Ck Ching

A retrospective and prospective study on the safety of discharging selected patients with duodenal ulcer bleeding on the same day as endoscopy

BACKGROUND Low risk of rebleeding has been observed in patients with gastrointestinal bleeding due to peptic ulcer without high-risk stigmata of recent hemorrhage. We aimed to evaluate the safety and acceptability of an aggressive early discharge policy in those patients admitted with upper gastrointestinal bleeding due to duodenal ulcers without high-risk stigmata of recent hemorrhage. METHOD Retrospective analysis was carried out in bleeding ulcer patients less than 60 years of age with stable vital signs and no stigmata or only flat spots on endoscopy. A prospective study was then performed that included only duodenal ulcer patients less than 60 years of age with stable vital signs, no concomitant serious medical illness, and no stigmata of recent hemorrhage. These patients were discharged on the same day that endoscopy was performed. RESULTS During a period of 18 months, 72 patients satisfied the criteria in the retrospective study. The mean hospital stay was 1.4 days (range, 1 to 5). There were no episodes of rebleeding nor significant drops in hemoglobin level 2 weeks after discharge (10.8 gm/dL +/- 1.4 vs 11.0 gm/dL +/- 1.5). Seventy-five patients were recruited into the prospective study. None of them had rebleeding nor significant drops in hemoglobin 1 week after discharge (12.1 gm/dL +/- 1.8 vs 11.7 gm/dL +/- 2.5). CONCLUSION We conclude that patients with gastrointestinal bleeding who have clean-based duodenal ulcers and are stable on admission can be safely discharged on the same day as endoscopy.

Does treatment of Helicobacter pylori with antibiotics alone heal duodenal ulcer? A randomised double blind placebo controlled study.

BACKGROUND: Treatment of Helicobacter pylori infection prevents duodenal ulcer relapse. It has not been established if treatment of the infection heals duodenal ulcer. AIM: To test the hypothesis that treatment of the infection was associated with healing of duodenal ulcer. METHODS: A randomised, double blind placebo controlled trial was performed to study the efficacy of an antibiotic only regimen consisting of 300 mg metronidazole, 500 mg amoxycillin, and 250 mg clarithromycin, each given four times daily for two weeks, in the healing of duodenal ulcer as assessed by endoscopy. Symptoms were controlled with acetaminophen and antacids. RESULTS: Of 100 consecutive patients with endoscopically established duodenal ulcer, 97 with positive rapid urease test on antral biopsy specimens were admitted into the study and 81 completed the trial. Of these, 40 were randomised to receive antibiotics and 41 to receive placebo. Treatment with antibiotics resulted in 92.5% (95% confidence interval (95% CI) 84.3-100) healing at four weeks and 100% at eight and 12 weeks; the corresponding healing rates for placebo treatment were respectively, 36.6%, 61%, and 63.4% (95% CIs 21.8-51.3, 46.0-75.9, and 48.7-78.2 respectively). The differences between the two treatment groups were significant at p < 0.001 at each time point and by life table analysis. Clearance of H pylori as assessed by urease test on antral biopsy specimens at four weeks and eradication of the organism as determined by 13C-urea breath test at eight weeks were achieved in 85% and 62.5% of patients respectively. Duodenal ulcer healed at four weeks in 87.2% and 86.2% (95% CIs 76.7-97.7 and 73.7-98.8) of patients in whom H pylori clearance or eradication, was achieved, versus 42.9% and 51.9% (95% CIs 27.9-57.8 and 38.3-65.5; p < 0.001 and < 0.003 respectively) in whom these processes failed. Stepwise discriminant analysis on 32 clinical, personal, and endoscopic characteristics as well as H pylori clearance and eradication identified H pylori clearance as the most discriminative variable for the healing of duodenal ulcer at four weeks, followed by ulcer depth and eradication of the organism. CONCLUSIONS: Treatment with an antibiotic only regimen was effective for the healing of duodenal ulcer, and clearance as well as eradication of H pylori contributed significantly to the healing. The results constituted the strongest evidence to date that H pylori infection was aetiologically related to duodenal ulceration, and support the concept of treating duodenal ulcer associated with H pylori as an infection and relieving its symptoms with acid reducing agents such as antacids.

Prevalence of metronidazole resistant Helicobacter pylori strains among Chinese peptic ulcer disease patients and normal controls in Hong Kong.

BACKGROUND--A study was conducted to evaluate the prevalence of metronidazole resistant Helicobacter pylori strains among the Chinese in Hong Kong. The efficacy of the triple therapy that contains metronidazole as one of the anti-microbial agents in eradication of the metronidazole susceptible and the metronidazole resistant strains was also assessed. METHODS--Culture for H pylori was attempted from antral biopsy specimens of 70 peptic ulcer and 51 control subjects. Successfully cultured H pylori strains were tested for metronidazole susceptibility. Twenty six peptic ulcer disease subjects who had received a course of triple therapy were also reassessed four to six weeks later for successful eradication of H pylori infection. RESULTS AND CONCLUSIONS--H pylori was successfully cultured from antral biopsy specimens in 69 of 80 (86%) of the infected subjects. The overall metronidazole resistance rate was 53.5% (37 of 69). There was a significantly higher metronidazole resistance rate among H pylori isolates from the asymptomatic controls (20 of 25) than the peptic ulcer disease subjects (17 of 44) (p = 0.0007). Twenty three of 32 (73%) women and 14 of 37 (38%) men harboured the metronidazole resistant strains. There was no sex or age difference as far as the prevalence of metronidazole resistant strains were concerned within each study group. Pre-treatment metronidazole susceptible H pylori were significantly more likely to respond to the triple therapy used than those with the metronidazole resistant ones (14 of 15 v five of 10) (p = 0.021).

Overexpression of protein kinase C-β1 isoenzyme suppresses indomethacin-induced apoptosis in gastric epithelial cells

BACKGROUND & AIMS We have previously reported that nonsteroidal anti-inflammatory drugs (NSAIDs) could induce apoptosis of gastric epithelial cells both in vivo and in vitro. This study investigated the role of protein kinase C (PKC) isoforms in the regulation of NSAID-induced apoptosis. METHODS Protein levels of 12 PKC isoforms in AGS cells, in the presence or absence of indomethacin, were determined by Western blot. The effect of PKC-beta1 overexpression by transfection with its complementary DNA (cDNA) on indomethacin-induced apoptosis and apoptosis-related genes, including p53, p21(waf1/cip1), and c-myc, was further investigated. RESULTS Treatment with indomethacin decreased the abundance of PKC-beta1 and increased that of PKC-beta2, eta, and epsilon, but did not alter the expression of PKC alpha, gamma, zeta, delta, iota, and micro. Overexpression of PKC-beta1 attenuated the apoptotic response of AGS cells to indomethacin, associated with overexpression of p21(waf1/cip1) in both messenger RNA and protein levels. Inhibition of PKC-beta1-mediated overexpression of p21(waf1/cip1) by its antisense cDNA partially reduced the antiapoptotic effect of PKC-beta1. CONCLUSIONS Indomethacin-induced apoptosis in gastric cancer cells is partly mediated by differential regulation of PKC isoform expression. Enhanced expression of exogenous PKC-beta1 protects against indomethacin-induced apoptosis through up-regulation of p21(waf1/cip1).

Differential Helicobacter pylori infection rates in two contrasting gastric cancer risk regions of South China

Background: Carriers of Helicobacter pylori are believed to have a three‐ to six‐fold increased risk of developing gastric cancer. We have recently conducted a simultaneous cross‐sectional population study on the prevalence of H. pylori infection in a cohort of asymptomatic adult volunteers in two contrasting gastric cancer risk regions of South China, Hong Kong and Changle of Fujian. Their mean annual gastric cancer mortality has been approximately 7.5 and 75/100 000 population, respectively, since the beginning of the last decade. The aim of this study was to evaluate if H. pylori prevalence bears any relationship to gastric cancer mortality rates in these two southern regions of China.

Non-steroidal anti-inflammatory drug-induced apoptosis in gastric cancer cells is blocked by protein kinase C activation through inhibition of c- myc

SummaryApoptosis plays a major role in gastrointestinal epithelial cell turnover, ulcerogenesis and tumorigenesis. We have examined apoptosis induction by non-steroidal anti-inflammatory drugs (NSAIDs) in human gastric (AGS) cancer cells and the role of protein kinase C (PKC) and apoptosis-related oncogenes. After treatment with aspirin or indomethacin, cell growth was quantified by MTT assay, and apoptosis was determined by acridine orange staining, DNA fragmentation and flow cytometry. The mRNA and protein of p53, p21waf1/cip1 and c-myc was detected by Northern and Western blotting respectively. The influence of PKC on indomethacin-induced apoptosis was determined by co-incubation of 12-O-tetradecanoylphorbol 13-acetate (TPA). The role of c-myc was determined using its antisense oligonucleotides. The results showed that both aspirin and indomethacin inhibited cell growth and induced apoptosis of AGS cells in a dose- and time-dependent manner, without altering the cell cycle. Indomethacin increased c-myc mRNA and protein, whereas p53 and p21waf1/cip1 were unchanged. Down-regulation of c-myc by its antisense oligonucleotides reduced apoptosis induction by indomethacin. TPA could inhibit indomethacin-induced apoptosis and accumulate cells in G2/M. Overexpression of c-myc was inhibited by TPA and p21waf1/cip1 mRNA increased. In conclusion, NSAIDs induce apoptosis in gastric cancer cells which may be mediated by up-regulation of c-myc proto-oncogene. PKC activation can abrogate the effects of NSAIDs by decreasing c-myc expression.

Triple therapy for Helicobacter pylori eradication is more effective than long-term maintenance antisecretory treatment in the prevention of recurrence of duodenal ulcer: a prospective long-term follow-up study.

: The effectiveness of Helicobacter pylori eradication treatment and long term acid suppression maintenance in the natural course of duodenal ulcer has not been directly compared.

Differential apoptosis by indomethacin in gastric epithelial cells through the constitutive expression of wild-type p53 and/or up-regulation of c-myc.

Nonsteroidal anti-inflammatory drug (NSAID)-induced apoptosis is considered to be an important mechanism in the antineoplastic effects and damage produced by the drugs in the gastrointestinal tract. In this study, two different gastric cancer cell lines, MKN28 (mutant-type p53) and AGS (wild-type p53), were compared as to growth inhibition, apoptosis, and cell cycle and apoptosis-related gene expression in response to indomethacin treatment. Cell growth was measured by MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Apoptosis was characterized by acridine orange staining and DNA fragmentation, and cell cycle kinetics by flow cytometry. The mRNA and protein levels of p53, p21waf1/cip1, and c-myc were determined by Northern and Western blotting. The results showed that indomethacin initiated growth inhibition and apoptosis in both cell lines without cell cycle shifting. AGS cells were more sensitive to growth inhibitory activity and apoptosis of indomethacin than MKN28 cells. In MKN28 cells, the levels of p53, p21waf1/cip1, and c-myc mRNA remained unchanged over the 24-hr treatment with indomethacin, but the p53 protein level was elevated after 4 hr. There was no change in the p21waf1/cip1 and c-myc protein levels in the MKN28 cells. In AGS cells, a progressive increase in c-myc mRNA and protein levels was noted, while p53 and p21waf1/cip1 remained unchanged. It can be concluded that wild-type p53 and/or up-regulation of c-myc is associated with indomethacin-mediated differential apoptosis in gastric epithelial cells.

Differential north to south gastric cancer-duodenal ulcer gradient in China

There are suggestions that duodenal ulcer protects individuals from gastric cancer and that rice is ulcerogenic while wheat is gastro‐protective. We aimed to examine the relationship of gastric cancer, duodenal and gastric ulcers in different geographical regions in China and identified dietary risk factors for duodenal ulcer and gastric cancer. The prevalence of peptic ulcer and gastric cancer among symptomatic patients in eight major cities, four each from the north and the south representing all the six defined regions of China were studied. Endoscopy and case records over a 10 year period were reviewed and cases of confirmed duodenal and gastric ulcer and gastric cancer, together with the total number of endoscopies performed per year, were recorded. Rates were expressed as cases/1000 endoscopies. Results were compared to another epidemiological study on diet and mortality in the same regions in China conducted at the same time. Duodenal ulcer rates were 2.4‐fold higher in southern China than northern China, whereas gastric cancer rates were 1.6‐fold higher in the north than in the south. Correlation studies showed for the first time an inverse linear relationship between the gastric cancer rates and the duodenal ulcer rates (r=‐0.8076, P=0.015), as well as the duodenal ulcer: gastric ulcer ratios (r=‐0.9133, P=0.002). Gastric ulcer rates were higher in southern China but did not correlate with the gastric cancer rates (r=0.1455, P=0.731). Duodenal ulcer rates were found to be related to daily rice intake (r=0.8554, P=0.029) and inversely related to daily wheat flour intake (r=‐0.8472, P=0.033). Gastric cancer rates were not related to any dietary risk factors tested. We concluded there was an inverse relationship between gastric cancer rates and duodenal ulcer rates. Although duodenal ulceration and gastric cancer are both linked to Helicobacter pylori infection, the findings of this study indicate independent additional aetiological factors for the pathogenesis of these conditions. Dietary factors such as rice or wheat intake may play a role.

Helicobacter pylori epidemiology in relation to peptic ulcer and gastric cancer in South and North China

Abstract Peptic ulcer disease is twice as common in people living in South China when compared with those in North China. However, the gastric cancer rate in North China is three times that of South China. The overall Helicobacter pylori prevalence rate is similar in North and South China populations and it is higher than Caucasians living in Western societies. However, there is a significantly higher prevalence of H. pylori seropositivity among those who live in the high gastric cancer areas of China. On the other hand, there is no significant difference in the H. pylori positive rate in the peptic ulcer disease patients between the two regions of China. Other permissive/associated co‐factors in the development of peptic ulcer disease or gastric cancer remain unknown at this stage.