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Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001.

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Surgical Treatment: Evidence-Based and Problem-Oriented.

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Cancer of the extrahepatic bile ducts (cholangiocarcinoma) is an uncommon malignancy. Meaningful experience with these tumors has been limited to a few centers. Recent reports with increasing numbers of patients have allowed the construction of a rational management approach. It is clear from these reports that complete resection with negative histologic margins is the only treatment that offers the possibility of longterm survival. Complete resection of hilar cholangiocarcinomas usually requires a partial hepatectomy. The majority of patients, however have advanced disease at the time of presentation and are candidates only for palliative measures. Adjuvant, neoadjuvant or palliative chemotherapy and radiation therapy have not been shown definitively to prolong survival. Photodynamic therapy is an emerging technique that may prove to be a useful adjunct to current therapy. Given the rarity of this malignancy, information upon which clinical decisions can be based is derived from retrospective reports.

Demographics and Etiology

Cholangiocarcinoma is an uncommon disease accounting for approximately 2% of all cancers encountered in the United States. The annual incidence in the United States is approximately 1 to 2 per 100,000. Men and women are equally affected. The majority of patients are greater than 65 years of age. Although most patients with cholangiocarcinoma have no obvious risk factors, several conditions are associated with an increased incidence. The most common of these is primary sclerosing cholangitis (PSC), an autoimmune disease characterized by inflammation of the periductal tissues and subsequent strictures of the intrahepatic and extrahepatic bile ducts. Seventy to 80% of patients with PSC have ulcerative colitis. The true incidence of cholangiocarcinoma in the setting of PSC is not known with certainty. In a large report of 305 patients with PSC followed for 5 years, 8% developed cholangiocarcinoma. Treatment of the underlying inflammatory bowel disease does not alter the subsequent risk of developing cholangiocarcinoma. Congenital biliary cystic disease (choledochal cysts, Caroli's disease) also carries an increased risk of cholangiocarcinoma. Malignant degeneration is uncommon in choledochal cysts diagnosed and excised early in life. However, the risk is substantially increased in patients in whom resection of the choledochal cyst is not performed before the age of 20 years (approximately 15–20%). Patients with hepatolithiasis (Oriental cholangiohepatitis) are known to carry an approximately 10% risk of cholangiocarcinoma. Infestation of the biliary tract with parasites (Clonorchis sinensis, Opisthorchis vierrini) is also a risk factor for biliary tract cancer.


Cholangiocarcinomas are most commonly located at the biliary confluence (50–60%). Distal bile duct tumors account for 20–30% of all cases. An intrahepatic location is seen in approximately 10% of patients. Less than 10% of patients will present with multifocal or diffuse involvement of the biliary tree. Histologically, over 90% of extrahepatic cholangiocarcinomas are adenocarcinomas. Three distinct macroscopic subtypes of cholangiocarcinoma have been described: sclerosing, nodular, and papillary. Sclerosing tumors are the most common and cause an annular thickening of the bile duct which is often accompanied by surrounding fibrosis of the periductal tissues. Papillary tumors account for approximately 10% and are more commonly located in the distal bile duct. They are soft and friable tumors often with little transmural invasion, and tend to expand rather than contract the duct. Papillary tumors may grow to significant size, but frequently arise from a well-defined base and may be mobile within the bile duct. Consequently they are more often resectable and have a more favorable prognosis in comparison to sclerosing and nodular tumors. Longitudinal spread along the duct wall and periductal tissues is an important pathologic feature of cholangiocarcinoma. There may be substantial extension of tumor beneath an intact epithelial lining, as much as 2 cm proximally and 1 cm distally. This feature underscores the importance of frozen section analysis of the duct margins during resection. Many express CEA and CA19-9 although these markers have limited diagnostic value. K-ras mutations have been identified in a high proportion of resected specimens.

Clinical Presentation and Diagnosis

Early symptoms are seen in the minority of patients and include abdominal pain, anorexia, weight loss, and pruritis. Most patients have few symptoms and come to attention because of jaundice or incidentally identified abnormal liver function tests. Segmental obstruction may go unrecognized for a long period of time resulting in ipsilateral lobar atrophy without overt jaundice. In some patients pruritis may precede jaundice by a number of weeks. Intermittent jaundice may occur with papillary tumors. In patients with jaundice, the bilirubin level is generally above 12 mg/dL in contradistinction to those with choledocholithiasis. Cholangitis is an uncommon presentation although 30% of patients without prior biliary tract instrumentation have bacterbilia. The incidence of bacterbilia approaches 100% following biliary intubation and greatly increases the risk of cholangitis.

Physical examination is often non-specific. Jaundice is an obvious finding when present. Significant pruritis may be manifest as multiple skin excoriations. The liver may be enlarged, but the gallbladder is usually decompressed and non-palpable with hilar obstruction. A palpable gallbladder suggests a more distal obstruction. Long-standing obstruction and/or direct portal vein involvement may lead to portal hypertension with its attendant physical findings in a small number of patients.

Radiographic studies are important in establishing the diagnosis of hilar cholangiocarcinoma and in selecting patients for resection. On cross-sectional imaging, a hilar mass associated with intrahepatic ductal dilatation, a decompressed gallbladder and normal caliber distal bile duct are classic findings. A distinct mass is frequently not visualized. Cholangiography is an essential study which provides detail on the location of the tumor and the biliary extent of disease. Percutaneous transhepatic cholangiography (PTC) more reliably displays the intrahepatic bile ducts than endoscopic retrograde cholangiography (ERC). Magnetic resonance cholangiopancreatography (MRCP) has recently emerged as a powerful investigative tool and has nearly replaced direct cholangiography in our practice. In addition to identifying the tumor and level of obstruction, it also can reveal obstructed and isolated ducts not appreciated by PTC. MRCP also provides information regarding the patency of hilar vascular structures. Since it does not require biliary intubation, potential infectious complications that may increase operative morbidity, are thus avoided. Duplex ultrasonography in experienced hands can be just as useful in assessing the regional extent of disease including vascular involvement. The authors’ current practice relies on the combination of MRCP and dulplex US as the preferred investigations.


Table I summarizes the criteria for unresectability. Despite improvements in radiological techniques, only a minority of patients explored are resected (20–50%). Enlarged inflammatory lymph nodes are common in patients with biliary stents and thus should not be considered a sign of metastatic disease unless proven histologically. In patients considered candidates for resection and without evidence of cholangitis, preoperative biliary decompression is unnecessary. Evidence has shown that preoperative biliary intubation does not improve outcome and the observed increase in perioperative complications outweighs any potential benefit.

Table I. Contraindications to resection with curative intent.

Table I

Contraindications to resection with curative intent.

The treatment goals in patients with hilar cholangiocarcinoma are resection with negative histologic margins and restoration of biliary-enteric continuity. Results from several recent series support the argument that partial hepatectomy is usually required to achieve this goal. These studies demonstrate a correlation between negative histologic and the percentage of patients undergoing partial hepatectomy. Principally left-sided tumors nearly always involve the major caudate lobe ducts which drain into the left hepatic duct. These tumors therefore require en bloc caudate lobectomy in most instances. Although a thorough description of the operative technique is outside the scope of this review, a few important points should be made. The operation begins with a thorough exploration of the abdomen searching for sites of metastases. The liver and duodenum are mobilized leaving a firm tie on the round ligament to retract the liver. The gallbladder is mobilized but left in continuity. The hilus is fully exposed anteriorly by lowering the hilar plate along the base of segment IV. The distal bile duct is then transected and elevated upwards. A sample of the distal bile duct margin is sent for frozen section analysis. A plane is then developed between the tumor and the anterior surface of the portal vein, provided there is no tumor invasion. Local resection is sometimes possible for small tumors confined to the hilus. Most patients are not candidates for local resection because, often the tumor extends into the intrahepatic bile ducts, or involves the right or left portal vein. In these instances, en bloc liver resection (often with caudate lobectomy) is required.

Long-term survival can be achieved with an acceptable operative mortality. Recent studies have shown that patients with negative histologic margins survive significantly longer than those with involved margins. In these reports, complete resection (negative margins) was associated with median survivals ranging from 26 to greater than 60 months, whereas survival after incomplete resection was substantially reduced (13 to 25 months).

Several studies have investigated the benefit of postoperative adjuvant radiation therapy in patients with hilar cholangiocarcinoma. In two separate reports from Johns Hopkins, Cameron and colleagues showed no benefit of adjuvant external beam and intraluminal radiation therapy. Given the relative infrequency of this disease, no controlled randomized trials have been reported with radiation therapy. Experiences with chemotherapy are limited and often grouped with gallbladder cancer. In summary, the use of 5-FU, alone or in combination with other agents has not been demonstrated to improve survival. Combinations of chemotherapy with radiation have been attempted by a number of groups. The numbers of patients studied have been small and without control groups and often combine patients treated after resection and those with unresectable disease. Median survival in these patients has ranged from 8 to 30 months.

Despite advances in the surgical treatment of cholangiocarcinoma, the majority of patients will have unresectable disease at presentation or at laparotomy. In these patients, palliative biliary decompression may be accomplished surgically or by percutaneous transtumoral biliary stenting. Most patients found to be unresectable at presentation are submitted for percutaneous drainage whereas those found to have unresectable disease at laparotomy can be drained adequately with an intrahepatic biliary-enteric bypass.

Percutaneous transhepatic biliary drainage and subsequent placement of a self-expandable metallic endoprosthesis can be successfully performed in most patients, but requires experienced interventional radiologists. Frequently hilar tumors isolate all 3 major hepatic ducts (left hepatic, right anterior sectoral hepatic, and right posterior sectoral hepatic) and 2 or more stents must be placed for adequate drainage. Jaundice arising from hepatic dysfunction secondary to portal vein occlusion and/or lobar atrophy is not relieved by percutaneous drainage. The median patency of metallic endoprosthesis at the hilus is approximately 6 months. In most series of Wallstent placement for hilar cholangiocarcinoma, the reintervention rate is approximately 25%.

Patients found to be unresectable at operation may be candidates for intrahepatic biliary-enteric bypass. The segment III duct is usually the most accessible and is our preferred approach. The right anterior or posterior sectoral hepatic ducts can also be used. Communication between the right and left hepatic ducts is not necessary, provided that the undrained lobe has not been percutaneously drained or otherwise contaminated. In this situation, selective decompression of the left liver will result in persistent biliary fistula and/or cholangitis.

Palliative radiation therapy for individuals with unresectable disease without evidence of widespread metastases has been investigated. Externalbeam radiation therapy may be used alone or in combination with intraluminal iridium-192. No direct comparisons with biliary decompression alone, without treatment, have been made in a controlled study, and median survival remains below 15 months. Ortner and colleagues recently reported their experience with photodynamic therapy in patients with unresectable hilar cholangiocarcinoma. After intravenous administration of a photosensitizing hematoporphyrin dreivative, intraluminal photoactivation of the compound is accomplished cholangioscopically. In this report, 9 patients in whom palliative biliary decompression could not be performed were treated more. All patients were adequately decompressed after therapy.


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Copyright © 2001, W. Zuckschwerdt Verlag GmbH.
Bookshelf ID: NBK7001


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