Gallbladder cancer
Gallbladder cancer is uncommon but important, and it has one feature that distinguishes it from almost every other cancer: a substantial proportion are discovered by accident, in a gallbladder removed for what was thought to be ordinary gallstone disease. What happens in the weeks after that finding — whether the patient is referred for further surgery, and how promptly — has a greater influence on outcome than almost anything else.
How it forms
The great majority are adenocarcinomas arising from the gallbladder lining. The dominant mechanism is chronic irritation: long-standing gallstones rubbing against the mucosa produce persistent inflammation, and the lining passes through metaplasia and dysplasia before becoming invasive cancer. This takes many years, which is why the disease occurs predominantly in older patients with a long history of stones.
Recognised risk factors, all reflecting chronic inflammation or abnormal bile exposure:
- Gallstones — present in the large majority of cases, with larger stones and longer duration carrying greater risk. The risk to any individual with stones remains very low.
- Porcelain gallbladder — calcification of the wall from chronic inflammation.
- Gallbladder polyps, particularly adenomas and those 10mm or larger.
- Chronic infection, including chronic typhoid carriage.
- Anomalous pancreaticobiliary duct junction — an abnormal union allowing pancreatic enzymes to reflux into the biliary tree, causing chronic damage. A recognised cause in younger patients without stones.
- Primary sclerosing cholangitis, obesity, and certain geographic and ethnic backgrounds.
Two anatomical facts explain the disease's behaviour. The gallbladder wall is thin, with only a scant muscular layer and, on the side attached to the liver, no serosa at all — so a tumour reaches and invades the liver early. And its lymphatic drainage passes directly to nodes along the cystic duct, bile duct and hepatic artery, so nodal spread occurs at an early stage. Both explain why apparently early tumours require more extensive surgery than the size alone would suggest.
Symptoms
Early disease is silent, or produces symptoms indistinguishable from gallstones — which is exactly why it is found incidentally. Advanced disease causes:
- persistent right upper abdominal pain
- jaundice, indicating involvement of the bile duct and usually advanced disease
- weight loss and anorexia
- a palpable mass
- persistent symptoms after a cholecystectomy that should have resolved them
How the diagnosis is made
Ultrasound may show wall thickening, a mass, or a polypoid lesion. Features that should raise suspicion before surgery are focal wall thickening over 4mm, a fixed mass, loss of the plane between gallbladder and liver, and a large sessile polyp.
CT and MRI with MRCP stage the disease — depth of invasion, liver involvement, bile duct involvement, vascular involvement, lymph nodes and distant spread. PET-CT is useful for detecting occult metastases, particularly before planning radical re-resection.
Staging laparoscopy is frequently used before major surgery, because peritoneal deposits too small to be seen on imaging are common and finding them avoids a futile laparotomy.
Percutaneous biopsy of a suspected gallbladder cancer is avoided where resection is planned, because of the risk of tract seeding.
Incidental gallbladder cancer — the common scenario
Most cases in practice present as a histology report after routine cholecystectomy. What follows depends on the depth of invasion:
- T1a — confined to the lamina propria. Cholecystectomy alone is generally adequate, provided the cystic duct margin is clear.
- T1b and beyond — invading muscle or deeper. Radical re-resection is indicated, comprising resection of the gallbladder bed (liver segments IVb and V), regional lymphadenectomy, and excision of the bile duct where the cystic duct margin is involved.
Several points deserve emphasis because they are where outcomes are lost. The original histology report should state depth of invasion and cystic duct margin status; if it does not, the slides should be reviewed. Re-resection should not be delayed. Port sites are no longer routinely excised, as this has not been shown to improve outcome. And if the gallbladder was perforated during the original operation, the prognosis is worse — spillage of bile containing tumour cells seeds the peritoneum, which is the practical reason gallbladders suspected of malignancy are handled intact and extracted in a bag.
Treatment
Surgery
Complete resection is the only curative treatment. The extent depends on stage: from simple cholecystectomy for T1a disease, through extended cholecystectomy with liver segments IVb/V and lymphadenectomy for most resectable disease, to major hepatectomy with bile duct resection and reconstruction for more advanced tumours. Adequate lymphadenectomy is essential both for cure and for accurate staging.
Disease involving the peritoneum, distant organs, or extensive nodes beyond the regional field is not resectable, and operating in those circumstances harms rather than helps.
Chemotherapy
Adjuvant chemotherapy is given after resection. For advanced disease, systemic chemotherapy combined with immunotherapy is the current standard, and molecular profiling is performed as a proportion of biliary tract cancers carry targetable alterations.
Palliative measures
Biliary stenting for jaundice, and pain control, including coeliac plexus block where appropriate.
Recovery
Extended cholecystectomy with liver resection typically means five to ten days in hospital and six to eight weeks to full recovery. Where bile duct resection and reconstruction are required, recovery is longer and bile leak is a recognised complication.
Follow-up
Clinical review, imaging and tumour markers at regular intervals, most intensively in the first two to three years when recurrence is most likely.
Common questions
My gallbladder was removed and they found cancer. What happens now?
This is the commonest way gallbladder cancer is found. The critical question is how deeply the cancer had grown into the gallbladder wall. If it was confined to the most superficial layer, no further surgery is usually needed. If it had grown into the muscle layer or deeper, a second, more extensive operation is generally recommended, and it should be arranged promptly rather than deferred.
Do gallstones cause gallbladder cancer?
Long-standing gallstones are associated with an increased risk, but the risk to any individual is very low. The great majority of people with gallstones never develop gallbladder cancer, and this is not a reason on its own to remove a gallbladder that causes no symptoms.
Why do I need a second operation if the gallbladder is already out?
Because the gallbladder wall is thin and has no protective outer layer where it sits against the liver, cancer reaches the liver and the nearby lymph nodes early. Removing a rim of liver and the regional lymph nodes deals with disease that may have spread beyond the gallbladder itself but is still curable.
Should I have my gallbladder removed to prevent cancer?
Not for that reason alone. Prophylactic removal is considered in specific situations — a calcified "porcelain" gallbladder, polyps of 10mm or more, or certain abnormalities of the duct anatomy — but not simply because gallstones are present.
Is gallbladder cancer curable?
When found early, particularly when confined to the gallbladder wall and completely removed, yes. Outcomes are considerably worse when it is found at an advanced stage, which is why acting promptly on an incidental finding matters so much.
Related conditions
Other conditions of the gallbladder & bile ducts covered on this site:
- Gallstones and biliary colic
- Acute cholecystitis
- Common bile duct stones and cholangitis
- Gallbladder polyps
- Obstructive jaundice
- Cholangiocarcinoma (bile duct cancer)
- Bile duct strictures, cysts and benign tumours
- Bile duct injury after gallbladder surgery
This page provides general information and does not replace an individual medical consultation. Assessment and treatment are decided for each patient after review of their history, examination and imaging, and in the setting of a multidisciplinary team.