ReviewRadical surgery for hilar cholangiocarcinoma
Introduction
More than 40 years have gone by since the first description of hilar cholangiocarcinoma as a distinct tumor entity by Altemeier and Klatskin. Hilar cholangiocarcinoma is the most common of all different types of malignant tumors arising within the biliary tree. Biliary tract cancer originates in more than 50% of the patients from the bile duct bifurcation within the hepatic hilum. The close vicinity of these tumors to the portal vein, to the liver arteries and the liver parenchyma is one of the main obstacles to accomplish this goal. Moreover, lateral infiltration occurs early, because of a late diagnosis. This late diagnosis results from the fact that a lateral extension of epithelial biliary tract tumors is not compromised by a strong muscular layer which almost lacks in the bile duct. On the other hand, the detergent properties of the bile will allow a sufficient flow even shortly before a complete luminal obstruction.1 The growth pattern of hilar cholangiocarcinomas adds to the technical difficulties of a resection, because nodular and well demarcated or even encapsulated tumors are a rarity, while a periductal infiltration is typical. Irrespective of a local growth along lymphatic tracts, a microscopic infiltration of perineurial sheathes occurs.2, 3 Identification of tumor boundaries is hardly possible by digital palpation or visualisation.
Hilar cholangiocarcinoma must be distinguished from carcinomas arising within the biliary epithelium in the periphery of the liver or distal to the cystic duct down to the Papilla Vateri. The surgical strategy for intrahepatic cholangiocarcinomas follows the principles established for other mass-forming tumors in non-cirrhotic livers, as for example colorectal liver metastasis or some forms of hepatocellular carcinoma. This strategy will generally result in an extended liver resection, because most of these tumors will only be diagnosed in an advanced stage, as early symptoms are usually absent. Biliary tract cancers located distal to the cystic duct mostly have a close proximity to the pancreatic head. Therefore their surgical management involves many of the principles which are also applied for pancreatic head cancer. In addition, patients suffering from these distal cholangiocarcinomas undergo resection of the extrahepatic biliary tract up to the hepatic hilum.
During the last 40 years, major progress had been made on the field of palliation. The most important step forward were the introduction of endoscopic interventional techniques including stent placement. However, more or less individual reports on long-term survivors after surgical resection had already been brought forward in the 1970s. In the 1980s, liver transplantation appeared as an enticing expansion of the therapeutic armamentarium, especially for advanced tumors. At that time, the surgical mortality rates were still high. In addition, long-term survival rates were disappointing as well and did not allow the allocation of scarce donor grafts to patients suffering from cholangiocarcinoma.
Today, resection still represents the only potential curative therapeutic option for hilar cholangiocarcinoma. Over the last 25 years, there has been an increase in radical surgery, however, without the formulation of a unified therapeutic concept. This development has peaked over the last few years, also in terms of long-term results. In 1999, we described the so-called Berlin concept as a combination of an extended right hepatic resection and a portal vein resection.4
Section snippets
Extended right hepatic resection and portal vein resection
This concept, which we had proposed in 1999, was a surprising result of a multivariate analysis of prognostic factors in 100 patients in whom we had performed various types of resection at that time. As expected, surgical radicality, lymphangiosis carcinomatosa, perineural sheath infiltration and histopathological grading could be identified as independent prognostic variables for the entire group of patients. Restricting the multivariate analysis to patients in whom a formally curative
Extrahepatic bile duct resection
Today, most centers are combining hepatic resection and extrahepatic bile duct resection in the treatment of hilar cholangiocarcinoma. Extrahepatic bile duct resections only, i.e. without additional major liver resection, must be considered as an oncologically inefficient procedure over the long term. This strategy has been applied in curative as well as in palliative intention. Probably, it is warranted in neither of these two approaches. The mainstay of palliative treatment are endoscopic or
Problems of left hepatic resections
Hilar cholangiocarcinoma extending far to the left beyond the umbilical fissure, atrophy of the segments 2 and 3, or vascular complications within the left hemiliver may render an extended right hepatectomy with portal vein resection impossible. Therefore, the rate of left hepatectomies is about 25–30% of all resections.18 From an oncological point of view, the major problem is the preservation of the right hepatic artery and the right portal vein branch resulting in an increased risk of tumor
Lymphadenectomy
Bismuth et al. had been among the first to describe positive lymph nodes in hilar cholangiocarcinoma to be a less important prognostic parameter than in other gastrointestinal cancers.20 Other reports, also involving more aggressive approaches, are not conclusive in this respect as well.10, 21 Even more uncertainty prevails regarding the role of a lymphadenectomy, which is so far hardly supported by clinical data. In our concept, the lymph nodes of the hepatic hilum and the hepatoduodenal
Liver transplantation
Although there is not a revival of liver transplantation as therapeutic strategy for hilar cholangiocarcinoma, its potential is reassessed in many centers due to the recently published data on neoadjuvant radiochemotherapy by the Mayo Clinic group. Their therapeutic regimen consists of an external beam irradiation and an intraluminal brachytherapy combined with 5 FU based chemotherapy, which was first published in 2000.24 Meanwhile, this group has reported on an experience in 38 patients with
Living donor liver transplantation
The concept of living donor liver transplantation gained broader support in the 1990s, especially in pediatric liver transplantation. In this setting, a donor graft usually consists of liver segments 2 and 3 (left lateral section). The advantage is an operation for the live donor with minimal complications, whereas the main disadvantage is the small size of the graft which is suitable for a small child, but not for an adult recipient. Living donation of a right liver lobe became more popular by
Summary
Surgical treatment of patients suffering from hilar cholangiocarcinoma is highly demanding during all steps of treatment. Pre-operatively, an outstanding expertise in hepatobiliary surgery is required in order to be able to assess resectability and to plan the intervention. Intra-operatively, resection and transplantation represent the high end of hepatobiliary surgery when considering standards, demands and risks. Post-operatively, specific risks, for example liver insufficiency, but also
References (34)
- et al.
Evaluation of morbidity and mortality after resection for hilar cholangiocarcinoma—a single center experience
Surgery
(2000) - et al.
Magnetic resonance cholangiopancreatography-guided unilateral endoscopic stent placement for Klatskin tumors
Gastrointest Endosc
(2001) Percutaneous palliation of unresectable pancreatic cancer
Surg Clin North Am
(1995)- et al.
Aggressive surgical approaches to hilar cholangiocarcinoma: hepatic or local resection?
Surgery
(1998) - et al.
Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma
Liver Transpl
(2000) - et al.
Liver transplantation for perihilar cholangiocarcinoma after aggressive neoadjuvant therapy: a new paradigm for liver and biliary malignancies?
Surgery
(2006) - et al.
Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma
Am J Transplant
(2002) - et al.
Adult-to-adult living donor liver transplantation at the Asan Medical Center, Korea
Asian J Surg
(2002) - et al.
Combined adult-to-adult living donor right lobe liver transplantation and pancreatoduodenectomy for distal bile duct adenocarcinoma in a patient with primary sclerosing cholangitis
J Am Coll Surg
(2003) - et al.
Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma: a study of 57 autopsy-proven cases
Cancer
(1977)