Tumors of the biliary tract

Chapter 34 Tumors of the biliary tract



Keith D. Lillemoe, MD, FACS, Michael G. House, MD



Key Points



1 Polypoid lesions of the gallbladder larger than 1 cm should be treated by cholecystectomy.

2 Carcinoma of the gallbladder, because of its late stage of presentation, has an overall 5-year survival of less than 10%.

3 Aggressive surgical resection, including partial hepatectomy, may result in increased survival in patients with cancers limited to the gallbladder wall.

4 Cholangiocarcinoma is strongly associated with cystic disease of the biliary tree (choledochal cysts, Caroli’s disease), Clonorchis sinensis infection, primary sclerosing cholangitis, and hepatolithiasis.

5 Patients with proximal (hilar) cholangiocarcinomas have poor overall survival, although aggressive resection that includes hepatectomy to achieve negative margins may improve the outcome.

6 Distal bile duct tumors, which manifest similarly to other periampullary malignant tumors, are associated with a higher rate of resectability and better long-term survival than more proximal cholangiocarcinomas.


Benign Tumors of the Gallbladder



Pseudopolyps (Cholesterol Polyps)



1. The most commonly observed polypoid lesion of the gallbladder; accounts for approximately 50% of such lesions

2. Not a true neoplasm, but rather cholesterol-filled projections of gallbladder mucosa protruding into the lumen

3. Usually less than 1 cm in size; visualized on gallbladder imaging studies (ultrasonography, oral cholecystography) as nonmobile filling defects

4. Usually asymptomatic unless associated with gallstones

5. No malignant potential


Adenomyosis



1. Consists of a thickened gallbladder muscular layer with Rokitansky-Aschoff sinuses

2. Three types: fundal (most common), appearing as a hemispheric lesion with a central dimple; segmental, consisting of an annular stricture; or diffuse, involving the entire gallbladder

3. May manifest as muscular hypertrophy secondary to gallbladder dysmotility; therefore, symptoms are relieved by cholecystectomy

4. May be associated with carcinoma of the gallbladder


Adenomas



1. True neoplastic epithelial tumors of the gallbladder mucosa

2. Usually manifest as solitary, nonmobile filling defects seen on gallbladder ultrasonography or oral cholecystography

3. Premalignant, with carcinoma in situ found in larger polyps

4. Unlikely to play a major role in the pathogenesis of most gallbladder cancers


Treatment



1. Because the histology of polypoid lesions of the gallbladder cannot be determined nonoperatively by current methods, patients with polyps larger than 1 cm should undergo cholecystectomy.

2. Polyps up to 1 cm in size, regardless of total number, should be followed by repeat imaging studies every 3 to 6 months.

3. Any patient with biliary symptoms and a gallbladder polyp should undergo cholecystectomy.


Benign Tumors of the Bile Duct



1. These are much less common than benign gallbladder tumors.

2. Histologic types
image Papillomas

image Adenomas

image Cystadenomas: tumors with inner layers of mucin-secreting epithelium, mesenchymal stroma, and an outer layer of hyalinized fibrous tissue

3. They may be solitary or multiple.

4. Symptoms are usually caused by bile duct obstruction, which results in intermittent jaundice or cholangitis.

5. The diagnosis can usually be made by magnetic resonance, endoscopic retrograde, or percutaneous transhepatic cholangiography.

6. Treatment consists of surgical resection of the bile duct, most commonly with reconstruction by hepaticojejunostomy.

7. Both benign cystadenomas and multiple papillomatosis of the bile duct can be associated with a high rate of local recurrence if complete resection is not accomplished.


Carcinoma of the Gallbladder



Incidence



1. Carcinoma of the gallbladder is the most common biliary tract malignancy and the fifth most common gastrointestinal cancer (3% to 4% of gastrointestinal tumors).

2. The incidence has increased as the population has aged. Currently, 6000 to 7000 new cases are diagnosed each year (2.5 cases per 100,000 population).

3. The female-to-male ratio is 3:1.

4. The usual age of onset is the sixth or seventh decade of life.

5. An increased incidence is seen in southwestern Native Americans, Native Alaskans, Mexicans, and Hispanics living in the United States and in residents of northern Japan, Israel, and Chile.

6. A much lower incidence is seen in African Americans and residents of India, Nigeria, and Singapore.


Etiology


Risk factors for gallbladder carcinoma:



image Gallstones/chronic cholecystitis

image Choledochal cysts

image Anomalous pancreatobiliary duct junction

image Carcinogens

image Estrogens

image Chronic typhoid infection

image Porcelain gallbladder

image Gallbladder polyps

1. Gallstones/chronic cholecystitis
image Gallstones are present in more than 90% of patients with gallbladder carcinoma; conversely, only 1% of patients with gallstones have gallbladder carcinoma.

image Larger stones (>3 cm) are associated with a 10-fold higher risk of gallbladder cancer compared with smaller stones.

image The role of gallstones in the development of gallbladder cancer is likely related to chronic inflammation.

image Gallstone composition does not seem to affect pathogenesis.

2. Choledochal cysts (see Chapter 33)
image Choledochal cysts are associated with carcinomas throughout the biliary tract including the gallbladder.

image The risk of biliary carcinoma increases with age.

image The risk may be related to an association with an anomalous pancreaticobiliary duct junction, which is frequently seen with choledochal cysts.

image Surgical removal of choledochal (and gallbladder) cysts is recommended to prevent further reflux of bile and stasis and to eliminate the cancer risk.

3. Anomalous pancreaticobiliary duct junction
image The long common channel of the pancreatic and common bile duct (type 3B anomaly) appears to be associated with a significantly increased risk of gallbladder cancer.

image Reflux of pancreatic juice into the biliary tree and bile stasis is the proposed mechanism.

4. Carcinogens
image Industrial exposure: rubber industry

image Animal studies: azotoluene, nitrosamines

5. Estrogens: This epidemiologic association may simply be related to the associated increased incidence of gallstones.

6. Salmonella typhi infection: This is likely related to chronic irritation and inflammation.

7. Gallbladder wall calcification: Diffuse calcification of the gallbladder wall (porcelain gallbladder) was formerly an indication for cholecystectomy because of the risk of cancer even in asymptomatic patients. More recent studies have suggested that this risk had been overestimated and is likely less than 5%. Calcification of the gallbladder mucosa is associated with a higher incidence of gallbladder cancer.

8. Gallbladder polyps
image Adenomas and adenomyosis have clear premalignant potential.

image Cholecystectomy is indicated for any polyp larger than 1 cm (see earlier).


Pathology and staging



1. Histologic type
a. Adenocarcinoma: 90%
image Scirrhous (90%): infiltrating, desmoplastic, obliterating gallbladder lumen, invading liver

image Papillary (5%): polypoid, slow growing, late to metastasize

image Colloid (5%): soft, gelatinous, mucinous tumors filling the gallbladder

b. Anaplastic: 5%

c. Squamous (adenosquamous): 2%

d. Miscellaneous types: 3%

2. Routes of spread
a. Spread occurs primarily by local extension, typically for fundus-based tumors.

b. Lymphatic drainage is to the adjacent lymph node basins first—cystic duct, pericholedochal, and hilar lymph nodes (N1). Secondary basins include the retropancreatic, celiac axis, and periaortic nodes (N2).

c. The veins of the gallbladder drain directly into the liver parenchyma and to branches of the portal vein of segments V and IVB of the liver.

d. Direct invasion of adjacent structures including the common hepatic duct, duodenum, and colon occurs.
e. Dissemination occurs to the liver or peritoneal surface.

3. Staging (Table 34.1)

TABLE 34.1 American Joint Commission on Cancer (tumor, node, metastasis [TMN]) staging: summary for carcinoma of the gallbladder
























Stage 0 Carcinoma in situ (T0)
Stage I (T1N0M0) Tumor invades lamina propria (T1a) or muscular layer (T1b)
Stage II (T2N0M0) Tumor invades perimuscular connective tissue; no extension beyond serosa or into liver (T2)
Stage IIIA (T3N0M0) Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ, such as stomach, duodenum, colon, pancreas, or extrahepatic bile ducts (T3); no lymph node involvement
Stage IIIB (T1–3N1M0) T1–3 with positive nodes confined to the hepatic hilus including nodes along the bile duct, hepatic artery, portal vein, and cystic duct (N1)
Stage IVA (T4N0M0) Tumor invades main portal vein or hepatic artery or invades two or more extrahepatic organs (T4); no lymph node involvement
Stage IVB (any T, any N, M1 or any T N2M0 or T4N1M0) Any T with distant metastases (M1); any T with lymph node metastases to celiac, periduodenal, peripancreatic, and/or superior mesenteric lymph nodes (N2); T4 with N1 nodes

Adapted from Edge S, Byrd D, Compton C, et al. AJCC Cancer Staging Manual, 7th ed. New York: Springer-Verlag, 2010.



Clinical features



1. Symptoms (frequency)
image Abdominal pain (80%): usually of less than 1 month’s duration and difficult to distinguish from symptoms of acute cholecystitis or biliary pain

image Nausea and vomiting (50%)

image Weight loss (40%)

image Jaundice (30% to 40%): usually a poor prognostic finding for fundus-based cancers

image Incidental finding at cholecystectomy for gallstones (10% to 20%; incidental cancers found in 1% of cholecystectomies for symptomatic gallstones)

2. Physical findings: usually indicate advanced disease
image Right upper quadrant mass

image Hepatomegaly

image Jaundice


Diagnosis and preoperative staging



1. Laboratory tests
image Abnormal liver biochemical test levels when tumor or periportal lymphadenopathy is associated with biliary obstruction

image No reliable tumor marker, including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9)

2. Radiologic studies
a. Ultrasonography
image Sensitivity of 75% to 80%

image Findings:
– Complex mass filling the gallbladder lumen

– Gallbladder wall thickening

– Polypoid gallbladder mass

– Gallstones

– Normal in up to 10% of patients

b. Computed tomography (CT)
image Findings are similar to those of ultrasonography with respect to gallbladder wall thickening or mass.

image CT defines the extent of disease better than ultrasonography; it demonstrates liver or adjacent organ invasion, liver metastases, lymph node involvement, vascular invasion, and biliary obstruction.

c. Magnetic resonance imaging (MRI)
image Magnetic resonance cholangiopancreatography (MRCP) provides a single noninvasive imaging modality that allows complete assessment of the hepatic parenchyma, biliary tree, vasculature, and lymph nodes.

d. Endoscopic ultrasonography (EUS) aids in determining the extent of local invasion and nodal involvement.

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Jun 4, 2016 | Posted by in GASTROENTEROLOGY | Comments Off on Tumors of the biliary tract

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