Review Article

Surgical, Neo-adjuvant and Adjuvant Management Strategies in Biliary Tract Cancer

J. R. A. Skipworth; S. W. M. Olde Damink; C. Imber; J. Bridgewater; S. P. Pereira; M. Malagó

Disclosures

Aliment Pharmacol Ther. 2011;34(9):1063-1078. 

In This Article

Abstract and Introduction

Abstract

Background The majority of patients with cholangiocarcinoma present with advanced, irresectable tumours associated with poor prognosis. The incidence and mortality rates associated with cholangiocarcinoma continue to rise, mandating the development of novel strategies for early detection, improved resection and treatment of residual lesions.
Aim To review the current evidence base for surgical, adjuvant and neo-adjuvant techniques in the management of cholangiocarcinoma.
Methods A search strategy incorporating PubMed/Medline search engines and utilising the key words biliary tract carcinoma; cholangiocarcinoma; management; surgery; chemotherapy; radiotherapy; photodynamic therapy; and radiofrequency ablation, in various combinations, was employed.
Results Data on neo-adjuvant and adjuvant techniques remain limited, and much of the literature concerns palliation of inoperable disease. The only opportunity for long-term survival remains surgical resection with negative pathological margins or liver transplantation, both of which remain possible in only a minority of selected patients. Neo-adjuvant and adjuvant techniques currently provide only limited success in improving survival.
Conclusions The development of novel strategies and treatment techniques is crucial. However, the shortage of randomised controlled trials is compounded by the low feasibility of conducting adequately powered trials in liver surgery, due to the large sample sizes that are required.

Introduction

Cholangiocarcinoma (CCa) arises from the epithelia of the biliary tract[1] and has an incidence of 1–2 per 100,000 UK population,[2,3] although the UK and worldwide incidence (particularly of intra-hepatic CCa[4]) and mortality rates associated with CCa continue to rise.[3–6] Approximately 60% of CCa patients are male and in their 7th decade of life,[7] as well as often being heavy smokers or diabetics.[4] Further known associations include primary sclerosing cholangitis (PSC), chronic or recurrent biliary infection, cirrhosis, hepatitis C, Caroli disease and hepatolithiasis.

Approximately 60–70% of CCa arise in the perihilar region (Klatskin tumours), involving the main extrahepatic bile duct and potentially extending to, and through, the bile duct bifurcation at the level of the liver.[1] Twenty to thirty per cent of tumours arise outside the liver from the common bile duct (CBD) beyond the cystic duct, sometimes extending to the ampulla, and often leading to strictures rather than compressive masses.[1] Patients with extrahepatic lesions generally present with painless jaundice, although approximately 10% will present with signs of sepsis and cholangitis. Tumours arising from smaller bile ducts within the liver parenchyma (intrahepatic) often form a solitary mass that contribute to nonspecific symptoms such as right upper quadrant discomfort, anorexia and nausea.

The natural history of CCa is characterised by the gradual infiltration of, and spread along, the biliary tract, resulting in the gradual development of cholestasis, cholangitis and hepatic failure. The majority of patients present late in the course of disease with signs of biliary obstruction and sepsis and death commonly results from recurrent or refractory obstruction and sepsis, rather than metastatic disease.

The increasing incidence and mortality rates associated with CCa mandate the development of techniques for early lesion detection, improved resection and treatment of inoperable and residual disease following surgery. Here, a search strategy incorporating PubMed and Medline search engines and utilising the key words biliary tract carcinoma; cholangiocarcinoma; management; surgery; chemotherapy; radiotherapy; photodynamic therapy; and radiofrequency ablation was used to review the current evidence base for surgical, adjuvant and neo-adjuvant management techniques for cholangiocarcinoma.

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