Kazuhiro Morise

Dipeptidyl peptidase-4 inhibitor anagliptin facilitates restoration of dextran sulfate sodium-induced colitis

Abstract Objective. Inflammatory bowel disease (IBD) is a chronic debilitating disease associated with severe damage to the intestinal mucosa. Glucagon-like peptide-2 (GLP-2) is a potent and specific gastrointestinal growth factor. GLP-2 released from enteroendocrine cells is inactivated by dipeptidyl peptidase-4 (DPP-4). The aim of this study was to examine whether the DPP-4 inhibitor anagliptin improves experimental murine colitis. Material and methods. Male C57BL/6 mice aged 8 weeks were exposed to 1.5% dextran sulfate sodium (DSS) in drinking water for 7 days to induce experimental colitis. Anagliptin (0.1% in diet) was administrated from 2 days before the beginning of DSS to 7 days after the end of DSS. Changes in body weight and disease activity index were evaluated daily. Histological colitis severity, cellular proliferation and gene expression were determined in colonic tissues. Results. Treatment with anagliptin clearly improved body weight loss and disease activity index in the recovery phase. Histological score in the DSS + anagliptin group at day 14 was significantly lower than that in the DSS alone group. Treatment with anagliptin increased the Ki67-positive rate at days 10 and 14, and tended to increase insulin-like growth factor-1 mRNA expression in the DSS + anagliptin group. Conclusion. In this model of experimental colitis, the DPP-4 inhibitor anagliptin facilitated the restoration of mucosal damage, thereby resulting in the acceleration of healing. These findings suggest a new and novel therapeutic approach for the treatment of IBD.

Importance of appropriate pharmaceutical management in pregnant women with ulcerative colitis

BackgroundUlcerative colitis (UC) often occurs in women of childbearing age. Compared to Western countries, however, few studies have investigated the impact of UC on the progress of pregnancy in Asian populations.MethodsWe retrospectively examined 91 pregnancies in 64 patients with UC experienced at our hospital and related institutions from 1991 to 2011, focusing on the relationship between the progression of UC during pregnancy, progress of the pregnancy itself, and the treatment of UC.ResultsIn 80 of 91 pregnancies the patient had already been diagnosed with UC at the time she became pregnant, of whom 31 (38.8%) experienced exacerbation during pregnancy. Regarding severity, moderate or severe active-stage disease during pregnancy was seen in 13.7% of those who had been in remission at the onset of pregnancy versus 58.6% of those who had been in the active stage at onset (OR 8.9: 95%CI 3.0~26.4; P<0.01). The incidence of miscarriage or abortion was 9.8% in pregnancies in which UC was in remission at onset versus 31% in those in which it was in the active stage at onset (OR 4.1: 95%CI 1.2~13.9; P=0.02). Among patients, 62.5% were receiving pharmaceutical treatment at onset of pregnancy. Exacerbation during pregnancy occurred in 26.5% of the group who continued to receive the same treatment during pregnancy versus 56.3% of those with a dose decrease or discontinuation after onset (OR 3.6: 95%CI 1.0~12.4; P=0.04).ConclusionsUC patients wishing to conceive should do so when in remission and continue appropriate pharmaceutical treatment during pregnancy.

Usefulness of Helicobacter pylori eradication for precancerous lesions of the gastric remnant.

Secondary stomach cancer in lesions of the remnant stomach occurs relatively soon after distal gastrectomy using the Billroth I reconstruction procedure. Prophylactic eradication of Helicobacter pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma. However, the effect of H. pylori eradication on the gastric remnant has not been clearly determined.

Clinical utility of a new endoscopic scoring system for Crohn’s disease

AIM To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohns disease (mSES-CD). METHODS Seventy-six Crohns disease (CD) patients who underwent transanal double balloon endoscopy (DBE) in our hospital between 2003 and 2012 were retrospectively reviewed. DBE is defined as small intestinal endoscopy using two attached balloons. We included patients with stenosis which hampered passage of the scope and those who underwent DBE with observation for at least 80 cm from the ileocecal valve. Our new mSES-CD assesses the endoscopic activity of two consecutive small intestinal segments located 0-40 cm and 40-80 cm from the ileocecal valve by DBE, in addition to the activity of four colorectal segments. To compare the usefulness of mSES-CD with SES-CD, we similarly divided the patients into two groups according to total mSES-CD score (low disease activity group, < 4; high disease activity group, ≥ 4). The clinical value of mSES-CD in predicting clinical outcome in patients with CD was evaluated using the occurrence of surgery after DBE as an endpoint. RESULTS Median age of the 76 CD patients was 36 years (range, 16-71). Thirty-nine patients had stenosis which hampered passage of the DBE to 80 cm on the proximal side from the ileocecal valve. Median evaluable length of small intestine by DBE was 80 cm (range, 3-200). A total of 74 patients had one or more small intestinal lesions detected by DBE, of which 62 (83.8%) were within 80 cm of the ileocecal valve on the proximal side. Only two patients (2.7%) with proximal-side lesions more than 80 cm from the ileocecal valve did not have lesions within 80 cm. Patients with high mSES-CD scores showed significantly shorter surgery-free survival than those with low scores (P < 0.05). In contrast, surgery-free survival did not significantly differ between the low and high SES-CD groups (P > 0.05). Multivariate analysis by a Cox proportional hazards model identified mSES-CD as an independent factor for surgery-free survival. CONCLUSION mSES-CD is useful in evaluating the risk of surgery-free survival in patients with CD.

Programmed Chemotherapy for Patients with Metastatic Unresectable Gastric Cancer

Background Recent advances in the treatment of metastatic unresectable gastric cancers (MGC) include the development of new antitumor drugs and new regimens for their use. However, the selection of individually designed regimens by gastric cancer (GC) subtype remains problematic. Here, we investigated the clinical usefulness of programmed chemotherapy. Methodology/Principal Findings MGC patients were classified into three groups by clinical condition. We implemented a chemotherapy program consisting of S-1 combination regimens. Median survival time (MST) of level 1 patients was 416 days (95% CI: 313–506 days), with an overall response rate of 47%. MSTs of level 2 and 3 patients were 208 (95% CI: 153–287 days) and 95 days (95% CI: 28–136 days), respectively. Grade 3–4 toxicities were neutropenia in 12% and anorexia in 6%. All treatment- related toxicities were resolved, and no treatment-related deaths occurred. Conclusions/Significance This program provided reasonable selection of case-matching regimens and may improve the survival of patients with MGC. Further, it may represent the first clinical tool to provide efficient chemotherapy course selection for MGC. Ongoing analysis of newly developed drugs and regimens will allow the efficacy of this chemotherapy program to be improved.

Su1241 Short- and Long-Term Efficacy of Tacrolimus in Patients With Refractory Ulcerative Colitis

disease (CD) or ulcerative colitis (UC)], had a measured low vit D 25 OH level ( ,30 ng/ mL), and were treated with high-dose vit D received high-dose vit D treatment (ergocalciferol 50,000 units once a week for eight weeks). Outcomes included duel-energy x-ray absorptiometry (DEXA) scan measures and repeat vit D 25 -OH level if obtained before and after high dose vit D treatment. Statistical analysis included Wilcoxon signed-rank test. Results: 52 pts with IBD (39 CD, 13 UC), low vit D 25 OH levels, and treatment with high dose vit D were identified. 34 were male (66%), and the median age was 57 (range 22, 83 yrs). 14 (27%) had one or more IBD-related surgeries. 11 were smokers (22%). 7 (13%) pts were on corticosteroids, 8 (15%) pts were on budesonide, 20 (38%) were on immunomodulator therapy, and 20 (38%) were on anti-TNF medications. 19 (37%) pts had a previous diagnosis of osteopenia, and 12 (23%) had osteoporosis. 19 (37%) were taking a bisphosphonate. 24 (46%) had documented daily non-prescription vit D supplementation. 29 pts had a DEXA scan before and after high dose vit D treatment after a median of 2.1 yrs (range 1, 6.5 yrs). Spine bone mineral density (BMD) scores improved significantly (1.05 ± 0.17 to 1.10 ± 0.20, p , 0.05). There was no significant change in BMD of the hip (0.79 ± .15 to 0.75 ± .31), and hip and spine T scores and Z scores did not change significantly. 36 pts had repeat vit D 25 OH levels checked after a median of 120 days (range 47, 964 days). Vit D 25 OH increased significantly (15.5 ± 8.4 to 29.4 ± 19.0, p , 0.05). However, 14 (36%) pts remained vit D deficient (vit D 25 OH levels , 20 ng/mL), and 8 (22%) pts remained vit D insufficient (vit D 25 OH levels 20-30 ng/mL). Persistent vit D insufficiency was not dependent on gender, surgical history, medication type, or disease type. Conclusion: In this study, the majority patients with IBD who are vit D insufficient failed to achieve normal serum vit D levels after treatment with high dose vit D, but bone health based on DEXA scan did not worsen significantly. Further research into appropriate calcium and vit D dosing in this patient population is warranted.

Cerebral air embolism as a complication of peptic ulcer in the gastric tube: case report

BackgroundThe reported incidence of ulcer formation in the gastric tube in esophageal replacement is rare.Case PresentationThis is the first report of a case of cerebral air embolism as a result of spontaneous perforation of an ulcer in the constructed gastric tube into the pulmonary vein during post-operative follow-up in a patient with esophageal cancer.ConclusionsCerebral air embolism is a rare complication of penetrating gastric ulcer, but should be considered in patients with a history of esophagectomy with gastric conduit that present with acute neurologic findings.