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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.

Eosinophilic infiltration is sometimes observed histologically in ulcerative colitis (UC), but the effect of the degree of infiltration on the treatment course for UC is not completely understood. We investigated whether short-term steroid administration in UC patients refractory to maintenance therapy, with high eosinophilic infiltration in the colonic mucosa, contributed to the clinical and endoscopic improvement. Ten patients with endoscopically active and pathologically high eosinophilic infiltration, based on pathological examination using endoscopic biopsy, were examined for the clinical background when starting steroid treatment. The clinical and endoscopic improvement before and after steroid use were assessed prospectively. The average initial steroid dosage and duration of use were 21.0 mg and 102.7 days, respectively. The mean values before and after steroid use of the clinical activity index, the Mayo endoscopic subscore, and the UC endoscopic index of severity were 2.4 and 1.0, 1.8 and 0.7, and 3.9 and 1.1, respectively. All scores improved significantly after steroid use (P = .042, P = .002, P = .002, respectively). Steroids were discontinued in all patients; no patients required steroid re-administration. There may be cases of UC with eosinophilic infiltration into the colonic mucosa and resistance to maintenance treatment, suggesting that short-term steroid administration may contribute to clinical and endoscopic improvements.

Background Biomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT. Methods One hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0–5, 6–13, and 14–38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES. Results In the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0–5, 6–13, and 14–38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0–5 year disease-duration group showed particularly higher values than those for the other two groups. Conclusions Similar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.

Backgrounds: Compared to proton pump inhibitors, vonoprazan exerts a greater inhibitory effect on gastric acid secretion and is useful for treating acid-related diseases, such as gastro-esophageal reflux disease. However, there is a problem that vonoprazan causes hypergastrinemia, which confers a risk of carcinoid tumor. A previous report demonstrated that pirenzepine, an M1 muscarinic receptor antagonist, enhances the acid inhibitory effects while suppressing hypergastrinemia induced by omeprazole. Here, we examined whether pirenzepine enhances the gastric acid inhibitory effects of vonoprazan without further increasing serum gastrin levels.Methods: Eleven healthy volunteers were subjected to 24-hour intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: pirenzepine 75mg alone, vonoprazan 10mg alone, and vonoprazan 10mg plus pirenzepine 75mg administered in a randomized crossover fashion.Results: Median pH 4 holding time ratios (range) achieved with pirenzepine 75mg, vonoprazan 10mg and vonoprazan 10mg plus pirenzepine 75mg were 6.9% (2.4–32.8%), 88.4% (54.6–100%), and 84.2% (40.3–100%), respectively. Respective serum gastrin levels were 79 (75–210) pg/ml, 310 (110–870) pg/ml, and 170 (140–930) pg/ml. In cases with hypergastrinemia (gastrin≥200pg/ml) induced by vonoprazan 10mg alone, concomitant treatment with pirenzepine significantly reduced serum gastrin levels from 370pg/ml to 180pg/ml (P=0.028).Conclusion: Although pirenzepine does not enhance acid inhibition, it does improve hypergastrinemia induced by vonoprazan to some extent.

Background Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most serious complications of ERCP. Various procedures can reduce the incidence of PEP, such as wire-guided cannulation, prophylactic pancreatic stent placement, and pretreatment anal insertion of NSAIDs. Recently, iso-osmolar contrast media (IOCM) have been used for ERCP in several hospitals to reduce the risk of PEP in Japan. However, the effect of IOCM is uncertain because few reports have examined IOCM in relation to PEP. Aim This study aimed to investigate the relationship between contrast media used and the incidence of PEP. Methods This retrospective study included all qualifying patients who had undergone ERCP at Hamamatsu University Hospital between January 2012 and January 2020. This study examined whether there was a difference in the onset of PEP between patients administered IOCM and high osmolar contrast medium (HOCM). Propensity score matching was used to analyze patient characteristics and ERCP procedures. Amidotrizoic acid was used as HOCM and iodixanol as IOCM. Results ERCP was performed on 458 patients, and 830 procedures were conducted. After propensity score matching, 162 patients from the amidotrizoic acid group and 162 patients from the iodixanol group were selected. The incidence of PEP was 10.5% (17) in the amidotrizoic acid group and 9.3% (15) in the iodixanol group (P = 0.71). Changes in serum amylase levels post- and pre-ERCP were 240.6 ± 573.8 U/L and 142.7 ± 382.1 U/L in the amidotrizoic acid and iodixanol groups, respectively (P = 0.072). Conclusion Iodixanol had no prophylactic effect on PEP and clinical outcomes.

AimsAlthough frameshift variants in the microsatellite area of shugoshin 1 (SGO1) have been reported in the context of microsatellite instability-high (MSI-H)/deficient mismatch repair gastrointestinal cancer, most have been evaluated only in early stage I–III patients, and only two of its five microsatellite regions have been evaluated. Therefore, we investigated the frequency and MSI status of microsatellite frameshift variants in gastric cancer cases, including stage IV.MethodsIn a total of 55 cases, 30 gastric cancer resection and 25 non-resection cases, DNA was extracted from both tumour and normal parts and PCR was performed. The variant was confirmed by TA cloning, and MSI was evaluated using GeneMapper software.ResultsA frameshift variant of c.973delA was observed in 16 of the 45 evaluable cases. Its frequency was 35.6%. Of the 25 cases that could be assessed for MSI status, two cases of MSI-H were associated with the c.973delA SGO1 variant. However, c.973delA SGO1 variant was also observed in four cases of microsatellite stable.ConclusionOur study shows that SGO1 frameshift variants are not always associated with MSI status.

Vonoprazan (VPZ) inhibits gastric acid secretion more potently than proton pump inhibitors. Recently, attention has been focused on the dual therapy with VPZ and amoxicillin (AMOX) for the eradication of H. pylori. The dual VPZ/AMOX therapy attains the sufficient eradication rate with lowering the risk of adverse events in comparison with the triple therapy and quadruple therapy. Therefore, the dual VPZ/AMOX therapy is considered a useful eradication regimen for H. pylori infection.

Eosinophilic infiltration is sometimes observed histologically in ulcerative colitis (UC), but the effect of the degree of infiltration on the treatment course for UC is not completely studied. We investigated whether short-term steroid administration in UC patients refractory to maintenance therapy, with high eosinophilic infiltration in the colonic mucosa, contributed to clinical and endoscopic improvement. Ten patients with endoscopically active and pathologically high eosinophilic infiltration, based on pathological examination using endoscopic biopsy, were examined for clinical background when starting steroid treatment; clinical and endoscopic improvement before and after steroid use were assessed prospectively. The average initial steroid dosage and duration of use were 21.0 mg and 102.7 days, respectively. The mean values before and after steroid use of clinical activity index, Mayo endoscopic subscore, and UC endoscopic index of severity were 2.4 and 1.0, 1.8 and 0.7, and 3.9 and 1.1, respectively. All these scores improved significantly after steroid use (P=0.04, P

Vonoprazan, a potassium-competitive acid blocker, inhibits gastric acid secretion and attenuates the antiplatelet function of clopidogrel more potently than esomeprazole. We investigated whether alternate-day dosing of vonoprazan might avoid this interaction with clopidogrel while providing sufficient gastric acid inhibition.Following 24 h of pH monitoring (control regimen), 12 healthy volunteers received three regimens (clopidogrel-only regimen: clopidogrel 75 mg daily [q.d.]; vonoprazan alternate-day regimen: vonoprazan 10 mg every other day [q.o.d.] + clopidogrel 75 mg q.d.; vonoprazan daily regimen: vonoprazan 10 mg q.d. + clopidogrel 75 mg q.d.) for 14 days in a randomized open-label crossover manner. Intragastric pH monitoring was performed for 24 h on day 13 in the clopidogrel-only and vonoprazan q.d. regimens and for 48 h on days 13 and 14 in the vonoprazan q.o.d. regimen. Serum gastrin and inhibition of platelet aggregation (IPA) were measured before the commencement of pH monitoring in each regimen.Twelve volunteers completed the study. Equivalent median IPA values in the q.o.d. and q.d. regimens were measured (21.8% and 25%, respectively) and were significantly lower than that with the clopidogrel-only regimen (40.8%). The median pH4 holding time ratio for the vonoprazan q.o.d. regimen (49.7%) was superior to that of the clopidogrel-only regimen (18.4%), but was significantly inferior to that of the vonoprazan q.d. regimen (77.0%; p 0.01).Alternate-day administration of vonoprazan could not prevent the interaction between vonoprazan and clopidogrel, and acid inhibition was inferior to that with vonoprazan daily administration. Alternate-day administration of vonoprazan thus appears to be of questionable clinical utility.

The fecal immunochemical occult blood test (FIT) and prostaglandin E-major urinary metabolite (PGE-MUM) have been reported to predict the relapse of ulcerative colitis (UC) during remission. In this study, we directly compared FIT and PGE-MUM in predicting relapse and examined the effect of disease duration on these biomarkers.Measurements of 2 biomarkers and endoscopic examination were performed in 73 patients with UC in remission. The patients were followed up for 12 months, and clinical relapse was evaluated. In addition, we divided the patients into long-term disease duration and short-term disease duration groups for analysis.Twenty-one patients (28.8%) relapsed within 12 months. FIT and PGE-MUM levels were significantly higher in the relapsed group than in the remission group. Cutoff values of FIT and PGE-MUM for predicting relapse using receiver operating characteristic analysis were 65.0 ng/mL (area under the curve [AUC]: 0.723) and 25.2 μg/g·Cr (AUC: 0.701), respectively. Patients with FIT ≥ 65.0 ng/mL and PGE-MUM ≥ 25.2 μg/g·Cr had a higher risk of clinical relapse. In the short-term disease duration group, the AUCs of FIT were larger than those of PGE-MUM using receiver operating characteristic analysis, in most instances. By contrast, the AUCs of PGE-MUM were larger than those of FIT in most cases in the long-term disease groups.FIT and PEG-MUM were highly accurate in predicting clinical relapse in UC patients with short and long disease durations in remission, respectively.

Advanced therapies for patients with mild-to-severe ulcerative colitis (UC) may result in treatment failure. We examined whether the lymphocyte-to-monocyte ratio (L/M ratio) could predict the failure of advanced therapies. This retrospective, observational, cohort study included 73 patients who were treated with advanced therapies at the Hamamatsu University School of Medicine (Shizuoka, Japan) between February 2011 and November 2020. The patients were divided into the non-failure and failure groups, and their leukocyte counts and ratios before induction were examined. Univariate and multivariate analyses were performed to identify the prognostic factors. Advanced therapies failed within 3 months in 15 (20.5%) patients. Only the L/M ratio was significantly lower in the failure group than in the non-failure group (P = 0.004). Receiver-operating characteristic (ROC) curve analysis revealed that an L/M ratio of ≤3.417 was predictive of treatment failure; the area under the curve (AUC) was 0.747 (95% CI, 0.620–0.874). Kaplan–Meier analysis revealed that the failure-free rate was significantly lower in the group with an L/M ratio of ≤3.417 than in the group with an L/M ratio of >3.417 (log-rank test P = 0.002). Cox proportional hazard regression analysis identified an L/M ratio of ≤3.417 as an independent risk factor for failure within 3 months after the induction of advanced therapies. Furthermore, ROC analysis of patients who did not receive immunomodulators also revealed that the cut-off L/M ratio was 3.417 and the AUC was 0.796 (95% CI, 0.666–0.925). In patients receiving advanced therapies for active UC, the L/M ratio can predict treatment failure within 3 months. L/M ratios could facilitate the transition from advanced therapies to subsequent treatments.

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.

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 106 patients (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 no-patency. 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.

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.

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.

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 (

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 (

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

Background: Cytomegalovirus (CMV) reactivation in the colon is common in patients with severe ulcerative colitis (UC) and in immunocompromised patients, and may be associated with poor prognosis. 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 colitis remains to date unknown. The present study aimed to investigate the prevalence of CMV UL97 gene mutations in Japanese patients with colonic CMV infection associated with or without UC.Methods: 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 of the PCR products was performed.Results: UL97 mutations were frequently detected in codons T75A (95.5%), Q126L (86.4%), and D605E (86.4%), and less frequently (Conclusions: We did not detect UL97 gene mutations associated with GCV resistance in GCV-naive patients with or without UC. In contrast, T75A, Q126L, and D605E mutations may be used as genetic markers for CMV in East Asian countries.

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.

Background: Adalimumab (ADA) trough level and anti-ADA antibody (AAA) positivity could influence mucosal healing and loss of response in patients with inflammatory bowel disease (IBD). This study aimed to clarify the correlation between ADA monitoring, including non-trough level and real-world IBD clinical outcomes.Methods: This retrospective, observational, single-center study included 19 patients with ulcerative colitis (UC) and 33 patients with Crohn’s disease (CD) treated with ADA from January 2007 to August 2018. Serum ADA and AAA levels were measured 4‒14 days after ADA administration.Results: The AAA positivity rate was 23.1% (12/52). The ADA continuity was higher in the AAA-negative group than in the AAA-positive group (P = 0.223). Receiver operating characteristic (ROC) analysis revealed that a serum AAA cut-off value of 9.2 µg/mL was associated with ADA continuity (area under the curve [AUC]: 0.767, 95% confidence interval [CI]: 0.636–0.899). The ADA level was significantly higher in the endoscopic remission group than in the non-remission group (12.4 vs. 6.4 µg/mL, P = 0.02). Based on the ROC curve analysis results of serum ADA level and endoscopic remission, the cut-off value of serum ADA level was set to 11.1 µg/mL (AUC: 0.716, 95% CI: 0.533–0.900).Conclusions: Regardless of infliximab administration history, under combined use of ADA with immunomodulators and AAA positivity, ADA continuity was significantly higher when the serum AAA level 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.

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 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.

Although frameshift variants in the microsatellite area of shugoshin 1 (In a total of 55 cases, 30 gastric cancer resection and 25 non-resection cases, DNA was extracted from both tumour and normal parts and PCR was performed. The variant was confirmed by TA cloning, and MSI was evaluated using GeneMapper software.A frameshift variant of c.973delA was observed in 16 of the 45 evaluable cases. Its frequency was 35.6%. Of the 25 cases that could be assessed for MSI status, two cases of MSI-H were associated with the c.973delAOur study shows that

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 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.

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 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 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.

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.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.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.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.

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.

Background: When administered at a standard dose, proton pump inhibitors (PPIs) do not always provide sufficient acid inhibition for all subjects, particularly in extensive metabolizers (EMs) of CYP2C19. Whether esomeprazole at a dose of 20 mg four times daily dosing (q.i.d.) can attain sufficient acid inhibition throughout 24 h in EMs remains unclear. We therefore investigated the efficacy of esomeprazole q.i.d. for acid inhibition. Methods: In a randomized cross-over design, 30 Helicobacter pylori-negative healthy young Japanese volunteers received esomeprazole at a dose of 20 mg two times a day (b.i.d.) or q.i.d. for 7 days. A pH monitoring was conducted before the trial as a control and on day 7 of both regimens. Results: Median pH values in the q.i.d. regimen were significantly higher than those with the b.i.d. regimen in EMs (b.i.d.: 5.3, q.i.d.: 6.6, p = 0.022), intermediate metabolizer (IM) (b.i.d.: 5.5, q.i.d.: 6.8, p = 0.005) and poor metabolizer (PM) (b.i.d.: 6.2, q.i.d.: 7.0, p = 0.047), respectively. Median pH with the b.i.d. regimen differed significantly by CYP2C19 genotypes (p = 0.004), but not the q.i.d. regimen (p = 0.384). Conclusion: Esomeprazole q.i.d. achieved potent acid inhibition in all Helicobacter pylori-negative subjects, irrespective of CYP2C19 genotype, which might be one of the rescue regimens for patients' refractory to PPI treatment.

Vonoprazan, a novel potassium-competitive acid blocker, elicits potent acid inhibition and hypergastrinemia at a dose of 20 mg. Its recommended maintenance dose for gastro-esophageal reflux disease is 10 mg, which is sometimes insufficient for preventing nocturnal acid breakthrough (NAB). Concomitant use of a histamine 2 receptor antagonist (H2RA) is effective for NAB. However, further acid inhibition by addition of H2RA has concern of hypergastrinemia again. Lafutidine (H2RA) is known to stimulate somatostatin release. The aim of this study is to compare the levels of acid inhibition and serum gastrin attained by addition of lafutidine to vonoprazan 10 mg with levels after a dose increase of vonoprazan from 10 to 20 mg. Thirteen healthy volunteers underwent 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg. Median pH 4 holding time ratios (range) by vonoprazan 10 mg, vonoprazan 10 mg plus lafutidine 10 mg, and vonoprazan 20 mg were 82% (47–88%), 88% (76–93%), and 99% (95–100%) while those at nighttime from 10 p.m. to 8 a.m. were 94% (29–100%), 100% (95–100%), and 100%, respectively. The incidences of NAB with vonoprazan 10 mg, vonoprazan plus lafutidine, and vonoprazan 20 mg were 38, 8, and 0%, respectively. Respective serum gastrin levels were 420 (173–508), 323 (196–521), and 504 (400–812) pg/ml. Addition of lafutidine 10 mg to vonoprazan 10 mg achieved sufficient acid inhibition, especially at nighttime, without further increase of serum gastrin levels.