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.

Fecal calprotectin mirrors inflammation of the distal ileum and bowel function after restorative proctocolectomy for pediatric-onset ulcerative colitis.

BACKGROUND: The goal was to cross-sectionally assess fecal calprotectin after restorative proctocolectomy for pediatric-onset ulcerative colitis (UC). METHODS: Fecal calprotectin, histology of the distal ileum, inflammation biochemistry, episodes of pouchitis, and bowel function were cross-sectionally determined at early adulthood in 32 patients who had undergone proctocolectomy with ileoanal anastomosis for UC at a mean (SD) age of 12.0 +/- 4.1 years. RESULTS: A total of 15 (47%) patients showed increased (>100 microg/g) fecal calprotectin (669 +/- 866 microg/g), although their serum C-reactive protein (5.2 +/- 3.8 mg/L), erythrocyte sedimentation rate (13 +/- 13 mm/h), and white blood cell count (6.7 +/- 1.7 E9/L) were normal or slightly elevated. Calprotectin correlated positively with the histological neutrophil count of the distal ileum (r = 0.715; P < 0.001), the frequency of pouchitis (r = 0.468; P < 0.01), and with the maximum daily frequency of bowel actions (r = 0.610; P < 0.001). Mean fecal calprotectin was 71 +/- 50 microg/g among patients with no history of pouchitis (n = 10), 290 +/- 131 microg/g among patients with a single episode of pouchitis (n = 15), and 832 +/- 422 microg/g among those with recurrent pouchitis (P = 0.019 between recurrent pouchitis and no pouchitis). Sensitivity, specificity, positive predictive value, and negative predictive value for fecal calprotectin concentration over 300 microg/g to detect recurrent pouchitis were 57%, 92%, 67%, and 89%, respectively. CONCLUSIONS: Neutrophilic inflammation of the distal ileum, as reflected by fecal calprotectin, is common after restorative proctocolectomy for pediatric-onset UC.

Sexual functions in adulthood after restorative proctocolectomy for paediatric onset ulcerative colitis.

BACKGROUND AND AIM: Proctocolectomy with straight or J-pouch ileoanal anastomosis is the standard surgical treatment (ST) for ulcerative colitis (UC) also in children. Pelvic dissection may damage structures essential for sexual functions (SF). We compared SF in adults with ST during childhood or adolescence with adults with medical treatment (MT). MATERIALS AND METHODS: Sixty-three sexually active patients (ST 25, males 8; MT 38, males 19) median age of 27 years (range 17-41) (ST) and 29 years (20-40) (MT) (P = NS) were included. UC was diagnosed 15 years (5.1-26) (ST) and 7.5 years (2-20) (MT) (P < 0.05) before. Median ages at and follow-up after ST was 13 years (5.0-19) and 13 years (4.4-22), respectively. In ST and MT groups the daily stooling frequency and the incidence of soiling were 6 (2-17) and 2 (1-12), and 13/25 (52%) and 3/38 (8%), respectively (P < 0.05). SF were assessed with a structured form. RESULTS: In ST and MT groups, 21/25 (84%) and 31/38 (82%) reported satisfactory SF and 17/25 (68%) and 28/38 (74%) enjoyable sex life (P = NS). Urinary and faecal incontinence disturbed SF in both ST and MT groups in 2/25 (8%) and 3/38 (8%) and 13/25 (52%) and 15/38 (39%) (P = NS in each). Faecal incontinence inversely correlated with sexual satisfaction in all patients (R range; 0.36-0.68, P < 0.05). No erectile problems occurred. One patient (MT) reported ejaculatory problems. In females, dysorgasmia and dyspareunia were reported by 1/17 (6%) and 6/17 (35%) (ST) and 1/19 (5%) and 11/19 (58%) (MT) (P = NS). With intention to conceive 2/5 females in ST and 2/3 in MT group became pregnant within 1 year (P = NS). Only 2/25 (8%) (ST) and 7/38 (18%) (MT) had received information of the effect of treatment on SF. CONCLUSION: Compared with adult CU patients with MT, SF in patients with ST for CU in childhood or adolescence were similar. ST at a young age does not seem to affect SF in adulthood. Faecal incontinency disturbed SF in MT and ST groups.

Long-term outcomes of restorative proctocolectomy in children with ulcerative colitis.

OBJECTIVE: Long-term outcomes of restorative proctocolectomy for pediatric-onset ulcerative colitis are unclear. METHODS: Questionnaires on health outcomes and quality of life were mailed to patients with childhood-onset ulcerative colitis who had undergone proctocolectomy with ileoanal anastomosis in 2 university hospitals between 1985 and 2005. Investigators not involved in the surgical management of the patients approached participants. Matched control children were randomly chosen from the Population Register Centre of Finland. RESULTS: Fifty-two (66%) patients and 117 (37%) controls responded. After a mean follow-up of 10 years, at least 1 surgical complication had occurred in 39 (75%) patients, and 28 (54%) had undergone reoperation. Only 1 failure of ileoanal anastomosis occurred. Ulcerative colitis had been reclassified as Crohn disease in 6 (12%) patients. Pouchitis occurred in 37 (73%) patients. The median stool frequency was 5 for day and 1 for night, but 46% used medication to control stool frequency. Nighttime soiling was reported by 56% of the patients. The mean overall quality-of-life score, the mean BMI (22 kg/m(2) for both), and the number of subjects (aged >20 years) with offspring (14% vs 15%) was similar to the population-based controls. CONCLUSIONS: Stool frequency after restorative proctocolectomy in children with ulcerative colitis is stable and comparable to those of adult patients. Although nighttime incontinence is common, general health status and overall quality of life are comparable to the normal population.