Taketo Otsuka

Influence of potassium-competitive acid blocker on the gut microbiome of Helicobacter pylori-negative healthy individuals

We read with great interest two recent reports by Imhann et al 1 and Jackson et al .2 Through large population-cohort study, each group revealed that gastric acid inhibition by long-term use of proton pump inhibitors (PPIs) changes the gut microbiome to predispose to enteric infection including Clostridium difficile (CD) . Potassium-competitive acid blockers (P-CABs) have been reported to exert more potent gastric acid suppression than PPIs.3 ,4 The inhibitory effect of vonoprazan (TAK-438), a new P-CAB, on H+, K+-ATPase in vitro is approximately 400 times more potent than that of PPI (lansoprazole) (inhibitory concentration (IC)50 of vonoprazan 0.019 μM and lansoprazole 7.6 μM).5 We describe below that vonoprazan induces more complex alteration of the gut microbiome as compared with lansoprazole. We enrolled serum Helicobacter pylori IgG-negative healthy individuals to eliminate the influence of H. pylori infection on gastric acid secretion (see online supplementary table S1). The PPI group (n=11) took 30 mg of lansoprazole daily for 4 weeks, and the P-CAB group …

Efficacy of the Kyoto Classification of Gastritis in Identifying Patients at High Risk for Gastric Cancer

Objective The Kyoto gastritis classification categorizes the endoscopic characteristics of Helicobacter pylori (H. pylori) infection-associated gastritis and identifies patterns associated with a high risk of gastric cancer. We investigated its efficacy, comparing scores in patients with H. pylori-associated gastritis and with gastric cancer. Methods A total of 1,200 patients with H. pylori-positive gastritis alone (n=932), early-stage H. pylori-positive gastric cancer (n=189), and successfully treated H. pylori-negative cancer (n=79) were endoscopically graded according to the Kyoto gastritis classification for atrophy, intestinal metaplasia, fold hypertrophy, nodularity, and diffuse redness. Results The prevalence of O-II/O-III-type atrophy according to the Kimura-Takemoto classification in early-stage H. pylori-positive gastric cancer and successfully treated H. pylori-negative cancer groups was 45.1%, which was significantly higher than in subjects with gastritis alone (12.7%, p<0.001). Kyoto gastritis scores of atrophy and intestinal metaplasia in the H. pylori-positive cancer group were significantly higher than in subjects with gastritis alone (all p<0.001). No significant differences were noted in the rates of gastric fold hypertrophy or diffuse redness between the two groups. In a multivariate analysis, the risks for H. pylori-positive gastric cancer increased with intestinal metaplasia (odds ratio: 4.453, 95% confidence interval: 3.332-5.950, <0.001) and male sex (1.737, 1.102-2.739, p=0.017). Conclusion Making an appropriate diagnosis and detecting patients at high risk is crucial for achieving total eradication of gastric cancer. The scores of intestinal metaplasia and atrophy of the scoring system in the Kyoto gastritis classification may thus be useful for detecting these patients.

Four‐times‐daily Dosing of Rabeprazole with Sitafloxacin, High‐Dose Amoxicillin, or Both for Metronidazole‐Resistant Infection with Helicobacter pylori in Japan

The bacterial resistance of Helicobacter pylori to antimicrobial agents such as clarithromycin and metronidazole has been increasing worldwide, leading to the failure of eradication treatment. Here, we present an eradication regimen consisting of four‐times‐daily dosing (q.i.d.) of rabeprazole with potent acid inhibition.

Letter: CYP3A4/5 genotype status and outcome of vonoprazan-containing Helicobacter pylori eradication therapy in Japan

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Letter: a potassium-competitive acid blocker vs a proton pump inhibitor for healing endoscopic submucosal dissection-induced artificial ulcers after treatment of gastric neoplasms

1. Hyun MH, Lee YS, Kim JH, et al. Systematic review with meta-analysis: the efficacy and safety of tenofovir to prevent mother-to-child transmission of hepatitis B virus. Aliment Pharmacol Ther. 2017;45:1493-1505. 2. Zanng C-Y, Ahri B-K, Wu G-B, Zhong J-H, Li L-Q. Letter: role of tenofovir to prevent mother-to-child transmission of hepatitis B virus. Aliment Pharmacol Ther. 2017;46:562-563. 3. Sun W, Zhao S, Ma L, et al. Telbivudine treatment started in early and middle pregnancy completely blocks HBV vertical transmission. BMC Gastroenterol. 2017;17:51. 4. Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359:2442-2455. 5. Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat. 2012;19:e18-e25. 6. Wen WH, Chang MH, Zhao LL, et al. Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention. J Hepatol. 2013;59:24-30. 7. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017; https://doi.org/10.1016/j.jhep.2017.03.021 8. Korean Association for the Study of the L. KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol 2016;22:18-75. 9. Chang MH, You SL, Chen CJ, et al. Long-term effects of hepatitis B immunization of infants in preventing liver cancer. Gastroenterology. 2016;151:472-480.e1. 10. Eke AC, Eleje GU, Eke UA, Xia Y, Liu J. Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus. Cochrane Database Syst Rev 2017;2:CD008545.

Severity of gastric mucosal atrophy affects the healing speed of post-endoscopic submucosal dissection ulcers

AIM To investigate factors associated with the healing of endoscopic submucosal dissection (ESD)-induced ulcers. METHODS We enrolled 132 patients with gastric tumors scheduled for ESD. Following ESD, patients were treated with daily lansoprazole 30 mg or vonoprazan 20 mg. Ulcer size was endoscopically measured on the day after ESD and at 4 and 8 wk. The gastric mucosa was endoscopically graded according to the Kyoto gastritis scoring system. We assessed the number of patients with and without a 90% reduction in ulcer area at 4 wk post-ESD and scar formation at 8 wk, and looked for risk factors for slower healing. RESULTS The mean size of gastric tumors and post-ESD ulcers was 17.4 ± 12.1 mm and 32.9 ± 13.0 mm. The mean reduction rates in ulcer area were 90.4% ± 0.8% at 4 wk and 99.8% ± 0.1% at 8 wk. The reduction rate was associated with the Kyoto grade of gastric atrophy at 4 wk (A0: 97.9% ± 0.6%, A1: 93.4% ± 4.1%, and A2: 89.7% ± 1.0%, respectively). In multivariate analysis, the factor predicting 90% reduction at 4 wk was gastric atrophy (Odds ratio: 5.678, 95%CI: 1.190-27.085, P = 0.029). CONCLUSION The healing speed of post-ESD ulcers was associated with the degree of gastric mucosal atrophy, and Helicobacter pylori eradication therapy is required to perform at younger age.

Usefulness of the clip-flap method of endoscopic submucosal dissection: A randomized controlled trial

AIM To prospectively investigate the efficacy and safety of clip-flap assisted endoscopic submucosal dissection (ESD) for gastric tumors. METHODS From May 2015 to October 2016, we enrolled 104 patients with gastric cancer or adenoma scheduled for ESD at Shiga University of Medical Science Hospital. We randomized patients into two subgroups using the minimization method based on location of the tumor (upper, middle or lower third of the stomach), tumor size (< 20 mm or > 20 mm) and ulcer status: ESD using an endoclip (the clip-flap group) and ESD without an endoclip (the conventional group). Therapeutic efficacy (procedure time) and safety (complication: Gastrointestinal bleeding and perforation) were assessed. RESULTS En bloc resection was performed in all patients. Four patients had delayed bleeding (3.8%) and two had perforation (1.9%). No significant differences in en bloc resection rate (conventional group: 100%, clip flap group: 100%), curative endoscopic resection rate (conventional group: 90.9%, clip flap group: 89.8%, P = 0.85), procedure time (conventional group: 70.8 ± 46.2 min, clip flap group: 74.7 ± 53.3 min, P = 0.69), area of resected specimen (conventional group: 884.6 ± 792.1 mm2, clip flap group: 1006.4 ± 1004.8 mm2, P = 0.49), delayed bleeding rate (conventional group: 5.5%, clip flap group: 2.0%, P = 0.49), or perforation rate (conventional group: 1.8%, clip flap group: 2.0%, P = 0.93) were found between the two groups. Less-experienced endoscopists did not show any differences in procedure time between the two groups. CONCLUSION For patients with early-stage gastric tumors, the clip-flap method has no advantage in efficacy or safety compared with the conventional method.

Successful Helicobacter pylori eradication therapy improves symptoms of chronic constipation: XXXX

Constipation is one of the most common gastrointestinal functional disorders. Recently, the gut microbiota has been implicated in the development of constipation. Helicobacter pylori infection is considered to be a possible factor influencing the gut microbiota profile. Here, we investigated the effect of H. pylori eradication therapy on symptoms of chronic constipation.

Cap polyposis refractory to Helicobacter pylori eradication treated with endoscopic submucosal dissection

Cap polyposis is a rare intestinal disorder. Characteristic endoscopic findings are multiple inflammatory polypoid lesions covered by caps of fibrous purulent exudate. Although a specific treatment has not been established, some studies have suggested that eradication therapy for Helicobacter pylori (H. pylori) is effective. We report a case of a 20-year-old man with cap polyposis presenting with hematochezia. Colonoscopy showed the erythematous polyps with white caps from the sigmoid colon to rectum. Histopathological findings revealed elongated, tortuous, branched crypts lined by hyperplastic epithelium with a mild degree of fibromusculosis in the lamina propria. Although H. pylori eradication was instituted, there was no improvement over six months. We then performed en bloc excision of the polyps by endoscopic submucosal dissection (ESD), which resulted in complete resolution of symptoms. ESD may be a treatment option for cap polyposis refractory to conservative treatments. We review the literature concerning treatment for cap polyposis and clinical outcomes.