Reduced antiviral seropositivity among patients with inflammatory bowel disease treated with immunosuppressive agents.

BACKGROUND: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy. AIMS: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy. METHODS: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays. RESULTS: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients. CONCLUSIONS: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

Accuracy of Ultrasound for Evaluation of Colorectal Segments in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The accuracy of ultrasound for evaluation of individual colorectal segments in patients with inflammatory bowel diseases (IBD) has not been evaluated in a systematic review. We evaluated the diagnostic accuracy of ultrasound in different colorectal segments of patients with IBD. METHODS: We searched publication databases from inception through March 2019 for studies that assessed the accuracy of ultrasound in detection of inflammation in right, transverse, and left colon and in rectum in patients with IBD, using findings from colonoscopy as the reference standard. Subgroup analyses were performed including IBD type, patient age, body mass index, and study design. The risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: Nineteen studies (1101 patients) were included in the qualitative synthesis. After we assessed the risk of bias, 7 studies (comprising 84 patients with Crohn's disease and 420 patients with ulcerative colitis) were included in the meta-analysis. Bowel wall thickness ≥ 3 mm identified colorectal segments with inflammation with 86.4% pooled sensitivity (95% CI, 76.1%-92.7%) and 88.3% pooled specificity (95% CI, 58.1%-97.6%). In rectum only, bowel wall thickness ≥ 3 mm identified inflammation with 74.5% sensitivity (95% CI, 53.0%-88.3%) and 69.5% specificity (95% CI, 33.6%-91.1%). Diagnostic accuracy was comparable among subgroups. Increased bowel wall flow and loss of stratification had higher true-positive odds ratios. CONCLUSIONS: Based on meta-analysis of patient-level data, ultrasound has higher diagnostic accuracy for detecting inflammation in colon than rectum in patients with IBD. Studies are needed to increase the accuracy of ultrasound detection of inflammation in rectum.

Enteral nutrition to suppress postoperative Crohn's disease recurrence: a five-year prospective cohort study.

PURPOSE: The aim of this study was to investigate the long-term effect of enteral nutrition (EN) as a maintenance therapy in Crohn's disease (CD) patients following surgery. METHODS: This study was an extension of our previous study to prolong the duration of intervention and follow-up from 1 to 5 years. Forty consecutive patients who underwent resection for ileal or ileocolic CD were included. Following surgery, 20 patients received continuous elemental diet infusion during the nighttime plus a low-fat diet during the daytime (EN group). Another 20 patients received neither nutritional therapy nor food restriction (control group). All patients were followed for 5 years after operation. No patient received corticosteroid, immunosuppressants, or infliximab except patients who developed recurrence. The end point of this study was recurrence requiring biologic therapy or reoperation. Recurrence rates were analyzed on an intention-to-treat basis. RESULTS: In the EN group, four patients could not continue tube intubation for elemental diet intake. Two patients (10 %) in the EN group and nine patients (45 %) in the control group developed recurrence requiring infliximab therapy (P = 0.03). The cumulative recurrence incidence rate requiring infliximab was significantly lower in the EN group vs the control group (P = 0.02). One patient (5 %) in the EN group and five patients (25 %) in the control group required reoperation for recurrence (P = 0.18). The cumulative incidence of reoperation was lower in the EN group vs the control group, the difference not being significant (P = 0.08). CONCLUSION: The outcomes of this study suggest that EN therapy reduces the incidence of postoperative CD recurrence.

Faecal calprotectin and lactoferrin as markers for monitoring disease activity and predicting clinical recurrence in patients with Crohn's disease after ileocolonic resection: A prospective pilot study.

BACKGROUND: Several studies have reported that faecal calprotectin and lactoferrin showed a close correlation with endoscopic inflammation in patients with inflammatory bowel disease. However, the clinical significance of faecal calprotectin or lactoferrin in postoperative Crohn's disease (CD) is not fully evaluated. This prospective study was to investigate the relationship between endoscopic activity, and faecal calprotectin and lactoferrin, and assess the predictive value of these markers for future recurrence. METHODS: Twenty patients who remained in remission during 6-12 months after ileocolonic resection for CD were included. All patients underwent ileocolonoscopy for assessing endoscopic activity (Rutgeerts score) in the neo-terminal ileum. A stool sample was collected for measurement of calprotectin and lactoferrin. All patients were then followed up for 12 months, and clinical recurrence was defined as a CDAI >150 with an increase of ≥70 points. RESULTS: The mean time between surgery and the endoscopic examination at entry was 7.2 months. The endoscopic scores were i0 or i1 in 10 patients, i2 in six patients, i3 in three patients, and i4 in one patient. Both calprotectin and lactoferrin positively correlated with the endoscopic scores (p = 0.0001 and p = 0.038, respectively). Six patients developed clinical recurrence during the 12-month follow-up. Both calprotectin and lactoferrin levels were significantly higher in patients with clinical recurrence than those in remission (p = 0.0007 and p = 0.025, respectively). A cutoff value of 170 µg/g for calprotectin had a sensitivity of 83% and a specificity of 93% to predict a risk of clinical recurrence, while a cutoff value of 140 µg/g for lactoferrin had a sensitivity of 67% and a specificity of 71%. CONCLUSIONS: Both calprotectin and lactoferrin levels correlate well with endoscopic activity after ileocolonic resection for CD. Calprotectin and lactoferrin could be clinically relevant biomarkers for predicting postoperative recurrence. Further well-designed large trials should strengthen the findings of the present investigation.

IL-10 deficiency leads to somatic mutations in a model of IBD.

Individuals with inflammatory bowel disease (IBD) are at increased risk of developing gastrointestinal cancer. Here, we have tested the possibility that chronic inflammation could trigger mutations. For this, we have used IL-10-deficient (IL-10-/-) mice, which spontaneously develop intestinal inflammation, in combination with a transgenic gpt gene and red/gam gene (gpt+IL-10-/-), which is a well-characterized mutation reporter locus. The total mutation frequency in the colon of gpt+IL-10-/- mice was about five times higher than that in normal gpt+IL-10+/+ mice. In the particular case of G:C to A:T transitions, the frequency of mutations in gpt+IL-10-/- mice was 4.1 times higher than that in control mice. Interestingly, the frequency of small deletions and insertions was also strikingly increased (approximately 10 times). The majority of the deletion or insertion mutations were observed in the monotonous base runs or adjacent repeats of short tandem sequences. In contrast, the frequency of large deletions, detected by loss of the Spi marker present in the red/gam transgene, was similar among the mouse strains. Finally, as a control, the mutation frequency in non-inflamed tissues, such as the liver, were similar between gpt+IL-10-/- mice and gpt+IL-10+/+ mice. Our data demonstrate that the chronic inflammatory environment in the colon promotes the generation of mutations.

IL-12 p40 prevents the development of chronic enterocolitis in IL-10-deficient mice.

T-helper-1 (Th1) cytokines play an important role in Crohn's disease, and interleukin-12 (IL-12), which is composed of two subunits, p40 and p35, drives Th1 differentiation. In previous reports, IL-12 p40 was shown to prevent IL-12 from binding to the receptor. We demonstrate here the effect of IL-12 p40 overexpression in intestinal epithelia on enterocolitis mediated by Th1 cells in IL-10-deficient (IL-10(-/-)) mice on a C57BL/6J background. IL-10 deficient (IL-10(-/-))/T3b-IL-12 p40+ (IL-12 p40+) mice and IL-10(-/-)/T3b-IL-12 p40- (IL-12 p40-) mice were generated by crossing T3b-IL-12 p40 transgenic mice and IL-10(-/-) mice. At 8 weeks of age, IL-12 p40+ mice did not show any clinical manifestations of colitis. The colon length of IL-12 p40- mice became shorter than that of IL-12 p40+ mice. The histological score of IL-12 p40+ mice was lower. Interferon-gamma (IFN-gamma) production was suppressed in both the mesenteric lymph node cell culture and colon tissue culture of IL-12 p40+ mice. There was no significant difference in IL-4 production and tumor necrosis factor-alpha (TNF-alpha) production between the two groups. These results show that overexpression of IL-12 p40 in intestinal epithelia prevents enterocolitis in IL-10(-/-) mice by suppressing IFN-gamma production, and suggest a potential clinical application of IL-12 p40 for Crohn's disease. Furthermore, these results also suggest that local gene transduction in the intestinal epithelium may be a potent therapeutic approach for Crohn's disease.

Multiparameter analysis for discreet differential diagnosis of mucosa-associated lymphoid tissue lymphoma in the intestine.

BACKGROUND: The diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma in the intestine is occasionally difficult from histological examination on small biopsy specimens obtained by endoscopy. This study focused on unusual cases of reactive lymphoproliferative disorders in the intestine in order to make a differential diagnosis of MALT lymphoma. MATERIALS AND METHODS: Five patients were examined with regards to clinical symptoms, endoscopic findings and multiparameter analysis (the morphological examination using routine hematoxylin and eosin staining by light microscopy, immunophenotyping by flow cytometry (FCM), immunohistochemistry and genotyping of extracted DNA). RESULTS: All cases showed an aggregation of lymphocytes and one case showed similar features to lymphoepithelial lesions. Analyses of FCM and genetic rearrangements denied the monoclonality in all cases. Consequently, we considered that all cases should be diagnosed as reactive lymphoid hyperplasia and inflammatory change. CONCLUSION: Multiparameter analysis is useful in making an exact diagnosis of MALT lymphoma and therefore contributes to prevent unnecessary overtreatment.

Panniculitis of the descending colon caused by enterocolic phlebitis: a case report.

A 73-year-old male was referred to our hospital for abdominal pain, diarrhea and general fatigue lasting for 3 weeks. Physical examination of the abdomen revealed a firm mass in the left abdominal region. Computed tomography revealed a mass around the descending colon. Colonoscopy and barium enema revealed poor extensibility of the lumen with edematous mucosa, and narrowing of the descending colon with rugged mucosal surface. Because of the clinical symptoms and findings, the patient was diagnosed clinically as suffering from panniculitis of the descending colon. He underwent the left hemi-colectomy with side-to-side colo-colostomy after making of a loop ileostomy. Histological analysis of the resected colon showed an infiltration of inflammatory cells, predominantly lymphocytes, into veins and venules of the submucosa, muscularis propria and fat tissue of the colonic mesentery, with an involvement of all layers of the vessel wall. Arteries were escaped from inflammatory changes. The histopathological diagnosis of enterocolic phlebitis and venulitis was made because of these findings.

Photodynamic therapy of intestinal tumors with mono-L-aspartyl chlorin e6 (NPe6): a basic study.

BACKGROUND: To clarify the usefulness of the second-generation photosensitizer, mono-L-aspartyl chlorin e6 (NPe6), we examined the possibility of photodynamic diagnosis and photodynamic therapy for intestinal tumors in a mouse model. MATERIALS AND METHODS: NPe6 was intravenously administered to the tumor-bearing mice through the tail vein. The intestinal tumor sites were irradiated with a 664-nm diode laser at constant intervals after the administration of photosensitizers. The tumors were excised and fluorescence was observed in frozen sections by microscope. RESULTS: We observed the fluorescent image and calculated that the mean fluorescence intensity was significantly higher in the tumors than the normal mucosa during 6 hours (p < 0.05). The fluorescence of NPe6 was chiefly accumulated in the intestinal tumors as red fluorescence on the fluorescent microphotographic image. CONCLUSION: We conclude that NPe6 may be a valuable photosensitizer for the photodynamic diagnosis and photodynamic therapy of intestinal tumors.