Serial change in gastric motility in eosinophilic gastritis with pyloric stenosis assessment by abdominal ultrasonography.

Eosinophilic gastritis (EoG) is defined as the presence of upper gastrointestinal symptoms combined with histologic findings of > 30 eosinophils/high-power field (eos/hpf) in 5 hpf in any part of the gastric mucosa, except for the secondary causes of gastric eosinophilia. This is the first case report of a serial change in gastric motility in EoG with pyloric stenosis using abdominal ultrasonography. A 56-year-old woman was diagnosed with pyloric stenosis by upper gastrointestinal radiographic examination during a medical checkup. She had nausea and loss of appetite, her gastrointestinal symptom rating scale (GSRS) score was 20, and her F scale score was 20. Esophagogastroduodenoscopy (EGD) demonstrated pyloric stenosis and multiple superficial ulcerations in the antrum. Histopathological findings of gastric biopsy specimens revealed severe eosinophilic infiltration (100 eos/HPF), and the diagnosis was EoG with pyloric stenosis. Before treatment, the gastric anterior wall thickness was 6.3 mm. The gastric motility in EoG was evaluated by intra-abdominal ultrasonography. Ultrasonography showed low motility in the antrum, especially the amplitude and motility index. After 6 months of steroid treatment, her symptoms improved. Her GSRS score was 13, and her F scale score was 19. Histological eosinophilic infiltration decreased to 50 eos/HPF, showing improvement. On ultrasonography, gastric motility also improved and recovered to normal. After 12 months, several examinations confirmed improvement, including gastric motility by ultrasonography.

Exercise Affects Mucosa-Associated Microbiota and Colonic Tumor Formation Induced by Azoxymethane in High-Fat-Diet-Induced Obese Mice.

The only reliable factor that reduces the risk of colorectal carcinogenesis is physical activity. However, the underlying mechanisms remain unclear. In this study, we examined the effects of physical activity against gut microbiota, including mucosa-associated microbiota (MAM) on azoxymethane-induced colorectal tumors in obese mice. We divided the subjects into four groups: normal diet (ND), high-fat diet (HFD), ND + exercise (Ex), and HFD + Ex groups. The Ex group performed treadmill exercise for 20 weeks. Thereafter, fecal and colonic mucus samples were extracted for microbiota analysis. DNA was collected from feces and colonic mucosa, and V3-V4 amplicon sequencing analysis of the 16SrRNA gene was performed using MiSeq. The HFD group had significantly more colonic polyps than the ND group (ND 6.5 ± 1.3, HFD 11.4 ± 1.5, p < 0.001), and the addition of Ex suppressed the number of colonic polyps in ND and HFD groups (ND 6.5 ± 1.3, ND + Ex 2.8 ± 2.5, p < 0.05). The HFD group showed significantly lower concentrations of succinic, acetic, butyric, and propionic acids (mg/g) in feces, compared with the ND group (succinic acid HFD 0.59, ND 0.17; acetic acid HFD 0.63, ND 2.41; propionic acid HFD 0.10, ND 0.47; and N-butyric acid HFD 0.31, ND 0.93). In the case of ND, succinic acid and butyric acid tended to decrease with Ex (succinic acid ND 0.17, ND + Ex 0.12; N-butyric acid ND 0.93, ND + Ex 0.74 0.74). Succinic acid, acetic acid, butyric acid, and propionic acid levels in feces were significantly lower in the HFD group than in the ND group; in both feces and mucus samples, Butyricicoccus and Lactobacillus levels were significantly lower in the HFD group. Akkermansia was significantly increased in ND + Ex and HFD + Ex groups. Diet and exercise affected the number of colorectal tumors. Furthermore, diet and exercise alter intestinal MAM, which may be involved in colorectal tumor development.

A Study of the Risk Factors for 402 Patients with Esophageal Squamous Cell Carcinoma - A Retrospective Comparison with Health Checkup Participants.

Objective Esophageal cancer is a gastrointestinal cancer with a poor prognosis. However, it is curable and can be treated endoscopically if it is detected at an early stage. The objective of this study was to identify the factors that contribute to early detection. Methods From April 2011 to December 2019, we retrospectively investigated consecutive patients diagnosed with esophageal squamous cell carcinoma (ESCC) through upper gastrointestinal endoscopy at two hospitals of Kawasaki Medical University based on medical records. The factors contributing to the early detection of ESCC were investigated by comparing patients with ESCC with those undergoing health checkups in whom no organic lesions were found in the upper gastrointestinal tract on endoscopy (controls). Patients Factors contributing to early detection were examined in 402 ESCC cases and 391 sex- and age-matched controls, and early and advanced cancers were compared along with the risk factors for ESCC. Results A multivariate analysis showed that alcohol consumption and smoking, concomitant cancer of other organs, and a low body mass index (BMI) were factors associated with ESCC (odds ratio [OR], 4.65; 95% confidence interval [CI], 2.880-7.520, OR,3.63; 95% CI, 2.380-5.540, OR, 2.09; 95% CI, 1.330-3.270, OR, 6.38; 95% CI, 3.780-10.800), whereas dyslipidemia was significantly less common in patients with ESCC (OR, 0.545; 95% CI, 0.348-0.853). Comparing early and advanced cancers, a history of endoscopic screening was the only factor involved in early detection (OR, 7.93; 95% CI, 4.480-14.00). Conclusion The factors associated with ESCC include alcohol consumption, smoking, concomitant cancer of other organs, and a low BMI. Endoscopy in subjects with these factors may therefore be recommended for the early detection of ESCC.

Current Status of Diagnosis and Treatment of Colorectal Cancer in Asian Countries: A Questionnaire Survey.

INTRODUCTION: Diagnostic and therapeutic methods for colorectal cancer (CRC) have advanced; however, they may be inaccessible worldwide, and their widespread use is challenging. This questionnaire survey investigates the current status of diagnosis and treatment of early-stage CRC in Asian countries. METHODS: Responses to the questionnaire were obtained from 213 doctors at different institutions in 8 countries and regions. The questionnaire consisted of 39 questions on the following four topics: noninvasive diagnosis other than endoscopy (6 questions), diagnosis by magnification and image-enhanced endoscopy (IEE) including artificial intelligence (AI) (10 questions), endoscopic submucosal dissection (ESD), proper use among other therapeutic methods (11 questions), and pathologic diagnosis and surveillance (12 questions). RESULTS: Although 101 of 213 respondents were affiliated with academic hospitals, there were disparities among countries and regions in the dissemination of advanced technologies, such as IEE, AI, and ESD. The NICE classification is widely used for the diagnosis of colorectal tumors using IEE, while the JNET classification with magnification was used in countries such as Japan (65/70, 92.9%) and China (16/22, 72.7%). Of the 211 respondents, 208 (98.6%) assumed that en bloc resection should be achieved for carcinomas, and 180 of 212 (84.9%) believed that ESD was the most suitable in cases with a diameter larger than 2 cm. However, colorectal ESD is not widespread in countries such as Thailand, the Philippines, and Indonesia. CONCLUSION: The promotion of advanced technologies and education should be continual to enable more people to benefit from them.

Pancreatic ductal adenocarcinoma with acinar-to-ductal metaplasia-like cancer cells shows increased cellular proliferation.

BACKGROUND/OBJECTIVES: Acinar-to-ductal metaplasia (ADM) has been shown to contribute to the development of pancreatic ductal adenocarcinoma (PDAC) in genetically engineered mouse models, but little is known about whether acinar cell plasticity contributes to carcinogenesis in human PDAC. We aimed to assess whether cancer cells that stain positive for amylase and CK19 (ADM-like cancer cells) are present in human resected PDAC and to investigate their role in tumor progression. METHODS: We immunohistochemically investigated the presence of ADM-like cancer cells, and compared the clinical and histological parameters of PDAC patients with and without ADM-like cancer cells. RESULTS: ADM-like cancer cells were detected in 16 of 60 (26.7%) PDAC specimens. Positive staining for anterior gradient protein 2 (AGR2) was observed in 14 of 16 (87.5%) PDAC specimens with ADM-like cancer cells. On the other hand, the intensity of AGR2 expression (negative, low/moderate or high) was lower in PDAC with ADM-like cancer cells (9/7) than in PDAC without these cells (11/33) (P = 0.032). The presence of ADM-like cancer cells was significantly correlated with increased cell proliferation (P = 0.012) and tended to be associated with MUC1 expression (P = 0.067). CONCLUSIONS: These results indicated that acinar cells may act as the origin of human PDAC, and that their presence may be useful for the stratification of human PDAC to predict prognosis.

Reduced abundance of butyric acid-producing bacteria in the ileal mucosa-associated microbiota of ulcerative colitis patients.

Compositional changes in the microbiota are associated with various inflammatory diseases, including ulcerative colitis (UC). Aim: This study aimed to investigate the mucosa-associated microbiota (MAM) in patients with UC and its difference related with disease activity and classification. Brush samples were collected from the terminal ileum and sigmoid colon during endoscopic procedures. The microbiota of samples was profiled using the Illumina MiSeq platform. The V3-V4 regions of the gene encoding 16S rRNA (460 bp) were amplified using PCR. Fifty UC patients and twenty healthy controls were enrolled. UC patients displayed significantly reduced α-diversity in both the ileum and sigmoid colon compared to controls. A difference in ß-diversity in the unweighted analysis was observed between the two groups. The abundance of Lactobacillus and Veillonella was significantly higher and that of Butyricicoccus, Ruminococcus and Lachnospiraceae was significantly lower in the ileum of UC patients than in controls. The abundance of Odoribacter in the ileum was significantly lower in left-sided colitis and pancolitis patients than in proctitis patients and lower in patients with highly severe disease activity than with mild disease activity. The reduction in abundance of butyric acid-producing bacteria, especially Odoribacter, in ileal MAM may play an important role in the pathophysiology of UC.

Reduction of butyric acid-producing bacteria in the ileal mucosa-associated microbiota is associated with the history of abdominal surgery in patients with Crohn's disease.

Fecal microbiota is a significant factor determining the cause, course, and prognosis of Crohn's disease (CD). However, the factors affecting mucosa-associated microbiota (MAM) remain unclear. This retrospective study examined the differences in ileal MAM between CD patients and healthy controls and investigated the factors affecting MAM in CD patients to clarify potential therapeutic targets. Ileal MAM was obtained using brush forceps during endoscopic examination from 23 healthy controls and 32 CD patients (most were in remission). The samples' microbiota was profiled using the Illumina MiSeq platform. Compared to controls, CD patients had significantly reduced α-diversity in the ileum and a difference in ß-diversity. The abundance of butyric acid-producing bacteria in the ileal MAM was significantly lower in CD patients with a history of abdominal surgery than in those without. Because butyric acid is a major energy source in the intestinal epithelium, its metabolism via ß-oxidation increases oxygen consumption in epithelial cells, reducing oxygen concentration in the intestinal lumen and increasing the abundance of obligate anaerobic bacteria. The suppression of obligate anaerobes in CD patients caused an overgrowth of facultative anaerobes. Summarily, reducing the abundance of butyric acid-producing bacteria in the ileal MAM may play an important role in CD pathophysiology.

Serial Changes in Intestinal Stenotic Stiffness in Patients with Crohn's Disease Treated with Biologics: A Pilot Study Using Ultrasound Shear Wave Elastography.

BACKGROUND/AIMS: Intestinal strictures represent an important serious complication of Crohn's disease. Shear wave elastography is a promising noninvasive ultrasound technique for assessing tissue stiffness. This study aimed to evaluate stiffness in the areas of intestinal stricture in patients with Crohn's disease using shear wave elastography and the changes in stiffness after biologics. MATERIALS AND METHODS: We enrolled 21 Crohn's disease patients having intestinal stricture. The patients consisted of 3 groups, which were the infliximab naïve (n = 6) group, the ustekinumab naïve (n = 8), and the bio-switch from infliximab to ustekinumab (n = 7) group. Bowell wall thickness was examined by ultrasound sonography, and the stiffness of Crohn's disease stricture lesions was evaluated using Shear wave speed before and 1 year after anti-tumor necrosis factor-alpha antibody infliximab, anti-interleukin 12/23 antibody ustekinumab, and bio-switch from infliximab to ustekinumab. RESULTS: Bowell wall thickness was significantly improved after infliximab, ustekinumab, and the bio-switch. However, shear wave speed indices only in the ustekinumab group significantly decreased after treatment (P = .028), but not in the other group. CONCLUSIONS: Shear wave elastography might be a useful method to evaluate stiffness in the areas of intestinal stricture in patients with Crohn's disease treated with biologics. However, a prospective randomized study evaluating the development of obstruction after biological treatment is needed to validate the study findings.

LONG-HOSP Score: A Novel Predictive Score for Length of Hospital Stay in Acute Lower Gastrointestinal Bleeding - A Multicenter Nationwide Study.

INTRODUCTION: Length of stay (LOS) in hospital affects cost, patient quality of life, and hospital management; however, existing gastrointestinal bleeding models applicable at hospital admission have not focused on LOS. We aimed to construct a predictive model for LOS in acute lower gastrointestinal bleeding (ALGIB). METHODS: We retrospectively analyzed the records of 8,547 patients emergently hospitalized for ALGIB at 49 hospitals (the CODE BLUE-J Study). A predictive model for prolonged hospital stay was developed using the baseline characteristics of 7,107 patients and externally validated in 1,440 patients. Furthermore, a multivariate analysis assessed the impact of additional variables during hospitalization on LOS. RESULTS: Focusing on baseline characteristics, a predictive model for prolonged hospital stay was developed, the LONG-HOSP score, which consisted of low body mass index, laboratory data, old age, nondrinker status, nonsteroidal anti-inflammatory drug use, facility with ≥800 beds, heart rate, oral antithrombotic agent use, symptoms, systolic blood pressure, performance status, and past medical history. The score showed relatively high performance in predicting prolonged hospital stay and high hospitalization costs (area under the curve: 0.70 and 0.73 for derivation, respectively, and 0.66 and 0.71 for external validation, respectively). Next, we focused on in-hospital management. Diagnosis of colitis or colorectal cancer, rebleeding, and the need for blood transfusion, interventional radiology, and surgery prolonged LOS, regardless of the LONG-HOSP score. By contrast, early colonoscopy and endoscopic treatment shortened LOS. CONCLUSIONS: At hospital admission for ALGIB, our novel predictive model stratified patients by their risk of prolonged hospital stay. During hospitalization, early colonoscopy and endoscopic treatment shortened LOS.

Predictive Factors for Efficacy of Oral Tacrolimus Induction Therapy in Moderate to Severe Ulcerative Colitis Patients: Large Multicenter Retrospective Cohort Study.

BACKGROUND: Tacrolimus (TAC), a calcineurin inhibitor, is used for remission induction therapy in patients with moderate to severe ulcerative colitis (UC), with short-term efficacy and related predictive factors shown in previous cohort studies. However, most studies reported data for only a limited number of patients enrolled from a single center. We performed a large multicenter retrospective cohort study to identify factors related to prediction of clinical remission in UC patients treated with oral TAC. METHODS: The medical records of patients with moderate to severe UC treated with oral TAC as induction therapy at 7 institutions between April 2009 and March 2017 were retrospectively reviewed. RESULTS: A total of 216 patients who received TAC for induction were analyzed, of whom 123 (56.9%) showed clinical remission at week 12. Logistic regression analysis indicated that previous or current use of antitumor necrosis factor (TNF)-α antibodies (odds ratio [OR], 0.259; P = .006), and concomitant treatment with 5-aminosalicylate (5-ASA) at the baseline (OR, 0.268; P = .005) were independent predictive factors correlated with failure of clinical remission, whereas higher levels of C-reactive protein (OR, 1.124; P = .014) predicted achievement of clinical remission. CONCLUSIONS: Results of this multicenter study clearly indicate the efficacy of TAC induction therapy for patients with moderate to severe UC. Notably, previous or current use of anti-TNF-α antibodies was associated with poor achievement of clinical remission by week 12.

Linked Color Imaging for Stomach.

Image-enhanced endoscopy (IEE) plays an important role in the detection and further examination of gastritis and early gastric cancer (EGC). Linked color imaging (LCI) is also useful for detecting and evaluating gastritis, gastric intestinal metaplasia as a pre-cancerous lesion, and EGC. LCI provides a clear excellent endoscopic view of the atrophic border and the demarcation line under various conditions of gastritis. We could recognize gastritis as the lesions of the diffuse redness to purple color area with LCI. On the other hand, EGCs are recognized as the lesions of the orange-red, orange, or orange-white color area in the lesion of the purple color area, which is the surround atrophic mucosa with LCI. With further prospective randomized studies, we will be able to evaluate the diagnosis ability for EGC by IEE, and it will be necessary to evaluate the role of WLI/IEE and the additional effects of the diagnostic ability by adding IEE to WLI in future.

Differences between patients with inpatient-onset and outpatient-onset acute lower gastrointestinal bleeding: An observational study.

BACKGROUND AND AIM: The clinical severity and course of acute lower gastrointestinal bleeding (ALGIB) are believed to differ between inpatient-onset and outpatient-onset cases, but no reports have investigated these issues in detail. We aimed to evaluate the clinical differences between inpatient-onset and outpatient-onset ALGIB. METHODS: Medical records of patients who had undergone emergency colonoscopy for ALGIB were retrospectively reviewed. The severity was evaluated using the NOBLADS score. Patients with obvious ALGIB relapse and/or persistent iron-deficiency anemia after emergency colonoscopy were considered to exhibit a poor clinical course. RESULTS: We reviewed 723 patients with ALGIB and divided them into the inpatient-onset cohort (172 patients) and outpatient-onset cohort (551 patients). Compared with the outpatient-onset cohort, the inpatient-onset cohort had a significantly higher proportion of patients with a poor clinical course (51.2% vs 21.6%; P < 0.001) and a significantly higher mean NOBLADS score (3.6 ± 1.1 vs 2.5 ± 1.0; P < 0.001). The most common bleeding source was acute hemorrhagic rectal ulcer (52.3%) in the inpatient-onset cohort and colonic diverticular bleeding (29.4%) in the outpatient-onset cohort. Multivariate analysis showed that a platelet count < 15 × 104 /µL and albumin concentration < 3 g/dL were significantly associated with a poor clinical course in the inpatient-onset cohort. CONCLUSIONS: The clinical course was significantly worse in the inpatient-onset cohort than in the outpatient-onset cohort. The bleeding source, clinical characteristics, and clinical course differed between the inpatient-onset and outpatient-onset cohorts. The clinical course in the inpatient-onset cohort may depend on the patient's condition at ALGIB onset.

Health Care Cost Analysis of PPI or P-CAB-First Treatment in Patients With Gastroesophageal Reflux Disease.

GOALS: The aim was to examine actual health care cost in patients with gastroesophageal reflux disease (GERD) who were initiated on proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) as first-line therapy in Japanese real-world clinical settings. BACKGROUND: To date, cost-utility evaluation of acid-suppressants treatment in Japan has only been conducted by model analysis. STUDY: A cost utilization analysis was performed using a Japanese nationwide hospital-based claim database by extracting patients with GERD initiated on either PPI or P-CAB (242,102 pairs) and esomeprazole (EPZ) or P-CAB (241,825 pairs). Health care costs were compared in each comparison cohort with propensity-score matched pairs. The switching rates of initial acid-suppressants were also examined. RESULTS: Baseline characteristics were well-balanced after matching. The 3-year mean cumulative GERD-related and hospitalization costs per patient were ¥142,620 and ¥122,444 in PPI-first and P-CAB-first treatment groups, and ¥105,263 and ¥121,958 in EPZ-first and P-CAB-first treatment groups, respectively. Most hospitalization costs were non-GERD related in all the groups. The switching rates of PPI to P-CAB and P-CAB to PPI in 12 months were 7.5% and 20.2%, respectively. CONCLUSIONS: In this propensity-score matched analysis, health care cost was higher in patients with GERD initiated on PPI than in those initiated on P-CAB mainly owing to non-GERD-related hospitalization cost, whereas it was lower in those initiated on EPZ than in those initiated on P-CAB. When considering health care costs except hospitalization costs, PPI-first treatment was less expensive than P-CAB-first treatment. Low switching rate from PPI to P-CAB in the real-world practice may partially explain the discrepancy.

Safety and efficacy of capsule endoscopy for patients with newly diagnosed Crohn's disease: A multicenter retrospective study.

Crohn's disease (CD) is a chronic inflammatory disease that develops at a young age and frequently leads to intestinal resection. Capsule endoscopy (CE) can directly and non-invasively inspect the entire small bowel mucosa. We suspected that CE could be a good diagnostic tool for detecting CD in young patients. The aim of this study was to investigate the safety and efficacy of CE in patients with newly diagnosed CD and to evaluate the CE findings, especially in the upper small bowel of young patients. We retrospectively investigated 32 patients with newly diagnosed CD from 5 institutions. Patient characteristics, clinical course, and characteristics of CE findings were analyzed. The total small intestine observation rate was 93%, and the retention rate was 3% (1/32). No abnormality was identified by ileocolonoscopy in 46% (15/32), and transition of small bowel lesions (TSL) was found in 35% (12/34) of the patients. The frequency of longitudinal ulcers and cobblestones in the upper small intestine was significantly higher in younger patients (≤20 years). Moreover, positive findings in the upper small intestine were predominantly observed in younger patients (≤20 years). CE for patients with newly diagnosed CD was safe and useful, especially for the detection of upper small bowel lesions in young patients.

Subjective factors affecting prognosis of 469 patients with esophageal squamous cell carcinoma: a retrospective cohort study of endoscopic screening.

BACKGROUND: To date, no in-depth studies have focused on the impact of various clinical characteristics of esophageal squamous cell carcinoma (ESCC), including its association with subjective symptoms, on patient prognosis. We aimed to investigate the clinical factors that affect the prognosis of patients with ESCC and to clarify how subjective symptoms are related to prognosis. METHODS: We retrospectively evaluated the clinical records of 503 consecutive patients with ESCC from April 2011 to December 2019. Six established prognostic factors for ESCC (body mass index, alcohol drinking, cigarette smoking, sex, clinical stage, and age) and subjective symptoms were used to subgroup patients and analyze survival differences. Next, the patients were divided into two groups: a symptomatic group and an asymptomatic group. In the symptomatic group, differences in the incidence of subjective symptoms according to tumor size, tumor location, macroscopic tumor type, and clinical stage were examined. Finally, subjective symptoms were divided into swallowing-related symptoms and other symptoms, and their prognosis was compared. RESULTS: Multivariate Cox regression analysis identified sex [hazard ratio (HR) 1.778; 95% CI 1.004-3.149; p = 0.049], TNM classification (HR 6.591; 95% CI 3.438-12.63; p < 0.001), and subjective symptoms (HR 1.986; 95% CI 1.037-3.803; p = 0.0386) as independent risk factors for overall survival. In the symptomatic group, the mean time from symptom onset to diagnosis was 2.4 ± 4.3 months. The incidence of subjective symptoms differed by clinical stage, and the prognosis of patients with swallowing-related symptoms was significantly worse than that of patients with other symptoms. CONCLUSION: The results of this study suggest that screening by upper gastrointestinal endoscopy, independent of subjective symptoms (especially swallowing-related symptoms), may play an important role in the early detection and improvement of prognosis of ESCC, although further validation in a large prospective study is needed.

Comparison of mucosa-associated microbiota in Crohn's disease patients with and without anti-tumor necrosis factor-α therapy.

Most studies on the gut microbiome of Crohn's disease have been conducted using feces, instead of intestinal mucus to analyze the mucosa-associated microbiota. To investigate the characteristics of mucosa-associated microbiota in Crohn's disease patients and the effect of anti-tumor necrosis factor (TNF)-α therapy on mucosa-associated microbiota, we analyzed microbiota in Crohn's disease patients using brushing samples taken from terminal ileum. The recruited subjects were 18 Crohn's disease patients and 13 controls. There were 10 patients with anti-TNF-α therapy in Crohn's disease group. Crohn's disease patients had significantly reduced α-diversity in Shannon index compared to the controls. The comparative analysis of the taxonomic composition at the genus level between the Crohn's disease group and the controls indicated that butyrate-producing bacteria were less abundant in the Crohn's disease group compared to the controls. There were no differences in the diversity between the patients taking anti-TNF-α therapy and the patients without. The comparative analysis of the taxonomic composition at the genus level between the two groups indicated that some of anti-inflammatory bacteria were less abundant in the anti-TNF-α therapy group than the other. Reduction of specific bacteria producing anti-inflammatory molecules, especially butyrate-producing bacteria may play important roles in the pathophysiology of Crohn's disease.

Subepithelial Serotonin Reduces Small Intestinal Epithelial Cell Tightness via Reduction of Occluding Expression.

BACKGROUND: The precise pathogenesis of irritable bowel syndrome (IBS) remains unresolved; however, recent studies have reported that patients with diarrhea-predominant IBS exhibit an increased small intestinal permeability and increased number of enterochromaffin cells containing high 5-hydroxytryptamine (5HT; serotonin) levels. In this study, we investigated whether 5HT has the potential to modulate small intestinal epithelial cell permeability, focusing on tight junction-associated proteins. METHODS: The differentiated Caco-2 cell monolayer on porous filters (Millicell) was used. Then, 5HT was added to the lower Millicell compartment for 7 days. Intestinal epithelial cell permeability was assessed by measuring the flux of paracellular permeability markers. We further assessed the expression of occludin in the 5HT-stimulated Caco-2 monolayer. RESULTS: We found that 5HT did not affect the viability of Caco-2 cells at concentrations up to 100 µM during the experimental period. Administration of 5HT to the basal side of Caco-2 cells increased the flux of 3H-labeled mannitol (182 Da) but did not increase that of FITC-dextran (4000 Da). Among the tight junction proteins, the expression of occludin was specifically decreased by stimulation with 5HT at a concentration of 100 µM. CONCLUSION: In conclusion, excessive 5HT in the basal side increased the permeability of intestinal epithelial cells via reduction of occludin expression.

The role of advanced endoscopy in the management of inflammatory digestive diseases (upper gastrointestinal tract).

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.