001 hpb giri..qxp

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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.
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I
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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
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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
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Eðer metindeki malzeme, ilaç ve aletlerden
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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
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34365 ÝSTANBUL.
Gönderilen yazýlarla ilgili olarak aþaðýdaki faks,
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ele alýnmalýdýr. Bir özet verilmelidir.
Özgün makaleler
Metin her biri ayrý sayfalarda baþlayan bölümler
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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
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
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
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 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.
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
[email protected]
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
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
Pankreatit
IV
Cerrahi giriþim
Eksternal drenaj
Eksternal drenaj
Eksternal drenaj
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
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
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
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
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
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
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
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.
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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.
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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.
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.
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
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
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
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
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
Þükrü Emre
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: [email protected]
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
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
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
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Tzakis A, Todo S, Stieber A, Starzl TE. Venous jump grafts for
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Langnas An, Marujo WC, Stratta RJ, et al. A selective approach
to preexisting portal vein thrombosis in patients undergoing
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Suchy FJ SR, Ballistreri WF. Liver Disease in Children.
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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
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 [email protected]
9
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
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
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
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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.
Canlýdan Karaciðer Naklinde Verici ve Alýcýlarýn
Deðerlendirilmesi
Þükrü Emre, Ýlhan Karabýçak
Türk HPB
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: [email protected]
1
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
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
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,
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7
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Transplant Week 2003. May 11, 2003; vol 4.
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