Surgical Therapy
Surgical excision of biliary tract tumors is the treatment of choice in cholangiocarcinoma as it is the only therapeutic option that offers the potential for cure. Surgical approaches have become increasingly aggressive over the last decade since it has become apparent that curative treatment is dependent upon aggressive excision. This often involves a major liver resection. The objective is complete removal of the tumor and biliary drainage. Operative mortality in the hands of an experienced surgeon is extremely low (close to 0% for local resections and less than 10% for procedures with hepatic resection). Surgical management provides improved survival rates and quality of life.
Surgical treatment is dependent upon the localization of the mass. Treatment of hilar cholangiocarcinoma requires resection of the bifurcation of common hepatic duct. The procedure starts with exploration of the peritoneal cavity to detect possible dissemination and resectability of the tumor. If the cholangiocarcinoma appears resectable, the gallbladder should be mobilized and the distal common bile duct divided. Careful dissection continues proximally until right and left hepatic ducts are separated above the tumor. Biliary reconstruction is achieved through bilateral hepatojejunostomy on a Roux-en-Y intestinal loop above the transhepatic silicone biliary stents. If cholangiocarcinoma extensively involves one lobe of the liver and relatively spares the other lobe, resection of the affected lobe or caudate lobe may be warranted with subsequent unilateral (in case of resection of right or left hepatic lobectomy) or bilateral (in case of caudate lobe resection) hepatojejunostomy (see Figures 21 and 22). Surgical treatment of peripheral cholangiocarcinoma is similar to hepatocellular carcinoma and requires hepatic lobectomy or segmentectomy depending upon the size of the tumor (Figure 20). Dissection of the hepatic ducts confluence and reconstructive hepatojejunostomy is not necessary after resection of peripheral cholangiocarcinoma. Surgical treatment of distal cholangiocarcinoma can be divided into three groups. For tumors of the proximal third of extrahepatic ducts, surgery usually includes resection of the tumor with subsequent hepatojejunostomy (Figure 21 and 22). For tumors of the middle third of extrahepatic duct, surgical options include resection of the mass with possible primary end-to-end bile duct anastomosis (for early small tumors) or hepatojejunostomy (if large portion of extrahepatic ducts should be removed). For tumors located in distal common bile duct, the Whipple procedure is recommended (same as for ampullary tumors). (Figure 20)
Surgery remains the primary treatment of cholangiocarcinoma, even for advanced stages of the tumor. Resectability of the tumor and survival rates in patients with cholangiocarcinoma depend on location of the tumor and spread of the disease at the time of presentation. Survival rates are higher in specialized institutions where a multidisciplinary team, including surgeon, oncologist, endoscopist, interventional radiologist and supporting staff are involved. Reported resectability increased with the more distal location of the tumor (50% for peripheral cholangiocarcinoma vs. 56% for hilar vs. 91% for distal tumors). Five-year survival rates for resected peripheral, hilar and distal cholangiocarcinoma were 44%, 11% and 28%, and median survival rates were 26, 19, and 22 months, respectively.
Endoscopic Therapy
Endoscopic biliary dilation may be used as a final palliative measure to relieve jaundice in patients who are poor surgical candidates, or as one of the steps prior to surgical intervention. This procedure requires use of a side-viewing endoscope to access the biliary duct and to introduce an inflatable balloon or series of endoscopic dilators over a guide wire. In many cases, a biliary sphincterotomy is performed prior to dilation and stent placement (Figure 24). After successful dilation, plastic or self-expanding metal stents (endoprostheses) may be placed into the biliary ducts (Figure 25 and 26). Plastic endoprostheses are smaller in diameter (ranging in size from 7.0–11.5 French) and are more prone to occlusion. Plastic stents should be replaced endoscopically at regular intervals (usually 8–12 weeks). In case of complete obstruction of biliary ducts, it may not be possible to advance an endoscopic guide-wire above the occlusion. In this situation, the percutaneous transhepatic approach may be preferable.
| | Figure 24.A-C,Endoscopic technique for biliary sphincterotomy.(Click on the blue letters to view the consecutive images) |
| | Figure 25. A-D,Technique for endoscopic balloon dilation and plastic biliary stent placement;A',B'D', corresponding cholangiograms.(Click on the blue letters to view the consecutive images |
| | Figure 26. A-D,Endoscopic technique for balloon dilation and expandable metal stent placement;A',B',D' corresponding cholangiograms. (Click on the blue letters to view the consecutive images) |
Radiological Therapy
Percutaneous transhepatic palliative biliary dilation is performed by an interventional radiologist and requires transcutaneous puncture of the peripheral bile ducts and the subsequent placement of 12–16 French polymeric catheters. In patients with hilar cholangiocarcinoma occluding both the right and left hepatic ducts, separate percutaneous tubes may be inserted into right and left biliary systems and advanced through the side of occlusion into the duodenum, if possible (Figure 27). These stents allow the drainage of bile into the duodenum. Percutaneous polymeric biliary stents are usually exchanged at regular intervals to prevent occlusion and infectious complications. Percutaneous self-expandable metallic stents are recommended as a definitive method of palliation in patients with cholangiocarcinoma who are not surgical candidates (Figure 28).
 | | Figure 28. Right and left percutaneous self-expandable metal stents restore patency around a hilar tumor. |
Other Therapeutic Approaches Chemotherapy and Radiotherapy
Currently, no chemotherapeutic approach has been shown to positively affect the clinical outcome in patients with cholangiocarcinoma. In addition, external beam radiation has not demonstrated efficacy. Reports on long-term survivors after radiotherapy have shown that some individuals may benefit from treatment, but potential complications are significant (duodenitis, bile duct stenosis, duodenal stenosis). Encouraging results have been demonstrated using interstitial or intraoperative radiation. Internal radiation or brachytherapy may be useful as adjuvant therapy following surgery or as a palliative therapy in combination with biliary enteric bypass. Further investigation is needed to fully assess the potential of such therapies. In unresectable cholangiocarcinoma, the therapeutic strategy is to improve cholestasis by placing an endoprosthesis across the tumor, or by performing a biliary bypass. These procedures do not affect tumor growth, and it is unclear if they improve survival. However, improvement of cholestasis does improve symptoms such as fatigue, diarrhea, anorexia, pruritis, jaundice and sleep pattern, thus improving quality of life. Because early morbidity and 30-day mortality is significantly higher with surgical procedures than endoscopic/percutaneous drainage, such interventional techniques are preferable. Independent of the type of stricture, technically successful endoprosthesis placement can be achieved in 84-96% of these patients. Successful drainage is achieved in 69-91% of Bismuth type I and II stenosis, and 15-73% in Bismuth type III and IV tumors, with an associated mean survival of approximately 150 days and 65 days in each group, respectively. Insertion of permanent metal endoprosthesis improves occlusion rates and reduces the number of therapeutic interventions; however, does not lessen median survival time. Chemotherapy and radiotherapy (external-beam radiotherapy and 192I brachytherapy) have been used to decrease tumor growth rates, however, no randomized prospective trial evaluating the effects of these therapies has been conducted. A retrospective study comparing palliative endoscopic stenting versus stenting combined with radiotherapy showed no significant difference in median survival time. Studies with chemotherapy are not interpretable because they include different liver malignancies and therapeutic regimens. The question remains whether additional radiotherapy or chemotherapy is of benefit to patients with unresectable cholangiocarcinoma. Photodynamic Therapy (PDT)
Photodynamic therapy (PDT) is a new therapy that selectively destroys tumor tissue. A photosensitizer is administered and selectively retained by the target tumor tissue. The photosensitizer is nontoxic in its native state, however, after activation by a light at a particular wavelength, the photosensitizer becomes cytotoxic and produces local tissue destruction. The only relevant side effect seen to date is phototoxicity, which lasts often for 4-6 weeks after drug administration. Animal and human pilot studies have shown a reduction of up to 60% of tumor volume after administration of PDT with hematoporphyrin. One trial using biliary PDT in patients with unresectable cholangiocarcinoma (Bismuth types III and IV tumors), who failed endoprostheses placement, has resulted in significant improvements in serum bilirubin levels and quality of life scores, with a 30-day mortality of 0% and median survival time of 439 days. Other trials investigating the effect of PDT in patients with unresectable hilar carcinoma who were treated with endoprostheses placement showed a six-month survival rate of 91%. Ninety-six percent of patients improved in terms of cholestasis, performance and quality of life. No adverse side effects were reported. PDT appears to be a promising therapeutic approach for unresectable cholangiocarcinoma, and combines the two aims of treating cholestasis and reducing tumor growth. The apparent benefit in survival time, however, needs to be confirmed with randomized, controlled trials.
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