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Leukocyte subtypes can be used to evaluate the severity of ulcerative colitis (UC). In this study, we examined the relationship between the lymphocyte-to-monocyte ratio (LMR) and the Mayo endoscopic score (MES) in assessing endoscopic activity in UC. Eighty-nine samples of leukocyte subtypes and biomarkers, including fecal calprotectin (FC), the fecal immunochemical occult blood test (FIT), and C-reactive protein (CRP), from 71 patients with UC were retrospectively investigated, along with the MES. The MES was significantly correlated with the LMR, FC, the FIT, and CRP. There were significant differences in the LMR, FC, the FIT, and CRP between groups with an MES &lt, 1 and &gt, 2 (p = 0.001, p = 0.003, p &lt, 0.001, and p &lt, 0.001, respectively). In the receiver operating characteristic (ROC) analysis for predicting mucosal healing (MES 0 or 1), the areas under the curve (AUCs) for the LMR, FC, the FIT, and CRP, were 0.712, 0.860, 0.908, and 0.796, respectively. In the analysis of patients without immunomodulators, the correlation of the MES with the LMR and CRP was significant. The LMR can be used to assess endoscopic activity in UC, particularly in patients without immunomodulators.

BACKGROUND AND AIM We retrospectively determined the safety and efficacy of the endoscopic delivery (ED) of capsule endoscopes. METHODS We enrolled 10,156 patients who underwent small bowel capsule endoscopy (SBCE), 3182 who underwent patency capsule (PC), and 1367 who underwent colon capsule endoscopy (CCE), at 11 gastroenterological and nine pediatric centers. RESULTS Small bowel capsule endoscopies, PCs, and CCEs were endoscopically delivered to 546 (5.4%), 214 (6.7%), and 14 (1.0%) patients, respectively. Only mild complications occurred for 21.6% (167/774), including uneventful mucosal damage, bleeding, and abdominal pain. Successful ED of SBCE to the duodenum or jejunum occurred in 91.8% and 90.7% of patients aged

Purpose The ulcerative colitis colonoscopic index of severity (UCCIS) evaluates the state of the entire colonic mucosa in ulcerative colitis. However, no cut-off values of scores for predicting clinical relapse in patients with ulcerative colitis have been established. This study aimed to determine the cut-off values for predicting clinical relapse in patients with ulcerative colitis. Methods The endoscopic scores (sum of Mayo endoscopic subscores (S-MES) and UCCIS) of 157 patients with ulcerative colitis experiencing clinical remission and their subsequent clinical course were retrospectively reviewed. The optimal cut-off values for predicting relapse and relapse-free rates were analyzed by receiver operating characteristic analysis. Results Forty patients with ulcerative colitis experienced relapse within 24 months. The median UCCIS for these patients at the time of study enrollment was significantly higher than that for patients with clinical remission (P P P = 0.004). Conclusions The data from this study indicate that the USSIC is a more relevant score than the S-MES for predicting the time to relapse in patients with ulcerative colitis in remission.

Background Oral tacrolimus is a therapeutic agent for moderate to severe steroid-dependent or resistant ulcerative colitis (UC), but remission induction is difficult, and it is necessary to treat the patient while considering the next treatment. Aim To examine serum albumin (Alb) level as a prognostic factor for the therapeutic effect of tacrolimus in clinical practice. Methods Forty-seven patients with UC treated with tacrolimus at our institution were divided into remission and failure groups (colectomy or switch to biologics), and the biological data at the start of observation and at weeks 1 and 2 were retrospectively examined. Kaplan-Meier and multivariate analyses were performed using Alb as a prognostic factor in UC treatment. Results During the three months observed, 17 (36.2%) patients failed treatment with tacrolimus. A comparison between the failure and remission groups showed a significant difference only in Alb in week 2, and in the week 2/week 0 Alb ratio, which showed the rate of change in Alb. The cut-off value of the week 2/week 0 Alb ratio that predicted failure was 1, and its area under the curve was 0.751 (95%CI: 0.604-0.898). In the Kaplan-Meier analysis, a week 2/week 0 Alb ratio ≤ 1 had a significantly higher failure rate than that of > 1; Cox proportional hazard regression analysis also showed that a week 2/week 0 Alb ratio ≤ 1 was an independent prognostic factor for failure within 3 mo after the start of tacrolimus treatment. Conclusion A week 2/week 0 Alb ratio ≤ 1 predicts failure within 3 mo of tacrolimus administration for UC. High failure risk exists with week 2 Alb values ≤ 1 on admission.

Background Tuberous sclerosis complex (TSC) is a rare inherited disease with non-cancerous tumor growths in the skin, brain, kidneys, heart, and lungs. The co-occurrence of neuroendocrine neoplasm (NEN) with TSC is even rarer. There have been few reports on the relationship between TSC and neuroendocrine tumors (NETs), and fewer on the relationship between TSC and neuroendocrine carcinoma (NEC), a subtype of NEN. This is the first reported case of NEC occurring at the esophagogastric junction in a patient with TSC. Case summary A 46-year-old woman visiting our hospital for the treatment of TSC was admitted to the emergency department with tarry stools and dizziness. Computed tomography scans revealed thickness of the gastric cardia, multiple metastatic lesions of the liver, and enlarged lymph nodes near the lesser curvature of the stomach. Esophagogastroduodenoscopy revealed a type 3 tumor located from the esophagogastric junction to the fundus, and the pathological diagnosis by biopsy was NEC. The patient was treated with seven courses of cisplatin + irinotecan, followed by eight courses of ramucirumab + nab-paclitaxel, one course of nivolumab, and two courses of S-1 + oxaliplatin. Twenty-three months after the first treatment, the patient died because of disease progression and deterioration of the general condition. Conclusion This case of NEC occurring in a patient with TSC indicates a difference in the occurrence of NETs and NECs.

Background & Aims The new curcumin derivative Theracurmin® has a 27–fold higher absorption rate than natural curcumin powder. Theracurmin® is an inhibitor of nuclear factor-κB, which mediates the expression of inflammatory cytokines. The effect of Theracurmin® on inflammatory bowel disease in humans has not been explored; therefore, we investigated the efficacy and safety of Theracurmin® in patients with Crohn’s disease. Methods In this randomized, double-blinded study performed at 5 independent medical centers in Japan, Theracurmin® (360 mg/day, n = 20) or placebo (n = 10) was administered to patients with active mild-to-moderate Crohn’s disease for 12 weeks. The agent’s efficacy was assessed by evaluating clinical and endoscopic remission, healing of anal lesions, and blood levels of inflammatory markers. Results In the Theracurmin® group, a significant reduction in clinical disease activity was observed in week 12 relative to that in week 0 (p = 0.005). On intention-to-treat analysis, clinical remission rates were 35%, 40%, and 40% at weeks 4, 8, and 12, respectively, which were significantly higher than those in the placebo group (all 0%; p = 0.033, p = 0.020, and p = 0.020, respectively). Furthermore, reduction in endoscopic Crohn’s disease severity (p = 0.032) was observed at week 12 in the Theracurmin® group. The endoscopic remission rates were 15% and 0% in the Theracurmin® and placebo groups, respectively. Significant healing of anal lesions (p = 0.017) was observed at week 8 in the Theracurmin® group. No serious adverse events were observed in either group throughout the study. Conclusions Theracurmin® shows significant clinical and endoscopic efficacy together with a favorable safety profile in patients with active mild-to-moderate Crohn’s disease. Clinical trial UMIN registration ID UMIN000015770.

Background Schlafen 11 (SLFN11) was recently identified as a dominant determinant of sensitivity to DNA-targeting agents including platinum-based drugs. SLFN11 also reportedly enhances cellular radiosensitivity. In this study, we examined the prognostic value of SLFN11 expression in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT), including the platinum derivative nedaplatin. Methods Seventy-three patients with ESCC who received dCRT were examined. SLFN11 expression was analyzed in pre-dCRT biopsies using immunohistochemistry and evaluated using a histo-score (H-score). Correlation between the H-score and overall survival was analyzed. An H-score ≥ 51 was provisionally defined as indicating high SLFN11 expression. Viability assays were performed using previously established isogenic human cell lines differentially expressing SLFN11 to test the usefulness of SLFN11 as marker of response to the dCRT regimen. Results High SLFN11 expression was independently associated with better prognosis in ESCC patients (hazard ratio = 0.295, 95% CI = 0.143–0.605, p = 0.001 for multivariate analysis). Kaplan-Meier survival curves showed that the prognostic value of high SLFN11 expression was most evident in patients at clinical stages II and III (p = 0.004). In in vitro study, SLFN11-proficient cells were highly sensitive to platinum derivatives compared to SLFN11-deficient cells. Conclusion SLFN11 expression is an independent prognostic factor for ESCC patients treated with dCRT and a potential biomarker for treatment selection of ESCC. Examination of SLFN11 may be particularly useful for clinical Stage II–III patients who wish to choose dCRT (instead of surgery) to preserve esophageal function.

The frequency of deficient mismatch repair (dMMR) or microsatellite instability-high colorectal cancer (CRC) is estimated to be ~15% of all patients with CRC; however, the patients reported are limited to surgical cases, and the frequency of patients exhibiting stage 0 disease is not considered, despite the currently increasing use of endoscopic techniques to cure a number of these patients. In the present study, the DNA MMR status for stage 0 patients with CRC treated using endoscopic submucosal dissection or endoscopic mucosal resection was analyzed via immunohistochemical staining of four types of proteins, namely MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6 and PMS1 homolog 2 MMR system component, in adenocarcinoma specimens. Notably, none of the endoscopically resected specimens exhibited dMMR among the 41 patients diagnosed with stage 0 CRC. Since tumors harboring dMMR progress more rapidly than tumors with chromosomal instability, the present results highlight the importance of tumor resection during very early phases that exist before the promoter region of MLH1 becomes hypermethylated, resulting in a loss of DNA MMR function.

Crohn's disease is recognized to increase the risk of gastrointestinal malignances. Adenocarcinoma is the most common malignancy in these patients. Association between Crohn's disease and adenocarcinoma in the small intestine has already been established, however, the association between neuroendocrine tumor and Crohn's disease remains uncertain. We report a 39-year-old man with Crohn's disease, who was diagnosed with NET in the rectum. He had suffered from fever and anal pain due to the anal fistula and abscess. The disease state was considered to be resistant to medical treatment. He underwent total proctocolectomy, small bowel resection, anal fistula drainage with ileostomy. Postoperative histology revealed a neuroendocrine tumor in the rectum. His postoperative course was uneventful, and he followed a good course under treatment with infliximab and mercaptopurine hydrate. This case highlights the need of careful observation of resected specimens in light of the possibility of NET, especially those with anal disorders.

In 2012, Japan approved the use of a tag-less patency capsule (PC), which evaluates gastrointestinal patency before small-bowel capsule endoscopy (SBCE). This study aimed to evaluate the validity of our modification on the passage criteria for this PC in clinical practice. We retrospectively enrolled 326 consecutive patients who underwent PC examination before SBCE. If X-ray could not reveal the PC in the body during the judgement time (30–33 h after ingestion), we defined it as ‘estimated patency’ and performed SBCE. We employed plain computed tomography (CT) for the second judgement, as needed. The overall patency rate was 95.1%. By X-ray, 41 (12.6%) patients were judged to have ‘estimated patency’, and SBCE could be safely performed. Plain CT judgement was necessary in 32.5%. One PC case had a residual coating film associated with stenosis in a patient with Crohn’s disease (CD), and one (0.3%) SBCE case had capsule retention resulting from false CT judgement. Multivariate analysis revealed that established CD and inpatient were factors related to patency loss. In conclusion, PC is useful for examining gastrointestinal patency, keeping in mind CT misjudgement. If PC was not found in the body via X-ray, performing SBCE as ‘estimated patency’ seemed appropriate.

Cytomegalovirus (CMV) reactivation in the colon is common in patients with severe ulcerative colitis (UC). Ganciclovir (GCV) resistance conferring CMV UL97 gene mutations have been reported in recent years. However, the prevalence of UL97 gene mutations in GCV-naive CMV infection in the colon remains unknown. We investigated the prevalence of CMV UL97 gene mutations in patients with colonic CMV infection associated with or without UC. Twenty-two GCV-naive patients with colonic CMV infection, 15 with UC and 7 with other diseases, were enrolled. Frozen biopsy samples or formalin-fixed paraffin-embedded samples were used for nested polymerase chain reaction (PCR) amplification of the UL97 gene. Sanger DNA sequencing was performed. In comparison with AD169 reference strain, natural polymorphisms were frequently detected in codons N68D (100%), I244V (100%), and D605E (86.4%). Seven polymorphisms were detected infrequently (

Adalimumab (ADA) trough level and anti-ADA antibody (AAA) positivity influence mucosal healing and loss of response in patients with inflammatory bowel disease (IBD). In this study, we clarified the correlation between ADA monitoring, including non-trough level, and real-world IBD clinical outcomes. This retrospective, observational, single-center study involved patients with ulcerative colitis (19) and Crohn’s disease (33) treated with ADA from January 2007 to August 2018. Serum ADA and AAA levels were measured 4‒14 days after ADA administration. The AAA positivity rate was 23.1% (12/52). ADA continuity was higher in AAA-negative patients than in AAA-positive patients (P = 0.223). Receiver operating characteristic (ROC) analysis revealed that a serum AAA cut-off of 9.2 μg/mL was associated with ADA continuity. The ADA level was significantly higher in the endoscopic remission group than in the non-remission group (P = 0.02). Based on the ROC curve analysis results of serum ADA level and endoscopic remission, the cut-off value of the serum ADA level was set to 11.1 μg/mL. Under the combined use of ADA with immunomodulators and AAA positivity, ADA continuity was significantly higher when the serum AAA level at 4–14 days after ADA administration was ≥9.2 μg/mL. Furthermore, endoscopic remission can be expected with a serum ADA level of ≥11.1 μg/mL. Overall, to predict clinical outcomes, it would be useful to measure the blood level of ADA regardless of the timing of the trough.

BACKGROUND Breathing frequency is rarely measured during a field walking test since the current monitoring system using a face mask is cumbersome for older adults. For effective clinical application, we aimed to validate the new respiratory monitor using wearable strain sensors during a 6-min walk test (6MWT) in young adults and patients with chronic obstructive pulmonary disease (COPD). METHODS The study included young adults and patients with stable COPD voluntarily recruited from three hospitals. Breathing frequency during 6MWT were measured by the strain sensor and a nasal capnometer. Total breathing frequencies were measured by the capnometer. The Bland-Altman method was used to estimate the mean limit of agreement for breathing frequency. RESULTS A total of 23 young adults (age = 23.1 ± 3.7, mean ± SD) and 50 patients with COPD (age = 75.2 ± 7.2, %FEV1 = 59.1 ± 19.7) were analyzed. During the entire test period, the total breathing frequencies were measured based on an average of 252 ± 46 breaths, and the total breathing frequency was higher in patients with COPD than in young adults (mean difference = -3.349, p

We evaluated the association between endoscopic scores of colonic inflammation and fecal calprotectin (FC), fecal immunochemical occult blood test (FIT), and C-reactive protein (CRP) in patients with ulcerative colitis (UC). Endoscopic scores reflecting the most severe lesion [maximum Mayo Endoscopic Subscore (M-MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS)] and those reflecting the inflammation of the entire colon [sum of MES (S-MES) and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS)] were evaluated. FC, FIT, and CRP were measured, and their association with the four endoscopic scores was evaluated. Endoscopic scores of 78 complete colonoscopies (66 UC patients) were evaluated using the three biomarkers. FC and CRP tended to correlate more strongly with S-MES and UCCIS than with M-MES and UCEIS. In the M-MES 0, 1 group, compared to CRP, FC and FIT showed stronger correlations with S-MES and UCCIS. Conversely, in the M-MES 2, 3 group, only CRP was significantly correlated with each descriptor. CRP more strongly reflects colon-wide mucosal inflammation than FC and allows reliable assessment of inflammation throughout the colon in active UC.

Prostaglandin E-major urinary metabolite (PGE-MUM) and C-reactive protein (CRP) are useful biomarkers in patients with ulcerative colitis. However, whether changes in endoscopic scores over time are reflected in the values of these biomarkers has not been verified. This prospective observational study aimed to assess the relationship between changes in biomarker levels and endoscopic scores in patients with ulcerative colitis. A total of 100 colonoscopy intervals of patients with ulcerative colitis were enrolled. The relationship between variations in the Mayo endoscopic subscore over time and the accompanying changes in biomarker values were investigated. PGE-MUM levels showed a significant rise in the increased endoscopic score group (P = 0.007) and a decrease with reduced endoscopic score group (P = 0.023). CRP levels showed a significant decline with lower endoscopic values (P

Cytomegalovirus (CMV) reactivation in the colon is common in patients with severe ulcerative colitis (UC). Ganciclovir (GCV) resistance conferring CMV UL97 gene mutations have been reported in recent years. However, the prevalence of UL97 gene mutations in GCV-naive CMV infection in the colon remains unknown. We investigated the prevalence of CMV UL97 gene mutations in patients with colonic CMV infection associated with or without UC. Twenty-two GCV-naive patients with colonic CMV infection, 15 with UC and 7 with other diseases, were enrolled. Frozen biopsy samples or formalin-fixed paraffin-embedded samples were used for nested polymerase chain reaction (PCR) amplification of the UL97 gene. Sanger DNA sequencing was performed. UL97 mutations were frequently detected in codons T75A (95.5%), Q126L (86.4%), and D605E (86.4%), and less frequently (

Backgrounds/Aims: Vonoprazan (VPZ) is the first clinically available potassium competitive acid blocker. This class of agents provides faster and more potent acid inhibition than proton pump inhibitors. Most strains of Helicobacter pylori are sensitive to amoxicillin. We hypothesized that dual therapy with VPZ and amoxicillin would provide the sufficient eradication rate for H. pylori infection. To evaluate this, we compared the eradication rate by the dual VPZ/amoxicillin therapy with that by the standard triple VPZ/amoxicillin/clarithromycin therapy. Methods: Non-inferiority of the eradication rate of H. pylori by the dual therapy with VPZ 20 mg twice daily (bid) and amoxicillin 500 mg 3 times daily (tid) for 1 week to that by the triple therapy with VPZ 20 mg bid, amoxicillin 750 mg bid and clarithromycin 200 mg bid for 1 week was retrospectively studied. Propensity score matching was performed to improve comparability between 2 regimen groups. Successful eradication was diagnosed using the [13C]-urea breath test at 1–2 months after the end of eradication therapy. Results: The intention-to-treat analysis demonstrated that the eradication rate by the dual therapy (92.9%; 95% CI 82.7–98.0%, 52/56) was not inferior to that of the triple therapy (91.9%; 95% CI 80.4–97.0%, 51/56; OR 1.275, 95% CI 0.324–5.017%, p = 0.728). There were no statistically significant differences in incidences of adverse events between 2 regimens. Conclusion: VPZ-based dual therapy (VPZ 20 mg bid and amoxicillin 500 mg tid for 1 week) provides an acceptable eradication rate of H. pylori infection without the need for second antimicrobial agents, such as clarithromycin.

AIM To examine whether second generation of colon capsule endoscopy (CCE-2) is acceptable for assessing the severity of mucosal inflammation and evaluating mucosal healing using CCE-2 is able to predict outcome in ulcerative colitis (UC) patients, especially in clinical remission. METHODS A total of 30 consecutive UC patients in clinical remission were enrolled to undergo CCE-2. Clinical remission was defined as clinical activity index (CAI) ≤ 4 according to Rachmilewitz index. The rate of total colon observation and colon cleansing level were evaluated. Severity of mucosal inflammation in UC was assessed according to the Mayo endoscopic subscore (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Relapse-free survival was assessed. Acceptability of CCE-2 was assessed using a questionnaire survey. RESULTS The rate of total colon observation within its battery life was 93.3%. The proportion of “excellent” plus “good” cleansing level was 73.3%. The rate of mucosal healing (MES 0, 1) assessed by CCE-2 was 77.0%. The relapse-free survival rate was significantly higher in MES 0, 1 than in MES 2, 3 (P = 0.0435), and in UCEIS 0-3 than in UCEIS 4-8 (P = 0.0211), whereas there was no significant difference between CAI 0 and CAI 1-4 groups. A questionnaire survey revealed an overall acceptability of CCE. CONCLUSION CCE-2 is acceptable for assessing the severity of mucosal inflammation in UC patients, especially in clinical remission. Evaluating mucosal healing using CCE-2 was able to predict outcome.

// Takuma Kagami 1 , Mihoko Yamade 1 , Takahiro Suzuki 1 , Takahiro Uotani 1 , Shinya Tani 2 , Yasushi Hamaya 1 , Moriya Iwaizumi 3 , Satoshi Osawa 2 , Ken Sugimoto 1 , Satoshi Baba 4 , Haruhiko Sugimura 5 , Hiroaki Miyajima 1 and Takahisa Furuta 6 1 First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan 2 Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan 3 Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan 4 Department of Diagnostic Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan 5 Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan 6 Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan Correspondence to: Takuma Kagami, email: t.kagami@hama-med.ac.jp Keywords: cancer stem-like cell; CD44v8-10; esophageal cancer; chemoradiotherapy; sulfasalazine Received: July 09, 2018 Accepted: September 13, 2018 Published: October 09, 2018 ABSTRACT Background: Strong reactive oxygen species (ROS) suppression in cancer stem-like cell components in various solid tumors is associated with therapeutic resistance. In this study, we investigated the influence of CD44v8-10 expression on the overall survival of esophageal squamous cell carcinoma (E-SCC) patients after definitive chemoradiotherapy (dCRT) and on radio-sensitivities of E-SCC cell lines treated with or without sulfasalazine, a CD44v8-10-xCT-GSH axis inhibitor. Methods: Seventy-three patients with E-SCC who received dCRT were examined retrospectively. CD44v8-10 expression was analyzed immunohistochemically using paraffin-blocked pre-dCRT biopsy specimens obtained by esophagoscopy and was expressed as a histo-score (H-score). The relationship between the H-score and overall survival was analyzed. From human E-SCC cell lines (T.T, T.Tn, or Kyse-3650), we collected CD44v8-10 High and CD44v8-10 Low subpopulations using a cell sorter. Water-soluble tetrazolium salt-8 (WST), glutathione-SH (GSH) and ROS assays were performed to compare the effect of sulfasalazine on the radio-sensitivities of these subpopulations in T.Tn and Kyse-3650. Results: High CD44v8-10 expression was independently associated with poor prognosis in E-SCC patients treated with dCRT (hazard ratio = 2.906, 95% CI = 1.277–6.611, p = 0.011). In CD44v8-10 High cells of each cell line, sulfasalazine decreased cellular GSH levels, resulting in increased radiation-induced ROS and reduced cell viability. In contrast, sulfasalazine had no significant effects in CD44v8-10 Low cells. Conclusion: High CD44v8-10 expression was an independent prognostic factor in E-SCC patients treated with dCRT. CD44v8-10-xCT-GSH axis inhibition sensitized CD44v8-10 High E-SCC cells to ROS-inducing treatments such as radiotherapy. Targeting CD44v8-10-xCT-GSH axis may improve the prognosis of post-dCRT E-SCC patients.

The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) was recently reported as a new scoring system to evaluate the mucosal lesions of patients with Crohn's disease (CD). We investigated whether CECDAI is useful for assessing the necessity of early additional treatment in patients with CD in clinical remission. Twenty-one patients with small intestinal CD in clinical remission underwent capsule endoscopy (CE). The CECDAI and Lewis score (LS) were used to evaluate the intestinal lesions. We analyzed the correlations between several biomarkers and CECDAI or LS and examined the changes in therapeutic regimens based on the CECDAI. CE identified intestinal abnormalities in most CD patients in clinical remission: 81.0% and 85.7%, as assessed using CECDAI and LS, respectively. A significant positive correlation was observed between the CDAI and LS (P = .025), as well as between CDAI and CECDAI (P = .014) in these cases. Compared to LS, CECDAI scores were more evenly distributed. No significant correlations were observed between endoscopic scores and serum markers, including CRP, hemoglobin, and albumin levels. Additional treatment was performed significantly more often in patients with moderate-severe disease activity (CECDAI ≥5.8) (P = .012) than in those with normal (CECDAI

INTRODUCTION: Prostaglandin E-major urinary metabolite (PGE-MUM) is a novel biomarker reflecting endoscopic activity in ulcerative colitis (UC). However, there are no studies investigating the efficacy of PGE-MUM as a biomarker for predicting relapse. We investigated whether PGE-MUM can predict clinical relapse of UC. METHODS: The measurement of PGE-MUM and endoscopic evaluation were performed in 70 patients with UC in clinical remission. The optimal cutoff values predicting relapse and relapse-free rate were analyzed. RESULTS: Sixteen patients (22.9%) relapsed during the 12-month follow-up. The median PGE-MUM value of relapsed patients at entry was significantly higher than that of patients in clinical remission (P = 0.008). The cutoff value of PGE-MUM predicting future relapse was 25.2 μg/g Cr by receiver-operating characteristic (ROC) analysis, and the area under the ROC curve was 0.721 (95% confidence interval: 0.556–0.886). The relapse-free rate of patients with PGE-MUM ≥25.2 μg/g Cr was significantly lower than that in patients with PGE-MUM

Background The serum N-terminal telopeptide of type I collagen (NTx) is significantly higher in patients with Crohn disease (CD) than in healthy individuals and patients with ulcerative colitis. This study aimed to investigate whether an elevated serum NTx level is a risk predictor of osteoporosis in patients with CD. Methods Based on whether the femoral Z-score decreased over a 2-year period, 41 CD patients were divided into the ΔZ-score Results Although there was no correlation between the mean CDAI and the ΔZ-score, the mean serum NTx and albumin levels were significantly correlated with the ΔZ-score (P Conclusions These observations indicated that an elevated serum NTx could be a useful marker for predicting a decrease in the femoral bone mineral density in CD patients. Anti-TNF-α therapy maintained an elevated serum NTx level, suggesting that treatment with anti-TNF-α may help control increased bone resorption in CD patients.

Although the Crohn's Disease Activity Index (CDAI) is often used to evaluate the disease activity in Crohn's disease (CD), the number of liquid or soft stools cannot be precisely evaluated, and thus accurate scores cannot be calculated, in patients with enterostomy. Therefore, we created the modified CDAI (mCDAI), without the defecation frequency item from the CDAI, and examined its usefulness.Study participants comprised 9 patients with CD with enterostomy and 20 patients with CD without enterostomy. Correlations between the mCDAI and serum albumin (Alb) levels or C-reactive protein (CRP) levels were examined using regression analysis. Additionally, regression analyses were conducted in patients with CD without enterostomy to determine the Alb and CRP levels corresponding to the CDAI at its cutoff value for remission status (150). The obtained values were applied to the mCDAI regression equations to determine the equivalent mCDAI cutoff value.mCDAI and Alb levels were significantly negatively correlated (P

Background and study aims We developed a novel “four-position method” for facilitating endoscopy of the upper gastrointestinal tract, and this study aimed to verify its usefulness for beginner endoscopists.Methods Medical students (n = 121) were divided into three groups. A simulator subsequently was used to perform endoscopy. Group A was taught how to hold the endoscope and move the dial; Group B was taught the “four-position method”; and Group C, in addition to being taught the “four-position method,” was permitted to use an endoscope before introduction to the simulator. In each group, the transit time to various parts of the upper digestive tract was recorded in addition to the time to grasp a clip in the stomach with the forceps. We also surveyed the groups with respect to their impression of the difficulty level of endoscopic operation before and after instructions.Results Transit time to the cardia was no different among the groups; however, with regard to other targets, Group C reached the sites significantly more quickly than did Groups A and B. Time to clip grasping was significantly shorter in Groups B and C than in Group A. Regarding the impression of the difficulty level, significantly more students in Groups B and C compared to Group A felt that endoscopy was easier after instructions.Conclusion Learning the “four-position method” made it possible to achieve stable endoscopic manipulation at an early stage and improve subsequent endoscopic procedures.

Background Serum pepsinogen (PG) levels correlate with the degree of gastric mucosal inflammation and atrophy, which correlate with gastric cancer risk, in patients infected with Helicobacter pylori (H. pylori). Serum PG levels change after eradication of H. pylori, but it is not known if there are corresponding changes in the gastric mucosa. We examined whether the degree of gastric atrophy correlated with PG levels measured after eradication of H. pylori. Methods We retrospectively examined the relationship between gastric atrophy and serum levels of PG I, PG II and PG I/II ratios measured after eradication of H. pylori. The degree of gastric mucosal atrophy before H. pylori eradication was scored (0, 1, 2) according to the Kyoto classification of gastritis. Results A total of 430 treated patients were enrolled. Serum levels of PG I (ρ = − 0.362 and P H. pylori eradication can be used to estimate the degree of gastric mucosal atrophy and are useful for selecting individuals with a high risk of gastric cancer after H. pylori eradication.

Decreased trough level of infliximab (TLI) is associated with diminished efficacy in patients with Crohn disease (CD). We examined whether TLI at 14 weeks subsequent to the start of infliximab (IFX) treatment would impact long-term clinical course. Serum IFX levels and antibodies to IFX (ATI) at 14 and 54 weeks after IFX administration were measured in 12 patients with mild to moderate CD. We examined patient background, clinical severity, blood test values, and the relationship between ATI and TLI up to 108 weeks. We compared the group with TLI 3 μg/mL (TLI(14) ≥ 3 group). Patients in the TLI(14) ≥ 3 group were significantly more likely to use immunomodulators before IFX treatment induction (P = .01). At 54 weeks, 2 cases of ATI production were observed in the TLI(14)

The efficacy of sustained-release preparations of mesalazine as a remission maintenance treatment for Crohn's disease remains to be established. We aimed to examine the changes in compliance rate and clinical data 2 years after switching from mesalazine tablet to granule formulation at our facility among patients with Crohn's disease in remission. We investigated the rate of continuous treatment of mesalazine granules and examined the changes in Crohn’s Disease Activity Index (CDAI) and serum C-reactive protein (CRP), albumin, and hemoglobin (Hb) levels 2 years after the switch. Compliance rate (continuous treatment vs. additional treatment) and continuous treatment rate [good (rate of ≥ 70%) vs. poor (rate P = 0.023) and Hb levels increased significantly (P = 0.002). No change in the compliance rate was found. Our results suggest that mesalazine granule formulation may have a remission maintenance effect that is superior to that of mesalazine tablets.

Purpose: The effects of ulcerative colitis (UC) duration on biomarker accuracy are unknown. We investigated the effects of UC duration on the predictive accuracy of biomarkers including immunochemical fecal occult blood test (FOBT, also known as FIT), prostaglandin E-major urinary metabolite (PGE-MUM), and C-reactive protein (CRP).Methods: We divided 133 samples into groups based on disease duration. Clinical and endoscopic remission was defined as Lichtiger’s clinical activity index (CAI) of ≤4, Mayo endoscopic subscore (MES) of 0, and UC endoscopic index of severity (UCEIS) of ≤1.Results: FIT results were significantly correlated with all activity scores when the disease duration was

BACKGROUND Dysphagia is a growing health problem in aging societies. An observational cohort study targeting community-dwelling populations revealed that 16% of elderly subjects present with dysphagia. There is a need in elderly communities for systematic dysphagia assessment. OBJECTIVE This study aimed to verify whether laryngeal elevation in the pharyngeal phase could be measured from the body surface using thin and flexible stretch sensors. METHODS Thirty-two elderly subjects (17 males, 15 females; mean age ± SD: 89.2 ± 6.2 years) with suspected dysphagia underwent a swallowing contrast examination in which seven stretch sensors were attached to the front of the neck. The elongation of the sensors was measured and compared to the laryngeal elevation time values obtained using videofluorography. The sensor signal detected the laryngeal elevation start time, conclusion of the descent of the larynx, and the laryngeal elevation time. The respective laryngeal elevation times obtained using videofluorography and using the sensor were compared using the Bland-Altman method. RESULTS The laryngeal elevation time was 1.34 ± 0.46 s with the stretch sensor and 1.49 ± 0.56 s with videofluorography. There was a significant positive correlation between the duration obtained by both methods (r = .69, P

Background Prostaglandin E-major urinary metabolite (PGE-MUM) may be a novel biomarker for evaluating disease activity in ulcerative colitis (UC). We compared its usefulness to that of the fecal immunochemical occult blood test (FIT). Methods PGE-MUM and FIT measurements were performed of 92 urinary and fecal samples obtained from 60 patients with UC. Endoscopic activity was determined by Mayo endoscopic subscore (eMayo) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score. Results PGE-MUM levels and FIT results showed a significant correlation with respect to eMayo (P P P = 0.012). Both biomarkers were significantly correlated with the UCEIS score (P P P = 0.012). PGE-MUM and FIT were significantly correlated with eMayo in the group with a disease duration P = 0.041 and P P = 0.012), FIT was not correlated with eMayo (P = 0.101). Conclusions PGE-MUM is useful as a biomarker as FIT for evaluating the endoscopic activity, particularly in long-term affected patients with UC.

Background Although autoimmune gastritis (AIG) is generally considered relatively rare, we frequently encounter AIG among patients at to our hospital who have experienced at least two episodes of Helicobacter pylori eradication failure. Aims We investigated the incidence of AIG in consecutive patients who consulted our department for H. pylori eradication with reference to eradication history. Methods A total of 404 consecutive patients who visited the H. pylori-specific out-patient unit of our hospital from June 2015 to June 2017 were enrolled. Of these, 137 were treatment-naive, 47 had failed treatment once (single failure), and 220 had failed treatment twice or more (multiple failures) by 13 C-UBT. Gastroscopy was performed in all patients. Culture tests of gastric mucosal samples were performed for H. pylori and other bacteria positive for urease activity. Anti-parietal cell antibody (APCA) was measured. Patients with severe atrophy in the gastric corpus and positivity for APCA were diagnosed as having AIG. Results A total of 43 patients were diagnosed as having AIG, of whom two were treatment-naive (1.5%, 2/137), 1 failed eradication once (2.1% 1/47), and 40 failed treatment at least twice (18.2%, 40/220). The incidence of AIG was significantly higher in the multiple failure group than in the single failure or treatment-naive groups. Urease-positive bacteria, such as Klebsiella pneumoniae and alpha-streptococcus, were identified in 33 of the 35 AIG patients who underwent culture testing. Conclusion AIG patients were often misdiagnosed as refractory to eradication therapy, probably because achlorhydria in AIG might allow urease-positive bacteria other than H. pylori to colonise the stomach, causing positive 13 C-UBT results.

// Satoshi Suzuki 1 , Moriya Iwaizumi 1 , Hidetaka Yamada 2 , Tomohiro Sugiyama 1 , Yasushi Hamaya 1 , Takahisa Furuta 3 , Shigeru Kanaoka 4 , Haruhiko Sugimura 2, 7 , Hiroaki Miyajima 1 , Satoshi Osawa 5 , John M. Carethers 6 and Ken Sugimoto 1 1 First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan 2 Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan 3 Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan 4 Department of Gastroenterology, Hamamatsu Medical Center, Hamamatsu, Japan 5 Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan 6 Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA 7 International Mass Imaging Center, Hamamatsu University School of Medicine, Hamamatsu, Japan Correspondence to: Moriya Iwaizumi, email: iwaizumi@hama-med.ac.jp Keywords: colorectal cancer; trifluridine; MBD4; microsatellite instability; frameshift mutation Received: January 23, 2017 Accepted: October 02, 2017 Published: November 15, 2017 ABSTRACT Backgrounds: Trifluridine is an active antitumor component of TAS-102 that resembles 5-fluorouracil. Although patients with advanced colorectal cancer (CRC) exhibiting a mismatch repair (MMR) deficiency reportedly do not benefit from 5-fluorouracil-based chemotherapy and we previously reported that truncated methyl-CpG binding domain protein 4 (MBD4) enhances 5-fluorouracil cytotoxicity in MMR-deficient CRC cells, little is known regarding the effect of MMR deficiency on trifluridine cytotoxicity in CRC. Aim: We investigated whether trifluridine induces cytotoxicity in a DNA MMR-dependent manner and evaluated how truncated MBD4 alters trifluridine cytotoxicity. Methods: We utilized the human CRC cell lines HCT116 (hMLH1-deficient cells) and HCT116+ch3 (hMLH1-restored cells) and compared their sensitivities to trifluridine. And we established 5-fluorouracil-refractory hMLH1-deficient cells and analyzed trifluridine cytotoxicity. Finally, we established truncated MBD4 overexpressed CRC cell lines, and compared trifluridine sensitivity. Results: The sensitivities of HCT116 and HCT116+ch3 to trifluridine were comparable. 5-Fluorouracil-refractory hMLH1-deficient cells treated with trifluridine showed an equal or greater sensitivity than non-5-fluorouracil-refractory cells. Moreover, MBD4tru cells were more sensitive than the control cells to trifluridine. Conclusions: Trifluridine induces cytotoxicity independently of the DNA MMR status as well as under 5-fluorouracil-refractory conditions, and the MBD4 frameshift mutation enhances trifluridine cytotoxicity.

Cervical inlet patch (CIP), also referred to as esophageal heterotopic gastric mucosa, is regarded as the residue of columnar epithelium of the embryonic esophagus. Narrow band imaging increases the detection rate of CIP. Herein, we present a 55-year-old man with symptomatic circumferential inlet patch. He exhibited globus and dysphagia, and esophagogastroduodenoscopy found cir-cumferential CIP, where im-munohistochemistry revealed the existence of pro-ton pumps (H+, K+-ATPase). His throat symptoms were relieved by acid suppressive therapy with pump inhibitors. This case indicated that CIP should be considered as a differential diagnosis for the cause of globus symptoms in rare cases.

Drug-drug interaction between antiacid and antiplatelet agents has not been fully elucidated. Vonoprazan, a new potassium competitive acid blocker, has been available in Japan. CYP2C19 and CYP3A4 are involved in the metabolism of clopidogrel, prasugrel, esomeprazole, and vonoprazan. Using a P2Y12 assay, we compared the effects of vonoprazan and esomeprazole on the antiplatelet functions of clopidogrel or prasugrel in 31 healthy Japanese volunteers (14 CYP2C19 homo-extensive (homo-EMs), nine hetero-extensive (hetero-EMs), and eight poor metabolizers (PMs)). Vonoprazan decreased the median inhibition of platelet aggregation (IPA) values of clopidogrel and prasugrel more potently than esomeprazole (P < 0.001 for clopidogrel and P = 0.011 for prasugrel). The same tendencies were observed when stratified by CYP2C19 genotype groups (P = 0.004 in homo-EMs, 0.033 in hetero-EMs, and 0.043 in PMs). Vonoprazan attenuated the antiplatelet function of clopidogrel more potently than esomeprazole. Esomeprazole did not affect that of prasugrel irrespective of CYP2C19 genotype.

We present a case of ulcerative colitis improved through benralizumab, which binds to the eosinophil IL-5 receptor and the Fcy receptor on natural killer cells, inducing antibody-dependent cell-mediated cytotoxicity, causing apoptosis, and directly removing eosinophils, in treating comorbid refractory bronchial asthma.

Background: Several studies have reported that cognitive impairment often occurred in bronchial asthma and chronic obstructive pulmonary disease (COPD). However, the relationship between cognitive function and ability to learn inhaler technique is unclear. Our aim was to investigate the effect of cognitive function on inhaler technique training. Methods: The study involved 75 inpatients (65≥ years) with asthma or COPD, who had received inhaler technique training by physical and occupational therapists. Data on Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), device type, training times, and inhaler technique were retrospectively collected through the clinical records. Mann-Whitney U test, Fisher’s exact test, and receiver operating characteristic curve analysis were used in statistical analysis. Results: Patients were divided into proper (n=20, 26.7%) and improper (n=55, 73.3%) use groups. Both MMSE and FAB scores were significantly lower in improper use group (all p Conclusions: Results suggest that cognitive dysfunction affect acquisition of inhaler technique. Notably, FAB result suggests the association between the reduced frontal lobe function and learning the proper inhaler technique. MMSE and FAB may help to identify potential patients who present incorrect use of the inhaler devices.

Background Abdominal compartment syndrome (ACS) is associated with mortality in patients with critical illness such as severe acute pancreatitis, but it remains unclear whether decompressive laparotomy for ACS can improve the prognosis of patients. Case presentation A woman in her 60s visited our hospital because of upper abdominal pain. On the basis of her laboratory data and abdominal contrast-enhanced computed tomography findings, acute gallstone pancreatitis was diagnosed. She underwent endoscopic sphincterotomy for the removal of the common bile duct stone. Then, a drainage tube was placed in the bile duct. However, on the 5th hospital day, her intra-abdominal pressure increased to 22 mmHg and renal dysfunction was observed, which led to the diagnosis of ACS. As intensive medical treatments did not improve her ACS, she underwent decompressive laparotomy on the 9th hospital day. Postoperatively, her laboratory data and intravesical pressure improved, and she was discharged from the hospital after abdominal closure, continuous drainage, and antibiotic therapy. Conclusion As the effectiveness of decompressive laparotomy for ACS has not been established, this treatment indication remains controversial. Decompressive laparotomy is considered useful for the management of ACS, if it is performed at an appropriate time, as in the present case.

Background: The new curcumin derivative, Theracurmin® has a 27-fold higher absorption rate than the natural curcumin powder. Its pharmacologic actions include inhibition of the nuclear factor NF-κB, known to mediate the expression of inflammatory cytokines. We were interested to evaluate efficacy of Theracurmin® in patients with Crohn's disease (CD). Methods: Theracurmin® (360mg/day, n=20) or placebo (n=10) was administered to patients with active mild to moderate CD for 12 weeks. Efficacy assessment included clinical and endoscopic remission, healing of anal lesions, and blood levels of inflammatory markers. Findings: In the Theracurmin® group, significant reduction of clinical disease activity was observed at 12 weeks relative to week 0 (P=0.005). The clinical remission rates were 35%, 40%, and 40% at weeks 4, 8, and 12, respectively, significantly higher than in the placebo group (P=0.033, P=0.020, and P=0.020). Further, in the Theracurmin® group, significant healing of anal lesions (P=0.017) and endoscopic CD severity (P=0.032) were observed at weeks 8 and 12, respectively, relative to week 0. However, the mucosal healing rate at week 12 in the Theracurmin® group was 15.0%. No serious adverse event was observed in either group throughout our observation time. Interpretation: In this study, Theracurmin® in patients with active mild to moderate CD produced significant clinical and endoscopic efficacy together with a favourable safety profile. Trial registration: UMIN000015770 Funding Statement: Theracurmin® was a gift from Theravalues Corporation, Tokyo, Japan. The authors received no external funding for this study. Declaration of Interests: All authors acknowledge having no conflict of interest in connection with the publication of this manuscript. Ethics Approval Statement: At each institution, the study protocol was reviewed and approved by the committee on the Ethics of Clinical Trials involving human subjects. Further, the trial was conducted by adherence to the principles of Good Clinical Practice (GCP) and the ethical standards laid down in the 1964 Helsinki Declaration and its subsequent amendments. Similarly, informed consent was obtained from all patients after explaining the purpose of the study and the nature of the procedures involved.

A phase II study of second-generation photodynamic therapy (PDT) using talaporfin sodium has shown excellent treatment results for esophageal cancer with local failure after chemoradiotherapy (CRT) or radiotherapy (RT). However, only a few studies have reported this therapy in clinical practice. This study aimed to confirm the efficacy and safety of salvage PDT using talaporfin sodium for esophageal cancer in various clinical situations. Twelve patients with esophageal cancer with local failure after definitive CRT or RT who underwent PDT using talaporfin sodium were enrolled from April 2016 to January 2020. Overall, 10 patients (83.3%) achieved a local complete response. No skin phototoxicity was observed, but esophageal stricture occurred in five patients (41.7%). Esophageal stricture was improved with endoscopic balloon dilation in all patients, and subsequent analysis found no significant factors causing esophageal stricture after PDT. Two patients with synchronous tumors were successfully rescued by combination therapy with endoscopic submucosal dissection. Two patients with carcinoma in situ of larger than 1/2 circumference were rescued by repeated PDT. The 2-year overall survival was 80.0% (95% confidence interval 0.409&ndash, 0.946). PDT using talaporfin sodium was an effective and safe salvage treatment for esophageal cancer with local failure after CRT or RT in various clinical situations.

Objective To date, no randomised trials have compared the efficacy of vonoprazan and amoxicillin dual therapy with other standard regimens for Helicobacter pylori treatment. This study aimed to investigate the efficacy of the 7-day vonoprazan and low-dose amoxicillin dual therapy as a first-line H. pylori treatment, and compared this with vonoprazan-based triple therapy. Design This prospective, randomised clinical trial was performed at seven Japanese institutions. Patients with H. pylori–positive culture test and naive to treatment were randomly assigned in a 1:1 ratio to either VA-dual therapy (vonoprazan 20 mg+amoxicillin 750 mg twice/day) or VAC-triple therapy (vonoprazan 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day) for 7 days, with stratification by age, sex, H. pylori antimicrobial resistance and institution. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment. Results Between October 2018 and June 2019, 629 subjects were screened and 335 were randomised. The eradication rates of VA-dual and VAC-triple therapies were 84.5% and 89.2% (p=0.203) by intention-to-treat analysis, respectively, and 87.1% and 90.2% (p=0.372) by per-protocol analysis, respectively. VA-dual was non-inferior to VAC-triple in the per-protocol analysis. The eradication rates in strains resistant to clarithromycin for VA-dual were significantly higher than those for VAC-triple (92.3% vs 76.2%; p=0.048). The incidence of adverse events was equal between groups. Conclusion The 7-day vonoprazan and low-dose amoxicillin dual therapy provided acceptable H. pylori eradication rates and a similar effect to vonoprazan-based triple therapy in regions with high clarithromycin resistance. Trial registration number UMIN000034140.