2] Other highly specific diagnostic modalities such as radiological imaging procedures or percutaneous aspiration have been proven to be useful tools in predicting overall disease severity and outcome. An early and reliable diagnosis, together with a prompt and adequate treatment including immediate surgical repair of the underlying abdominal pathology, significantly contributes to a decreased mortality and morbidity.[3] The management of postoperative complications or new onset abdominal sepsis occurring in patients after initial surgical repair still remains a compelling issue to the attending surgeon. The need for novel approaches to overcome this clinical dilemma has arisen 343

Akcay et al. The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis

and recent studies have investigated the role of easy, fast, and non-invasive diagnostic modalities in predicting the outcome during postoperative course. Non-specific signs of sepsis and infections include clinical symptoms such as fever, tachycardia, tachypnea, and leukocytosis on laboratory findings. Scoring systems have been proven to be useful tools in predicting overall disease severity and outcome; however, they fail to distinguish between infectious and non-infectious related complications. In contrast, other highly specific diagnostic modalities such as radiological imaging procedures or percutaneous aspiration techniques are costly, carry a considerable risk of complications and pose an additional stress on the patients.[2,4,5] Facing this clinical quandary, the clinical appraisal of inflammatory markers in helping to establish a fast, reliable, and non-invasive diagnosis algorithm for sepsis in surgical patients has gained considerable interest among clinicians since the late 1980s. Among the large array of inflammatory parameters, CRP and PCT have obtained special interest in identifying patients at risk for severe complications following surgical intervention of secondary peritonitis.[6-8] PCT, under normal conditions, is the 116-amino acid peptide precursor of the biologically active hormone calcitonin secreted by the c-cells of the thyroid gland. With the advent of the semi-automated assay technique, PCT assessment has become feasible in recent years. Its levels are relatively low in healthy subjects but known to increase in patients with bacterial infections or sepsis and fall dramatically after appropriate antimicrobial therapy.[9] However, PCT levels do not change in response to severe viral infections or other inflammatory response syndromes. Hence, PCT has been confirmed as the only biochemical indicator closely correlating with the inflammatory host response to bacterial infections.[10-12] Low levels of thyroid hormones have been reported in cases of sepsis, severe stress, trauma, and critical conditions such as cirrhosis. Euthyroid sick syndrome is characterized by abnormal thyroid findings in the presence of non-thyroidal illness (NTIs) without evidence of pre- existing hypothalamic pituitary conditions. The most common alternations are low T3, normal or low T4, and normal TSH levels. Studies have described a relationship between the severity of NTIs and low T3 and T4 levels with T3 and T4 levels gradually normalizing as the patients recover. Other studies have also associated low serum levels of T3 and T4 with a higher mortality in sepsis and severe bacterial infections. Even-though recent efforts into the development of an easier, faster and much more reliable diagnostic algorithm that can also serve as a predictor of outcome in postoperative sepsis related complications are encouraging, the exact role of inflammatory markers in predicting outcome in patients diagnosed with secondary peritonitis hasnâ&#x20AC;&#x2122;t still been clarified. Existing data is scarce and evidence to support them are lacking. In the sight of these, it was aimed to investigate the 344

prognostic values of inflammatory markers (CRP, PCT and thyroid hormones) in secondary peritonitis. PCT, CRP and thyroid hormones can be useful prognostic parameters for predicting disease severity and outcome in patients diagnosed with secondary peritonitis.

MATERIALS AND METHODS Our study is a single center prospective cohort study conducted on patients operated on for secondary peritonitis between January 2008 and January 2010. A total of 120 patients were operated on for secondary peritonitis within the study period. Patients with localized peritonitis and those whose laboratory values (thyroid function tests, CRP and PCT) couldnâ&#x20AC;&#x2122;t be determined were excluded from the study. Patients operated on for generalized peritonitis were included into the study. Of the 120 patients, eighty-four were found to be eligible for the study. Among the 84 patients, there were two patients with ovarian malignancy and one with colon malignancy. There were no cases of typhoid perforation. Patientsâ&#x20AC;&#x2122; data was reviewed and recorded into an institutional review board-approved database. The database was analyzed to identify those patients with secondary peritonitis. Patients were divided into six groups according to the diagnosis confirmed during surgery, including Group 1: perforated appendicitis, Group 2: perforated peptic ulcer disease, Group 3: small bowel perforation (iatrogenic, typhoid, vasculitis), Group 4: colon perforation (iatrogenic, diverticula, foreign body), Group 5: anastomosis dehiscence, and Group 6: gallbladder perforation. The data collected included patient demographics, and PCT, CRP, and thyroid hormone (ft3, ft4, TSH) concentration values of the preoperative and first, third, fifth, seventh, and fourteenth postoperative days. Informed consent was sought and approval received from each subject participating in the study. In addition, the presence of limiting factors such as co-morbid conditions, previous drug, medical and surgical history were thoroughly investigated. Patients with previous history of thyroid surgery, usage of drugs such as beta blockers, amiodarone and steroids were determined and noted. Moreover, the absence of any other focus of infection besides peritonitis was investigated and recorded. During the postoperative course, post-operative complications, cases of mortality developing one month after surgery and their causes were established and recorded. Post-operative early or late morbidity/mortality was defined as complications/death developing during one month or one month following surgery. The median age, PCT, CRP and thyroid hormone (ft3, ft4, TSH) concentration values, morbidity and mortality rates of classified groups were examined and statistical analysis was performed. Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Akcay et al. The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis

Clinical Follow-up At the time of admission and on the first, third, fifth, seventh, and fourteenth postoperative days, venous blood was drawn from all patients and centrifuged at 1.000×g for 10 min at 4°C after a full blood cell count. All samples were tested for PCT, CRP, and thyroid hormones within 30 min after acceptance by the clinical laboratory. Patients presented with small bowel perforation and colon perforation, two patients presented with gallbladder perforation and one patient with perforated acute appendicitis were followed up in the surgical intensive care unit. All other patients were followed up in hospital wards. During follow-up, wounds of all patients were carefully followed and appropriate anti-microbial therapy was given in cases of skin infections.

Laboratory Measurements PCT quantification was performed using automated immunoanalysis with the Liaison analyzer (Diasorin, Saluggia, Italy). For CRP, an immunoturbidimetric assay with ADVIA Chemistry CRP_2R (Siemens Medical Solutions Diagnostics, Tarrytown, NY, USA) was used. The thyroid hormone (fT3, fT4, TSH) levels were determined using the the Sysmex XT 2000-i (Roche Diagnostics Gmb H. Mannheim, Germany) instrument.

USA). Collected data was tested for normality and found to be normally distributed and were therefore expressed as mean ± standard deviation (SD). Continuous data was evaluated using the Student’s t-test and nonparametric data analyzed using the Friedman’s test. Descriptive data was given as absolute numbers (percentages) or as medians (interquartile ranges or 95% confidence intervals [CIs]). Independent samples were compared using the student’s t-test and non-parametric data was evaluated using the Friedman test. Statistical significance was accepted as p≤0.05.

RESULTS Between January 2008 and January 2010, eighty-four patients undergoing surgery for secondary peritonitis were included into the study. Among these, there were perforated appendicitis (n=21), peptic ulcer perforation (n=20), small bowel perforation (n=14) (iatrogenic, typhoid, vasculitis), colon perforation (n=13) (iatrogenic, diverticula, foreign body), gallbladder perforation. (n=3), and anastomosis dehiscence (n=6) cases. The study included 47 (56%) males and 37 (44%) females with a median age of 52.3 years (15-87). The ages of patients according to the diagnosis made at presentation are shown in Table 1. Thirty-four patients included in the study Table 1. The ages of patients according to diagnosis

Surgical Technique

Diagnosis Age

The procedure was performed with the patients under general anesthesia. Laparotomy type was decided based on clinical, laboratory, and radiological findings at presentation. Of the twenty-one patients diagnosed with perforated appendicitis, a McBurney incision was made on 4, right para-median incision on 15 and lower midline incision (due to radiologically detected air fluid levels) on 2. An upper midline incision was employed in all other patients. Primary suture was performed in all patients diagnosed with peptic ulcer perforation. Appendectomy was performed in all patients with perforated appendectomy. For patients with perforated small bowel, primary suturing or anastomosis was performed proximal or distal to the location of perforation when abdominal contents weren’t contaminated. In cases of contamination, stoma was performed. Anastomosis was performed in four patients presented with colon perforation, repair in 2 patients and stoma in 7 patients. Stoma was performed in all patients (6 in total) diagnosed with anastomosis dehiscence.

Mean±SD Min-Max

Perforated appendicitis

43.9±20.2

15-79

Peptic ulcer perforation

53.8±20.1

25-80

Small bowel perforation

53.7±16.7

24-87

Colon perforation

52.6±17.6

29-80

Anastomosis dehiscence

61.1±7.6

51-71

Gall-bladder perforation

72.6±8.3

66-82

Drainage was placed in patients falling within the following category: old age, contaminated abdominal contents, or those who had the potential of developing abdominal abscesses (72% of all patients).

Statistical Analysis All data was entered and analyzed using the Statistical Package for Social Sciences, version 15.0 (SPSS, Inc. Chicago, IL, Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Table 2. Other diseases Other diseases

COPD

6 7.1

Coronary artery disease

7.1

Hypertension (HT)

8.3

Diabetes mellitus (DM)

7.1

Atrial Fibrillation

2.4

Polyposis Coli

2.4

Chronic liver disease

2.4

Ovarian cancer

2.4

DM-HT

2 2.4

Other

15 17.8

Absent

34 40.5

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Akcay et al. The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis

had no prior history of co-morbid conditions in contrast with 50 subjects who had chronic obstructive pulmonary disease (COPD) (n=6), coronary artery disease (n=6), hypertension (n=6), diabetes mellitus (n=2), chronic atrial fibrillation (n=2) (Table 2). Drug history revealed no history of drug use (n=44), beta-blockers (n=14), steroids (n=3), and insulin (n=3). The median preoperative serum PCT and CRP levels of patients in Group 1 (n=21) were 9.9 ng/ml and 190 mg/L. These values regressed to 0.19 ng/ml and 63 mg/L respectively, for both parameters on postoperative day 14. Median preoperative serum PCT and CRP levels of patients in Group 2 (n=20) were 10.1 ng/ml and 180 mg/L. There was a decrease in serum levels of PCT to 6.7 ng/L on postoperative day 5; however, levels fluctuated between 2-3 ng/L after day 5 until postoperative day 14. In contrast, there was a constant decrease in serum CRP levels till 78 mg/L on postoperative day 14.

hormone levels of patients who survived (+) and those who died (-) among the various groups are illustrated in Tables 4, 5, 6, and 7. When the patients were further grouped into surviving (+) and deceased (-), the median serum CRP levels in patients with small bowel perforation on postoperative day 3 was found to be (+) 192 mg/ml, (-) 90 mg/ml, (p=0.036). Pre and postoperative data regarding CRP compared among other groups did not reach statistical significance. The role of thyroid hormones in determining prognosis and severity in secondary peritonitis was also investigated by comparing median pre and postoperative thyroid hormone levels among complication free or bound patients and patients who survived or died during follow-up.

With the aim of determining a relationship between PCT levels and morbidity, the PCT levels of patients developing complications during follow-up and those who didn’t were compared. Median preoperative PCT levels in patients developing complications (+) and those who didn’t (-) were 15.5 ng/L and 3.4 mg/ml, respectively (p=0.043).

When results of median thyroid hormone levels in patients were compared among groups based on occurrence of complication during follow-up, they were found to be statistically significant. For complication bound (+) and complication free (-) patients in Group 2; postoperative day: 3 T4 (+) 0, 83, (-) 1, 46 (p=0.003), and postoperative day 5: T4 (+) 0, 96, (-) 1, 49 (p=0.031). Complication bound (+) and complication free (-) patients in Group; postoperative day 1: T3 (+) 3, 58, (-) 1, 93 (p=0.025), postoperative day 1: TSH (+) 1, 01, (-) 1, 39 (p=0.031), postoperative day 7: T4 (+) 1, 07, (-) 1, 51 (p=0.27), and postoperative day 14: T3 (+) 2, 16, (-) 3,09 (p=0,28). Complication bound (+) and complication free (-) patients in Group 4; postoperative day 1: TSH (+) 1, 26, (-) 2, 72 (p=0.035), and postoperative day 7: T3 (+) 1, 91, (-) 2, 59 (p=0.009).

The prognostic value of PCT, CRP and thyroid hormones in predicting mortality was also investigated among the groups by comparing the pre and postoperative serum levels in patients who survived and those who died during follow-up. Table 3 shows the number and percentage of patients who died and survived within each of the six groups during follow-up. Pre and postoperative serum PCT, CRP and thyroid

Laboratory data findings in patients who survived and those who died during follow-up were also analyzed for a possible correlation. Data of surviving patients (+) and patients who died (-) in the various groups revealed the following: Group 2; postoperative day 3: T4 (+) 1, 37, (-) 0, 58 (p=0.002), postoperative day 5: T4 (+) 1, 39, (-) 0, 69 (p=0.039), and postoperative day 7: T3 (+) 2, 40, (-) 1, 64 (p=0.019). Group 3; postop-

The median preoperative serum PCT levels of patients in Group 3 (n=14) showed a rather different pattern by remaining above 7ng/L till postoperative day 7 when it began to follow a falling trend. A similar pattern was true for CRP values in this group of patients.

Table 3. Numbers of discharged and deceased patients operated on for secondary peritonitis Diagnosis

346

Discharged

Deceased Total

n % n %

Perforated appendicitis

100

–

Peptic ulcer perforation

Small bowel perforation

Colon perforation

Anastomosis dehiscence

Gallbladder perforation

100

–

Total

64 76 20 24 84

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Akcay et al. The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis

Table 4. Comparison of CRP, PCT and Thyroid Hormone levels among deceased and discharged patients diagnosed with peptic ulcer perforation

Peptic ulcer perforation (n=20) Discharged (n=13)

Deceased (n=7)

Mean±SD Mean±SD

Preop. T3

2.18±0.61

2.23±0.6

1.47±.040

1.03±0.67 NS

Thyroid-stimulating hormone

1.64±0.89

1.42±1.38

150±79

234±143

C-reactive protein

Procalcitonin

9.30±18.65

11.9±9.8

Postop1 T3

1.93±0.57

2.31±0.82

1.39±0.32

1.18±0.61 NS

Thyroid-stimulating hormone

1.86±1.63

1.66±1.32

C-reactive protein

151±82

186±84

Procalcitonin

7.19±15.49

5.73±2.28

Postop. 3 T3

2.29±0.76

2.52±1.8

1.37±0.37

0.58±0.38 0.002

Thyroid-stimulating hormone

2.24±1.47

1.15±0.73

116±58

173±54

Procalcitonin

2.14±3.4

17.9±19.5

0.010

Postop. 5 T3

2.24±0.76

1.44±0.28

C-reactive protein

1.39±0.42

0.69±0.34 0.039

Thyroid-stimulating hormone

2.48±1.75

0.86±0.61

C-reactive protein

119±38

157±40

1.27±2.37

2.05±0.88

Postop. 7 T3

2.4±0.57

1.64±0.18

0.019

1.46±0.35

1.06±0.04 NS

Thyroid-stimulating hormone

2.22±1.51

1.56±0.87

62±36

93±55

Procalcitonin

1.92±5.68

0.80±0.36

Postop. 14 T3

2.49±0.88

1.44±0.33

Procalcitonin

C-reactive protein

1.16±0.36

0.98±0.16 NS

Thyroid-stimulating hormone

3.41±3.72

1.98±0.98

C-reactive protein Procalcitonin

80±109

65±46

3.88±8.45

0.70±47

erative day 1: T3 (+) 2, 49, (-) 3, 64 (p=0.026), postoperative day 3: T4 (+) 1, 45, (-) 1, 00 (p=0.012), and postoperative day 7: T4 (+) 1, 43, (-) 0, 87 (p=0.023). Group 4; postoperative day 1: TSH (+) 2, 54, (-) 0, 57 (p=0.020) and postoperative day 3: TSH (+) 2, 35, (-) 0, 67 (p=0.006). We found that thyroid hormone levels changed much among patients with small bowel perforation and peptic ulcer perforation that had postoperative complications and those who died. Findings from our study showed postoperative T4 and T3 levels lower than 1 µg/l and 3.64 µg/respectively, which Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

can be associated with a higher morbidity and mortality in these groups.

DISCUSSION Mortality in secondary bacterial peritonitis is reported to be over 60% and known to correlate with the severity of the disease which is usually accessed by scoring systems such as the APACHE II/III and Mannheim Peritonitis Index (MPI).[2] These scoring systems fail to distinguish between infectious and non-infectious related complications but other highly specific 347

Akcay et al. The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis

Table 5. Comparison of CRP, PCT and Thyroid Hormone levels among deceased and discharged patients diagnosed with small bowel perforation

Small Bowel Perforation (n=21) Discharged (n=14)

Mean±SD Mean±SD

Preop. T3

1.95±1.67

4.51±3.37

1.36±0.44

1.48±0.47 NS

Thyroid-stimulating hormone

1.01±0.64

1.42±0.87

C-reactive protein

175±105

130±54

Procalcitonin Postop. 1 T3

11.3±15 2.49±1.70

0.042

6.9±5.8 NS 3.64±0.64

0.026

1.38±0.39

1.17±0.47 NS

Thyroid-stimulating hormone

1.40±1.30

0.67±0.42

C-reactive protein

166±89

121±72

Procalcitonin

14.7±28

6.8±9.1 NS

Postop. 3 T3

2.95±1.56

2.82±0.64

1.45±0.35

1.0±0.16 0.012

Thyroid-stimulating hormone

2.35±2.94

1.55±2.18

C-reactive protein

192±102

90±26

0.036

Procalcitonin

15.1±29.3

Postop. 5 T3

3.0±1.59

2.6±3.9 NS 4.03±1.97

1.34±0.38

1.01±0.37 NS

Thyroid-stimulating hormone

2.01±2.41

1.33±0.38

135±94

128±38

C-reactive protein Procalcitonin

11.9±27.7

6.0±7.0 NS

Postop. 7 T3

3.15±1.77

1.81±0.74

1.43±035

0.87±0.33 0.023

Thyroid-stimulating hormone

2.23±2.05

4.54±4.01

105±77

78±25

C-reactive protein

Procalcitonin

7.1±13.6

0.80±1.08 NS

Postop. 14 T3

2.71±0.81

2.28±0.62

1.47±0.33

1.14±0.16 NS

Thyroid-stimulating hormone

2.62±3.61

3.08±3.37

61±32

C-reactive protein Procalcitonin

66±37 0.90±1.50

diagnostic modalities such as radiological imaging procedures or percutaneous aspiration have been proven to be useful tools in predicting overall disease severity and outcome. The clinical appraisal of inflammatory markers has gained considerable interest in identifying patients at risk for severe complications following surgical intervention[3-12] of secondary peritonitis with recent studies identifying CRP and PCT as prospective prognostic markers in secondary peritonitis. [3] In the sight of these, it was aimed to investigate the prognostic values of inflammatory markers (CRP, PCT and thy348

Deceased (n=7)

1.3±1.5 NS

roid hormones) in secondary peritonitis. Viñas Trullen X et al. prospectively enrolled fifty-seven patients into a study that found a positive and significant correlation between preoperative PCT-Q and postoperative MPI. PCT Values >10ng/ml were reported to be significant for admission to the ICU and a poor clinical prognosis.[13] In another study conducted by Nenad Ivančević et al., PCT concentrations in ninety-eight patients with acute abdominal conditions, divided into two groups namely sepsis and systemic inflammatory response syndrome (SIRs), were found Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Akcay et al. The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis

Table 6. Comparison of CRP, PCT and Thyroid Hormone levels among deceased and discharged patients diagnosed with colon perforation

Colon Perforation (n=13) Discharged (n=9)

Deceased (n=4)

Mean±SD Mean±SD

Preop. T3

2.09±0.91

2.10±0.08

1.14±0.18

1.11±0.04 NS

Thyroid-stimulating hormone

3.38±3.33

0.66±0.88

C-reactive protein

199±176

288±315

Procalcitonin Postop. 1 T3

7.7±4.7 1.55±0.72

1.6±2.0 NS 2.07±1.20

133±0.27

1.16±0.22 NS

Thyroid-stimulating hormone

2.54±1.38

0.57±0.43

0.020

C-reactive protein

172±85

201±154

Procalcitonin

20±33

5.4±1.9 NS

Postop. 3 T3

1.87±0.55

2.4±1.75

1.24±0.26

1.25±0.32 NS

Thyroid-stimulating hormone

2.35±0.98

0.67±0.51

0.006

146±53

142±89

C-reactive protein Procalcitonin

24.2±54.8

Postop. 5 T3

1.92±0.50

2.9±1.3 NS 1.73±0.68

1.30±0.30

1.12±0.48 NS

Thyroid-stimulating hormone

3.20±2.49

0.92±0.74

C-reactive protein

165±103

131±66

Procalcitonin

2.6±3.6

6.1±4.1 NS

Postop. 7 T3

2.35±0.53

1.96±0.09

1.48±0.30

1.68±0.21 NS

Thyroid-stimulating hormone

2.73±1.86

1.39±0.07

112±70

102±3

C-reactive protein

PCT

2.37±5.16

Postop. 14 T3

2.39±0.43

–

1.50±0.22

– NS

Thyroid-stimulating hormone

2.53±1.58

–

C-reactive protein

83±51

–

Procalcitonin

0.4±0.6

– NS

to be significantly higher in the sepsis group than in the SIRs group suggesting PCT as a useful criteria for early, preoperative diagnosis of abdominal sepsis. Also, in the same study, a group of patients with abdominal symptoms lasting for more than 24 h had higher PCT levels when compared with those with symptoms lasting less than 24 h. This study shows a meaningful relationship between the severity of peritonitis and serum levels of PCT.[14] Consistent with the results from these studies, our findings revealed significantly higher PCT levels in patients developing complications when compared to those who did not. Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

0.97±0.75 NS NS

Reith and colleagues in their study reported that serum CRP and PCT levels were superior to TNF-α, IL-1 and IL-6 levels in predicting prognosis in 246 patients with abdominal sepsis, CRP and PCT levels were found to be higher in patients with postoperative infection and sepsis when compared to patients who had an uneventful postoperative course. In this study, levels of markers such as TNF-α, CRP, IL-1, and IL-6 were reported to only increase with response to conditions like trauma and surgery. In spite of this, PCT was described to be more sensitive in sepsis and bacterial infections.[15] 349

Akcay et al. The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis

Table 7. Comparison of CRP, PCT and Thyroid Hormone levels among deceased and discharged patients diagnosed with anastomosis dehiscence

Anastomosis dehiscence (n=6) Discharged (n=4)

Mean±SD Mean±SD

Postop. 1 T3

2.24±0.78

4.10±3.14

1.17±0.09

1.21±0.03 NS

Thyroid-stimulating hormone

1.35±0.87

0.40±0.48

C-reactive protein

150±102

265±57

Procalcitonin

10.8±14.1

0.55 ± -

Postop. 3 T3

2.14±0.50

5.45±2.99

1.15±0.17

1.23±0.62 NS

Thyroid-stimulating hormone

1.28±0.79

0.21±0.26

C-reactive protein

141±86

139±53

Procalcitonin

9.0±14.2

3.7±4.1 NS

Postop. 5 T3

2.76±1.65

7.04±3.57

1.15±0.36

1.21±0.61 NS

Thyroid-stimulating hormone

1.71±1.11

0.04±0.02

108±63

124±5

C-reactive protein Procalcitonin Postop. 7 T3

3.6±5.7 2.82±0.63

2.1±1.4 NS 4.41±3.91

1.31±0.37

1.09±0.26 NS

Thyroid-stimulating hormone

2.17±1.33

0.13±0.11

161±47

C-reactive protein

75±35

Procalcitonin

0.3±0.2

1.16±0.96 NS

Postop. 14 T3

3.0±1.60

3.96±3.50

1.11±0.26

1.53±0.42 NS

Thyroid-stimulating hormone

2.41±1.57

0.0±0.0

C-reactive protein

92±98

199±55

Procalcitonin

0.1±0.1

2.0±2.4 NS

Bell at al., measured the serum PCT levels alone or in combination with CRP and pointed out their role in discriminating septicemia/bacteremia with associated SIRs from noninfectious SIRS in an ICU setting with 123 patients. They went on to report twelve different studies describing serum procalcitonin levels to be more important than serum CRP levels in differentiating bacterial infections from other causes of systemic inflammatory responses.[16,17] In another study evaluating the relationship between procalcitonin, CRP and the severity of appendicitis in the pediatric population, 212 pediatric patients operated on for acute appendicitis were grouped into five groups according to surgical and histological findings. Group 1 had (n=58) normal findings, Group 2 (n=24) follicular hyperplasia, Group 3 (n=66) acute appendicitis, Group 4 (n=36) Perforated appendicitis, and Group 5 (n=28) necrotizing appendicitis. Preoperative antibiotic 350

Deceased (n=2)

therapy wasn’t given to any of the five groups. Serum procalcitonin levels were >0, 5 in 81% of patients in Group 4 and 64% of patients in Group 5. For CRP levels, 57% of patients in Group 4 and 32% of patients in Group 5 had a serum CRP level greater than 50 mg/dl. The clinical presentation of appendicitis was found to be severe in patients with higher serum procalcitonin and CRP levels. This showed the importance of procalcitonin and CRP as a prognostic marker in appendicitis.[18] In our study, the median preoperative serum PCT and CRP levels of patients with perforated appendicitis (n=21) were 9.9 ng/ml and 190 mg/L. These values regressed to 0.19 ng/ml and 63 mg/L respectively, for both parameters on postoperative day 14. Moreover, although levels of PCT and CRP in the other five groups (perforated peptic ulcer disease, small bowel perforation (iatrogenic, typhoid, vasculitis), colon perforation (iatrogenic, diverticula, foreign body), Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Akcay et al. The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis

anastomosis dehiscence, and gallbladder perforation) from our study remained high during the first week after surgery, a rather fluctuating pattern of PCT and CRP levels was observed towards postoperative day 14. We were also able to demonstrate that serum PCT levels follow a falling trend after surgery as long as postoperative course remained uneventful. In addition, we showed that after surgical intervention for secondary peritonitis, PCT was a better marker than CRP in following postoperative complications besides peritonitis. Thyroid hormone levels are known to decrease in situations such as infection, severe stress, trauma, and chronic conditions like cirrhosis and chronic kidney disease.[19,20] Euthyroid sick syndrome is characterized by abnormal thyroid findings in the presence of non-thyroidal illness (NTIs) without evidence of pre- existing hypothalamic pituitary conditions. The most common alternations are low T3, normal or low T4 and normal TSH levels. This syndrome is generally associated with sepsis, malignancy, AIDS and myocardial infarction. Prognosis of patients with this syndrome is correlated with serum levels of T3 and T4.[21-24] In our study, low T3, T4 levels among groups with higher mortality and complication rates were found. Glembot et al. in their stimulated physiologic stress model did not see a decrease in mortality when thyroid hormones were added.[24] In most studies, low serum T3 and T4 has been associated with a higher mortality in sepsis and severe bacterial infections. While the reported mortality ratio in patients with T4 levels lower than 3 µg/dl is between 64% and 84%, patients with the same disease but normal thyroid levels were found to have mortality below 22%.[25,26] We found that thyroid hormone levels changed much among patients with small bowel perforation and peptic ulcer perforation that had postoperative complications and those who died. Findings from our study showed postoperative T4 and T3 levels lower than 1 µg/l and 3.64 µg/l respectively, which can be associated with a higher morbidity and mortality in these groups. We are of the thought that PCT in addition to T3, T4 and TSH especially can be important parameters in predicting both systemic complications that may develop and the prognosis of secondary peritonitis.

rate in orthopaedics. The University of Pennsylvania Orth J 2002;15:13-6. 4. 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. 5. Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE, et al. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001;164:396-402. 6. Marshall JC, Vincent JL, Fink MP, Cook DJ, Rubenfeld G, Foster D, et al. Measures, markers, and mediators: toward a staging system for clinical sepsis. A report of the Fifth Toronto Sepsis Roundtable, Toronto, Ontario, Canada, October 25-26, 2000. Crit Care Med 2003;31:1560-7. 7. Copp DH, Davidson AG. Direct humoral control of parathyroid function in the dog. Proc Soc Exp Biol Med 1961;107:342-4. 8. 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. 9. Meisner M. Pathobiochemistry and clinical use of procalcitonin. Clin Chim Acta 2002;323:17-29. 10. Baumann H, Gauldie J. The acute phase response. Immunol Today 1994;15:74-80. 11. Beutler B, Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med 1987;316:379-85. 12. Cassatella MA. The production of cytokines by polymorphonuclear neutrophils. Immunol Today 1995;16:21-6. 13. Viñas Trullen X, Rodríguez López R, Porta Pi S, Salazar Terceros D, Macarulla Sanz E, Besora Canal P, et al. Prospective study of procalcitonin as a diagnostic marker of the severity of secondary peritonitis. [Article in Spanish] Cir Esp 2009;86:24-8. [Abstract] 14. Gregoric P, Sijacki A, Stankovic S, Radenkovic D, Ivancevic N, Karamarkovic A, et al. SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors. Hepatogastroenterology 2010;57:349-53. 15. Reith HB, Mittelkötter U, Wagner R, Thiede A. Procalcitonin (PCT) in patients with abdominal sepsis. Intensive Care Med 2000;26 Suppl 2:165-9. 16. Bell K, Wattie M, Byth K, Silvestrini R, Clark P, Stachowski E, et al. Procalcitonin: a marker of bacteraemia in SIRS. Anaesth Intensive Care 2003;31:629-36. 17. Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 2004;39:206-17. 18. Kafetzis DA, Velissariou IM, Nikolaides P, Sklavos M, Maktabi M, Spyridis G, et al. Procalcitonin as a predictor of severe appendicitis in children. Eur J Clin Microbiol Infect Dis 2005;24:484-7. 19. Pearce CJ. The euthyroid sick syndrome. Age Ageing 1991;20:157-9. 20. McIver B, Gorman CA. Euthyroid sick syndrome: an overview. Thyroid 1997;7:125-32.

Conflict of interest: None declared.

21. Santini F, Chopra IJ. A radioimmunoassay of rat type I iodothyronine 5’-monodeiodinase. Endocrinology 1992;131:2521-6.

REFERENCES

22. Ongphiphadhanakul B, Fang SL, Tang KT, Patwardhan NA, Braverman LE. Tumor necrosis factor-alpha decreases thyrotropin-induced 5’-deiodinase activity in FRTL-5 thyroid cells. Eur J Endocrinol 1994;130:502-7.

1. Guarner C, Soriano G. Spontaneous bacterial peritonitis. Semin Liver Dis 1997;17:203-17. 2. Dudley HAF. Intraperitoneal sepsis: peritonitis and abdominal abscesses. Hamilton Baileys Emergency Surgery. HA.F Dudley. Wright. Bristol 276-85.

23. Fujii T, Sato K, Ozawa M, Kasono K, Imamura H, Kanaji Y, et al. Effect of interleukin-1 (IL-1) on thyroid hormone metabolism in mice: stimulation by IL-1 of iodothyronine 5’-deiodinating activity (type I) in the liver. Endocrinology 1989;124:167-74.

3. Husain TM, Kim DH. C-reactive protein and erytrocyte sedimentation

24. Girvent M, Maestro S, Hernández R, Carajol I, Monné J, Sancho JJ, et

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351

Akcay et al. The prognostic value of pro-calcitonin, CRP and thyroid hormones in secondary peritonitis al. Euthyroid sick syndrome, associated endocrine abnormalities, and outcome in elderly patients undergoing emergency operation. Surgery 1998;123:560-7. 25. Chopra IJ, Hershman JM, Pardridge WM, Nicoloff JT. Thyroid function

in nonthyroidal illnesses. Ann Intern Med 1983;98:946-57. 26. Arem R, Wiener GJ, Kaplan SG, Kim HS, Reichlin S, Kaplan MM. Reduced tissue thyroid hormone levels in fatal illness. Metabolism 1993;42:1102-8.

KLİNİK ÇALIŞMA - ÖZET OLGU SUNUMU

Sekonder peritonitte prokalsitonin, CRP ve tiroit hormonlarının prognostik değeri; ileriye yönelik çalışma Dr. Idris Akcay,1 Dr. Alexis K. Okoh,2 Dr. Orcun Yalav,3 Dr. Ismail C. Eray,3 Dr. Ahmet Rencuzogullari,3 Dr. Kubilay Dalci,3 Dr. Hasan Elkan,4 Dr. Ali H. Alparslan3 Doc. Doktor Yasar Eryılmaz Dogubeyazıt Devlet Hastanesi, Genel Cerrahi Kliniği, Agrı; Ankara Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Ankara; Çukurova Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Adana; 4 Balıklıgöl Devlet Hastanesi, Genel Cerrahi Kliniği, Şanlıurfa 1 2 3

AMAÇ: Enfeksiyon ve sepsis, sekonder peritonitli hastalarda morbidite ve mortalitenin en önemli sebeplerinden biri olmaya devam etmektedir. Klinisyenler helen septik komplikasyonların erken ve güvenilir tanı yöntemini bulma konusunda çaba sarfetmektedir. Bu çalışmada sekonder peritonitin şiddetini belirlemede enflamatuvar markır olarak Prokalsitonin (PKT), C-reaktif protein (CRP) ve tiroit hormonlarının yerini değerlendirmeyi amaçladık. GEREÇ VE YÖNTEM: Ocak 2008-Ocak 2010 tarihleri arasında, sekonder peritonit nedeniyle ameliyat olan 84 ardışık hasta üzerinde ameliyat öncesi ve sonrası 1-3-5-7-14. günlerde PKT, CRP ve tiroit hormaon seviyeleri incelendi. Veriler Statistical Package for Social Sciences 15.0 (SPSS 15.0) programında analiz edildi. BULGULAR: Organ perforasyonu (peptik ülserperforasyonu, ince bağırsak ve kolon perforasyonu) olan olgular değerlendirildiğinde, PKT anlamlı olarak düşük seyretti. Ameliyat sonrası komplikasyonu olan veya ölen hastalara göre ameliyat sonrası dönemi sorunsuz olan veya taburcu olan hastalarada yüksek tiroit hormon düzeyler gözlendi. PKT düzeyleri ise CRP düzeylerleri ve beyaz küre sayısıyla anlamalı olarak ilişkili bulundu. TARTIŞMA: Ameliyat sonrası komplikasyonların yokluğunda PKT, sekonder peritonit tanısında CRP’den daha iyi bir belirliyicidir. Çalışmamız sekonder peritonitin şiddetini belirlemede düşük tiroit hormon düzeylerinin önemli bir prognostik faktör olduğunu ortaya koymuştur. Anahtar sözcükler: C-reaktif protein; prokalsitonin; sekonder peritonit; tiroit hormonları. Ulus Travma Acil Cerrahi Derg 2014;20(5):343-352

352

doi: 10.5505/tjtes.2014.98354

Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

ORIGIN A L A R T IC L E

Features of the traffic accidents happened in the province of Aydın between 2005 and 2011 Musa Dirlik, M.D.,1 Başak Çakır Bostancıoğlu, M.D.,2 Tülay Elbek, M.D.,1 Bedir Korkmaz, M.D.,1 Füsun Çallak Kallem, M.D.,1 Berk Gün, M.D.3 1

Department of Forensic Medicine, Adnan Menderes University Faculty of Medicine, Aydın;

Ministry of Justice, Forensic Medicine Institution, Antakya;

Ministry of Justice, Forensic Medicine Institution, İzmir

ABSTRACT BACKGROUND: In this study, it was aimed to analyze the traffic accidents with postmortem examinations and autopsies. METHODS: From the one thousand eight hundred and fifteen forensic autopsies, reports of 334 traffic accidents were searched. Features such as the scene of the accident, type of the accident, type of the vehicles involved in the accident, the year, season, day and hour of the accident, the positions of the victims in the traffic, concomitant orthopedic injuries, whether autopsy was performed, and cause of death were investigated. RESULTS: Among the one thousand eight hundred and fifteen forensic death cases, observed cause of death was determined to be traffic accidents in 334 (18.4%) cases. Male cases accounted 84.1%, and male to female ratio was 5.3 to 1. From the reports, 32.6% of the accidents happened in summer and most commonly during holidays (33%). The rate of the accidents happened in the city center was 35.3% and 32.9% of these cases died due to pedestrian collision. Moreover, it was determined that the most injured person was the driver. Automobiles took the lead in the causes of the traffic accidents. CONCLUSION: It is realized that traffic accident-related deaths have a substantial place among forensic deaths and continue to be an important public health problem. It is conspicuous that improving public education on traffic safety, increasing traffic management and control measures are of great significance. Key words: Traffic accidents; forensic medicine; autopsy.

INTRODUCTION World Health Organization (WHO) defines a road traffic injury as any injury caused by vehicle crashes on a public highway.[1] Traffic accidents rank first among accidents leading to injuries worldwide.[1,2] Although the number of traffic accidents has decreased in recent years as a consequence of efforts in developed countries, it is still among the most important public health problems in developing countries.[1-3] In Turkey, thousands of people get injured or die each year due Address for correspondence: Musa Dirlik, M.D. Adnan Menderes Üniversitesi Tıp Fakültesi, Adli Tıp Anablim Dalı, Şehir Hastanesi, 09100 Aydın, Turkey Tel: +90 256 - 444 12 56 / 4347 E-mail: musadirlik@hotmail.com Qucik Response Code

Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

to traffic accidents.[4] Therefore, it is important to determine causes of death and the potential factors affecting death in traffic accidents. This is only possible with a detailed and attentive autopsy procedure and laboratory analyses. The present study aimed to assess demographic characteristics of the subjects that died due to the traffic accidents in the province of Aydın, Turkey and to evaluate them in terms of forensic medicine, as well as to establish recommendations within the frame of data obtained.

MATERIALS AND METHODS In the present study, subjects, who died due to traffic accidents, were selected among all forensic death cases referred to the Department of Forensic Medicine of Adnan Menderes University between January 2005 and December 2011. From the one thousand eight hundred and fifteen forensic autopsies, reports of 334 traffic accidents were searched. External examination/autopsy reports of the selected cases were reviewed retrospectively, and the following data including de353

Dirlik et al. Features of the traffic accidents happened in the province of Aydın between 2005 and 2011

mographic characteristics of the dead subjects, scene of the accident, type of the accident, type of the vehicles involved in the accident, the year, season, day and hour of the accident, the position of the victims in the traffic, concomitant orthopedic injuries, whether autopsy was performed, and cause of death were evaluated. The data of the study were analyzed using the Statistical Package for the Social Sciences version 14 (SPSS, Inc., Chicago, IL, USA).

RESULTS Among the one thousand eight hundred and fifteen forensic death cases observed within the 6-year period and covered by the present study, cause of death was determined to be traffic accidents in 334 (18.4%) cases, which were included in the study. Of these three hundred and thirty-four cases, 331 were citizens of Turkey, one was a citizen of the Netherlands, one of Lithuania, and the identity of one could not be determined. Of the cases, 281 (84.1%) were male and 53 (15.9%) were female with a male-to-female ratio of 5.3. Deaths due to traffic accidents were observed to be most common in a group aged between 21 and 30, with a rate of 18.9% and least common in a group aged 81 and over, with a rate of 3.00%; the mean age of the dead cases was 44.39 years (minimum: 40; maximum: 93 years of age). Number of males was higher than that of females in each age group. The distribution of the cases among age groups is presented in Table 1. The evaluation of the distribution of cases over the years revealed that deaths were more prevalent in 2007 and 2008 with 57 (17.1%) cases in each year and least prevalent in 2010 with 31 (9.3%) cases. Accidents occurred most frequently in summer with 109 (32.6%) cases and in autumn with 83 (24.9%) cases; 13.2% of the accidents occurred in July, 12.6% of the accidents occurred in September, and 10.8% of the accidents occurred in August. Accidents occurred least frequently in November (3.6%) and December (5.1%).

Table 1. Distribution of the dead cases according to age groups Age groups (years)

(%)

0-10

12 3.6

11-20

29 8.7

21-30

63 18.9

31-40

54 16.2

41-50

47 14.1

51-60

42 12.6

61-70

39 11.7

71-80

38 11.4

≥81

10 3.0

Total

334 100.0

According to the distribution of traffic accidents over the days, it was determined that the accidents occurred most frequently on off days, Sunday (17.4%) and Saturday (15.6%), whereas the accidents occurred least frequently on Monday (11.4%), which is the first day of work. It was observed that the accidents were more common in rush hours between 12:01 and 18:00. Of the accidents, one hundred and eighteen (35.3%) occurred within the city limits, whereas 133 (39.8%) occurred outside city limits. Of the accidents occurred within the city limits, 17.4% occurred in downtown, 3.3% occurred in Nazilli County, 2.7% occurred in Çine County, and 2.1% occurred in Kuşadası County. The distribution of the scenes of accidents over the years is demonstrated in Table 2. The present study determined that one hundred and fortytwo (42.5%) cases experienced traffic accidents inside the vehicle, whereas 192 (57.5%) cases experienced traffic accidents outside the vehicle. It was observed that traffic accidents outside the vehicle mostly occurred within the city limits, whereas traffic accidents inside the vehicle mostly oc-

Table 2. Distribution of the scenes of accidents over the years Years 2005

354

Scene of accident Within the city center 22

Outside the city center

Other

Total

5 48

2006

10 53

2007

15 57

2008

17 57

2009

10 37

2010

11 31

2011

15 51

Total

118

133

83 334

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Dirlik et al. Features of the traffic accidents happened in the province of Aydın between 2005 and 2011

Table 3. Distribution of accident types according to the scene of accident Accident type Inside the vehicle

Crime scene Within the city center

Outside the city center

Other

Total

142 192

Outside the vehicle

Total

118

133

83 334

curred outside city limits. The distribution of the accident type according to the scene of accident is presented in Table 3. In the present study, of the cases, one hundred and ten (32.9%) were pedestrians hit by a vehicle, whereas 175 were drivers and 16 were front seat passengers. Among the vehicles involved in the traffic accidents, automobiles ranked first (27.2%), followed by motorcycles (20.1%). Tractor accidents accounted for 8.7% and each of the bicycle and minibus accidents accounted for 4.2% (Table 4). Among the cases, 41.6% died during clinical treatment, 29.0% died at the scene of the accident, 19.8% died during the first treatment in the emergency room, 9.3% died during transfer, and one case died after being discharged from the health care center. Seventy-five (22.5%) of the cases underwent autopsy examination, whereas 259 (77.5%) underwent external examination; samples for histopathological examination were obtained from nine (2.7%) cases, and a causal connection was determined between death and traffic accident in six of them. Bone fracture was detected in 280 (83.8%) cases. It was observed that one hundred and fifty-two cases had a single bone fracture and 128 had multiple bone fractures. Skull fractures were the leading fractures present in one hundred and sixtyeight (50.3%) cases. The fracture was in the ribs in 37.7% of the cases, femur in 11.1% of the cases, tibia-fibula in 9.9% of the cases, pelvis in 8.4% of the cases, maxilla in 6.9% of the cases, humerus in 6% of the cases, clavicle in 5.7% of the cases, vertebra in 4.8% of the cases, sternum in 4.2% of the cases, wrist in 4.2% of the cases, radius-ulna in 3.3% of the cases, ankle in 3.3% of the cases, patella in 2.1% of the cases, and scapula in 1.5% of the cases. The leading cause of death due to traffic accidents was wholebody trauma involving one hundred and forty-eight (44.3%) cases, followed by head trauma in 40.4% of the cases, chest trauma in 11.1% of the cases, and abdominal trauma in 1.8% of the cases. It was determined that two cases died of drowning, five cases died of myocardial infarction and one case died of pulmonary embolism. Since we were not informed about the overall results of analyses of blood samples obtained during autopsy or external examination, definite information Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Table 4. Type of vehicles involved in deaths due to traffic accidents Pedestrian

n (%)

Cumulative %

110 (32.9)

32.9

Bicycle

14 (4.2)

37.1

Motorcycle

67 (20.1)

57.2

Automobile

91 (27.2)

84.4

Truck/pick-up

7 (2.1)

86.5

Minibus-bus

14 (4.2)

90.7

Tractor

29 (8.7)

99.4

Tanker

1 (0.3)

99.7

1 (0.3)

100.0

334 (100.0)

–

Ambulance Total

about blood alcohol concentration of the dead subjects could not be obtained.

DISCUSSION Traffic accidents are among the most important causes of death in developed countries.[5-7] It is estimated that each year more than two million people die worldwide.[8] In the countries of the European Union, 50,000 deaths and 1,5 million injuries are being reported each year due to traffic accidents. [5] According to the 2010 data of Turkish Statistical Institute, a total of 116,804 traffic accidents occurred resulting in 4,045 deaths and 211,496 injuries.[4] These injuries appear as an important public health problem not just due to high economic burden, but also to the relevant social problems.[9] Among the one thousand eight hundred and fifteen forensic death cases within the 6-year period covered by the present study, cause of death was determined to be traffic accidents in 334 (18.4%) cases. In other studies conducted in Turkey, this rate has been reported to be 35.9% by Tıraşçı and Gören,[10] 47.8% by Çakıcı et al.,[11] 48.7% by Karagöz et al.,[12] 31.3% by Gören et al.,[13] and 38.8% by Karbeyaz et al.[14] A study from Sri Lanka has reported this rate to be 43.5%,[15] while it has been reported to be 57.9% in a study from Nigeria[16] and 18.6% in a study from Norway.[17] The present study comprised 281 (84.1%) male cases and 355

Dirlik et al. Features of the traffic accidents happened in the province of AydÄąn between 2005 and 2011

53 (15.9%) female cases with a male to female ratio of 5.3, which was consistent with the findings reported in the relevant studies.[13,18-26] This was attributed to the higher male count in traffic. Studies conducted in Turkey have reported that the cases involved in traffic accidents are predominantly in the young age group.[10,12,13,27,28] The present study also determined that traffic accident-related deaths occurred most frequently in the group aged between 21 and 30 (18.9%), followed by the group aged between 31 and 40 (16.2%). Likewise, traffic accident-related deaths have been reported to occur most frequently in the group aged between 21 and 30 (17.3%) in the study by Karbeyaz et al.[14] On the other hand, Demirel et al.[19] have reported traffic accident-related deaths to be most common in the group aged between 60 and 69 (20.5%). It has been stated that traffic accidents are one of the basic causes of death particularly among young population under the age of 50 years and is more prevalent in the age groups that are physically and socially more active.[21] Consistent with the findings reported in the literature, the present study determined that traffic accidents most frequently occurred on off days, in summer and between the hours of 12:01 and 18:00.[5,13,14] This was attributed to heavier traffic at the weekends and in summer days. The present study found that the accidents which occurred outside the vehicle (57.5%) were more prevalent than those which occurred inside the vehicle (42.5%). The accidents inside the vehicle occurred more commonly within the city limits, whereas accidents outside the vehicle occurred more commonly outside the city limits. These findings were also consistent with the findings of previous studies.[13,14,18] In the present study, evaluation of the vehicle types involved in traffic accidents resulting in deaths revealed that 27.2% were automobiles, 8.7% were tractors, 67 (20.1%) were motorcycles, 14 (4.2%) were bicycles, 4.2% were bus-minibuses, 2.1% were truck/pick-ups, one was a tanker, and one was

an ambulance, whereas 14 deaths occurred due to train accidents. It has been reported that automobile and minibusbus accidents are frequent as these vehicles are widely found in traffic, motorcycle-bicycle accidents are frequent due to rare use of helmets by motorcyclists and cyclists, and tractor accidents are frequent due to uncontrolled use of tractors in the rural areas for both agricultural labor and passenger transport.[13,14,29-33] Evaluation of the position of the dead cases in the present study showed that 110 (32.9%) cases were pedestrians hit by a vehicle, 175 cases were drivers and sixteen cases were front seat passengers (Table 5). In other studies conducted in Turkey, the rate of pedestrians has been reported to be 55.5% by GĂśren et al.[13] and 41.0% by Karbeyaz et al.[14] In other studies around the world, this rate has been reported to be 46.2% by Sharma et al.,[21] 77.1% by El-Sadig et al.,[22] and 59% by Cameron et al.,[23] and 57% by Hijar et al.[34] The rate of pedestrian death is gradually decreasing in developed countries. However, pedestrian death, particularly in childhood, is more prevalent in developing countries due to the fact that children usually play in the streets with heavy traffic and are involved in economic activity.[13,35] In our study, 41.6% of the cases died during clinical treatment, 29.0% died at the scene of accident, and 19.8% died during the first treatment in the emergency room. Similar studies have reported that cases are usually brought dead to the health institution due to lack of knowledge and experience about first aid at the scene of accident and delayed patient transfer.[13,14,21,36] In Turkey, the prevalence of autopsy is low in traffic accidentrelated deaths.[14,19,37] The rate of autopsy has been found to be 1.2% and 1.1% in the studies by GĂśren et al.[13] and Karbeyaz et al.,[14] respectively. Different from the findings of previous studies in Turkey, the present study determined that 75 (22.5%) cases underwent autopsy and 259 (77.5%) cases

Table 5. Distribution of causes of death according to the position of the dead cases

Location of the dead cases

Pedestrian Driver Causes of death

Other

Total

Head trauma

45 74 4 12 135

Chest trauma

Abdominal trauma

4 0 0 2 6

Whole-body trauma

51 75 10 12 148

Drowning

0 1 0 1 2

Myocardial infarction

0 5 0 0 5

Pulmonary embolism Total

356

Front seat passanger

0 0 0 1 1 110 175 16

33 334

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Dirlik et al. Features of the traffic accidents happened in the province of Aydın between 2005 and 2011

underwent external medical examination.

REFERENCES

Head trauma has been reported to be the leading cause of death in traffic accident-related deaths, and particularly pedestrians, drivers, passengers not wearing seat-belts, and motorcyclists-cyclist not wearing helmets have been reported to be more prone to head trauma. In the present study, head trauma (40.4%) was the second leading cause of death after whole body trauma (44.3%). This rate has been reported to be 59.1% in the study by Gören et al.,[13] 83.3% in the study by Karbeyaz et al.,[14] and 61.5% in the study conducted by Hilal et al.[18] In a study evaluating the cases presented to emergency rooms after traffic accidents in the province of Sivas, Turkey, head trauma has been detected in 18.6% of the cases. [38] Çırak et al.[39] have reported traffic accidents as the cause in 48% of head trauma cases presented to the emergency room. In the present study, skull fracture was detected in 168 cases. Pakiş et al.[40] have reported abdominopelvic trauma in 22.78% of the traffic accident-related deaths, of which 51% were pelvic bone fractures. While blunt or penetrating abdominopelvic injuries could occur during traffic accidents, it has been reported that blunt injuries take the lead and are usually associated with seat-belt use known as “seat-belt syndrome”.[41-43] In the present study, abdominal trauma alone was the cause of death in six cases and chest trauma alone was the cause of death in 37 cases. Costal fracture was detected in 126 cases, clavicle fracture in 19 cases, and sternum fracture in 14 cases. Cangır et al.[44] have reported that the etiology was traffic accidents in 66.17% of thorax trauma cases presented to the clinic.

1. WHO Injury Chart Book. Department of Injuries and Violence Prevention Noncommunicable Diseases and Mental Health Cluster. Geneva: 2002. p. 19-27.

Conclusion It is realized that traffic accident-related deaths have a substantial place among forensic deaths and continue to be an important public health problem. It has been concluded that automobiles are the vehicles most involved in traffic accidents, drivers neglect wearing seat-belts, motorcyclists-cyclists do not wear helmets, tractors are inappropriately driven by individuals of various ages both for agriculture labor and to transfer passengers, pedestrians, particularly children and the elderly, are frequently exposed to traffic accidents within the city limits, and accidents are more prevalent in summer and at the weekends due to heavy traffic. It is conspicuous that improving public education on traffic safety, building more public awareness on road safety, increasing traffic management and control measures, and educating drivers on traffic rules and regulations are the basic measures necessary to be taken for the prevention of and controlling traffic accidents. Moreover, we are in the opinion that safe playing areas and public gardens should be established for children, cycle tracks need to be constructed in cities, public transportation should be popularized, education on first aid should be generalized, and problems during patient transfer should be eliminated. Conflict of interest: None declared. Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

2. The World Report on Road Traffic Injury Prevention. Geneva: 2004. p. 1-9. 3. Bertan M, Çakır B. Halk sağlığı yönünden kazalar. Ankara: Güneş Kitabevi; 1995. p. 462-72. 4. Turkish Statistical Institute. Traffic Accident Statistics, Road. 1st ed. Ankara: Publications of Turkish Statistical Institute; 2010. p. 1-95. 5. Töro K, Hubay M, Sótonyi P, Keller E. Fatal traffic injuries among pedestrians, bicyclists and motor vehicle occupants. Forensic Sci Int 2005;151:151-6. 6. Sirlin CB, Brown MA, Andrade-Barreto OA, Deutsch R, Fortlage DA, Hoyt DB, et al. Blunt abdominal trauma: clinical value of negative screening US scans. Radiology 2004;230:661-8. 7. Brown MA, Casola G, Sirlin CB, Patel NY, Hoyt DB. Blunt abdominal trauma: screening us in 2,693 patients. Radiology 2001;218:352-8. 8. Hodgson NF, Stewart TC, Girotti MJ. Autopsies and death certification in deaths due to blunt trauma: what are we missing? Can J Surg 2000;43:130-6. 9. Meliker JR, Maio RF, Zimmerman MA, Kim HM, Smith SC, Wilson ML. Spatial analysis of alcohol-related motor vehicle crash injuries in southeastern Michigan. Accid Anal Prev 2004;36:1129-35. 10. Tıraşçı Y, Gören S. Diyarbakır’da adli ölü muayenesi ve otopsiler ile bu olgularda adli tıp şube müdürlüğü’nün etkinliği. II. Adli Bilimler Kongresi Özet, Bursa: 1996. 11. Çakıcı M, Polat O, Albayrak M, İnanıcı MA, Tansel E. A retrospective analysis of autopsies and external medical examinations in Turkish Republic of Northern Cyprus. 8. National Forensic Medicine Meeting Poster Book. Antalya: 1995:111-7. 12. Karagöz YM, Karagöz Demirçin S, Atılgan M, Demircan C. Analysis of medicolegal deaths, 8. National Forensic Medicine Meeting Poster Book Antalya: 1995. p. 119-24. 13. Gören S, Subaşı M, Tıraşçı Y, Kaya Z. Deaths related to traffic accidents. J Foren Med 2005;2:9-13. 14. Karbeyaz K, Balcı Y, Çolak E, Gündüz T. Charateristics of the traffic accidents in Eskişehir between the years 2002 and 2007. J Foren Med 2009;6:65-73. 15. Fernando R. A study of the investigation of death (coroner system) in Sri Lanka. Med Sci Law 2003;43:236-40. 16. Aligbe JU, Akhiwu WO, Nwosu SO. Prospective study of coroner’s autopsies in Benin City, Nigeria. Med Sci Law 2002;42:318-24. 17. Nordrum I, Eide TJ, Jørgensen L. Medicolegal autopsies of violent deaths in northern Norway 1972-1992. Forensic Sci Int 1998;92:39-48. 18. Hilal A, Meral D, Arslan M, Gülmen MK, Eryılmaz M, Karanfil R. Evaluation of the deaths due to traffic accidents in Adana. The Bulletin of Legal Medicine 2004;9:74-8. 19. Demirel B, Akar T, Özdemir Ç, Cantürk N, Erdönmez F. Factors influencing autopsy decision in deaths due to road accidents. The Bulletin of Legal Medicine 2005;10:77-83. 20. Pentilla A, Luretta P. Transportation medicine. In: Payne J, Busuttil A, Smock W, editors. Forensic medicine clinical and pathological aspects. 1st ed. London: Greenwich Medical Media Ltd; 2003. p. 525-43. 21. Sharma BR, Harish D, Sharma V, Vij K. Road-traffic accidents--a demographic and topographic analysis. Med Sci Law 2001;41:266-74. 22. El-Sadig M, Norman JN, Lloyd OL, Romilly P, Bener A. Road traffic

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33. Çetinus E, Ekerbiçer H. Analysis of the motorcycle accidents in Kirikhan, Antakya. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2000;6:216-21. 34. Híjar MC, Kraus JF, Tovar V, Carrillo C. Analysis of fatal pedestrian injuries in Mexico City, 1994-1997. Injury 2001;32:279-84. 35. Byard RW, Green H, James RA, Gilbert JD. Pathologic features of childhood pedestrian fatalities. Am J Forensic Med Pathol 2000;21:101-6. 36. Montazeri A. Road-traffic-related mortality in Iran: a descriptive study. Public Health 2004;118:110-3. 37. Balcı Y. Autopsy. Herkes için adli tıp cep kitabı. 1st ed. Eskişehir: Osmangazi University Press; 2008. p. 135-9. 38. Varol O, Eren ŞH, Oğuztürk H, Korkmaz İ, Beydilli İ. Investigation of the patients who admited after traffic accident to the emergency department. Cumhuriyet Medical Journal 2006;28:55-60. 39. Çırak B, Berker M, Özcan O.E, Özgen T. An epidemiologic study of head trauma: causes and results of treatment. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 1999;5:90-2. 40. Pakiş I, Akçay Turan A, Karayel F, Akyıldız E, Ersoy G, Üstündağ TE, et al. Abdominal and pelvic trauma in traffıc accidents; an autopsy study. Journal of Forensic Medicine 2008;22:31-5. 41. Bennett MK, Jehle D. Ultrasonography in blunt abdominal trauma. Emerg Med Clin North Am 1997;15:763-87. 42. Vorko-Jović A, Kern J, Biloglav Z. Risk factors in urban road traffic accidents. J Safety Res 2006;37:93-8. 43. Valent F, Schiava F, Savonitto C, Gallo T, Brusaferro S, Barbone F. Risk factors for fatal road traffic accidents in Udine, Italy. Accid Anal Prev 2002;34:71-84. 44. Cangır AT, Nadir A, Akal M, Kutlay H, Özdemir N, Güngör A, et al. Thoracic Trauma: analysis of 532 patients. Thoracic trauma: analysis of 532 patients. [Article in Turkish] Ulus Travma Acil Cerrahi Derg 2000;6:100-5.

KLİNİK ÇALIŞMA - ÖZET OLGU SUNUMU

2005-2011 yıllarında Aydın ilindeki trafik kazalarının özellikleri Dr. Musa Dirlik,1 Dr. Başak Çakır Bostancıoğlu,2 Dr. Tülay Elbek,1 Dr. Bedir Korkmaz,1 Dr. Füsun Çallak Kallem,1 Dr. Berk Gün3 Adnan Menderes Üniversitesi Tıp Fakültesi, Adli Tıp Anabilim Dalı, Aydın; Adalet Bakanlığı, Adli Tıp Şube Müdürlüğü, Antakya; 3 Adalet Bakanlığı, Adli Tıp Grup Başkanlığı, İzmir 1 2

AMAÇ: Bu çalışmada, ölü muayene veya otopsisi yapılan trafik kazalarının irdelenmesi amaçlandı. GEREÇ VE YÖNTEM: Adli nitelikli 1815 ölüm olgusu arasından, trafik kazası nedeniyle ölen 334 olgu seçildi. Seçilen olgularda olay yeri, kaza türü, kazaya karışan araçların cinsi, yıllar, mevsimler, günler ve saatle ile olan ilişkisi, kurbanların trafikteki konumları, birlikte olan ortopedik yaralanmaları, otopsi yapılıp yapılmadığı ve ölüm nedenleri araştırıldı. BULGULAR: Çalışmanın kapsadığı 1815 adli ölüm olgusunun %18.4’ünün ölüm sebebi trafik kazası idi. Olguların %84.1’i erkek ve Erkek/Kadın oranı 5.3/1 olduğu saptandı. Kazaların en sık 109 (%32.6) olgu ile yaz aylarında ve en çok tatil günlerinde olduğu saptandı. Araç dışı trafik kazalarının şehir içinde daha sık görüldüğü, ölümlü kazaların ise en çok yayalara çarpma sonucu meydana geldiği ve kazalarda otomobillerin birinci sırada olduğu saptandı. TARTIŞMA: Trafik kazasına bağlı ölümlerin önemli bir halk sağlığı sorunu olmaya devam ettiği anlaşıldığından, trafik güvenliği eğitiminin güçlendirilmesi, trafik yönetim ve kontrol önlemlerinin artırılması gibi konulara verilen önemin arttırılarak devam etmesi uygun olacaktır. Anahtar sözcükler: Adli tıp; otopsi; trafik kazaları. Ulus Travma Acil Cerrahi Derg 2014;20(5):353-358

358

doi: 10.5505/tjtes.2014.18828

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ORIGIN A L A R T IC L E

Evaluation of liver injury in a tertiary hospital: a retrospective study İsmail Bilgiç, M.D.,1 Sibel Gelecek, M.D.,1 Ali Emre Akgün, M.D.,1 Mehmet Mahir Özmen, M.D.2 1

Department of General Surgery, Ankara Numune Training and Research Hospital, Ankara;

Department of General Surgery, Hacettepe University Faculty of Medicine, Ankara

ABSTRACT BACKGROUND: Liver is the most frequently injured intraabdominal organ following abdominal trauma. Liver injury in polytraumatized patients can vary from minor contusions to major lacerations and is associated with morbidity and mortality. The objective of this study was to evaluate the outcome of liver injury in polytraumatized patients. METHODS: Only surgically treated 82 patients with liver injury over an eight year period (2005-2013) were included in this study and analyzed retrospectively. Data collected included demographics, laboratory findings, intraoperative findings, operative management, and outcome. The patients were divided into two groups and the mortality and survival data were compared. RESULTS: The overall mortality rate was 18.3% (15 of 82 patients). 34 (41.5%) patients had blunt, forty-eight (48.5%) had penetrating trauma. There were multiple traumas in forty-seven (57%) patients. Forty-seven (57%) patients had total of seventy one coexisting intraabdominal injuries. Forty-six (56.1%) patients had stable and thirty-six (43.9%) had unstable hemodynamics on admission. In mortality group AST, ALT, LDH, APTT, PT, INR, and creatinine levels were high, fibrinogen levels and platelet counts were low on admission. CONCLUSION: Hemodynamic instability, coexisting musculoskeletal and chest injury, high APTT, PT, INR, AST, ALT, LDH levels, and low fibrinogen levels and platelet counts on admission should be considered as predictive factors for mortality. Key words: Liver enzymes; liver injury; mortality.

INTRODUCTION

MATERIALS AND METHODS

Liver is the most frequently injured organ following abdominal trauma[1] and associated injuries contribute significantly to morbidity and mortality. Liver is a particularly vulnerable organ because of its size and the fixed position in the right hypochondria. Mortality rates have fallen from 66% in World War II to current levels of 28%;[2,3] however, mortality rates from complex liver trauma still remain high despite improvements in resuscitation, anesthesia and intensive care facilities.[4]

This retrospective clinical study was performed in the Emergency Service of Ankara Numune Teaching and Research Hospital between August 2005 and January 2013. Only surgically treated 82 patients were included in this study and analyzed. All patients had either unstable hemodynamics or signs of abdominal injuries requiring operation. Clinical data regarding patient demographics, AST (aspartate aminotransferase), ALT (alanine aminotransferase), LDH (lactate dehydrogenase), APTT (activated partial thromboplastin time), PT (prothrombin time), INR (international normalized ratio), fibrinogen, urea, creatinine, hemoglobin levels, platelet counts, and white blood cell counts on admission, mechanism of injury, hemodynamic status on presentation, hepatic injury grade, operative procedures, coexisting abdominal and extraabdominal injuries, number of blood transfusion, outcome in terms of liver injury related morbidity and mortality were collected. Coexisting extra-abdominal injuries were divided broadly into cranial injury, chest injury (including rib fracture, haemothorax or pneumothorax, lung and cardiac), musculoskeletal system injuries (including long bone fracture) and retroperitoneal hematoma (including pelvic fracture and great vessel injury).

The aim of this retrospective study was to document the outcome of the patients treated operatively. Address for correspondence: İsmail Bilgiç, M.D. Ülkü Mah., Talatpaşa Bulvarı, No: 5, Altındağ, 06100 Ankara, Turkey Tel: +90 312 - 508 51 33 E-mail: drismailbilgic@gmail.com Qucik Response Code

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359

Bilgiç et al. Evaluation of liver injury in a tertiary hospital

In accordance with the current Advanced Trauma Life Support (ATLS) protocols, patients were divided into two main groups according to the hemodynamics at presentation: stable and unstable.[5] Hemodynamic instability was defined as systolic blood pressure less than 90 mmHg and pulse rate higher than 100 beats per minute at the time of presentation in our hospital. Three patients were in cardiopulmonary arrest on admission and were operated soon after resuscitation. Those patients were classified in a third group called “cardiopulmonary arrest”. Based on the operation record, liver injuries were graded according to the Organ Injury Scale of the American Association for the Surgery of Trauma.[6] The surgical techniques used to control bleeding during the operations were grouped into five categories including non-therapeutic, simple hemostatic measures, hepatorrhaphy with primary saturation, segmentectomy and lobectomy. Intervention was considered non-therapeutic when no active bleeding from the liver injury was detected. Superficial lacerations were managed by simple hemostatic measures such as diathermy and application of biomaterials (collagen sponge, oxidized regenerated cellulose gauze). Hepatorrhaphy was performed applying deep horizontal mattress stitches with polyglycolic acid. Peripherally located large lacerated segments were resected in non-anatomical fashion. Lobectomy was carried out as right hepatectomy in anatomical fashion.

Statistical Method Data were analyzed using the statistical package, PASW 18.0 for Windows (SPSS, Chicago, IL, USA). The KolmogorovSmirnov test was applied to evaluate the distribution of values in continuous variables. The chi-squared test or Fischer’s exact test was used to compare categorical data. For the parametric distribution, Student’s t-test was used to compare the mean values of two groups. For nonparametric variables, the Kruskal-Wallis test or Mann-Whitney U-test was used to compare the median values of the response variable. Correlation analysis was performed using Pearson or Spearman. A stepwise logistic regression analysis was also carried out. The model included explanatory or predictive factors as variables suggested in the univariate analysis to be more strongly and significantly associated with mortality. Mortality was the outcome variable for multivariate analysis. The odds ratio (OR) was calculated as an estimate of relative risk between two groups on the basis of mortality as an outcome. Statistical significance was defined as p<0.05.

RESULTS From August 2005 to January 2013, 82 patients with liver trauma were surgically treated in the Department of Emergency Service of Ankara Numune Teaching and Research Hospital. Among these eighty-two patients, there were 77 (94%) males and 5 (6%) females, with a mean age of 34 years (range, 17360

90) (Table 1). The overall mortality rate was 18.3%. Patients’ white blood cell count (WBC), platelet count, hemoglobin, AST, ALT, LDH, APTT, PT, INR, fibrinogen, urea and creatinine levels were measured on admission (Table 1). Age had no significant effect on mortality (p=.08); however, the female gender was found to be significant on mortality (p=.04). Injury was defined as blunt trauma in thirty-four (41.5%) patients, stab wounds in thirty-eight (46.3%) and gunshot injury in ten (12.2%) patients. Forty-six (56.1%) patients had stable, thirty-three (40.2%) had unstable hemodynamics and three (3.7%) were in cardiopulmonary arrest on admission. Considering the intraabdominal injury; 35 patients had isolated liver injury and the remaining forty-seven (57%) had a total of seventy one coexisting intraabdominal injuries. Liver injury occurred as a component of multiple traumas in forty-seven (57%) patients. Musculoskeletal system injuries were the most common coexisting injuries (Table 2). In operative findings, according to the Organ Injury Scale of the American Association for the Surgery of Trauma, 27 (33%) patients had Grade I, thirty-seven (45%) had Grade II, fifteen (18%) had Grade III, two (3%) had Grade IV and one (1%) had Grade V injuries (Table 2). No active bleeding from the liver in 10 (12%) patients undergoing non-therapeutic intervention during surgery was detected. Simple hemostatic measures such as diathermy, application of biomaterials (collagen sponge, oxidized regenerated cellulose gauze) were performed in fifteen (18%) patients. Hepatorrhaphy was the most common surgical procedure employed to control the bleeding in fifty-four (66%) patients. Two patients (3%) had peripherally located large lacerated segments and non-anatomical segmental resections were performed. A patient had central crush

Table 1. Laboratory findings Parameter Mean±SD Age (year)

34.0 ±13.4

Hemoglobin (gr/dl)

13.1 ±2.3

White blood cells

14784.4±6940.3

Platelet (/mm3) 246500±78200 Urea levels Creatinine levels

34.07±19.7 1.08±.44

Aspartate aminotransferase

277.6±382.4

Alanine aminotransferase

272.9±394.02

Lactate dehydrogenase

648.4±624.4

Activated partial thromboplastin time

33.2±3.7

Prothrombin time

16.4±1.0

International normalized ratio

1.3±.08

Fibrinogen 195.6±89.5 Transfusion requirement

2.3±3.8 (0-16)

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BilgiĂ§ et al. Evaluation of liver injury in a tertiary hospital

Table 2. Clinical features

Type of injury

Blunt trauma

41.5

Stab wounds

46.3

Gunshot wounds

12.2

3.7

Hemodynamic status on admission

Cardiopulmonary arrest

Unstable

33 40.2

Stable

46 56.1

Grade of liver injury

Grade I

Grade II

Grade III

Grade IV

Grade V

Non-therapeutic

Hepatorrhaphy

Segmentectomy

Lobectomy

Diaphragm

Spleen

Stomach

Kidney

Colon

Operative procedure Simple hemostatic measures

Coexisting intraabdominal injury

Small intestine

injury (Table 4). LDH levels on admission were found as an independent risk factor for mortality in multivariate analysis (p=0.008). Preoperative blood transfusion requirement ranged from 0-16 units (mean: 2.3Âą3.8) and it was statistically correlated with the grade of liver injury (p=0.003) (Table 4). Hemodynamic instability on admission and the type of injury were found to be significantly correlated with mortality (p=.001 and p=.04, respectively) (Table 5). Accompanying abdominal injuries were not observed to be associated with mortality; however, the grade of the liver injury, presence of musculoskeletal system and chest injury were found to be associated with mortality (Table 5). Packing was performed in 6 patients. In those patients, three had grade III and two had grade IV and one had grade V injuries. Among the two patients who died in the packing group, one had grade IV and the other had grade III injuries. A significant relationship between the grade of the liver injury and packing application was observed (Table 4). Out of 82 patients, fifteen did not survive. Two of them had isolated liver injury and both injuries were caused by blunt trauma. The mean age in the mortality group was 35 (range, 20-61) years. Among the fifteen patients, 12 (80%) were males and 3 (20%) were females. Ten (66.7%) patients had blunt trauma, 3 (20%) had stab wounds and 2 (13.3%) had gunshot wounds. One (6.7%) patient was in cardiopulmonary arrest, 2 (13.3%) were hemodynamically stable and 12 (80%) were hemodynamically unstable on admission. The grade of the liver injury, applied surgical technique and laboratory results were shown on Table 6.

Duodenum

Gallbladder

Pancreas

Eight patients (9.75%) required re-laparotomy for various reasons including the removal of packs (3), no improvement (2), and intra-abdominal abscess formation (2). There was only one bile leak treated non-operatively.

DISCUSSION

Coexisting extra-abdominal injury

Musculoskeletal system

Chest trauma

Retroperitoneal injury

Cranial injury

injury resulting in a stellate-type laceration including segment 5, 6, 7, 8 and right hepatic vein injury in the liver. Right hepatectomy was performed for this patient (Table 2). High levels of AST, ALT, LDH, APTT, PT, INR, creatinine and low levels of fibrinogen and low platelet counts on admission were found to be associated with mortality (Table 3). In addition, AST, ALT, APTT, PT, INR, and LDH levels on admission were found to be correlated with the grade of liver Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Although splenic injuries are more common following blunt abdominal trauma, liver is the most frequently injured intraabdominal organ.[4] Complex liver injuries are still a challenging problem with high mortality rates (50%) despite improvements in resuscitation, surgical skills, anesthesia and intensive care. High grade liver injuries are usually associated with extra and intra-abdominal injuries due to high magnitude of the trauma, increasing the rate of mortality. The aim of this retrospective research was to evaluate the outcomes of surgically treated patients. Seventy seven (94%) patients were male in our study. A male predominance has been demonstrated in almost every other liver trauma series, including studies from England (79%),[7] other parts of Western Europe (67%- 74%),[8-10] South Africa 361

Bilgiç et al. Evaluation of liver injury in a tertiary hospital

Table 3. Significant laboratory findings for mortality

Mortality group

Survival group

Age

34.8 (±11.5)

33.8 (±13.8)

.08

Hemoglobin

12.2 (±2.8)

13.3 (±2.1)

.117

White blood cells

18046 (±8687)

14111 (±6400)

.062

205000 (±76000)

257000 (±75000)

.025

40.54 (±41.75)

32.65 (±10.16)

.193

1.4 (±.75)

1.0 (±.3)

.003

Aspartate aminotransferase

559.2 (±462.2)

217.3 (±338.2)

.001

Alanine aminotransferase

546.0 (±495.6)

215.4 (±347.7)

.001

Platelet Urea Creatinine

Lactate dehydrogenase

1378 (±775.4)

533.2 (±521.5)

.009

Activated partial thromboplastin time

40.2 (23.8-133)

23.6 (17.5-51.9)

.000

Prothrombin time International normalized ratio

20 (12.7-47)

13.8 (12-19)

.004

1.56 (1.02-3.75)

1.1 (.95-1.68)

.004

129.2 (±56)

219.7 (±85.77)

.002

Fibrinogen

Table 4. Factors correlated with the grade of the liver injury

r p

Aspartate aminotransferase

.346

Alanine aminotransferase

.324

0.007

Lactate dehydrogenase

.561

<0.001

Activated partial thromboplastin time

.30

0.046

Prothrombin time

.36

0.019

0.004

International normalized ratio

.36

0.02

Blood transfusion requirement

.322

0.003

Packing

.352 0.001

(81%)[11] and North America (61%- 79%).[12] Although the female gender was found to have a statistically significant effect on mortality, no homogeneity in gender distribution could be observed in our study as there were only five female patients. A higher frequency of liver trauma among younger patients was determined in the present study. Wilson et al.[13] have reviewed many series of liver trauma and emphasized that the patient average age tended to lie between 25 and 30. Continuity of this global pattern has been shown in more recent works. Large liver trauma series have shown mean ages of 35, 32, and 30, respectively in Germany,[10] South Africa,[11] and North America.[12] In the present study, liver injuries were caused by blunt trauma in 41.5% of the patients (12.2% falls from height, 29.3% road traffic accidents) and penetrating trauma was seen in 58.5% of the patients (46.3% stab wounds, 12.2% gunshot 362

Grade of the liver injury

wounds). Scollay et al.[14] have shown that European authors have reported high frequencies of blunt trauma. On the contrary, Krige,[11] reporting the South African experience, found that 66% of 446 patients had sustained penetrating liver injury. Feliciano et al.[15] have reviewed 1000 patients with liver trauma and found that penetrating trauma was responsible for 86% of hepatic injuries. On the other hand, incidence of stab wounds in penetrating trauma in the present study was similar to the European series having significantly higher incidence of stab injuries and a lower incidence of gunshot wounds.[14] It has also been shown that blunt injuries have consistently been associated with a higher mortality rate than penetrating injuries.[16,17] In the present study, mortality has been found to be significantly higher in blunt trauma patients. This might partly be explained by blunt traumas being usually associated with extra and intra-abdominal injuries increasing mortality rates due to the high magnitude of trauma. Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Bilgiรง et al. Evaluation of liver injury in a tertiary hospital

Table 5. Gender, coexisting extra-abdominal and intra-abdominal injuries and hemodynamic status

Mortality group

n %

Female (Gender)

Survivor group

n %

.04

10/5

29/10

24/43

71/90

.04

Musculoskeletal system

33.3

66.7

.03

Chest trauma

36.4

63.6

.02

Type of trauma (Blunt/penetrant)

Retroperitoneal injury

Cranial injury

42.9

57.1

Diaphragm

22.2

14 77.8

Spleen

4 30.8

9 69.2

Stomach

2 18.2

9 81.8

1.0

Kidney

1 12.5

7 87.5

1.0

Colon

3 42.9

4 57.1

Hemodynamic instability

In the present study, hemodynamic instability was recorded in 40% of liver trauma patients. These patients had a higher mortality rate than those who had a blood pressure higher than 90 mmHg (p=0.001). Several studies have identified hemodynamic instability as an early predictor of outcome after severe injuries.[4,9,14,18-21] It has been shown by Clarke et al.[22] that mortality increases by 1% every 3 minutes after a trauma involving hematogenic shock. Also, Wilson have emphasized that shock on admission is thought to double the mortality rates.[23] High mortality rates due to hemodynamic instability may be the result of severe exsanguinating hemorrhage resulting in catastrophic final pathway of hypothermia, coagulation, and acidosis. Table 6. Demographic and clinical features of the mortality group

Grade of liver injury

Grade I

6.7

Grade II

Grade III

Grade IV

6.7

Grade V

6.7

Non-therapeutic

Operative procedure 1

6.7

Hepatorrhaphy

Simple hemostatic measures

Segmentectomy

6.7

Lobectomy

6.7

Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

.1 .001

Hemorrhage accounts for over the third of early trauma deaths[24] and is a leading cause of preventable mortality.[25] Acute traumatic coagulopathy is known to occur in about 28% to 34% of patients with multiple injuries.[26] Most of the literature characterizes the condition by reference to an elevated INR, PT and/or PTT of 1.5 or 2 times normal.[27] It has been shown in many studies that patients arriving in the emergency department with a coagulopathy are three to four times more likely to die and eight times more likely to die within the first 24 hours.[26,28,29] In the present study, we found that PT, APTT and INR were significantly high in the mortality group than in the survivors. There are controversies about fibrinogen levels in acute traumatic coagulopathy. Martini et al.[30] have shown that fibrinogen levels rarely decrease in patients with acute traumatic coagulopathy. On the other hand, it has been shown that fibrinogen concentrations rapidly decline after injury especially in hypoperfusion.[31] Significantly low fibrinogen levels were detected in the mortality group. Platelet counts are mildly reduced by trauma and this appears to be associated with poor outcomes.[31] Brown et al.[32] have reported that platelet count on admission is inversely correlated with 24-hour mortality. In the present study, low platelet counts were significantly correlated with mortality. All these parameters are important since recent therapeutic and observational studies have demonstrated improved survival rates with better and early management of hemostasis after injury.[31] Additionally, early identification of the need for massive transfusion (MT) may increase the speed and success of hemostatic intervention in trauma patients. The use of massive transfusion protocols standardizing blood component therapy that automatically delivers at specific points within resuscitation may be of benefit to prevent and treat early coagulopathy. 363

Bilgiç et al. Evaluation of liver injury in a tertiary hospital

It is well-known that liver injuries almost always accompany injuries to other organ systems and liver injury has been found to be associated with high mortality rates with the presence of coexisting injuries.[33,34] Also, Nishida et al.[18] have founded that the presence of a coexisting injury is an independent prognostic factor for mortality in their multivariate analysis. In the present study, the presence of musculoskeletal injury and chest injury were both found to be associated with high mortality rates (p=.03 and p=.02). Elevated serum liver enzymes, AST and ALT, are known to be associated with blunt traumatic liver injury. It has been shown in animal models and human studies that not only does the increase in the enzyme occur within a few hours after blunt liver trauma, but the amount of the increase in the enzyme also correlates to the severity of liver injury, as in the present study.[35] Similarly, statistically significant and increasing ALT levels were observed among patients with increasing grades of liver injury.[7] Tan et al.[21] have reported that there is an important relationship between ALT, AST and hepatic injuries after blunt abdominal trauma and also patients with normal ALT, AST and LDH are unlikely to have major liver injury. Nishida et al.[18] have shown that ALT is an independent risk factor for mortality in their multivariate analysis. AST and ALT levels on admission were found to be correlated with mortality and severity of liver injury in the present study. LDH is a cytoplasmic enzyme present essentially in all major organ systems. The extracellular appearance of LDH is used to detect cell damage or cell death. It is released into the peripheral blood after cell death caused by ischemia, excess heat or cold, starvation, dehydration, injury, exposure to bacterial toxins, ingestion of certain drugs, and chemical poisonings. Due to its extraordinarily widespread distribution in the body, the total serum LDH is a highly sensitive, but nonspecific test. In the present study, LDH levels on admission were found to be correlated with mortality and severity of the liver injury; in addition, LDH was found as an independent risk factor for mortality in multivariate analysis in the present study. High LDH levels may reflect the number and severity of effected organs. AST, ALT and LDH together may be useful for prognostic factors in liver injury.

Conclusion Hemodynamic instability, coexisting musculoskeletal and chest injury, and high APTT, PT, INR, AST, ALT, LDH levels and low fibrinogen levels and low platelet counts on admission should be considered as predictive factors for mortality in patients who sustained liver injury due to trauma. It is crucial to keep in mind that the high AST, ALT and LDH levels on admission might also reflect the high grade of liver injury. Conflict of interest: None declared. 364

REFERENCES 1. Feliciano DV. Surgery for liver trauma. Surg Clin North Am 1989;69:273-84. 2. Richardson JD. Changes in the management of injuries to the liver and spleen. J Am Coll Surg 2005;200:648-69. 3. Trunkey DD. Hepatic trauma: contemporary management. Surg Clin North Am 2004;84:437-50. 4. Parks RW, Chrysos E, Diamond T. Management of liver trauma. Br J Surg 1999;86:1121-35. 5. American College of Surgeons Committee on Trauma. Advanced Trauma Life Support Student Manuel. 5th ed. Chicago, Illionis: American College of Surgeons; 1995. 6. Moore EE, Cogbill TH, Jurkovich GJ, Shackford SR, Malangoni MA, Champion HR. Organ injury scaling: spleen and liver (1994 revision). J Trauma 1995;38:323-4. 7. John TG, Greig JD, Johnstone AJ, Garden OJ. Liver trauma: a 10-year experience. Br J Surg 1992;79:1352-6. 8. Talving P, Beckman M, Häggmark T, Iselius L. Epidemiology of liver injuries. Scand J Surg 2003;92:192-4. 9. Menegaux F, Langlois P, Chigot JP. Severe blunt trauma of the liver: study of mortality factors. J Trauma 1993;35:865-9. 10. Matthes G, Stengel D, Seifert J, Rademacher G, Mutze S, Ekkernkamp A. Blunt liver injuries in polytrauma: results from a cohort study with the regular use of whole-body helical computed tomography. World J Surg 2003;27:1124-30. 11. Krige JE, Bornman PC, Terblanche J. Liver trauma in 446 patients. S Afr J Surg 1997;35:10-5. 12. Pachter HL, Knudson MM, Esrig B, Ross S, Hoyt D, Cogbill T, et al. Status of nonoperative management of blunt hepatic injuries in 1995: a multicenter experience with 404 patients. J Trauma 1996;40:31-8. 13. Wilson RH, Moorehead RJ. Hepatic trauma and its management. Injury 1991;22:439-45. 14. Scollay JM, Beard D, Smith R, McKeown D, Garden OJ, Parks R. Eleven years of liver trauma: the Scottish experience. World J Surg 2005;29:7449. 15. Feliciano DV, Mattox KL, Jordan GL Jr, Burch JM, Bitondo CG, Cruse PA. Management of 1000 consecutive cases of hepatic trauma (19791984). Ann Surg 1986;204:438-45. 16. Fabian TC, Croce MA, Stanford GG, Payne LW, Mangiante EC, Voeller GR, et al. Factors affecting morbidity following hepatic trauma. A prospective analysis of 482 injuries. Ann Surg 1991;213:540-8. 17. Rivkind AI, Siegel JH, Dunham CM. Patterns of organ injury in blunt hepatic trauma and their significance for management and outcome. J Trauma 1989;29:1398-415. 18. Nishida T, Fujita N, Nakao K. A multivariate analysis of the prognostic factors in severe liver trauma. Surg Today 1996;26:389-94. 19. Sikhondze WL, Madiba TE, Naidoo NM, Muckart DJ. Predictors of outcome in patients requiring surgery for liver trauma. Injury 2007;38:65-70. 20. Velasco RA, Martínez FB, Fernández GB, Peck GS. Management of hepatic trauma: four years experience. [Article in Spanish] Cir Esp 2011;89:511-6. [Abstract] 21. Tan KK, Bang SL, Vijayan A, Chiu MT. Hepatic enzymes have a role in the diagnosis of hepatic injury after blunt abdominal trauma. Injury 2009;40:978-83. 22. Clarke JR, Trooskin SZ, Doshi PJ, Greenwald L, Mode CJ. Time to laparotomy for intra-abdominal bleeding from trauma does affect survival for delays up to 90 minutes. J Trauma 2002;52:420-5.

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Bilgiç et al. Evaluation of liver injury in a tertiary hospital 23. Wilson RH, Moorehead RJ. Hepatic trauma and its management. Injury 1991;22:439-45. 24. Sauaia A, Moore FA, Moore EE, Moser KS, Brennan R, Read RA, et al. Epidemiology of trauma deaths: a reassessment. J Trauma 1995;38:18593. 25. Gruen RL, Jurkovich GJ, McIntyre LK, Foy HM, Maier RV. Patterns of errors contributing to trauma mortality: lessons learned from 2,594 deaths. Ann Surg 2006;244:371-80. 26. Brohi K, Cohen MJ, Ganter MT, Matthay MA, Mackersie RC, Pittet JF. Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the protein C pathway? Ann Surg 2007;245:812-8. 27. Cosgriff N, Moore EE, Sauaia A, Kenny-Moynihan M, Burch JM, Galloway B. Predicting life-threatening coagulopathy in the massively transfused trauma patient: hypothermia and acidoses revisited. J Trauma 1997;42:857-62. 28. Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma 2003;54:1127-30. 29. MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma 2003;55:39-44.

30. Martini WZ, Dubick MA, Pusateri AE, Park MS, Ryan KL, Holcomb JB. Does bicarbonate correct coagulation function impaired by acidosis in swine? J Trauma 2006;61:99-106. 31. Frith D, Davenport R, Brohi K. Acute traumatic coagulopathy. Curr Opin Anaesthesiol 2012;25:229-34. 32. Brown LM, Call MS, Margaret Knudson M, Cohen MJ. (Trauma Outcomes Group). A normal platelet count may not be enough: the impact of admission platelet count on mortality and transfusion in severely injured trauma patients. J Trauma 2011;71(2 Suppl 3):337-42. 33. Croce MA, Fabian TC, Menke PG, Waddle-Smith L, Minard G, Kudsk KA, et al. Nonoperative management of blunt hepatic trauma is the treatment of choice for hemodynamically stable patients. Results of a prospective trial. Ann Surg 1995;221:744-55. 34. Domínguez Fernández E, Aufmkolk M, Schmidt U, Nimtz K, Stöblen F, Obertacke U, et al. Outcome and management of blunt liver injuries in multiple trauma patients. Langenbecks Arch Surg 1999;384:453-60. 35. Ritchie AH, Williscroft DM. Elevated liver enzymes as a predictor of liver injury in stable blunt abdominal trauma patients: case report and systematic review of the literature. Can J Rural Med 2006;11:283-7.

KLİNİK ÇALIŞMA - ÖZET OLGU SUNUMU

Üçüncü basamak hastanede karaciğer travmalarının değerlendirilmesi: Geriye dönük bir çalışma Dr. İsmail Bilgiç,1 Dr. Sibel Gelecek,1 Dr. Ali Emre Akgün,1 Dr. Mehmet Mahir Özmen2 1 2

Ankara Numune Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Ankara; Hacettepe Üniversitesi Tıp Fakültesi, Genel Cerrahi Kliniği, Ankara

AMAÇ: Abdominal travmalarda karaciğer en sık yaralanan organdır. Politravmatik bir hastada karaciğer yaralanması minör yaralanmalardan majör yaralanmalara kadar değişen bir şekilde etkilenebilir. Bu yaralanma derecesine göre morbidite ve mortaliteye katkıda bulunur. Bu çalışmanın amacı ameliyatta karaciğer yaralanması tespit edilen hastaların sonuçlarının değerlendirilmesidir. GEREÇ VE YÖNTEM: 2005 ve 2013 yılları arasında, sadece cerrahi sırasında karaciğer hasarı tespit edilen 82 hasta geriye dönük olarak incelendi. Hastaların demografik verileri, laboratuvar verileri, ameliyat bulguları ve yapılan ameliyatları incelendi. Hastalar iki gruba ayrıldı: Mortalite grubu ve yaşayan hastalar grubu. BULGULAR: Çalışmadaki erkek hasta sayısı 77 (%94), kadın hasta sayısı beş (%6) olarak bulundu. Ortalama yaş 34 (17-90) idi; 15 (%18.3) hastada mortalite gözlendi, 34 (%41.5) hastada künt karın travması, 48 (%48.5) hastada penetran yaralanma mevcuttu. Hastaların 47’sinde (%57) çoklu travma mevcuttu, 47 (%57) hastada 71 adet eşlik eden karıniçi diğer organ yaralanmaları mevcuttu. Başvuru anında hemodinamik olarak 46 (%56.1) hasta stabil, 36 (%43.9) hasta unstabil idi. Başvuru anındaki AST, ALT, LDH, APTT, PT, INR ve kreatinin değerleri mortalite grubunda yaşayan hasta grubuna göre daha yüksek, fibrinojen ve trombosit sayısı ise daha düşük idi. TARTIŞMA: Hemodinamik instabilite, eşlik eden iskelet sistemi göğüs travması, başvuru anındaki yüksek APTT, PT, INR, AST, ALT, LDH ve düşük fibrinojen ve trombosit değerleri mortalite açısından prognostik faktörler olabilir. Anahtar sözcükler: Karaciğer enzimleri; karaciğer hasarı; mortalite. Ulus Travma Acil Cerrahi Derg 2014;20(5):359-365

doi: 10.5505/tjtes.2014.22074

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ORIGIN A L A R T IC L E

Comparison of early surgery (unroofing-curettage) and elective surgery (Karydakis flap technique) in pilonidal sinus abscess cases Burhan Hakan Kanat, M.D.,1 Mehmet Buğra Bozan, M.D.,1 Fatih Mehmet Yazar, M.D.,1 Mesut Yur, M.D.,2 Fatih Erol, M.D.,1 Zeynep Özkan, M.D.,1 Seyfi Emir, M.D.,3 Aykut Urfalıoğlu, M.D.4 1

Department of General Surgery, Elazığ Training and Research Hospital, Elazığ;

Department of General Surgery, Adıyaman State Hospital, Adıyaman;

Department of General Surgery, Namık Kemal University Faculty of Medicine, Tekirdağ;

Department of Anesthesia, Elazığ Training and Research Hospital, Elazığ

ABSTRACT BACKGROUND: The aim of this study is to compare the effectiveness and success of early (acute) period local surgical intervention (unroofing-curettage) followed by dressing and secondary healing with the surgery performed in elective conditions (pilonidal sinus excision and Karydakis flap) following conventional abscess treatment (drainage-antibiotic therapy) in pilonidal sinus abscess cases. METHODS: The data of the patients treated for pilonidal sinus abscesses in our clinic between January 2012 and March 2013 were analyzed, retrospectively. Those who had early surgery were determined as Group S, and those who had elective surgery following drainage-antibiotic therapy were determined as Group K. Patients in both groups were compared in terms of age, gender, complications, recurrence rate and healing time. Patients were followed for an average of 14 months. RESULTS: Of the 53 patients included in the study, 28 were in Group S and 25 in Group K. The mean age and gender distribution of both groups were similar and a significant difference was not found between the groups in terms of complication development and recurrence. However, there was a statistically significant difference between the groups in terms of treatment duration (p=0.02). CONCLUSION: In treating acute pilonidal abscesses, the Karydakis method, following drainage-antibiotic therapy, is a preferable method due to its shorter treatment duration and higher patient comfort. Key words: Antibiotic therapy; drainage; incision; Karydakis; pilonidal abscess.

INTRODUCTION Pilonidal sinus disease (PSD), which was first described by Anderson in 1847, still remains a controversial disease for which modern surgery has not created a precise treatment algorithm and the etiology has still not been illuminated.[1] PSD, which is observed at a rate of 0.7% in the general population, most commonly affects young adults between the ages of 15-25.[2] Address for correspondence: Fatih Mehmet Yazar, M.D. Elazığ Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Elazığ, Turkey Tel: +90 424 - 237 44 21 E-mail: fmyazar@hotmail.com Qucik Response Code

366

The treatment of this disease is one of the most actively discussed topics in surgery. Many methods have been presented in the literature. There are many surgical methods described, varying from the simple incision, drainage, unroofing, curettage and spontaneous secondary healing to excision-flap sliding, Karydakis, Bascom, and MacFee methods. Conservative methods including phenol solution, the crystallized phenol method, cauterization and alcohol injection have also been used.[3,4] However, among these treatment methods, an optimal treatment type has not been described yet. Although there is no accepted precise treatment method, a consensus does exist regarding the symptoms and clinical findings of the disease. Patients may either be asymptomatic or may present in any of the four distinct forms of acute pilonidal abscess, chronic fistula form or recurrent complex PSD. Although the chronic fistulizing form is the most common type seen on admission, the ratio of the patients admitted with acute pilonidal abscess reaches about 30%.[5] Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Kanat et al. The treatment of acute pilonodal abscess

When an acute pilonidal abscess is formed, within a short period of time, hyperemia, swelling and complaints of pain are observed in the sacrococcygeal area. While abscesses with these complaints may spontaneously drain, surgical intervention is usually required. The initial treatment for acute abscess is urgent drainage. However, despite drainage, antibiotic therapy, regular dressing and meticulous hygiene measures, the abscess usually reoccurs and chronic PSD develops. Surgical treatment usually awaits the patient in the chronic process. [5,6] This condition both negatively affects the patient comfort and increases treatment cost. In fact, a successful and reliable treatment method is one with a low rate of recurrence, high patient satisfaction and low costs. Therefore, in cases of acute pilonidal abscess, treatment should be performed either during drainage or right after the acute infection subsides before a basis for chronic disease can be formed. Most debates in the literature are about how the most commonly encountered clinical form of chronic fistulization should be treated. Although there are publications regarding the abscess form, they are few in number.[7,8] The aim of our study was to retrospectively compare the unroofing-curettage-secondary healing we performed during drainage with the Karydakis method followed by drainageantibiotic therapy in patients admitted to our clinic with acute pilonidal abscesses.

MATERIALS AND METHODS Patients who were treated for acute pilonidal abscess in our clinic between January 2012 and March 2013 were analyzed, retrospectively. When selecting acute abscess cases, previous complaints were ignored and patients with a few days history of painful swelling and hyperemia in the sacrococcygeal region were accepted.

(a)

(b)

(c)

A total of 64 patients treated in the same center by the same team were included in the study. Data was obtained from the records in the archive of the hospital (operation notes, epicrisis and polyclinic dressing records). Patients were questioned on the phone for recurrence. Suspicious patients were called back and controlled. Eleven patients who could not be reached and whose data was incomplete were excluded and the study was completed with 53 patients. In twenty-eight patients, unroofing and curettage was performed and left for secondary healing and in 25 patients the Karydakis method was performed following drainage-antibiotic therapy [Group S (n=28) secondary healing and Group K (n=25) Karydakis following drainage-antibiotic therapy]. The age, gender, complications, recurrence rates, and healing times of the patients were analyzed and compared. The procedure of the removal of the sinus roof (unroofing) and subsequent secondary healing were performed under sterile conditions with local anesthesia in the operating room. After the infiltration of a local anesthetic agent, the abscess was drained and the sinus tract was determined by placing a metal probe or a stile along the whole sinus tract (Figure 1a). The tract was opened by cutting the skin towards the probe. Afterwards, unroofing was performed by removing the sinus tissue and the roof of all the extensions. The sinus base was currettaged removing all the debris, hair and granulation tissue. The surgical field was washed with oxygenated water and saline solution after curettage. The fibrotic posterior wall of the sinus tract was left so as not to include any epithelium or hair tissue (Figure 1b).[7-11] Patients were prescribed oral antibiotics and analgesic drugs following dressing and were discharged. Daily wound dressings were recommended for the first week followed by three dressings the second week and then two dressings a week thereafter (Figure 1c). The patients were recommended to periodically clean hair and take

(d)

Figure 1. (a) Insertion of a metal probe along the whole length of the sinus tract. (b) Unroofing by removal of the whole roof of the sinus tissue and extensions. (c) Appearance of the same patient 21 days after unroofing. (d) Postoperative appearance of a patient following the Karydakis technique.

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Kanat et al. The treatment of acute pilonodal abscess

care of hygiene. When calculating the treatment duration; the time from the drainage of the abscess to the total healing of the sinus opening with the patient not requiring any dressings was considered. This procedure did not require hospitalization except for those who developed complications. In patients, on whom the Karydakis technique was performed after antibiotic therapy, the abscess was drained with local anesthesia, antibiotic therapy was given and the abscess regressed clinically. The surgical technique described by Karydakis was performed under spinal anesthesia (Figure 1d).[12] In these patients, the duration of treatment was calculated as the time from the abscess drainage, including the days of antibiotic use, to the day on which the sutures were removed. All patients were called in the morning of surgery and discharged on the day the drainage tube was removed. The drainage tube was removed when the amount of fluid drained was below 20 ml. By using the SPSS for Windows 11.5 program to statistically evaluate the data, the Student’s t-test and the qui-square test were applied. A p level of <0.05 was accepted to be statistically significant. The trial was initiated upon approval of the protocol by the Ethical Committee of Fırat University Medical Faculty, dated January-2014 and designated number 2014-02/01.

RESULTS

No statistically significant difference was found between the groups in terms of gender distribution (p=0.05). The mean duration of treatment was 34.7±3.3 (28-42) days in Group S and 25.9±6.6 (21-46) in Group K. This difference was found to be statistically significant (p=0.0) (Figure 1a). The duration of treatment was observed to be significantly shorter in Group K. The mean duration of follow-up was 14.09±2.9 (8-21) months in Group S and 14±2.7 (8-20) in Group K and this difference was not found to be statistically significant (p=0.55). While complications were observed in four of the 53 patients (7.5%), recurrence was detected in two (3.77%). Complications developed in two patients (7.1%) in Group S and two (8%) in Group K. There was no statistically significant difference between the groups in terms of complication rate (p=0.52). While bleeding was seen in two patients in Group S, wound infection developed in two patients in Group K. Patients who developed bleeding were treated with compression dressings and observed. No additional interventions were required. The wounds of the patients who developed wound infection were opened and treated with oral antibiotics. One of these patients had recurrence during follow-up. One of the recurrences (3.5%) was in the secondary healing group and another was in Group K (4%). A statistically significant difference was not observed between the groups in terms of recurrence (p=0.46). Patients in both groups with recurrence had a second operation where a rhomboid excision + Limberg flap method was performed. One of the recurrences was detected on the 11th month follow-up and another on the 14th month follow-up.

Of the 53 patients included in the study who were treated for acute pilonidal abscess in our clinic, twenty-eight had unroofing-secondary healing performed (Group S) (52.8%) and twenty-five (47.2%) had the Karydakis operation following antibiotic therapy (Group K) (Table 1).

DISCUSSION

The mean age of the secondary healing group was 22.7±3.3 (20-33) and the mean age of Group K was 23.4±4.8 (16-35) and this difference was not found to be statistically significant (p=0.21). While all patients in Group S were male, in Group K, 3 patients (12%) were female and 22 (88%) were male.

PSD is commonly observed between the ages of 15 and 25 and is 3-4 times more common among males than females. While its incidence decreases after the age of 25, it is quite rare in the middle and advanced ages.[13] In our study, the mean age of the patients was consistent with that of the literature.

Table 1. Comparison of patient data Number of patients (n) Distribution of gender (F/M)

Unroofıng-curettage-secondary healing (Group S)

Karydakis following antibiotic therapy (Group K)

28 (52.8%)

25 (47.2%)

–

0/28

3/22

0.05

Age (years)

22.7±3.3 (20-33)

23.4±4.8 (16-35)

0.21

Duration of treatment (days)

34.7±3.3 (28-42)

25.9±6.6 (21-46)

0.02

Duration of follow-up (months)

14.09±2.9 (8-21)

14±2.7 (8-20)

0.55

Complications

2 (7.1%)

2 (8%)

0.52

Recurrence

1 (3.5%)

1 (4%)

0.46

368

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Kanat et al. The treatment of acute pilonodal abscess

The main complaint of the patients is painless, continuous or periodic discharge. However, with a carefully taken medical history, a large percentage will reveal previously experienced abscesses.[11] Many treatment options are available in the literature for this disease. The main principle of treatment is to have the patients return to their daily routine and work pattern and eliminate recurrence. The aim should be to obtain a low recurrence rate and have the patient return to a functional daily routine as soon as possible. Patient comfort should also be remembered. Successful treatment should include a minimally invasive and cost effective operation, and easy postoperative care. Karydakis introduced a novel method for the treatment of PSD in 1973 and published the largest pilonidal sinus series in the world in 1992. In his paper, he presented the data of 7471 patients between the years 1966-1990 and reported a less than 1% recurrence rate on follow-ups of 2-20 years.[12] Most patients with a chronic, painless discharge do not immediately apply to physicians. However, when an abscess develops, there is swelling, hyperemia and severe pain in the sacrococcygeal area of the patient. In these cases, patients usually admit to the hospital as soon as possible. Sinus abscesses present as severe pain and loss of labor. The primary treatment option is the regression of the complaints caused by the abscess. However, again, patients usually apply to physicians after the primary treatment. Due to after drainageantibiotic therapy, a high rate of chronicity, reported as high as 90% in some series, is observed.[11,14] Leaving the patient for secondary healing after abscess, drainage negatively affects patient comfort. A painless discharge occurs on the chronic background and this condition upsets the patient. Therefore, in our opinion, treatment should be planned and performed on admission. In our study, the morbidity ratio was detected to be 8% in patients who underwent the Karydakis technique. This ratio was found to be 7.1% in the secondary healing group. While the recurrence rate was 1% in Karydakisâ&#x20AC;&#x2122; own study, this was reported being 4% in a study by Kitchen.[15] In our study, the recurrence rate was found to be 4% in the Karydakis group. The recurrence rate has been reported to vary between 1-19% in patients who undergo unroofing-curettage[7,8] and this ratio was found to be 3.5% in our study. The duration of healing varies between 4-6 weeks in patients with chronic pilonidal sinus having excision and been left for secondary healing and followed up with dressings.[16] While long healing period is the main disadvantage of this method, the need for dressing at certain intervals seems to be another disadvantage. However, this technique, which reduces the likelihood of chronicity in patients with abscesses, is easily applicable, and besides the abscess drainage, the treatment may Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

be done in a single session. The most important advantage is that it can be performed under local anesthesia. Performing abscess drainage and the Karydakis method after antibiotic therapy seems to treat the acute pilonidal abscess making it chronic. In this method, the operation is performed after clinical regression of the abscess. In fact, the interval between the day of abscess development and the operation day is shortened, thus, the chronic symptoms of the patient are prevented. The duration of treatment varies between 2-3 weeks in different studies conducted with similar methods. However, in many patients operated on due to chronic pilonidal sinus complaints, the postoperative period is accepted as the duration of treatment.[17,18] The duration of antibiotic therapy applied after drainage is not calculated. In this study, as different from the literature, the duration of treatment was accepted as the time from the day of abscess drainage to the day of suture removal, thus including the days of antibiotic therapy. With this method, the duration of treatment was found to be statistically significant compared to the unroofing-curettage secondary healing group (p=0.02). Long durations of treatment and dressing requirement negatively affect patient comfort. Therefore, the secondary healing method is not preferred by the patients despite being performed under local anesthesia and eliminating the need for a second intervention. Acute pilonidal abscesses are common in the young population and therefore prolonged curative therapy leads to the loss of labor. Performing surgical procedures earlier or later may affect the overall success of treatment. Therefore, we suggest that the Karydakis flap application should be preferred after abscess treatment as it shortens the duration of treatment. Conflict of interest: None declared.

REFERENCES 1. Anderson AW. Hair extracted from an ulcer. Boston Med Surg J 1847;36:74-6. 2. Onder A, Girgin S, Kapan M, Toker M, Arikanoglu Z, Palanci Y, et al. Pilonidal sinus disease: risk factors for postoperative complications and recurrence. Int Surg 2012;97:224-9. 3. Girgin M, Kanat BH. The results of a one-time crystallized phenol application for pilonidal sinus disease. Indian J Surg 2014;76:17-20. 4. Kayaalp C, Olmez A, Aydin C, Piskin T, Kahraman L. Investigation of a one-time phenol application for pilonidal disease. Med Princ Pract 2010;19:212-5. 5. Bendewald FP, Cima RR. Pilonidal disease. Clin Colon Rectal Surg 2007;20:86-95. 6. Burnstein M. Managing anorectal emergencies. Can Fam Physician 1993;39:1782-5. 7. Kepenekci I, Demirkan A, Celasin H, Gecim IE. Unroofing and curettage for the treatment of acute and chronic pilonidal disease. World J Surg 2010;34:153-7. 8. Vahedian J, Nabavizadeh F, Nakhaee N, Vahedian M, Sadeghpour A.

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10. 11.

12. 13.

Comparison between drainage and curettage in the treatment of acute pilonidal abscess. Saudi Med J 2005;26:553-5. Abbas MA, Tejerian T. Unroofing and marsupialization should be the first procedure of choice for most pilonidal disease. Dis Colon Rectum 2006;49:1243. Lee SL, Tejirian T, Abbas MA. Current management of adolescent pilonidal disease. J Pediatr Surg 2008;43:1124-7. Eryilmaz R, Sahin M, Alimoğlu O, Kaya B. The comparison of incision and drainage with skin excision and curettage in the treatment of acute pilonidal abscess. Ulus Travma Acil Cerrahi Derg 2003;9:120-3. Karydakis GE. Easy and successful treatment of pilonidal sinus after explanation of its causative process. Aust N Z J Surg 1992;62:385-9. Ghnnam WM, Hafez DM. Laser hair removal as adjunct to surgery for pilonidal sinus: our initial experience. J Cutan Aesthet Surg 2011;4:1925.

14. Matter I, Kunin J, Schein M, Eldar S. Total excision versus non-resectional methods in the treatment of acute and chronic pilonidal disease. Br J Surg 1995;82:752-3. 15. Kitchen PR. Pilonidal sinus: experience with the Karydakis flap. Br J Surg 1996;83:1452-5. 16. Dudink R, Veldkamp J, Nienhuijs S, Heemskerk J. Secondary healing versus midline closure and modified Bascom natal cleft lift for pilonidal sinus disease. Scand J Surg 2011;100:110-3. 17. Sakr MF, Ramadan MA, Hamed HM, Kantoush HE. Secondary healing versus delayed excision and direct closure after incision and drainage of acute pilonidal abscess: a controlled randomized trial. Arch Clin Exp Surg 2012;1:8-13. 18. Moran DC, Kavanagh DO, Adhmed I, Regan MC. Excision and primary closure using the Karydakis flap for the treatment of pilonidal disease: outcomes from a single institution. World J Surg 2011;35:1803-8.

KLİNİK ÇALIŞMA - ÖZET OLGU SUNUMU

Pilonidal sinüs apse olgularında erken cerrahi (unroofıng-küretaj) ile elektif cerrahinin (Karydakis flep tekniği) karşılaştırılması Dr. Burhan Hakan Kanat,1 Dr. Mehmet Buğra Bozan,1 Dr. Fatih Mehmet Yazar,1 Dr. Mesut Yur,2 Dr. Fatih Erol,1 Dr. Zeynep Özkan,1 Dr. Seyfi Emir,3 Dr. Aykut Urfalıoğlu4 Elazığ Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Elazığ; Adıyaman Devlet Hastanesi, Genel Cerrahi Kliniği, Adıyaman; 3 Namık Kemal Üniversitesi Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, Tekirdağ; 4 Elazığ Eğitim ve Araştırma Hastanesi, Anestezi ve Reanimasyon Kliniği, Elazığ 1 2

AMAÇ: Pilonidal sinüs apse olgularında erken (akut) dönemde uygulan lokal cerrahi müdahale (unroofıng-küretaj) ve sonrasında pansuman takibi ve sekonder iyileşme ile apsenin klasik tedavisini takiben (drenaj-antibiyoterapi) elektif şartlarda uygulanan cerrahinin (pilonidal sinüs eksizyonu ve Karydakis flep uygulama) etkinlik ve başarısını karşılaştırmak. GEREÇ VE YÖNTEM: Ocak 2012 ile Mart 2013 tarihleri arasında kliniğimizde pilonidal sinüs apsesi nedeniyle tedavi uygulanan hastaların verileri geriye dönük olarak incelendi. Erken dönemde cerrahi uygulananlar Grup S, drenaj-antibiyoterapi sonrası elektif şartlarda cerrahi uygulananlar Grup K olarak belirlendi. Her iki gruptaki hastalar yaş, cinsiyet, komplikasyonlar, nüks oranları, iyileşme süreleri incelenerek karşılaştırıldı. Hastalar ortalama 14 ay takip edildi. BULGULAR: Çalışmaya alınan 53 hastanın dağılımı Grup S (n=28) ve Grup K (n=25) olduğu görüldü. Her iki grubun yaş ortalaması, cinsiyet dağılımı benzerdi ve komplikasyon gelişimi ve nüks açısından iki grup arasında anlamlı fark bulunmadı. Buna karşın tedavi süresi açısından arada istatistiksel olarak anlamlı fark vardı (p=0.02). TARTIŞMA: Drenaj-antibiyoterapi sonrası Karydakis yöntemi daha kısa tedavi süresi ve yüksek hasta konforu nedeniyle akut pilonidal apse tedavisinde tercih edilebilecek bir yöntemdir. Anahtar sözcükler: Antibiyoterapi; drenaj; insizyon; Karydakis; pilonidal apse. Ulus Travma Acil Cerrahi Derg 2014;20(5):366-370

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ORIGIN A L A R T IC L E

A practice report of bladder injuries due to gunshot wounds in Syrian refugees Mehmet Inci, M.D.,1 Ali Karakuş, M.D.,2 Mehmet Murat Rifaioglu, M.D.,1 Erhan Yengil, M.D.,3 Nesrin Atçi, M.D.,4 Ömer Akin, M.D.,5 Kasım Tuzcu, M.D.,6 Ahmet Kiper, M.D.,1 Onur Demirbaş, M.D.,1 Mustafa Şahan, M.D.2 1

Department of Urology, Mustafa Kemal University Faculty of Medicine, Antakya;

Department of Emergency Medicine, Mustafa Kemal University Faculty of Medicine, Antakya;

Department of Family Medicine, Mustafa Kemal University Faculty of Medicine, Antakya;

Department of Radiology, Mustafa Kemal University Faculty of Medicine, Antakya;

Department of Urology, Hatay State Hospital, Antakya;

Department of Anesthesiology, Mustafa Kemal University Faculty of Medicine, Antakya

ABSTRACT BACKGROUND: This study was intended to report our recent experience of bladder injuries due to gunshots in the Syrian conflict and review the literature regarding diagnosis and treatment. METHODS: Twenty-two cases with abdominal and inguinal firearm wounds and bladder ruptures sustained in the Syrian conflict were reported. Age, mechanism/location of damage, associated injuries, Revised Trauma Score (RTS), Injury Severity Score (ISS), Trauma Injury Severity Score (TRISS), and complications were analyzed. The severity of the bladder injuries was classified according to the American Association for the Surgery of Trauma Organ Injury Scaling (AAST-OIS grade ≥II database).The type of the bladder rupture was defined according to the classification System for Bladder Injury Based on Findings at CT Cystography. RESULTS: The mean age was 26 years (range, 18-36). The mean ISS was 22 (10-57), mean TRISS was 0.64 (0.004-0.95), and mean RTS was 6.97 (3.30-7.84). In the mortality group, the mean ISS, TRISS, and RTS were 48 (36-57), 0.016 (0.004-0.090), and 4.10 (3.304.92), respectively; whereas, the mean ISS, TRISS, and RTS were found as 21 (10-26), 0.64 (0.49-0.95), and 7.24 (5.65-7.84), respectively in the survival group (P=0.06). CT-cystography showed seventeen type 2, three type 4, and two type 5 bladder injuries. According to AAST-OIS, there were nine grade IV, six grade III, five grade II, and two grade V injuries. CONCLUSION: In war settings, when injuries are often severe and multiple surgical exploration and closure are mandatory, mortality risk is associated with high ISS and low TRISS and RTS values. Key words: Bladder injuries; gunshot wounds; Syrian refugees.

INTRODUCTION Bladder injury is uncommon after external trauma and it usually results from blunt or penetrating trauma. The lower urinary tract is involved in less than 1% of all firearm inju-

Address for correspondence: Mehmet Inci, M.D. Mustafa Kemal Üniversitesi Tıp Fakültesi, Üroloji Anabilim Dalı, Antakya, Turkey Tel: +90 326 - 229 10 00 E-mail: mehmetinci@gmail.com Qucik Response Code

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ries among men.[1] Of the bladder ruptures in the USA and Europe, 67-86% is caused by blunt traumas, while 14-33% is caused by penetrating trauma.[2-4] It has been reported that there is a considerable association between bladder injuries and multi-system trauma. Given the fact that it occurs 3590% of the times in association with a pelvic trauma indicating a high energy trauma, it has a remarkable mortality rate ranging from 10-22%.[5-7] Surgical procedures for penetrating genitourinary (GU) injuries are some of the more uncommon and diverse injuries to be confronted by the practicing urologist except in wartime and the military arena.[8-12] Gunshot wounds (GSWs) usually cause serious consequences. GSWs are complex injuries including soft tissue lesion where anal sphincter, pelvic bones, the gluteal masses or the abdominopelvic structures are sometimes involved. In addition to clinical examination, assessing findings such as urine outlet, 371

İnci et al. A practice report of bladder injuries due to gunshot wounds in Syrian refugees

ability of voiding with or without bladder extension and urethral bleeding, and most importantly standard pelvic X-rays to establish bone lesions and the projectile, a mental reconstruction of the projectile path are required for a definitive diagnosis of the lesions. In case of suspected bladder injury, retrograde plain film cystography and computed tomography (CT) cystography should always be performed. Laparotomy for hemostasis and other organ injuries are justified. The final diagnosis of the lesions can only be made in surgery and urinary drainage is mandatory. Moreover, performing a conservative excision of the damaged tissue before primary closure may be required, depending on the infection and hemodynamic status. Wounds involving the bladder can be closed in 95% of the cases. Trauma scores have been widely used over decades in an attempt to establish general status and prognosis of the patients, since these scores can accurately state the patients’ condition and estimate their survival probability.[13-16] To our knowledge, there is limited number of studies on bladder trauma caused by gunshot in war situations. In the present study, it was aimed to describe anatomic distribution, associated injuries, management, outcomes in terms of mortality and factors associated with mortality in patients who sustained GU trauma resulting from war GSWs and to review its diagnosis and treatment in the related literature.

MATERIALS AND METHODS This study, which was approved by the Institutional Review Board and Ethics Committee, included a total of 22 patients, twenty-one males and one female, with abdominal and inguinal gunshot wounds received in war zones. These patients were managed at Mustafa Kemal University Faculty of Medicine Hospital between September 2011 and July 2012 and written informed consents were obtained from patients and/ or relatives. The patients, all coming from Syria, arrived to the hospital by their own means. Often, there was a time period of 8 to 18 hours between injury and arrival to the hospital. In the present study, normalization standards established by Advanced Trauma Life Support (ATLS) were adopted for the sequences of diagnostic and therapeutic procedures. All patients underwent preoperative pelvic X-ray studies and abdominal and pelvic CT scan. Bladder injuries were diagnosed by CT cystography. The type of the rupture was defined according to the Classification System for Bladder Injury Based on Findings at CT Cystography.[17] In addition, severity of bladder injuries was classified according to American Association for the Surgery of Trauma Organ Injury Scaling (AAST-OIS grade ≥II database),[13] Revised Trauma Score (RTS),[14] Injury Severity Score (ISS),[15] Trauma Injury Severity Score (TRISS) [16] and the length of stay (LOS) were analyzed. The Glasgow Coma Scale (GCS), systolic blood pressure (SBP) and the respiratory rate (RR) were used in calculat372

ing the RTS score with values ranging from 0 to 7.84, where lower values referred to the greater severity of physiologic disability. ISS is an anatomical scoring system providing an overall score (score varies from 0 to 75 for patients with multiple injuries, in which scores from 16 to 25 represent severe and those >25 represent very severe anatomical injury. TRISS or Ps estimates the probability of survival in trauma patients, which ranges from 0 to 0.99. All cases underwent exploratory laparotomy for evaluation of other associated injuries. The treatment was determined by the location and extent of injury identified in the preoperative or intraoperative evaluations. Briefly, surgical repair was performed for intra-peritoneal bladder ruptures, while extra-peritoneal injuries was repaired via transvesical approach by opening the dome and avoiding violation of the pelvic hematoma.[18] In all cases, a two-layered suture was used during the surgery. In all cases, clear urine flow was seen at bilateral ureteral orifices. Any intra-abdominal and pelvic bone and metal fragments that were visible and palpable in the preoperative period were removed during the operation. Debridement was performed in necrotic bladder tissue. In two cases with complex injuries associated with urethral tears, a supra-pubic cystostomy catheter was inserted in order to protect the repair. All patients received third generation cephalosporin for over two weeks after operation in addition to standard medication protocols including analgesics. Moreover, mechanism of the injury (blunt or penetrating), associated organ system injuries (i.e. kidney, head/neck, large vessels (aorta, vena cava), other vascular injuries, other injuries involving heart, diaphragm, lungs, liver, gallbladder, esophagus, stomach, small bowel, large bowel, spleen, upper extremity, lower extremity, spine), complications (urinary and non-urinary) were recorded. The specific type of weapons (bullet or missile), velocity of projectile (low- or high-velocity) and number of gunshot per cases were also analyzed.

Statistical Analyses All data were performed using SPSS for Windows 15.0. (SPSS Inc., Chicago, IL, USA). The mean ISS, TRISS and RTS parameters between survival and death groups with abnormal distribution were expressed as median (minimum-maximum). Chi-square test was used for categorical variables. Comparisons of medians were performed with Mann-Whitney U-test. A P value < 0.05 was accepted as statistically significant.

RESULTS Overall, 22 patients (21 male and 1 female) with bladder injuries were treated. The mean age was 26 years (range 18 to 36)). The mean ISS was 22 (10-57), mean TRISS 0.64 (0.0040.95), and RTS 6.97 (3.30-7.84). Mortality rate was estimated as 13.6%. In the mortality group, the mean ISS, TRISS, and RTS were 48 (36-57), 0.016 (0.004-0.090), and 4.10 (3.304.92), respectively; whereas, the mean ISS, TRISS, and RTS were found as 21 (10-26), 0.64 (0.49-0.95), and 7.24 (5.657.84), respectively in the survival group (P=0.06) (Table 1). Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Ä°nci et al. A practice report of bladder injuries due to gunshot wounds in Syrian refugees

Table 1. Trauma scores of patients with bladder injuries due to gunshot wounds

Patients Survival group Death group p (n=22) (n=19) (n=3)

Age (year)

26 (18-36)

27 (25-28)

0.885

ISS

48 (36-57) 0.006

22 (10-57)

21 (10-26)

TRISS

0.64 (0.004-0.95)

0.64 (0.49-0.95)

0.016 (0.004-0.090)a 0.006

RTS

6.97 (3.30-7.84)

7.24 (5.65-7.84)

4.10 (3.30-4.92)a 0.006

p: 0.006 compared to the survival group; ISS: Injury Severity Score; RTS: Revised Trauma Score; TRISS: Trauma Injury Severity Score.

Table 2. Grade and type of the bladder injuries due to gunshot wounds (n=22) Grade

1 2 3 4 5

Bladder injuries, n (%)

5 (23%)

6 (27%)

9 (41%)

2 (9%)

Type

1 2 3 4 5

Bladder injuries, n (%)

17 (77%)

On CT-cystography, seventeen (77%) patients had type 2 bladder injuries, 3 patients (14%) had type 4 bladder injuries, and 2 (9%) patients had type 5 bladder injuries (Table 2). According to intraoperative findings, it was found that there were grade IV injuries in nine patients (41%), grade III injury in 6 patients (27%), grade II injury in 5 patients (23%) and grade V injury in 2 patients (9%) (Table 2). Other organ injuries are presented in Table 3. Among twenty-two patients, the physical materials were implied for bladder injuries in nineteen patients (86%) with bullet wounds; whereas, explosion wounds were caused by missile fragments in the remaining 3 patients (14%). All cases had high-velocity GSWs. The mean number of gunshot per cases was 1.[1-2] Postoperative urinary complications included urinary infections diagnosed in two patients (9%) (Escherichia coli) and urinary fistula in one patient (4.5%). Non-urinary (systemic) complications included pneumonia, sepsis, coagulopathy and thromboembolic events. In three patients, metallic foreign bodies were removed from the abdomen during operation. Three deaths occurred due to systemic complications such as sepsis, thromboembolic events. In seventeen patients, sufficient level of self-care was achieved allowing discharge. Two patients with spinal injury failed to recover well and required continued care in a medical facility.

3 (14%)

2 (9%)

Nicely et al.[19] reported gunshot wounds of the urinary bladder in World War II. The first vesical symptoms experienced by the patient were the urge to void, vesical tenesmus, pain over the bladder region, retention of urine or frequent voiding of bloody urine. Pereira et al.[20] have shared their 20 yearsâ&#x20AC;&#x2122; experience of bladder injuries after external trauma showing that gross hematuria (80%) and abdominal tenderness (60%) are most common signs of bladder injury. Other symptoms Table 3. Other organ injuries associated with bladder injuries due to gunshot (n=22) Injuries

n (%)

Lower extremity

(9.0)

Pelvic fracture

3 (13.6)

Liver

4 (18.1)

Lungs

1 (4.5)

Small bowel

8 (36.3)

Rectum

2 (9.0)

Large bowel

6 (27.2)

Diaphragm

2 (9.0)

Pancreas

1 (4.5)

DISCUSSION

Iliac vessels

The particular localization of the bladder deep within the bony pelvis protects it against trauma, especially when empty. Gunshot wounds of the urinary bladder, either penetrating or perforating, are usually accompanied by associated injuries to abdominal viscera.

Stomach

2 (9.0)

Duodenum

1 (4.5)

Spleen

1 (4.5)

Spinal collum

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(9.0)

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İnci et al. A practice report of bladder injuries due to gunshot wounds in Syrian refugees

include inability to void, bruises at supra-pubic area, and extravasation of urine. In the present study, an external urethral catheter was implanted in all cases. All cases had hematuria. Salvatierra et al.[21] have reported their Vietnam experience with 252 urological war injuries stating that thirty-five bladder injuries were secondary to fragment or gunshot wounds. They reported that the bladder damage was very extensive and intraperitoneal in case off high velocity missiles. Corriere et al.[22] have reported 111 patients with bladder rupture during a 7-year period. Authors forwarded that bladder ruptures in sixteen patients were caused by penetrating injuries with intraperitoneal injuries. Nicely et al.[19] founded that intraperitoneal injuries were significantly higher than extraperitoneal injuries among GSW of bladder injuries. Pereira et al.[20] showed that the incidence of intraperitoneal rupture was higher in penetrating injury than in blunt trauma. Quagliano et al.[23] reported that both the sensitivity and specificity were 100% for CT cystography in detecting bladder rupture. In our study, CT cystography was performed in twenty-two patients. In agreement with the literature, we observed that seventeen patients had intraperitoneal injuries while 3 patients had extraperitoneal injuries and 2 patients had both intraperitoneal and extraperitoneal injuries. Najibi et al.[24] have identified 309 patients sustaining penetrating trauma to the GU system due to GSWs. Bladder injuries were most frequently associated with small and large bowel injuries. Some patients had upper urinary tract injury. Nicely et al.[19] have reported that bladder injuries are associated with ileum, rectum, ileum-rectum and ureteral injuries. Pereira et al.[20] have shown that bladder injuries are associated with injuries of kidney, ureter, vena cava, other vascular structures, diaphragm, liver, stomach, small bowel, large bowel and rectum. Salvatierra et al.[21] indicated that rectal injuries were frequently associated with bladder injuries. Hence, our study is in agreement to the literature. Previous studies[22] have presented that pelvic fractures are common in association with bladder rupture after blunt trauma. However, Nicely et al.[19] showed there was a pelvic fracture in one of 5 patients. Pereira et al.[20] reported that pelvic fractures were less commonly associated to in GSW compared to blunt trauma. Similarly, there was pelvic fracture in three of 22 patients in our study. Najibi et al.[24] have reported that there is a correlation between mortality and ISS in bladder injuries. In a study by Pereira et al.,[20] it was shown that ISS>25, RTS<7 and pelvic fracture were closely associated with poor prognosis and death in bladder injuries. The authors reported that important factors impacting survival in patients with bladder trauma were the presence of pelvic fracture and physiologic and anatomic trauma scores (physiologic and anatomic). Correspondingly, high ISS, TRISS, and low RTS values were associated with poor prognosis and the death in the current study. 374

Depending on the status of the patient and the severity of other comorbid injuries, management of GU injuries must be combined with surgical exploration of other organ systems in war settings where injuries are common, severe and multiple. A multidisciplinary approach is required in the evaluation and management of these patients. Early surgical exploration, drainage, direct repair/realignment, if possible, and delayed definite reconstruction, if needed, are common strategies. The attending urologist should take associated injuries into consideration in all patients with a GSW in the GU system and maintain high index of suspicion. There is a strong correlation between mortality and presence of other organ injuries or high ISS, TRISS, and low RTS scores. In stable patients, standard pelvic X-ray evaluations in attempt to reveal bone lesions and the projectile, abdominal and pelvic CT scans allow us to rule out associated injuries and classify the bladder trauma; however, the facility may not have the required staff, instruments and other sources. Conflict of interest: None declared.

REFERENCES 1. Mianné D, Guillotreau J, Lonjon T, Dumurgier C, Argeme M. Firearm wounds of the lower urinary tract in men. Surgical management in emergency context. [Article in French] J Chir (Paris) 1997;134:139-53. [Abstract] 2. Srinivasa RN, Akbar SA, Jafri SZ, Howells GA. Genitourinary trauma: a pictorial essay. Emerg Radiol 2009;16:21-33. 3. Lynch TH, Martínez-Piñeiro L, Plas E, Serafetinides E, Türkeri L, Santucci RA, et al. EAU guidelines on urological trauma. Eur Urol 2005;47:1-15. 4. Reis LO, Barreiro GC, D’Ancona CA, Netto NR. Arteriovesical fistula as a complication of a gunshot wound to the pelvis: treatment dilemma. Int J Urol 2007;14:569-70. 5. Tezval H, Tezval M, von Klot C, Herrmann TR, Dresing K, Jonas U, et al. Urinary tract injuries in patients with multiple trauma. World J Urol 2007;25:177-84. 6. Morey AF, Iverson AJ, Swan A, Harmon WJ, Spore SS, Bhayani S, et al. Bladder rupture after blunt trauma: guidelines for diagnostic imaging. J Trauma 2001;51:683-6. 7. Corriere JN Jr, Sandler CM. Diagnosis and management of bladder injuries. Urol Clin North Am 2006;33:67-71. 8. Kunkle DA, Lebed BD, Mydlo JH, Pontari MA. Evaluation and management of gunshot wounds of the penis: 20-year experience at an urban trauma center. J Trauma 2008;64:1038-42. 9. Kansas BT, Eddy MJ, Mydlo JH, Uzzo RG. Incidence and management of penetrating renal trauma in patients with multiorgan injury: extended experience at an inner city trauma center. J Urol 2004;172(4 Pt 1):135560. 10. Tausch TJ, Cavalcanti AG, Soderdahl DW, Favorito L, Rabelo P, Morey AF. Gunshot wound injuries of the prostate and posterior urethra: reconstructive armamentarium. J Urol 2007;178(4 Pt 1):1346-8. 11. Velmahos GC, Degiannis E. The management of urinary tract injuries after gunshot wounds of the anterior and posterior abdomen. Injury 1997;28:535-8. 12. Tiguert R, Harb JF, Hurley PM, Gomes De Oliveira J, Castillo-Frontera RJ, Triest JA, et al. Management of shotgun injuries to the pelvis and

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İnci et al. A practice report of bladder injuries due to gunshot wounds in Syrian refugees lower genitourinary system. Urology 2000;55:193-7. 13. Moore EE, Cogbill TH, Jurkovich GJ, McAninch JW, Champion HR, Gennarelli TA, et al. Organ injury scaling. III: Chest wall, abdominal vascular, ureter, bladder, and urethra. J Trauma 1992;33:337-9. 14. Champion HR, Sacco WJ, Copes WS, Gann DS, Gennarelli TA, Flanagan ME. A revision of the Trauma Score. J Trauma 1989;29:623-9. 15. Baker SP, O’Neill B, Haddon W Jr, Long WB. The injury severity score: a method for describing patients with multiple injuries and evaluating emergency care. J Trauma 1974;14:187-96. 16. Boyd CR, Tolson MA, Copes WS. Evaluating trauma care: the TRISS method. Trauma Score and the Injury Severity Score. J Trauma 1987;27:370-8. 17. Vaccaro JP, Brody JM. CT cystography in the evaluation of major bladder trauma. Radiographics 2000;20:1373-81. 18. Gomez RG, Ceballos L, Coburn M, Corriere JN Jr, Dixon CM, Lobel B, et al. Consensus statement on bladder injuries. BJU Int 2004;94:27-32.

19. Niceley EP. Gunshot wounds of the urinary bladder in wartime. J Urol 1946;56:59-67. 20. Pereira BM, de Campos CC, Calderan TR, Reis LO, Fraga GP. Bladder injuries after external trauma: 20 years experience report in a populationbased cross-sectional view. World J Urol 2013;31:913-7. 21. Salvatierra O Jr, Rigdon WO, Norris DM, Brady TW. Vietnam experience with 252 urological war injuries. J Urol 1969;101:615-20. 22. Corriere JN Jr, Sandler CM. Bladder rupture from external trauma: diagnosis and management. World J Urol 1999;17:84-9. 23. Quagliano PV, Delair SM, Malhotra AK. Diagnosis of blunt bladder injury: A prospective comparative study of computed tomography cystography and conventional retrograde cystography. J Trauma 2006;61:41022. 24. Najibi S, Tannast M, Latini JM. Civilian gunshot wounds to the genitourinary tract: incidence, anatomic distribution, associated injuries, and outcomes. Urology 2010;76:977-81.

KLİNİK ÇALIŞMA - ÖZET OLGU SUNUMU

Suriyeli mültecilerde ateşli silah yaralanmalarından dolayı mesane yaralanmalarındaki tecrübelerimiz Dr. Mehmet Inci,1 Dr. Ali Karakuş,2 Dr. Mehmet Murat Rifaioglu,1 Dr. Erhan Yengil,3 Dr. Nesrin Atçi,4 Dr. Ömer Akin,5 Dr. Kasım Tuzcu,6 Dr. Ahmet Kiper,1 Dr. Onur Demirbaş,1 Dr. Mustafa Şahan2 Mustafa Kemal Üniversitesi Tıp Fakültesi, Üroloji Anabilim Dalı, Antakya; Mustafa Kemal Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Antakya; Mustafa Kemal Üniversitesi Tıp Fakültesi, Aile Hekimliği Anabilim Dalı, Antakya; 4 Mustafa Kemal Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, Antakya; 5 Hatay Devlet Hastanesi, Üroloji Kliniği, Antakya; 6 Mustafa Kemal Üniversitesi Tıp Fakültesi, Anesteziyoloji Anabilim Dalı, Antakya 1 2 3

AMAÇ: Suriyeli mültecilerde mesane rüptürlerindeki tecrübelerimizi paylaşmak, tanı ve tedaviye göre literatürü taramak. GEREÇ VE YÖNTEM: Suriye’deki çatışmalarda abdominal ve ingüinal ateşli silah yaralanması ve mesane rüptürü olan 22 olgu sunuldu. Yaş, mekanizma/hasar bölgesi, ilişkili yaralanmalar; revize travma skoru (RTS) hasar ciddiyet skoru (ISS), travma yaralanması şiddet skoru (TRISS) ve komplikasyonları analiz edildi. Mesane yaralanma ciddiyeti Amerikan travma semptom skoru birliğine (AAST-OIS grade >II veritabanı) göre sınıflandırıldı. Mesane rüptür tipi BT sistografi bulguları temelli mesane yaralanma sistemi sınıflamasına göre tanımlandı. BULGULAR: Ortalama yaş 26 (18-36) ortalama hasar ciddiyet skoru 22 (10-57) idi. Ortalama travma yaralanması şiddet skoru 0.64 (0.004-0.95) ve revize travma skoru 6.97 (3.30-7.84) idi. Mortalite grubunda ortalama ISS, TRUS ve RTS sırasıyla 48 (36-57), 0.016 (0.004-0.090) ve 4.10 (3.30-4.92) idi. Oysa ortalama ISS, TRISS ve RTS sırasıyla yaşayan grupta (p=0.06) sırasıyla 21 (10-26), 0.64 (0.49-0.95) ve 7.24 (5.65-7.84) olarak bulundu. CT sistografide 17 tip 2, 3 tip 4 ve 2 tip 5 mesane yaralanması gösterildi. AAST-OIS’ye göre dokuz adet grade IV, altı adet grade VII, beş adet grade II ve iki adet grade V yaralanma vardı. TARTIŞMA: Savaş ortamında yaralanmalar ciddi ve multipl olduğunda cerrahi explorasyon ve kapama zorunludur. Mortalite riski yüksek ISS düşük TRISS ve düşük RTS değerleri ile ilişkiliydi. Anahtar sözcükler: Mesane yaralanması; ateşli silah yaralanması; Suriyeli mülteciler. Ulus Travma Acil Cerrahi Derg 2014;20(5):371-375

doi: 10.5505/tjtes.2014.13693

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ORIGIN A L A R T IC L E

Multi-detector angio-CT and the use of D-dimer for the diagnosis of acute mesenteric ischemia in geriatric patients Burak Gün, M.D.,1 Sadiye Yolcu, M.D.,2 Vermi Değerli, M.D.,1 Gökhan Elçin, M.D.,1 Önder Tomruk, M.D.,3 Bülent Erdur, M.D.,4 İsmet Parlak, M.D.1 1

Department of Emergency Medicine, Bozyaka Training and Research Hospital, İzmir;

Department of Emergency Medicine, Bozok University Faculty of Medicine, Yozgat;

Department of Emergency Medicine, Süleyman Demirel University Faculty of Medicine, Isparta;

Department of Emergency Medicine, Pamukkale University Faculty of Medicine, Denizli

ABSTRACT BACKGROUND: There is no specific laboratory method for the diagnosis of acute mesenteric ischemia (AMI). In this study, we aimed to determine the efficacy of the D-dimer test in selected cases prior to multi-detector angio-CT, which is expensive and has side effects. METHODS: Patients, over 65, with abdominal pain were included in this study. The D-dimer test was applied to 230 (34%) of 676 abdominal pain patients admitted to our emergency service. The D-dimer levels of the patients diagnosed with AMI by angio-CT were compared. RESULTS: In AMI patients sensitivity of the D-dimer test was 84.6% and the specificity was 47.9%. Elevated D-dimer levels and AF were observed in 90.9% of the patients diagnosed with AMI by CT. CONCLUSION: D-dimer levels were elevated in the AMI patients. Patients suspected of having AMI with unclear clinical results and patients with D-dimer levels above 1000 ng/ml and AF should undergo further evaluation. Key words: Acute mesenteric ischemia; D-dimer; multi-detector angio-CT.

INTRODUCTION Abdominal pain in elderly patients has a broad spectrum of pathologic etiologies of which certain emergency conditions such as acute mesenteric ischemia (AMI) must be ruled out early on. When all causes of abdominal pain in the elderly are considered, mortality in AMI increases should the time for diagnosis lengthen.[1] This disease accounts for 10-14% mortality.[1,2] The incidence of AMI is 1-2% worldwide but can reach 18% in patients over the age of 65.[3] Delays in diagnosis cause the mortality rate to increase up to 50-70%.[4-6] The prognosis for AMI is positively affected by reperfusion Address for correspondence: Sadiye Yolcu, M.D. Bozok Üniversitesi Tıp Fakültesi Acil Tıp Anabilim Dalı, Yozgat, Turkey Tel: +90 354 - 212 70 50 E-mail: sadiyeyolcu@yahoo.com Qucik Response Code

376

within the first 6 hours, particularly in cases of embolic ischemia. In recent years, the diagnostic tools for this disease have improved, but the mortality rates have not changed. Unclear physical examination findings and symptoms, patients’ inability to provide correct complaints, the inability to acquire sufficient patient histories, and anatomical differences complicate the diagnosis of AMI in elderly patients.[4-6] There is no specific laboratory test for early-stage AMI. Although amylase, aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) levels have been shown to be elevated in these patients, none of these parameters provide diagnostic sensitivity or specificity.[3] Markers such as D-dimer, alpha-glutathione, S-transferase, D-lactate, intestinal fatty acid binding protein (IFABP), alkaline phosphatase (ALP), procalcitonin and diamine oxidase (DAO) have been researched in this context; however, definitive results have not been reported.[3,7,8] Thus, research into the early diagnosis of AMI continues. Angiography can provide a certain diagnosis of AMI, having recent studies report that multi-detector angio-CT is as effective as angiography in the diagnosis of AMI. When other causes of acute abdomen are considered, CT Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Gün et al. Multi-detector angio-CT and the use of D-dimer for the diagnosis of acute mesenteric ischemia in geriatric patients

may come into prominence in AMI suspected patients for differencial diagnosis.[9,10] The diagnostic tools for this disease have improved; however, the mortality rates remain unchanged. Unproportional pain on physical examination is still noted to be a characteristic finding in AMI (generally of the venous thrombus type), raising clinical suspicion and pretest probability. Given the other potential causes of acute abdominal pain, CT may become prominent in the differential diagnoses of patients suspected of having AMI.[9,10] Kurt et al.[11] have reported that an elevated D-dimer level is 88.8% sensitive in detecting superior mesenteric artery (SMA)-bound rats. Altinyollar et al.[12] have determined that D-dimer levels rise 30 min after the binding of the SMA, and Akyıldız[13] have reported high D-dimer levels in AMI patients (sensitivity: 94.7% and specificity: 78.6%). These findings indicate that D-dimer level may be useful as an early marker of AMI. Thus, we sought to investigate the use of D-dimer and multi-detector angio-CT in selected geriatric patients suspected of having AMI instead of using CT for AMI-suspected patients who cannot be diagnosed with Doppler ultrasound (USG).

MATERIALS AND METHODS After receiving approval from the ethics committee for this cross-sectional study, we examined 676 suspected AMI patients with abdominal pain over the age of 65, who were admitted to our emergency service between January and June 2012. Patient risk factors for AMI, physical examination findings, the presence of atrial fibrillation (AF) on electrocardiogram (ECG), laboratory results (D-dimer, white blood cell (WBC) and creatine kinase (CK) tests), radiological findings (USG, Doppler USG, and multi-detector angio-CT), and patient outcomes were noted. D-dimer levels were measured with the Trinity Biotech latex-based immune measuring method. The normal range of the results of this test is 0-470 ng/ml. Values over 470 ng/ml were accepted elevated. WBC levels were measured with a Mindray BC 6800 device. The normal range of the outcome of this test in our hospital is 4.300-10.300/mm3. Values over 10.300/mm3 were accepted high. CK levels were measured with a Trinity Biotech device. The normal range for the outcome of this test is 39-308 U/L. Values over 308 U/L were accepted elevated.

Statistical Analyses Descriptive results are reported as the means ± the SD or as medians and ranges as appropriate. The evaluations of the associations of categorical variables with the diagnoses of AMI were performed with Pearson χ2 tests (or Fisher’s exact tests when appropriate), and Mann-Whitney U-tests were used for continuous data. The groups were compared with MannWhitney U tests for numerical data and Pearson χ2 tests for categorical data. Receiver operating characteristic (ROC) curves were applied to determine the most suitable diagnostic D-dimer level. All statistical analyses were performed with SPSS version 13.0 (Chicago, Ill). P values below 0.05 were considered significant. Confidence interval was 95%.

RESULTS Of 676 patients, 34% (n=230) were suspected of AMI and the D-dimer levels of these patients were measured. The other 66% (n=446) of the patients underwent necessary tests for diagnosing other conditions based on their complaints. The cause of abdominal pain in 30.6% (n=207) of the 676 patients could not be determined and these patients were diagnosed with nonspecific abdominal pain. Medical treatment was administered to 53.6% (n=111) of these patients. All patients diagnosed with nonspecific abdominal pain were discharged from the emergency service and referred to gastroenterology and general surgery clinics. 1.9% (n=13) of the 676 patients were diagnosed with AMI. The D-dimer levels of 53.9% (124) of the AMI suspected patients who underwent D-dimer assessment were high and 22% (n=28) of the patients with elevated D-dimer levels were diagnosed with nonspecific abdominal pain. AMI was diagnosed in the remaining 8.9% (n=11) of the patients. Abdominal USG was indicated for 45.7% (n=309) of the 676 patients due to rebound, defensiveness and tenderness during physical examination. Cholelithiasis was detected in 12.6% (n=39) of the patients. AMI was determined in 4.2% (n=13) of the patients who underwent USG. The desired USG ratio in the patients who underwent D-dimer testing was 59.1% (n=136) and 9.6% (n=13) of these patients were diagnosed with AMI.

The sensitivity and specificity of multi-detector angio-CT in the diagnosis of AMI is 90-100%.[14] In this study, all patients suspected of having AMI underwent CT scanning (64-section LightSpeed Volume CT; GE Healthcare, Milwaukee, Wisconsin).

Of our 676 patients, 31.9% (n=216) underwent CT for differential diagnosis due to insufficient USG findings. CT was indicated for 49.1% (n=106) of these patients owing to the suspected presence of AMI and for 50.9% (n=110) of patients for differential diagnoses.

All patients were over the age of 65, had abdominal pain and were suspected of having AMI. Patients who were under the age of 65, with abdominal pain but without AMI suspicion, and were not stable enough for CT or had contrast allergies were excluded.

Although 15.1% (n=29) of all the patients who underwent CT scanning had positive abdominal findings on physical examination, we could not find any pathological findings in the laboratory results or radiological evaluations of these patients who could explain their clinical situations. The

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Gün et al. Multi-detector angio-CT and the use of D-dimer for the diagnosis of acute mesenteric ischemia in geriatric patients

patients with unexplained abdominal pain received consultations with a general surgeon and were hospitalized. Of the patients who underwent CT scans, 12.3% (n=13) were diagnosed with AMI. Of the 230 patients, whose D-dimer levels were elevated, 4.8% (n=11) were diagnosed with AMI. Among the patients with AMI diagnoses, 84.6% (n=11) exhibited elevated D-dimer levels, 92.3% (n=12) exhibited elevated WBC levels and 23% (n=3) exhibited elevated CK levels. D-dimer (p<0.05), WBC (p<0.05) and CK (p<0.05) values

were significantly correlated with mesenteric ischemia. When the patients were grouped according to the presence of AMI, we found significant differences in D-dimer (p<0.05), WBC (p<0.05) and CK (p<0.05) levels between groups. The mean D-dimer, WBC and CK levels of the groups are provided in Table 1. Eleven of the 13 AMI diagnosed patients had AF, 9 had HT, 8 had DM, 5 had CAD and 3 had CHF (Table 2). Three of the CT-scanned and AMI diagnosed patients had AF, DM and HT. Four AF patients had rapid ventricle response AF.

Table 1. Mean D-Dimer, WBC and CK Values According to the Presence of AMI

Myocardial infarction

Yes No

n Mean.±SD n Mean.±SD

D-Dimer

13 1177.77±710.4 217 744.89±1752.4 0.003

White blood cells

20.38±7.18

629

10.28±5.32

0.001

Creatine kinase

347.92±380.64

630

124.44±164.05

0.010

*Mann-Whitney U analysis.

Table 2. Comorbid disease distribution according to the presence of acute mesenteric ischemia

Acute mesenteric ischemia

Total

Yes No

n % n % n % Hypertension

Yes 9 69.2 408 61.5 417 61.7 0.775

No 4 30.8 255 38.5 259 38.3

Diabetes mellitus

Yes 8 61.5 217 32.7 225 33.3 0.038

No 5 38.5 446 67.3 451 66.7

Coronery artery disease Yes 5 38.5 114 17.2 119 17.6 0.061

No 8 61.5 549 82.8 557 82.4

Congestive heart failure Yes 3 23.1 132 19.9 135 20.0 0.730

No 10 76.9 531 80.1 541 80.0

COPD

Yes 1 7.7 120 18.1 121 17.9 0.482

No 12 92.3 543 81.9 555 82.1

SVD

Yes 1 7.7 49 7.4 50 7.4 1.000

No 12 92.3 614 92.6 626 92.6

Cancer

Yes 2 15.4 90 13.6 92 13.6 0.694

No 11 84.6 573 86.4 584 86.4

Atrial fibrillation

Yes 11 84.6 110 16.6 121 17.9 0.001

No 2 15.4 553 83.4 555 82.1

Total

13 1.9 663 98.1 676 100.0

COPD: Chronic obstructive pulmonary disease.

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GĂźn et al. Multi-detector angio-CT and the use of D-dimer for the diagnosis of acute mesenteric ischemia in geriatric patients

Table 3. D-dimer level distribution in patients underwent CT according to the presence of atrial fibrillation

D-Dimer

Total p

High Normal

Atrial fibrillation n % n % n % (+)

10 90.9 1 50.0 11 84.6 0.295

(â&#x20AC;&#x201C;)

1 9.1 1 50.0 2 15.4

Total

11 84.6 2 15.4 13 100.0

Table 4. D-Dimer level distribution of myocardial Infarction patients according to survival Survival

D-Dimer

Total p

High Normal n % n % n %

Not exitus

6 54.5 1 50 7 53.8 1.000

Exitus

5 45.5 1 50 6 46.2

Total

11 84.6 2 15.4 13 100.0

The D-dimer levels of the CT scanned patients according to the presence of AF were not significantly different (p>0.05) (Table 3). Eleven of the 13 AMI diagnosed patients underwent emergency surgery. Two patients were deemed inoperable due to total ischemia and were hospitalized in the intensive care unit. One of these 2 patients died within 24 hours and the other patient died 2 days later. The operation of one patient was terminated due to total necrosis and he also died within 24 hours. A right hemicolectomy was performed in one patient and intestinal resection was performed in the other 9 patients. Three of the intestinal resection patients died after the operations (Table 4). D-dimer levels were not related to the survival of the AMI patients (p>0.05).

DISCUSSION Abdominal pain accounts for 5-10% of all emergency service admissions. The distributions of the causes of abdominal pain based on age, gender, comorbid diseases, symptoms and physical examination findings help to determine the causes of abdominal pain in specific patients. Moreover, early and specific diagnostic tools are needed for accurate and early diagnoses.[15] One study found that 6% of geriatric emergency service patients are admitted with abdominal pain.[16] In this study, it was 6.39% (n=676). Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

AMI is a geriatric disease. In most AMI studies, the mean age of the study is above 65. Kougias et al.[17] reported that the mean age of their study group was 71, and Huang[18] and Hawkins[19] studied a group with a mean age of 65. These findings indicate that AMI is common after the age of 65 and thus we studied patients over the age of 65. Nonspecific abdominal pain was diagnosed in 30.6% of our patients. Bugliosi et al.[20] have reported that 23% of geriatric abdominal pain patients are diagnosed with nonspecific abdominal pain in the emergency department. AMI was diagnosed in 1.9% (n=13) of our patients, and this percentage is similar to that found in the literature.[21] The usage of biomarkers for the early diagnosis of AMI is quite limited, but the use of D-dimer levels for this purpose has been researched in recent years. Acosta et al.[7] have reported that D-dimer levels are elevated in (17.5 mg/l) in SMA occluded patients. Elevations in D-dimer levels are specific to AMI. Some studies have revealed elevations in D-dimer levels in acute pancreatitis and coeliac diseases. Radenkovic have reported that D-dimer levels are 90% sensitive and 89% specific for the diagnosis of acute pancreatitis.[22] A study conducted by Block found that D-dimer level was 60% sensitive and 82% specific in the diagnosis of AMI.[23] Kurt et al.[11] have found that D-dimer level produces a sensitivity of 88.8%, a positive prediction rate of 379

Gün et al. Multi-detector angio-CT and the use of D-dimer for the diagnosis of acute mesenteric ischemia in geriatric patients

88.8%, and a negative prediction rate of 100% in rats. Another study has found a sensitivity of 94.7% and a specificity of 78.6%.[13] Our results showed that the sensitivity of the Ddimer level was 84.6% and that the specificity was 47.9%. The sensitivity of WBC level in our study was 92.3%. Meyer and Akyüz have put forward that the sensitivity and specificity of WBC level in the diagnosis of AMI are 90% and 86.6%, respectively.[24,25] Similar to the findings reported in the literature, we found elevated CK levels in our AMI patients.[26,27]

Acknowledgments

The sensitivities and specificities of multi-detector CT in the diagnosis of AMI have been reported to be between 90-100% in the literature.[28,29] We found that the sensitivity of this test was 100%.

3. Hamzaoğlu I, Ulualp K, Balkan T, Şirin F. Abdominal Emergencies in Octogenerians. Ulus Trav Derg 2000;6:36-8.

Comorbid diseases prolong the time until diagnosis and increase the occurrence and severity of complications. AF is the major comorbid situation in AMI patients.[13,30,31] In our study, 84.6% of AMI patients had AF. Furthermore, 62.2% (n=9) of the AMI patients had HT, and 61.5% (n=8) had DM. These proportions are higher than those reported in the literature.[32]

5. Schnitzler J. Zur symptomatologie des darmarterienverschlesses. Wien Med Wochensch 1901;51:505.

The mortality of the AMI patients in our study was 46.2%. The mortalities reported in the literature range between 4051%.[33-35] The extent to which D-dimer levels are incremented in acute abdominal diseases has not been clearly determined in the literature. In our study, the mean D-dimer value of the cases of nonspecific abdominal pain was 425 ng/ml. The results of our study showed that D-dimer values over 1000 ng/ml are significant for patients suspected of having AMI. However, Ddimer levels alone are not sufficient to exclude the diagnosis of AMI.

Limitations This is a single center cross-sectional study, which is a major limitation. Moreover, patients did not receive the gold standard angiography to determine presence of AMI. CTA is nonspecific for non-occlusive MI and these cases may have been missed and identified as non-specific abdominal pain. In our hospital, D-dimer levels were measured using latex. The measurement of D-dimer levels with the ELISA method may have produced more significant results.

Conclusion The sensitivity of D-dimer level in the diagnosis of AMI was found to be 84.6% and that of the specificity was 47.9%. WBC values above 15000/mm3 were significant for AMI patients. The sensitivity of multi-detector angio-CT was 100%. Abdominal pain patients with suspected AMI over the age of 65 with AF, DM and HT should undergo multi-detector angio-CT to avoid delaying certain diagnosis of this condition. 380

All authors declare that they have no conflict of interest.

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4. Lobo Martínez E, Meroño Carvajosa E, Sacco O, Martínez Molina E. Embolectomy in mesenteric ischemia. [Article in Spanish] Rev Esp Enferm Dig 1993;83:351-4. [Abstract]

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Gün et al. Multi-detector angio-CT and the use of D-dimer for the diagnosis of acute mesenteric ischemia in geriatric patients 21. Oldenburg WA, Lau LL, Rodenberg TJ, Edmonds HJ, Burger CD. Acute mesenteric ischemia: a clinical review. Arch Intern Med 2004;164:105462. 22. Radenkovic D, Bajec D, Ivancevic N, Milic N, Bumbasirevic V, Jeremic V, et al. D-dimer in acute pancreatitis: a new approach for an early assessment of organ failure. Pancreas 2009;38:655-60. 23. Block T, Nilsson TK, Björck M, Acosta S. Diagnostic accuracy of plasma biomarkers for intestinal ischaemia. Scand J Clin Lab Invest 2008;68:242-8. 24. Meyer T, Klein P, Schweiger H, Lang W. How can the prognosis of acute mesenteric artery ischemia be improved? Results of a retrospective analysis. [Article in German] Zentralbl Chir 1998;123:230-4. [Abstract] 25. Akyüz M, Sözüer E, Akyıldız H, Akcan A, Küçük C, Poyrazoğlu B. Result of surgical therapy in acute mesenteric ischemia. [Article in Turkish] Kolon Rektum Hast Derg 2010;20:121-6. 26. Graeber GM, Cafferty PJ, Reardon MJ, Curley CP, Ackerman NB, Harmon JW. Changes in serum total creatine phosphokinase (CPK) and its isoenzymes caused by experimental ligation of the superior mesenteric artery. Ann Surg 1981;193:499-505. 27. Uncu H, Uncu G, İlcol Y. Diagnosis of intestinal ischemia by measurement of serum phosphate and enzyme changes and the effectiveness of vitamin E treatment. The Turkish J of Gastroenterol 1999;10:272-5. 28. Yikilmaz A, Karahan OI, Senol S, Tuna IS, Akyildiz HY. Value of mul-

tislice computed tomography in the diagnosis of acute mesenteric ischemia. Eur J Radiol 2011;80:297-302. 29. Ofer A, Abadi S, Nitecki S, Karram T, Kogan I, Leiderman M, et al. Multidetector CT angiography in the evaluation of acute mesenteric ischemia. Eur Radiol 2009;19:24-30. 30. Acosta S, Björck M. Acute thrombo-embolic occlusion of the superior mesenteric artery: a prospective study in a well defined population. Eur J Vasc Endovasc Surg 2003;26:179-83. 31. Vokurka J, Olejnik J, Jedlicka V, Vesely M, Ciernik J, Paseka T. Acute mesenteric ischemia. Hepatogastroenterology 2008;55:1349-52. 32. Kozuch PL, Brandt LJ. Review article: diagnosis and management of mesenteric ischaemia with an emphasis on pharmacotherapy. Aliment Pharmacol Ther 2005;21:201-15. 33. Kassahun WT, Schulz T, Richter O, Hauss J. Unchanged high mortality rates from acute occlusive intestinal ischemia: six year review. Langenbecks Arch Surg 2008;393:163-71. 34. Haghighi PH, Lankarani KB, Taghavi SA, Marvasti VE. Acute mesenteric ischemia: causes and mortality rates over sixteen years in southern Iran. Indian J Gastroenterol 2008;27:236-8. 35. Haga Y, Odo M, Homma M, Komiya K, Takeda K, Koike S, et al. New prediction rule for mortality in acute mesenteric ischemia. Digestion 2009;80:104-11.

KLİNİK ÇALIŞMA - ÖZET OLGU SUNUMU

Geriatrik hastalarda akut mezenterik iskemi tanısında multidedektör anjiyo BT ve D-dimer kullanımı Dr. Burak Gün,1 Dr. Sadiye Yolcu,2 Dr. Vermi Değerli,1 Dr. Gökhan Elçin,1 Dr. Önder Tomruk,3 Dr. Bülent Erdur,4 Dr. İsmet Parlak1 Bozyaka Eğitim ve Araştırma Hastanesi, Acil Tıp Kliniği, İzmir; Bozok Üniversitesi Tıp Fakültesi Acil Tıp Anabilim Dalı, Yozgat; 3 Süleyman Demirel Üniversitesi Tıp Fakültesi Acil Tıp Anabilim Dalı, Isparta; 4 Pamukkale Üniversitesi Tıp Fakültesi, Acil Tıp Anabilim Dalı, Denizli 1 2

AMAÇ: Akut mezenter iskemi (AMİ) tanısında belirli bir laboratuvar yöntemi yoktur. Çalışmamızda AMİ şüphesinde yüksek maliyet ve yan etkilere sahip bir tanı yöntemi olan multi dedektör anjiyo BT öncesi D-dimer düzeyi bakılarak, seçilmiş olgularda bu incelemenin kullanımının uygunluğunu araştırdık. GEREÇ VE YÖNTEM: Çalışmamıza 65 yaş üzeri karın ağrılı hastalar alındı. Acil servisimize başvuran toplam 676 hastanın 230’una (%34) D-dimer testi yapıldı. Anjiyo BT ile AMİ tanısı konulan hastaların D-dimer düzeyleri değerlendirildi. BULGULAR: Çalışmamızda AMİ tanısı olan hastalarda D-dimer %84.6 sensitif %47.9 spesifik bulundu. BT ile AMİ tanısı konan hastaların %90.9’unda D-dimer yüksekliği ile AF birlikteliğini saptadık. TARTIŞMA: AMİ’den iskemiden şüphelenilen kliniği net olmayan hastalarda D-dimer değeri 1000 ng/ml ve üzerinde AF’si olan hastalarda ise mezenter iskemiden şüphelenilmesi ve ileri incelemeye gidilmesi faydalı olacaktır. Anahtar sözcükler: Akut mezenter iskemi; D-dimer; multi dedektör anjiyo BT. Ulus Travma Acil Cerr Derg 2014;20(5):376-381

doi: 10.5505/tjtes.2014.57639

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A shocking craniofacial penetrating injury by a steel bar Po Yuan Chen, M.D.,1 Sheng Fa Yao, M.D.,2 An Xiu Dai, M.D.,3 Han Jung Chen, M.D.,1 Kuo Wei Wang, M.D.1 1

Department of Neurosurgery, E-da Hospital, I-shou University, Kaohsiung, Taiwan;

Department of Plastic Surgery, E-da Hospital, I-shou University, Kaohsiung, Taiwan;

Department of Otolaryngology, E-da Hospital, I-shou University, Kaohsiung, Taiwan

ABSTRACT Owing to the diversity in cause and damage, there is no standard surgical treatment method for a complicated penetrating craniofacial injury.The treatment of a complicated penetrating head injury caused by a steel bar is presented here. A 66-year-old woman fell onto a steel bar at a construction site and it penetrated the mandible, entered the sinus and orbital cavities, and reached the base of the frontal bone. A multi-disciplinary team including a neurosurgeon, otolaryngologist, and plastic surgeon was involved in removing the steel bar. The patient survived without sequelae except for blindness in the right eye. Despite the lack of standardized surgical treatment for a complicated penetrating craniofacial injury, aggressive treatment by a multidisciplinary team can result in good outcomes. Key words: Cerebrospinal fluid leak; foreign bodies; mandibular injuries; orbital fractures.

INTRODUCTION Owing to the diversity in mechanisms and patterns, there is no standard surgical treatment method for a complicated penetrating craniofacial injury. The treatment of a complicated penetrating head injury caused by a steel bar is presented here.

CASE REPORT A 66-year-old woman fell onto a steel bar at a construction site and maintained consciousness. The steel bar penetrated upwardly from the left submandibular area (Fig. 1) and was viewable in the oral cavity. The bar limited the patientâ&#x20AC;&#x2122;s head and neck movements. A slight degree of exophthalmos was observed on the right side. She was brought directly to our emergency department.

Address for correspondence: Kuo Wei Wang, M.D. Department of Neurosurgery, E-Da Hospital, I-Shou University, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan, R.O.C. 82445 Kaohsiung, Taiwan Tel: 886-7-6150011 / 5327 E-mail: u8801051@gmail.com Qucik Response Code

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The brain computed tomography (CT) scan with a 3-dimensional reconstruction revealed a metallic foreign body penetrating the head from the left submandibular space through the right orbital roof to the right sub frontal lobe (Figs. 2a, b). Following consultation, the steel bar was removed in the following order by a multidisciplinary team including a neurosurgeon, otolaryngologist, and plastic surgeon. The neurosurgeon performed bicoronal craniotomy and deep dissection in the right frontal base to expose the tip of the steel bar. The otolaryngologist performed multiple sinusectomy with inferior turbinectomy of the right side to expose the intranasal section of the steel bar. The plastic surgeon pulled the steel bar out under the supervision of the neurosurgeon, who visually monitored the frontal base, and the otolaryngologist, who used an endoscope to view the nasal sinus. This step was performed to prevent active bleeding and enable direct action in case of bleeding. Fortunately, no injuries occurred in major vessels resulting in active bleeding. A perforated hole in the base of the right frontal bone was observed with a small amount of cerebrospinal fluid (CSF) leakage through the torn dura. Following debridement, the dura was repaired, and the skull defect was covered with a rotational muscle flap from the right temporalis muscle. A dural sealant was sprayed on the dura and the muscle flap. The otolaryngologist performed Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Chen et al. A shocking craniofacial penetrating injury by a steel bar

eign body for decompression, debridement to prevent and treat infection, prevention of vascular injury to all possible extents, and achieving hemostasis for repair of the dura for prevention of CSF leaks.[2]

Figure 1. A view of the patient with the steel bar penetrating the head upwardly from the left submandibular area.

debridement and hemostasis, and the plastic surgeon performed submandibular debridement, applied wet dressing, and closed the wound one week later. Finally, preventive tracheostomy was performed and the tube was removed without any complications one month later. Antibiotics (vancomycin and ceftriaxone) were administered for ten days to prevent possible infection. The patient survived without sequelae except for blindness of the right eye.

DISCUSSION A variety of unusual cranial penetrations have been reported until today.[1] The goals of treatment are removal of the for-

(a)

Our patient received a multidisciplinary surgical intervention resulting in good recovery. During the two-year follow up period, no CSF leaks, seizures, or formation of brain abscesses were noted. The recommendations in the literature regarding antibiotic treatment (>7 days of treatment)[3] were followed with the administration of antibiotics for ten days. This led, in part, to the success of the intervention. Our approach could have been improved by a pre-operative angiography or a CT-angiography recommended for the evaluation of the possibility of vascular injury.[3-5] Although these types of preoperative imaging study were not performed, we visually observed the area surrounding the trajectory of the steel bar, and we were confident that there was no major vasculature in contact with the steel bar before its removal. The intervention may have also benefited from an intraoperative consultation with an ophthalmologist. The preoperative consultation with the ophthalmologist resulted in a diagnosis of blindness in the right eye. In our case, an intraoperative consultation was not likely to change this outcome. However, the outcomes may be different for other patients.

(b)

Figure 2. (a) A 3-dimensional computed tomography scan showing the trajectory of the steel bar. (b) A coronal view of the brain computed tomography scan showing the steel bar penetrating to the base of the right frontal bone.

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Hybrid treatment using surgery and an intraoperative endovascular intervention has also been suggested.[2] This type of treatment requires a hybrid operating room, which is not available in our hospital. The benefit to our patient would have been minimal in the absence of bleeding in any major vessels. The general treatment guidelines for a penetrating craniofacial injury are to decompress, debride, and avoid neurovascular injury and the subsequent complications. A multidisciplinary surgical intervention is always required, particularly in the absence of a standard surgical method. Instead, the surgical approach must be tailored according to the mechanisms, patterns, and materials of the injury. By sharing our treatment experience of this unique and shocking case of a penetrating injury, we hope that it can be used as a reference if other similar injuries are encountered.

Acknowledgements There were no grants or other financial or material support.

REFERENCES 1. Bartholomew BJ, Poole C, Tayag EC. Unusual transoral penetrating injury of the foramen magnum: case report. Neurosurgery 2003;53:989-91. 2. Natrella M, Duc L, Lunardi G, Cristoferi M, Fanelli G, Meloni T. Treatment of a transorbital penetrating injury: a particular endovascular approach. Interv Neuroradiol 2012;18:191-4. 3. Kazim SF, Bhatti AU, Godil SS. Craniocerebral injury by penetration of a T-shaped metallic spanner: A rare presentation. Surg Neurol Int 2013;4:2. 4. Skoch J, Ansay TL, Lemole GM. Injury to the Temporal Lobe via Medial Transorbital Entry of a Toothbrush. J Neurol Surg Rep 2013;74:23-8. 5. Offiah C, Hall E. Imaging assessment of penetrating injury of the neck and face. Insights Imaging 2012;3:419-31.

OLGU SUNUMU - ÖZET

Çelik parmaklık üstüne düşme sonucu oluşan şok edici kraniyofasiyal penetran travma Dr. Po Yuan Chen,1 Dr. Sheng Fa Yao,2 Dr. An Xiu Dai,3 Dr. Han Jung Chen,1 Dr. Kuo Wei Wang1 I-shou Üniversitesi, E-da Hastanesi, Nöroşirurji Anabilim Dalı, Kaohsiung, Tayvan; I-shou Üniversitesi, E-da Hastanesi, Plastik Cerrahi Anabilim Dalı, Kaohsiung, Tayvan; 3 I-shou Üniversitesi, E-da Hastanesi, Kulak Burun Boğaz Anabilim Dalı, Kaohsiung, Tayvan 1 2

Etiyoloji ve hasarlanmada oluşan farklılıklar nedeniyle komplike penetran yaralanmaların standart bir cerrahi tedavi yöntemi yoktur. Burada çelik parmaklık üstüne düşme sonucu oluşmuş komplike bir penetran kafa travmasının tedavisi sunuldu. Bu yazıda, inşaat sahasında çelik parmaklığın üzerine düşen 66 yaşındaki kadın hasta sunuldu. Alt çenesi, sinüs ve göz çukuruna giren çelik çubuk alın kemiğinin tabanına kadar ilerlemişti. Beyinsinir, kulak-burun-boğaz ve plastik cerrahlardan oluşan çok uzmanlı bir ekip çelik çubuğu çıkardı. Hasta sağ gözünde körlük dışında herhangi bir sekeli olmadan sağ kurtuldu. Komplike penetran kraniyofasiyal yaralanmanın standartlaşmış bir cerrahi tedavisi olmamasına rağmen çok uzmanlı bir ekiple agresif tedavi iyi sonuçlar sağlayabilmektedir. Anahtar sözcükler: Serebrospinal sıvı kaçağı; yabancı cisimler; mandibular yaralanmaları; orbita kırıkları. Ulus Travma Acil Cerrahi Derg 2014;20(5):382-384

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Partial penectomy after debridement of a Fournier’s gangrene progressing with an isolated penile necrosis Fatih Akbulut, M.D., Onur Kucuktopcu, M.D., Erkan Sonmezay, M.D., Abdulmuttalip Simsek, M.D., Faruk Ozgor, M.D., Zafer Gokhan Gurbuz, M.D. Department of Urology, Haseki Training and Research Hospital, İstanbul

ABSTRACT Fournier’s gangrene (FG) is a rare and often fulminant necrotizing fasciitis of the perineum and genital region frequently due to polymicrobial infection. This truly emergent condition is typically seen in elderly, diabetic and immune compromised patients. Here, we report an unusual case of FG with isolated glans penis necrosis in a diabetic 77-year-old male patient presented to the emergency department complaining 5 days of pain and darkening of the glans penis. Examination of the patient’s glans penis was consistent with FG and included significant erythema and infectious discharge. He was given intravenous antibiotics and emergency debridement was done. On following days, the necrotic area spread to distal parts of both cavernosal areas. Partial penectomy was performed. Isolated penile involvement in FG is very rare. Performing partial penectomy in appropriate cases can save penile length, stop the progression of disease, and increase the quality of life. Key words: Fournier’s gangrene; partial penectomy.

INTRODUCTION

CASE REPORT

Fournier’s gangrene (FG) is a rare and rapidly progressive necrotizing fasciitis of male genitalia, perineal and perianal region leading to sepsis and death, if not rapidly treated.[1,2] FG was first described by Jean Alfred Fournier as necrotizing fasciitis of male genitalia.[3] This urgent disease is generally seen with poor hygiene of genital area of immunosuppressed old patients and patients with diabetes mellitus (DM).[4] In rare cases, penile amputation and orchiectomy is needed. [5] Number of patients with isolated penile involvement is very low.

A 77-year-old male patient referred to our emergency clinic with pain, edema and darkening of the glans penis. He indicated that those complaints appeared after insertion of urethral catheter 5 days prior due to acute urinary retention. Physical examination revealed 3 cm of necrotic and gangrenotic field close to external urethral meatus and infectious discharge nearby the catheter. He had had DM and coronary arterial disease for about 20 years. Both legs were amputated beneath the knees because of DM. Vital signs were: blood pressure: 140/80 mmHg; pulse: 102 bpm; body temperature: 37.0 Celsius and respiration rate was 20. Laboratory tests showed: hematocrit, 29.8; hemoglobin, 9.5 mg/dl; leukocyte, 6600 / uL; C-reactive protein, 147 mg/dl; thrombocyte, 168000/uL; creatinine, 0.90 mg/dl; sodium, 136 mmol/L; potassium, 4.47 mmol/L; and glucose, 105 mg/dl. Urine tests showed WBC 309 /uL and RBC 118 /uL. The patient was diagnosed with isolated penile FG and an emergency debridement of the necrotic areas was planned. Before the operation, the bladder was filled with saline and percutaneous suprapubic cystostomy was inserted by ultrasound guide. Afterwards, the necrotic areas were debrided and samples were collected for pathological and microbiological investigation.

In this case report, we aimed to present a case of FG with only glans penis necrosis irresponsive to emergency debridement.

Address for correspondence: Fatih Akbulut, M.D. Haseki Eğitim ve Araştırma Hastanesi, Üroloji Kliniği, Haseki, Fatih, İstanbul, Turkey Tel: +90 212 - 529 44 00 E-mail: drfakbulut@hotmail.com Qucik Response Code

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Infectious diseases consultation suggested an empirical treatment of meropenem (3 g/day) and vancomycin (1 g/day). Mi385

Akbulut et al. Partial penectomy after debridement of a Fournierâ&#x20AC;&#x2122;s gangrene progressing with an isolated penile necrosis

(a)

(b)

(c)

Figure 1. (a) Necrotic fields before the emergent debridement and situation after operation. (b) Spiral pelvic CT and macroscopic view of penis before partial penectomy. (c) Post operative view and macroscopic view of the excised penis part.

crobiological specimen resulted as extended spectrum beta lactamase (ESBL) producing Escherichia Coli (E.Coli) sensitive for meropenem and the existing antibiotic regimen was carried on. During follow-up, the necrotic areas spread to cavernosal tissue. On pelvic computed tomography (CT), necrotic area widened to the distal parts of both corpus cavernosum. Eight days after first operation, partial penectomy was decided to be made. Penile skin was degloved after marking with sterile pen. By inserting forceps through the hole on the glans penis, the depth of cavernosal necrosis and approximate site of excision was 386

predicted. Penile tourniquet was not needed because of poor blood supply to cavernosal tissue. Dorsal vessel and nerves were sutured and cut. Corpus cavernosum and urethra were separated and urethra was cut 1 cm distal to the penectomy line. Afterwards, both cavernosal bodies were resected. Corporeal ends were sutured continuously by horizontal mattress sutures passing through buck fascia, tunica albuginea and intercavernosal septum. Urethra was spatulated at 12 PM. Penile skin was laid on cavernosal bodies and sutured to the urethral mucosa. Urethral catheter was inserted. The urethral catheter was taken on post-operative 4th day. Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

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nosis negatively.[11] Our patient had a predisposing factor of 20 years of DM, resulting in his bilateral lower extremities to be amputated. Laor and colleagues have formed a scoring system named Fournier’s Gangrene Severity Index (FGSI) to evaluate the prognosis of FG patients. According to this scoring system, body temperature, pulse, respiration rate, serum sodium, serum creatinine, hematocrit, leukocyte and bicarbonate levels are evaluated. Scores ≤5 are recorded as low, 6-7 as intermediate and ≥8 as high scores. FSGI score >9 indicates 75% death and ≤9 indicates 78% survival rates.[3] Our patient had a FSGI score of 2. Treatment consists of early and aggressive debridement.[5] Empirical broad spectrum antibiotics are given as first choice and can be changed according to the isolated bacteria.[13] Patients without diffuse penile and urethral involvement usually don’t need suprapubic catheterization and urethral catheter is usually enough.[7] Patients seldom need penis amputation and orchidectomy is indicated.[5] Hyperbaric oxygen treatment can be useful for the treatment of FG.[13] Figure 2. Urethra and penis during discharge from hospital.

Patient had no urinating symptoms. At the end of the 20th day of first referral to the hospital and on the post-operative 12th day of partial penectomy, patient was discharged.

DISCUSSION FG is a rare disease accounting less than 0.02% of hospital admissions and with an incidence of 1.6 of 100.000 male patients. Females are affected very rarely. Mortality rate was reported as 16% in a study including 1726 FG patients.[6-8] FG is a polymicrobial process starting with a triggering event. In etiology, both aerobic and anaerobic microorganisms play role. Escherichia coli, Streptococcus, Staphylococcus, Enterococcus and Bacteroides strains are the mostly seen bacteria.[9] Bacterial infections result in thrombosis and lead to insufficient tissue oxygenation, thus resulting in an anaerobic environment. Heparinase excreted from aerobic bacteria leads to enzymatic destruction of the tissue by anaerobes. The source of infection is usually urogenital and colorectal diseases or traumas of perineal region and scrotum.[10] In our patient, isolated penis involvement of FG occurred after insertion of urethral catheter and Escherichia coli was isolated. Most common factors facilitating the occurrence of FG are: diabetes mellitus (DM), steroid treatment, chronic alcohol abuse, old age, HIV infection, heart diseases, renal failure, peripheral artery diseases, chemotherapy, and malignancies. DM is the most common predisposing factor but it doesn’t affect the mortality rate or the prognosis of the disease. DM, together with chronic alcohol usage, affects the progUlus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

Early partial penectomy usually decreases morbidity in patients with gangrenous necrosis of glans penis. Chiang et al.[14] performed partial penectomy to five dry gangrenous necrosis cases. In one year follow up, no infection and complication were seen and all patients survived. Three patients could urinate from neourethra and two needed suprapubic catheterization because of benign prostatic obstruction and bed dependency. In our case, partial penectomy was performed and urination from neourethra was good. Isolated penile involvement in FG is very rare. Performing partial penectomy in appropriate cases can save penile length, stop the progression of disease, and increase the quality of life. Conflict of interest: None declared.

REFERENCES 1. Erol B, Tuncel A, Hanci V, Tokgoz H, Yildiz A, Akduman B, et al. Fournier’s gangrene: overview of prognostic factors and definition of new prognostic parameter. Urology 2010;75:1193-8. 2. Anchi T, Tamura K, Inoue K, Ashida S, Yasuda M, Kataoka S, et al. Localized Fournier’s gangrene of the penis: a case report. [Article in Japanese] Hinyokika Kiyo 2009;55:153-6. [Abstract] 3. Laor E, Palmer LS, Tolia BM, Reid RE, Winter HI. Outcome prediction in patients with Fournier’s gangrene. J Urol 1995;154:89-92. 4. Heiner JD, Eng KD, Bialowas TA, Devita D. Fournier’s Gangrene due to Masturbation in an Otherwise Healthy Male. Case Rep Emerg Med 2012;2012:154025. 5. Fajdic J, Gotovac N, Hrgovic Z. Fournier gangrene: our approach and patients. Urol Int 2011;87:186-91. 6. Sorensen MD, Krieger JN, Rivara FP, Broghammer JA, Klein MB, Mack CD, et al. Fournier’s Gangrene: population based epidemiology and outcomes. J Urol 2009;181:2120-6.

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Akbulut et al. Partial penectomy after debridement of a Fournier’s gangrene progressing with an isolated penile necrosis 7. Koukouras D, Kallidonis P, Panagopoulos C, Al-Aown A, Athanasopoulos A, Rigopoulos C, et al. Fournier’s gangrene, a urologic and surgical emergency: presentation of a multi-institutional experience with 45 cases. Urol Int 2011;86:167-72. 8. Eke N. Fournier’s gangrene: a review of 1726 cases. Br J Surg 2000;87:718-28. 9. Martínez-Rodríguez R, Ponce de León J, Caparrós J, Villavicencio H. Fournier’s gangrene: a monographic urology center experience with twenty patients. Urol Int 2009;83:323-8. 10. Jeong HJ, Park SC, Seo IY, Rim JS. Prognostic factors in Fournier gangrene. Int J Urol 2005;12:1041-4.

11. Shyam DC, Rapsang AG. Fournier’s gangrene. Surgeon 2013;11:222-32. 12. Yanar H, Taviloglu K, Ertekin C, Guloglu R, Zorba U, Cabioglu N, et al. Fournier’s gangrene: risk factors and strategies for management. World J Surg 2006;30:1750-4. 13. Janane A, Hajji F, Ismail TO, Chafiqui J, Ghadouane M, Ameur A, et al. Hyperbaric oxygen therapy adjunctive to surgical debridement in management of Fournier’s gangrene: usefulness of a severity index score in predicting disease gravity and patient survival. [Article in Spanish] Actas Urol Esp 2011;35:332-8. [Abstract] 14. Chiang IN, Chang SJ, Kuo YC, Liu SP, Yu HJ, Hsieh JT. Management of ischemic penile gangrene: prompt partial penectomy and other treatment options. J Sex Med 2008;5:2725-33.

OLGU SUNUMU - ÖZET

Fournier gangreni debridmanı sonrası devam eden izole penis nekrozunda parsiyel penektomi Dr. Fatih Akbulut, Dr. Onur Kucuktopcu, Dr. Erkan Sonmezay, Dr. Abdulmuttalip Simsek, Dr. Faruk Ozgor, Dr. Zafer Gokhan Gurbuz Haseki Eğitim ve Araştırma Hastanesi, Üroloji Kliniği, İstanbul

Fournier gangreni (FG) perine ve genital bölgenin nadir görülen ve sıklıkla kötü seyirli nekrotizan fasiitidir. Genellikle polimikrobiyal enfeksiyona bağlıdır. Acil olan bu durum sıklıkla yaşlı, diyabetik ve immün sistemi zayıf hastalarda görülür. Bu yazıda, FG’nin nadir bir formu olan izole glans penis tutulumu ile başvuran bir hasta sunuldu. Yetmiş yedi yaşında erkek hasta beş gündür glans peniste ağrı ve siyah renk değişikliği ile başvurdu. Glans penisin muayenesinde belirgin eritem ve iltihabi akıntı mevcuttu ve görünümü FG ile uyumlu idi. Antibiyoterapisi başlanıp erken debridmanı yapıldı ancak takibin ilerleyen günlerinde nekrotik bölge kavernozal cisimlerin distaline doğru ilerledi. Hastaya parsiyel penektomi yapıldı. FG’de izole penis tutulumu nadir olarak görülür ve uygun olgularda zamanında parsiyel penektomi yapmak kalan penis boyutunu koruyup, hastalığın ilerlemesini önleyerek hayat kalitesini artırabilir. Anahtar sözcükler: Fournier gangreni; parsiyel penektomi. Ulus Travma Acil Cerrahi Derg 2014;20(5):385-388

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The journey of gastric phytobezoar followed by tomography Deniz Çebi Olgun, M.D.,1 Yasemin Kayadibi, M.D.,1 Osman Şimşek, M.D.,2 Zekeriya Karaduman, M.D.2 1

Department of Radiology, İstanbul University Cerrahpaşa Faculty of Medicine, Istanbul;

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

ABSTRACT Phytobezoars are a rare cause of intestinal obstruction. They are usually present in patients with predisposing factors such as previous gastric surgery, diabetes, and edentulousness. In this case report, an uncommon cause of intestinal obstruction due to the migration of gastric phytobezoar in a patient with no known predisposing factor is reported. Key words: Intestinal obstruction; migration; persimmon; phytobezoar.

INTRODUCTION Pyhtobezoars are the most common type of bezoars in adults. Diospyrobezoars formed after massive ingestion of persimmons are a special subtype of phytobezoars that can be endemic in some countries.[1-3] They are usually found in the stomach and rarely cause intestinal obstruction. Diagnosis is always made by a combination of patient history, clinical and radiological findings. In this combination, radiologic findings are very important since computer tomography (CT) could be a problem solver with characteristic findings for bezoars.[3] In the presented case, it is aimed to discuss the imaging features of the journey of a gastric bezoar.

CASE REPORT A 53-year-old woman was admitted to our emergency department with vomiting, constipation, abdominal pain, and distension of a few hours. She had an additional medical history of gastric bezoar diagnosed by CT performed in advance for abdominal pain and confirmed by endoscopy a week ago (Fig. 1a, b). She confirmed no surgical intervenAddress for correspondence: Deniz Çebi Olgun, M.D. İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Radyoloji Anabilim Dalı, İstanbul, Turkey Tel: +90 212 - 414 31 67 E-mail: ysmnkurdoglu@gmail.com Qucik Response Code

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tions were conducted beforehand. On physical examination, bowel sounds were hyperactive and there was no palpable mass in the rectum. Plain X-ray graph of abdomen showed multiple air-fluid levels with no free air under diaphragm. Her complete blood count and biochemical profile were in normal limits. CT of the abdomen revealed dilated jejunal and ileal intestinal loops reaching up to 4-5 cm and a welldefined intraluminal mass within mottled gas pattern at the point of transitional zone (Fig. 1c, d). Under the transitional zone, distal ileal loops were collapsed. With the history of gastric bezoar and imaging findings, patient was diagnosed as intestinal obstruction due to migration of the gastric bezoar. Under general anesthesia, patient underwent laparoscopic exploration. Intra-surgical findings were dilated edematous ileal loops extending 150 cm from ileocaecal junction and intraluminal mass causing obstruction at the level of transition zone. The incision of suprapubic trocar was enlarged, enterotomy performed (“mini-lap” technique), and suggested obstructing pathology of bezoar measuring 5 cm was removed (Fig. 1e, f ). Postoperative period was uneventful and patient was discharged 5 days later.

DISCUSSION Bezoars are compact forms of undigested material found in the gastrointestinal tract. There are many types of bezoars differing by material content including phytobezoars containing undigested vegetable or fruit, trichobezoars containing hair, lactobezoars containing milk and pharmacobezoars containing drugs such as cholestyramine, kayexalate, resin, cavafate, and antacids.[1,2] Diospyrobezoar, the most common subtype of phytobezoar, 389

Ă&#x2021;ebi Olgun et al. The journey of gastric phytobezoar followed by tomography

occur after excessive intake of the fruit, persimmon. In some countries like Japan and Israel, epidemics have been reported. Tannin found in the skin of persimmon reacts with the gastric fluid and reactants and play role in the nucleus formation of bezoars.[4] Normally, pylorus does not allow undigested materials such as vegetable fibers to pass until soft enough. In patients with previous gastric surgery and vagotomy, gastric functions fail in digestion, facilitating bezoar formation. With patients of no history of gastric surgery, diabetic gastroparesis, vegetarian diet, hypothyroidism or edentulousness could be the other predisposing factors.[2-7] Our patient had none of these factors. However, out patientâ&#x20AC;&#x2122;s history revealed that there was an excessive consumption of persimmon. Phytobezoars are usually diagnosed incidentally without giving any symptoms when in the stomach. They rarely pass to small bowel and cause intestinal obstruction consisting only 0.4 to 4% of total intestinal obstructions. Strictures or adhesions of the small bowel due to diseases such as Crohnâ&#x20AC;&#x2122;s or tuberculosis or previous surgery are causes of primary intestinal bezoars.[2,3,6] Terminal ileum is the most common site of obstruction followed by jejunum. Symptoms such as abdominal pain, vomiting or dyspepsia are the common presenting symptoms assisting in locating the bezoars.[2-7]

Radiologically, plain X-ray graphics are not diagnostic otherwise showing air-fluid levels. However, series of X-ray graphics may be helpful in the follow-up of possible obstruction due to fragmented bezoars in treatment. CT has 7393% success rate of diagnosis.[7] In CT, gastric or intestinal, intraluminal, well-defined mass with mottled gas pattern is the characteristic imaging feature for bezoars. If this image is recognized at the point of transitional zone, bezoar as an obstructing factor may be suggested when a patient comes with ileus. Sometimes small bowel feces may mimic bezoars but generally feces are placed more proximal to the transitional zone and they usually appear as tubular structures not round like bezoars.[1,2,7] These CT findings, combined with the history of primary gastric bezoar in our patient, were very helpful in diagnosis. Surgery is the best modality of treatment, if obstruction occurs. However, in patients without obstruction, endoscopic therapy of fragmentation, treatment with enzymes such as papain and cellulose or chemical dissolution with pineapple juice or Coca-Cola are other treatment modalities described for bezoars. After treatment, recurrence is not expected, if there is no predisposing factor.[1,2,5] On the other hand, if patients left untreated, apart from intestinal obstruction,

(a)

(b)

(e)

(c)

(d)

(f)

Figure 1. (a, b) Axial and coronal CT scan of abdomen showing intra-gastric well-defined mass with mottled gas pattern typical for bezoars. (c, d) Axial and coronal CT scan of the abdomen showing dilated intestinal loops and intraluminal well-defined mass with mottled gas pattern. (e) Intraoperative appearance of small intestinal obstruction. (f) Macroscopic appearance of diospyrobezoar.

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Çebi Olgun et al. The journey of gastric phytobezoar followed by tomography

ischemic ulceration, perforation and gastrointestinal bleeding are reported as complications.[8]

Conclusion Diospyrobezoars rarely cause intestinal obstruction; however, this possibility must always be considered. If a bezoar is discovered in the gastrointestinal system, treatment (especially non-surgical ones) should be planned immediately since by the journey of the bezoar from the stomach to the intestine, obstruction may develop in a very short time. Conflict of interest: None declared.

REFERENCES 1. Andrus CH, Ponsky JL. Bezoars: classification, pathophysiology, and treatment. Am J Gastroenterol 1988;83:476-8.

2. Erzurumlu K, Malazgirt Z, Bektas A, Dervisoglu A, Polat C, Senyurek G, et al. Gastrointestinal bezoars: a retrospective analysis of 34 cases. World J Gastroenterol 2005;11:1813-7. 3. Altintoprak F, Degirmenci B, Dikicier E, Cakmak G, Kivilcim T, Akbulut G, et al. CT findings of patients with small bowel obstruction due to bezoar: a descriptive study. ScientificWorldJournal 2013;18:298392. 4. Gayà J, Barranco L, Llompart A, Reyes J, Obrador A. Persimmon bezoars: a successful combined therapy. Gastrointest Endosc 2002;55:5813. 5. Teng H, Nawawi O, Ng K, Yik Y. Phytobezoar: an unusual cause of intestinal obstruction. Biomed Imaging Interv J 2005;1:e4. 6. Ezzat RF, Rashid SA, Rashid AT, Abdullah KM, Ahmed SM. Small intestinal obstruction due to phytobezoar: a case report. J Med Case Rep 2009;3:9312. 7. Pujar KA, Pai AS, Hiremath VB. Phytobezoar: a rare cause of small bowel obstruction. J Clin Diagn Res 2013;7:2298-9. 8. de Toledo AP, Rodrigues FH, Rodrigues MR, Sato DT, Nonose R, Nascimento EF, et al. Diospyrobezoar as a cause of small bowel obstruction. Case Rep Gastroenterol 2012;6:596-603.

OLGU SUNUMU - ÖZET

Gastrik bezoarın tomografik yolculuğu Dr. Deniz Çebi Olgun,1 Dr. Yasemin Kayadibi,1 Dr. Osman Şimşek,2 Dr. Zekeriya Karaduman2 1 2

İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Radyoloji Anabilim Dalı, İstanbul; İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi, Genel Cerrahi Anabilim Dalı, İstanbul

Fitobezoarlar nadiren intestinal tıkanıklığa yol açarlar. Genelde önceden geçirilmiş mide cerrahisi, diyabet veya ağız-diş problemi gibi predispozan sebepleri bulunan hastalarda saptanırlar. Bu yazıda gastrik bezoarın migrasyonu sebebiyle oluşan nadir bir intestinal tıkanıklık sebebini sunmayı amaçladık. Anahtar sözcükler: Fitobezoar; intestinal tıkanıklık; migrasyon; Trabzon hurması. Ulus Travma Acil Cerrahi Derg 2014;20(5):389-391

doi: 10.5505/tjtes.2014.59422

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CA S E R EP O RT

Successful treatment of a hepatic abscess formed secondary to fish bone penetration by laparoscopic removal of the foreign body: report of a case Mehmet Nuri Koşar, M.D.,1 İhsan Oruk, M.D.,1 Murat Burç Yazıcıoğlu, M.D.,2 Çiğdem Erol, M.D.,3 Birgül Çabuk, M.D.4 1

Department of General Surgery, Acıbadem Hospital, Eskişehir;

Department of General Surgery, Derince Training and Research Hospital, Kocaeli;

Department of Infectious Diseases, Acıbadem Hospital, Eskişehir;

Department of Radiology, Acıbadem Hospital, Eskişehir

ABSTRACT Although foreign body ingestion is a common problem in children, it is also seen among adults. Perforation of the gut by a foreign body, followed by migration of the foreign body to the liver is quite rare. Most fish bone ingestions have uneventful outcome. However, occasionally, it can cause serious complications if the gastrointestinal tract is perforated. Herein, a case of liver abscess caused by a fish bone is reported. To the best of our knowledge, it is the first case in our country. Key words: Fish bone; hepatic abscess; laparoscopic surgery.

INTRODUCTION

CASE REPORT

Hepatic foreign bodies are rare.[1] Uncomplicated hepatic foreign bodies can be followed without surgical intervention.[1] The majority of ingested foreign bodies pass through the gastrointestinal (GI) tract uneventfully.[1] In less than 1% of patients who develop gastrointestinal perforation have been reported.[2] Endoscopy may be helpful if performed before foreign body migration and mucosal healing.[2] Ultrasonography and CT may help to diagnose these unusual presentations of migrating foreign bodies and to plan how to manage. Complicated hepatic foreign bodies as in our case should be removed by laparoscopy or laparotomy after the diagnosis.

A 73-year-old female patient was admitted to the infectious diseases department due to high fever (39°C). She was hospitalized with a diagnosis of pneumonia and antibiotherapy was started but high fever persisted. Abdominal computed tomography (CT) was scheduled revealing a left lobe liver abscess (5-6 cm in diameter). A foreign body located at abscess–stomach neighborhood with a sharp surface was observed, showing a non-metal density (Fig. 1a).

Address for correspondence: Mehmet Nuri Koşar, M.D. Uluç Mahallesi, 1144. Sokak, Mega Sitesi, C Blok, Daire: 10, Konyaaltı, 07070 Antalya, Turkey Tel: +90 242 - 249 44 62 E-mail: drkome@hotmail.com Qucik Response Code

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The patient was questioned about her past medical history. She remembered that she had abdominal pain after eating something but could not tell what it was. Upper gastrointestinal endoscopy was performed; however, no luminal pathology was found. Later, laparoscopic operation and liver abscess drainage was performed. Fibrous structures were observed between the small curvature of the stomach and inferior line of left lobe of the liver, and the adhesions were dissected. After the drainage of the abscess, a fish bone was identified and removed laparoscopically. Operation was completed after inserting a drain at the operation area (Fig. 1b). Postoperative antibiotherapy continued for three more days and the patient was discharged without experiencing any problems. Ulus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

KoĹ&#x;ar et al. Successful treatment of a hepatic abscess formed secondary to fish bone penetration

(a)

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Figure 1. (a) Radiologic view of abscess and foreign body in the liver. (b) Laparoscopic view of abscess and foreign body in the liver.

DISCUSSION The majority of ingested foreign bodies pass through the gastrointestinal (GI) tract uneventfully.[1,3] In far-eastern countries, foreign body ingestion, especially that of the fish bone, is a common clinical problem of emergency departments. [2,4] Fish bone in digestive tract may cause serious complications when compared to other foreign bodies.[5] The most common symptoms are related to the location of the foreign body in the proximal esophagus.[6] Gastrointestinal perforation have been reported in less than 1% of the cases and may cause peritonitis, localized abscess or inflammatory mass, bleeding or fistula.[1,7] In some cases, pancreatitis, appendicitis, and liver abscesses have been reported.[8-10] Hepatic foreign bodies are rare.[3] Foreign bodies reach the liver by one of the three ways: direct penetration through the abdominal or thoracic wall, migration from the gastrointestinal tract, or through blood.[11] Majority of hepatic foreign bodies have been reported to penetrate into the liver by transmigration from the gastrointestinal tract (stomach, duodenum, and transverse colon).[11] In our patient, we could not find the trajectory of fish bone migration. Rapid diagnosis and early intervention of gastrointestinal foreign bodies are required to prevent morbidity and mortality. [3] Plain radiography, ultrasound, CT, upper gastrointestinal series, upper endoscopy, colonoscopy, and laparotomy can be used to investigate foreign bodies in the gastrointestinal tract. [3] Traditionally, diagnosis and localization of the foreign body is made by plain abdominal radiograph.[12] If the object is not recovered in stool, a radiograph is taken weekly to determine whether it has left the stomach and is progressing satisfactorily.[12] Endoscopy may be helpful if performed before foreign body migration and mucosal healing.[7] In our case, endoscopy was not helpful for the event had taken place considerably a long time ago. Ultrasonography and CT may help to diagnose these unusual presentations of migrating foreign bodies and plan the management. CT gives excellent results in the deUlus Travma Acil Cerrahi Derg, September 2014, Vol. 20, No. 5

tection of foreign bodies because of its high resolution and accuracy.[7] Ultrasound should be considered as an alternative method to demonstrate metallic foreign bodies. In our case, ultrasound was less sensitive than CT since the foreign body had a non-metallic density. Uncomplicated hepatic foreign bodies can be followed without surgical intervention.[1] However, complicated hepatic foreign bodies, as in our case, should be removed by laparoscopy or laparotomy, and hepatic abscess drainage or hepatic segmentectomy must be done in the same sĂŠance, if necessary. Conflict of interest: None declared.

REFERENCES 1. Crankson SJ. Hepatic foreign body in a child. Pediatr Surg Int 1997;12:426-7. 2. Santos SA, Alberto SC, Cruz E, Pires E, Figueira T, Coimbra E, et al. Hepatic abscess induced by foreign body: case report and literature review. World J Gastroenterol 2007;13:1466-70. 3. Lee KF, Chu W, Wong SW, Lai PB. Hepatic abscess secondary to foreign body perforation of the stomach. Asian J Surg 2005;28:297-300. 4. Nandi P, Ong GB. Foreign body in the oesophagus: review of 2394 cases. Br J Surg1978;65:5-9. 5. Chung CH, Lau CK, Chow TL. Swallowed foreign bodies in adults. HK Pract 1991;13:1805-6. 6. Singh B, Kantu M, Har-El G, Lucente FE. Complications associated with 327 foreign bodies of the pharynx, larynx, and esophagus. Ann Otol Rhinol Laryngol 1997;106:301-4. 7. Ngan JH, Fok PJ, Lai EC, Branicki FJ, Wong J. A prospective study on fish bone ingestion. Experience of 358 patients. Ann Surg 1990;211:45962. 8. Dabadie A, Roussey M, Betremieux P, Gambert C, Lefrancois C, Darnault P. Acute pancreatitis from a duodenal foreign body in a child. J Pediatr Gastroenterol Nutr 1989;8:533-5. 9. Sukhotnik I, Klin B, Siplovich L. Foreign-body appendicitis. J Pediatr Surg 1995;30:1515-6. 10. Broome CJ, Peck RJ. Hepatic abscess complicating foreign body perforation of the gastric antrum: an ultrasound diagnosis. Clin Radiol 2000;55:242-3. 11. Nishimoto Y, Suita S, Taguchi T, Noguchi S, Ieiri S. Hepatic foreign body - a sewing needle - in a child. Asian J Surg 2003;26:231-3. 12. Spina P, Minniti S, Bragheri R. Usefulness of ultrasonography in gastric foreign body retention. Pediatr Radiol 2000;30:840-1.

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OLGU SUNUMU - ÖZET

Balık kılçığı penetrasyonuna bağlı oluşmuş karaciğer apsesinin laparoskopik olarak başarılı tedavisi: Olgu sunumu Dr. Mehmet Nuri Koşar,1 Dr. İhsan Oruk,1 Dr. Murat Burç Yazıcıoğlu,2 Dr. Çiğdem Erol,3 Dr. Birgül Çabuk4 Acıbadem Hastanesi, Genel Cerrahi Kliniği, Eskişehir; Derince Eğitim ve Araştırma Hastanesi, Genel Cerrahi Kliniği, Kocaeli; 3 Acıbadem Hastanesi, Enfeksiyon Hastalıkları Kliniği, Eskişehir; 4 Acıbadem Hastanesi, Radyoloji Kliniği, Eskişehir 1 2

Yabancı cisim yutulması özellikle çocuklarda olmak üzere her yaş grubunda görülebilir. Çoğu yabancı cisim herhangi bir hasara yol açmadan gastrointestinal sistemi boydan boya geçer. Yutulan bir yabancı cismin karaciğere geçmesi çok nadir görülür. Fakat bazen gastrointestinal bütünlüğü bozan yabancı cisimler ciddi komplikasyonlara yol açarlar. Bu yazıda balık kılçığı nedeni ile oluşmuş karaciğer apsesinden bahsetmekteyiz. Bu bildiğimiz kadarı ile ülkemizde bildirilen ilk olgudur. Anahtar sözcükler: Balık kılçığı; karaciğer apsesi; laparoskopi. Ulus Travma Acil Cerrahi Derg 2014;20(5):392-394

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