Tam Metin - Marmara Medical Journal
Transkript
Tam Metin - Marmara Medical Journal
2009 , Cilt 22, Sayı 3 Marmara Medical Journal Marmara Üniversitesi Tıp Fakültesi Dergisi ISSN: 1309-9469 Marmara Medical Journal Marmara Üniversitesi Tıp Fakültesi Dergisi Sahibi Marmara Üniversitesi Tıp Fakültesi adına Dekan Prof. Dr. Davut Tüney Editör Prof Dr Emel Demiralp Editör Yardımcıları Doç. Dr. Dilek Gogas Yavuz Doç Dr. Önder Ergönül İstatistik Editörü Doç. Dr. Nural Bekiroğlu Seza Arbay, MA Koordinatörler Dr. Vera Bulgurlu Editörler Kurulu Prof. Dr. Mehmet Ağırbaşlı Prof. Dr. Serpil Bilsel Prof. Dr. Safiye Çavdar Prof. Dr. Tolga Dağlı Prof. Dr. Haner Direskeneli Prof. Dr. Kaya Emerk Prof. Dr. Mithat Erenus Prof. Dr. Zeynep Eti Prof. Dr. Rainer W. Guillery Prof. Dr. Oya Gürbüz Prof. Dr. Hande Harmancı Prof. Dr. Hızır Kurtel Prof. Dr. Ayşe Özer Prof. Dr. Tülin Tanrıdağ Prof. Dr. Tufan Tarcan Prof. Dr. Cihangir Tetik Prof. Dr. Ferruh Şimşek Prof. Dr. Dr. Ayşegül Yağcı Prof. Dr. Berrak Yeğen Doç. Dr. İpek Akman Doç. Dr. Gül Başaran Doç. Dr. Hasan Batırel Doç. Dr. Nural Bekiroğlu Doç. Dr. Şule Çetinel Doç. Dr. Mustafa Çetiner Doç. Dr. Arzu Denizbaşı Doç. Dr. Gazanfer Ekinci Doç. Dr. Dilek Gogas Doç. Dr. Sibel Kalaça Doç. Dr. Atila Karaalp Doç. Dr. Bülent Karadağ Doç. Dr. Handan Kaya Doç. Dr. Gürsu Kıyan Doç. Dr. Şule Yavuz Asist. Dr. Asım Cingi Asist. Dr. Arzu Uzuner Marmara Medical Journal Marmara Üniversitesi Tıp Fakültesi Dergisi DERGİ HAKKINDA Marmara Medical Journal, Marmara Üniversitesi Tıp Fakültesi tarafından yayımlanan multidisipliner ulusal ve uluslararası tüm tıbbi kurum ve personele ulaşmayı hedefleyen bilimsel bir dergidir. Marmara Üniversitesi Tıp Fakültesi Dergisi, tıbbın her alanını içeren özgün klinik ve deneysel çalışmaları, ilginç olgu bildirimlerini, derlemeleri, davet edilmiş derlemeleri, Editöre mektupları, toplantı, haber ve duyuruları, klinik haberleri ve ilginç araştırmaların özetlerini , ayırıcı tanı, tanınız nedir başlıklı olgu sunumlarını, , ilginç, fotoğraflı soru-cevap yazıları (photo-quiz) ,toplantı, haber ve duyuruları, klinik haberleri ve tıp gündemini belirleyen güncel konuları yayınlar. Periyodu: Marmara Medical Journal -Marmara Üniversitesi Tıp Fakültesi Dergisi yılda 3 sayı olarak OCAK,MAYIS VE EKİM AYLARINDA yayınlanmaktadır. Yayına başlama tarihi:1988 2004 Yılından itibaren yanlızca elektronik olarak yayınlanmaktadır Yayın Dili: Türkçe, İngilizce eISSN: 1309-9469 Temel Hedef Kitlesi: Tıp alanında tüm branşlardaki hekimler, uzman ve öğretim üyeleri, tıp öğrencileri İndekslendiği dizinler: EMBASE - Excerpta Medica ,TUBITAK - Türkiye Bilimsel ve Teknik Araştırma Kurumu , Türk Sağlık Bilimleri İndeksi, Turk Medline,Türkiye Makaleler Bibliyografyası ,DOAJ (Directory of Open Access Journals) Makalelerin ortalama değerlendirme süresi: 8 haftadır Makale takibi -iletişim Seza Arbay Marmara Medical Journal (Marmara Üniversitesi Tıp Fakültesi Dergisi) Marmara Üniversitesi Tıp Fakültesi Dekanlığı, Tıbbiye cad No:.49 Haydarpaşa 34668, İSTANBUL Tel: +90 0 216 4144734 Faks: +90 O 216 4144731 e-posta: mmj@marmara.edu.tr Yayıncı Plexus BilişimTeknolojileri A.Ş. Tahran Caddesi. No:6/8, Kavaklıdere, Ankara Tel: +90 0 312 4272608 Faks: +90 0312 4272602 Yayın Hakları: Marmara Medical Journal ‘in basılı ve web ortamında yayınlanan yazı, resim, şekil, tablo ve uygulamalar yazılı izin alınmadan kısmen veya tamamen herhangi bir vasıtayla basılamaz. Bilimsel amaçlarla kaynak göstermek kaydıyla özetleme ve alıntı yapılabilir. www.marmaramedicaljournal.or Marmara Medical Journal Marmara Üniversitesi Tıp Fakültesi Dergisi YAZARLARA BİLGİ Marmara Medical Journal – Marmara Üniversitesi Tıp Fakültesi Dergisine ilginize teşekkür ederiz. Derginin elektronik ortamdaki yayınına erişim www.marmaramedicaljournal.org adresinden serbesttir. Marmara Medical Journal tıbbın klinik ve deneysel alanlarında özgün araştırmalar, olgu sunumları, derlemeler, davet edilmiş derlemeler, mektuplar, ilginç, fotoğraflı soru-cevap yazıları (photo-quiz), editöre mektup , toplantı, haber ve duyuruları, klinik haberleri ve ilginç araştırmaların özetlerini yayınlamaktadır. Yılda 3 sayı olarak Ocak, Mayıs ve Ekim aylarında yayınlanan Marmara Medical Journal hakemli ve multidisipliner bir dergidir.Gönderilen yazılar Türkçe veya İngilizce olabilir. Değerlendirme süreci Dergiye gönderilen yazılar, ilk olarak dergi standartları açısından incelenir. Derginin istediği forma uymayan yazılar, daha ileri bir incelemeye gerek görülmeksizin yazarlarına iade edilir. Zaman ve emek kaybına yol açılmaması için, yazarlar dergi kurallarını dikkatli incelemeleri önerilir. Dergi kurallarına uygunluğuna karar verilen yazılar Editörler Kurulu tarafından incelenir ve en az biri başka kurumdan olmak üzere iki ya da daha fazla hakeme gönderilir. Editör, Kurulu yazıyı reddetme ya da yazara(lara) ek değişiklikler için gönderme veya yazarları bilgilendirerek kısaltma yapmak hakkına sahiptir. Yazarlardan istenen değişiklik ve düzeltmeler yapılana kadar, yazılar yayın programına alınmamaktadır. Marmara Medical Journal gönderilen yazıları sadece online olarak http://marmaramedicaljournal.org/submit. adresinden kabul etmektedir. Yazıların bilimsel sorumluluğu yazarlara aittir. Marmara Medical Journal yazıların bilimsel sorumluluğunu kabul etmez. Makale yayına kabul edildiği takdirde Yayın Hakkı Devir Formu imzalanıp dergiye iletilmelidir. Gönderilen yazıların dergide yayınlanabilmesi için daha önce başka bir bilimsel yayın organında yayınlanmamış olması gerekir. Daha önce sözlü ya da poster olarak sunulmuş çalışmalar, yazının başlık sayfasında tarihi ve yeri ile birlikte belirtilmelidir. Yayınlanması için başvuruda bulunulan makalelerin, adı geçen tüm yazarlar tarafından onaylanmış olması ve çalışmanın başka bir yerde yayınlanmamış olması ya da yayınlanmak üzere değerlendirmede olmaması gerekmektedir. Yazının son halinin bütün yazarlar tarafından onaylandığı ve çalışmanın yürtüldüğü kurum sorumluları tarafından onaylandığı belirtilmelidir.Yazarlar tarafından imzalanarak onaylanan üst yazıda ayrıca tüm yazarların makale ile ilgili bilimsel katkı ve sorumlulukları yer almalı, çalışma ile ilgili herhangi bir mali ya da diğer çıkar çatışması var ise bildirilmelidir.( * ) ( * ) Orijinal araştırma makalesi veya vaka sunumu ile başvuran yazarlar için üst yazı örneği: "Marmara Medical Journal'de yayımlanmak üzere sunduğum (sunduğumuz) "…-" başlıklı makale, çalışmanın yapıldığı laboratuvar/kurum yetkilileri tarafından onaylanmıştır. Bu çalışma daha önce başka bir dergide yayımlanmamıştır (400 sözcük – ya da daha az – özet şekli hariç) veya yayınlanmak üzere başka bir dergide değerlendirmede bulunmamaktadır. Yazıların hazırlanması Derginin yayın dili İngilizce veya Türkçe’dir. Türkçe yazılarda Türk Dil Kurumu Türkçe Sözlüğü (http://tdk.org.tr) esas alınmalıdır. Anatomik terimlerin ve diğer tıp terimlerinin adları Latince olmalıdır. Gönderilen yazılar, yazım kuralları açısından Uluslararası Tıp Editörleri Komitesi tarafından hazırlanan “Biomedikal Dergilere Gönderilen Makalelerde Bulunması Gereken Standartlar “ a ( Uniform Requirements For Manuscripts Submittted to Biomedical Journals ) uygun olarak hazırlanmalıdır. (http://www. ulakbim.gov.tr /cabim/vt) Makale içinde kullanılan kısaltmalar Uluslararası kabul edilen şeklide olmalıdır (http..//www.journals.tubitak.gov.tr/kitap/ma www.marmaramedicaljourna knasyaz/) kaynağına başvurulabilir. Birimler, Ağırlıklar ve Ölçüler 11. Genel Konferansı'nda kabul edildiği şekilde Uluslararası Sistem (SI) ile uyumlu olmalıdır. Makaleler Word, WordPerfect, EPS, LaTeX, text, Postscript veya RTF formatında hazırlanmalı, şekil ve fotoğraflar ayrı dosyalar halinde TIFF, GIF, JPG, BMP, Postscript, veya EPS formatında kabul edilmektedir. Yazı kategorileri Yazının gönderildiği metin dosyasının içinde sırasıyla, Türkçe başlık, özet, anahtar sözcükler, İngilizce başlık, özet, İngilizce anahtar sözcükler, makalenin metini, kaynaklar, her sayfaya bir tablo olmak üzere tablolar ve son sayfada şekillerin (varsa) alt yazıları şeklinde olmalıdır. Metin dosyanızın içinde, yazar isimleri ve kurumlara ait bilgi, makalede kullanılan şekil ve resimler olmamalıdır. Özgün Araştırma Makaleleri Türkçe ve İngilizce özetler yazı başlığı ile birlikte verilmelidir. (i)özetler: Amaç (Objectives), Gereç ve Yöntem (Materials and Methods) ya da Hastalar ve Yöntemler (Patients and Methods), Bulgular (Results) ve Sonuç (Conclusion) bölümlerine ayrılmalı ve 200 sözcüğü geçmemelidir. (ii) Anahtar Sözcükler Index Medicus Medical Subject Headings (MeSH) ‘e uygun seçilmelidir. Yazının diğer bölümleri, (iii) Giriş, (iv) Gereç ve Yöntem / Hastalar ve Yöntemler, (v) Bulgular, (vi) Tartışma ve (vii) Kaynaklar'dır. Başlık sayfası dışında yazının hiçbir bölümünün ayrı sayfalarda başlatılması zorunluluğu yoktur. Maddi kaynak , çalışmayı destekleyen burslar, kuruluşlar, fonlar, metnin sonunda teşekkürler kısmında belirtilmelidir. Olgu sunumları İngilizce ve Türkçe özetleri kısa ve tek paragraflık olmalıdır. Olgu sunumu özetleri ağırlıklı olarak mutlaka olgu hakkında bilgileri içermektedir. Anahtar sözcüklerinden sonra giriş, olgu(lar) tartışma ve kaynaklar şeklinde düzenlenmelidir. Derleme yazıları İngilizce ve Türkçe başlık, İngilizce ve Türkçe özet ve İngilizce ve Türkçe anahtar kelimeler yer almalıdır. Kaynak sayısı 50 ile sınırlanması önerilmektedir. Kaynaklar Kaynaklar yazıda kullanılış sırasına göre numaralanmalıdır. Kaynaklarda verilen makale yazarlarının sayısı 6 dan fazla ise ilk 3 yazar belirtilmeli ve İngilizce kaynaklarda ilk 3 yazar isminden sonra “ et al.”, Türkçe kaynaklarda ise ilk 3 yazar isminden sonra “ ve ark. “ ibaresi kullanılmalıdır. Noktalamalara birden çok yazarlı bir çalışmayı tek yazar adıyla kısaltmamaya ve kaynak sayfalarının başlangıç ve bitimlerinin belirtilmesine dikkat edilmelidir. Kaynaklarda verilen dergi isimleri Index Medicus'a (http://www.ncbi.nim.nih.gov/sites/entrez/qu ery.fcgi?db=nlmcatalog) veya Ulakbim/Türk Tıp Dizini’ne uygun olarak kısaltılmalıdır. Makale: Tuna H, Avcı Ş, Tükenmez Ö, Kokino S. İnmeli olguların sublukse omuzlarında kas-sinir elektrik uyarımının etkinliği. Trakya Univ Tıp Fak Derg 2005;22:70-5. Kitap: Norman IJ, Redfern SJ, (editors). Mental health care for elderly people. New York: Churchill Livingstone, 1996. Kitaptan Bölüm: Phillips SJ, Whisnant JP Hypertension and stroke. In: Laragh JH, Brenner BM, editors. Hypertension: Pathophysiology, Diagnosis, and Management. 2nd ed. New York: Raven Pres, 1995:465-78. Kaynak web sitesi ise: Kaynak makalerdeki gibi istenilen bilgiler verildikten sonra erişim olarak web sitesi adresi ve erişim tarihi bildirilmelidir. Kaynak internet ortamında basılan bir dergi ise: Kaynak makaledeki gibi istenilen bilgiler verildikten sonra erişim olarak URL adresi ve erişim tarihi verilmelidir. Kongre Bildirileri: Bengtsson S, Solheim BG. Enforcement of data protection, privacy and security in medical informatics. In: Lun KC, Degoulet P, Piemme TE, Rienhoff O, editors. MEDINFO 92. Proceedings of the 7th World Congress on Medical Informatics; 1992 Sep 6-10; Geneva, Switzerland. Amsterdam: North-Holland; 1992:1561-5. Tablo, şekil, grafik ve fotoğraf Tablo, şekil grafik ve fotoğraflar yazının içine yerleştirilmiş halde gönderilmemeli. Tablolar, her sayfaya bir tablo olmak üzere yazının gönderildiği dosya içinde olmalı ancak yazıya ait şekil, grafik ve fotografların her biri ayrı bir imaj dosyası (jpeg yada gif) olarak gönderilmelidir. www.marmaramedicaljourna Tablo başlıkları ve şekil altyazıları eksik bırakılmamalıdır. Şekillere ait açıklamalar yazının gönderildiği dosyanın en sonuna yazılmalıdır. Tablo, şekil ve grafiklerin numaralanarak yazı içinde yerleri belirtilmelidir. Tablolar yazı içindeki bilginin tekrarı olmamalıdır. Makale yazarlarının, makalede eğer daha önce yayınlanmış alıntı yazı, tablo, şekil, grafik, resim vb var ise yayın hakkı sahibi ve yazarlardan yazılı izin almaları ve makale üst yazısına ekleyerek dergiye ulaştırmaları gerekmektedir. Tablolar Metin içinde atıfta bulunulan sıraya göre romen rakkamı ile numaralanmalıdır. Her tablo ayrı bir sayfaya ve tablonun üst kısmına kısa ancak anlaşılır bir başlık verilerek hazırlanmalıdır. Başlık ve dipnot açıklayıcı olmalıdır. Sütun başlıkları kısa ve ölçüm değerleri parantez içinde verilmelidir. Bütün kısaltmalar ve semboller dipnotta açıklanmalıdır. Dipnotlarda şu semboller: (†‡¶§) ve P değerleri için ise *, **, *** kullanılmalıdır. SD veya SEM gibi istatistiksel değerler tablo veya şekildin altında not olarak belirtilmelidir. Grafik, fotoğraf ve çizimler ŞEKİL olarak adlandırılmalı, makalede geçtiği sıraya gore numaralanmalı ve açıklamaları şekil altına yazılmalıdır Şekil alt yazıları, ayrıca metinin son sayfasına da eklenmelidir. Büyütmeler, şekilde uzunluk birimi (bar çubuğu içinde) ile belirtilmelidir. Mikroskopik resimlerde büyütme oranı ve boyama tekniği açıklanmalıdır. Etik Marmara Medical Journal’a yayınlanması amacı ile gönderilen yazılar Helsinki Bildirgesi, İyi Klinik Uygulamalar Kılavuzu,İyi Laboratuar Uygulamaları Kılavuzu esaslarına uymalıdır. Gerek insanlar gerekse hayvanlar açısından etik koşullara uygun olmayan yazılar yayınlanmak üzere kabul edilemez. Marmara Medical Journal, insanlar üzerinde yapılan araştırmaların önceden Araştırma Etik Kurulu tarafından onayının alınması şartını arar. Yazarlardan, yazının detaylarını ve tarihini bildirecek şekilde imzalı bir beyan ile başvurmaları istenir. Çalışmalar deney hayvanı kullanımını içeriyorsa, hayvan bakımı ve kullanımında yapılan işlemler yazı içinde kısaca tanımlanmalıdır. Deney hayvanlarında özel derişimlerde ilaç kullanıldıysa, yazar bu derişimin kullanılma mantığını belirtmelidir. İnsanlar üzerinde yapılan deneysel çalışmaların sonuçlarını bildiren yazılarda, Kurumsal Etik Kurul onayı alındığını ve bu çalışmanın yapıldığı gönüllü ya da hastalara uygulanacak prosedürlerin özelliği tümüyle kendilerine anlatıldıktan sonra, onaylarının alındığını gösterir cümleler yer almalıdır. Yazarlar, bu tür bir çalışma söz konusu olduğunda, uluslararası alanda kabul edilen kılavuzlara ve TC. Sağlık Bakanlığı tarafından getirilen ve 28 Aralık 2008 tarih ve 27089 sayılı Resmi Gazete'de yayınlanan "Klinik araştırmaları Hakkında Yönetmelik" ve daha sonra yayınlanan 11 Mart 2010 tarihli resmi gazete ve 25518 sayılı “Klinik Araştırmalar Hakkında Yönetmelikte Değişiklik Yapıldığına Dair Yönetmelik” hükümlerine uyulduğunu belirtmeli ve kurumdan aldıkları Etik Komitesi onayını göndermelidir. Hayvanlar üzerinde yapılan çalışmalar için de gereken izin alınmalı; yazıda deneklere ağrı, acı ve rahatsızlık verilmemesi için neler yapıldığı açık bir şekilde belirtilmelidir. Hasta kimliğini tanıtacak fotoğraf kullanıldığında, hastanın yazılı onayı gönderilmelidir. Yazı takip ve sorularınız için iletişim: Seza Arbay Marmara Universitesi Tıp Fakültesi Dekanlığı, Tıbbiye Caddesi, No: 49, Haydarpaşa 34668, İstanbul Tel:+90 0 216 4144734 Faks:+90 0 216 4144731 e-posta: mmj@marmara.edu.tr www.marmaramedicaljourna İÇİNDEKİLER Orjinal Araştırma FACTORS EFFECTING MORTALITY IN PATIENTS WITH GUNSHOT INJURIES Savaş Eriş, Murat Orak, Behçet Al, Cahfer Güloğlu, Mustafa Aldemir…………………………………181 D VİTAMİNİ TEDAVİSİNİN ETKİNLİĞİ FALANGEAL RADYOGFRAFİK ABSORPSİYOMETRİ İLE İZLENEBİLİR Mİ? Ümran Kaya, Evrim Karadağ Saygı, Işıl Üstün, Gülseren Akyüz………………………………………………………………………………………………….192 INCIDENTAL DETECTION OF CORONARY ARTERY CALCIFICATIONS ON NONCARDIAC THORACIC CT EXAMINATIONS Kadriye Orta Kılıçkesmez, Özgür Kılıçkesmez, Neslihan Taşdelen, Duygu Kara, Yüksel Işık, Arda Kayhan, Bengi Gürses, Nevzat Gürmen………..197 RADİKAL PROSTATEKTOMİ SPESMENLERİNDEKİ VEGF’İN, E-CADHERİN’İN VE BIM’İN İMMÜNOHİSTOKİMYASAL EKSPRESYONLARININ PROGNOSTİK DEĞERİ Erem Kaan Başok, Asıf Yıldırım, Adnan Başaran, Ebru Zemheri, Reşit Tokuç………………………..203 CYTOGENETIC ANALYSIS IN INFERTILE MALES WITH SPERM ANOMALIES Ebru Önalan Etem, Hüseyin Yüce, Deniz Erol, Şükriye Derya Deveci, Gülay Güleç Ceylan, Halit Elyas………………………………………………………………………………………………………217 THE COMPARISON OF THE RECOVERY CHARACTERISTICS OF EITHER SPINAL OR EPIDURAL ANESTHESIA WITH PRILOCAINE FOR KNEE ARTHROSCOPY Hatice Türe, Binnaz Ay, Zeynep Eti, F. Yılmaz Göğüş…………………………………………………………………….225 Olgu Sunumu ABDOMINAL TUBERCULOSIS IN A 3-YEAR-OLD CHILD Atilla Şenaylı, Taner Sezer, İsmail Hakkı Göl, Ünal Bıçakçı……………………………………………………………………………………….233 GIANT EPIDERMAL CYST OF THE FOREARM Elif Karadeli, Esra Meltem Kayahan Ulu, Ahmet Fevzi Ozgur, Emine Tosun…………………………………………………………………………….237 POST-CAESAREAN RECTUS SHEATH HAEMATOMA: A CASE REPORT Imtiaz Wani...240 RETROPERITONEAL CASTLEMAN’S DISEASE: REPORT OF FOUR CASES Pinar Yazıcı, Ünal Aydin, Oktay Tekesin, Murat Zeytunlu, Murat Kılıç, Mine Hekimgil, Ahmet Coker…………….243 ENDOVASCULAR TREATMENT OF A VERTEBRAL ARTERIOVENOUS FISTULA: CASE REPORT Feyyaz Baltacıoğlu…………………………………………………………………………………248 BEHÇET OLGUSUNDA DİŞ ÇEKİMİ SONRASI GELİŞEN EKSTERNAL KAROTİD ARTER PSEUDOANEVRİZMASI VE İNTERNAL JUGULER VEN TROMBOZU Figen Palabıyık, Arda Kayhan, Esra Karaçay, Ercan İnci, Tan Cimilli………………………………………...252 ORIGINAL RESEARCH FACTORS AFFECTING MORTALITY IN PATIENTS WITH GUNSHOT INJURIES Savaş Eriş1, Murat Orak2, Behçet Al3, Cahfer Güloğlu2, Mustafa Aldemir2 1 Adıyaman Devlet Hastanesi, Acil Tıp, Adıyaman, Türkiye 2Dicle Universitesi Tıp Fakültesi, Acil Tıp, Diyarbakır, Türkiye 3Gaziantep Universitesi Tıp Fakültesi, Acil Tıp, Gaziantep, Türkiye ABSTRACT Objective: We planned this study in order to determine the factors affecting mortality in patients with gunshot injuries in more than one organ. Methods: We retrospectively reviewed the hospital records of 714 patients admitted to the Emergency Department of Dicle University, between January 2000 and December 2004. The factors that we considered would affect mortality such as age, sex, attempts suicide, long barrelled gun injuries, pellet injuries, contact/near contact shot, delayed admission time, presence of serious anemia and shock during admission, more than four entrance wounds, injury areas, serious cranial, thorax and abdominal injuries, vascular injuries in the extremities, administration of multiple transfusion, and trauma scores as GCS, RTS, PATI were analyzed. Results: As a result of unvaried statistical analyses, we determined that suicide attempts (p=0.001), presence of serious anemia (p=0.001) and shock (p=0.001) during admission, presence of serious cranial (p=0.001), thorax (p=0.001) and abdominal (p=0.001) injury, femoral artery injury (p=0.001), multiple blood transfusion (p=0.009), , GCS 0-7, GCS 8-12 (p=0.001) and low RTS (p=0.001)were significant factors affecting mortality. Conclusion: Multivariate analysis showed that serious anemia during admission, serious cranial injury, serious abdominal injury and low RTS were independently significant in predicting mortality (p<0.05). Keywords: Factors, Gunshot, Mortality, Injury, Serious anemia, Suicide İletişim Bilgileri: Behçet Al, M.D. Gaziantep Universitesi Tıp Fakültesi, Acil Tıp, Gaziantep, Türkiye e-mail: behcetal@gmail.com 181 Marmara Medical Journal 2009;22(3);000-000 Marmara Medical Journal 2009;22(3);000-000 Savaş Eriş, et al. Factors affecting mortality in patients with gunshot injuries ATEŞLİ SİLAH YARALANMALI HASTALARDA MORTALİTEYİ ETKİLEYEN FAKTÖRLER ÖZET Amaç: Bu çalışmada birden fazla organda silah yaralanmasına maruz kalan hastalarda mortalitede etkili faktörleri tespit etmeyi amaçladık. Yöntem: Dicle Üniversitesi Tıp Fakültesi Acil Tıp Kliniğine Ocak 2000 ile Aralık 2004 arasında ASY nedeniyle başvuran 714 hastanın kayıtları geriye dönük olarak incelendi. Sağ kalanlar ve ölenler arasında mortalite üzerine etkisi olabileceğini düşündüğümüz; ileri yaş, cinsiyet, öz kıyım amaçlı olması, uzun namlulu silahla yaralanma, saçma atan silahlarla yaralanma, yakın atış, gecikmiş başvuru zamanı, başvuruda derin anemi ve şok varlığı, ateşli silah giriş sayısı ≥4 olması, yaralanma bölgeleri, ciddi kafa, toraks ve batın yaralanmasının olması, ekstremite vasküler yaralanması, multiple kan transfüzyonu yapılması, GKS, RTS ve PATİ değerleri analiz edildi. Bulgular: Ünivariete istatistiksel analizler neticesinde; öz kıyım amaçlı yaralanma (p=0.001), başvuruda derin anemi (p=0.001) ve şok varlığı (p=0.001), ciddi kafa yaralanması (p=0.001), ciddi toraks yaralanması (p=0.001) ve ciddi batın yaralanmasının olması (p=0.001), femoral arter yaralanması (p=0.001), multiple kan transfüzyonu (p=0.009), GKS’nın 0–7 ve 8–12 olması (p=0.001) ve düşük RTS skoru (p=0.001)’nun mortalite üzerinde anlamlı etkisinin olduğunu tespit ettik. Sonuç: Multivarite analiz sonucunda; başvuruda derin anemi varlığı, ciddi kafa travması varlığı, ciddi batın travması olması ve düşük RTS skoru mortaliteyi etkileyen en önemli bağımsız değişkenler olarak bulundu (p<0.05). Anahtar Kelimeler: Faktörler, Silah atışı, Mortalite, Yaralanma, Ciddi anemi, Öz kıyım INTRODUCTION Nowadays, independent of how socially or economically developed the country is, trauma is one of the main public health problems. In USA, trauma is the leading cause of death among 1 – 44 year-old people1-4. In order to decrease the death rates related to trauma, factors effecting mortality should be determined and the patients should be evaluated accordingly. Recent studies are aimed at determining deaths due to trauma which could have been prevented4. Many studies have been made on patients exposed to gunshot injuries. But the main factor affecting the mortality is still controversial. Although, there are mortality studies related to one system, we have not come across studies related to the factors affecting mortality in patients with gunshot injuries in multiple organs and systems in the literature. We planned this study in order to determine the factors affecting mortality in patients with gunshot injuries in more than one organ. Gunshot injuries are one of the leading cause of high mortality and morbidity in the hospitals related to trauma surgery in Turkey, as in all over the world5. Damage is proportional to the energy transferred to the tissue, properties of the tissue and how the tissue distributes the energy1. Damage is made by the cavitation effect and fragmentation3. The bullet causes damage not only in the organ it enters but also in the nearby tissues because of the blasting effect, changing direction in the body. Organ injuries apart from the entrance trace cause the difficulties in the diagnosis and treatment of the injuries1,5,6. MATERIAL AND METHOD Nine hundred and twenty-two patients were admitted to the Emergency Department of Dicle University for gunshot injuries, between January 2000 and December 2004. Seven hundred and fourteen of these patients’ hospital records were reviewed retrospectively. Patient data were recorded to the standard forms. The parameters used in the form were age, gender, cause of the injury, type of gun used, distance of injury, admittance time, hematocrit, blood pressure, pulse rate, respiration rate, consciousness status, entrance number of gunshot, entrance 182 Marmara Medical Journal 2009;22(3);000-000 Savaş Eriş, et al. Factors affecting mortality in patients with gunshot injuries region of gunshot, grade of injured organs, applied treatment, number of blood transfusions, period of hospitalization, period of intensive care and results of treatment. Glasgow Coma Scale (GCS), revised trauma score (RTS) and penetrating abdominal trauma indexes (PATI) were evaluated independently for each patient. Patients with missing data in their hospital records, who were dead on arrival at the hospital, and penetrating injuries not caused by guns were not included in this study. Seven hundred and fourteen patients used in this study were divided into two groups as alive (Group 1; n=606) and dead (Group 2; n=108). The reasons we considered as affecting mortality between Group 1 and Group 2 such as old age, gender, aimed of suicide, long barrelled injuries, pellet injuries, contact/near contact shot, delayed admission time, serious anemia during admission, presence of shock during admission, more than four entrance wounds, injury regions (1, 2, 3), serious cranial injury, serious thorax injury, serious abdominal injury, vascular injury in the extremities, femoral artery injury, administration of multiple transfusion, hospitalization time and trauma scores as GCS, RTS, PATI were analyzed. While preparing the statistical data; old age (≥55 years old), gender, cuase of the injury (murder, suicide, accident), type of gun used (long barrelled guns, pellet guns, shell guns, shrapnel or mine), contact/near contact shot (0 – 10 m), delayed admission time (longer than 2 hours after the injury), serious anemia during admission (hematocrit <20%), presence of shock during admission (systolic blood pressure <90 mmHg and heart beat rate >100 beats/min ) were evaluated. The entrance regions to the body were determined as: first region: region covered by the frontal, parietal, occipital and temporal bones; second region: region between the left clavicula, sternum, left rib arc and left medium axillary line; third region: upper abdominal region between the horizontal line passing through the umbilical cord and the rib arcs. Suicide attempts, serious anemia during admission, presence of shock during admission, serious cranial injury, serious thorax injury, serious abdominal injury, femoral artery injury, administration of multiple transfusion, GCS score of 0 – 7, GCS score of 8 – 12 and RTS score were evaluated in the multivariable analysis. Univariable analyses were made by using chisquare test (χ2) for categorical variables and Student t test for continuous variables. Mann Whitney U test was applied for the nonhomogenous continuous variables. To determine the predictive factors affecting mortality, multivariable analyses were made by using the Backward Stepwise (Wald) Logistic Regression method. Mean values were calculated as Mean ± SEM (Standart Error Mean). Values of p<0.05 were considered as statistically significant. Serious cranial injury (basilar skull fracture, cerebral contusion/ intracerebral hemorrhage, subarachnoid hemorrhage, epidural hematoma, subdural hematoma, diffuse axonal injury, cerebral laceration and contusion, diffuse cerebral edema), serious thorax injury (hemothorax, pneumothorax, hemopneumothorax, pulmonary contusions, cardiac injury, diaphragm and mediastinal injuries), serious abdominal injury (solid visceral injuries, major vascular injuries), vascular injury in the extremities, femoral artery injury, administration of multiple blood transfusion(≥4 Unite), hospitalization time and trauma scores as GCS, RTS, PATI were evaluated as probable risk factors for mortality in gunshot injuries. RESULTS Seven hundred and fourteen patients (616 males and 98 females) were included in the study. Of these patients, 84.9% (n=606) lived (Group 1), 15.1% (n=108) died (Group 2). There was no statistical significant difference between the patients who died or lived according to gender (p=0.335). While mean age was 27.25±0.48 (1–82) among all patients, it was 26.81± 0.51 (1–82) in group 1 and 29.71±1.32 (1–65) in group 2. Seven 183 Marmara Medical Journal 2009;22(3);000-000 Savaş Eriş, et al. Factors affecting mortality in patients with gunshot injuries (6.5%) of the patients who died and 22 (3.6%) of the patients who lived were old age patients, but there were no statistical differences related to old age between the group 1 and 2 (p=0.167) (Table I). Table I: Distribution according to gender and old age. Gender Male Female Old age ≥55 <55 Total Group 1 n (%) Group 2 n (%) Total n Statistics χ2 P value 526 (86.8) 80 (13.2) 90 (83.3) 18 (16.7) 616 (86.3) 98 (13.7) 0.930 0.335 22 (3.6) 584 (96.4) 7 (6.5) 101 (93.5) 29 (4.1) 685 (95.9) 1.912 0.167 606 (84.9) 108 (15.1) 714 (100) Table II: Distribution of clinical properties of the patients, multiple gunshot injuries and serious organ injuries. P value Group 1 Group 2 Total Statistics n(%) n(%) n(%) χ2 Contact/near contact shot 512 (84.5) 102 (94.5) 614 (86) 7.544 0.006 Delayed admission time 271 (44.7) 39 (36.1) 310 (43.4) 2.765 0.096 Severe anemia 16 (3.0) 55 (51.0 71 (10.0) 238.650 0.001 Presence of shock 92 (15.0) 89 (82.0)) 181 (25.4) 218.908 0.001 138 (22.8) 30 (27.7) 168(23.7) 1.276 0.259 1.region (Head region) 22 (3.6) 44 (40.7) 66(9.2) 150.476 0.001 2.region (Left thorax region) 36 (5.9) 19 (17.6) 55(7.7) 17.504 0.001 3.region (Upper abdomen region) 95 (15.7) 26 (24.1) 121(16.9) 4.593 0.032 Cranial injury 18 (3.0) 45 (41.7) 63 (8.8) 170.614 0.001 Thorax injury 89 (14.7) 30 (27.8) 119 (16.7) 11.311 0.001 Abdominal injury 50 (8.3) 33 (30.5) 83 (11.6) 44.390 0.001 Vascular injury in the extremities 62 (10.2) 15 (13.9) 77( 10.8) 1.275 0.259 Femoral artery injury 14 (2.3) 9 (8.3) 23 (3.2) 10.667 0.001 Clinical properties of the patients Multiple gunshot injuries and regions Multiple gun shot injury Serious organ injuries 184 Marmara Medical Journal 2009;22(3);000-000 Savaş Eriş, et al. Factors affecting mortality in patients with gunshot injuries Of the injuries, 45 (6.3%) occurred due to suicide, 184 (25.8%) due to accidents and 485 (67.9%) due to violence. The suicide rate in group 2 (n=27, 25%) was significantly higher than in group 1(n=18, 3%) (χ2=75.331, p=0.001) (Figure 1). were admitted with delay, for which the difference between the groups was not significant (p=0.096). Sevent-one (10%) of the patients had hematocrit values of 20 mg/dl or less. Of the patients, who had severe anemia during admission, 55 (51%) died and 16 (3%) lived. This was statistically significant for the mortality (χ2=238.650, P=0.001). Presence of shock during admission was 15% (n=92) in group 1 and 82% (n=89) in group 2. That was significant as well (χ2=218.908, p=0.001) (Table II). Of the gun types, 172 (24.1%) were pellet, 445 (62.3%) were bullet, 41 (5.7%) were guns with long barrells, 47 (6.6%) were mines or shrapnel and 9 (1.3%) were something else. There was no statistical difference related to guns with long barrells and pellet guns between the group 1 and group 2 (p=0.928 and p=0.327, respectively) (Figure 2). One hundred and sixty eight (23.5%) of the patients had more than four entrance wounds. Increase in the number of entrance wounds did not have a significant effect on the mortality rate (p=0.259). Distributions of injuries to the three regions were found to be statistically significant (Table II). When Group 2 and Group 1 were compared; it was determined that, head, thorax and abdomen region injuries were significantly higher in Group 1. Sixty two patients (10.2%) in Group 1 and 15 patients in Group 2 (13.9%) had vascular injury in the extremities. While vascular injury in the extremities did not have a significant effect on the mortality (χ2=1.275, p=0.259), femoral artery injury did (χ2=10.667, p=0.001) (Table II). Figure 1: Distribution of gunshot exposure because of suicide, accident and violence in the groups. Of the patients with abdominal injuries (n=220), 37 (16.8%) died, while 183 (83.2%) survived. 55 (25%) of the injuries did not penetrate to the abdomen. The most commonly injured organs were the small bowel and the large intestine. The average PATI value calculated was 14.31±1.03 for Group 1, while it was 39.51±2.99 for Group 2. The effect of PATI on the mortality was found to be extremely important. Of the patients with ≥25 PATI value, 40 (21.8%) survived, while 29 (78.4%) died. The difference between the groups was found to be significant (χ2=45.673, p=0.001). Figure 2: Distribution of the guns’ type that were used. Five hundred and twelve (84.5% ) patients from group 1 and 102 (94.5%) patients from group 2 were exposed to contact/near contact shots. Contact/near contact shots affected mortality significantly (χ2=7.544, p=0.006). Three hundred and ten (43.4%) of the patients One hundred and seventy six (24.6%) of the patients had thorax trauma. While 144 (81.8%) of them survived, 32 (18.2%) died. 104 of the patients had hemopneumothorax, 185 Marmara Medical Journal 2009;22(3);000-000 Savaş Eriş, et al. Factors affecting mortality in patients with gunshot injuries was 14.60±0.045 in group 1 and 5.73±0.285 in group 2, which was found to be statistically significant (p=0.001). The mean RTS value of the patients was 11.75±2.94 in group 1 and 5.45±0.32 in group 2. We found out that, the effect of low RTS value had a statistically significant effect on the mortality (p=0.001). 76 had pulmonary contusions, 13 had major vascular injury, 15 had cardiac injury, and 57 patients had extrathoracic injury. In 119 (16.7%) patients, the wounds had penetrated the thorax. Twenty seven (15.3%) patients underwent thoracotomy and 86 (48.9%) patients had a chest tube installed. The heart injury ratio was 8.5% (n=15). The following factors were found to have significant effect on mortality by using invariable statistical analyses: suicide attempts (p=0.001), serious anemia during admission (p=0.001), presence of shock during admission (p=0.001), serious cranial injury (p=0.001), serious thorax injury (p=0.001), serious abdominal injury (p=0.001), femoral artery injury (p=0.001), administration of multiple transfusion (p=0.009), GCS score of 0 – 7 (p=0.001), GCS score of 8 – 12 (p=0.001) and low RTS score (p=0.001). These variables were entered into the logistic regression model for revealing the risk factors causing mortality. Twenty one (19.4%) of the patients who died and 64 (10.6%) of the patients who survived received blood transfusions ≥4 Unite, and the effect of multiple blood transfusion was found to be significant (χ2=6.897, p=0.009). While 365 (51.1%) patients were operated, 349 (48.9%) were medically treated. Mean hospitalization duration was 1.65±0.23 (1–15) and 11.15±0.51 (1–80) days for the dead and alive groups, respectively. The hospitalization duration had a significant effect on the mortality (p=0.001). Four (0.7%) patients from the alive group and 89 (82.4%) patients from the dead group had 0 – 7 GCS values and were evaluated as being in the severe group. Twenty one (3.5%) patients from the alive group and 13 (12%) patients from the dead group had 8 – 12 GCS values which were evaluated as being in the medium group. We found that, having 0 – 7 GCS value and 8 – 12 GCS value had a very significant effect on the mortality (χ2=540.714, p=0.001 and χ2=14.850, p=0.001; respectively). The mean GCS value In the multivariate analyses, serious anemia during admission [Odds ratio (OR)=0.085, %95 confidence interval (CI) =0.019–0.369, p=0.001], serious cranial injury (OR=0.006, CI=0.001–0.038, p=0.001), serious abdominal injury (OR=0.130, CI=0.026–0.640, p=0.012) and low RTS score (OR=0.199, CI=0.121– 0.328, p=0.001) were found as significantly important for mortality (Table III). Table III: Logistic Regression analysis results of the risk factors. Factors Odds Ratio (OR) %95 Confidence interval (CI) P value Anemia during admission 0.085 0.019–0.369 0.001 Serious cranial injury 0.006 0.001–0.038 0.001 Serious abdominal injury 0.130 0.026–0.640 0.012 Low RTS 0.199 0.121–0.328 0.001 186 Marmara Medical Journal 2009;22(3);000-000 Savaş Eriş, et al. Factors affecting mortality in patients with gunshot injuries common23-25. Suicide cases accounted for 6.3% in our study and were found to have an effect on mortality by invariable analysis. The reason for the high mortality rate in the suicide cases were shots in the head region and late arrival to the hospital. DISCUSSION Trauma is one of the main public health problems in every country. Injuries occur in all age groups and in both genders, but are more often observed in young men1-4. 25% of all the deaths in the United States of America occur as a result of trauma4. Gunshot injuries are one of the leading factors causing high mortality and morbidity in the hospitals dealing with trauma surgery in our country and all over the world5. In the study of Gören et al.7, a 5.6/100000 death rate was found to be caused by gunshot injuries in 1996 – 2001; which is fairly high compared to the other studies8,9. 14.3% of the autopsies in Diyarbakir are the result of gunshot injury cases7. We did not come across a general mortality rate in the literature because there are no gunshot injury studies related to the whole body. But in some series, cranial injuries the mortality rates were 23 – 92% and considering the neurological conditions, the mortality rates increased to 87 – 100%10-14. The mortality rates in which the thorax region was exposed to the gunshot injuries varied between 14.3% and 36.8%15,16. And the mortality rates in which the abdominal region was exposed to the gunshot injuries varied between 3% and 31.4% in different studies1721 . The general mortality rate for our study was 15.1%. The type of gun used is one of the effective factors on mortality and morbidity for gunshot injuries. Mortality and complication rates are especially higher for the injuries which are caused by high-accelerated guns and hunting guns15,23. It is stated in the literature that mortality and morbidity rates differ highly in the bullet and pellet injuries5,17,24,25. For the contact shot pellet injuries, the whole kinetic energy of the gun is diffused into the tissue and causes effects like those of high-accelerated guns26. For the injuries of distant pellet shots, each pellet behaves as a low kinetic energized particle before arriving at the tissue27. In a study of Glezer et al.24, the mortality rates caused by pellet injuries were 20 – 38%. In the study of Feliciano et al.17, the mortality rates caused by bullet injuries were 5 – 12%. The type of gun used was not found to be effective on mortality in our study. The reason for this may be due to patients who had solely abdominal region injuries in the abovementioned studies. It might be stated that the type of gun used is effective on the mortality rate for the abdominal region. But when the whole body and other factors are considered, the effect of the type of gun used decreases. In our study, cases shot from 0 – 15 m had a high mortality rate. This might be because of the high probability of having mortal injuries in the vital organs from contact shots and the decreasing kinetic energy of the gun while the distance increases. The age of the patient with trauma is an effective factor in mortality. For patients over 50, mortality rate increases significantly4,22. 4.1% of the patients in our study were over 50 (≥55). 86.3% of the patients in our study were men and the average age was 27.2. Gender and old age were not found to affect mortality. The reason was that young and active people carry guns, argue and fight more often. Most of the patients in our study were young and active people and the number of old patients in our study was low. In the study of Baker et al.28, it is stated that the duration between injury and treatment is effective on the mortality. Some other studies19,20 support this statement. In studies with a smaller number of cases5,29, the situation is adverse. A longer duration causes the duration of shock to be longer and deeper28. Parallel to this, it is stated in most of the studies that the most common cause of In the study of Gören et al7 which was carried out in our geographic region, it was found that 66.7% of the gunshot injury cases were due to murder. In our study, gunshot injury cases caused by violence accounted to 67.9%. But in some societies, suicide cases are more 187 Marmara Medical Journal 2009;22(3);000-000 Savaş Eriş, et al. Factors affecting mortality in patients with gunshot injuries death is the hypovolemic shock4,17,18,30,31. Britt et al.32 stated that hypovolemic shock has a 5.5% to 100% role in patients who died because of trauma. In our study, 82% of the patients who died were in shock during admittance, which is statistically meaningful. Also, there are studies which state the relationship between continuing hypotension and increasing mortality33. Losing blood and not substituting the blood, being unable to control the bleeding are important problems for the patients with trauma. According to Carillo et al.34, 4 – 5 l of early blood loss is very effective on the mortality rate and is a valid parameter for deciding on the type of surgery for the patient. 51% of the patients in the dead group and 3% of the patients in the alive group had less than or equal to 20 mg/dl hematocrit value. This situation had an effect on the mortality independent of the delayed admittance or presence of shock during admittance. If the hematocrit value of the patient is less than or equal to 20 mg/dl during admission, bleeding should be controlled and replacement therapy should be applied very urgently. We have also observed in our study that, ≥4 Unite blood transfusions increased the rate of mortality. very frequently used scoring system for the evaluation of the neurologic condition in cranial traumas, usually in emergency services41,42 and is a good indication of prognosis10. This scoring system is simple and very useful for the evaluation of mortality and morbidity of the patient. It is in good correlation with the severity of the cranial trauma43. Of the GCS scores in our patients who died, 82.4% were 0–7 and 12% were 8– 12 GCS. Decreasing GCS score is one of the factors affecting mortality, according to the literature. We have found out in our study that both low scores (0 – 7) and moderate scores (8 – 12) affect mortality. However, by using multivariable analyses, we observed that the most important factor was the presence of severe cranial damage. Presence of severe cranial injury is an important factor which increases the mortality rate. Thorax injuries are still dangerous and they constitute 20 – 25% of the deaths caused by trauma in the first four decades of human life44. Thorax injuries are more common among young people. Except for thoracotomy, treatment methods are sufficient for most of the thorax injuries45. Parenchymal injuries such as pulmonary contusion have an important effect on the mortality for most of the patients with thorax injuries46,47. Mortality varies between 14.3% and 36.8% in thorax injury cases15,16. Right thorax region injuries are more common, while left thorax injuries are more vital48,49. The mortality rate for 176 patients with thorax injuries in our study was 18.2%. While the thoracotomy frequency was 15.3%, chest tube was placed in 48.9% of the patients with thorax injuries in our study. 119 patients had severe thorax trauma. Hemopneumothoraks took the first place as 59.1% while contusion was in the second place. In our study, the hearth injury ratio was 8.5%. By using invariable analysis, it was found that severe thorax trauma affected the mortality rate. Multivariable analysis showed that it did not affect mortality as much as the cranial and abdominal injuries. Lower extremity, the abdominal region and upper extremity regions are the most frequent injury regions for the gunshot injuries, respectively35. The frequency order was similar in our study 33.6% in the lower extremity, 30.8% in the abdominal region and 24.9% in the upper extremity. Regarding the entrance regions, there were three. Of the injury regions of patients who died in our study, 40.7% were cranial, 17.6% were in the left thorax region and 24.1% were upper abdominal. Injuries in these regions significantly affected the mortality rate. Entrance wounds in these three regions should alert the clinician. Deaths caused by cranial region traumas take first place among all the deaths caused by The mortality rate for trauma36-38. craniocerebral gunshot injuries is declared as 23% - 92% in different studies11-14,38-40. The mortality rate of patients with cranial gunshot injuries in our study was 71.4%. GCS is a Establishing sufficient ambulance services, blood banks and regional trauma centers decreased mortality rates to 9.5% in the 188 Marmara Medical Journal 2009;22(3);000-000 Savaş Eriş, et al. Factors affecting mortality in patients with gunshot injuries 1990s31,50,51. Delayed admission time, insufficient blood support and the high rate of large intestine injuries affected the postoperative infectious complications and the death incidence52,53. The risk factors related to post-operative infections for abdominal gunshot injuries are uncontrolled shock, duration of surgery, transfusion requirement, number of injured organs and the PATI54,55. It was stated in the literature that mortality rate for the abdominal region gunshot injuries was 3% to 31.4% in different studies18,21,56. The mortality rate for the abdominal injuries in our study was 16.8%. The high mortality rate in our study might be due to the insufficient pre-hospital services. It was found out in different studies that there is a direct relationship between the number of injured organs and the mortality and morbidity18-21,57. According to the literature concerning injured organs; the small bowel, large intestine and liver take the first three places5,17,21,56. Frequencies of organ injuries in our study are similar. The morbidity rate for cases with abdominal trauma index greater than or equal to 25 is 42%, while it is 7% for the cases with abdominal trauma index less than 25 according to Thomsen and friends58. The average PATI was 14.3 for group 1 and 39.5 for group 2 in our study. Mortality was found to be 78% for patients with >25 PATI score. PATI is an independent factor affecting mortality significantly in abdominal injuries, as compatible with the literature. The presence of severe abdominal trauma has significantly affected mortality in our multivariable analyses. artery injury affected mortality in our study. This result might be explained by the excessive loss of blood from the femoral artery. The other veins or arteries of the extremity are narrower and between the compartments, so they can be easily affected by thromboses and the patient can gain time. Vascular examination on the part of the clinician in extremity gun shot injuries is very important. Revised trauma score is the indicative factor of mortality for patients with trauma, as stated in many studies60,61. Low RTS affected mortality in our study, as in the literature. CONCLUSION We have established the factors affecting mortality in gunshot injuries in all body regions. As a result of invariable statistical analyses, we determined that attempted suicide, presence of serious anemia during admission, shock, serious cranial trauma, serious thorax injury, serious abdominal injury, femoral artery injury, multiple blood transfusion, GCS 0-7, GCS 8-12, low RTS were significant factors affecting mortality. While these results were evaluated by using multivariable analysis; we found out that serious anemia during admission, serious cranial injury, serious abdominal injury and low RTS were independently significant in predicting mortality. It can be stated by using these results that; taking the surgery decision at the emergency service without losing time, promptly starting treatment for patients in shock and with serious anemia and examining carefully the cranial and abdominal injuries lead to a decrease in mortality rates. The emergency treatment of penetrating extremity trauma is gaining importance nowadays, as compared with the past. The most frequent cause of the vascular injuries in the extremities was penetrating injuries (82%). Sixty five percent of these injuries were related to hunting rifles and pistols. The percent of complications in extremity injuries is related to the amount of energy transferred to the tissue. Complications are wound infection, neurovascular injury and compartment syndrome, ununion and malunion59. While vascular extremity injuries had no significant effect on mortality, femoral Acklowledgement The work has been funded by the Institutional recources of Emergency Department of Dicle University. REFERENCES 1. 189 Hoyt DB, Potenza BM, Cryer HG, et al. Trauma. In: Greenfield LJ, Mullholland MW, Oldham KT, Zelenock GB, Lilimoe KD eds. Surgery:Scientific Principles and Practise. 2nd edn. Philadelphia: Lippincott-Raven, 1997:267–421. Marmara Medical Journal 2009;22(3);000-000 Savaş Eriş, et al. 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Comparing logistic models based on modified GCS motor component with other prognostic tools in prediction of mortality: Results of study in 7226 trauma patients. Injury. 2005; 36: 900– 904. 61. Kuhls DA, Malone DL, McCarter RJ, Napolitano LM. Predictors of mortality in adult trauma patients: the Physiologic Trauma Score is equivalent to the Trauma and Injury Severity Score. J Am Coll Surg 2002:194: 695–704. 191 ARAŞTIRMA YAZISI D VİTAMİNİ TEDAVİSİNİN ETKİNLİĞİ FALANGEAL RADYOGFRAFİK ABSORPSİYOMETRİ İLE İZLENEBİLİR Mİ? Ümran Kaya, Evrim Karadağ Saygı, Işıl Üstün, Gülseren Akyüz Marmara Üniversitesi Hastanesi, Fiziksel Tıp ve Rehabilitasyon AD, İstanbul, Türkiye ÖZET Amaç: Radyografik absorpsiyometri (RA) 2, 3 ve 4. parmakların orta falankslarından kemik mineral yoğunluğu (KMY) ölçümü yapan ucuz ve uygulaması kolay bir tekniktir. Bu çalışmada D vitamini eksikliği bulunan ileri yaştaki hastalarda kısa süreli D vitamini tedavisinin falangeal RA ile izleminin yapılıp yapılamayacağı ve dual enerji x-ışını absorpsiometri (DXA) ile ölçüm sonuçlarının uyumunun karşılaştırılması amaçlanmaktadır. Gereç ve Yöntem: Çalışmaya 65 yaş ve üzerinde D vitamini eksikliği saptanan (<50nmol/l) 57 osteopenik hasta alındı. 30 hastaya günde 1 µg alfakalsidol ve 500 mg elemanter kalsiyum, kontrol grubuna ise günde 500 mg elemanter kalsiyum verildi. Tüm hastaların tedavi başlangıcında ve 6. ayda el falangeal KMY; lomber omurga ve kalça KMY ölçümleri yapıldı. Serumda D vitamini düzeyindeki yüzde değişim ile RA ve DXA sonuçlarının uyumluluğu istatistiksel olarak karşılaştırıldı. Bulgular: Tüm hastaların başlangıçta yapılan DXA KMY ölçümleri ile RA ölçüm sonuçları uyumlu idi. 6 aylık alfakalsidol tedavisi sonucunda D vitamini düzeylerindeki değişim hem DXA hem de RA ile istatistiksel ilgileşim göstermedi. Sonuç: Falangeal radyografik absorpsiyometri güvenilir ve pratik bir yöntem olmakla birlikte D vitamini tedavisinin kısa dönemli takibinde kullanımının sınırlı olacağı düşünülmektedir. Anahtar sözcükler: D vitamini, Dual enerji x-ışını absorpsiyometri (DXA), Falangeal radyografik absorpsiyometri (RA) IS IT POSSIBLE TO FOLLOW-UP THE EFFICACY OF VITAMIN D TREATMENT BY PHALANGEAL RADIOGRAPHIC ABSORPSIOMETRY? ABSTRACT Aim: Radiographic absorptiometry (RA) is a cheap and easily applicable technique for measuring bone mineral density (BMD) of the medium phalanges of fingers 2, 3 and 4. In this trial with elderly patients suffering from vitamin D deficiency, the aim is to investigate whether it is possible to follow short-term vitamin D treatment with phalangeal RA or not and to compare the consistency of measurement results with dual energy x-ray absorptiometry (DXA). Materials and Methods: Fifty-seven patients over 65 years old who had been determined as vitamin D deficiency (<50nmol/l) were included in this trial. Thirty patients received 1 µg of alphacalcidol and 500 mg elemenatry calcium once a day and the control group received 500 mg elementary calcium. Hand phalangeal, lumbar spinal and hip BMD measurements of all patients were performed at the beginning and the 6th month of the treatment. The consistency of percentage change of serum levels of vitamin D with RA and DXA results were statistically compared. Results: Baseline DXA BMD measurements of all of the patients were consistent with the RA measurement values. After 6 months of alphacalcidol and elementary calcium treatment, the difference in the levels of vitamin D was not statistically relevant, neither with DXA nor with RA. Conclusion: Although phalangeal radiographic absorptiometry is a reliable and practical method, its use in the short term follow-up of vitamin D treatment is thought to be limited. Keywords: Vitamin D, Dual energy x-ray absorptiometry (DXA), Phalangeal radiographic absorptiometry (RA) İletişim Bilgileri: Dr. Evrim Karadağ Saygı Marmara Üniversitesi Hastanesi, Fiziksel Tıp ve Rehabilitasyon AD, İstanbul, Türkiye e-mail: evrimkaradag4@hotmail.com 192 Marmara Medical Journal 2009;22(3);000-000 Marmara Medical Journal 2009;22(3);000-000 Ümran Kaya, ark. D vitamini tedavisinin etkinliği falangeal radyogfrafik absorpsiyometri ile izlenebilir mi? GİRİŞ Osteoporoz kemik gücünü etkileyerek kırık riskinde artma ile karakterize, ilerleyici bir iskelet sistemi hastalığıdır. D vitamini eksikliği yaşlanmaya bağlı olarak gelişen senil osteoporozun en önemli risk faktörlerindendir1. Osteoporoz tanısında günümüzde en geçerli teknik çift-enerji x-ışın absorpsiyometridir (DXA). Buna karşın, osteoporoz tanı ve tedavi izleminde DXA’nın pahalı bir yöntem olması, taşınabilme ve uygulama zorluğu kullanımını kısıtlamaktadır2. Toplumda osteoporoz hastalarını belirlemek için tarama amaçlı kullanılan falangeal radyografik absorbsiyometri (RA) ise ucuz ve hızlı bir yöntemdir3. Bu çalışmada, D vitamini eksikliği bulunan ileri yaştaki hastalarda kısa süreli D vitamini tedavisinin RA ile takibinin yapılıp yapılamayacağı ve DXA ile ölçüm sonuçlarının uyumunun karşılaştırılması amaçlanmaktadır. kontrol grubuna ise günde 500 mg kalsiyum verildi. Tüm hastaların tedavi başlangıcında ve 6. ayda falangeal (dominant olmayan elin, 2.,3.,4. parmaklarının orta falankslarından) kemik mineral yoğunluğu (KMY) RA (Metriscan-ALARA) ile; lomber omurga ve kalça KMY ölçümleri DXA (Lunar) ile yapıldı. DXA sonuçlarından lomber bölgeye ait değerlerin L1,2,3,4 vertebraların ortalama KMY’leri, T ve Z skorları değerlendirmeye alındı. Başlangıçtaki DXA ve RA skorları (KMY, T ve Z skorları) arasındaki uyumun yanı sıra, tedavi sonrası serumda D vitamini düzeyindeki yüzde değişim ile RA ve DXA sonuçlarının uyumluluğu istatistiksel olarak karşılaştırıldı. GEREÇ-YÖNTEM Çalışmaya Marmara Üniversitesi Tıp Fakültesi Fiziksel Tıp ve Rehabilitasyon Anabilim Dalı polikliniklerine başvuran, 65 yaş ve üzerinde D vitamini eksikliği saptanmış (<50nmol/l), 57 osteopenik (lomber ve/veya femoral bölge T skoru -1,5 ile -2,5 arasında) hasta dahil edildi. D vitamini metabolizmasını etkileyen hastalık varlığı, tiroid ve/veya paratiroid bozukluğu, malignite varlığı, ciddi renal yetmezlik (kreatinin klirensi < 30ml/dk) ve D vitamini metabolizmasını bozabilecek ilaç kullanımı (hipnotikler, sedatifler veya antikonvülzanlar gibi) ve eli tutan hastalık varlığı (romatoid artrit, el osteoartriti gibi) çalışma dışı bırakılma nedenleri olarak belirlendi. . Çalışmamız randomize kontrollü bir araştırma olup, çalışma için hastanemiz Etik Kurul’undan onay alındı. Hastalar, çalışmanın içeriği hakkında sözlü ve yazılı olarak bilgilendirildi ve onayları alındıktan sonra çalışmaya dahil edildi. 30 hastaya günde 1 µg alfakalsidol ve 500 mg elemanter kalsiyum, BULGULAR D vitamini grubundaki hastaların yaş ortalaması 70,03±6,04; kalsiyum grubundaki hastaların ise 69,48±4,27 idi. Gruplar arasında demografik veriler açısından istatistiksel farklılık saptanmadı (p>0,05) (Tablo I). Her iki grubun da başlangıçtaki 25(OH) Vitamin D3 düzeyleri arasında farklılık yoktu. Başlangıçtaki lomber, femoral bölgelerden yapılan DXA ölçümleri ile RA ölçüm sonuçları uyumlu idi (Tablo II). D vitamini+kalsiyum ve kalsiyum tedavisi alan gruplarda 3. ve 6. ay sonunda başlangıca göre serum D vitamini düzeylerindeki yüzde değişim oranları hesaplandı. 3. ayda D vitamini düzeyleri her iki grupta da yükselirken, 6. ayda alfacalcidol alan grupta anlamlı artış göze çarptı (Şekil 1). Gruplarda D vitamini değişim oranları ile RA sonuçları arasında uyum tespit edilmedi. Benzer şekilde başlangıca göre 6. ay D vitamini yüzde değişim oranları DXA ile istatistiksel ilgileşim göstermedi (Tablo III). Verilerin değerlendirmesi SPSS for Windows 11,5 istatistik paket programında yapıldı. Karşılaştırmalarda Mann Whitney U, Ki-kare testleri kullanıldı. Pearson korelasyon analizi ile ilişikiler değerlendirildi. P<0,05 anlamlı kabul edildi. 193 Marmara Medical Journal 2009;22(3);000-000 Ümran Kaya, ark. D vitamini tedavisinin etkinliği falangeal radyogfrafik absorpsiyometri ile izlenebilir mi? Tablo I: Demografik özellikler Yaş (ort±SS) (yıl) Ağırlık (kg) Boy (cm) Vücut kütle indeksi (kg/cm2) (ort±SS) D vitamini ve kalsiyum grubu (n=30) Ortalama 70,03±6,04 67,90±10,68 153,27±7,06 28,94±4,42 Kalsiyum grubu (n= 27) Ortalama 69,48±4,27 70,33±10,10 153,93±5,79 29,75±4,5 P ,695 ,382 ,703 ,501 Tablo II: Tedavi öncesi hastaların RA ve DXA ölçümlerinin uyumlulukları Falangeal RA KMY T skoru Z skoru DXA KMY lomber KMY femur KMY total T skor lomber T skor femur T skor total Z skor lomber Z skor femur Z skor total Korelasyon r=0,43 (p<0,01) r=0,42 (p<0,01) r=0,4 (p<0,01) r= 0,45 (p<0,01) r=0,38 (p<0,05) r=0,38 (p<0,05) r=0,43 (p<0,01) r=0,49 (p<0,01) r=0,86 (p<0,001) Tablo III: D vitamini+kalsiyum ve Kalsiyum gruplarında başlangıca göre 6. ay sonunda serum vitamin D düzeylerindeki % değişim oranları ile DXA, RA değerlerinin uyumu DXA ve RA % değişim oranları (başlangıç-6. ay) Gruplar D vitamini serum düzeyleri % değişim oranları (başlangıç– 6. ay) D vitamini ve kalsiyum grubu Kalsiyum grubu KMY T skoru Z skoru KMY T skoru Z skoru Korelasyon p>0,05 p>0,05 p>0,05 p>0,05 p>0,05 p>0,05 Şekil 1: 25-hidroksi vitamin D3 düzeylerinin başlangıç, 3. ve 6. aylarda karşılaştırması 194 Marmara Medical Journal 2009;22(3);000-000 Ümran Kaya, ark. D vitamini tedavisinin etkinliği falangeal radyogfrafik absorpsiyometri ile izlenebilir mi? Bizim çalışmamızda ise 6 aylık alfakalsidol tedavisi sonucunda serumda D vitamini düzeylerindeki değişim ne DXA ne de RA ile istatistiksel ilgileşim gösterdi. Bu sonucun hasta takip süremizin kısa olmasına verilen D vitamini tedavisi ne kadar uzunsa KMY üzerinde yaratacağı pozitif etki de o kadar belirgin olacaktır) ve hasta sayımızın az oluşuna bağlı olarak geliştiği kanısındayız. TARTIŞMA D vitamini eksikliği tüm geriyatrik yaş grubunda önemli bir sağlık sorunudur ve bu dönemde görülen osteoporozun en sık nedenidir1,4. Senil osteoporozun tanı ve tedavi izleminde en çok tercih edilen yöntem DXA’dır. Falangeal RA gibi periferik ölçümü değerlendiren yöntemler, daha çok osteoporozun toplum içi taramalarında kullanılmaktadır. Yapılan çalışmalarda RA’nın periferik KMY’yi doğru ve hassas olarak ölçebildiği gösterilmiştir5,6. RA ile yapılan periferik KMY ölçümü ile lomber ve kalça bölgesi KMY ölçümünün uyumunun incelendiği çalışmalar bulunmaktadır7,8. Aktaş ve ark. yaptığı bir tarama çalışmasında lomber vertebra DXA sonuçları, RA ile yüksek derecede uyumlu bulunmuştur7. Ayrıca Swezey ve ark. lomber-femoral DXA ve RA ile anlamlı korelasyon saptamıştır8. Bizim çalışmamızda da D vitamini eksikliği bulunan yaşlı hastalarda başlangıçtaki DXA KMY ölçümleri ile RA ölçüm sonuçları uyumlu bulunmuştur. Bu sonuca göre RA D vitamini eksikliği bulunan hastalarda osteoporoz tanısında kullanılabilir güvenli ve pratik bir yöntemdir. Sonuç olarak, falangeal radyografik absorpsiyometri, D vitamini eksikliğine bağlı osteoporoz tanısında güvenilir ve pratik bir yöntem olmakla birlikte D vitamini tedavisinin kısa dönemli takibinde kullanımının sınırlı olacağı düşünülmektedir. KAYNAKLAR 1. 2. 3. D vitamini eksikliğine bağlı olarak gelişen osteoporoz tedavisinde de kemik kaybı DXA ile takip edilmektedir. Yapılan çalışmalarda alfakalsidol ile tedavi edilen osteoporoz hastalarında KMY’nin artış gösterdiği tespit edilmiştir9,10. Fenkçi ve ark.larının 1 yıl süreyle alfakalsidol alan osteoporoz hastalarında DXA ile yapılan ölçümlerinde femur boynunda %0,07, L2-4’te %0,09 ve totalde %0,08’lik artış saptanmıştır9. Başka bir çalışmada, Orimo ve ark.ları, senil osteoporozlu hastalarda 1 yıl süre ile 1mcg alfakalsidol tedavisi sonucunda DXA’da KMY’nda artış tespit etmişlerdir10. Menczel ve ark.’nın yaptığı bir çalışmada ise 3 yıl süreyle alfakalsidol alan osteoporoz hastalarının distal radius KMY ölçümlerinde, plaseboya göre %2’lik artış saptanmıştır11. Literatürde, osteoporoz tedavisinin takibinde RA’nın kullanıldığı herhangi bir çalışmaya rastlanmamıştır. 4. 5. 6. 7. 8. 9. 195 Eriksen EF, Glerup H. Vitamin D deficiency and aging: implication for general health and osteoporosis. Biogerontology 2002; 3: 73-77. Cadarette SM, Jaglal SB, Murray TM, et al. Canadian Multicentre Osteoporosis Study. Evaluation of decision rules for referring women for bone densitometry by dual-energy x-ray absorptiometry. JAMA 2001:286:5763. Boonen S, Nijs J, Peeters H, et al. Identifying postmenopausal women with osteoporosis by calcaneal ultrasound, metacarpal digital X-ray radiogrammetry and phalangeal radiographic absorptiometry: a comparative study. Osteoporos Int 2005:16:93-100. Atlı T, Erdoğan G, Güllü S. The prevalance of vitamin D deficiency and effects of ultraviolet light on vitamin D levels of elderly Turkish population. Arch Gerontol Geriatr.2005;40: 53-60 Yang SO, Hagiwara S, Engelke K, et al. Radiographic absorptiometry for bone mineral measurement of the phalanges: precision and accuracy study. Radiology 1994:192:857-859. Elliot JR, Fenton AJ, Young T, et al. The precision of digital X-ray radiogrammetry compared with DXA in subjects with normal bone density or osteoporosis. J Clin Densitom 2005:8:187-190. Aktaş İ, Akgün K, Sarıdopan M.E. Kalkaneal kantitatif ultrason ve falangeal radyografik absorpsiometrinin osteoporoz tanısındaki değeri: karşılaştırmalı çalışma. Osteoporoz Dünyasından. 2006;12:43-46 Swezey RL, Draper D, Swezey AM. Bone densitometry: Comparison of dual energy x-ray absorptiometry to radiographic absorptiometry. J Rheumatol 1996:23: 1734-1438. Fenkci I V, Doğanay M, Tanrıöver S, Gökmen O. Effects of alfacalcidol treatment on bone mineral density and calcium metabolism in postmenopausal osteoporosis. J Gynecol Obst 2001;28:243-246. Marmara Medical Journal 2009;22(3);000-000 Ümran Kaya, ark. D vitamini tedavisinin etkinliği falangeal radyogfrafik absorpsiyometri ile izlenebilir mi? 10. Orimo H, Shiraki M, Hayashi Y. Effects of 1αhydroxyvitamin D3 on lumbar bone mineral density and vertebral fractures in patients with postmenopausal osteoporosis. Calcif Tissue Int 1994; 54: 370-376. 11. Menczel J, Foldes J. Alfacalcidol (alpha D3) and calcium in osteoporosis. Clin Orthop 1994;300: 241247. 196 ORIGINAL RESEARCH INCIDENTAL DETECTION OF CORONARY ARTERY CALCIFICATIONS ON NON-CARDIAC THORACIC CT EXAMINATIONS Kadriye Orta Kılıçkesmez1, Özgür Kılıçkesmez2, Neslihan Taşdelen2, Duygu Kara2, Yüksel Işık2, Arda Kayhan3, Bengi Gürses2, Nevzat Gürmen2 1 İstanbul Üniversitesi Kardiyoloji Enstitüsü, Kardiyoloji, İstanbul, Türkiye 2Yeditepe Üniversitesi, Radyoloji, İstanbul, Türkiye 3Namık Kemal Üniversitesi, Radyoloji, Tekirdağ, Türkiye ABSTRACT Objective: Strong relationships have been demonstrated between the presence of occlusive coronary artery disease and coronary artery calcifications detected at autopsy, fluoroscopy, or computed tomography (CT). The aim of our study was to evaluate the frequency of incidental coronary artery calcifications during thoracic CT examinations and to correlate them with cardiac risk factors. Materials and Methods: Thoracic CT scans obtained over a period of 6 months from 113 patients (72 male and 41 female) with a mean age of 62,7 (31-92 years) were retrospectively evaluated. The thoracic scans were performed using standard 9 mm consecutive slices from the apex to the base of the thorax, using a standard thoracic protocol, on a Siemens 16 channel multislice CT scanner. Coronary arteries were evaluated for calcifications. Results: Thirty-seven patients (32.7%) had coronary calcifications.18 patients (15.9%) had one, 9 patients (7.9%) two, 7 patients (6.2%) three, and 3 patients (2.6%) had four vessels with calcifications. The frequency of coronary calcifications was correlated with hypertension, diabetes mellitus, hypercholesterolemia, nicotine abuse, and cardiomegaly. Diabetes mellitus, hypercholesterolemia, cardiomegaly and male gender were significantly associated with coronary calcifications (p<0.05). Conclusion: With the advent of multislice faster CT scanners, coronary artery calcifications are more frequently and easily detectable during non-cardiac thoracic CT examinations. This retrospective study showed increased incidence of coronary calcifications in patients with cardiac risk factors. Among these factors diabetes mellitus, hypercholesterolemia, cardiomegaly and male gender were statistically significant. Keywords: Multidetector computed tomography, Heart, Coronary calcification İletişim Bilgileri: Kadriye Orta Kılıçkesmez, M.D. İstanbul Üniversitesi Kardiyoloji Enstitüsü, Kardiyoloji, İstanbul, Türkiye e-mail: kadriye11@yahoo.com 197 Marmara Medical Journal 2009;22(3);000-000 Marmara Medical Journal 2009;22(3);000-000 Kadriye Orta Kılıçkesmez, et al. Incidental detection of coronary artery calcifications on non-cardiac thoracic CF examinations NON-KARDİYAK TORAKS BT İNCELEMELERİNDE RASTLANTISAL OLARAK SAPTANAN KORONER ARTER KALSİFİKASYONLARI ÖZET Amaç: Bilgisayarlı tomografi (BT), floroskopi veya otopside saptanan koroner arter kalsifikasyonları ile okluzif koroner arter hastalığı arasında güçlü ilişkiler tanımlanmıştır. Bu çalışmanın amacı, toraks BT incelemeleri esnasında insidental olarak saptanan koroner kalsifikasyonların sıklığını belirlemek ve risk faktörleri ile korele etmekti. Gereç ve Yöntem: Altı ay süresince toraks BT uygulanan ve ortalama yaşları 62,7 (31-92) olan 113 olgu (72 erkek, 41 kadın hasta) retrospektif olarak değerlendirilmiştir. Toraks BT incelemeleri Siemens Somatom Sensation 16 dedektörlü BT cihazında apeksten toraks bazaline dek, 9 mmlik ardışık kesitlerle elde olunmuş ve koroner arterler kalsifikasyonlar açısından değerlendirilmiştir. Bulgular: On sekiz hastada (15.9%) tek damar, 9 hastada (7.9%) çift damar, 7 hastada (6.2%) üç damar ve 3 hastada (2.6%) dört damar kalsifikasyonu olmak üzere toplam 37 hastada (32.7%) koroner kalsifikasyon belirlendi. Koroner kalsifikasyonların sıklığı hipertansiyon, diabetes mellitus, hiperkolesterolemi, nikotin bağımlılığı ve kardiyomegali ile karşılaştırıldı. Hiperkolesterolemi, kardiyomegali ve erkek cinsiyet ile koroner arter kalsifikasyonları arasında istatistiksel anlamlı farklılık bulundu (p<0.05). Sonuç: Daha hızlı, çok dedektörlü BT cihazlarının geliştirilmesiyle, non kardiyak BT incelemeleri esnasında koroner kalsifikasyonlar daha kolay ve sık tespit edilmeye başlandı. Bu retrospektif çalışma kardiyak risk faktörleri olan hastalarda koroner arter kalsifikasyonlarında artmış insidansı gösterdi. Bu faktörler arasında diabetes mellitus, hiperkolesterolemi, kardiyomegali ve erkek cinsiyet istatistiksel anlamlı farklılık bulundu. Anahtar Kelimeler: Multidedektör bilgisayarlı tomografi, Kalp, Koroner kalsifikasyon stents, a history of previous bypass surgery, or non-diagnostic scans with poor resolutions. The thoracic scans were performed using standard 9 mm consecutive slices from the apex to the base of the thorax, using a standard thoracic protocol, on a Siemens 16 channel multislice CT scanner. A standard tissue window was used (WL: 50, WW: 500) for the assessment of slices. INTRODUCTION The presence of coronary artery calcification is a significant indicator of atheromatous disease and it may indicate the presence of severe stenosis. While the absence of calcification does not correlate with the absence of coronary artery disease, an incidental finding of calcium has important prognostic implications. Most of the previous work documenting calcification has been observed in patients with a known history of heart disease undergoing further cardiac investigations1,2. The coronary arteries were evaluated for calcifications. The number and location of coronary calcifications were noted for each patient. The investigated cardiac risk factors were gender, hypertension, diabetes mellitus, hypercholesterolemia, and nicotine abuse. The diagnosis of cardiomegaly was achieved with the calculation of transverse heart ratio (>0,5) on plain thoracic x-rays. Early diagnosis of atherosclerosis is therefore highly important in predicting and preventing myocardial infarction. Imaging modalities especially CT scans have been proved to be helpful1. The aim of this study was to evaluate the frequency of incidental coronary artery calcifications during thoracic CT examinations, and to correlate this with cardiac risk factors. Medical records were reviewed and the data related to age, sex, smoking history, risk factors for vascular disease, and general medical condition were noted in a standardized form. Evidence of previous cardiac disease was determined on the basis of electrocardiographic evidence of arrhytmias, ischemia or previous myocardial infarction. Prior infarctions were documented by evaluation of enzyme levels, history of MATERIAL AND METHOD Thoracic CT scans obtained over a period of 6 months from 113 patients (72 male and 41 female) with a mean age of 62,7 (31-92 years) were retrospectively evaluated. The exclusion criteria were existing implanted coronary 198 Marmara Medical Journal 2009;22(3);000-000 Kadriye Orta Kılıçkesmez, et al. Incidental detection of coronary artery calcifications on non-cardiac thoracic CT examinations four vessel calcifications (left main coronary, circumflex, LAD and RCA). treatment for angina or congestive heart failure, and findings of any available studies of cardiac function such as cardiac echocardiography, exercise thallium myocardial perfusion imaging and exercise tolerance testing. The incidence of calcifications were significantly higher in males (p<0.05), as well as in patients with diabetes mellitus (12.3%), hypercholesterolemia (16.8%) and cardiomegaly (20.3%) (p<0.05). Although nicotine abuse, and hypertension are associated with increased risk of calcification, these were not statistically significant. (TableI). Image interpretation CT scans were transferred to an independent Workstation (Leonardo console, software version 2.0; Siemens) for postprocessing, and the 3D multiplanar reconstruction (MPR) images were reconstructed in the coronal and sagittal planes in addition to the axial source slices. The left anterior descending (LAD), circumflex and right coronary arteries (RCA) were evaluated for presence of calcifications by two radiologists on the basis of the knowledge of the CT anatomy of the coronary arteries in consensus. The readers were experienced in reading images of the coronary anatomy. The presence of coronary calcifications was evaluated with a contiguous-slice method. A calcified lesion was defined as a hyperdense area inside the artery with a Hounsfield unit (HU) of greater than 90 and that measured 0.5 mm2 or larger. Figure 1: Axial thorax CT image at the level of heart demonstrates left main coronary and circumflex artery calcifications. Statistical Analysis All statistical analysis were performed using Statistical Package for Social Sciences (SPSS) for Windows 10.0. The number of calcifications, locations, and the risk factors of the patients were reported as the mean ± standard deviation. Student’s t test was performed to compare the subgroups with and without calcifications. A p value of less than 0.05 was considered to indicate a statistically significant difference. RESULTS A total of 113 thoracic CT scans were reviewed. The scans were performed with various clinical indications. The most common indication was for identification of primary or secondary lung carcinomas, followed by airway disease evaluation. Figure 2: Coronal 3D MPR CT image of the thorax at the level of heart demonstrates left main, anterior descending and circumflex coronary artery calcifications. Thirty-seven patients (32.7%) had coronary calcifications. Of the 37, 18 patients (15.9%) had one, 9 patients (7.9%) had two, 7 patients (6.2%) had three, and 3 patients (2.6%) had 199 Marmara Medical Journal 2009;22(3);000-000 Kadriye Orta Kılıçkesmez, et al. Incidental detection of coronary artery calcifications on non-cardiac thoracic CT examinations Table I: Association of cardiac risk factors with coronary calcifications. The group with coronary calcifications 62,5% male Gender 45,7% female 15(13,2%) Nicotine abuse 21(18,3%) Hypertension 14 (12,3%) Diabetes Mellitus Hypercholesterolemia 19 (16,8%) 23 (20,3%) Cardiomegaly 13 (11,5%) Known cardiac disease The group without coronary calcifications 37,5% male 54,3% female 14(12,3%) 15 (13,2%) 6 (5,3 %) 7 (6,1%) 12 (10,6%) 10 (8,8%) Statistical difference (p) p<0.05 p>0.05 p>0.05 p>0.05 p<0.05 P<0.05 P<0.05 p>0.05 calcium score had a 100% predictive value in the exclusion of angiographic evidence of obstructive epicardial coronary lesions. The higher the calcium score, the more likely the presence of angiographic obstructive 10 disease . DISCUSSION Autopsy studies have shown that there is a close link between coronary artery calcification and the extent of vascular stenosis with a subsequent risk of myocardial infarction. A variety of imaging modalities have been used for detecting coronary artery calcifications of which, plain chest radiography and fluoroscopy have the lowest sensitivity. CT imaging is superior to fluoroscopy for detecting coronary calcifications1. Results of autopsy studies indicate that coronary artery calcification is invariably associated with the presence of atherosclerotic plaques11. In a previous study performed with 450 consecutive patients, Callaway et al., found atherosclerotic plaques in 26% of male and 15.6% of female scans. When they limited their sample to those over 40 years for age, the incidence increased to 48% from 41.6% 12. Ultrafast CT has high-resolution contrast, a rapid image acquisition, and allows elimination of the image blurring caused by heart movement. Due to these features, ultrafast CT has a high sensitivity for detecting calcium in the coronary arteries3. In different series, the sensitivity and specificity of the examination ranged from 88 to 100% and 43 to 100%, respectively2,4,5. Coronary calcification is strongly associated with the prognosis. Indeed, the extent of coronary atherosclerosis (total calcium score) is the most powerful predictor of subsequent or recurrent cardiac events. This was true in the former years when calcium was detected with fluoroscopy and conventional CT13. Arterial calcification occurs in the intima of the blood vessels, as a part of atherosclerosis. In general population, coronary artery calcification correlates with the atherosclerotic plaque burden and with coronary vessel stenosis, and has consistently been shown to be predictive for future cardiac events6-9. Janowitz et al., analyzed the evolution of the amount of calcium in atherosclerotic plaques by ultrafast CT in patients with and without coronary artery disease3. Ninety-eight percent of the calcium deposits identified on the initial examination were confirmed in consequent imagings, and there was a significant increase in the calcification volume and in the total calcified area of the atherosclerotic plaque in the evolution. Patients with coronary artery disease have a Coronary segments with a luminal obstruction greater than 50% are likely to have some calcification that is detectable with electronbeam CT. In a trial, it was shown that, a 0 200 Marmara Medical Journal 2009;22(3);000-000 Kadriye Orta Kılıçkesmez, et al. Incidental detection of coronary artery calcifications on non-cardiac thoracic CT examinations large amount of new calcium deposits, which are not found in asymptomatic patients. In patients with no evidence of calcification, both in the first approach and later, the prevalence of ischemic heart disease is extremely low. accurate event predictor asymptomatic adults16. in high-risk The present study had some limitations. Our sample size was small and a relatively old CT technology was used. Moreover, there was no gold standard angiographic demonstration of stenotic effects of the calcium deposits. In a study searching the presumptive detection of coronary stenosis on the basis of existing calcification by means of CT, higher sensitivities have been found in the calcified arteries (78% for LAD, 63% for the circumflex and 16% for RCA). Specificities were 78%, 80% and 100%, and positive predictive values (PPV) were 88%, 83% and 100%, respectively. The high PPV suggested that significant coronary artery disease was likely to be present when coronary calcification was seen on CT14. In a study performed by Shirazi et al., of the total 100 patients (62 males), 69 had coronary artery obstruction (>50% stenosis was detected by angiography). Angiography was normal in the rest. For the diagnosis of coronary artery disease, a spiral CT scan had a sensitivity of 94% and a specificity of 61%. PPV and negative predictive value (NPV) were 84% and 79%, respectively1. In conclusion, coronary calcifications were easily discernible with CT. Our study showed that calcified deposits were more frequently encountered with increasing age and male gender. In addition, to the increased association of coronary calcification with the male gender, a relationship to diabetes mellitus, hypercholesterolemia and cardiomegaly was detected. Acknowledgement: There was no financial support for this study. REFERENCES 1. 2. 3. In their series performed with double-helix CT, Shemesh et al., stated that calcification was significantly more prevalant in patients with obstructive coronary artery disease (>83%) than in patients with normal coronary arteries (27%) or in healthy control subjects (34%, p<0.1). The researchers found a high sensitivity (91%), however, the specificity was low (52%) due to calcification in nonobstructive lesions15. When CT and angiographic findings were compared, CT was found to have 84% accuracy with PPV and NPVof 89% and 59%, respectively15. 4. 5. 6. In contrast, some investigators claim that the technique is useless16. Detrano et al., in their series performed with 1196 asymptomatic high-coronary-risk subjects that underwent risk-factor assessment and cardiac CT, showed that CT calcium score did not add significant incremental information to risk factors in clinical screening. The researchers claimed that neither risk-factor assessment nor the calcium detected with CT was an 7. 8. 9. 201 Shirazi AS, Nasehi N, Sametzadah M, Saberi H, Shabani MA. Spiral CT scan for detecting coronary artery stenosis. Iran. J Radiol 2005; 3:11-15. Feldman C, Vitola D, Schiavo N. Detection of coronary artery disease based on the calcification index obtained by helical computed tomography. Arq Bras Cardiol 2000;75:471-480. Janowitz WR, Agatston S, Kaplan G, Viamonte M. Differences in prevalence and extent of coronary artery calcium detected by ultrafast computed tomography in asymptomatic men and women. Am J Cardiol 1993; 72: 247-254. Tanenbaum SR, Kondos GT, Veselick KE, Prendergast MR, Brundage BH, Choomka EV. Detection of calcific deposits in coronary arteries by ultrafast computed tomography and correlation with angiography. Am J Cardiol 1989; 63: 870-871. Wong ND, Abrahamson D, Tobis JM, Eisenberg H, Detrano RC. Detection of coronary artery calcium by ultrafast computed tomography and its relation to clinical evidence of coronary artery disease. Am J Cardiol 1994; 73: 223-227. Wexler L, Brundage B, Crouse J, et al. Coronary artery calcification: Pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing Group. Circulation 1996; 94:1175– 1192. Keelan PC, Bielak LF, Ashai K, et al. Long-term prognostic value of coronary calcification detected by electron-beam computed tomography in patients undergoing coronary angiography. Circulation 2001; 104:412– 417. Budoff MJ. Prognostic value of coronary artery calcification. JCOM 2001; 8:42–48. Greenland P, LaBree L, Azen SP, et al. Coronary Artery Calcium Score combined with Framingham Score for risk prediction in asymptomatic individuals. JAMA 2003; 291:210–215. Marmara Medical Journal 2009;22(3);000-000 Kadriye Orta Kılıçkesmez, et al. Incidental detection of coronary artery calcifications on non-cardiac thoracic CT examinations 10. Rumberger JA, Brundage BH, Rader DJ. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc 1999;74:243-252. 11. McNamara JJ, Molot MA, Stremple JF, Cutting RT. Coronary artery disease in combat casualties in Vietnam. JAMA 1971; 216: 1185-1187. 12. Callaway MP, Richards P, Goddard P, Rees M. The incidence of coronary artery calcification on standard thoracic CT scans. Br J Radiol 1997; 70: 572-574. 13. Selby JB, Morris PB. Coronary Artery Calcification – CT. url:http://emedicine.medscape.com/article/352189overview 14. Timins ME, Pinsk R, Sider L, Bear G. The functional significance of calcification of coronary arteries as detected on CT. J Thorac Imaging 1991;7:79-82. 15. Shemesh J, Apter S, Rozenman J, et al. Calcification of coronary arteries: detection and quantification with double-helix CT. Radiology 1995;197:779-783. 16. Detrano RC, Wong ND, Doherty TM, et al. Coronary calcium does not accurately predict near-term future coronary events in high-risk adults. Circulation. 1999 May 25;99:2633-2638. 202 ARAŞTIRMA YAZISI RADİKAL PROSTATEKTOMİ SPESMENLERİNDEKİ VEGF’İN, E-CADHERİN’İN VE BIM’İN İMMÜNOHİSTOKİMYASAL EKSPRESYONLARININ PROGNOSTİK DEĞERİ Erem Kaan Başok1, Asıf Yıldırım1, Adnan Başaran1, Ebru Zemheri2, Reşit Tokuç1 1 SB İstanbul Göztepe Eğitim ve Araştırma Hastanesi, 1. Üroloji, İstanbul, Türkiye 2SB İstanbul Göztepe Eğitim ve Araştırma Hastanesi, Patoloji, İstanbul, Türkiye ÖZET Giriş: Bu çalışmanın amacı radikal prostatektomi spesmenlerindeki vasküler büyüme faktörü (VEGF), ECadherin ve Bim ekspresyonlarını değerlendirmek ve prognoz üzerine etkisini araştırmaktır. Gereç ve Yöntem: Radikal prostatektomi uygulanan 66 hastanın (51 hasta pT2, 13 hasta pT3, 2 hasta pT4) spesmenleri VEGF, E-Cadherin ve Bim antikorları ile boyandı. VEGF, E-Cadherin ve Bim immünoreaktivite sonuçlarının Gleason skoru ve biyokimyasal nüks ile olan ilişkileri araştırıldı. İmmünohistokimyasal ve klinik verilere göre istatistiksel analiz yapıldı. Bulgular: Hastalar Gleason skoruna (Gleason score <7 and Gleason ≥7) ve biyokimyasal nükse (Prostat spesifik antijen (PSA) >0,2 ng/ml) göre gruplara ayrıldı. Gruplar arasında VEGF, E-Cadherin ve Bim ekspresyonlarında anlamlı fark olmamasına rağmen, biyokimyasal nüks saptanan hastalarda VEGF ekspresyonu %59,74 ve biyokimyasal nüks saptanmayan hastalarda %44,47 bulundu (p=0,058). Spearman korelasyon testi uygulandığında, VEGF ve E-Cadherin arasında anlamlı bir ilişki tespit edildi (p=0,05). Sonuç: Tedaviye karar aşamasında yüksek riskli hasta grubunun belirlenmesinde kullanılabilecek biyobelirteçe henüz sahip değiliz. Düşüncemiz daha büyük sayılı çalışmalarda bu biyobelirteçlerin araştırılması ve immünohistokimyasal değerlendirmede imaj analiz yönteminin kullanılmasıdır. Anahtar sözcükler: Prostat kanseri, VEGF, E-Cadherin, Bim PROGNOSTIC VALUE OF IMMUNOHISTOCHEMICAL EXPRESSION OF VEGF, ECADHERIN AND BIM IN RADICAL PROSTATECTOMY SPECIMENS ABSTRACT Objective: The aim of this study was to evaluate the expressions of vascular endothelial growth factor (VEGF), E-Cadherin and Bim in radical prostatectomy specimens and to assess their prognostic value. Materials and Methods: Sixty-six radical prostatectomy specimens from prostate cancer (51 stage pT2, 13 pT3, 2 pT4) were stained using VEGF, E-cadherin and Bim antibody. The correlations of VEGF, E-Cadherin and Bim immunoreactivity levels with Gleason scores and biochemical recurrence were examined. A statistical analysis was then performed according to the immunohistochemical and clinical data. Results: Patients were grouped according to the Gleason score (Gleason score <7 and Gleason ≥7) and biochemical recurrence (Prostate specific antigen (PSA)>0.2 ng/ml). Although there were insignificant differences in the expressions of VEGF, E-Cadherin and Bim in these groups, the expressions of VEGF were 59.74% in patients with biochemical recurrence and 44.47% in patients without biochemical recurrence (p=0,058). In a Spearman correlation test, there was a significant correlation between expressions of VEGF and E-Cadherin (p=0.05). Conclusion: We currently have no useful biomarker for the early identification of high risk patients and for deciding on treatment. These biomarkers should be studied in larger series of patients and immunohistochemical staining could be examined with quantitative image analysis method. Keywords: Prostate cancer, VEGF, E-Cadherin, Bim İletişim Bilgileri: Dr. Asıf Yıldırım SB İstanbul Göztepe Eğitim ve Araştırma Hastanesi, 1. Üroloji, İstanbul, Türkiye e-mail: asifkad@superonline.com 203 Marmara Medical Journal 2009;22(3);000-000 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEGF’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri ve hücre-dışı matriks yıkımından sorumlu olan matriks metalloproteazların, ürokinazın, doku tipi plasminojen aktivatörlerinin salınımını da uyarır. Böylelikle invazyon ve metastazı da kolaylaştırır9. GİRİŞ Prostat kanseri erkeklerde en sık görülen ve insidansı yaş ile artan bir hastalıktır. Avrupa’da erkek kanserlerinin %11’ini ve erkekler arasında kanser ölümlerinin %9’unu oluşturmaktadır1. Prostat spesifik antijen’in (PSA) tarama amaçlı kullanılmasından sonra organa sınırlı prostat kanseri insidansında belirgin bir artış görülmüştür2,3. Prostat kanserlerinin büyük çoğunluğu oldukça yavaş seyirlidir ve oldukça büyük bir kısmı hastanın yaşamına tehdit oluşturmaz, fakat hızla ilerleme gösterip hastanın sağlığına ve yaşamına ciddi tehdit oluşturabilecek olanları da ayırt etmek gereklidir. Organa sınırlı prostat kanseri tedavi alternatiflerinden olan radikal prostatektomi sırasında lenf nodu pozitifliği veya postoperatif erken ve geç dönemde rekürrens görülebilmektedir. Preoperatif PSA, transrektal ultrasonografibiyopsi Gleason skoru, parmakla rektal muayene kullanarak hazırlanan nomogramlar ve bunlara patolojik Gleason skoru, cerrahi sınır tutulumu, ekstraprostatik yayılım, kapsüler ve seminal vezikül invazyon gibi histopatolojik bulgular ile hastalığın klinik progresyonunun önceden belirlenmesini amaçlanmaktadır3-5. Patolojik Gleason skoru progresyonu belirlemede en kuvvetli prognostik faktördür6. Henüz patolojik Gleason skorundan daha iyi prognostik bilgi veren parametre bulunmamasına rağmen, birçok yeni biyobelirteçin prognostik önemi araştırılma aşamasındadır. Prostat kanserinde prognostik faktör olarak kullanılması gündemde olan p53, p27, p21, insülin benzeri büyüme faktörü (IGF), androjen reseptör durumu ve mikrodamar dansitesi yakın zamanda bu konuda araştırılan biyobelirteçlerin en önemlilerindendir6. E-Cadherin epitelyal hücrelerdeki önemli adezyon molekülüdür ve hücreler arasındaki moleküler bağlantıyı, yapışma kavşaklarında fermuara benzer yapılar oluşturarak sağlarlar. Tümör hücrelerinde E-Cadherin ekspresyonunun azaldığı ve epitel hücrelerinin göç kabiliyetlerinin arttığı belirlenmiştir. Böylece, E-Cadherin’in invaziv özelliğe karşı koruyucu olduğu sonucuna varılmıştır6. Apoptozisi tetikleyen stres faktörlerinin kaspaz aktivasyonu yoluyla hücre ölümünde Bcl-2 proteinleri önemli rol oynamaktadır. Bcl-2 proteinleri, mitokondri dış zarının geçirgenliğini değiştirmek suretiyle etki göstermektedir. Bcl-2 ailesindeki üç alt gruptan biri olan ‘BH3-only’ Bcl-2 ailesinde Bad, Bik, Hrk, Noxa, Bid, Bmf, p53 upregulated modifier of apoptosis (PUMA) ve Bim yer alır10-12. Bu çalışmada amaç, radikal prostatektomi uygulanmış hastaların doku örneklerinde VEGF, E-Cadherin, ve Bim biyobelirteçlerini immünohistokimyasal yöntemlerle değerlendirmek ve prostat kanserinin prognozu üzerine öngörü değerlerini ortaya koymaktır. GEREÇ-YÖNTEM Hastane Etik Kurulundan onay alındıktan sonra S.B. İstanbul Göztepe Eğitim ve Araştırma Hastanesi 1.Üroloji Kliniği’nde 2002–2007 tarihleri arasında klinik organa sınırlı prostat kanseri tanısı ile radikal prostatektomi operasyonu uygulanmış ve günümüze kadar takiplerine düzenli olarak gelmiş olan 66 hastanın patoloji örnekleri çalışmaya alınmıştır (onay tarihi: 26.09.2007, karar no: 39/A). Olguların yaş, preoperatif ve postoperatif prostat spesifik antijen (PSA), klinik ve patolojik evre, transrektal ultrasonografi-prostat biyopsi ve radikal prostatektomi Gleason skoru, tümör çapı, Vasküler endotelyal büyüme faktörü (VEGF) endotel hücrelerinin proliferasyonunu, migrasyonunu ve diferansiyasyonunu sağlamaktadır7,8. Ayrıca, VEGF muhtemel temel anjiyojenik faktör olmanın yanında, VEGF’e maruz kalan damarlarda, endotel hücreleri arasında fenestrasyon, veziküler organeller ve transsellüler aralık oluşumuna olanak sağlayarak damar geçirgenliğini arttırır 204 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri sinir, kapsül ve seminal vezikül tutulumu, ekstrakapsüler uzanım (ekstraprostatik yayılım), cerrahi sınır pozitifliği, lenf nodu metastazı, biyokimyasal rekürrens, klinik progresyon verileri değerlendirildi (Tablo I). Hastaların klinik ve patolojik evrelemesi için TNM evreleme sistemi (2002) kullanıldı5. Hastalarda izlem sırasında ölçülebilen PSA değerinin 0,2 ng/ml ve üzerinde olması biyokimyasal rekürrens, kemik sintigrafisi veya diğer görüntüleme yöntemleri ile metastaz saptanması progresyon olarak değerlendirildi3,5. Patoloji örnekleri tek bir patoloji uzmanı tarafından önceki patoloji sonucu bilinmeksizin tekrar değerlendirildi. Bu 66 olguya ait patoloji örneklerinin hematoksilineosin boyalı kesitleri incelenerek, olgulara ait bloklar arasından her bir olgu için tümörü en iyi örnekleyen, immünohistokimyasal çalışması için uygun yeterlilikte doku bulunduran, 66 parafin blok çalışma için seçildi. Çalışmaya seçilen bloklardaki doku örnekleri tümöral ve nontümöral alanları birlikte içermekteydi. Seçilen her parafin bloğa VEGF, E-Cadherin ve Bim boyaları immünohistokimyasal olarak uygulandı. Tablo I. Hastaların klinik ve histopatolojik özellikleri. <4 4,1-10 10,1-20 >20 <7 ≥7 T1 T2 T2 T3 T4 Yok Var Yok Var Yok Var Yok Var Yok Var Yok Var Yok Var Preoperatif PSA (ng/ml) Gleason skoru Klinik evre Patolojik evre Kapsüler invazyon Cerrahi sınır tutulumu Ekstraprostatik yayılım Seminal vezikül invazyonu Perinöral invazyon Vasküler invazyon Lenf nodu metastazı 205 n 6 25 23 12 47 19 29 37 51 13 2 42 24 42 24 55 11 57 9 20 46 61 5 61 5 (%) 9 38 35 18 71 29 44 56 77 20 3 64 36 64 36 83 17 86 14 33 67 92 8 92 8 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri gözlemlemek için AEC kromojen sistemi (AEC Substrate system, Thermo Fisher Scientific Anatomical Pathology, CA USA) kullanıldı. Yirmi mikrolitre AEC kromojen, 1 ml AEC substrat ile karıştırıldıktan sonra kesitlere 10 dakika süre ile uygulandı. Daha sonra kesitler distile su ile yıkanıp zıt boya olarak 1,5 dakika hematoksilen ile boyandı. Su bazlı kapama maddesi damlatılarak kesitler kapatıldı. İmmünhistokimyasal boyama işlemleri: Seçilen parafin bloklardan elde edilen 5 mikrometre kalınlıktaki kesitler, önceden poly-L-Lysin ile kaplanmış lamlara alındı. Kesitler bir gece önce 57 C º’lik sıcaklıkta etüvde bekletildi. Deparafinizasyon işlemi için etüvden alınan kesitler 30 dakika süresince 3 ayrı şale ile ksilolden geçirildi. Daha sonra derecesi azalan alkollerden 20 dakikada geçirilen kesitler distile su ile yıkandı. Antijen retrieval amacıyla plastik taşıyıcıya alınan kesitler, kesit yüzeyini örtecek şekilde pH6 sitrat buffer solusyonu içine yerleştirildi. Üç kez 5’er dakikalık sürelerle toplam 15 dakika mikrodalga fırında şoklandı. Oda sıcaklığında 10 dakika bekletildikten sonra kesitler distile su ile yıkandı. Dokuların etrafı hidrofobik kalem ile çizildi ve kesitler PBS (phosphate buffered saline) ile yıkandı. Dokudaki endojen peroksidaz aktivitesini ortadan kaldırmak amacıyla, kesitlerin üzerine hidrojen peroksidin %0,3’lük çözeltisi damlatılarak 15 dakika bekletildi. Kesitler tekrar PBS ile yıkandı. Nonspesifik bağlanmaları engellemek amacıyla kesitler üzerine Ultra V Block Nonspesific Blocking Reagent (Lab Vision Corporation, CA, USA ) 10 dakika uygulandı. Ardından VEGF (Epitope Spesific Rabbit Antibody, Thermo Fisher Scientific Anatomical Pathology, CA USA), E-Cadherin (Epitope Spesific Rabbit Antibody, Thermo Fisher Scientific Anatomical Pathology, CA USA), BIM/BOD (bcl-2-related Ovarian Death Gene) Ab-1 (Rabbit polyclonal antibody, Thermo Fisher Scientific Anatomical Pathology, CA USA) damlatılıp 60 dakika bekletildi. Dört ayrı PBS banyosunda 10 dakika yıkandı. Sekonder antikor olarak Biotinylated Goat AntiPolyvalent (Lab Vision Corporation, CA USA) uygulandı ve 15 dakika bekletildi. Kesitler tekrar 4 ayrı PBS banyosunda yıkandı ve kesitlerin üzerine immün reaksiyonu gözlemlemek için işaretleyici (label) olarak Streptavidin Peroxidase (Lab Vision Corporation, 47790 CA, USA) damlatılarak 15 dakika beklendi. PBS ile yıkanan kesitlerin üzerine immün reaksiyonu İmmunreaktivitenin değerlendirilmesi Bu çalışmada pozitif kontrol için çevre malign olmayan prostat dokusu dikkate alındı. VEGF, E-Cadherin, Bim immünreaktivitesi sitoplazmik boyanmanın varlığında pozitif kabul edildi. Boyanma yaygınlık ve boyanma şiddeti açısından değerlendirildi. VEGF boyanma şiddetinin değerlendirilmesinde sitoplazmik boyanma dikkate alındı. Boyanma yok ise (-), hafif boyanma (+), orta derecede boyanma (++), kuvvetli boyanma (+++) ve VEGF boyanma yaygınlığı boyanma yok (-), %0-%25 (+), %25-%50 (++) ve %50’nin üstünde (+++) kabul edildi. ECadherin ile boyanmanın değerlendirilmesinde ise membranöz boyanma dikkate alındı. Boyanma yok (-), hafif boyanma (+), orta derecede boyanma (++) ve kuvvetli boyanma (+++) kabul edildi. Bim ile boyanmanın değerlendirilmesinde nükleer boyanma dikkate alındı ve boyanmanın olmaması (-), %10’un altında boyanma (+), %10-%25 boyanma (++) ve %25’in üstünde boyanma (+++) olarak değerlendirildi (Resim 1)13. İstatistiksel değerlendirme: İstatistiksel analizler NCSS 2007 paket programı ile yapılmıştır. Verilerin değerlendirilmesinde tanımlayıcı istatistiksel metotların (ortalama, standart sapma) yanı sıra ikili grupların karşılaştırmasında bağımsız t testi, nitel verilerin karşılaştırmalarında ki-kare testi kullanılmıştır. Biyobelirteçlerin (VEGF, ECadherin ve Bim) immünohistokimyasal çalışmalarından elde edilen verilerin birbirleri ile ilişkilerinin değerlendirilmesinde Spearman korelasyon testi kullanıldı. 206 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri Sonuçlar, anlamlılık değerlendirilmiştir. p<0,05 düzeyinde BULGULAR Tüm olgular Gleason skoru <7 ve Gleason skoru ≥7 olmak üzere gruplandırıldı. Bu iki grubun operasyon öncesi verileri, patoloji örnekleri ve izlem sonuçları karşılaştırıldı. Yaş, tümör çapı, izlem süresi ve prostatik intraepitelyal neoplazi (PİN) dışında kalan tüm veriler arasında istatistiksel olarak anlamlı fark saptandı (p<0.05) (Tablo II ve III). Yapılan immünhistokimyasal boyama sonucunda VEGF ve E-Cadherin ekspresyon yüzdeleri karşılaştırıldığında her iki grup arasında istatistiksel olarak anlamlı fark görülmedi (p>0.05) (Tablo II). Resim 1: Boyanma dereceleri: I-VEGF (sitoplazmik) kuvvetli [A] ve orta [B], II-E – Cadherin (membranöz) orta [A] ve kuvvetli [B], III-Bim (nükleer) %10-25(++) [A] ve %25’in üstünde (+++) boyanma [B]. Tablo II. Hastaların radikal prostatektomi Gleason skoruna göre dağılımları. Gleason <7 Gleason ≥7 t p Yaş (yıl) 63,02±5,89 64,63±6,46 -0,98 0,332 Preoperatif PSA (ng/ml) 10,37±8,42 25,86±17,69 -3,66 0,001 TRUS-biyopsi Gleason skoru 5,68±0,75 6,11±1,05 -1,84 0,07 Tümör çapı (cm) 1,46±0,89 1,85±0,81 -1,67 0,1 İzlem süresi (ay) 40,89±12,26 39,21±15,62 0,47 0,643 VEGF en şiddetlinin %si 44,79±26,88 58,95±34,46 -1,78 0,079 E-cadherin en şiddetlinin %si 47,98±30,67 38,16±29,78 1,19 0,239 E-cadherin en yaygın şiddetin %si 72,02±12,58 69,47±13,93 0,72 0,473 207 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri PSA rekürrensi gözlenen hasta sayısı 19 (%29) iken rekürrens saptanmayan hasta sayısı 47 (%71) idi. Rekürrens durumuna göre hastaların verileri karşılaştırıldığında, tümör çapı, histopatolojik Gleason skoru ve preoperative PSA arasında istatistiksel olarak anlamlı fark saptandı (p<0.05). Yapılan immünhistokimyasal boyama sonucunda VEGF en şiddetli ekspresyonunun PSA rekürrensi olanlarda %59,74 ve rekürrens saptanmayanlarda %44,47 olduğu gözlendi (p=0,058). E-Cadherin en şiddetli düzeyde ekspresyonu rekürrens olanlarda %45,21 ve rekürrens olmayanlarda %45,27 (p=0,98) iken, E-Cadherin en yaygın şiddetinde ekspresyonunun rekürrens olanlarda %72,2 ve rekürrens olmayanlarda %68,9 olduğu izlendi. Tüm veriler karşılaştırıldığında, aradaki farkın istatistiksel olarak anlamlı olmadığı belirlendi (p=0,354) (Tablo IV). ve %42,1 (p=0,29), E-Cadherin kuvvetli immünreaktivite gösterme oranlarının %91,5 ve %78,9 (p=0,157), E-Cadherin kuvvetli yaygınlık immünreaktivite gösterme oranlarının %46,8 ve %26,3 olduğu gözlendi (p=0,303). Ayrıca Gleason 7’nin altında olanlarda Bim kuvvetli immünreaktivite gösterme oranı %12,8 iken Gleason 7 ve üzerinde olanlarda bu oran %21,1 idi (p=0,657). Tüm biyobelirteçler arasında istatistiksel olarak anlamlı fark saptanmadı (Tablo VI). PSA rekürrensi gözlenen olgularda immünhistokimyasal boyamalar yapıldıktan sonra sırası ile VEGF kuvvetli immünreaktivite gösterme oranı %52,6 (p=0,161), VEGF kuvvetli yaygınlık immünreaktivite gösterme oranı %47,4 (p=0,099), E-Cadherin kuvvetli immünreaktivite gösterme oranı %78,9 (p=0,157), E-Cadherin kuvvetli yaygınlık immünreaktivite gösterme oranı %36,8 (p=0,896) ve Bim kuvvetli immünreaktivite gösterme oranı %31,6 idi (p=0,895). Hiçbir biyobelirteçin kuvvetli immünreaktivite gösterme oranlarında istatistiksel olarak anlamlı fark saptanmadı (Tablo VII). PSA rekürrensi gözlenen ile rekürrens gözlenmeyen olguların operasyon öncesi verilerinin, patoloji örneklerinin ve izlem sonuçlarının kendi aralarında karşılaştırılması Tablo V’te gösterilmiştir. Klinik evre, PİN, sağkalım ve hastalığa bağlı mortalite dışında tüm veriler arasında istatistiksel olarak anlamlı fark saptandı (p<0.05) Gleason skoru ve rekürrens gelişimi açısından biyobelirteçlerde istatistiksel anlam görülmemesine karşın immünohistokimyasal çalışmalarından elde edilen verilerin birbirleri ile ilişkilerini belirlemede Spearman korelasyon testi kullanıldığında E-Cadherin ve VEGF arasında istatistiksel anlamda korelasyon saptandı (p=0,05) (Tablo VIII ve IX). Patoloji örneklerinin biyobelirteçlerle boyanma şiddetleri Gleason skoru ve PSA rekürrensine göre değerlendirildi. Gleason skoru <7 ve ≥7 olarak ayrılan her iki grupta sırası ile VEGF kuvvetli immünreaktivite gösterme oranlarının %27,7 ve %47,4 (p=0,196), VEGF kuvvetli yaygınlık immünreaktivite gösterme oranlarının %21,3 208 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri Tablo III. Histopatolojik Gleason skoruna göre prognostik faktörlerin karşılaştırması. Preoperatif PSA (ng/ml) TRUS-biyopsi Klinik evre Patolojik evre Kapsüler invazyon Cerrahi sınır tutulumu Ekstraprostatik yayılım Seminal vezikül invazyonu Perinöral invazyon Vasküler invazyonu PİN Lenf nodu metastazı Klinik progresyon Yaşam Ölüm nedeni PSA rekürrensi <4 4,1-10 10,1-20 >20 <7 ≥7 T1 T2 T2 T3 T4 Yok Var Yok Var Yok Var Yok Var Yok Var Yok Var Yok Var Yok Var Yok Var Eksitus Hayatta Prostat kanseri Diğer Yok Var Gleason <7 %12,8 %48,9 %27,7 %10,6 %91,5 %8,5 %53,2 %46,8 %91,5 %8,5 %0,0 35 %74,5 12 %25,5 35 %74,5 12 %25,5 44 %93,6 3 %6,4 45 %95,7 2 %4,3 19 %40,4 28 %59,6 46 %97,9 1 %2,1 28 %59,6 19 %40,4 46 %97,9 1 %2,1 47 %100,0 0 %0,0 2 %4,3 45 %95,7 0 %0,0 2 %4,3 42 %89,4 5 %10,6 6 23 13 5 43 4 25 22 43 4 0 2 10 7 11 8 4 15 8 9 2 7 12 7 12 11 8 12 7 1 18 15 4 14 5 15 4 17 2 4 15 2 2 5 14 Gleason ≥7 %0,0 %10,5 %52,6 %36,8 %57,9 %42,1 %21,1 %78,9 %42,1 %47,4 %10,5 %36,8 %63,2 %36,8 %63,2 %55,6 %44,4 %63,2 %36,8 %5,3 %94,7 %78,9 %21,1 %73,7 %26,3 %78,9 %21,1 %89,5 %10,5 %21,1 %78,9 %10,5 %10,6 %26,3 %73,7 χ²:15,2 p=0,002 χ²:10,2 p=0,001 χ²:5,67 p=0,017 χ²:19,5 p=0,0001 χ²:8,27 p=0,004 χ²:8,27 p=0,004 χ²:13,4 p=0,0001 χ²:12,2 p=0,0001 χ²:7,92 p=0,005 χ²:6,92 p=0,009 χ²:1,16 p=0,281 χ²:6,92 p=0,009 χ²:5,1 p=0,024 χ²:4,61 p=0,032 χ²:5,47 p=0,019 χ²:26,2 p=0,0001 Tablo IV. Hastaların PSA rekürrensi durumuna göre dağılımları. Yaş (yıl) Preoperatif PSA (ng/ml) TRUS-biyopsi Gleason skoru Histopatolojik Gleason skoru Tümör çapı (cm) İzlem süresi (ay) VEGF en şiddetlinin %si E-cadherin en şiddetlinin %si E-cadherin en yaygın şiddetin %si Nüks (-) 63,13±5,98 10,29±8,32 5,7±0,75 5,89±0,56 1,41±0,84 41,43±13,18 44,47±28,54 45,21±31,79 72,23±12,46 209 Nüks (+) 64,37±6,32 26,05±17,62 6,05±1,08 7,42±1,35 1,96±0,86 37,89±13,29 59,74±30,48 45±27,94 68,95±14,1 t -0,75 -3,74 -1,51 -4,78 -2,41 0,98 -1,93 0,03 0,93 p 0,455 0,001 0,136 0,0001 0,019 0,329 0,058 0,98 0,354 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri Tablo V. PSA rekürrensi olup olmamasına göre diğer prognostik faktörlerin karşılaştırması. <4 4,1-10 Preoperatif PSA (ng/ml) 10,1-20 >20 <7 TRUS-biyopsi skoru ≥7 T1 Klinik evre T2 T2 Patolojik evre T3 T4 <7 Patolojik Gleason skoru ≥7 Yok Kapsül invazyonu Var Yok Cerrahi sınır tutulumu Var Yok Ekstra prostatik yayılım Var Yok Seminal vezikül invazyonu Var Yok Perinöral invazyon Var Yok Vasküler invazyon Var Yok PİN Var Yok Lenf nodu metastazı Var Yok Klinik progresyon Var Eksitus Yaşam Hayatta Prostat kanseri Ölüm nedeni Diğer Rekürrens (-) % 6 12,8 24 51,1 12 25,5 5 10,6 42 89,4 5 10,6 24 51,1 23 48,9 43 91,5 4 8,5 0,0 42 89,4 5 10,6 34 72,3 13 27,7 34 72,3 13 27,7 44 93,6 3 6,4 46 97,9 1 2,1 18 38,3 29 61,7 46 97,9 1 2,1 27 57,4 20 42,6 47 100,0 0,0 47 100,0 0,0 3 6,4 44 93,6 0 0,0 3 6,4 210 Rekürrens (+) % 0,0 1 5,3 11 57,9 7 36,8 12 63,2 7 36,8 5 26,3 14 73,7 8 42,1 9 47,4 2 10,5 5 26,3 14 73,7 8 42,1 11 57,9 8 42,1 11 57,9 10 55,6 8 44,4 11 57,9 8 42,1 2 10,5 17 89,5 15 78,9 4 21,1 15 78,9 4 21,1 14 73,7 5 26,3 17 89,5 2 10,5 3 15,8 16 84,2 2 10,5 1 5,3 χ²:19 p=0,0001 χ²:6,24 p=0,012 χ²:3,36 p=0,067 χ²:19,5 p=0,0001 χ²:26,23 p=0,0001 χ²:5,34 p=0,021 χ²:5,34 p=0,021 χ²:13,4 p=0,0001 χ²:18,3 p=0,0001 χ²:4,94 p=0,026 χ²:6,92 p=0,009 χ²:2,7 p=0,1 χ²:13,3 p=0,0001 χ²:5,1 p=0,024 χ²:1,44 p=0,229 χ²:6,32 p=0,097 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri Tablo VI. Hastaların Gleason skoruna göre biyobelirteçlerin dağılımları. Biyobelirteç VEGF şiddet VEGF yaygınlık E-Cadherin en şiddetli E-Cadherin en yaygın şiddet Bim Şiddet (-) (+) (++) (+++) (-) (+) (++) (+++) (++) (+++) (+) (++) (+++) (-) (+) (++) (+++) Gleason <7 n % 5 10,6 9 19,1 20 42,6 13 27,7 5 10,6 8 17,0 24 51,1 10 21,3 4 8,5 43 91,5 6 12,8 19 40,4 22 46,8 21 44,7 18 38,3 2 4,3 6 12,8 Gleason ≥7 n % 2 10,5 5 26,3 3 15,8 9 47,4 2 10,5 1 5,3 8 42,1 8 42,1 4 21,1 15 78,9 3 15,8 11 57,9 5 26,3 9 47,4 6 31,6 0 0,0 4 21,1 χ²:4,68 p=0,196 χ²:3,74 p=0,29 χ²:1,99 p=0,157 χ²:2,38 p=0,303 χ²:1,61 p=0,657 Tablo VII. Hastalarda PSA rekürrensi saptanmasına göre biyobelirteçlerin dağılımları. Biyobelirteç VEGF Şiddet VEGF yaygınlık E-Cadherin en şiddetli E-Cadherin en yaygın şiddet Bim Şiddet (-) (+) (++) (+++) (-) (+) (++) (+++) (++) (+++) (+) (++) (+++) (-) (+) (++) (+++) Rekürrens (-) n % 6 12,8 10 21,3 19 40,4 12 25,5 6 12,8 8 17,0 24 51,1 9 19,1 4 8,5 43 91,5 6 12,8 21 44,7 20 42,6 22 46,8 19 40,4 2 4,3 4 8,5 211 Rekürrens (+) n % 1 5,3 4 21,1 4 21,1 10 52,6 1 5,3 1 5,3 8 42,1 9 47,4 4 21,1 15 78,9 3 15,8 9 47,4 7 36,8 8 42,1 5 26,3 0 0,0 6 31,6 χ²:5,15 p=0,161 χ²:6,26 p=0,099 χ²:1,99 p=0,157 χ²:0,22 p=0,896 χ²:6,36 p=0,095 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri Tablo VIII. E-Cadherin ve VEGF’ nin Spearman korelasyon testi ile karşılaştırılması Gleason skoru E-Cadherin en şiddetli E-Cadherin en yaygın şiddetli Bim VEGF şiddet 0,128 0,307 0,243 0,05 0,161 0,196 0,185 0,136 r p r p r p r p VEGF yaygınlık 0,176 0,156 0,093 0,457 0,099 0,429 0,137 0,273 Tablo IX. E-Cadherin ve VEGF’ nin Spearman korelasyon testi ile karşılaştırılması Gleason skoru VEGF Şiddet VEGF yaygınlık r p r p r p E-Cadherin en şiddetli -0,04 0,749 0,243 0,05 0,093 0,457 E-Cadherin en yaygın şiddetli -0,067 0,591 0,161 0,196 0,099 0,429 Bim 0,037 0,769 0,185 0,136 0,137 0,273 Yapılan çalışmalarda, bu prognostik faktörlere ilave olarak insülin benzeri büyüme faktörü (IGF), androjen reseptör durumu, mikrodamar dansitesi, Ki-67 indeksi ve p53 geni mutasyonu gibi tümöre ait histopatolojik biyobelirteçlerin de hastalık progresyonun önceden belirlenmesinde faydalı olabileceği belirtilmektedir6. TARTIŞMA Prostat kanserinin biyolojik heterojenitesi, her hastaya özgü bir karar almayı gerektirmektedir. Prognoz hakkında bilgi sahibi olmak, prostat kanseri tedavi alternatifleri arasında seçim yapmak ve daha sonraki dönemdeki riskleri belirlemek açısından önemlidir. Prognostik parametreler ve bunlar üzerinden oluşturulan birçok nomogram yardımıyla patolojik evrenin ve izlemde olası senaryoların önceden 3-5 belirlenmesi amaçlanmıştır . Buna rağmen, literatürde organa sınırlı prostat kanseri tanısı ile radikal prostatektomi uygulanan hastaların %30-45’inde, bizim çalışmamızda % 17’sinde patolojik olarak ekstraprostatik yayılım gözlenmiştir14. Bu nedenle, kısa sürede progresyon gösterecek yüksek riskli hasta gruplarının önceden belirlenmesi amacıyla birçok yeni patolojik faktörün prognostik önemi araştırılmaktadır. Ancak bu faktörlerden hiçbirisi henüz Gleason skorunun ötesinde prognostik bilgi verememektedir3-6. Prostat kanseri progresyonu, anjiyogenez sayesinde yeterli vaskülarizasyon ve bölgesel lenf nodu, kemik metastazları ile ilişkilidir. Tümör hücreleri anjiyojenik faktörleri salgılayarak neovaskularizasyonu uyarır. Bu faktörler olmadan tümör hücreleri besin maddeleri ve oksijeni yeterli düzeyde alamayacağı için 2-3 mm’den fazla büyüyemeyecektir. Anjiyojenik faktörlerden biri olan VEGF’in hipoksi ile indüklenerek sentezinin artması neovaskularizasyona giden yolda çok önemli bir adımdır15. Artmış VEGF ekspresyonu progresyon ile yakından ilişkilidir. VEGF anjiyogenezi stimüle eder ve mikrodamar yoğunluğunu arttırır; böylece 212 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri tümör dokusunun büyümesi kolaylaşır16. VEGF prostat kanseri progresyonunu, nöroendokrin farklılaşmış prostat kanser hücrelerinden salıverilerek anjiyogenezi uyarması ve mikrodamar yoğunluğunu arttırmasının yanı sıra doğrudan prostat kanser hücrelerinde büyümeyi uyardığı düşünülmektedir6,16. Tüm bu verilere rağmen güncel literatürde prostat kanseri ile VEGF ekspresyonu arasındaki ilişki tartışmalıdır. Daha önceki çalışmalarda, prostat kanser epitelyumunda normal ve benign prostat dokusuna göre VEGF ekspresyonunun daha yüksek olduğu gösterilmiştir15,16. Bu bulguların aksine, Wu ve ark. çalışmalarında malign ve benign prostatik epitelyum arasında VEGF immünreaktivitesi açısından fark saptamamışlardır17. Joseph ve Isaacs, androjen tarafından kontrol edilen VEGF’in prostat kanseri büyümesinde etkili olduğunu bildirirken, West ve ark. tümör epitelindeki artmış VEGF immünreaktivitesinin daha yüksek serum PSA seviyesi ile anlamlı oranda ilişkisinin olduğunu göstermişlerdir18,19. E-Cadherin epitelyal hücrelerdeki önemli adezyon molekülüdür. E- Cadherin bağımlı adezyonun kaybı, birçok kanser için kötü progresyon belirtisidir. E-Cadherin ekspresyonundaki azalmanın uzak metastaz, rekürrens ve azalmış toplam sağkalım ile ilişkili olduğunu bildiren çalışmalar 25,26 . vardır Çok yeni bir çalışmada; klinik önemli prostat kanserinde E-Cadherin anormal şekilde boyanmış iken klinik önemsiz prostat kanserinde E-Cadherin boyanmasının normal olduğunu göstermişlerdir26. İmmunohistokimyasal E-Cadherin seviyesi üzerine yapılan bir çalışmada malign prostat dokusunda %50 oranında azalma ve hatta bazı örneklerde E-Cadherin’in tamamen ortadan kalktığı, benign prostat dokusunun ise homojen kuvvetli pozitif boyandığını belirlemişlerdir27. Yine 89 prostat kanseri olgusunda düşük E-Cadherin immunohistokimyasal ekspresyonu saptananlarda yüksek ekspresyon saptananlara oranla daha kısa sağkalım süresi gözlenmiştir27,28. Van Oort ve ark. prostat kanserinde E-Cadherin ekspresyonu ile progresyon ve sağkalım arasındaki ilişkiyi incelemişlerdir. Altmış beş radikal prostatektomi olgusunun histopatoloji örneği incelendiğinde; 36 olguda (%55,4) normal ECadherin boyanması izlenirken E-Cadherin ile normal boyananlarda 5 yıllık sağkalımın %79,2, boyanmayanlarda ise bu oranın % 26,8 olduğu saptadılar (p<0.05)29. Musial ve ark. E-Cadherin anormal boyanmasının sağkalım süresi üzerinde negatif etkisi olan bağımsız bir prediktör faktör olduğunu bulmuşlardır30. De Marzo ve ark. azalmış ECadherin seviyesinin RP sonrası Gleason skoru yüksekliği (p=0.003) ve patolojik evre (p=0.008) ile ilişkili olduğunu, ve ECadherin’in progresyonu belirleyen bir biyobelirteç olarak kullanılabileceğini 31 bildirdiler . Aynı zamanda E-Cadherin’in metastazla ilişkisi de çalışmalarda bildirilmiştir. Yapılan bir çalışmada Junior ve ark. 28 kemik metastazlı hastada prostat kanseri ve kemik örneklerini histopatolojik olarak incelediklerinde kemik metastazı olan örneklerde E-Cadherin ekspresyonundaki Birçok hayvan çalışmasında VEGF aşırı ekspresyonu ile lenfanjiyogenez ve lenf metastazı arasındaki ilişki tespit edilmiştir. VEGF lenf damarlarında hiperplazi ve yeni lenf damarı oluşumundan sorumlu tutulmuştur20,21. Ancak, prostat kanseri için bu bulgular da tartışmalıdır. Tsurusaki ve ark. VEGF ve lenf nodu metastazı arasında anlamlı bir ilişki olduğunu bildirirken, Zeng ve ark. tam tersine anlamlı bir ilişki saptamamışlardır22,23. Yine, VEGF ekspresyonu ve yüksek Gleason skoruna sahip tümörler arasındaki ilişki bazı çalışmalarda bildirilmiş, bazılarında bildirilmemiştir17-23. Ferer ve arkadaşları iyi diferansiye tümörlerde daha yoğun VEGF boyanmasını göstermişlerdir24. Bizim çalışmamızda bu belirsizliği destekler şekilde; Gleason skoru ve rekürrens verilerine göre gruplandırıldıktan sonra kendi aralarında immünohistokimyasal boyanma özelliklerine göre karşılaştırıldıklarında VEGF ile boyanma oranları Gleason skoru yüksek ve rekürrens gözlenen grupta daha fazla bulunmasına rağmen aradaki fark istatistiksel olarak anlamlı değildi. 213 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri kaybın %86 olduğunu, primer prostat kanserinde ise %83 oranında E-Cadherin ekspresyonunun normal olduğunu gösterdiler32. Bizim çalışmamızda E-Cadherin ile anormal boyanma oranları Gleason skoru yüksek ve rekürrens saptanan grupta daha fazla bulunmasına rağmen aradaki fark istatistiksel olarak anlamlı değildi. sırasında kanser hücrelerinin androjensiz ortamda kalmaları yoğun Bcl-2 ekspresyonuyla hücreleri apoptozisten korumakta ve androjen duyarlı hücreler hormona dirençli hale gelmektedir40. Bim’in prostat kanserindeki prognostik değerini araştıran çalışma sayısı sınırlıdır33. Bim’in klinik önemi tedavide hedef olarak kullanılabilmesindendir. Yapılan bir çalışmada invivo ortamda 1,3-thiazolidione (DBPT) maddesinin Bim fosforilasyonu yaparak Bcl-2 ekspresyonu fazla olan hücrelerde de apoptozisi, indüklediği ve VEGF ekspresyonunu azalttığı 41 gösterilmiştir . Bizim çalışmamızda yine Bim seviyesinin de radikal prostatektomi sonrası prognozu belirlemede Gleason skoru ile kıyaslandığında ek bir katkı sağlamadığı görüldü. Birçok tümörde anti-apoptotik proteinler, yüksek düzeyde pro-apoptotik moleküllerle beraber bulunur. İlk bakışta çelişkili görünen bu durum 30’dan fazla proteini içeren ve bir kısmı apoptozisi indükleyen bir kısmı da baskılayan Bcl-2 ailesi ile açıklanabilir. Bcl-2 ailesinden biri olan Bim’in apoptozisi uyarıcı etkisi olduğu düşünülmektedir. Tümör baskılayıcı bir protein olan p53 ile antiapoptotik etkili Bcl-2 kompleks oluşturur. Böylece proapoptotik etkisi olan Bim antiapoptotik proteinden ayrılır ve aktivasyon gerçekleşir33. Çalışmamızda boyanma özellikleri açısından gruplar arasında istatistiksel anlamlı fark olmamasına rağmen biyobelirteçler arasında spearman korelasyon testi ile karşılaştırma yapıldığında bazı alanlarda kendi aralarında anlamlı ilişki saptandı. E-Cadherin en şiddetli boyanması ile VEGF şiddeti arasında istatistiksel olarak anlamlı ilişki bulundu. Howard ve ark. E-Cadherin’in azalmış ve Bcl-2’nin aşırı ekspresyonunun dolaşımdaki tümör hücreleri ile ilişkili olduğunu göstermişlerdir34. Hipoksi ile indüklenen streste Bcl-2 aşırı ekspresyonu ve anjiogenezin uyarılması, tümör hücrelerinin apoptozisten kaçarak yaşam sürelerini uzatır. Yapılan invivo bir çalışmada hipoksi koşulları oluşturulduktan sonra Bcl-2 aşırı ekspresyonu olan prostat kanser hücrelerinde daha yüksek oranda VEGF olduğunu göstermişlerdir35. Sinha ve ark. hormonal tedavi alan lokal ileri veya metastatik prostat kanserli hastalarda Bcl-2 aşırı ekspresyonunun sağkalım ile ters ilişkili olduğunu göstermişlerdir36. Diğer bir çalışmada da Bcl-2 ve mikrodamar yoğunluğunun prostat kanserli hastalardaki ölümü gösteren bağımsız prediktör faktörler olduğu bulunmuştur37. Bcl-2 aşırı ekspresyonunun erken evre tümörlerde de görülebilmesine karşın ileri evre prostat kanserlerinde ekspresyon artışına çok daha sık saptanır38. Ayrıca McDonnell ve ark. androjen bağımsız olan prostat kanserinde yaygın ve yüksek oranda Bcl-2 boyanması gösterilmiştir. Bcl-2 ekspresyonunun prostat kanserinin androjen bağımlı halden androjen bağımsız duruma geçişi ile ilişkisi olduğu gösterilmiştir39. Androjen ablasyonu tedavisi Son yıllarda bizim çalışmamızda da olduğu gibi prostat kanserinin anjiyogenez, proliferasyon ve genetik özelliklerinin beraber değerlendirildiği çalışmalar planlanarak pratik uygulamada kullanılabilecek veriler elde edilmek istenmektedir. Ancak bu çalışmalarda da farklı sonuçlar elde edilmektedir. Çalışmamızın sonucunda VEGF ve ECadherin’in biri birleri ile ilişkili olmalarına rağmen Gleason skoru ve PSA rekürrensi ile ilişkisi bulunamamıştır. Böylece, VEGF, ECadherin ve Bim biyobelirteçlerinin radikal prostatektomi sonrası progresyonu belirlemede ek bir katkı sağlamadığını düşünmekteyiz. Bu nedenle patolojik evre ve Gleason skoru gibi histopatolojik parametreler bugün için en iyi prognostik belirteçlerdir. İmmünohistokimyasal boyamanın değerlendirilmesinde bilgisayar programı ile yapılan imaj analiz yöntemi günümüzde yaygın olarak kullanılmaktadır. Bu yöntemde 214 Marmara Medical Journal 2009;22(3);000-000 Erem Kaan Başok, ark. Radikal prostatektomi spesmenlerindeki VEG’in, E-Cadherin’in ve Bim’in immünohistokimyasal ekspresyonlarının prognostik değeri immünohistokimyasal reaksiyon sonucu oluşan boyamanın derecesi objektif olarak bilgisayar programı ile değerlendirilmektedir42. İmaj analiz bilgisayar programının pahalı olması ve hastanemizde olmamasından dolayı imaj analiz yöntemi çalışmamızda kullanılmadı. Gleason skoru halen en önemli prognostik faktör olmasına rağmen, klinik lokalize prostat kanseri tanısı ile radikal prostatektomi operasyonu olan hastaların yaklaşık üçte birinde gözlenen rekürrensi, önceden belirlememize yetmemektedir. Bu nedenle hastanın prognozunu önceden ortaya koyacak yeni biyobelirteçlere ihtiyaç vardır. Radikal prostatektomi patoloji örneklerinin Gleason skorları literatürdeki verilerle uyumlu olarak daha agresif tümörlerle ve daha kötü progresyon ile uyumlu idi. Preoperatif ve postoperatif veriler de incelendiğinde nüks gözlenen hastalarda daha olumsuz veriler saptandı. Biyobelirteçlerin (VEGF, ECadherin ve Bim) immünohistokimyasal çalışmalarla elde edilen verileri değerlendirildiğinde; gruplar arasında istatistiksel anlamda fark olmamasına karşın özellikle VEGF’de anlamlılığa yakın derecede fark gözlendi. Bu durum olgu sayısının az olması ile açıklanabilir. Daha çok sayıda olgu ile immünohistokimyasal boyanın ‘İmaj Analiz’ yöntemi ile değerlendirilmesinin biyobelirteçlerin prognostik değerini daha net ortaya koyacağı düşüncesindeyiz. KAYNAKLAR 1. 2. 3. 4. 5. Bray F, Sankila R, Ferlay J, Parkin DM. Estimates of cancer incidence and mortality in Europe in 1995. Eur J Cancer 2002; 38: 99-166. 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Clin Cancer Res 2000; 6: 2295-2308. 216 ORIGINAL RESEARCH CYTOGENETIC ANALYSIS IN INFERTILE MALES WITH SPERM ANOMALIES Ebru Önalan Etem, Hüseyin Yüce, Deniz Erol, Şükriye Derya Deveci, Gülay Güleç Ceylan, Halit Elyas Fırat Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji ve Genetik, Elazığ, Türkiye ABSTRACT Objective: In a half of all childless partnerships the infertility is caused by the male. Chromosomal abnormalities are more prevalent in infertile men compared to fertile men. Chromosomal abnormalities are known to be associated with spermatogenetic failure. The present study investigates the frequency and types of major chromosomal abnormalities by using standard cytogenetic methods in infertile men with sperm anomalies. Materials and Methods: A total of 214 infertile males (138 were azoospermic, 76 oligospermic) were studied for the cytogenetic evaluation. Chromosomal analysis of peripheral blood lymphocytes was performed according to standard protocols. Results: Of the 214 infertile men, 24 (11.2%) had a chromosomal abnormality in the form of a Klinefelter syndrome/variant (16/24; 7.5%), XYY syndrome (1/24; 0.5%), XX male syndrome (1/24; 0.5%), 45,X, mar(Y) (1/24; 0.5%), 46,XX, inv(Y)(p11q11) (1/24; 0.5%), 46,XY, der(1)t(1;5)(p33;qter) (1/24; 0.5%), 46,XY, t(15;15) (1/24; 0.5%) or 46,XY,t(14;21) (1/24; 0.5%). Conclusions: This study shows that chromosomal anomalies were found in 11.2% of the infertile men. The potential risk of transmitting these genetic disorders to offspring provides a rationale for screening infertile men prior to intra cytoplasmic sperm injection (ICSI). In addition, genetic screening and counseling should be offered to infertile patients routinely. Keywords: Infertility, Chromosome, Cytogenetic, Azoospermia, Oligoospermia SPERM ANOMALİSİ GÖSTEREN ERKEKLERDE SİTOGENETİK ANALİZLER ÖZET Amaç: Erkek infertilitesi çocuk sahibi olamayan çiftlerin yarısından sorumludur. Kromozomal abnormaliteler fertil erkeklerle karşılaştırıldığında infertil erkeklerde daha sıktır. Kromozomal anomalilerin spermotogenezde başarısızlığa neden olarak erkek infertilitesine neden olduğu bilinmektedir. Çalışmada sperm anomalisi gösteren infertil erkeklerde major kromozomal anomalilerin tipleri ve sıklığının araştırılması amaçlanmıştır. Gereç ve Yöntem: Toplam 214 (138 azospermik, 76 oligospermik) infertil erkek bireye sitogenetik inceleme yapıldı. Tüm hastaların periferik kan lenfositlerinin kromozomal analizleri sdandart yöntemlere göre yapıldı. Bulgular: Toplam 214 infertil erkeğin 24 (%11.2)’ünde klinifelter sendromu (16/24; %7.5), XYY sendromu (1/24; %0.5), XX erkek sendromu (1/24; %0.5), 45,X, mar (Y) (1/24; %0.5), 46,XX, inv(Y)(p11q11) (1/24; %0.5), 46,XY, der(1)t(1;5)(p33;qter) (1/24; %0.5), 46,XY, t(15;15) (1/24; %0.5) ve 46,XY,t(14;21) (1/24; %0.5) kromozomal anomalileri tespit edildi. Sonuçlar: Bu çalışma infertil erkeklerde kromozomal anomalilerin sıklığı %11.2 olduğunu göstermektedir. Bu genetik bozuklukların yeni nesillere aktarılmasındaki potansiyel risk infertil erkeklerin ICSI’dan önce taranması için bir sebep oluşturmaktadır. Ayrıca, genetik tarama ve danışmanın infertil hastalara rutin olarak yapılması gerekmektedir. Anahtar Kelimeler: İnfertilite, Kromozom,Sitogenetik, Azospermi, Oligospermi İletişim Bilgileri: Ebru Önalan Etem, M.D. Fırat Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji ve Genetik, Elazığ, Türkiye e-mail: ebruetem@gmail.com 217 Marmara Medical Journal 2009;22(3);000-000 Marmara Medical Journal 2009;22(3);000-000 Ebru Önalan Etem, et al. Cytogenetic analysis in infertile males with sperm anomalies causes of azoospermia and oligozoospermia among infertile Turkish men. The prevalence and types of cytogenetic abnormalities were analyzed using standard cytogenetic methods. INTRODUCTION Infertility affects about 15 per cent of all couples attempting pregnancy, with a malefactor identified in approximately half of the cases1. Numerous factors contribute to male infertility, genetic factors including chromosomal abnormalities and genetic syndromes cause gene defects, and other factors include the hormonal milieu, genital infections, chemical and physical agents. infection, varicose, spermatic duct obstruction, antisperm antibodies, cryptorchidism, retrograde ejaculation, systemic diseases, testicular cancer, testicular trauma, etc. Male infertility can also be caused by a variety of other factors, apart from these, and in 30–40% of male infertile cases that are referred to as idiopathic, a genetic abnormality is suspected2. MATERIAL AND METHOD Patients The study was conducted retrospectively according to the records of the patients referred to the Department of Medical Biology and Genetics at Fırat University. From January 1998 to August 2009, 214 infertile Turkish men were enrolled in the study. Among these 214 men, 138 had azoospermia and 76 had oligoospermia. The average age was 33, ranging from 18 to 51 years. A complete semen analysis was performed in all patients according to the guidelines of the World Health Organization (1999). Semen was collected by masturbation at the laboratory after 3–5 days of sexual abstinence, and examined as soon as liquefied. Cases were classified into groups using sperm counts. Azoospermia was defined as the total absence of sperm cells and oligozoospermia was defined as a sperm cell count of less than 5×106 cells/ml in seminal liquid. The examination of male infertility should be complex, including a detailed history, physical examination, semen analysis, hormonal screening, and chromosomal and genetic analysis of somatic cells3. The fact that chromosomal abnormalities are increased in infertile men relative to fertile men is well established. Most studies report a wide range of frequencies of chromosomal abnormalities, from 2.2% to 10.3%, due to different cytogenetic procedures and case inclusion criteria1. In cases of non-obstructive azoospermia, there is a 15% risk of an associated chromosome abnormality including both aneuploidies and structural rearrangements4. Nevertheless, all of them point to an increasing percentage of chromosomal abnormalities concomitant with a decreasing sperm count. In addition, the nature of chromosomal abnormalities differs depending on whether a patient has oligoospermia or azoospermia. An early mutational event in the stem cells could produce structural rearrangements (translocations, inversions, or small deletions) during spermatogenesis, persisting through mitotic and meiotic divisions to the mature sperm stage1. Cytogenetic Analysis Chromosomal analysis of peripheral blood lymphocytes was performed according to standard protocols5. Peripheral blood (2 ml) was collected in heparin vacutainers (Becton Dickinson, USA). For every subject whole blood (0.5 ml) cultures were set up in 5 ml Roswell Park Memorial Institute (RPMI) 1640 media (GIBCO BRL, USA) containing 15% fetal calf serum (Biological Industries, KBH, Israel), antibiotic mixture and phytohemagglutinin P (DIFCO Lab, USA) for 72 h. Chromosome preparations were obtained from lymphocyte cultures and analyzed after Giemsa-Trypsin-Giemsa (GTG) -banding6. In all cases, at least 20 metaphases were analyzed. In cases of suspected mosaicism, 50 cells were counted. The karyotypes were interpreted using the recommendation of the International System for Human Cytogenetic Nomenclature7. The main purpose of this study was the investigation of the possible cytogenetic 218 Marmara Medical Journal 2009;22(3);000-000 Ebru Önalan Etem, et al. Cytogenetic analysis in infertile males with sperm anomalies frequency of 11.2%. The frequency of abnormalities was 13.7% in the cases of azoospermia, and 6.5% in men with oligoospermia (Table III). Numerical and structural chromosomal abnormalities, which were detected in 24 patients, are summarized in Table I. Patients with Klinefelter Syndrome had azoospermia. The frequency of autosomal chromosome anomalies detected in the present study was 1.9% (4/214 patients), one patient who was a t(15;15) carrier was azoospermic (138/1), other translocation carriers were oligoospermic (3/76). There was a statistically significant difference in the autosomal translocation carrier between oligoospermic and azoopermic infertile male goups (p<0.05). Fluorescence in situ hybrizidation (FISH) Analysis FISH for 46,XX and 47,XYY male patients, to exclude mosaicism was performed on lymphocyte metaphase spreads using the Y centromere-specific DNA probe: CEP Y alpha-satellite spectrum orange (32-130025) (Vysis, Illinois, USA). It was also performed using the X centromere and sex-determining region Y gene (SRY)-specific DNA probe: LSI SRY Yp11.3 spectrum orange/CEP X spectrum green (32-191007) (Vysis, Illinois, USA). The Y centromere-specific DNA single color probe was labeled with biotin and detected by FITC avidin. The chromosomal DNA was then counterstained with propidium iodide (PI). FISH using the locus specific identifier (LSI) SRY/CEP X DNA dual color probe was performed following the manufacturer’s instructions (VYSIS) and chromosomal DNA was counterstained with 4’,6-diamidino-2-phenylindole (DAPI). Statistical analysis was carried out by the Statistical Package for Social Science for Windows, version 11.0 (SPSS; Chicago, IL, USA). The unpaired t-test, Mann-Whitney Utest and Chi-squared test were used. P < 0.05 was considered significant. Polymorphisms were detected in 25 (11,6%) patients (Table II). Abnormality in the heterochromatin region of the Y chromosome and inv(9) was the most frequently identified polymorphism in 10/214 (4.6%) and 9/214 (4.2%) in infertile men, respectively. For patients with a 47,XYY karyotype mosaicism was shown by FISH in Y chromosome content: 47,XYY (76%)/46,XY (24%). Hybridization with the Y centromereSRY specific DNA dual probe in 46,XX male patients was positive, ruling out any hidden mosaicism with a Y-bearing cell line in peripheral blood cells. RESULTS Among the 214 infertile men studied, 24 showed some kind of constitutional chromosomal abnormality corresponding to a Table I: Chromosomal abnormalities in azoospermic and oligospermic men. Chromosomal Finding 46,XX male Numerical 47,XXY 47,XYY 45,X, mar(Y) Structural Inversion 46,XX,inv(Y)(p11q11) Translocation 46,XY,der(1)t(1;5)(p33;qter) 46,XY,t(15;15) 46,XY,t(14;21) 46,XY,t(9;15)(q21.1:q11.1) Total (n=214) 0.5 % (1) 7.5 % (16) 0.5 % (1) 0.5 % (1) 0.5 % (1) 0.5 % (1) 0.5 % (1) 0.5 % (1) 0.5% (1) 11.2 % (24) 219 Marmara Medical Journal 2009;22(3);000-000 Ebru Önalan Etem, et al. Cytogenetic analysis in infertile males with sperm anomalies Table II: Chromosomal polymorphisms Chromosomal polymorphism Frequency 46,XY, inv(9) 46,XY, 9qh+ 46,XY,16qh+ 46,XY,Yqh(-) 46,XY, Yqh(+) 4.2 % (9) 0.5 % (1) 0.5 % (1) 1.8 % (4) 4.6 % (10) 11.6 % (25) Table III: The cytogenetic findings in the literature Author Vincert et al (8) Zuffardi and Tiepolo et al (9) Chandley et al (10) Clementini et al (11) Tuerlings et al (12) Nakamura et al (13) Yoshida et al (14) Koulischer et al (15) Salahshourifar et al (16) Şamlı et al (17) Mohammed et al (18) Akgul et al (19) Vutyavanic et al (20) Nagvankar et al (21) Balkan et al (22) Our study Total Patient Number/chromosomal Azoospermia Oligospermia CytogeneticAbnormalities Frequencies Structural Numerical frequencies 2651/204 111/792 (14%) - 93/1859 (5%) - 2542/215 2372/51 2078/42 1792/62 1790/225 1007/65 - - - - - - - - - - - 819/52 289/23 179/18 130/6 88/9 80/9 214/24 17.905/1174 131 40 175 33 18 6 36 6 24 64 126 24 41 6 27 7.69% 8.6% 2.1% 2.02% 3.45% 12.5% 6.5% - 1000/33 874/136 73 106/444 (23.8%) 42/383 (10.9%) - 11/175 (6.2%) 10/436 (2.2%) - 15/86 (17.4%) - 5/73 (6.85%) - 6/42 (%14.3) - 3/46 (%6.5) - 19/138 (13.7%) 299/1885 (15.8%) 5/76 (6.5%) 127/2665 (4.7%) 220 20 116 13 39 3 20 2 16 2 4 5 4 2 7 6 18 305(1.7%) 802 (4.4%) 3.3% 15.5% 5.9% 7.9% 11.74% 4,6% 10.2% 11.2% 11.2% 6.5 % Marmara Medical Journal 2009;22(3);000-000 Ebru Önalan Etem, et al. Cytogenetic analysis in infertile males with sperm anomalies SRY gene is translocated on the X chromosome. The SRY gene is present in this case (SRY+ XX males), but such patients have azoospermia. DISCUSSION Male infertility may be caused by a variety of chromosomal abnormalities, including abnormalities in the sex chromosomes and autosomes, gain or loss of an entire single chromosome resulting in aneuploidy or structural abnormalities, as in balanced and unbalanced tranlocations. The frequency of an abnormal karyotype in this study was within the previously reported range of 2.2–14.3% for infertile men (Table III) 8-22. The incidence of cytogenetic abnormalities has been estimated at 5.8% in infertile men and only 0.5% in the normal population1. Possible explanations for the divergent frequencies of chromosomal abnormalities in infertile males may be populational, geographical, environmental or genetic heterogeneities, methodological detection problems (expecially for minor chromosomal abnormalities), patients’ inclusion criteria or various chromosomal abnormality frequencies including the absence or the presence of chromosomal polymorphisms. A relationship between balanced autosomal translocations and infertility has been reported among severely oligozoospermic and azoospermic men26-29. In our study, reciprocal translocations t(1;5), t(9;15) and t(14;21) were seen in oligoospermic males and t(15;15) was seen in one azoospermic male. The exact mechanism by which chromosomal anomalies induce infertility is not clear. Sperm karyotyping studies of 37 reciprocal translocation heterozygotes have shown that 19–77% of spermatozoa are unbalanced29. When delineating the genetic basis of male infertility, it is very important to emphasize that about 50% of all translocations found in sterile men involved an acrocentric chromosome, which implicates their role in male hypofertility30. Guichaoua et al. emphasized the correlation between the involvement of the acrocentric chromosome in infertile translocation carriers and the severity of the spermatogenic defect31. It has been hypothesized that balanced translocations interfere with normal chromosome pairing and segregation at meiosis I, thus providing a potential for formation of unbalanced gametes and subsequent unbalanced abnormal offspring32. Another hypothesis is based on the assumption of potential autosomal genes involved in male gametogenesis that might be deregulated by chromosome breakpoints. The relation between chromosomal breakpoints and male infertility has been investigated, and it has been found that there is a nonrandom distribution of breakpoints associated with infertility32,33. The presence of abnormally distributed chromatin interferes with meiotic division and thus reduces sperm production. Spermatozoa bearing abnormal chromosomes may cause abnormal embryonic development, which can in turn, cause early pregnancy loss26. Further research in this direction is necessary. Vincent et al., reported that autosomal structural anomalies (Table III) were encountered primarily in severe In the total population, aneuploidy (10.8%) was the most frequent chromosome-related cause among infertile males. The most common abnormality was Klinefelter’s syndrome (16/24), which was in agreement with a previous study by Foresta et al.23. Men with a 47,XYY karyotype are generally fertile, but they are seen more frequently in infertile populations. There have been a few reports of 47,XYY syndromes in azoospermic males as in our study23,24. Since many 47,XYY men have normal semen parameters, the severe oligoospermia observed in these men may indicate more perturbations during meiotic pairing, subsequent loss of germ cells and the production of aneuploid sperm24. The clinical features of male sex reversal syndrome patients are azoospermia associated with one or more of the following: abnormal external genitalia, gynecomastia, short stature, and pelvic cyst25. Males with a 46, XX karyotype were mainly found in the group of azoospermic males (Table I). Most XX males originate from a crossing over between Xp and Yp during paternal meiosis, so that the 221 Marmara Medical Journal 2009;22(3);000-000 Ebru Önalan Etem, et al. Cytogenetic analysis in infertile males with sperm anomalies oligoospermia8. Our study confirms this finding because of detected three autosomal translocation in oligospermic males. syndrome (KALIG1) and A-kinase anchor proteins (AKAP82) etc., but cytogenetic examinations should be made prior to molecular studies42. Common cytogenetic polymorphisms detected by G banding are considered as heteromorphisms and include heterochromatin regions of chromosomes 1, 9, 16 and Y34. The role of chromosome heteromorphisms in infertility has been studied previously35-37. Şahin et al., reported that the chromosomal polymorphisms frequency is 7.9% in infertile males. We found that the polymorphism frequency is 11.6%38. The occurrence of long Y (Yqh+) and short Y (Yqh-) in our study was 4,6% and 1,8% respectively. These frequencies were remarkably close to the frequencies of 4.4 and 1.6 per cent reported in literature39,40. Inv (9) is commonly seen in normal humans and the frequency has been estimated to be 1 to 3% in the general population41. As the frequency of inv(9) (4.2%) in infertile men was similar to that in the general population, these inversions definitely have role in the development of infertility especially in cases with de novo inversions. We advise parent’s karyotyping for inv(9) carriers because the determination of unbalanced chromosomal content is important for the detection of de novo or familial inv(9) carriers.The contribution of variants to alter the carrier’s fertility is still a controversial topic and further studies are required to understand this. In conclusion, cytogenetic investigations in infertile men undoubtedly confirm previous reports in spite of differences in the incidence of chromosomal abnormalities in literature and they point to a risk of chromosomal abnormalities that is 20-fold higher in patients with severe oligoospermia or nonobstructive azoospermia, than in the general population. Consequently, high resolution chromosome preparations are crucial for a group with low sperm quality to detect complicated rearrangements. Therefore, genetic testing and counselling can provide support for patterns of inheritance, recurrence risks, natural history of diseases, increased risk for birth defects and genetic testing options when planning a pregnancy in patients with abnormal karyotypes. These patients can be advised as regards in vitro fertilization (IVF) and genetic screening of embryos in relation to assisted reproductive techniques. Acknowledgement The authors express their heartfelt gratitude to the staff and members of the Department of Medical Biology and Genetic for their assistance in various experiments, other organizational aspects of this study and Firat University Hospital. We are grateful to all volunteers who participated in this study. Among numerous etiologic factors, genetic factors play a primary role in male infertility. 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Cytogenet Cell Genet 1986;43:154–160. 31. Guichaoua MR, Quack B, Speed RM, Noel B, Chandley AC, Luciani JM. Infertility in human males with autosomal translocations: meiotic study of a 14;22 Robertsonian translocation. Hum Genet 1990;86: 162– 166. 32. Zhou-Cun A, Yang Y, Zhang SZ, Zhang W, Lin L. Chromosomal abnormality and Y chromosome microdeletion in Chinese patients with azoospermia or severe oligozoospermia. Yi Chuan Xue Bao 2006; 33:111–116. 33. Bache I, Van Assche E, Cingoz S, et al. An excess of chromosome 1 breakpoints in male infertility. Eur J Med Genet. 2004;12:993–1000. 34. Brothman AR, Schneider NR, Saikevych I, et al. Cytogenetics Resource Committee, College of American Pathologists/American College of Medical Genetics. Cytogenetic heteromorphisms: Survey results and reporting practices of Giemsa-band regions that we have pondered for years. Arch Pathol Lab Med 2006;130:947–949. 35. Cortés-Gutiérrez EI, Cerda-Flores RM, DávilaRodríguez MI, Hernández-Herrera R, Vargas-Villarreal J, Leal-Garza CH. Chromosomal abnormalities and polymorphisms in Mexican infertile men. Arch Androl 2004;50:261–265. 36. Nakamura Y, Kitamura M, Nishimura K, et al. Chromosomal variants among 1790 infertile men. Int J Urol 2001;8:49–52. 37. Yakin K, Balaban B, Urman B. Is there a possible correlation between chromosomal variants and spermatogenesis? Int J Urol 2005;12:984–989. 38. Sahin FI, Yilmaz Z, Yuregir OO, Bulakbasi T, Ozer O, Zeyneloglu HB. Chromosome heteromorphisms: an impact on infertility. J Assist Reprod Genet 2008; 25:191–195. 223 Marmara Medical Journal 2009;22(3);000-000 Ebru Önalan Etem, et al. Cytogenetic analysis in infertile males with sperm anomalies 39. Abramsson L, Beckman G, Duchek M, Nordenson I. Chromosomal aberrations and male infertility. J Urol 1982; 128 : 52-53. 40. Retief AE, Van Zyl JA, Menkveld R, Fox MR, Kotze GM, Brusnicky J. Chromosome studies in 496 infertile males with a sperm count below 10 million/ml. Hum Genet 1984; 66 : 162-164. 41. Rao BV, Kerketta L, Korgaonkar S, Ghosh K Pericentric inversion of chromosome 9[inv(9)(p12q13)]: Its association with genetic diseases. Indian J Hum Genet 2006; 12: 129-132. 42. Shah K, Sivapalan G, Gibbons N, Tempest H, Griffin DK. The genetic basis of infertility. Reproduction 2003;126:13-25. 224 ORIGINAL RESEARCH THE COMPARISON OF THE RECOVERY CHARACTERISTICS OF EITHER SPINAL OR EPIDURAL ANESTHESIA WITH PRILOCAINE FOR KNEE ARTHROSCOPY Hatice Türe, Binnaz Ay, Zeynep Eti, F. Yılmaz Göğüş Marmara Üniversitesi, Tip Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, İstanbul, Türkiye ABSTRACT Objective: The aim of our study was to compare the recovery characteristics of single-dose spinal and epidural anesthesia with 2 % prilocaine for outpatient knee arthroscopy. Methods: Forty patients were randomly assigned to receive either spinal or epidural anesthesia with prilocaine. Maximum sensory level, recovery of the motor and sensorial functions, time to ambulate, time to voiding, side effects, and medications used for the treatment were recorded. After 48 hours, the patients were questioned for pain and need for analgesia, their opinion about the quality of anesthesia, side effects such as nausea, vomiting, pruritus, backache, post-dural puncture headache (PDPH), urinary difficulties and transient neurological symptoms (TNS). Results: Maximum sensory level was similar in the groups. The time from injection to recovery of motor and sensory functions and ambulation time were significantly shorter in the epidural group than the spinal group (p < 0.05). The percentage of patients who required additional analgesic was 9 versus 6% in spinal versus epidural groups. One of the patients in the spinal group had PDPH postoperatively. None of the patients had postoperative nausea, vomiting, pruritus, backache, urinary difficulties or TNS. Conclusion: Relatively fast recovery time make epidural anesthesia with prilocaine a good alternative for outpatient knee arthroscopy. Keywords: Spinal, Epidural, Prilocaine DİZ ARTROSKOPİSİ CERRAHİSİNDE PRİLOKAİN İLE YAPILAN SPİNAL VE EPİDURAL ANESTEZİNİN DERLENME ÖZELLİKLERİNİN KARŞILAŞTIRILMASI ÖZET Amaç: Bu çalışma spinal ve epidural anestezide kullanılan tek doz prilokainin hastanın derlenme özellikleri üzerine etkisinin karşılaştırılması amacıyla planlanmıştır. Yöntem: Diz artroskopisi geçirecek 40 hasta, 2 mL %2 prilokain ile spinal ya da 15-20 mL %2 prilokain ile epidural anestezi yapılacak şekilde randomize olarak 2 gruba ayrıldı. Hastaların maksimum duyu bloğu seviyeleri, motor ve duyu bloğunun geri dönüş süreleri, ayağa kalkma zamanları, ilk idrar yapma zamanları, yan etkiler ve tedavisinde kullanılan ilaçlar kaydedildiler. Hastalar taburcu olduktan 48 saat sonra, telefonla aranarak, operasyon sonrası ağrıları, analjezik ihtiyaçları, anestezi yönteminden memnuniyetleri, bulantı, kusma, kaşıntı, belağrısı, dura delinmesine bağlı baş ağrısı, idrar yaparken zorlanma ve geçici nörolojik semptomlar açısından sorgulandılar. Bulgular: Maksimum duyu bloğu seviyesi her iki grupta benzerdi. İlacın verilişinden duyu ve motor bloğun sonlanmasına dek geçen süre ve ayağa kalkma süresi epidural anestezi sonrası belirgin kısa bulundu (p < 0.05). Ek analjezik kullanan hasta sayısı, spinal anestezi sonrası %9 iken, epidural anestezi sonrası %6 idi. Spinal gruptan bir hastada dura delinmesine bağlı başağrısı görüldü. Hastaların hiçbirinde postoperatif bulantı, kusma, kaşıntı, bel ağrısı, idrar zorluğu ya da gecici norolojik semptomlar görülmedi. Hasta memnuniyeti açısından gruplar arasında fark bulunmadı. Sonuç: Hızlı derlenme süresi nedeniyle prilokain ile epidural anestezi diz artroskopilerinde iyi bir alternatiftir. Anahtar Kelimeler: Spinal, Epidural, Prilokain İletişim Bilgileri: Hatice Türe, M.D. Yeditepe Üniversitesi Tıp Fakültesi, Anesteziyoloji ve Reanimasyon A.D., İstanbul, Türkiye e-mail: htcture@yahoo.com Hatice Türe was recently affiliated to Yeditepe University School of Medicine, Department of Anesthesiology and Reanimation, İstanbul, Türkiye. 225 Marmara Medical Journal 2009;22(3);000-000 Marmara Medical Journal 2009;22(3);000-000 Hatice Türe, et al. The comparison of the recovery characteristics of either spinal or epidural anesthesia with prilocaine for knee arthroscopy (allergy, coagulopathy, infection, or neurologic disease) and pregnant patients were excluded from the study. Each patient’s age, sex, weight, and height were recorded prospectively by the anesthesiologist on a preprinted form. All patients in both groups received 500 mL of intravenous isotonic saline before anesthesia was induced. Monitors for routine measurements were as follows: pulse oximeter, electrocardiogram, and noninvasive systolic/diastolic and mean arterial blood pressure. INTRODUCTION Knee arthroscopy is a common procedure of orthopaedic surgery. Recent advances in this surgical practice combined with “fasttracking” anesthetic techniques have increased the number of patients discharged on an outpatient basis after knee arthroscopic surgery1. Complete recovery from sensory and motor blocks is a critical discharge criterion for outpatient surgery. Any deficiencies in these areas limit the patient’s ability to be self-caring after discharge2,3. The discharge time, that is, the length of time from the end of surgery until the patient is discharged, is greatly affected by the anesthetic technique used4. The ideal anesthetic technique for outpatient surgery should be easily administered, should have a quick onset of action and should provide good surgical conditions with a rapid recovery and minimal side effects5. There are several published studies citing advantages of different anesthetic techniques2,3,5-13. Spinal or epidural anesthesia may provide many of these advantages; however, comparison of the single dose spinal and epidural techniques each with a short acting local anesthetic, prilocaine, is not well documented. We performed a prospective, randomized clinical study to compare the recovery characteristics of single dose spinal and epidural anesthesia each with 2% prilocaine for outpatient knee arthroscopy. Spinal anesthesia (Group S) (n=20) was administered at the L4-5 intervertebral space using a 25-gauge pencil point spinal needle through the midline approach with the patient placed in the lateral decubitus position. After the free flow of cerebrospinal fluid was observed, 2 mL of prilocaine 2% (Citanest, AstraZenaca Ltd, Istanbul, TR) was injected. Patients were then immediately turned to the supine position. Epidural anesthesia (Group E) (n=20) was performed after cutaneous anesthesia with 1.5 mL of 2% lidocaine. An 18-gauge Tuohy epidural needle was introduced midline at the L4-5 intervertebral space, using a loss-of-resistance to saline technique with the patient placed in the lateral decubitus position and the operative knee dependent. If no blood or cerebrospinal fluid was aspirated, 15-20 mL of 2% prilocaine was given in 5-mL increments. Patients were immediately turned to supine position. MATERIAL AND METHOD Following the Institutional Ethics Committee approval and written informed patient consent, forty patients scheduled for knee arthroscopy (no prior medication, American Society of Anesthesiologists (ASA) score I-II, age between 20-60 years) were randomly assigned to receive either epidural or spinal anesthesia. This study was performed according to the recommendation for conduct of clinical research of the Declaration of Helsinki. Patients with respiratory or cardiac disease, diabetes, those receiving chronic analgesic therapy, those with contraindications to regional anesthesia Sensory block level was assessed with bilateral pinprick testing in the midclavicular line in all the patients. Motor block was assessed with modified Bromage score (0= full flexion of knee and ankles; 1= partial flexion of knees, full flexion of ankles; 2= inability to flex knees, partial flexion of ankles; 3= inability to flex knees and ankles). The maximum level of the sensory block and duration of surgery were recorded. All the patients were transferred to the postanesthesia care unit (PACU) after the operation and clinical observations were made by same investigators who were blinded to the groups. Side effects such as bradicardia (>30% decreases from baseline); hypotension (>30% 226 Marmara Medical Journal 2009;22(3);000-000 Hatice Türe, et al. The comparison of the recovery characteristics of either spinal or epidural anesthesia with prilocaine for knee arthroscopy decrease from baseline), drowsiness, nausea, vomiting, pruritus, shivering, pain, and medications used for the treatment were noted. Sensory and motor block levels were measured at 10-min intervals during the PACU period. Sensory block resolution occurred when the dermatomal level receded to S1. Motor recovery was defined as a Bromage score 0 and the ability to do a deep knee bend. When the patients’ vital signs were stable and sensory and motor blocks were resolved, they were transferred to their beds. RESULTS Demographic data were similar between the groups (Table I). Anesthesia was found to be satisfactory for surgical incision in all the patients. After the injection of prilocaine, maximum sensory level was similar and T9 (T7- T10) in group S, T10 (T6- T11) in group E (Table II). No differences were observed between the groups regarding the incidence of hypotension or the number of the patients requiring ephedrine. The maximum level of the sensory block was above the T12 dermatome in all the patients. The time from local anesthetic injection to recovery of motor function was significantly longer [119± 42 min] in group S compared to [85±10 min] in group E (p< 0.05). Prolonged recovery of the sensory block time (< S1) was also observed in group S [143±39 min] compared to group E (110±2 min, p< 0.05). Time to first urination was reported as 272±97 min in group S and 203±63 min in group E (p< 0.05). During the follow-up report, none of the patients noted voiding difficulty. Early postoperative side effects during the PACU period are shown in Table III. None of the patients noted hypotension, bradycardia, nausea, vomiting, pruritis, shivering, pain or respiratory depression and there were no major surgical or anesthetic complications (Table III). All the surgeons described their opinion about the anesthetic quality as good. Time to sensorial (< S1) and motor block resolution, time to first urination, time to ambulation were recorded. All times were defined as the time from injection of the drugs to the time to the sensorial or motor block resolution. Patients were asked to score the degree of pain themselves and to write down the respective times and severity on a follow-up form they were given after the surgery (Appendix). Patients were discharged with a prescription for paracetamol as required, up to six tablets a day. Forty-eight hours after discharge, the patients were contacted by telephone and questioned for the side effects, medication requirement, and their opinion about the quality of anesthesia (good, satisfactory or poor). The data collected, such as pain, nausea, vomiting, backache, post dural puncture headache (PDPH), urinary difficulties, transient neurological signs (TNS), need for analgesia, and patient satisfaction about the quality of anesthesia were recorded. TNS was defined as pain or dysesthesia in the buttocks, thighs or calves occurring within 24 hrs and resolving within 72 hrs. A power analysis indicated that a sample size of 18 patients per group was required to show a 30 min difference in discharge time among groups at a p value <0.05 with 80% power. A statistical analysis of the data recorded from the two groups was carried out with the Chisquare test, unpaired t-test and Mann Whitney-U test where appropriate. The number of patients who needed an additional analgesic during the first 48 hrs after surgery was lower in group E than in group S (p< 0.05). Postoperative pain relief was adequate with acetaminophen in these patients (Table II). The quality of anesthesia as determined by the patients was either satisfactory or good (Table II). None of the patients had symptoms of postoperative nausea, vomiting, pruritus, urinary difficulties, or TNS following discharge from the hospital. Only one patient in group S had postoperative mild PDPH which resolved within 2 days without treatment. 227 Marmara Medical Journal 2009;22(3);000-000 Hatice Türe, et al. The comparison of the recovery characteristics of either spinal or epidural anesthesia with prilocaine for knee arthroscopy Table I. Demographic data (mean ± SD). Spinal (n=20) Epidural (n=20) Age (yrs) 47 ± 14 47 ± 14 Weight (kg) 76 ± 10 76 ± 9 Height (cm) 168 ± 7 171 ± 11 Sex (male/female) 8/12 11/9 No significant difference was observed between the groups (p> 0.05). Table II. Duration of surgery and anesthetic characteristics (mean± SD) (min). Spinal(n=20) Epidural (n=20) Duration of surgery 38 ± 14 44 ± 12 Maximum sensory level T9 [T7- T10] T10 [T6- T11] Recovery of motor function (Bromage 0) 119 ± 42 85 ± 10* Recovery of sensation (<S1) 143 ± 39 110 ± 2* Time to ambulate 167± 14 123± 10* Time to void 272± 97 203± 63* Postoperative analgesic use (%) 9 (45%) 6 (10%)* *There were significant differences between the groups (p< 0.05). 228 Marmara Medical Journal 2009;22(3);000-000 Hatice Türe, et al. The comparison of the recovery characteristics of either spinal or epidural anesthesia with prilocaine for knee arthroscopy Appendix. Patient Questionnaire Please note down time 1. You feel pain when you get back home……………… 2. How much pain are you in (0: no pain, 1: mild pain, 2: moderate pain, 3: severe pain) 3. Please also note down if you have to take painkillers, how many and approximately at what time. 4. Please note down when you were able to void the first time after the surgery………… . 5. Do you have any of following side effects after your surgery: None Mild Moderate Severe Treatment /Time Nausea, Vomiting Pruritus Backache Headache Inable to void Transient neurological symptoms* * Transient neurological symptoms may be defined as pain or dysesthesia in your buttocks, thighs or calves occuring within 24 hrs. 6. Your satisfaction with the whole procedure ranging from 1 (poor), 2 (satisfactory) or 3 (good)……. You will be phoned forty-eight hours after discharge from hospital and you will be asked these questions. Any further comments you wish to make. We thank you for your time! 229 Marmara Medical Journal 2009;22(3);000-000 Hatice Türe, et al. The comparison of the recovery characteristics of either spinal or epidural anesthesia with prilocaine for knee arthroscopy for transurethral resection of the prostate in elderly patients and prilocaine appeared to be a safe local anesthetic for either method. Since patients undergoing knee arthroscopy are mostly younger patients than the patients scheduled for prostate resection, incremental dosing of local anesthetics to avoid their toxic and untoward effects is unlikely to be as important as in an elderly population. A younger population needs to be discharged and ready to work as soon as possible. Prilocaine, one of the short acting local anesthetics, is known as having lower incidence of transient neurological symptoms when applied intrathechally and is therefore recommended for use in surgical procedures of short duration18. Recovery of motor and sensorial functions was significantly prolonged after spinal anesthesia compared to epidural anesthesia as expected. DISCUSSION The main finding in this study is that, both single dose spinal and epidural anesthesia with 2% prilocaine provided satisfactory surgical and anesthetic conditions; However, epidural anesthesia provided faster recovery compared to spinal anesthesia following outpatient arthroscopic surgery. The optimum anesthetic technique for outpatient knee arthroscopy should provide rapid onset and recovery from anaesthesia. Complete recovery from sensory and motor block is of critical importance as discharge criteria in outpatient surgery, because it limits the ability of patients’ self-caring after discharge12. Some authors have pointed out that regional anesthesia provides rapid discharge times comparable to that of general anesthesia2,13. However, recent data suggest that both spinal and epidural anesthesia require longer discharge times than new short-acting general anesthetic drugs and opioids, propofol and sevoflurane4,12. Epidural anesthesia is advocated for outpatient surgery because of the minimal side effects and excellent patient acceptance14. There are also studies comparing the spinal technique with the epidural during outpatient surgery showing similar discharge times5,15. Local anesthetics were not standardized in some of the studies comparing spinal and epidural techniques5,10,16. Mulroy and colleagues have compared epidural 2chloroprocaine to procaine combined with fentanyl for spinal anesthesia16. Neal17 and Pollock5 have compared epidural 2chloroprocaine to lidocaine with fentanyl for spinal anesthesia. We compared recovery and discharge characteristics of spinal and epidural anesthesia with 2% prilocaine for ambulatory arthroscopic knee surgery, therefore this study gives important results about the behavior of the same drug used with two different regional anesthesia techniques. However, prilocaine has previously been scantily documented15,18. Reisli et al18 concluded that both continuous spinal and continuous epidural anesthesia were reliable Prilocaine is not a popular local anesthetic today in anesthesia practice, due to a wellknown side effect, methemoglobinemia. This side effect is usually of clinical importance with larger doses. The maximum prilocaine dose used in our study was 400 [20 mLx 20 mg/ml] mg, below the maximum recommended dose, and therefore this agent may be safely used for single dose epidural anesthesia in adult patients. However, care must be taken during repeated doses and continuous infusion for regional anesthesia. In clinical practice there are many choices of local anaesthetics with intermediate duration of action for outpatient regional anaesthesia such as lidocaine, prilocaine and mepivacaine. Although prilocaine is preferred, with less risk of neurotoxicity, it was recently suggested that intrathecal mepivacaine and prilocaine are less neurotoxic than highly concentrated lidocaine in a rat intrathecal model18. Our study was designed to search for an optimal central block type (spinal or epidural) in outpatients, not to document the recovery charactheristics or side effects of prilocaine. However, in clinical settings other local anesthestics may be preferable to prilocaine for short surgical procedures. 230 Marmara Medical Journal 2009;22(3);000-000 Hatice Türe, et al. The comparison of the recovery characteristics of either spinal or epidural anesthesia with prilocaine for knee arthroscopy A potential limitation of this finding is the sample size studied. In clinical settings, a recovery difference of 30 minutes is unlikely to be clinically significant, as institutional costs may not appear to be affected by such differences19,20. However, discharge from hospital is not the end of the recovery process, as far as the patient is concerned. The patients in whom the side effects extend to 24 hour postoperatively have less functional recovery. Probable complications following regional anesthesia include postoperative pain, backache, PDPH and TNS. None of the patients reported backache or TNS in this study. Only one patient in the spinal group had symptoms of mild PDPH in this study. The incidence of PDPH can be reduced to 1% or less in hospitalized patients through meticulous selection of patients, needles, and technique21. The use of a thinner spinal needle with a pencil-point tip design has the advantage of being associated with low incidence of PDPH21. TNS is another postoperative side effect of regional anaesthesia. Lidocaine, lithotomy position, knee arthroscopy and outpatient status have been implicated as risk factors for TNS22. In a recent study, the incidence of TNS using prilocaine for spinal anaesthesia has been reported as 4% and was not significantly different between the patients given prilocaine or lidocaine23. However, there were no reports of TNS in our study with prilocaine. Recent studies suggest that the frequency of TNS with a small dose of the agent is decreased; therefore we chose a relatively small dose of prilocaine to reduce the probability of TNS2,24. However, further studies are needed to determine the etiology and significance of TNS in such a practice with higher doses. Pain is one of the most important problems following the regional anesthesia after outpatient surgery. Local anesthetics with long duration of action are useful in an outpatient setting because of their prolonged analgesic effects. On the other hand, a longer duration of action may lead to prolonged ambulation and recovery times. We found that the percentage of patients who needed additional analgesic was 9% in the spinal group, and 6% in the epidural group with prilocaine. Postoperative pain relief was satisfactory with acetaminophen in these patients. These results were probably related to the relatively painless type of surgery chosen in our study. In conclusion, our study supports the hypothesis that epidural anesthesia with 2% prilocaine is suitable for outpatient knee arthroscopy due to its short-duration of action. Furthermore, both spinal and single dose epidural anesthesia provided satisfactory surgical, anesthetic conditions for surgeons and patients. Acknowlegement There has been no financial support for his study. REFERENCES 1. Jenkins K, Grady D, Wong J, Correa R, Armanious S, Chung F. Post-operative recovery: day surgery patients’preferences. Br J Anaesth 2001; 86: 272-274. 2. Ben David B, Levin H, Solomon E, Admoni H, Vaida S. 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Reisli R, Celik J, Tuncer S, Yosunkaya A, Otelcioglu S. Anaesthetic and haemodynamic effects of continuous spinal versus continuous epidural anaesthesia with prilocaine. Eur J Anaesthesiol. 2003; 20: 26-30. 19. Takenami T, Yagishita S, Nara Y, Hoka S. Intrathecal mepivacaine and prilocaine are less neurotoxic than lidocaine in a rat intrathecal model. Reg Anesth Pain Med 2004; 29: 446-453. 20. Lubarsky DA. Understanding cost analysis. Part I. A practitioners guide to cost behavior. J Clin Anesth 1995; 7: 519-521. 21. Halpern S, Preston R. Postdural puncture headache and spinal needle design. Metaanalyses. Anesthesiology 1994; 81:1376-1383. 22. Freedman J, Li De-Kun, Drasner K, Jaskela M, Larsen B, Wi S. Transient neurologic symptoms after spinal anesthesia. An epidemiologic study of 1.863 patients. Anesthesiology 1998; 89: 633-641. 23. Østgaard G, Hallaråker O, Ulveseth OK, Flaatten H. A randomised study of lidocaine and prilocaine for spinal anaesthesia. Acta Anaesthesiol Scand 2000; 44: 436440. 24. Ben David B, DeMeo PJ, Lucyk C, Solosko D. A comparison of minidose lidocaine-fentanyl spinal anesthesia and local anesthesia/propofol infusion for outpatient knee arthroscopy. Anesth Analg 2001; 93: 319-25. 232 CASE REPORT ABDOMINAL TUBERCULOSIS IN A 3-YEAR-OLD CHILD Atilla Şenaylı1, Taner Sezer2, İsmail Hakkı Göl1, Ünal Bıçakçı3 1 Gaziosmanpaşa Üniversitesi, Tıp Fakültesi Çocuk Cerrahisi Anabilim Dalı, Tokat, Türkiye 2Gaziosmanpaşa Üniversitesi, Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları Anabilim Dalı, Tokat, Türkiye 3Nafiz Kurt Devlet Hastanesi-Bafra, Çocuk Cerrahisi Bölümü, Samsun, Türkiye ABSTRACT We report the first case of abdominal tuberculosis in our region, deciding to share our experience in the diagnosis and treatment. In our report, we discussed the diagnostic and treatment criteria of the abdominal tuberculosis case. A multiple drug regimen might be useful for abdominal tuberculosis and at least 9 months of follow-up is needed. In the light of the literature, we found out that laboratory and radiological examinations might have been confusing and the real diagnosis could be reached through explorative laparotomy or laparoscopy Keywords: Tuberculosis, Extrapulmonary, Abdominal, Children ÜÇ YAŞINDAKİ BİR ÇOCUKTA ABDOMİNAL TÜBERKULOZ ÖZET Bölgemizdeki ilk abdominal Tüberkuloz vakası rapor edilmiştir ve teşhis ve tedavideki tecrübemizin paylaşılması düşünülmüştür. Yazımızda, teşhis ve tedavi kriterleri tartışılmıştır. Çoklu ilaç uygulaması abdominal tüberkuloz tedavisi için uygun görülmektedir ve en az 9 ay tedavi gerekmektedir. Literatür ışığında laboratuar ve radyolojik değerlendirmelerin karışıklığa sebep olabileceği ve gerçek teşhisin sadece eksploratif laparotomi ile yapılabileceği düşünülmüştür. Anahtar Kelimeler: Tüberkuloz, Ekstrapulmoner, Abdominal,Çocuk pediatric patients were from Turkey. In a study, it was reported that five of 1700 pediatric tuberculosis patients were defined with abdominal tuberculosis in Centers for Disease Control and Prevention (CDC) reports in 19923. Two reports from Turkey were about abdominal tuberculosis and one of them contained adult patients too.2,4. INTRODUCTION Abdominal tuberculosis is a rare manifestation of tuberculosis1. Treatment may be delayed because diagnosis is difficult due to lack of specific symptoms and pathognomonic findings. However, early diagnosis is important in order to perform an effective management and to decrease morbidity and mortality. As it is a rare disease, we aimed to discuss the diagnosis and treatment of the abdominal tuberculosis in the light of the literature and In Turkey, abdominal tuberculosis has been seen in 27/100 000 people2. A few of the İletişim Bilgileri: Atilla Şenaylı, M.D. Gaziosmanpaşa Üniversitesi, Tıp Fakültesi Çocuk Cerrahisi Anabilim Dalı, Tokat, Türkiye e-mail: ysenayli@e-kolay.net 233 Marmara Medical Journal 2009;22(3);000-000 Marmara Medical Journal 2009;22(3);000-000 Atilla Şenaylı, et al. Abdominal tuberculosis in a 3-year-old child mg/kg) P.O., for one year, streptomycin (20 mg/kg) I.M., for two months and isoniazid (10 mg/kg) P.O., for one year. to report our difficulties and experiences with a 3-year-old patient. CASE REPORT A three-year-old patient was referred to our pediatric surgery clinic after suffering from abdominal distention for a month. He had lack of appetite, breathing difficulties and drowsiness. Blood chemistry and urinary analyses were normal. The erythrocyte sedimentation rate (ESR) and blood counts were non-specific. Blood smear revealed lymphoid activity. Tumor markers were normal. Abdominal X-ray seemed to be normal. The tuberculin skin test was not performed because tuberculosis was not considered as the cause. In the abdominal ultrasound examination (USG), ascites was defined and multiple polypoid lesions were seen in the parietal and visceral peritoneum. The computerized tomography (CT) findings were the same as the USG, and nothing additional was reported. Explorative laparotomy was performed to evaluate the peritoneal carcinomatosis-like lesions (Fig.1). There were dense adhesions between the intestinal segments and multiple polyps were detected on the peritoneum and on the intestines. Peroperatively, tuberculosis was suspected because of the granulomatous lesions. Biopsies from the mesentery and the peritoneum were obtained, but biopsies from the intestine were not obtained because of the high risk of fistula formation. Treatment was concluded with remission in a year. No complications occurred during this period. After the treatment, abdominal computerized tomography and USG evaluations were performed and no lesions on the mesenteric, intestinal and peritoneal regions were detected. Figure 1: Peroperative photograph showing multiple polypoid lesions on the small intestine. DISCUSSION Abdominal tuberculosis is a rare disease that can be challenging in diagnosis even for a reference hospital. Routine evaluations may be done for tuberculosis but pathognomonic laboratory or radiodiagnostic tests are absent2,4. In our institute, this patient was the first case of abdominal tuberculosis, causing another difficulty in diagnosis. There were differences in the laboratory findings according to the literature. Pathological evaluation of the specimens revealed fibroblastic proliferation with histiocytes, lymphocytes and polymorphonuclear leucocytes in all specimens. Langhans cells were defined in granulomatous lesions. Acid-Fast bacilli (AFB) were not detected. Bacillus Calmette-Guerin (BCG) vaccine had been administered to the patient through Ministry of Health Vaccination Program. In the literature, patients of different ages were reported. The pediatric patients were between 6 months and 16 years old. There were two series for all ages reported from Turkey for abdominal tuberculosis2,4. In these reports, a high percentage was from the pediatric population and median ages were reported as 7 years and 16.2 years. The patient was diagnosed as abdominal tuberculosis with mesenteric, intestinal and peritoneal invasion and given a treatment protocol consisting of pyrazinamide (30 mg/kg) P.O., for 2 months, prednisolone (1/mg/kg) P.O., for 15 days, rifampisin (20 234 Marmara Medical Journal 2009;22(3);000-000 Atilla Şenaylı, et al. Abdominal tuberculosis in a 3-year-old child Our patient had had the BCG vaccination in his history. Progressive primary complex among the BCG vaccinated group has been increasing5. However, the prevalence of abdominal tuberculosis is reported to be almost same over the last 16 years and occurs more in the BCG non-vaccinated children5. Disseminated mycobacterial infection after bacillus Calmette-Guerin vaccination is a very rare disorder, and often occurs in patients with immunologic deficiency6. Patients with abdominal tuberculosis may be treated with chemotherapy if they have had the BCG vaccination and if other findings are obviously targeting the disease2. amplification using real-time polymerase chain reaction (PCR) testing in the peritoneal fluid sample8. For appropriate treatment, PCR is a rapid diagnosis of abdominal tuberculosis9. Granulomas constitute the characteristic lesions of tuberculosis3. In our case, as the biopsies revealed granulomatous lesions and the clinical progression differentiated some of the other granulomatous lesions like Crohn’s disease, we started chemotherapy without PCR evaluation. Chemotherapy is defined as multiple antituberculosis drugs for at least one year of therapy. In a study, isoniasid (10 mg/kg P.O., for one year), rifampicin (20 mg/kg P.O., for one year), pyrazinamide (30 mg/kg P.O., for the first 2 months), and streptomycin ( 20 mg/kg I.M., for the first month was used for treatment4. In another study, ethambutol (20 mg/kg per day) was also used2. We also used prednisolone, 1mg/kg/day for 15 days. The recommended antituberculous treatment of extrapulmonary TB in children includes the use of a three-drug regimen( ısoniazide, rifampin, and pyrazinamide)3,4,10. Also streptomycin can be used in this combination4. Some clinicians administer corticosteroids routinely for the first 2 or 3 months against fibrosis3. Mortality has decreased from 50 to 3% with the introduction of anti-TB drugs1. Erythrocyte sedimentation rate can be helpful in evaluating the tuberculosis2. ESR was reported to be high in the literature, but not in our patient. If suspected, ESR may be a guide for the diagnosis, but, as in our patient, it may be within the normal range. Ultrasonography and computed tomography may be used for the diagnosis2. The most common findings have been reported to be ascites, lymphadenopathy, thickness of the mesenterium and the peritoneum2,3,7. In a study, thickness and fine septation was found to be the most common findings2. USG and CT may be added to the BCG vaccination, ESR elevation, positive tuberculin test and family story to treat the tuberculosis, if biopsy is not possible2. Peritoneal biopsy with explorative laparotomy or laparoscopy may be indicated2,4,7. If the treatment is planned without biopsy, careful evaluation of the laboratory findings have to be performed2. In biopsy evaluations, mycobacterium tuberculosis may not be detected but granulomatous lesions with caseous necrosis are almost always revealed with the disease. Cytological evaluation of the organism is not always helpful for the microorganisms. We followed-up the patient for a year with the therapy. The patient is healthy and has no symptoms of the disease now. We will continue to evaluate the patient with clinical and radiological examinations. In one of series reported from Turkey, patients were followed-up for 9 months and all of them recovered from the disease. We also followed up our patient for a year and evaluated the progress of the disease. In our region, this is the first patient reported and there are some clinical and laboratory differences from the other patients reported in the literature. Our patient was admitted to our clinic with abdominal distention and he did not suffer from abdominal pain. Also it was reported that ESR would be high in reported As the culture and AFB positivity of the peritoneal fluid are rarely seen, histological and bacteriologic confirmation may be the only way to make a diagnosis2,3. In a study, it was reported that Mycobacterium tuberculosis DNA was detected by nucleic acid 235 Marmara Medical Journal 2009;22(3);000-000 Atilla Şenaylı, et al. Abdominal tuberculosis in a 3-year-old child 5. patients but in our patient ESR was within the normal range. We experienced that exploration of the abdomen and peritoneal and mesenteric biopsies were the only ways to help make a diagnosis. 6. 7. REFERENCES 1. 2. 3. 4. Tawfik R, Thomas A, Bruce J, Mandal B. Smallbowel obstruction caused by tuberculous strictures in an infant. J Pediatr Gastroenterol Nutr 1996; 23: 324325. Tanrıkulu AC, Aldemir M, Gurkan F, Suner A, Dağlı CE, Ece A. Clinical review of tuberculous peritonitis in 39 patients in Diyarbakır, Turkey. J Gastroenterol Hepatol 2005; 20: 906-909. Veeragandham RS, Lynch FP, Canty TG, Collins DL, Dankner WM. Abdominal tuberculosis in children: review of 26 cases. J Ped Surg 1996; 31: 170-176. Özbey H, Tireli GA, Salman T. Abdominal tuberculosis in children. Eur J Ped Surg 2003; 13: 116-119. 8. 9. 10. 236 Somu N, Vijayasekaran D, Ravikumar T, Balachandran A, Subramanyam L. Tuberculous disease in a pediatric referral centre: 16 years experience. Indian Pediatr 1994;10:1245-1249. Chandrabhushanam A, Han TI, Kim IO, Kim WS, Yeon KM. Disseminated BCG infection in a patient with severe combined immunodeficiency. Korean J Radiol 2000; 2:114-117. Saczek KB, Schaaf HS, Voos M, Cotton MF, Moore SW. Diagnostic dilemmas in abdominal tuberculosis in children. Ped Surg Int 2001; 17: 111-115. Dervisoglu E, Sayan M, Sengul E, Yilmaz A. Rapid diagnosis of Mycobacterium tuberculous peritonitis with real-time PCR in a peritoneal dialysis patient. APMIS 2006 ;114:656-658. Gilroy D, Sherigar J. Concurrent small bowel lymphoma and mycobacterial infection: use of adenosine deaminase activity and polymerase chain reaction to facilitate rapid diagnosis and treatment. Eur J Gastroenterol Hepatol 2006;3:305-307. Balasubramanian R, Nagarajan M, Balambal R, et al. Randomised controlled clinical trial of short course chemotherapy in abdominal tuberculosis: a five-year report. Int J Tuberc Lung Dis 1997;1:44-51. CASE REPORT GIANT EPIDERMAL CYST OF THE FOREARM Elif Karadeli1, Esra Meltem Kayahan Ulu1, Ahmet Fevzi Ozgur2, Emine Tosun3 1 Başkent Üniversitesi Tıp Fakültesi, Radyoloji Ana Bilim Dalı, Ankara, Türkiye 2Başkent Üniversitesi Tıp Fakültesi, Ortopedi ve Travmatoloji Ana Bilim Dalı, Ankara, Türkiye 3Başkent Üniversitesi Tıp Fakültesi, Patoloji Ana Bilim Dalı, Ankara, Türkiye ABSTRACT An epidermoid cyst is a benign, intradermal subcutaneous soft tissue tumor. Subcutaneous epidermal cysts commonly involve the scalp, face, neck, trunk and back: fewer than 10 % occur in the extremities. We reported clinical, magnetic resonance imaging (MRI) and pathologic findings of a big epidermal cyst in the forearm. Keywords: Forearm, Giant epidermal cyst, MRI ÖN KOLUN DEV EPİDERMAL KİSTİ ÖZET Epidermoid kist benign, intradermal subkutanoz yumuşak doku tümörüdür. Subkutanöz epidermal kistler sıklıkla kranium derisi, yüz, boyun, gövde ve sırtta yerleşir. Ekstremitelerde %10'dan azı yerleşim gösterir. Biz ön kolun büyük epidermal kistinin klinik, patolojik ve manyetik rezonans görüntüleme bulgularını sunduk. Anahtar Kelimeler: Ön kol, Dev epidermal kist, MRG and pathologic findings of a big epidermal cyst in the forearm. INTRODUCTION An epidermoid cyst is a benign, intradermal subcutaneous soft tissue tumor. The tumor is considered to be a migration of an epidermal component into the dermis1. The diagnosis is clinical without imaging. Subcutaneous epidermal cysts commonly involve the scalp, face, neck, trunk and back: fewer than 10 % occur in the extremities2. We reported clinical, magnetic resonance imaging (MRI) CASE REPORT A 30-year-old man presented with a right forearm mass, which had been slowly growing for 5 years. The patient had no trauma or pain. Physical examination demonstrated a big, firm, subcutaneous mass of the right forearm (Figure 1). In İletişim Bilgileri: Elif Karadeli, M.D. Başkent Üniversitesi Tıp Fakültesi, Radyoloji Ana Bilim Dalı, Ankara, Türkiye e-mail: elifkaradeli@gmail.com 237 Marmara Medical Journal 2009;22(3);000-000 Marmara Medical Journal 2009;22(3);000-000 Elif Karadeli, et al. Giant epidermal cyst of the forearm ultrasonographic examination, the tumor had a regular contour, and was heterogenously hypoechoic. Some vascularity was noted in the color Doppler sonography, mimicking a solid mass. Then, MRI was performed (1.5 Tesla, Philips Gyroscan) for detailed investigation. The MRI showed a large, welldefined, oval, homogeneous mass measuring 3.5x3x2 cm in diameter. The lesion was hypointense on T1- weighted images and hyperintense on T2- weighted images relative to the muscle. The lesion had some low signal intensity foci and serpiginous structures in it on T2-weighted images. After intravenous injection of gadolinium, there was no enhancement of the lesion (Figure 2). The excisional biopsy of the mass was performed under local anesthesia. The gross pathological examination showed that the mass was welldefined, nodular and cystic in nature. The histopathological examination showed that the lumen of the cyst was filled with keratin materials arranged in laminated layers. The wall of the cyst was composed of stratified squamous epithelium with keratohyalin granules (Figure 3). The pathologic diagnosis was keratinous cyst (epidermoid type). Figure 2: MR imaging. Axial T1(A), T2(B), coronal T1(D) and fat supressed T2(E) images showed lobulated mass in the subcutaneous fat of the forearm, which had low signal intensity on T1 and high signal intensity on T2 images. Postcontrast axial T1(C) and fat suppressed T1(F) images show no enhancement of the tumor. Figure 3: The histopathological examination showed that the lumen of cyst was filled with keratin materials arranged in laminated layers. Figure 1: A round lobulated mass in the forearm is evident. 238 Marmara Medical Journal 2009;22(3);000-000 Elif Karadeli, et al. Giant epidermal cyst of the forearm DISCUSSION Epidermoid cysts probably occur from inflammation of pilosebaceous structures. The second theory is that the formation of an epidermoid cyst is related to the implantation of epidermis into the dermis through trauma (example: intramuscular injection) and migration during embryogenesis. A later theory frequently valid is for intracranial lesions3. The epidermoid cyst of our case is located on the forearm but the patient had no trauma or injection history. Lee et al4 showed the sonographic findings of epidermoid cysts, which can have lobulated contours and show color Doppler signals, mimicking a solid mass. Similar to his study we showed that the mass was not anechoic as a cyst, instead it was hypoechoic, heterogeneous and showed color Doppler signals as solid masses. Unfortunately, we did not record the ultrasonographic images of our patient. Hong et al reported that MRI findings of unruptured epidermal cysts were hypointense on T1 and hyperintense on T2-weighted images relative to the muscle5. On postcontrast T1- weighted images, peripheral rim enhancement was seen. Epidermoid cysts may have hyperintense regions on T1weighted images compared to muscle6, and may be hypointense on T1 and T2-weighted images related to dense debris and calcification components7. Shibata et al reported that no enhancement was observed inside the tumors and the variety of signal intensities on T1 and T2-weighted images reflects differences in chemical components of the epidermoid cysts2. Our case was hypointense on T1-weighted images, hyperintense on T2-weighted images compared to muscle. This case had a variable amount of serpiginous lower signal foci on T2- weighted images. We thought that heterogeneity on T2-weighted images related to the cyst lumen was filled with keratin arranged in laminated layers. The differential diagnosis of an epidermal cyst contains a fibrous tissue tumor, such as benign fibroma, xanthoma, malignant fibrous histiocytoma or fibrosarcoma, other subcutaneous cystic masses, vascular lesions, cystic degeneration and hemorrhage, lymphangioma with hemorrhage, cystic teratoma, large ganglion cyst and echinococcal cyst5,6 Ganglion cysts are hyperintense on T2-weighted images, and show peripheral rim enhancement on postcontrast images. The heterogeneous signals of epidermoid cysts on T2-weighted images may help differentiation of epidermal cysts from other fluid cysts (ganglion cyst, bursitis). Some solid tumors such as neurogenic tumors, nodular fasciitis, myxoid tumors may be hyperintense on T2-weighted images, so they mimic cystic masses. The enhancement pattern of these solid masses can be used to differentiate epidermal cysts5. In conclusion, an epidermal cyst should be thought in the differential diagnosis of a cystic soft tissue masses. Useful features for the diagnosis of an epidermoid cyst of the extremity are a well-defined border, round or oval lesion, subcutaneous location, hypointense on T1- weighted images, hypointense foci in the hyperintense background on T2- weighted images, and no enhancement on postcontrast images. REFERENCES 1. 2. 3. 4. 5. 6. 7. 239 Shimizu Y, Sakita K, Arai E, et al. Clinicopathologic features of epidermal cysts of the sole: comparison with traditional epidermal cysts and trichilemmal cyst. J Cutan Pathol 2005, 32:280-285 Shibata T, Hatori M, Satoh T, Ehara S, Kokubun S. Magnetic resonance imaging features of epidermoid cyst in the extremities. Arch Orthop Trauma Surg 2003; 123:239-241. Bostroem E. Ueber die pialen epidermoide, dermoide and duralen dermoide. Zentbl allg Path Anat 1897; 8:1-98. Lee HS, Joo KB, Song HT, et al. Relationship between sonographic and pathologic findings in epidermal inclusion cysts. J Clin Ultrasound 2001; 29: 374-383. Hong S, Chung H, Choi J, et al. MRI findings of subcutaneous epidermal cysts: Emphasis on the presence of rupture. AJR 2006; 186:961-966. Fujimoto T, Murakami K, Kashimada A, et al. Large epidermoid cyst involving the ischiorectal fossa: MR demonstration. Clin Imaging 1993; 17:146-148. Fu YT, Wang HH, Yang TH, et al. Epidermoid cysts of the testis: diagnosis by ultrasonography and magnetic resonance imaging resultin in organpreserving surgery. Br J Urol 1996;78:116-118. CASE REPORT POST-CAESAREAN RECTUS SHEATH HAEMATOMA: A CASE REPORT Imtiaz Wani S.M.H.S Hospital , Srinagar, Surgery, Srinagar, India ABSTRACT The author reports a case of rectus sheath haematoma after lower segment caesarean section (LSCS).The haematoma extended to the pelvic wall. The aberrant course of vessels or injudicious dissection may contribute to this catastrophe. Clinical suspicion, Carnett’s test and ultrasonography were used to confirm the diagnosis. The management was conservative. Keywords: Rectus sheath hematoma, Post caesarean SEZARYAN OPERASYONU SONRASI GELİŞEN REKTUS KILIFI HEMATOMU: VAKA SUNUMU ÖZET Alt segment sezaryen operasyonu sonrasında rektus kılıfı hematomu saptanan bir olgu sunulmuştur. Hematom, pelvis duvarına kadar uzanmakta idi. Damar yapısı veya diseksiyon hataları bu olumsuz tabloya neden olmaktadır. Klinik şüphe nedeni ile Carnett’s testi ve ultrasonografi kesin tanı için kullanılmıştır. Hastaya konservatif tedavi uygulanmıştır. Anahtar Kelimeler: Rektus kılıfı hematomu, Sezaryan operasyonu INTRODUCTION In developing countries, where simple diagnostic facilities are not available all times, diagnosis of rectus sheath haematoma remains elusive and has to rely on the doctors clinical judgment to diagnose this uncommon, but well-documented mimic of acute abdominal pain1. A keen clinical sense, ultrasound and the invaluable Carnett’s test for diagnosis is available in developing countries. Prompt consideration of this rare mimic of acute abdominal pain may reduce the burden of performing expensive and invasive diagnostic tests and in some cases unnecessary hospitalization and laparotomy2. CASE REPORT A 26-year-old female was referred to our surgical services with persistent lower abdominal pain of two days duration .She had undergone LSCS three days previously. She was primi. The patient has already received pain killers. Initially, the pain was attributed to the wound site pain of LSCS. Tachyardia was present. The rest of parameters were normal. Perabdominal examination revealed tenderness on palpation of lower abdomen. Due to the tenderness, no swelling could be assessed. Carnett’s test was positive. Haemoglobin was 10 gm%. There was no significant finding on the abdomen X-ray. İletişim Bilgileri: Imtiaz Wani, M.D. S.M.H.S Hospital , Srinagar, Surgery, Srinagar, Hindistan e-mail: imtazwani@gmail.com Marmara Medical Journal 2009;22(3);000-000 240 Marmara Medical Journal 2009;22(3);000-000 Imtiaz Wani, et al. Post-caesarean rectus sheath haematoma: a case report Abdominal sonography showed a multiseptate cystic swelling of 11.4×8.1 cm. in front of the bladder extending int the anterior abdominal wall, as shown in Fig.1 suggestive of rectus sheath haematoma. In our case, the abnormal course of vessels in the rectus sheath, abnormal insertion of the rectus muscle which was torn during insertion with lax and thinned out abdominal wall layers may account for rectus sheath haematoma. The patient was managed conservatively, discharged on the seventh day and is routinely attending our follow up clinics. DISCUSSION Rectus sheath hematoma has been a wellknown entity from the ruin of ancient Greece3 Rectus sheath presents as acute abdominal pain. Females are more prone to develop rectus sheath haematoma.The presentation is a painful, tender abdominal swelling of sudden onset. This haematoma results from bleeding into the rectus sheath due to damage to the superior and the inferior epigastric arteries or their branches, or a direct tear of the rectus muscle when small branches bleed. Sometimes it can expand and lead to hypovolemic shock and subsequent death. This haematoma usually lies posterior to the muscle. Haematomas near the umbilicus are rare. Considered causes for rectus sheath are severe exertion4, pregnancy5, insulin 6, injection laparoscopy and cholecystectomy7. Berna et al, proposed that rectus sheath haematoma should be suspected in women of advancing age undergoing treatment with anticoagulants who present with triad of acute abdominal pain, infraumbilical mass and anemic syndrome8. Other causes being coughing, thrombocytopenia and contusion9. Ultrasound is a good investigation for diagnosis10, showing the mass of mixed echogenicity with no internal vascularity5. CT abdomen in particular is more useful, permits a more correct diagnosis and is considered the investigation of choice11. Technetium -99 labeled red blood cell (RBC) scintigraphy confirms the presence of the haematoma, site of bleeding and reveals continued bleeding6. Selective percutaneous transcatheter arterial embolisation is considered an effective haemostatic in the treatment of a patient with a large haematoma12. Because of the diagnostic dilemma of differentiating this condition from other acute abdominal conditions the majority of cases are treated with operative procedures3. Non-surgical therapy is considered appropriate, but leads to a greater need for analgesics. Surgical intervention is necessary in cases with large haematomas or free intra operational ruptures10. Early diagnosis permits conservative management even in large haematomas. Figure 1: A multiseptate cystic swelling in front of the bladder extending into the anterior abdominal wall, suggestive of rectus sheath hematoma. 241 Marmara Medical Journal 2009;22(3);000-000 Imtiaz Wani, et al. Post-caesarean rectus sheath haematoma: a case report 6. Stress is laid on clinical examination, Carnett’s test and ultrasonography in the diagnosis of rectus sheath haematoma. A persistent pain in the lower abdomen should arouse suspicion of rectus sheath hematoma in post LSCS. Management is most of the time by conservative measures. 7. 8. 9. REFERENCES 1. 2. 3. 4. 5. 10. Maharaj D, Ramdass M, Teelucksingh S. Rectus sheath haematoma :a new set of diagnostic features. PMJ 2002;78:755-758. Edlow JA, Juang P, Margulies S, et al. Rectus sheath hematoma. Ann Emerg Med 1999;34:671–675. Miyauchi T, Ishikawa M, Miki H. Rectus sheath hematoma in an elderly woman under anti-coagulant therapy. J Med Invest 2001;48:216–220. Hecker RB, Bradshaw WH, Pinkerton SF. Rectus sheath hematoma: report of a case. Tex Med 1990;86:68–70. Humphrey R, Carlan SJ, Greenbaum L. Rectus sheath hematoma in pregnancy. J Clin Ultrasound 2001;29:306–311. 11. 12. 242 Monsein LH, Davis M. Radionuclide imaging of a rectus sheath hematoma caused by insulin injections. Clin Nucl Med 1990;15:539–541 Neufeld D, Jessel J, Freund U. Rectus sheath hematoma: a complication of laparoscopic cholecystectomy. Surg Laparosc Endosc 1992;2:344– 345. Berna JD, Zuazu I, Madrigal M, et al. Conservative treatment of large rectus sheath hematoma in patients undergoing anticoagulant therapy. Abdom Imaging 2000;25:230–234. Hegenbarth R, Reiser C, Leib P.The sonographic diagnosis of a spontaneous rectus sheath hematoma. Aktuelle Radiol 1991;1:201–203. Klingler PJ, Wetscher G, Glaser K, et al. Use of ultrasound to differentiate rectus sheath hematoma from other acute abdominal disorders. Surg Endosc 1999;13:1129–1134. Berna JD, Garcia-Medina V, Guirao J, et al. Rectus sheath hematoma: diagnostic classification by CT. Abdom Imaging 1996;21:62–64. Rimola J, Pirendru J, Falco J. Clinical observations. Percutaneous arterial embolisation in the management of rectus sheath haematoma. AJR 2007;188: W497W502. ORIGINAL RESEARCH RETROPERITONEAL CASTLEMAN’S DISEASE: REPORT OF FOUR CASES Pinar Yazıcı1, Ünal Aydin1, Oktay Tekesin2, Murat Zeytunlu1, Murat Kılıç1, Mine Hekimgil3 Ahmet Coker1 1 Ege University, School of Medicine, Department of General Surgery, Izmir, Türkiye 2 Ege University, School of Medicine, Gastroenterology Division, Izmir, Türkiye 3 Ege University, School of Medicine, Department of Pathology,, Izmir, Türkiye ABSTRACT Castleman’s Disease (CD) located in the retroperitoneum is a rare entity which has both benign and malignant potential. We presented our series of four patients with retroperitoneal neoplasm of the lymphatic chain and evaluated the management of these patients. Over a five-year period, all patients who had intraabdominal lymphadenomegaly with an unknown etiology or were diagnosed with Castleman’s Disease of the retroperitoneum were retrospectively reviewed. Data included demographic features, surgical management and outcomes. Four patients with CD were detected, three males and one female with a mean age of 54 years. All patients had a unicentric mass located in the retroperitoneal area. Three cases complete excision of the mass and one with a mass associated to the pancreatic head underwent a pancreaticoduodenectomy. Three of the histological examinations were revealed to be of the hyaline vascular type and one was a mixed type microscopically. The recovery period was uneventful for all the patients. In the follow-up period, no recurrence was detected. This unusual anomaly of the lymphatic chain, particularly in the retroperitoneal area, should be kept in mind in the differential diagnosis of retroperitoneal tumors. The histological examination can reveal a mixed type CD even in this location. For unicentric tumors, surgical excision is the effective curative management and our series proved the efficacy of this method. Keywords: Intraabdominal lymphadenomegaly, Castleman’s disease, Total excision RETROPERİTONEAL CASTLEMAN HASTALIĞI: DÖRT OLGU SUNUMU ÖZET Castleman Hastalığı hem malign hem de benign olma riski olan retroperitoneal yerleşimli olan nadir bir patolojidir. Biz bu çalışmada retroperitoneal lenfatik zincirde malignitesi olan dört hastayı ve tedavi yaklaşımlarını değerlendireceğiz. Beş yılı aşkın bir süredir etiyolojisi bilinmeyen karın içi lenfadenopatisi ya da Castleman hastalığı tanılı hastalar retrospektif olarak tarandı. Cerrahi tedavileri ve sonuçlar değerlendirildi. Castleman hastalığı tanılı, yaş ortalaması 54 olan üç erkek bir kadın hasta bulundu. Tüm hastalarda retroperitoneal alanda yerleşimli izole bir kitle mevcuttu. Üç hastaya total eksizyon uygulanırken pankreas başı ile ilişkili bir kitleye pankreatikoduodenektomi uygulandı. Bir tane mikst tip haricinde tüm patolojik değerlendirmeler hiyalin vasküler tip olarak rapor edildi. Tüm hastaların iyileşme periyodu sorunsuz geçti ve takip periyodunda nüks saptanmadı. Özellikle retroperitoneal alan yerleşimli lenfatik zincirdeki bu nadir anomali retroperitoneal tümörlerin ayırıcı tanısında mutlaka akılda bulundurulmalıdır. Bu bölge yerleşimli Castleman hastalığı mikst tip de olabilir. Tek odaklı tümörlerde etkin küratif tedavi için cerrahi eksizyon yeterlidir ve bu yazı sonuçları bunu desteklemektedir. Anahtar Kelimeler: Karın içi lenfadenopatiler, Castleman Hastalığı, Total eksizyon İletişim Bilgileri: Pinar Yazici, M.D. Ege University, School of Medicine, General Surgery, Izmir, Türkiye e-mail: drpinaryazici@gmail.com 243 Marmara Medical Journal 2009;22(3);000-000 Marmara Medical Journal 2009;22(3);000-00 Pınar Yazıcı, et al. Retroperitoneal Castleman’s Disease: Report of four Cases ultrasonography and computed tomography (CT) of the abdomen. All of the masses were found in unicentric localization and the most frequent localization of the masses was the retroperitoneal area (Figure 2a) and next to the pancreatic head, mostly at the posterior side. In case no 2, CT revealed a solid mass arising from the mesentery of the transverse colon and extending to the infero-posterior of the pancreatic head (Figure 2b). Mean diameter of the tumors was 4,1 cm ranging between 3cm and 5,5 cm. Three patients underwent only total excision of the mass, whereas one patient required pancreticoduodenectomy. Pathological examinations revealed hyaline-vascular type lymphadenomegaly (Figure 3, case no. 3) in all patients except one patient (case no.2) whose histological findings demonstrated mixed cellular type including both hyalinevascular and plasmacytic type cell features (Figures 4a-b). All patients had an uneventful recovery period. Mean hospital stay and follow-up was 6 days (range: 3-14 days) and 34.5 months (13-72 months), respectively. No recurrence was revealed by radiological studies in the follow-up period. INTRODUCTION Castleman’s disease (CD), or angiofollicular lymph node hyperplasia, is a rare entity characterized by formation of benign lymph node masses, first described by Castleman et al. in 19561. It is mostly recognized in the mediastinum, but it rarely manifests clinically within the retroperitoneum. CD in the retroperitoneum is especially unusual, accounting for only 7% of all reported cases (400 patients so far)2. The importance of localization is that there is a relatively high potential risk for the development of malignancy with the retroperitoneal tumors. CD can be histologically divided into two types: the plasma cell type, and the hyalinevascular type which is more common, accounting for 90% of all cases3. Isolated case reports have described the plasma cell type and rare hyaline vascular type arising in the retroperitoneum4-6. To our knowledge, a mixed type of plasma cell and hyalinevascular types occurring in the retroperitoneum has not been previously reported. In this series of four patients with retroperitoneal CD, we also presented a case of mixed type tumor arising in this location, which was diagnosed due to periodical abdominal pain. CASE REPORTS Between May 1999 and March 2006, four patients were detected with CD after a retrospective review of the case records. Demographic variables, clinical features, diagnostic methods, operative procedures were evaluated. Data also included the postoperative complications, hospital stay, pathological examination and follow-up period. The informed consent form was obtained from the patients in question. Three male and one female with a mean age of 54 (46-62) were detected. Two patients were asymptomatic whereas other two had abdominal pain. Laboratory evaluation and hematological parameters were within normal ranges. C-reactive protein, one of the acute phase reactants, was also normal. All patients had routinely performed chest X-rays, Figure 1: Isolated solid mass, 24x32mm in size, (lymphadenomegaly) located between vena cava inferior and aorta (case no 3). 244 Marmara Medical Journal 2006;20(3);001-006 Pinar Yazici, et al. Retroperitoneal Castleman’s disease: report of four cases Figure 2: a) solid mass (about 3 cm in diameter) located posterior to the vena cava inferior, b) right paraaortic mass arising from the mesentery of the transverse colon Figure 3: Concentric layering of mantle zone cells around the hyalinized germinal centers in case no. 3 Figure 4: a) Glomerulization of germinal centers and plasma cell infiltration of the interfollicular area in case no. 2 (H&E, x20) b) Immunohistochemical staining of plasma cells with CD138 (DAB, x20). 245 Marmara Medical Journal 2006;20(3);001-006 Pinar Yazici, et al. Retroperitoneal Castleman’s disease: report of four cases Table 1. Demographic characteristics and treatment modalities of the patients Patient number P1-FY Age Gender Clinical features Abdominal pain, weight loss Diagnostic methods USG, CT Localization and diameter of LAM Pancreatic head 30*18mm Operative procedure Pancreaticoduodenectomy Pathological Examination Hyalinevascular Hospital stay(days) 14 Follow-up (months) 72 62 F P2-NT 53 M Abdominal pain, fatigue USG, CT** Arising from mesentery of the transverse colon, posterior of the pancreatic head, right paraaortic area, 55*31mm Total excision of the mass Mixed type; Hyalinevascular type + plasma cell type 3 13 P3-GG 46 M asymptomatic USG, CT*, MRI Posterior to the uncinat process, interaortocaval LAM, 24x37 mm Total excision of the mass Hyalinevascular type 6 18 P4-RA 57 M asymptomatic USG, CT Posterior to the inferior vena cava 32x45mm Total excision of the mass Hyalinevascular type 4 36 P:patient , USG: ultrasonography, CT: computed tomography, MRI: magnetic resonance imaging, LAM: lymphadenomegaly * picture 1, ** picture 2b characteristics of this rare entity make it difficult to obtain the precise diagnosis prior to surgery. The usual appearance of this entity by CT is that of a nonspecific homogeneous mass and homogeneously hypoechoic feature on US. In our patients, US and CT imaging demonstrated almost typical characteristics, but no remarkable evidence of malignancy. Additionally, magnetic resonance imaging (MRI) is also one of the diagnostic techniques. Although MRI has some advantages like higher soft tissue contrast, the intensity characteristic is not specific for CD. DISCUSSION Tumors located in the retroperitoneum include various groups of neoplasms of benign or malignant origin. However, malignant potential is considerable for retroperitoneal masses. On the other hand, benign retroperitoneal tumors comprise only about 20% of all primary retroperitoneal neoplasms7. Because of deeper location on the lymphatic chain, clinical presentation of these patients with retroperitoneal CD constitutes a real problem for the physician to diagnose. As with the patients presented in our study, patients with the plasma cell type tumor of CD usually present some symptoms, whereas those with the other types are generally asymptomatic. In our series, only one patient had symptoms related to the abdomen and it was considered due to close relationship of the tumor with the pancreatic head, preoperatively. The hyaline vascular histological subtype is the most common, accounting for 90% of cases whereas the plasma cell type (10%) is less common and less vascular8. In addition, CD is mostly indistinguishable from other diseases despite preoperative radiographic work-ups and even after operative observation. These two Once localized CD is removed, the prognosis is very good, but not for multicentric disease. Unicentric CD has generally no progression or association with other tumors and simple resection is curative in 90-95% of cases, whereas multicentric CD can progress to lymphoma (5%) and usually requires systemic therapy. Those patients generally follow an aggressive, often fatal clinical course associated with hepatosplenomegaly, multifocal lymphadenopathy, and abnormal liver/renal function, mostly caused by infectious complications or the development of malignancies3. In some cases, the surgeon cannot safely remove all the disease, but this 246 Marmara Medical Journal 2006;20(3);001-006 Pinar Yazici, et al. Retroperitoneal Castleman’s disease: report of four cases does not necessarily mean it will come back. Because partial removal may help the prognosis and the disease may not return, the tumoral mass should be extracted as much as possible. These recommendations are not conforming for both the patients with multicentric disease or associated HIV infection. In one study, 50% of the people with multicentric CD had died by the end of2½ years. In our series, fortunately, none of them had multicentric masses. All but one underwent total excision without remnant tissue in the abdomen. One had to have advanced resectional procedure due to close relation with the pancreatic head and suspicious frozen section results.If the frozen section is feasible intraoperatively, it should be used to determine the operative strategy and the resection margins. REFERENCES 1. 2. 3. 4. 5. 6. 7. In conclusion, although retroperitoneal CD is a rare entity, it should be included in the differential diagnosis. We suggest that when CD is clinically suspected for retroperitoneal solid masses after meticulous preoperative evaluation, only total excision of the mass is curative with a good outcome. 8. 247 Castleman B, Iverson L, Menendez VP. Localized mediastinal lymph node hyperplasia resembling thymoma. Cancer 1956; 9:822- 830 Rare diseases in numbers. [http://ec.europa.eu/health/ph_threats/non_com/docs] it is available from this website. Ziv Y, Shikiar S, Segat M, Orda O. Bilateral localized Castleman disease of the retroperitoneum. Eur J Surg Oncol 1993; 19:188-191 Moon WK, Kim WS, Kim IO, Yeon KM, Han MC. Castleman disease in the child: CT and ultrasound findings. Pediatr Radiol 1994;24:182–184 Joseph N, Vogelzang RL, Hidveg D, Neiman HL. Computed tomography of retroperitoneal Castleman disease (plasma cell type) with sonographic and angiographic correlation. J Comput Assist Tomogr 1985;9:570–572 Singletary L. A, Karcnik T. J, Abujudeh H. Hyaline vascular-type Castleman disease: a rare cause of a hypervascular retroperitoneal mass. Abdom Imaging 2000; 25:207–209 Okada S, Maeta H, Maeba T, Goda F, Mori S. Castleman Disease of the Pararenal Retroperitoneum: Report of a Case. Surg Today 1999; 29:178-181 Keller AR, Hochholzer L, Castleman B. Hyaline vascular and plasma cell types of giant lymphnode hyperplasia of the mediastinum and other locations. Cancer 1972;29:670–683. CASE REPORT ENDOVASCULAR TREATMENT OF A VERTEBRAL ARTERIOVENOUS FISTULA: CASE REPORT Feyyaz Baltacıoğlu Marmara Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı, İstanbul, Türkiye ABSTRACT In this report, we present a patient with high flow vertebral arteriovenous fistula and its endovascular treatment. The patient was a 25-year-old female with neurofibromatosis type I, presenting with quadriparesis due to the compression of highly dilated epidural venous pouches to cervical spinal cord, and treated with endovascular stent-graft. Keywords: Vertebral, Arteriovenous, Fistula, Endovascular VERTEBRAL ARTERİOVENÖZ FİSTÜLÜ VE ENDOVASKÜLER TEDAVİSİ: VAKA SUNUMU ÖZET Bu yazıda yüksek debili bir vertebral arteriovenöz fistülü ve endovasküler tedavisini sunduk. Hasta nörofibromatozis tip-I nedeni ile takip edilen 25 yaşında bayandır.Genişlemiş epidural venlerin yol açtığı servikal spinal kord basısı nedeni ile ortaya çıkan kuadriparezi ile başvurmuştur. Anahtar Kelimeler: Vertebral, Arteriovenöz, Fistül, Endovasküler with coil or baloon embolization or with stent-graft were reported for treatment2,3. INTRODUCTION Vertebral arteriovenous (AV) fistulas are defined as abnormal communications between the extracranial vertebral artery and an adjacent vein. Most of these lesions are traumatic in origin, due either to blunt or penetrating trauma or iatrogenic trauma1. Spontaneous cases may be congenital or may be associated with abnormal vessels. In the treatment, preservation of the parent artery is important, and must be attempted, but it is hardly ever achieved by surgical means. Endovascular treatment is a minimally invasive treatment modality, and does not have the disadvantages of open surgery. Different types of endovascular approaches, via both transvenous and transarterial routes, CASE REPORT The patient was a 25-year-old female with a neurofibromatosis (NF) type I. She had presented to another hospital with sudden onset of quadriparesis. Her past medical history was uneventful up to two weeks prior to admission. During the last two weeks, she experienced numbness and weakness at all four extremities progressing slowly to quadriparesis. There was no clearly defined trauma in her history. There was a strong thrill over her left neck. Cervical MR examination revealed a left sided mass lesion of 2x4 cm in size at C3 level. The lesion was İletişim Bilgileri: Feyyaz Baltacıoğlu, M.D. Marmara Üniversitesi Tıp Fakültesi, Radyoloji Anabilim Dalı,Altunizade, İstanbul, Türkiye e-mail: fbaltaci@yahoo.com Marmara Medical Journal 2009;22(3);000-000 248 Marmara Medical Journal 2009;22(3);000-000 Feyyaz Baltacıoğlu, et al. Endovascular treatment of a vertebral arteriovenous fistula: case report vertebral artery distal to the fistula site did not fill efficiently. Since there was a single hole, the fistula site was clearly defined, and there was no apparent difference between the size of the vertebral artery proximal and distal to the fistula site, endovascular treatment with stent-graft was decided to preserve the patency of the parent artery. Under local anesthesia, a baloon expandable Jomed coronary stent graft (Jomed International AB, Helsingborg, Sweden) of 4x25 mm in size was placed across the fistula site. Control angiography revealed that the fistula was fully filled with contrast material. After that, the proximal part of the stent was overdilated with a 5x20 mm baloon. The last control angiogram showed no residual filling of the fistula. The distal filling of the vertebral artery became normal. The neck thrill disappeared immediately after the procedure. The patient was discharged with aspirin 300 mg (life-long) and clopidrogel 75 mg (1 month) the next day. She underwent a surgery for cervical neurinoma about one month later. an extradural mass, compressed the spinal cord, and passed through the left neural foramen to outside the spinal canal. It was hypo/isointense with spinal cord on T1W images, hyperintense on T2W images and showed dense contrast enhancement. The lesion was diagnosed as neurinoma. Beside this, there were dilated signal void epidural venous pouches severely compressing the spinal cord and filling the spinal canal at the level of C5-C6. At this level, it communicated with the left vertebral artery through the left intervertebral foramen. The patient underwent a digital subtraction angiography (DSA) examination to clear up the architecture of the arteriovenous fistula, and to plan the treatment. Left vertebral artery injection showed a single high flow side-to-side fistula between the left vertebral artery and an epidural vein. The size of the fistula site was about 15 mm, and immediate post-fistula vein showed aneurysmatic dilatation. The large epidural venous pouch drained further to paravertebral veins bilaterally. Due to the steal of the fistula, the segment of the left Figure 1: A. Axial T1W, contrast enhanced cervical MR imaging. An extradural, highly contrast enhanced mass lesion (white arrows) compressing the spinal cord, and passing through the left neural foramen to outside the spinal canal. B. Axial T2W, cervical MR imaging. A dilated signal void epidural venous pouch (white arrows) that severely compressing the spinal cord (curved arrow) is seen. It passes through the left foramina and communicates with the left vertebral artery (large arrow). C. Sagittal T2W, cervical MR imaging. Note the hyperintense neurinoma at C2 level (white arrow) and, signal void venous pouch at C5-6 level (curved arrow). D. Left vertebral artery DSA examination. A-P view. A single high flow side-to-side fistula between the left vertebral artery and an epidural vein is seen (curved arrow). The large epidural venous pouch draines further to bilateral paravertebral veins. Distal left vertebral artery does not fill efficiently (white arrow). E. Post-embolization control DSA examination after placement of stent graft (between white arrows). No residual filling of the fistula is seen. Distal filling of the vertebral artery becomes normal. 249 Marmara Medical Journal 2009;22(3);000-000 Feyyaz Baltacıoğlu, et al. Endovascular treatment of a vertebral arteriovenous fistula: case report essential during the treatment procedure. The fistula site must be well visualized. Sometimes, contralateral vertebral artery injection with or without ipsilateral proximal vertebral artery occlusion with balloon is better for detecting the exact fistula site. The bilateral carotis system should also, be studied in order to reveal the probable concomitant injuries, which are important in the planning of the therapy. DISCUSSION Extracranial vertebral arteriovenous fistulas are rare lesions and they are usually traumatic in origin. Traumatic fistulas are most commonly of iatrogenic cause, secondary to internal jugular vein puncture or to neck surgery. Beaujeux et al reported that, most of the traumatic fistulas affect the lower portion of the vertebral artery (below C5), while spontenous ones involve the upper portion (at or above C2), which is contrary to both of our patients4. Non-traumatic fistulas can be congenital or spontaneous. Spontaneous ones can complicate primary vascular pathologies like neurofibromatosis type I, fibromuscular dysplasia, Marfan’s syndrome or EhlerDanlos syndrome type IV5,6. There has been an increasing awareness of vascular lesions in patients with NF I. Dysplastic smooth muscle or neurofibromatosis proliferation in the vessel wall lead to vasculopathy, aneurysm formation, leakage, and ultimately rupture into the adjacent vein7. The AVF’s in NF type I were reported to be more common in women more often left-sided, as in our case 8. The goal of treatment should be occlusion of the fistula site, and preservation of the patency of the vertebral artery. These lesions are difficult to treat by surgical means, because of the anatomic location, the critical condition of the patient especially in the cases with hematoma, and the difficulty in localizing the exact site of the fistula. Endovascular intervention has been increasingly used to treat AV fistulas. If the contralateral vertebral artery can supply sufficient vertebrobasiler circulation despite the steal effect, transarterial occlusion of the affected vertebral artery with detachable balloons or coils can be an effective way of treatment. For the complete elimination of the fistula, the embolic material should be placed both proximal and distal to the fistula site, in order to prevent the retrograde filling of the fistula. To preserve the vertebral artery perfusion, not the parent artery, but the fistula site itself can also be selectively embolized with coils or balloons. On the other hand, both coils and balloons have some disadvantages. Coils may not produce occlusion of the fistula, because of their poor thrombogenicity and the difficulty in achieving dense coil packing. Also they may migrate intracranially causing inadvertent arterial occlusion, or flow through the draining veins, because of the high flow fistula. In such cases, balloon aided coil embolization can be applied, in order to prevent coil migration and achieve a dense coil packing9. Sometimes it is impossible to pass a balloon through the narrow orrifice of the fistula. The balloon, on the other hand, is a flow guided device and, in the case of a large bore high flow fistula, it is hard to pass Symptomatology differs according to the site of the fistula and the flow patterns. Sometimes a neck bruit may be the only presenting sign. In the case of a proximal fistula, due to the effects on cardiac funtion, cardiac failure is seen. In cases with central venous occlusion of the superior vena cava, reversal of increased internal jugular vein flow causes increase in cerebral venous pressure, which in turn, causes cerebral edema and headache. Severe life-threatening neck hematoma is another important sequela, due to the rupture of a pseudoaneurysm. Finally, with the enlargement of the fistula, dilated epidural venous pouches cause neuronal compression syndrome, which in turn cause motor and sensory deficits, as in our case. In the evaluation of the vertebral fistulas, all possible vascular pedicles should be angiographically assessed, including both carotid, costo-cervical, and thyro-cervical arteries which probably supply the fistula. Knowledge of the hemodynamics of the contralateral vertebral artery circulation is 250 Marmara Medical Journal 2009;22(3);000-000 Feyyaz Baltacıoğlu, et al. Endovascular treatment of a vertebral arteriovenous fistula: case report the balloon distal to the fistula site for the parent artery occlusion. Sealing of the fistula with a stent graft is the treatment of choice to preserve the vertebral artery. Stent grafts are of two types: balloon expandable and self-expandable. Both of them have advantages and disadvantages. Self expandable stent grafts have thick shafts of 810 French in size, and they are stiff. That is why, it is hard to propagate them to the distal segments of the vertebral artery. They are more suitable for the proximal lesions. They are also better in cases at where the vessel diameter is different at the proximal and distal end of the fistula. Balloon expandable stent grafts, on the other hand, have thinner catheter shafts. Jomed coronary stent graft is premounted on a monorail balloon system of 4 French catheter size. It is easier to navigate distal vasculature. The main disadvantages is that, it is not firmly fixed in the vessel at where the proximal and distal end of the fistula show great mismatch in diameter. Generally the proximal diameter is larger than the distal one. If any leak is observed after the deployment of the stent-graft, the proximal half of the stent may be overdilated with a balloon of larger diameter, as in our case. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. In conclusion, endovascular treatment of the vertebral arteriovenous fistulas is safe and efficacious. Different types of endovascular means, like coils, balloons or stent-grafts can be used for this purpose. Preservation of the parent artery should be aimed for when possible. 251 Cosgrove G, Theron J. Vertebral arteriovenous fistula following anterior cervical spine surgery. J Neurosurg 1987;66:297-299. Barkhordarian S. Stent graft repair of traumatic vertebral pseudoaneurysm and arteriovenous fistula. Vascular and Endovascular Surgery 2007;41:153-157. Guglielmi G, Vinuela F, Duckwiler G, Dion J, Stocker A. High-flow, small-holes arteriovenous fistulas: treatment with electrodetachable coils. AJNR 1995;16:325-328. Beaujeux RL, Reizine DC, Casasco A, et al. Endovascular treatment of vertebral arteriovenous fistula. Radiology 1992;183:361-367. Bahar S, Chiras J, Carpena JF, Bories J. Spontenous vertebro-vertebral arteriovenous fistula associated with fibromuscular dysplasia. Report of two cases. Neuroradiology 1984;26:45-49. Kahara V, Lehto U, Ryymin P, Helen P. Vertebral epidural arteriovenous fistula and radicular pain in neurofibromatosis type I. Acta Neorochir 2002;144:493-496. Schievink WI, Piepgras DG. Cervical vertebral artery aneurysms and arteriovenous fistulae in neurofibromatosis type I. Case reports. Neurosurgery 1991;29:760-765. Hasegawa H, Bitoh S, Katoh A, Tamura K. Bilateral vertebral arteriovenous fistulas and atlantoaxial dislocation associated with neurofibromatosis. Neurol Med Chir 1989;29:55-59. Yılmaz MH, Kantarcı F, Gülşen F, et al. Yüksek akımlı vertebrojuguler fistül endovasküler tedavisinde eş zamanlı transarteryel ve transvenöz yaklaşım. Olgu sunumu. Bilgisayarlı Tomografi Bülteni 2005;8:177180. OLGU SUNUMU BEHÇET OLGUSUNDA DİŞ ÇEKİMİ SONRASI GELİŞEN EKSTERNAL KAROTİD ARTER PSEUDOANEVRİZMASI VE İNTERNAL JUGULER VEN TROMBOZU Figen Palabıyık, Arda Kayhan, Esra Karaçay, Ercan İnci, Tan Cimilli Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Radyoloji, İstanbul, Türkiye ÖZET Behçet hastalığı nedeni bilinmeyen, vaskülit ile seyreden multisistemik enflamatuar bir hastalıktır. Klinik bulgulardan sorumlu küçük damar vaskülitine ek olarak olgularda büyük ven ve arter tutulumu ve buna bağlı psödoanevrizma, tromboz gibi komplikasyonlar gelişebilir. Büyük arter komplikasyonları sıklık sırasına göre aort, pulmoner , femoral, subklavian ve karotid arterlerde meydana gelir. Literatürde ekstrakranial yerleşim ve özellikle eksternal karotid arter tutulumu ve bu lokalizasyonda gelişen komplikasyon nadir olarak bildirilmiştir. Ayrıca literatürde Behçet hastasında diş çekimi sonrası oral aftöz lezyon oluşumu mevcut iken büyük damar tutulumu bildirilmemiştir.Olgu sunumumuzda, erkek Behçet hastasında diş çekimi sonrası meydana gelen eksternal karotid arter psödoanevrizması ve internal juguler ven trombozu klinik ve radyolojik bulgular eşliğinde değerlendirilmiştir. Anahtar Kelimeler: Behçet hastalığı, Dental manipulasyon, Eksternal karotid arter pseudoanevrizması, Internal juguler ven trombozu EXTERNAL CAROTID ARTERY PSEUDOANEURYSM AND INTERNAL JUGULAR VEIN THROMBOSIS FOLLOWING TOOTH EXTRACTION IN A CASE OF BEHÇET’S DISEASE ABSTRACT Behçet’s disease is a multisystemic inflammatory disease of unknown cause, presenting with vasculitis. Complications such as pseudoaneurysm or thrombosis may be seen due to major vein and artery involvement in addition to vasculitis causing clinical manifestations. Major artery complications are seen most commonly in the aorta, pulmonary, femoral, subclavian or carotid artery. The involvement of an extracranial artery, particularly the external carotid artery is uncommon in the literature. In our case, the clinical and radiologic findings of a young male Behçet patient with an external carotid artery pseudoaneurysm and internal jugular vein thrombosis following tooth extraction is presented together with the relevant literature. No such complication of Behçet’s disease following a dental manipulation has previously been reported in the literature. Keywords: Behçet’s disease, Dental manipulation, External carotid artery pseudoaneurysm, Internal jugular vein thrombosis İletişim Bilgileri: Dr. Arda Kayhan, Bakırköy Dr. Sadi Konuk Eğitim ve Araştırma Hastanesi, Radyoloji, İstanbul, Türkiye e-mail: arda_kayhan@yahoo.com 252 Marmara Medical Journal 2009;22(3);000-000 Marmara Medical Journal 2009;22(3);000-000 Figen Palabıyık, Ark. Behçet olgusunda diş çekimi sonrası gelişen eksternal karotid arter pseudoanevrizması ve internal juguler ven trombozu üst kısmına ve yüze doğru uzanım gösteren pulsatil ve dokunmakla hassas düzgün konturlu, yuvarlak bir şişlik saptandı. Behçet hastalığı anamnezi veren olgunun, 6 gün önce bir diş hekimi tarafından sol üst 2. molar dişinin çekildiği öğrenildi. Hasta öyküsünde, işlemden 2 gün sonra boynunda oluşan şişliğin diş çekimi sonrasında geliştiğini düşünerek önce diş hekimine başvurduğunu, olası abse gelişimine yönelik 4 gün boyunca antibiyotik tedavisi aldığını ancak yakınması geçmeyince diş hekiminin bunun yapılan işlemle ilgisi olmadığını söyleyerek kendisini hastaneye yönlendirdiğini bildirdi. GİRİŞ Behçet hastalığı, tekrarlayan oral ve genital aftöz ülserler, oküler lezyonlar ve cilt lezyonları, ayrıca eklem, damar ve sinir sistemi tutulumu ile seyreden nedeni bilinmeyen enflamatuar bir hastalıktır. Behçet olgularının yaklaşık %7-37’sinde, hastalığın bir döneminde vasküler lezyonlara bağlı yakınmalar ortaya çıkmaktadır1. Kardiyovasküler tutulum hem arterleri hem de venleri içermekte, arteriyel oklüzyondan anevrizmaya, yüzeyel trombozdan süperior vena kava oklüzyonuna kadar uzanan geniş bir spektrumu içine almaktadır. Vasküler ölümler genellikle anevrizma rüptürleri sonucu ortaya çıkarlar2,3. Türkiye’de yapılan çalışmalarda vasküler tutulum oranının %24.3-38.4 arasında değiştiği bildirilmiştir4. Behçet hastalığında venöz lezyonlar büyük arter tutulumuna göre daha sık izlenmektedir. Ayrıca oral hijyenin bozuk olması, yapılan dental manipulasyonlarda oral aftöz lezyon oluşumunu tetiklemekte olup relaps ve komplikasyonlara yol açmaktadır5,6. Olgu sunumumuzda, diş çekimi sonrası gelişen eksternal karotid arter ( EKA) anevrizması ve internal jugular ven (İJV) trombozu saptanan genç erkek Behçet hastasında, klinik ve radyolojik bulguları literatür eşliğinde tartışmayı amaçladık. Olguya, kliniğimizde gri skala ve renkli Doppler US ( RDUS) uygulandı. Gri skala US incelemede boynun sol yarımında, yüzün sol kısmı ve anterior servikal bölgeden posterior servikal bölgeye uzanım gösteren, sol ana karotid arteri (AKA) anteriora deplase eden, yaklaşık 90x68 mm boyutlu, yuvarlak şekilli, heterojen eko yapısında, öncelikle hematom olarak değerlendirilen kitle izlendi. RDUS incelemede bu kitlenin içerisinde 29x25 mm boyutlarında, sol EKA’nın superior tiroid dalını verdikten sonraki ana gövdesi ile ilişkili (Şekil 1), ying-yang paterni (Şekil 2) ve EKA ile arasındaki fistül hattında ileri-geri akım paterni izlenen (Şekil 3) pseudoanevrizma olduğu saptandı. Fistül hattı 5 mm uzunlukta olup çapı 3.2 mm idi. Debisi 190ml/dk olarak ölçüldü. Ayrıca sol İJV lümenini tamamen dolduran trombüs saptandı. OLGU SUNUMU 29 yaşında, yaklaşık 7 yıldır Behçet hastalığı tanısı ile izlenen, düzensiz kortikosteroid ve immunosupresyon tedavisi alan erkek hasta, boynun sol yarımında ani gelişen şişlik yakınması ile hastanemize başvurdu. Genel durumu stabil olan olgunun fizik muayenesinde boynun sol yarımında boynun Olgu kendi isteği ile başka bir merkezde izlenmek istediği için, vasküler değerlendirme için bilgisayarlı tomografi anjiyografi ya da digital subtraksiyon anjiyografi incelemesi yapılamadı. 253 Marmara Medical Journal 2009;22(3);000-000 Figen Palabıyık, Ark. Behçet olgusunda diş çekimi sonrası gelişen eksternal karotid arter pseudoanevrizması ve internal juguler ven trombozu Şekil 1: RDUS incelemede pseudoanevrizmanın ECA ile olan ilişkisi Şekil 2: RDUS incelemede pseudoanevrizmada ying-yang görünümü Şekil 3: Spektral incelemede pseudoanevrizma boynunda ileri geri akım paterni 254 Marmara Medical Journal 2009;22(3);000-000 Figen Palabıyık, Ark. Behçet olgusunda diş çekimi sonrası gelişen eksternal karotid arter pseudoanevrizması ve internal juguler ven trombozu kalınlaşma ve fibrozis ile perivasküler lenfositik infiltrasyon, mediada elastik ve kas liflerinin kaybı, intimada düz kas ve fibroblastik hücre artışıdır. TARTIŞMA Behçet hastalığı oral ve genital ülserler, deri ve göz tutulumu ile seyreden sistemik inflamatuar bir hastalıktır. Behçet hastalığının patogenezinde genetik ve mikrobiyolojik ajanlar sorumlu tutulmaktadır. HLA51 varlığı ana genetik faktör olup Streptococcus sanguis gibi enfeksiyon ajanların hastalığın patogenezinde önemli rol oynadığı klinik çalışmalar ile gösterilmiştir. Behçet hastalığı %70 oranında oral aftöz lezyonlar ile başlamakta olup oral mikrobiyal flora patogenezde rol oynamaktadır. Olgularda oral streptekok kolonizasyonunda artış ve oral florada atipik sterptekokal ajanlara rastlanmıştır. Behçet hastalığının streptekok enfeksiyonları ile ilişkisi dental tedaviler sonrası oral ülserlerin oluşması, streptekokal deri testlerine karşı hipersensivite, streptekok antijenlerine karşı pro-inflamatuar cevapta artış ve tedavide anti-bakteriyal ilaçların yararlı olması ile açıklanmaktadır. Olgularda kötü ağız hijyeni, multiple çürüklere bağlı diş çekimleri, oral pH değişiklikleri izlenmekte olup bunlar hastalığın şiddetini arttırmaktadır5,6. Behçet olgularında, oral aftların dental manipulasyonlardan sonra arttığıda bilinmektedir7. Epidemiyolojik çalışmalar ise, Behçet hastalığı olan olgularda, sağlıklı olgular ile karşılaştırıldığında, yüksek oranda tonsilit ve dental manipulasyon öyküsü varlığını ortaya koymuştur8,9. Behçet hastalığında arteriyel oklüzyon, anevrizma, venöz oklüzyon ve varis olmak üzere dört büyük vasküler lezyon 12 bildirilmiştir . Hastalığın bilinen en önemli vasküler komplikasyonları anevrizma gelişimi, arteriyel oklüzyon ve venöz trombozdur13. Oklüzyon özellikle alt ekstremitelerde sık izlenir. Arterlerde anevrizma oklüzyona göre daha iyi prognoz gösterir14. Vasküler tutulum oranı %7-29 olup büyük ven tutulumu %14, arteriyel tutulum %1.5 dur3. Büyük arter komplikasyonları genç erkeklerde %2-6 oranında olup sıklık sırasına göre aort, pulmoner, femoral, subklavian ve karotid arterlerde meydana gelir11. Karotid arter pseudoanevrizması nadir bir komplikasyondur15,16. Kuzu ve arkadaşları 1200 vakalık geniş bir seride yaptıkları çalışmada 173(%14.4) hastada venöz tutulum, 19 (%1.6) hastada arteriyal tutulum bildirmişlerdir. Aynı çalışmada, venöz tutulum izlenen olgularda 154(%12.8) venöz tromboz, 17(%1.4) superior vena kava sendromu, 5(%0.4) inferior vena kava sendromu, 5(%0.4) varis, 2 üst ekstremite ven trombozu, 1 kavernöz sinüs trombozu,1 internal juguler ven trombozu ve 1 hepatik ven trombozu saptanmıştır. Arteriyel tutulum izlenen olguların 7’sinde femoral, 3’ünde abdominal, 3’ünde popliteal, 2’sinde iliak, 2’sinde pulmoner, 1’inde aksiller arter anevrizması ve 3’ünde arteriyel oklüzyon izlendiği belirtilmiştir12. Behçet olgularında , neredeyse tüm majör damarların tutulumu rapor edilmekle birlikte, en sık büyük damar tutulumu izlenmekte olup, visseral damar tutulumu nadir 17 görülmektedir . Santral sinir sistemi ve vasküler tutulum ise hastalığın ileri evrelerinde görülür ve ölüme yol açabilir. Vasküler tutulum erkeklerde kadınlara göre daha sıktır ve venöz sistem daha sıklıkla etkilenmektedir. Arteriyel tutulum nadir ama Behçet hastalığının ciddi ve önemli bir komplikasyonudur10. Behçet hastalığında büyük arter lezyonlarının nedeninin media ve adventisyadaki enflamasyon olduğu düşünülmektedir. Arteriyel duvarda vaza vazorumlarda enflamatuar obliterasyona bağlı akım kesilmesi sonucu perforasyon ve pseudoanevrizma gelişir11. Behçet hastalarında anevrizma duvarında saptanan patolojik değişiklikler, adventisyada Literatürde Behçet hastalığında ekstrakranial tutulum internal karotid arterde bildirilmiş olup9,13,14, eksternal karotid arter tutulumu ve komplikasyonu bildirilmemiştir. Ayrıca diş çekimi sonrası oral aftöz ülser oluşumu bildirilmiş olmasına rağmen literatürde büyük 255 Marmara Medical Journal 2009;22(3);000-000 Figen Palabıyık, Ark. Behçet olgusunda diş çekimi sonrası gelişen eksternal karotid arter pseudoanevrizması ve internal juguler ven trombozu damar komplikasyonuna rastlanmamıştır. Bu olgu ile Behçet hastalarında eksternal karotid arter tutulumu olabileceği; sadece oral aftöz ülserlerin değil, ciddi ve önemli büyük arter ve/veya ven tutulumunun klinik olarak dental girişimlerden sonra bir komplikasyon olarak karşımıza gelebileceği akılda tutulmalıdır. 2. 3. 4. Aoki K, Ohno S. Studies on the constitution and past history of patients with Behcet’s disease. 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Arch Surg 1988 ; 123:1004-1008. James DG, Thomson A. Recognition of the diverse cardiovascular manifestations in Behcet’s disease. Am Heart J 1982; 103:457-458. 14. Agrawal S, Jagadeesh R, Aggarwal A, et al. Aneurysm of the internal carotid artery in a female patient of Behcet\'s disease: a rare presentation. Clin Rheumatol 2007; 26:994-995. Müftüoğlu AU, Yurdakul S, Yazini H, et al. Vascular involvement in Behcet\'s disease: A review of 129 cases. In: Lehner T, Barnes CG, eds. Recent Advances in Behcet\'s Disease. London: Royal Society of Medicine Services Limited, 1986:1:255-260. 15. Ozyazicioglu A, Kocak H, Vural U. Carotid artery pseudoaneurysm in Behcet’s disease. Eur J Cardiothroc Surg 2001; 19:938-939. 5. Mumcu G, Ergun E, Inanc N, et al. Oral health is impaired in Behcet’s disease and is associataed with disease severity. Rheumatology 2004; 43:1028-1033. 16. Suzuki J, Akashi K, Shimada M, Abe S, Kawakami Y. A case of Behcet’s disease with a rapidly enlarging aneurysm in the common carotid artery. Jpn J Med 1991; 30:251-254. 6. Direskeneli H. Autoimmunity vs autoinflammation in Behcet’s disease: do we oversimplify a complex disorder? Rheumatology 2006; 45:1461-1465. 17. Park J, Han M, Bettrnann M. Arterial manifestations of Behcet disease. AJR 1984; 143:821-825. 7. The Behcet\'s Disease Research Committee of Japan. Skin hypersensitivity to streptococcal antigens and the induction of systemic symptoms by the antigens in Behcet\'s disease-a multicenter study. J Rheumatol 1989; 16:506-511. 256