001 hpb giri..qxp
Transkript
001 hpb giri..qxp
Türk HPB Türk Hepato-Pankreato-Bilier Cerrahi Dergisi Türk Hepato-Pankreato-Bilier Cerrahi Derneði Yayýn Organýdýr ©Ýstanbul Medikal Yayýncýlýk SÜRELÝ YAYINLAR dizisi “Türk HPB” Dergisi Editör: Prof. Dr. Ali Emre Ýstanbul Üniversitesi, Ýstanbul Týp Fakültesi, Genel Cerrahi Anabilim Dalý 2006 Cilt 2 Sayý 1 ISSN 1305 - 4708 www.hpb.org.tr “TÜRK HPB DERGÝSÝ”NÝN YAYIN HAKLARI TÜRK HEPATO PANKREATO BÝLÝER CERRAHÝ DERNEÐÝ’NE AÝTTÝR. Yasalar uyarýnca, bu yapýtýn basým haklarý Ýstanbul Medikal Yayýncýlýk Ltd. Þti.'ye aittir. Yazýlý izin alýnmadan ve kaynak olarak gösterilmeden, elektronik, mekanik ve diðer yöntemlerle kýsmen veya tamamen kopya edilemez; fotokopi, teksir, baský ve diðer yollarla çoðaltýlamaz. 2005 Ýstanbul Medikal Yayýncýlýk Ltd. Þti. Deniz Abdal Mah., Baþvekil Cad., Çeþme Sok., No. 3, 34104, Çapa - ÝSTANBUL • Tel: (0212) 584 20 60 • • Faks: (0212) 584 20 61 • www.istanbultip.com info@istanbultip.com Ýstanbul Medikal Yayýncýlýk Yayýna Hazýrlayan / Ýstanbul Medikal Yayýncýlýk Ltd. Þti. Redaksiyon ve Düzelti / Prof. Dr. Yaman Tekant, Prof. Dr. Cumhur Yeðen Sayfa Düzeni / E. Recai Tosun (0212) 584 20 60/18 - 0532 410 77 19 Kapak / Özlem Arabacý (0212) 584 20 60/13 Baský ve Cilt / Elma Matbaacýlýk Ltd. Þti. (0212) 670 05 25 Türk HPB Dergisi’nin basýmýnda asitsiz kaðýt kullanýlmaktadýr I Türk HPB Türk Hepato-Pankreato-Bilier Cerrahi Dergisi TÜRK HEPATO - PANKREATO - BÝLÝER CERRAHÝ DERGÝSÝ YAZIM KURALLARI “Türk HPB Dergisi” Türk Hepato-PankreatoBiliyer Cerrahi Derneði yayýn organýdýr. Yazým dili Türkçe’dir. Derlemeler, özgün makaleler, klinik notlar, deneysel notlar, vaka sunumlarý, hýzlý yayýnlar ve editöre mektuplar yayýnlar. Dergi yýlda dört kez (Ocak - Nisan - Temmuz - Ekim) yayýnlanýr. Daha önce herhangi bir dilde özet dýþýnda yayýnlanmadýklarý veya deðerlendirme aþamasýnda olmadýklarý bildirilen yazýlar yayýn kurulu tarafýndan ele alýnýr ve hakem deðerlendirmesine sunulur. 1997;277:927-934). Bu belge www.icmje.org adresinde de bulunabilir. Gönderilen bütün yazýlara, yazarlarýn tümü tarafýndan imzalanan, okunup onaylandýðýný belirten bir mektup eklenmelidir. Yazý kabul edildiði takdirde bütün baský haklarý (copyright) dergiye geçmiþ olur. Eðer metindeki malzeme, ilaç ve aletlerden yazarlarýn yarar saðlamasý durumu veya böyle bir olasýlýk varsa bu durum belirtilmelidir. Dergi bu bilgiyi yayýnlar veya yayýnlamaz. Ýnsan denekleri üstündeki çalýþmalar 1975 Helsinki Bildirgesinin 1983’te düzenlenmiþ þekline uygun olmalý, her denekten bilgilendirilmiþ onay alýnmalýdýr. Haberleþme Çalýþmanýn asýl metni ve üç kopyasý (asýl metni içeren CD ile beraber) aþaðýdaki adrese gönderilmelidir: Prof. Dr. Ali Emre Türk HPB Dergisi Editörü Niþantaþý, Valikonaðý Cad. 159/5, Birlik Apt. 34365 ÝSTANBUL. Gönderilen yazýlarla ilgili olarak aþaðýdaki faks, e-posta ve telefonlara baþvurulabilir: hpbcer@superonline.com aemre@tnn.net ytekant@istanbul.edu.tr yegen@superonline.com Metin kategorisi Derleme Yazar ilgili konuda yayýnlanmýþ çalýþmalarý ile tanýnmýþ olmalýdýr. Bir konu detaylý bir biçimde ele alýnmalýdýr. Bir özet verilmelidir. Özgün makaleler Metin her biri ayrý sayfalarda baþlayan bölümler þeklinde gönderilmelidir: Özet (Türkçe ve Ýngilizce, en fazla 250 sözcük)-giriþ-gereç ve yöntemlerbulgular-sonuçlar-kaynaklar-þekil veya resim alt yazýlarý. Telefon: 0212 631 21 13 Fax: 0212 635 30 82 - 0212 233 19 37 Klinik notlarý veya deneysel notlar Özgün gözlemler, bir yöntemin yararlý varyasyonlarý, sýk rastlanan teknik güçlükler için pratik çözümler bildirilebilir. Altýyüz kelimeyi aþmamalý, kýsa bir özet verilmelidir. Yazým kurallarý Yazarlar "Biyomedikal Dergilere Gönderilen Yazýlar Ýçin Tek Tip Kurallar”dan yararlanmalýdýrlar (Ann Intern Med 1997;126:36-47, JAMA II 2. 3. 4. 5. 6. 7. Vaka sunumu 500 kelimeyi geçmemeli, kýsa bir özet verilmelidir. Hýzlý yayýnlar Araþtýrýcýlar çabuk iletmek istedikleri özgün bulgularý 600-1200 kelimelik ön raporlar halinde bu bölümde deðerlendirebilirler. Bir özet verilmeli, bu kategoride bildirilme nedeni anlatýlmalýdýr. Yazarlarýn isim ve soyisimleri Çalýþmanýn yapýldýðý kurum veya kurumlar Haberleþme adresi (telefon, faks ve e-posta) Mali destek kaynaklarý Metin kategorisi Anahtar sözcük (3-10 kelime) Özet Her yazýda en fazla 200 sözcük içeren Türkçe ve Ýngilizce özet olmalýdýr. Özet þu þekilde yapýlandýrýlmalýdýr: amaç, yöntem, bulgular ve sonuçlar. Editöre mektuplar Yayýnlanan herhangi bir yazý halinde görüþler bu bölümde iletilebilir. Ayrýca özgün makale boyutlarýnda olmayan yazýlara yer verilebilir. Bu yazýlar toplam 1200 kelime, 10 kaynak, 2 adet resim, þekil veya tabloyu aþmamalýdýr. Kaynaklar Metinde geçiþ sýralarýna göre numaralandýrýlmalýdýr. Dergi adlarý Index Medicus sistemine göre kýsaltýlmalýdýr. Kaynaklara atýflar "tek tip kurallar"a uygun olmalýdýr. Kaynaklarýn doðruluðu yazarýn sorumluluðundadýr. Tablo, resim ve þekiller Kullanýlan gereç özgün olmalýdýr. Alýntý yapýldýðýnda ilgili yayýnevinin yazýlý izni gereklidir. Her tablo veya þekil ayrý sayfada verilmelidir. Resmin arkasýna aþaðýdaki bilgiler kaydedilmelidir: 1. Üst taraf okla gösterilmelidir. 2. Tablo, þekil veya resmin numarasý yazýlmalýdýr. 3. Ýlk yazarýn ismi belirtilmelidir. 4. Fotoðraflar kaliteli olmalýdýr. Renkli basým, masraf yazarlar tarafýndan karþýlandýðý takdirde mümkündür. Örnek Makale: Hermanek P, Sobin L, Wittekind C. How to improve the present TNM staging system. Cancer 1999;86:2189-91. Kitap: Büchler M, Malfertheiner P, Friess H, Senn T, Beger H.G. Chronic pancreatitis with inflammatory mass in the head of the pancreas.: a special entity. In: Chronic pancreatitis (Beger HG, Büchler M, Ditschuneit H, Malfertheiner P, eds). 2nd-ed. Springer-Verlag, Heidelberg 1990:41-47. Baþlýk sayfasý 1. Makalenin baþlýðý (Türkçe ve Ýngilizce) III Türk HPB Türk Hepato-Pankreato-Bilier Cerrahi Dergisi Ýçindekiler 1 Canlýdan Karaciðer Naklinde Verici ve Alýcýlarýn Deðerlendirilmesi Þükrü Emre, Ýlhan Karabýçak 9 Infectious Disease Complications in Pediatric Solid Organ Recipients Roberto Posada 17 Assessment of Pediatric Liver Transplant Recipients Þükrü Emre 23 Hepatic Retransplantation Susan M. Lerner 32 Pankreas Travmalarýnda Cerrahi Tedavi Hayrullah Derici, Okay Koç, Tuðrul Tansuð, Ali Doðan Bozdað, Okay Nazlý 38 Situs Ýnversus Totalisli Hastada Laparoskopik Kolesistektomi: Olgu Sunumu Oktay Banlý, Burak Kavlakoðlu, Hasan Altun IV Türk HPB Türk Hepato-Pankreato-Bilier Cerrahi Dergisi Editör Ertuðrul Göksoy, Ýstanbul Haldun Gündoðdu, Ankara Selim Gürel, Bursa Cem Kalaycý, Ýstanbul Sedat Karademir, Ýzmir Kaan Karayalçýn, Ankara Selim Karayalçýn, Ankara Zeki Karasu, Ýzmir Murat Kýlýç, Ýzmir Sadýk Kýlýçturgay, Bursa Nezihi Oygür, Antalya Atilla Ökten, Ýstanbul Durkaya Ören, Erzurum Ýlgin Özden, Ýstanbul Yýlmaz Özen, Bursa Ömer Özütemiz, Ýzmir Yalçýn Polat, Erzurum Ýzzet Rozanes, Ýstanbul Ýskender Sayek, Ankara Erdoðan Sözüer, Kayseri Özlem Süoðlu, Ýstanbul Hakan Þentürk, Ýstanbul Ýlkay Þimþek, Ýzmir Ethem Tankut, Ýzmir Ertan Tatlýcýoðlu, Ankara Yaman Tokat, Ýzmir Nurdan Tözün, Ýstanbul Özgür Yaðmur, Adana Rýfat Yalýn, Ýstanbul Hasan Yersiz, Los Angeles Sezai Yýlmaz, Malatya Zeki Yýlmaz, Kayseri Cihan Yurdaydýn, Ankara Yýldýray Yüzer, Ýzmir Ali Emre, Ýstanbul Yardýmcý editörler Yaman Tekant, Ýstanbul Cumhur Yeðen, Ýstanbul Bilimsel danýþma kurulu Osman Abbasoðlu, Ankara Koray Acarlý, Ýstanbul Bülent Acunaþ, Ýstanbul Ulus Akarca, Ýzmir Alper Akýnoðlu, Adana Hikmet Akkýz, Adana Þükrü Aktan, Antalya Nusret Akyürek, Ankara Ethem Alhan, Trabzon Aydýn Alper, Ýstanbul Nusret Aras, Ankara Orhan Arýoðul, Ýstanbul Hüseyin Astarcýoðlu, Ýzmir Ýbrahim Astarcýoðlu, Ýzmir Orhan Bilge, Ýstanbul Hakan Bozkaya, Ankara Mehmet Çaðlýkülekçi, Mersin Yýlmaz Çakaloðlu, Ýstanbul Ahmet Çoker, Ýzmir Fügen Çullu, Ýstanbul Aydýn Dalgýç, Ankara Alper Demirbaþ, Antalya Haluk Demiryürek, Adana Abdulkadir Dökmeci, Ankara Þükrü Emre, New York Sadýk Ersöz, Ankara V Türk HPB Türk Hepato-Pankreato-Bilier Cerrahi Dergisi Editörden, Deðerli meslektaþlarým, Karaciðer transplantasyonu konusunda ülkemizde son yýllarda büyük ilerleme kaydedilmiþtir. 2005 yýlýnda Türkiye'de yapýlan karaciðer transplantasyonu sayýsý 146 olup bir önceki yýla göre önemli oranda artýþ saðlanmýþtýr. Dergimizin bu sayýsýnda sizlere karaciðer nakli konusundaki geliþmeler doðrultusunda, yararlý olacaðýný sandýðýmýz bir sempozyum sunuyoruz. Bu sempozyum, Þükrü Emre yönetiminde, ABD' nin önde gelen karaciðer nakli merkezlerinden NewYork Mt. Sinai Hastanesinin transplantasyon bölümü elemanlarý tarafýndan hazýrlandý. Çok yoðun çalýþma ortamý içinde büyük özveri ile zaman ayýrarak bu sunumu hazýrlayan Þ. Emre, S. Lerner ve R. Posada'ya teþekkürlerimizi sunuyoruz. Bu sayýmýzda bir istisna olarak yabancý yazarlarýn bölümlerini Ýngilizce yayýnlamayý uygun gördük. Bundan sonraki sayýlarýmýzda da sempozyum biçimindeki sunumlara yer vermeyi yararlý bulmaktayýz. Deðerli meslektaþlarýmýzýn Türk HPB Dergisi içeriði konusunda eleþtiri ve katkýlarýna her zaman açýk olduðumuzu belirtir, saygýlar sunarýz. Ali Emre Dr. Þükrü Emre 1977’de Ýstanbul Üniversitesi, Ýstanbul Týp Fakültesi’nden mezun oldu. Ayný fakültede Genel Cerrahi ihtisasý yaparak 1982’de Genel Cerrahi Uzmaný ünvanýný aldý. 1988 yýlýnda doçent oldu. Daha sonra ABD New York Mount Sinai Medical Center’de transplantasyon bölümünde çalýþmaya baþladý. Dr. Emre halen ayný merkezin Pediatri ve Cerrahi departman baþkanlýðý ile pediatrik ve yetiþkin karaciðer transplantasyon programýný yönetmektedir Degimizi elktronik ortamda okuyabilirsiniz VI Türk HPB Türk Hepato-Pankreato-Bilier Cerrahi Dergisi Türk Hepato Pankreato Bilier Cerrahi Derneði “Samsun Bölgesel Toplantýsý” Bilimsel Programý 28 Nisan 2006 09.15 - 10.00 Açýlýþ Konferansý: Karaciðerin metastatik tümörleri Dr. Ýbrahim Astarcýoðlu 10.15 - 11.35 Safra yolu yaralanmalarý 10.15 - 10.35 10.35 - 10.55 10.55 - 11.15 11.15 - 11.35 11.35 - 12.35 Baþkan: Dr. Ali Naki Ulusoy Hangi hastaya kolesistektomi? Dr. Kenan Erzurumlu Güvenli kolesistektomi Dr. Kaan Karayalçýn Akut yaralanmalara endoskopik yaklaþým Dr. Yaman Tekant Akut yaralanmalara cerrahi yaklaþým Dr. Yýlmaz Özen Olgu tartýþmalarý Baþkan: Dr. Ýlgin Özden 13.30 - 13.50 13.30 - 13.50 13.50 - 14.10 14.10 - 14.30 14.30 - 14.50 15.20 - 15.35 15.35 - 17.05 Pankreatitler Baþkan: Dr. Necati Özen Etyoloji, terminoloji, sýnýflama Dr. Mustafa Þare Pankreatitte radyoloji, laboratuar ve prognostik faktörler Dr. Mete Kesim Pankreatitte cerrahi dýþý tedavi seçenekleri Dr. Sadýk Kýlýçturgay Hangi hastaya, ne zaman cerrahi? Dr. Ahmet Çoker Pankreatitler - Samsun deneyimleri Dr. Bülent Güngör Olgu tartýþmalarý Baþkan: Dr. Ali Emre Dr. Zafer Malazgirt Dr. Necla Tülek Dr. Ahmet Bektaþ VII Türk HPB 2006 Cilt 2 Sayý 1 Situs Ýnversus Totalisli Hastada Laparoskopik Kolesistektomi: Olgu Sunumu Türk HPB Oktay Banlý , Burak Kavlakoðlu , Hasan Altun 1 2 1 Ankara Etlik Ýhtisas Hastanesi, Genel Cerahi Bölümü1, ANKARA Ankara Meslek Hastalýklarý ve Hizmet Hastanesi, Genel Cerrahi Bölümü2, ANKARA Özet Sol üst kadranda yemeklerden sonra rahatsýzlýk hissi ile baþvuran 55 yaþýndaki kadýn hastaya daha önce baþvurduðu hastanede ultrasonografi ile situs inversus totalis ve kolelitiazis tanýsý konuldu. Kliniðimizde yapýlan tetkiklerle situs inversus totalis ve kolelitiazis tanýsý teyit edildi. Hastaya semptomatik safra kesesi taþý nedeniyle laparoskopik kolesistektomi yapýldý. Situs inversus totalisli hastalarda laparoskopik kolesistektomi yapýlýrken ayna görüntüsü anatomiye adaptasyon güçlüðüne ve sað el ile çalýþan cerrahlarda diseksiyon zorluðu olduðundan daha dikkatli olunmalýdýr. Anahtar kelimeler: situs inversus totalis, laparoskopik kolesistektomi Laparoscopic Cholecystectomy in a Patient with Situs Inversus Totalis: A Case Report Summary A 55-year old woman with a known diagnosis of situs inversus totalis and cholelithiasis presented with left upper quadrant discomfort. The diagnosis of situs inversus totalis and chlolelithiasis was confirmed in our hospital.This patient has undergone laparoscopic cholecystectomy for symptomatic cholelithiasis. Mirror image of this anomaly may cause difficulty in adaptation to the anatomy in patients with situs inversus totalis and right-handed surgeons must be more careful because of dissection difficulties. Key words: situs inversus totalis, laparoscopic cholecystectomy yeterli deneyime sahip olmadýklarýndan hasta hastanemize sevk edildi. Hastaya kliniðimizde de ultrasonografi, bilgisayarlý tomografi, akciðer grafisi tetkikleri yapýlarak situs inversus totalis ve kolelitiazis tanýsý teyit edildi (Resim 1). Kalp ve dalak saðda, karaciðer ve safra kesesi solda idi. Ameliyat öncesi yapýlan tetkiklerde aberran anatomik bir oluþum izlenmedi. Hastaya laparoskopik kolesistektomi planlandý. Cerrah hastanýn sað tarafýndan ameliyatý gerçekleþtirdi. Ýlk olarak göbek altýna yapýlan insizyonla trokar direkt yöntemle karýna girilip 12 mmHg basýnçta CO2 insuflasyonu saðlandý. Ardýndan subksifoid 1 adet 10 mm'lik, sol subkostal 2 adet 5 mm’lik trokarlar yerleþtirildi. Calot üçgen diseksiyonu sað el ile 5 mm'lik subkostal midklavikular hattaki trokardan yapýldý (Resim 2). Anatomi ayna görüntüsü þeklindeydi. Subksifoid trokardan endoclinch yardýmýyla kese fundusu sefalik yönde traksiyone edildi. Önce önde sistik kanal bulundu, di- Giriþ Son yýllarda semptomatik safra kesesi taþlarýnda laparoskopik kolesistektomi altýn standarttýr. Situs inversus totalis bilindiði gibi çok nadir rastlanan bir anatomik anomalidir1. Bu hastalarda safra kesesi, karaciðer, tüm safra yollarý ve vasküler yapýlar ayna görüntüsü þeklinde sol taraftadýr. Kliniðimizde situs inversus totalisi ve semptomatik kolelitiazisi olan bir hastaya laparoskopik kolesistektomi yapýlmasý nedeniyle bu hastalarda yapýlan kolesistektomiyi literatür ýþýðýnda tartýþtýk. Olgu sunumu Sol üst kadranda yemeklerden sonra rahatsýzlýk hissi ile baþvuran 55 yaþýndaki kadýn hastaya daha önce baþvurduðu hastanede ultrasonografi ile situs inversus totalis ve kolelitiazis tanýsý konuldu. Ýlk tanýnýn konulduðu merkezdeki cerrahlarýn laparoskopik kolesistektomi konusunda Oktay Banlý, 38 Situs Ýnversus Totalisli Hastada Laparoskopik Kolesistektomi Resim 2. Ameliyat esnasýna Calot üçgeni diseksiyonu esnasýndaki laparoskopik görünüm. Resim 1. Hastanýn toraksta kalbinin ters tarafta olduðunu gösteren akciðer grafisi. Situs inversus totalisli hastalarda inferior sistik arter gibi aberran vasküler yapýlarla karþýlaþma olasýlýðý daha fazla olduðundan diðer radyolojik görüntüleme tekniklerine ek olarak preoperatif abdominal anjiyografi yapýlmasýný önerenler de vardýr2. Laparoskopik kolesistektomi sýrasýnda situs inversus totalisli hastalarda ayna görüntüsü þeklinde yerleþtirilen trokarlarýn yerleþtirilme açýlarý çalýþmayý zorlaþtýrdýðýndan dikkat edilmelidir5. Sað el ile çalýþan cerrahlarda Calot üçgeninin diseksiyonunun zor olduðu unutulmamalýdýr5. Sol el ile çalýþan cerrahlar diseksiyonu sol elleri ile de yapabildiklerinden daha az zorluk yaþamaktadýrlar6. Laparoskopik cerrahide yeterince tecrübesi olan cerrahlar olabilecek anatomik varyasyonlara dikkat ederek kolesistektomiyi rahatlýkla yapabilirler. seke edilip askýya alýndý ve klipslenerek kesildi. Ardýndan sistik arter bulunup klipslenerek kesildi. Kolesistektomi künt ve keskin diseksiyon kullanýlarak tamamlandý. Operasyon sýrasýnda da aberran anatomik yapý ile karþýlaþýlmadý. Hasta ameliyattan sonraki 1. gün taburcu edildi. Ameliyat sonrasý 7. gün cilt dikiþleri alýnan hastada herhangi bir sorun saptanmadý. Hastanýn patoloji sonucu kronik kolesistit olarak rapor edildi. Tartýþma Situs inversus totalis çok nadir bir anatomik anomalidir (1:5000-1:10.000)1. Laparoskopik kolesistektominin sýk kullanýlmasýyla situs inversus totalis nedeniyle bildirilen vaka sayýsý da literatürde artmaktadýr2. Karýn içi organlarýn yerleþimi ayna görüntüsü olduðundan orientasyonda zorluklar yaþanmakta ve iatrojenik yaralanma riski artmaktadýr3. Laparoskopik kolesistektomi yapýlýrken cerrahlar, ameliyat hemþire masasýný ve enstrüman dizilimini situs inversus totalisli hastalarda ayna görüntüsü anatomiye uygun olarak kurmaya dikkat etmelidirler4. Sonuç Situs inversus totalisli hastalarda laparoskopik kolesistektomi sýrasýnda cerrahlarýn ayna görüntüsü þeklindeki anatomiye adapte olmalarý, çýkabilecek anatomik varyasyonlara dikkat etmeleri gerekir ve sað el ile çalýþan cerrahlarýn tekniklerini situs inversusa göre modifiye etmeleri gerekebilir. 39 O. Banlý ve ark. Kaynaklar 1. 2. 3. Mayo CW, Rice RG. Situs inversus totalis statistical review of data on 76 cases with special reference to diseases of the biliary tract. AMA Arch Surg 1949;58:724-30. Kamitani S, Tsutamoto Y, Hanasawa K, Tani T. Laparoscopic cholecystectomy in situs inversus totalis with "inferior" cystic artery: A case report. World J Gastroenterol 2005;11:5232-4. Polychronidis A, Karayiannakis A, Botaitis S, Perente S, Simopoulos C. Laparoscopic cholecystectomy in a patient with 4. 5. 6. 40 situs inversus totalis and previous abdominal surgery. Surg Endosc 2002;16:1110. Mc Kay D, Blake G. Laparoscopic cholecystectomy in situs inversus totalis:a case report. BMC Surg 2005;17:5. Docimo G, Manzi F, Maione L, et al. Case report: laparoscopic cholecystectomy in situs viscerum inversus. Hepatogastroenterology 2004;51:958-60. Oms LM, Badia JM. Laparoscopic cholecystectomy in situs inversus totalis: The importance of being left-handed. Surg Endosc 2003;17:1859-61. Türk HPB 2006 Cilt 2 Sayý 1 Pankreas Travmalarýnda Cerrahi Tedavi Hayrullah Derici, Okay Koç, Tuðrul Tansuð, Ali Doðan Bozdað, Okay Nazlý Türk HPB Atatürk Eðitim ve Araþtýrma Hastanesi, 3. Genel Cerrahi Kliniði, ÝZMÝR Özet Amaç: Pankreas yaralanmalarýnda klinik ve cerrahi yaklaþýmlarýmýzý sunmak amaçlandý. Yöntem: Ýzmir Atatürk Eðitim ve Araþtýrma Hastanesi 3. Genel Cerrahi Kliniði'nde Ocak 1996 - Aðustos 2005 arasýnda travmatik pankreas yaralanmasý sebebiyle cerrahi tedavi gören 19 olgunun dosya kayýtlarý incelendi. Olgularda yaþ, cinsiyet, travmanýn þekli, taný yöntemleri, pankreasýn yaralanma yeri ve derecesi, eþlik eden organ yaralanmalarý, uygulanan cerrahi tedavi, morbidite ve mortalite deðerlendirildi. Bulgular: I. ve II. derece pankreas yaralanmasý olan oniki olguya hemostaz ve eksternal drenaj, III. derece yaralanmasý olan olgularýn üçüne distal pankreatektomi, birine Roux-en-Y pankreatikojejunostomi ile internal drenaj, IV. derece yaralanmasý olan olgularýn ikisine distal pankreatektomi, splenektomi, diðerine ise Roux-en-Y pankreatikojejunostomi ve tüp duodenostomi iþlemleri uygulandý. Ýzole pankreas yaralanmasý iki olguda (%11) tespit edilirken, 17 olguda (%90) yandaþ organ yaralanmalarý saptandý. Postoperatif dönemde yedi olguda (%37) 10 major morbidite geliþti. Dört olguda (%21) cerrahi mortalite görüldü. Sonuçlar: Karýn travmalarýnda pankreas yaralanmalarý az görülmekle beraber hayatý ciddi derecede tehdit eden, morbidite ve mortalitesi yüksek olan yaralanmalardýr. Yandaþ organ yaralanmalarý ve kanal hasarý varlýðý morbidite ve mortalitenin baþlýca sebepleri olarak görüldü. Anahtar kelimeler: pankreas yaralanmasý, travma, cerrahi tedavi Surgical Treatment in Pancreatic Trauma Summary Aim: We aimed to present our clinical and surgical approach towards pancreatic injury cases. Methods: Records of 19 patients with traumatic pancreas injury that underwent surgical treatment in Third Surgical Clinic of Atatürk Training and Research Hospital between January 1996 and August 2005 were reviewed retrospectively. Age, gender, type of trauma, diagnostic methods, site and grade of the injury, associated organ injuries, surgical treatment, rates of morbidity and mortality were the parameters that were evaluated. Results: Surgical treatment was hemostasis and external drainage for 12 cases with grade I and II pancreatic injuries. Considering grade III injuries, three patients received distal pancreatectomy and one case internal drainage with a Roux-en-Y pancreaticojejunostomy. As for the cases with grade IV injuries, two cases underwent distal pancreatectomy and splenectomy, and one case underwent Roux-en-Y pancreaticojejunostomy and duodenostomy procedures. Isolated pancreatic injury encountered in two patients (11%). Associated organ injuries were present in 17 patients (90%). Ten major morbidities developed in seven (37%) patients during the postoperative period. Four cases (21%) died in the early postoperative period. Conclusion: Pancreatic injury, although infrequently seen in abdominal trauma, is a serious condition with high morbidity and mortality rates. Associated organ injuries and ductal damage seem to be leading causes of morbidity and mortality. Key words: pankreatic injury, trauma, surgical treatment likle yüksek morbidite ve mortalite ile seyreder1-3. Bu çalýþmada, pankreas yaralanmasý sebebiyle cerrahi tedavi gören olgulara klinik yaklaþýmlarýmýzý sunmayý amaçladýk. Giriþ Son yýllardaki tanýsal ve giriþimsel radyolojik yöntemler, cerrahi teknikler, monitörizasyon, solunum ve beslenme desteðindeki geliþmelere raðmen, pankreas yaralanmalarý travmaya baðlý ölümler içerisinde önemli bir yer tutmaktadýr. Retroperitoneal yerleþimi, çevre organlar tarafýndan sarýlarak korunmuþ olmasý, travmatik yaralanmalarda taný güçlüðü, sýkça yandaþ organ yaralanmalarý ile birlikte görülmesi ve major vasküler yapýlara olan yakýn komþuluðu nedeniyle pankreas yaralanmalarý genelHayrullah Derici, 156 sok., No 5/13, Bornova, ÝZMÝR. Tel: (0232) 374 78 99 GSM: 0532 434 02 34 hayrullahderici@yahoo.com Gereç ve Yöntemler Ýzmir Atatürk Eðitim ve Araþtýrma Hastanesi 3. Genel Cerrahi Kliniði'nde Ocak 1996-Aðustos 2005 arasýnda travmatik pankreas yaralanmasý sebebiyle cerrahi tedavi gören 19 olgunun dosya kayýtlarý incelendi. Olgularda yaþ, cinsiyet, trav- 32 H Derici ve ark. Tablo 1. Olgularýn özellikleri Yaralanma nedeni Künt travma - Yüksekten düþme - Trafik kazasý - Darp Penetran travma - KDAY - ASY Taný yöntemleri Batýn USG Batýn BT Tanýsal periton lavajý Pankreas yaralanma derecesi I. derece II. derece III. derece IV. derece Tablo 2. Pankreas yaralanmasýna eþlik eden yandaþ organ yaralanmalarý Hasta sayýsý (%) Yaralanan organ Karaciðer Dalak Mide Böbrek Duodenum Diyafragma V. mesenterica sup. A. mesenterica sup. A. vertebralis Thoraks travmasý Ekstremite fraktürü Kafa travmasý 3 (%16) 2 (%11) 2 (%11) 9 (%47) 3 (%16) 10 (%53) 6 (%32) 7 (%37) 8 4 4 3 (%42) (%21) (%21) (%16) Hasta sayýsý (%) 5 5 4 3 2 2 2 1 1 2 1 1 ten düþme, ikisinde (%11) trafik kazasý ve diðer ikisinde (%11) darp idi. Anstabil hemodinami ve abdominal hassasiyet saptanan yedi olguda fizik muayene ile batýna nafiz yaralanma saptanmasý üzerine, diðer taný yöntemlerine baþvurmadan ameliyat kararý alýndý. Olgularýn 10'una batýn USG'si, altýsýna batýn BT ve yedisine TPL uygulandý. BT ile karýn içi serbest sývýyla birlikte, pankreasta hematom ve kontüzyon saptanan iki olguda ameliyat öncesi pankreas yaralanmasýndan þüphelenildi, 17 olguda ise taný ameliyat sýrasýnda kondu. Olgularýn sekizinde (%42) I., dördünde (%21) II., dördünde (%21) III. ve üçünde (%16) IV. derece yaralanma mevcuttu. Olgularýn yedisinde yaralanma pankreas baþýnda, sekizinde gövdede, dördünde kuyruk bölümündeydi. Olgularýn demografik özellikleri, yaralanma nedenleri, tanýsal yöntemler ve pankreas yaralanma dereceleri tablo 1'de görülmektedir. Ýzole pankreas yaralanmasý sadece iki olguda (%11) tespit edilirken, 17 olguda (%90) yandaþ organ yaralanmalarý saptandý. Bunlar karaciðer, dalak, mide, böbrek, mezenterik damarlar, diafragma, duodenum, vertebral arter yaralanmalarý idi. Yandaþ karýn dýþý yaralanmalar olarak iki olguda hemopnömotoraks, birer olguda ise frontal bölgede çökme fraktürü ve ekstremite fraktürü mevcuttu (Tablo 2). Karaciðer yaralanmasý olan olgulara primer sütür ile kanama kontrolü saðlandý. Dalak yaralanmasý olan beþ olgunun üçüne splenektomi, ikisine splenorafi, mide yaralanmasý olan beþ olguya primer tamir uygulandý. Böbrek yaralanmasý olan üç olgudan ikisine primer onarým, birine ise manýn þekli, taný yöntemleri, pankreasýn yaralanma yeri ve derecesi, eþlik eden organ yaralanmalarý, uygulanan cerrahi tedavi, morbidite ve mortalite deðerlendirildi. Pankreas yaralanmalarýnýn derecelendirilmesi Amerika Travma Cerrahisi Birliði tarafýndan bildirilen "Pankreatik Yaralanma Skalasý"na göre yapýldý4. Karýn yaralanmalarýnda ameliyat kararý; fizik muayene, vital bulgularýn deðerlendirilmesi, karýn ultrasonografisi (USG) ve bilgisayarlý tomografisi (BT), tanýsal periton lavajý (TPL) ve laboratuar bulgularýna göre verildi. Kesici-delici alet yaralanmalý (KDAY) tüm olgularda lokal anestezi ile yaralanmanýn batýna nafiz olup olmadýðý kontrol edildi. Tansiyon arteryal 90/50 mm Hg'nýn altýnda, nabýz 100/dk'nýn üzerinde, hematokrit deðeri %25'in altýnda olan olgular vital bulgularý stabil olmayan olgular olarak deðerlendirildi. III. ve IV. derece pankreas yaralanmalý tüm olgulara nazoenterik feeding tüpü ile postoperatif erken dönemde enteral beslenme uygulandý. Bulgular Olgularýn 16'sý (%84) erkek, üçü (%16) kadýn olup, yaþ ortalamasý 33 (11-44) idi. Olgularýn 12'sinde (%63) penetran, yedisinde (%37) künt travma mevcuttu. Travma nedenleri olgularýn dokuzunda (%47) KDAY, üçünde (%16) ateþli silah yaralanmasý (ASY), üçünde (%16) yüksek- 33 Pankreas Travmalarýnda Cerrahi Tedavi sýnýrlarda idi. Dört olguda (%21) cerrahi mortalite görüldü. Bu olgularýn üçünde ameliyat öncesi hemorajik þok tablosu mevcuttu ve postoperatif erken dönemde mortalite geliþti. Dördüncü olgu ise pankreatikoduodenal fistül ve abse sonrasý geliþen çoklu organ yetmezliði nedeniyle eksitus oldu. Ýntraperitoneal hemoraji nedeniyle erken dönem mortalite geliþen olgulardan birisi pankreasta ikinci derece yaralanma ile birlikte vertebral arter dallarýnda þiddetli kanamasý olan, diðeri pankreasta ikinci derece yaralanma ile birlikte sol böbrek ve dalakta yaralanma, diafragma rüptürü, frontal çökme fraktürü olan ve üçüncü olgu ise pankreasta üçüncü derece yaralanma ile birlikte süperior mezenterik arter ve ven yaralanmasý olan olguydu. Mortalite geliþen dördüncü olgu ise dördüncü derece pankreas ve beraberinde duodenal yaralanma nedeniyle tüp duodenostomi ve Roux-en-Y pankreatikojejunostomi uygulanan olgu idi. Yaralanmanýn derecesine göre uygulanan cerrahi giriþimler ve geliþen morbidite tablo 3'te, mortalite tablo 4'de görülmektedir. Olgularýn hastanede kalýþ süresi ortalama 14 gün (1-53) idi. Tablo 3. Morbidite geliþen olgular Morbidite Derece Atelektazi I Psödokist, Abse I Fistül I Fistül III Fistül, ABY* III Pankreatikojejunostomi Fistül, Abse IV Pankreatikojejunostomi Pankreatit IV Cerrahi giriþim Eksternal drenaj Eksternal drenaj Eksternal drenaj Distal pankreatektomi Distal pankreatektomi subtotal nefrektomi yapýldý. Diyafragma rüptürü olan iki olguya primer tamir, mezenterik vasküler yaralanmasý olan iki olgudan birinde superior mezenterik arter ve ven yaralanmasý, diðerinde sadece superior mezenterik ven yaralanmasý saptandý, her iki olguya da primer onarým uygulandý. Hemopnömotoraks saptanan iki olguya tüp torakostomi ile kapalý su altý drenajý, duodenum yaralanmasý olan iki olgudan birine tüp duodenostomi, diðerine duodenum dördüncü kýsým rezeksiyonu ve anastomoz uygulandý. Vertebral arter dallarýnda yaralanma olan olguda sütür ile hemostaz saðlandý. I. ve II. derece pankreas yaralanmasý olan oniki olguya hemostaz ve eksternal drenaj, III. derece yaralanmasý olan olgularýn üçüne distal pankreatektomi, birine Roux-en-Y pankreatikojejunostomi ile internal drenaj, IV. derece yaralanmasý olan olgularýn ikisine distal pankreatektomi, splenektomi, diðerine ise Roux-en-Y pankreatikojejunostomi ve tüp duodenostomi iþlemleri uygulandý. Postoperatif dönemde yedi olguda (%37) fistül, abse, psödokist, akut böbrek yetmezliði, atelektazi ve pankreatit gibi toplam 10 major morbidite geliþti. Pankreatik fistül geliþen dört olguda batýn dreninden gelen sývýda amilaz deðeri yüksek iken (5000, 12000, 16000, 30000 U/L) eþzamanlý ölçülen kan amilaz düzeyi normal Tartýþma Cerrahlar için sorunlu olabilen pankreas travmalarý, karýn travmalarýnýn %3 -12'sinde görülür ve yaralanmalarýn %65-90'ý penetran tiptedir1,3,5,6. Pankreas gövdesi, vertebral kolonun önünde yer almasý nedeniyle önden gelen künt travmalarda ezilme ya da kopma tarzýnda yaralanabilir. Son yýllarda emniyet kemerine baðlý bu tür yaralanmalar bildirilmektedir6. Fleming ve arkadaþlarý, literatürden farklý olarak, Melbourne'de penetran travmalarýn çok az görülmesinden dolayý, pankreas yaralanmalarýnýn büyük çoðunluðunun trafik kazalarýna baðlý görüldüðünü bildirmektedirler2. Tablo 4. Mortalite geliþen olgular Mortalite Kanama Kanama Kanama ÇOY* Derece II II III IV Yandaþ yaralanma A.vertebralis Böbrek, dalak, diafragma, kafa travmasý Superior mezenterik damarlar Duodenum *ÇOY: Çoklu organ yetmezliði 34 Cerrahi giriþim Eksternal drenaj Eksternal drenaj Distal pankreatektomi Pankreatikojejunostomi H Derici ve ark. Serimizde olgularýn %63'ünde penetran, %37'si künt travma mevcuttu. Karýn travmalarýnda taný amaçlý en sýk kullanýlan yöntem batýn USG'sidir. USG ile batýn içi sývý birikimleri kolayca tespit edilebildiði gibi, solid organlardaki laserasyon ve hematomlar da saptanabilir. BT ise, hemodinamik olarak stabil olgularda, nonoperatif tedavinin uygulanabildiði merkezlerde, batýn travmalý olgularda taný ve takip amacýyla kullanýlmakta olan bir yöntemdir1-3. BT, pankreas gibi spesifik organ yaralanmalarýnda da, yaralanmanýn derecesi ve kanama miktarý hakkýnda da bilgiler saðlar7. Ancak genel olarak USG ve BT, pankreas yaralanmalarýndan çok, batýn içi sývý ve eþlik eden yandaþ organ yaralanmalarý hakkýnda daha deðerli bilgiler verir8. TPL ise, travma skoru yüksek, anstabil olgularda daha sýk kullanýlan bir taný yöntemidir, ancak penetran yaralanmalarda taný deðeri sýnýrlýdýr1,3,7. Çalýþmamýzda anstabil hemodinami nedeniyle, yedi olguda sistemik ve lokal muayene sonrasý ameliyat kararý alýnýrken, ameliyat öncesi dönemde olgularýn 10'una (%53) USG ve altýsýna (%32) BT gibi radyolojik tetkikler yapýldý. Yedi (%37) olguya TPL uygulandý. Olgularýn sadece ikisinde pankreas yaralanmasýndan þüphe edildi ve 17 olguya taný ameliyat sýrasýnda kondu. Pankreas yaralanmalarýnda preoperatif dönemde serum amilaz deðerinin özgün ve duyarlý olmadýðý, dolayýsýyla yüksek serum amilaz deðerinin pozitif belirleyicilik deðerinin az olduðu, pankreas yaralanmasýnýn olmadýðý birçok hastada da görüldüðü bildirilmektedir6,9,10. Çalýþmamýzda künt ve penetran batýn travmasý nedeniyle acil cerrahi giriþim uygulanan olgulara ameliyat öncesi dönemde serum amilaz tetkiki yapýlmadý. Postoperatif dönemde pankreatik fistül geliþen üç olgunun dren sývýsýndan alýnan tetkikte amilaz deðerleri yüksek gelmesine raðmen, eþ zamanlý çalýþýlan serum amilaz deðerleri normal deðerde bulundu. Pankreas yaralanmalarý genelde ameliyat esnasýnda belirlenir, olgularýn çoðuna karýn içi kanama veya içi boþ organ yaralanmasý nedeniyle laparotomi uygulanýr2,3,6. Cerrahi tedavi þeklini belirleyen, morbidite ve mortaliteyi etkileyen en önemli nokta yandaþ organ yaralanmasý ve pankreatik kanal hasarýdýr1,3,6,11. Genel durumu uygun olan künt pankreas travmalý olgularda pankreatik kanalýn deðer- lendirilmesi için preoperatif dönemde endoskopik retrograd pankreatografi (ERP) uygulanmasýný öneren yazarlar vardýr12-14. ERP büyük merkezlerde bile her saatte uygulanabilen bir yöntem olmadýðý gibi, ameliyat öncesinde uygulanmasý teknik olarak güçtür. Bazý yazarlar15,16 ameliyat sýrasýnda ERP önermelerine raðmen, Jacobi ve arkadaþlarý iþlemin teknik olarak oldukça zor olduðunu, ameliyatta pankreasýn dikkatli inspeksiyon ve eksplorasyonunun yeterli olduðunu bildirmektedirler3. Duktal yaralanmanýn belirlenmesinde alternatif bir diðer iþlem, duodenotomi yaparak ampulla vateriden kanalý kateterize ederek görüntülemek olup, bu yöntem de oldukça tartýþmalýdýr4,17. Bu iþlemin en önemli avantajý duktal yaralanmayý net bir þekilde göstermesidir. Ancak duodenuma yönelik cerrahi giriþim gerektirmesi, basit pankreatik yaralanmalarýn kombine pankreatikoduodenal yaralanma þekline dönüþtürülmesi ve de postoperatif morbiditenin artmasý iþlemin dezavantajlarýdýr18. Pankreas kuyruðundan kanalý kateterize ederek ya da safra kesesinden kontrast madde vererek çekilen pankreatografilerde kanal hasarýný tespit etmek her zaman mümkün olmayabilir4. ERP'nin bir diðer kullaným yeri yaralanma sonrasý gecikmiþ bulgularla baþvuran olgularýn deðerlendirilmesindedir, geç dönemde psödokist ya da kronik pankreatit sebebiyle baþvuran olgularda kanal hasarýný ve derecesini belirlemede çok yararlýdýr2. Çalýþmamýzda eþlik eden yandaþ yaralanmalar ve anstabil hemodinami nedeniyle ameliyat öncesi ve esnasýnda hiçbir olguya pankreatografi uygulanmadý. Postoperatif ikinci ayda psödokist geliþen olguda kist, spontan regresyona uðradýðý için ERP'ye gereksinim duyulmadý. Pankreas yaralanmasý olan olgularýn %90'ýnda en az bir baþka organda da yaralanma vardýr3,5. En sýk yaralanan yandaþ organ karaciðerdir, bunu kolon ve ince barsak, büyük damarlar, duodenum, mide, dalak ve böbrek yaralanmalarýnýn eþlik ettiði bildirilmektedir2,5,19. Çalýþmamýzda yandaþ organ yaralanmasý oranýnýn %90 olduðu ve en sýk yaralanan yandaþ organlarýn karaciðer (%26), dalak (%26) ve mide (%21) olduðu görüldü. I. ve II. derece pankreas yaralanmalarýnýn cerrahi tedavisinde sadece hemostaz ve eksternal drenaj yeterlidir2-4,6,16,18. Kapsül ayrýlmýþ ise sütüre edilmemesi gerekir, çünkü pankreas sekresyonlarýnýn kapsül altýnda birikimi sonucu psödokist 35 Pankreas Travmalarýnda Cerrahi Tedavi oluþabilir2,3. Pankreasýn III. derece yaralanmalarýnda distal pankreatektomi tercih edilen bir ameliyat yöntemidir2-4. Kuyruða yakýn yaralanmalarda distal rezeksiyon en uygun tedavi yöntemi olarak belirtilmektedir3,4. Smego ve arkadaþlarý distal kanal yaralanmalarýnda dekompresyon yerine distal rezeksiyon uyguladýklarý olgularda mortalitenin %19'dan %3'e düþtüðünü tespit etmiþlerdir20. Çalýþmamýzda, I. ve II. dereceden yaralanmasý olan 12 olguya hemostaz ve eksternal drenaj, III. dereceden yaralanmasý olan olgularýn üçüne distal pankreatektomi, birine Roux-en-Y pankreatikojejunostomi uygulandý. Pankreasýn IV. derece yaralanmasýnda pankreatikojejunostomi veya distal rezeksiyon uygulanabilir3,6,11. Watt ve arkadaþlarý, pankreas baþýndaki yaralanmalarda internal drenaj yerine geniþletilmiþ distal rezeksiyonu tercih etmekte, böylece internal drenajýn morbiditesinden kaçýnýlacaðýný savunmaktadýr21. Acil þartlarda uygulanan pankreatikoduodenektominin %30'lara varan mortalitesi vardýr5,22. Pankreas'ýn nonfibrotik yapýsý ve safra kanallarýnýn normal çaplarýndan dolayý, erken dönemde fistül ve geç dönemde biliyer darlýk gibi ciddi komplikasyonlarý da beraberinde getirir. Major bir rezeksiyon %2 oranýnda gerekli olup, pankreas baþýnda kanal hasarý ile beraber olan duodenum, koledok, ampulla vateri yaralanmalarýnda ya da pankreas baþýndan kaynaklanan kontrol edilemeyen kanamalarda uygulanmalýdýr. Bu tip giriþimlerde kiþisel cerrahi deneyim yanýnda merkezin þartlarý da önemlidir4,18,23. Çalýþmamýzda Tip IV yaralanmalý olgulardan ikisine distal pankreatektomi, splenektomi, diðerine ise Roux-en-Y pankreatikojejunostomi ve tüp duodenostomi uygulandý. Pankreas yaralanmalarýnda morbidite %30-40 ve mortalite %5-30 arasýnda görülür1,4-6,19,23. Pankreatik fistül (%10-25), posttravmatik pankreatit (%10), kanama (%9), psödokist (%5), pankreas absesi (%5), intraabdominal sepsis (%2), malabsorbsiyon ve diabetes mellitus gibi ciddi komplikasyonlar oluþabilir2-4. Pankreatik fistüllerin tedavisi mümkün olduðunca konservatif olmalýdýr. Somatostatin ile fistül debisinin azaldýðý ve kapandýðý bir çok çalýþmada gösterilmiþtir4,6. Son yýllarda stentli ya da stentsiz, endoskopik sfinkterotomi yapýlarak baþarý saðlanmýþtýr18. Psödokist geliþen olgularda, Endoskopic retrograde cholan- giopancreatography (ERCP) ile pankreatik kanal yaralanmasý saptanýrsa lokalizasyona göre Rouxen-Y pankreatikojejunostomi veya distal pankreatektomi uygulanmalýdýr4,19. Olgularýmýzda en sýk görülen komplikasyon pankreatik fistül (%21) olup, genel morbidite oranýmýz %37'dir. Pankreas lojunda apse, atelektazi, kanama, akut böbrek yetmezliði, pankreatit ve psödokist görülen diðer komplikasyonlar idi. Erken mortalitenin en sýk sebebi eþlik eden major kanamalar ve sonrasý pýhtýlaþma bozukluðuna baðlý geliþen durdurulamayan kanamalardýr4. Çalýþmamýzda erken mortalite sebebi dört olgunun üçünde kanama, diðer olguda ise sepsis ve çoklu organ yetmezliðidir. Sonuç olarak karýn travmalarý içinde pankreas yaralanmalarý az görülmekle beraber hayatý ciddi derecede tehdit eden, morbidite ve mortalitesi yüksek olan yaralanmalardýr. Genel durumu bozuk, anstabil hemodinamik bulgularý olan olgular acilen ameliyata alýnmalýdýr. Pankreas travmalý olgularýn çoðunda, yandaþ organ yaralanmalarý sýkça görülür ve taný genelde ameliyat sýrasýnda konur. Bu nedenle ameliyatta dikkatli eksplorasyon ve gerekli cerrahi giriþim yapýlmalý ve yoðun bakým desteði saðlanmalýdýr. Kaynaklar 1. Bedirli A, Þakrak Ö, Sözüer EM, ve ark. Kompleks pankreas yaralanmalarýnda cerrahi yaklaþýmlar. Ulusal Travma Dergisi 2003;9:194-8. 2. Fleming WR, Collier NA, Banting SW. Pancreatic trauma: Universities of Melbourne HPB Group. Aust. N. Z. J. Surg 1999;69:357-62. 3. Jacobi T, Nagel M, Saeger HD. Verletzungen des Pankreas. Chirurg 1997;68:624-9. 4. Jurkovich GJ. The duodenum and pancreas. In: Trauma (Mattox KL, Feliciano DV, Moore EE, eds). 4th ed. McGrawHill, NewYork 2000:735-62. 5. Dalkýlýç G, Öncel M, Vural S, ve ark. Travmatik hastalarda Whipple prosedürü: üç olgunun analizi. Ulusal Travma Dergisi 1998;2:111-5. 6. Þirin F. Pankreas ve duodenum yaralanmalarý. In: Travma (Ertekin C, Taviloðlu K, Güloðlu R, Kurtoðlu M, eds). 1. Baský, Ýstanbul Medikal Yayýncýlýk, Ýstanbul 2005;921-8. 7. Yanar H, Güven H. Karýn travmalarýnda genel yaklaþým. Türkiye Klinikleri Cerrahi Dergisi 2004;3:205-11. 8. Kudsk KA, Temizer D, Ellison EC, et al. Post-traumatic pancreatic sequestrum: Recognition and treatment. J Trauma 1986;26:320-4. 9. Jones RC. Management of pancreatic trauma. Am J Surg 1985;150:698-704. 10. Takishima T, Sugimoto K, Hirata M, et al. Serum amylase level on admission in the diagnosis of blunt injury to the pancreas. Ann Surg 1997; 226:70-6. 11. Patton JH, Fabian TC. Complex pancreatic injuries. Surg Clin North Am 1996;76: 783-95. 36 H Derici ve ark. Gastrointest Endosc 1988;34:102-5. 18. Yalçýn O. Pankreatik ve duodenal yaralanmalar. In: Güncel Cerrahi Tedavi (Ergüney S, Çiçek Y, eds). 1. Baský, Avrupa Týp Kitapçýlýk, Ýstanbul 2001;929-34. 19. Kozak O, Uzar AÝ, Güleç B, et al. Ateþli silahlarla oluþan karýn yaralanmalarý. Türkiye Klinikleri Cerrahi Dergisi 1997;3:13948. 20. Smego DR, Richardson JD, Flint LM. Determinants of outcome in pancreatic trauma. J Trauma 1985;25:771-6. 21. Watt GM, Ozanne Smith J. Non-fatal injuries to young Victorians 1986-91. Med J Aust 1994;160:790-4. 22. Függer R, Kail M, Fritsch A. Trauma des biliopankreatischen Kompartiments. Chirurg 64:869-873. 23. Feliciano DV, Martin TD, Cruse PA, et al. Management of combined pancreatoduodenal injuries. Ann Surg 1987;205:673-80. 12. Clements RH, Reisser JR. Urgent endoscopic retrograde pancreatography in the stable trauma patient. Am Surg 1996;62:446-8. 13. Whittwell AE, Gomez GA, Byers P, et al. Blunt pancreatic trauma: Prospective evaluation of early endoscopic retrograde pancreatography. South Med J 1989;82:586-91. 14. Stone A, Sugawa C, Lucas C, et al. The role of endoscopic retrograde pancreatography (ERP) in blunt abdominal trauma. Am Surg 1990;56: 715-20. 15. Blind PJ, Mellbring G, Hjertkvist M, et al. Diagnosis of traumatic pancreatic duct rupture by on-table endoscopic retrograde pancreatography. Pancreas 1994;9:387-9. 16. Cirillo RL, Koniaris LG. Detecting blunt pancreatic injuries. J Gastrointest Surg 2002;6:587-98. 17. Barkin SJ, Ferstenberg RM, Panullo W, et al. Endoskopic retrograde cholangiopancreatography in pancreatic trauma. 37 Türk HPB 2006 Cilt 2 Sayý 1 Hepatic Retransplantation Susan M. Lerner Türk HPB Mount Sinai School of Medicine, New York, USA Summary Retransplantation is still the only alternative for patients with failing liver grafts. The most common causes for liver graft loss are primary non-function, hepatic artery thrombosis, and chronic rejection. The leading cause of retransplantation in children is hepatic artery thrombosis. Along with the improvements in the results of primary grafting, a comparable trend is noted with retransplantation outcomes. The multi-center 1-year survival after retransplantation is currently about 70%. Certain clinical criteria and models have been found to predict the outcome of retransplantation. The most important factors appear to be preoperative organ system failure as indicated by ventilator dependence and renal dysfunction. Donor cold ischemia time, recipient age, and preoperative bilirubin are also key factors in outcome prediction. Intervals between transplants of less than one week or greater than 30 days have been shown to be associated with improved survival. The overall impact of retransplantation on the survival of all patients awaiting liver transplantation and the cost-effectiveness of this procedure are issues of debate. For that reason, mathematical models based on key predictive factors are being developed. It is hoped that such models will identify that subset of patients awaiting retransplantation who will have survival and graft outcomes similar to those patients who have received their first graft. Despite the ethical and economic considerations, retransplantation is the only option for transplant patients whose grafts fail. Given those desperate situations, as well as the use of this operation as a salvage option for those with marginal livers, retransplants cannot and should not be abandoned. However, these decisions should proceed with some discretion. Retransplantation in subgroups of patients with little chance of successful outcome should likely be avoided. Various models have been developed that identify factors that influence survival and therefore are useful for identifying patients at high risk for poor outcome after retransplantation of the liver. These models should provide valuable information on which to base sound clinical judgment for the selection of candidates suitable and appropriate for retransplantation. Key words: primary non-function, chronic rejection, survival Karaciðer Retransplantasyonu Özet Greftin çalýþmadýðý karaciðer nakillerinde retransplantasyon halen tek seçenektir. Greft kaybýnýn en sýk nedenleri primer 'nonfunction', hepatik arter trombozu ve kronik rejeksiyondur. Çocuklarda retransplantasyonun en sýk nedeni ise hepatik arter trombozudur. Retransplantasyon sonuçlarýnda primer greft sonuçlarýndaki olumlu geliþmelere paralel bir durum mevcuttur. Çoðu merkezde retransplantasyon sonrasý 1 yýllýk saðkalým yaklaþýk %70 civarýndadýr. Retransplantasyon sonuçlarýnýn öngörülebilmesi için bazý klinik ölçüt ve metotlar geliþtirilmiþtir. En önemli etken ameliyat öncesi dönemde ventilatöre baðýmlýlýk ve böbrek iþlevlerinde bozukluk ile kendini gösteren organ yetmezlikleridir. Verici soðuk iskemi zamaný, alýcý yaþý ve ameliyat öncesi bilirubin deðeri, sonucun öngörülmesinde önemli ölçütlerdir. Bir haftadan az veya bir aydan uzun dönemde yapýlmýþ transplantlar ile uzun saðkalým arasýnda doðru iliþki olduðu gösterilmiþtir. Retransplantasyonlarýn nakil bekleyen tüm hastalar ele alýndýðýnda ortalama saðkalýma nasýl bir etkide bulunduðu ve yapýlan iþin maliyet-etkinliði tartýþmalý konulardýr. Bu bakýmdan, en önemli ölçütler üzerinden matematik modeller geliþtirilmektedir. Umulan, retransplantasyon hastalarýnda, ilk nakil yapýlanlardakine benzer bir saðkalým beklenecek alt grup hastalarýn belirlenebilmesidir. Etik ve mali sorunlara raðmen, retransplantasyon, grefti çalýþmayan hastalarda tek seçenektir. Umutsuz durumlarda ve sýnýrda karaciðerli hastalarda bu ameliyatýn bir kurtarma seçeneði olarak uygulandýðý da düþünüldüðünde, retransplantasyondan vazgeçilemez ve vazgeçilmemelidir. Ancak bu kararlar bir takdir sonucu alýnmalýdýr. Baþarý olasýlýðý düþük hastalarda uygulanmamalýdýr. Saðkalým üzerine etkenleri ortaya çýkaran modeller geliþtirilmiþtir ve baþarýsýz retransplantasyon açýsýndan yüksek risk grubundaki hastalarý belirlemede faydalýdýr. Bu modeller retransplantasyona uygun hastalarýn seçimini saðlam temellere oturtacak deðerli bilgiler verebilirler. The dramatic success of organ transplantation in the last 20 years has led to a growing imbalance in the number of patients awaiting transplantation and the number of organs available for that pur- pose. As a result, the process of prioritizing individual patients for organ allocation is constantly a source of debate. Nowhere is this issue more pressing than in the discussion of the appropriate 23 Hepatic Retransplantation with potential pitfalls, and the surgeon must pay particular attention during dissection of the liver and porta hepatis. Finally, this group of recipients, when compared to recipients of primary transplants, tends to be more critically ill at the time of retransplantation. Moreover, they are fully immunosuppressed. These factors combine to affect the patient and graft survival rates for retransplantation. A review of the Organ Procurement Transplant Network data registry reveals a 3-year survival of 60.3% versus 79.9% for primary liver transplant patients1. With increased health care costs and a finite number of available donors, serious financial and ethical issues are brought to bear regarding this procedure as well. Hospital charges are significantly higher and length of stay is longer for patients undergoing retransplantation3. Moreover, there is an obligatory net loss from the donor organ pool, affecting all other patients listed, particularly those waiting for a first transplant. Those patients who have not yet received their primary transplant tend to have a greater chance of survival and thus, in monetary terms, would appear to be a more economical use of limited resources4. Because of these clinical, financial, and ethical concerns, it has become imperative to study retransplantation in order to not only determine predictors of survival but also to develop potential models to maximize chances of overall patient survival. allocation of livers to patients with a failed first graft. During 2004, 6,168 liver transplants were performed in the United States; 1,856 people died waiting for a liver transplant; and yet 478 people received a repeat liver transplant1. Despite the success over the last decade in liver transplantation, patients who have undergone a first transplant can still experience graft failure technical problems and thus require retransplantation. Retransplants account for approximately 8-10% of all transplants performed in the United States per year1 While advances in immunosuppression have resulted in prolonged graft and patient survival, virtually all liver diseases that necessitate orthotopic liver transplantation can recur. When disease recurs, graft failure can ensue, often necessitating retransplantation2. Several approaches to salvaging failing grafts have been used, including complicated revascularization techniques and the use of prostaglandins or highly potent immunosuppressants. Unfortunately, in the absence of effective methods of extracorporeal support, hepatic retransplantation provides the only available option for patients in whom an existing graft has failed, regardless of the cause. Placing a second or even a third liver graft into a patient poses clinical, financial, and ethical challenges. From a technical point of view, retransplantation varies from primary liver transplantation in several significant ways. Revascularization of the graft can be complex, particularly if thrombosis is the etiology of the graft failure. The surgeon must procure vascular grafts for retransplantation and occasionally is required to take creative approaches to arterializing the organ. Given the development of adhesions, the recipient hepatectomy can be fraught Incidence The overall reported rate of retransplantation varies between 7 and 17%3-15, as illustrated in table 1. These rates have not remained constant over time. The University of Pittsburgh examined the rates of retransplantation and the etiologies of liver failure in those patients who were retransplanted over various periods. The time periods were set arbitrarily, covering 18 years of clinical activity: Era A accounted for all liver transplants (n=478) between 1981 and 1985; Era B covered transplants (n=1382) between 1986 to 1990; and Era C was comprised of those transplants (n=2140) that took place between 1991 to 1998. The overall rate of retransplantation declined significantly with the three time periods, starting at 33.4% in Era A, decreasing to 23.7% in Era B, and further Table 1. Incidence of retransplantation Author, Era, N Cases Retransplantation % 11 Powelson4 1983-91, 73 Azoulay3,14,15 1986-2000, 139 12 De Carlis5 1986-2000, 41 8.1 Kashyap6 1991-98, NA 13.4 Meneu Diaz12 1986-97, 122 12.6 Jimenez8 1986-99, 41 11.5 Dudek9 1989-2001, 6 7.0 Lerut10 1984-97, 54 14.5 Kumar11 1981-97, 72 9.1 Wong13 1987-94, 70 23 Markmann14 1984-96, 356 17 24 S. M. Lerner hyperacute rejection, and posttransplantation lymphoproliferative disease6,22 (Figure 1). However, just as the overall rate of retransplantation has changed over time, so have its indications. In a series of 114 patients retransplanted in Hanover, Germany, the major causes of retransplantation during the early 1980s were acute rejection and chronic rejection, each with an incidence of 27%23. By the late 1980's, acute and chronic rejection were no longer the dominant diagnoses associated with retransplantation. In a series of 356 retransplant operations performed at UCLA from 1984 to 1996, PNF was the predominant etiology of graft failure, occurring in 27.9% of all retransplantation cases22. The University of Pittsburgh identified this same trend. According to data from Pittsburgh's retrospective study of retransplantation over the last nineteen years, the rate of retransplantation for rejection at their institution has declined from 13.2% to 1%. The rate of retransplantation for hepatic artery thrombosis also declined from 8.1% to 3.8%. Conversely, the rate of retransplantation for primary non-function increased from 4.6% to 6.0%6. These trends in disease patterns are attributable in part to the improvement in donor organ preservation and in immunosuppression. Unfortunately, there has not been a similar decline in the rates of retransplantation for other disease processes15,22. Hepatic arterial thrombosis, for example, despite a low general incidence of 3% to 9%, remains a life-threatening problem once it occurs. Often, a patient diagnosed with hepatic artery thrombosis (HAT) has precious few options except for retransplantation and will have a hospital course characterized by markedly increased morbidity and mortality. Neuhaus et al. reviewed 7000 liver transplant cases that were performed in 15 transplant centers. The overall incidence of HAT was less than 5% but the patients' mortality rate, once diagnosed, was as high as 55% and the retransplantation rate reached 80%24. Fibrinolysis during angiography, surgical thrombectomy, or immediate vascular reconstruction have all been utilized, alone or together, in treating HAT. These approaches have had varying success rates, and in some circum- Figure 1. Diagnoses in patients undergoing retransplantation P=primary nonfunction D=delayed nonfunction H=hepatic artery thrombosis R=rejection B=biliary RD=recurrent disease Mi=miscellaneous (From Markmann JF, Markowitz JS, Yersiz H, et al. Long-term survival after retransplantation of the liver. Annals of Surgery 226(4), 1997) decreasing to 13.4% in Era C6. This decline likely reflects advancements made in the field of transplantation in general. Immunosuppression improved, technical skills advanced, and effective antiviral therapy was instituted. Compared to the adult population, pediatric patients have higher retransplantation rates. These rates are generally quoted to be between 15 to 29%16-20. Two specific considerations that pertain primarily to children - reduced-size grafts and hepatic artery thrombosis - are predisposing factors for the higher incidence of retransplantation in this population. Similar to the adult situation, new advances have tempered these rates of retransplantation. For instance, new microsurgical techniques of arterial reconstruction have decreased the incidence of hepatic artery thrombosis in children21. Indications Currently, the most common causes for hepatic graft loss and subsequent retransplantation are primary non-function, hepatic artery thrombosis, and chronic rejection. Recurrence of primary disease is the next most common etiology. Less frequent indications for retransplantation are acute rejection, biliary complications, portal vein thrombosis, 25 Hepatic Retransplantation stances, patients have been able to avoid retransplantation, reserving such an option instead for those patients with a nonfunctioning or deteriorating liver graft24. A diagnosis of primary non-function (PNF) is a diagnosis of exclusion made if a graft never shows evidence of initial function and this failure cannot be attributed to technical or other causes. The more stringent definition of PNF, used for allocation of a second organ, defines such graft dysfunction as occurring in the first week post transplant and leading to either retransplantation or eventual patient demise. The current practice of using "marginal" or extended livers as a way to mitigate the organ pool shortage has increased the risk of PNF25. Such organs are procured from higher risk donors based on demographic, clinical, laboratory, or histological data. When transplant centers first began using marginal grafts, desperate high-risk patients were usually the recipients. Not surprisingly, the placement of a marginal graft in the most critically ill of patients was often associated with dismal graft and patient survival. More recently, however, these grafts have been used in relatively healthier recipients, resulting in improved clinical outcomes. Nevertheless, these marginal organs still occasionally fail to work, and the practice of using extended liver grafts likely also accounts for the increased rate of retransplantation for PNF25. As seen in the review from the University of Pittsburgh, the higher rate of PNF has been associated with a rise in organs procured from donors over 50 years of age, which went from 1.5% of all organs used in era A (1981-85) to 3.3% of utilized organs in era B (1986-90) to 22.5% of the total in era C (1991-98)6. From an ethical perspective, the practice of retransplantation may indirectly expand the total donor pool by providing a safety net if the marginal organ does not function. More controversial than the use of marginal organs is the patient retransplanted for recurrent hepatitis B or hepatitis C. Chronic hepatitis B (HBV) is a common cause of advanced liver disease; the disease affects an estimated 1.25 million people in the United States and more than 300 million people worldwide. Liver transplantation is the treatment of choice for those patients who develop decompensated liver disease but historically was limited by high rates of hepatitis B virus reinfection and decreased patient survival. In addition, recurrent HBV resulted in rapidly progressive hepatic deterioration and extremely high mortality rates. However, with the advent of hepatitis B immunoglobulin (HBIg) and effective antiviral agents such as lamivudine, HBV recurrence has been significantly reduced. Patient and graft survival for HBV patients is now equivalent to that seen in patients with other indications for OLT, and these patients now represent a smaller percentage of those needing retransplantation26-29. A recent retrospective study from UCLA analyzed 166 patients who underwent transplantation from 1984 to 2001 for end-stage liver disease secondary to chronic HBV infection. Of the 23 patients requiring a second transplant, only six of them required retransplantation for recurrent HBV. Of these six, only one occurred in the group that had received combination prophylaxis. The other patients with recurrent HBV had received their initial transplant when such treatment was not yet available or when only monotherapy with either HBIg or lamivudine was used. The median time to retransplantation for recurrent HBV was 30.5 months26. The actual incidence of HBV recurrence for those recipients treated with combination prophylaxis at UCLA was 2.8%26. Although Figure 2. Frequency of retransplantation according to pretransplantation disease V=viral hepatitis A=alcohol abuse C=cholestatic disease M=metabolic B=biliary atresia F=fulminant failure H=hepatocellular cancer Mi=miscellaneous (From Markmann JF, Markowitz JS, Yersiz H, et al. Long-term survival after retransplantation of the liver. Annals of Surgery 226(4), 1997) 26 S. M. Lerner with immunosuppressive regimens, thus leading to premature graft loss, have also been proven false37. In all, this group of patients seems at no increased risk for retransplantation than the general transplant population. A diagnosis of recurrent autoimmune hepatitis (AIH) has also been believed to predispose a patient to retransplantation. Currently, liver transplantation for autoimmune hepatitis is highly successful, accounting for approximately 6% of all liver transplantation in the United States. However, according to a review by Sheiner et al., there is a high risk of rejection and of severe recurrent AIH. In their series, 32 patients underwent a transplant for AIH alone from 1988 to 1995. Among the 24 recipients with long-term follow-up, recurrence occurred in six of the 18 patients transplanted for chronic disease, but not a single one of the six patients who were diagnosed with fulminant AIH at the time of transplant developed recurrence. Furthermore, of the six who did develop recurrent AIH, only three required retransplantation, two of whom developed a subsequent re-recurrence. It would thus appear that recurrent AIH necessitating one retransplantation is the only identifiable risk factor for recurrence38. Although initially controversial, recurrence of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) has been reported by several centers. A study from the Mayo Clinic reports evidence of recurrent PSC in 24 out of 120 (20%) of transplanted patients, either by histologic or cholangiographic criteria. The mean time to diagnosis of recurrent disease was 421 days, and two of the patients ultimately required retransplantation39. Recurrence of PBC also is possible but the rate is uncertain. Currently, PBC recurrence seems to have little impact on longterm graft function and survival, but with longer follow-up, these patients may be found to develop additional problems40. significant benefit has been attributed to combination therapy, the optimal dosing schedule and regimen has not yet been established and logistic and economic factors, as well as potential induction of viral resistance, continue to plague the practice of transplantation for HBV. Hepatitis C (HCV), on the other hand, remains a more difficult disease to eradicate. End-stage liver disease secondary to HCV has become the most common indication for transplantation. Recurrence of HCV after transplant is nearly universal and its recurrence may lead to graft loss requiring retransplantation30-35. Unlike HBV, no therapy has been conclusively shown to alter HCV recurrence or disease progression30, but the natural history of post-transplant HCV infection is more indolent than that of recurrent HBV infection. Fewer than 10% of those patients who develop recurrent HCV will develop graft failure35. Among those recurrent HCV patients with graft failure, the majority of second transplants are performed for causes other than recurrent viral disease31, a situation analogous to that of recurrent HBV patients. Moreover, when retransplant survival is analyzed, there is little difference between patients whose etiology is recurrent HCV and those patients with other causes. Retransplantation should therefore be considered an important option in the treatment of recurrent HCV, but a careful selection process should be undertaken prior to decompensation25,33. Recurrence of any primary liver disease is actually only responsible for a small percentage of those patients undergoing retransplantation. In the UCLA series, recurrent disease accounted for only 3.6%22 (Figure 2). Even when accounting for specific disease processes, recurrent disease, other than in historical HBV studies, plays a minor role in retransplantation. Alcoholic liver disease (ALD), for example, is the second most common cause of liver failure leading to transplantation. Multiple studies have looked at recidivism rates and recurrent disease. ALD recipients use alcohol after their transplants at a similar rate as non-ALD recipients, but those with ALD may consume more alcohol when drinking36. In addition, earlier arguments which suggested that alcohol recidivism would lead to poor compliance Results of Retransplantation Early studies in liver transplantation showed significantly worse patient and graft survival after retransplantation when compared to primary 27 Hepatic Retransplantation Figure 3. Results of retransplantation % survival vs. years post transplant22 vival rates for these patients in the UCLA series was 64% for the group retransplanted greater than 30 days after first transplant, versus 58% for those retransplanted less than 1 week of primary transplant and 42% for those retransplanted between 8 and thirty days after initial grafting22. This finding emphasizes the need for early recognition of patients who require retransplantation, especially those who require second grafts for PNF or HAT. Other studies make the distinction in timing in more general terms, as urgent versus elective retransplantation. In these studies, the elective group, often corresponding to those retransplanted many months after the primary transplant, had survival curves indistinguishable from those of the single transplant group. The urgent group, likely corresponding to those in need of retransplant within the first 30 days after surgery, had worse survival. Moreover, their primary graft failure is more likely to be secondary to PNF, and these patients were more likely to incur higher hospital charges and longer length of stay3. While the operations performed in the urgent group may be easier from a technical point of view, the poor clinical condition prior to retransplantation ultimately predisposes the recipient to higher mortality rates5. transplants (68.5% versus 49%)23,41. During the next decade, the general results of liver transplantation improved and many centers are now reporting 1-year survival greater than 75%1. More specifically, similar trends can be seen with retransplantation, although these outcomes remain significantly worse than that of first-time recipients. In a retrospective study at UCLA, a total of 356 retransplants in 299 patients performed from 1984 to 1996 were analyzed. Survival of retransplanted patients at 1, 5, and 10 years was 62%, 47%, and 45% respectively. This survival is significantly less than that seen in patients undergoing primary hepatic transplantation at the same center during the same period (83%, 74%, and 68%)22. (Figure 3) A similar differential has been demonstrated at other centers3,6,10-12,15,42. While the retransplant recipient has a poorer prognosis than the first-time recipient does, several recent studies have indicated that these outcomes can be reliably predicted and even modeled. Several clinical criteria, including timing of the retransplant, can predict the mortality of patients after retransplantation3,15,22,25,42. Timing of Retransplantation The timing of retransplantation has an important role in both patient and graft outcome4,15,22. Patients retransplanted more than 30 days after their initial transplant fared better than those retransplanted between eight and 30 days after receiving their first liver; and the survival in patients transplanted within 1 week of primary transplant was nearly equivalent to that seen in the chronic group22. The respective 1-year sur- Causes of Death The development of sepsis and multiorgan failure accounts for the majority of deaths in the retransplanted patients. In addition, the largest proportion of deaths occur in the first four weeks after transplant11,13,15,22,42. The incidence of death secondary to sepsis in the UCLA series was significantly higher in retransplanted patients compared to 28 S. M. Lerner Figure 4. Survival by risk score - survival vs. years post transplantation43 those receiving just one graft (60.7% versus 29%)22. In those retransplanted patients for whom sepsis was the primary cause of death, there was a striking incidence of fungal infection, nearly 50%22. A high incidence of graft loss due to sepsis, in retransplanted patients has also been reported by others5,8,15,42. This increased incidence of sepsis may reflect the higher cumulative dose of immunosuppression in retransplanted patients. Collectively, these studies suggest that interventional strategies should be designed to reduce immunosuppression or to initiate more effective antimicrobial prophylaxis for patients undergoing retransplantation5,22. Whether the apparent "over immunosuppression" of retransplanted patients is also reflected in lower rejection rates remains to be determined. Less frequent causes of death in retransplant patients include technical problems such as arterial and portal vein thrombosis, brain damage and intracerebral hemorrhage, recurrent cholangiocarcinoma, intraoperative mortality, and persistent liver failure11,13. retransplantation functions as a backup option when marginal donors are utilized, eliminating retransplants would inhibit these much needed efforts to expand the organ pool15. In an attempt to optimize the use of valuable organs, many have sought to develop a model that might accurately predict outcome and survival in patients undergoing liver retransplantation. A multivariate analysis was performed at UCLA on a cohort of patients to determine independent risk factors predictive of poor patient survival in retransplantation. Donor cold ischemia time greater than 12 hours, preoperative mechanical ventilator requirement, age greater than 18 years, preoperative serum creatinine greater than 1.6 mg/dl and preoperative serum total bilirubin greater than 13 mg/dl were all independently predictive of a patient's poor outcome22. Similar findings have been described from research out of the University of Pittsburgh. They identified three other significant factors: donor age, donor gender, and type of primary immunosuppression15. A recent study at Mount Sinai Medical Center also looked at predictors of mortality in retransplant patients and found that recipient age greater than 50 years, a preoperative creatinine greater than 2 mg/dl, and the use of intraoperative blood products had a significant impact upon survival in those patients requiring late retransplantation more than 6 months after primary transplant42. The critical shortage of donor organs and the increasing waiting periods before transplantation have prompted many to not only investigate the preoperative factors predictive of poor outcome but also to define a mathematical model that adequately predicts survival after retransplantation. Analy- Selection of Patients for Retransplantation The only therapeutic option for patients with a failing liver allograft is retransplantation. All the studies demonstrate quite conclusively however, that there is worse patient and graft survival after retransplantation when compared to primary grafting22. These poorer outcomes have prompted many to question the appropriateness of hepatic retransplantation on both economic and ethical grounds. Conversely, prohibiting retransplantation would raise its own ethical questions regarding patient abandonment. Moreover, since 29 Hepatic Retransplantation zing the UCLA data, a mathematical model based on five noninvasive and readily available clinical parameters was created. A complex Cox regression equation was simplified into what has been called the UCLA Risk Classification System. This system groups patients into five classes based on a 5-point scoring system. A single point is received for each of the following parameters: age greater than 18 years, organ cold ischemia time greater than 12 hours, preoperative mechanical ventilator requirement, total bilirubin greater than 13 mg/dl, and creatinine greater than 1.6 mg/dl. Patients scoring a 4 or 5 out of a possible 5 points had a 1-year survival of approximately 27% when using the UCLA patient database. The survival of patients scoring 4 or 5 was significantly less than the 67% 1-year survival seen in patients with a risk class of 3 or less (Figure 3). When applied retrospectively to three other databases (UCLA, Baylor University Medical Center, and the UNOS registry), this risk classification system adequately discriminated high-risk / low-survival patients. By utilizing this type of model as part of the selection process, survival after retransplantation should theoretically improve, as well as the efficiency of organ utilization43. A final approach to improving the outcome of retransplantation is modification of the underlying cause of graft failure. An aggressive approach to HAT with early detection and revascularization can reduce the need for retransplantation. If a second graft is still required, the operation should be performed before the patient deteriorates significantly. For cases of PNF, the most common cause of early retransplantation, it is hoped that work currently underway may decrease the incidence of this diagnosis. Improving organ preservation, developing better methods to predict graft viability, and developing salvage therapy regimens for marginal grafts, such as prostaglandin use, all may help to decrease the need for retransplantation. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. References 1. 2. 3. 4. 23. Based on OPTN data as of May 30, 2003. Rosen H. Disease recurrence following liver transplantaion. Clinics of Liver Disease 2000;4:675-89. Azoulay D, Linhares M, Huguet E, et al. Decision for retransplantation of the liver: an experience- and cost-based analysis. Annals of Surgery 2002;236:713-21. Powelson J, Cosimi A, Lewis W, et al. Hepatic retransplantation in New England a regional experience and survival model. 24. 25. 30 Transplantation 1993;55:802-6. De Carlis L, Slim A, Giacomoni A, et al. Liver retransplantation: Indications and results over a 15-year experience. Transplantation Proceedings 2001;33:1411-3. Kashyap R, Jain A, Reyes J, et al. Causes of retransplantation after primary liver transplantation in 4000 consecutive patients: 2 to 19 years follow-up. Transplantation Proceedings 2001;33:1486-7. Meneu Diaz J, Moreno Gonzalez E, Vicente E, et al. Early mortality in liver retransplantatio: a multivariate analysis of risk factors. Transplantation Proceedings 2002;34:301-2. Jimenez M, Turrion V, Alvira L, Lucena J, Ardaiz J. Indications and results of retransplantation after a series of 406 liver transplantations. Transplantation Proceedings 2002;34:262-3. Dudek K, Nyckowski P, Zieniewicz K, et al. Liver retransplantation: indications and results. Transplantation Proceedings 2002;34:638-9. Lerut J, Laterre P, Roggen F, et al. Adult hepatic retransplantatio. UCL experience. Acta Gastroenterologica Belgica 1999;62:261-6. Kumar N, Wall W, Grant D, et al. Liver retransplantation. Transplantation Proceedings 1999;31:541-2. Meneu Diaz J, Vicente E, Moreno Gonzalez E, et al. Indications for liver retransplantation: 1087 orthotopic liver transplantation between 1986 and 1997. Transplantation Proceedings 2002;34:306. Wong T, Devlin J, Rolando N, Heaton N, Williams R. Clinical characteristics affecting the outcome of liver retransplantation. Transplantation 1997;61:878-81. Sanchez-Bueno F, Acosta F, Ramirez P, et al. Incidence and survival rate of hepatic retransplantation in a series of 300 orthotopic liver transplants. Transplantation Proceedings 2000;32:2671-2. Doyle H, Morelli F, McMichael J, et al. Hepatic retransplantation an analysis of risk factors associated with outcome. Transplantation 1996;61:1499-505. Achilleos O, Mirza D, Talbot D, et al. Outcome of liver transplantation in children. Liver Transplantation and Surgery 1999;5:401-6. Newell K, Alonso E, Millis J, et al. Retransplantation for failed hepatic allografts in children. Transplantation Proceedings 1997;29. Newell K, Millis J, Bruce D, et al. An analysis of hepatic retransplantation in children. Transplantation 1998;65:1172-7. Hamada H, Valayer J, Gauthier F, Yandza T, Takahashi H. Liver retransplantation in children. Journal of Pediatric Surgery 1995;30:705-8. Deshpande R, Rela M, Girlanda R, et al. Long-term outcome of liver retransplantation in children. Transplantation 2002;74:1124-30. Shakleton C, Goss J, Swenson K, et al. The impact of microsurgical hepatic arterial reconstruction on the outcome of liver transplantation for congenital biliary atresia. American Journal of Surgery 1997;5:431-5. Markmann J, Markowitz J, Yersiz H, et al. Long-term survival after retransplantation of the liver. Annals of Surgery 1997;226:408-20. Fangmann J, Ringe B, Hauss J, Pichlmayr R. Hepatic retransplantation: The Hanover experience of two decades. Transplantation Proceedings 1993;25:1077. Stange B, Glanemann M, Nuessler N, Settmacher U, Steinmuller T, Neuhaus P. Hepatic artery thrombosis after adult liver transplantation. Liver Transplantation 2003;9:612-20. Biggins S, Beldecos A, Rabkin J, Rosen H. Retransplantation for hepatic allograft failure: Prognostic modeling and ethical considerations. Liver Transplantation 2002;8:313-22. S. M. Lerner suppression. Transplantation Proceedings 1998;30:1740-1. 35. Rosen H, Martin P. Hepatitis C infection in patients undergoing liver retransplantation. Transplantation 1998;66:1612-6. 36. Bravata D, Olkin I, Barnato A, Keefe E, Owens D. Employment and alcohol use after liver transplantation for alcoholic and nonalcoholic liver disease: A systematic review. Liver Transplantation 2001;7:191-203. 37. Pageaux G, Michel J, Coste V, et al. Alcoholic cirrhosis is a good indication for liver transplantation, even for cases of recidivism. Gut 1999;45:421-6. 38. Reich D, Fiel I, Guarrera J, Emre S, Guy S, Schwartz M, Miller C, Sheiner P. Liver Transplantation for autoimmune hepatitis. Hepatology 2000;32:693-700. 39. Graziadei I, Wiesner R, Batts K, et al. Recurrence of Primary Sclerosing Cholangitis following liver transplantation. Hepatology 1999;29:1050-6. 40. Neuberger J. Recurrent Primary Biliary Cirrhosis. Liver Transplantation 2003;9:539-46. 41. Shaw B, Gordon R, Iwatsuki S. Hepatic retransplantation. Transplantation Proceedings 1985;17:264. 42. Facciuto M, Heidt D, Guarrera J, et al. Retransplantation for late liver graft failure: predictors of mortality. Liver Transplantation 2000;6:174-9. 43. Markmann J, Gornbein J, Markowitz J, et al.A simple model to estimate survival after retransplantation of the liver. Transplantation 1999;67:422-30 26. Anselmo D, Ghobrial R, Jung L, et al. New era of liver transplantation for hepatitis B: a 17-year single-center experience. Annals of Surgery 2002;235:611-20. 27. Ishitani M, McGory R, Dickson R, et al. Successful retransplantation for recurrent posttransplant hepatitis B virus infection in the primary allograft. Transplantation Proceedings 1996;28:1714-6. 28. Ishitani M, McGory R, Dickson R, et al. Retransplantation of patients with severe posttransplant hepatitis B in the first allograft. Transplantation 1997;64:410-4. 29. Roche B, Samuel D, Feray C, et al. Retransplantation of the liver for recurrent hepatitis B viurs infection the Paul Brousse experience. Liver Transplantation and Surgery 1999;5:166-74. 30. Rosen H. Retransplantation for hepatitis C: implications of different policies. Liver Transplantation 2000;6:41-6. 31. Ghobrial R. Retransplantation for recurrent hepatitis C. Liver Transplantation 2002;8:38-43. 32. Berenguer M, Prieto M, Palau A, et al.Severe recurrent hepatitis C after liver retransplantation for hepatitis C virus-related graft cirrhosis. Liver Transplantation 2003;9:228-35. 33. Ghobrial R, Farmer D, Baquerizo A, et al. Orthotopic liver transplantation for hepatitis C: Outcome, effect of immunosuppression, and causes of retransplantation during an 8-year single-center experience. Annals of Surgery 1999;229:824-33. 34. Ghobrial R, Colquhoun S, Rosen H, et al. Retransplantation for recurrent hepatitis C following tacrolimus or cyclosporine immuno- 31 Türk HPB 2006 Cilt 2 Sayý 1 Assessment of Pediatric Liver Transplant Recipients Türk HPB Þükrü Emre Mount Sinai School of Medicine, New York, USA Summary Liver failure due to chronic liver disease and the need for liver transplantation is a serious health problem in the pediatric age population. Besides hepatitis, the most frequent causes of liver failure in this age group are congenital and metabolic diseases. The most important aspect is to enable these children to return to a healthy and active life before serious complications and growth retardation occurs. In order to achieve this goal, timely referral of these children by their hepatologists to liver transplantation centers is necessary. Keywords: living donor, pediatric liver transplantation, recipient assessment Pediatrik Karaciðer Nakli Alýcýlarýnýn Deðerlendirilmesi Özet Kronik karaciðer hastalýklarý sonucu geliþen karaciðer yetmezliði ve organ nakli gereksinimi çocuklarda da oldukça önemli bir problemdir. Yaygýn görülen hepatit vakalarý yaný sýra doðmalýk ve metabolik sorunlar en sýk görülen nedenlerdir. Önemli olan ciddi komplikasyonlar ve büyüme-geliþme geriliði oluþmadan çocuðu saðlýklý ve aktif yaþama döndürmektir. Bu nedenle bu hastalarý takip eden hepatologlarýn hastalarý zamanýnda karaciðer nakli merkezlerine sevki baþarý için þarttýr. Liver transplantation has revolutionized the care of children and adults with end-stage liver disease. Transplantation has become a widely accepted therapeutic modality for irreversible acute and chronic liver diseases. The results with liver transplantation have improved considerably over time with advances in operative techniques, immunosuppression and post-operative care. The emphasis now is on improving the quality of life after liver transplantation as patient and graft survival rates are over 80% in several centers world-wide1. This chapter will focus on essential issues that need to be addressed before a child can be listed for liver transplant. Who should be referred for liver transplant? What are the contraindications to transplantation? What assessment is necessary before listing for liver transplant? How much time does assessment take? When should the transplant be done? What is unique in pediatric liver transplantation? If there is combined transplant, which organ should be first? What is different when the living donor option is available? Þükrü Emre, Mount Sinai School of Medicine One Gustave L. Levy Place, Box 1104, New York, NY 10029 Tel: 212-659-8060, email: Sukru.Emre@msnyuhealth.org Who should be referred for liver transplant? Historically, children with acute liver failure and those with progressive liver dysfunction with coagulopathy and/or complications of cirrhosis have been referred for transplant evaluation. With improving results, the trend is moving towards referral before irreversible complications develop especially in the setting of metabolic diseases, liver tumors and viral hepatitis. The indications for liver transplant in children are listed in (Table 1). Children should be referred for transplant evaluation sooner rather than later as it allows adequate time for making the correct diagnosis, opportunity for appropriate medical therapy of underlying disease or associated complications, improvement of nutritional status, setting up of help in cases with social/financial difficulties and allow education of family members. This also facilitates the best outcome in a given situation. The pediatrician should be clear that early referral does not necessarily mean immediate trans- 17 Assessment of Pediatric Liver Transplant Recipients Table 2. Laboratory blood tests to be done during liver transplant assessment Table 1. Indication for pediatric liver transplant • Cholestatic conditions - Extrahepatic biliary atresia - Alagille syndrome/non syndromic paucity of bile ducts - Sclerosing cholangitis - TPN associated cholestasis (especially in the setting of short gut) - Bile acid transport/synthetic defects - Idiopathic cholestasis • Fulminant liver failure • Autoimmune hepatitis • Metabolic liver disease - Wilson's disease - Alpha-1-antitrypsin deficiency - Tyrosinemia - Hyperoxaluria - Urea cycle defects - Cystic fibrosis - Glycogen storage disease - Criggler- Najjar syndrome - Neonatal hemochromatosis • Miscellaneous - Hepatoblastoma - Hepatocellular carcinoma - Hepatitis C - Cryptogenic cirrhosis - Congenital hepatic fibrosis - Langerhan cell histicytosis • Type and screen • Serologies - HIV - Hepatitis A, B, C - CMV IgG for children > 1yr - Urine shell vial culture <1 yr - EBV IgG and IgM - Toxoplasma IgG - Varicella IgG - MMR IgG - RPR, HSV in select cases • Disease specific - Hepatitis B HBVDNA, HBeAg, HBeAb, delta ab, AFP - Autoimmune hepatitis/sclerosing cholangitis ANA, SMA, LKM, IgG, ANCA - Alpha 1 antitrypsin phenotype - Wilson disease Ceruloplasmin, 24 hr urine copper - Metabolic: glucose, blood gas, lactate, ammonia, pyruvate, urinary organic acids including succinyl acetone, serum aminoacids, alphafetoprotein, acyl carnitine profile in select cases - Neonatal hemochromatosis: ferritin, iron studies, salivary gland biopsy, MR pancreas - Malignancy: CA 19 - Cholestasis: serum bile acids • Procoagulant screen in select cases extra-hepatic metastasis that cannot be eradicated with medical therapy is considered a contraindication to effective transplantation. In children with inborn errors of metabolism, the developmental and neurological status should be adequate, as existing neurological deficits will not be cured by liver transplant. Another contraindication to transplantation is ongoing non-adherence to medical treatment, drug/alcohol addiction. Terminal progressive systemic disease is also a contraindication to transplantation. plant and that given the current organ shortage world-wide, organ allocation is being directed towards those who need it most. What are the contraindications for liver transplant? There are few absolute medical or surgical contraindications to liver transplantation. Children with uncontrolled systemic infection are not candidates for liver transplant as they will not be able to tolerate high-dose immunosuppression. The cardiac and pulmonary function should be sufficient to tolerate major surgery. Absence of a viable splanchnic venous inflow system is the most commonly encountered surgical contraindication to transplant2. While thrombosis of the main portal vein can be successfully bypassed, if the entire portal system is occluded, attempts at transplantation have rarely been successful3,4. In cases of liver tumors like hepatoblastoma, any What assessment is necessary before listing a child for transplant? First, extensive laboratory blood tests need to be done as detailed in table 2. Diagnostic studies like chest X-ray, echocardiogram, abdominal sonogram with Doppler should be performed in all candidates. Further imaging would depend on the clinical circumstances. For 18 Þ. Emre example, magnetic resonance imaging of the vascular system is indicated in cases when thrombosis is identified in any vessel. Upright oxygen saturation should be measured in all children with cirrhosis to rule out hepatopulmonary syndrome. Macroaggregated albumin scan would be indicated in a child with hepatopulmonary syndrome to quantify the degree of shunt. In children with suspected mitochondrial disease, procedures like muscle biopsy and magnetic resonance spectroscopy may need to be performed to establish diagnosis and to determine the distribution of affected tissues. CT scan of the head to rule out cerebral edema may be necessary in children with encephalopathy. Intracranial pressure monitoring may also be needed in selected cases. The child should be seen at the initial consultation by the pediatric hepatologist and the liver transplant surgeon. The transplant coordinator can then schedule the necessary investigations. All children should be assessed by the infectious disease team and given appropriate immunization as needed. Complete cardiac evaluation is also necessary. Further consultation should be organized depending on clinical need. The social worker should meet the family and relevant insurance/psychosocial issues should be addressed. The end of the transplant assessment should establish a relationship between the patient and the transplant team. A mechanism for contacting parents should be in place. Educational material regarding transplantation should be provided. An opportunity to visit to the intensive care unit and talk to families of other patients who have undergone liver transplant provided if necessary. A plan for interim medical care until the transplant is performed should be formulated, with special attention to address nutritional issues. How much time does assessment take? This depends on the clinical situation. In our unit at Mount Sinai Medical Center, standard evaluation in non-urgent situations is done over 2-3 days. This can take longer in complicated cases when additional consultations and investigations are needed. In fulminant liver failure, when speed is of the essence, evaluation can be completed within 24 hours. When should the transplant be done? This can sometimes be difficult to answer and the answer may differ in various centers around the world. Biliary atresia is the most common indication for pediatric liver transplant. Infants who present after a Kasai portoenterostomy have a combination of recurrent cholangitis, progressive portal hypertension with ascites, hypersplenism, Table 3. Score indicating need for a liver transplant assessment. A score of 10 or more indicates the need for assessment for liver transplantation Indication Portal hypertension score Splenomegaly* must be present Varices present Varices bleed requiring blood transfusion once or twice Variceal bleed >twice or single lifethreatening bleed ¶ Ascites Albumin <30 g/L Prothrombin time >19 secs WBC <4 x 10/1 Platelets <100 x 10/1 Body mass index <16 Mid-arm circumference <5th centile * splenomegaly to be assessed by ultrasound scan ** only one item to be score ¶ Patient in shock or requiring transfusion of 20 ml/kg or more Adapted from Noble-Jamieson et al., JR Scoc Med 1996, 89: 31-37 19 4* 8** 10** 6 2 2 2 2 6 6 Assessment of Pediatric Liver Transplant Recipients development are areas that need special consideration. Children with chronic cholestasis are extremely malnourished. Strong nutritional support is needed with naso-gastric tube feeds and/or total parenteral nutrition in extreme cases. Supplementation of fat soluble vitamins particularly Vitamin K must be done. Outcome after liver transplant is better when the nutrition is optimal as this allows quicker wean off the ventilator post-transplant and shortens intensive care stay and attendant complications. Metabolic defects usually present in infancy for the first time and it is important to distinguish those that can be fully corrected by liver transplantation for example urea cycle defects from others like methymalonic aciduria where results are not uniformly good in spite of combined liver/kidney transplants. Irreversible neurological deficits can be difficult to diagnose in small children and appropriate imaging and neurological consultation should be done in relevant clinical circumstances. In cases with acute liver failure, where there is a possibility of mitochondrial deficits, appropriate investigations like muscle biopsy and MRSpec should be done. Baseline neurological status should be established. Parents should be counseled that while liver transplantation replaces mitochondria in the liver; long term outcome after transplant would depend on mitochondrial function in the rest of the body. Since there is a wide spectrum of mitochondrial disease, it is difficult to predict how the neurological function will evolve given current levels of knowledge. Liver transplant should only be undertaken as a life saving procedure with full informed consent of family. Neonatal hemochromatosis is a condition that must not be overlooked especially when dealing with neonatal liver failure. The anti-oxidant cocktail infusion should be continued as the transplant workup is in progress8. Transplantation for viral hepatitis is unusual in children, while it is one of the more common indications in adults. In children when liver transplant is needed for hepatitis C, the goal should be to eliminate the HCV with medical treatment before liver transplant. In general, recurrence of the disease that led to the need for liver transplant is a less common problem in pediatrics compared to adults. This is because the vast majority of pediatric patients are transplanted for biliary atresia and acute liver failure. In adults, the majority of liver trans- gastrointestinal hemorrhage, malnutrition and progressive hepatic synthetic liver failure5. Most children with failed Kasai require liver transplantation within the first year or two of life. Two thirds of those with successful bile drainage may still develop cirrhosis with stigmata of portal hypertension and require transplantation later in childhood when synthetic function begins to deteriorate as evidenced by prolonged INR and low albumin. In children with inborn errors of metabolism, for example, urea cycle defects liver transplant is indicated to provide enzyme replacement. The current strategy is to do the liver transplant in the first year of life before repeated metabolic decompensations can cause irreversible neurological deficits. In fulminant liver failure, the goal is to transplant as soon as possible. In cases where mitochondrial deficit is suspected, the decision to transplant can be a difficult one to make. It is important to perform all the necessary investigations including MRSpectroscopy and muscle biopsy to make/rule out diagnosis. Then, it is essential to explain to the family, that while the liver transplant can save the life of the baby, the long-term neurological outcome is variable. Liver transplant should only be performed after full counseling and informed consent of the family. In the setting of chronic liver disease with cystic fibrosis, patient selection and timing of transplant are critically important for a good outcome. Noble-Jamieson et al.6, devised a simple scoring system that can be used as a guide to suggest when a child with cystic fibrosis should be referred to a transplant center (Table 3)7. Liver transplantation in cystic fibrosis should be performed before severe decompensation. Colonization with organisms like multi-resistant pseudomonas aeroginosa or aspergillosis carries a high risk of severe and often lethal postoperative infections. Their presence can constitute a contraindication in such patients. Pretransplant management of portal hypertension with a porto-systemic shunt procedure should be considered in those with well preserved synthetic liver function. What is unique in pediatric liver transplantation? Growth and development especially neurologic 20 Þ. Emre plants are due to hepatitis C where the recurrence rate is high; also there is a considerable recurrence rate for hepatocellular carcinoma, nonalcoholic steatohepatitis, primary biliary cirrhosis and autoimmune hepatitis. function as indicated by pulmonary function tests, then isolated liver transplant can be undertaken. The scoring system outlined above in table 3 can be utilized as a guideline. Care must be taken to ensure there is no colonization with multi-resistant organisms. If there is combined transplant, which organ should be first? What is different when the living donor option is available? This is a complex issue and the answer depends on the organs involved, examples of some commonly encountered situations in our center are described below. Generally speaking, in cases of short gut with TPN associated cholestasis; usually combined liver and small bowel transplants are performed. In selected cases, where there is sufficient functional small bowel; liver transplant can be performed first with the understanding that small bowel transplant may need to be performed subsequently. We have one ex-premature baby in our center that is post liver transplant and is now stable more than a year after transplant successfully weaned off TPN in the first few weeks after transplant. In cases of immunodeficiency where bone-marrow transplant and liver transplant are needed, the present consensus is to perform the liver transplant first and then the bone marrow transplant. With metabolic problems, the trend is changing with conditions like hyperoxaluria. Previously, isolated kidney transplants were done; but then graft failure and systemic oxalosis was noted in a large proportion of cases, as the defective enzyme was not replaced9. Then, combined liver and kidney transplants were advocated10. With the ability to diagnose conditions like hyperoxaluria early before renal damage and systemic oxalosis has occurred, isolated liver transplant to cure the enzymatic defect has been11,12. With autosomal recessive polycystic kidney disease/congenital hepatic fibrosis; isolated kidney transplant is usually sufficient in early childhood. Combined liver and kidney transplant is indicated in children with ARPKD/CHF repeated episodes of cholangitis and/or in those with advanced portal hypertension. In cystic fibrosis, liver disease is the second most common cause of death7. Combined lung-liver transplant can be considered for patients with advanced pulmonary disease. Those with well preserved pulmonary The most important advantage is that it gives the clinician and the family a safety net should the transplant candidate's status deteriorate severely before an organ becomes available from the cadaveric list. Also, in cases of acute liver failure, it allows time for necessary tests to be done and allows valuable time for medical therapy to work; while not compromising on the outcome as the clinician can choose if/when to transplant, rather than just when the organ is available. The other advantage is the convenience any planned procedure has over an emergency procedure. The improved quality of the organ and reduced ischaemia times can all be advantages, but the real risk to the donor should not be forgotten under any circumstances. In conclusion, the field of pediatric liver transplantation is increasingly becoming the therapeutic option of choice for an increasing number of diseases. It is important for the pediatric hepatologist and the liver transplant surgeon to work together and keep abreast of the latest developments so that the liver transplant is performed at the optimal time for the correct indication. Good teamwork from all members of the transplant team ensures a complete timely transplant assessment, with family members and child adequately educated and appropriately informed before the procedure. References 1. 2. 3. 4. 5. 21 Kogan-Liberman D, Emre S, Shneider BL. Recent advances in pediatric liver transplantation. Curr Gastroenterol Rep 2002;4:84-97. Carithers RL, JR. Liver transplantation. American Association for the Study of Liver Diseases. Liver Transpl 2000;6:122-35. Tzakis A, Todo S, Stieber A, Starzl TE. Venous jump grafts for liver transplantation in patients with portal vein thrombosis. Transplantation 1989;48:530-1. Langnas An, Marujo WC, Stratta RJ, et al. A selective approach to preexisting portal vein thrombosis in patients undergoing liver transplantation. Am J Surg 1992;163:132-6. Suchy FJ SR, Ballistreri WF. Liver Disease in Children. Assessment of Pediatric Liver Transplant Recipients 6. 7. 8. 9. Philadelphia, PA: Lippincot Williams & Wilkins, 2001. Noble-Jamieson G, Barnes N, Jamieson N, Friend P, Calne R. Liver transplantation for hepatic cirrhosis in cystic fibrosis. J R Soc Med 1996;89 Suppl 27:31-7. Genyk YS, Quiros JA, Jabbour N, Selby RR, Thomas DW. Liver transplantation in cystic fibrosis. Curr Opin Pulm Med 2001;7:441-7. Sigurdsson L, Reyes J, Kocoshis SA, Hansen TW, Rosh J, Knisely AS. Neonatal hemochromatosis: outcomes of pharmacologic and surgical therapies. J Pediatr Gastroenterol Nutr 1998;26:85-9. Broyer M, Brunner FP, Brynger H, et al. Kidney transplantation in primary oxalosis: data from the EDTA Registry. Nephrol Dial Transplant 1990;5:332-6. 10. Gagnadoux MF, Lacaille F, Niaudet P, et al. Long term results of liver-kidney transplantation in children with primary hyperoxaluria. Pediatr Nephrol 2001;16:946-50. 11. Nolkemper D, Kemper MJ, Burdelski M, et al. Long-term results of pre-emptive liver transplantation in primary hyperoxaluria type 1. Pediatr Transplant 2000;4:177-81. 12. Cochat P, Scharer K. Should liver transplantation be performed before advanced renal insufficiency in primary hyperoxaluria type 1? Pediatr Nephrol 1993;7:212-8; discussion 218-9. 22 Türk HPB 2006 Cilt 2 Sayý 1 Infectious Disease Complications in Pediatric Solid Organ Recipients Türk HPB Roberto Posada Department of Pediatrics, Mount Sinai School of Medicine, New York, USA Summary Infectious disease complications are common following solid organ transplantation in children and result in significant morbidity and mortality. This review will focus on the epidemiology, timing and clinical presentation of the most clinically important infections seen after transplantation in children, based on the frequency at which they occur and the complications associated with them. Early diagnosis, aggressive treatment, and preventive strategies are critical to improve patient outcomes and will be discussed as well. Key words: pediatric liver transplantation, infectious complications Pediatrik Solid Organ Alýcýlarýnda Ýnfeksiyöz Komplikasyonlar Özet Çocuklarda solid organ nakli sonrasý geliþen infeksiyöz komplikasyonlar anlamlý oranda morbidite ve mortaliteye neden olmaktadýr. Bu derleme, çocuklarda nakil sonrasý görülen, sýklýk ve komplikasyonlarý yönünden en ciddi infeksiyonlarýn epidemiyoloji, zamanlama ve klinik bulgularý üzerine odaklanmýþtýr. Erken taný, saldýrgan tedavi ve önleyici yaklaþýmlar prognozu iyileþtirme açýsýndan yaþamsal öneme sahiptir. Anahtar kelimeler: pediatrik organ nakli, infeksiyöz komplikasyonlar Infections that can be acquired during transplantation include bacterial and fungal infections caused by organisms colonizing the skin or the respiratory, gastrointestinal or genitourinary tracts that can be introduced during the surgical procedure. The specific type of infections seen will vary with the type of transplant. In chronically ill children who require hospitalization and use of antimicrobials prior to transplantation, these organisms can be resistant to commonly used antimicrobials, and difficult to treat (John M, submitted). In addition, infections such as CMV, EBV, toxoplasmosis, hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV) can be introduced with the transplanted organ or with transfusions of blood products required during or after the transplant. Recently, cases of rabies and West Nile virus transmitted from infected organ donors have been reported2,3. Following transplantation, exposure to nosocomial flora poses a risk for infection with resistant organisms. CMV, EBV, VZV, HSV I and II, adenovirus, toxoplasmosis, and pneumocystis pneumonia (PCP) can also be acquired after transplantation as well as more typical agents of community acquired infections, such Introduction Infectious complications cause significant morbidity and mortality following solid organ transplantation. This review will focus on the timing, clinical presentation, diagnosis, and management of those infections that are of greater clinical relevance. Highly effective prophylactic strategies are available to prevent many of these complications, and they will be discussed as well. The risk for disease due to infection after transplantation is determined by exposure to specific infectious agents, and by the so-called net state of immunosuppression1. Exposure to specific infectious agents may occur prior, during, or after transplantation. Chronic infections that can be acquired prior to the procedure and that can reactivate following transplantation, include tuberculosis, cytomegalovirus (CMV), Epstein Barr virus (EBV), herpes simplex (HSV) I and II viruses, varicellazoster virus (VZV), histoplasmosis and other endemic mycosis, toxoplasmosis, and strongyloidiasis. Infants and young children are less likely than older patients to have chronic latent infections. Roberto Posada, Department of Pediatrics Mount Sinai School of Medicine 1 Gustave L. Levy Place, Box 1657, New York, NY 10029 roberto.posada@mssm.edu 9 Infectious Disease Complications in Pediatric Solid Organ Recipients as influenza, parainfluenza, respiratory syncitial virus, rotavirus, and cryptosporidium parvum. The net state of immunosuppression1 is determined by a variety of factors. The effect of immunosuppressive agents can persist for a period of time after they have been discontinued, and as a result current and recently used agents influence the state of immunosuppression. The presence of other underlying illnesses or immunodeficiencies, such as neutropenia or HIV infection, poor nutritional status and loss of integrity of the skin and mucosal barriers, such as in patients with mucositis or who require indwelling devices, can all increase the susceptibility to infections. Finally, the presence of concomitant infections with immunomodulatory effects, most notably CMV (see below), is also associated with increased risk of infection. For some infections, prior seropositivity due to either vaccination or prior infection will also alter the risk of disease following transplantation. It is useful to discuss infectious complications of transplantation based on the timing of their occurrence after transplantation. Early infections are those that occur in the first 30 days following transplantation, the intermediate period occurs between the second and sixth month after transplantation, and late infections are those that occur after the sixth month post-transplant1. However, it is important to keep in mind that the typical pattern of infections seen during each of these periods can vary based on the specific immunosuppressive and prophylactic regimens been used. For example, a patient that requires aggressive treatment for acute rejection 1 year after transplantation, although technically in the late period, may be at risk for infectious complications typical of the intermediate period. pany focal infections or can develop as a complication of the use of intravascular catheters. Wound infections can be seen following any type of transplant. Mediastinitis and pneumonia can follow heart or lung transplantation, and dehiscence of the bronchial anastomosis can be associated with infection after lung transplant. Patients with cystic fibrosis are at particular risk for pneumonia caused by resistant gram negative organisms, including pseudomonas spp, and for aspergillus infections. Liver transplantation can be complicated by biliary strictures and bile leaks, and infections commonly seen include cholangitis, hepatic or inta-abdominal abscesses, and peritonitis. These are usually caused by enteric gram negatives and enterococci. Anaerobic bacteria, which are part of the normal gastrointestinal flora are not frequently isolated, but this could be due to the fact that these organisms are difficult to grow in culture, and therefore empiric coverage against anaerobic bacteria should be considered when managing these patients. Infections due to candida spp. also occur. Increased amounts of blood product transfusions and longer duration of the surgical procedure have been associated with an increase in the risk for infection4. Other technical aspects of the procedure can also increase the risk of infection. For example, liver transplant recipients that require a choledocojejunostomy may be at increased risk for ascending cholangitis5. Intra-abdominal infections caused by organisms similar to those seen following liver transplantation are also seen after small bowel transplantation (John M, submitted). Following renal transplantation patients may experience urinary leaks, perigraft hematomas, and lymphoceles. Urinary infections, and pneumonia are commonly seen, and the causative organisms frequently are gram negative bacteria, enterococci, and candida spp. Not surprisingly, longer duration of bladder catheterization is associated with an increased risk of infection6. Early Infections Early infections are often related to underlying conditions or to complications of the surgical procedure, and are usually caused by bacteria or candida spp. colonizing the patient. Infections are similar to those seen after other major surgical procedures and frequently occur in proximity to the surgical site. Bacteremia or fungemia may accom- Intermediate Period Disease due to CMV and EBV, and PCP and toxoplasmosis become more important during this period in which the cumulative effect of the immunosuppressive medications results in a higher degree 10 R. Posada of immunosuppression1. Complications due to primary infection or reactivation of VZV or HSV 1 or 2 also occur7, as well as infections due to molds such as aspergillus spp. or zygomycetes8. Community acquired respiratory and gastrointestinal viruses can cause severe disease during this period9,10. Patients who have experienced complications leading to persistent strictures or other anatomic abnormalities can continue to have infections characteristic of the early period. for primary infection) and manage them accordingly (see below), unless it can be demonstrated that they have had prior CMV infection (e.g. by a positive CMV urine culture). CMV can cause a non-specific febrile illness as well as end organ manifestations such as hepatitis, pneumonitis, enteritis, and bone marrow suppression. It also has immunomodulatory effects and may increase the risk of other infections such as PCP, and has been associated with rejection and decreased graft survival in renal and liver transplant recipients, and with allograft atherosclerosis in heart transplant recipients11. The diagnosis of CMV disease is strongly supported by the presence of viremia which can be detected by quantitative competitive (qc) PCR or by pp65 antigen. Culturing CMV from urine or respiratory samples does not constitute evidence of disease, as immunocompromised patients can shed virus in the absence of disease. IgM assays lack sufficient specificity to be useful for diagnostic purposes. Obtaining biopsy specimens of the affected organ for histopathologic evaluation and immunohistochemistry studies is the gold standard for diagnosing CMV disease. CMV disease is managed with ganciclovir which is usually administered for at least two weeks, and until clinical findings improve and viremia resolves. Ganciclovir has poor bioavailability and management of CMV disease or viremia generally requires IV therapy. Valganciclovir is a prodrug of ganciclovir with higher bioavailability which may allow for oral therapy in selected cases. A liquid formulation of valganciclovir is not currently commercially available in the US. Two general approaches for the prevention of CMV disease are available. In the universal prophylaxis approach all patients are given prophylaxis during the period of highest risk for infection. Acyclovir, ganciclovir, valganciclovir, intravenous immunoglobulin (IVIG), and CMV hyperimmunoglbulin (CMV-IVIG) have been used as prophylactic agents for periods ranging from two weeks to 1 year, with varying results in limited studies11. The preemptive treatment strategy is based on the premise that a period of asymptomatic viremia precedes the onset of disease. In this strategy, patients are closely moni- Late Infections In most patients it is possible to lower the amount of immunosuppression during this period, which decreases the incidence of infections. EBV associated post-transplant lymphoproliferative disease (PTLD) remains an important infectious complication during this phase. A subset of patients that continues to experience episodes of acute rejection constitutes an exception and can continue to have infectious complications characteristic of the intermediate period during this late stage. Similarly, patients with persistent strictures and other anatomic abnormalities can continue to have infections characteristic of the early period. Specific Infections Bacterial infections have been discussed in the section on early infections. Other important pathogens associated with transplantation in children are discussed below. In addition to the specific therapies outlined below, reduction of the immunosuppression is often critical in the management of these infections. CMV The risk of CMV disease following transplantation depends on the serostatus of the recipient and the donor, and is highest in CMV negative recipients of CMV positive organs, as determined by serum CMV IgG. Because a positive serum CMV IgG in an infant can represent antibody passively acquired from the mother in utero rather than prior infection, the conservative approach for risk stratification of infants younger than 1 year of age is to consider them CMV negative (i.e. at risk 11 Infectious Disease Complications in Pediatric Solid Organ Recipients disorder characterized by uncontrolled lymphocyte proliferation at various sites, to frank lymphoma. Patients can present with hepatitis, ulcerative gastrointestinal tract disease, bone marrow suppression, lymphadenitis, hepatosplenomegaly, tonsillar hypertrophy, pulmonary nodules, or CNS disease. Disease due to EBV may be clinically indistinguishable from CMV disease. Detecting virus in peripheral blood using qcPCR can identify patients at higher risk for developing EBV associated disease, who should be targeted for further work-up and treatment15. However, not all patients with detectable EBV viremia will have evidence of EBV disease. Tissue diagnosis is often necessary and should be attempted promptly looking for evidence of polyclonal or monoclonal lymphocyte proliferation. Nucleic acid techniques, including the EBVencoded small RNAs (EBER) assay, can be used to confirm the diagnosis. The treatment of EBV PTLD is complicated, depends on the stage of disease, and requires a multidisciplinary approach including pediatric oncologists. In addition to reducing the immunosuppression, acyclovir or ganciclovir, and immunoglobulin preparations are frequently used. Antivirals, however, can only be expected to have a modest effect on disease, as they only act on virus in lytic cycle, as opposed to the latent cycle virus found in transformed lymphocytes. An anti-CD20 monoclonal antibody has been used for disease associated with CD20 positive B cells. Cancer chemotherapy is often required. The use of ganciclovir as a prophylactic agent has been reported to decrease the incidence of EBV PTLD by 50% in pediatric liver transplant recipients16. Immunoglobulin preparations have also been used for this purpose but their benefit has not been demonstrated. Similar to our strategy for prevention of CMV disease, at our center we use universal prophylaxis with a 14 day course of ganciclovir and CMV-IVIG starting immediately after transplantation for all seronegative recipients from donors who are seropositive or of unknown serostatus. Infants younger than 1 year of age may have a positive IgG as a result of transplacental transmission of maternal antibody, and thus should always be considered seronega- tored for evidence of CMV viremia. Those patients that develop viremia are then treated preemptively with ganciclovir. Both the universal prophylaxis and the preemptive treatment methods are highly effective in preventing CMV disease. The later has the advantage of decreasing the incidence of adverse events due to ganciclovir, preventing the selection of ganciclovir resistant strains, and being less expensive. Pediatric liver transplant recipients at our institution are managed with a combination of universal prophylaxis and preemptive strategies. CMV negative recipients of CMV positive organs are given a 14 day course of IV ganciclovir (5 mg/kg every 12 hours) immediately after transplant. CMV-IVIG is also given at a dose of 150mg/kg within 72 hours of transplant and at weeks 2, 4, 6, and 8. Two additional doses of 100 mg/kg are given at weeks 12 and 16. CMV positive recipients, and CMV negative recipients of CMV negative organs, do not receive prophylaxis. All recipients are then followed with CMV qcPCR every 2 weeks for the first three months, and every month until a year after transplantation. If CMV viremia is detected, appropriate diagnostic tests to rule out CMV disease are performed, and IV ganciclovir is given for at least 14 days, with weekly monitoring of the qcPCR until it becomes undetectable again. Patients who require aggressive intensification of immunosuppression for treatment of acute rejection are also monitored every 2 weeks. EBV Similar to CMV, the risk of developing EBV disease following transplantation is highest in EBV negative recipients of EBV positive organs. CMV mismatch between donor and recipient, CMV disease, type and intensity of immunosuppression and young age at transplantation have also been found to increase the incidence of EBV disease12,13. Incidence of EBV disease varies according to the organ transplanted, and can be as high as 51% following small intestine transplantation in children14, and mortality rates of up to 60% have been reported13. Clinically, disease caused by EBV ranges from a mild febrile illness, to a mononucleosis syndrome, to PTLD which is a 12 R. Posada cella that are in the contagious period. A course of acyclovir may also be effective at preventing severe varicella and should be considered in patients who are beyond 96 hours of exposure. A live virus vaccine against VZV is available and should be offered to future transplant recipients as long as the transplant is not expected to occur within 6 weeks of vaccination, because of concern of disease caused by vaccine virus. The efficacy of the vaccine is lower in infants under the age of 12 months. tive for the purpose of risk stratification. All recipients are followed with monthly EBV PCR. A new positive PCR, or a significant increase from prior levels should trigger further work-up and reducing the immunosuppression should be strongly considered. VZV Immunocompromised children are at risk for severe illness due to VZV. Primary infection with VZV causes Varicella and reactivation of latent infection causes Zoster. Transmission of VZV occurs by airborne spread from patients with Varicella or by direct contact with the lesions of Varicella or Zoster. Varicella is most contagious from 2 days before the onset of the rash until all the lesions have crusted over. In immunocompromised subjects the rash of varicella can be more aggressive and of longer duration, and the disease can be associated with hepatitis, pneumonia, encephalitis, bacterial superinfection of the skin, and other complications. In immunocompromised subjects Zoster can involve multiple dermatomes and can occasionally disseminate causing a disease similar to primary Varicella infection. The diagnosis of VZV disease can be confirmed by viral culture or DFA staining of material obtained by scraping the base of a freshly unroofed vesicle. Several drugs are available for the treatment of VZV. Acyclovir is effective and is usually the drug of choice, although higher doses than those required to treat HSV infections are needed. In addition, it is poorly absorbed from the gastrointestinal tract. Valacyclovir, a prodrug of acyclovir, and other related compounds which are much better absorbed, are also available, and are preferred if oral therapy is been considered. Patients with more severe immunosuppression, more aggressive disease, or in whom close outpatient monitoring is not possible should be treated with IV acyclovir until there is clinical improvement. Alternative agents include ganciclovir and foscarnet. Varicella-Zoster immunoglobulin is highly effective at preventing or decreasing the severity of disease and should be administered within 96 hours of exposure to susceptible transplant recipients who come in contact with patients with vari- HSV I and II HSV I and II cause characteristic crops of vesicles in the oral mucosa, lips, perioral region, and in the genitalia, accompanied by regional lymphadenopathy. Occasionally lesions at other sites can also be seen. Lesions in immunocompromised subjects can be more extensive and persist for a longer period of time. The severity of the lesions often impair oral intake, and IV hydration is frequently required. Dissemination to other organs including CNS and liver can occur but is not common. Like with other herpes viruses, primary infection is followed by latency and episodes of reactivation. Although most of oral lesions are due to HSV I and the genital lesions are due to HSV II, considerable overlap exists, and clinical differentiation is not possible. The diagnosis can be confirmed by viral culture or DFA staining of material obtained by scraping the base of a freshly unroofed vesicle. Treatment is similar to the treatment for VZV, although lower doses of acyclovir are needed. Adenovirus Infection with adenovirus in solid organ transplant recipients can result in hepatitis, enteritis and pneumonitis9,17. Conjunctivitis is a less serious manifestation. Small bowel transplant recipients may be at higher risk of severe disease than recipients of other organs9. In renal transplant recipients, adenovirus has been associated with hemorrhagic cystitis. The diagnosis can be confirmed by viral culture, PCR, or histology. Initial treatment involves lowering the immunosuppression. If there is disease progression, or in patients who are very ill on presentation, the 13 Infectious Disease Complications in Pediatric Solid Organ Recipients easy to administer21,22. It is the agent of choice at our institution. A dose of 150 mg/m2 2 or 3 times a week is adequate for PCP prophylaxis, but more frequent dosing might be required for protection against other organisms. use of cidofovir should be considered. However, prospective efficacy data in pediatric solid organ transplant recipients is not available. Pneumocystis pneumonia PCP is caused by Pneumocystis jiroveci, a ubiquitous unicellular fungus which is acquired through inhalation. The risk for PCP in solid organ transplant recipients is highest during the periods of higher immunosuppression that follow transplantation or the treatment of acute rejection, and incidence rates as high as 14% have been reported in the absence of prophylaxis18. Clinically, PCP is characterized by a pneumonitis accompanied by significant hypoxemia with an increased alveolar-arterial PO2 gradient. Bilateral alveolar infiltrates are typically described, but the disease can have very different radiological manifestations, including a normal radiograph early in the disease. The diagnosis can be confirmed by direct examination of respiratory secretions obtained by induced sputum, deep tracheal aspiration or bronchoalveolar lavage. Giemsa, Grocott-Gomori, or Fluorecent antibody stains can be used to visualize the organism. However, the yield of direct examination of respiratory secretions is lower in solid organ transplant recipients than in patients with AIDS due to a decreased number of organisms, and lung biopsy may be necessary to confirm the diagnosis. Patients suspected of having PCP should receive empiric therapy pending confirmation of the diagnosis. The agent of choice is trimethoprimsulfamethoxazole because of its proven efficacy, safety and ease of administration. Other available agents include intravenous pentamidine, dapsone and atovaquone19. Based on the experience in patients with AIDS, the use of corticosteroids as adjuvant therapy should be considered in patients with moderate to severe disease20. Several highly effective prophylactic regimens are available, including trimethoprim-sulfamethoxazole, intravenous or aerosolized pentamidine, dapsone, and atovaquone. Trimethoprim-sulfamethoxasole has been shown to be the most effective, has the added advantages of protecting against toxoplasmosis and bacterial infections, and is inexpensive and Toxoplasmosis Disease caused by Topxoplasma gondii is more commonly seen following heart transplantation, but several reports have described the illness in other type of solid organ recipients23,24. Disease can result from reactivation of latent infection acquired prior to transplant, transmission through the transplanted organ, or acquisition after transplantation. Infection that is not acquired through the transplanted organ can be acquired trough inadvertent ingestion of sporozoites contaminating the food supply (e.g. uncooked and unwashed vegetables), through direct exposure to sporozoites present in the stool of infected cats, or through ingestion of bradyzoites contained in cysts present in the skeletal muscle of latently infected animals (e.g. meat that is not thoroughly cooked). Diagnosis requires a high index of suspicion because manifestations can be non-specific. Patients frequently have fever, respiratory or neurologic symptoms or bone marrow suppression, but other symptoms, including multiorgan involvement have been described (Campbell A, in preparation). Detection of antibodies in serum or CSF can be used to support the diagnosis. A negative Toxoplasma serum IgG makes the diagnosis highly unlikely. The presence of IgM, IgA, or IgE is associated with recent infection, but available assays vary in their sensitivity and specificity so it is important to use a laboratory experienced in the diagnosis of toxoplasmosis. The diagnosis can be confirmed by PCR (blood, CSF, broncho-alveolar lavage fluid), or by direct examination of respiratory secretions or tissue specimens looking for tachyzoites, which is the form of the parasite associated with symptomatic disease. Toxoplasmosis is treated with a combination of pyrimethamine and sulfadiazine which should be continued for 4-6 weeks after clinical improvement25. Folinic acid should be used in conjunction with pyrimethamine to prevent bone marrow toxicities. As mentioned earlier, 14 R. Posada trimethoprim-sulfamethoxazole has been shown to have a protective effect against toxoplasmosis. HIV should be done. In infants younger than 1 year of age who are CMV IgG positive, urine cultures for CMV should be obtained (see discussion on CMV). A tuberculin skin test should be placed followed by a chest X-ray if positive. Patients with latent tuberculosis should initiate treatment as early as possible before transplant. Screening for other infections should be done based on local epidemiology and risk factors (e.g screening for strongyloides in endemic areas). In general, all intercurrent infections should be treated prior to transplantation. However, a decision to transplant a patient with an active infection may be considered when the risk of delaying the transplant is greater than the risk of complications derived from progression of the infection following the transplant and subsequent immunosuppression. Anticipatory guidance regarding avoidance of exposure to infectious agents should be provided to the child and family. Pretransplant Evaluation All prospective candidates for transplant should be evaluated as early as possible and then followed periodically by a physician with expertise in pediatric infectious diseases. History, physical exam and laboratory testing should be directed towards identifying active infections requiring immediate treatment, latent infections (eg. tuberculosis) that could reactivate following transplantation, and infections for which the prospective recipient lacks immunity and that can be problematic if acquired after transplant (e.g. CMV, EBV, varicella). In chronically ill patients with prior bacterial or fungal infections, information regarding the causative organisms as well as their susceptibility pattern and prior antimicrobial exposure may aid in selecting antibiotics to use following transplantation. Specific prophylactic strategies tailored to the individual patient should be delineated and discussed with the transplant team. A history of recent exposure to diseases that might be in their incubation period (e.g. varicella) is particularly important in patients in whom transplantation is imminent. It is also important to inquire about the health status of other household members, looking for information suggestive of contagious infections, such as tuberculosis. Tuberculosis testing of household members is advisable in high prevalence areas. The immunization record of the child should be reviewed, and any outstanding vaccines should be administered as soon as possible, with the caveat that live virus vaccines should not be given if transplantation is expected to occur within less than 6 weeks, due to the risk of disease caused by vaccine virus. Serologic testing for evidence of immunity against vaccine preventable diseases may be useful, particularly in children with an incomplete vaccination record or in those with chronic illnesses associated with poor vaccine responses. An accelerated immunization schedule can be used if necessary. Serologic screening for CMV, EBV, toxoplasmosis, Varicella-Zoster, syphilis, viral hepatitis (A,B,C), and References 1. Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med 1998;338:1741-51. 2. Kusne S, Smilack J. Transmission of West Nile virus by organ transplantation. Liver Transpl 2005;11:239-41. 3. Srinivasan A, Burton EC and Kuehnert MJ, et al. Transmission of rabies virus from an organ donor to four transplant recipients. N Engl J Med 2005;352:1103-11. 4. Hollenbeak CS, Alfrey EJ, Sheridan K, Burger TL and Dillon PW. Surgical site infections following pediatric liver trtansplantation: risks and costs. Transpl Infect Dis 2003;5:72-8. 5. Hadley S, Samore MH, Lewis WD, Jenkins RL, Karchmer AW and Hammer SM. Major infectious complications after orthotopic liver transplantation and comparison of outcomes in patients receiving cyclosporine or FK506 as primary immunosuppression. Transplantation 1995;59:851-9. 6. Marah B, Bonten H, van Hoof H, Fiolet H, Biuting AG and Stobberingh EE. Infectious complications and antibiotic use in renal transplant recipients during a 1-year follow-up. Clin Microbiol Infect 2001;7:619-25. 7. Dodd DA, Burger J, Edwards KM and Dummer JS. Varicella in a pediatric heart transplant population on nosteroid maintenance immunosuppression. Pediatrics 2001;108:E80. 8. Brown RS, Jr, Lake JR and Katzman BA, et al. Incidence and significance of Aspergillus cultures following liver and kidney transplantation. Transplantation 1996;61:666-9. 9. Pinchoff RJ, Kaufman SS and Magid MS, et al. Adenovirus infection in pediatric small bowel transplantation recipients. Transplantation 2003;76:183-9. 10. Kaufman SS, Chatterjee NK and Fuschino ME, et al. Characteristics of human enteritis in intestinal transplant recipients. J Pediatr Gastroenterol, Nutr 2005;40:328-33. 11. Campbell AL, Herold BC. Strategies for the prevention of cytomegalovirus infection and disease in pediatric liver transplantation recipients. Pediatr Transplantation 2004;8:619-27. 12. Manez R, Breinig MC and Linden P, et al. Posttransplant lym- 15 Infectious Disease Complications in Pediatric Solid Organ Recipients 13. 14. 15. 16. 17. 18. 19. phoproliferative disease in primary Epstein-Barr virus infection after liver transplantation: the role of cytomegalovirus disease. J Infect Dis 1997;176:1462-7. Newell KA, Alonso EM and Whitington PF, et al. Posttransplant lymphoproliferative disease in pediatric liver transplantation. Interplay between primary Epstein-Barr virus infection and immunosuppression. Transplantation 1996;62:370. Finn L, Reyes J, Bueno J and Yunis E. Epstein-Barr virus infections in children after transplantation of the small intestine. Am J Surg Pathol 1998;22:299-309. Kogan-Liberman D, Burroughs M, Emre S, Mosocna A and Shneider BL. The role of quantitative Epstein-Barr viruis polymerase chain reaction and preemptive immunosuppression reduction in pediatric liver transplantation: a preliminary experience. J Pediatr Gastroentrol Nutr 2001;33:442-4. McDiarmid SV, Jordan S and Kim GS, et al. Prevention and preemptive therapy of postransplant lymphoproliferative disease in pediatric liver recipients. Transplantation 1998;66:1604-11. Michaels MG, Green M, Wald ER and Starzl TE. Adenovirus infection in pediatric liver transplant recipients. J Infect Dis 1992;165:170-4. Lufft V, Kliem V, Behrend M, Pichlmayr R, Koch KM and Brunkhorst R. Incidence of Pneumocystis carinii pneumonia after renal transplantation. Impact of immunosuppression. Transplantation 1996;62:421-3. Bozzette SA, Finkelstein DM and Spector SA, et al. A random- 20. 21. 22. 23. 24. 25. 16 ized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med 1995;332:693-9. MacFadden DK, Edelson JD, Hyland RH, Rodriguez CH, Inouye T and Rebuck AS. Corticosteroids as adjunctive therapy in treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. Lancet 1987;1:1477-9. Schneider MM, Hoepelman AI and Eeftinck Schattenkerk JK, et al. A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. The Dutch AIDS Treatment Group. N Engl J Med 1992;327:1836-41. Baden LR, Katz JT and Franck L, et al. Successful toxoplasmosis prophylaxis after orthotopic cardiac transplantation with trimethoprim-sulfamethoxazole. Transplantation 2003;75:339-43. Mayers JT, O'Connor BJ, Avery R, Castellani W and Carey W. Transmission of Toxoplasma gondii infection by liver transplantation. Clin Infect Dis 1995;21:511-5. Munir A, Zaman M and Eltroky M. Toxoplasma gondii pneumonia in a pancreas transplant patient. South Med J 2000;93:614-7. Boye KM, McLeod RL. Toxoplasma gondii (Toxoplasmosis). In: Long SS, Pickering LK and Prober CG, ed. Principles and Practice of Pediatric Infectious Diseases. Philadelphia: Churchill Livingston, 2003:1303-22. Türk HPB 2006 Cilt 2 Sayý 1 Canlýdan Karaciðer Naklinde Verici ve Alýcýlarýn Deðerlendirilmesi Þükrü Emre, Ýlhan Karabýçak Türk HPB Mount Sinai School of Medicine, New York, USA Özet Canlýdan karaciðer nakli genellikle uygun verici bulunamayan çocuk hastalarýn karaciðer nakli gereksinimini karþýlamak amacýyla geliþtirilmiþ bir yöntemdir. Ancak her yaþta görülen organ sýkýntýsý giderek bu tekniðin her yaþ grubunda uygulanýr olmasýna yol açmýþtýr. Ameliyatýn en önemli özelliði elektif þartlarda yapýlmasýdýr. Bunun getirdiði avantajlar yaný sýra farklý bir cerrahi deneyim gerektirmekte ve saðlýklý vericide ciddi komplikasyonlar ortaya çýkabilmektedir. Bu nedenle vericinin titiz bir þekilde hazýrlanmasý, olasý risk faktörlerinin elenmesi, vericiden alýnacak karaciðerin alýcýya, geride kalanýn ise vericiye yetebileceðinin ameliyat öncesi dönemde tayini büyük önem taþýmaktadýr. Aþaðýdaki derlemede canlý karaciðer naklinde verici ve alýcý hazýrlýðýnýn detaylarýný bulacaksýnýz. Anahtar kelimeler: canlý verici, organ nakli, verici deðerlendirmesi, alýcý deðerlendirmesi Donor and Recipient Assessment in Living-related Liver Transplantation Summary Living donor liver transplantation, initially developed to overcome the difficulties arising from shortage of suitable cadavre donors for pediatric patients, has found widespread acceptance in all age groups requiring liver transplantation. The most important aspect of the technique is that it is performed in elective conditions. Despite its advantages, it requires special experience with the surgical technique and carries the possibility of serious complications on the otherwise healthy living donor. Therefore it is extremely important that the donor is prepared with utmost care, risk factors eliminated and precise assessment made to ensure that the remnant liver is sufficient for the donor as well as the transplanted liver for the recipient. In this review, you will find details of the assessment of donor and recipients for living-related liver transplantation. Key words: living donor, organ transplantation, donor assessment, recipient assessment ðerin kalitesi, vericinin detaylý bir þekilde hazýrlanmasý nedeni ile vericiden alýcýya belirli hastalýklarýn geçme sansýnýn hemen hemen tamamýyla ortadan kalkmasý, ve soðuk iskemi zamanýnýn tamamen ortadan kaldýrýlmasý canlýdan karaciðer naklinin avantajlarý olarak nitelenebilir. Bunun yanýnda, canlýdan karaciðer naklinin cerrahi deneyim gerektirmesi, ameliyat sonrasý teknik problemlerin, özellikle, safra yollarý problemlerinin kadavra transplanta göre daha sýklýkla ortaya çýkmasý, saðlýklý vericilerde ortaya çýkabilecek komplikasyonlar ve mortalite ihtimali bu ameliyatýn dezavantajlarý olarak sýralanabilir. Bu yazýnýn amacý canlýdan karaciðer naklinde alýcý ve vericinin deðerlendirilmesinin nasýl yapýldýðýný bizim Mount Sinai Hastanesindeki deneyimlerimiz ýþýðýnda okuyucuya aktarmaktýr. Giriþ Canlýdan karaciðer nakli ilk olarak çocuk hastalardaki organ sýkýntýsýný aþmak amacýyla denenmiþtir1,2. Eriþkin hastalarda canlýdan karaciðer nakli ise kadavradan organ naklinin imkansýz olduðu uzak doðu ülkelerinde organ sýkýntýsýný aþmak için baþvurulan bir yöntem olarak baþlamýþtýr3-5. Çocuk hastalarda canlýdan karaciðer naklinden ve kadavradan split-karaciðer naklinden kazanýlan tecrübeler eriþkinlerde canlýdan karaciðer naklinin yaygýnlaþmasýna yardýmcý olmuþtur. Eriþkinlerde canlýdan karaciðer nakli, karaciðer nakli bekleyen hasta sayýsýnda ve buna baðlý olarak karaciðer nakli için bekleme listesindeki mortalitede artýþýný önlemek amacýyla önceleri belirli merkezlerde uygulanmýþ ve daha sonra giderek yaygýnlýk kazanmýþtýr6,7. Ameliyat zamanýnýn planlanabilmesi, karaciÞükrü Emre, Mount Sinai School of Medicine One Gustave L. Levy Place, Box 1104, New York, NY 10029 Tel: 212-659-8060, email: Sukru.Emre@msnyuhealth.org 1 Canlýdan Karaciðer Naklinde Verici ve Alýcýlarýn Deðerlendirilmesi Canlýdan ilk karaciðer nakli 1989 yýlýnda Brezilya'da yapýlmýþtýr. Canlýdan baþarýlý karaciðer nakli ise 1 yýl sonra Avustralya'da anneden oðluna sol lateral lob þeklinde gerçekleþtirilmiþtir9,10. Eriþkin hastada canlýdan sað lob nakli ilk olarak Japonya'da 1994 yýlýnda gerçekleþtirilmiþtir. Amerika Birleþik Devletleri'nde ise çocuk hastada canlýdan ilk karaciðer nakli 1990 yýlýnda, eriþkin hastada ilk sað lob nakli ise 1997 yýlýnda gerçekleþtirilmiþtir9,10. Akut karaciðer yetmezliði olan çocuk hastaya canlýdan ilk karaciðer nakli 1992, eriþkin hastaya ise ilk 1994 yýlýnda yapýlmýþtýr11,12. Canlýdan karaciðer nakli ilk yýllarda kronik karaciðer hastalýðý olan çocuk hastalarda sol lateral lob nakli þeklinde uygulanmýþtýr. Canlýdan karaciðer naklinin ameliyat zamanýnýn planlanabilmesi ve soðuk iskemi zamanýnýn kýsa olmasý gibi avantajlarýnýn yanýnda saðlýklý olan bir vericide morbidite ve mortalite geliþme riski taþýmasýndan dolayý etik olup olmadýðý uzun süre tartýþýlmýþtýr. Ýlk yýllardaki sonuçlarýn kadaverik karaciðer nakli ile ayný düzeyde olmasý canlýdan karaciðer naklinin yaygýnlaþmasýna, hepatosellüler kanserin küratif tedavisinde ve hatta akut karaciðer yetmezlikli çocuk ve eriþkin hastalarda yaygýn olarak uygulanýlmasýna olanak saðlamýþtýr13. Tüm dünyada þimdiye kadar çoðunluðu pediatrik hastalar olmak üzere 2000'den fazla canlýdan karaciðer nakli yapýlmýþtýr. Mount Sinai Hastanesi'nde ise canlýdan ilk karaciðer nakli kronik karaciðer hastalýðý olan bir çocuk hastaya 1993 yýlýnda yapýlmýþtýr. Kan grubu uygunluðu Elektif ameliyatlarda ABO uygunluðu gerekmektedir. Þayet vericinin kan gurubu O ise, alýcýnýn kan gurubu A, B yada AB olabilir (compatible mismatch). Çocuk alýcýlarda, akut karaciðer yetmezliði durumunda ABO uygunluðu aranmayabilir16,17. Bizim akut karaciðer yetmezliði nedeniyle canlýdan karaciðer nakli yaptýðýmýz 22 çocuk hastalý serimizde, 1 hastada ABO uygunluðu bulunmamaktaydý18. Alýcý ile kan baðý ve emosyonel iliþkisinin olmasý Alýcý ile verici arasýnda ya kan baðý ya da emosyonel iliþkinin bulunmasý kesinlikle gereklidir. Bu çerçeve içinde, karý-koca, birinci derece yakýn akrabalar, ya da çok yakýn arkadaþlar birbirleri için baðýþta bulunabilirler. Verici adayý deðerlendirilirken baský yapýlýp yapýlmadýðý çok iyi deðerlendirilmelidir. Özellikle acil nakil gereken durumlarda vericilere baský yapýlabilir. Verici güvenliðinin daha önemli olduðu bu tip durumlarda verici saðlýðýný riske edecek giriþimlerden kaçýnýlmalýdýr. Vericilerde yaþ sýnýrý 18-55 yaþlarý arasýnda olmalýdýr Vericinin rýza verebilmesi için reþit olmasý gereklidir. Bunun için alt yaþ sýnýrý 18 olarak belirlenmiþtir. Üst sýnýrýn 55 olarak belirlenmesindeki nedenleri ise, 55 yaþýndan sonra karaciðer rejenerasyonun azalmasý ve 55 yaþýn üzerindekilerde yapýlan titiz çalýþmalara raðmen, verici hepatektomisi sonrasýnda önceden tahmin edilemeyen medikal problemler çýkma ihtimalinin artmasýdýr. Verici Adayýnýn Belirlenmesi Alýcý ile vericinin boy ve kilo olarak birbirine yakýn olmasý Canlýdan karaciðer nakli yapan merkezlerin amacý verici morbiditesini en aza indirmek, mortalite geliþmesini önlemek ve alýcýda, vericide oluþabilecek sorunlarý göze alacak kadar iyi sonuçlar elde etmek olmalýdýr. Verici adayýnýn doðru deðerlendirilmesi hem verici hem de alýcý sonuçlarýnýn baþarýlý olabilmesi için çok önemlidir. Bu nedenle verici adayý olarak deðerlendirilen kiþilerin ancak %30'u verici olabilmektedir14,15. Mount Sinai Hastanesi'nde karaciðer verici adayý olarak baþvuran kiþilerden aþaðýdaki þartlara uygunluðu istenilmektedir. Vericiden alýnacak karaciðer sað/sol lobunun alýcýda fonksiyon görebilmesi ve alýcýnýn metabolik ihtiyaçlarýný karþýlayabilmesi için belirli bir hacmin üzerinde olmasý gerekmektedir. Baþarýlý bir transplant için, bu kritik hacmin hesaplanmasý son derece önemlidir. Bu hesaplama için takýlacak karaciðer aðýrlýðý ile alýcýnýn vücut aðýrlýðý arasýndaki oran kullanýlmaktadýr (graft/recipent weight ratio- GRWR). Bu oranýn %0.8'in üzerinde olmasý arzu edilir oranýn %1'in üzerinde olmasý ise idealdir. GRWR %0.8'in altýnda olacak þekilde ka2 Þ. Emre ve ark. raciðer nakli yapýlmasý durumunda hepatik disfonksiyon, uzamýþ kolestaz, karaciðer yetmezliði ve mortalite geliþmesi söz konusudur4,19. GRWR %0.8'in altýnda olan hastalarýn saðkalýmlarý daha kýsa olduðu bilinmektedir4,20. "Small for size" greftler artmýþ portal perfüzyonun sinuzoidal hücrelerde hasar oluþturmasý nedeniyle yeteri kadar fonksiyon göremezler21. Alýcýda yeterli karaciðer volümü saðlamak amacýyla eriþkinlerde sað lob, pediatrik hastalarda ise sol lateral lob nakli yapýlmaktadýr. Verici deðerlendirmesi sýrasýnda karaciðer volümü BT veya MRI ile ölçülmelidir22,23. Eriþkin alýcýlarda vücut yapýsý küçük olan vericiler deðerlendirilirken dikkatli olunmalýdýr. Karaciðer volümü preoperatif dönemde yanlýþ deðerlendirilebilir. Graft aðýrlýðý; görüntüleme yöntemleri orta hepatik venin periferal uzanýmýný tespit edememeleri, rezeksiyon sýrasýnda orta hepatik venden uzak olan diseksiyon hattý seçilmesi ve radyologlarýn perfüze olan karaciðer hacmini ölçerlerken postoperatif ölçülen karaciðerin kanlanmýyor olmasý gibi nedenlerden dolayý gerçek aðýrlýðýndan daha fazla hesaplanabilir24. Ciddi medikal sorunun olmamasý Diabet, ciddi ve kontrol edilemeyen HT, karaciðer, kalp, böbrek ve akciðer hastalýðý gibi medikal sorunu olan kiþiler karaciðer verici adayý olamazlar. Ailesel amiloid polinöropati nedeniyle karaciðer nakli gereken kiþilerin karaciðerleri ile uygun alýcý bulunduðunda domino karaciðer nakli yapýlabilir. Psikiyatrik hastalýk olmamasý Altta yatan bir psikiyatrik hastalýðýn olup olmadýðýnýn araþtýrýlmasý yanýnda, vericinin motivasyonunun araþtýrýlmasý son derece önemlidir. Bu konuda psikiyatristlerin çok dikkatli olmasý gerekmektedir. Bizim serimizde iki hastada Munchausen Sendromu tespit edilmiþtir. Normal kan biyokimyasý Verici adayýnýn karaciðer fonksiyon testleri ve serum elektrolitlerinin normal, HbsAg, HbcAg, Hepatit C ve HIV antikorlarýnýn negatif olmasý gerekmektedir. Yukarýdaki þartlarýn yanýnda, alkol veya madde baðýmlýlýðýnýn olmamasý, saðlýk sigortasýnýn olmasý, ve geçirilmiþ üst batýn ameliyatýnýn olmamasý adaylýk için aranýlan diðer koþullarý oluþturmaktadýr. Verici karaciðerdeki yaðlanma oranýnýn saptanmasý (BMI <=26) Verici adaylarýnýn deðerlendirilmesi sýrasýnda karaciðer biopsisi yapýlan kiþilerin %30-50'sinde steatoz saptanmaktadýr25. Hepatik steatoz majör karaciðer rezeksiyonlarýnda ameliyat süresini, transfüzyon gereksinimini, morbiditeyi ve mortaliteyi arttýrmaktadýr26. BMI'i 25'den küçük olan kiþilerde steatoz çok nadiren görülmektedir. BT ve MRI, BMI'i 28'den büyük olan kiþilerde steatozun derecesini belirlemede yeteri kadar sensitif olmadýðýndan biopsi yapmak gerekebilir27. Biz BMI'i 29'un üzerinde olan adaylara biyopsi yapmaktayýz. Canlýdan nakilde soðuk iskemi süresi daha kýsa olduðu için steatoz ciddi sorun oluþturmasa da transplant merkezlerinin kabul ettiði oran %10-30 arasýnda deðiþmektedir6,27,28. Bizim merkezimizde bu oran %10 olarak kabul edilmektedir. Kadavradan karaciðer naklinde ise %30'a kadar olan makrosteatoz kabul edilmektedir29. Verici Adayýnýn Deðerlendirilmesi Yukarýdaki þartlara uyan kiþiler verici adayý olarak kabul edilir. Bizim merkezimizde verici adayýnýn deðerlendirilmesi baþlýca 4 baþlýk altýnda yapýlmaktadýr; Bilgilendirme ve eðitim Verici adayý olarak belirlenen kiþiler baðýmsýz verici deðerlendirme ekibi tarafýndan konsülte edilir. Aday medikal, cerrahi, psikolojik ve sosyal yönden deðerlendirilir. Cerrahi iþlem, geliþebilecek erken ve geç dönem komplikasyonlar, þimdiye kadar görülen mortaliteler ve nedenleri, verici olmanýn getirdiði potansiyel ve psikolojik etkiler, erken ve geç dönem takip prensipleri, saðlýk sigortasýnýn durumu, alýcýya yapýlacak cerrahi iþlem ve bizim ve tüm dünyanýn bu konudaki istatistiki sonuçlarý hakkýnda bilgi verilir. Verici adayýnýn aday olmaktan hiç bir gerekçe 3 Canlýdan Karaciðer Naklinde Verici ve Alýcýlarýn Deðerlendirilmesi anjiografi (MRA) ve magnetik rezonans kolanjiopankreatografi (MRCP) rutin olarak kullanýlmaktadýr. a) Safra yollarý anatomisi: Vericinin bilier anatomisini deðerlendirmek için BT, MRI, ERCP ve intraoperatif kolanjiografi kullanýlabilir. Bu tekniklerden noninvazif bir yöntem olan MRCP daha sýk kullanýlmaktadýr32. Sað arka duktusun doðrudan sol hepatik duktus ile birleþmesi safra yollarýnýn en sýk görülen anatomik varyasyonudur ve %13-19 oranýnda görülmektedir33,34. Daha az görülen ve daha komplike olan anatomik varyasyonlar ise aberran ve aksesuar safra kanallarýnýn olmasýdýr35. Aberran kanalýn baðlanmasý drene ettiði karaciðer segmentinde atrofiye neden olacaðý için safra yollarý anatomisi ameliyat öncesinde dikkatli bir þekilde deðerlendirilmelidir. Anatomik varyasyonlar genellikle sað lob rezeksiyonuna engel olmasa da, saptanmasý durumunda birden fazla safra yolu anastomozu yapmak gerekebilir36. b) Damarsal yapýlar: Karaciðerin arteryel yapýsý verici seçimini etkilemektedir. Bu yapý en iyi multidetektör BT ve gadoliniyumlu magnetik rezonans anjiografi ile deðerlendirilir37,38. Çoðu merkezde kompleks arteriyel problemi olan vericilere sað hepatektomi yapýlmamaktadýr39. Sað hepatektomi sýrasýnda IV. segmentin kanlanmasýnýn bozulmamasýna dikkat edilmelidir40,41. Alýcýnýn hepatik arter çapý greftin kanlanmasý açýsýndan önemlidir. Çap uygunsuzluðu ve/veya birden fazla küçük arter varlýðý durumunda aortohepatik interpozisyon greftleri kullanmak gerekebilir42. Portal venöz anatomide %20 civarýnda varyasyon görülmektedir. Sað portal venin olmamasý, ana portal venin sað ön, sað arka ve sol portal ven þeklinde trifurkasyonu, sað arka segmentin ana portal venden ayrýlmasý, sað ön dalýn soldan köken almasý veya sol portal venin olmamasý en sýk görülen portal ven varyasyonlarýdýr. Bu varyasyonlar ultrason veya BT arteryel portografi ile saptanabilir43,44. Portal ven trifurkasyonunda birden fazla anastomoz yapmak gerektirdiðinden, bazý merkezlerde, verici hepatektomi görece kontrendikedir. Sol portal venin sað portal ven ön dalýndan köken göstermeden vazgeçebileceði söylenir. Alýcýya verici adayýnýn deðerlendirilmesi ile ilgili bilgi verilmediði bildirilir30. Fizik muayene ve temel biyokimyasal incelemeler Ýkinci aþamada verici adayýnýn anamnezi alýnýr, fizik muayenesi ve psikososyal deðerlendirmesi yapýlýr. Elektrokardiografi ve akciðer filmi çekilir. Verici karaciðer parankimi kronik karaciðer hastalýðý ve yaðlanma varlýðý açýsýndan deðerlendirilmelidir. Bu amaçla karaciðer fonksiyon testleri, bilirubin, ALP, albumin, INR, serum transferrin satürasyonu, ferritin, seruloplazmin, antinükleer antikoru, düz kas antikoru, antimitokondrial antikoru, α1-antitripsin fenotipi, hepatit serolojisine bakýlmalýdýr14. Verici deðerlendirilmesinde en önemli konulardan biri de vericinin pulmoner emboli geliþme riski taþýyýp taþýmadýðýdýr. Verici ameliyatý sonrasý pulmoner emboli geliþmesi karþýlaþýlan bir komplikasyondur ve pulmoner emboliye baðlý verici ölümleri bildirilmiþtir31.Bunun için verici deðerlendirilmesi sýrasýnda faktör V Leiden gen mutasyonu varlýðý, protein C ve S, antitrombin III seviyesi, faktör VIII seviyesi, ve antifosfolipid veya antikardiolipin bakýlmasý önerilmektedir16. Þiþmanlýk, östrojen tedavisi, ileri yaþ, variköz ven varlýðý, sigara içme hikayesi pulmoner emboli için bilinen risk faktörleridir16. Bizim merkezimizde aktif sigara kullanan ve östrojen tedavisi alan kiþiler sigara kullanmayý ve östrojen tedavisini býraktýktan 3 ay sonra verici olarak kabul edilmektedir. Görüntüleme yöntemleri ile karaciðerin ve damarsal yapýnýn deðerlendirilmesi Karaciðer boyutunu ve damarsal yapýlarý deðerlendirmek için bir veya daha fazla görüntüleme yöntemine baþvurulur. Radyolojik inceleme tekniklerindeki geliþmeler daha önceden rutin olarak uygulanan ve komplikasyonlara yol açabilen hepatik anjiografi ve endoskopik retrograd kolanjiopankreatografi (ERCP) gibi invazif tetkikleri ortadan kaldýrdý. Görüntüleme yöntemi olarak magnetik rezonans görüntülemesi (MRI) ve/veya bilgisayarlý tomografi (BT) kullanýlabilir16. Mount Sinai Hastanesi'nde MRI, magnetik rezonans 4 Þ. Emre ve ark. aldýðý kiþilerde greft portal veninin kýsa olmasý, birden fazla anastomoz gereksinimi ve artmýþ portal ven trombozu riski nedeniyle verici sað lob hepatektomisi yapmak görece kontrendikedir36. kalmasýdýr. Ýkinci unsur ise vericide yapýlmasý gerekli bazý testlerin sonuçlarýnýn kýsa sürede alýnamadýðý durumlardýr. Bu da verici seçiminin saðlýklý yapýlma sansýný ortadan kaldýrmakta ve ameliyat sonrasý vericide birtakým komplikasyonlarýn ve mortalitenin ortaya çýkmasýna sebep olabilmektedir. Bunun yanýnda, akut karaciðer yetmezliði olan hastalarda yoðun bakým ünitelerinde uygulanan plazmaferez, taze donmuþ plazma ve uzun süre devamlý hemofiltrasyon tedavisine raðmen mortalite %70 civarýndadýr45. Bu tip eriþkin hastalarda canlýdan nakil yapýldýðýnda karaciðer hacmi yeterli olmayabilir. Çocuk hastalarda uygun kadaverik karaciðerin zamanýnda temini çok zor olmaktadýr ve bekleme döneminde hastalarda organ yetmezliðinin derecesi artabilir hatta geri dönüþümsüz nörolojik hasarlar ve beyin ölümü oluþabilir46. Buna ilave olarak, çocuk hastalarda genellikle verici karaciðerinin %25'ini çýkarmak gerektiðinden, vericinin riski çok azalmaktadýr. Bu hastalarda canlýdan karaciðer nakli seçeneði her zaman akýlda tutulmalý ve gerektiðinde hazýrlýklar çok hýzlý yapýlmalýdýr. Akut karaciðer yetmezlikli hastada karaciðer nakli planlanýrken verici üzerinde baský olup olmadýðý çok iyi deðerlendirilmelidir. Vericiler elektif vericiler gibi detaylý bir þekilde fakat çok daha hýzlý deðerlendirilmelidir. Bizim 22 hastalýk serimizdeki verici hazýrlanmasý 18 saat ile 3 gün arasýnda deðiþmektedir. Verici adayýna düþünme süresinin verilmesi Bütün iþlemler tamamlandýktan sonra, verici olmasýnda sakýnca olmayan kiþilere bir kez daha düþünmesi için 2 hafta süre verilir. Bu sürenin sonunda adaylar karar deðiþtirmemiþlerse ameliyat günü belirlenir. Düþünme süresi sonrasýnda verici olmaktan vazgeçen kiþilerin týbbi olarak uygun olmadýklarý söylenir (belirtilir). Canlýdan Karaciðer Nakli Alýcýlarýnýn Deðerlendirilmesi ve Nakil Ýçin Uygunluðun Araþtýrýlmasý Canlýdan karaciðer nakli yapýlmasý planlanan hastalarýn kadavradan nakil için liste edilmeleri gerekmektedir. Kadavradan karaciðer nakline uygun olmayan hastalar canlýdan nakle de uygun deðillerdir. Bunun yanýnda, canlýdan karaciðer nakli yapýlan hastalarda ameliyatýn baþarýlý olabilmesi için vericide aranýlan belirli þartlar vardýr. Aþaðýda belirtilen bu þartlara uymayan hastalarda canlýdan karaciðer nakli uygun deðildir16: a- MELD skoru >25 olan eriþkin hastalar: Dekompanse sirozlu ve MELD skoru 25'in üzerinde olan hastalarda ameliyat sonrasý morbidite ve mortalite yüksek olduðu için canlýdan karaciðer nakline sýcak bakýlmamaktadýr. Bu hastalarda bütün karaciðerin kullanýlmasý hem hastaya daha fazla karaciðer volümü saðlamak açýsýndan hem de rezeksiyon yapýlmýþ karaciðerlerde ortaya çýkabilecek cerrahi komplikasyonlarý azaltma açýsýndan daha yararlýdýr. c- Akut alkolik hepatit: Alkole baðlý karaciðer yetmezliði geliþen hastalara alkolü býrakmasý ve alkol rehabilitasyon merkezinde tedavi görmesi istenir. Alkolü býrakan hastalara medikal tedavi uygulanýr ve 6 aylýk tedavi sonrasý karaciðer nakli listesine alýnýrlar. d- Hepatosellüler karsinoma: Karaciðer dýþýna metastazý olan, komorbiditesi olan ve hastalýksýz dönem beklentisi 1 yýldan az olan hastalar canlýdan karaciðer nakline uygun deðillerdir. b- Fulminan karaciðer yetmezlikli eriþkin hastalar: Fulminan karaciðer yetmezliði olan hastalarda canlýdan karaciðer yetmezliði iki nedenden dolayý uygun görülmemektedir. Birinci neden, vericinin deðerlendirilmesinin çok kýsa bir zamanda yapýlmasý zorunluluðu nedeni ile vericinin karar verme konusunda baský altýnda e- Kolanjiokarsinoma f- Hepatit C için retransplantasyon: Hepatit C için 5 Canlýdan Karaciðer Naklinde Verici ve Alýcýlarýn Deðerlendirilmesi intraabdominal abse, plevral efüzyon ve aðrý görülebilir14,47,50,51. Canlýdan karaciðer nakli sonrasý vericilerde kolestaz kýsmen sýk görülmesine raðmen vericilerin sadece %5'i klinik bulgu vermektedir. Azalmýþ karaciðer volümü, rejenerasyona baðlý karaciðer fonksiyon bozukluðu, anestezi ilaçlarý, cerrahi stres kolestazýn baþlýca nedenleridir. Transaminaz seviyesi yüksek, koagülopatisi olan, albumin seviyesi düþük ve postoperatif erken dönemde hiperbilirubinemisi olan hastalarda kolestaz daha sýk görülmektedir. Kolestaz tipik olarak yavaþ düzelir ve tam düzelmesi bir kaç ay sürebilir47. Verici ameliyatlarýndan sonra erken dönemde Budd Chiari sendromu ve fulminan karaciðer yetmezliði geliþmesi nedeniyle kadavradan karaciðer nakli yapýlan vericiler bildirilmiþtir.52,53-55. Canlýdan karaciðer nakli sonrasý pulmoner emboli, batýn içi sepsis, gazlý gangren, gibi nedenlere baðlý geliþen 10 (%0.2) civarýnda verici ölümü mevcuttur56-59. retransplantasyon gerektiren sirozlu hastalarýn morbiditesi çok yüksektir. Bu hastalarýn çoðu tekrar nakil yapýlmadan liste dýþýna çýkmaktadýr. Tekrar karaciðer nakli gereken hepatit C'li hastalara kadavradan karaciðer nakli yapýlarak hem gerekli olan karaciðer volümü saðlanmalý hem de verici riske edilmemelidir. g- Diyaliz gerektiren hastalar h- Simultane kombine karaciðer/böbrek nakli gerekmesi: Kronik böbrek yetmezliði olan ve karaciðer nakli gerektiren hastalara kadavradan kombine karaciðer ve böbrek nakli yapýlmalýdýr. i- Morbid obez hastalar Vericilerde Görülen Morbidite ve Mortaliteler Vericiler hastanede ortalama 10 günden az kalýrlar. Verici hepatektomi sýrasýnda 400-800 cc kan kaybý olmaktadýr ve kan transfüzyonuna gerek duyulmamaktadýr. Vericilerin ortalama %1520'sinde komplikasyon geliþmektedir ve bunlarýn yarýsý cerrahi veya radyolojik giriþim gerektirmektedir. Eriþkinler için yapýlan canlýdan karaciðer nakli sonrasý daha büyük cerrahi iþlem olmasý, remnant karaciðerin ve metabolik rezervin daha az olmasý nedeniyle çocuklar için yapýlan verici hepatektomilerine göre daha fazla komplikasyon görülmektedir47. Vericilerde görülen komplikasyonlar ameliyat sonrasý ilk ayda görülen erken komplikasyonlar ve geç dönem komplikasyonlarý olmak üzere ikiye ayrýlýr. Safra yollarý komplikasyonlarý sýk görülen komplikasyonlarýn baþýnda gelir ve vericilerin yaklaþýk %5-10'unda görülmektedir48. Sað lobektomi sonrasý safra yollarý komplikasyonlarý daha sýk görülmektedir49. Safra kaçaðý hastanede uzun süre kalmaya sebep olabilir ve genellikle perkütan drenajla, bazen de cerrahi giriþim ile tedavi etmek gerekir. Kesi yüzeyinden kanama, hemoperitonyum, portal ven stenozu, portal ven, hepatik arter ya da hepatik ven trombozu görülen baþlýca diðer komplikasyonlardýr47. Bu hastalarda normal cerrahi iþlemler sonrasý görülen insizyonel herni, ileus, postoperatif gastrik disfonksiyon, Kaynaklar 1- Raia S, Nery JR, Mies S. Liver transplantation from live donors. Lancet 1989;2:497 2- Broelsch CE, Emond JC, Whitington PF, Thistlethwaite JR, Baker AL, Lichtor JL.Application of reduced-size liver transplants as split grafts, auxiliary orthotopic grafts, and living related segmental transplants. Ann Surg 1990;212:368-75. 3- Lo CM, Chan KL, Fan ST, et al. Living donor liver transplantation: the Hong Kong experience. Transplant Proc 1996;28:2390-2. 4- Lo CM, Fan ST, Chan JK, Wei W, Lo RJ, Lai CL. Minimum graft volume for successful adult-to-adult living donor liver transplantation for fulminant hepatic failure. Transplantation 1996;62:696-8. 5- Kawasaki S, Makuuchi M, Matsunami H, et al. Living related liver transplantation in adults. Ann Surg 1998;227:269-74. 6- Marcos A, Ham JM, Fisher RA, Olzinski AT, Posner MP. Singlecenter analysis of the first 40 adult-to-adult living donor liver transplants using the right lobe. Liver Transpl 2000;6:296-301. 7- Malago M, Burdelski M, Broelsch CE. Present and future challenges in living related liver transplantation. Transplant Proc 1999;31:1777-81. 8- Otte JB, Reding R, de Ville de Goyet J, et al. Experience with living related liver transplantation in 63 children. Acta Gastroenterol Belg 1999;62:355-62. 9- Yamaoka Y, Washida M, Honda K, et al. Liver transplantation using a right lobe graft from a living related donor. Transplantation 1994;57:1127-30. 10- Wachs ME, Bak TE, Karrer FM, et al. Adult living donor liver transplantation using a right hepatic lobe. Transplantation 1998;66:1313-6. 11- Matsunami H, Makuuchi M, Kawasaki S, et al. Living-related liver transplantation in fulminant hepatic failure. Lancet 1992;340:1411-2. 12- Hashikura Y, Makuuchi M, Kawasaki S, et al. Successful liv- 6 Þ. Emre ve ark. 1314151617181920- 2122- 23- 24- 252627282930313233- ing-related partial liver transplantation to an adult patient. Lancet 1994;343:1233. Singer PA, Siegler M, Whitington PF, et al. Ethics of liver transplantation with living donors. N Engl J Med 1989;321:620-2. Brandhagen D, Fidler J, Rosen C. Evaluation of the donor liver for living donor liver transplantation. Liver Transpl 2003;9:16-28. Trotter JF, Wachs M, Everson GT, Kam I. Adult-to-adult transplantation of the right hepatic lobe from a living donor. N Engl J Med 2002;346:1074-82. Sauer P, Schemmer P, Uhl W, Encke J. Living-donor liver transplantation: evaluation of donor and recipient. Nephrol Dial Transplant 2004;19:11-5. Hashikura Y, Kawasaki S, Miyagawa S, et al. Donor selection for living-related liver transplantation. Transplant Proc 1997;29:3410-1. Sukru Emre: Personal communication. Kiuchi T, Kasahara M, Uryuhara K, et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. ransplantation 1999;67:321-7. Lo CM, Fan ST, Chan JK, Wei W, Lo RJ, Lai CL. Minimum graft volume for successful adult-to-adult living donor liver transplantation for fulminant hepatic failure. Transplantation 1996;62:696-8. Emond JC, Renz JF, Ferrell LD, et al. Functional analysis of grafts from living donors. Implications for the treatment of older recipients. Ann Surg 1996;224:544-52. Bogetti JD, Herts BR, Sands MJ, Carroll JF, Vogt DP, Henderson JM. Accuracy and utility of 3-dimensional computed tomography in evaluating donors for adult living related liver transplants. Liver Transpl 2001;7:687-92. Fulcher AS, Szucs RA, Bassignani MJ, Marcos A. Right lobe living donor liver transplantation: preoperative evaluation of the donor with MR imaging. AJR Am J Roentgenol 2001;176:1483-91. Kamel IR, Kruskal JB, Warmbrand G, Goldberg SN, Pomfret EA, Raptopoulos V. Accuracy of volumetric measurements after virtual right hepatectomy in potential donors undergoing living adult liver transplantation. AJR Am J Roentgenol 2001;176:483-7. Rinella ME, Alonso E, Rao S, et al. Body mass index as a predictor of hepatic steatosis in living liver donors. Liver Transpl 2001;7:409-14. Behrns KE, Tsiotos GG, DeSouza NF, Krishna MK, Ludwig J, Nagorney DM. Hepatic steatosis as a potential risk factor for major hepatic resection. J Gastrointest Surg 1998;2:292-8. Ryan CK, Johnson LA, Germin BI, Marcos A. One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver Transpl 2002;8:1114-22. Marcos A, Fisher RA, Ham JM, et al. Liver regeneration and function in donor and recipient after right lobe adult to adult living donor liver transplantation. Transplantation 2000;69:1375-9. Fishbein TM, Fiel MI, Emre S, et al. Use of livers with microvesicular fat safely expands the donor pool. Transplantation 1997;64:248-51. Emre S.Living-donor liver transplantation in children. Pediatr Transplant 2002;6:43-6. Malago M, Rogiers X, Burdelski M, Broelsch CE. Living related liver transplantation: 36 cases at the University of Hamburg. Transplant Proc 1994;26:3620-1. Mortele KJ, Ros PR. Anatomic variants of the biliary tree: MR cholangiographic findings and clinical applications. AJR Am J Roentgenol 2001;177:389-94. Puente SG, Bannura GC. Radiological anatomy of the biliary tract: variations and congenital abnormalities. World J Surg 1983;7:271-6. 34- Gazelle GS, Lee MJ, Mueller PR. Cholangiographic segmental anatomy of the liver. Radiographics 1994;14:1005-13. 35- Hirao K, Miyazaki A, Fujimoto T, Isomoto I, Hayashi K. Evaluation of aberrant bile ducts before laparoscopic cholecystectomy: helical CT cholangiography versus MR cholangiography. AJR Am J Roentgenol 2000;175:713-20. 36- Mortele KJ, Cantisani V, Troisi R, de Hemptinne B, Silverman SG. Preoperative liver donor evaluation: Imaging and pitfalls. Liver Transpl 2003;9:6-14. 37- Goyen M, Barkhausen J, Debatin JF, et al. Right-lobe living related liver transplantation: evaluation of a comprehensive magnetic resonance imaging protocol for assessing potential donors. Liver Transpl 2002;8:241-50. 38- Mortele KJ, McTavish J, Ros PR. Current techniques of computed tomography. Helical CT, multidetector CT, and 3D reconstruction. Clin Liver Dis 2002;6:29-52. 39- Mortele KJ, Cantisani V, Troisi R, de Hemptinne B, Silverman SG. Preoperative liver donor evaluation: Imaging and pitfalls. Liver Transpl 2003;9:6-14. 40- Marcos A, Fisher RA, Ham JM, Selection and outcome of living donors for adult to adult right lobe transplantation. Transplantation 2000;69:2410-5. 41- Couinaud C. A "scandal": segment IV and liver transplantation. J Chir (Paris) 1993;130:443-6. 42- Nghiem HV. Imaging of hepatic transplantation. Radiol Clin North Am 1998;36:429-43. 43- Soyer P, Bluemke DA, Choti MA, Fishman EK. Variations in the intrahepatic portions of the hepatic and portal veins: findings on helical CT scans during arterial portography. AJR Am J Roentgenol 1995;164:103-8. 44- Fraser-Hill MA, Atri M, Bret PM, Aldis AE, Illescas FF, Herschorn SD. Intrahepatic portal venous system: variations demonstrated with duplex and color Doppler US. Radiology 1990;177:523-6. 45- Takahashi Y, Kumada H, Shimizu M, et al. A multicenter study on the prognosis of fulminant viral hepatitis: early prediction for liver transplantation. Hepatology 1994;19:1065-71. 46- Liu CL, Fan ST, Lo CM, et al. Live donor liver transplantation for fulminant hepatic failure in children. Liver Transpl 2003;9:1185-90. 47- Renz JF, Roberts JP. Long-term complications of living donor liver transplantation. Liver Transpl 2000;6:73-6. 48- Yamaoka Y, Morimoto T, Inamoto T, et al. Safety of the donor in living-related liver transplantation-an analysis of 100 parental donors. Transplantation 1995;59:224-6. 49- Fujita S, Kim ID, Uryuhara K, et al. Hepatic grafts from live donors: donor morbidity for 470 cases of live donation.Transpl Int 2000;13:333-9. 50- Durand F, Ettorre GM, Douard R, et al. Donor safety in living related liver transplantation: underestimation of the risks for deep vein thrombosis and pulmonary embolism. Liver Transpl 2002;8:118-20. 51- Ohkohchi N, Katoh H, Orii T, Fujimori K, Shimaoka S, Satomi S. Complications and treatments of donors and recipients in livingrelated liver transplantation.Transplant Proc 1998;30:3218-20. 52- Lee SY, Ko GY, Gwon DI, et al. Living donor liver transplantation: complications in donors and interventional management. Radiology 2004;230:443-9. 53- Kawagishi N, Ohkohchi N, Fujimori K, et al. Safety of the donor operation in living-related liver transplantation: analysis of 22 donors. Transplant Proc 1998;30:3279-80. 54- Grewal HP, Thistlewaite JR Jr, Loss GE, et al. Complications in 100 living-liver donors. Ann Surg 1998;228:214-9. 55- Pomfret EA, Pomposelli JJ, Lewis WD, et al. Live donor adult liver transplantation using right lobe grafts: donor evaluation and surgical outcome. Arch Surg 2001;136:425-33. 7 Canlýdan Karaciðer Naklinde Verici ve Alýcýlarýn Deðerlendirilmesi 56- Miller C, Florman S, Kim-Schluger L, et al. Fulminant and fatal gas gangrene of the stomach in a healthy live liver donor. Liver Transpl 2004;10:1315-9. 57- Strong RW. Whither living donor liver transplantation? Liver Transpl Surg 1999;5:536-8. 58- Pomfret EA.Early and late complications in the right-lobe adult living donor. Liver Transpl 2003;9:45-9. 59- Liver donor dies from postoperative complications in Japan. Transplant Week 2003. May 11, 2003; vol 4. 8