Characterization of colorectal cancer by hierarchical clustering analyses of five immune cell markers.

The present study analyzed the expression of five independent immunohistochemical markers, CD4, CD8, CD66b, CD68, and CD163, on immune cells within the colorectal cancer (CRC) tumor microenvironment (TME). Using hierarchical clustering, patients were successfully classified according to significant associations with clinicopathological features and/or survival. Patients with mismatch repair-proficient (pMMR) CRC were categorized into four groups with survival differences (p = 0.0084): CD4Low , CD4High , MΦHigh , and CD8Low . MΦHigh tumors showed significantly higher expression of CD47 (p < 0.0001), a phagocytosis checkpoint molecule. These tumors contained significantly greater numbers of PD-1+ (p < 0.0001), TIM-3+ (p < 0.0001), and SIRPA+ (p < 0.0001) immune cells. Notably, 10% of the patients with pMMR CRC expressed PD-L1 (CD274) on tumor cells with significantly worse survival (p = 0.00064). The Cox proportional hazards model identified MΦ High (hazard ratio [HR] = 2.02, 95%, p = 0.032), CD8Low (HR = 2.45, p = 0.011), and tumor PD-L1 expression (HR = 2.74, p = 0.0061) as potential risk factors. PD-L1-PD-1 and/or CD47-SIRPA axes targeting immune checkpoint therapies might be considered for patients with pMMR CRC according to their tumor cells and tumor immune microenvironment characteristics.

Simultaneous Expression of CD70 and POSTN in Cancer-Associated Fibroblasts Predicts Worse Survival of Colorectal Cancer Patients.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide, with high morbidity and mortality rates. The evidence for the tumor-supporting capacities of cancer-associated fibroblasts (CAFs) that modulate cancer cell proliferation, invasion, metastasis, and tumor immunity, including in CRC, has been attracting attention. The present study examined the expression status of CD70 and POSTN in CRC and analyzed their association with clinicopathological features and clinical outcomes. In the present study, in total 15% (40/269) and 44% (119/269) of cases exhibited CD70 and POSTN expression on CAFs, respectively. Co-expression of CD70 and POSTN was detected in 8% (21/269) of patients. Fluorescent immunohistochemistry identified the co-expression of CD70 and POSTN with FAP and PDPN, respectively. ACTA2 was not co-expressed with CD70 or POSTN in CRC CAFs. CRC with CD70+/POSTN+ status in CAFs was significantly associated with distant organ metastasis (p = 0.0020) or incomplete resection status (p = 0.0011). CD70+/POSTN+ status tended to associate with advanced pT stage (p = 0.032) or peritoneal metastasis (p = 0.0059). Multivariate Cox hazards regression analysis identified CD70+/POSTN+ status in CAFs [hazard ratio (HR) = 3.78] as a potential independent risk factor. In vitro experiments revealed the activated phenotypes of colonic fibroblasts induced by CD70 and POSTN, while migration and invasion assays identified enhanced migration and invasion of CRC cells co-cultured with CD70- and POSTN-expressing colonic fibroblasts. On the basis of our observations, CD70 and POSTN immunohistochemistry can be used in the prognostication of CRC patients. CRC CAFs may be a promising target in the treatment of CRC patients.

Background factors of idiopathic peptic ulcers and optimal treatment methods: a multicenter retrospective Japanese study.

This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer.

Relationships between body mass index and constipation, gastroesophageal reflux disease, stool forms based on the Bristol Stool Form Scale, and education level: results from an internet survey in Japan.

Detailed evaluations of body mass index (BMI) and stool form based on the Bristol Stool Form Scale (BSFS) in individuals with constipation, gastroesophageal reflux disease (GERD), and concomitant constipation and GERD have not been performed in Japan. This study was an internet survey conducted to examine the relationships between BMI and constipation, GERD, stool forms based on the BSFS, and education level. This internet-based survey recruited participants from general public survey panels. 10,000 individuals meeting the eligibility criteria were enrolled. Questions included demographics, medical data, and assessments based on validated measures for constipation and GERD. BMI was significantly lower in males with versus without constipation. BMI was significantly higher with GERD both males and females. Mean BMI increased from the BSFS-1/2 group through the BSFS-3/4/5 to the BSFS-6/7 groups in both sexes. BMI was highest in individuals with a maximum education level of junior high school and second highest in individuals completing high school. This is the first real-world survey that closely examines the relationship between BMI and stool forms of individuals in Japan. When the BMI increased, stool forms varied from hard to watery in Japanese people. BMI was related with education level in Japan. (Trial registration: UMIN000039688).

Long-term outcomes of nasogastric tube with Gastrografin for adhesive small bowel obstruction.

BACKGROUND: We had previously reported that the administration of Gastrografin through a nasogastric tube (NGT-G) followed by long tube (LT) strategy could be a novel standard treatment for adhesive small bowel obstruction (ASBO); however, the long-term outcomes after initial improvement remain unknown. This study aimed to analyze the long-term outcomes of first-line NGT-G. METHODS: Enrolled patients with ASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018. Thereafter, the cumulative surgery rate, cumulative recurrence rate, and overall survival (OS) rate were analyzed. In addition, subset analysis was conducted to determine the cumulative recurrence rate according to colonic contrast with Gastrografin at 24 h. RESULTS: A total of 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed over a median follow-up duration of 550 days. The cumulative 1-year surgery rates, cumulative 1-year recurrence rates, and 1-year OS rates in the LT and NGT-G groups were 18.8% and 18.1%, 30.0% and 31.7%, and 99.1% and 96.6%, respectively; no significant differences were observed between both groups. In the NGT-G group, a negative colonic contrast at 24 h demonstrated a higher tendency for future recurrence compared with a positive colonic contrast at 24 h (1-year recurrence rate: negative contrast, 46.9% vs positive contrast, 27.6%). CONCLUSIONS: Gastrografin through a nasogastric tube followed by LT can be a promising treatment strategy for ASBO, with long-term efficacies equivalent to initial LT placement.

The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer.

p53 immunohistochemistry is considered an accurate surrogate marker reflecting the underlying TP53 mutation status and has utility in tumor diagnostics. In the present study, 269 primary CRCs were immunohistochemically evaluated for p53 expression to assess its utility in diagnostic pathology and prognostication. p53 expression was wild-type in 59 cases (23%), overexpressed in 143 cases (55%), completely lost in 50 cases (19%), and cytoplasmic in 10 cases (4%). p53 immunoreactivity was associated with tumor size (p = 0.0056), mucus production (p = 0.0015), and mismatch repair (MMR) system status (p < 0.0001). Furthermore, among CRCs with wild-type p53 expression, a significantly higher number of cases had decreased CDX2 than those with p53 overexpression (p = 0.012) or complete p53 loss (p = 0.043). In contrast, among CRCs with p53 overexpression, there were significantly fewer ALCAM-positive cases than p53 wild-type cases (p = 0.0045). However, no significant association was detected between p53 immunoreactivity and the "stem-like" immunophenotype defined by CDX2 downregulation and ALCAM-positivity. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.17, p < 0.0001), younger age (HR = 0.52, p = 0.021), and female sex (HR = 0.55, p = 0.046) as potential favorable factors. The analysis also revealed complete p53 loss (HR = 2.16, p = 0.0087), incomplete resection (HR = 2.65, p = 0.0068), and peritoneal metastasis (HR = 5.32, p < 0.0001) as potential independent risk factors for patients with CRC. The sub-cohort survival analyses classified according to chemotherapy after surgery revealed that CRC patients with wild-type p53 expression tended to have better survival than those with overexpression or complete loss after chemotherapy. Thus, immunohistochemistry for p53 could be used for the prognostication and chemotherapy target selection of patients with CRC.

SPATA18 Expression Predicts Favorable Clinical Outcome in Colorectal Cancer.

Dysregulation of mitochondrial quality control has been reported to be associated with cancer and degenerative diseases. SPATA18 (spermatogenesis-associated 18, also known as Mieap) encodes a p53-inducible protein that can induce lysosome-like organelles within mitochondria that eliminate oxidized mitochondrial proteins and has tumor suppressor functions in mitochondrial quality control. In the present study, 268 primary colorectal cancers (CRCs) were evaluated immunohistochemically for SPATA18 expression to assess its predictive utility and its association with cellular proliferation activity. Furthermore, the association with p53 immunoreactivity, a surrogate marker for TP53 mutation, was analyzed. Non-neoplastic colonic mucosa showed cytoplasmic SPATA18 expression. Seventy-two percent of the lesions (193/268) displayed high SPATA18 expression in the cytoplasm of CRC cells. Univariate analyses revealed significant associations between SPATA18 expression and tumor size (p < 0.0001), histological differentiation (p = 0.0017), and lymph node metastasis (p = 0.00039). The log-rank test revealed that patients with SPATA18-high CRCs had significantly better survival than SPATA18-low patients (p < 0.0001). Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio [HR] = 0.25), age < 70 years (HR = 0.50), and SPATA18-high (HR = 0.55) as potential favorable factors. Lymph node metastasis (HR = 1.98) and peritoneal metastasis (HR = 5.45) were cited as potential independent risk factors. Cellular proliferation activity was significantly higher in SPATA18-high tumors. However, no significant correlation was detected between SPATA18 expression and p53 immunoreactivity or KRAS/BRAF mutation status. On the basis of our observations, SPATA18 immunohistochemistry can be used in the prognostication of CRC patients.

Optimal definition of coagulation syndrome after colorectal endoscopic submucosal dissection: a post hoc analysis of randomized controlled trial.

PURPOSE: Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition. METHODS: In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air. RESULTS: A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups. CONCLUSION: Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031). TRIAL REGISTRATION NUMBER: UMIN000027031 DATE OF REGISTRATION: April 18, 2017.

High phospho-histone H3 expression uniquely predicts favorable survival among four markers of cellular proliferation in colorectal cancer.

Colorectal cancer (CRC) is one of the most frequent gastrointestinal cancers worldwide, with high morbidity and mortality rates. Despite numerous attempts to identify prognostic markers for the CRC patients, the significance of the association of cellular proliferation markers with survival is controversial. Here we used immunohistochemistry to detect four markers of cellular proliferation expressed in primary CRC tissue specimens (n = 269) to assess their potential to serve as prognostic factors. CRC cells variably expressed phospho-histone H3 (PHH3) (range, 0-76 per high-powered field (HPF); median, 7 per HPF), cyclin A (CCNA) (range, 11.3-73.7%; median, 32%), geminin (GMNN) (range, 7.8-82.0%; median, 37.1%), and marker of proliferation Ki-67 (MKI67) (range, 4.9-96.6%; median, 49.6%). Among them, patients with PHH3-high (≥7 per HPF) tumors uniquely experienced significantly longer 5-year survival than those with PHH3-low (≤6 per HPF) (81.8% vs. 65.5%; P = 0.0047). Multivariable Cox hazards regression analysis identified PHH3-high (hazard ratio, 0.54; 95% confidence interval, 0.31-0.92; P = 0.025) as potential favorable factors. PHH3 levels inversely associated with pT stage (P < 0.0001) and were significantly and inversely associated with tumor diameter (ρ = -0.314, P < 0.0001). These findings support the use of PHH3 immunohistochemistry for predicting the prognoses of patients with CRC.

Expression and Prognostic Significance of CD47-SIRPA Macrophage Checkpoint Molecules in Colorectal Cancer.

Despite the confirmed anti-cancer effects of T-cell immune checkpoint inhibitors, in colorectal cancer (CRC) they are only effective in a small subset of patients with microsatellite-unstable tumors. Thus, therapeutics targeting other types of CRCs or tumors refractory to T-cell checkpoint inhibitors are desired. The binding of aberrantly expressed CD47 on tumor cells to signal regulatory protein-alpha (SIRPA) on macrophages allows tumor cells to evade immune destruction. Based on these observations, drugs targeting the macrophage checkpoint have been developed with the expectation of anti-cancer effects against T-cell immune checkpoint inhibitor-refractory tumors. In the present study, 269 primary CRCs were evaluated immunohistochemically for CD47, SIRPA, CD68, and CD163 expression to assess their predictive utility and the applicability of CD47-SIRPA axis-modulating drugs. Thirty-five percent of the lesions (95/269) displayed CD47 expression on the cytomembrane of CRC cells. CRCs contained various numbers of tumor-associated immune cells (TAIs) with SIRPA, CD68, or CD163 expression. The log-rank test revealed that patients with CD47-positive CRCs had significantly worse survival than CD47-negative patients. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio (R) = 0.23), age < 70 years (HR = 0.48), and high SIRPA-positive TAI counts (HR = 0.55) as potential favorable factors. High tumor CD47 expression (HR = 1.75), lymph node metastasis (HR = 2.26), and peritoneal metastasis (HR = 5.80) were cited as potential independent risk factors. Based on our observations, CD47-SIRPA pathway-modulating therapies may be effective in patients with CRC.

Novel urinary protein biomarker panel for early diagnosis of gastric cancer.

BACKGROUND: With the goal of discovering non-invasive biomarkers for early diagnosis of GC, we conducted a case-control study utilising urine samples from individuals with predominantly early GC vs. healthy control (HC). METHODS: Among urine samples from 372 patients, age- and sex-matched 282 patients were randomly divided into three groups: 18 patients in a discovery cohort; 176 patients in a training cohort and 88 patients in a validation cohort. RESULTS: Among urinary proteins identified in the comprehensive quantitative proteomics analysis, urinary levels of TFF1 (uTFF1) and ADAM12 (uADAM12) were significantly independent diagnostic biomarkers for GC, in addition to Helicobacter pylori status. A urinary biomarker panel combining uTFF1, uADAM12 and H. pylori significantly distinguished between HC and GC patients in both training and validation cohorts. On the analysis for sex-specific biomarkers, this combination panel demonstrated a good AUC of 0.858 for male GC, whereas another combination panel of uTFF1, uBARD1 and H. pylori also provided a good AUC of 0.893 for female GC. Notably, each panel could distinguish even stage I GC patients from HC patients (AUC = 0.850 for males; AUC = 0.845 for females). CONCLUSIONS: Novel urinary protein biomarker panels represent promising non-invasive biomarkers for GC, including early-stage disease.

A multicenter, single-blind randomized controlled trial of endoscopic clipping closure for preventing coagulation syndrome after colorectal endoscopic submucosal dissection.

BACKGROUND AND AIMS: Post endoscopic submucosal dissection coagulation syndrome (PECS) occasionally occurs after colorectal endoscopic submucosal dissection (ESD), presenting with localized abdominal pain and inflammation. We conducted a randomized controlled trial (RCT) to assess the usefulness of endoscopic clipping closure to prevent PECS and delayed perforation (DP). METHODS: This is a multicenter, single-blind RCT. Prospectively enrolled patients undergoing colorectal ESD were randomly allocated to endoscopic clipping closure and nonclosure after ESD, stratifying by institution and tumor size. All participants underwent a computed tomography scan after ESD. PECS was defined as visual analog scale (VAS) ≥30 mm, an increase in VAS ≥20 mm from baseline, body temperature ≥37.5°C or white blood cells ≥10,000/µL after colorectal ESD. DP was defined as PECS accompanied by extraluminal air. The preplanned sample size was 320 patients, and the primary endpoint was the rate of PECS/DP. RESULTS: At the planned interim analysis, this trial was terminated by recommendation of the independent data and safety monitoring committee because conditional power with superiority was lower than the preplanned futility limit. Finally, 155 patients were analyzed. The rate of PECS/DP was 16% (95% confidence interval [CI], 8%-23%) in the nonclosure group and 24% (95% CI, 14%-34%) in the closure group (P = .184). All cases of DP were within minor criteria, and all PECS/DP patients were managed conservatively without surgical treatment. Simple periluminal air without PECS was observed in 16% (95% CI, 8%-23%) in the nonclosure group and 10% (95% CI, 3%-17%) in the closure group. CONCLUSION: Endoscopic clipping closure could not reduce the high incidence of PECS/DP after colorectal ESD. (University Hospital Medical Network Clinical Trials Registry number: UMIN000027031.).

Gut Environment and Dietary Habits in Healthy Japanese Adults and their Association with Bowel Movement.

INTRODUCTION: Constipation is a common symptom that impairs the quality of life (QOL). This study aimed to investigate the relationship between bowel movement and gut microbiota and dietary intake. METHODS: To investigate correlations among bowel movement, food intake, and gut environment, 60 healthy Japanese participants were recruited. Bowel movement was assessed using the Bristol stool form scale (BSFS) and constipation scoring system (CSS). Dietary habit was assessed with a self-administered questionnaire wherein the food intake frequency was classified into 8 categories for 72 food/food groups. Gut microbiota was analyzed using terminal restriction fragment length polymorphism analysis. RESULTS: The constipation rate was significantly higher in females than in males. The QOL was significantly impaired in the constipated group. The fecal count of Bacteroides was decreased and that of Clostridium cluster IV was increased in participants with constipation. The BSFS score was negatively associated with the fecal count of Clostridium cluster XI and positively associated with the fecal count of Clostridium cluster XVIII and consumption of green tea. The total CSS score was positively associated with the fecal Prevotella count and negatively associated with fecal acetate levels and consumption of vegetables. Discriminant analysis estimated that constipation could be predicted correctly in 83% (p < 0.001) of the participants based on fecal microbiota and fecal short-chain fatty acids. DISCUSSION/CONCLUSION: Bowel movement was strongly affected by gut environment and food intake in Japanese participants. Improvement in dietary habits could promote bowel movement through the improvement of the environment in the gut, resulting in ameliorated QOL issues in healthy adults.

The association among enterobacterial flora, dietary factors, and prognosis in patients with ulcerative colitis.

The role of enterobacterial flora in the onset and progression of inflammatory bowel diseases is a topic of considerable interest. Here, we assessed the association among enterobacterial flora, dietary factors, and ulcerative colitis (UC) progression. Forty-six patients with UC who were diagnosed as being in remission were enrolled. We collected each patient's stool sample one or two days before diagnostic colonoscopy. After colonoscopy, we observed the patients for one year and then retrospectively divided them into two groups: remission (n = 39) and relapse (n = 7) groups, depending on whether the relapse occurred during the follow-up period, and analyzed the relationship among patient characteristics, dietary factors, enterobacterial flora, and UC relapse. Overall, there were no significant differences in bacterial community populations between the remission and relapse groups, except that the order Lactobacillales was detected at a significantly higher rate in the relapse than in the remission group (100% vs 71.4%, p<0.05). Vitamin C intake was significantly higher in the remission than in the relapse group (p<0.05). Although there were no obvious differences in enterobacterial flora between the remission and relapse groups, there was a relationship among enterobacterial flora, diet, and UC progression. Given that the enterobacterial flora was only analyzed at the initiation of the study, we conclude that in future analyses, enterobacterial flora should be sampled at numerous time points to examine its role in UC progression. Further long-term longitudinal studies examining enterobacterial flora, dietary factors, and UC progression are also required.

Convenient Method of Measuring Baseline Impedance for Distinguishing Patients with Functional Heartburn from those with Proton Pump Inhibitor-Resistant Endoscopic Negative Reflux Disease.

BACKGROUND: Combined 24-h intraesophageal pH-multichannel intraluminal impedance (24MII-pH) used for assessing gastroesophageal reflux disease by measuring baseline impedance (BI) requires a 24-h measuring period. In the present study, we developed a quick method of measuring BI and evaluated its usefulness in classifying patients with proton pump inhibitor (PPI)-refractory non-erosive reflux diseases (NERD) as having functional heartburn (FH) or endoscopic-negative reflux disease (ENRD). METHODS: Ninety-one NERD patients without esophageal motility disorder underwent 24MII-pH monitoring while on a PPI. The measurements of the mean nocturnal BI (MNBI) and short MNBI were assessed at 3 times (at about 1: 00, 2: 00, and 3: 00 am) for 10 min and 30 s respectively. The measurement of the simple mean BI (MBI) was performed once 30 s at about 11: 00 am. RESULTS: Ninety-one patients were divided into 2 groups: 59 with ENRD and 32 with FH. The cutoff, specificity, and sensitivity for distinguishing patients with FH were as follows: MNBI, 2,874.1 Ω, 72%, and 72%; short MNBI, 2,857.6 Ω, 74%, and 84%; and simple MBI, 2,874.1 Ω, 86%, and 78% respectively. CONCLUSION: Measuring the simple MBI is a quick method and is useful for distinguishing patients with FH from those in a cohort with PPI-refractory NERD.

Treatment Adherence in Patients with Ulcerative Colitis Is Dependent on the Formulation of 5-Aminosalicylic Acid.

BACKGROUND/AIMS: It is unclear whether 5-aminosalicylic acid (5-ASA) formulation is associated with treatment adherence in ulcerative colitis (UC). Thus, we aimed to investigate the adherence rate after switching from 5-ASA tablets to granules. METHODS: This prospective study included 121 UC outpatients treated using 5-ASA tablets. They were grouped based on choice: Group 1 (continued with tablets) and Group 2 (switched to granules without regimen change). Group 2 was further divided into Group 3 (returned to tablets) and Group 4 (continued with granules). The patients completed a self-administered questionnaire regarding the treatment. The primary endpoint was change in adherence after switching to granules. RESULTS: Seventy-nine patients continued with tablets, while 42 patients switched to granules. The adherence rate to the tablet was not significantly different between Group 1 and 2 before switching. In Group 2, switching to granules did not affect adherence. However, in Group 4, adherence significantly improved after switching to granules. Group 3 showed no significant change in adherence before and after switching from tablets. Full-time work and difficulty taking tablets were significant predictors of continuing with granules in Group 4. CONCLUSION: Patients who continued with 5-ASA granules showed significantly increased adherence, suggesting that patient-tailored drug formulations improved treatment adherence.

Characteristics and Predictive Factor of Helicobacter pylori-Associated Functional Dyspepsia in Japanese Patients.

BACKGROUND/AIM: Helicobacter pylori (HP) eradication therapy was first recommended as pharmacotherapy for functional dyspepsia (FD). However, the mechanism and effect of eradication on FD symptom improvement have not been fully investigated. This study aimed to investigate the pathology of patients with HP-associated FD, and predictive factors for HP-associated FD. METHODS: Ninety-seven patients with chronic gastritis caused by HP infection were divided into the group with FD symptoms and the group -without FD symptoms. Patient backgrounds, QOL, gastric mucosal atrophy severity, and serum pepsinogen (PG) value were compared between the 2 groups. Twelve months after eradication, those factors were evaluated between HP-associated FD and HP-non-associated FD, and predictive factors of HP-associated FD were analyzed. RESULTS: The FD-positive group existed in 45 (46.3%) out of 97 patients. Twelve months after eradication, there were 34 patients (75.6%) in the HP-associated FD. The mean PG I value in the HP-associated FD was significantly lower than that in the HP-non-associated FD, while the PG II values in the HP-associated FD tended to be lower than those in the HP-non-associated FD. QOL in the HP-associated FD significantly improved after HP eradication. On multivariate logistic regression analysis, it was found that PG II value was a significant predictive factor for FD symptom improvement in the HP-associated FD. CONCLUSION: HP eradication is an effective initial therapy for FD. PG II value is considered a predictive factor for FD symptom improvement through HP eradication.

Gut microbiota disorders cause type 2 diabetes mellitus and homeostatic disturbances in gut-related metabolism in Japanese subjects.

Few studies have investigated the host-microbe metabolic axis in people with type 2 diabetes mellitus (T2DM). This study aimed to determine and compare the nutrient intakes and metabolic markers and to elucidate the relationships among these factors in Japanese T2DM patients and control individuals. Fifty-nine Japanese T2DM patients and 59 matched healthy control individuals participated in this study. We examined the differences regarding the participants' dietary habits, microbiota, and fecal short-chain fatty acids, and analyzed the relationships between the gut microbiota and blood metabolic markers in the T2DM patients and the control subjects. The T2DM patients consumed more carbohydrates, and had lower fecal propionate and butyrate concentrations, larger fecal populations of Bifidobacterium spp. and bacteria of the order Lactobacillales, and smaller fecal Bacteroides spp. populations than the control individuals. In the T2DM patients, the level of Bifidobacterium spp. correlated negatively with the carbohydrate intake and the level of bacteria of the order Lactobacillales correlated negatively with the protein intake. T2DM patients have gut dysbiosis that may contribute to disease onset and influence its prognosis. Furthermore, homeostatic disturbances in the gut-related metabolism may underlie the pathogenesis of T2DM.

[Mucosa-associated lymphoid tissue lymphoma of the appendix concomitant with appendicitis:a case report].

An 82-year-old man with abdominal pain was admitted to our hospital. Laboratory tests revealed the following:white blood cells, 14300/µl;serum hemoglobin level, 12.9g/dl;serum C-reactive protein level, 0.38mg/dl;and negative anti-Helicobacter pylori immunoglobulin G test. Abdominal computed tomography revealed a tumor in the appendix along with multiple swollen lymph nodes. Colonoscopy revealed a submucosal tumor (SMT) of approximately 30mm in diameter with central ulceration. However, a tumor tissue specimen could not be obtained for biopsy;thus, the tumor could not be diagnosed. In esophagogastroduodenoscopy, abnormalities or gastric mucosal atrophy was not observed. A rapid urease test yielded negative results. Hence, endoscopic ultrasound-guided fine needle aspiration for the SMT was recommended;however, the patient preferred to undergo a definitive surgery to establish exact diagnosis. Therefore, right hemicolectomy and lymph node dissection (D3) were performed. Histopathologically, the resected tumor specimen showed atypical lymphocytes. Additionally, immunohistochemical evaluation demonstrated positive staining of the tumor cells for CD20 and BCL2 and negative staining for CD34, CD4, CD10, and BCL6. The tumor was finally diagnosed as a stage II2 mucosa-associated lymphoid tissue lymphoma (Lugano classification). Postoperatively, the patient received chemotherapy with four cycles of rituximab based on his age and activities of daily living.

[Internet survey of the actual situation of constipation in Japanese general population REACTION-J:Research for Actual Situation of Constipation in the Japanese].

Although chronic constipation is highly prevalent, its definition remains unclear. Therefore, the prevalence varies depending on reports, and the understanding of actual situations is unclear. Hence, we performed an internet survey on constipation among the Japanese general population to study the background factors and actual situations. Preliminary study on the awareness of constipation was conducted among 10000 people in which 9523 of them was asked if they had constipation at the time of the survey. In this population, 51.5% realized that they had constipation. Multivariate analysis showed the significant association of constipation to age, sex, and past histories or complications of diabetes, hemorrhoids, and cerebrovascular diseases. In a main research composed of 3000 general Japanese population, approximately 30.9% of the subjects reported the use of laxatives to treat constipation, and 43.8% of them were found to use irritant laxatives. Moreover, 67.5% of the subjects purchased laxatives at a pharmacy. The frequency of bowel movement less than 3 times per week was manifested in 36.3% of the subjects, and more than once per week in 21.4%. The percentage of hard (Bristol Stool Form Scale [BSFS] Type 1-2), normal (BSFS Type 3-5), and diarrhea stools (BSFS Type 6-7) was 33.1%, 60.0%, and 6.9%, respectively. The quality of life (QOL) of the subjects with hard and diarrhea stools evaluated by SF-8 was significantly lower than that of those with normal stools. Furthermore, the actual monthly cost for the therapeutic drugs used for treating constipation was less than 1000 yen in 75% of the subjects. Analysis of the IBS-QOL-J indicated that the ≥5000 yen payable group had the lowest satisfaction of defecation among the study groups. At present, many Japanese patients with constipation have not been receiving enough treatment for constipation. Therefore, appropriate medication by physicians as well as instruction to patients is required.