Fecal Calprotectin Test Performed at Home: A Prospective Study of Pediatric Patients With Inflammatory Bowel Disease.

OBJECTIVES: Measuring fecal calprotectin (FC) in a laboratory is time-consuming and that is why home tests have been developed. We studied the use of an FC home test in pediatric patients with inflammatory bowel disease (PIBD) in real-life settings. METHODS: The patients were asked to perform the IBDoc FC home test monthly for 6 months and to report their clinical disease activity at testing. Clinical decision-making, however, was guided by routine FC enzyme-linked immunosorbent assay (ELISA) for patients with raised IBDoc values. Spare frozen samples were analyzed using ELISA and IBDoc in the laboratory. The participants completed a questionnaire about FC testing at the start and end of the study. RESULTS: Of the 52 patients, 35 (67%) ages 5 to 18 years completed the study, and 197 home tests were performed. Of these, 15% failed, mainly because of technical reasons. Just under half of the patients (47%) considered home testing comparable or superior to routine testing. In contrast, the parents were unsatisfied (61%), mostly because the IBDoc results were significantly different from ELISA and they found the phone application difficult to handle but whenever the IBDoc was performed by a laboratory professional it was comparable with ELISA, suggesting that practical issues hampered home testing. Despite their reservations, more than 80% of parents felt that home testing would improve disease management. CONCLUSIONS: PIBD patients and their families were interested in FC home monitoring and willing to adopt testing as a part of their disease management, but this approach requires thorough guidance.

Long-term outcomes after elective ileocecal resection in children with active localized Crohn's disease--a multicenter European study.

PURPOSE: The aim of this study was to investigate the therapeutic role of an elective ileocecal resection in children with active localized Crohn's disease. METHODS: This was a retrospective multicenter study which included five European referral centers which included all children with Crohn's disease who underwent ileocecal surgery from 2000 to 2011 and had a minimum of 12 months follow-up. RESULTS: Altogether 68 patients fulfilled inclusion criteria. Median age at diagnosis was 13.7 years (6.6-17.9 years) and at surgery 15.2 years (8.6-18.5 years). Median duration of postoperative clinical remission was 20 months (3-95 months). Overall 54 patients (79.4%) were in remission one year after surgery and 38 (55.9%) during the total postsurgical follow up (median 30 months; range 12-95 months). Z score height for age significantly improved postoperatively in children who were at the time of surgery younger than 16 years of age (mean difference 0.232 SD; p=0.029). Cox proportional hazard regression model failed to indicate risk factors associated with postsurgical relapse. CONCLUSION: Elective ileocecal resection is a valid treatment option which should be considered in a subset of pediatric patients with localized Crohn's disease with the aim of achieving clinical remission and to improve growth.

Treatment of complex perianal fistulas with seton and infliximab in adolescents with Crohn's disease.

BACKGROUND AND AIMS: Treatment of complex perianal fistulas associated with Crohn's disease is challenging. In adults, seton drainage combined with infliximab therapy has proven to be more effective than either one alone. Results following such treatment among pediatric patients have not been reported previously. The aim of this study was to describe outcomes after combined seton and infliximab treatment for complex perianal fistulas in adolescents with Crohn's disease. METHODS: We performed a retrospective medical record review of all consecutive Crohn's disease patients treated for perianal fistulas with seton drainage and infliximab between 2007 and 2013 (n=13). A follow-up interview was conducted at median of two years. RESULTS: Median age at fistula diagnosis was 14years. Following seton placement in fistula tracks, infliximab induction was administered at weeks 0, 2, and 6 and maintenance therapy at 8-week intervals. Over 90% responded to seton drainage and infliximab induction. Final fistula response was obtained at median of 8weeks, being complete in 77% and partial in 15%. Setons were kept in place for median of 8months. Fistulas recurred in 23% over a year after the final response. At last follow-up, 85% still had a response and 70% were free from perianal symptoms. Most were still on anti-TNF-α therapy, but one third had switched to adalimumab. Patients' anorectal function was well preserved and overall satisfaction with the treatment was high. CONCLUSIONS: The results suggest that combining seton drainage with infliximab therapy improves the perianal fistula response rates in pediatric patients.

Low trypsinogen-1 expression in pediatric ulcerative colitis patients who undergo surgery.

AIM: To investigate whether matrix metalloproteinases-9 (MMP-9) or trypsinogens could serve as histological markers for an aggressive disease course in pediatric ulcerative colitis (UC). METHODS: We identified 24 patients with pediatric onset (≤ 16 years) UC who had undergone surgery during childhood/adolescence a median of 2.1 years (range 0.1-7.4 years) after the diagnosis (between 1990 and 2008) in Children's Hospital, Helsinki, Finland. We also identified 27 conservatively treated UC patients and matched them based on their age at the time of diagnosis and follow-up at a median of 6 years (range 3-11 years) to serve as disease controls. Twenty children for whom inflammatory bowel disease (IBD) had been excluded as a result of endoscopy served as non-IBD controls. Colon biopsies taken by diagnostic endoscopy before the onset of therapy were stained using immunohistochemistry to study the expression of MMP-9, trypsinogen-1 (Tryp-1), Tryp-2, and a trypsin inhibitor (TATI). The profiles of these proteases and inhibitor at diagnosis were compared between the surgery group, the conservatively treated UC patients and the non-IBD controls. RESULTS: The proportions of Tryp-1 and Tryp-2 positive samples in the colon epithelium and in the inflammatory cells of the colon stroma were comparable between the studied groups at diagnosis. Interestingly, the immunopositivity of Tryp-1 (median 1; range 0-3) was significantly lower in the epithelium of the colon in the pediatric UC patients undergoing surgery when compared to that of the conservatively treated UC patients (median 2; range 0-3; P = 0.03) and non-IBD controls (median 2; range 0-3; P = 0.04). For Tryp-2, there was no such difference. In the inflammatory cells of the colon stroma, the immunopositivities of Tryp-1 and Tryp-2 were comparable between the studied groups at diagnosis. Also, the proportion of samples positive for TATI, as well as the immunopositivity, was comparable between the studied groups in the colon epithelium. In the stromal inflammatory cells of the colon, TATI was not detected. In UC patients, there were significantly more MMP-9 positive samples and a higher immunopositivity in the stromal inflammatory cells of the colon when compared to the samples from the non-IBD patients (P = 0.006 and P = 0.002, respectively); the immunopositivity correlated with the histological grade of inflammation (95%CI: 0.22-0.62; P = 0.0002), but not with the other markers of active disease. There were no differences in the immunopositivity or in the proportions of MMP-9 positive samples when examined by epithelial staining. The staining profiles in the ileal biopsies were comparable between the studied groups for all of the studied markers. CONCLUSION: For pediatric UC patients who require surgery, the immunopositivity of Tryp-1 at diagnosis is lower when compared to that of patients with a more benign disease course.

Long-term outcomes after surgery on pediatric patients with Crohn disease.

OBJECTIVE: Of pediatric patients with Crohn disease, 20% to 30% undergo surgery within 10 years. Although disease relapses and reoperations are common, long-term functional outcomes and quality of life (QoL) are unclear. METHODS: In 2010, we reviewed the hospital records of all pediatric patients with CD who had undergone intestinal resections during childhood in 2 major tertiary care hospitals between 1985 and 2008 and mailed out questionnaires that asked about health outcomes and QoL. We compared the QoL of the patients and a group of matched controls randomly chosen from the Population Register Centre. RESULTS: In total, 36 children had undergone bowel resection a median of 10 years earlier and had at least 2 years of follow-up. Disease activation (verified at endoscopy) requiring medical or surgical treatment occurred in 94% (median 1.8 years after primary resection). At least 1 surgical complication occurred in 77%, and 54% underwent re-resection. The patients reported a median stool frequency of 3 stools during the day and zero at night, with 33% being totally continent. Overall, 96% were completely or moderately satisfied with the outcome of the surgery. The QoL was comparable between the patients and controls, but school or work absences diminished the QoL of the patients. CONCLUSIONS: Surgery for pediatric-onset CD is risky even under expert care. Disease relapses and bowel re-resections are common during the first decade after primary surgery. In the long term, however, bowel function is acceptable and the QoL is comparable between patients and their peers.

Matrix metalloproteinases in the restorative proctocolectomy pouch of pediatric ulcerative colitis.

AIM: To investigate matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pouch mucosa of pediatric onset ulcerative colitis (UC). METHODS: In this cross-sectional study, 28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years (median) after proctocolectomy. Expression of MMPs-3, -7, -8, -9, -12 and -26 and TIMPs-1, -2 and -3 in samples was examined using immunohistochemichal methods, and another biopsy was used to evaluate the grade of histological inflammation. Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion, using a scale marking staining intensity as follows: 0 = less than 20 positive cells; 1 = 20-50 positive cells; 2 = 50-200 positive cells; 3 = over 20 positive cells. Fecal calprotectin and blood inflammatory markers [serum C-reactive protein (CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs. RESULTS: Of the 28 patients with pediatric onset UC, nine had not experienced pouchitis, whereas thirteen reported a single episode, and six had recurrent pouchitis (≥ 4 episodes). At the time of the study, six patients required metronidazole. In all of the others, the most recent episode of pouchitis had occurred over one month earlier, and none were on antibiotics. Only four samples depicted no sign of inflammation, and these were all from patients who had not had pouchitis. Two samples were too small to determine the grade of inflammation, but both had suffered pouchitis, the other recurrent. No sample depicted signs of colonic metaplasia. Most pouch samples showed expression of epithelial (e) and stromal (s) MMP-3 (e, n = 22; s, n = 20), MMP-7 (e, n = 28; s, n = 27), MMP-12 (e, n = 20; s, n =24), TIMP-2 (e, n = 23; s, n = 23) and MMP-3 (e, n = 23; s, n = 28) but MMP-8 (e, n = 0; s, n = 1), MMP-9 (e, n = 0; s, n = 9) and MMP-26 (e, n = 0; s, n = 3) and TIMP-1 (n = 0, both) were lacking. In samples with low grade of inflammatory activity, the epithelial MMP-3 and MMP-7 expression was increased (r = -0.614 and r = -0.472, respectively, P < 0.05 in both). MMPs and TIMPs did not correlate with the markers of inflammation, fecal calprotectin, erythrocyte sedimentation rate, or CRP, with the exception of patients with low fecal calprotectin (< 100 µg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMP- or TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes. Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP- or TIMP-expression. CONCLUSION: The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease, but inflammation cannot be classified as a reactivation of the disease.