Background/aimsThe natural history of pancreatic branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) is still unknown. This retrospective study aims to determine the morphological changes of BD-IPMNs with attention to the history of surgical resection for extrapancreatic malignancies.Methods and materialsThis study included 427 subjects with BD-IPMN at the Osaka Medical College from January 2001 to December 2019; 134 patients were included. The predictive factors for the progression of BD-IPMN based on morphological changes were evaluated by univariate as well as multivariate analyses. Furthermore, the clinical features of BD-IPMNs with progressive lesions during follow-up were investigated.ResultsThe average interval of follow-up was 35.8 months (with a range between 12.1 and 157 months). Disease progression occurred in 6 subjects (4.5%). In two of them (1.5%), IPMN-related invasive carcinoma was found. Multivariate analysis demonstrated that surgical resection for extrapancreatic malignancies was a significant predictor of BD-IPMN progression.ConclusionThe history of resection of extrapancreatic malignancies should be considered during the follow-up of BD-IPMN.

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.

In recent years, the cases of small rectal carcinoid less than 5mm have been increasing by reason of the increasing number of colonoscopy and the improvement in diagnostic capability. While explicit criteria have not been defined about the treatment strategy and the radical cure judging, endoscopic therapy including endoscopic mucosal resection (EMR) has been a first choice in many cases. Up to now, we have performed two channel method (EMR-2T), and recently endoscopic submucosal dissection method (ESD) has been applied to the treatment of rectal carcinoid tumors.

Geranylgeranylacetone (GGA), an isoprenoid compound, is an anti-ulcer drug developed in Japan. GGA protects a variety of cells and tissues against numerous stresses via induction of heat shock protein (HSP) 70, and it has recently been reported to protect mice from experimental ulcerative colitis (UC). However, it is unknown whether GGA exhibits a preventive effect on UC-associated neoplasia. In the present study, we evaluated the preventive effects of GGA on colitis-related carcinogenesis in the mouse colon. Mice were administered 1,2-dimethylhydrazine (DMH) subcutaneously three times within a week, followed by 2 cycles of dextran sulfate sodium (DSS) (each cycle, 3% DSS for 7 days and then distilled water for 14 days) and they were sacrificed 28 days after the completion of the 2 cycles. The mice were divided into the following groups according to the diet received during the experiment: group A, which received a standard diet and served as a disease control; group B, which received a diet mixed with 0.25% GGA; group C, which received a diet mixed with 0.5% GGA; group D, which received a diet mixed with 1.0% GGA; group E, which received a diet mixed with 2.0% GGA; and group F, which received a diet containing no agents, including DSS and served as a normal control. The incidence of neoplasia was assessed. The expression of inducible nitric oxide synthase (iNOS) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was also determined. In addition, the expression of HSP70 in the colon tissues was determined by immunohistochemistry and western blot analysis. The mean number of tumors was 16.6, 11.0, 9.4, 5.8, 5.4 and 0 in groups A-F, respectively. GGA significantly suppressed the occurrence of neoplasia in a dose-dependent manner. GGA treatment enhanced the expression of HSP70 and suppressed the oxidative damage in the background mucosa (i.e. lesion-free colon). These results suggest that GGA could be useful in the prevention of UC-associated neoplasia.

Introduction: The presence of mural nodule (MN) is an important factor for the management of branch duct type intraductal papillary mucinous neoplasm (BD-IPMN).International consensus guidelines 2012 recommend clinical follow-up to BD-IPMN without MNs.However, it is not clear whether BD-IPMNs with MNs need surgical treatment regardless of the height of MNs.Aim: To compare the pathological and follow-up outcomes between BD-IPMNs with MNs ≤6mm in height (MN+) and those without MNs (MN-).Methods: The patients who were diagnosed as BD-IPMNs with MNs ≤6mm or without MNs since April 2004 to December 2013 were retrospectively analyzed.Inclusion criteria were the obtaining of contrast enhanced CT and EUS at initial diagnosis, and surgical resection in our center or follow-up with annual/semi-annual CT/MRCP.The cyst size and main pancreatic duct (MPD) diameter were measured by CT/MRCP, while MN height was measured by EUS.Tumor progression during follow-up was defined as follows; increased cyst size ≥10mm; increased MPD diameter ≥10mm; new development of MN or increased MN height ≥2mm.Evaluation points: 1) pathological diagnosis of resected BD-IPMN, 2) follow-up outcomes Results: Among 656 patients of BD-IPMNs diagnosed in our center, MN height was evaluated as less than or equal to 6mm in 511(78%; MN+ 50, MN-352).After initial diagnosis, 17(3%; MN+ 8, MN-9) of them underwent immediate resection and 385(75%; MN+ 42, MN-343) of them received regular follow-up, who were eligible for this analysis.The median cyst size and MPD diameter were 20(10-70) mm and 3(2-12) mm, respectively.The median height of MNs in MN+ were 3(1-6) mm. 1) The pathological diagnosis of the patients with MN-were all low/intermediate-grade dysplasia (LID), while those of the patients with MN+ were LID in 5, high-grade dysplasia (HD) in 2, and invasive carcinoma (IC) in 1.There were no significant differences in pathological diagnosis between MN+ and MN-(p=0.17,chi-square test).2) During a median follow-up period of 3.4(0.5-10.6)years, 49(13%; MN+ 9, MN-40) patients exhibited tumor progression.The 5-years cumulative tumor progression rate was higher in MN+ than those in MN-(MN+ 19% vs MN-9%; p<0.01,Log-rank test).Among 49 patients with tumor progression, 11(22%; MN+ 4, MN-7) patients underwent surgical resection, whose pathological diagnosis were LID in 6(MN+ 2, MN-4), HD in 3(MN+ 1, MN-2), and IC with minimal invasion in 2(MN+ 1, MN-1).The other 38 patients continued to be followed during a median period of 0.6(0.0-4.2) years.Meanwhile, concomitant pancreatic ductal adenocarcinoma (PDAC) was appeared in 9(2%; MN+ 1, MN-8) patients.Conclusion: Although tumor progression rate was higher, BD-IPMN with MNs ≤6mm in height on EUS could be managed conservatively.However, careful attention should be paid to the development of PDAC during follow-up.

To evaluate role of endoscopic ultrasonography fine needle aspiration (EUS-FNA) in diagnosis of autoimmune pancreatitis (AIP).

Small bowel capsule endoscopy (CE) enables observation of lesions in the small bowel in patients with Crohn's disease (CD). However, lesions in the small bowel cannot be assessed by CE in patients classified as "patency not confirmed". Therefore, we evaluated the usefulness of a method to assess lesions in the small bowel in patients with CD who had preliminarily undergone examination using a patency capsule.

AIM:To determine the efficacy and safety of rapid induction therapy with oral tacrolimus without a meal in steroid-refractory ulcerative colitis (UC) patients.METHODS:This was a prospective, multicenter, observational study. Between May 2010 and August 2012, 49 steroid-refractory UC patients (55 flare-ups) were consecutively enrolled. All patients were treated with oral tacrolimus without a meal at an initial dose of 0.1 mg/kg per day. The dose was adjusted to maintain trough whole-blood levels of 10-15 ng/mL for the first 2 wk. Induction of remission at 2 and 4 wk after tacrolimus treatment initiation was evaluated using Lichtiger's clinical activity index (CAI).RESULTS:The mean CAI was 12.6 ± 3.6 at onset. Within the first 7 d, 93.5% of patients maintained high trough levels (10-15 ng/mL). The CAI significantly decreased beginning 2 d after treatment initiation. At 2 wk, 73.1% of patients experienced clinical responses. After tacrolimus initiation, 31.4% and 75.6% of patients achieved clinical remission at 2 and 4 wk, respectively. Treatment was well tolerated.CONCLUSION:Rapid induction therapy with oral tacrolimus shortened the time to achievement of appropriate trough levels and demonstrated a high remission rate 28 d after treatment initiation. Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory UC.

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 glucagon‑like 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. Real‑time 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.

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.

Crohn's disease (CD) is characterized by transmural inflammation of the gastrointestinal tract, which predisposes patients to the formation of a fistula. The efficacy of adalimumab (ADA) for an enterocutaneous fistula remains unclear. In this report, we present a case series of 3 patients with enterocutaneous fistulizing CD treated with ADA. ADA treatment achieved sustained complete fistula closure in one patient. The other two cases, which failed to achieve fistula closure, had intestinal stenosis and were not receiving concomitant azathioprine. Combination therapy with ADA and azathioprine may be a useful option and an alternative to surgery for enterocutaneous fistulizing CD.

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.

Duodenal tumors are rare. Their biological malignancy remains to be clarified, and a consensus regarding therapeutic strategies has not been reached. Furthermore, there are few reports on endoscopic treatment. It is technically difficult, and complications may become serious. In this article, we present the results of endoscopic treatment for tumorous duodenal lesions in our hospital, and compare them among different procedures.