| Introduction:Extrahepatic malignant biliary obstruction mainly caused by the bile duct carcinoma, carcinoma of head of pancreas, duodenal ampulla cancer, is a relatively rare and highly malignant tumors-group, which have the similar effects to common bile duct drainage. In developed countries, the incidence rate is about 1.7/100,000. There is no large-scale epidemiological survey in China. Progress of malignant extrahepatic bile duct obstruction is always occult and often late to be diagnosed. The global rate of 5 year survival is only 5% to 10% total. Only about 20% of the extrahepatic bile duct malignant obstruction patients could be considered about operation. And for unresectable patients, the overall survival time was 3-6 month.With the continuous development of digestive endoscopy equipments and technology, endoscopic palliative treatment to relieve biliary obstruction has gradually become the mainstream for these unresectable patients of extrahepatic bile duct malignant obstruction or with recurrence. Endoscopic experts put plastic stents or metallic stents into bile ducts through retrograde cholangiopancreatography(Endoscopic Retrograde Cholangiopancreatography, ERCP) to relieve the obstruction temporarily. But with the growth of tumors, stents were soon blocked and lost their efficacy. Other treatments just like neoadjuvant chemotherapy, radiotherapy, hyperthermia-therapy, had been confirmed that was ineffective for unresectable extrahepatic malignant biliary obstruction.In recent years, ERCP-assisted endoscopic in-bile-duct photodynamic therapy(Photodynamic therapy, PDT) and radio frequency therapy(Radiofrequency ablation, RFA) have been proved to be effective to extend the patency period of stents, but the influence on the overall survival time remains to be further understanding.From this point of view, our research is divided into four parts, with the clinical data of unresectable extrahepatic malignant biliary obstruction in China, in order to summarize the experience of treatment, compare the efficacy and safety of PDT and RFA. It will build the theoretical foundation for promotion of PDT or RFA. The fifth part is the summary and review.The first part: The ERCP-assisted photodynamic therapy can prolong stent patency and survival time of the unresectable malignant biliary obstruction patients.The second part: Radiofrequency ablation in ERCP prolongs patency of bile duct and overall survival time for unresectable extrahepatic malignant biliary obstruction.The third part: ERCP-assisted photodynamic therapy and radiofrequency have the similar curative effects for unresectable of extrahepatic malignant biliary obstruction.The fourth part: Negative methylation status of Vimentin predicts improved progrosis in pancreatic carcinoma.The fifth part: Research progress in endoscopic diagnosis and treatment of extrahepatic biliary malignant obstruction.Materials and methods:The equipments and materials of ERCP list in the materials and methods section. All of the ERCP and related operations are completed by experienced ERCP experts.Photodynamic therapy(PDT) destroys cancer tissue with the principle of the photosensitizer concentration in active cancer cell. The specific wavelength of laser from probe activates photosensitizer to produce oxygen free radicals in ERCP. High concentration of oxygen free radicals in the cancer cells induces them into apoptosis or necrosis. Radiofrequency ablation(RFA) can transfer the high-frequency alternating current into heat energy by the RFA bipolar probe and destroy tumor tissue directly. Specific technical was list in each part.Using retrospective analysis method in all parts.The first part: Retrospective analysis of 39 cases with unresectable of extrahepatic malignant biliary obstruction were included in this study. Twenty cases in the control group were implanted with uncovered metallic stents in ERCP, and 19 cases in PDT group received 1-time PDT and were implanted with plastic stents in ERCPs. We analyzed the overall survival time and stent patency rate of the two groups of patients with the Kaplan-Meier analysis and the log rank test.The second part: By the retrospective analysis 51 cases of unresectable extrahepatic malignant biliary obstruction underwent ERCP, twenty-six cases in the control group were diagnosed by ERCP and then put into stents for biliary drainage; and 25 patients in RFA group were recorded with the biliary tract stenosis lumen diameter and length of stricture before RFA. After 1-week endoscopic nasobiliary drainage(ENBD), a single large diameter plastic stent was implanted. After 3 months, the stent would be changed and the length, diameter were recorded by angiography. The clinical data of patients in both groups were recorded, including with the operation complications within 30 days, stent patency and survival time until 1 years.The third part: Retrospective analysis of 41 cases unresectable extrahepatic malignant biliary obstruction underwent ERCP. The stenosis lumen diameter and length of bile duct stricture before and after 3 months of PDT or RFA therapies were recorded by ERCP angiography. The clinical data of complications 30 days after the operation, bile duct patency and overall survival time were also recorded.The fourth part: Retrospective analysis of 64 cases of pancreatic cancer from three medical centers. The clinical data and tumor marker in pathological tissues(Vimentin gene methylation level) were recorded. We analyzed the relationship between Vimentin methylation status and prognosis by square test, Kaplan-Meier survival analysis and Cox regression model.The specific operation process were introduced in each part detailedly.Results:The first part: Age, sex, serum bilirubin concentration and tumor stage were comparable in the PDT group and the control group of patients. The incidence rate of complications after operation was 15.8% and 10% in the PDT group and in the control group, respectively. All complications cured by conservative treatment successfully. Fifteen cases occured stent occlusion in PDT group(15/19,78.9%) and 16 cases occurred in the control group(16/20,80%). Seventeen of 31 cases of stent occlusion were changed with new stents, 7 cases were treated with PTCD external drainage. PDT could significantly prolong the patency of stent(224.6±52days and 156.4±44 days, respectively, p = 0.006) and survival time(336±56days and 224±42 days, respectively,p= 0.014) than the control group.The second part: Fifty-one cases accepted the ERCP treatment and 47 cases of them were followed up. Four patients were lost to follow-up. There was no significant difference with age(p=0.659),tumor location(p=0.350) and metastasis(p=0.864) between the RFA group and the control group, but the significant difference(p=0.001) in the survival rates of 1-year. The biliary patency and the survival time of the RFA group was significantly longer than that of the control group(p=0.021 and p=0.031). In RFA group, the preoperative total bilirubin level decreased significantly than the level of postoperative 3 months(p=0.001), and the diameter of common bile duct stricture broadened significantly(p=0.001), but the length of tumor increased(p=0.007). Postoperative complications rate had no significant difference(p=0.821), and were cured by conservative treatment successfully.The third part: The clinic data of 41 cases of unresectable extrahepatic malignant biliary obstruction underwent ERCP were recorded detailedly, including 19 cases underwent photodynamic therapy and 22 patients received radiofrequency ablation. Between the two groups, patient's age(p=0.978), gender(p=0.831), CEA(p=0.410), CA-199(p=0.981) and metastasis(p=0.793) had no significant difference. The biliary patency was 166.5 and 188.7(p=0.439) in the PDT group and the RFA group, respectively. The average survival time was 225.2 days in the PDT group and 236.5 in RFA group(p=0.692). There were 2 cases of mild acute pancreatitis, 2 cases of acute cholangitis in the group PDT and 1 cases of mild acute pancreatitis, 2 cases of acute cholangitis in group RFA. All complications were cured by conservative treatment in department of internal medicine. All patients of the two groups had no serious bleeding.The fourth part: Vimentin gene methylation status was positive in the 21 cases among the 64 cases of pancreatic cancer tissue, but negative in 43 cases. The tumor location of pancreatic cancer was related to the methylation status of Vimentin. Pancreatic cancer T stage(P < 0.001), adjuvant chemotherapy(P = 0.003) and Vimentin methylation status(P = 0.037) were independent factors affecting the prognosis of pancreatic cancer.Conclusion:For unresectable extrahepatic malignant extrahepatic biliary obstruction, ERCP assisted in-bile-duct photodynamic therapy(PDT) and endoscopic radiofrequency(RFA) can prolong the stent drainage period and the survival time compared with the stent drainage alone. There are no significant differences about survival time and patancy between the PDT group and the RFA group. The complication rates were low in both of the groups and had no significant difference. In summary, ERCP-assisted PDT or RFA treatment is safe and effective palliative treatment for the unresectable extrahepatic malignant biliary obstruction. |
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