Octreotide 24-h prophylaxis in patients at high risk for post-ERCP pancreatitis: results of a multicenter, randomized, controlled trial.

BACKGROUND: Pharmacological prophylaxis of post-ERCP pancreatitis is costly and not useful in most non-selected patients, in whom the incidence of pancreatitis is 5% or less. However, it could be useful and probably cost-effective, in patients at high risk for this complication, where the post-procedure pancreatitis rate is 10% and more. AIM: To assess the efficacy of octreotide in reducing the incidence and severity of post-ERCP pancreatitis and procedure-related hospital stay, in subjects with known patient-related risk factors. METHODS: A total of 120 patients were randomly allocated to receive octreotide or not, in a multicentre, randomized, controlled trial. The drug was given subcutaneously, 200 microg t.d.s., starting 24 h before the ERCP procedure, in patients with either sphincter of Oddi dysfunction, or a history of relapsing pancreatitis or post-ERCP pancreatitis, or who were aged under 35 years, or who had a small common bile duct diameter (< 8 mm). RESULTS: A total of 114 patients (58 in the octreotide group and 56 in the control group) completed the trial. Post-procedure pancreatitis occurred in seven octreotide-treated patients (12.0%) and eight controls (14.3%). The two groups showed no significant differences in the incidence or severity of pancreatitis. Twenty-four hours after the procedure, severe hyperamylasemia (more than five times the upper normal limit) without pancreatic-like pain was recorded in three octreotide-treated patients (5.2%) and six controls (10.7%), the difference being not significant. CONCLUSION: Twenty-four-hour prophylaxis with octreotide proved ineffective in preventing post-ERCP pancreatitis and in avoiding 24-h severe hyperamylasemia in high-risk patients.

Prospective randomized trial comparing Tannenbaum Teflon and standard polyethylene stents in distal malignant biliary stenosis.

BACKGROUND: Our aim was to compare the clinical efficacy of the Tannenbaum (TB) biliary prostheses, a recently designed Teflon stent without side holes, with the Cotton-Huibregtse (CH) polyethylene stent. METHODS: Fifty-seven patients (26 men, mean age 75.5 years) with unresectable malignant tumors and distal biliary stenosis were included (38 pancreatic head cancer, 17 cholangiocarcinoma, 2 ampullary cancer). Patients were prospectively randomized to have a 10F, 7 cm long TB (29 patients) or CH (28 patients) stent inserted endoscopically. Four patients (2 TB and 2 CH) were excluded: 3 because of the failure of stent insertion and 1 because of a protocol violation. The patients were evaluated clinically and, if necessary, with biochemical tests every month until death or until they needed surgery for symptoms of gastric outlet obstruction. When occlusion or dislocation occurred, the stent was replaced with one of the same type. Cumulative stent patency and patient survival were estimated with the Kaplan-Meier life-table analysis and compared by log-rank chi-square test. RESULTS: The two groups were comparable in mean age, gender, and diagnosis. The patients were followed for a mean of 145.5 days (range 24 to 613); by the end of the study 47 patients (81%) had died or developed symptoms of gastric outlet obstruction. Median survival was 88 days (range 24 to 613) in the TB group and 75.6 days (23 to 486) in the CH group. Stent exchange (occlusion 16, dislocation 3) was necessary for 5 patients in the TB group and 7 in the CH group. No statistical difference was found on comparing the mean duration of function of the first, second, and third stents (analysis of variance, p = 0.80). The median duration of stent function was 96 days (range 11 to 613) in the TB group and 75.5 days (range 23 to 323) in the CH group. No significant difference was found in either survival time (p = 0.48) or stent patency (p = 0.12). CONCLUSION: This study found no significant advantage of the Tannenbaum prostheses over the standard polyethylene stent in the palliation for patients with distal malignant biliary stenosis with regard to survival or length of stent patency.

[The topical therapy of ulcerative colitis. A multicenter study with beclomethasone dipropionate foam]. / Terapia topica della colite ulcerosa. Studio multicentrico con beclometasone dipropionato schiuma.

BACKGROUND AND AIMS: The use of steroids was recently extended to the various forms of ulcerative rectocolitis by the introduction of topical formulations, above all steroids with an hepatic "first pass" devoid of systemic interference. The aim of this study was to evaluate the efficacy and tolerability of Beclomethasone dipropionate (BDP) in a rectal foam formulation, in the treatment of patients suffering from ulcerative colitis. METHODS: The experimental protocol took the form of a 28-day open prospective trial using BDP rectal foam in patients suffering from ulcerative colitis. Endoscopic, histological, clinical and tolerability parameters were evaluated. The centres taking part in the trial collected data for 60 cases out of a total of 80 patients enrolled in the study, of both sexes and aged between 20 and 81 years old, suffering from proctosigmoiditis (46.7%) and ulcerative rectocolitis (53.3%). RESULTS: Endoscopic parameters showed an improvement after 28 days of treatment in 74.5% of patients; a clinical improvement was achieved in 65.2% of cases. In percentage terms of the mean value of all the improved parameters, histological parameters were altered in 56.9% of patients. With regard to tolerability 82% of patients judged the treatment to be good/excellent. CONCLUSIONS: In conclusion, in line with recent reports regarding other pharmaceutical forms of BDP, including the use of rectal foam, these data confirm the efficacy and tolerability of this molecule and emphasise the validity of its use in the treatment of ulcerative colitis and proctosigmoiditis.

[Topical beclomethasone dipropionate (BDP) in intestinal inflammatory diseases: the results of a multicentre trial]. / Beclometasone dipropionato topico nelle malattie infiammatorie intestinali: risultati di un'indagine multicentrica.

The authors assessed the efficacy and tolerability of BDP in an open protocol using rectal enemas and suppositories and in a double-blind protocol vs mesalazine using rectal enemas. A total of 47 patients suffering from ulcerous rectocolitis were enrolled in the study and treated for 42 days while undergoing endoscopic, histologic and clinical controls. In conclusion, the authors affirm that BDP may represent a useful new therapeutic instrument in the treatment of slight to moderately severe forms of inflammatory intestinal disease.

Effectiveness of cisapride in gastric ulcer. Results of a double-blind randomized trial versus ranitidine and versus cisapride plus ranitidine.

Among the factors involved in the pathogenesis of gastric ulcer, the reduced clearing capacity of the stomach seems to play an important role. On this basis, cisapride, which improves gastrointestinal motility, enhances gastric emptying, and prevents duodenogastric reflux, may be effective in the treatment of the gastric ulcer. We randomly allocated 60 consecutive patients, with uncomplicated antral gastric ulcer (diameter 5-25 mm), into three groups of treatment: cisapride 20 mg b.i.d. (C), ranitidine 150 mg b.i.d. (R), cisapride 20 mg b.i.d. + ranitidine 150 mg b.i.d. (C+R). Endoscopic examination with biopsy specimens was performed on admission, after 4 weeks and (if ulcer not healed) after 8 weeks of therapy. Three patients were lost to follow-up (two in C and one in C+R), and three were withdrawn, due to malignant ulcer (one case in R) or to side effects (one case of diarrhea in C, one case of headache in C+R). Healing rates at 4 weeks were 41.1% in C, 52.6% in R, and 50.0% in C+R; at 8 weeks they were 88.2% in C, 89.4% in R, and 94.4% in C+R. Though the lack of a placebo arm makes final considerations difficult, the results were similar in all three groups, with no evident differences. In conclusion, therapy with cisapride appears as effective as H2-blocker alone or combined treatments in healing benign gastric ulcer.

Prostaglandin-stimulated recovery of the human duodenal epithelium: effects of misoprostol on ethanol damage.

This study was designed to determine whether prostaglandins can stimulate the repair of human duodenal epithelium. Ten healthy volunteers were given 50 ml 40% ethanol through an endoscope onto the duodenal mucosa 1-7 cm from the pyloric sphincter; 3 min later, misoprostol (200 micrograms) or inert vehicle (5 ml) was given locally in the same way. One and 5 h later, endoscopy was repeated to evaluate the damage. The conditions of the mucosa were evaluated by endoscopy and by scanning and transmission electron microscopy in biopsies taken at time 0 and 3 min, 1 and 5 h after ethanol. The study was double-blind with a cross-over balanced design. Three minutes after ethanol administration, the duodenal mucosa showed hyperemia with hemorrhagic lesions. Under the electron microscope, the lesions were caused by vascular engorgement or red blood cell extravasation into the submucosa; the epithelium underlining lesions showed loss of superficial cells and damage to the upper layer of the mucosa. One hour after ethanol, there was a striking difference between the two treatment groups, with a substantial recovery of the duodenal epithelium in the misoprostol-treated volunteers. Although spontaneous recovery was evident in the control group, there was also a significant difference at 5 h. Our results suggest that prostaglandins are able to stimulate the recovery of the duodenal epithelium after acute damage.

Prostaglandin cytoprotection in man: effectiveness of rosaprostol.

We studied the effect of a new prostaglandin analogue, 9-hydroxy-19,20-bis-norprostanoic acid (rosaprostol), on the duodenal mucosa of humans after administration of 40% ethanol. Eighteen healthy volunteers entered the study, which followed a blind cross-over design. At time 0 all the volunteers received rosaprostol or placebo; 5 minutes later, 40% ethanol (50 ml dose) was given. The mucosa was examined for lesions 3, 60 and 180 min later under endoscopy, light and scanning microscopy. It was found that: (i) 40% ethanol damaged the duodenum, with blood extravasation, inflammation and necrosis of the mucosa, (ii) rosaprostol significantly protected the mucosa 3 min after 40% ethanol, and (iii) the damage became worse after 3 h when placebo was given, whereas it was reduced after 1 h when PG was administered. The results suggest that PGs not only protect the mucosa against ethanol damage, but also stimulate its recovery.

Adaptive cytoprotection: an endoscopic study in man.

We studied the protective effect of the mild irritant 20% ethanol against the damage caused by the strong irritant 40% ethanol to the duodenal mucosa of 10 healthy volunteers. At time 0, placebo (1% ethanol) or 20% ethanol (6 ml) was sprayed directly onto the duodenal wall through an endoscope. After 15 min 40% ethanol (50 ml) was given; damage was assessed by endoscopic examination 30 min after ethanol. The damage was scored arbitrarily: score 0, no damage; 1, duodenal hyperemia; 2, one hemorrhagic lesion; 3, two to five hemorrhagic lesions; 4, five hemorrhagic lesions. In separate experiments, the effect of acetylsalicylic acid (20 mg/kg iv) on adaptive cytoprotection was evaluated. It was found that 1) 20% ethanol does not damage the duodenal mucosa, whereas 40% ethanol does; 2) duodenal hyperemia and hemorrhagic lesions caused by 40% ethanol can be prevented by the previous administration of 20% ethanol; and 3) acetylsalicylic acid does not damage the duodenal mucosa but abolishes the protective effect of 20% ethanol. "Adaptive cytoprotection" is a physiological phenomenon in humans too and further supports the probable defensive role of endogenous prostaglandins in the gastrointestinal tract.

Acidrine in the management of gastritis and duodenitis. A double-blind placebo controlled clinical trial.

Thirty-nine adult out-patients with dyspepsia and endoscopically proven gastritis and/or duodenitis without ulcer, completed a double-blind, placebo controlled, 8-week clinical trial of either Acidrine (twenty-one patients) or placebo (eighteen patients), at a daily dosage of 2 tablets t.i.d. Treatment with Acidrine resulted in a significant improvement in symptoms and in the endoscopic appearance of the gastritis and duodenitis when compared with placebo.

Long-term management of duodenal ulcer with pirenzepine and cimetidine: a double-blind controlled clinical trial.

The effectiveness of pirenzepine in the prevention of duodenal ulcer relapses was assessed by means of a double-blind controlled trial versus cimetidine. Seventy duodenal ulcer out-patients endoscopically healed after a 6-week treatment with either pirenzepine or cimetidine were admitted to the trial. The former pirenzepine patients were treated again with pirenzepine: 1 tablet at breakfast and 2 tablets at bedtime (75 mg daily). The former cimetidine patients were treated again with cimetidine: 2 tablets at bedtime (400 mg daily). They received one placebo tablet at breakfast. Both treatments lasted 12 months. Tablets of a mild antacid were permitted only if necessary to relieve severe ulcer pain and heartburn. Patients underwent clinical and endoscopic assessments after 4, 8 and 12 months of treatment and whenever ulcer symptoms lasted more than 4-5 consecutive days. Only 47 out of the 70 patients that entered the trial underwent all clinical and endoscopic controls. Sixteen out of 23 patients on pirenzepine (70%) and 17 out of 24 patients on cimetidine (71%) did not relapse after 12 months. The difference is not statistically significant. Both treatments were well tolerated. The results show that pirenzepine was as effective as cimetidine in the prevention of duodenal ulcer relapses when administered at a dosage of 75 mg daily (of which 50 mg at bedtime) for one year.