Comparison of endoscopic submucosal resection with ligation and endoscopic submucosal dissection for small rectal neuroendocrine tumors: A multicenter retrospective study.

Objectives: Endoscopic submucosal resection with band ligation (ESMR-L) and endoscopic submucosal dissection (ESD) are both standard endoscopic resection methods for rectal neuroendocrine tumors (NETs) <10 mm in size. However, there is no definitive consensus on which is better. Here, we compared the efficacy of ESMR-L and ESD for small rectal NETs. Methods: This was a multicenter retrospective cohort study including 205 patients with rectal NETs who underwent ESMR-L or ESD. Treatment outcomes were compared by univariate analysis, multivariate analysis, and inverse probability treatment weighting (IPTW) using propensity scores. Subgroup analysis evaluated the impact of the endoscopist's experience on the technical outcome. Results: Eighty-nine patients were treated by ESMR-L and 116 by ESD. The R0 resection rate was not significantly different between the two (90% vs. 92%, p = 0.73). The procedure time of ESMR-L was significantly shorter than for ESD (17 min vs. 52 min, p < 0.01) and the hospitalization period was also significantly shorter (3 days vs. 5 days, p < 0.01). These results were confirmed by multivariate analysis and also after IPTW adjustment. The procedure time of ESD was significantly prolonged by a less-experienced endoscopist (49 min vs. 70 min, p = 0.02), but that of ESMR-L was not affected (17 min vs. 17 min, p = 0.27). Conclusions: For small rectal NETs, both ESMR-L and ESD showed similar high complete resection rates. However, considering the shorter procedure time and shorter hospitalization period, ESMR-L is the more efficient treatment method, especially for less-experienced endoscopists.

Risk stratification for advanced colorectal neoplasia based on the findings of the index and first surveillance colonoscopies.

Risk stratification by index colonoscopy is well established for first surveillance endoscopy, but whether the previous two colonoscopies affect the subsequent advanced neoplasias has not been established. Therefore, the subsequent risk based on the findings of the index and first surveillance colonoscopies were investigated. This retrospective, cohort study was conducted in two clinics and included participants who had undergone two or more colonoscopies after index colonoscopy. High-risk was defined as advanced adenoma (≥ 1 cm, or tubulovillous or villous histology, or high-grade dysplasia). Based on the findings of the index and first surveillance colonoscopies, patients were classified into four categories: category A (both colonoscopy findings were normal), category B (no high-risk findings both times), category C (one time high-risk finding), and category D (high-risk findings both times). The incidence of subsequent advanced neoplasia was examined in each category. A total of 13,426 subjects were included and surveyed during the study periods. The subjects in category D had the highest risk of advanced neoplasia (27.4%, n = 32/117). The subjects in category A had the lowest risk (4.0%, n = 225/5,583). The hazard ratio for advanced neoplasia of category D compared to category A was 9.90 (95% Confidence interval 6.82-14.35, P<0.001). Classification based on the findings of index and first surveillance colonoscopies more effectively stratifies the risk of subsequent advanced neoplasia, resulting in more proper allocation of colonoscopy resources after two consecutive colonoscopies.

Machine Learning-Based IoT-Botnet Attack Detection with Sequential Architecture.

With the rapid development and popularization of Internet of Things (IoT) devices, an increasing number of cyber-attacks are targeting such devices. It was said that most of the attacks in IoT environments are botnet-based attacks. Many security weaknesses still exist on the IoT devices because most of them have not enough memory and computational resource for robust security mechanisms. Moreover, many existing rule-based detection systems can be circumvented by attackers. In this study, we proposed a machine learning (ML)-based botnet attack detection framework with sequential detection architecture. An efficient feature selection approach is adopted to implement a lightweight detection system with a high performance. The overall detection performance achieves around 99% for the botnet attack detection using three different ML algorithms, including artificial neural network (ANN), J48 decision tree, and Naïve Bayes. The experiment result indicates that the proposed architecture can effectively detect botnet-based attacks, and also can be extended with corresponding sub-engines for new kinds of attacks.

Correction to: Short-Term Symptomatic Relief in Gastroesophageal Reflux Disease: A Comparative Study of Esomeprazole and Vonoprazan.

The original version of the article unfortunately contained percentage errors in second and third paragraphs of GerdQ Score section. Below is the corrected version.

Short-Term Symptomatic Relief in Gastroesophageal Reflux Disease: A Comparative Study of Esomeprazole and Vonoprazan.

BACKGROUND AND AIM: Proton pump inhibitors and vonoprazan (a potassium-competitive acid blocker) are recommended as first-line treatments for gastroesophageal reflux disease (GERD). However, few reports have investigated the onset of action of these agents for GERD symptom relief. The present study compared the symptom relief of esomeprazole with that of vonoprazan via monitoring self-reported GERD symptoms after treatment initiation. METHODS: This was a prospective, multicenter, randomized, open-label, parallel group, comparative clinical study between esomeprazole (20 mg/day) and vonoprazan (20 mg/day) administered for 4 weeks to patients with GERD symptoms. Patients who had scores ≥ 8 on the Gastroesophageal Reflux Disease Questionnaire (GerdQ) were defined as having GERD and enrolled in this study. Sixty patients were randomly assigned to either the esomeprazole group (n = 30) or the vonoprazan group (n = 30). Treatment response rates in each drug group were evaluated according to the GerdQ. The Frequency Scale for the Symptoms of GERD (FSSG) scores from the 1st day after treatment initiation and the Global Overall Symptom (GOS) scale scores during treatment were also evaluated. RESULTS: At 4 weeks, the treatment response rates for symptom relief according to the GerdQ were 88.0% in the esomeprazole group and 81.8% in the vonoprazan group. The GOS scales, which reflect the impact of GERD symptoms, were similar for both groups. The FSSG scores decreased from the 1st to the 14th day in both groups. CONCLUSIONS: There were no substantial differences in the symptom relief between the two groups at any time point in this short-term study.

Impact of retroflexion in the right colon after repeated forward-view examinations.

BACKGROUND AND AIM: Right colon polyps can especially be overlooked when they are located on the backs of haustral folds. Previous studies have reported that repeated forward-view examinations in the right colon were effective in reducing adenoma miss rates. The aim of this study was to clarify the impact of retroflexion in the right colon after repeated forward-view examinations. METHODS: This multicenter, prospective, observational study was conducted at three institutions in Kumamoto, Japan, between February 2014 and December 2015. Subjects who were over 40 years old and scheduled for colonoscopy were recruited. For the forward view, after cecal intubation, the colonoscope was withdrawn to the hepatic flexure. The colonoscope was sequentially reinserted to the cecum and then withdrawn to the hepatic flexure. For the retroflexion view (RV), the colonoscope was reinserted to the cecum, retroflexed, and then withdrawn to the hepatic flexure. All polyps were resected at the time of detection. The primary outcome of this study was the adenoma miss rate for the repeated forward-view examinations. RESULTS: Of the 777 enrolled participants, retroflexion was successful in 730 (94.0%). The repeated forward-view withdrawal technique detected 291 adenomas, while the third withdrawal in the RV detected 53. The adenoma miss rate for the repeated forward-view withdrawal was 15.4%. No severe adverse events occurred during retroflexion. CONCLUSION: Because adenomas located on potential blind spots can be missed when only using forward-view examinations, retroflexion in the right colon after repeated forward-view examinations might improve colonoscopy detection rates.

Comparative study: Vonoprazan and proton pump inhibitors in Helicobacter pylori eradication therapy.

AIM: To compare the effectiveness and safety of vonoprazan-based therapy with proton pump inhibitor (PPI)-based therapies to treat Helicobacter pylori (H. pylori). METHODS: We retrospectively analysed data from first-line (vonoprazan or PPI with 200 mg clarithromycin and 750 mg amoxicillin twice daily for 7 d) (n = 1353) and second-line (vonoprazan or PPI with 250 mg metronidazole and 750 mg amoxicillin twice daily for 7 d) (n = 261) eradication treatments for H. pylori -positive patients with associated gastrointestinal diseases from April 2014 to December 2015 at Hattori Clinic, Japan. The primary endpoint was the eradication rate, which was assessed with a full analysis set. The secondary endpoints were adverse events and related factors. RESULTS: After the first-line treatments, the eradication rates for vonoprazan, esomeprazol, rabeprazole, and lansoprazole were 87.9% (95%CI: 84.9%-90.5%), 71.6% (95%CI: 67.5%-75.5%), 62.9% (95%CI: 52.0%-72.9%), and 57.3% (95%CI: 50.4%-64.1%), respectively. The vonoprazan eradication rate was significantly higher than that of the PPIs (P < 0.01). Interestingly, smoking did not affect the H. pylori eradication rate in the vonoprazan group (P = 0.34), whereas it decreased the rates in the PPI groups (P = 0.013). The incidence of adverse events in the vonoprazan group was not different from the PPI group (P = 0.054), although the vonoprazan group exhibited a wider range of adverse events. Vonoprazan-based triple therapy was highly effective as a second-line treatment, with an eradication rate similar to that of PPI-based therapy. CONCLUSION: Vonoprazan might be superior to PPIs in first-line H. pylori therapy, particularly for smokers. However, caution is required due to possible adverse events.

Factors associated with complicated erosive esophagitis: A Japanese multicenter, prospective, cross-sectional study.

AIM: To assess the clinical characteristics of patients with complicated erosive esophagitis (EE) and their associated factors. METHODS: This prospective, cross-sectional study included patients diagnosed with EE by upper gastrointestinal endoscopy between October 2014 and March 2015 at 106 Japanese hospitals. Data on medical history, general condition, gastrointestinal symptoms, lifestyle habits, comorbidities, and endoscopic findings were collected using a standard form to create a dedicated database. Logistic regression analysis was used to calculate adjusted odds ratios (aOR) and 95%CI for the association with complicated EE. RESULTS: During the study period, 1749 patients diagnosed with EE, 38.3% of whom were prescribed proton pump inhibitors (PPIs) were included. Of them, 143 (8.2%) had EE complications. Esophageal bleeding occurred in 84 (4.8%) patients, esophageal strictures in 45 (2.6%) patients, and 14 (0.8%) patients experienced both. Multivariate analysis showed that increased age (aOR: 1.05; 95%CI: 1.03-1.08), concomitant use of psychotropic agents (aOR: 6.51; 95%CI: 3.01-13.61), and Los Angeles grades B (aOR: 2.69; 95%CI: 1.48-4.96), C (aOR: 15.38; 95%CI: 8.62-28.37), and D (aOR: 71.49; 95%CI: 37.47-142.01) were significantly associated with complications, whereas alcohol consumption 2-4 d/wk was negatively associated (aOR: 0.23; 95%CI: 0.06-0.61). Analyzing associated factors with each EE complication separately showed esophageal ulcer bleeding were associated with increased age (aOR: 1.05; 95%CI: 1.02-1.07) and Los Angeles grades B (aOR: 3.60; 95%CI: 1.52-8.50), C (aOR: 27.61; 95%CI: 12.34-61.80), and D (aOR: 119.09; 95%CI: 51.15-277.29), while esophageal strictures were associated with increased age (aOR: 1.07; 95%CI: 1.04-1.10), gastroesophageal reflux symptom (aOR: 2.51; 95%CI: 1.39-4.51), concomitant use of psychotropic agents (aOR: 11.79; 95%CI: 5.06-27.48), Los Angeles grades C (aOR: 7.35; 95%CI: 3.32-16.25), and D (aOR: 20.34; 95%CI: 8.36-49.53) and long-segment Barrett's esophagus (aOR: 4.63; 95%CI: 1.64-13.05). CONCLUSION: Aging and severe EE were common associated factors, although there were more associated factors in esophageal strictures than esophageal ulcer bleeding. Despite the availability and widespread use of PPIs, EE complications are likely to remain a problem in Japan owing to the aging population and high-stress society.

Cryptanalysis and Improvement of "A Secure Password Authentication Mechanism for Seamless Handover in Proxy Mobile IPv6 Networks".

Proxy Mobile IPv6 is a network-based localized mobility management protocol that supports mobility without mobile nodes' participation in mobility signaling. The details of user authentication procedure are not specified in this standard, hence, many authentication schemes have been proposed for this standard. In 2013, Chuang et al., proposed an authentication method for PMIPv6, called SPAM. However, Chuang et al.'s Scheme protects the network against some security attacks, but it is still vulnerable to impersonation and password guessing attacks. In addition, we discuss other security drawbacks such as lack of revocation procedure in case of loss or stolen device, and anonymity issues of the Chuang et al.'s scheme. We further propose an enhanced authentication method to mitigate the security issues of SPAM method and evaluate our scheme using BAN logic.

Clinical characteristics of elderly patients with proton pump inhibitor-refractory non-erosive reflux disease from the G-PRIDE study who responded to rikkunshito.

BACKGROUND: The incidence and severity of gastroesophageal reflux disease (GERD) in Japan tends to increase in elderly women. Rikkunshito (RKT), a traditional Japanese medicine, acts as a prokinetic agent and improves gastric emptying and gastric accommodation. Our previous prospective randomized placebo-controlled study showed that RKT combined with a standard-dose of rabeprazole (RPZ) significantly improved the acid-related dysmotility symptoms (ARD) in elderly patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study aimed to evaluate clinical characteristics of elderly PPI-refractory NERD patients with ARD symptoms who responded to RKT. METHODS: Two hundred forty-two patients with PPI-refractory NERD were randomly assigned to 8 weeks of either RPZ (10 mg/q.d.) + RKT (7.5 g/t.i.d.) (RKT group) or RPZ + placebo (PL group). Among them, 95 were elderly (≥65 years) with ARD (RKT group: n = 52; PL group: n = 43). We analyzed the changes using the 12 subscale score of frequency scale for the symptoms of GERD (FSSG) and 15 items of the Gastrointestinal Symptom Rating Scale at 4 and 8 weeks and compared the therapeutic efficacy between the 2 groups. RESULTS: There were no marked differences in baseline demographic or clinical characteristics in the 2 groups except for rate of current smoking. The FSSG score (mean ± SD at 0, 4, and 8 weeks) in both the RKT (16.0 ± 7.0; 9.9 ± 8.4; 7.0 ± 6.4) and PL (15.1 ± 6.4; 10.9 ± 6.7, 11.1 ± 8.5) groups significantly decreased after treatment. However, the degree of improvement of total and ARD scores of FSSG after the 8-week treatment was significantly greater in the RKT group than in the PL group. Combination therapy with RKT for 8 weeks showed significant improvement in 3 subscale scores (abdominal bloating, heavy feeling in stomach and sick feeling after meals) of the ARD domain and 1 subscale score (heartburn after meals) of the reflux symptom domain. CONCLUSIONS: RKT may be useful for improving GERD symptoms in elderly PPI-refractory NERD patients with ARD. Thus, RKT was particularly effective for resolving postprandial GERD symptoms (heavy feeling in stomach, sick feeling, and heartburn after meals). TRIAL REGISTRATION: (UMIN000005880).

A multicentre randomised trial to compare the efficacy of omeprazole versus rabeprazole in early symptom relief in patients with reflux esophagitis.

BACKGROUND: Proton pump inhibitors (PPIs) are affected by cytochrome P450 2C19 (CYP2C19) polymorphisms. This study compared the effect of two PPIs on early symptom relief in Japanese patients with reflux esophagitis, classified by the CYP2C19 phenotype. METHODS: Patients with reflux esophagitis were randomised to treatment with omeprazole 20 mg or rabeprazole 10 mg once daily. The CYP2C19 phenotype [homozygous extensive metaboliser (homoEM), heterozygous extensive metaboliser (heteroEM) or poor metaboliser (PM)] of each patient was determined. The primary efficacy endpoint was early, sufficient (Global Overall Symptom scale score 1 or 2), sustained (maintained for ≥7 days) reflux symptom relief. RESULTS: Of the 199 patients included in this analysis, the proportion achieving sufficient, sustained reflux symptom relief was higher with omeprazole than with rabeprazole on day 1 (35.6 vs. 22.4%; p = 0.041) and day 2 (43.6 vs. 28.6%; p = 0.028); there was no significant difference between the two groups on days 3-7. Among patients with the CYP2C19 PM phenotype, sufficient, sustained reflux symptom relief was higher with omeprazole than with rabeprazole on days 4-7 (62.5-66.9 vs. 31.6%; p ≤ 0.03); differences were not significant on days 1-3, or among those with the homoEM or heteroEM phenotypes on days 1-7. CONCLUSIONS: In Japanese patients with reflux esophagitis, omeprazole 20 mg is more effective than rabeprazole 10 mg at achieving early, sufficient, sustained reflux symptom relief in individuals with the CYP2C19 PM phenotype, and is similarly effective to rabeprazole 10 mg in those with heteroEM or homoEM phenotypes.

Electrocautery therapy combined with oral steroid administration for refractory corrosive esophageal stenosis prevents restenosis.

A 61-year-old female with refractory corrosive esophageal stenosis repeatedly underwent endoscopic balloon dilation at another hospital; however, no improvements were observed in the esophageal stenosis. Consequently, she had been on a liquid diet for the previous three years. She was admitted to our department for further treatment. A radial incision was made, by use of the SB knife Jr, for a pinhole-like stenosis in a short segment 39 cm from the incisor, and dilation was safely performed by use of a CRE balloon dilator. Subsequently, prednisolone was orally administered to prevent re-stenosis. This was followed by a favorable clinical course.

Pancreatic metastasis from mixed adenoneuroendocrine carcinoma of the uterine cervix: a case report.

Metastatic cancers of the pancreas are rare, accounting for approximately 2-4% of all pancreatic malignancies. Renal cell carcinoma is the most common solid tumor that metastasizes to the pancreas. Here, we present a case of uterine cervical carcinoma metastasizing to the pancreas and review the literature regarding this rare event. A 44-year-old woman with a uterine cervical tumor had undergone radical hysterectomy and had been diagnosed pathologically with stage Ib mixed adenoneuroendocrine carcinoma in 2004. She underwent concurrent radiotherapy and chemotherapy postoperatively. Pulmonary metastases subsequently appeared in 2008 and 2011, and she underwent complete resection of the lung tumors by video-assisted thoracic surgery. Although she was followed up without any treatment and with no other recurrences, positron emission tomography revealed an area of abnormal uptake within the pancreatic body in 2012. Enhanced computed tomography demonstrated a 20-mm lesion in the pancreatic body and upstream pancreatic duct dilatation. Endoscopic ultrasonography-guided fine needle aspiration was performed and pathological examination suggested neuroendocrine carcinoma (NEC). On the basis of these results and the patient's oncological background, lesions in the pancreatic body were diagnosed as secondary metastasis from the cervical carcinoma that had been treated 8 years earlier. No other distant metastases were visualized, and the patient subsequently underwent middle pancreatectomy. Pathological examination showed NEC consistent with pancreatic metastasis from the uterine cervical carcinoma. The patient has survived 7 months since the middle pancreatectomy without any signs of local recurrence or other metastatic lesions.

Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: a multicenter study of 2283 cases.

BACKGROUND: The relationship between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia is still not well understood. Towards obtaining a better understanding, concentrations of bile acids were measured. PATIENTS AND METHODS: This study was carried out with the participation of 14 facilities in Japan, and 2283 samples were collected. The subjects with bile acid concentrations equal to or higher than the limit of detection were divided into four groups of equal size (group A: 0-25%, group B: 26-50%, group C: 51-75%, and group D: 76-100%). Thus, including the control group, there were five groups in total. The odds that the control group would develop atrophic gastritis and intestinal metaplasia was set as 1,and the odds ratios (OR) in groups A, B, C and D were calculated based on the odds in the control group. RESULTS: Regarding the development of atrophic gastritis, no increased risk was observed in either the Helicobacter pylori (H. pylori)-positive or -negative cases. The OR for the development of intestinal metaplasia were significantly higher, for both cases with and without H. pylori infection, in group D. CONCLUSION: High concentrations of bile acid seem to be associated with an elevated risk of intestinal metaplasia.

Primary hepatic gastrinoma as an unusual manifestation of zollinger-ellison syndrome.

We report a rare case of primary hepatic gastrinoma. A 77-year-old woman exhibited continuous watery diarrhea for 8 months and weight loss. Bacterial cultures of the stools were negative and colonoscopy revealed no abnormalities. Esophagogastroduodenoscopy showed severe reflux esophagitis and multiple duodenal erosions. Computed tomography and magnetic resonance imaging detected two solid masses measuring <2 cm in diameter in the right lobe of the non-cirrhotic liver. Microscopically, the tumor was consistent with neuroendocrine tumor (grade 2) with abundant gastrin-immunoreactive cells. Endoscopic ultrasound detected no other alternative primary source of an endocrine tumor. The serum gastrin levels exceeded 40,000 pg/ml in the absence of H(2) receptor antagonist and proton pump inhibitor administrations. Based on an arterial stimulation and venous sampling test, the patient was diagnosed as primary gastrinoma of the liver. Our findings demonstrated the presence of Zollinger-Ellison syndrome in a patient who was subsequently cured by surgical resection of the liver tumors.

[A case of severe acute pancreatitis with hyperlipidemia in a pregnant woman].

A 29-year-old pregnant woman was referred to our hospital with suspected acute pancreatitis. On admission, the serum levels of pancreatic enzyme, total cholesterol and triglyceride were markedly elevated, which suggesting acute pancreatitis with hyperlipidemia. Treatment consisted of continuous hemodiafiltration, LDL apheresis, heparin and insulin combination therapy. On the 24th day of hospitalization, a cesarean section delivery resulted in the birth of a healthy infant. We reported a case of hyperlipidemia-induced acute pancreatitis in a woman with second trimester pregnancy, where multidisciplinary treatment was quite effective.

Efficacy of omeprazole, famotidine, mosapride and teprenone in patients with upper gastrointestinal symptoms: an omeprazole-controlled randomized study (J-FOCUS).

BACKGROUND: In Japan, treatment guidelines are lacking for patients with upper gastrointestinal symptoms. We aimed to compare the efficacy of different drugs for the treatment of uninvestigated upper gastrointestinal symptoms. METHODS: This was a randomized, open-label, parallel-group multicenter study. Helicobacter pylori-negative, endoscopically uninvestigated patients ≥ 20 years of age with upper gastrointestinal symptoms of at least moderate severity (Global Overall Symptom score [GOS] ≥ 4 on a 7-point Likert scale) were randomized to treatment with omeprazole (10 mg once daily), famotidine (10 mg twice daily), mosapride (5 mg three times daily) or teprenone (50 mg three times daily). The primary endpoint was sufficient relief of upper gastrointestinal symptoms after 4 weeks of treatment (GOS ≤ 2). UMIN clinical trial registration number: UMIN000005399. RESULTS: Of 471 randomized patients, 454 were included in the full analysis set. After 4 weeks of treatment, sufficient symptom relief was achieved by 66.9% of patients in the omeprazole group, compared with 41.0%, 36.3% and 32.3% in the famotidine, mosapride and teprenone groups, respectively (all, p < 0.001 vs omeprazole). There were no treatment-related adverse events. CONCLUSIONS: The favorable efficacy and safety profiles of omeprazole in relieving uninvestigated upper gastrointestinal symptoms support its use as first-line treatment in this patient group in Japan. Patients who show no improvement in symptoms despite PPI use, and those with alarm symptoms (such as vomiting, GI bleeding or acute weight loss) should receive further investigation, including prompt referral for endoscopy. TRIAL REGISTRATION: UMIN000005399.

Brain metastasis from gastrointestinal stromal tumor: a case report and review of the literature.

Metastasis of gastrointestinal stromal tumor (GIST) into the central nervous system is extremely rare. We report a patient with synchronous GIST and brain metastasis. At disease onset, there was left hemiplegia and ptosis of the right eyelids. Resection cytology of the brain tumor was reported as metastasis of GIST. After positron emission tomography examination, another tumor in the small bowel was discovered, which suggested a small bowel GIST associated with intracranial metastasis. Immunohistochemical analysis of the intestinal tumor specimen obtained by double balloon endoscopy showed a pattern similar to the brain tumor, with the tumors subsequently identified as intracranial metastases of jejunal GIST. After surgical resection of one brain tumor, the patient underwent whole brain radiation therapy followed by treatment with imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Mutational analysis of the original intestinal tumor revealed there were no gene alterations in KIT or PDGFRα. Since the results indicated the treatment had no apparent effect on either of the tumors, and because ileus developed due to an intestinal primary tumor, the patient underwent surgical resection of the intestinal lesion. However, the patient's condition gradually worsen and she subsequently died 4 months after the initial treatment.

Lifestyle change influences on GERD in Japan: a study of participants in a health examination program.

BACKGROUND: Though gastroesophageal reflux disease (GERD) has been a prevalent disease in Western countries, the incidence of GERD has only just started to increase in Japan. AIM: The aim of this study was to determine which lifestyle factors may be associated with GERD in Japan. METHODS: A total of 2,853 participants who took part in a health examination program between July 2004 and March 2005 were enrolled. GERD symptoms were assessed using the Japanese version of the Carlsson-Dent self-administered questionnaire (QUEST). The GERD group consisted of participants with a QUEST score ≥6 and/or endoscopic findings. The GERD group was divided into asymptomatic ERD (erosive reflux disease with no symptoms), symptomatic ERD (erosive reflux disease with symptoms) and NERD (non-erosive reflux disease) groups. Associated factors for these diseases were analyzed by logistic regression analysis. RESULTS: GERD was diagnosed in 667 (23.4%) participants. Among the subjects placed in the GERD group, asymptomatic ERD, symptomatic ERD and NERD were diagnosed in 232 (8.1%), 91 (3.2%) and 344 (12.1%) participants, respectively. Factors associated with GERD included a high BMI (body mass index), hiatus hernia, fewer hours of sleep, lack of exercise, and drinking green tea. CONCLUSIONS: Relationships between lifestyle, gender and GERD were investigated in the present study. Both lifestyle improvements and consideration of gender differences can be used to help prevent GERD development.