We assessed the prevalence and the risk factors of endoscopic and clinical postoperative recurrence (POR) in the era of biologics and therapeutic intensification based on early endoscopic findings in Crohn’s disease (CD). From a prospectively maintained database, we consecutively enrolled all CD patients who underwent intestinal resection and anastomosis between 2011 and 2016 with colonoscopy at 6 months (6m) and follow-up >6 months. Endoscopic POR was defined as Rutgeerts’ Index (RI) ≥i2. Clinical POR was defined as recurrence of symptoms (HBI > 4) leading to hospitalisation or therapeutic intensification after exclusion of other causes of recurrent symptoms. Overall, 316 patients were included (median follow-up 31 months (range 16.0–45.3)): mean CD duration = 11.7 ± 10.8 years, 50.6% female, 11.7% smokers, 22.8% with perianal lesions and 37.6% with prior intestinal resection. The Montreal classification was: L1 = 35.8 %, L2 = 5.7% and L3 = 58.5%, and B1 = 6.3%, B2 = 48.1% and B3 = 45.6%. The rate of endoscopic POR at 6m was 35.8% (i0 = 50.9%, i1 = 13.3%, i2a = 7.0%, i2b = 13.3%, i3 = 8.2%,i4 = 7.3%). In multivariate analysis, >2 anti-TNF prior to surgery (OR = 3.4 [1.2–9.8], p = 0.026), resection length >30 cm (OR = 1.8 [1.1–3.0], p = 0.025) and surgery for refractoriness to medical therapy (OR = 8.6 [1.5–50.5], p = 0.017) were risk factors of endoscopic POR, while female gender (OR = 0.5 [0.3–0.8], p = 0.006), CD duration >10 years (OR = 0.5 [0.3–0.9], p = 0.049) and combination therapy with anti-TNF and immunosuppressive therapies (IS) (OR = 0.4 [0.2–0.8], p = 0.009) decreased this risk. The rate of clinical POR was 9.3% at 1 year and 24.4% at 2 years. In multivariate analysis, prior intestinal resection (HR = 1.6 [1.1–2.4], p = 0.041), >3 biologics before surgery (HR = 2.7 [1.1–6.5], p = 0.031) and RI≥i2 (HR = 2.5 [1.6–3.9], p < 0.0001) were associated with higher risk of clinical POR. Lower risk for clinical POR was found for CD duration >10 years (HR = 0.6 [0.4–0.9], p = 0.037) and post-op combination therapy (anti-TNF + IS) (HR = 0.5 [0.3–0.9], p = 0.028). In patients who did not receive anti-TNF to prevent endoscopic POR and who experienced endoscopic POR (RI ≥ i2) at 6m, starting combination therapy decreased the risk of clinical POR (HR = 0.4 [0.1–0.9], p < 0.05). In our referral centre, the prevalence of endoscopic POR was the lower than historical reporting, suggesting the positive impact of biological therapy. Combination therapy was the most effective approach to prevent and to treat endoscopic POR. This study also provided external validation of the RI (Figure 1). Kaplan Meier curve showing the value of the Rutgeerts’ index to predict clinical postoperative recurrence in Crohn’s disease despite the large use of biologics and a therapeutic intensification based on early endoscopic findings.
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Background/Aims Mesalazine is an effective drug for treating ulcerative colitis (UC), but causes allergic symptoms in a few cases. Therefore, the objective of this study was to evaluate the usefulness of the drug-induced lymphocyte stimulation test (DLST) for the diagnosis of mesalazine allergy. Methods Patients with UC treated with mesalazine with or without a history of associated adverse events (AEs) were enrolled at Kyorin University Hospital from July 2016 to April 2017. Results The DLST was performed in 104 patients with UC, of which 24 had a history of AEs due to mesalazine treatment. The control value of DLST was 337.4±296.3 counts per minute (cpm) in the AE+ group and 408.0±371.9 cpm in the AE− group. The measured value of DLST was 578.8±424.7 cpm in the AE+ group and 476.5±471.8 cpm in the AE− group. The stimulation index (SI) was 243.9%±291.1% in the AE+ group and 119.8%±53.0% in the AE− group. The SI value and DLST positivity were significantly higher in the AE+ group than in the AE− group (P=0.030 and P=0.029, respectively). The test sensitivity and specificity were 0.240 and 0.805, respectively, and the false-positive and false-negative rate was 0.195 and 0.760, respectively. Conclusions The DLST for mesalazine showed low sensitivity and high specificity, suggesting that it may be useful for the definitive diagnosis of allergy to mesalazine. Keywords: Mesalamine; Drug-induced lymphocyte stimulation test; Colitis, ulcerative
Background and Aims: Familial mediterranean fever (FMF), an autoinflammatory disease, is characterized by periodic fever and serositis. An MEFV gene mutation has been identified as the cause of FMF. Recently, patients with MEFV gene mutations and chronic gastrointestinal mucosal inflammation mimicking inflammatory bowel disease (IBD) have been reported. In this retrospective study, we analyzed the clinical characteristics of patients with IBD unclassified (IBDU) with MEFV gene mutations. Methods: MEFV gene analysis was performed on 8 patients with IBDU among 710 patients with IBD who had been treated at Kyorin University Hospital from April 2016 to December 2018. Clinical manifestations, endoscopic findings, and serological markers were also analyzed. Results: The average of the 8 patients with IBDU (3 men, 5 women) was 32.7 ± 6.4 years (range 26–76 years). Their symptoms comprised diarrhea (n = 8, 100%), hematochezia (n = 3, 37.5%), abdominal pain (n = 3, 37.5%), high fever (n = 2, 16.5%), and other periodic symptoms (n = 2, 16.5%). MEFV gene mutation was confirmed in 4/8 of these patients. Colonoscopy showed various mucosal lesions, rectal sparing, right side dominant colitis, pseudopolyposis, and granular protrusions. Colchicine was administered to 5 of the 8 patients (4 with and 1 without MEFV mutation) who were resistant to conventional treatment for ulcerative colitis. Clinical and endoscopic improvement was observed in all of 5 patients treated with colchicine. Conclusions: Some patients diagnosed as having IBDU have enterocolitis related to MEFV gene mutation and respond to colchicine therapy.
Faecal biomarkers are non-invasive markers of inflammation activity in patients with ulcerative colitis (UC) and reflect intestinal inflammation activity. However, whether disease extension affects the value of faecal biomarkers has not been fully investigated. In the present study, to identify the effect of disease extension on faecal biomarkers we assessed the correlation between faecal biomarkers and endoscopic activity in each inflammatory location type. We conducted a retrospective observational study. 108 UC patients from February 2017 to March 2018 in Kyorin University hospital who underwent faecal biomarkers test within 2 months of colonoscopy were studied. Faecal calprotectin level (FC), faecal lactoferrin level (FL) and faecal immunochemical test (FIT) were measured simultaneously in the same sample. We examined the correlation between Mayo Endoscopic Subscore (MES), and faecal biomarkers in inflammatory location of Montreal classification (proctitis, left sided colitis, total colitis). Correlation was analysed using the Spearman’s rank correlation index (SPSS). In all cases, all faecal biomarkers were correlated with MES (FC: ρ = 0.645, p < 0.001, FIT: ρ = 0.627, p < 0.001, FL: ρ = 0.646, p < 0.001). In proctitis, all faecal biomarkers were not correlated with MES (FC: ρ = 0.148, p = 0.613, FIT: ρ = 0.542, p < 0.045, FL: ρ = 0.342, p < 0.231). On the other hand, in left colitis and total colitis, all faecal biomarkers were correlated with MES (FC: ρ = 0.554, p < 0.001, FIT: ρ = 0.736, p < 0.001, FL: ρ = 0.567, p < 0.001 and FC: ρ = 0.741, p < 0.001, FIT: ρ = 0.563, p < 0.001, FL: ρ = 0.713, p < 0.001). The correlation coefficients of FC and FL were higher in pancolitis than in left sided colitis (Table 1). Spearman’s rank correlations between faecal biomarkers and MES by extension of inflammation. Spearman’s rank correlations between faecal biomarkers and MES by extension of inflammation. Faecal biomarkers showed correlation satisfactory in overall patients, except for in proctitis patients. These results suggested that value of faecal biomarkers is affected by extension of inflammation.
