Eligibility for Liver Transplantation in Patients with Perihilar Cholangiocarcinoma

Abstract

Background Liver transplantation (LT) has been performed in a select group of patients presenting with unresectable or primary sclerosing cholangitis (PSC)-associated perihilar cholangiocarcinoma (pCCA) in the Mayo Clinic with a reported 5-year overall survival (OS) of 53% on intention-to-treat analysis. The objective of this study was to estimate eligibility for LT in a cohort of pCCA patients in two tertiary referral centers. Methods Patients diagnosed with pCCA between 2002 and 2014 were included from two tertiary referral centers in the Netherlands. The selection criteria used by the Mayo Clinic were retrospectively applied to determine the proportion of patients that would have been eligible for LT. Results A total of 732 consecutive patients with pCCA were identified, of whom 24 (4%) had PSC-associated pCCA. Overall, 154 patients had resectable disease on imaging and 335 patients were ineligible for LT because of lymph node or distant metastases. An age limit of 70 years led to the exclusion of 50 patients who would otherwise be eligible for LT. After applying the Mayo Clinic criteria, only 34 patients (5%) were potentially eligible for LT. Median survival from diagnosis for these 34 patients was 13 months (95% CI 3–23). Conclusion Only 5% of all patients presenting with pCCA were potentially eligible for LT under the Mayo criteria. Without transplantation, a median OS of about 1 year was observed.

EASL Clinical Practice Guidelines on sclerosing cholangitis

“…336 Only highly selected cases with early-stage CCA are eligible, most often after neoadjuvant therapy, including external beam radiotherapy and endoluminal brachytherapy. 399,400 Strict selection is likely a critical success factor, 401,402 and results have been generally better in people with PSC (74% 5-year overall survival) than in people with spontaneous CCA (58% 5-year overall survival). 399 One reason for this difference may be the intra-and periductal pattern of growth and lower frequency of a detectable tumour among people with PSC in these series, 399 leaving the question open as to what radial tumour size (traditionally below 3 cm) should be allowed.…”

Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis

“…Detailed evaluation of genetic and epigenetic determinants is expected to outline useful insights and provide guidance in prioritising targetable molecules and pathways for the prevention, diagnosis and treatment of PSC-associated CCA[ 6 ]. It has been suggested that significant differences may exist between patients with de novo PHCCA and those with PSC-associated PHCCA, who have an aberrant DNA methylation profile and may be noted to have oncogenic mutations prior to clinical manifestations[ 198 ]. Non-surgical management of PSC-associated cancers remains a therapeutic conundrum, partly because of their genetic heterogeneity and rapid development of therapeutic resistance with genetic evolution of the tumour.…”

“…Non-surgical management of PSC-associated cancers remains a therapeutic conundrum, partly because of their genetic heterogeneity and rapid development of therapeutic resistance with genetic evolution of the tumour. The genetic aberrations of PSC-associated CCA, as well as the clinical implications of such differences with de novo CCA, have yet to be elucidated[ 119 , 198 ]. Molecular profiling of CCA tissue is highly recommended, as it could lead to effective, personalised treatment options[ 148 ].…”

Surgical Therapy for Perihilar Cholangiocarcinoma: State of the Art

“…Due to the extent and complexity of the disease, resection is unfortunately associated with substantial morbidity (50%) [3] and mortality (14%) [5]. In highly selected cases, especially young patients and patients with primary sclerosing cholangitis, liver transplantation may be an option as well [1, 24]. Minimally invasive surgery for pCCA is mainly due to the complexity of the disease, still in its infancy.…”