Circumferential Stenosis of the Second Part of the Duodenum Caused by Eosinophilic Gastroenteritis.

Isolated eosinophilic gastroenteritis (EGE) of the second part of the duodenum is rare. We herein report a case of EGE limited to the second part of the duodenum that caused circumferential stenosis due to massive wall thickening. A boring biopsy was useful to verify the accumulation of eosinophils. Induction of remission by prednisolone was accompanied by a marked reduction in the mRNA expression of interleukin-6, C-C motif chemokine ligand 17 (CCL17), and CCL26 without any reduction in prototypical EGE-associated T helper type 2 cytokines (IL-5, IL-13). Thus, the enhanced expression of IL-6, CCL17, and CCL26 might be involved in the development of EGE in this case.

Activation of nucleotide-binding oligomerization domain 2 by muramyl dipeptide negatively regulates Toll-like receptor 9-mediated colonic inflammation through the induction of deubiquitinating enzyme A expression.

Mutations in nucleotide-binding oligomerization domain 2 (NOD2) are associated with Crohn's disease (CD). Although NOD2 activation contributes to the maintenance of intestinal homeostasis through the negative regulation of pro-inflammatory cytokine responses mediated by Toll-like receptors (TLRs), the effects of NOD2 activation on interferon (IFN)-α responses induced by TLR9 have been poorly defined. To explore the cross-talk between NOD2 and TLR9, human monocytes or dendritic cells (DCs) were stimulated with NOD2 and/or TLR9 ligands to measure IFN-α production. The severity of dextran sodium sulfate (DSS)-induced colitis was compared in mice treated with NOD2 and/or TLR9 ligands. Expression of IFN-α and IFN-stimulated genes (ISGs) was examined in the colonic mucosa of patients with inflammatory bowel disease (IBD). NOD2 activation reduced TLR9-induced IFN-α production by monocytes and DCs in a deubiquitinating enzyme A (DUBA)-dependent manner. Activation of DUBA induced by the co-stimulation of TLR9 and NOD2 inhibited Lys63-linked polyubiquitination of TRAF3 and suppressed TLR9-mediated IFN-α production. NOD2 activation in hematopoietic cells protected mice from TLR9-induced exacerbation of DSS-induced colitis by down-regulating IFN-α responses and up-regulating DUBA expression. Colonic mucosa of patients with active and remitted IBD phases was characterized by the enhanced and reduced expression of ISGs, respectively. Expression levels of IFN-α and IL-6 positively correlated in the active colonic mucosa of patients with ulcerative colitis and CD, whereas DUBA expression inversely correlated with that of IFN-α in patients with CD. Collectively, these data suggest that DUBA-dependent negative effect of NOD2 on TLR9-mediated IFN-α responses contributes to the maintenance of intestinal homeostasis.

Endoscopic submucosal dissection with reinforcement using a laparoscopic approach for a duodenal cavernous hemangioma.

Video 1Endoscopic submucosal dissection with reinforcement using a laparoscopic approach (duodenal-laparoscopic and endoscopic coordinated surgery with endoscopic submucosal dissection) for a duodenal cavernous hemangioma. The mucosal defect was reinforced with laparoscopic seromuscular sutures after duodenal endoscopic submucosal dissection was performed.

Expression levels of cellular inhibitor of apoptosis proteins and colitogenic cytokines are inversely correlated with the activation of interferon regulatory factor 4.

Cellular inhibitors of apoptosis proteins 1 (cIAP1) and 2 (cIAP2) are involved in signaling pathways mediated by Toll-like receptors (TLRs) and tumor necrosis factor (TNF)-α. Excessive activation of TLRs and TNF-α underlies the immunopathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). However, the roles played by cIAP1 and cIAP2 in the development of CD and UC remain poorly understood. In this study, we attempted to clarify the molecular link between cIAP1/cIAP2 and colonic inflammation. Human monocyte-derived dendritic cells (DCs) treated with siRNAs specific for cIAP1 or cIAP2 exhibited reduced pro-inflammatory cytokine responses upon stimulation with TLR ligands. Expression of cIAP1 and cIAP2 in human DCs was suppressed in the presence of interferon regulatory factor 4 (IRF4). This effect was associated with inhibition of cIAP1 and cIAP2 polyubiquitination. To verify these in vitro findings, we created mice overexpressing IRF4 in DCs and showed that these mice were resistant to trinitrobenzene sulfonic acid-induced colitis as compared with wild-type mice; these effects were accompanied by reduced expression levels of cIAP1 and cIAP2. Pro-inflammatory cytokine production by mesenteric lymph node cells upon stimulation with TLR ligands was reduced in mice with DC-specific IRF4 overexpression as compared with that in wild-type mice. Finally, in clinical samples of the colonic mucosa from patients with CD, there was a negative relationship between the percentage of IRF4+ DCs and percentages of cIAP1+ or cIAP2+ lamina propria mononuclear cells. These data suggest that the colitogenic roles of cIAP1 and cIAP2 are negatively regulated by IRF4.

Castor oil as booster for colon capsule endoscopy preparation reduction: A prospective pilot study and patient questionnaire.

BACKGROUND: Preparation for colon capsule endoscopy (CCE) requires a large liquid laxative volume for capsule excretion, which compromises the procedure's tolerability. AIM: To assess the safety and utility of castor oil-boosted bowel preparation. METHODS: This prospective cohort study including 20 patients (age range, 16-80 years; six men and 14 women) suspected of having colorectal disease was conducted at Kindai University Hospital from September 2017 to August 2019. All patients underwent CCE because of the following inclusion criteria: previous incomplete colonoscopy in other facility (n = 20), history of abdominal surgery (n = 7), or organ abnormalities such as multiple diverticulum (n = 4) and adhesion after surgery (n = 6). The exclusion criteria were as follows: Dysphagia, history of allergic reactions to the drugs used in this study (magnesium citrate, polyethylene glycol, metoclopramide, and castor oil), possibility of pregnancy, possibility of bowel obstruction or stenosis based on symptoms, or scheduled magnetic resonance imaging within 2 wk after CCE. The primary outcome was the capsule excretion rate within the battery life, as evaluated by the total large bowel observation rate, large bowel transit time, and bowel creasing level using a five-grade scale in different colorectal segments. The secondary outcomes were complications, colorectal lesion detection rates, and patients' tolerability. RESULTS: The castor oil-based regimen was implemented in 17 patients. Three patients cancelled CCE because they could tolerate castor oil, but not liquid laxatives. The capsule excretion rate within the battery life was 88% (15/17). The mean large bowel transit time was 236 min. Approximately 70% of patients had satisfactory colon cleansing levels. CCE detected colon polyps (14/17, 82%) and colonic diverticulum (4/12, 33%). The sensitivity, specificity, and diagnostic accuracy rates for detecting colorectal polyps (size ≥ 6 mm) were 76.9%, 75.0%, and 76.4%, respectively. The sensitivity, specificity, and diagnostic accuracy rates for detection of diverticulum were 100% each. Twelve patients (71%) rated CCE as more than "good", confirming the new regimen's tolerability. No serious adverse events occurred during this study. CONCLUSION: The castor oil-based regimen could reduce bowel preparation dose and improve CCE tolerability.