Specialist Viewpoint – or cholangiocarcinoma as they see it …

Article 3

Surgery for Cholangiocarcinoma

By Professor Brian R Davidson
Consultant HPB and Liver Transplant Surgeon, University Department of Surgery, Royal Free Hospital
Professor of Surgery, Head of HPB and Liver transplant Research, UCL
UK Editor, Cochrane HPB Group for Evidence based Healthcare

Cholangiocarcinoma is a rare cancer occurring in 1 or 2 people out of every 100,000, resulting in about 1800 new patients every year in the UK.  As surgery is the only cure all patients should be carefully evaluated in a specialist HPB Unit where there is a surgeon with experience in managing this condition.

The cancer may present within the liver in which case the affected portion of the liver is removed. Fortunately the liver is able to fully regenerate after surgery. Other cancers may present with jaundice due to occlusion of the distal bile duct in a similar fashion to pancreatic cancer. These cancers are treated, as with pancreatic cancers, by resecting the duodenum and the head of pancreas in an operation named Whipple, after an American surgeon (Allen Whipple 1935).  The commonest site of developing a bile duct cancer is where the bile tubes exit the liver and this is given a special name of a Klatskin tumour, after a famous American physician (Gerald Klatskin) who described the condition.

These Klatskin tumours spread into the liver, to the tissue glands around the major liver blood vessels and often block the blood supply to the liver itself.  They require very careful evaluation to determine the exact extent of the cancer, presence of spread and how to optimally resolve the jaundice by insertion of drainage tubes prior to surgery. The surgical resection usually involves resection of a large proportion of the liver, the entire bile duct and all the lymph nodes around the liver.  If the tumour is affecting the blood supply to the liver then these blood vessels also need to be resected and reconstructed, adding to the length and complexity of the surgery. Until the liver has had an opportunity to regenerate the patient is at risk of liver failure, which can be fatal. Until recent years this type of complex surgery was rarely performed in the UK, but pioneers in Japan have demonstrated that it can be done safely and with good cancer cure rates. These complex procedures have been adopted in selected centres in the UK, but many clinicians feel that some patients are not offered surgery as expertise is not available locally.

A major aim of the surgery is to obtain complete cancer resection (called an R0 resection) which is achieved in highly specialist units in over 80% of cases. This gives the best possible chance of cure.  One of the important developments regarding liver surgery is individualising the surgical approach dependent on the extent of an individual patient’s cancer. This individualised plan allows safe surgery whilst giving the best possible chance of achieving a complete resection.  As part of this planning, the volume of liver which will be left after surgery is measured by a special computer programme. If there is a low volume, pre-operative occlusion of a branch of the vein to the liver to be removed can be done by the radiology team through a small skin puncture reducing the risk of pre-operative liver failure. This procedure allows the future liver remnant to grow prior to the surgery and is known as portal vein embolisation (PVE).

Major progress in the outcome of surgery could be achieved if funding was available to develop centres of excellence for the management of cholangiocarcinoma. Although it is classified as a rare cancer, its incidence has increase dramatically and the cause of the increase is unknown.  Specialist centres would link across the UK (by teleconferencing) and would have the necessary experience in endoscopy, interventional radiology, complex major surgery and intensive care for the management of post operative care.  In parallel with the facilities and expertise, to obtain the results seen in the premier Japanese centres, the Units need to be part of or linked with a Liver Transplant Unit as the results for liver transplantation following chemotherapy and radiotherapy for unresectable cholangiocarcinoma (The Mayo Clinic Protocol) have been improving steadily and require to be evaluated in the UK.

In parallel a research programme is required to explore cancer markers for early diagnosis, an understanding of the genetic cause of cholangiocarcinoma and to explore new molecular targets for therapy.  We currently consent all patients to have cancer samples stored for future research and samples are anonymously stored in a special cryopreserved tissue bank. These fresh preserved tissues are vital for cancer research.
Currently there is no evidence that patients benefit from either pre-op or post op chemotherapy or radiotherapy.  However, specialist units would have sufficient patients to allow exciting new trials to be established. Centres of Excellence for Cholangiocarcinoma management are a major unmet need in the UK and should be considered for direct Department of Health funding via specialist commissioning.

Professor Brian R Davidson
Consultant HPB and Liver Transplant Surgeon,
University Department of Surgery, Royal Free Hospital
Professor of Surgery, Head of HPB and Liver transplant Research, UCL
UK Editor, Cochrane HPB Group for Evidence based Healthcare

July 2012