Gallbladder cancer is a common malignant tumor of the biliary system, ranking as the 6th most common digestive tract tumor. The overall 5-year survival rate for patients with gallbladder cancer is only 5%.
Etiology
Cholelithiasis
Approximately 85% of gallbladder cancer patients have concomitant gallstones. The risk of gallbladder cancer in patients with gallstones is 13.7 times higher than in those without gallstones. For individuals with a single gallstone larger than 3 cm, the risk of gallbladder cancer is 10 times higher than for those with stones smaller than 1 cm. Gallstones combined with chronic inflammation represent the most common risk factor for gallbladder cancer.
Gallbladder Polyps
About 60% of gallbladder polyps are pseudopolyps, which have no malignant potential. However, certain polyps larger than 10 mm, those associated with gallstones or cholecystitis, solitary or sessile polyps, rapidly growing polyps, or adenomatous polyps carry an increased risk of malignancy.
Chronic Inflammation of the Gallbladder
Chronic inflammation of the gallbladder accompanied by inhomogeneous calcification of the gallbladder wall is considered a precancerous condition. Porcelain gallbladder, characterized by a hardened and brittle calcified gallbladder wall, is highly associated with gallbladder cancer.
Other Potential Risk Factors
Other risk factors include the presence of the gallbladder after "gallstone-preserving" surgery, congenital anomalies of the pancreaticobiliary ductal junction, adenomyomatosis of the gallbladder, biliary tract infections, obesity, diabetes, age over 65 years, female, smoking, and exposure to chemical agents.
Pathology and Clinical Staging
Gallbladder cancer may occur in the fundus, body, neck, or cystic duct of the gallbladder. It can be categorized into mass-forming and infiltrative types. Histologically, adenocarcinoma is the predominant type, accounting for 80%–90% of cases. Lymphatic metastasis is common, and liver metastasis frequently occurs. The TNM staging system is useful for guiding treatment decisions and assessing prognosis.
Clinical Manifestations
Gallbladder cancer has an insidious onset, with no specific symptoms in the early stages. In advanced stages, symptoms such as upper abdominal pain, a palpable mass in the right upper quadrant, and jaundice may develop. Abdominal pain is nonspecific, while the presence of an abdominal mass and progressive jaundice often indicates late-stage disease. Other symptoms may include abdominal distension, loss of appetite, weight loss, anemia, hepatomegaly, and even systemic failure.
Laboratory and Imaging Examinations
Laboratory Tests
Tumor markers such as CEA, CA19-9, and CA125 may be elevated, with CA19-9 being more sensitive but lacking specificity. Tumor marker analysis of bile obtained via fine-needle aspiration may provide greater diagnostic value.
Imaging Examinations
Ultrasound is the preferred initial screening method and is useful for preliminary diagnosis and follow-up. CT and/or MRI, as well as EUS, can provide further information on tumor infiltration, involvement of the liver and blood vessels, and the presence of lymph node or distant metastases. PET-CT is helpful in assessing both local and systemic metastatic lesions.
Pathology
Pathological or cytological specimens can be obtained through surgical biopsy, bile exfoliative cytology, or fine-needle aspiration biopsy.
Diagnosis
A preliminary diagnosis can be made based on positive imaging findings and significantly elevated tumor markers. However, pathological histological and/or cytological examination remains the only definitive method for diagnosing gallbladder cancer.
Treatment
Surgical resection is the preferred treatment, with radical resection being the only potential curative approach for gallbladder cancer. The surgery emphasizes achieving negative resection margins whenever possible. Non-surgical treatments for gallbladder cancer include chemotherapy, radiotherapy, molecular targeted therapy, and immunotherapy.
Prevention
Gallbladder removal should be considered in the presence of the following risk factors:
- Gallstones with a diameter greater than 3 cm;
- Cholecystitis associated with uneven calcification of the gallbladder wall, punctate calcifications, multiple small calcifications, or porcelain gallbladder;
- Gallbladder polyps with a diameter of 1 cm or larger; gallbladder polyps smaller than 1 cm if accompanied by gallstones or cholecystitis; solitary or sessile polyps with rapid growth (growth exceeding 3 mm within 6 months);
- Adenomyomatosis of the gallbladder combined with gallstones or cholecystitis;
- Anomalies of the pancreaticobiliary ductal junction combined with space-occupying lesions in the gallbladder;
- Gallstones combined with diabetes.
For individuals with the following conditions, dynamic monitoring of the gallbladder every 6–12 months is recommended:
- Gallbladder polyps;
- Age over 65 years, particularly in females;
- Obesity;
- A family history of gallstones or gallbladder cancer.