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.

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.

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.

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.

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.

Diagnosis of histological gastritis based on the Kyoto classification of gastritis in Japanese subjects - including evaluation of aging and sex difference of histological gastritis.

OBJECTIVES: The Kyoto classification of gastritis was established for diagnosing Helicobacter pylori (H. pylori) infection via endoscopic findings. We investigated the role of the Kyoto classification of gastritis in the diagnosis of H. pylori infection and histological gastritis in Japanese individuals. Moreover, the histological findings of gastritis in H. pylori infection were examined based on age and sex differences. METHODS: We selected 561 patients aged 20-79 years who underwent gastroduodenal endoscopy at our hospital between 2010 and 2018. Endoscopic biopsy specimens from the antrum and corpus were used to investigate H. pylori infection and histology. Endoscopic findings were based on the Kyoto classification of gastritis, and histological findings were based on the updated Sydney System. RESULTS: Endoscopic findings based on the Kyoto classification of gastritis (H. pylori positive, 303 patients; H. pylori negative, 258 patients, based on endoscopic findings) had 98.7% sensitivity and 98.4% specificity for histological gastritis. In addition, endoscopic findings in the three age groups (20-39, 40-59, and 60-79 years) had high sensitivity and specificity. Atrophy and intestinal metaplasia were found only in the H. pylori-positive group and progressed with age. Histological inflammation of pyloric mucosa in the younger age group of H. pylori-positive patients was significantly higher than that in the elderly group. Significant inflammation was observed in young women. CONCLUSIONS: The Kyoto classification of gastritis can not only diagnose H. pylori infection but also detect histological gastritis. Histological gastritis has varying characteristics of inflammation, atrophy, and intestinal metaplasia, depending on age and sex.

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.

A Questionnaire-Based Survey on the Impact of the COVID-19 Pandemic on Gastrointestinal Endoscopy in Asia.

INTRODUCTION: The COVID-19 outbreak abruptly restricted gastrointestinal (GI) endoscopy services during the first wave of the pandemic. We aimed to assess the impact of COVID-19 on the practice of GI endoscopy in Asian countries. METHODS: This was an International Questionnaire-based Internet Survey conducted at multiple facilities by the International Gastrointestinal Consensus Symposium. A total of 166 respondents in Japan, China, Hong Kong, South Korea, Philippines, Thailand, Indonesia, and Singapore participated in this study. RESULTS: The volume of endoscopic screening or follow-up endoscopies and therapeutic endoscopies were markedly reduced during the first wave of the pandemic, which was mainly attributed to the decreased number of outpatients, cancellations by patients, and adherence to the guidelines of academic societies. The most common indications for GI endoscopy during the first wave were GI bleeding, cholangitis or obstructive jaundice, and a highly suspicious case of neoplasia. The most common GI symptoms of COVID-19 patients during the infected period included diarrhea, nausea, and vomiting. The pandemic exacerbated some GI diseases, such as functional dyspepsia and irritable bowel syndrome. There were cases with delayed diagnosis of cancers due to postponed endoscopic procedures, and the prescription of proton pump inhibitors/potassium-competitive acid blockers, steroids, immunosuppressive agents, and biologics was delayed or canceled. The personal protective equipment used during endoscopic procedures for high-risk patients were disposable gloves, disposable gowns, N95 or equivalent masks, and face shields. However, the devices on the patient side during endoscopic procedures included modified surgical masks, mouthpieces with filters, and disposable vinyl boxes or aerosol boxes covering the head. Furthermore, the time for education, basic research, clinical research, and daily clinical practice decreased during the first wave. CONCLUSION: This study demonstrated that the COVID-19 pandemic profoundly affected the method of performing GI endoscopy and medical treatment for patients with GI diseases in Asian countries.

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.

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.

Evaluation of efficacy and safety of lubiprostone in patients with chronic constipation.

OBJECTIVES: Lubiprostone is an apical type 2 chloride channel activator approved for the treatment of chronic constipation (CC), and nausea is the most common adverse symptom. However, the associated factors with the efficacy and the precise mechanism of nausea remain unclear. The aim of this study is to characterize clinical backgrounds related with the efficacy and the adverse symptoms of lubiprostone. MATERIALS AND METHODS: Subjects were patients with CC who were prescribed lubiprostone from April 2017 to October 2019. The efficacy and safety of lubiprostone were retrospectively examined using the electronic medical record. RESULTS: Hundred and fifty-five patients (76 men, and mean age 69) were evaluated. Lubiprostone was effective in 74 patients (47.8%), and the discontinuation due to adverse in 34 patients (21.9%). including nausea, diarrhea and abdominal pain in 16, 12 and 3 patients, respectively. The efficacy was significantly associated with gender, age, body mass index (BMI), diabetes mellitus, hypertension, calcium channel blockers and antipsychotics. In multivariate analysis, the efficacy was significantly associated with men (odds ratio [OR], 3.21; 95% confidence interval (CI), 1.42-7.27) and BMI (OR, 1.14; 95% CI, 1.02-1.28). The incidence of nausea was higher in patients under 65 years old, and hypertension was the significant protective factor for nausea. CONCLUSIONS: Lubiprostone was effective for men patients with CC, and hypertension seems to be the protective factor for nausea.

Differences in emergency endoscopy outcomes according to gastrointestinal bleeding location.

BACKGROUND AND AIM: With recent technological advances in the field of endoscopic hemostasis, the prognosis of patients with gastrointestinal (GI) bleeding has improved. However, few studies have reported on the clinical course of patients with GI bleeding. This study aimed to evaluate the differences in clinical outcomes of patients with lower GI bleeding (LGIB) compared with upper GI bleeding (UGIB) and the factors related to their prognosis. METHODS: Patients who had undergone emergency endoscopy for GI bleeding were retrospectively reviewed. The severity of GI bleeding was evaluated using the Glasgow-Blatchford (GB), AIMS65, and NOBLADS scores. Patients in whom obvious GI bleeding relapsed and/or iron deficiency anemia persisted after emergency endoscopy were considered to exhibit rebleeding. RESULTS: We reviewed 1697 consecutive patients and divided them into UGIB (1054 patients) and LGIB (643 patients) groups. The proportion of patients with rebleeding was significantly greater in the UGIB group than in the LGIB group; the mortality rate was significantly higher in the UGIB group than in the LGIB group. Multivariate analysis showed that a GB score ≥12 and an AIMS65 score ≥2 were significantly associated with rebleeding in the UGIB group, whereas a NOBLADS score ≥4 was significantly associated with rebleeding in the LGIB group. Notably, the influence of emergency endoscopy differed according to GI bleeding location. CONCLUSIONS: The clinical course was significantly worse in patients with UGIB than in patients with LGIB. The influence of emergency endoscopy differed according to GI bleeding location.

Inflammatory Cell Numbers in the Stomach of Japanese Subjects with Endoscopically Normal Mucosa without Helicobacter pylori Infection.

INTRODUCTION: Since inflammatory cells, such as lymphocytes and plasma cells, normally inhabit the stomach, the border between normal and mild inflammation is difficult to visually determine using the updated Sydney system scale of gastritis. Additionally, eosinophils in the gastric mucosa must be counted to diagnose eosinophilic gastritis. We aimed to determine the normal number of inflammatory cells in patients with endoscopically normal mucosa and without Helicobacter pylori infections. METHODS: We assessed patients aged 20-79 years, who had undergone upper gastrointestinal endoscopy at Kawasaki Medical School Hospital between January 2010 and December 2014. Inflammatory cells were counted in 1,000 µm2 fields of pyloric and fundic gland mucosal biopsy specimens. We finally included 325 (male, n = 141; female, n = 184; average age = 49.3 years) patients without inflammation who had H. pylori-negative endoscopic results and negative histological findings interpreted based on the updated Sydney System and the Kyoto classification of gastritis. RESULTS: The average numbers of nucleated cells were 83.3 ± 14.2 and 65.4 ± 12.6/mm2 in the pyloric and fundic gland mucosae, respectively. Inflammatory cells were significantly more abundant in the pyloric mucosa than in the fundic gland mucosa (p < 0.05). Age and sex distribution did not significantly differ. Eosinophils were absent or scanty in the gastric mucosae of both glands in all patients. CONCLUSION: We determined the absolute values of inflammatory cells, including eosinophils, in normal mucosae of pyloric and fundic glands. These findings could be important in defining gastric mucosal inflammation, including eosinophilic gastritis diagnosis.

Vonoprazan-containing Helicobacter pylori triple therapies contribution to global antimicrobial resistance.

Amoxicillin and proton pump inhibitor dual Helicobacter pylori therapy has proved not to be reliably highly effective primarily because of traditional proton pump inhibitors' inability to maintain a high intragastric pH. Clarithromycin and proton pump inhibitor H. pylori dual therapy failed in part because clarithromycin resistance emerged during therapy causing treatment failures. The combination of amoxicillin, clarithromycin, and proton pump inhibitor was subsequently undermined by increasing clarithromycin resistance. Although vonoprazan appeared to restore the effectiveness of triple therapy, the improvement was almost entirely to improved effectiveness of amoxicillin dual therapy component and resulted in the majority (>85% currently in Japan) of those receiving vonoprazan-amoxicillin plus a second antibiotic (e.g. clarithromycin, metronidazole, fluoroquinolone, or rifabutin) receiving no benefit from the second antibiotic. The results in somewhere between 2800 and 5600 kg of unnecessary clarithromycin per one million H. pylori treatment courses per year in Japan. The only contribution of the second antibiotic is to increase global antimicrobial resistance. There are now sufficient data to prove that optimized vonoprazan-amoxicillin dual therapy can reliably achieve cure rates ≥95%. This manuscript discusses use of the principles of antimicrobial stewardship to develop potassium-competitive acid blocker-containing H. pylori therapies that will reliably achieve high H. pylori cure rates with minimal or no use of excess antibiotics. Such therapies are urgently needed so that use of vonoprazan triple therapies can be curtailed while also improving overall H. pylori cure rates.

The Cutting Edge Research of Functional Gastrointestinal Disorders in Japan: Review on JGA Core Symposium 2018-2020.

Highly impacted articles on functional gastrointestinal (GI) disorders research presented at the core symposium held in the Japanese Gastroenterological Association (JGA) annual meeting 2018-2020 are selected and summarized. Regarding visceral hypersensitivity and sensor in GI tracts, transient receptor potential vanilloid 4 ion channel and acid-sensitive ion channel were candidates for hypersensitivity in GI tracts. ATP release from vesicular nucleotide transporter may be a key pathway to sensitize the nerve endings. Regarding inflammation and mucosal immune responses, patients infected with H. pylori having Ser70 type single nucleotide polymorphism of NapA gene was associated with H. pylori-related dyspepsia via gastric dysmotility. Gastric histology infected with Ser70 type NapA was shown severe infiltration of neutrophils into intramuscular layer. Macrophages, mast cells, and neutrophils are infiltrated in the colon of irritable bowel syndrome (IBS) patients and the locally produced IL-1ß upregulated brain-derived neurotrophic factor (BDNF) in enteric glia cells. BDNF can also stimulate nerve endings and might be linked to pain in the colon. Dysbiosis in the composition of commensal bacteria communities is associated with the pathogenesis of various diseases including IBS and gut-brain interaction. The investigation on the mucosa-associated microbiota (MAM) is essential for understanding the interactions. The α-diversity and ß-diversity of MAM indices are significantly different among IBS-D, IBS-C, and controls, and the different diversity might contribute to the pathophysiology of IBS. As research works on psychosocial factors show, maternal separation animal model was used and it is early life stress. The stress had induced colonic hyper-contraction, gastric hypersensitivity, and delayed emptying. The precise molecular mechanisms are still under investigations.

Mucosa-Associated Microbiota in Patients with Irritable Bowel Syndrome: A Comparison of Subtypes.

BACKGROUND: Most studies on gut microbiome of irritable bowel syndrome (IBS) have focused on fecal microbiota, instead of mucosa-associated microbiota (MAM). AIMS: The aim of this study wasto investigate the MAM in IBS patients including the difference in subtypes of IBS, namely, diarrhea-predominant IBS (IBS-D) and constipation-predominant IBS (IBS-C). METHODS: Endoscopic brush samples were taken from terminal ileum and sigmoid colon of patients with IBS (17 IBS-D patients and 7 IBS-C patients) and 10 healthy controls. The MAM of samples was profiled by 16S rRNA gene amplicon sequencing. Potential changes in the MAM at the functional level were evaluated using PICRUSt software and the KEGG database. RESULTS: There were no differences in MAM composition between terminal ileum and sigmoid colon according to ß-diversity based on the UniFrac distance. In view of α-diversity, Shannon (evenness) but not Chao1 (richness) or observed operational taxonomic units tended to be lower in sigmoid colon MAM of IBS-C and IBS-D than the control group. The abundance of 4 genera in the sigmoid colon and 7 genera in the terminal ileum was significantly different among the 3 groups. Linear discriminant analysis effect size (LEfSe) showed that the genera of Ruminococcus, Akkermansia, Butyrivibrio, Methylobacterium, and Microbacterium and the family Erysipelotrichaceae were significantly higher in the IBS-C group, and the abundance of the genera Streptococcus, Acidaminococcus, Butyricicoccus, and Parvimonas was significantly higher in the IBS-D group. In addition, the proportion of genes responsible for the secretion system and LPS biosynthesis was significantly higher and that for methane metabolism, lysine biosynthesis, and enzyme families was significantly lower in the IBS-D group than in the IBS-C group. CONCLUSION: Dysbiosis pattern and the function of the microbiome seem to be different among subtypes of IBS, and MAM may play a crucial role in IBS symptom generation.

PDZK1 induces resistance to apoptosis in esophageal adenocarcinoma cells.

BACKGROUND: Esophageal cancer is a lethal malignancy with a poor prognosis. The incidence of esophageal adenocarcinoma, which develops from Barrett's esophagus (BE), has recently been increasing. In a previous study, we found that PDZK1 expression is higher in long segment BE compared to that in short-segment BE. However, the function of PDZK1 in the mucosa of BE is unclear. AIMS: Clarify the role of PDZK1 in BE mucosa using PDZK1 overexpressed cells. METHODS: Human adenocarcinoma-derived OE33 cells were used as a parental cell line and transfected to generate PDZK1 overexpressed OE33 cells (PC cells) or transfected with empty vector as control cells (NC cells). Cell growth of NC and PC cells in 10% fetal bovine serum was evaluated by cell counting. The effect of PDZK1 on proteasome inhibitor (PSI)-induced apoptosis was qualified by fluorescence microscopy and quantified by flow cytometry. Expression of apoptosis-related proteins was evaluated by western blotting. RESULTS: There were no significant differences in cell growth between NC and PC cells. PSI significantly increased apoptosis in NC cells, but not in PC cells. In response to PSI, increased levels of cleaved-caspase3 and decreased pro-caspase3 levels were found in NC cells, but not in PC cells. In NC cells, PSI significantly decreased Bcl-2 expression without affecting Bax levels. In contrast, high expression of both Bcl-2 and Bax was observed in PC cells. CONCLUSION: Overexpression of PDZK1 protein induces an apoptosis-resistant phenotype in BE cells, which may be a potential therapeutic target.

Molecular biomarker identification for esophageal adenocarcinoma using endoscopic brushing and magnified endoscopy.

BACKGROUND: Barrett's esophagus (BE) is a predisposing factor for esophageal adenocarcinoma (EAC); however, the precise mechanism underlying this association remains unclear. The identification of biomarkers that are associated with an increased risk of BE progression to EAC would facilitate diagnosis and early treatment. Toward this goal, we aimed to identify biomarkers associated with BE and EAC in patients. METHODS: In conjunction with high-resolution magnified endoscopy with narrow-band imaging (ME-NBI), we obtained brushing samples from the long-segment BE (LSBE) or short-segment BE (SSBE) of patients with EAC or without EAC (control). To identify candidate biomarker genes, microarray analysis was performed for a training set of 28 American samples. To confirm the microarray results, expression levels of the 16 candidate biomarkers were evaluated by real-time polymerase chain reaction analysis, using samples collected from an additional 53 American patients. In addition, we also performed a functional analysis for these genes using Gene Ontology (GO) enrichment analysis. RESULTS: Among the 16 genes identified as differentially expressed by microarray analysis, the GO analysis indicated matrix metalloproteinase (MMP) family associated with 'collagen metabolic process' and 'multicellular organismal macromolecule metabolic process' as the two top biological processes. Brushing samples of patients with EAC showed up-regulated expression of decay-accelerating factors (DAF and CD55) and topoisomerase type Iiα (TOP2A), and down-regulated expression of the sodium channel epithelial 1 beta subunit (SCNN1B). CONCLUSIONS: The up-regulation of CD55 and TOP2A, and the down-regulation of SCNN1B were common to the brushing samples and might serve as molecular biomarkers for identifying EAC in patients with SSBE. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) (000004004).

Questionnaire-Based Survey on Epidemiology of Functional Gastrointestinal Disorders and Current Status of Gastrointestinal Motility Testing in Asian Countries.

BACKGROUND/AIMS: Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the latest Rome IV criteria, released in 2016. Epidemiology of FGID diagnosed by the Rome IV criteria and current clinical application of gastrointestinal motility testing in Asian countries are not well known. The aims of this survey are to elucidate the present situation of epidemiology and diagnostic tests of FGID in clinical practice in some East and Southeast Asian countries. METHODS: The questionnaire focusing on current situation of FGID diagnosis and gastrointestinal motility testing was distributed to members of the International Gastroenterology Consensus Symposium study group and collected to be analyzed. RESULTS: The prevalence rates of subtypes of both functional dyspepsia (FD) and irritable bowel syndrome (IBS) are relatively similar in all Asian countries. In these countries, most patients underwent both upper endoscopy and Helicobacter pylori test to diagnose FD. Colonoscopy was also frequently performed to diagnose IBS and chronic constipation. The frequency of gastrointestinal motility testing to examine gastric emptying and colonic transit time varied among Asian countries. CONCLUSIONS: This survey revealed epidemiology of FGIDs and current status of gastrointestinal motility testing in some East and Southeast Asian countries.