Gallbladder cancer overview

# Overview
Gallbladder cancer may be classified according to histology findings into various subtypes and are as follows Adenocarcinoma, Papillary adenocarcinoma, Mucinous adenocarcinoma, Signet ring cell carcinoma, Adenosquamous carcinoma, Squamous cell carcinoma, Neuroendocrine carcinoma, Small cell carcinoma, undifferentiated carcinoma, spindle cell undifferentiated carcinoma, giant cell undifferentiated carcinoma.It is understood that GBC is the result of persistent irritation of the gallbladder mucosa over a period of years which predispose to malignant transformation or act as an enhancer for carcinogenic exposure.The primary mechanism involves cholelithiasis and resultant cholecystitis and appears to be the driving force in most areas of the arena.Chronically inflamed gallbladder may additionally express both pyloric gland and intestinal metaplasia.But, fluke-infested gallbladders more commonly shows intestinal metaplasia and p53 mutations than sporadic gallbladder cancers.Dysplastic lesions have molecular genetic proof that supports progression towards CIS.There are also histologic and molecular differences in GBCs related to anomalous pancreaticobiliary duct junction and in the ones related to gallstones, Providing further proof that two different pathogenetic pathways are involved.Less than 3% of early gallbladder carcinomas have adenomatous remnants, indicating this mechanism has less importance within the carcinogenic pathway.Around 80 t0 95% of biliary tract cancers are gallbladder cancers.Epidemiological research has recognized striking geographic and ethnic difference. An excessive incidence in American Indians and Southeast Asia, but pretty low in the America and the arena.Gallstones, Porcelain gallbladder, Gallbladder polyps, Primary sclerosing cholangitis (PSC) , chronic infection, congenital biliary cysts, pancreaticobiliary maljunction (PBM).There is no screening recommended for gallbladder cancer. According to the National Comprehensive Cancer Network (NCCN) guidelines, gallbladder cancer may be diagnosed as an incidental finding in patients who undergo laparoscopic cholecystectomy.Gallbladder cancer must be differentiated from hepatitis, gallstones, cholecystitis, peptic ulcer, pancreatic cancer and pancreatitis.Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor.Most tumors are adenocarcinomas, with a small percent being squamous cell carcinomas. The cancer commonly spreads to the liver, pancreas, stomach and duodenum. The survival rate depends on the extent of cancer at the time of diagnosis with gallbladder cancer and early detection is key for good prognosis.According to the AJCC, there are 4 stages of gallbladder cancer based on the tumor spread.Symptoms of gallbladder cancer include jaundice, pain, fever, burping and weight loss.Laboratory findings consistent with the diagnosis of gallbladder cancer include abnormal liver function tests and elevated CA 19-9 and CEA levels.On abdominal CT scan, gallbladder cancer appears as large heterogeneous mass with areas of necrosis.Palliative therapy in gallbladder cancerinvolves percutaneous transhepatic radiologic catheter bypass or endoscopically placed stents, standard external-beam radiation therapy, palliative surgery or standard chemotherapy.Research suggests that lifestyle factors such as changes in diet, exercise, and maintenance of weight can influence the likelihood of an individual developing gallbladder cancer.Research suggests that lifestyle factors such as changes in diet, exercise, and maintenance of weight can influence the likelihood of an individual developing gallbladder cancer

# Historical Perspective
In 1777 Maxmillan de Stol described the gallbladder cancer and since studies have established in the identification of the disease and ineffective treatment of this disease.Gallbladder cancer(GBC) are often clinically asymptomatic and an surprising finding at incision, most commonly detected incidentally on histological examination.GBC is characterised by local invasion, intensive regional lymphoid tissue metastasis and distant metastases. In general, GBC is that the most aggressive of the biliary cancers with the shortest median survival period.

# Classification
Gallbladder cancer may be classified according to WHO into various subtypes like adenocarcinoma, papillary adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma, adenosquamous carcinoma, squamous cell carcinoma, neuroendocrine carcinoma, small cell carcinoma, undifferentiated carcinoma, spindle cell undifferentiated carcinoma, giant cell undifferentiated carcinoma.

# Pathophysiology
Gallbladder cancer usually develops in the setting of chronic inflammation of the gallbladder.The most common source of chronic inflammation is cholesterol gallstones. The gallbladder cancer risk increases to 4-5% in the presence gallbladder cancer (GBC) is the result of 2 or more different biological pathways based on morphological, genetic, and molecular evidence. Metaplasia is believed to be one of the pathological reason behind the development of gallbladder carcinoma. Although the definite relationship between metaplasia and dysplasia, is not clearly established yet. On gross pathology, fibrosis and thickening of the gallbladder are characteristic findings of the gallbladder cancer. On microscopic histopathological analysis, outer portion is often better differentiated than deeper portion are characteristic findings of gallbladder cancer.

# Causes
Definite cause of the gallbladder cancer is not determined, but several risk factors are involved in this cancer, such as gallstones, gallbladder polyps, infections, and Primary sclerosing cholangitis.

# Epidemiology and Demographics
Around 80 t0 95% of biliary tract cancers are gallbladder cancers. Epidemiological research has recognized striking geographic and ethnic difference. An excessive incidence in American Indians and Southeast Asia, but pretty low in the America and the arena.

# Risk Factors
The most potent risk factor in the development of gallbladder carcinoma is gallstones. Other risk factors include Porcelain gallbladder, gallbladder polyps, Primary sclerosing cholangitis, chronic infection, pancreaticobiliary maljunction (PBM) and biliary cysts.

# Screening
According to the National Comprehensive Cancer Network (NCCN) guidelines, gallbladder cancer may be diagnosed as an incidental finding in patients who undergo laparoscopic cholecystectomy.

# Differential diagnosis
Gallbladder cancer must be differentiated from hepatocellular carcinoma liver hemangioma, Liver abscess, cirrhosis, inflammatory lesions, cholangiocarcinoma, pancreatic carcinoma, Focal nodular hyperplasia.

# Natural History, Prognosis, and Complications
Depending on the extent of the tumor at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor.

# Diagnosis

## Diagnostic Study of Choice
There is no single diagnostic study of choice for the diagnosis of gallbladder cancer. According to Nevin's staging system and TNM staging system of the American Joint Committee on Cancer there are several stages of gallbladder cancer.

## History and Symptoms
The majority of patients with early stages of gallbladder cancer are asymptomatic. Symptoms of gallbladder cancer include jaundice, pain, fever, burping and weight loss.

## Physical Exam
Patients with gallbladder cancer usually appear asymptomatic. Physical examination of patients with gallbladder cancer is usually remarkable for nonspecific symptoms that are due to cholelithiasis or cholecystitis. The preoperative diagnosis rate for gallbladder cancer was only 10 to 15 percent.

## Laboratory Findings
There are some diagnostic laboratory findings associated with gallbladder cancer, such as alkaline phosphatase, serum bilirubin, carcinoembryonic antigen (CEA), CA 19-9.

## Electrocardiogram
There are no electrocardiogram findings associated with gallbladder cancer.

## CT scan
CT scan may be helpful in the diagnosis of gallbladder cancer. Findings on CT scan suggestive of gallbladder cancer include invasion of liver and lymphadenopathy, polyps, and mass replacing gallbladder.

## MRI
The combination of MRI (magnetic resonance imaging) with MRA (magnetic resonance angiography) is particularly useful in diagnosing the following: Involvement of biliary tract, vascular invasion, involvement of liver, and involvement of lymph nodes.

## Ultrasound
According to the NCCN guidelines, screening for gallbladder cancer patients is recommended with endoscopic ultrasonography (EUS).

## Other Imaging Findings
Given the rate of high incidence of metastases in gallbladder cancer, FDG(fluorodeoxyglucose), PET(positron emission tomography) scan is particularly useful in identifying metastases. PET scan is useful in diagnosing abnormal lesions and detecting residual disease after cholecystectomy. PET scan has the ability to detect occult metastasis in patients with potentially resectable tumors and changes the management in almost 25% of the patients. Percutaneous transhepatic cholecystoscopy and Percutaneous transhepatic fine needle aspiration are helpful in the evaluation of gallbladder polyps.

# Treatment

## Medical Therapy
Gallbladder cancer (GBC) is a rare but highly fatal malignancy. The therapy for gallbladder cancer depends largely on the disease progression and the stage of cancer at the time of diagnosis. Palliative therapy in gallbladder cancer involves percutaneous transhepatic radiologic catheter bypass or endoscopically placed stents, standard external-beam radiation therapy, palliative surgery or standard chemotherapy.

## Surgical Therapy
Surgery is the only mainstay of treatment for gallbladder cancer. Complete surgical tumour resection is the only curative treatment for the gallbladder cancer.Radicalcholecystectomy and extended radical cholecystectomy are the surgery of choice for gallbladder cancer.

## Primary Prevention
Effective measures for the primary prevention of gallbladder cancer include diet, exercise and maintenance of weight.

## Secondary Prevention
There are no established measures for the secondary prevention of gallbladder cancer.