Signs and symptoms GALLBLADDER CANCER
Early disease In the early stages, gallbladder cancer is usually asymptomatic. Late disease Later, symptoms similar to those of benign gallbladder disease arise; they include right upper quadrant pain, nausea, vomiting, fatty food intolerance, anorexia, jaundice, and weight loss. This nonspecificity of symptoms delays presentation for medical attention and contributes to the low curability of gallbladder cancer. Physical findings may include tenderness, an abdominal mass, hepatomegaly, jaundice, fever, and ascites. BILE DUCT CANCER
Jaundice is the most frequent symptom found in patients with high bile duct tumors; it is present in up to 98% of such patients. Nonspecific signs and symptoms Patients who do not present with jaundice have vague complaints, including abdominal pain, weight loss, pruritus, fever, and an abdominal mass. Diagnosis GALLBLADDER CANCER
Gallbladder carcinomas are often diagnosed at an advanced stage, such that by the time symptoms have developed, most tumors are unresectable. Laboratory values in patients with gallbladder carcinoma are nonspecific but may include anemia, leukocytosis, and an elevated bilirubin level. Ultrasonography is useful for defining a thickened gallbladder wall and may show tumor extension into the liver. CT is more helpful than ultrasonography in assessing adenopathy and spread of disease into the liver, porta hepatis, or adjacent structures. MRI may be used to evaluate intrahepatic spread. Endoscopic retrograde cholangiopancreatography (ERCP) or transhepatic cholangiography (THC) may be useful in the presence of jaundice to determine the location of biliary obstruction and involvement of the liver. BILE DUCT CANCER
Cholangiocarcinoma may present earlier than gallbladder cancer by virtue of the development of biliary obstruction with jaundice, which may be painless. Tissue confirmation of suspected bile duct cancer can be difficult. The goals of the diagnostic evaluation include the determination of the level and extent of obstruction, the extent of local invasion of disease, and the identification of metastases. Many patients with cholangiocarcinoma are thought to have metastatic adenocarcinoma of an unknown primary, although occasionally the metastatic lesion may produce biliary dilatation without the primary lesion itself being radiographically visualized. Ultrasonography It is generally accepted that ultrasonography should be the first imaging procedure in the evaluation of the jaundiced patient. CT is a complementary test to ultrasonography, but both tests are accurate for staging in only 50% of patients and for determining resectability in < 45% of patients. Cholangiography is essential to determine the location and nature of the obstruction. Percutaneous THC is used for proximal lesions and ERCP for distal lesions. Magnetic resonance cholangiopancreatography (MRCP) may replace invasive studies in the near future. Histologic confirmation of tumor can be made in 45%-85% of patients with the use of exfoliative or brush cytology during cholangiography. Pathology GALLBLADDER CANCER
Histologic types Over 85% of gallbladder neoplasms are adenocarcinomas and the remaining 15% are squamous cell or mixed tumors. Route of spread The initial route of spread of gallbladder cancer is locoregional rather than distant. For patients undergoing resection for presumed high-risk gallbladder masses or preoperatively defined disease limited to the gallbladder, 25% of patients will have lymphatic involvement and 70% will have direct extension of disease into the liver defined at operation. BILE DUCT CANCER
Adenocarcinoma Morphologically, more than 90% of bile duct tumors are adenocarcinomas. Three macroscopic appearances have been identified: The papillary and nodular types occur more frequently in the distal bile duct, whereas the sclerosing type is found in the proximal bile duct. Patients with papillary lesions have the best prognosis. Other histologic types Unusual malignant diseases of the biliary tract include adenosquamous carcinoma, leiomyosarcoma, and mucoepidermoid carcinoma. Route of spread Most bile duct tumors grow slowly, spreading frequently by local extension and rarely by the hematogenous route. Nodal metastases are found in up to one-third of patients. Staging and prognosis GALLBLADDER CANCER
Gallbladder cancer is staged primarily at the time of surgery, and staging is determined by lymphatic involvement and extension of disease into adjacent structures (Table 2). Stage Survival of gallbladder carcinoma is directly related to disease stage. The 5-year survival rate is 83% for tumors that are confined to the gallbladder mucosa; this rate decreases to 33% if the tumor extends through the gallbladder. For patients who have involvement of the lymph nodes or metastatic disease, 5-year survival rates range from 0%-15%. Type of therapy Median survival is also improved in patients who have undergone curative resection, as compared with those who have had palliative procedures or no surgery (17 months vs 6 and 3 months, respectively). BILE DUCT CANCER
Over 70% of patients with cholangiocarcinoma present with local extension, lymph node involvement, or distant spread of disease. The AJCC (American Joint Committee on Cancer) staging system for extrahepatic tumors is shown in Table 3. Stage Survival for these patients is poor and is directly related to disease stage. Median survival is 12-20 months for patients with disease limited to the bile ducts and ≤ 8 months when the disease has spread. Tumor location Survival is also related to tumor location, with patients with distal lesions doing better than those with mid or proximal tumors. Success of therapy Curative resection and negative margins result in improved survival. Treatment In the absence of polyps identified ultrasonographically and confirmed by CT during the work-up of suspected cholelithiasas, relatively few patients with gallbladder cancer are diagnosed prior to surgery. Only 1%-2% of cholecystectomy specimens are found to contain malignancy. SURGERY FOR GALLBLADDER CANCER
Surgical management of gallbladder carcinoma is based on the local extension of the tumor. Early-stage disease Tumors that invade the mucosa, those that do not penetrate the muscularis, and those that penetrate full thickness but do not abut the liver or muscularis require cholecystectomy alone. Laparoscopic cholecystectomy may be adequate for T1 tumors. If there is direct extension of disease to or through the serosa, the resection should include the gallbladder bed (segments IVb and V) and a porta hepatis lymphadenectomy. Disease that involves the gallbladder node is particularly curable and should be resected. Nodal disease beyond the pericholedochal nodes defines the surgically incurable patient. SURGERY FOR BILE DUCT CANCER
The rate of resectability is 15%-20% for high bile duct tumors and up to 70% for distal lesions. Assessing resectability Higher resolution CT or MRI with biliary reconstruction may be supplemented with hepatic arteriography, portal venography, or duplex imaging preoperatively to assess resectability. Preoperative treatments Three randomized trials have shown no benefit to preoperative decompression of the biliary tree in patients with obstructive jaundice. Some authors advocate the preoperative placement of biliary stents to facilitate dissection of the hilus. This procedure should be performed immediately prior to resection to reduce the risk of cholangitis and maintain the duct at its maximally dilated size. Proximal tumors Local excision is often possible for proximal lesions. Hepatic resection is indicated for high bile duct tumors with quadrate lobe invasion or unilateral intrahepatic ductal or vascular involvement. Resection is not indicated in situations in which a clear surgical margin cannot be obtained. Mid-ductal and distal tumors Mid-ductal lesions can often be removed by resection of the bile duct with associated portal lymphadenectomy. Distal or mid-ductal lesions that cannot be locally excised should be removed by pancreaticoduodenectomy. Reconstruction techniques Biliary-enteric continuity is usually reconstructed with a Roux-en-Y anastomosis to the hilum for high lesions and in a standard drainage pattern following pancreaticoduodenectomy. Liver transplantation has been attempted for unresectable tumors, but early recurrence and poor survival have prevented the widespread application of this approach. Surgical bypass For patients found to have unresectable disease at surgical exploration, operative biliary bypass may be performed using a variety of techniques. Bypass results in excellent palliation and obviates the need for further intervention.