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

Abstract

Primary sclerosing cholangitis (PSC) is a premalignant condition and a well-documented risk factor for cholangiocarcinoma (CCA) which is the most common malignancy in this setting and the leading cause of deaths in the recent years, with an increasing incidence. PSC-associated CCA has a geographical distribution that follows the incidence of PSC, with an observed ascending gradient from the Eastern to the Western and from the Southern to the Northern countries. It may arise at any location along the biliary tree but is most common in the perihilar area. Patients with PSC and intrahepatic or perihilar CCA are typically not suitable for liver resection, which is otherwise the treatment of choice with curative intent in patients with resectable tumours, providing a radical resection with clear margins can be achieved. This largely relates to the commonly advanced stage of liver disease at presentation, which allows consideration for liver resection only for a very limited number of suitable patients with PSC. On the other hand, remarkable progress has been reached in the last decades with the implementation of a protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) for the treatment of perihilar CCA, within specific criteria. Excellent results have been achieved particularly for PSC patients with this cancer, who seem to benefit the most from this treatment, having converted this into an accepted indication for transplantation and the standard of care in several experienced centres. Intrahepatic CCA as an indication for OLT remains controversial and has not been accepted given disappointing previous results. However, as recent studies have shown favourable outcomes in early intrahepatic CCA, it may be that under defined criteria, OLT may play a more prominent role in the future. Distal CCA in the context of PSC requires aggressive surgical treatment with curative intent, when feasible. This review provides insight about particular features of CCA in the setting of PSC, with a main focus on its incidence, considerations relating to its anatomical location and implications to treatment and outcomes, through the viewpoint of historical evolution of management, and future perspectives.

Stereotactic radiotherapy for intrahepatic cholangiocarcinoma

“…CCA can be further subdivided by the site of origin in the biliary tract (Figure 1 ): Intrahepatic CCAs (iCCA) arise from sites proximal to the second order branches of the right or left hepatic duct up to the canals of Hering, while perihilar CCAs (phCCA), also known as Klatskin tumours, arise between the second order branches of the right and/or left hepatic duct and the cystic duct confluence. Distal CCAs (dCCA) arise between the cystic duct confluence and the ampulla of Vater[ 5 - 7 ]. phCCA and dCCAs are collectively termed extrahepatic CCAs (eCCAs) and account for approximately 80% of all diagnoses of CCAs overall, while the remainder are intrahepatic[ 6 , 8 ].…”

“…Morphologically, depending on their pattern of growth and appearance, they are categorised in three different types. The mass-forming type, which is the most frequent, accounts for presentation with a mass, the periductal-infiltrating type is characterised by growth along the wall of the bile duct, and the intraductal-growing type by intraluminal growth[ 7 ].…”

“…Complete surgical resection is the only prospect for cure in CCA, but this is only possible in < 30% of patients due to advanced disease at presentation[ 14 , 15 ]. Surgery ranges from hepatectomy in iCCA, hepatectomy and/or hilar resection in phCCA, or pancreatoduodenectomy in extrahepatic tumours, to liver transplantation in selected cases of CCA[ 7 , 16 ].…”

Current Status of 68Ga-Pentixafor in Solid Tumours

“…It is aggressive and fatal with a median survival of less than 24 months [ 103 ]. While surgery is the most effective treatment for resectable CCA [ 104 ], unfortunately the clinical symptoms of CCA are non-specific and early diagnosis is often difficult. As a result, the majority of CCA patients are diagnosed at an advanced stage, at which therapeutic options are limited [ 105 ].…”

Cholangiocarcinoma cell proliferation is enhanced in primary sclerosing cholangitis: A role for IL‐17A

“…Five-year survival of PSC-related CCA (PSC-CCA) is only 10%. 5,6 Compared with sporadic CCA, PSC-CCA occurs at a significantly younger age of 48 years old vs 65 in sporadic CCA. 5 Biological differences between PSC-CCA and sporadic CCA and related consequences for cancer management have only recently gained attention.…”