P. Dotto

Markers of Slow-Healing Peptic Ulcer in the Elderly A Study on 1,052 Ranitidine-Treated Patients

Little is known about ulcer outcome in the elderly. The aims of the present paper were to establish whether risk factors of slow-healing peptic ulcer can be demonstrated in the elderly and whether clinical differences exist between ulcer patients whose age of onset of the disease was before or after 65 years old. The short-term, open study, involving 1052 elderly patients (over 65 years) in 37 gastroenterology centers throughout Italy aimed to compare two schedules of ranitidine treatment: 150 mg twice daily versus 300 mg at bedtime. As nonsignificant differences were found between these two schedules, the sample was considered as a whole. It included 319 gastric ulcer (GU) patients, 699 duodenal ulcer (DU) patients, and 34 concomitant GU and DU cases. Ninety-three patients dropped out of the trial; 79/294 GU, 138/635 DU, and 10/30 GU+DU were found still unhealed after four weeks and 20 GU, 15 DU, and 1 GU+DU remained so after eight weeks. Statistical analysis was performed using likelihood-ratio and Pearsons chi-squared tests and Coxs models. Univariate analysis showed that the indicators of slow-healing GU were ulcer size (P=0.002) and persisting ulcer symptoms (P=0.0001); indicators of slow-healing DU were ulcer size (P=0.0001), persisting ulcer symptoms (P=0.0001), alcohol (P=0.0003), and NSAID (P=0.0088) consumption. DU patients taking antiplatelet drugs have significantly better results after four weeks and worse results after eight weeks (P=0.0352). Coxs models revealed that the persistence of ulcer symptoms is the most important factor predicting unhealing ulcers (GU,P=0.0008; DU,P=0.0002), while ulcer size is only important for DU (P=0.0215). Patients with ulcer disease onset before 65 years of age were more frequently males; DU subjects were more frequently smokers, with a family history of ulcer and no NSAID consumption. In conclusion, persistence of ulcer symptoms and ulcer size are indicators of slow-healing ulcer in the elderly; in the case of DU, NSAID and alcohol consumption may be additional factors.

Serum pepsinogens as markers of Helicobacter pylori eradication

Abstract Various methods, both invasive and noninvasive, are used to verify Helicobacter pylori eradication, with varying degrees of accuracy. The purpose of this study was to verify the relationship between H pylori eradication and serum levels of pepsinogen A (PGA) and pepsinogen C (PGC). The study involved 79 patients who tested positive for H pylori infection after histologic examination and the urease test. Patients were treated with various drug regimens for 7 to 25 days. Two months after discontinuing treatment, endoscopy was performed to verify H pylori eradication; 33 of 79 patients were found to be free of infection. Venous blood samples were taken to measure PGA and PGC levels before and after treatment. Patients in whom H pylori infection was eradicated had a significant drop in PGA and PGC levels, whereas in patients with persisting H pylori infection, there was a trend in which pepsinogen levels coincided with the quantity of bacteria detected. These preliminary data suggest that it may be possible to evaluate H pylori eradication by means of serum pepsinogen levels, sparing patients a follow-up endoscopy.

Pepsin concentration in gastroduodenal biopsy homogenates in chronic ulcer disease

A modification of Berstads spectrophotometric method was tested and proved capable of detecting pepsin concentrations in mucosal perendoscopic biopsy homogenates. The relationship between this parameter and pepsin in gastric juice and pepsinogen group I in serum and in biopsy homogenates was analyzed. From the biochemical point of view, the assay was found sufficiently accurate. Mucosal pepsinogen group I, but not mucosal pepsin, concentration was found higher in gastric and duodenal ulcer patients than in controls. Patients with corpus-fundic gastric ulcer showed significantly lower mucosal pepsin and mucosal pepsinogen group (PG) I. Aging and smoking did not influence either parameter but male duodenal ulcer subjects presented higher mucosal pepsinogen group I concentration. The lack of any relationship between serum and mucosal PG I and between pepsin in gastric juice and in mucosa raises a question, at least in methodological terms, about the validity of using serum pepsinogen group I and pepsin as indicators of peptic output.

A PRELIMINARY REPORT ON HELICOBACTER PYLORI AND ANTRAL GASTRIN CONCENTRATION IN PATIENTS WITH DUODENAL ULCER

This study analyzed the relationship between Helicobacter pylori infection, mucosal gastrin concentration, and basal serum gastrin levels in duodenal ulcer patients with dyspepsia. Patients with duodenal ulcers who were H pylori positive showed higher antral gastrin concentrations than either H pylori-positive patients with dyspepsia or H pylori-negative patients with duodenal ulcers. No correlation was found between serum gastrin and antral gastrin concentrations. The increased antral gastrin concentrations were not correlated with an inhibition of acid-gastrin feedback. These preliminary data confirm that H pylori infection impairs gastrin physiology.

H2 antagonists and gastric ulcer: A multicenter, randomized, double-blind, controlled study comparing nizatidine with ranitidine*

An 8-week, multicenter, randomized, double-blind study was performed with the aim of comparing nizatidine 300 mg at bedtime with nizatidine 150 mg twice daily (BID) and with ranitidine 150 mg twice daily in 114 patients with benign acute gastric ulcer. Healing rates did not significantly differ among groups at 4 weeks, but they were lower in the once-daily group (53%) than in the BID groups (approximately 69%). At 8 weeks, healing rates with nizatidine 150 mg BID (97%) were significantly higher than those observed in the groups that received nizatidine 300 mg at bedtime (78%) or ranitidine 150 mg BID (83%). Smoking was found to affect the therapeutic efficacy of the bedtime dosing. The results of this study show that nizatidine is an efficacious and safe drug in the treatment of benign acute gastric ulcer when given twice daily, especially in smokers.

HEMORRHAGIC DUODENAL ULCER DISEASE: CLINICAL AND BIOCHEMICAL FINDINGS IN A CASE-CONTROL PILOT STUDY

Abstract A retrospective study of 31 consecutive bleeding duodenal ulcer (DU) patients and, as controls, 62 active DU subjects without bleeding episodes was conducted in order to ascertain whether bleeding DU patients have particular clinical or functional characteristics. The patients were followed for 15.6 and 17.4 months, respectively, after diagnosis. The following parameters were taken into account: sex, age, family history of ulcer, blood group (ABO system), ulcer pain, nonsteroidal anti-inflammatory drug (NSAID) consumption, cigarette smoking, alcohol and coffee consumption, ulcer site, fasting serum gastrin and pepsinogen group A, basal acid output (BAO), and maximal acid output (MAO). Statistics were gathered using the Students t test and Fishers exact test. Bleeding DU patients had less ulcer pain ( P P

CYTOPROTECTIVE EFFECTS OF COLLOIDAL BISMUTH SUBCITRATE IN PATIENTS WITH ULCER DISEASE

Abstract Helicobacter pylori is capable of altering the structure of the mucus gel adhering to the surface of the gastric antral wall. Thirty patients (22 men and 8 women) with endoscopic evidence of active duodenal ulcer and histologically confirmed H pylori antral gastritis participated in this prospective study. The study objective was to evaluate the effects of 6 weeks of treatment with colloidal bismuth subcitrate (two 120-mg tablets twice daily) on peptic secretion and the gastric mucosal barrier. Samples of gastric juice were collected during endoscopy to measure pepsin levels. Also during endoscopy, four biopsies were taken (two antral and two from the body/fundus) for histological examination, H pylori detection, and the quantification of pepsinogen group A (PGA), gastrin, and pepsin in the tissues. All of the above parameters were repeated with endoscopy after 6 weeks of treatment. Ulcer healing was obtained in 26 (87%) of 30 patients after treatment. H pylori infection was cleared in 15 (50%) patients. No significant changes were detected in concentrations of pepsin in the gastric juice or concentrations of PGA, gastrin, or pepsin in the tissues. Mucus depletion was visibly lower after treatment, suggesting that colloidal bismuth subcitrate may alter the bacterial microenvironment, regenerating the quantity of mucus.

Different doses of omeprazole in the maintenance treatment of patients with peptic ulcers resistant to H2-blockers

Abstract A 6-month, open, randomized study was performed to evaluate different dosage regimens for maintenance therapy with omeprazole in patients refractory to treatment with standard histamine 2 (H 2 )-blockers. One hundred two patients with gastric and/or duodenal ulcers, unhealed after 8 weeks of full-dose H 2 -antagonist treatment but healed after a further 4 to 8 weeks of omeprazole 20–40 mg/d, were randomized into four treatment groups: omeprazole 20 mg once daily (group A), omeprazole 20 mg every other day (group B), omeprazole 20 mg twice weekly (group C), and ranitidine 150 mg at bedtime (control). Endoscopic and clinical examinations were performed at 3 and 6 months and at every symptomatic relapse. Eleven patients dropped out for reasons of noncompliance. Relapses were detected in 14.8% of 27 cases in group A, 19.4% of 31 cases in group B, 42.9% of 21 cases in group C, and 66.7% of 12 controls. The better outcomes in groups A and B, as compared with group C and the control group were statistically significant. These findings confirm the efficacy of omeprazole in maintenance therapy for refractory ulcers and suggest that drug administration should be daily or every other day, as twice-weekly dosages are less effective.

Personality traits and gastric acid secretion in ulcer disease

investigators of gallstone pathogenesis to obtain bile samples for our analysis. We hope that our study and the response of our colleagues at the University of Pennsylvania will stimulate similar interest by surgeons at other institutions to cooperate with investigators in obtaining adequate bile samples. KEITH D. LILLEMOE, MD STEVEN A. AHRENDT, MD THOMAS H. MAGNUSON, MD HENRY A. PITT, MD Department of Surgery Johns Hopkins Hospital Baltimore, Maryland

Thrice-yearly rhythm of duodenal ulcer disease

Abstract Various studies have emphasized a periodic trend in ulcer disease, with a higher incidence of relapse, complications, and painful symptoms in spring and autumn for duodenal ulcer (DU) and in winter for gastric ulcer (GU). It has been suggested that this seasonal trend may be linked with experimentally demonstrated year-round rhythmic changes in gastric acid output. This study retrospectively evaluated the seasonal nature of ulcer activity, symptoms, and complications in 293 endoscopically diagnosed patients (52 GU: 20 women, 32 men, mean age 56 years, range 22 to 82 years; 241 DU: 56 women, 185 men, mean age 51 years, range 21 to 87 years) with a mean follow-up of 20.3 months. Relapses occurred in 27% of the GU and 22% of the DU cases, and complications occurred in 6% of the GU and 12% of the DU cases. Clinical endoscopic check-ups were repeated every 6 to 12 months. A record was kept of alcohol and coffee intake, smoking habits, symptoms at time of diagnosis and check-up, endoscopic results, relapses, remission, and complications. Statistical analysis was made by Students t test and the chi-square test. On diagnosis, 63% of patients reported a seasonal trend in symptoms (68% in the DU group and 44% in the GU group). During follow-up, painful symptoms occurred mainly in February, June–July, and October in DU cases whereas in GU cases the picture was more varied. Endoscopy revealed that in DU cases symptoms were closely related to activity, found mainly in February, May, and October. As for complications, no significant difference was found at different times of the year for either DU or GU cases. This study confirmed a thrice-yearly trend in DU (probably linked with the year-round rhythm demonstrated for basal acid outputs and maximal acid outputs), but no such seasonal trend for GU (although the low number of GU cases studied may influence this finding). These data may have useful therapeutic implications for a tailored seasonal maintenance therapy, thus ensuring better relapse prevention and avoiding unnecessary expense.