BACKGROUND AND AIM:Intestinal metaplasia (IM) of the gastric mucosa is strongly associated with the risk of gastric cancer (GC). This study was performed to investigate the usefulness of endoscopic and histological risk stratification for GC using IM. METHODS:This was a post-hoc analysis of a multicenter prospective study involving 10 Japanese facilities (UMINCTR000027023). The ridge/tubulovillous pattern, light blue crest (LBC), white opaque substance (WOS), endoscopic grading of gastric IM (EGGIM) score using non-magnifying image-enhanced endoscopy, and operative link on gastric IM assessment (OLGIM) were evaluated for their associations with GC risk in all patients. RESULTS:In total, 380 patients (115 with GC and 265 without GC) were analyzed. The presence of an LBC (limited to antrum: odds ratio [OR] 2.4 [95% confidence interval 1.1-5.0], extended to corpus: OR 3.6 [2.1-6.3]), the presence of WOS (limited to antrum: OR 3.0 [1.7-5.3], extended to corpus: OR 4.2 [2.1-8.2]), and histological IM (limited to antrum: OR 3.2 [1.4-7.4], extended to corpus: OR 8.5 [4.5-16.0]) were significantly associated with GC risk. Additionally, the EGGIM score (5-8 points: OR 8.8 [4.4-16.0]) and OLGIM (stage III/IV: OR 12.5 [6.1-25.8]) were useful for stratification of GC risk. The area under the receiver operating characteristic curve value for GC risk was 0.740 for OLGIM and 0.706 for EGGIM. CONCLUSIONS:The LBC, WOS, EGGIM, and OLGIM were strongly associated with GC risk in Japanese patients. This finding can be useful for GC risk assessment in daily clinical practice.

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. 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. 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). 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.

Objectives Limited information is available on the efficacy and safety of endoscopic resection (ER) of gastric submucosal tumors (SMTs) in Japanese endoscopic practice where ER for gastric tumors is extremely popular. Methods We conducted this study to elucidate the current scenario of ER for gastric SMTs in Japanese endoscopic practice. Patients (from 12 institutions) with gastric SMTs who underwent ER were enrolled from the first case until August 2020. Results We enrolled 117 patients with 118 lesions. The number of patients who underwent ER increased over the years. The mean endoscopic tumor size was 20 ± 7.2 (8–40) mm. The growth type was primarily intraluminal (90%). The mean resection and wound closure times were 58 ± 38 (range, 12–254) min and 31 ± 41 (range, 3–330) min, respectively. Complete ER was achieved for 117 (99%) lesions. Full‐thickness resection rate was 44%; however, only 12 (10%) patients required abdominal paracentesis for decompression. Endoscopic treatments were completed in 115 (97%) lesions, while three lesions required conversions to laparoscopic surgery due to luminal collapse, uncontrolled bleeding, and difficulty in defect closure. Gastrointestinal stromal tumors were the most common pathology (74%). No recurrence was observed during the mean follow‐up period of 4.3 ± 2.9 years. The 5‐year overall survival rate was 98.9% (95% confidence interval 97.8–100%). Conclusion Performance of ER for gastric SMTs is increasing in Japan. The technique seems feasible in Japanese endoscopic practice, warranting further validation in a prospective study.

Department of Endoscopy, Fukushima Medical University Hospital, Japan; Department of Gastroenterology, Fukushima Medical University, Japan; Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan; Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University, Japan; Department of Gastroenterology, Sendai City Medical Center, Japan; Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan; Department of Gastroenterology, Ohara General Hospital, Japan; Division of Gastroenterology Tohoku Medical and Pharmaceutical University, Japan; Department of Gastroenterology, Iwate Prefectural Isawa Hospital, Japan; Department of Gastroenterology, Osaki Citizen Hospital, Japan; Department of Gastroenterology and Neurology, Akita University Graduate School of Medicine, Japan; Department of Gastroenterology, Yokote Municipal Hospital, Japan; Department of Gastroenterology, Miyagi Cancer Center, Japan; Division of Endoscopy, Aomori Prefectural Central Hospital, Japan; Department of Gastroenterology, Iwate Prefectural Central Hospital, Japan; Department of Gastroenterology, Faculty of Medicine, Yamagata University, Japan; Division of Gastroenterology, Noshiro Kosei Medical Center, Japan; Department of Gastroenterology, Akita City Hospital, Japan; Digestive Disease Center, Akita Red Cross Hospital, Japan; Division of Gastroenterology, Aomori city hospital, Japan; Department of Gastroenterology, Hiraka General Hospital, Japan; Department of Gastroenterology, National Hospital Organization Sendai Medical Center, Japan; Department of Gastroenterology, Iwate Prefectural Ninohe Hospital, Japan; Division of Gastroenterology, Tohoku Rosai Hospital, Japan; Department of gastroenterology, Japanese Red Cross Morioka Hospital, Japan; Department of gastroenterology, Hachinohe Red Cross Hospital, Japan; Department of Gastroenterology, Iwate Prefectural Kuji Hospital, Japan; Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Japan; Department of Gastroenterology, Omagari Kosei Medical Center, Japan; Department of Internal Medicine and Gastroenterology, Iwate Prefectural Ofunato Hospital, Japan; Department of Gastroenterology, Iwate Prefectural Miyako Hospital, Japan; Department of Gastroenterology, Southern-Tohoku General Hospital, Japan.

Waku Hatta: NO financial relationship with a commercial interest | Tomoyuki Koike: NO financial relationship with a commercial interest | Sho Asonuma: NO financial relationship with a commercial interest | Hideki Okata: NO financial relationship with a commercial interest | Kaname Uno: NO financial relationship with a commercial interest | Tomoyuki Oikawa: NO financial relationship with a commercial interest | Wataru Iwai: NO financial relationship with a commercial interest | Makoto Yonechi: NO financial relationship with a commercial interest | Daisuke Fukushi: NO financial relationship with a commercial interest | Itaru Sato: NO financial relationship with a commercial interest | Shoichi Kayaba: NO financial relationship with a commercial interest | Fumitake Ishiyama: NO financial relationship with a commercial interest | Hirohiko Shinkai: NO financial relationship with a commercial interest | Ryosuke Kikuchi: NO financial relationship with a commercial interest | Hiroki Kikuchi: NO financial relationship with a commercial interest | Motoki Ohyauchi: NO financial relationship with a commercial interest | Hirotaka Ito: NO financial relationship with a commercial interest | Jun Fushiya: NO financial relationship with a commercial interest | Takeharu Shiroki: NO financial relationship with a commercial interest | Ryuhei Maejima: NO financial relationship with a commercial interest | Yasuhiko Abe: NO financial relationship with a commercial interest | Makoto Yagi: NO financial relationship with a commercial interest | Masashi Kawamura: NO financial relationship with a commercial interest | Satoshi Yokosawa: NO financial relationship with a commercial interest | Junya Honda: NO financial relationship with a commercial interest | Yutaka Kondo: NO financial relationship with a commercial interest | Naohiro Dairaku: NO financial relationship with a commercial interest | Tomohiro Masaka: NO financial relationship with a commercial interest | Kazuaki Norita: NO financial relationship with a commercial interest | Kenta Watanabe: NO financial relationship with a commercial interest | Kiichi Takahashi: NO financial relationship with a commercial interest | Masahiro Saito: NO financial relationship with a commercial interest | Yasushi Takahashi: NO financial relationship with a commercial interest | Hiroharu Echigo: NO financial relationship with a commercial interest | Yasuaki Abe: NO financial relationship with a commercial interest | Hiroyuki Endo: NO financial relationship with a commercial interest | Tomoki Okata: NO financial relationship with a commercial interest | Tatsuya Hoshi: NO financial relationship with a commercial interest | Taku Fujiya: NO financial relationship with a commercial interest | Katsunori Iijima: NO financial relationship with a commercial interest | Atsushi Masamune: NO financial relationship with a commercial interest

Little is known about the prognostic factors for survival after endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer (EGC). The aim of this study is to determine prognostic factors and a prediction model of 3-year survival after ESD for EGC in patients aged ≥ 85 years. We retrospectively evaluated the clinical outcomes of 740 patients with EGC aged ≥ 85 years, who were treated by ESD at 30 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were calculated with the Kaplan–Meier method. Prediction models for 3-year OS after ESD were estimated using the Cox proportional hazards model based on Uno’s C-statistics. During the follow-up period, 309 patients died of any cause and 10 patients died of gastric cancer. OS and DSS after 3 years were 82.7

54歳，女性．8年前に完全型Behçet病（Behçet's disease：BD）と診断．インフリキシマブ投与で安定していた．また，ラベプラゾール10 mgを長期内服していた．体重減少の精査で，回盲部に円形の深掘れ潰瘍を認め，腸管BDと診断した．高度下痢が持続し，上下肢のしびれ・脱力を伴い，Ca 6.0 mg/dl，Mg 0.5 mg/dlと著明な電解質異常を認めた．プロトンポンプ阻害薬（proton pump inhibitor：PPI）の長期内服とBDの腸管病変のため，Mg吸収障害を来たし，二次的に低Ca血症を呈したと考えられた．

OBJECTIVES:The usefulness of endoscopic and histological risk assessment for gastric cancer (GC) has not been fully investigated in Japanese clinical practice. METHODS:In this multicenter observation study, GC and non-GC patients were prospectively enrolled in 10 Japanese facilities. The Kyoto classification risk scoring system, the Kimura-Takemoto endoscopic atrophy classification, the endoscopic grading of gastric intestinal metaplasia (EGGIM), the operative link on gastritis assessment (OLGA) and the operative link on gastric intestinal metaplasia assessment (OLGIM) were applied to all patients. The strength of an association with GC risk was compared. In addition, important endoscopic findings in the Kyoto classification were identified. RESULTS:Overall, 115 GC and 265 non-GC patients were analyzed. Each risk stratification method had a significant association with GC risk in univariate analysis. In multivariate analysis, OLGIM stage III/IV (odds ratio [OR] 2.8 [95% CI 1.5-5.3]), high EGGIM score (OR 1.8 [1.0-3.1]) and opened-type Kimura-Takemoto (OR 2.5 [1.4-4.5]) had significant associations with GC risk. In the Kyoto classification, opened-type endoscopic atrophy, invisible regular arrangement of collecting venules (RAC), extensive (>30%) intestinal metaplasia in the corpus in image-enhanced endoscopy, and map-like redness in the corpus were independent high-risk endoscopic findings. The modified Kyoto classification risk scoring system using these four findings demonstrated a better area under the receiver operating characteristic curve value (0.750, P = 0.052) than that of the original Kyoto classification (0.706). CONCLUSIONS:The OLGIM stage III/IV, high EGGIM score and open-typed Kimura-Takemoto had strong association with GC risk in Japanese patients. The modified Kyoto classification risk scoring system may be useful for GC risk assessment, which warrants further validation. (UMIN000027023).

Although a recent study showed the cancer incidence of Barrett's esophagus (BE) to be 1.2%/year in 251 patient‐years in Japan, the long‐term outcomes remain unclear. The present study estimated the cancer risk of BE in Japan using our original prospective multicenter cohort.

BACKGROUND AND STUDY AIMS:The feasibility of endoscopic resection for synchronous early colon cancer after placement of self-expandable metallic stents (SEMS) for malignant colorectal obstruction is unknown. Herein we evaluated 3 cases of endoscopic resection for synchronous early colorectal cancers after SEMS placement. Patient 1 was an 82-year-old man with obstructive sigmoid colon cancer. We curatively treated the synchronous descending colon cancer with endoscopic submucosal dissection (ESD) and the rectal cancer with endoscopic mucosal resection (EMR) after SEMS placement. This is the first reported case of a successful ESD for synchronous early colon cancer via the use of a colonic stent. Patient 2 was an 81-year-old man with obstructive ascending colon cancer. We resected the synchronous transverse colon cancer via ESD. Histologic findings indicated that the carcinoma cells had invaded the submucosal layer. Therefore, we immediately performed expanded right-hemicolectomy. Patient 3 was an 81-year-old man with obstructive sigmoid colon cancer. We curatively treated the synchronous transverse colon cancer with EMR after SEMS placement. There were no complications associated with the endoscopic treatments in any of the cases. Our results indicate that preoperative endoscopic resection combined with the ESD technique for synchronous colorectal cancer after SEMS placement could be effective as a surgical strategy for patients with malignant colorectal obstruction.

OBJECTIVES:Few studies have simultaneously evaluated the long-term outcomes of endoscopic resection (ER) for squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus in Japan. The objective of this study was to evaluate the long-term outcomes of ER for superficial esophageal cancer in consecutive patients. METHODS:This was a retrospective study from a single institution. From April 2001 to June 2012, 204 patients with SCC and 26 patients with AC were included from a total of 355 consecutive patients who were treated by esophageal ER at the Tohoku University Hospital. Patients with submucosal invasion deeper than 200 μm and lymphovascular involvement were excluded. The intervention followed was endoscopic therapy. RESULTS:Overall survival, disease-free survival, and recurrence rates were evaluated as long-term outcomes. In the SCC group, during the median observation time of 36.5 months (range, 6-120 months), 22 (10.8%) patients experienced metachronous recurrence, 4 (2.0%) patients experienced local recurrence, and 27 (13.2%) patients died from causes unrelated to SCC. In the AC group, during the median observation time of 45.5 months (range, 6-131 months), one patient (3.8%) experienced metachronous recurrence and two (7.7%) died from causes unrelated to AC. The cumulative 5-year overall survival rates were not significantly different between SCC (75.9%) and AC (88.9%) (P=0.120). The cumulative 5-year disease-free survival rates of SCC (57.1%) were significantly lower than those of AC (85.2%; P=0.017). The cumulative 5-year recurrence rates of SCC (32.0%) were significantly higher than those of AC (4.2%; P=0.023). CONCLUSIONS:The rate of recurrence after ER was higher in patients with SCC than that in patients with AC. These findings suggest that, by detecting AC of the esophagus earlier, a satisfactory prognosis without recurrence can be expected after ER in Japan, and more rigorous endoscopic follow-up is necessary after ER in patients with SCC than in those with AC.

Objectives. Self-expandable metallic stent (SEMS) is widely used to treat malignant colonic obstruction. However, most reports about SEMS insertion have concentrated on the left colon. This study aimed to (1) investigate the effectiveness of SEMS insertion compared with conventional decompression tube for right-sided colonic obstruction and (2) compare the safety and technical success of SEMS insertion between left- and right-sided colonic obstructions. Methods. The data from thirty-seven patients who underwent SEMS or conventional decompression tube placement for malignant colonic obstruction in our hospital were analyzed retrospectively. Technical and clinical success, complications, and technical difficulties were analyzed. We compared the results between SEMS insertion and decompression tube placement in right colons and the outcomes of SEMS insertion between right- and left-sided colonic obstructions. Results. For right colons, the clinical success rate of SEMS insertion (100%) was significantly higher than that of decompression tube placement (55.9%). Concerning SEMS insertion, the technical difficulty and safety of SEMS insertion were similar between right- and left-sided colonic obstructions. Conclusion. SEMS insertion for right-sided colon is significantly more effective than conventional decompression tube placement, and this procedure was safer and less technically challenging than expected. SEMS insertion should be considered for treating right-sided malignant colonic obstruction.

Gastric acid measurement is useful in assessing the effectiveness of antisecretory drugs, however, the conventional tests involve invasive nasogastric intubation. Orally administered ¹³C-labeled calcium carbonate (Ca¹³CO₃) reacts with gastric acid to produce ¹³C-labeled carbon dioxide (¹³CO₂), which is then excreted in the breath. The objective of this study was to evaluate the suitability of Ca¹³CO3 breath test for estimating gastric acid secretion in human noninvasively. First, the Ca¹³CO₃ breath test and the measurement of pooled gastric acid under a fasting condition were performed in 6 healthy volunteers to evaluate the correlation between the two parameters. Next, endoscopic gastric acid collection and the Ca¹³CO₃ breath test were performed on different days after pentagastrin injection in 20 subjects to evaluate the correlation between the tests and the reproducibility. Finally, the same studies were repeated in 4 subjects before and after 1-week rabeprazole, a proton pump inhibitor, administration. The maximum CO₂ concentration (Cmax) correlated very well with the amount of pooled gastric acid (r = 0.95), suggesting that Ca¹³CO₃ breath test values well reflected the fasting intragastric acidity. The ¹³CO₂ concentration after pentagastrin injection correlated well with pentagastrin-stimulated maximal acid output (r = 0.79 at 20 min). The reproducibility of the Ca¹³CO₃ breath test under pentagastrin-stimulation was good (coefficient of variation = 0.11). Rabeprazole administration markedly reduced the values of the Ca¹³CO₃ breath test, suggesting that it can sensitively assess the efficacy of rabeprazole. The Ca¹³CO₃ breath test can potentially be a useful method for non-invasive estimation for gastric acid secretion in human.

Background: We investigated the association between long-segment Barrett's esophagus and obesity in the Japanese population in a multicenter case-control trial. Methods: One hundred thirteen patients with endoscopically detected Barrett's esophagus with a length of more than 2 cm and the same number of sex- and age-matched controls were prospectively enrolled. Barrett's esophagus was diagnosed based on the Prague C and M criteria. The body mass index (BMI) of the subjects was categorized into the following groups: normal, BMI <22.9; overweight, BMI 23.0-24.9, and obese, BMI >25.0. To determine the association between BMI and the risk of Barrett's esophagus, multivariate logistic regression analyses were performed. Results: The basically adjusted regression model adjusted for smoking and alcohol consumption revealed that overweight and obesity were significantly associated with an elevated risk of Barrett's esophagus (OR 2.4, 95% CI 1.2-4.7, and OR 2.5, 95% CI 1.3-4.6, respectively). The intensity of the association was not attenuated even after adjustment for gastroesophageal reflux disease-related parameters. Conclusions: An increased BMI was associated with an increased risk for Barrett's esophagus through a gastroesophageal reflux-independent mechanism in the Japanese population. Further, unlike in Caucasian populations, being even slightly overweight with a BMI of 23.0-24.9 was an independent risk factor in the Japanese population.

in PSC death or proliferation compared with negative control.In the presence of tobacco at 0.01mg/mL, ethanol at 5, 10 and 50mM increased PSC migration in a dose-dependent manner (p,0.05).However, neither alcohol nor tobacco alone did have any effect in PSC migration.Conclusions: Tobacco at concentrations of 0.1mg/mL or higher induces cell death and decreases PSC proliferation.In the presence of non-cytotoxic concentrations of tobacco, ethanol induces a dose-dependent increase of PSC migration.In conclusion, combined consumption of alcohol and tobacco is probably involved in the process of fibrogenesis in chronic pancreatitis.

Objectives: To evaluate the influence of meals on the pharmacokinetics of omeprazole and rabeprazole and to investigate these PPIs with reference to CYP2C19 genotypes in healthy Japanese men.Methods: This was a randomized, open label, four-way crossover study.Twelve healthy Japanese male volunteers received a single oral dose of either 20 mg omeprazole or 10 mg rabeprazole, in the fasted state and after a standardized breakfast.Results: Between the administration of omeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC, Tmax, and half-life.Between the administration of rabeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC and half-life, whereas the Tmax of rabeprazole after breakfast was significantly delayed (2.8 ± 1.0 vs 5.3 ± 1.8 h, respectively; p = 0.006).PMs demonstrated the highest Cmax and AUC after drug intake under the fasting state and after breakfast, and homo EMs showed a significantly delayed Tmax.Conclusion: When a single dose of either PPI was administered, the pharmacokinetics of omeprazole was not affected by the meal, whereas the Tmax of rabeprazole after the meal was significantly delayed.

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause dyspeptic symptoms, including abdominal pain. Gastric mucus is important as the first line of defense against luminal irritants. In the present study, we investigated whether gastric mucus secretion could influence the severity of gastric mucosal injuries or NSAID-induced dyspeptic symptoms. Fifteen Helicobacter pylori-negative, healthy males were administered two types of NSAIDs, a non-selective cyclooxygenase inhibitor, naproxen (300 mg, twice a day), or a cyclooxygenase-2-selective inhibitor, etodolac (200 mg, twice a day), for 1 week in a crossover study, with an interval of ≥ 4 weeks. Study participants underwent endoscopic examinations before and after treatment. Pentagastrin-stimulated gastric secretions were collected for 10 min during endoscopic examinations, and were analyzed for gastric acid levels (mEq/10 min) and mucus output (mg hexose/10 min). The grade of gastric mucosal injury was assessed endoscopically. Among 29 subjects who completed the crossover study, 11 individuals reported abdominal pain following the administration of naproxen or etodolac for 1 week, as judged by elevated pain scores, while 18 individuals did not report abdominal pain. The occurrence of symptoms was not associated with the type of NSAIDs administered or the occurrence of erosive injury visualized by endoscopy. Gastric mucus secretion was significantly increased in subjects without drug-induced abdominal pain (P < 0.05), whereas it was significantly reduced in those with drug-induced abdominal pain (P < 0.05). In conclusion, the occurrence of NSAID-induced abdominal pain is associated with reduced levels of gastric mucus secretion rather than the occurrence of endoscopic mucosal injury.

RPM in all) but minimally expressed in gastric mucosa (200 RPM).Conclusion These results made the novel observation that there is a gradient in miRNA expression along the gastrointestinal tract as a function of the proximity of the organs.Although the correlation was highest with the gastric mucosa, overall the BE miRNA profiles do not favor a specific organ in the luminal GI tract.Expression of specific miRNA appears to be organ restricted and may be an important determinant of the epithelial phenotype and needs to be further studied.