You are in: eMedicine Specialties > General Surgery > Abdomen Gallbladder TumorsArticle Last Updated: Aug 2, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Michael K McLeod, MD, FACE, FACS, Associate Professor of Surgery, College of Human Medicine, Program Director of Surgery and Assistant Chairman of the Department of Surgery, Kalamazoo Center for Medical Studies, Michigan State University Michael K McLeod is a member of the following medical societies: American Association of Clinical Endocrinologists, American Association of Endocrine Surgeons, American College of Surgeons, American Medical Association, Association for Academic Surgery, Association of VA Surgeons, Central Surgical Association, Eastern Association for the Surgery of Trauma, International Association of Endocrine Surgeons, Michigan State Medical Society, Midwest Surgical Association, National Medical Association, Society of American Gastrointestinal and Endoscopic Surgeons, and Western Surgical Association Coauthor(s): Tara Mancl, MD, Staff Physician, Department of Surgery, Michigan State University, Kalamazoo Center for Medical Studies; Michel M Murr, MD, Associate Professor, Department of Surgery, Director, Department of Bariatric Surgery, University of South Florida Editors: Alex Jacocks, MD, Program Director, Professor, Department of Surgery, University of Oklahoma School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Michael A Grosso, MD, Department of Cardiothoracic Surgery, St Francis Hospital; Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy; John Geibel, MD, DSc, MA, Professor, Department of Surgery, Section of Gastrointestinal Medicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital Author and Editor Disclosure Synonyms and related keywords: carcinoma of the gallbladder, cancer of the gallbladder, gallbladder cancer, cholecystectomy, gallstones, porcelain gallbladder, cholecystitis, gallbladder lesions INTRODUCTIONSection 2 of 12
  Lesions of the gallbladder are quite rare; however, with the increased use of diagnostic studies, such as computed tomography (CT) and ultrasound, the rate of incidental detection of lesions of the gallbladder is increasing. In patients undergoing cholecystectomy for biliary disease, the incidence of detecting a benign gallbladder lesion is less than 3%, while the incidence of detecting a malignant lesion is less than 1%. As such, gallbladder cancer is the fifth most common malignancy of the gastrointestinal tract. Benign lesionsCholesterol polyps Cholesterol polyps account for approximately 50% of all polypoid lesions of the gallbladder. These lesions are thought to originate from a defect in cholesterol metabolism. They appear as yellow spots on the mucosal surface of the gallbladder and are characterized as epithelial-covered macrophages laden with triglycerides and esterified sterols in the lamina propria of the mucosal layer of the gallbladder. As a rule, cholesterol polyps exist as multiple lesions and are usually less than 10 mm. Cholesterol polyps are generally asymptomatic. Inflammatory polyps These lesions result from chronic inflammation. They extend into the gallbladder lumen by a narrow vascularized stalk. Adenomas Adenomas are either tubular or papillary. They arise from the epithelial layer, and, if multiple, they are termed papillomatosis. Adenomas are premalignant lesions and are at risk of harboring malignant foci when the adenomas are greater than 12 mm. Adenomyomatosis Adenomyomatosis is considered to be a hyperplastic premalignant lesion. Ultrasound reveals a thickened gallbladder wall with intramural diverticuli. Other lesions Other rare benign lesions found in the gallbladder include leiomyomas, lipomas, hemangiomas, granular cell tumors, and heterotropic tissue, including gastric, pancreatic, and intestinal epithelium. Malignant lesionsAdenocarcinoma Adenocarcinoma comprises approximately 80-90% of gallbladder cancer cases, and approximately 6,000-7,000 new cases of adenocarcinoma of the gallbladder are diagnosed each year. This malignancy is primarily seen in elderly patients, most commonly diagnosed during the seventh decade of life. Adenocarcinoma is associated with preexisting gallstone disease, in that, 70-90% of patients have associated cholelithiasis. The size of the gallstones plays a role in the development of gallbladder cancer. Gallbladders containing gallstones that are greater than 3 cm in diameter have a 10 times greater risk for developing malignancy than those containing gallstones that are 1 cm in diameter. The risk is hypothesized to be due to chronic inflammation. Adenocarcinoma is often discovered incidentally during a workup for gallstone disease. An increased incidence exists in both Native Americans and Hispanics in the United States and in Mexico. Females have a higher risk of developing adenocarcinoma than males, and the female-to-male ratio is 3:1. This is, in part, due to the higher incidence of gallbladder disease in females than in males. Environmental risk factors, such as exposure to rubber or petroleum, are associated with the development of gallbladder cancer. Chronic Salmonella typhi infection has also been linked to adenocarcinoma of the gallbladder. Pancreaticobiliary maljunction, anomalous junction of the cystic duct and the common bile duct, and cystic disorders of the biliary tree are associated with an increased risk of developing gallbladder cancer; this is postulated to be due to reflux of pancreatic enzymes. Squamous cell carcinoma Squamous cell carcinoma accounts for up to 12.7% of gallbladder cancers. When compared with adenocarcinoma, it generally presents a worse prognosis. Squamous cell carcinoma is found more often in females than in males; the female-to-male ratio is 3:1. Typically, squamous cell carcinoma presents at an earlier age than adenocarcinoma, generally from the fourth to sixth decades of life. This cancer grows rapidly, metastasizes early, and generally has diffuse local and regional spread. However, lymph node metastasis and peritoneal seeding are rare. These tumors tend to invade the liver and adjacent organs by direct spread. Papillary and anaplastic lesions and angiosarcomas These lesions are rare and account for less than 10% of all gallbladder cancers. FrequencyApproximately 6000 new cases of gallbladder cancer are diagnosed in the United States annually. Gallbladder cancer causes about 2800 deaths per year in the United States. Considerable variation exists in the incidence of gallbladder cancer throughout the world. EtiologySome studies have shown that approximately 39-59% of gallbladder cancers are associated with the k-ras mutation and greater than 50% of gallbladder cancers are associated with a p53 mutation. PathophysiologyCurrently, the tumor node metastasis (TNM) system is used to stage gallbladder cancer, as follows:
ClinicalAs with most gallbladder lesions, early stage adenocarcinoma tends to present with symptoms similar to cholelithiasis or biliary dyskinesia. Later stage adenocarcinoma presents with more significant symptoms, such as weight loss, hepatomegaly, ascites, and right upper quadrant mass. Given this presentation, less than 50% of gallbladder cancers are diagnosed preoperatively. Most gallbladder cancers are diagnosed at the later stages, and the overall survival rate is less than 5% at 5 years for patients diagnosed with gallbladder cancer. INDICATIONSSection 3 of 12
Diagnosis or suspicion of gallbladder neoplasia based on intraoperative findings during surgery or based on preoperative diagnostic radiographic findings is an acceptable indication to proceed with resection of the gallbladder. RELEVANT ANATOMYSection 4 of 12
The gallbladder is a saccular structure located at the inferior surface of the liver, at the division of the right and left lobes of the liver, just below segments IV and V of the liver. The gallbladder is composed of 4 different areas: fundus, body, infundibulum, and neck. The gallbladder is approximately 7-10 cm long and is approximately 2.5-3.5 cm wide. The gallbladder normally contains approximately 30-50 mL of fluid, but it can distend and hold up to 300 mL of fluid. Gallbladder cancer generally spreads via the lymphatic channels and venous drainage, and peritoneal metastasis is common. CONTRAINDICATIONSSection 5 of 12
In general, a contraindication to operative intervention for gallbladder cancer, as with most other cancers, is the presence of metastatic disease. However, operative intervention may be considered for palliative purposes. WORKUPSection 6 of 12
Lab Studies
Imaging Studies
Diagnostic Procedures
TREATMENTSection 7 of 12
Medical therapyOperative treatment is the primary therapy for gallbladder tumors. Surgical therapyOperative resection offers the only chance for long-term survival. Management considerationsBenign lesions Regarding gallbladder polyps, the risk for malignancy is increased when the lesion is greater than 1 cm. The current recommendations for resection of gallbladder polyps include any lesion that is enlarging, symptomatic, or greater than 1 cm. The recommendations for lesions less than 1 cm include follow-up and reevaluation of the lesion via repeat imaging studies. Because of the increased risk of gallbladder cancer with choledochal cysts and pancreaticobiliary maljunction, surgical resection with removal of the gallbladder is indicated at the time of diagnosis. Such lesions should be resected when found in childhood. On the other hand, extrahepatic biliary duct resections and biliary diversion remain controversial forms of therapy for these patients. Malignant lesions Surgery remains the only curative treatment of biliary neoplasms. The type of operative intervention depends on the stage of the cancer. Surgery may be used for palliation in cases of tumor causing obstruction of the biliary tree. TreatmentBenign lesions Management of benign lesions depends on size and symptomatology. The indications for cholecystectomy include a polyp greater than 1 cm in patients older than 50 years with a wide-based lesion and a single polyp lesion or an enlarging lesion. Operative intervention is also indicated in patients with a polyp and coexisting biliary disease, such as cholelithiasis or cholecystitis. Another indication for operative intervention includes patients who have symptomatic lesions. Patients who have polyps at the neck of the gallbladder or polyps with a big or long pedicle that extends into the lumen may have symptoms similar to biliary colic, thus meeting the criteria for a cholecystectomy. Malignant lesions Adenocarcinoma The only curative treatment of adenocarcinoma of the gallbladder is surgical resection. As with squamous cell carcinoma, the extent of tumor spread determines the extent of surgical excision. For stage I disease, an open cholecystectomy is the procedure of choice to prevent peritoneal spreading; however, recent studies have suggested that laparoscopic removal with confined disease does not increase the risk of peritoneal spread. For stages II and III, the treatment remains controversial. The current accepted procedure is to perform an en bloc resection of the gallbladder with resection of segments IV-b and V of the liver with regional lymphadenectomy (see Image 1). If the cancer is found postoperatively, the patient should undergo a partial hepatectomy with lymph node dissection and laparoscopic port-site resection for the occurrence of micrometastasis (see Image 2). Stage IV usually represents extensive disease that is not amenable to surgical resection. With advanced disease, the indication for operative intervention includes the intent to palliate the patient by obviating biliary and/or intestinal obstruction. This can be accomplished by either surgery or endoscopic intervention, as the individual case warrants. The use of chemotherapy and radiation therapy in adenocarcinoma of the gallbladder remains controversial. A few studies demonstrate that radiation therapy may be useful for palliative purposes in gallbladder cancer. Recent literature reviews have advocated the use of gemcitabine alone or in combination with such agents as capecitabine for stage IV gallbladder cancer. However, this literature is sparse. Squamous cell carcinoma Surgery remains the mainstay of treatment of squamous cell carcinoma of the gallbladder. The type and extent of resection are dependent upon the amount of local and regional spread. Surgical management includes cholecystectomy with wedge resection of the liver. Resection of the involved organs is also indicated if no evidence exists of metastasis or peritoneal spread. Hepato-pancreatic duodenectomy has been studied as a radical therapy for this lesion; however, the long-term benefits of this procedure need further study before it can be uniformly recommended. Adjuvant chemotherapy and radiation therapy may be used for palliative purposes; however, the study results have been inconclusive as to the benefits of such therapy. COMPLICATIONSSection 8 of 12
The overall complication and morbidity rate is approximately 25%. Complications are similar to those experienced with cholecystectomy and include infection, hematoma, and bile leaks. Complication rates are higher in patients undergoing more extensive resections and lymphadenectomy. OUTCOME AND PROGNOSISSection 9 of 12
The overall survival rate for adenocarcinoma is less than 5% at 5 years. The survival rates for stage-based disease are as follows: 95-100% for stage I disease, 67% for stage III disease, and 33% for stage IV disease. The median survival rate after diagnosis of squamous cell carcinoma is 6 months without operative intervention. The most important prognostic factor is the amount of tumor infiltration and spread at the time of diagnosis. FUTURE AND CONTROVERSIESSection 10 of 12
The future of gallbladder cancer includes further study of neoadjuvant chemotherapy and radiation therapy. With the newer chemotherapy agents, the future of chemopalliation has the potential to grow. Further clinical trials are needed to determine the use and regimen of chemotherapeutic agents. Further study is also needed to determine the usefulness of surgery in extensive stage IV disease, along with the correct surgical procedure for stages II and III disease. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
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