Palliation of unresectable cholangiocarcinoma: can we do more than merely drain?

Oncologically radical surgical resection (R0) is the only chance of cure for perihilar and distal cholangiocarcinomas with 5-year survival rates of 25 % – 50 % and 70 %, respectively [1] [2]. Orthotopic liver transplantation (OLT) in patients with unresectable perihilar cholangiocarcinoma is also performed with curative intent, but in only a few centers around the world [3]. While surgical resection is the favored surgical treatment modality, OLT might be preferred in patients with cholangiocarcinoma occurring in the setting of primary sclerosing cholangitis (PSC), because of the limited hepatic reserves and the risk of recurrent cholangiocarcinoma in the liver remnant. In patients in whom resectability is restricted by the risk of hepatic failure because of the small volume of the hepatic remnant, preoperative portal vein embolization of the hemiliver that will be resected to induce hypertrophy of the contralateral hemiliver may be practiced [4]. Unfortunately, the vast majority of patients with perihilar cholangiocarcinoma are inoperable and/or unresectable at the time of diagnosis because of extensive local biliary and vascular invasion or, less frequently, distant metastases. The typical clinical presentation includes progressive cholestasis, itching, jaundice, and, more rarely, recurrent cholangitis resulting from progressive biliary obstruction due to the tumor’s growth along the biliary tree. Obstructive biliary symptoms usually require a palliative treatment, which is aimed at improving quality of life and prolonging survival. The mainstay of palliative treatment in this setting is biliary drainage, which may be obtained surgically, endoscopically, or via the percutaneous transhepatic route (or by a combination of the last two approaches). Surgical palliation has lost much of its importance in the last three decades thanks to the development of less invasive techniques such as endoscopy and interventional radiology. However, palliative surgical resection might still have a role in patients who are fit for surgery, because of better results in terms of survival [5], which reflect the long natural history of these tumors. Palliation is currently obtained mainly by endoscopic or percutaneous transhepatic placement of self-expandable metal stents (SEMSs). SEMSs have shown better results in terms of long-term efficacy compared with plastic stents in randomized controlled trials, also in the setting of perihilar malignant strictures [6]. In patients with complex perihilar cholangiocarcinoma, involving the main hepatic confluence, only uncovered SEMSs should be used in order to avoid potential septic complications due to the blockage of intrahepatic biliary radicles by covered stents. In contrast, it is still unclear how much hepatic parenchyma should be drained to achieve the best palliation. The current tendency is to drain as much as possible, and, when feasible, to obtain a complete drainage of the intrahepatic branches, even in complex strictures, by placement of multiple SEMSs, either side by side or in a Y shape. In fact, because of the long natural history of these tumors, which have a low propensity to metastasize, septic complications due to bile infection in undrained segments represent a major cause of death before the tumor itself has disseminated. Adequate biliary drainage therefore seems to be the pillar of palliative treatment in perihilar cholangiocarcinoma. However, can we do more than merely drain? Mukewar et al. [7] herein report on the use of endoscopically delivered high dose-rate (HDR) brachytherapy as part of neoadjuvant therapy for unresectable perihilar cholangiocarcinoma in patients who were candidates for OLT: 40 patients were included in a treatment protocol with curative intent that comprised external beam radiotherapy (EBRT), chemotherapy, and HDR brachytherapy, eventually followed by OLT. This experience shows that HDR brachyth