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.
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.
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.