Liver transplantation for cholangiocarcinoma: current best practice.

Current opinion in organ transplantation (Impact Factor: 2.38). 06/2014; 19(3):245-52. DOI: 10.1097/MOT.0000000000000087
Source: PubMed

ABSTRACT Cholangiocarcinoma is a rare tumour with dismal prognosis. Only radical resection offers a chance for cure with reported survivals ranging from 25 to 45% at 5 years. Considering the low rate of resectability and lack of efficacy of other treatments, liver transplantation has emerged as a reasonable approach to cure selective patients with unresectable diseases. The use of liver transplantation, however, is associated with the inherent risk of early tumour recurrence due to the need for immunosuppression and the poor survival rate. This review will focus on the role of liver transplantation in treating patients with cholangiocellular cancer.
The indication of liver transplantation for cholangiocarcinoma has evolved over time moving from an absolute to a relative contraindication until eventually becoming the best indication for a small group of patients presenting with unresectable perihilar cholangiocarcinoma, when associated with a neoadjuvant chemoradiotherapy. In contrast, the indication of liver transplantation for intrahepatic cholangiocarcinoma is far from being established and should be offered only under protocol, mainly for small tumours in the setting of cirrhosis.
The poor outcome of cholangiocarcinoma, irrespective of the therapy, justifies the search for novel approaches. Only selective patients with perihilar cholangiocarcinoma subjected to a neoadjuvant protocol may qualify for liver transplantation.

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    ABSTRACT: In the treatment of adenocarcinoma of the proximal bile duct, our current strategy is to resect the tumor radically and to offer patients with unresectable tumors the chance of hepatic transplantation, if extrahepatic tumor growth is exluded. Tumor resection is performed by resection of the hilum alone or combined with partial hepatectomy. The latter procedure enables radical treatment of more advanced tumor stages and, eventually, a higher degree of radically is achieved, and is recommended. This concept is based on our experience with 108 patients with proximal bile duct carcinoma operated on between February, 1975 and October, 1986. In 10 patients, no therapeutic or palliative surgical procedure could be performed during laparotomy because of advanced tumor stage. In 30 patients, various drainage procedures were performed. Fifty-two patients underwent resection: 25 underwent resection of the hilum only, and 27 underwent resection of the hilum combined with partial liver resection. Twenty-eight of these resections were classified as curative and 24 as palliative. Sixteen patients with unresectable tumors had hepatic transplantation. In 7 of these patients, extrahepatic tumor growth was already present at the time of liver transplantation. Median survival times were: laparotomy only, 1 month; drainage procedures, 5 months; total resection, 15 months; curative resection, 23 months; palliative resection, 7 months; liver grafting, 16 months. Seven patients are alive up to 21 months posttransplantation. On the basis of favorable results in our more recent group of patients, liver grafting as the ultimate chance for tumor removal in patients otherwise treatable only by palliative drainage procedures may be justified.Nuestra estrategia actual en el tratamiento del adenocarcinoma de la porcin proximal del canal biliar es la reseccin radical del tumor y, para los pacientes con tumores no resecables, la posibilidad de trasplante heptico si se ha demostrado que no hay crecimiento tumoral extraheptico. La reseccin tumoral es realizada mediante la reseccin del hilio solamente o combinada con hepatectoma parcial. Este ltimo procedimiento, que hace posible el tratamiento radical de los estados tumorales ms avanzados y que eventualmente logra un mayor grado de radicalidad, es el recomendado. El concepto se fundamenta en la experiencia con 108 pacientes con carcinoma del canal biliar proximal operados entre febrero de 1975 y octubre de 1986.En 10 pacientes no fue posible realizar procedimiento alguno de tipo teraputico o paliativo durante la laparotoma debido al avanzado estado del tumor. Diversos procedimientos de drenaje fueron ejecutados en 30 pacientes. Cincuenta y dos pacientes fueron sometidos a reseccin, 25 con reseccin del hilio solamente, 27 con reseccin combinada con reseccin parcial del hgado; 28 de las resecciones fueron clasificadas como curativas y 24 como paliativas; 16 pacientes con tumores no resecables reciberion trasplante heptico, y en 7 de ellos haba crecimiento tumoral extraheptico en el momento del trasplante heptico.Las supervivencias medias fueron: laparotoma, 1 mes; procedimientos de drenaje, 5 meses; reseccin total, 15 meses; reseccin curativa, 23 meses; reseccin paliativa, 7 meses; trasplante heptico, 16 meses. Siete pacientes se hallan vivos a los 21 meses posttrasplante. Con base en los resultados favorables en el grupo ms reciente de nuestros pacientes, el trasplante de hgado como la ltima posibilidad de remocin del tumor en pacientes que no podran ser tratados sino mediante procedimientos paliativos de drenaje, puede estar justificado.Pour traiter le cancer de la partie suprieure de l'arbre biliaire la stratgie actuelle des auteurs est de procder l'exrse radicale de la tumeur ou de pratiquer une transplantation lorsque la tumeur ne peut tre rsque ds lors qu'il n'y a pas d'extension extra-hpatique du processus tumoral. L'exrse de la tumeur est effectue par rsection isole du hile biliaire ou rsection associe de la lsion et d'un segment du foie; cette dernire mthode qui s'applique aux cancers plus tendus est recommande car plus radicale. Leur conception repose sur leur exprience concernant 108 cas oprs de fvrier 1975 octobre 1986.Chez 10 malades aucune intervention radicale ou palliative ne put tre pratique en raison du stade avanc de la tumeur. Chez 30 patients: diffrentes oprations de drainage furent pratiques. En revanche, 52 sujets subirent une exrse: 25 une rsection biliaire, 27 une rsection du hile associe une hpatectomie partielle; 28 de ces rsections tant considres comme opration palliative, 24 comme palliative. Seize malades qui prsentaient une lsion inacessible l'exrse ont t traits par une transplantation hpatique mais 7 d'entre eux accusrent ultrieurement une extension extra-hpatique du processus tumoral.Les temps de survie furent de 1 mois aprs laparotomie, 5 mois aprs intervention de drainage, 15 mois aprs rsection, 23 mois aprs opration dite curative, 7 mois aprs opration dite palliative, 21 mois aprs transplantation chez 7 malades. En raison des rsultats favorables chez les derniers malades, la transplantation hpatique constitue pour les auteurs l'ultime chance de traitement radical des patients qui relveraient autrement d'une opration palliative de drainage du fait de l'importance de la tumeur.
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    ABSTRACT: Although the surgical treatment of hilar cholangiocarcinoma represents the only potentially curative option, survival figures remain low over the long term. After hilar and partial hepatic resections for hilar cholangiocarcinoma, loco-regional tumor recurrence appears as the primary site of failure. From April 1992 to April 1996, 14 patients underwent extended bile duct resections. Extended bile duct resections combine total hepatectomy, partial pancreatoduodenectomy, and liver transplantation in an attempt to eradicate the entire biliary tract without dissecting the hepatoduodenal ligament. The postoperative 60-day mortality rate was 14% (n = 2). The rate of curative resections was 93% (13 of 14 extended bile duct resections). One- and 4-year survival rates after curative resections were 56% and 30%, respectively. The rate of curative resections increased by combining total hepatectomy, partial pancreatoduodenectomy, and liver transplantation, i.e., extended bile duct resection. However, survival figures have not improved accordingly. Therefore, this extended surgical procedure has to be implemented with caution and possibly not without modifications (e.g., multimodal treatment).
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    ABSTRACT: The objective of this article is to introduce a simple method for classifying cholangiocarcinomas and to apply this system to analyze a large number of patients from a single institution. For the past 2 decades, most western reports on cholangiocarcinoma have separated intrahepatic from extrahepatic tumors and have subclassified this latter group into proximal, middle, and distal subgroups. However, "middle" lesions are uncommon and are managed most often either with hilar resection or with pancreatoduodenectomy. The spectrum of cholangiocarcinoma, therefore, is best classified into three broad groups: 1) intrahepatic, 2) perihilar, and 3) distal tumors. These categories correlate with anatomic distribution and imply preferred treatment. The records of all patients with histologically confirmed cholangiocarcinoma who underwent surgical exploration at The Johns Hopkins Hospital over a 23-year period were reviewed. Of 294 patients with cholangiocarcinoma, 18 (6%) had intrahepatic, 196 (67%) had perihilar, and 80 (27%) had distal tumors. Age, gender, race, and associated diseases were similar among the three groups. Patients with intrahepatic tumors, by definition, were less likely (p < 0.01) to be jaundiced and more likely (p < 0.05) to present with abdominal pain. The resectability rate increased with a more distal location (50% vs. 56% vs. 91%), and resection improved survival at each site. Five-year survival rates for resected intrahepatic, perihilar, and distal tumors were 44%, 11%, and 28%, and median survival rates were 26, 19, and 22 months, respectively. Postoperative radiation therapy did not improve survival. In a multivariate analysis resection (p < 0.001. hazard ratio 2.80), negative microscopic margins (p < 0.01, hazard ratio 1.79), preoperative serum albumin (p < 0.04, hazard ratio 0.82), and postoperative sepsis (p < 0.001, hard ratio 0.27) were the best predictors of outcome. Cholangiocarcinoma is best classified into three broad categories. Resection remains the primary treatment, whereas postoperative adjuvant radiation has no influence on survival. Therefore, new agents or strategies to deliver adjuvant therapy are needed to improve survival.
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