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Cholangiocarcinoma as an Indication for Liver Transplantation in the Era of Transplant Oncology.

ABSTRACT: Cholangiocarcinoma (CCA) arises from the biliary tract epithelium and accounts for 10-15% of all hepatobiliary malignancies. Depending on anatomic location, CCA is classified as intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA). The best treatment option for pCCA is liver resection and when a radical oncological surgery is obtained, 5-year survival rate are around 20-40%. In unresectable patients, following a specific protocol, liver transplantation (LT) for pCCA showed excellent long-term disease-free survival rates. Fewer data are available for iCCA in LT setting. Nevertheless, patients with very early unresectable iCCA appear to achieve excellent outcomes after LT. This review aims to evaluate existing evidence to define the current role of LT in the management of patients with CCA.

SUBMITTER: Gringeri E

PROVIDER: S-EPMC7290472 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Cholangiocarcinoma as an Indication for Liver Transplantation in the Era of Transplant Oncology.

Gringeri Enrico E Gambato Martina M Sapisochin Gonzalo G Ivanics Tommy T Lynch Erica Nicola EN Mescoli Claudia C Burra Patrizia P Cillo Umberto U Russo Francesco Paolo FP

Journal of clinical medicine 20200505 5

Cholangiocarcinoma (CCA) arises from the biliary tract epithelium and accounts for 10-15% of all hepatobiliary malignancies. Depending on anatomic location, CCA is classified as intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA). The best treatment option for pCCA is liver resection and when a radical oncological surgery is obtained, 5-year survival rate are around 20-40%. In unresectable patients, following a specific protocol, liver transplantation (LT) for pCCA showed excellent long-term ...[more]

PMID: 32380750

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Project description:Despite numerous advances and emerging data, liver transplantation in the setting of gastrointestinal malignancies remains controversial outside of certain accepted indications. In an era of persistent organ shortage and increasing organ demand, allocation of liver grafts must be considered carefully. While hepatocellular carcinoma and hilar cholangiocarcinoma have become accepted indications for transplantation, tumor size and standardized multi-disciplinary treatment protocols are necessary to ensure optimal patient outcomes. As more studies seeking to expand the oncologic indications for liver transplantation are emerging, it is becoming increasingly clear that tumor biology and response to therapy are key factors for optimal oncologic outcomes. In addition, time from diagnosis to transplantation appears to correlate with survival, as stable disease over time portends better outcomes post-operatively. Identifying aggressive disease pre-transplant remains difficult with current imaging and tissue sampling techniques. While tumor size and stage are important prognostic predictors for most malignancies, patient and tumor selection protocols are necessary. As the fields of medical and surgical oncology continue to evolve, it is clear that a protocolized interdisciplinary treatment approach is necessary for combatting any cancer effectively. Disease stability over time and response to neoadjuvant therapy may be the best predictors for successful patient outcomes and can be easily incorporated in our treatment paradigms. Current data evaluating liver transplantation for expanded oncologic indications such as: expanded criteria hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed tumors, and liver limited metastatic colorectal carcinomas, incorporate multi-modal therapies and evaluation of tumor treatment response. While further investigation is necessary, initial results suggest there is an expanded role for transplant surgery in malignancy in a new era of liver transplant oncology.

Project description:Background & aimsLittle is known about outcomes of liver transplantation for patients with non-alcoholic steatohepatitis (NASH). We aimed to determine the frequency and outcomes of liver transplantation for patients with NASH in Europe and identify prognostic factors.MethodsWe analysed data from patients transplanted for end-stage liver disease between January 2002 and December 2016 using the European Liver Transplant Registry database. We compared data between patients with NASH versus other aetiologies. The principle endpoints were patient and overall allograft survival.ResultsAmong 68,950 adults undergoing first liver transplantation, 4.0% were transplanted for NASH - an increase from 1.2% in 2002 to 8.4% in 2016. A greater proportion of patients transplanted for NASH (39.1%) had hepatocellular carcinoma (HCC) than non-NASH patients (28.9%, p <0.001). NASH was not significantly associated with survival of patients (hazard ratio [HR] 1.02, p = 0.713) or grafts (HR 0.99; p = 0.815) after accounting for available recipient and donor variables. Infection (24.0%) and cardio/cerebrovascular complications (5.3%) were the commonest causes of death in patients with NASH without HCC. Increasing recipient age (61-65 years: HR 2.07, p <0.001; >65: HR 1.72, p = 0.017), elevated model for end-stage liver disease score (>23: HR 1.48, p = 0.048) and low (<18.5 kg/m2: HR 4.29, p = 0.048) or high (>40 kg/m2: HR 1.96, p = 0.012) recipient body mass index independently predicted death in patients transplanted for NASH without HCC. Data must be interpreted in the context of absent recognised confounders, such as pre-morbid metabolic risk factors.ConclusionsThe number and proportion of liver transplants performed for NASH in Europe has increased from 2002 through 2016. HCC was more common in patients transplanted with NASH. Survival of patients and grafts in patients with NASH is comparable to that of other disease indications.Lay summaryThe prevalence of non-alcoholic fatty liver disease has increased dramatically in parallel with the worldwide increase in obesity and diabetes. Its progressive form, non-alcoholic steatohepatitis, is a growing indication for liver transplantation in Europe, with good overall outcomes reported. However, careful risk factor assessment is required to maintain favourable post-transplant outcomes in patients with non-alcoholic steatohepatitis.

Project description:Hilar cholangiocarcinoma (CCA) is a difficult malignancy to treat surgically because of its anatomical location and its frequent association with primary sclerosing cholangitis. Neoadjuvant chemoradiotherapy followed by liver transplantation in lymph node-negative patients has been advanced by select liver transplant centers for the treatment of patients with unresectable disease. This approach has most commonly used external-beam radiotherapy in combination with biliary brachytherapy and 5-fluorouracil-based chemotherapy. Our center recently embarked on a protocol using stereotactic body radiation therapy (SBRT) followed by capecitabine in lymph node-negative patients until liver transplantation. We, therefore, retrospectively determined the tolerability and pathological response in this pilot study. During a 3-year period, 17 patients with unresectable hilar CCA were evaluated for treatment under this protocol. In all, 12 patients qualified for neoadjuvant therapy and were treated with SBRT (50-60 Gy in 3-5 fractions over the course of 2 weeks). After 1 week of rest, capecitabine was initiated at 1330 mg/m(2) /day, and it was continued until liver transplantation. During neoadjuvant therapy, there were 35 adverse events in all, with cholangitis and palmar-plantar erythrodysesthesia being the most common. Capecitabine dose reductions were required on 5 occasions. Ultimately, 9 patients were listed for transplantation, and 6 patients received a liver transplant. The explant pathology of hilar tumors showed at least a partial treatment response in 5 patients, with extensive tumor necrosis and fibrosis noted. Additionally, high apoptotic indices and low proliferative indices were measured during histological examinations. Eleven transplant-related complications occurred, and the 1-year survival rate after transplantation was 83%. In this pilot study, neoadjuvant therapy with SBRT, capecitabine, and liver transplantation for unresectable CCA demonstrated acceptable tolerability. Further studies will determine the overall future efficacy of this therapy.

Dataset Information

Cholangiocarcinoma as an Indication for Liver Transplantation in the Era of Transplant Oncology.

Publications

Cholangiocarcinoma as an Indication for Liver Transplantation in the Era of Transplant Oncology.

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