Gallbladder Cancer

Lee Surgery and Endoscopy was founded by Dr. Lee Chin Li, with the mission to deliver accessible and quality healthcare to our patients. We are committed to ensuring your comfort from consultation to procedures.

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18+ Years’ Experience

in HPB Surgery

Founding Head of the Division

of Hepatobiliary, Pancreatic & Gallbladder Surgery at Juronghealth Campus (NUHS)

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What is gallbladder cancer?

Gallbladder cancer is a rare but fast-growing cancer that starts in the lining of the gallbladder and often spreads silently.

Gallbladder cancer is an uncommon malignancy that begins in the tissues of the gallbladder—a small, pear-shaped organ located beneath the liver. The gallbladder’s primary function is to store bile, a digestive fluid produced by the liver that helps break down fats. While most gallbladder conditions, such as gallstones or inflammation (cholecystitis), are benign and manageable, gallbladder cancer is particularly concerning due to its tendency to remain asymptomatic in its early stages and its potential for rapid spread.

The majority of gallbladder cancers are adenocarcinomas, meaning they arise from the glandular cells lining the inner surface of the gallbladder. Less commonly, other types such as squamous cell carcinoma, adenosquamous carcinoma, and neuroendocrine tumours may occur. Gallbladder cancer is typically diagnosed at a late stage because early symptoms often mimic more common and less serious conditions, such as gallstones or digestive discomfort.

Because of its anatomical proximity to the liver and other vital structures, gallbladder cancer can easily invade surrounding tissues and spread through lymphatic and vascular channels. Early detection is therefore critical, but challenging, and treatment success heavily depends on the stage at diagnosis.

What are the stages of gallbladder cancer?

Gallbladder cancer is staged using the TNM (Tumour, Node, Metastasis) system, which helps describe the extent of the disease and guides treatment planning. The stages reflect how deeply the cancer has penetrated the gallbladder wall, whether it has reached nearby lymph nodes, and if it has spread to distant organs. These stages range from early and localised to advanced and metastatic.

Stage 0 (Carcinoma in situ) — the cancer is confined to the innermost layer of the gallbladder lining and has not invaded deeper tissues. It is often discovered incidentally and has the best prognosis.
Stage I — cancer has grown into the connective tissue or muscle layer of the gallbladder wall but has not spread to lymph nodes or other organs. Surgical removal may be curative at this stage.
Stage II — the tumour has invaded the outer layers of the gallbladder and possibly the nearby liver tissue but remains localised, with no lymph node involvement. Extended surgery is typically required.
Stage IIIA — cancer has spread beyond the gallbladder into one nearby organ, such as the liver, stomach, or small intestine, but still without lymph node involvement.
Stage IIIB — cancer has spread to nearby lymph nodes and may have also invaded surrounding organs or tissues.
Stage IVA — the tumour has extensively invaded two or more adjacent organs or major blood vessels, with or without lymph node involvement.
Stage IVB — cancer has either spread to distant lymph nodes or metastasised to distant organs such as the lungs, liver (distant sites), or peritoneum. Treatment at this stage is typically palliative, aiming to relieve symptoms and improve quality of life.

Accurate staging usually involves a combination of imaging tests (such as CT, MRI, or PET scans), endoscopic procedures, and sometimes exploratory surgery. Early-stage gallbladder cancer may be curable with surgery, but outcomes worsen significantly as the disease progresses.

What causes gallbladder cancer?

Gallbladder cancer occurs when the cells lining the gallbladder undergo abnormal changes that lead to uncontrolled growth. These changes are usually triggered by prolonged inflammation, exposure to concentrated bile, or disruptions at the genetic level. While risk factors may set the stage, the root causes lie in how the gallbladder tissue responds to injury over time.

Chronic inflammation of the gallbladder lining — long-standing inflammation, often caused by gallstones or infection, damages the epithelial cells and increases the likelihood of malignant transformation.
Bile stasis and chemical irritation — reduced or obstructed bile flow allows harmful bile acids and toxins to build up, irritating the gallbladder wall and promoting DNA damage.
Genetic mutations in gallbladder cells — alterations in tumour suppressor genes and oncogenes, such as TP53, KRAS, and ERBB2, disrupt normal cell growth and repair, leading to cancer formation.
Metaplasia and dysplasia — repeated injury can cause the gallbladder lining to undergo cellular changes, first replacing normal cells (metaplasia) and then forming abnormal, pre-cancerous cells (dysplasia).

In most cases, it is a combination of these factors that initiates the process of cancer development. The longer the gallbladder lining is exposed to harmful stimuli, the greater the chance for irreversible cellular damage that can evolve into cancer.

What are the symptoms of gallbladder cancer?

Gallbladder cancer can be difficult to detect early, as it often causes no symptoms in its initial stages or mimics more common conditions like gallstones or indigestion. Many cases are discovered incidentally during gallbladder removal surgery for unrelated issues. When symptoms do appear, they usually indicate that the cancer has grown or spread beyond the gallbladder.

Abdominal pain — typically felt in the upper right side of the abdomen, and may be constant or dull in nature.
Jaundice — yellowing of the skin and eyes due to bile duct obstruction caused by tumour growth.
Unintended weight loss — unexplained weight reduction that occurs without changes in diet or activity level.
Loss of appetite — a marked reduction in hunger, often accompanied by nausea or a feeling of fullness after eating small amounts.
Fever — a persistent low-grade fever, which may result from secondary infections or the body’s response to tumour activity.
Nausea and vomiting — digestive discomfort caused by impaired bile flow or tumour invasion into nearby organs.
Abdominal bloating or a palpable lump — swelling or a noticeable mass in the right upper abdomen, particularly in more advanced cases.
Dark urine and pale stools — caused by bile duct obstruction, which alters the normal colour of waste products.

Because these symptoms are non-specific and often resemble other biliary or digestive issues, gallbladder cancer is frequently diagnosed at a late stage. Anyone experiencing persistent or unexplained symptoms, especially if they have known risk factors, should seek medical evaluation without delay.

Gallbladder cancer may cause right upper abdominal pain, especially as the tumour grows or blocks bile flow.

Who is at risk of gallbladder cancer in Singapore?

Gallbladder cancer is relatively rare in Singapore, with an incidence of approximately 1.7 cases per 100,000 people. However, certain individuals within the local population may have an elevated risk due to specific medical, demographic, and lifestyle factors .

Women — females are about twice as likely to develop gallbladder cancer compared to males.
Older adults — the risk increases with age, particularly in individuals over 65 years old.
History of gallstones — approximately 75–90% of gallbladder cancer patients have a history of gallstones, which can cause chronic irritation of the gallbladder lining.
Chronic gallbladder inflammation — conditions such as cholecystitis or porcelain gallbladder (calcification of the gallbladder wall) can increase cancer risk.
Gallbladder polyps — gallbladder polyps especially those larger than 1 cm, may carry a higher chance of becoming cancerous.
Obesity — being overweight is associated with a higher risk of gallbladder cancer.
Smoking — tobacco use is linked to an increased risk of various cancers, including gallbladder cancer.
Family history — individuals with a family history of gallbladder cancer or gallstones may have a higher risk.
Chronic infections — persistent infections of the gallbladder, such as those caused by Salmonella bacteria, can elevate cancer risk.
Congenital biliary anomalies — conditions like choledochal cysts or primary sclerosing cholangitis, which affect the bile ducts, are associated with a higher risk of gallbladder cancer.

How is gallbladder cancer diagnosed?

Diagnosing gallbladder cancer can be challenging, as early symptoms are often vague or absent. Many cases are discovered incidentally during gallbladder removal surgery for suspected gallstones or cholecystitis. When gallbladder cancer is suspected, doctors use a combination of imaging tests, laboratory investigations, and sometimes surgical procedures to confirm the diagnosis and determine the extent of disease.

Physical examination and medical history — doctors assess symptoms, risk factors, and perform a physical exam to check for jaundice, abdominal tenderness, or masses.
Blood tests — liver function tests may reveal elevated bilirubin or liver enzymes if the bile ducts are obstructed. Tumour markers such as CEA and CA 19-9 may be elevated, though they are not specific to gallbladder cancer.
Ultrasound — often the first imaging test used, it can detect gallbladder wall thickening, masses, or bile duct dilation.
CT (computed tomography) scan — provides detailed cross-sectional images of the abdomen to identify tumour size, lymph node involvement, or spread to the liver and surrounding tissues.
MRI and MRCP (magnetic resonance cholangiopancreatography) — useful for visualising the biliary tree and detecting soft tissue involvement or obstruction.
Endoscopic ultrasound (EUS) — combines endoscopy with ultrasound to get close-up images of the gallbladder and surrounding organs, and allows for fine-needle aspiration of suspicious lesions.
ERCP (endoscopic retrograde cholangiopancreatography) — may be used to visualise and relieve obstruction in the bile ducts, and obtain brushings or biopsies for analysis.
Biopsy — a tissue sample may be taken through image-guided fine needle aspiration or during surgery to confirm the diagnosis under a microscope.
Staging laparoscopy — a minimally invasive surgery that allows doctors to directly visualise the abdominal cavity to assess tumour spread, especially before major surgery.

An accurate diagnosis requires not just confirming the presence of cancer, but also evaluating how far it has spread. This staging process is vital to guide treatment decisions and estimate prognosis.

What are the treatment options for gallbladder cancer in Singapore?

Treatment for gallbladder cancer in Singapore is customised according to the cancer's stage, the patient's overall health, and specific tumour characteristics. A multidisciplinary team, including hepatobiliary surgeons, oncologists, and radiologists, collaborates to provide optimal care. The primary treatment modalities include:

Surgery — for early-stage gallbladder cancer

Surgical removal offers the best chance for cure in early-stage gallbladder cancer. Procedures include:

Cholecystectomy — removal of the gallbladder, suitable for cancers confined to the gallbladder lining.
Extended cholecystectomy —involves removing the gallbladder along with portions of the liver and nearby lymph nodes, applicable when cancer has invaded surrounding tissues.
Radical gallbladder resection — may entail removing the gallbladder, larger sections of the liver, and parts of adjacent organs if the cancer has extensively spread.

Chemotherapy — systemic treatment to target cancer cells

Chemotherapy uses drugs to destroy cancer cells and may be administered:

Neoadjuvantly — before surgery to shrink tumours.
Adjuvantly — after surgery to eliminate residual cancer cells.
Palliatively — when surgery isn’t feasible, to control symptoms and slow disease progression.

Radiation therapy — high-energy beams to destroy cancer cells

Radiation therapy can be employed:

Postoperatively — to eradicate remaining cancer cells.
Palliatively — to relieve symptoms in advanced stages.

Targeted therapy and immunotherapy — comprehensive treatments for specific cases

These therapies focus on particular genetic mutations or enhance the immune system’s ability to fight cancer:

Targeted therapy — drugs that interfere with cancer cell growth mechanisms.
Immunotherapy — boosts the body’s natural defences to combat cancer. Availability may be through clinical trials or specific indications.

Palliative care — improving quality of life in advanced stages

For advanced gallbladder cancer where curative treatment isn’t possible, palliative measures focus on symptom relief:

Biliary drainage procedures — to alleviate jaundice caused by bile duct obstruction.
Pain management and nutritional support — to enhance comfort and well-being.

Early detection and a personalised treatment approach are crucial for improving outcomes in gallbladder cancer. Patients are encouraged to consult with healthcare professionals to determine the most appropriate treatment strategy.

Summary

Gallbladder cancer is a rare but aggressive disease that often presents without symptoms in its early stages. It arises when abnormal cellular changes, typically triggered by chronic inflammation or genetic mutations, lead to uncontrolled growth within the gallbladder lining. While the exact cause is not always clear, long-standing gallstones, bile stasis, and certain structural abnormalities are known contributors.

Symptoms such as right upper abdominal pain, jaundice, weight loss, and digestive discomfort tend to appear only once the cancer has advanced. Diagnosis involves a combination of imaging, blood tests, and biopsy to confirm the disease and determine its stage. In Singapore, treatment is tailored based on cancer staging and may include surgery, chemotherapy, radiation therapy, and palliative care, with more comprehensive options like targeted therapy available in selected cases.

If you are experiencing persistent abdominal symptoms or have risk factors for gallbladder cancer, schedule a consultation with Dr Lee Chin Li for a thorough evaluation and personalised treatment planning.

Frequently asked questions

Can gallbladder cancer be cured?

Yes, if detected early, gallbladder cancer can often be cured with surgery. However, early detection is challenging due to the lack of specific symptoms in initial stages.

Is gallbladder cancer hereditary?

While most cases aren’t inherited, a family history of gallbladder cancer may slightly increase risk. Genetic factors are still being studied.

Is gallbladder cancer aggressive?

Yes, gallbladder cancer is considered aggressive because it often spreads quickly to nearby organs like the liver and is usually diagnosed at a late stage. Its silent progression and vague symptoms make early detection difficult.

Can gallstones lead to gallbladder cancer?

Gallstones are a significant risk factor, as they can cause chronic inflammation, which may increase the likelihood of developing gallbladder cancer.

How is gallbladder cancer staged?

Staging is based on tumour size, lymph node involvement, and spread to other organs, typically categorised from Stage I (early) to Stage IV (advanced).

What is the prognosis for gallbladder cancer?

Prognosis depends on the stage at diagnosis. Early-stage cancers have a better outcome, while advanced stages have a lower survival rate.

Are there any screening tests for gallbladder cancer?

Currently, there is no screening test for gallbladder cancer. It is often detected incidentally during imaging or surgery for other conditions.

Can lifestyle changes reduce the risk of gallbladder cancer?

Maintaining a healthy weight, managing gallstones, and avoiding smoking may help reduce risk, though some factors like age and genetics are non-modifiable.

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