Follow-up After Resection of Cholangiocarcinoma

Recurrence following resection of ICC is within the liver in 60% of patients. While data are lacking,

there is some evidence to suggest that there is a role for reresection in highly selected patients. The

most likely site of recurrence after resection of hilar cholangiocarcinoma is locally within the bile duct,

regional lymph nodes, or liver. Therapy for recurrence is palliative. Surgical reexcision is usually

impossible because of the challenging anatomic location and the radical procedures that are required for

resection of the primary tumor. The main symptoms of recurrence that demand palliation are pruritus

or cholangitis associated with jaundice. For biliary drainage to relieve jaundice or cholangitis, either

surgical drainage or drainage by PTC can be effective. Endoscopic drainage has little role in the relief of

jaundice in patients who have had Roux-en-Y biliary reconstruction. For limited recurrences,

intraluminal brachytherapy or external beam radiotherapy may improve palliation and, potentially,

survival.132

Routine follow-up consists of office visits every 3 months with physical examination and

measurement of liver function tests. Although a rising alkaline phosphatase level is a reliable indicator

of evolving biliary obstruction, patients recovering from liver resection and biliary obstruction can have

persistent elevations of alkaline phosphatase. Up to 10% of patients with biliary surgical reconstruction,

however, may develop a benign anastomotic stricture. Most patients with recurrence or a benign

stricture will present with jaundice or cholangitis. Surveillance cross-sectional imaging is recommended

every 3 to 6 months for the first 2 years following resection and should be individualized thereafter.

Issues for the Future

Further studies are needed to develop effective adjuvant, and potentially neoadjuvant, therapies for

cholangiocarcinoma. Continued assessment of novel drugs and radiosensitizers, and biologic agents is

warranted. A better understanding of the molecular pathogenesis and genetics of bile duct cancers may

lead to new therapeutic strategies and possibly preventive strategies for high-risk populations.

BENIGN GALLBLADDER NEOPLASMS

Incidence

Benign tumors of the biliary tract are rare, but have been reported more frequently as imaging

modalities (e.g., ultrasound and CT scan) have come into widespread and frequent use. In patients

undergoing cholecystectomy, the reported incidence of benign gallbladder tumors is less than 3%.

Pathology

Polyps and Pseudotumors

Benign gallbladder tumors are most frequently polyps or polypoid lesions. The incidence of polyps in

asymptomatic patients is about 5%.3 Cholesterol polyps (cholesterolosis), accounting for half of all

gallbladder polypoid lesions, result from epithelium-covered, cholesterol-laden macrophages in the

lamina propria.133 These lesions are likely a result of an error in cholesterol metabolism. They extend

from the mucosa on a narrow stalk, grossly appearing as yellow spots on the mucosal surface. Nearly all

are multiple, and most are less than 10 mm in size.133,134 When a polyp is pedunculated, it is benign in

most cases; alternatively, sessile “polyps” are more often malignant (Fig. 63-10). Inflammatory polyps

result from chronic inflammation and extend by a narrow vascularized stalk into the gallbladder lumen.

None of these lesions are considered premalignant, although isolated cases of cholesterolosis associated

with in situ carcinoma have been reported.135

Adenomas

Gallbladder adenomas are found infrequently. They may be tubular or papillary, both arising from the

epithelial layer of the gallbladder. Multiple papillary adenomas, or papillomas, are called papillomatosis.

A direct association between benign adenoma, adenoma containing carcinoma in situ, and invasive

carcinoma has been demonstrated; thus these lesions are considered premalignant.136 Malignant

transformation, however, has only rarely been reported, primarily from large adenomas. In one series,

all benign adenomas were less than 12 mm in diameter, whereas the adenomas with cancerous foci

were greater than 12 mm.135

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Figure 63-10. T2-weighted magnetic resonance imaging scan showing a sessile polyp within the gallbladder (arrow) that was

malignant on histologic examination.

Adenomyomatosis

Adenomyomatosis of the gallbladder is characterized by localized or diffuse hyperplastic extensions of

the mucosa into, and often beyond, a hypertrophied gallbladder muscular layer. Hyperplasia occurs at

outpouchings of the mucosa of the gallbladder through the wall (Rokitansky–Aschoff sinuses) and

through the crypts of Luschka. This can result in focal thickening of the gallbladder wall, resembling

gallbladder adenocarcinoma. The etiology is unknown. This lesion may be premalignant, because cases

of adenocarcinoma arising in or near adenomyomatosis have been reported, but this relationship is

unclear.127,138

Other Benign Gallbladder Tumors

Other benign lesions include tumors arising from the tissue of the gallbladder wall, such as leiomyomas,

lipomas, hemangiomas, granular cell tumors, and heterotopic tissue, including gastric, pancreatic, or

intestinal epithelium.

Clinical Findings

Patients with benign gallbladder tumors typically present with symptoms consistent with

choledocholithiasis, including right upper quadrant pain, fatty food intolerance, and nausea. Many

benign gallbladder lesions are also discovered incidentally after elective cholecystectomy. Therefore,

symptoms caused by benign lesions are difficult to separate from those caused by gallstones. Most

lesions, however, are asymptomatic and are discovered incidentally during imaging for other abdominal

conditions.

Diagnosis

Diagnosis of benign gallbladder polyps is usually made when an ultrasound study is obtained to evaluate

a patient for symptoms consistent with gallstones. On ultrasound, a filling defect that does not change

with position is likely a polyp or carcinoma and not a gallstone. Cholesterol polyps are typically small,

submucosal, multiple, and hyperechoic on ultrasound because of their high cholesterol content. Other

than this typical appearance and the fact that malignant polyps are usually more than 1 cm in size, it is

difficult to differentiate benign from malignant polyps.

Both intravenous contrast-enhanced and unenhanced CT may be important in distinguishing benign

from malignant polyps. In a recent series examining 31 polypoid lesions of the gallbladder, contrastenhanced CT detected all of the lesions. Benign polyps were not visualized with unenhanced CT, unlike

neoplastic tumors, thus improving the ability to distinguish these lesions when both enhanced and

unenhanced CT scans were obtained.9 Endoscopic ultrasound has also been used to image these lesions,

and may be more accurate than transabdominal ultrasound in differentiating benign from malignant

tumors.22

Treatment

Large polyps, greater than 10 mm, have the greatest malignant potential.9,133,134 Without the evidence

of invasion or metastatic disease, however, no radiologic test can reliably differentiate benign from

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malignant lesions. Therefore, if large (>1 cm) polyps are present, even in asymptomatic patients

without stones, cholecystectomy is warranted.139 Additionally, resection is recommended for smaller

pedunculated lesions with evidence of a vascularized stalk. Small pedunculated lesions with the gross

characteristics of a benign cholesterol polyp may be observed and resected only if symptomatic.

Although these lesions have routinely been followed with ultrasound, a recent prospective study

suggested that polyps smaller than 1 cm do not progress to carcinoma.140 Cholecystectomy, however, is

still considered the standard of care if there is any increase in size.

BENIGN BILE DUCT NEOPLASMS

Incidence

Benign bile duct tumors, at times clinically resembling hilar cholangiocarcinoma, are less common,

occurring in less than 1% of patients.4

Pathology

Attesting to the rarity of these lesions, only two cases of benign extrahepatic bile duct disease occurred

in 4,200 biliary tract operations in one institution.141 The most common benign tumors of the

extrahepatic biliary tree arise from the glandular epithelium lining the ducts; about two-thirds of benign

tumors are polyps, adenomatous papilloma, or bile duct adenomas. Most are found in the periampullary

region, but they can be distributed throughout the entire biliary tree (Fig. 63-11). Multiple papillomas

also have been reported throughout the intrahepatic and extrahepatic biliary tree, termed multiple biliary

papillomatosis. Although local recurrence and progression to death from obstructive jaundice and

cholangitis occur frequently in these rare cases, these tumors have little, if any, malignant potential.

Other benign tumors (e.g., cystadenoma, granular cell myoblastoma, leiomyoma, and heterotopic

tissue) have also been reported.

One condition that deserves consideration is the case of “malignant masquerade,” an inflammatory,

fibrotic lesion clinically resembling hilar cholangiocarcinoma, but pathologically consisting only of

extensive fibrosis and inflammatory cells without evidence of dysplasia or preneoplastic change.142–144

In patients being considered for palliative treatment alone with presumed hilar cholangiocarcinoma, it is

essential to obtain a tissue diagnosis. It is inappropriate to treat benign lesions by percutaneous stenting

because of the excellent outcome after resection of these lesions.

Clinical Findings

Biliary obstruction, with resultant jaundice or cholangitis, is frequently the presenting symptom in

patients with benign bile duct tumors. Symptoms may also include epigastric pain or nausea. Because

these tumors are indolent, symptoms may be intermittent or gradually progressive.

Figure 63-11. Distribution of papillomas and adenomas of the biliary tree. The ampulla and common bile duct are the most

frequent sites.

Diagnosis

1651

Because of the presence of jaundice, benign bile duct tumors are usually initially evaluated with

ultrasound. Many patients then undergo ERCP or PTC and CT scan. A diagnosis of malignant

masquerade should be suspected in patients with mass lesions that resemble hilar cholangiocarcinomas,

but without lobar atrophy or portal vein involvement.

Treatment

Resection and reconstruction are performed to relieve jaundice and cholangitis. The preferred

reconstruction is a Roux-en-Y choledochojejunostomy to decrease the risk of postoperative biliary

stricture or recurrent cholangitis.

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