January 16, 2007

Gallbladder Cancer

Synonyms and related keywords: biliary cancer, biliary tract cancer, cancer of the biliary tree, gallbladder cancer, gallstones, chronic typhoid infections, abnormal pancreaticobiliary duct junctions, inflammatory bowel disease, polyposis coli, cholangiocarcinomas


INTRODUCTION

Background: Cancers of the biliary tract include cholangiocarcinomas (cancers arising from the bile duct epithelium) and gallbladder cancers. Both types of biliary tract cancers are rare and have an overall poor prognosis. They also both present difficulties in diagnosis. These diseases are often discussed together and are co-mingled in therapeutic trials. However, this leads to significant confusion. Despite some similarities, gallbladder cancer is a distinct clinical entity from cholangiocarcinoma and will be discussed separately in this article.

Pathophysiology: Gallbladder cancer arises in the setting of chronic inflammation. In the vast majority of patients (>75%), the source of this chronic inflammation is gallstones. Other more unusual causes of chronic inflammation are also associated with gallbladder cancer. These causes include patients with chronic typhoid infections, abnormal pancreaticobiliary duct junctions, inflammatory bowel disease, or polyposis coli.

Chronic gallbladder inflammation is likely only part of the cause of the malignant transformation seen in gallbladder cancer. Ingestion of certain medications (oral contraceptives, INH, and methyldopa) as well as certain occupational chemical exposures may play a significant contributing role. The role of various oncogenic mutations in gallbladder cancer is an area of active research.

Gallbladder cancer incidence increases with age and is more common in women.

The tumor is usually located in the fundus of the gallbladder. Local spread through the gallbladder wall can lead to direct liver invasion, or, if in the opposite direction, leads to transperitoneal spread (20% of patients at presentation), with implants on the liver, on the bowel, and in the pelvis. Tumor may also directly invade other adjacent organs such as the stomach, duodenum, colon, pancreas and extrahepatic bile duct. At diagnosis, the gallbladder is often replaced or destroyed by the cancer, and approximately 50% of patients have regional lymph node metastases.

Frequency:

Mortality/Morbidity: Survival is correlated with staging based on the American Joint Committee on Cancer (AJCC) tumor, node, metastases (TNM) staging system.

Patients with stage IA disease (T1N0M0) should be cured with a simple cholecystectomy. In selected surgical series, patients with stage IB (T2N0M0) disease treated with extended cholecystectomy have a 5-year survival rate of 70-90%, and patients with stage IIB (T1-3N1M0) treated with extended cholecystectomy have a 5-year survival of 45-60%. Stage III (T4, any N,M0) gallbladder cancer is generally not surgically curable. The 1-year survival rate for advanced gallbladder cancer is less than 5%. The median survival is 2-4 months.

The SEER registry from 1995-2001 shows 5-year survival rates for localized gallbladder cancer of approximately 40%. The 5-year survival rate for regional disease is approximately 15%, and the 5-year survival rate for distant metastatic disease is less than 10%.

Unfortunately, only about 10-20% of patients present with tumor confined to the gallbladder wall. At diagnosis, 40-60% of patients have lesions that perforate the gallbladder wall and invade adjacent organs (T3) and 45% of patients have regional lymph node involvement (N1). Approximately 30% of patients present with metastatic disease.

Race: The highest rates of gallbladder cancer are found in the US Native American and Hispanic populations, and in South America, Israel, and Japan.

Sex: A substantial female predominance exists worldwide, with female-to-male ratios of approximately 2.5:1-3:1.

Age: Gallbladder cancer is most typically diagnosed in the seventh decade, with a median age of 62-66 years.


CLINICAL

History: The symptoms of gallbladder cancer overlap with the symptoms of gallstones and biliary colic. Abdominal pain may be of a more diffuse and persistent nature than the classic right upper quadrant pain of gallstone disease. Jaundice, anorexia, and weight loss often indicate more advanced disease.

Physical:

Causes: See Pathophysiology. Associated conditions include the following:

  • Chronic gallstones
  • Calcification of the gallbladder (porcelain gallbladder) - 10-25% incidence of gallbladder cancer
  • Crohn ileocolitis
  • Ulcerative colitis
  • Occupational chemical exposure
  • Estrogens
  • Typhoid carriers
  • Anomalous pancreatobiliary duct junction
  • Gallbladder polyps

DIFFERENTIALS

Acalculous Cholecystitis
Acalculous Cholecystopathy
Ampullary Carcinoma
Bile Duct Strictures
Bile Duct Tumors
Biliary Colic
Biliary Disease
Biliary Obstruction
Carcinoma of the Ampulla of Vater
Cholangiocarcinoma
Cholangitis
Cholecystitis
Choledochal Cysts
Choledocholithiasis
Cholelithiasis
Clostridial Cholecystitis
Gallbladder Mucocele
Gallbladder Volvulus
Hepatic Carcinoma, Primary
Liver Abscess
Neoplasms of the Endocrine Pancreas
Pancreatic Cancer
Pericholangitis
Primary Biliary Cirrhosis
Primary Sclerosing Cholangitis


WORKUP

Lab Studies:

Imaging Studies:

Procedures:

Histologic Findings: Adenocarcinoma is the primary histologic finding in 80-85% of gallbladder carcinomas, with several histologic subtypes, including papillary, nodular, and infiltrative. The papillary type appears to be less aggressive and more often localized and has a better prognosis than the other forms. Additional rare histologic types of gallbladder cancer exist. These include squamous cell cancer, sarcomas, carcinoid, lymphoma, and melanoma.

Grade also is important, with poorly differentiated tumors associated with a poorer prognosis than the typically less infiltrative, better differentiated tumors with metaplasia.

Staging: Staging of tumor extent is essential in selection of the appropriate treatment approach.

The AJCC 6th edition guidelines follow the TNM system, with depth of tumor penetration and regional spread defined pathologically . Survival is correlated directly with stage of disease.

Primary tumor


TREATMENT

Medical Care: Although complete surgical resection is the only therapy to afford a chance of cure, en bloc resections of the gallbladder and portal lymph nodes carry a high morbidity and mortality (similar to bile duct carcinoma). Adequate surgical margins may be difficult to achieve. The role of adjuvant radiation therapy is to control microscopic residual deposits of carcinoma in the tumor bed and regional lymph nodes. The rationale for radiation therapy with or without concurrent chemotherapy in patients with unresectable disease is to provide palliation of symptoms. Rarely it may also increase survival.

Surgical Care: Complete surgical resection is the only therapy to offer a chance of cure in this disease. Unfortunately, only a minority of patients present with early-stage disease and are, therefore, considered for curative resection.

Consultations: A radiation oncologist and medical oncologist should be part of the multidisciplinary team participating in the treatment of patients with gallbladder cancer.


MEDICATION

Historically, chemotherapy has not shown significant activity in gallbladder carcinoma. Typically, 5-flurouracil (5-FU) has been used with response rates of 10-24% in advanced disease. Often 5-FU is administered either as a bolus or as a prolonged infusion regimen with radiation. Capecitabine is a currently available oral alternative to a prolonged 5-FU infusion.

More recently, gemcitabine has shown activity in gallbladder cancer. Early phase studies show an increased response rate with gemcitabine combination therapy over historical treatment response rates with 5-FU alone. Gemcitabine has been studied in combination with cis-platinum and capecitabine.

Currently, no clearly defined standard exists for chemotherapy in gallbladder cancer. Patients should be encouraged to participate in clinical trials.


FOLLOW-UP

Further Outpatient Care:

Deterrence/Prevention:

Prognosis:


MISCELLANEOUS

Medical/Legal Pitfalls:

2 comments:

Medical Information said...

When anyone observes symptoms of cancer, should go for tests. Some tests for Gall bladder cancer is Ultrasound Scan, CT scan, ERCP, Angiogram, Laparoscopy, Laparotomy etc. Surgery, radiotherapy, chemotherapy are some of the treatments for Gall bladder cancer. Without the person’s consent, no medical treatment could be offered. For details on different types of cancer, refer Cancer information

CancerconsultIndia said...

Thanks for your post. I found it very informative. Thanks for the post and keep updating.

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