Search

The 2019 World Health Organization (WHO) Classification of Tumours of the Digestive System (5th edition) introduced the term "sessile serrated lesion" (SSL) to replace the term "sessile serrated adenoma/polyp" (SSA/P). SSLs are early precursor lesions in the serrated neoplasia pathway that result in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potential. The 2019 WHO classification noted that dysplasia arising in an SSL most likely is an advanced polyp, regardless of the morphologic grade of the dysplasia. Detecting SSLs with or without dysplasia is critical; however, detection of SSLs is challenging, and their identification by endoscopists and pathologists is inconsistent. Furthermore, indications for their endoscopic treatment have not been established. Moreover, SSLs are considered to contribute to the development of post-colonoscopy colorectal cancers. Herein, the clinicopathological and endoscopic characteristics of SSLs, including features determined using white light and image-enhanced endoscopy, therapeutic indications, therapeutic methods, and surveillance are reviewed based on the literature. This information may lead to more intensive research to improve detection, diagnosis, and rates of complete resection of these lesions and reduce post-colonoscopy colorectal cancer rates.

The Japan Gastroenterological Endoscopy Society held four serial symposia between 2019 and 2020 on the state-of-the-art of issues related to upper GI inflammatory diseases. This review discusses some of the topics addressed in these symposia. The papers regarding nonerosive reflux disease, recent improvements in intraesophageal pH-impedance monitoring and endoscopic diagnosis using image-enhanced endoscopy have been published. Many publications have addressed its usefulness in endoscopic treatment of gastroesophageal reflux disease such as anti-reflux mucosectomy. In the management of eosinophilic esophagitis, since the symptoms are subjective, objective indicators have been sought, and ultrasonography and high-resolution manometry may be useful tools for evaluation. The natural course of this condition, especially of asymptomatic cases, is not well clarified. Some newly developed anti-acid or anti-inflammatory medicines are now under investigation. With regard to autoimmune gastritis, because of widespread medical examinations, diagnosis of asymptomatic cases has been increasing. Recently, its endoscopic characteristics have become clear and the natural history of these conditions is being elucidated. The Kyoto Classification of Gastritis has been reported to be useful not only for Helicobacter pylori diagnosis but also for identification of risks of gastric cancer. Its usefulness is now recognized in Asia and Europe.

McKittrick–Wheelock syndrome (MWS) is a rare entity that has been described as electrolyte and fluid depletion secondary to secretory diarrhea caused by a large villous tumor in the colon or rectum. Most tumors associated with MWS are large but benign villous adenomas. Advanced cancers are seldom reported. We report a rare case of advanced rectal cancer with multiple liver and bone metastases presenting with MWS. A 59‐year‐old man was admitted to our hospital with a more than 3‐year history of chronic mucous diarrhea. Laboratory data revealed hyponatremia, hypokalemia, hypochloremia, and renal failure. Based on the findings on colonoscopy, computed tomography, and magnetic resonance imaging, he was diagnosed with advanced rectal cancer with liver and bone metastases, and MWS. Following intravenous fluid treatment, abdominoperineal resection of the rectum with lymph node dissection was performed. The surgically resected specimen was a circumferential villous tumor measuring 110 × 80 mm. Histological examination of the resected specimens revealed signet ring cell carcinoma with villous adenoma and metastasis in regional lymph nodes. The renal dysfunction and electrolyte abnormalities that were present before surgery improved. Two courses of capecitabine were administered as adjuvant chemotherapy after the surgery. However, approximately 2 months after surgery, he died of poor general condition due to progression of the liver metastases., McKittrick–Wheelock syndrome (MWS) is a rare entity that has been described as electrolyte and fluid depletion secondary to secretory diarrhea caused by a large villous tumor in the colon or rectum. Most tumors associated with MWS are large but benign villous adenomas. Advanced cancers are seldom reported. We report a rare case of advanced rectal cancer with multiple liver and bone metastases presenting with MWS.

Background and study aim Management of bile duct stones (BDSs) in patients with surgically altered anatomies (SAAs) remains challenging. An endoscopic ultrasound-guided antegrade (EUS-AG) procedure and double-balloon enteroscopy-assisted endoscopic retrograde cholangiography (DB-ERC) have been used to remove BDSs from patients with SAAs. However, few comparative data have been reported. Therefore, we compared the efficacy and safety of the techniques. Methods This was a single-center retrospective study. Patients with SAA who underwent the EUS-AG procedure or DB-ERC to remove intra- or extra-BDSs between November 2010 and March 2020 were included. The primary outcome was the technical success rate, defined as stent insertion or stone removal during the initial session. The secondary outcomes were the procedure time, incidence of adverse events (AEs), and complete stone removal rate. Results Of the 54 patients enrolled, 23 underwent the EUS-AG procedure and 31 DB-ERC. The technical success rates of EUS-AG and DB-ERC were 87.0% and 64.5%, respectively (P = 0.11). The procedure time was significantly shorter in the EUS-AG group than in the DB-ERC group (51.9 ± 15.4 vs 72.6 ± 32.2 min; P = 0.01), and the early AE rates were 26.1% and 12.9%, respectively (P = 0.71). The complete stone removal rates in patients who underwent previous stone removal were 94.1% in the EUS-AG group and 85.7% in the DB-ERC group (P = 0.61). Conclusion The EUS-AG afforded technical success and complete stone removal rates comparable with those of DB-ERC, but the former procedure was shorter. The AE rate was acceptable.

Pyoderma gangrenosum (PG) is an extra-intestinal skin lesion in inflammatory bowel disease (IBD) as is erythema nodosum. Vedolizumab (VED) is a monoclonal antibody that targets α4β7 integrin and has an intestinal selective mechanism. Despite good therapeutic effects on colitis, the effect on extra-intestinal manifestations (EIMs) remains unclear. Here we report a case of ulcerative colitis complicated by PG during treatment with VED, which was successfully treated with prednisolone in combination with adsorptive granulocyte and monocyte apheresis (GMA). The patient was a 50-year-old woman with a past medical history of extensive ulcerative colitis managed by golimumab (GLM). She developed flare symptoms due to loss of response to GLM, and treatment was switched to VED. Her gastrointestinal symptoms were improved with VED treatment with less frequent bowel movements. However, infiltrative erythema with pain appeared on the right lower leg and right knee, and expanded and gradually ulcerated. Her skin lesions were treated with corticosteroid, but showed poor improvement. Therefore, granulocyte and monocyte apheresis (GMA) treatment was administered in combination with prednisolone. After 3 months, the ulcer gradually improved, and at the time of this writing, the eruptions were nearly replaced by epithelial tissue. This case study showed that patients with UC and EIMS may respond well to combination therapy of VED and GMA. GMA has a very favorable safety profile. On the other hand, the causal connection between VED and PG is still unclear. We believe that a combination therapy involving VED and GMA in IBD patients with EIMs warrants consideration.

BACKGROUND AND AIM Aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was recently reported to be upregulated in some chronic liver diseases. However, its relevance in hepatocellular carcinoma (HCC) development is not fully assessed, especially in patients with chronic hepatitis C virus (HCV) infection. METHODS Aldo-keto reductase family 1 member B10 expression in the liver of 550 patients with chronic HCV infection was immunohistochemically assessed and quantified. A multivariate Cox model was used to estimate the hazard ratios (HRs) of AKR1B10 expression for HCC development, and the cumulative incidence of HCC was evaluated using the Kaplan-Meier method. RESULTS Aldo-keto reductase family 1 member B10 expression in the patients ranged from 0% to 80%. During the median follow-up of 3.2 years, 43 of 550 patients developed HCC. Multivariate analysis demonstrated that high AKR1B10 expression (≥6%) was an independent risk factor for HCC (HR, 6.43; 95% confidence interval, 2.90-14.25; P

Aim Recent reports have indicated that aldo-keto reductase family 1 member B10 (AKR1B10), a cancer-related oxidoreductase, was upregulated in some chronic liver diseases. However, few studies have reported AKR1B10 expression in chronic hepatitis B virus (HBV)-infected patients. The aim of the present study was to analyze AKR1B10 expression and its relevance on hepatocellular carcinoma (HCC) development in patients with chronic HBV infection. Methods Expression of AKR1B10 in the liver of 119 chronic HBV-infected patients was assessed and quantified immunohistochemically. A multivariate Cox model was used to estimate the hazard ratios of AKR1B10 expression for HCC development. The cumulative incidences of HCC were evaluated using Kaplan–Meier analysis. Results Expression of AKR1B10 in the study cohort ranged from 0% to 84%. During the median follow-up time (6.2 years), 13 patients developed HCC. Multivariate analysis revealed that high AKR1B10 expression (≥15%) was an independent risk factor for HCC (hazard ratio, 10.8; 95% confidence interval, 3.0–38.6; P

Background Although Helicobacter pylori infection among adults is a major risk factor for the development of gastric cancer and initial infection with H. pylori may occur before 5 years of age, the direct effects of H. pylori infection since childhood on gastric mucosa are unknown. The aim of this study was to evaluate gene expression in the H. pylori-infected gastric mucosa of children. Methods Gastric mucosal samples were obtained from 24 patients (12 adults and 12 children) who had undergone endoscopic evaluation of chronic abdominal complaints and were examined by the adult and pediatric gastroenterologists at Juntendo University Hospital. Six adult and pediatric patients with and six without H. pylori infection were enrolled. Their gastric mucosal samples obtained from the antrum and corpus were used for microarray, real-time polymerase chain reaction, and immunohistochemical analyses to examine the expression of inflammatory carcinogenic molecules. Results The expression of inflammatory molecules was upregulated in the H. pylori-infected gastric mucosa from both adults and children. The expression of olfactomedin-4 was only upregulated in adult patients, while that of pim-2, regenerating islet-derived 3 alpha, lipocalin-2, and C-X-C motif chemokine ligand 13 was equally upregulated in the infected gastric mucosa of both adults and children. Conclusions Because several carcinogenic molecules are upregulated in H. pylori-infected gastric mucosa even in children, early eradication therapy from childhood may be beneficial to decrease the incidence of gastric cancer. Although increased expression of olfactomedin-4 can be important in suppressing gastric cancer in adults, the increase was not detected in children.

Background and Aim This prospective pilot study investigated whether it is possible to predict the therapeutic response in both the early phase (1 week) and sustained phase (4 weeks) before starting proton pump inhibitor (PPI) therapy for functional dyspepsia (FD) or non-erosive reflux disease (NERD). Methods We administered rabeprazole 10 mg for 4 weeks to NERD/FD patients, who also answered a modified version of the Frequency Scale for Symptoms of gastroesophageal reflux disease (GERD) (FSSG), which added a pain score to the FSSG. Total score (TS), reflux score (RS), dysmotility score (DS), and pain score (PS) were analyzed. Symptom improvement was defined as ≥ 50% improvement in each score. Results We enrolled 83 patients (age [mean ± SD] 50.8 ± 15.8 years, 29 males, 54 females), of whom 62 could be classified into four groups: achieved symptom improvement within 1 week and maintained it for 4 weeks (Early-R, 40.3%); achieved symptom improvement within 1 week but lost it after 4 weeks (Temp-R, 9.7%); did not achieve symptom improvement within 1 week but did after 4 weeks (Late-R, 9.7%); and no improvement (Non-R, 40.3%). Mean TS, RS, DS, and PS in the Non-R group were significantly higher than in the Early-R group (23.9, 10.5, 11.0, and 2.4 vs 14.3, 6.8, 6.4, and 1.2). However, the Temp-R, Late-R, and Non-R groups could not be distinguished by TS, RS, or DS. Conclusion The magnitude of the pretreatment modified FSSG score seemed to be associated with the response at 1 week and 4 weeks.

Background and Aim Helicobacter pylori (H. pylori) infection is a strong risk factor for the development of gastric cancer. In 2013, the Japanese government approved H. pylori eradication therapy in patients with chronic gastritis as well as peptic ulcer. However, the continuing decline in eradication rates for first-line H. pylori eradication therapies is an urgent problem. In this study, we investigated changes in the first-line eradication rate from 2001 to 2010. Methods Eradication rates for 7-day triple therapy [proton pump inhibitor (rabeprazole 20 mg, lansoprazole 60 mg, or omeprazole 40 mg) + amoxicillin 1500 mg + clarithromycin (CAM) 400 or 800 mg, daily] were collated from 14 hospitals in the Tokyo metropolitan area. The urea breath test was used for the evaluation of eradication. The cut-off value was less than 2.5%. Results The yearly eradication rates (intention to treat/per protocol) were 78.5/79.5% (2001, n = 242), 71.2%/72.9% (2002, n = 208), 67.8%/70.5% (2003, n = 183), 75.6%/84.6% (2004, n = 131), 56.4%/70.5% (2005, n = 114), 70.5%/75.8% (2006, n = 271), 67.4%/82.0% (2007,n = 135), 64.0%/76.3% (2008, n = 261), 60.5%/74.3% (2009, n = 329), and 66.5%/78.8% (2010, n = 370), respectively. Examination of eradication rates according to CAM dosage revealed an eradication rate of 65.6% (383/584) for CAM 400 mg daily, and 68.5% (1124/1642) for CAM 800 mg daily, with no significant difference seen between dosages. Conclusion In recent years, eradication rates for first-line triple therapy have obviously decreased, but no noticeable decrease has occurred after 2001.

SummaryBackground The efficacy of proton pump inhibitors (PPIs) for treating functional dyspepsia (FD) is not well established. Aim This study, named the SAMURAI study, aimed to assess the efficacy and dose–response relationship of rabeprazole in Japanese patients with FD in a multicentre, double-blinded, randomised, placebo-controlled trial. Methods Investigated FD was diagnosed using the Rome III criteria. Subjects who did not respond to 1 week of single-blind placebo treatment in a run-in period were randomly assigned to 8 weeks of double-blind treatment with rabeprazole 10 mg, 20 mg, 40 mg or placebo, once daily. Dyspeptic symptoms were assessed by a dyspepsia symptom questionnaire (7-point Likert scale) and symptom diary. Results Of 392 subjects entered into the run-in period, 338 were randomly assigned. Although there was no significant difference between placebo and rabeprazole groups in complete symptom relief for four major dyspeptic symptoms, the satisfactory symptom relief of rabeprazole 20 mg was significantly higher than placebo according to the dyspepsia symptom questionnaire (45.3% vs. 28.2%, P = 0.027) and the symptom diary assessment (48.7% vs. 30.0%, P = 0.016). The efficacy was not influenced by syndrome type or Helicobacter pylori status. No statistically significant differences in the incidence of adverse events were seen among treatment groups. Conclusions Rabeprazole 20 mg once daily but not 10 or 40 mg significantly provides satisfactory symptom relief for functional dyspepsia (ClinicalTrials.gov, Number NCT01089543).

Background In Japan, the eradication rate of first-line therapy for Helicobacter pylori (H. pylori) with a proton pump inhibitor (PPI), amoxicillin (AMPC) and clarithromycin (CAM) has been decreasing because of a high prevalence of CAM resistance. A possible decrease of the eradication rate for second-line therapy with a PPI, AMPC and metronidazole (MNZ) is of concern. The aim of this study is to assess the trends in second-line eradication therapy for H. pylori in Japan. Materials and Methods We accumulated data retrospectively on patients administered second-line eradication therapy for Helicobacter pylori with a PPI, AMPC, and MNZ for 1 week after failure of first-line eradication therapy with a PPI, AMPC and CAM at 15 facilities in the Tokyo metropolitan area in Japan from 2007 to 2011. Trends for second-line eradication rates in modified intention-to-treat (ITT) analyses were investigated. Second-line eradication rates were categorized by three PPIs (rabeprazole (RPZ), lansoprazole (LPZ) or omeprazole (OMZ)) and evaluated. Results We accumulated data on 1373 patients. The overall second-line eradication rate was 92.4%. Second-line eradication rates in 2007, 2008, 2009, 2010 and 2011 were 97.7, 90.6, 94.5, 91.8 and 91.8%, respectively, with no significant trends revealed. Second-line eradication rates categorized by three PPIs for the entire 5-year period were 91.6, 93.4 and 92.4% (RPZ, LPZ and OPZ, respectively) with no significant differences among the three PPIs. Conclusions From 2007 to 2011, there were no significant trends in the second-line eradication rates and the rates remained consistently high. From the viewpoint of high prevalence of CAM resistance in Japan, triple therapy with PPI, AMPC and MNZ may be a better strategy for first-line therapy compared to triple therapy with PPI, AMPC and CAM.

Background and Aim: Functional magnetic resonance imaging (fMRI) is a useful technology for investigating regional metabolic activity in the brain. Many experiments using fMRI have been performed, but because of variations in protocols and analytic techniques, the results vary. When a priori information of the task is known, a model-based technique, such as statistical parametric mapping, is often used for analysis. In the case of acid stimulation of the esophagus the task model is unclear, so we analyzed brain activity during an acid or isotonic saline infusion to the esophagus using independent component analysis (ICA), which does not depend on a priori information of the task. Methods: Six healthy male volunteers (29–45 years) participated in the study. A multi-lumen catheter was inserted transnasally and side-hole infusions ports were approximately 15 cm proximal to the lower esophageal sphincter. The experimental protocol was 5-min interval, 5-min saline infusion, 5-min interval, 5-min 0.1 N HCl, and a final 5-min interval. After magnetic resonance scanning, fMRI image data were analyzed using group ICA. Results: The cerebral regions activated during the first interval, saline infusion, and HCl infusion were the thalamus, insula, cingulate gyri, temporal pole and some parts of the frontal, parietal, temporal and occipital lobes. Activation of the postcentral and precentral gyri occurred during both infusions, but was not observed during the first interval. Conclusion: ICA, which can show the cerebral areas activated in relation to liquid in the esophagus, may be a powerful technique for studying the brain's response to visceral stimulation.

Background and Aim: Prevalence of gastroesophageal reflux disease (GERD) varies in regions, but few reports on clinical features and quality of life (QOL) of asymptomatic GERD exist in Japan. Methods: Endoscopy was performed in our department between April 2008 and September 2010. Among 6409 cases answering Frequency of Scale for the Symptoms of GERD (FSSG) and SF8 QOL (PCS: physical component summary; MCS: mental component summary), proton pump inhibitor or histamine 2 receptor antagonist users were excluded, and 388 cases diagnosed as reflux esophagitis (RE) (Los Angeles Classification grade A, B, C, D) were analyzed. Asymptomatic cases with FSSG total score = 0 were defined as asymptomatic RE (AsymRE) and FSSG total score ≥ 1 as symptomatic RE (SymRE). Each clinical feature was analyzed. Results: The frequency of AsymRE was 11.6% of RE (AsymRE, n = 45; SymRE, n = 343). Patient characteristics in AsymRE, SymRE were male/female = 35/10; 239/104 (not significant), mean age (year) = 63.5 ± 14.3; 58.3 ± 12.7 (P

Aliment Pharmacol Ther 2011; 33: 323–332 Summary Background Proton pump inhibitors (PPIs) are less effective in non-erosive reflux disease (NERD) patients than in reflux oesophagitis patients. Whether the addition of prokinetics to PPIs improves NERD patients’ symptoms remains unknown. Aim To evaluate the efficacy of mosapride in NERD patients when used with PPI. Methods A total of 200 NERD patients were randomised to one of two arms: omeprazole (10 mg once daily) plus mosapride citrate (5 mg three times a day) (treatment arm) and omeprazole plus placebo (placebo arm). The primary endpoint was the rate of responders [visual analogue scale (VAS) was zero or

Background and Aims: Identifying the invasive depth of cancers less than 10 mm in diameter remains a challenge. This study examines the clinicopathological characteristics of colorectal cancers less than 10 mm in diameter and invading submucosal layer (SM)3 and below, which require surgery and must never be treated by endoscopic mucosal resection. Methods: We studied 54 cases of colorectal cancer less than 10 mm in diameter and invading the submucosa and deeper tissues, by dividing them into two groups: those invading SM1 and SM2 versus those invading SM3 and below. We investigated the clinicopathological characteristics of cancers invading SM3 and below by comparing them with cancers invading SM1 and SM2. Similarly, 38 cases, whose endoscopic findings could be analyzed, were selected and examined. Results: In cases invading SM3 and below, the rates of moderately to poorly differentiated adenocarcinoma, lymphatic and venous permeation and lymph node metastasis were significantly higher than those invading SM1 and SM2. Among cases invading SM3 and below, the presence of endoscopic findings—including white spots of the protruded type, and fullness, white spots, hardness and protruded lesions in the depressed area of the depressed type—was significantly higher than among those invading SM1 and SM2. Conclusion: Colorectal cancers less than 10 mm in diameter and invading SM3 and below have high malignant potential. Cancers of this invasive depth can be identified by looking for characteristics such as white spots, fullness, hardness and protruded lesions in the depressed area. Careful endoscopic observation for these signs aids in determining the appropriate treatment.

Background and Aims: It is still controversial which drugs, proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA), are more effective for dyspepsia in the Japanese population. Methods: Patients with uninvestigated dyspepsia (n = 104; male/female 41/63) were treated with either rabeprazole 10 mg o.d. (n = 62) or lafutidine 10 mg b.i.d. (n = 42) for 4 weeks. Questionnaires (modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease [mFSSG] and quality of life [QOL], SF-8) were administered before and after therapy. The mFSSG was classified into a total score (Q-T), reflux score (Q-R), dyspepsia score (Q-D) and pain score (Q-P). The SF-8 had a physical component summary (PCS) and mental component summary (MCS). The predominant type of symptom was reflux (R-S), pain (P-S) or dysmotility (D-S). Results: R-S was 19.2%, P-S 48.1%, D-S 24.0% and overlap 8.7%. In the R-S, Q-T and Q-R significantly improved with rabeprazole, but neither scale improved with lafutidine. MCS significantly improved with rabeprazole. In P-S, Q-T, Q-R, Q-D and Q-P significantly improved with both drugs. PCS significantly improved with both, whereas the MCS significant improved with rabeprazole. In D-S, Q-R and Q-D significant improved with rabeprazole, but neither improved with lafutidine. QOL did not improve with either. With overlap, neither scale nor the QOL reached a significant difference. Conclusion: Both PPI and H2RA have a positive effect on P-S, but H2RA therapy is limited for R-S and D-S, whereas PPI therapy is generally effective. Therefore, careful prescription based on symptoms is important.

Aim The effects of short- or long-term administration of nonsteroidal anti-inflammatory drugs (NSAIDs) on the colon have not been well characterized. We assessed the risk of developing colonic mucosal lesions according to the duration of exposure to NSAIDs: short-term and/or long-term use. Method A case-controlled study was performed by reviewing medical records for endoscopic findings, underlying disease, pre-endoscopic symptoms, category of NSAIDs used and duration of use. The patients underwent colonoscopy between January and October 2004, and 75 colitis cases and 1801 non-colitis controls were identified. The prevalence of NSAID use was compared between the cases and controls. The age- and sex- adjusted odds ratios (OR) were estimated using multiple logistic regression models. Results NSAIDs had been used in colitis cases and non-colitis controls for over six months in 20.0% and 12.7%, and for one week in 4.0% and 2.1%. Overall 76.0% and 85.2% had not received NSAIDs. The adjusted OR (95% confidence interval) for colonic mucosal lesions with short- and long term NSAID administration combined vs. non-use was 2.04 (1.16–3.61). When determined separately for short- and long-term NSAID users, the adjusted ORs were 1.48 (0.42–5.25) and 2.21 (1.19–4.11), compared to non-users. These values signify a trend toward an increased frequency of colonic mucosal lesions with longer use of NSAIDs (P=0.011 for trend). Conclusion Long-term use of NSAIDs increased the risk of colonic mucosal lesions, suggesting that NSAIDs may contribute to the pathogenesis of colonic ulcer or colitis.

Summary Background Few studies have compared the efficacy of proton pump inhibitors in resolving the symptoms of non-erosive reflux disease (NERD) and of erosive gastro-oesophageal reflux disease (GERD) in Japan. Aim To investigate and compare the efficacy of 4-week course of rabeprazole 10 mg/day on symptom resolution in NERD and erosive GERD in Japan. Methods The modified Los Angeles classification was used to grade endoscopically GERD in patients with heartburn (Grades N and M: NERD, Grades A and B: mild reflux oesophagitis (RO), and Grades C and D: severe RO). Rabeprazole 10 mg/day was administered for 4 weeks to 180 patients who kept symptom diaries. Results Complete relief of the symptoms was achieved in 35.8% of the NERD group and 55.4% of the erosive GERD group (mild RO: 51.1% and severe RO: 77.8%). Rabeprazole was significantly more effective in erosive GERD than in NERD patients. Among the NERD subgroups (Grades N and M), no difference in symptom improvement was observed. Conclusions Four-week, rabeprazole 10 mg/day acid suppression therapy was effective in resolving symptoms in Japanese GERD patients. This therapy was more effective in erosive GERD than in NERD patients, and in those with severe RO than in those with mild RO.

Summary Background Effects of long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) on the colon have not been well characterized. Aim To investigate colonoscopic findings and prevalence of adverse events following long-term use of NSAIDs. Methods The study included 425 patients (mean 66.4 years) treated for over one year with NSAIDs, and 2125 age- and sex-matched patients without NSAIDs as controls. Eligible candidates were selected by medical record review for underlying diseases, pre-endoscopic symptoms, category of NSAIDs used, and duration of use. We used endoscopy to study lesion characteristics. Results The occurrence rate of colonic lesions or bleeding in the NSAIDs user (13/425, 3.1%) was higher than that in controls (28/2125, 1.3%) (p = 0.017). Colitis was found in 10 of the 13 patients. The sigmoid colon, descending colon or both (70.0%) was commonly involved, and showed segmental ischemic colitis features in 8 of the 13 patients (61.5%). Among these, duration of use ranged from 1-30 years (mean 7.8). Nine of 13 patients (69.2%) took low-dose aspirin. Conclusion The prevalence of colonic lesions in long-term NSAIDs users is much lower than that of upper gastrointestinal side effects, but higher than that of colonic lesions in non-NSAIDs users. The most common features of NSAIDs-associated colitis were segmental ischeznia.

Background: Previously, we reported that most gastrointestinal tumors could be distinguished with the Light-Induced Fluorescence Endoscopy for GastroIntestine system (LIFE-GI system) using a fiberscope. However, the quality of the fiberscopic images was inferior compared with videoscopic images. Therefore, we developed a new Auto-Fluorescence Imaging (AFI) videoscope system (manufactured by Olympus Corp.). Methods: We evaluated the clinical usefulness of the AFI videoscope system for the detection of colonic neoplasms. Using this system, we observed 168 colonic polyps. Results: Images obtained by AFI provided better brightness than autofluorescence fiberscopic images and lesion margins were clearly evident. It demonstrated excellent recognition capability to a small lesion that was difficult to be detected by conventional observation. Sensitivity was 89% and specificity 81%, with specificity higher than that of the autofluorescence fiberscopic images. Conclusions: This newly developed AFI videoscope system will be useful for the detection of colonic neoplasms.

Background: Visceral hypersensitivity plays a major role in the pathogenesis of non-erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients. Aim: To investigate oesophageal hypersensitivity in Japanese NERD patients. Patients and methods: We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus-response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups. Results: The mean value of the lag time, intensity rating, and acid perfusion scores in NERD patients (4.6 ′ 3.4, 4.4 ′ 3.4, 27.8 ′ 26.7, respectively) were higher than in erosive GERD (3.2 ′ 3.3, 3.0 ′ 3.2, 18.2 ′ 24.8) and Barrett patients (2.5 ′ 4.0, 1.8 ′ 3.3, 15.0 ′ 28.8), and significantly higher than in the control group (1.7 ′ 2.7, 1.1 ′ 2.0, 5.4 ′ 11.8). The ratio of patients with higher sensory scores was also greater in the NERD group (57.7%) than in erosive GERD (32.3%) and Barrett group (16.7%), and significantly greater than in control group (6.7%). Conclusion: Our findings suggest that oesophageal sensitivity is likely to be enhanced especially in NERD patients also in Japanese population in comparison with erosive GERD, Barrett's oesophagus and controls.

Summary Background: An antimicrobial susceptibility test for Helicobacter pylori before second-line treatment is often performed, although whether the test is truly necessary remains unknown. Patients and methods: Eighty-two patients with H. pylori infection for whom first-line treatment with a 1-week proton pump inhibitor/amoxicillin–clarithromycin (AC) regimen had failed were randomly assigned to two groups: those having or not having the susceptibility test before re-treatment. The cure rates for these two groups were compared. Results: Five of the 82 patients were excluded from the analysis. For 38 patients in the susceptibility-test group, we used what we considered the best regimen based on susceptibility testing: 10 patients [no resistance to clarithromycin (CAM)] received the lansoprazole–amoxicillin–clarithromycin regimen, 22 patients [19 CAM resistant, metronidazole (MNZ) susceptible; three failure of culture] were given the lansoprazole-amoxicillin-metronidazole (LAM) regimen, and six patients (both MNZ and CAM resistant) received dual therapy with omeprazole (OPZ) and amoxicillin (AMOX) in which the OPZ dose was determined by the CYP2C19 gene polymorphism. For 39 patients in the group with no susceptibility testing, LAM regimens were prescribed. The intention-to-treat (ITT)-based cure rates in the groups with and without susceptibility testing were 81.6% (95% confidence interval; 66–92%) and 92.4% (79–98%), respectively, and there was no significant difference between these two groups. Conclusion: Susceptibility testing is not necessarily required before second-line therapy if the first-line treatment has been performed using proton pump inhibitor/AC regimens.

Background and Aim: A proton pump inhibitor (PPI)-based triple therapy consisting of a PPI, amoxicillin (A) and clarithromycin (C) or metronidazole (M) provides an eradication rate ranging from 80 to 90%. However, there have been few controlled studies with regard to the most effective regimen to re-treat patients after failure of the first-line therapy. Accordingly, we retrospectively reviewed our experiences and compared regimens with different combinations of antimicrobials to determine the optimal retreatment regimen. Methods: Out of 133 patients who had received second-line therapy after failure of first-line PPI/AC therapy, we selected, for review, patients who took the prescribed drugs for first-line therapy equal to, or more than 80%. As a result, data on 114 patients (83 males and 31 females; mean age 49.1 ± 13.0 years; peptic ulcer n = 89; non-ulcer dyspepsia, n = 25) were eligible for evaluation. They had either repeated the PPI/AC regimen (n = 34; 5–14 days), or had been administered the PPI/AM regimen (n = 80; 10 days). The cure rates of the two regimens were compared. Results: The eradication rates for second-line therapy with the PPI/AC regimen versus the PPI/AM regimen were 52.9% (95% CI, 35–70) versus 81.3% (95% CI, 71–89) by intention-to-treat analysis (P < 0.01), and 62.1% (95% CI, 42–79) versus 91.4% (95% CI, 81–97) by per-protocol analysis (P < 0.01). Conclusion: The eradication rate for the PPI/AM retreatment regimen was significantly higher than for the repeated PPI/AC regimen, suggesting that a 10-day PPI/AM regimen can be recommended as a retreatment regimen for patients who had first-line eradication therapy by PPI/AC regimens.

Background: There have been no reports that describe whether 5-day quadruple therapy (rabeprazole + amoxicillin + clarithromycin + metronidazole; RACM) could substitute for standard 7-day triple therapy as a first-line therapy for Helicobacter pylori. Patients and methods: This study was designed as a randomized prospective single centre study. A total of 160 H. pylori-positive patients who had not received therapy were given either a 5-day RACM regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d.) or a 7-day RAC regimen (n=80, rabeprazole 20 mg b.d., amoxicillin 750 mg b.d. and clarithromycin 200 mg b.d.). Cure of the infection was assessed by a 13C urea breath test 1 month after the completion of therapy. Results: The eradication rates of the 5-day RACM regimen and the 7-day RAC regimen were 93% (95% CI: 84–97%) and 81% (95% CI: 71–89%) by intention-to-treat analysis, 94% (95% CI: 86–98%) and 83% (95% CI: 73–91%) by all-patients-treated analysis analysis and 95% (95% CI: 87–98%; P

Background. New triple therapy for eradication of Helicobacter pylori based on a proton pump inhibitor (PPI) provides a cure rate of approximately 90% with few adverse effects. Recently, a PPI-based quadruple therapy, which consists of a PPI plus bismuth-based triple therapy for 7 days, has been studied, and a sufficient eradication rate has been achieved. However, a shorter duration results in improved compliance. In this study, newly developed short-term, simple twice-daily quadruple therapy consisting of rabeprazole, amoxicillin, clarithromycin, and metronidazole (RACM) was compared with a PPI-based triple-therapy regimen for eradication of H. pylori. Patients and Methods. This study was designed as a randomized open, prospective single-center study. Of a total of 105 H. pylori–positive patients, 55 received the RACM regimen for 5 days (rabeprazole, 10 mg bid; amoxicillin, 750 mg bid; clarithromycin, 200 mg bid; and metronidazole, 250 mg bid), and 50 received the RAC regimen for 5 days (rabeprazole, 10 mg bid; amoxicillin, 750 mg bid; and clarithromycin, 200 mg bid). Cure of the infection was assessed by HpSA (H. pylori stool antigen immunoassay) 1 month after completion of therapy. Results. The rates of eradication of H. pylori by RACM versus RAC were 94.5% (95% CI, 85–99) versus 80.0% (95% CI, 66–90) by intention-to-treat analysis; 98.1% (95% CI, 90–100) versus 87.0% (95% CI, 74–95) by all-patients-treated analysis; and 98.1% (95% CI, 90–100) versus 86.7% (95% CI, 73–95) by per-protocol analysis. No major adverse effects were reported, and 98.0% of patients reported complete compliance. Conclusions. The simple twice-daily and short-term quadruple regimen for only 5 days provided an excellent eradication rate. Compliance with the regimen was high, and serious adverse effects were few. Therefore, the RACM regimen can be considered as safe and effective.

Background: It remains controversial whether the cure of H. pylori infection improves NUD symptoms. Aim: To conduct a double-blind placebo-controlled single centre study with concealed allocation to investigate this question. Patients and methods: Ninety NUD patients with H. pylori infection were randomly assigned to either the treatment group (50 patients) or placebo group (40 patients). The treatment group received omeprazole, amoxycillin, clarithromycin and the placebo group received omeprazole and placebos for 7 days. Symptoms were assessed every week for up to 12 weeks after completion of medication by a symptom questionnaire. Alteration of histological parameters for gastritis was also evaluated. Results: The infection was cured in 41 out of 48 patients in the treatment group and none in the placebo group. There was no significant difference in the mean symptom scores at any assessment point up to 12 weeks between the treatment and placebo groups. Regarding histological parameters, activity and inflammation, not atrophy or intestinal metaplasia, were significantly improved in the treatment group. Conclusion: Although histological parameters were significantly improved in the treatment group, there was no significant improvement in symptoms of NUD in the treatment group compared to placebo.

Summary Aim: To investigate the incidence of reflux oesophagitis after antibacterial therapy for Helicobacter pylori infection in our patient population. Methods: Subjects were 451 H. pylori-infected patients (primary symptom: peptic ulcer disease in 347, nonulcer dyspepsia in 100, and reflux oesophagitis in four); 11 of these patients had reflux oesophagitis on study entry. H. pylori infection was treated by a proton pump inhibitor/amoxycillin-clarithromycin regimen for either 7 or 14 days. Each patient was examined by endoscopy before treatment and more than 6 months after treatment to compare oesophageal findings. In addition, 227 patients were interviewed regarding reflux symptoms, using symptom questionnaires, before and more than 6 months after treatment. Results: Among 440 patients who did not have reflux oesophagitis prior to antibacterial treatment (340 peptic ulcer patients and 100 nonulcer dyspepsia patients), 23 patients whose infection was eradicated developed reflux oesophagitis (5.4%). The 11 patients who had reflux oesophagitis prior to treatment were all successfully cured of infection. Six of these patients showed no change in their oesophagitis, while the condition improved in three and worsened in two. Symptom scores improved in 34 of the 36 patients who reported reflux symptoms. Among 19 patients who showed persistent infection, only one developed reflux oesophagitis (5.2%), while none complained of newly developed symptoms following treatment. Conclusions: Development of reflux oesophagitis after treatment of H. pylori infection was observed in a Japanese population. However, the incidence of this condition was comparable between those with persistent H. pylori infection and those in whom the infection was eradicated.

Background : A recent trend in curative therapy for Helicobacter pylori infection is the so-called triple therapy, which consists of a proton pump inhibitor (PPI) and two different antimicrobials. Various regimens employing this triple therapy have been reported. However, little is known about the effectiveness of rabeprazole, a recently developed proton pump inhibitor, when used in the triple therapy. Aim : To validate its usefulness by comparing rabeprazole with omeprazole and lansoprazole, in combination with amoxycillin and clarithromycin. Patients and methods : 221 H. pylori-positive patients with peptic ulcer disease were randomized to receive one of three different proton pump inhibitor/amoxycillin–clarithromycin (PPI/AC) regimens for 7 days. (i) OAC regimen (n = 75): omeprazole 20 mg b.d., amoxycillin (AMOX) 500 mg t.d.s. and clarithromycin (CAM) 200 mg b.d.; (ii) LAC regimen (n = 74): lansoprazole 30 mg b.d., AMOX 500 mg t.d.s. and CAM 200 mg b.d.; and (iii) RAC regimen (n = 72): rabeprazole 20 mg b.d., AMOX 500 mg t.d.s. and CAM 200 mg b.d. Cure of the infection was determined by the 13C urea breath test 1 month after completion of the treatment. Results : Intention-to-treat based cure rates for OAC, LAC and RAC regimens were 85% (95% CI, 75–92), 84% (95%, CI 73–91) and 88% (95% CI, 78–94), respectively, and per protocol based cure rates of these regimens were 88% (95% CI, 78–94), 91% (95%, CI 82–99) and 93% (95% CI, 84–98), respectively. Adverse effects in the entire study population, which included diarrhoea, glossitis or skin rash, were reported by 15% of the patients, and complete compliance was achieved in 95% of these patients. Conclusion : 1-week proton pump inhibitor/AC regimens for H. pylori infection were effective in the Japanese population. Rabeprazole can be considered as equivalent to omeprazole and lansoprazole in the PPI/AC triple therapy.

Background. Omeprazole or lansoprazole, amoxicillin, clarithromycin (PPI/AC) therapy has been reported to provide a high cure rate of H. pylori infection with few adverse effects. Effectiveness of H. pylori therapy may vary among different geographic regions and patient populations. However, there are few reports in Japan as to its effectiveness. We have, therefore, studied the effectiveness of H. pylori therapy in a large group of Japanese patients. Methods. For this study, 366 H. pylori-positive patients with peptic ulcer disease or non-ulcer dyspepsia (263 men and 103 women, mean age 48.5 years) were assigned to 6 groups, each receiving a different PPI/AC regimen. Group 1 received omeprazole (OPZ) 20 mg, amoxicillin (AMOX) 1500 mg, and clarithromycin (CAM) 400 mg; Group 2 OPZ 40 mg, AMOX 1500 mg, and CAM 400; and Group 3 OPZ 20 mg, AMOX 2000 mg, and CAM 600 mg daily for 14 days. The group treated with lansoprazole (LPZ) 30 mg, AMOX 1500 mg and CAM 400 mg was used for 14 days in Group 1L. OPZ 20 mg, AMOX 750 mg, and CAM 200 mg were given to Group 4 for 28 days and OPZ 20 mg, AMOX 1500 mg, CAM 400 mg was administered to Group 5 for 7 days. Cure of infection was assessed by the 13C urea breath test one month after completion of therapy. Results. Cure rates calculated by excluding the patients who showed borderline value of 13C urea breath test (Δ13C value between 5 and 10‰ in Groups 1, 1L, 2, 3, 4, and 5 were 82.7% (95% CI; 74–90), 88.9% (76–96), 84.9% (72–93), 81.3% (67–91), 84.6% (72–93), and 85.1% (72–94) on an intention-to-treat basis, and 88% (80–94), 95.2% (84–99), 95.6% (85– 99), 90.7% (78–97), 95.7% (85–99) and 88.9% (76–96) on a per-protocol basis, respectively. Adverse effects that affected compliance were observed in 10 of 237 patients on 14-day regiments, one of 47 on a 28-day regimen and one of 46 on a 7-day regimen. Conclusion. Two weeks PPI/AC therapy is highly effective for cure of H. pylori infection in the Japanese population. The low dose one month regimen and the one week OAC regimen were also effective in our patient population.

Background: Several studies have been reported on the effects of various therapeutic agents in enhancing or suppressing the carcinogenic activity of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). However, it is still unknown whether a mucosal protective agent could suppress its carcinogenic activity. Methods: Twenty-five Wistar male rats were divided into four groups: group 1, MNNG alone; group 2, MNNG + tetraprenylacetone; group 3, control; group 4, tetraprenylacetone alone. MNNG 100 mg/mL was freely given to groups 1 and 2, and tetraprenylacetone (200 mg/kg intraperitoneal) was additionally administered every other day to the rats in groups 2 and 4. The animals were sacrificed at 10 weeks and the gastric mucosa examined. Results: Atrophic changes were observed in the antrum after 8 weeks of oral administration of MNNG. Furthermore, using immunohistological analysis with 5-bromo-2′-deoxyuridine (BrdU), the proliferative zone was found to be enlarged and shifted upward, although the BrdU labelling index of the proliferative zone was unaltered. Intraperitoneal administration of tetraprenylacetone every other day suppressed the MNNG-induced atrophic change and the alterations proliferative markers. Tetraprenylacetone alone did not have an effect either on morphological or proliferative markers. Conclusion: These observations suggest that gastric mucosal defensive factors may play critical roles in suppressing atrophic change inducing carcinogenesis by an exogenic carcinogen.