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Fecal calprotectin (FC) is a promising biomarker for diagnosis and treatment of inflammatory bowel disease, ulcerative colitis (UC), and Crohn’s disease (CD). An enzyme immunoassay (EIA) is widely used for FC detection, though the considerable lag time, up to several days, causes clinical management delay. This study was performed to examine the new rapid kit fCAL-turbo, which is based on a particle-enhanced turbidimetric immunoassay (15 minutes), by comparing FC values with other EIA assays (EliA, PhiCal, Bühlmann) and endoscopic scores. Using 94 samples, fCAL-turbo showed strong significant positive correlations with the other kits (Spearman’s r = 0.9178 − 0.9886). Of 74 UC patients, 69 underwent an endoscopy and fCAL-turbo reflected endoscopic activity with a moderate correlation with Mayo endoscopic subscore (MES) (r = 0.6945, others r = 0.6682 − 0.7013). Receiver operating characteristic analyses based on MES 0 vs. 1 − 3 showed a similar efficacy as compared to the other kits (cut-off and area under the curve: 89.70 µg/g and 0.8592, respectively, others 62.35 − 138.4 µg/g and 0.8280 − 0.8611, respectively). All 20 CD patients underwent endoscopy examinations and fCAL-turbo results had a moderate correlation with modified simple endoscopic score for CD (r = 0.5471, others r = 0.3049 − 0.6731). fCAL-turbo showed strong correlations with the other kits and also demonstrated excellent performance for predicting endoscopic remission of UC.

Purpose The incidence of gastric neoplasms in Helicobacter pylori (Hp)-naïve patients has recently increased due to a remarkable decrease in the Hp–infected population in Japan. We investigated the clinicopathologic differences between patients with Hp-infected gastric neoplasms (HpIGNs) and those with Hp-naïve gastric neoplasms (HpNGNs) that have not been fully elucidated so far. Methods This retrospective study investigated 887 patients with 1010 gastric dysplasia or cancers who underwent endoscopic or surgical treatment for the recent decade. Clinical and neoplastic features were compared between HpIGN and HpNGN cases. Results HpNGNs accounted for 4.5% (45/1010) of all gastric neoplasm cases, but were found concentratedly in the latter five-years. Nine hundred sixty-five HpIGNs included 774 differentiated-type and 191 undifferentiated-type. Forty-five HpNGNs included 4 undifferentiated type, 5 fundic-gland type, 32 foveolar type, 3 intestinal type, and 1 other differentiated type. HpNGNs occurred in significantly younger patients (59.9 vs. 71.8 years, pConclusions HpNGN occurrence has recently been increasing along with an increase in Hp-naïve population and in knowledge about this type of tumor, though with a lower grade of biological malignancy regardless of histologic type.

Endoscopic submucosal dissection (ESD) for extensive esophageal cancer is sometimes associated with post-ESD stenosis, despite preventative steroid therapy. In this retrospective multicenter analysis, we evaluated the factors associated with therapy resistance.We enrolled 73 patients with 75 extensive esophageal cancers treated with ESD. Stenosis prevention was performed using two esophageal triamcinolone acetonide (TA)-fillings, and repeated if stenosis was found on follow-up. Therapy-resistance factors associated with incidence of severe stenosis requiring endoscopic balloon dilation (EBD) were evaluated, including age, gender, previous treatment history, tumor location, morphology, resection size, histologic type, invasion depth, and horizontal resection grade (HR-grade 1, ≥ 9/12 and10/12 of the circumference; grade 2, ≥ 10/12 and11/12; grade 3, ≥ 11/12 but not circumferential; and grade 4, entirely circumferential).Severe stenosis occurred in 17.3%(13/75) of cases, with a median of two EBDs (range, 1-6 times). Severe stenosis was significantly associated with HR-grade elevation and previous treatment history (Esophageal TA-filling is a promising stenosis-preventive steroid therapy, even in entirely circumferential ESD cases. However, HR-grade 2 or more elevation and previous treatment history were independently associated with therapy resistance.

Background/Aims Unsedated transnasal esophagogastroduodenoscopy (EGD) is affected by a poor scope lens-cleaning function. We have previously reported good, albeit limited, effects of an oolong tea washing solution; here, we evaluated the effectiveness of a 5% lens cleaning solution for cleaning an EGD lens. Methods Five percent lens cleaning solution (C), 5% dimethicone solution (D), and distilled water (W) were prepared. Study I: Lenses were soiled with pork grease, washed with each washing solution, and their image quality was judged. Study II: Patients (n=996) scheduled for transnasal EGD were randomly assigned to the C- or W-group. Lens cleanliness level, washing solution volume used, and endoscopist stress due to lens contamination were determined. Results Study I: The image quality of the lenses washed with (C) was significantly superior. (D) was clinically unsuitable because of spray nozzle clogging. Study II: Lens cleaning in the C-group was significantly superior (p

Background and aim The most common adverse event following an endoscopic retrograde cholangiopancreatography (ERCP) procedure is post-ERCP pancreatitis (PEP). Rectal nonsteroidal anti-inflammatory drug (NSAID) administration has shown promise to reduce the risk of PEP in high-risk patients. However, in contrast to high-risk patients, the role of NSAID administration in patients with low risk remains controversial. Methods We performed a prospective, single-center, single-blinded, two-arm parallel group, randomized controlled trial to clarify the efficacy of low dose (50 mg) rectal NSAID administration for preventing PEP in at-risk patients. Patients scheduled to undergo ERCP were randomized into two groups, those with and without rectal administration of diclofenac. Patients in the diclofenac group received 50 mg of rectal diclofenac 30 min before undergoing ERCP. The primary endpoint was rate of PEP. Results A total of 303 were randomized into the study groups. Four patients declined participation following randomization, and another two were withdrawn. As a result, a total of 147 patients were assigned to the diclofenac group and 150 to the control group. The baseline and procedural characteristics were similar in both groups. The primary endpoint of PEP occurrence was seen in 13 of 297 patients (4.4%), including eight (5.4%) in the diclofenac group and five (3.3%) in the control group (P = 0.286). Additionally, those results were not significantly different when patients were classified as low or high risk. Conclusions Prophylactic low-dose rectal diclofenac did not reduce the incidence of PEP following ERCP in patients classified as low or high risk.

Objective We evaluated the efficacy of vonoprazan-based eradication therapy for Helicobacter pylori (H. pylori), including the effects of age, gender, and grade of atrophy in comparison to proton pump inhibitor-based therapy. Method We retrospectively reviewed the records of 1,172 patients who received first-line triple therapy with amoxicillin, clarithromycin, and vonoprazan or a proton pump inhibitor (PPI) for H. pylori eradication, as well as 157 patients treated with second-line therapy consisting of amoxicillin, metronidazole, and vonoprazan or a PPI. Results The eradication rate of all cases treated with first-line triple therapy was 86.9% (1,019/1,172), while that in those treated with vonoprazan-based therapy was 92.5% (384/415). Our analysis showed that the use of vonoprazan resulted in a significantly improved success rate of first-line eradication therapy in comparison to proton pump inhibitor-based therapy [odds ratio (OR), 2.36; 95% confidence interval (CI) 1.55 to 3.56]. The superiority of vonoprazan was remarkable in non-elderly patients, while its effect was unclear in elderly patients. When used as second-line eradication therapy, the advantage of vonoprazan over PPI administration was not clear. Conclusion The inclusion of vonoprazan increased the success rate of first-line eradication therapy; however, the advantage was reduced with aging and remained unclear in elderly patients.

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

Objectives The aim was to clarify the sensitivity and specificity of diffusion-weighted imaging, as well as of that in combination with magnetic resonance cholangiopancreatography for pancreatic tumor diagnosis in real-world clinical setting. Methods Subjects were 217 consecutive patients who underwent both magnetic resonance imaging and contrast-enhanced ultrasound sonography. Cases positive for a pancreatic tumor were confirmed based on pathological diagnosis, whereas negative cases were defined when no solid pancreatic tumor was detected by contrast-enhanced ultrasound sonography or a solid mass was detected but the diagnosis was ultimately denied based on pathological results. Diffusion-weighted imaging-positive was defined as a case with high signals and magnetic resonance cholangiopancreatography-positive when localized main pancreatic duct stenosis with caudal dilation was detected.We calculated sensitivity and specificity of each modality and those in combination based on sequential use for pancreatic tumor diagnosis. Results Diffusion-weighted imaging showed a sensitivity of 94.4% and specificity of 94.5%, whereas those values for magnetic resonance cholangiopancreatography alone were 83.3% and 99.0%, respectively, and for the modalities in combination were 100% and 94.5%, respectively. Conclusions Diffusion-weighted imaging was more sensitive than magnetic resonance cholangiopancreatography, whereas those used in combination resulted in increased sensitivity.

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 clini...

Background There have been very few studies on the association of polypharmacy with clinical course. In this paper, we seek to evaluate the relationship between polypharmacy and hospitalization period. Methods We retrospectively analyzed 322 patients hospitalized from February to September 2017, after excluding short-term and orthopedic cases. Patients with polypharmacy were defined as those who were prescribed more than five drugs at the time of admission. The primary endpoint for all subjects regardless of polypharmacy was the hospitalization period. Using Mann-Whitney U test results, we compared the average number of hospital days between patients with and without polypharmacy. Secondary endpoints were hospitalization period with and without polypharmacy for each disease type. Results The hospitalization period was significantly extended for patients with polypharmacy as compared to those without (31.6 vs. 23.2 days, p: 0.002). Those with an infection had significantly longer hospitalization than those without polypharmacy (27.6 vs. 18.1 days, p: 0.007). Malignancy, heart disease, and cerebrovascular disease did not have a significant effect on hospitalization regardless of polypharmacy. Conclusion Polypharmacy is related to an extended hospitalization period and is found to occur more frequently in patients hospitalized for an infection.

Highlight Fukuba and colleagues report a case of lower common bile duct cancer with the extremely rare anomaly of left and right bile ducts parallel with the duodenal papilla, and joined distally to form a single short common bile duct. Fully covered metallic stents were placed in a side-by-side manner.

Aim: Few reports of the prophylactic use of soft coagulation with hemostatic forceps for postendoscopic papillectomy hemorrhage (PEPH) have been presented. The aim of this study was to clarify the utility of that procedure for prophylaxis. Materials and Methods: From April 2009 to March 2012, PEPH was treated in four patients after the development of the condition with a conventional procedure at our institution. Thereafter, from April 2012 to March 2016, soft coagulation using hemostatic forceps was performed as prophylactic hemostasis following an EP in five patients. For the latter procedure, the hemostatic forceps device (FD411‑QR, Olympus, Tokyo, Japan) was used in a closed position, with the coagulation wave set at 60 W (VIO 300D; ERBE, Tubingen, Germany). The primary outcome was the onset of PEPH, which was defined as a decrease in hemoglobin ≥2 g/dL after EP. Secondary endpoints were the success rate and the incidence of adverse events of soft coagulation using hemostatic forceps for emergency bleeding cases after EP. Results: The incidence of PEPH was 20% (1 of 5 cases) in the prophylactic procedure group, which was lower than that in the conventional procedures group (75%, 3 of 4 cases), though the difference was not statistically significant (P = 0.206, Fisher’s exact test). All cases of PEPH were successfully treated by soft coagulation using hemostatic forceps. Conclusion: Soft coagulation with hemostatic forceps may be suitable for use as a routine technique following EP to prevent PEPH.

Epidermal differential complex (EDC) proteins, such as filaggrin, involucrin, and loricrin, play key roles to protect the mucosal surface against invading pathogens. Eosinophilic esophagitis (EoE) is an allergic gastrointestinal disease that features eosinophilic infiltration of esophageal mucosa, though the function of EDC proteins in its pathogenesis remains unknown. The aim of this study was to investigate possible differences of EDC protein expression in the epithelium of the esophagus, pharynx, and tongue. Furthermore, we examined that expression in esophageal specimens obtained from patients with EoE. For evaluating EDC protein expression in epithelium from different locations, we enrolled 72 patients who underwent surgical resection for esophageal, pharyngeal, or tongue squamous cell carcinoma. Pathological samples were used for analysis of expression by immunohistochemistry. In addition, samples were obtained from 10 patients with EoE and 11 healthy subjects, and compared for esophageal epithelial expression of EDC proteins. In epithelium samples obtained from the esophagus, pharynx, and tongue, the presence of EDC proteins was confirmed by immunohistochemistry analysis findings, though the expression patterns were notably different in comparison to that in epidermis samples. In EoE patients, the expression of involucrin was dramatically down-regulated in esophageal mucosa, whereas down-regulation of filaggrin and loricrin did not reach a statistically significant level. EDC protein expression was clearly detected in pharyngoesophageal epithelium samples, while that of involucrin alone was markedly reduced in patients with EoE.

A 70-year-old woman with loss of appetite was referred to our hospital for further examinations. Computed tomography revealed a low density tumor in the body of the pancreas measuring 4 cm in diameter. The main pancreatic duct was dilated on both the head and caudal side of the tumor. Magnetic resonance imaging showed the mass as a low intensity area in T1-weighted and high intensity area in T2-weighted images. Endoscopic retrograde cholangiopancreatography findings indicated that the main pancreatic duct was continuous with the lumen of the tumor. A cytological examination of pancreatic juice showed a class IV tumor. A distal pancreatectomy was performed as a curative resection procedure. The findings of hematoxylin eosin staining and mucus trait led to a diagnosis of invasive cancer derived from an intraductal papillary mucinous neoplasm (IPMN). We also performed sequencing analysis to investigate GNAS and K-RAS mutations in the tumor, though neither the GNAS mutation c602G>A nor K-RAS mutation c35G>A were observed. Cases negative for a GNAS mutation can be considered to have an increased risk of invasive cancer derived from an IPMN.

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.

Objectives Several studies report on the outcomes of self-expandable metallic stents (SEMSs) deployment for malignant gastric outlet obstruction (GOO). However, data was mostly based on the analysis of single-center studies including only a small number of patients. This study aimed to evaluate clinical outcomes after the deployment of SEMS in patients with malignant GOO and to compare the clinical outcomes of two metallic stents with different designs. Methods Altogether 125 consecutive patients from five institutions were included. Clinical outcomes were evaluated according to technical success, clinical success, stent patency period, survival period and complications. A comparison of clinical outcomes between Niti-S pyloric/duodenal and WallFlex duodenal stents was also undertaken. Results Rates for clinical and technical success were 100% and 92.0%, respectively. The median stent patency and survival periods were 72.0 days (range 3–775 days) and 75.0 days (range 3–775 days), respectively. The rate of overall adverse events was 28.8%. The rate of stent dysfunction was 16.8%, and that of adverse events, except stent dysfunction was 12.0%. Massive bleeding occurred in two patients as a late complication. The clinical success rate for Niti-S stent was significantly higher than that for WallFlex stent (96.2% vs 84.8%, P = 0.023). Conclusions We successfully deployed a SEMS in malignant GOO. The selection of a SEMS with a lower axial force may be important for patients to resume the oral food intake. Additionally, consideration must be given to the appropriate management of fatal bleeding as a late complication.

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.

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).

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.

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

The correct name of the corresponding author should be ''Nobuhiko Fukuba'', and not ''Nobuhiko Fukuban'' as given in the original publication of the article.

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.This study was conducted to evaluate the correlation of SAA with CD-related endoscopic disease activity.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.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%.SAA may be a possible biomarker for evaluating MH in CD patients.

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.

A 50-year-old male underwent abdominal computed tomography at a city hospital in Japan, which revealed a tumor 38 mm in diameter in the tail of the pancreas. Based on findings from endoscopic ultrasonography-guided fine needle aspiration using a 22-gauge needle with a side hole, the tumor was diagnosed as an invasive ductal carcinoma. The patient was referred to our hospital and underwent a distal pancreatectomy. Esophagogastroduodenoscopy performed as part of a medical checkup at another hospital 2 years later revealed a 20-mm-sized submucosal tumor in the posterior wall of the upper body of the stomach. Examination of a biopsy specimen obtained from the top of the lesion revealed adenocarcinoma. Partial resection of the stomach was performed and pathological findings showed an adenocarcinoma in all layers of the stomach wall, consistent with recurrence derived from needle tract seeding of the previously excised cancerous tumor from the pancreatic tail. Additional experimentation performed for confirmation with an agar model showed that agar on the deep side leaked to the shallow side following puncture with a needle with a side hole used with a slow-pull technique.

Background and study aims Recurrence of common bile duct stones (CBDS) in patients treated with endoscopic sphincterotomy (ES) can lead to deterioration in their quality of life. Although the pathology and related factors are unclear, we speculated that proton pump inhibiter (PPI) administration increases the risk of CBDS recurrence by altering the bacterial mixture in the bile duct. Patients and methods The primary endpoint of this retrospective study was recurrence-free period. Several independent variables considered to have a relationship with CBDS recurrence including PPI use were analyzed using a COX proportional hazard model, with potential risk factors then evaluated by propensity score matching analysis. Results A total of 219 patients were analyzed, with CBDS recurrence found in 44. Analysis of variables using a COX proportional hazard model demonstrated that use of PPIs and ursodeoxycholic acid (UDCA), as well as the presence of periampullary diverticula (PD) each had a hazard ratio (HR) value greater than 1 (HR 2.2, P = 0.007; HR 2.0, P = 0.02; HR 1.9, P = 0.07; respectively). Furthermore, propensity score matching analysis revealed that the mean recurrence-free period in the oral PPI cohort was significantly shorter as compared with the non-PPI cohort (1613 vs. 2587 days, P = 0.014). In contrast, neither UDCA administration nor PD presence was found to be a significant factor in that analysis (1557 vs. 1654 days, P = 0.508; 1169 vs. 2011 days, P = 0.121; respectively). Conclusion Our results showed that oral PPI administration is a risk factor for CBDS recurrence in patients who undergo ES.

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.

During intestinal inflammation, a variety of signaling events are activated to perform several cell functions. Although the distinct roles of these pathways have been elucidated, the effects of their crosstalk activities remain to be clarified. We evaluated the crosstalk between two evolutionary conserved cell signaling systems, toll-like-receptor (TLR) 5 and Notch1, in intestinal epithelial cells during inflammation. Significant induction of the expression of Notch1 and Jagged1 was observed in the distal part of the colon, together with abundant localization of Notch1 intracellular domain (N1ICD) in the surface epithelium of inflamed colonic mucosa. By targeting intestinal epithelial cells, it was shown that recombination-signal-binding-protein-Jκ (RBP-Jκ)-mediated Notch functions are dependent on a flagellin-TLR5-mediated pathway. Conversely, using a γ-secretase inhibitor, we demonstrated that Notch synergistically increases TLR5‑mediated NF-κB activation. In addition, the effects of Notch on the NF-κB target gene interleukin-6 (IL-6) expression were revealed by evaluating the RBP-Jκ responsive element in the IL-6 promoter in vitro. Modulation of TLR5 and Notch crosstalk by transient blocking of Notch during the acute phase of colitis was beneficial for ameliorating colonic inflammation as well as disease status. In conclusion, the results suggest the effectiveness of Notch-targeted drug strategy for the treatment of intestinal inflammation.

Systemic AA amyloidosis is a complication of various inflammatory diseases including Crohn's disease (CD). Amyloid nephropathy is the most common clinical presentation of AA amyloidosis leading to renal failure, and affected patients often require hemodialysis and ultimately renal transplantation. We herein report the successful use of infliximab as maintenance therapy for amyloid nephropathy in a patient with CD. In the present patient, surgical treatment and infliximab infusion immediately induced a remission of CD, and scheduled infliximab therapy successfully maintained the patient's stable condition for three years, with a significant decrease in the serum creatinine level.

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

Several studies report on the outcomes of self-expandable metallic stents (SEMSs) deployment for malignant gastric outlet obstruction (GOO). However, data was mostly based on the analysis of single-center studies including only a small number of patients. This study aimed to evaluate clinical outcomes after the deployment of SEMS in patients with malignant GOO and to compare the clinical outcomes of two metallic stents with different designs.Altogether 125 consecutive patients from five institutions were included. Clinical outcomes were evaluated according to technical success, clinical success, stent patency period, survival period and complications. A comparison of clinical outcomes between Niti-S pyloric/duodenal and WallFlex duodenal stents was also undertaken.Rates for clinical and technical success were 100% and 92.0%, respectively. The median stent patency and survival periods were 72.0 days (range 3-775 days) and 75.0 days (range 3-775 days), respectively. The rate of overall adverse events was 28.8%. The rate of stent dysfunction was 16.8%, and that of adverse events, except stent dysfunction was 12.0%. Massive bleeding occurred in two patients as a late complication. The clinical success rate for Niti-S stent was significantly higher than that for WallFlex stent (96.2% vs 84.8%, P = 0.023).We successfully deployed a SEMS in malignant GOO. The selection of a SEMS with a lower axial force may be important for patients to resume the oral food intake. Additionally, consideration must be given to the appropriate management of fatal bleeding as a late complication.

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.

A 51-year-old woman with an unresectable pancreatic tumor that was histologically diagnosed as an adenosquamous carcinoma underwent chemoradiotherapy with 5-fluourouracil (FU) and low-dose cisplatin (low-dose FP). Because we recognized a partial response to the chemoradiotherapy, we subsequently administered combined chemotherapy with S-1 and cisplatin. After one course of this combined chemotherapy, the tumor was further reduced in size and became difficult to discern on abdominal computed tomography (CT). We have continued to administer the S-1 and cisplatin combined chemotherapy, and the patient is still alive. After 20 months of treatment, the tumor has not recurred (as assessed by abdominal CT). Additionally, we have not seen elevation of tumor markers. This report presents the successful use of chemoradiotherapy with low-dose FP and additional combined chemotherapy with S-1 and cisplatin for unresectable pancreatic adenosquamous carcinoma.

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.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.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.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.

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.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.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.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.

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.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).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.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.

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.

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.