A. Tittobello

Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP pancreatitis

OBJECTIVES:A continuous 13-h infusion of gabexate starting 30–90 min before endoscopic cholangiopancreatography (ERCP) can reduce postprocedural pancreatitis, the onset of which is generally observed within the first 6 h after ERCP. This study was designed to verify whether a 6.5-h infusion of gabexate was as effective as a 13-h infusion, at the same concentration, for reducing the incidence of post-ERCP pancreatitis (primary endpoint) and pancreatic hyperenzymemia and pain (secondary endpoints).METHODS:A total of 434 patients (201 male and 233 female; mean age 63.9 yr, range 18–96 yr) scheduled for ERCP were prospectively recruited in 25 Italian centers. Patients were randomized double-blind to two treatment groups. All subjects enrolled were first treated with a 500-mg continuous intravenous infusion of gabexate, starting 30 min before the endoscopic maneuvers and continuing up to 6.5 h after it. Over the next 6.5 h, 214 patients (group I) continued the infusion of gabexate (for a total of 1 g over 13 h) and 220 patients (group II) were given placebo (saline solution).RESULTS:The overall incidence of acute pancreatitis was 1.8% (eight patients), which included 1.4% in group I (three of 214 patients) and 2.2% in group II (five of 220 patients). Serum amylase and lipase values over time, peak levels of the two enzymes, pancreatic pain, and need for analgesics did not significantly differ in the two groups.CONCLUSIONS:These results suggest that a 6.5-h infusion of gabexate (for a total of 500 mg) is not less effective than a 13 h infusion, with evident savings.

Outcome of ulcerative colitis after treatment with transdermal nicotine

Objective Transdermal nicotine appears to be of benefit in the short-term treatment of patients with ulcerative colitis. The aim of this study was to determine its long-term effects. Design A randomized, comparative study. Patients and methods Patients with mild to moderate clinical relapses of left-sided ulcerative colitis during maintenance treatment with mesalamine 1 g b.i.d. were allocated to an additional treatment with either transdermal nicotine or prednisone for 5 weeks. The first consecutive 15 patients per group, with clinical and endoscopie signs of remission, were followed up for 6 months, while continuing mesalamine maintenance treatment. Results Relapses of active colitis were observed in 20% of patients formerly treated with nicotine and in 60% of patients in the prednisone group (P = 0.027). Relapses occurred earlier in the latter group. Conclusion Our results confirm that nicotine is useful in cases of ulcerative colitis with mild or moderate activity and suggest that remissions induced by nicotine may last longer than those obtained with oral corticosteroids.

Different interdigestive antroduodenal motility patterns in chronic antral gastritis with and withoutHelicobacter pylori infection

Fasting antroduodenal motor activity was studied in 15 dyspeptic patients with chronic superficial antral gastritis andHelicobacter pylori infection (group A), 10 dyspeptic patients with chronic superficial antral gastritis withoutHelicobacter pylori infection (group B), and eight healthy control subjects (group C) by manometric recording of phases of the interdigestive migrating motor complex (MMC) prolonged over 240 min. A significantly lower incidence of activity fronts (phase III of MMC) starting from the antrum was observed in patients with gastritis andHelicobacter pylori infection vs patients without bacterial colonization (P=0.013) and in these latter vs control subjects (P=0.013). Likewise, the overall number of activity fronts was smaller in patients with gastritis than in healthy subjects (P=0.034). Symptomatic evaluation was performed in the two groups of dyspeptic patients, without detecting any differences in frequency and severity of complaints. Our results show a significant reduction in the occurrence of interdigestive antral phase III of MMC in chronic gastritis associated withHelicobacter pylori infection, suggesting a possible relationship between fasting motility and bacterial colonization.

Longterm oral cisapride improves interdigestive antroduodenal motility in dyspeptic patients.

We have evaluated the effect of cisapride on interdigestive antroduodenal motility during a prolonged oral therapy in 20 consecutive dyspeptic subjects. Individuals with less than two migrating motor complexes (MMCs) starting from the antral region in 240 minutes and without evidence of upper gastrointestinal tract diseases were randomly treated with either cisapride (10 cases), or placebo (10 cases) for 15 days. Computerised manometry of antroduodenal region was performed for 240 minutes, in basal conditions and on the 15th day of therapy. Symptomatic evaluation of patients was also performed before and after treatment. After cisapride administration, a significant increase in the incidence of antral migrating motor complexes was noticed (p = 0.022); likewise, the motility index, calculated for phase-2 periods, appeared to be significantly higher both in the antrum and in the duodenum (p less than 0.001). Symptomatic improvement was observed in both groups, with a hardly significant (p = 0.049) reduction of dyspeptic symptoms severity only but not of frequency in cisapride treated patients v controls. We conclude that longterm oral therapy with cisapride improves interdigestive antroduodenal motor activity.

PILOT TRIAL OF NICOTINE PATCHES AS AN ALTERNATIVE TO CORTICOSTEROIDS IN ULCERATIVE COLITIS

In ten patients with mild to moderate clinical relapses of ulcerative colitis during treatment with mesalazine (1 g t.i.d.) and with a previous history of poorly tolerated steroid courses, transdermal nicotine (15 mg daily) was added for 4 weeks. Clinical findings were assessed by employing Rachmilewitzs activity index. In 7 of the patients, clinical remission was achieved, the results persisting for up to 3 months after nicotine withdrawal. Endoscopic and histological examination, when performed, confirmed the clinical findings. Nicotine patches may represent a good alternative to steroids in selected patients with mild to moderate relapses of ulcerative colitis. The precise mechanism of action remains unknown.

Esophageal Motility in Cirrhotics with and without Esophageal Varices

Esophageal manometry was performed in 45 cirrhotics with varices, in 15 cirrhotics without varices, and in 20 normal subjects, to define the effect of varices on esophageal motility. Cirrhotics with varices showed a decreased amplitude of motor waves in the lower half of the esophagus (p less than 0.01), an increased duration of primary peristaltic waves along the entire length of the esophagus (upper esophagus, p less than 0.05; lower esophagus, p less than 0.01), and an increased peak-to-peak speed of primary peristaltic waves (p less than 0.01). Resting lower esophageal sphincter pressure and duration of sphincter relaxation were similar in patients and controls. The above-mentioned abnormalities might be due to the mechanical effect of the presence of varices.

Effects of cimetropium bromide on gastrointestinal transit time in patients with irritable bowel syndrome

Cimetropium bromide is a new antimuscarinic compound with strong antispasmodic activity. The aim of this study was to evaluate the effects of oral cimetropium bromide on total gut transit time in patients with irritable bowel syndrome. Forty patients, divided according to their initial total gastrointestinal transit times and presenting symptoms, were treated with cimetropium bromide 50 mg t.d.s. or placebo for 1 month according to a double‐blind, parallel group design. Before and after treatment all subjects ingested 24 radio‐opaque markers. The total intestinal transit time was determined by evaluating the rate of disappearance of markers from plain X‐ray films of the abdomen taken every 24 h for 4 days. Pain and bowel habits were also monitored. Seven patients did not complete the study. Cimetropium bromide significantly (P < 0.01) shortened the whole gut transit time in patients with prolonged transit time (80.8 ± 4.0 h before vs 60.8 ± 6.7 h after treatment) and improved the global clinical condition significantly compared with placebo (P= 0.029). In patients with a short total intestinal transit time, cimetropium bromide had no effect on whole gut transit time and did not significantly improve symptoms. The results of this study indicate that oral cimetropium bromide is effective both objectively and subjectively in a subgroup of irritable bowel syndrome patients with constipation.

Congestive Gastropathy versus Chronic Gastritis: A Comparison of Some Pathophysiological Aspects

In order to investigate some pathophysiological aspects of the two diseases, 15 patients with congestive gastropathy and 15 with chronic gastritis have been studied and compared with 15 healthy controls. Gastric blood flow as determined during endoscopy by means of laser Doppler flowmetry was found to be significantly increased (p < 0.001) in congestive gastropathy, whereas a significant reduction (p < 0.001) was noted in chronic gastritis. On the other hand, Helicobacter pylori was detected in 80% of cases in chronic gastritis, while the prevalence of the microorganism in congestive gastritis was similar to that in healthy controls. It is concluded that chronic gastritis and congestive gastropathy are related to different pathogenetic factors and require different therapeutic approaches.

Gastric cancer in chronic atrophic gastritis: Associated gastric ulcer adds no further risk

Atrophic gastritis with intestinal metaplasia is generally considered a precancerous lesion. We followed 261 patients with chronic atrophic gastritis and intestinal metaplasia, with and without gastric ulcer, every 12 months for 9 +/- 2 years by means of endoscopic and histological examination. In the presence of dysplasia, however, studies were carried out every 6 months in moderate cases, or every 3 months in severe cases. Patients with gastric ulcer received medical therapy for 8 weeks; if healing did not occur, treatment was continued. Only subjects with healed ulcers were admitted to the follow-up. To date, 205 subjects have been included in the study. Over a 10-year period, 16 patients with recurrent gastric ulcer and 12 patients with cancer in situ or in an early stage, were subjected to surgery. One case of advanced cancer was observed. Cancer has been found in five of 95 cases of atrophic gastritis with gastric ulcer (5.2%), and in 7 of 166 cases of atrophic gastritis without gastric ulcer (4.2%). The difference was not statistically significant. Our results confirm that gastric ulcer per se is not a high-risk condition, but it must be considered as an epiphenomenon on a background of epithelial atrophy.

Area under pH 4: a more sensitive parameter for the quantitative analysis of esophageal acid exposure in adults

Objective:Traditional quantitative analysis of 24-h esophageal pH monitoring data does not include the pH of reflux episodes. Area under pH 4 (AU4) is a recently introduced parameter that describes the acid exposure rate through both duration and depth of pH falls.Methods:In Study A, we enrolled 20 healthy controls and 42 patients (18 without esophagitis, 24 with Savary I–III esophagitis) in a study evaluating reference values for 24-h reflux time at pH <4 (RT) and 24-h AU4 by means of receiver operating characteristic (ROC) discriminant analysis. For Study B, we next prospectively applied the resulting cutoffs to 16 healthy controls and to 110 gastroesophageal reflux (GERD) patients (55 with esophagitis) to adjust sensitivity, specificity, and predictive values of both RT and AU4.Results:In Study A, the best cutoff values were 5.1% for RT (Area Index ± SE, 0.899 ± 0.038; 95% confidence interval [C.I.], 0.796 ± 0.961) and 36.1 pH × min for AU4 (Area Index ± SE, 0.935 ± 0.03; 95% C.I., 0.842 ± 0.981); AU4 gave the best performance (p= 0.038vs RT) in discriminating controls and GERD patients. In Study B, RT was abnormal in three controls and 79 patients; AU4 identified all the controls and patients with abnormal RT and also 10/31 patients (32.3%) with so-called “normal” acid exposure (according to RT). In the whole GERD group of patients, AU4 and RT specificity was 81.2%, whereas sensitivity was 71.8% for RT and 80.9% for AU4 (χ2, 61.831; DF, 1; p < 0.005); PPV/NPV were 96.3%/29.5% for RT, and 96.7%/38.2% for AU4.Conclusions:AU4 appears to be a simple and sensitive quantitative parameter to measure the esophageal acid exposure in adults submitted to 24-h pH monitoring, and it could be an useful clinical aid in evaluating normal RT tests where, from a clinical point of view, a reflux disease is highly likely.