Risk factors for reflux esophagitis after eradication of Helicobacter pylori.

Objective: While there is an association between successful eradication of Helicobacter pylori (HP) and reflux esophagitis (RE), risk factors associated with RE remain obscure. The aim of this study is to determine risk factors associated with the development of RE after HP eradication.Materials and methods: Among all patients treated with successful HP eradication from 2008 to 2016, we retrospectively analyzed those who were free from RE at initial esophagogastroduodenoscopy (EGD) and who were followed up with EGD after eradication. Patients were classified according to the presence or absence of RE at the follow-up EGD. RE was defined as mucosal breaks proximal to the squamous-columnar junction. Demographic data, underlying diseases, medications and endoscopic findings at the initial EGD were compared between patients with and without RE.Results: Among 1575 patients, 142 (9.0%) had RE at the follow-up EGD. The time interval from HP eradication until EGD ranged from 4 to 24 months. The endoscopic grade of RE was higher in males than in females. Multivariate analysis revealed that male sex (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.24), body mass index ≥25 kg/m2 (OR, 2.91; 95% CI, 2.00-4.22), use of calcium channel blockers (OR, 1.70; 95% CI, 1.12-2.55), and hiatal hernia (OR, 3.46; 95% CI, 2.41-5.00) were associated with the development of RE.Conclusions: Calcium channel blocker use was found to be a risk factor for the development of RE after eradication of HP.

Proton Pump Inhibitors Increase Incidence of Nonsteroidal Anti-Inflammatory Drug-Induced Small Bowel Injury: A Randomized, Placebo-Controlled Trial.

BACKGROUND & AIMS: Some studies have reported a high incidence of small bowel injuries in 60%-80% of subjects who take nonselective nonsteroidal anti-inflammatory drugs and PPIs simultaneously. We performed a randomized, double-blind, controlled study to determine whether proton pump inhibitors (PPIs) exacerbate nonsteroidal anti-inflammatory drug-induced small bowel injury. METHODS: Fifty-seven healthy subjects were randomly assigned groups given the cyclooxygenase (COX) 2 inhibitor celecoxib (200 mg, twice daily) plus placebo for 2 weeks (COX-2 + placebo group, n = 30), or celecoxib plus the PPI rabeprazole (20 mg, once daily) for 2 weeks (COX-2 + PPI group, n = 27). The study was performed from October 2012 through September 2013 at a tertiary medical center in Japan. All subjects were evaluated by capsule endoscopy at the start of the study and then after 2 weeks administration of celecoxib with rabeprazole or placebo. The incidence rates and the numbers of small bowel injuries (ulcers and erosions) that were observed under capsule endoscopy were compared between groups. The primary endpoint was the incidence of mucosal injuries at the second capsule endoscopy examination. RESULTS: A significantly higher proportion of subjects in the COX-2 + PPI group developed small bowel injury (12 of 27 subjects; 44.4%) than in the COX-2 + placebo group (5 of 30 subjects; 16.7%; P = .04). Subjects in the COX-2 + PPI group had a significant increase in risk of small bowel injury compared with the COX-2 + placebo group (relative risk, 2.67; 95% confidence interval, 1.08-6.58). The number of erosions in each member of the COX-2 + PPI group was greater than in each member of the COX-2 + placebo group (P = .02). The number of ulcers did not differ between groups. Twenty-six percent of subjects in the COX-2 + PPI group developed mucosal injury in the jejunum, compared with none of the subjects in the COX-2 + placebo group (P = .003); no such trend was found in the ileum. CONCLUSIONS: In a randomized, controlled trial, PPIs increased the risk of short-term nonsteroidal anti-inflammatory drug-induced small bowel injury. UMIN clinical trial registry number: UMIN000008883.

Comparison of the therapeutic efficacy and safety between tacrolimus and infliximab for moderate-to-severe ulcerative colitis: a single center experience.

OBJECTIVE: Both tacrolimus (Tac) and infliximab (IFX) are effective for moderate-to-severe ulcerative colitis (UC). The aim of this study was to compare the therapeutic efficacy and safety of both drugs. MATERIALS AND METHODS: We performed a retrospective analysis of 46 patients with moderate-to-severe UC who were treated either by Tac (n = 21) or IFX (n = 25). We compared the remission and response rates for 10 weeks between the two groups. In patients who achieved a clinical response, the subsequent relapse rate was compared. The overall adverse events were also compared between the two groups. RESULTS: The remission and response rates at week 10 did not differ between patients treated with Tac (67% and 86%, respectively) and patients treated with IFX (76% and 92%, respectively). Among 41 patients showing a clinical response, eight of 23 patients treated with IFX and eight of 18 patients treated with Tac showed a subsequent relapse. The risk of relapse was not different between the two groups. While no serious adverse events were observed, the incidence of adverse events was higher in patients treated with Tac than in those treated with IFX. CONCLUSION: Tac and IFX may be equally efficacious for the induction and maintenance of remission in patients with UC while minor adverse events are more frequent with the former treatment.

Therapeutic strategy for Crohn's disease with a loss of response to infliximab: a single-center retrospective study.

BACKGROUND/AIMS: Infliximab (IFX) is an effective treatment for maintaining clinical remission in patients with initially moderate-to-severe Crohn's disease (CD). However, a certain number of patients become unresponsive to IFX, subsequently requiring intensified therapy. The aim of this study was to compare the short- and long-term therapeutic efficacy of intensified regimens in CD patients who fail to respond to IFX. METHODS: The clinical courses of 33 CD patients who failed to respond to treatment with IFX were investigated retrospectively. An intensified regimen involving doubling the dose of IFX was chosen in 13 patients (DD group) versus shortening the IFX interval in 13 patients (SI group) and switching to adalimumab (ADA) in 7 patients (SA group). RESULTS: The clinical response and rate of clinical remission at 4 weeks were 62 and 54% in the DD group, 77 and 62% in the SI group and 57 and 43% in the SA group, respectively (p = 0.59 for clinical response, p = 0.90 for clinical remission). The rate of sustained remission at 48 weeks was 44% in the DD group, 54% in the SI group and 33% in the SA group (p = 0.88). CONCLUSION: The short- and long-term efficacy of doubling the dose of IFX, shortening the interval of IFX or switching to ADA is similar for CD patients who no longer respond to IFX.

Risk of cancer in the rectal remnant after ileorectal anastomosis in patients with familial adenomatous polyposis: single center experience.

BACKGROUND AND AIM: We aimed to evaluate the long-term risk of cancer in the rectal remnant in patients with familial adenomatous polyposis after ileorectal anastomosis. METHODS: Cumulative incidence and clinicopathological characteristics of cancer in the rectal remnant were retrospectively investigated in 27 patients with familial adenomatous polyposis who had undergone ileorectal anastomosis. RESULTS: During the follow-up period ranging from 3.0 to 35.0 years (median, 21.1 years), cancer in the rectal remnant developed in 10 patients. Cumulative risk of cancer in the rectal remnant 30 years after surgery was 57%. Five patients had metastases and three patients died of cancer in the rectal remnant after proctectomy. There was a trend towards a higher incidence of cancer in the rectal remnant in patients with small-intestinal adenoma and congenital hypertrophy of the retinal pigment epithelium. Multivariate analysis revealed that the ocular lesion was an independent risk factor associated with cancer in the rectal remnant. CONCLUSION: Subtotal colectomy with ileorectal anastomosis does not seem to be an appropriate prophylactic surgery in patients with familial adenomatous polyposis.

Duodenal adenomatosis in Japanese patients with familial adenomatous polyposis.

Duodenal adenomatosis is the most frequent extracolonic manifestation of familial adenomatous polyposis (FAP), and duodenal cancer has been assumed to be the second most significant cause of death in patients with the disease. To stratify the risk of duodenal cancer, Spigelman's classification was proposed for the staging of duodenal adenomatosis. According to Western guidelines, patients with stage IV of the classification are candidates for prophylactic duodenectomy. Since our institutional experience disclosed only 2% of duodenal or ampullary cancers among 130 patients with FAP, and because most duodenal adenomatosis remains unchanged under endoscopic surveillance, it seems likely that aggressive endoscopic or surgical removal is unnecessary for most FAP patients with duodenal adenomatosis. In the present article, we demonstrate our data and present our strategy for duodenal adenomatosis of FAP.

Endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors in Japan: Multicenter case series.

BACKGROUND AND AIM: To verify the current status in Japan on endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADET) by a multicenter case series through a questionnaire survey. METHODS: Nine endoscopists and a surgeon responded to a questionnaire on endoscopic diagnosis of SNADET. The subjects of this survey were histologically confirmed SNADET that were endoscopically or surgically resected from 2007 to 2012. This survey collected data of 364 patients with 396 SNADET. RESULTS: Of the 396 SNADET, 121 were histologically diagnosed as low-grade dysplasia (LGD), 112 as high-grade dysplasia (HGD), and 163 as superficial adenocarcinoma (SAC) including 153 mucosal carcinomas and 10 submucosal carcinomas. Total number of SNADET increased from 125 in the first half to 271 in the second half of the survey period. Compared to LGD, a significantly greater number of HGD or SAC was found in the tumors having a diameter >5 mm as well as solitary or predominantly red color. Preoperative endoscopic diagnosis indicated significantly higher sensitivity and accuracy and significantly lower specificity for HGD or SAC of final histology than preoperative biopsy. Ten submucosal carcinomas had 0-I or 0-IIa+IIc macroscopic-type tumors with red color. CONCLUSIONS: This multicenter case series study suggested that the number of resected SNADET is dramatically increasing in Japan. Tumor diameter >5 mm and red color seemed to be signs for tumors of HGD or SAC. Preoperative endoscopy may provide a more reliable diagnosis of final histology of HGD or SAC than preoperative biopsy. Further studies are warranted for establishing endoscopic features of submucosal carcinoma.

Long-term effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer.

BACKGROUND: A prospective, randomized trial proved that Helicobacter pylori eradication significantly reduces the incidence of metachronous gastric cancer during a 3-year follow-up. OBJECTIVE: To investigate the long-term effect of H pylori eradication on the incidence of metachronous gastric cancer after endoscopic resection of early gastric cancer. DESIGN: Retrospective, multicenter study. SETTING: Kyushu University Hospital and 6 other hospitals in Fukuoka Prefecture, Japan. PATIENTS AND INTERVENTIONS: Follow-up data for 268 H pylori-positive patients who had undergone endoscopic resection of early gastric cancer were retrospectively investigated. A total of 177 patients underwent successful H pylori eradication (eradicated group), whereas 91 had persistent H pylori infection (persistent group). MAIN OUTCOME MEASUREMENTS: The incidence of metachronous gastric cancer was compared in these 2 groups. RESULTS: When the follow-up period was censored at 5 years, the incidence rate in the eradicated group was lower than that observed in the persistent group (P = .007). During the overall follow-up period ranging from 1.1 to 11.1 years (median 3.0 years), metachronous gastric cancer developed in 13 patients (14.3%) in the persistent group and in 15 patients (8.5%) in the eradicated group (P = .262, log-rank test). Based on a multivariate logistic regression analysis, baseline severe mucosal atrophy and a follow-up of more than 5 years were found to be independent risk factors for the development of metachronous gastric cancer. LIMITATIONS: Retrospective study. CONCLUSIONS: H pylori eradication does not reduce the incidence of metachronous gastric cancer. H pylori eradication should be performed before the progression of gastric mucosal atrophy.

Risk of surgery in patients with stricturing type of Crohn's disease at the initial diagnosis: a single center experience.

BACKGROUND/AIMS: It remains uncertain which patients with stricturing-type Crohn's disease (CD) require early small bowel surgery after the initial diagnosis. We aimed to clarify clinical characteristics associated with the intervention in such condition of CD. METHODS: We retrospectively evaluated the clinical course of 53 patients with CD and small bowel strictures who were initially treated with medications after the initial diagnosis. We investigated possible associations between small bowel surgery and the following: clinical factors and radiologic findings at initial diagnosis and the types of medications administered during follow-up. RESULTS: Twenty-eight patients (53%) required small bowel resection during a median follow-up period of 5.0 years (range, 0.5-14.3 years). The cumulative incidence rates of small bowel surgery at 2, 5, and 10 years were 26.4%, 41.0%, and 63.2%, respectively. Univariate analysis indicated that obstructive symptoms (P=0.036), long-segment stricture (P<0.0001), and prestenotic dilation (P<0.0001) on radiography were associated with small bowel surgery, and immunomodulatory (P=0.037) and biological therapy (P=0.008) were significant factors during follow-up. Multivariate analysis revealed that long-segment stricture (hazard ratio [HR], 4.25; 95% confidence interval [CI], 1.78-10.53; P=0.001) and prestenotic dilation (HR, 3.41; 95% CI, 1.24-9.62; P=0.018) on radiography showed a positive correlation with small bowel surgery, and biological therapy (HR, 0.40; 95% CI, 0.15-0.99; P=0.048) showed a negative correlation. CONCLUSIONS: CD patients with long-segment stricture and prestenotic dilation on radiography seem to be at a higher risk of needing small bowel surgery. For such patients, early surgical intervention might be appropriate, even at initial diagnosis.

Anti-tumor necrosis factor therapy decreases the risk of initial intestinal surgery after diagnosis of Crohn's disease of inflammatory type.

BACKGROUND: Anti-tumor necrosis factor (TNF) therapy induces and maintains clinical remission in patients with Crohn's disease (CD). However, the effect of anti-TNF therapy on the natural course of CD remains controversial. We aimed to investigate the effect of anti-TNF therapy on the initial intestinal surgery for CD. METHODS: In this single-center retrospective cohort study, clinical course of 199 CD patients of inflammatory type at the initial diagnosis (the period between 1973 and 2014) was precisely reviewed until the end of 2016. Patients were divided into TNF and non-TNF groups based on anti-TNF agent use. After comparisons of clinical characteristics and medical treatments, propensity scores were calculated for covariates. Risk of intestinal surgery was compared by a Cox proportional hazards model using the propensity scores. The effect of immunomodulators on initial intestinal surgery was assessed in the TNF group. RESULTS: During the study period, 108 patients received anti-TNF therapy. The patients in the TNF group were diagnosed more recently, and more frequently had isolated colonic involvement, and perianal disease. Immunomodulators were more frequently used in the TNF group. Cumulative probability of initial intestinal surgery was significantly lower in the TNF group (P < 0.0001). The hazard ratio in the TNF group was 0.32 (95% CI 0.13-0.74). Immunomodulators did not decrease the risk of initial intestinal surgery. CONCLUSIONS: Anti-TNF therapy can decrease the risk of intestinal surgery among patients with inflammatory-type CD at the initial diagnosis. Further studies should be necessary to determine the additive effect of immunomodulators on the risk of intestinal surgery.

Characteristics of Primary and Metachronous Gastric Cancers Discovered after Helicobacter pylori Eradication: A Multicenter Propensity Score-Matched Study.

BACKGROUND/AIMS: Gastric cancers develop even after successful Helicobacter pylori eradication. We aimed to clarify the characteristics of early gastric cancers discovered after H. pylori eradication. METHODS: A total of 1,053 patients with early gastric cancer treated by endoscopic submucosal dissection were included. After matching the propensity score, we retrospectively investigated the clinicopathological features of 192 patients, including 96 patients who had undergone successful H. pylori eradication (Hp-eradicated group) and 96 patients who had active H. pylori infection (Hp-positive group). RESULTS: In the Hp-eradicated group, early gastric cancers were discovered 1 to 15 years (median, 4.1 years) after H. pylori eradication. Compared with Hp-positive patients, Hp-eradicated patients showed a more frequently depressed configuration (81% vs 53%, respectively, p<0.0001) and a higher trend toward submucosal invasion (18% vs 8%, respectively, p=0.051). A multivariable analysis revealed the macroscopic depressed type to be characteristics of early gastric cancers after H. pylori eradication. Among patients in the Hp-eradicated group, metachronous cancers showed less frequent depressed lesions (68% vs 84%, respectively, p=0.049) and smaller tumor sizes (median, 11 mm vs 14 mm, respectively, p=0.014) than primary cancers. CONCLUSIONS: Early gastric cancers after H. pylori eradication are characterized by a depressed configuration. Careful follow-up endoscopies are necessary after H. pylori eradication.

Contribution of susceptibility variants at FCGR2A and 13q12 to the risk of relapse among Japanese patients with ulcerative colitis.

BACKGROUND: Recent genome-wide association studies have identified nearly 100 susceptibility genes for ulcerative colitis (UC). However, the contribution of susceptibility variants for UC to clinical outcome has scarcely been reported. The aim of this study was to investigate whether UC-associated genetic variants confer a risk of clinical relapse. METHODS: One hundred and nine consecutive Japanese subjects with quiescent UC were recruited. Four genetic variants of HLA-DRB1*1502, rs6671847 at FCGR2A, rs17085007 at 13q12, and rs2108225 at SLC26A3 were genotyped by Invader assay. The clinical courses were followed after blood sampling, and the risk of relapse according to these genotypes was calculated by Cox proportional hazard model. RESULTS: During the mean follow-up period of 35 months (range 1-81 months), 49 of 109 subjects (45 %) relapsed. Carriers of the G allele of rs6671847 showed an increased risk of relapse compared with non-carriers [adjusted hazard ratio (HR), 2.27; 95 % confidence interval (CI), 1.20-4.32; p = 0.01]. Patients with the CT or TT genotypes of rs17085007 also had an increased risk of relapse compared to subjects with the CC genotype (for CT: adjusted HR, 2.16; 95 % CI, 1.10-4.23; p = 0.03; for TT: adjusted HR, 3.25; 95 % CI, 1.18-8.95; p = 0.02). These two risk variants multiplied the risk of relapse by 2.74 times (95 % CI, 1.10-4.23; p = 0.01) in patients with one risk genotype and 5.40 times (95 % CI, 2.06-14.13; p = 0.0006) in patients with both risk genotypes. CONCLUSIONS: Genetic variants of rs6671847 at FCGR2A and rs17085007 at 13q12 conferred a risk of relapse in patients with UC.

Small bowel injury induced by selective cyclooxygenase-2 inhibitors: a prospective, double-blind, randomized clinical trial comparing celecoxib and meloxicam.

BACKGROUND: Selective cyclooxygenase (COX)-2 inhibitors are less harmful to the small bowel mucosa than non-selective anti-inflammatory drugs. We aimed to compare the severity of small bowel mucosal injury in healthy volunteers induced by two selective COX-2 inhibitors, celecoxib and meloxicam, in a randomized, double-blind trial, using capsule endoscopy (CE). METHODS: Twenty-nine healthy subjects were randomized to take either celecoxib (200 mg twice daily) or meloxicam (10 mg once daily) for 2 weeks. The incidence and the number of small bowel mucosal injuries (bleeding, ulcers, and erosions) observed by CE were compared between the two groups. RESULTS: The overall incidence of small bowel mucosal injury was not different between the celecoxib group (6 of 14 subjects, 42.9%) and the meloxicam group (4 of 15 subjects, 26.7%, P = 0.45). In subjects with positive CE findings, the number of ulcers was greater in the meloxicam group than in the celecoxib group (P = 0.02), while such a trend was not found with regard to erosions (P = 0.52). The distribution of mucosal lesions within the small bowel was similar in the two groups. CONCLUSIONS: Selective COX-2 inhibitors are not completely safe for the small bowel. The mucosal lesions may be less severe with celecoxib than with meloxicam.