Randomised trial of prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin. Prevention of biliary stent occlusion using cyclical antibiotics and ursodeoxycholic acid. Prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin: a multicenter randomized trial. A combination of ciprofloxacin and Rowachol does not prevent biliary stent occlusion. A prospective, randomized multicenter trial comparing DoubleLayer and polyethylene stents for malignant distal common bile duct strictures. Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction. "Tannenbaum" Teflon stents versus traditional polyethylene stents for treatment of malignant biliary stricture. A randomized trial of endoscopic drainage methods for inoperable malignant strictures of the common bile duct. A prospective, randomized, controlled trial of metal stents for malignant obstruction of the common bile duct.
Biliary stents are liable to clog. We investigated whether a choleretic plus an antibiotic could delay clogging. 20 consecutive patients with a malignant biliary stricture were randomised after endoscopic insertion of a polyethylene stent to receive ursodeoxycholic acid plus norfloxacin (13-15 mg/kg and 400 mg, daily) or conservative treatment. The drug combination was associated with: a longer median patency of first (49 vs 6 weeks) and all stents (38 vs 7 weeks); a prolonged median survival (67 vs 18 weeks); and a shorter mean hospital stay (0.2 vs 1.0 days per week of survival). Thus ursodeoxycholic acid plus norfloxacin may prevent stent clogging. This study reports an open randomised controlled trial of cyclical antibiotics and ursodeoxycholic acid in prevention of plastic biliary stent occlusion. Seventy patients with malignant distal bile duct obstruction were randomised to either active treatment with cyclical antibiotics (ampicillin, metronidazole, ciprofloxacin) and ursodeoxycholic acid or no treatment after successful stent insertion. The two groups were well matched. The follow up was complete with stent occlusion or death being the end points. There was no difference in the incidence of stent occlusion between the two groups and the overall survival was similar. In conclusion, this study did not show any benefit of treatment with antibiotics and ursodeoxycholic acid in prolonging stent patency or improving survival. We report a prospective randomized multicenter trial that tested the efficacy of combining ursodeoxycholic acid and norfloxacin in the prevention of polyethylene stent clogging in patients with obstructive jaundice due to an unresectable malignancy at the level of the common bile duct. After insertion of a 10-Fr straight polyethylene stent, patients were allocated to receive oral treatment with ursodeoxycholic acid and norfloxacin, or conservative treatment. The primary outcome measure was stent blockage within six months. Thirty-three patients (group I) received ursodeoxycholic acid and norfloxacin, and 29 received conservative treatment (group II). At six months, cumulative stent patency rate did not differ significantly between group I (47+/-11%, mean +/- SE, median 149 days) and group II patients (24+/-10%, mean +/- SE, median 100 days, P = 0.23, log-rank test). Four stents were clogged by ursodeoxycholic acid. Survival did not differ between the two groups. Combined therapy with ursodeoxycholic acid and norfloxacin failed to improve stent patency. Moreover, ursodeoxycholic acid can cause stent obstruction. Endoscopic insertion of biliary prostheses is now an established palliative treatment for frail and elderly patients with distal extrahepatic malignant biliary strictures who are unable to tolerate major surgery. The major limitation to long-term biliary stenting is late stent occlusion caused by bacterial adherence followed by encrustation with amorphous bacterial products. We studied the effect on the duration of stent patency of combination therapy with ciprofloxacin and Rowachol, a choleretic agent, in a group of patients who underwent stent insertion for extrahepatic malignant biliary strictures.
                Patients with this diagnosis were randomized to either active treatment with ciprofloxacin (500 mg twice daily) and Rowachol (2 tablets 3 times daily) or no drug treatment (control group). They were followed up prospectively and the end points of the study were stent occlusion and patient survival.
                Forty-eight patients who had successful stent placement were recruited; 8 patients were excluded from the final analysis because of death in less than 1 month (5 patients) or stent replacement within a month because of persistent jaundice (3 patients). Twenty patients were randomized to the active and control groups. One patient in the active group withdrew because of nausea. The 2 groups were comparable with regard to age, gender, causes of extrahepatic malignant biliary strictures, and levels of serum alkaline phosphatase and bilirubin. There were significant reductions in mean serum bilirubin and alkaline phosphatase concentrations 1 month after stent placement. At the time of analysis, 12 patients were still alive (7 patients from the control group). Median survival was 23 weeks in both the active treatment group and the control group. There were 9 episodes (45%) of stent occlusions in the active treatment group and 10 episodes (50%) in the control group. The median time to stent occlusion was 23 (range 7 to 68) weeks for the active treatment group and 21 (range 6 to 56) weeks for the control group, p = 0.23. There was no significant difference in the duration of patient survival and of stent patency between the 2 groups. The lack of difference between treated and untreated patients in survival duration and stent patency was also shown if the results were analyzed on an intent-to-treat basis and the 8 patients who were excluded in the final analysis were also analyzed.
                Prophylactic therapy with ciprofloxacin and Rowachol does not prolong stent patency or patient survival. Endoscopic biliary stenting is an established treatment for malignant obstructive jaundice. Stent clogging continues to be a major problem with plastic stents. The aim of this study was to carry out a prospective comparison of two stents with different materials and shapes: the Olympus DoubleLayer stent (DLS; perfluoro alkoxy, without sideholes) and the standard polyethylene (PE) stent (with sideholes).
                A total of 120 patients (70 women; mean age 71, range 36 - 91) with jaundice due to malignant strictures of the middle to distal third of the common bile duct were randomly assigned to receive either DLS (n = 60) or PE (n = 60) biliary stents. Patients with cholangitis, hemobilia, previous biliary drainage, hilar stricture, or ampullary cancer were excluded.
                In all, 28 DLS patients (47 %) and 17 PE stent patients (29 %) died without clinical evidence of stent occlusion after a mean of 114 and 105 days, respectively ( P < 0.05). Twenty-six DLS patients (43 %) and 38 PE stent patients (63 %) had symptoms of stent clogging after a mean of 144 and 99 days, respectively ( P < 0.05). Stent dysfunction (stent orifice impacted on the bile duct or duodenal wall, stent migration) was recorded in six DLS patients (10 %) and five PE patients (8 %) (n. s.). Kaplan-Meier analysis of DLS and PE stent clogging-free survival showed a significantly longer patency period with the DLS stents (P = 0.0005).
                These results show that DoubleLayer stents have a longer patency period than PE stents. Patients who received PE stents had a higher risk of stent occlusion (relative risk 3.05; 95 % CI, 1.57 - 5.89) before death than DLS patients. The development of non-surgical techniques for the relief of malignant low bileduct obstruction has cast doubt on the best way of relieving jaundice, particularly in patients fit for surgery whose life expectancy is more than a few weeks. We did a randomised prospective controlled trial comparing endoscopic stent insertion and surgical biliary bypass in patients with malignant low bileduct obstruction. 204 patients were randomised (surgery 103, stent 101); 3 subsequently proved to have benign disease and were excluded, leaving 101 surgical and 100 stented patients for assessment. Technical success was achieved in 94 surgical and 95 stented patients, with functional biliary decompression obtained in 92 patients in both groups. In stented patients, there was a lower procedure-related mortality (3% vs 14%, p = 0.01), major complication rate (11% vs 29%, p = 0.02), and median total hospital stay (20 vs 26 days, p = 0.001). Recurrent jaundice occurred in 36 stented patients and 2 surgical patients. Late gastric outlet obstruction occurred in 17% of stented patients and 7% of the surgical group. Despite the early benefits of stenting there was no significant difference in overall survival between the two groups (median survival: surgical 26 weeks; stented 21 weeks; p = 0.065). Endoscopic stenting and surgery are effective palliative treatments with the former having fewer early treatment-related complications and the latter fewer late complications. Premature stent clogging is the major limitation with plastic stents used in the treatment of malignant biliary structures. A pilot study suggested improved duration of patency of the Tannenbaum stent compared with polyethylene stents. The aim of this prospective, multicenter randomized trial was to compare the Tannenbaum Teflon stent with a conventional polyethylene endoprosthesis (Cotton-Leung biliary stent set) for the treatment of malignant biliary strictures.
                Patients over age 18 years with symptoms caused by nonhilar malignant biliary strictures were enrolled. Patients were randomized to receive a 10F Tannenbaum or polyethylene stent after a guidewire was passed beyond the stricture. One hundred six patients (mean age 72 years and 71 years, respectively) were enrolled (54 Tannenbaum, mean age 72 years; 52 polyethylene, mean age 71 years).
                Tannenbaum and polyethylene stent placement was successful in, respectively, 100% and 96% of procedures without complications. The mean (SD) 90-day stent patency of the Tannenbaum stent was 67% (7%) compared with 73% (7%) for the polyethylene stents.
                The present study demonstrated no difference in ease of implantation or stent patency between Tannenbaum and polyethylene stents. Although metallic stents remain patent longer than plastic stents, the optimal palliation of inoperable malignant biliary strictures remains controversial because of the high cost of metallic stents and short patient survival.
                A total of 101 patients (mean age 72.5+/-12.9 years) with malignant strictures of the common bile duct were included in this study, after three exclusions for technical failure (n = 3) and one for noncompliance with study design. The etiology of the strictures included pancreatic cancer (65), cholangiocarcinoma (21), ampullary tumor (3), and metastatic lymph nodes (12). Patients were randomized to receive either an 11.5F polyethylene stent to be exchanged in case of dysfunction (group 1, n = 33), an 11.5F stent to be exchanged every 3 months (group 2, n = 34), or a self-expanding metallic Wallstent (group 3, n = 34).
                Endoscopic procedures were successful (including complete relief of jaundice) in 97.1 % of cases. Procedure-related morbidity was 11.9%, and mortality was 2.9%. Bilirubinemia after 48 hours (37.2%+/-21.7% decrease from the preoperative level) did not differ between groups. Patients were followed for a mean of 166 days (median 143, range 0 to 596 days). Overall survivals were not different between groups, but complication-free survival for groups 2 and 3 was longer than that of group 1 (p < 0.05). Cumulated hospital days were 7.4+/-1.5, 10.6+/-1.7, and 5.5+/-1.4 (groups 1, 2, and 3, respectively) (p < 0.05; analysis of variance). Cost analysis showed that metallic stents were advantageous in patients surviving more than 6 months, whereas a plastic stent was advantageous in patients surviving 6 months or less.
                Metallic stents and plastic stents exchanged every 3 months are valuable alternatives for increasing complication-free survival in patients with malignant strictures of the common bile duct. Metal stents are advantageous in patients with the longest life expectancy. Endoscopic insertion of biliary stents is the preferred method of palliation for inoperable malignant biliary obstruction; however, migration and clogging are frequent problems with conventional endoprostheses. We sought to determine if expandable metal stents offer improved palliation compared to conventional stents. Sixty-two patients with common bile duct lesions were randomized to receive polyethylene or metal stents. Stents were placed endoscopically or by the combined percutaneous-endoscopic route. Early results (< 1 month) were similar in both groups. Long-term follow-up (n = 28 polyethylene, median: 5 months; n = 27 metal, median: 5 months) showed a higher stent failure rate in the polyethylene (n = 12; 43%) compared to the metal group (n = 6; 22%). The incidence of cholangitis was significantly higher (p < 0.05) in the polyethylene (n = 10; 36%) compared to the metal group (n = 4; 15%). Life-table analysis showed a significantly reduced incidence of stent failure (p = 0.0035) in the metal stent compared to the polyethylene group. The total duration of hospital stay for treatment of stent related problems was significantly higher in the polyethylene (11.8 +/- 3 days) compared to the metal group (4 +/- 1.9 days; p = 0.02). The costs for retreatment because of stent failure were significantly higher in the plastic (DM 5900 +/- 1516) compared to the metal group (DM 2070 +/- 977). As a result, the overall costs (treatment of stent related complications & stents) were higher in the polyethylene group (DM 6000 +/- 1500).(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment with UDCA and/or antibiotics to prevent clogging of biliary stents in patients with malignant stricture of the biliary tract cannot be recommended routinely on the basis of the existing randomised clinical trials. Further trials are needed with rigorous methodology and sufficient statistical power.