Bile Duct Tumors Treatment & Management

Medical therapy is indicated for patients who are unfit for surgery or who have an unresectable tumor. Jaundice and itching can be reduced with the placement of an endoprosthesis, either endoscopically or percutaneously, across strictures.

Endoscopic techniques for the relief of obstruction include sphincterotomy, balloon dilatation of the stricture, and the placement of stents.^[11] Larger, expandable metal stents, which have better patency rates than do plastic stents, include Metal-Palmaz, Strecker, Gianturco Z stent, and Wall stents.^[15] One meta-analysis suggests that covered self-expandable metal stents have a trend toward later obstruction compared with uncovered self-expandable metal stents.^[16]

Percutaneous, transhepatic endoprosthetic insertion also is successful, but an increased risk of complications, such as blood and bile leakage, exists. Ninety percent of stents can be placed by a combination of endoscopic and percutaneous techniques after a failed endoscopic attempt.

Chemotherapy has been tried in these patients but has not been proven to be of definite benefit.^[17]

Radiotherapy may be administered by external beam therapy; intraoperative radiotherapy using biliary stents with iridium (¹⁹² Ir), radium, or cobalt (⁶⁰ Co); radioimmunotherapy using sodium iodide (¹³¹ I) anti-CEA as a component of therapy; or charged particle irradiation. Internal radiotherapy may be combined with biliary drainage, but the value is unproven.^{[18, 19]}

Pain may be relieved with the injection of 50% alcohol for chemical splanchnicectomy.

Resection is the best treatment for bile duct tumors and provides the best palliation in terms of duration and freedom from infectious complications.^{[20, 21]} Benefits of resection include the possibility of cure or long-term survival, especially for patients with distal tumors. The type of surgical procedure performed depends on the site and extent of the disease.

Proximal tumors (Klatskin tumors) may be managed by a variety of techniques, including the following:

• Patients with perihilar tumors (Bismuth classification I and II), without evidence of vascular invasion, are candidates for local excision. If achieving negative margins are not possible with local excision, resection of the corresponding lobe is indicated.
• Type III tumors are managed best by right or left hepatic lobectomy. Resection of the adjacent caudate lobe (segment I) may ensure adequate tumor-free margins in cases of involvement of the hepatic duct bifurcation.
• Sometimes, extended right or left hepatectomy and (rarely) central liver resection may need to be combined for adequate resection of the tumor.

Following resection of the bile duct, which may be combined with hepatic resection, reconstruction can be performed by unilateral or bilateral hepaticojejunostomy, using transhepatic stents.^[15]

Surgical exploration is indicated in patients who are fit for surgery when preoperative evidence of metastases is absent or when locally unresectable disease exists. If metastases are detected at the time of surgical exploration, bilateral stents that may have been placed preoperatively are left in situ, and cholecystectomy is performed to prevent the subsequent development of acute cholecystitis. Locally advanced and unresectable perihilar tumors also can be managed by Roux-en-Y cholecysto(docho)jejunostomy with intraoperative placement of silastic biliary catheters or a segment III or V cholangiojejunostomy.

Mid-duct tumors can be managed using bile duct resection and Roux-en-Y reconstruction. Distal tumors may be amenable to Whipple resection (radical pancreaticoduodenectomy) (see image below) or pylorus-preserving pancreaticoduodenectomy. Unresectable tumors may be managed by cholecystectomy, a Roux-en-Y hepaticojejunostomy, or choledochojejunostomy proximal to the tumor, and additional gastrojejunostomy and chemical sympathectomy are considered.

Reconstruction involves anastomosis of bile ducts to a loop of jejunum (see image below).

Palliation

Surgical bypass is indicated in patients in whom placing a stent by either endoscopic or percutaneous techniques is impossible and in patients who are found to have unresectable disease or metastases at exploration.^[11]

Bypass may be performed by either a Roux-en-Y hepaticojejunostomy with intraoperative placement of a silastic transhepatic stent or a segment III bypass to the left intrahepatic ducts. In patients with distal bile duct tumors, the operation of choice is biliary enteric bypass using the upper end of the extrahepatic bile duct or gallbladder. Consider prophylactic gastrojejunostomy in these patients, because some of these individuals may develop gastroduodenal obstruction prior to death. Bypass is less commonly required, because stents have improved, and even duodenal obstruction can now be effectively palliated.

Staging of the disease is determined by evaluating findings of CT scanning and MRI.^{[6, 7]}

Delineation of the tumor and its extent may be assessed by cholangiography (endoscopic and transhepatic) and magnetic resonance cholangiography.^[9]

Vascular involvement can be identified and assessed by CT scan, MRI, and angiography, as previously described (see Imaging Studies).

Patient risk for surgery and anesthesia is determined, and cardiac and pulmonary assessment is performed.

If the clinical condition of the patient does not rule out surgical intervention, the resectability and extent of tumor involvement are assessed, and metastases are sought. Low and mid – bile duct tumors usually are resectable if angiography and venography exclude vascular invasion. Cancer of the hilar region tends to be less amenable to resection.

At surgery, further assessment is performed with intraoperative ultrasonographic scanning and a search for lymph node involvement.

Laparoscopy in patients with bile duct tumors can be useful in the identification of metastases and peritoneal disease and, hence, may assist in assessing resectability.

Intraoperative ultrasonography also is useful and may be combined with laparoscopy.

Exploratory laparotomy is performed in patients who are fit for surgery and who are without any definite evidence of metastases or unresectability on preoperative investigation. One half of these patients are found to have evidence of intraperitoneal dissemination of the tumor or extensive involvement of the porta hepatis; therefore, they are candidates for minimal intervention, including bypass.

These patients are at risk for the development of general complications, including pneumonia, deep venous thrombosis, and infection. Routine perioperative antibiotic prophylaxis and coagulopathy are administered. Active physiotherapy, breathing exercises, and early ambulation are encouraged.

Complications specific to the procedure performed include anastomotic leak and bile leakage. Stents may be placed across anastomoses and removed after cholangiography confirms the absence or healing of leak.^[15]

Patients who have evidence of positive tumor margins after resection or who develop recurrence may be candidates for adjuvant radiotherapy.^{[18, 19]} This usually takes the form of extracorporeal therapy for positive surgical margins and intraluminal radiotherapy for positive duct margins. Chemotherapy has not been shown to be of benefit.^[17]

Postoperative complications may be general or local. General complications include the following:

• Myocardial infarction (MI)
• Pneumonia
• Surgical site infection
• Deep venous thrombosis
• Pulmonary embolism (PE)

Technical complications related to the procedure performed include the following:

• Bile leak
• Stricture
• Postoperative hemorrhage
• Pancreatic fistula – May occur after radical pancreaticoduodenectomy

Complications arising from the placement of stents include the following:

• Early - Cholangitis (7%) and perforation
• Late - Blockage and migration of stent

In patients with bile duct tumors, the choice of treatment and the prognosis are influenced greatly by the location of the tumor. Prognosis is better for distal bile duct tumors, histologically differentiated, and polypoidal tumors. Factors that suggest poor prognosis include involvement of lymph nodes, vascular invasion, advanced T stage, positive tumor margins of the resected specimen, and the presence of mutations of P53 gene.^[5]

With hilar cholangiocarcinoma, the overall resection rate in most series varies form 40-60%. The mean survival rate for patients undergoing curative resection is 67-80% at 1 year and 11-21% at 5 years. Local resection has a lower operative mortality rate (8%) than does major hepatic resection (15%), with a mean survival of 21 months compared with 24 months for major hepatic resection. No clear indication exists that survival is improved significantly by major hepatic resection when compared with local bile duct resection, though some studies suggest that hepatic resection is associated with a greater incidence of tumor-free margins and, consequently, survival.

In distal bile duct cancers, the resection rate is more than 60%, and the prognosis is better than for hilar tumors, the mean survival being 39 months. The survival rate varies from 50-70% at 1 year to 17-39% at 3 years.

Diffuse intrahepatic tumors have a dismal prognosis; most patients with these tumors die within 1 year of diagnosis.

If left untreated, 50% of patients with bile duct cancer may survive for 1 year, 20% may survive for 2 years, and 10% may survive for 3 years.

The role of adjuvant radiotherapy and chemotherapy is controversial.^{[17, 18, 19]} The use of hormones in treatment, including somatostatin analogs, cholecystokinin, and cholecystokinin antagonists, is being investigated.

It has been suggested that preoperative endoscopic retrograde cholangiopancreatography (ERCP) with biliary drainage in patients with tumors of the bile duct increases the risk of implantation metastases after resection of the tumor.^[22] Therefore, preoperative radiotherapy is advocated in such patients, but the benefit has not been definitely proven.^[23]

Transarterial chemoembolization (TACE), infusion of 5-fluorouracil into the hepatic artery or bile ducts, and percutaneous injection of ethanol (PEI) into the lesions are other modalities that are investigational.

Photodynamic therapy may be useful in relieving obstruction, especially when obstruction occurs as a result of tumor outgrowth into an endoprosthesis.^[24]

Liver transplantation, when performed for cholangiocarcinoma, is associated with poor survival.^[25]