The Superiority of Vonoprazan-based First-line Triple Therapy with Clarithromycin: A Prospective Multi-center Cohort Study on Helicobacter pylori Eradication.

Objective We evaluated the safety and efficacy of vonoprazan-based amoxicillin and clarithromycin 7-day triple therapy (VAC) in comparison to proton pump inhibitor (PPI)-based (PAC) as a first-line treatment and vonoprazan-based amoxicillin and metronidazole 7-day triple therapy (VAM) in comparison to PPI-based (PAM) as a second-line treatment for the eradication of Helicobacter pylori in Japan. Methods We performed a non-randomized, multi-center, parallel-group study to compare first-line VAC to PAC and second-line VAM to PAM. A pre-planned subgroup analysis on CAM resistance was also performed. Safety was evaluated with an adverse effects questionnaire (AEQ), which was completed by patients during therapy. Results The first-line eradication rates (ER) in the intention-to-treat (ITT) and per protocol (PP) analyses were 84.9% (95% CI: 81.9-87.6%, n=623) and 86.4% (83.5-89.1%, n=612), respectively, for VAC and 78.8% (75.3-82.0%, n=608) and 79.4% (76.0-82.6%, n=603), respectively, for PAC. The ER of VAC was higher than that of PAC in the ITT (p=0.0061) and PP analyses (p=0.0013). The ERs for VAC in patients with CAM-resistant and CAM-susceptible bacteria were 73.2% (59.7-84.2%, n=56) and 88.9% (83.4-93.1%, n=180), respectively. PAC was associated with higher AEQ scores for diarrhea, nausea, headache, and general malaise. In the second-line ITT and PP analyses VAM achieved ERs of 80.5% (74.6-85.6%, n=216) and 82.4% (76.6-87.3%, n=211), respectively, while PAM achieved ERs of 81.5% (74.2-87.4%, n=146) and 82.1% (74.8-87.9%, n=145), respectively. No significant differences were observed in the ITT (p=0.89) or PP (p=1.0) analyses. Conclusion The ER of first-line VAC was higher than that of PAC, but still <90%. No difference was observed between second-line VAM and PAM. Vonoprazan-based triple therapy was safe and well tolerated.

Factors associated with poor therapeutic response in outpatients with irritable bowel syndrome: a multicenter study in Japan.

BACKGROUND: Some patients with irritable bowel syndrome (IBS) show poor response to treatment. However, risk factors associated with poor therapeutic response have not been determined. METHODS: This multicenter trial evaluated consecutive outpatients with IBS undergoing treatment for more than 1 month. Mental health status and physical function were evaluated using the Japanese version of the SF-8. Therapeutic response was evaluated using the IBS severity index-Japanese version (IBS-SIJ). Patients with IBS-SIJ scores ≥175 were defined as poor responders to treatment, whereas those with IBS-SIJ scores <175 were defined as good responders. The demographic and clinical characteristics of these two groups, along with medications, were compared. RESULTS: The study enrolled 131 participants, 75 with IBS-SIJ scores ≥175-56 with IBS-SIJ scores <175. Multiple logistic regression analysis showed that female sex [odds ratio (OR) 2.67, 95 % confidence interval (CI) 1.19-5.97, p = 0.0167] and mental component summary (MCS) of the SF-8 <40 (OR 2.58, 95 % CI 1.12-5.97, p = 0.0263) were independent risk factors for poor therapeutic response in patients with IBS. CONCLUSIONS: Lower MCS and female sex were risk factors for poor therapeutic response in patients with IBS. Ascertaining the mechanisms by which lower MCS and female sex are associated with poor therapeutic response in IBS may help design better treatments (Trial registration number: UMIN000016804).

[Outcomes of laparoscopic surgery after preoperative metallic stent placement for obstructive colorectal cancer].

AIM: To assess the outcomes of preoperative colonic stent placement for obstructive colorectal cancer. PATIENTS AND METHODS: A total of 30 patients with colorectal cancer were treated after preoperative colonic metallic stent placement between July 2012 and March 2014. We reviewed their medical records to assess the usefulness of stent placement and the clinical course. The effects of various clinicopathological variables on post-operative complications were analyzed statistically. RESULTS: Stent insertion was effective in 93% of the 30 patients with obstructive colorectal cancer. Preoperative colonoscopy or enema for proximal colonic survey was possible in 70% of the patients after stent placement; colonic lesions requiring simultaneous resection were noted in 5 patients (24%). The mean interval between stent insertion and operation was 19 days, and 23%of the patients underwent laparoscopic surgery. Statistical analysis revealed that the occurrence of complications was associated with laparoscopic surgery and the amount of operative blood loss. CONCLUSION: Preoperative stent placement in patients with obstructive colorectal cancer is feasible and laparoscopic surgery can be selected after stent placement.

Influence of pretreatment with H2 receptor antagonists on the cure rates of Helicobacter pylori eradication.

BACKGROUND: Pretreatment with a proton pump inhibitor (PPI) reportedly decreases the efficacy of Helicobacter pylori (H. pylori) eradication, however, the effect of pretreatment with an H2 receptor antagonist (H2RA) on H. pylori eradication has not yet been studied. We compared the efficacy of eradication regimen (lansoprazole/amoxicillin/clarithromycin) in patients with H. pylori infection with or without H2RA pretreatment. MATERIAL/METHODS: In this retrospective study conducted at three centers, 310 patients with H. pylori infection were treated. The diagnosis of H. pylori infection was made using the rapid urease test, bacterial cultures and histological examination of endoscopic biopsy specimens. The patients were assigned to receive an eradication regimen first or following pretreatment with H2RA. Eradication was assessed using the 13C-urea breath test more than 4 weeks after the completion of therapy. RESULTS: Overall, H. pylori was eradicated in 79.7% of the cases: the eradication rate was 81.6% in the pretreatment group, and 77.6% in the eradication first group (p=0.3799, chi-square test). No significant difference in the eradication rate was observed between the two groups. CONCLUSIONS: Pretreatment with H2RA had no significant influence on the efficacy of H. pylori eradication therapy.

Does pretreatment with proton pump inhibitors influence the eradication rate of Helicobacter pylori?

BACKGROUND/AIMS: Pretreatment with a proton pump inhibitor (PPI) has been reported to decrease the efficacy of Helicobacter pylori (H. pylori) eradication. We compared the efficacy of an eradication regimen (lansoprazole/amoxicillin/clarithromycin) first or following pretreatment with a PPI. METHODOLOGY: In this retrospective study conducted at three centers, 353 patients infected with H. pylori were treated. The H. pylori status was determined using the rapid urease test, bacterial cultures, and the histological examination of endoscopic biopsy specimens, The patients were assigned to receive an eradication regimen first or following pretreatment with a PPI. Eradication was assessed using the 13C-urea breath test more than 4 weeks after the completion of therapy. RESULTS: Overall, H. pylori was eradicated in 78.8% of the cases: 79.6% in the pretreatment group, and 77.6% in the eradication first group (p = 0.6541 by chi square test). No significant difference in the eradication rates was observed between the two groups. CONCLUSIONS: This retrospective study indicated that pretreatment with a PPI does not significantly reduce the efficacy of eradication therapy in patients infected with H. pylori.

Gastroesophageal reflux disease in hemodialysis patients.

BACKGROUND: The association between gastroesophageal reflux disease (GERD) and chronic renal failure (CRF) remains unclear. The aim of the present study is to assess the prevalence of GERD and also attempt to identify possible pathogenic factors in the development of reflux in hemodialysis (HD) patients. PATIENTS AND METHODS: This study consisted of 418 stable CRF patients who underwent HD and did not necessarily undergo gastroendoscopy. Instead of gastroendoscopy, QUEST, a structured questionnaire for the assessment of symptomatic GERD, was used to diagnose GERD. We checked the age, sex, body mass index, etiology of renal disease, QUEST score, medication, alcohol consumption, smoking and laboratory data, and compared GERD group with non-GERD group. RESULTS: In the 418 stable CRF patients who did not undergo gastroendoscopy, the prevalence of GERD was 24.2%. There were no statistically significant differences in age, sex, BMI, alcohol consumption, smoking, etiology of CRF, laboratory data and medication between GERD group and non-GERD group. CONCLUSIONS: Compared to the reported prevalence of GERD in Japan (16.3%), the prevalence of GERD in CRF patients who underwent HD (24.2%), was increased. The risk factor for this increased GERD in CRF patients was not clear in the present study.

Gastroesophageal reflux disease in chronic renal failure patients: evaluation by endoscopic examination.

BACKGROUND: The association between gastroesophageal reflux disease (GERD) and chronic renal failure (CRF) remains unclear. The aim of the present study is to assess the gastroendoscopic findings and the prevalence of GERD in CRF patients by endoscopic examination. PATIENTS AND METHODS: This study consisted of 156 CRF patients (97 men and 59 women, mean age: 64.2 years) whose creatinine level was more than 2 mg/dl and who underwent endoscopic examination. We checked their renal function, gastrointestinal symptoms and gastroendoscopical findings, and examined the relationship between renal function and gastroendoscopic findings, and the prevalence of GERD. RESULTS: In the gastroendoscopic findings of the 156 CRF patients who underwent endoscopic examination, the prevalence of GERD was 34.0%. Especially, in symptomatic cases, the prevalence of GERD was 44.0%. In hemodialysis patients, the prevalence of GERD was 50.0%. The prevalence of GERD tended to increase as renal function become worse. There were statistically significant differences between the patients on hemodialysis and pre-dialysis in the prevalence of GERD (P < 0.01). The severity of GERD tended to be mild. CONCLUSIONS: Compared to the reported prevalence of GERD in 6010 Japanese adults (16.3%), the prevalence of GERD in CRF patients, especially who underwent hemodialysis (50.0%), was increased.

Quantitive cytokine mRNA expression profiles in the colonic mucosa of patients with steroid naïve ulcerative colitis during active and quiescent disease.

BACKGROUND: Cytokines have validated roles in the immunopathogenesis of inflammatory bowel disease (IBD). This study was to investigate the expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-10 mRNAs in the colonic mucosa of patients with ulcerative colitis (UC) during active and quiescent UC. METHODS: At colonoscopy, biopsies were taken from inflamed and non-inflamed mucosa of patients with steroid-naive UC (n = 15), non-IBD inflammatory colitis controls (ICC, n = 6), and non-colitis controls (NCC, n = 14). The presence of extensive mononuclear cells and neutrophils infiltrate in the lamina propria, cryptitis, and epithelial damage defined an inflammatory lesion in the mucosa. Quantitative cytokine mRNA expressions in biopsies were measured by real-time polymerase chain reaction (PCR). RESULTS: Of 15 UC patients, 3 remitted with 5-aminosalicylate and 11 received granulocytapheresis; of these, 10 remitted. At baseline, IL-6, IL-8, TNF-alpha, and IL-10 mRNAs were high in inflamed mucosa compared with NCC (P < 0.01). In active UC, IL-6, IL-8 and IL-10 mRNAs were high compared with non-inflamed mucosa (P = 0.03, P = 0.03, P < 0.05, respectively). Both TNF-alpha mRNA (P = 0.03) and IL-6 mRNA (P = 0.04) were higher in UC compared with ICC. Even in non-inflamed mucosa, IL-8 and TNF-alpha mRNA expressions were high compared with NCC. Both IL-6 and IL-8 mRNAs decreased to normal levels after granulocytapheresis. CONCLUSIONS: During active UC, all 4 cytokine mRNA levels were high; only IL-6 and IL-8 mRNAs decreased to normal levels during remission. IL-8 mRNA was high even at sites of endoscopically quiescent UC during active disease. Steroid naïve patients respond well to granulocytapheresis.

Protein-losing enteropathy, deep venous thrombosis and pulmonary embolism in a patient with generalized inflammatory polyposis in remission stage of ulcerative colitis.

We experienced a patient with severe protein-losing enteropathy and generalized inflammatory polyposis. In addition, this case was complicated by deep venous thrombosis and pulmonary embolism. Patients with inflammatory bowel disease are at increased risk for thromboembolic events, most commonly in the setting of active colitis. However, our patient was in the remission stage. We report the occurrence of deep venous thrombosis and pulmonary embolism as a complication of inflammatory polyposis and protein-losing enteropathy in the remission stage of ulcerative colitis.

Roles for host and tumor angiotensin II type 1 receptor in tumor growth and tumor-associated angiogenesis.

Angiotensin II (AII) is a multifunctional bioactive peptide, and host renin-angiotensin system (RAS) is closely associated with tumor growth. Recent reports have described that AII is a proangiogenic growth factor, and that Angiotensin II type 1 (AT1) receptor antagonists reduce tumor growth and tumor-associated angiogenesis. In this paper, we investigated the participation of AT1 receptor-signaling in cancer progression using murine Lewis lung carcinoma (LLC) cells, which express AT1 receptor, and AT1a receptor gene-deficient (AT1a-/-) mice. When LLC cells were implanted subcutaneously into wild-type (WT) mice, developed tumors showed intensive angiogenesis with an induction of vascular endothelial growth factor (VEGF) a. Compared with WT mice, tumor growth and tumor-associated angiogenesis was reduced in AT1a-/- mice with reduced expression of VEGFa. In AT1a-/- mice, administration of the AT1 receptor antagonist, TCV-116, showed further reductions of tumor growth, tumor-associated angiogenesis, and VEGFa expression. In vitro study, the expression of VEGFa mRNA and the production of VEGFa protein in LLC cells were significantly increased by AII, which were cancelled by AT1 receptor antagonist, CV-11974. Although the expression of other angiogenic factors, such as angiopoietin-1, angiopoietin-2, epidermal growth factor, and VEGF receptor 2 mRNA, was also investigated in tumor tissues, the expression of VEGFa was most correlated with tumor size among those other angiogenic factors. VEGFa induction by AT1 receptor-signaling in both host and tumor tissues is one of key regulators of tumor growth and tumor-associated angiogenesis. In conclusion, tumor tissue RAS as well as host tissue RAS were found to have an important role in tumor growth. AT1 receptor-signaling blockade may be a novel and effective target in the treatment of cancer.

Helicobacter pylori prevalence in dentists in Japan: a seroepidemiological study.

BACKGROUND: The infection mode of Helicobacter pylori is not well known. In order to prove that frequent exposure to saliva and dental plaque does not constitute a risk for acquiring H. pylori infection, we tested the hypothesis that the prevalence of H. pylori in dentists in Japan is the same as that in controls. We also studied factors associated with H. pylori prevalence by multivariate analysis. METHODS: We examined serum anti-H. pylori-IgG in 232 Japanese subjects (116 dentists and 116 age- and sex-matched nonclinical controls). Participants were given a questionnaire that included demographic data, life style, past history, and gastrointestinal symptoms, and dental practice. RESULTS: We analyzed the results for 111 dentists and 111 controls after exclusion of those who had an equivocal titer. The seroprevalence of H. pylori was 42.3% in dentists and 40.0% in controls. With multiple logistic regression, age was selected as the only independent variable correlated with seroprevalence (P = 0.0002; coefficient of determination 0.11). Factors associated with dental practice were not significant. CONCLUSIONS: We conclude that dental practice in Japan does not increase the risk of H. pylori infection for dentists.