TUMOR KANTONG EMPESDU

Background
Gallbladder tumors are recognized with increasing frequency due to improvements in imaging
techniques and increased utilization of these studies. Approximately 5% of patients evaluated
with ultrasonography for abdominal pain will have a gallbladder polyp. Cancer of the gallbladder
is uncommon, although it is the fifth most common gastrointestinal malignancy. It is possible to
cure gallbladder cancer when tumors are treated surgically at an early stage. Since gallbladder
polyps are common, it is important to identify those that carry a high risk of malignancy. The
size of a gallbladder polyp is generally the strongest predictor of malignant transformation.[1]
Benign lesions of the gallbladder are relatively common, but only adenomatous polyps are
considered to have malignant potential. Although ultrasonography can be useful in evaluating
these lesions, considerable difficulty may be encountered in establishing the diagnosis
preoperatively.
In 1924, Blalock suggested avoiding surgery on patients with gallbladder cancer if the diagnosis
could be made preoperatively.[2] Therapeutic nihilism continued to define the approach to
gallbladder cancer through most of the 20th century. Although most patients with gallbladder
cancer continue to present with advanced disease, advances in imaging and hepatobiliary surgical
techniques have made curative surgery possible in a greater number of cases.
The surgical approach to gallbladder cancer includes prevention, early detection, appropriate
staging, and curative resection.

Cholesterol 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 identified histologically 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.

Adenomyomatosis
Adenomyomatosis is characterized by extensions of Rokitansky-Aschoff sinuses through the
muscular wall of the gallbladder. Ultrasonography reveals a thickened gallbladder wall with
intramural diverticula. Although adenomyomatosis is generally considered a benign condition,
serial evaluation with ultrasonography is indicated to rule out enlarging adenomatous polyps and
gallbladder cancer. Some authors have reported gallbladder cancer occurring in localized
adenomyomatosis and have suggested a more aggressive approach to the benign lesions.

Adenomatous polyps
Adenomatous polyps are benign epithelial neoplasms with malignant potential. Papillary
adenomas grow as pedunculated, complex, branching tumors projecting into the gallbladder
lumen. Tubular adenomas arise as a flat, sessile neoplasm. Consequently, it can be difficult to

distinguish some adenomas from other gallbladder polyps by ultrasonography. Like many
gastrointestinal tumors, an adenoma-carcinoma sequence is generally thought to occur in these
lesions.

Other lesions
Other rare, benign lesions found in the gallbladder include fibromas, leiomyomas, lipomas,
hemangiomata, granular cell tumors, and heterotropic tissue, including gastric, pancreatic, and
intestinal epithelium.

Malignant lesions
The incidence of gallbladder cancer is 1.2 cases 100,000 persons in the United States; the
frequency is much higher in Mexican Americans and Native Americans, although the greatest
incidence is found in the indigenous peoples of the Andes Mountains, in northeastern Europeans,
and in Israelis. The female-to-male ratio for gallbladder cancer is about 3:1; incidence of the
disease peaks in the seventh decade of life.[3]
The most common risk factor for gallbladder cancer is gallstones, which are present in 75%-90%
of gallbladder cancer cases. The size of the gallstones plays a role in the risk of developing of
gallbladder cancer. Gallbladders containing gallstones that are greater than 3 cm in diameter have
a 10-fold greater risk for developing malignancy than do those containing gallstones that are 1
cm in diameter. Causality is difficult to establish, but other chronic inflammatory conditions,
such as cholecystoenteric fistula, primary sclerosing cholangitis, pancreaticobiliary maljunction,
and chronic infection with Salmonella typhi, have also been associated with an increased risk of
gallbladder cancer.
Modern series report about a 10% incidence of gallbladder cancer in porcelain gallbladders (in
which the gallbladder wall is calcified), a much lower rate than that reported in older series.
Stippled calcification of the mucosa is thought to carry a higher risk of gallbladder cancer than
does generalized calcification of the gallbladder wall.[4, 5] Based on these associations, chronic
inflammation is postulated to be involved in the pathogenesis of gallbladder cancer.
Gallbladder cancer is often discovered incidentally during a workup for gallstone disease, and
about 50% of gallbladder cancer cases are diagnosed incidentally in cholecystectomy specimens.
Unfortunately, about 35% of patients have distant metastases at the time of diagnosis.
Histologically, adenocarcinoma is found in 90% of gallbladder cancer cases, and squamous cell
carcinoma is found in 2% of cases. Rare types of gallbladder cancer include sarcoma,
adenosquamous carcinoma, oat cell carcinoma, carcinoid, lymphoma, melanoma, and metastatic
tumors. A number of histologic subtypes of adenocarcinoma have been described, but papillary
adenocarcinoma represents about 5% of gallbladder cancers; it tends to be well-differentiated
and carries a more favorable prognosis.
Anatomy
The gallbladder is a saccular structure located at the inferior surface of the liver, at the division of
the right and left lobes, just below segments IV and V. The gallbladder is composed of 4 different
areas: the fundus, body, infundibulum, and neck. The gallbladder is approximately 7-10 cm long
and about 2.5-3.5 cm wide. It 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. Since the gallbladder is
immediately adjacent to the liver, bile duct, portal vein, hepatic artery, duodenum, and transverse
colon, involvement of these structures is common.

The cystic plate is the reflection of the visceral peritoneum between the liver and the gallbladder.
The dissection between the gallbladder and the liver during cholecystectomy divides the plane
between the cystic plate and the muscle layer of the gallbladder. This is the anatomic basis for
the improved survival in patients undergoing liver resection for T1b gallbladder cancer.
The lymphatic drainage of the gallbladder proceeds from the cystic node to the pericholedochal
nodes and then to the regional nodal basins, including the superior mesenteric, retropancreatic,
retroportal, and celiac. Interestingly, direct drainage from the gallbladder to the aortocaval nodes
has been demonstrated. For this reason, exposure of this region is a necessary step in the
operative staging of gallbladder cancer.[6]
Pathophysiology
Chronic inflammation from a variety of stimuli has been implicated in the pathogenesis of
gallbladder cancer. Numerous studies have investigated genetic abnormalities in gallbladder
cancer and have shown that approximately 39-59% of gallbladder cancers are associated with the
K-ras mutation, while more than 90% of them are associated with a p53 mutation. Other studies
have identified higher levels of microsatellite instability and loss of heterozygosity when
gallbladder cancers develop in a background of chronic cholecystitis. A number of other genetic
abnormalities have been associated with gallbladder cancer including overexpression of the cerb-2 gene, upregulation of cyclin D1, p16, p27, and MSH2.[7]
An adenoma-carcinoma sequence is thought to be involved in many cases of gallbladder cancer.
Gallbladder cancer spreads early via lymphatic, hematogenous, and transcoelomic dissemination.
Local invasion into the liver and surrounding organs is common.
Etiology
Gallstones are present in 75-90% of gallbladder cancer cases, but an etiologic influence remains
unproven. Risk factors for developing gallbladder cancer include the inflammatory conditions
listed above, advanced age, and the presence of a gallstone larger than 3 cm. Anomalous
pancreatobiliary junction also may be a risk factor for the development of gallbladder cancer.
Some authors have implicated bile acid composition, methyldopa, oral contraceptives, and
occupational exposure to rubber, but these associations remain unproven. A 2008 study found
evidence that excess body weight in women, specifically a 5 kg/m2 increase in the body-mass
index, is strongly associated with an increased risk of gallbladder cancer.[8]