Gall bladder cancer

What causes gall bladder cancer?

What causes gall bladder cancer?

Gall bladder cancer is the most common biliary malignancy in Central & South America (Native American Indians, Hispanics), parts of Eastern Europe (Poland, Czech Republic, Slovakia), Japan, and northern parts of India. Underlying genetic predisposition or dietary factors may be the reason for this. Gallstones are, perhaps, the single most important risk factor for gall bladder cancer, though the mechanism is unclear. Usually patients with large stones of long duration are at increased risk for cancer. Calcium deposits in the wall of the gall-bladder, such as Porcelain gall bladder, also increases the risk of gall bladder cancer. Chronic Salmonella infection of the gall bladder, which predisposes to gall stone formation, also predisposes to gall bladder cancer.  Patients with abnormalities at the point where the pancreatic and bile ducts join and enter the bowel are also known to be at increased risk for gall bladder cancer. Sometimes patients are found to have polyps (little growths) on the lining of the gall bladder. Polyps are generally benign, but patients with a single, large (> 1cm) polyp are more likely to develop cancer within their polyp.

Ultrasound picture of the gall bladder
Ultrasound picture of the gall bladder showing small polyps arising from the inner lining of the gall bladder wall. These particular polyps were deemed non-cancerous
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How does gall bladder cancer spread?

How does gall bladder cancer spread?

Gall bladder cancer typically spreads to adjacent organs like the liver, bile ducts, stomach, colon and duodenum, in that order. Distant spread can occur to lymph nodes, liver, peritoneum and lungs.

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What are the symptoms and signs of gall bladder cancer?

What are the symptoms and signs of gall bladder cancer?

The commonest presentation for gall bladder cancers is pain, loss of appetite, weight loss and obstructive jaundice. A gall bladder mass may be felt in half the patients on presentation.

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What are the tests for gall bladder cancer?

What are the tests for gall bladder cancer?

CT scan gall bladder
CT scan picture showing a cancer that has arisen from the gall bladder. A gallstone can also be seen

(This section picks up from the earlier section on tests for bile duct cancer, and we have tried to avoid repeated explanations of the same tests) Initial blood tests for suspected gall bladder cancer will always include liver function tests. Blood levels of the tumour markers CEA and CA 19-9 should be measured and may be raised.

The first imaging test is ultrasound of the liver and biliary tract. Ultrasound (US) detects thickening of the wall of the gall bladder (the differential diagnosis being inflammation). Polyps or lumps in the gall bladder may also be detected. Ultrasound also helps assess if the bile duct and liver are involved.

Spiral CT scan probably gives the best estimate of the extent of disease. However, MRI scanning gives equally high-resolution images, with the additional benefit of providing an MRCP. CT and MR usually give adequate information about the localblood vessels, and hepatic angiography is rarely indicated.

Many patients undergo an ERCP and stenting to relieve the obstructive jaundice and therefore, ERCP provides information on the extent to which the bile duct is involved. In those cases where ERCP is difficult, PTC may be helpful. EUS (endoscopic ultrasound) is used only occasionally.

Fine needle aspiration biopsy is not recommended as routine because of the risk of peritoneal or needle tract seeding in curable cases (though the instances are anecdotal), but is perfectly acceptable in patients with irresectable tumours  being considered for palliative therapy. The differential diagnosis on imaging is essentially stone disease and its sequelae. Certain types of chronic inflammation of the gall bladder and stone disease causing Mirrizzi’s syndrome (a swollen gall bladder compressing the bile duct) can be quite difficult to distinguish from gall bladder cancer.

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What is the treatment of gall bladder cancer?

What is the treatment of gall bladder cancer?

Surgery

There are three groups of patients who warrant discussion:

  • Patients with the chance finding of a gall bladder polyp on a scan
  • When an unsuspected gall bladder cancer is found at the time of cholecystectomy for gallstone disease, or reported afterwards in the pathologist’s report on a removed gall bladder
  • When gall bladder cancer is suspected or diagnosed in a patient with symptoms

Gall bladder polyps are often discovered incidentally on scans, and not all of them warrant a cholecystectomy. Polyps which are single, sessile (do not have a stalk) and 1 cm or more in diameter should be deemed as highly suspicious. Also, polyps that have developed in older patients (over the age of fifty years), developed in association with stones or are associated with symptoms, are at a higher risk of being malignant or subsequently turning malignant. Laparoscopic cholecystectomy is the treatment of choice in these patients (unless the suspicion of malignancy is high, in which case open exploration is preferable, with preparation for extended resection if necessary). For polyps that are deemed low-risk, our practice is to recommend six-monthly ultrasonographic follow-up at first, which can stop after 2 years if they remain unchanged.

If a surgeon suspects gall bladder carcinoma at the time of a laparoscopic or open cholecystectomy for stone disease, it is reasonable to take tissue samples for histopathology and then end the operation, with the intention of subsequently referring the patient to a specialist centre. If an expert biliary surgeon is at hand, it may be reasonable to proceed immediately to a major operation, with confirmation of cancer on frozen section (this is a rapid analysis of a tissue sample) as the first step. But the surgeon will then have to very carefully evaluate the extent of disease (without the benefit of CT or MR scans) and determine if it is appropriate to proceed to a major operation that the patient has not been prepared for.

If gall bladder cancer is described in the pathologist’s report after a routine cholecystectomy, the two important questions are: How deeply had the tumour invaded through the gallbladder wall, and did it reach up to the surgical margins? These are the two major indicators of prognosis. Simple cholecystectomy is adequate for T1 tumours, which are confined to the mucous membrane or the muscle layer deep to that, and further surgery is not necessary. For T2 tumours, which have gone through the muscle layer in the gall bladder wall, but not much further, and tumours where the surgical resection margins are involved, a second, more radical operation should be performed. This may involve a resection of the part of the liver that adjoins the gall bladder (called an extended cholecystectomy) or even a formal excision of liver segments 4b and 5, with removal of the regional lymph nodes, and excision of the extra-hepatic bile duct. The laparoscopic port sites (the entry points of the instruments) may also be excised.

Gall bladder cancers that have caused symptoms and then been identified on scans, are already quite advanced. The prognosis is poor, and the majority of patients have unresectable disease. But radical surgery offers the only chance of cure or prolongation of survival time, and a specialist surgical opinion should be sought in all patients who do not have distant spread. A diagnostic laparoscopy (keyhole examination) prior to laparotomy may be useful in further staging the extent of disease. If the possibility of benign disease is being considered, then a laparotomy (i.e. a look inside the abdomen through a proper incision) and frozen section confirmation of the nature of the disease should be the first step. Radical excision involves a substantial liver resection, depending on the extent of liver involvement. This is combined with regional lymph node clearance and removal of the extra-hepatic bile duct with creation of a Roux-loop hepatico-jejunostomy. A formal pancreato-duodenectomy (Whipple operation) may be necessary in some instances to achieve complete excision.

Following surgical resection with clear margins, 5-year survivals of 62-100% have been reported in patients with T2 lesions, and 20-50% in patients with more advanced lesions. Adjuvant treatments have been tried, in the form of chemotherapy (5FU with Mitomycin C), chemotherapy (5FU) combined with external beam radiation, and intra-operative radiotherapy. They seem to confer modest benefit.

Radiotherapy

Gall bladder cancer is generally considered relatively radioresistant. Patients with advanced disease do have some survival benefit from radiotherapy, but the studies are too few and too small to allow any effective judgement of the value of various types of radiotherapy.

Chemotherapy

Various drugs in single agent or combination have been tried. These include gemcitabine, paclitaxel, 5-Fluorouracil and mitomycin C (all given as single agents), 5-Fluorouracil and folinic acid with hydroxyurea, and 5-Fluorouracil with carboplatin, Thus far, the benefits have been found to be very modest.

© 2016 hpblondon.com
These treatment options are described here in a very general sense, and individual patients should discuss their treatment with their own medical team.
These treatment options are described here in a very general sense, and individual patients should discuss their treatment with their own medical team.