Endoscopic diagnosis of Whipple disease in a patient without gastrointestinal symptoms: A case report.

Whipple's disease is a systemic chronic bacterial infection caused by Tropheryma whipplei, a gram-positive bacillus. T. whipplei infection in the small intestine often causes malabsorption and is often accompanied by gastrointestinal symptoms such as diarrhea and abdominal pain. In this report, we describe our experience with a case of Whipple's disease in which the affected patient did not have the typical gastrointestinal symptoms. The patient was an 80-year-old male who presented with complaints of weight loss and lower leg edema due to malabsorption and shortness of breath during exertion. A blood test revealed a decreased albumin level and an elevated C-reactive protein level. Endoscopic images revealed diffuse white villi, the presence of which extended from the duodenum to the upper jejunum. We made a diagnosis of Whipple's disease based on pathological findings associated with the duodenum, electron microscopic findings, and findings of polymerase chain reaction (PCR) tests (performed using mucosal tissue). Clinical symptoms and endoscopic findings improved with antibiotics. Real-time PCR tests were performed for a quantitative evaluation of the effect of treatment. Endoscopy is useful for diagnosing Whipple's disease when there is an absence of gastrointestinal symptoms, and hypoalbuminemia of unknown etiology is observed.

Novel adsorptive type apheresis device Immunopure for ulcerative colitis from clinical perspectives based on clinical trials: Japan and Europe.

Several adsorptive type devices for ulcerative colitis are used for the induction of remission in patients with active severe disease worldwide. In 2020, the novel apheresis device Immunopure for ulcerative colitis was launched in Japan. Immunopure, like the polyethylene terephthalate column, uses polyarylate, a type of polyester resin, as the adsorbent. Similar to the cellulose acetate column, Immunopure is filled with adsorbent beads and expected to provide ease of use, with minimal risk of column clogging. Immunopure adsorbs leukocytes and platelets, especially activated platelets and platelet-leukocyte aggregates. In this article, the capability of Immunopure is evaluated from clinical perspective based on a clinical trial in Japan/Europe. As a result, Immunopure is comparable to other products in clinical effectiveness and indicated for the treatment of patients with refractory moderate ulcerative colitis, making it highly useful in clinical practice.

The Differential Diagnosis of Colorectal Polyps Using Colon Capsule Endoscopy.

Objective Although colorectal polyps (CPs) can be observed with colon capsule endoscopy (CCE), it is difficult to determine the type of polyp using CCE. The objective of this study was to differentiate adenomatous polyps (APs) from hyperplastic polyps (HPs) with CCE. Methods In this single-center retrospective study, an analysis was conducted on the same CPs with both CCE and colonoscopy (CS) and histopathologically diagnosed as AP or HP. The color difference (ΔE) between the polyp surface and the surrounding mucosa was calculated using the CIE1976 L*a*b* color space method on white light (WL), flexible spectral imaging color enhancement (FICE), and blue mode (BM) CP images. We investigated the ability of the ratio of the color differences (ΔE') to differentiate between APs and HPs. Results The size of all 51 polyps (34 APs, 17 HPs) was 7.5±4.6 mm with CCE and 7.3±4.2 mm with CS, and this difference was not significant (p=0.28). The FICEΔE' of APs was 3.3±1.8, which was significantly higher than the FICEΔE' of HPs (1.3±0.6; p<0.001). A receiver operating characteristic analysis showed that FICEΔE' was useful for differentiating between APs and HPs, with an area under the curve of 0.928 (95% confidence interval, 0.843-1). The sensitivity was 91.2%, and the specificity was 88.2% with a cut-off value of 1.758. Conclusion Using FICE on CCE images of CPs and applying the CIELAB color space method, we were able to differentiate between APs and HPs with high accuracy. This method has the potential to reduce unnecessary CS procedures.

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.

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.

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.

Systemic Lupus Erythematosus from Lupus Enteritis.

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Dual antiplatelet therapy does not affect the incidence of low-dose aspirin-induced small intestinal mucosal injury in patients after percutaneous coronary intervention for coronary stenosis: a multicenter cross-sectional study.

Although low-dose aspirin (LDA) is known to induce small intestinal mucosal injury, the effect of dual antiplatelet therapy (DAPT; LDA + clopidogrel) on small intestinal mucosa in patients after percutaneous coronary intervention (PCI) for coronary stenosis is unknown. Fifty-one patients with a history of PCI and LDA use were enrolled, and 45 eligible patients were analyzed. Patients were grouped based on DAPT (DAPT: n = 10 and non-DAPT: n = 35) and proton pump inhibitor (PPI) use (PPI user: n = 22 and PPI-free patients: n = 23) to compare small intestinal endoscopic findings. The relationship between LDA-use period and small intestinal endoscopic findings was also examined. Multivariate analysis was performed to identify risk factors for LDA-induced mucosal injury using age, sex, DAPT, PPI, gastric mucoprotective drug, and LDA-use period. The rate of small intestinal mucosal injury incidence did not significantly differ between DAPT and non-DAPT patients (50% vs 51.1%, respectively; p = 0.94), or PPI users and PPI-free patients (50% vs 52.2%, respectively; p = 0.88). Additionally, LDA-use period of ≤24 months (n = 15) yielded a significantly higher rate of small intestinal mucosal injury incidence than LDA-use period >24 months (n = 30) (80% vs 36.7%, respectively; p = 0.006). Multivariate analysis revealed that a LDA-use period of ≤24 months was a significant risk factor for small intestinal mucosal injury (odds ratio: 19.5, 95% confidence interval: 2.48-154.00, p = 0.005). Following PCI for coronary stenosis, neither DAPT nor PPI affected LDA-induced small intestinal mucosal injury. Moreover, patients who used LDA within the last 24 months were at a greater risk of small intestinal mucosal injury.

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.

New-generation full-spectrum endoscopy versus standard forward-viewing colonoscopy: a multicenter, randomized, tandem colonoscopy trial (J-FUSE Study).

BACKGROUND AND AIMS: Although colonoscopy is the criterion standard for detection of colorectal adenomas, some adenomas are missed. Full-spectrum endoscopy (FUSE) allows for observation with a 330-degree angle of view, which is expected to decrease the miss rate. However, no consensus has been reached regarding the superiority of FUSE over standard forward-viewing colonoscopy (SFVC) for detection of adenomas; we therefore compared new-generation FUSE and SFVC regarding colorectal adenoma miss rate (AMR) in this, the first reported randomized control trial using new-generation FUSE. METHODS: We enrolled individuals aged 40 to 75 years who had been referred for screening, surveillance, fecal occult blood test positivity, or symptoms in a prospective randomized trial of tandem colonoscopy in 8 institutions. Patients were randomly assigned (1:1) via computer-generated stratified randomization. Neither the endoscopists nor patients were blinded to the allocation. The primary endpoint was AMR per patient (AMR-PP). RESULTS: We enrolled 345 patients and included 319 in the per-protocol analyses. AMR-PP was significantly lower with FUSE (11.7%; 95% confidence interval [CI], 8.0%-15.4%) than with SFVC (22.9%; 95% CI, 17.5%-28.3%; P < .001). AMR-PP for lesions ≤5 mm in size was significantly lower with FUSE (10.4%; 95% CI, 6.5%-14.3%) than with SFVC (20.0%; 95% CI, 14.4%-25.6%; P = .0057). Furthermore, AMR-PP in the ascending colon was significantly lower with FUSE (4.3%; 95% CI, 1.4%-7.2%) than with SFVC (10.6%; 95% CI, 6.1%-15.1%; P = .0212). CONCLUSIONS: FUSE is superior to SFVC regarding both AMR-PP and AMR; additionally, AMR-PP is both significantly lower with FUSE than SFVC for lesions ≤5 mm in size and in the ascending colon. (Clinical trial registration number: UMIN000020448.).

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.

A comparison of the resection rate for cold and hot snare polypectomy for 4-9 mm colorectal polyps: a multicentre randomised controlled trial (CRESCENT study).

OBJECTIVE: To investigate the success rate of cold snare polypectomy (CSP) for complete resection of 4-9 mm colorectal adenomatous polyps compared with that of hot snare polypectomy (HSP). DESIGN: A prospective, multicentre, randomised controlled, parallel, non-inferiority trial conducted in 12 Japanese endoscopy units. Endoscopically diagnosed sessile adenomatous polyps, 4-9 mm in size, were randomly assigned to the CSP or HSP group. After complete removal of the polyp using the allocated technique, biopsy specimens from the resection margin after polypectomy were obtained. The primary endpoint was the complete resection rate, defined as no evidence of adenomatous tissue in the biopsied specimens, among all pathologically confirmed adenomatous polyps. RESULTS: A total of 796 eligible polyps were detected in 538 of 912 patients screened for eligibility between September 2015 and August 2016. The complete resection rate for CSP was 98.2% compared with 97.4% for HSP. The non-inferiority of CSP for complete resection compared with HSP was confirmed by the +0.8% (90% CI -1.0 to 2.7) complete resection rate (non-inferiority p<0.0001). Postoperative bleeding requiring endoscopic haemostasis occurred only in the HSP group (0.5%, 2 of 402 polyps). CONCLUSIONS: The complete resection rate for CSP is not inferior to that for HSP. CSP can be one of the standard techniques for 4-9 mm colorectal polyps. (Study registration: UMIN000018328).

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.

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.

Reocclusion after Self-Expandable Metallic Stent Placement for Relieving Malignant Colorectal Obstruction as a Palliative Treatment.

Self-expandable metallic stent (SEMS) placement has been practiced in several hospitals in Japan, including ours, since January 2012. Here, we report the case of an 82-year-old Japanese man who presented to the hospital with a 1-week history of right hypochondrial pain. Computed tomography (CT) findings indicated colorectal cancer. The laboratory findings on admission indicated severe anemia (red blood cell count, 426 × 104/µL; hemoglobin, 7.9 g/dL). We performed SEMS placement because the patient refused to undergo surgery. He did not attend any of the scheduled follow-up visits after SEMS placement. However, a year and a half after the SEMS placement, the patient attended the hospital because of difficulty in passing stool. A plain abdominal CT scan showed bowel reobstruction due to the ascending colon cancer after SEMS placement. We performed an emergency operation, ascending colostomy, on the same day. Colorectal stent placement may be a good treatment option for patients who refuse to undergo conventional therapeutic treatments or in those with unresectable colorectal cancer. Patients should be carefully followed up every few months after SEMS placement because of the risk of reocclusion.

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.

[A case of ruptured giant splenic artery aneurysm].

A 68-year-old woman presented with general malaise. Her vital signs were unstable, and abdominal computed tomography revealed giant (10 cm) splenic artery aneurysm with evidence of rupture. We first occluded the root of the splenic artery using a balloon catheter. Next, we resected the distal pancreas and spleen because of the aneurysm size and destruction of the related vasculature. After surgery, the patient's condition improved, and she was discharged from the hospital on postoperative day 18. Because ruptured giant splenic artery aneurysms are very rare, we report this case with a review of the literature.