Takao Horiuchi

Disappearance of Hyperplastic Polyps in the Stomach after Eradication of Helicobacter pylori: A Randomized, Controlled Trial

Although the malignant potential of hyperplastic gastric polyps was originally denied, a low risk for carcinomatous conversion (1.5% to 3%) is now recognized [1, 2]. Patients with gastric polyps may present with bleeding of the upper gastrointestinal tract, abdominal pain, or gastric outlet obstruction [3]. Therefore, most endoscopists agree that large gastric polyps or polyps associated with complications should be removed endoscopically or surgically [4]. In a previous investigation of the relation of Helicobacter pylori infection to various gastric polyps [5], we found that H. pylori infection was closely associated with hyperplastic polyps and that H. pylori was present in 100% of hyperplastic polyps. This relation is supported by two case reports [6, 7] indicating that clearance and eradication of H. pylori led to the disappearance of hyperplastic polyps. We also reported that 15 polyps (8 to 26 mm in diameter) in a patient with hyperplastic polyps had disappeared by 12 months after eradication of H. pylori [8]. However, these observations were made in only a few patients. We conducted a randomized, controlled trial to see whether hyperplastic polyps would disappear after eradication of H. pylori. Methods Patients We enrolled 35 patients (19 men and 16 women; age range, 29 to 75 years) with H. pylori infection and hyperplastic polyps of the stomach diagnosed by endoscopic biopsy. These patients were randomly assigned to one of two groups and sequentially numbered. In the treatment group (n = 17), patients received a proton-pump inhibitor (omeprazole or lansoprazole), amoxicillin, and either clarithromycin or ecabet sodium; in the control group [n = 18], patients had endoscopic examination but did not receive treatment. Our criteria for hyperplastic gastric polyps were 1) hyperplasia of the foveolar epithelium on histologic examination and 2) infiltration of inflammatory cells into the stroma in biopsy specimens [9]. Polyps were diagnosed by two blinded pathologists. Two patients who had hyperplastic polyps 2 mm or less in diameter and 1 patient who did not have H. pylori infection were excluded. Written, informed consent was obtained from each study participant in accordance with the Declaration of Helsinki (1964) and revisions thereof. The protocol was planned according to the guidelines of the H. pylori eradication trial approved by the committee of the Japanese Society of Gastroenterology. If polyps progressed and were accompanied by malignant transformation, the study was stopped and the polyps were removed endoscopically. After our study was completed, treatment for controls and for patients in whom the first attempt at eradication had failed was proposed in the form of endoscopic removal of polyps or eradication of H. pylori. Data entry and data analyses were done by code so that treatment assignments remained concealed. Compliance with treatment was assessed by pill count. Endoscopy and Assessment of Eradication of Helicobacter pylori Patients in the treatment group underwent endoscopy 1 to 3, 7 to 9, and 12 to 15 months after the end of treatment. On each occasion, biopsy specimens were taken from the same areas (three from the antrum and three from the body, exclusive of polyps) for culture, rapid urease testing, and histologic examination. Controls underwent endoscopy 12 to 15 months after enrollment. The H. pylori cultures were done by using a modified Skirrow agar with 10% horse blood and were incubated for 5 to 7 days at 37C in a microaerobic atmosphere. We identified H. pylori by colony morphology and biochemical tests, such as urease, catalase, and oxidase activity tests. Rapid urease testing was done with the CLO test (Delta West Pty. Ltd., Bentley, Australia), and the result was considered positive if the color changed after 24 hours. Biopsy specimens for histologic examination were immediately placed in 10% neutral buffered formalin, embedded in paraffin wax, stained with hematoxylin and eosin and with Giemsa, and evaluated for the presence of H. pylori. After patients had fasted overnight, the 13C-urea breath test was done by using 100 mg of urea per 100 mL of 13C-urea solution. The test result was considered negative if the excess delta 13CO2/sup 12 CO2 after 15 minutes was less than 5 parts per million. The presence of H. pylori was determined at each endoscopic examination and was defined by positive results on at least two of four tests: culture, urease testing, histologic examination, and urea breath testing. Eradication of H. pylori was confirmed by negative results on all four tests 1 to 3 months after the end of treatment and at each endoscopic examination. Endoscopists were blinded to treatment assignments. The size and number of polyps were measured at each endoscopic examination by using biopsy forceps (FB-25K, Olympus, Tokyo, Japan) placed near the polyp (open size, 6 mm in diameter; closed size, 2 mm in diameter), and the endoscopic film data on the disappearance and regression of polyps were reviewed independently by two blinded endoscopists. Histologic Examination, Gastrin Levels, and Titer of IgG to Helicobacter pylori Histologic diagnosis of the biopsied mucosa of the antrum and body was made by two blinded pathologists. The severity of activity, inflammation, atrophy, and metaplasia was graded on a scale from 1 to 4 and expressed by using the histologic index according to the updated Sydney System [10]: 1 = normal, 2 = mild, 3 = moderate, and 4 = marked. The serum gastrin level for each patient in both study groups was measured under fasting conditions before the start of treatment and 1, 3, and 12 months after the end of treatment by using radioimmunoassay (GASTRIN-RIA KIT II, Dinabot Co. Ltd., Tokyo, Japan [normal range, 37 to 172 pg/mL]). The titer of IgG to H. pylori was measured by using an enzyme immunoassay kit (HEL-pTEST II, AMRAD Operations Pty. Ltd., Victoria, Australia [range indicating negativity, <30 U/mL]) in serum specimens obtained before treatment and 1, 3, and 12 months after the end of treatment. Laboratory analyses were done by code so that treatment assignments remained concealed. Statistical Analysis Pretreatment clinical and laboratory data were analyzed by using the unpaired t-test (for age), the Wilcoxon rank-sum test (for number and size of polyps, histologic findings, serum gastrin levels, and titer of IgG to H. pylori), and the Fisher exact test (for sex, coexisting disease, and distribution of polyps). Post-treatment data were analyzed by using the Fisher exact test (for rates of disappearance, regression of polyps, and eradication of H. pylori) and the Wilcoxon rank-sum test (for histologic and laboratory data). P values less than 0.05 were considered statistically significant. All statistical analyses were done by using STATVIEW software (version 4.02, Japanese edition, Nankodo, Inc., Tokyo, Japan). Results The treatment and control groups were similar with respect to number of patients; age; sex; coexisting disease; number, size, and distribution of polyps; histologic findings; serum gastrin levels; and titers of IgG to H. pylori (Table 1). All patients in both groups completed the entire study protocol and had coexisting chronic atrophic gastritis. Table 1. Baseline Characteristics of the Treatment and Control Groups* During the follow-up period in the control group, no hyperplastic polyps regressed or disappeared (Table 2). Polyps enlarged or increased in number in 3 of the 18 patients. However, no polyps in the control group were accompanied by malignant transformation. Table 2. Results of Analyses of the Treatment and Control Groups In the treatment group (Table 2), H. pylori was successfully eradicated without serious side effects in 15 of 17 patients (88% [95% CI, 64% to 98%]), and polyps disappeared in 12 of 17 patients (71% [CI, 44% to 89%]). In 12 of the 15 patients (80% [CI, 52% to 95%]) in whom eradication was successful, disappearance of the polyps and histologic confirmation of a reduction of the inflammatory cell infiltration in the gastric mucosa were seen. The polyps had disappeared in these 12 patients by 3 to 15 months (average, 7.1 1.2 months) after the end of treatment. Smaller polyps tended to disappear within a few months. However, in the 2 patients in whom H. pylori was not eradicated, no polyps showed regression at 12 to 15 months after the end of treatment and no diminution of the inflammatory cell infiltration in the gastric mucosa was seen. The rates of disappearance of polyps in the treatment group were significantly higher than those in the control group (P < 0.001). In patients who received eradication therapy, a significant decrease was seen in serum gastrin levels and titers of IgG to H. pylori compared with those in patients who did not receive eradication therapy (P < 0.001 for serum gastrin levels; P < 0.002 for titers of IgG to H. pylori) (Table 2). Discussion In our study, the disappearance of hyperplastic polyps with histologic confirmation of a reduction in the inflammatory cell infiltration in the gastric mucosa was seen in 12 of the 15 patients (80%) in whom eradication of H. pylori was successful. The polyps had disappeared in the 12 patients by 3 to 15 months (average, 7.1 1.2 months) after the end of treatment. However, none of the polyps in any of the controls or in either of the patients in whom H. pylori was not eradicated showed regression. These results strongly suggest that eradication of H. pylori leads to regression and disappearance of hyperplastic gastric polyps. The patients in both study groups had high serum gastrin levels (251 pg/mL in the treatment group and 299 pg/mL in the control group) at baseline. Bonilla and associates [11] also reported that patients with hyperplastic polyps had high serum gastrin levels. Because gastrin has a trophic effect on the enterochromaffin-like cells of the gastric mucosa [12] and colonic mucosa [13], an elevated plasma gastrin level is of intere

Helicobacter pylori DNA in Drinking Water in Japan

Helicobacter pylori has been detected in drinking water in Peru and Sweden, suggesting the possibility of water‐borne transmission. To date there have been few reports of H. pylori being detected in water; one was of the ureA gene of H. pylori in wells and springs in rural Japan. We examined water sampled in or near urban areas of Japan for H. pylori DNA by three assays using the polymerase chain reaction (PCR). Near Tokyo, samples were obtained: 10 of tap water, 6 of well water, 10 of river water, and 10 of sea water. Samples were filtered with membranes with 0.05‐ or 0.22‐μm pores, which bacterial cells are caught by. Bacterial nucleic acids were extracted and purified and the PCR was done to amplify adhesin specific for H. pylori and the ureA gene, if present. Real‐time PCR that measured the yield in terms of fluorescence was done with primers for 16S rRNA. None of the samples of tap, river, or sea water contained adhesin, ureA or 16S rRNA. None of the 6 samples of well water contained adhesin or ureA, but 2 of the 6 samples contained 16S rRNA. Some of the users of the well had had H. pylori infection in the past H. pylori DNA was detected in well water and the users had been infected, so water‐borne transmission via well water may occur even in towns in Japan.

Changes in serum pepsinogen, gastrin, and immunoglobulin G antibody titers in Helicobacter pylori-positive gastric ulcer after eradication of infection

There are no studies of changes in immunoglobulin G (IgG) titers to Helicobacter pylori, serum pepsinogen, and gastrin in patients with H. pylori-positive gastric ulcers. We investigated the effect of therapy for H. pylori-positive gastric ulcer on IgG titers to H. pylori, serum pepsinogen I and II, and gastrin. Thirty-six patients with H. pylori-positive gastric ulcer were treated with lansorazole and antibiotics for 2 weeks. Serum pepsinogen I and II concentrations, serum gastrin, and IgG titers to H. pylori were measured before treatment and then at 4 and 12 weeks after stopping the treatment. The presence or eradication of H. pylori was determined using the rapid urease test and by histologic H. pylori staining. For 19 patients in whom H. pylori had been successfully eradicated, the pepsinogen I/II ratio increased, pepsinogen II levels decreased, and the anti-H. pylori IgG decreased compared with the results from before therapy and with those from 4 and 12 weeks after therapy. Gastrin levels decreased compared with pretreatment results and those from 4 weeks after the end of treatment. In 17 patients in whom the therapy failed to eradicate H. pylori infection, there were no sequential significant changes in the pepsinogen I/II ratio or in the levels of pepsinogen I, pepsinogen II, anti-H. pylori IgG, and gastrin. A decrease in the serum levels of the IgG antibody to H. pylori and gastrin and also an increase in the pepsinogen I/II ratio could be used as predictors for the eradication of H. pylori infection in gastric ulcer.