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Background: Prophylactic chemoradiation therapy (CRT) using 40-41.4 Gy post-endoscopic submucosal dissection (ESD) for clinical T1N0M0 esophageal cancer reportedly yields favorable outcomes. However, it cannot completely prevent locoregional lymph node (LN) metastases. We retrospectively analyzed outcomes and adverse events associated with our dose-escalated treatment regimen (definitive-dose radiotherapy [RT] of 50-61.2 Gy, with/without chemotherapy) for these patients, and predictors of progression-free survival (PFS) and overall survival (OS)., Methods: Between 2006 and 2018, 44 consecutive patients (42 men and 2 women; median age, 70 years) who underwent definitive-dose RT post-ESD and had a pathological depth of the muscularis mucosa with lymphovascular invasion (LVI) or the upper-middle submucosal third at our institution were included. We excluded patients who could not obtain a margin-free resection by ESD. If feasible, systemic chemotherapy with 5-fluorouracil plus high- or low-dose cisplatin or nedaplatin was administered concurrently., Results: Five-year PFS, OS, and disease-specific survival rates were 78.8%, 88.4%, and 97.7%, respectively. Six metachronous esophagus (14%), two locoregional LN within the irradiated area with a prophylactic dose of 41.4 Gy (5%), and two locoregional LN plus liver (5%) recurrences occurred. No LN recurrence occurred within the definitive dose of ≥ 50 Gy in the irradiated area. Metachronous esophageal recurrence involved areas receiving ≥ 50 Gy. Univariate and multivariate analyses revealed that age was an independent prognostic factor for both PFS and OS., Conclusions: Definitive-dose RT/CRT post-ESD could provide favorable locoregional LN control and PFS/OS regardless of patient characteristics, including pathological findings and chemotherapy regimen/course, except for age. These results need to be interpreted carefully given several limitations, therefore, definitive-dose RT/CRT should be conducted with caution in clinical practice until high-quality prospective clinical trials evaluating the effectiveness and safety., (© 2024. Japanese Society of Gastroenterology.)

Background: The cancer risk for each length of Barrett's esophagus (BE) in Japanese is unknown. This nationwide, multi-institutional study aims to clarify the cancer risk by length of BE in the general Japanese population., Methods: Consecutive subjects who underwent upper endoscopic screening at 17 centers between 2013 and 2017 and had at least one follow-up endoscopy by December 2022 were included. The presence/absence of BE and, if present, its length were retrospectively assessed using the retrieved endoscopic images recorded at baseline. Information on the subsequent occurrence of esophageal adenocarcinoma and other upper gastrointestinal cancers was also collected. Cancer incidence was calculated and expressed as %/year., Results: A total of 33,478 subjects were enrolled, and 17,884 (53.4%), 10,641 (31.8%), 4889 (14.6%), and 64 (0.2%) were diagnosed as absent BE, BE < 1 cm, 1-3 cm, and ≥ 3 cm, respectively. During a median follow-up of 80 months, 11 cases of esophageal adenocarcinoma developed. The annual incidence of esophageal adenocarcinoma is 0%/year for absent BE, 0.0032 (0.00066-0.013)%/year for BE < 1 cm, 0.026 (0.011-0.054)%/year for 1-3 cm, and 0.58 (0.042-2.11)%/year for ≥ 3 cm, respectively. Meanwhile, the incidence of esophageal squamous cell carcinoma and gastric cancer were 0.039 (0.031-0.049)%/year and 0.16 (0.14-0.18)%/year, respectively., Conclusions: By enrolling a large number of subjects with long-term follow-up, this study demonstrated that the risk of cancer increased steadily with increasing length of BE in the Japanese population. Therefore, it is important to consider the length of BE when determining the management strategy for BE., (© 2024. Japanese Society of Gastroenterology.)

Background: No studies have evaluated the relationship between lifestyle and synchronous gastric cancers (SGCs) in patients with endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs). Using data from the Tohoku gastrointestinal (GI) study, we aimed to identify factors associated with SGCs., Methods: Tohoku GI study is a multicenter prospective cohort study investigating the relationship between lifestyle and metachronous gastric cancers. Patients who had a schedule to undergo ESD for primary EGCs were enrolled. We used logistic regression analysis to examine the relationship of 15 candidate factors, including lifestyle, with the prevalence of SGCs in this study., Results: Of 850 patients between 2016 and 2019, 16.0% (136 patients) had SGCs. In multivariate analysis, smoking history (odds ratio [OR], 1.93; p = 0.048) and severe atrophic gastritis assessed by pepsinogen (OR, 1.92; p = 0.004) were risk factors for the prevalence of SGCs. Regarding smoking, current smoking (OR, 2.33; p = 0.021), but not former smoking (OR, 1.76; p = 0.098), was a significant risk factor for its prevalence. In the stratified analysis, severe atrophic gastritis assessed by pepsinogen was a risk factor in patients without Helicobacter pylori (H. pylori) eradication (OR, 2.10; p = 0.002), but not a risk factor in those with H. pylori eradication (OR, 0.75; p = 0.737)., Conclusion: Smoking history was a risk factor for the prevalence of SGCs in patients with ESD for EGCs, and severe atrophic gastritis assessed by pepsinogen was also a risk factor when H. pylori was not eradicated., (© 2023. Japanese Society of Gastroenterology.)

Background: The guidelines recommend additional gastrectomy after noncurative endoscopic resection for early gastric cancers (EGCs). However, no additional treatment might be acceptable in some patients aged ≥ 85 years. We aimed to identify this patient group using the data in a highly aged area., Methods: We enrolled patients aged ≥ 85 years after noncurative endoscopic resection for EGCs at 30 institutions of the Tohoku district in Japan between 2002 and 2017. Treatment selection and prognosis after noncurative endoscopic resection were investigated. Fourteen candidates were evaluated using the Cox model to identify risk factors for poor overall survival (OS) in patients with no additional treatment., Results: Of 1065 patients aged ≥ 85 years, 143 underwent noncurative endoscopic resection. Despite the guidelines' recommendation, 88.8% of them underwent no additional treatment. The 5-year OS rates in those with additional gastrectomy and those with no additional treatment were 63.1 and 65.2%, respectively. Multivariate analysis showed independent risk factors for poor OS in patients with no additional treatment were the high-risk category in the eCura system (hazard ratio [HR], 2.91), Charlson comorbidity index (CCI) ≥ 3 (HR, 2.78), and male (HR, 2.04). In patients with no additional treatment, nongastric cancer-specific survival was low (69.0% in 5 years), whereas disease-specific survival rates were very high in the low- and intermediate-risk categories of the eCura system (100.0 and 97.1%, respectively, in 5 years)., Conclusions: No additional treatment may be acceptable in the low- and intermediate-risk categories of the eCura system in patients aged ≥ 85 years with noncurative endoscopic resection for EGCs., (© 2023. Japanese Society of Gastroenterology.)

In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD., (© 2022. The Author(s).)

Background: No prediction scores for the mortality of both inpatients and outpatients who developed nonvariceal upper gastrointestinal bleeding (UGIB) without endoscopic findings have been established. We aimed to derive and validate a novel prediction score for in-hospital mortality., Methods: We conducted a three-stage, multicenter retrospective study. In the derivation stage, patients with nonvariceal UGIB at six institutions were enrolled to derive the prediction score by logistic regression analysis. External validation of the score was performed to analyze discrimination by patients at six other institutions. Then the performance of this score was compared with that of four existing scores., Results: We enrolled 1380 and 825 patients in the derivation and validation cohorts, respectively. A prediction score (CHAMPS-R Score) comprising seven variables (Charlson Comorbidity Index ≥ 2, in-hospital onset, albumin < 2.5 g/dL, altered mental status, Eastern Cooperative Oncology Group performance status ≥ 2, steroids, and rebleeding) with equal-weight scores was established, with high discriminative ability in both derivation and validation cohorts (c statistic, 0.91 and 0.80, respectively). When rebeeding was excluded from the score (an onset model; CHAMPS Score), this score also achieved high discriminative ability (c statistic, 0.90 and 0.81, respectively). The prediction scores had significantly higher discriminative ability than the Glasgow Blatchford Score, AIMS65, ABC Score, and clinical Rockall Score in both cohorts (all, p < 0.05)., Conclusions: We derived and externally validated prediction scores for in-hospital mortality in patients with nonvariceal UGIB. The CHAMPS Score might be optimal for managing such patients. Its mobile application is freely available ( https://apps.apple.com/app/id1565716902 for iOS and https://play.google.com/store/apps/details?id=hatta.CHAMPS for Android)., (© 2021. Japanese Society of Gastroenterology.)

Background: We aimed to elucidate the risk of metastatic recurrence after endoscopic resection (ER) without additional treatment for esophageal squamous cell carcinomas (ESCCs) with tumor invasion into the muscularis mucosa (pT1a-MM) or submucosa (T1b-SM)., Methods: We retrospectively enrolled patients with pT1a-MM/pT1b-SM ESCC after ER at 21 institutions in Japan between 2006 and 2017. We compared metastatic recurrence between patients with and without additional treatment, stratified into category A (pT1a-MM with negative lymphovascular invasion [LVI] and vertical margin [VM]), B (tumor invasion into the submucosa ≤ 200 µm [pT1b-SM1] with negative LVI and VM), and C (others). Subsequently, using multivariate Cox analysis, we evaluated risk factors for metastatic recurrence after ER without additional treatment., Results: We enrolled 593 patients, and metastatic recurrence occurred in 38 patients. Metastatic recurrence after additional treatment was significantly lower than that after no additional treatment in category C (9.1% vs. 23.6% in 5 years, p = 0.001), whereas no significant difference was noted in categories A (0.0% vs. 2.6%) and B (0.0% vs. 4.3%). In patients without additional treatment after ER, risk factors for metastatic recurrence were lymphatic invasion (hazard ratio [HR], 5.61), positive VM (HR, 4.55), and tumor invasion into the submucosa > 200 μm (HR, 3.25), and, but near half of the patients with metastatic recurrence had no further recurrence after salvage treatment, resulting in excellent 5-year disease-specific survival in categories A (99.6%) and B (100.0%)., Conclusions: Closed follow-up with no additional treatment may be an acceptable option after ER in pT1a-MM/pT1b-SM1 ESCC with negative LVI and VM., (© 2021. Japanese Society of Gastroenterology.)

Background: The incidence of peptic ulcers unrelated to H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs), termed idiopathic peptic ulcers (IPUs), has increased worldwide. We recently reported that IPUs were refractory to proton pump inhibitor (PPI) treatment. Vonoprazan, which was recently developed in Japan, has shown a more potent acid-inhibitory effect than ordinary PPIs. In the present study, we compared the healing rates among peptic ulcers of different etiologies following treatment with vonoprazan., Method: A multicenter observational study was performed at six participating hospitals in Akita Prefecture, Japan. Consecutive patients who had endoscopically confirmed gastro-duodenal ulcers were enrolled between August 2016 and March 2018. For each patient, the Helicobacter pylori infection status and NSAID use, including aspirin, were checked, and 20 mg vonoprazan was administered for 6 weeks for duodenal ulcers and 8 weeks for gastric ulcers. The healing status was checked by endoscopy at the end of vonoprazan treatment. Patients were divided into four subgroups according to the H. pylori status and NSAID usage., Results: The proportion of IPUs was 18.2%. A total of 162 patients completed the study protocol. The healing rate of IPUs was marginally lower than that of simple H. pylori-associated ulcers (81.2% vs. 93.5%, P = 0.05). Similarly, the healing rate of NSAID-related ulcers, irrespective of concomitant H. pylori infection, was significantly lower than that of simple H. pylori-associated ulcers., Conclusions: Six- or 8-week vonoprazan treatment still seems to be insufficient for healing IPUs. Longer-term vonoprazan or another treatment option may be required to heal potentially refractory peptic ulcers.

Background: At present, squamous cell carcinoma accounts for most esophageal cancers in Japan; however, there is concern that the incidence of esophageal adenocarcinoma in Japan is increasing in comparison to Western countries. Akita Prefecture, with a population of 1 million, has the highest rate of esophageal cancer-associated mortality in Japan; the vast majority of these cases are squamous cell carcinoma. The aim of the present study was to investigate the latest trends in the incidence of esophageal adenocarcinoma in Akita Prefecture using a registration system., Methods: We examined the data from a collaborative hospital-based registration system for cancer patients. Eleven of the main hospitals in Akita Prefecture participate in this system, which covers 90% of the cancer cases in the region and which provides near population-based data. Using this registration system, we examined the sequential trends in the percentage of adenocarcinoma cases in relation to total esophageal cancer cases in Akita Prefecture from 2007 to 2014., Results: In 2007-2014, a total of 2527 esophageal cancer patients were registered in the system. Among these, only 43 (1.8%) had adenocarcinoma. However, the number of adenocarcinoma patients gradually increased from 1 case in 2007 to 14 cases in 2014. Consequently, the percentage of adenocarcinoma cases showed a significant increase from 0.66% in the first 4 years of the study period to 2.5% in the latter 4 years of the study period (P < 0.01)., Conclusions: The latest hospital-based registration data for 2007-2014 suggest that the incidence of esophageal adenocarcinoma may have begun to increase in Akita Prefecture; this may reflect recent trends in other parts of Japan.

Background: The gastric acid secretion level is an important determinant for the manifestation of the gastroesophageal reflux disease spectrum, finally leading to the development of esophageal adenocarcinoma (EAC). Although the incidence of EAC has remained low in Asia, understanding the recent trend in gastric acid secretion should be helpful in estimating future incidences of EAC in that area. We investigated the latest chronological change (1995-2014) in gastric acid secretion in normal Japanese patients., Methods: A total of 307 asymptomatic Japanese men who attended the clinic for annual endoscopic checkups from 1995 to 2014 were enrolled in this analysis. Gastrin-stimulated gastric acid secretion was estimated with the endoscopic gastrin test. The association between gastric acid secretion and chronological period was assessed with a multivariate linear regression analysis., Results: Overall gastric acid secretion gradually increased over the 20-year period in the entire cohort in the unadjusted analysis (p < 0.05). However, the apparent increase was largely related to the relative decreasing rate of H. pylori infection, which profoundly inhibited gastric acid secretion. Gastric acid secretion did not change over the 20-year period in H. pylori-negative subjects, and it showed only a mild increase during this period in H. pylori-positive subjects., Conclusions: Considering that gastric acid secretion remained unchanged in H. pylori-negative Japanese men over a 20-year period at a level much lower than that in Occidental subjects, upper gastrointestinal disease profiles in the Japanese population will differ from those in Western countries in the post-H. pylori era.

Background: We recently demonstrated in humans that the extent of low-dose aspirin (LDA)-induced gastropathy was directly related to the individual gastric acid secretion level. We also established reliable cutoff serum pepsinogen (PG) values to predict gastric acid secretion status. In this study, we investigated the clinical usefulness of measuring the serum pepsinogen values for identifying a high-risk group for gastric mucosal injury among chronic LDA users., Methods: One hundred long-term LDA users were enrolled in this analysis. Serum from each subject was subjected to determination of H. pylori status and measurement of pepsinogen values. According to our recent report, a PG I value ≥ 50 ng/mL was defined as estimated hyperchlorhydria in H. pylori-negative subjects, while a PG I/II ≥ 3.3 was defined as estimated hyperchlorhydria in H. pylori-positive subjects. The grade of gastric mucosal injury was assessed endoscopically, and multiple logistic regression analyses were used to estimate the risk., Results: Estimated hyperchlorhydria was a strong independent risk for intensive gastric mucosal injury with an OR (95% CI): 34.0 (4.5-259) and for gastric ulcer with an OR (95% CI): 10.2 (1.8-58.3) in H. pylori-positive subjects, while it was not a significant risk in H. pylori-negative subjects. The association persisted even after excluding those with conventional risks for LDA-gastropathy such as ulcer histories., Conclusion: Using simple serum measurement of H. pylori antibody and pepsinogen concentrations, an extremely high-risk group for LDA-induced gastropathy could be extracted, and these patients should become a therapeutic target for prevention of LDA-induced gastropathy.

Background: We have reported that the total number of peptic ulcers (PUs) had increased 1.5-fold after the Great East Japan Earthquake compared with those of the previous year, and that hemorrhagic ulcers were more prominently increased by 2.2-fold. The aim of this study is to determine the risk factors for bleeding ulcers after the Great East Japan Earthquake., Methods: Clinical data of all peptic ulcer subjects endoscopically detected at the 7 major hospitals in the middle of the stricken area during the 3 months after the earthquake were retrospectively collected. Based on endoscopic and laboratory findings, peptic ulcer cases were divided into 227 bleeding ulcer cases and 102 non-bleeding controls. Other than ordinary risk factors for bleeding ulcers, the refugee shelter was included in the analysis as a unique confounder after the earthquake. Multiple logistic regression analyses were used to adjust for potential confounders., Results: Eighty-seven (27%) of 329 PUs emerged from refuge shelters, and the majority (76 of 87) of PUs occurring in such shelters was the bleeding type. Multivariate regression showed that residence in a shelter was a strong risk factor for ulcer bleeding with OR (95% CI): 4.4 (2.1-9.6, p < 0.0001), independent of the progressiveness of ulcer diseases., Conclusions: Accommodation in a refugee shelter can be a strong risk factor for ulcer bleeding after a large-scale disaster. Since acid-suppressive drugs are supposed to decrease the risk for stress-induced ulcer bleeding, our results will encourage effective use of a limited medical resource in such catastrophic events.

Background: Societal stress derived from an event that affects the whole society, e. g., a natural disaster, provides a unique, indirect way of determining the relationship between psychological stress and peptic ulcer disease in humans. In this study, we investigated the changing patterns of the incidence of peptic ulcers before and after the Great East Japan earthquake, which occurred on 11 March, 2011., Methods: Clinical data of patients with peptic ulcers were retrospectively collected during the 3 months after the earthquake (2011) from 7 major hospitals in the middle of the stricken area, and were compared with the data for the same period of the previous year (2010). The eligible subjects were classified into four groups according to Helicobacter pylori infection status and intake of nonsteroidal anti-inflammatory drugs (NSAIDs)., Results: The incidence of all types of peptic ulcers was 1.5-fold increased after the earthquake, and in particular, the incidence of hemorrhagic ulcers was 2.2-fold increased; the gastric ulcer/duodenal ulcer ratio in hemorrhagic ulcers was also significantly increased (p < 0.05). Regarding the etiology of the peptic ulcers, the proportion of non-H. pylori and non-NSAID ulcers was significantly increased, from 13 % in 2010 to 24 % in 2011 after the earthquake (p < 0.05)., Conclusion: In addition to the increased incidence of peptic ulcers, compositional changes in the disease were observed after the Great East Japan earthquake. The significant increase in the proportion of non-H. pylori and non-NSAID ulcers after the earthquake indicated that psychological stress alone induced peptic ulcers in humans independently of H. pylori infection and NSAID intake.

Background: Gender and gastric acid have been suggested to be independently involved in the pathophysiology of functional dyspepsia, but the interrelationship among gender, dyspeptic symptoms, and gastric acid secretion remains to be evaluated. We sought to explore this issue in dyspeptic patients., Methods: A total of 89 outpatients (male, 36; mean age, 55.6 years) with dyspeptic symptoms were analyzed. The degree of dyspeptic symptoms was evaluated and scored using a symptom questionnaire consisting of 3 subcategories: dysmotility-related symptoms, reflux-related symptoms, and epigastric pain-related symptoms. Stimulated gastric acid secretion was directly measured using an endoscopic gastrin test., Results: The total symptom scores and the epigastric pain-related symptom scores were significantly higher in female patients than in male patients. The dysmotility-related and reflux-related symptom scores were also higher, but not significantly, in the female patients. Multiple regression analysis of age, gender, habitual drinking, smoking, Helicobacter pylori infection, and gastric acid secretion revealed that gender and gastric hypochlorhydria, defined as less than 2.1 mEq/10 min in the endoscopic gastrin test, were significantly associated with higher dyspeptic symptom scores. The total scores and the dysmotility-related scores were significantly higher in the patients with gastric hypochlorhydria than in those with gastric non-hypochlorhydria, and this difference was found to be present only in females., Conclusions: Gastric hypochlorhydria in female dyspeptic patients may be involved in the exacerbation of dyspeptic symptoms. Differences in the responsiveness to gastric hypochlorhydria between males and females may be partly responsible for the gender differences in the prevalence and severity of dyspeptic symptoms.

Background: The association of Helicobacter pylori infection with aspirin-induced gastropathy is controversial. H. pylori infection exerts diverse effects on gastric acid secretion. In this study, the interaction between H. pylori infection and aspirin was investigated with reference to the individual gastric acid secretion level in H. pylori-positive subjects., Methods: Ninety-three (81 men, mean age: 70 years) long-term low-dose aspirin takers were prospectively enrolled. H. pylori infection was evaluated by serum IgG antibody determination, and gastrin-stimulated acid output was assessed with the endoscopic gastrin test. H. pylori-positive aspirin-takers were classified into 2 subgroups (hyposecretors and non-hyposecretors). The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score; intensive aspirin-induced gastropathy was defined as a modified Lanza score of ≥4. Multiple logistic regression analyses were used to adjust for potential confounders., Results: With H. pylori-negative patients taken as the reference, H. pylori infection was found to be positively associated with intensive gastropathy among non-hyposecretors, with an odds ratio (OR) (95 % confidence interval [CI]) of 4.2 (1.1-17.1), while the infection was negatively associated with gastropathy among hyposecretors, with an OR (95 % CI) of 0.3 (0.08-0.9). Aspirin-induced gastropathy occurred preferentially in the antrum among H. pylori-positive non-hyposecretors, while it affected the fundus among H. pylori-positive hyposecretors., Conclusion: The effect of H. pylori infection on the aspirin-induced gastropathy was biphasic depending on the individual gastric acid secretion level. In the presence of sufficient amounts of gastric acid, H. pylori infection and aspirin could synergistically damage gastric mucosal integrity, while in the absence of sufficient amounts of gastric acid, the synergistic effect could be completely counteracted and the infection could even suppress the aspirin-induced gastropathy.

Background: Low-dose aspirin is known to cause upper gastrointestinal complications. The mechanism by which the aspirin disrupts gastric mucosal integrity remains to be clarified. In this study we investigated the temporal association of gastric secretory parameters (acid and mucus) with aspirin-induced gastropathy., Methods: In 42 long-term low-dose aspirin-takers and the same number of sex- and age-matched controls, pentagastrin-stimulated gastric juice was collected for 10 min during endoscopic examination. The collected gastric juice was divided and half was submitted to analysis for gastric acid (mEq/10 min) and the other half was analyzed for mucin (mg hexose/10 min) output. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score, and a score of more than 4 was defined as the presence of severe gastropathy., Results: While gastric acid secretion did not differ significantly between aspirin-takers and controls, gastric mucus secretion, in terms of mucin output, was significantly increased in aspirin-takers compared to controls (4.1 (SD 4.8) vs. 2.3 (1.4) mg hexose/10 min, P < 0.05). Consequently, the acid/mucin ratio was significantly decreased in aspirin-takers compared to controls (1.2 (1.0) vs. 1.7 (1.4), P < 0.05). In the subanalysis of 25 aspirin-takers without severe gastropathy, gastric mucus secretion was increased and the acid/mucus ratio was decreased compared with controls, but there was no such association in the remaining 17 aspirin-takers with severe gastropathy., Conclusion: Overall, gastric mucus secretion is increased in aspirin-takers, suggesting a functional adaptive response to long-term administration of the drug. However, it is possible that the adaptive response is impaired in some aspirin takers, who might be susceptible to severe upper gastrointestinal complication.

Background: The relative contribution of gastric acid secretion and Helicobacter pylori infection to low-dose aspirin-induced gastropathy remains to be clarified. This is partly because the capability of the infection to modify gastric acid secretion complicates the interaction. The aim of this study was to estimate the association of aspirin-induced mucosal injury, as well as H. pylori infection, with gastric acid output., Methods: A total of 186 male outpatients, comprising 60 aspirin takers, on 100 mg of enteric-coated aspirin daily and 126 non-aspirin takers were prospectively enrolled in this study. Gastrin-stimulated acid output was estimated by the endoscopic gastrin test. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score. Multiple logistic regression analyses were used to adjust for potential confounders., Results: The gastric acid secretion level, with an odds ratio (OR) (95% confidence interval [CI]) of 10.5 (3.0-36.9) and aspirin administration, with an OR (95% CI) of 7.4 (3.0-18.3) were independently associated with gastric mucosal injury, and the co-existence of both factors greatly elevated the risk of mucosal injury, with an OR (95% CI) of 77.0 (13.5-440.0). H. pylori infection, itself, did not show any significant effect on the aspirin-induced mucosal injury after adjusting for gastric acid secretion., Conclusions: This study has demonstrated that aspirin-induced gastropathy is directly associated with gastric acid secretion. In addition, it also suggested that the gastric acid secretion level modulates the association between H. pylori infection and aspirin-induced gastropathy.

Background: The impact of obesity on gastroesophageal reflux disease remains controversial. We undertook this study, with a large sample size, to investigate risk factors for endoscopic erosive esophagitis by multivariate analysis, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) as covariates., Methods: Japanese males who visited our institute for a comprehensive medical survey between 2007 and 2010 were enrolled. All subjects voluntarily participated in a self-paid health check-up program including blood test screening, physical examinations, and esophagogastroduodenoscopy. VAT and SAT were measured by computed tomography at the navel level. Independent and significant predictors of erosive esophagitis were determined by multivariate analysis., Results: Of 9840 eligible subjects, 1831 (18.6%) were diagnosed with erosive esophagitis. Body mass index and triglyceride were predictors of an increased prevalence of erosive esophagitis (odds ratios [ORs] = 1.063 and 1.001; 95% confidence intervals [CIs] = 1.020-1.108 and 1.001-1.002; p = 0.004 and <0.001, respectively). Heavy alcohol consumption, heavy smoking, and hiatal hernia were also associated with an increased prevalence of erosive esophagitis (ORs = 1.276, 1.399, and 2.758; 95% CIs = 1.085-1.501, 1.220-1.605, and 2.474-3.075; p < 0.001 for all). Helicobacter pylori infection significantly and independently decreased the prevalence of erosive esophagitis (OR = 0.346, 95% CI = 0.299-0.401, p < 0.001). Central obesity, as determined by VAT and waist girth, did not confer an increased risk of erosive esophagitis after adjusting for confounders., Conclusions: Lifestyle factors including heavy alcohol consumption, heavy smoking, metabolic disorders, and hiatal hernia increased the risk of erosive esophagitis, but central obesity did not.

Background: Eosinophilic esophagitis (EoE) has been a rarely recognized condition in Asian populations, and its clinical manifestation is rarely documented. Our aim was to describe clinically, endoscopically, and pathologically the features of patients with esophageal eosinophilia, including EoE., Methods: Twelve patients histologically proven to have esophageal eosinophilia were investigated. The histological diagnostic cutoff value was defined as a peak of ≥15 eosinophils/high-power field (HPF) in esophageal biopsies. Symptoms, endoscopic and pathological findings, and treatment outcome were evaluated., Results: Nine of the 12 patients were male and the 12 patients had a mean age of 47.7 years. Allergic conditions were concurrent in a total of 3 patients. Mild peripheral eosinophilia was observed in only 2 patients. The predominant symptom was solid-food dysphagia, but some patients complained of heartburn, or chest, epigastric, or back pain. Three asymptomatic subjects were also incidentally diagnosed during endoscopic screening. Linear furrows, concentric rings, and white exudates in the esophagus were frequently observed. In 4 of 5 patients who were administered a proton pump inhibitor (PPI), esophageal eosinophilia was histologically decreased or disappeared with symptom relief and endoscopic improvement. In 2 patients unresponsive to PPI, topical steroid therapy, administered by the swallowing of fluticasone propionate, led to symptomatic and histological remission., Conclusions: The endoscopic recognition of linear furrows, concentric rings, and white exudates is important in the diagnosis of eosinophilic esophageal inflammation. In a subset of patients this condition improves clinicopathologically with PPI treatment, and typical EoE, as strictly defined by unresponsiveness to PPI, appears to be a rather rare condition.

Background: We recently reported the expansion of the acid-secreting mucosa following Helicobacter pylori eradication with Congo red chromoendoscopy for a short-term follow-up of up to 7 months. We aimed to extend the observation period and to clarify the characteristic features of acid-secreting and non-acid-secreting mucosa., Methods: In 24 H. pylori-positive patients with fundic atrophy, Congo red chromoendoscopy was performed prior to, 1 month, 7 months, and finally more than 2 years after the eradication. The areas of the acid-secreting mucosa were evaluated semiquantitatively. Two gastric biopsy specimens were taken from the acid-secreting and non-acid-secreting areas at the final chromoendoscopy and were subjected to histologic evaluation and immunohistochemistry for Ki-67 as a proliferation index., Results: After a gradual increase in acid-secreting areas for up to 7 months after eradication, they further increased in 79% subjects between 7 months and the final observation at a mean follow-up of 62 months. However, there still existed non-acid-secreting mucosa in the fundic area in all subjects, indicating that the expansion of acid-secreting mucosa remained partial. Compared with the neighboring acid-secreting area, the non-acid-secreting area was characterized histologically by higher degrees of residual inflammation, mucosal atrophy, and intestinal metaplasia, and by sustained hyperproliferation as well., Conclusions: Functionally irreversible (non-acid-secreting) gastric mucosa after eradication was associated with extensive intestinal metaplasia and sustained hyperproliferation, suggesting that such mucosa still possesses malignant potential. Congo red chromoendoscopy may be useful for estimating the risk of subsequent development of gastric cancer following successful H. pylori eradication by determining the distribution of functionally irreversible mucosa.

Purpose: The measurement of serum pepsinogens is clinically useful to represent gastric acid secretion. Since both serum pepsinogens and gastric acid secretion are considerably altered by H. pylori eradication, the correlation between these two parameters could be different prior to and after eradication. In this study, we investigated the correlation between the two parameters prior to and after eradication., Methods: One hundred eighteen H. pylori-positive patients with peptic ulcers or chronic gastritis were enrolled in this retrospective analysis. In all participants both the measurement of serum pepsinogens and the determination of gastric acid secretion were performed prior to and at 1 month after successful eradication. In 85 subjects, the same assessments were repeated at 7 months. Correlations between serum pepsinogens and gastric acid secretion were assessed using linear regression analysis., Results: The pepsinogen I/II ratio (r = 0.56) was a better indicator of gastric acid secretion in H. pylori-infected subjects than pepsinogen I itself (r = 0.31). Eradication of H. pylori altered the association, causing pepsinogen I (r = 0.55) to become a better indicator of gastric acid secretion compared with the pepsinogen I/II ratio (r = 0.40) at 1 month after eradication, followed by similar tendencies at 7 months., Conclusion: Using different serum biomarkers (pepsinogen I/II ratio prior to eradication or pepsinogen I after eradication), the measurement of serum pepsinogens is useful for predicting the individual gastric acid secretion level not only in H. pylori-infected subjects, but also in subjects with histories of eradication of the infection.

Background: Although previous studies have indicated that serum pepsinogen I levels, as well as the pepsinogen I/II ratio, were positively correlated with maximal gastric output, the relationship may be different between Helicobacter pylori-negative and -positive subjects. The aim of this study was to investigate the relation between serum pepsinogen concentrations and gastric acid secretion in H. pylori-positive and -negative subjects separately., Methods: The presence of H. pylori infection, the serum pepsinogen concentrations, and gastric acid secretion were investigated in 182 subjects without localized lesions in the upper gastrointestinal tract. Serum pepsinogen concentration was measured by radioimmunoassay, and maximal gastric acid output was estimated by an endoscopic gastrin test, as we have previously shown., Results: In H. pylori-positive subjects, serum pepsinogen I levels and the pepsinogen I/II ratio were significantly correlated with gastric acid secretion, although the latter showed a better correlation (r=0.40 and 0.53, respectively). On the other hand, in H. pylori-negative subjects, serum pepsinogen concentrations were well correlated with acid secretion (r=0.57), but there was no relation between the pepsinogen I/II ratio and acid secretion., Conclusions: The correlations between serum pepsinogens and gastric acid secretion differ, depending on the presence or absence of H. pylori infection. With the use of serum pepsinogens as a simple measure of gastric acid secretion, therefore, consideration of H. pylori infection status is needed. Because the determination of the acid secretory level has some clinical implications in both H. pylori-positive and -negative subjects, its estimation by serum pepsinogen concentrations can be of practical use.

Background: Recent studies have reported that proton pump inhibitor (PPI)/amoxicillin (A) metronidazole (M) therapy for Helicobacter pylori infection provides a sufficient cure rate in Japan in patients who have failed first-line treatment with PPI/amoxicillin and clarithromycin (AC). To validate the efficacy of this regimen as second-line therapy, our experience with second-line treatment using a PPI/AM regimen was reviewed., Methods: We analyzed data on 151 patients who had been prescribed a 10-day PPI/AM re-treatment regimen after eradication failure of 1 to 2 weeks' first-line PPI/AC therapy. The PPI/AM regimen was given according to results of susceptibility testing (S+) in 31 patients. The group that had undergone susceptibility testing was further divided into two subgroups according to dosage: standard dose of omeprazole (O)/AM (n = 11) and double dose of lansoprazole (L)/AM (n = 20). The PPI/AM regimen was given without susceptibility testing (S-) to 120 patients. These patients were also divided into two subgroups according to whether they received omeprazole or lansoprazole: OAM (n = 61) and LAM (n = 59). Cure rates and adverse effects in each group were analyzed., Results: The intention-to-treat (ITT)-based cure rate with/without susceptibility testing was 93.5% (95% confidence interval [CI], 79%-99%) and 87.5% (95% CI, 80%-93%), respectively (not significant [NS]). The ITT-based cure rate in S+/S- for OAM and S+/S- for LAM was 90.9% (95% CI, 59%-100%)/82% (95% CI, 70%-91%), and 95% (95% CI, 75%-100%)/93.2% (95% CI, 84%-98%), respectively (NS). Adverse effects were seen in 26.3% and 32.5% of patients in the OAM group and the LAM group, respectively (NS)., Conclusions: The 10-day PPI/AM re-treatment regimen is safe and effective, suggesting its usefulness as second-line treatment in Japan in patients who have failed initial treatment with the PPI/AC regimen.

We present a case of primary malignant melanoma arising in the rectum of a 71-year-old woman who had presented with intermittent rectal bleeding following bowel movement 2 months previously. Digital and sigmoidoscopic examination of the rectum revealed a 3 x 2 x 1 cm exophytic tumor with a granular surface in the rectum 35 mm from the dentate line. No increased pigmentation was detected. Biopsy revealed degenerated mucosa accompanied by severe infiltration of inflammatory cells, but no malignant cells. The tumor and normal mucosa surrounding the tumor was excised 12 days after the biopsy. Light microscopy revealed the tumor to consist of malignant melanocytes and showed that the tumor was surrounded by normal mucosa. Immunohistochemical staining with antimelanoma antibody and HMB-45 substuntiated the diagnosis. Clinical and laboratory examination excluded the presence of melanoma at sites other than rectum. The patient refused an abdomino-perineal resection of the rectum and combination chemotherapy was performed. She died 18 months after the initial operation due to local recurrences and metastases to pelvic lymph nodes, liver, and lung.