Relationship between colonic diverticulosis and colon neoplasms in Japanese patients.

BACKGROUND AND AIM: Colonic diverticulosis (CD) has been reported to be associated with presence of colon neoplasms (CNs) in Western patients, since most of the associated risk factors are common between them. However, such correlation has not been fully investigated in Asian patients. In this study, the association of CNs with CD was evaluated in a multicenter investigation. METHODS: We enrolled 5633 patients who underwent both colonoscopy and esophagogastroduodenoscopy due to annual follow-up, screening for positive occult blood testing and abdominal symptoms between January 2016 and December 2017 at three institutions. The relationship between the presence of CNs and CD was investigated, and predictors for presence of CNs were determined by multivariate logistic analysis. RESULTS: The enrolled patients consisted of 1799 (31.9%) with CD (average age 70.0 years, male 64.0%) and 3834 without CD (66.0 years, male 52.9%), with the prevalence of CNs in those groups 46.6% and 44.2%, respectively (P = 0.090). Predictors for early colon cancer were shown to be age (OR 1.02, 95% CI 1.01-1.04, P = 0.010), laxatives use (OR 1.76, 95% CI 1.17-2.64, P = 0.007), gastric neoplasms (OR 2.16, 95% CI 1.23-3.81, P = 0.008), and CD (OR 1.64, 95% CI 1.16-2.31, P = 0.005). Early colon cancer in the distal colon was most frequently detected in patients with right-sided CD (RR 2.50, P = 0.001). CONCLUSION: In Japanese patients, early colon cancer was more frequently found in those with as compared to those without CD. The presence of CD may be an important indicator for an index colonoscopy examination to detect colon cancer. (Clinical-trial-registry: UMIN000038985).

Comorbid irritable bowel syndrome symptoms and headache have greater association with anxiety than depression: Annual health check-up survey results.

High rates of co-existing irritable bowel syndrome (IBS) and headache have been reported in western countries. We investigated that comorbidity in individuals in Japan, along with anxiety and depression in subjects with and without IBS symptoms and/or headache.This cross-sectional study was performed from April 2012 to January 2013 at the Matsue Seikyo General Hospital Health Check Center. Questionnaires concerning symptoms related to IBS (Rome III) and headache, as well as anxiety/depression score were sent to individuals scheduled to undergo an annual health check-up, then returned during the visit and analyzed in a blinded manner.A total of 2885 individuals returned completed questionnaires and were enrolled, of whom 218 (7.6%) met the IBS criteria. The rates of co-existing headache in subjects with and without IBS symptoms were 44.0% (96/218) and 22.9% (611/2667), respectively, indicating a significantly higher rate of co-existing headache in subjects with as compared to without IBS (odds ratio [OR] 2.65, P < .001). Furthermore, the percentage of subjects with anxiety along with comorbid IBS symptoms and headache was significantly greater as compared to those with IBS (OR 3.01, P = .001) or headache (OR 2.41, P < .001) alone. Unlike anxiety, the percentage of subjects with depression was not significantly different among the IBS/non-headache, non-IBS/headache, and IBS/headache groups.Subjects with IBS symptoms had a higher rate of co-existing headache as compared to those without IBS. Furthermore, those with comorbid IBS symptoms and headache had a greater association with anxiety than with depression, as compared to those with only IBS or headache.

Prevalence of functional dyspepsia-like symptoms in ulcerative colitis patients in clinical remission and overlap with irritable bowel syndrome-like symptoms.

Objective: Quiescent ulcerative colitis (UC) patients often have irritable bowel syndrome (IBS)-like symptoms and we recently showed that the prevalence of IBS-like symptoms in UC patients in clinical remission was significantly higher as compared to healthy control subjects. However, the prevalence of functional dyspepsia (FD)-like symptoms in quiescent UC patients remains unknown. The purpose of this study was to evaluate the prevalence of FD-like symptoms and the overlap with IBS-like symptoms in such patients.Materials and Methods: We reanalyzed the records of UC patients in remission using the subject cohort from our previous study. Clinical remission was defined as a clinical activity index (CAI) value ≤4 for at least 6 months. Diagnoses of FD- and IBS-like symptoms were evaluated by questionnaire according to the Rome III criteria.Results: One hundred seventy-two UC patients in clinical remission and 330 healthy control subjects were analyzed. Of the 172 patients, 9 (5.2%) met the criteria of FD, which was comparable with the controls (22/330, 6.7%). The prevalence rate of FD-like symptoms in UC patients with IBS-like symptoms (7/46, 15.2%) was lower as compared to that of the control subjects (6/16, 37.5%). On the other hand, a high percentage of the UC patients with FD-like symptoms also had IBS-like symptoms (7/9, 77.8%).Conclusions: Although the prevalence of FD-like symptoms in quiescent UC patients with IBS-like symptoms was low, UC patients with FD-like symptoms frequently had IBS-like symptoms.

Relationship between Barrett's esophagus and colonic diseases: a role for colonoscopy in Barrett's surveillance.

BACKGROUND: Given that risk factors for Barrett's carcinogenesis are predictive, appropriate management and surveillance of Barrett's esophagus (BE) may be provided. The presence of colorectal neoplasms (CRNs) is a possible predictor of the development of BE and the progression to esophageal adenocarcinoma (EAC). We evaluated the relationship between BE or EAC and colonic diseases, including neoplasms and diverticulosis. METHODS: Patients (N = 5606) who underwent both colonoscopy and esophagogastroduodenoscopy between January 2016 and December 2017 at three institutions were enrolled. The relationships between the presence of colonic diseases and BE or EAC and other clinical or endoscopic predictors of the presence of BE were investigated retrospectively. RESULTS: The prevalence of BE ≥ 1 cm and ≥ 3 cm in length was 13.0% and 0.52%, respectively. BE was closely related with the presence of colorectal adenoma (48.4% vs. 37.2% in non-BE; P < 0.001), adenocarcinoma (16.6% vs. 8.4%, P < 0.001) and colonic diverticulosis (CD) (34.1% vs. 29.3%, P < 0.001). In patients with long-segment BE, CRNs (79.3%, P < 0.001) and CD (48.2%, P = 0.038) were more common. EAC patients also had a statistically significantly higher incidence of CRNs than non-BE patients (87.5% vs. 45.6%, P = 0.027). Diverticulosis at the distal colon correlated significantly with EAC and BE (50.0%, P = 0.010 and 15.4%, P = 0.024, vs. 12.0% in non-BE). Multivariate analysis showed that CRNs (t = 8.55, P < 0.001), reflux esophagitis (t = 5.26, P < 0.001) and hiatal hernia (t = 11.68, P < 0.001) were predictors of BE. CONCLUSIONS: The presence of CRNs was strongly associated with BE and EAC. Therefore, colonoscopy may be useful for establishing a strategy for the surveillance of BE.

Capabilities of fecal calprotectin and blood biomarkers as surrogate endoscopic markers according to ulcerative colitis disease type.

Fecal calprotectin level in ulcerative colitis patients is correlated with endoscopic findings. However, its association with various ulcerative colitis disease types has not been elucidated. In the present study, we investigated the correlation of fecal calprotectin level with endoscopic findings as compared to blood biomarkers according to ulcerative colitis disease type. Fecal calprotectin as well as the blood biomarkers: C-reactive protein (CRP), white blood count (WBC), erythrocyte sedimentation rate (ESR), hemoglobin, platelet count (PLT), and serum albumin (Alb) were measured in patients who underwent a complete colonoscopy. Disease type was divided into proctitis, left-sided colitis, and extensive colitis. Correlations of fecal calprotectin and blood biomarker levels with Mayo endoscopic subscore were analyzed. A total of 186 colonoscopy examinations were performed in 124 patients with ulcerative colitis. Fecal calprotectin level showed a significant correlation with Mayo endoscopic subscore regardless of disease type (proctitis, r = 0.54, p<0.01; left-sided colitis, r = 0.75, p<0.01; extensive colitis, r = 0.78, p<0.01), and clearly discriminated inactive (Mayo endoscopic subscore 0) from active stages (Mayo endoscopic subscore 1-3). On the other hand, none of the examined blood biomarkers showed a correlation with Mayo endoscopic subscore in the proctitis group, while weak correlations of several biomarkers (CRP, WBC, ESR, PLT and Alb) with Mayo endoscopic subscore were found in left-sided colitis and extensive colitis cases. This is the first report to elucidate the capabilities of fecal calprotectin and blood biomarkers as endoscopic surrogate markers according to ulcerative colitis disease type.

Irritable Bowel Syndrome-Like Symptoms in Ulcerative Colitis Patients in Clinical Remission: Association with Residual Colonic Inflammation.

Ulcerative colitis (UC) patients in clinical remission often experience irritable bowel syndrome (IBS)-like symptoms. The prevalence rate of UC patients meeting the definition of IBS, such as shown by the Rome criteria, is significantly higher in those without ongoing clinical activity as compared to healthy controls. Several studies have investigated residual low-grade inflammation found in colonic mucosa of quiescent UC patients and its association with development of IBS-like symptoms. In these patients, residual colonic inflammation was evaluated using endoscopy and histology findings, as well as fecal calprotectin level and shown to not be simply associated with the presence of IBS-like symptoms in UC patients in clinical remission. However, these results are limited by the low number of related investigations conducted. Additional appropriately designed studies are necessary to confirm the relationship of low-grade colonic inflammation with IBS-like symptoms associated with UC.

Serum amyloid A level correlated with endoscopic findings in patients with Crohn's disease-Possible biomarker for evaluating mucosal healing.

BACKGROUND: Mucosal healing (MH) has been proposed as an essential therapeutic goal for treatment of Crohn's disease (CD) patients. The utility of serum amyloid A (SAA) for prediction of MH in CD patients is lacking. AIMS: This study was conducted to evaluate the correlation of SAA with CD-related endoscopic disease activity. METHODS: SAA levels in serum samples obtained from CD patients as well as endoscopic findings based on a simple endoscopic score for CD (SES-CD) were assessed in relation to CD activity index (CDAI). The diagnostic ability of MH in correlation with SAA level was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Fifty-five patients with CD were enrolled. Mean SAA level was significantly higher in clinical and endoscopic active phases as compared to an inactive phase. SAA level was also significantly correlated with SES-CD (r = 0.64, p < 0.01) and CDAI (r = 0.42, p < 0.01). The area under the ROC curve for SAA level was 0.77 and the optimal cut-off value for SAA to predict MH was 5.9 µg/dl. SAA level was shown to be associated with MH, with a sensitivity of 68% and specificity of 83%. CONCLUSIONS: SAA may be a possible biomarker for evaluating MH in CD patients.

Fecal Calprotectin More Accurately Predicts Endoscopic Remission of Crohn's Disease than Serological Biomarkers Evaluated Using Balloon-assisted Enteroscopy.

BACKGROUND: Fecal calprotectin (FC) has emerged as a reliable surrogate marker of endoscopic remission in Crohn's disease (CD), which has been mainly evaluated using ileocolonoscopy. We conducted this study to clarify the predictability of FC level for predicting endoscopic remission using balloon-assisted enteroscopy (BAE) findings in patients with CD and compare with that of conventional serological biomarkers. METHODS: Patients with CD scheduled to undergo BAE were prospectively enrolled, and fecal and blood samples collected before the procedures. We used a modified simple endoscopic score for CD, in which the parameter "presence of narrowing" was removed from conventional simple endoscopic score for CD. Endoscopic remission was defined as modified simple endoscopic score for CD 0 to 2. RESULTS: Seventy BAE procedures were performed in 53 patients with CD and evaluated. The area under the curve in receiver operating characteristic curve analysis of FC to predict endoscopic remission was 0.93, with an optimal cut-off value of 252.9 µg/g, and 96% sensitivity and 83% specificity, which was higher than that for C-reactive protein, albumin, white blood cell count, and platelet count (0.76, 0.66, 0.39, and 0.65, respectively). The area under the curve of FC for predicting endoscopic remission was high in patients with ileal and ileocolonic disease location (0.86 and 0.96, cut-off values 204.2 and 253.7 µg/g, respectively), and also higher than the area under the curve values of serological markers. CONCLUSIONS: BAE findings showed that FC was more accurate for predicting endoscopic remission in CD than C-reactive protein, albumin, white blood cell count, and platelet count. Even in small-bowel CD, FC may be a more reliable surrogate marker of endoscopic remission than serological biomarkers.

Evaluation of esophageal intramural pseudo-diverticulosis using high-resolution manometry.

Esophageal intramural pseudo-diverticulosis (EIPD) is a rare disease characterized by multiple small flask-shaped pouches in the esophageal wall, with the predominant symptom of chronic progressive or intermittent dysphagia. However, its etiology and pathogenesis remain unknown. We present a case of EIPD evaluated with high-resolution manometry in a 75-year-old man with food impaction after eating beef, who came to our emergency department. The patient experienced similar episodes three times previously, though the cause was unknown. Computed tomography (CT) findings revealed diffuse wall thickness in the upper intrathoracic esophagus, while esophagogastroduodenoscopy showed multiple small depressions and several white plaque patches, and a barium meal esophagogram showed characteristic multiple small outpouching areas. From these findings, we diagnosed the patient with EIPD. In addition, high-resolution manometry revealed strong contractions in the distal esophagus. We started an administration of isosorbide dinitrate, because abnormal esophageal motility may have been causative of the condition and development of pseudo-diverticulosis. Thereafter, the patient had a good clinical course without food impaction. Elevated intra-esophageal luminal pressure caused by abnormal esophageal motility seems to be an important factor in the pathogenesis of EIPD in some cases.

Usefulness of computed tomography with air insufflation of the stomach prior to percutaneous endoscopic gastrostomy procedure.

We examined the results of computed tomography (CT) with and without air insufflation of the stomach prior to performing percutaneous endoscopic gastrostomy (PEG). We retrospectively analyzed 366 patients who underwent PEG. CT images obtained with and without air insufflation were examined for the presence or absence of contact between the gastric anterior wall and abdominal wall. PEG outcome based on CT findings was also examined. CT with and without air insufflation was performed in 272 and 94 patients, respectively. Contact between the gastric anterior wall and abdominal wall was shown in 254 (93.4%) with and 45 (47.9%) without air insufflation, all of whom underwent a successful PEG procedure. In patients without contact between the gastric anterior wall and abdominal wall, PEG was not successful in 3 of 49 (6.1%) examined by CT without and 6 of 18 (33.3%) examined with air insufflation (p = 0.004). Values for diagnostic accuracy for contact between the gastric anterior wall and abdominal wall shown by CT with and without air insufflation in successful PEG cases were 0.96 and 0.51, respectively. In conclusion, CT with air insufflation more often revealed contact between the gastric anterior wall and abdominal wall as compared to CT without air insufflation, which may help to predict PEG procedure success.

Fecal calprotectin level correlated with both endoscopic severity and disease extent in ulcerative colitis.

BACKGROUND: The relationship between fecal calprotectin (FC) and disease extent in ulcerative colitis (UC) has not been fully elucidated. The aim of this study was to clarify the correlation of FC with disease extent and severity in UC patients. METHODS: UC patients scheduled to undergo an ileocolonoscopy were enrolled and fecal samples for FC measurement were collected prior to the procedure. A Mayo endoscopic subscore (MES) was determined for each of 5 colonic segments. To evaluate the association of FC with extent of affected mucosa as well as disease severity, we assessed the correlation of FC level with the sum of MES (S-MES) for the 5 colonic segments as compared to the maximum score of MES (M-MES). RESULTS: FC measurements in conjunction with findings from 136 complete colonoscopies in 102 UC patients were evaluated. FC level showed a stronger correlation with S-MES (correlation coefficient r = 0.86, p < 0.001) as compared to M-MES (r = 0.79, p < 0.001). In patients with an M-MES of 1, 2, and 3, FC level showed a significant correlation with S-MES (r = 0.67, p < 0.001; r = 0.70, p < 0.001; r = 0.47, p = 0.04, respectively). Our findings indicate that FC level is elevated in patients with greater areas of affected mucosa even in those with the same M-MES value. CONCLUSIONS: FC level was shown to be correlated with the extent of affected mucosa as well as severity in UC patients, thus it is useful for precise assessment of mucosal inflammation.

Primary Pancreatic Malignant Lymphoma Diagnosed from Endoscopic Ultrasound-guided Fine-needle Aspiration Findings.

A 60-year-old woman was admitted to our hospital with upper abdominal pain and jaundice. Computed tomography showed a 9-cm mass that was penetrated by the common hepatic artery in the pancreatic head area. Endoscopic retrograde pancreatography revealed no stenosis or obstruction of the main pancreatic duct, and a cytologic examination of the patient's pancreatic juice was negative. Next, endoscopic ultrasound-guided fine needle aspiration was performed. The immunohistological findings of the specimen revealed a diffuse large B-cell lymphoma. The size of the tumor was significantly reduced after 8 cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone).

Decreased Frequency of Intestinal Regulatory CD5+ B Cells in Colonic Inflammation.

BACKGROUND: CD5+ B cells are a type of regulatory immune cells, though the involvement of this B cell subset in intestinal inflammation and immune regulation is not fully understood. METHODS: We examined the distribution of CD5+ B cells in various mouse organs. Expression levels of CD11b, IgM, and toll-like receptor (TLR)-4 and -9 in B cells were evaluated. In vitro, TLR-stimulated IL-10 production by colonic lamina propria (LP) CD5+ and CD5- B cells was measured. In vivo, mice with acute or chronic dextran sulfate sodium (DSS)-induced colonic injury were examined, and the frequency of colonic LP CD5+ B cells in those was assessed by flow cytometry. RESULTS: The expression level of TLR9 was higher in colonic LP CD5+ B cells as compared to CD5- B cells. Colonic LP CD5+ B cells produced greater amounts of IL-10 following stimulation with TLR ligands, especially TLR9, as compared with the LP CD5- B cells. Acute intestinal inflammation transiently decreased the frequency of colonic LP CD5+ B cells, while chronic inflammation induced a persistent decrease in colonic LP CD5+ B cells and led to a CD5- B cell-dominant condition. CONCLUSION: A persistent altered mucosal B cell population caused by chronic gut inflammation may be involved in the pathogenesis of inflammatory bowel diseases.

Downregulation of serotonin reuptake transporter gene expression in healing colonic mucosa in presence of remaining low-grade inflammation in ulcerative colitis.

BACKGROUND AND AIM: The serotonin reuptake transporter (SERT) terminates serotonin activity by removing it from interstitial space. Downregulated colonic SERT expression has been reported in irritable bowel disease (IBS), and symptoms resembling IBS occur in cases of inflammatory bowel disease (IBD) in remission; thus, a common pathogenesis for IBS and IBD is possible. However, little is known regarding SERT expression in colonic mucosa of IBD patients during healing. METHODS: Twenty-two ulcerative colitis (UC) patients underwent colonoscopy examinations, during which inflamed mucosa was distinguished from that undergoing healing. Healing mucosa was classified into regular and irregular vessel patterns by narrowband imaging magnifying colonoscopy. Expressions of SERT and various inflammation-related genes in biopsy samples were assessed using a polymerase chain reaction array system and real-time polymerase chain reaction. Colitis model mice were established by administration of dextran sodium sulfate or transfer of CD4(+) T cells isolated from SAMP1 mice, then time-course changes of SERT and inflammatory gene expressions were observed in colonic mucosa. RESULTS: In UC patients, SERT expression in inflamed mucosa was significantly lower than in healing mucosa. SERT expression was decreased in healing mucosa with an irregular vessel pattern with mildly increased levels of inflammatory gene expression. In mice, SERT expression was suppressed in inflamed mucosa and continuously observed with low-grade mucosal inflammation during colitis healing. CONCLUSIONS: Sserotonin reuptake transporter expression is downregulated in healing colonic mucosa of UC patients and that suppression may be dependent on the presence of remaining low-grade colonic inflammation.

Simplified classification of capillary pattern in Barrett esophagus using magnifying endoscopy with narrow band imaging: implications for malignant potential and interobserver agreement.

The classification of Barrett esophagus (BE) using magnifying endoscopy with narrow band imaging (ME-NBI) is not widely used in clinical settings because of its complexity. To establish a new simplified available classification using ME-NBI.We conducted a cross-sectional study in a single-referral center. One hundred eight consecutive patients with BE using ME-NBI and crystal violet (CV) chromoendoscopy, and histological findings were enrolled. BE areas observed by ME-NBI were classified as type I or II on the basis of capillary pattern (CP), and as closed or open type on the basis of a mucosal pit pattern using CV chromoendoscopy; then, biopsy samples were obtained. We evaluated the relation between CP and pit pattern, expression of the factors with malignant potential, percentage of microvascular density, and interobserver agreement.One hundred thirty lesions from 91 patients were analyzed. Type II CP had more open type pit pattern areas and significantly greater microvascular density than type I. The presence of dysplasia, specialized intestinal metaplasia, expressions of COX-2, CDX2, and CD34, and PCNA index were significantly higher in type II, whereas the multivariate analysis showed that type II was the best predictor for the presence of dysplasia (OR 11.14), CD34 expression (OR 3.60), and PCNA (OR 3.29). Interobserver agreement for this classification was substantial (κ = 0.66).A simplified CP classification based on observation with ME-NBI is presented. Our results indicate that the classification may be useful for surveillance of BE with high malignant potential.

Role of milk fat globule-epidermal growth factor 8 in colonic inflammation and carcinogenesis.

BACKGROUND: Milk fat globule-epidermal growth factor 8 (MFG-E8) promotes phagocytic clearance of apoptotic cells to maintain normal tissue homeostasis. However, its functions in intestinal inflammation and carcinogenesis are unknown. METHODS: Experimental colitis was induced in MFG-E8 knockout (KO) and wild-type (WT) mice by dextran sodium sulfate (DSS) administration. Colon tissues were used for assessments of colitis activity and epithelial proliferation. A mouse colitis-associated cancer (CAC) model was induced by intraperitoneal injection of azoxymethane (AOM) and then the animals were given a single administration of DSS. A sporadic colon cancer model was established by repeated intraperitoneal injections of AOM. The role of MFG-E8 in epithelial proliferation with or without treatment of siRNA targeting α(v)-integrin was examined in vitro using a WST-1 assay. RESULTS: The severity of colitis in KO mice was greater than that in WT mice, while the proliferative potential of colonic epithelial cells in KO mice was lower during the regenerative phase. In both CAC and sporadic models, tumor size in KO was lower as compared to WT mice, while decreased tumor incidence was only found in the CAC model. In vitro findings showed that MFG-E8 promotes epithelial cell proliferation, and treatment with a siRNA targeting α(v)-integrin reduced the proliferation of Colon-26 cells stimulated with recombinant MFG-E8. CONCLUSIONS: MFG-E8 promotes tumor growth regardless of the presence or absence of colonic inflammation, whereas colon tumor development is initiated by MFG-E8 under inflammatory conditions. These MFG-E8 functions may be dependent on integrin-mediated cellular signaling.

Therapeutic efficacy of pH-dependent release formulation of mesalazine on active ulcerative colitis resistant to time-dependent release formulation: analysis of fecal calprotectin concentration.

PURPOSE: Few reports have compared the clinical efficacy of a pH-dependent release formulation of mesalazine (pH-5-ASA) with a time-dependent release formulation (time-5-ASA). We examined whether pH-5-ASA is effective for active ulcerative colitis (UC) in patients resistant to time-5-ASA. METHODS: We retrospectively and prospectively analyzed the efficacy of pH-5-ASA in mildly to moderately active UC patients in whom time-5-ASA did not successfully induce or maintain remission. The clinical efficacy of pH-5-ASA was assessed by clinical activity index (CAI) before and after switching from time-5-ASA. In addition, the efficacy of pH-5-ASA on mucosal healing (MH) was evaluated in a prospective manner by measuring fecal calprotectin concentration. RESULTS: Thirty patients were analyzed in a retrospective manner. CAI was significantly reduced at both 4 and 8 weeks after switching to pH-5-ASA. In the prospective study (n=14), administration of pH-5-ASA also significantly reduced CAI scores at 4 and 8 weeks in these patients who were resistant to time-5-ASA. In addition, fecal calprotectin concentration was significantly decreased along with improvement in CAI after switching to pH-5-ASA. CONCLUSIONS: Our results suggest that pH-5-ASA has clinical efficacy for mildly to moderately active patients with UC in whom time-5-ASA did not successfully induce or maintain remission.

Gastric mixed adenoneuroendocrine carcinoma with a good prognosis.

A flat, elevated lesion measuring 5 mm in diameter was found in the gastric body of an 80-year-old man. A biopsy showed moderately differentiated adenocarcinoma, and endoscopic ultrasonography revealed a hypoechoic mass located in the submucosa. Endoscopic submucosal dissection was subsequently performed, and a pathological examination revealed a tumor composed of adenocarcinoma and neuroendocrine carcinoma with submucosal infiltration. The pathological diagnosis was gastric mixed adenoneuroendocrine carcinoma (MANEC). An additional gastrectomy procedure was performed, and no recurrence was noted for at least three years. This case is interesting with respect to the carcinogenesis of endocrine cell carcinoma and MANEC.

Prevalence of irritable bowel syndrome-like symptoms in ulcerative colitis patients with clinical and endoscopic evidence of remission: prospective multicenter study.

OBJECTIVE: Irritable bowel syndrome (IBS)-like symptoms are often found in ulcerative colitis (UC) patients in remission. However, the prevalence of those symptoms in UC patients with endoscopic evidence of remission shown by mucosal healing remains unknown. MATERIAL AND METHODS: IBS diagnosis was evaluated by questionnaire results according to the Rome III criteria. Clinical remission was assessed by clinical activity index (CAI), whereas endoscopic remission was evaluated by endoscopic index (Matts grade). RESULTS: We enrolled 172 patients in clinical remission (CAI ≤ 4), after excluding 36 for incomplete questionnaire results or nonremission findings, as well as 330 control subjects. Of the 172 UC patients, 46 (26.7%) met the Rome III criteria, which was a significantly higher rate as compared with the controls (4.8%). The prevalence rate of IBS-like symptoms in UC patients with endoscopic remission findings (Matts grade ≤2) was 25.6%, which was similar to that of those with clinical remission. When endoscopic remission was defined as Matts grade 1, the prevalence rate of IBS-like symptoms was decreased to 15.4%, although the prevalence rate remained higher than that of the control subjects. CONCLUSIONS: The prevalence of IBS-like symptoms in UC patients with clinical and endoscopic remission findings was significantly higher than that of control subjects. Furthermore, the prevalence rate in patients with complete endoscopic remission was decreased. These findings suggest that residual low-grade inflammation may influence the presence of IBS-like symptoms in UC patients in remission.

Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn's disease.

The role of regulatory B cells (Bregs) producing interleukin (IL)-10 in the pathogenesis of inflammatory bowel diseases remains unknown. We investigated IL-10 production in B cells from patients with inflammatory bowel diseases and immunoregulatory functions of Bregs in experimental colitis mouse models. CpG DNA-induced IL-10 production in peripheral blood B cells isolated from patients with inflammatory bowel diseases and control subjects was examined. CD19 and CD1d were used for evaluating possible cell surface markers of Bregs. Colitis models of severe combined immunodeficiency mice were established by adoptive transfer of whole CD4 T cells or regulatory T cell (Treg)-depleted T cells (CD4CD25) isolated from SAMP1/Yit mice and the function of Bregs in intestinal inflammation was elucidated by evaluating the effects of cotransfer of whole or Breg-depleted B cells. CpG DNA-induced IL-10 production was significantly decreased in B cells from patients with Crohn's disease (CD), as compared with those from healthy controls, whereas Bregs were found to be enriched in a population of CD19 and CD1d B cells isolated from both human and mouse samples. The severity of intestinal inflammation was significantly increased in the Breg-depleted mice, with similar results also found in adoptive transfer colitis model mice even after Treg depletion. Our findings show that Bregs, characterized by the cell surface markers CD19 and CD1d, significantly reduced experimental colitis regardless of the presence or absence of Tregs. These results suggest that a deficiency or decrease of Bregs function exacerbates intestinal inflammation, which may be associated with the pathogenesis of CD.