Risk factors for postoperative bleeding and early death in percutaneous endoscopic gastrostomy: A multicenter retrospective study.

BACKGROUND AND AIM: Comprehensive reports on the risk factors for bleeding and early death after percutaneous endoscopic gastrostomy (PEG) are limited. In this multicenter study, we retrospectively investigated the risk factors for bleeding and early death after PEG. METHODS: Patients (n = 1234) who underwent PEG between 2015 and 2020 at Osaka Medical and Pharmaceutical University and its affiliated hospitals (11 institutions in total) were evaluated for postoperative bleeding and early death (within 60 days) after PEG according to patient characteristics, construction method, medical history, medications, preoperative hematological findings, and perioperative adverse events. Multivariate logistic regression was performed to identify independent predictors of bleeding and early death after PEG. RESULTS: The risk factors for bleeding after PEG were PEG tube insertion using the modified introducer method (odds ratio [OR], 4.37; P = 0.0003), low platelet count (OR, 0.99; P = 0.014), antiplatelet therapy (OR, 2.11; P = 0.036), and heparinization (OR, 4.50; P = 0.007). Risk factors for early death were low body mass index (BMI) (OR, 0.89; P = 0.015), low serum albumin levels (OR, 0.50; P = 0.035), and comorbidity of active cancer (OR, 4.03; P < 0.0001). There was no significant association between bleeding and early death after PEG. CONCLUSIONS: We identified several risk factors for bleeding and early death after PEG. Risk factors for bleeding were PEG tube insertion using the modified introducer method, low platelet count, antiplatelet therapy, and heparinization. Risk factors for early death were low BMI, low serum albumin levels, and comorbidity of active cancer.

Evaluation of Alkylamine Modified Pt Nanoparticles as Oxygen Reduction Reaction Electrocatalyst for Fuel Cells via Electrochemical Impedance Spectroscopy.

Organically (octyl amine, OA) surface modified electrocatalyst (OA-Pt/CB) was studied for its oxygen reduction reaction (ORR) activity via dc methods and its charge and mass transfer properties were studied via electrochemical impedance spectroscopy (EIS). Comparison with a commercial catalyst (TEC10V30E) with similar Pt content was also carried out. In EIS, both the catalysts showed a single time-constant with an emerging high-frequency semicircle of very small diameter which was fitted using suitable equivalent circuits. The organically modified catalyst showed lower charge-transfer resistance and hence, low polarization resistance in high potential region as compared to the commercial catalyst. The dominance of kinetic processes was observed at 0.925-1.000 V, whereas domination of diffusion based processes was observed at lower potential region for the organic catalyst. No effect due to the presence of carbon was observed in the EIS spectra. Using the hydrodynamic method, higher current penetration depth was obtained for the organically modified catalyst at 1600 rpm. Exchange current density and Tafel slopes for both the electrocatalysts were calculated from the polarization resistance obtained from EIS which was in correlation with the results obtained from dc methods.

Cytomegalovirus infection in ulcerative colitis assessed by quantitative polymerase chain reaction: risk factors and effects of immunosuppressants.

We investigated the risk factors of and appropriate treatment for cytomegalovirus colitis in patients with ulcerative colitis, using quantitative polymerase chain reaction analysis to detect cytomegalovirus in the colonic mucosa. Between February 2013 and January 2017, patients with exacerbated ulcerative colitis who were admitted to our hospital were consecutively enrolled in this retrospective, single-center study. Patients were evaluated for cytomegalovirus using serology (antigenemia) and quantitative polymerase chain reaction analyses of the colonic mucosa, which were sampled during colonoscopy. Of 86 patients, 26 (30.2%) had positive quantitative polymerase chain reaction results for cytomegalovirus; only 4 were also positive for antigenemia. The ages of the cytomegalovirus DNA-positive patients were significantly higher than those of negative patients (p = 0.002). The mean endoscopic score of cytomegalovirus DNA-positive patients was significantly higher than that of cytomegalovirus DNA-negative patients. Treatment with combined immunosuppressants was associated with an increased risk of cytomegalovirus. Fourteen of 15 (93.3%) cytomegalovirus DNA-positive patients who were negative for antigenemia showed a clinical response to treatment with additional oral tacrolimus, without ganciclovir. cytomegalovirus reactivation in active ulcerative colitis is associated with age and combined immunosuppressant therapy. Because additional treatment with tacrolimus was effective, patients who are negative for antigenemia and cytomegalovirus DNA-positive colonic mucosa may recover without antiviral therapy.

Effect of egualen sodium hydrate on small-intestinal mucosal damage induced by low-dose aspirin: a prospective randomized clinical trial.

Low-dose aspirin, which is widely used to reduce the risk of cardio- and cerebrovascular thrombosis, often induces gastroenteropathy by increasing the permeability of the mucosa. However, therapeutic strategies for patients with low-dose aspirin-induced small intestinal injury have not been determined. We evaluated the preventative effect of egualen sodium hydrate, a gastro-protective agent that suppresses indomethacin-induced small-intestinal damage in rats, against small-intestinal mucosal damage induced by low-dose aspirin in healthy adult male volunteers. Participants were randomly allocated to receive aspirin 100 mg/kg daily (control group, n = 10) or aspirin 100 mg/kg plus egualen sodium 30 mg daily (egualen sodium group, n = 10). Small intestinal mucosal injury was evaluated by capsule endoscopy two weeks after initiation of drug administration. Fecal analyses (occult blood test, immunochemical test, transferrin measurement and calprotectin measurement) were carried out before and after treatment. Egualen sodium significantly suppressed the total number of small intestinal injuries detected by capsule endoscopy and the positive ratio for the fecal occult blood test. Daily use of 30 mg of egualen sodium showed a preventative effect on low-dose aspirin-induced small intestinal injury. Since acid suppression therapy was reported to exacerbate NSAIDs-induced enteropathy via dysbiosis, egualen sodium may be useful for patients treated with low-dose aspirin.

Intermittent fasting prompted recovery from dextran sulfate sodium-induced colitis in mice.

Fasting-refeeding in mice induces transient hyperproliferation of colonic epithelial cells, which is dependent on the lactate produced as a metabolite of commensal bacteria. We attempted to manipulate colonic epithelial cell turnover with intermittent fasting to prompt recovery from acute colitis. Acute colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium in the drinking water for 5 days. From day 6, mice were fasted for 36 h and refed normal bait, glucose powder, or lactylated high-amylose starch. On day 9, colon tissues were subjected to analysis of histology and cytokine expression. The effect of lactate on the proliferation of colonocytes was assessed by enema in vivo and primary culture in vitro. Intermittent fasting resulted in restored colonic crypts and less expression of interleukin-1ß and interleukin-17 in the colon than in mice fed ad libitum. Administration of lactate in the colon at refeeding time by enema or by feeding lactylated high-amylose starch increased the number of regenerating crypts. Addition of lactate but not butyrate or acetate supported colony formation of colonocytes in vitro. In conclusion, intermittent fasting in the resolution phase of acute colitis resulted in better recovery of epithelial cells and reduced inflammation.

The effects of a TGR5 agonist and a dipeptidyl peptidase IV inhibitor on dextran sulfate sodium-induced colitis in mice.

BACKGROUND AND AIM: Luminal nutrients stimulate enteroendocrine L cells to release gut hormones, including intestinotrophic glucagon-like peptide-2 (GLP-2). Because L cells express the bile acid receptor TGR5 and dipeptidyl peptidase-IV (DPPIV) rapidly degrades GLPs, we hypothesized that luminal TGR5 activation may attenuate intestinal injury via GLP-2 release, which is enhanced by DPPIV inhibition. METHODS: Intestinal injury was induced in mice by administration of dextran sulfate sodium (DSS) in drinking water (free access to water containing 5% DSS for 7 days). The selective TGR5 agonist betulinic acid (BTA) and the DPPIV inhibitor sitagliptin phosphate monohydrate (STG) were administered orally for 7 days. Male C57BL/6 mice (6-7 weeks old) were divided into five groups: normal control group, disease control group, BTA low group (drinking water containing 15 mg/L BTA), BTA high group (50 mg/L BTA), and BTA high + STG (3 mg/kg, i.g.) group. RESULTS: The selective TGR5 agonist BTA dose-dependently suppressed disease activity index and mRNA expression of the pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α in the colon. Nevertheless, STG administration had little additive effect on BTA-induced protection. Fibroblast activation protein mRNA expression, but not expression of other DPP family members, was increased in the colon of DSS-treated mice with increased mucosal DPPIV. Co-administration of the selective GLP-2 antagonist GLP-2 (3-33) reversed the effect of BTA. CONCLUSION: The selective TGR5 agonist BTA ameliorated DSS-induced colitis in mice via the GLP-2 pathway with no effect of DPPIV inhibition, suggesting that other DPP enzymatic activity is involved in GLP-2 degradation.

Effect of long-term proton pump inhibitor therapy and healing effect of irsogladine on nonsteroidal anti-inflammatory drug-induced small-intestinal lesions in healthy volunteers.

This study assessed time-course changes of the small intestinal lesions during long-term treatment with diclofenac sodium plus omeprazole and the effects of irsogladine on such lesions. Thirty two healthy volunteers were treated with diclofenac sodium (75 mg/day) plus omeprazole (10 mg/day) for 6 weeks, with irsogladine (4 mg/day) added from weeks 6 to 10 (Group A) or with diclofenac sodium plus irsogladine for 6 weeks (Group B). Five volunteers received diclofenac sodium plus omeprazole for 10 weeks (Group C). Subjects underwent capsule endoscopy at each time. In Group A, the number of lesions remarkably increased at week 2, but the worse was not found at week 6 compared with week 2, whereas no exacerbation of lesions was observed in Group B. Additional treatment with irsogladine from weeks 6 to 10 in Group A significantly decreased the number of lesions at weeks 10 compared with Group C. In Group C, no significant change in lesions was observed since weeks 2. In conclusions, a PPI did not prevent the occurrence of small intestinal damage. However such lesions were not aggravated since weeks 2. These suggested mucosal adaptation may occur in the small intestine. Irsogladine was effective in both preventing and healing such lesions.

Combined treatment with dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin and elemental diets reduced indomethacin-induced intestinal injury in rats via the increase of mucosal glucagon-like peptide-2 concentration.

The gut incretin glucagon-like peptide-1 (GLP-1) and the intestinotropic hormone GLP-2 are released from enteroendocrine L cells in response to ingested nutrients. Treatment with an exogenous GLP-2 analogue increases intestinal villous mass and prevents intestinal injury. Since GLP-2 is rapidly degraded by dipeptidyl peptidase 4 (DPP4), DPP4 inhibition may be an effective treatment for intestinal ulcers. We measured mRNA expression and DPP enzymatic activity in intestinal segments. Mucosal DPP activity and GLP concentrations were measured after administration of the DPP4 inhibitor sitagliptin (STG). Small intestinal ulcers were induced by indomethacin (IM) injection. STG was given before IM treatment, or orally administered after IM treatment with or without an elemental diet (ED). DPP4 mRNA expression and enzymatic activity were high in the jejunum and ileum. STG dose-dependently suppressed ileal mucosal enzyme activity. Treatment with STG prior to IM reduced small intestinal ulcer scores. Combined treatment with STG and ED accelerated intestinal ulcer healing, accompanied by increased mucosal GLP-2 concentrations. The reduction of ulcers by ED and STG was reversed by co-administration of the GLP-2 receptor antagonist. DPP4 inhibition combined with luminal nutrients, which up-regulate mucosal concentrations of GLP-2, may be an effective therapy for the treatment of small intestinal ulcers.

Interleukin-13 damages intestinal mucosa via TWEAK and Fn14 in mice-a pathway associated with ulcerative colitis.

BACKGROUND & AIMS: TWEAK, a member of the tumor necrosis factor (TNF) superfamily, promotes intestinal epithelial cell injury and signals through the receptor Fn14 following irradiation-induced tissue damage and during development of colitis in mice. Interleukin (IL)-13, an effector of tissue damage in similar models, has been associated with the pathogenesis of ulcerative colitis (UC). We investigated interactions between TWEAK and IL-13 following mucosal damage in mice. METHODS: We compared patterns of gene expression in intestinal tissues from wild-type and TWEAK knockout mice following γ-irradiation. Intestinal explants from these mice were used to detect cell damage induced by IL-13 and TNF-α. Levels of messenger RNA for IL-13, TWEAK, and Fn14 were measured in mucosal samples from patients with UC. RESULTS: Based on gene expression analysis, TWEAK mediates γ-irradiation-induced epithelial cell cycle arrest and apoptosis. However, TWEAK alone did not induce damage or apoptosis of primary intestinal epithelial cells. On the other hand, exogenous IL-13 activated caspase-3 in naïve intestinal explants; this process required TWEAK, Fn14, and secretion of endogenous TNF-α which was mediated by ADAM17. Conversely, activation of caspase by exogenous TNF-α required IL-13, TWEAK, and Fn14. In mucosa from patients with UC, messenger RNA levels of IL-13, TWEAK, and Fn14 increased with level of disease severity. CONCLUSIONS: IL-13-induced damage of intestinal epithelial cells requires TWEAK, its receptor (Fn14), and TNF-α. IL-13, TNF-α, TWEAK, and Fn14 could perpetuate and aggravate intestinal inflammation in patients with UC.

Simvastatin attenuates intestinal fibrosis independent of the anti-inflammatory effect by promoting fibroblast/myofibroblast apoptosis in the regeneration/healing process from TNBS-induced colitis.

BACKGROUND: Intestinal deformity and stenosis are induced by fibrosis during the process healing of intestinal chronic inflammation in inflammatory bowel disease (IBD). Potent anti-inflammatory treatment of patients with Crohn's disease (CD) may induce fibrous stenosis, and this is often difficult to treat in clinical practice. Therefore, it is necessary to develop a treatment strategy that concomitantly exhibits repair/regenerative and anti-fibrotic effects, in addition to the current anti-inflammatory effect, for the treatment of inflammatory bowel diseases. However, the relationship between the course of inflammatory activity and the healing process and fibrogenesis has not been elucidated; although the complex involvement of various factors in the mechanism of biological fibrosis has been investigated. Simvastatin (SIMV), an HMG-CoA reductase inhibitor, exhibits anti-inflammatory and anti-fibrotic effects. The current study established a model of the regeneration/healing process from TNBS-induced colitis and investigated the anti-inflammatory and anti-fibrotic effects of SIMV. SUBJECTS AND METHODS: Four groups of TNBS-induced colitis model were prepared using male SJL/J mice: A: Normal control group, B: control group, and C and D: treatment groups. The mucosal healing process was classified into three phases (an early phase: inflammation period, a mid-phase: regeneration promoting period, and a late phase: regeneration-converging period), and inflammation, the expression of fibrosis-related growth factors, and induction of apoptosis of fibrosis-related cells were compared in each period. RESULTS: (1) The clinical findings showed that SIMV showed anti-inflammatory effects with body weight gain and improvement of epithelial injury in the late phase. Histological (macroscopic/microscopic) improvement was noted in the mid- and late phases. The inflammatory cytokine (TNF-α) level significantly decreased in the mid- and late phases in the high-dose treatment group. (2) SIMV also had anti-fibrotic effects characterized by a dose-dependent decrease in the level of a fibrosis-related growth factor (CTGF) in the early and mid-phases, irrespective of inflammation or changes in the TGF-ß(1) level. Dose-dependent induction of apoptosis was noted in both fibroblasts and myofibroblasts from a relatively early stage. CONCLUSIONS: The results suggested that SIMV induces anti-fibrotic activity that is not directly involved in the anti-inflammatory effect from a relatively early stage the healing process of TNBS-induced colitis.

Synthesis of BMS-309403-related compounds, including [¹4C]BMS-309403, a radioligand for adipocyte fatty acid binding protein.

Adipocyte fatty acid binding protein (A-FABP; FABP4), which is predominantly expressed in macrophages and adipose tissue, regulates fatty acid storage and lipolysis, and is also an important mediator of inflammation. Here, we report a synthesis of (14)C-labeled 2-[2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy]acetic acid (BMS309403), a potent and selective small-molecular FABP4 inhibitor, as a chemical tool for investigating the roles of FABP4 in inflammatory and metabolic disorders. The structure-activity relationship of several BMS derivatives for inhibition of FABP4 is also reported.

Comprehensive analysis of chemokines and cytokines secreted in the peritoneal cavity during laparotomy.

We recently found that chemokine-driven peritoneal cell aggregation is the primary mechanism of postoperative adhesion in a mouse model. To investigate this in humans, paired samples of peritoneal lavage fluid were obtained from seven patients immediately after incision (preoperative) and before closure (postoperative), and were assayed for the presence of 27 cytokines and chemokines using multiplex beads assay. As a result, IL-6 and CCL5 showed the most striking increase during operation. Recombinant CCL5 or lavage fluid induced chemotaxis of human peripheral blood mononuclear cells. We propose that CCL5 is possibly involved in the mechanism of postoperative adhesion in humans.

Evaluation of bowel preparation before colonoscopy by ultrasonographic monitoring of colonic fecal retention: a case series.

AIMS: While bowel preparation for colonoscopy is the key to successful examination, taking laxatives and showing stools to others causes both physical and mental distress to the patient. Thus, an alternative method to evaluation bowel preparation is necessary. In the current study, we studied the colonic fecal retention by ultrasonography (US) and examined the US finding which reflected completion of BP. MATERIAL AND METHODS: The subjects were outpatients who underwent colonoscopy. This report summarizes the ultrasonographic images of patients who underwent multiple US examinations for all five sites of the colon just before, during, and immediately after bowel preparation. According to the standard protocol, the patients took 2 L of polyethylene glycol-ascorbic acid as a laxative, which was discontinued when the nurse visually judged the stool to be clear. RESULTS: Seven patients in their 50s-80s, none of whom were unable to complete a colonoscopy due to residual feces were included in study. Following bowel preparation, the US images showed anechoic areas with haustration in four or all five areas of the colon. Three of the seven patients received low-dose laxatives (1.1-1.2 L); all three had watery stools in three or more colon areas and none of them were constipated at the time of taking 1 L of laxatives. CONCLUSIONS: Completion of bowel preparation can be assessed by the observation of anechoic areas with haustration in multiple colonic sites by ultrasonography.

Enhancement of O-linked N-acetylglucosamine modification promotes metastasis in patients with colorectal cancer and concurrent type 2 diabetes mellitus.

Reversible post-translational modification of serine and threonine residues by O-linked N-acetylglucosamine (O-GlcNAc), termed O-GlcNAcylation has been indicated to regulate the activities of a number of different proteins. Augmented O-GlcNAcylation contributes to the etiologies of type 2 diabetes mellitus (T2DM) and cancer. Moreover, diabetic conditions increase the risk of colorectal cancer. However, the effect of O-GlcNAcylation in patients with colorectal cancer and concurrent T2DM has not been elucidated. The current study evaluated the level of O-GlcNAcylation in patients with colorectal cancer with or without T2DM. Notably, O-GlcNAcylation levels were significantly higher in tissues from patients with T2DM compared with those in patients without T2DM, and higher in cancer tissues compared with corresponding adjacent tissues. O-GlcNAcylation and cancer stage were more strongly correlated in cancer tissues from patients with T2DM compared with those from patients without T2DM. Additionally, distant metastasis was significantly correlated with O-GlcNAcylation in cancer tissues from patients with T2DM. ß-catenin levels in colorectal cancer tissues were the highest in patients with advanced-stage cancer and concurrent T2DM. In SW480 human colon cancer cells, thiamet G (TMG) treatment and OGA silencing, which increased O-GlcNAcylation, significantly increased ß-catenin and SNAIL in high-glucose, but not during normal-glucose conditions. These data suggest that O-GlcNAcylation is closely associated with distant metastasis, most likely through upregulation of the ß-catenin/SNAIL signaling pathway in colorectal cancer patients with T2DM.

Evaluation of the impact of linked color imaging for improving the visibility of colonic polyp.

Linked color imaging (LCI) is a novel endoscopic system used to increase color contrast. As LCI does not decrease luminal brightness, it may improve the detection of colonic neoplasms. However, the extent to which LCI improves the visibility of colonic polyps has not yet been determined. Between December 2016 and May 2017, patients who received total colonoscopy were consecutively recruited into this retrospective, single-center study. For each polyp identified, images obtained from white light (WL) imaging, blue laser imaging (BLI), and LCI of the same lesion and its surrounding mucosa were evaluated. The color differences (ΔE) between each lesion and its surrounding mucosa in non-magnified images were computed quantitatively using the CIELAB color space, which defines color perception according to colorimetric values, and compared among WL, BLI, LCI, and chromoendoscopy. The ΔE between the vessel and non-vessel areas in magnified images was also assessed. Of the 64 patients who were incorporated into this study, non-magnified and magnified (×80) images from 113 and 95 polyps, respectively, were assessed. The ΔE was intensified by LCI and chromoendoscopy compared with WL and BLI. The ΔE of neoplastic lesions was also intensified by LCI. In magnified images, BLI and LCI significantly increased the ΔE between the vessel and non-vessel areas compared with WL. Luminal brightness, indicated by L*, was not impaired by LCI; however, was reduced by BLI compared with WL and LCI. These results suggest that LCI enhanced the detection of colonic neoplasms without impairing luminal brightness. We propose the routine use of LCI for colonic polyp detection and BLI for magnifying observations of colonic polyps detected by LCI.

Autophagy deficiency exacerbates colitis through excessive oxidative stress and MAPK signaling pathway activation.

BACKGROUND AND AIM: Autophagy is an essential process involved in the pathogenesis of inflammatory bowel disease (IBD). Although there are many data showing the roles of autophagy in intestinal epithelial cells (IECs), the mechanisms involved remain to be fully elucidated. We investigated the influence of autophagy in IECs on gastrointestinal tract inflammation. METHODS: Mice with conditional knockout of Atg5 in IECs (Atg5flox/flox/villin-Cre mice) were subjected to dextran sulfate sodium (DSS)-induced colitis and analyzed for colitis susceptibility. Additionally, we used Atg5-silenced rat IECs (IEC6shAtg5 cells) for in vitro assays. RESULTS: Sensitivity to DSS markedly increased in Atg5flox/flox/villin-Cre mice compared to that in wild-type mice. In IEC6shAtg5 cells, apoptosis was enhanced, and cell viability significantly decreased compared to IEC-6 cells. The expression of proinflammatory cytokines increased upon suppression of autophagy. Furthermore, silencing of Atg5 was associated with inflammation of IECs, activation of the mitogen-activated protein kinase (MAPK) signaling pathway by the intracellular reactive oxygen species accumulation, and NF-κB p65 phosphorylation. CONCLUSIONS: Autophagy in IECs plays an essential role in the maintenance of intestinal homeostasis, and autophagy deficiency triggers inflammation. Development of methods targeting autophagy might be beneficial in the treatment of IBD.

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, suppresses CXCL5 and SDF-1 and does not accelerate intestinal neoplasia formation in ApcMin/+ mice fed a high-fat diet.

The relationship between type 2 diabetes mellitus and intestinal neoplasia has been shown epidemiologically. A high-fat diet (HFD) is also known to promote insulin resistance, which is a risk factor for intestinal neoplasia. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used in the clinic for the treatment of type 2 diabetes and also to prolong the effects of glucagon-like peptide-1 (GLP-1). However, since the intestinotrophic hormone GLP-2 and chemokines, such as CXCL5 and stromal cell-derived factor-1 (SDF-1), are also substrates of DPP-4, DPP-4 inhibitors may increase the risk of intestinal carcinogenesis. In this study, we evaluated the impact of a DPP-4 inhibitor on intestinal tumorigenesis in ApcMin/+ mice fed a HFD. Six-week-old male ApcMin/+ mice were randomized to either a normal diet (10 kcal% fat) group, a HFD (60 kcal% fat) group, or a HFD group treated with sitagliptin (STG). The mice were euthanized nine weeks after the start of treatment. Daily treatment with STG did not increase number of intestinal tumors in the HFD group; however, this increase was not statistically significant. The mucosal concentration of total GLP-2 was significantly increased in the HFD group. The chemokine protein array showed elevated plasma concentrations of CXCL5 and SDF-1 in the HFD group. The administration of STG significantly suppressed the levels of plasma CXCL5 and SDF-1 in mice fed a HFD. Since CXCL5 expression is increased in patients with type 2 diabetes, and GLP-2, CXCL5 and SDF-1 are associated with tumor progression, DPP-4 inhibition may have potential as an agent for decreasing the risk of cancer in obese or diabetic patients.

The dipeptidyl peptidase-4 inhibitor sitagliptin suppresses mouse colon tumorigenesis in type 2 diabetic mice.

Patients with type 2 diabetes mellitus are known to have an increased risk of colorectal neoplasia. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been used as a new therapeutic tool for type 2 diabetes. Since the substrates for DPP-4 include intestinotrophic hormones and chemokines such as GLP-2 and stromal cell-derived factor-1 (SDF-1), which are associated with tumor progression, DPP-4 inhibitors may increase the risk of colorectal tumors. However, the influence of DPP-4 inhibitors on colorectal neoplasia in patients with type 2 diabetes remains unknown. In the present study, we show that long-term administration of a DPP-4 inhibitor, sitagliptin (STG), suppressed colon carcinogenesis in leptin-deficient (ob/ob) C57BL/6J mice. Colonic mucosal concentrations of glucagon­like peptide-1 (GLP-1) and GLP-2 were significantly elevated in the ob/ob mice. However, mucosal GLP concentrations and the plasma level of SDF-1 were not affected by the administration of STG. Real­time PCR analysis revealed that colonic mucosal IL-6 mRNA expression, which was significantly upregulated in the ob/ob mice, was significantly suppressed by the long-term administration of STG. These results suggest that a DPP-4 inhibitor may suppress colon carcinogenesis in mice with type 2 diabetes in a GLP-independent manner. Since DPP-4 has multiple biological functions, further studies analyzing other factors related to colon carcinogenesis are needed.

Multiple Mesenteric Panniculitis as a Complication of Sjögren's Syndrome Leading to Ileus.

Mesenteric panniculitis (MP) is a benign fibroinflammatory process characterized by the presence of fat necrosis, chronic inflammation and fibrosis in the mesentery. Although various causal factors, such as malignancy, chronic inflammatory conditions and autoimmune processes, have been identified, the precise etiology remains unknown. We herein report a rare case of MP accompanying Sjögren's syndrome in which a mass lesion and intestinal stenosis were observed simultaneously. This condition led to ileus, which was effectively treated using prednisolone.