Factors Influencing the Relapse of Gastric Ulcers During H2-Receptor Antagonist Maintenance Therapy

Abstract: We performed H₂-receptor antagonist maintenance therapy for 2 years on 146 patients with healed gastric ulcers (including those with concurrent duodenal ulcers), and determined the cumulative endoscopic and symptomatic recurrence rates. We also investigated the factors involved in ulcer recurrence in the first 12 months of maintenance therapy. The cumulative endoscopic non-recurrence rate was 70.0% at 12 months and 57.2% at 24 months, while the cumulative symptomatic non-recurrence rate was 84.8% at 12 months and 75.0% at 24 months. The factors contributing to endoscopic recurrence were the presence of a concomitant disease, the presence of duodenal ulcer, the type of ulcer, and the endoscopic stage at healing. The factors related to symptomatic recurrence were smoking and the type of ulcer. Multivariate analysis showed that the type of ulcer, smoking, and the endoscopic stage at healing influenced the risk of recurrence.     

Treatment of Gastroduodenal Ulcers with Cimetidine in Combination with Low-Dose Propantheline

ABSTRACT Fifty-eight adult outpatients with endo-scopically verified gastric, prepyloric or duodenal ulcers completed a double-blind trial of treatment with either Cimetidine, 1 g daily, plus propantheline, 45 mg daily (group A) or Cimetidine, 1 g daily, plus placebo (group B). After neither three nor six weeks of treatment was there any significant difference between the two groups with regard to ulcer healing or symptomatic relief. The ulcers of 22 (79%) of the 28 patients in group A and 25 (83%) of the 30 patients in group B were healed after six weeks, and 93 % of the patients in both groups became painfree. We were thus not able to show any advantage in combining Cimetidine treatment for ulcer healing with low-dose propantheline. In a small open trial the patients with healed ulcers received prophylactic treatment for 12 months with 1) Cimetidine 800 mg daily, 2) Cimetidine 400 mg at bedtime plus propantheline 45 mg daily or 3) propantheline 90 mg daily. No significant differences were found between the ulcer recurrence rates, but it cannot be excluded that a larger number of patients in each group might have yielded real differences.     

Influence of Smoking and Helicobacter pylori on Gastric Phospholipids

Smokers show higher rates of peptic ulcer disease (PUD) than nonsmokers, probably due to detrimental effects on the gastric mucosa. Surface-active phospholipids (SPL) are believed to play a key part in gastric cytoprotection. The aim of this study was to determine the chronic effects of smoking on the gastric SPL and to relate them to H. pylori (Hp) -induced effects. Gastric juice was aspirated in 52 patients, with normal findings at planned upper gastrointestinal endoscopy, and concentrations of seven phospholipid subclasses were analyzed. Concentrations of lysophosphatidylethanolamine (l-PE) were increased (P = 0.006) in smokers compared to nonsmokers in non-Hp-infected samples. Nonsmokers infected with Hp showed increased levels of l-PE (P = 0.01) and phosphatidylinositol (PI) (P = 0.02) compared to subjects not infected. In human gastric juice PI seems to be the dominating PL subclass, in contrast to the composition in biopsy specimens. We also found both Hp-infected and smoking subjects to have higher concentrations of more polar phospholipid subclasses, ie, l-PE, making the mucosa more vulnerable to acid attack as the gastric surfactant becomes less hydrophobic.     

Long-Term Effects of Helicobacter pylori Eradication on Intestinal Metaplasia in Patients with Duodenal and Benign Gastric Ulcers

This study was conducted to investigate whether or not the eradication of H. pylori could lead to the regression of intestinal metaplasia (IM) in patients with either duodenal ulcer (DU) or benign gastric ulcer (BGU). The initial antral IM grade was 0.21 in the 72 patients of the H. pylori-eradicated DU group, this decreased to 0.17, 0.14, 0.13, and 0.09 after periods of four weeks, one year, two years, and four years, respectively, but without statistical significance. In the corpus of the DU group, where IM grade was low (0.02), there was no detectable change in IM. The initial antral IM grade of 0.69 in the 41 patients of the H. pylori-eradicated BGU group decreased substantially to 0.61, 0.44, and 0.39 after periods of four weeks and one and two years, respectively, but again without statistical significance. The initial corporal IM grade of the BGU group of 0.27 decreased to 0.20, 0.15, and 0.06 after periods of four weeks and one and two years, again without statistical significance. In contrast, the IM grades of the noneradicated DU group (N = 20) and the BGU group (N = 16) showed nearly no change in the antrum and corpus. Gastritis grades of antrum and corpus in the H. pylori-eradicated DU or BGU group significantly decreased with respect to time (P = 0.0001), but there were no significant changes in the corresponding noneradicated groups. Although there was no statistical significance, IM decreased in the antrum and corpus of the stomach with BGU and in antrum of those with DU over a two to four-year period after H. pylori eradication, suggesting the possible reversibility of IM.     

Maintenance therapy with H2-receptor antagonist until assessment of Helicobacter pylori eradication can reduce recurrence of peptic ulcer after successful eradication of the organism: prospective randomized controlled trial

PURPOSE: This study examined the possible relationship between peptic ulcer recurrence and the presence or absence of maintenance therapy with an H(2)-receptor antagonist performed until evaluation of Helicobacter pylori eradication. METHODS: The subjects were 483 patients with peptic ulcer (281 gastric ulcer and 202 duodenal ulcer) who were diagnosed as H. pylori positive. After receiving eradication therapy for H. pylori, patients were allocated at random to one of three different maintenance therapies: control group (no maintenance therapy), H(2)-receptor antagonist half-dose group, and H(2)-receptor antagonist full-dose group. The maintenance therapy was performed for 4 weeks until evaluation of H. pylori eradication. RESULTS: Among the 25 patients with a recurrent ulcer, 18 patients (72%) had a recurrence at the time of or before evaluation of H. pylori eradication. In the control group, the rate of ulcer recurrence occurring before evaluation of H. pylori eradication was 10.5% (14/133). This rate was significantly higher than those in the H(2)-receptor antagonist half-dose group (2.9%, 4/136) and the full-dose group (0%, 0/135). CONCLUSION: The results of this study suggest that maintenance therapy with an H(2)-receptor antagonist performed after eradication therapy until evaluation of H. pylori eradication is likely to greatly reduce the ulcer recurrence rate without affecting evaluation of H. pylori eradication.     

Helicobacter pylori: Past, present and future

Abstract Much has been achieved in Helicobacter pylori research, to the point that the growth of new knowledge is bound to slow down. However, expectations for further developments remain high. Knowledge about the characteristic organism and behaviour is already extensive. Particularly intriguing are the differences in genetic make-up in the various geographical regions. Sadly, detailed knowledge on how the organism spreads is still lacking. The spectrum of clinical presentation in humans is largely known. Helicobacter pylori is disappearing worldwide, allowing the relative frequency of H. pylori n-egative ulcer disease to increase. The extent to which H. pylori disappearance and eradication is responsible for decreasing prevalence of gastric cancer remains speculative. Antimicrobial therapy is dominated by proton pump inhibitor triple therapy as first line therapy, with quadruple therapy as second rescue line therapy. The long-term consequences of the rising resistance to the 'key' antimicrobials are so far unknown, because few data are available on therapeutic outcomes in routine practice outside pharmaceutical trials.     

Gastric mucosa lesions induced by duodenogastric reflux increase penetration of N-[3H]-methyl-N-nitro-N-nitrosoguanidine into corpus mucosa of rats

The mucosal changes by which duodenogastric reflux may predispose to gastric cancer have not been fully clarified. In this study in rats, duodenal fluid was directed into the stomach through a gastroenterostomy (jejunal reflux, N = 29) or through the pylorus (pyloric reflux, N = 30) and compared with 30 controls. Twenty-four weeks later the stomach was exposed to N-[³H]methyl-N-nitro-N-nitrosoguanidine ([³H]MNNG). The corpus mucosa was examined for proliferating cells (bromodeoxyuridine labeled) and cells at risk of methyl-N-nitro-N-nitrosoguanidine-induced carcinogenesis (cells labeled with bromodeoxyuridine and [³H]MNNG). The number of double-labeled cells increased from 0.8 ± 0.1/mm mucosa in the control group to 5.2 ± 0.9 in the jejunal reflux group (P < 0.05) and 2.7 ± 0.5 in the pyloric reflux group (P < 0.05). An erosion or ulcer appeared at the gastroenterostomy in 52% of animals with jejunal reflux and 17% of those with pyloric reflux (P < 0.006). Within erosions the mean number of double-labeled cells was 9.6 ± 2.2 in the jejunal reflux group and 7.7 ± 4.8 in the pyloric reflux group, and significantly higher than in the nonlesion area of the mucosa (0.6 ± 0.2 and 0.8 ± 0.3). In erosions the distance between the gastric lumen and the proliferating cells was significantly shorter and the cell proliferation significantly higher than in the nonlesion area of the mucosa. We conclude that duodenogastric reflux increases the penetration of [³H]MNNG into the corpus mucosa of rats and also induces mucosa lesions, which further increase the penetration of [³H]MNNG into the corpus mucosa.     

Gastric Apoptosis and Helicobacter pylori Infection: an Intricate Matter

Central venous pressure (CVP) was measured in 142 patients with massivegastroduo denal haemorrhage. The normal range was found to be 55-135 mm H₂O using the mid-axillary line as the reference level. In 53 patients, a decreased CVP gave an earlier indication of hypovolaemia than did changes in arterial blood pressure (ABP) or pulse rate (PR).

In 32 patients an elevated CVP was the only sign indicating impending over-transfusion. There was no case of pulmonary congestion when the CVP was within the normal range.

CVP measurements were used as a safeguard against circulatory overloading during blood transfusion treatment of anaemic patients, making such therapy feasible even in patients with an elevated CVP. CVP measurements made it possible to estimate the rate of bleeding. Haemorrhage from a major artery was characterized by a bleeding rate of more than 600 ml per hour and/or a sudden decrease in CVP.     

Effect of Helicobacter pylori Eradication on 24-Hour Gastric pH and Duodenal Gastric Metaplasia

Published data on the regression of the extent of duodenal gastric metaplasia (DGM) after the eradication of Helicobacter pylori infection and the normalization of the organism-induced alterations in gastric physiology are scanty and controversial. Therefore, we decided to assess the circadian pattern of gastric acidity and the degree of DGM before and one year after H. pylori eradication in a group of duodenal ulcer patients. Fifteen consecutive H. pylori-positive patients with endoscopically proven duodenal ulcer were recruited for this study. The diagnosis of H. pylori infection was based on CLO-test and histology, and DGM was assessed on four bulb biopsies taken before and one year after H. pylori eradication. At the same time, gastric pH was measured by 24-hr continuous intraluminal recording. H. pylori eradication was ascertained by means of concomitant negative CLO-test and histology performed both four weeks after the end of the eradicating treatment and at the one-year endoscopic control. After successful cure, all patients discontinued any antiulcer medication. The mean 24-hr gastric pH was 1.7 ± 0.4 before and 1.6 ± 0.4 after one year of H. pylori eradication (P = 0.75). DGM improved in three cases, worsened in four cases, and was unchanged in eight cases at the one-year control (P = 0.87). No correlation was found between 24-hr gastric pH and DGM (P = NS) both at baseline and one year after eradication. Our results show that neither circadian gastric acidity nor DGM change significantly one year after H. pylori eradication in duodenal ulcer patients. Thus, the disappearance of H. pylori infection does not determine any increase in gastric pH and any reversal of gastric-type epithelium in the duodenum.     

One-week versus two-week furazolidone-based quadruple therapy as the first-line treatment for Helicobacter pylori infection in Iran

Background and Aim: Furazolidone‐based regimens for the eradication of Helicobacter pylori are low cost and effective although less tolerable. Our aim was to compare the efficacy and compliance of 1‐week furazolidone‐based quadruple therapy (furazolidone, amoxicillin, bismuth subcitrate, omeprazole; FABO) with 2‐week quadruple therapy using the same drugs. Methods: One hundred and fifty‐six consecutive patients with H. pylori related diseases were enrolled in our study. The patients were randomized into two groups of FABO1 and FABO2 groups receiving, 1 or 2 weeks' quadruple H. pylori eradication therapies, respectively, as follows: furazolidone (200 mg twice daily), amoxicillin (1 g twice daily), bismuth (240 mg twice daily) and omeprazole (20 mg twice daily). The χ² test was used to compare the efficacy of the therapies. Results: The per‐protocol eradication rate in FABO1 and FABO2 groups were 56/66 (84.8%) and 57/69 (82.6%), respectively. The intention‐to‐treat eradication rate was 56/78 (71.8%) in FABO1 group and 57/78 (73.1%) in FABO2 group. There was not any significant statistical difference between two groups. A significant decrease in compliance in FABO2 group was seen. Conclusion: This is an encouraging report showing a therapy with possible success in decreasing the duration of H. pylori infection as well as reaching the eradication rate of 80%.     

消化性溃疡和胃癌病人血清可溶性IL－2受体和纤维结合素的观察

用多克隆单克隆夹心ＥＬＩＳＡ法和单向扩散法测定溃疡病和胃癌患者血清可溶性白细胞介素２受体（ｓｏｌｕｂｌｅＩＬ－２ｒｅｃｅｐｔｏｒｓ，ＳＩＬ－２Ｒ）和纤维结合素（ｆｉｂｒｏｎｅｃｔｉｎ，ＦＮ）。结果显示溃疡病血清ＳＩＬ－２Ｒ和ＦＮ分别为２１２．９２±１２２．２７Ｕ／ｍｌ和２９８．０９±３３．４６ｎｇ／ｍｌ，胃癌分别为５５９．２７±２３４．０１Ｕ／ｍｌ和３３６．６５±３９．２１ｎｇ／ｍｌ。与正常人２４０．０±９７．０７Ｕ／ｍｌ和３２３．６４±２８．２１ｎｇ／ｍｌ比较，胃癌患者ＳＩＬ－２Ｒ水平明显升高（Ｐ＜０．００１），其中肿瘤有转移者低于无转移者（Ｐ＜０．０５）。这表明血清ＳＩＬ－２Ｒ和ＦＮ检测可做为胃癌病人病情监测和判断预后的指标，亦可用以签别良性和恶性溃疡。     

Endoscopic Urease Sensor System for Detecting Helicobacter pylori on Gastric Wall Using a pH-sensitive Field Effect Transistor

An endoscopic tube-tip type urease sensor was developed for the purpose of on-site detection of Helicobacter pylori (H. pylori) using a pH-sensitive field effect transistor (pH-FET). The sensor is composed of an endoscopic-tube connected to a feed pump with a urea solution and a pH-FET attached to a sensor holder at the open end of the tube. The urease activity on the gastric wall can be measured by bringing the sensor into contact with the gastric wall just after replacing gastric juice with the urea solution. The presence of H. pylori causes a pH change in the urea solution inside the sensor holder in 20 seconds due to the strong urease activity of this bacterial species. After measurement, the sensor is detached from the wall, and washed with urea solution by turning on the urea pump. A measurement at one site is completed within 30 seconds. Repetition of the procedure makes multi-site measurements possible. In preliminary evaluations, it was found that clinical sensitivity and specificity were 89% and 86%, respectively, using standard bacteriological testing results as a reference.     

Helicobacter pylori eradication in the healing of atrophic gastritis: A one-year prospective study

Objective. Whether gastric atrophy or intestinal metaplasia heals after successful treatment of Helicobacter pylori (H. pylori) infection is still a matter of controversy. The aim of this article was to clarify whether, after one year, H. pylori eradication is associated with healing in glandular atrophy and intestinal metaplasia in the corpus and antrum. Material and methods. Ninety-two H. pylori-positive peptic ulcer patients with atrophic gastritis (panatrophy, antral or corpus predominant) participated in the baseline study, 1-year prospective follow-up data being available from 76 patients. Mean age was 58±12.6 years (mean±SD) and the male/female ratio 2/1. The patients participated in an H. pylori eradication study in which they randomly received active eradication therapy. Endoscopy was performed before H. pylori eradication therapy and after 8 and 52 weeks, with specimens examined according to the Sydney system. Results. Of the 92 patients, 8 (9%) had panatrophy, 58 (63%) had antral- and 26 (28%) had corpus-predominant atrophic gastritis. After H. pylori eradication, the mean atrophy score declined in patients with antral-predominant atrophy from 1.5 (mean) to 0.7 (p<0.05), in corpus-predominant atrophy from 1.7 to 0.2 (p=NS) and in patients with panatrophy from 1.2 to 0.8 (p=NS). Atrophy healing was seen in 55% of antral-predominant atrophy patients who had successful H. pylori eradication.The mean antral atrophic score in one year declined in patients with duodenal ulcer (from 1.0 mean to 0.4) whereas it remained the same (1.3) in those with gastric ulcer (p<0.05). Conclusions. Atrophy can diminish or even disappear, especially in the antrum, during a 1-year follow-up after eradication of infection. Atrophy progression seems milder in patients with duodenal ulcer than in patients with gastric ulcer.     

Omeprazole plus Amoxicillin for Cure of Helicobacter pylori Infection Factors Influencing the Treatment Success

Labenz J, Leverkus F. Börsch G. Omeprazole plus amoxicillin for cure of Helicobacter pylori infection. Factors influencing the treatment success. Scand J Gastroenterol 1994;29:1070-1075.

Background: Omeprazole plus amoxicillin may cure Helicobacter pylori infection. However, the published results vary rather widely, and the factors influencing the treatment success remain unclear.

Methods: Four hundred and twenty-three H. pylori-positive patients were treated with 1- or 2-week regimens comprising 411 mg or 80 mg omeprazole and amoxicillin in 11 prospective protocols. A complete set of data was available for 405 patients (ulcer disease, n = 383; dyspepsia, n = 22) and was submitted to uni- and multi-variate statistical analyses to elucidate the factors affecting the cure rates of the infection; 18 patients were lost to follow-up.

Results: The overall proportion of H. pylori cure was 76%. Insufficient compliance (p < 0.001), a short duration of treatment (p < 0.001), smoking (p = 0.003), and omeprazole pretreatment (p = 0.041) were the significant independent factors predicting treatment failure, whereas advanced age (p = 0.002), high scores of grade and of activity of gastritis (p = 0.035 and p = 0.019. respectively), and gastric ulcer disease (p = 0.058) were independent factors predicting treatment success. Conclusions: Several patient- and therapy-related factors diminish or increase the rate of H. pylori cure obtained by omeprazole/amoxicillin. These should be considered in future studies comparing different treatment regimens for curing H. pylori infection and also when designing treatment regimens applicable for routine clinical practice.     

Changing epidemiology of Helicobacter pylori in Asia

As in developed societies, the prevalence of Helicobacter pylori has declined rapidly in Asia. This has been shown in both seroprevalence-based and endoscopy-based studies. While the decline in the incidence of gastric cancer has now been observed, a decrease in peptic ulcer disease has not been so clearly evident. This apparent paradox can be explained by an increase in non-H. pylori associated ulcers - such as those related to non-steroidal anti-inflammatory drugs or idiopathic ulcers. The increase of gastroesophageal reflux disease in Asia has been widely observed and commented on and its relationship to the decline in H. pylori speculated upon. However there have been few conclusive studies from Asia on this subject. While the improved diagnosis and elimination of H. pylori has contributed to its decline, a more basic change involving large segments of the Asian population must be responsible. An improvement in hygiene and living conditions that results from more affluent Asian societies is thought to be a possible cause.     

Significance of Helicobacter Pylori Infection in Human Peptic Ulcers

Abstract: Experimental studies have suggested that the continuous administration of 0.02% NH, solution, induced by Helicobacter pylori (H, Pylori), leads to a glandular atrophy of the gastric mucosa, and adversely affects healing of acetic acid ulcers in rats, because of the suppression of cell kinetics of the regenerative epithelial cells and connective tissues at ulcer margins. To visualize the distribution of H. pylori in human gastric mucosa, a phenol red dye spraying endoscopy was performed in 45 patients with gastric ulcers, and 43 patients with duodenal ulcers, who were medicated with a full dose of H₂-blocker until ulcer healing, and with half doses thereafter. In the H. pylori negative cases, 8 (88.9%) of 9 gastric ulcers healed within 3 months after medication, with no relapse discernible up to 6 months after healing of the preceding ulcer. The relapse rate was 25% up to 12 months after ulcer healing. In contrast, only 22 (66.1%) of 36 gastric ulcers healed within 3 months after medication in the H. pylori positive cases. The relapse rate was 12.5% up to 3 months, 30.4% UP to 6 months and 63.6% up to 12 months after ulcer healing. In addition, all 6 duodenal ulcers healed within 2 months after medication in the H. pylori negative cases, with no relapse discernible up to 12 months after healing of the preceding ulcer. In contrast, in the H. pylon positive cases, 20 (53.1%) of 37 duodenal ulcers healed within 2 months, and the relapse rate was 14.3%, 33.3%, and 66.7% up to 3, 6 and 12 months respectively after healing of the preceding ulcer. These data suggest that H. pylori is likely to interfer with ulcer healing, and promotes peptic ulcer relapse.     

Heterotopic Gastric Mucosa in Middle Esophagus Complicated with Esophageal Ulcers

Heterotopic gastric mucosa (HGM) of esophagus, primarily occurring in cervical esophagus, is usually asymptomatic. A healthy woman (mid-40s) with postprandial heartburn was diagnosed with middle esophageal HGM and esophageal ulcers by esophagogastroduodenoscopy. Using 8-channel pH monitoring, a sensor near the HGM area detected postprandial acid phase (pH 3-4), while areas adjacent to the proximal and distal sensors were neutral, suggesting acid secretion from the HGM. A biopsy showed fundic gland tissue expressing H⁺/K⁺-ATPase and pepsinogen-I. Oral vonoprazan improved the clinical symptoms and endoscopic findings. This is the first report using 8-channel pH monitoring to diagnose extremely rare middle esophageal HGM.