Clinical characteristics and associated factors of Japanese patients with adenocarcinoma of the esophagogastric junction: a multicenter clinicoepidemiological study.

Gastroesophageal reflux disease-related diseases, such as Barrett's esophagus and adenocarcinoma of the esophagogastric junction (AEGJ), are believed to occur less frequently in Asia than in Western countries. However, the number of reported cases is increasing, yet little is known regarding the epidemiology of AEGJ in Japan. The primary study aim is to investigate the clinicoepidemiological characteristics of AEGJ. The secondary aim is to identify factors associated with it. In the 6.5 years between January 2008 and June 2014, we reviewed 88,199 esophagogastroduodenoscopy (EGD) reports and associated medical records (Study 1). We conducted a case-control study to identify factors associated with AEGJ (Study 2). Control subjects were randomly selected and age and sex matched from among subjects who underwent EGD during medical evaluations. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using an unconditional logistic regression method. During the study period, 83 patients with AEGJ (72 men and 11 women; mean age 68 years) were diagnosed. Six cases were Siewert type I and 77 were type II. The incidence rate of AEGJ was 0.6-1.7/100,000 person-years. Compared with the 101 control subjects, obesity (body mass index ≧ 25 kg/m2; [OR = 2.82; 95% CI: 1.13-7.01]) was associated with AEGJ. The incidence rate of AEGJ is lower in Japan than in Western countries, but associated factors similar to those in Western patients were detected, including obesity, a hiatal hernia, smoking, and the male sex.

Identification of serum miRNAs as novel non-invasive biomarkers for detection of high risk for early gastric cancer.

BACKGROUND: Many micro-RNAs (miRNAs) are differentially expressed in Helicobacter pylori-infected gastric mucosa and in gastric cancer tissue and previous reports have suggested the possibility of serum miRNAs as complementary tumour markers. The aim of the study was to investigate serum miRNAs and pepsinogen levels in individuals at high risk for gastric cancer both before and after H. pylori eradication. METHODS: Patients with recent history of endoscopic resection for early gastric cancer and the sex- and age-matched controls were enrolled. Serum was collected from subjects before or after eradication and total RNA was extracted to analyse serum levels of 24 miRNAs. Serum pepsinogen (PG) I and II levels were measured using enzyme-linked immunosorbent assay kits. RESULTS: Using miR-16 as an endogenous control, the relative levels of miR-106 and let-7d before and after H. pylori eradication and miR-21 after eradication were significantly higher in the high-risk group than in the controls. H. pylori eradication significantly decreased miR-106b levels and increased let-7d only in the control group. After eradication, the combination MiR-106b with miR-21 was superior to serum pepsinogen and the most valuable biomarker for the differentiating high-risk group from controls. CONCLUSION: Serum miR-106b and miR-21 may provide a novel and stable marker of increased risk for early gastric cancer after H. pylori eradication.

Efficacy of adding sodium alginate to omeprazole in patients with nonerosive reflux disease: a randomized clinical trial.

Nonerosive reflux disease (NERD) is the most common form of gastroesophageal reflux disease. Patients with NERD have a lower response rate to proton pump inhibitors (PPIs) than patients with erosive esophagitis when gauged from relief of heartburn. Sodium alginate decreases the acidity of refluxate and protects the esophageal mucosa. However, whether the addition of sodium alginate to PPI therapy can improve NERD symptoms remains unknown. Accordingly, the aim of this study was to evaluate the efficacy of adding sodium alginate to basal PPI therapy for NERD. Patients who had experienced heartburn on at least 2 days per week during the 1-month period before entering the study and had no endoscopic mucosal breaks (grade M or N according to Hoshihara's modification of the Los Angeles classification) were randomized to one of two treatments for 4 weeks: omeprazole (20 mg once daily) plus sodium alginate (30 mL four times a day) (group A) or omeprazole (20 mg once daily) alone (group B). Eighty-seven patients were enrolled, and 76 patients were randomly assigned to group A (n = 36) or group B (n = 40). Complete resolution of heartburn for at least 7 consecutive days by the end of treatment was significantly more common in group A (56.7%) than in group B (25.7%). One patient from group A had mild drug-related diarrhea that was not clinically serious. In conclusion, omeprazole combined with sodium alginate was better than omeprazole alone in Japanese patients with NERD.

Generation of dyspeptic symptoms by direct acid infusion into the stomach of healthy Japanese subjects.

OBJECTIVE: The relationship between acid and dyspeptic symptoms has not been fully understood. AIM: To investigate the type and severity of dyspeptic symptoms induced by direct acid infusion into the stomach of Japanese healthy subjects. METHODS: This was a multi-centre, cross-over, randomized, double-blind study in 27 healthy subjects (mean age 27). Each fasted subject received two tests with 150 mL of 0.1 mol/L hydrochloric acid infusion (15 mL/min for 10 min) and the same volume of pure water infusion. The type and severity of symptoms were assessed by a 10 cm visual analogue scale administered every 2 min up to 30 min. RESULTS: Various symptoms were reported after both acid and water infusions. Most of the symptoms were more severe after acid infusion compared with water infusion (acid vs. water: discomfort 1.8 +/- 0.4 vs. 0.5 +/- 0.1, pain 0.6 +/- 0.3 vs. 0.1 +/- 0.1, reflux 1.0 +/- 0.3 vs. 0.3 +/- 0.1 and satiety 1.1 +/- 0.4 vs. 0.2 +/- 0.1). The area under curve for dysmotility like symptoms (heavy feeling in the stomach, bloating, nausea or feeling sick, and belching) was significantly higher in acid infusion, and symptoms continued after infusion of the acid. CONCLUSION: Acid induced into stomach induced dysmotility-like predominant dyspeptic symptoms in Japanese healthy control subjects, demonstrating the possible importance of acid in symptom generation.

Exhaled carbon monoxide concentration is not elevated in patients with inflammatory bowel disease.

The present study was initiated to examine whether the concentration of CO in the breath is elevated in patients with inflammatory bowel disease (IBD). Twenty-three clinically stable patients with IBD in the outpatient clinic (11 with Crohn's disease, 12 with ulcerative colitis), who are non-smokers and non-passive smokers, were selected and the concentration of CO in their breath was measured using a breath gas analyser (TRI lyser mBA-3000). The concentration of CO in the breath of 23 patients with IBD was 2.5+/-0.9 (1.1-4.3) ppm. This concentration comes within the range of standard values in our previous reports (2.5+/-2.2 ppm). Any significant difference was not observed between 2.4+/-0.9 (1.5-4.3) ppm for the 11 Crohn's disease patients and the 2.6+/-1.0 (1.1-3.9) ppm for the 12 ulcerative colitis patients. The results suggest that clinically stable patients with IBD do not show high values for concentration of CO in the breath.

Optimal dose of ramosetron in female patients with irritable bowel syndrome with diarrhea: A randomized, placebo-controlled phase II study.

BACKGROUND: Previous studies showed that 5 µg of ramosetron, a serotonin (5-hydroxytryptamine: 5-HT)-3 receptor antagonist, is only effective in male patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D). We hypothesized that either dose 1.25, 2.5, or 5 µg of ramosetron would be effective in female patients with IBS-D. METHODS: This randomized, double-blind, placebo-controlled, phase II dose-finding exploratory trial included 409 female outpatients with IBS-D treated in Japan. They were administered oral placebo (n=102), or 1.25 µg (n=104), 2.5 µg (n=104), or 5 µg (n=99) of ramosetron once daily for 12 weeks after a 1-week baseline period. The primary endpoint was monthly responder rates of global improvement of IBS symptoms in the first month. Secondary endpoints included global improvement in the other months, abdominal pain/discomfort, weekly mean changes in the Bristol Stool Form Scale (BSFS), and IBS-QOL. KEY RESULTS: Middle dose (2.5 µg) of ramosetron significantly improved abdominal pain/discomfort at second month (62.5%, P=.002), third month (60.6%, P=.005), and the last evaluation point (63.5%, P=.002) and weekly BSFS (P<.05) except at Week 8, 11, and 12 than placebo. IBS-QOL did not change. Ramosetron induced more constipation than placebo. CONCLUSIONS & INFERENCES: The trial suggested that 2.5 µg of ramosetron is the most effective and least harmful option for treating female patients with IBS-D (Clinicaltrials.gov ID: NCT01274000).

The usefulness of transabdominal ultrasound for the diagnosis of lower gastrointestinal bleeding.

BACKGROUND: Lower gastrointestinal bleeding is a frequent cause of hospitalization, but diagnostic methods for this condition are not fully established. Transabdominal ultrasound is a widely accepted diagnostic tool in bowel diseases. AIM: To evaluate the usefulness of transabdominal ultrasound for lower gastrointestinal bleeding. METHODS: We reviewed the medical records of consecutive patients who underwent transabdominal ultrasound as the first diagnostic procedure for acute haematochezia during the period June 1999 to June 2004. The study group comprised 111 patients and all underwent colonoscopy thereafter. Detection and diagnosis of lower gastrointestinal bleeding by ultrasonographic examination were evaluated by comparing the ultrasound diagnosis with the colonoscopic findings and final diagnosis. RESULTS: The bleeding site was localized by colonoscopy in 90 of the 111 patients (81%). The bleeding site was localized by ultrasound in 59 of the 90 patients (66%). When the bleeding site was in the rectum, ultrasonographic detectability was 30% (10/33); ultrasonographic detectability was 82-100% when the bleeding site was elsewhere. Rectal bleeding and diverticular bleeding were difficult to diagnose by ultrasound, but for the other diseases, diagnosis by ultrasonographic examination was possible in 91-100% of cases. CONCLUSIONS: Ultrasonographic examination may be an effective screening method for lower gastrointestinal bleeding.

Anti-parietal cell antibody and serum pepsinogen assessment in screening for gastric carcinoma.

BACKGROUND: Anti-parietal cell antibody is found in patients with Helicobacter pylori-positive gastritis and is related to atrophic gastritis and gastric carcinoma. AIM: To identify the characteristics of patients at high-risk for gastric carcinoma in terms of anti-parietal cell antibody and serum pepsinogen. PATIENTS AND METHODS: Subjects were 92 H. pylori-positive patients (54 men, 38 women; mean age, 57.9 years; range, 15-88 years). The serum concentrations of pepsinogen I and II were determined by radioimmunoassay, and the presence of anti-parietal cell antibody was assessed by enzyme-linked immunosorbent assay. Degrees of inflammation and atrophy in the corpus of the stomach were evaluated histologically. RESULTS: Patients were classified into four groups according to anti-parietal cell antibody status and pepsinogen I/II ratio. Anti-parietal cell antibody-negative/pepsinogen I/II-low patients had the highest risk for gastric carcinoma (prevalence of gastric carcinoma: 7/13=53.8%, odds ratio=7.6, 95% confidence interval, 1.2-48.0). Anti-parietal cell antibody titre was high when inflammation in the corpus was severe (p=0.06) and significantly low when atrophy in the corpus was severe (p=0.01). CONCLUSION: Our results showed that patients with a negative anti-parietal cell antibody titre and low pepsinogen I/II ratio are at high-risk for gastric carcinoma.

Frequent loss of heterozygosity on chromosomes 1q, 5q, and 17p in human gastric carcinomas.

Recently, loss or inactivation of genes at specific chromosomal loci has been considered to be one of the important mechanisms during the development of human tumors. In order to identify tumor suppressor genes for gastric carcinoma, we performed restriction fragment length polymorphism analysis on 48 human gastric carcinomas. Allele losses were investigated for 14 specific loci on chromosomes 1, 5, 6, 7, 10, 11, 12, and 17. Loss of heterozygosity on chromosome 17p13.1 (p53 locus) was detected in 13 (68%) of 19 informative cases. Well-differentiated adenocarcinoma showed high frequencies of allele losses on chromosomes 5q (60%) and 17p (67%) in early cancers and on chromosomes 1q (67%), 5q (36%), 7p (33%), 7q (39%), and 17p (73%) in advanced cancers. In poorly differentiated adenocarcinomas, loss of heterozygosity was detected on chromosomes 1p (38%), 12q (31%), and 17p (60%). Allele losses on chromosomes 1q, 5q, and 7p were not detected in poorly differentiated adenocarcinoma, their frequencies being significantly different between the two histological types. These results suggest that allele loss on chromosome 17p is a common event in gastric carcinoma, regardless of histological type, and that allele loss on chromosome 5q may play a role in the carcinogenesis of well-differentiated adenocarcinoma. Additionally, allele losses on chromosomes 1q and 7p may be involved in the progression of well-differentiated adenocarcinoma.

Famotidine prevents canine gastric blood flow reduction by NSAIDs.

AIM: To investigate the effect of famotidine on gastric blood flow reduction induced by diclofenac sodium, a common non-steroidal anti-inflammatory drug in Japan, using laser Doppler flowmetry in the canine stomach. METHODS: The gastric mucosal blood flow was measured by laser Doppler flowmetry in 15 healthy male beagles before and 60 min after the administration of diclofenac suppository (1.0 mg/kg) into the rectum. The examination was done in a crossover, single-blinded fashion. All dogs underwent both famotidine (0.5 mg/kg) and placebo (saline) injection simultaneously with the administration of diclofenac. In addition, the tissue concentration of prostaglandin E2 was measured. RESULTS: The blood flow decreased by 18.3 +/- 9.1% in the gastric body, by 26.3 +/- 8.1% in the antrum in the placebo group after the administration of diclofenac sodium, while the decreases seen were significantly smaller in the famotidine group: 3.2 +/- 12.6% in the gastric body and 7.9 +/- 16.5% in the antrum (P = 0.001 for the gastric body, P = 0.0034 for the antrum). Conversely, the percentage of mucosal prostaglandin E2 concentration decrease in each group did not show a significant difference. CONCLUSION: Famotidine alleviates the reduction of gastric blood flow induced by diclofenac sodium. Further, not only mucosal prostaglandins but also gastric acid may play an important role in non-steroidal anti-inflammatory drugs-induced gastric microcirculatory disturbance.

Effect of long-term half-dose famotidine therapy on corpus gastritis in peptic ulcer disease.

BACKGROUND: Recent studies showed that acid-suppressive therapy aggravates corpus gastritis in patients with Helicobacter pylori infection. AIM: The aim of this study was to evaluate the effect of famotidine, a histamine receptor antagonist on corpus gastritis in patients with peptic ulcer disease. METHODS: We enrolled 287 patients, 173 with duodenal ulcer and 114 with gastric ulcer and 100 patients with H. pylori-positive gastritis as control subjects. Patients with peptic ulcer were classified according to whether or not they received famotidine-maintenance therapy (20 mg/day) after primary treatment. At the time of endoscopy, biopsy specimens were obtained from the antrum and the corpus. The degrees of neutrophil and lymphocyte infiltration, atrophy and intestinal metaplasia were scored according to the updated Sydney System. RESULTS: The degrees of neutrophil infiltration and atrophy in the corpus were significantly less in patients with gastric ulcer or duodenal ulcer than in patients with H. pylori-positive gastritis (P < 0.01). Differences in the degrees of neutrophil infiltration and atrophy in the corpus between the non-maintenance group and the maintenance group were not significant. CONCLUSION: Long-term therapy with famotidine does not appear to lead to an increase in the incidence of corpus gastritis or corpus atrophy in patients with peptic ulcer disease.

Clinical features of gastric cancer discovered after successful eradication of Helicobacter pylori: results from a 9-year prospective follow-up study in Japan.

BACKGROUND: Eradication of Helicobacter pylori is expected to prevent the development of gastric cancer. However, gastric cancer is sometimes discovered after successful eradication of H. pylori. AIM: To conduct a prospective study to determine the clinical features of patients who underwent successful eradication and were later diagnosed with gastric cancer. METHODS: A total of 1787 patients (1299 males and 488 females; mean age, 58.2 years; range: 15-84) who underwent successful eradication therapy between April 1994 and March 2001 were our study subjects. RESULTS: Gastric cancer occurred at a rate of 1.1% (20 of 1787) during the follow-up period. Gastric cancer comprises six of 105 (5.7%) with early gastric cancer after endoscopic resection, 12 of 575 (2.1%) with gastric ulcer and two of 453 (0.4%) with atrophic gastritis. Gastric cancer did not develop in any patient with duodenal ulcer. All patients with gastric cancer had baseline severe atrophic gastritis in the corpus. CONCLUSION: Careful endoscopic examination is necessary even after successful eradication of H. pylori in patients with early gastric cancer or gastric ulcer with severe mucosal atrophy in the corpus.

Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a short-term follow-up.

BACKGROUND: It is controversial as to whether the development of gastric cancer is influenced by Helicobacter pylori eradication. If eradication itself influences the tumour morphology, this may affect the tumour discovery rate. AIM: To investigate the morphological changes in the gastric neoplasm after H. pylori eradication. METHODS: We studied 37 patients with eradication therapy. After a 1-month follow-up, endoscopic re-evaluation was performed and the appearance was compared with first image. All lesions were resected endoscopically, and were subjected to histological assessment and to immunohistochemistry. Serum gastrin levels were determined before and after eradication. RESULTS: Twenty-nine of 37 patients underwent successful eradication. The appearance of 11 lesions (33% of 33 lesions) became indistinct after successful eradication. All lesions were of the superficial-elevated type and the height of the lesions decreased. We detected normal columnar epithelium over the neoplasm in eight of the lesions. Higher expression of single-stranded deoxyribonucleic acid in the deep area was characteristic in tumours with an indistinct appearance. These changes did not correlate with the serum gastrin levels. CONCLUSIONS: The morphology of the gastric neoplasm change after eradication in the short-term. This may contribute to the decreased tumour discovery rate.

Effect of famotidine on recurrent bleeding after successful endoscopic treatment of bleeding peptic ulcer.

AIM: We investigated the effect of acid suppression therapy on recurrent bleeding after successful endoscopic treatment of bleeding peptic ulcer. METHODS: A total of 400 patients with bleeding peptic ulcer received either intravenous infusion of famotidine (40 mg/day) (n = 207, 163 males, 44 females, mean age 61.5 years) or drip infusion of omeprazole (40 mg/day; n = 193, 134 males, 59 females, mean age 59.8 years) after successful endoscopic treatment. The fasting duration, hospital stay, volume of transfused blood, incidence of rebleeding and mortality were compared between the two groups. RESULTS: The incidence of rebleeding did not differ significantly between the famotidine group (9%) and the omeprazole group (8%). The mean hospital stay was significantly shorter in the omeprazole group (18.4 days) than in the famotidine group (21.5 days, P = 0.009). However, there was no statistically significant difference in fasting duration, volume of transfused blood or mortality. CONCLUSION: Our findings indicate that intravenous infusion of famotidine after successful endoscopic treatment is equivalent to drip infusion of omeprazole for prevention of recurrent bleeding.

Eradication of Helicobacter pylori increases the incidence of hyperlipidaemia and obesity in peptic ulcer patients.

BACKGROUND: Eradication of Helicobacter pylori improves clinical symptoms and quality of life in patients with peptic ulcer. AIM: To investigate the effect of eradication of H. pylori on body mass index and incidence of hyperlipidaemia in patients with peptic ulcer. PATIENTS AND METHODS: The study population comprised 50 patients (42 men, 8 women; mean age, 51 years; 28 gastric ulcer, 22 duodenal ulcer) who underwent physical and blood examination before and 1 year after undergoing eradication therapy and 100 sex- and age-matched control subjects. Body mass index, total cholesterol and triglyceride were measured before and 1 year after therapy. RESULTS: The eradication therapy group showed a significant increase in body mass index (22.7+/-2.5 kg/m2 before eradication versus 23.6+/-2.6 kg/m2 after eradication, p < 0.01), serum total cholesterol (204.1+/-33.2 mg/dL versus 221.2+/-38.8 mg/dL, p < 0.01), and triglyceride. Additionally, the eradication therapy group showed a significant increase in the incidence of hypercholesterolemia (30% versus 58%, p<0.01), hypertriglyceridaemia (28% versus 44%, p < 0.01) and obesity (12% versus 22%, p <0.05) 12 months after therapy. CONCLUSION: Our findings show that eradication of H. pylori significantly increases the incidence of hyperlipidaemia and obesity in patients with peptic ulcer.

Enhanced expression of inducible nitric oxide synthase and nitrotyrosine in gastric mucosa of gastric cancer patients.

Recent studies (K. Komoto et al., Am. J. Gastroenterol., 93: 1271-1276, 1998) have shown that Helicobacter pylori infection is associated with gastric cancer. However, the mechanism of H. pylori in carcinogenesis has not been clarified. H. pylori infection leads to a sustained production of reactive nitrogen species that may contribute to cause DNA damage. In this study, we examined the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine in gastric mucosa. The expression of iNOS and nitrotyrosine was examined by immunohistochemistry in 93 patients who initially underwent gastric biopsies between 1975 and 1992. Thirty-four individuals were later found to have gastric cancer at least 2 years after the initial biopsies (group A). The other 59 subjects have shown no evidence of gastric cancer during long-term follow-up. Fifty-one of these patients were positive for H. pylori (group B), and eight were negative for H. pylori (group C). The expression of iNOS and nitrotyrosine in the gastric mucosa was significantly higher in H. pylori-positive groups A and B than in H. pylori-negative group C. Among the H. pylori-positive patients, the expression of iNOS and nitrotyrosine was significantly higher in group A than in group B. These results suggest that high production of iNOS and nitrotyrosine in the gastric mucosa infected with H. pylori may contribute to the carcinogenesis of gastric cancer.

Regulation of disease-progression genes in human gastric carcinoma cells by interleukin 8.

The expression of interleukin 8 (IL-8) by human gastric carcinomas directly correlates with tumor vascularity and disease progression. To determine whether IL-8 can act in an autocrine manner to regulate the expression of other disease-progression genes, we examined the expression of IL-8 receptors IL-8RA (CXCR1) and IL-8RB (CXCR2) in six different human gastric carcinoma cell lines and 38 surgical specimens of human gastric carcinomas. All of the gastric carcinoma cell lines expressed mRNA and protein for IL-8RA and IL-8RB protein. In all surgical specimens, the majority of the tumor cells and small vessel endothelial cells stained positive for IL-8RA and IL-8RB protein. In vitro treatment of human gastric cancer MKN-1 cells with exogenous IL-8 enhanced the expression of epidermal growth factor receptor, type IV collagenase (metalloproteinase-9), vascular endothelial growth factor, and IL-8 mRNA. In contrast, treatment with exogenous IL-8 decreased expression of E-cadherin mRNA. IL-8 treatment increased invasive capacity of MKN-1 cells, which was associated with activity of metalloproteinase-9. Collectively, these results demonstrate that human gastric carcinoma cells express receptors for IL-8 and that IL-8 may play a role in the progressive growth of human gastric carcinoma by autocrine/paracrine mechanisms.

Significance of vessel count and vascular endothelial growth factor in human esophageal carcinomas.

The purpose of this study was to determine the angiogenic profile of human esophageal carcinomas. The expression of vascular endothelial growth factor (VEGF) was examined in 6 esophageal carcinoma cell lines and 119 human esophageal carcinoma tissues by Northern blot analysis and immunohistochemistry, respectively. Immunohistochemistry using antibodies against CD34 (endothelial cell specific) was carried out on archival specimens, and microvessels were quantitated by counting vessels in a x200 field in the most vascular area of the tumor. All of the cell lines constitutively expressed VEGF mRNA at various levels. A total of 71 of 119 (59.7%) tumors showed intense VEGF immunoreactivity in the cytoplasm of cancer cells. Vessel count was significantly higher in the VEGF-positive tumors than it was in the VEGF-negative tumors. VEGF expression correlated with the depth of tumor invasion, tumor stage, venous invasion, and lymphatic invasion. The survival rate of patients with high vessel density in the tumor was significantly worse than that of patients with low vessel density in the tumor. There was a tendency for poorer prognosis in the group with VEGF-positive tumors compared with that of the group with VEGF-negative tumors. Overall, these results suggest that VEGF is associated with tumor progression by stimulating angiogenesis in human esophageal carcinoma.

Pilot study of Biomarkers for predicting effectiveness of ramosetron in diarrhea-predominant irritable bowel syndrome: expression of S100A10 and polymorphisms of TPH1.

BACKGROUND: Serotonin type 3 receptor (5-HT3 R) antagonists are potentially useful therapeutic agents for diarrhea-predominant irritable bowel syndrome (IBS-D). To identify biomarkers predicting effectiveness of the 5-HT3 R antagonist (ramosetron) in IBS-D. METHODS: Irritable bowel syndrome-D Japanese subjects received 2.5 or 5 µg of ramosetron once daily for 4 weeks. Colonic mucosal S100A and tryptophan hydroxylase (TPH) mRNA expression levels were measured before treatment. Genomic DNA was extracted from blood and polymorphisms of TPH1 and TPH2 were analyzed. KEY RESULTS: Forty-two patients (27 men and 15 women, mean age 42 years) with IBS-D were included for analysis. Improvement of IBS symptoms was seen in 26 (61.9%). Baseline S100A10 (p = 0.02) and TPH1 (p = 0.02) expression were significantly higher in the ramosetron responders than in the non-responders. The frequencies of the TPH1 rs4537731G allele in linkage disequilibrium with the TPH1 rs7130929 T allele (11.5% vs 50%, p = 0.003; OR: 12; 95% CI: 2.1-69) along with TPH1 rs211105 C allele (3.8% vs 43.8%, p = 0.0003; OR: 19; 95% CI: 2.1-181) were significantly lower in the responders than in the non-responders. The mean scores of diarrhea at baseline were significantly higher (5.2 vs 3.7, p = 0.005) in patients with TPH1 rs211105 T/T than those with the G allele. CONCLUSIONS & INFERENCES: TPH1 gene polymorphisms and S100A10 expression, which correlate with 5-HT signaling were associated with ramosetron effectiveness in IBS-D, and may possibly lead to prospective identification of the resistance to treatment.

Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer.

Although epidemiological studies strongly suggest an association between gastric cancer and Helicobacter pylori infection, there has been no clinical report indicating that cure of the infection prevents cancer. We conducted a nonrandomized H. pylori eradication trial in patients whose gastric cancer was removed by endoscopic resection (ER). We investigated the effect of treatment on the histopathology of the gastric mucosa, as well as on the incidence of metachronous gastric cancer during the long-term clinical and endoscopic follow-up. One hundred and thirty-two patients with early gastric cancer underwent ER and had H. pylori infection. Sixty-five (group A) were treated with omeprazole and antibiotics to eradicate the infection, and 67 (group B) were not. All patients were followed for 2 years post ER. After eradication treatment in group A, the disappearance of neutrophil infiltration in the antrum and body of the stomach was observed as was a decrease of the severity of intestinal metaplasia. Endoscopy after ER detected no new gastric cancers in these patients. After 3 years of follow-up, 6 (9%) of the 67 patients in group B had a new early-stage, intestinal-type gastric cancer endoscopically diagnosed. The above results suggest that H. pylori eradication may improve neutrophil infiltration and intestinal metaplasia in the gastric mucosa and inhibit the development of new carcinomas. This finding should be confirmed in a randomized, controlled trial.