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    Carcinoma of the Gall Bladder

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Carcinoma of the gall bladder is the fifth most common tumour in the gastrointestinal tract.

Gallbladder carcinomas are epithelial in origin and account for 98% of all gallbladder malignancies.

The remainder are sarcomas, lymphomas, carcinoid, metastases, and other unusual malignancies.

Sarcomatoid Carcinoma/Carcinosarcoma of Gall Bladder ; Lymphoma of Gall Bladder ; Metastatic Tumours of Gall Bladder

Epidemiologic studies have shown that female sex, age, postmenopausal status, and cigarette smoking are risk factors.

Chronic Salmonella typhi infection is associated with bile carcinogens and contributes to an increased risk of hepatobiliary carcinoma and gallbladder carcinoma.

Exposure to chemicals used in the rubber, automobile, wood finishing, and metal fabricating industries has been associated with an increased risk of gallbladder carcinoma.

Cholelithiasis is a well-established risk factor for the development of gallbladder carcinoma, and gallstones are present in 74%–92% of affected patients. Gallstones cause chronic irritation and inflammation of the gallbladder, which leads to mucosal dysplasia and subsequent carcinoma.

The calcified gallbladder (Porcelain Gall Bladder), which represents an extreme variant of chronic cholecystitis, is particularly prone to the development of gallbladder cancer.

The average age of the patients affected by the tumour is between 60-65 years. Most patients are females.

Symptoms are typically indolent. Chronic abdominal pain, anorexia, or weight loss are common initial complaints. Physical examination may demonstrate a palpable mass, hepatomegaly, and jaundice. Jaundice occurs more frequently as a result of malignant  obstruction of the biliary tree rather than hepatic metastasis or coexistent choledocholithiasis. Elevated serum levels of alpha-fetoprotein and carcinoembryonic antigen have been reported in association with gallbladder carcinoma.

A correct pre-operative diagnosis is made in less than 10% of patients.

The majority of gallbladder carcinomas are diffusely infiltrating lesions, and the remainder exhibit intraluminal polypoid growth.

Approximately 60% of tumours originate in the gallbladder fundus, 30% in the body, and 10% in the neck.

Submucosal spread of infiltrating carcinomas appears grossly as focal or diffuse areas of wall thickening, nodularity, or induration in the gallbladder wall.

In some cases of direct invasion, a thick neoplastic wall encases the gallbladder when direct extension to the liver has occurred.

Adenocarcinomas may be papillary or mucinous, giant cell and intestinal type and occasionally with choriocarcinoma like areas.

It is usually desmoplastic, and thus the wall of the gallbladder becomes thickened and leathery.

Squamous metaplasia may be so conspicuous that the tumour is thought to be a squamous carcinoma.

Occasionally, the tumour grows into the lumen of the gallbladder and assume a papillary configuration.

Squamous cell carcinoma only occur in about 4% of cases.

Undifferentiated carcinoma, comprising 5% of gall bladder tumours, are undifferentiated anaplastic carcinomas, which are bulky and replace most of the gall bladder.

Anaplastic, giant cell, and spindle cell forms of gallbladder carcinoma have been reported. Anaplastic small cell carcinoma is exceptionally rare.

The complications of tumour include fistula formation, perforation, cholecystitis and empyema.

The rich lymphatic plexus of the gallbladder provide the most common route of metastasis.

The tumour spreads by lymphovascular invasion, peritoneal spread, intraductal, and lymph node invasion. Lymph nodes are involved in 35% of cases.  5 year survival is approximately 5%.

Direct spread into the liver and contiguous structures occurs.

Survival is usually limited to those with papillary tumours or with localized disease where the tumours are an incidental finding by the pathologist  on examination of a cholecystectomy specimen. Papillary Adenocarcinoma of the Gall Bladder

                     

Abstracts:

Gallbladder cancer--a comprehensive review.Surgeon. 2008 Apr;6(2):101-10.

AIM: Gallbladder cancer is the fifth most common cancer involving the gastrointestinal tract, but it is the most common malignant tumour of the biliary tract worldwide. The percentage of patients diagnosed to have gallbladder cancer after simple cholecystectomy for presumed gallbladder stone disease is 0.5-1.5%. This tumour is traditionally regarded as a highly lethal disease with an overall 5-year survival of less than 5%. The marked improvement in the outcome of patients with gallbladder cancer in the last decade is because of the aggressive radical surgical approach that has been adopted, and improvements in surgical techniques and peri-operative care. This article aims to review the current approach to the management of gallbladder cancer. METHODS: A Medline, PubMed database search was performed to identify articles published from 1990 to 2007 using the keywords 'carcinoma of gallbladder', 'gallbladder cancer', 'gallbladder neoplasm' and 'cholecystectomy'. RESULTS AND CONCLUSIONS: The overall 5-year survival for patients with gallbladder cancer who underwent Ro curative resection was reported to range from 21% to 69%. Laparoscopic cholecystectomy is absolutely contraindicated when gallbladder cancer is known or suspected pre-operatively. Patients with a pre-operative suspicion of gallbladder cancer should undergo open exploration and cholecystectomy after proper pre-operative assessment. For patients whose cancer is an incidental finding on pathological review, a second radical resection is indicated except for Tis and T1a disease. There is still controversy for the optimal management of T1b disease. Although the role of surgery for advanced disease remains controversial, patients with advanced gallbladder cancer can benefit from radical resection, provided a potentially curative Ro resection is possible. There is still no effective adjuvant therapy for gallbladder cancer.

Primary gallbladder cancer: recognition of risk factors and the role of prophylactic cholecystectomy. Am J Gastroenterol. 2000 Jun;95(6):1402-10.

The objective of this article is to review the available literature on the epidemiology, predisposing factors, and conditions associated with primary gallbladder cancer, and to discuss the role of prophylactic cholecystectomy in high-risk patient populations. Gallbladder cancer is a highly malignant tumor with a poor 5-yr-survival rate. It is a tumor of the elderly and has striking genetic, racial, and geographic characteristics, with an extremely high prevalence in Native Americans and Chileans. Cholelithiasis is a well-established risk factor for gallbladder cancer and the risk seems to correlate with stone size. Polyps that are >1 cm, single, sessile, and echopenic are associated with a higher risk of malignancy. Anomalous junction of pancreaticobiliary ducts (AJPBD), especially without choledochal cyst, and porcelain gallbladder are additional factors that predispose to gallbladder cancer. Lesser associations include chronic bacterial infections of the gallbladder, typhoid carrier state, certain occupational and environmental carcinogens, hormonal changes in women, and certain social, dietary, and familial factors. It is important to identify high-risk groups for gallbladder cancer because of the dismal nature of this tumor. In patients with porcelain gallbladder and anomalous junction of the pancreatic and biliary ducts, cholecystectomy is recommended provided that the patient is a good operative candidate. Patients with large solitary polyps or gallstones require close ultrasonic follow-up. With the advent of endoscopic ultrasound it is expected that early changes of malignancy in polyps will be reliably detected, and more patients will potentially be cured with a simple cholecystectomy. Through a MEDLINE/PAPERCHASE search we identified and reviewed articles regarding gallbladder cancer published in English-language journals between 1966 and 1999, using the key words biliary tract and gallbladder diseases, cancer, neoplasms, surgery, cholelithiasis, gallstones, cholecystitis, gallbladder polyps, risk factors, chemical industry, occupational diseases, typhoid, porcelain gallbladder, bacteremia, and precancerous conditions. We also used the bibliography of relevant articles to increase our search. A total of 122 publications were selected using the mentioned data source.

Carcinoma of the gallbladder and cholecystostomy. Arch Surg. 1982 Jul;117(7):946-8.

Seven cases of carcinoma of the gallbladder after cholecystostomy were seen at the University of Virginia Medical Center, Charlottesville, between 1926 and 1979. These cases represented 6.7% of all cases of carcinoma of the gallbladder treated at that institution during that period. The interval between cholecystostomy and diagnosis of carcinoma ranged from three months to 40 years. Five patients had "gallbladder" symptoms intermittently during the interval, and two patients did not. One of the patients had a confirmed calcified or porcelain gallbladder five years before the development of carcinoma. At operation, none was found to have localized disease, and most had extensive metastatic disease. There were no survivors. Primary carcinoma of the gallbladder is an aggressive disease and difficult to diagnose. Few specific characteristics are available to the clinician and surgeon to detect this disease in its early stages. Patients who undergo cholecystostomy or have undergone cholecystostomy, with or without symptoms, should have elective cholecystectomy if they are acceptable operative risks. Such a policy would prevent a small, but substantial, number of cases of carcinoma of the gallbladder.

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