• Biomarker
• Ulcerative colitis
• complication
• fecal calprotectin
• ileal pouch–anal anastomosis
• pouchitis

• biomarker
• ileal pouch-anal anastomosis
• inflammatory bowel disease
• pouchitis
• ulcerative colitis

• R01 DK123233 NIDDK NIH HHS
• R01 DK132038 NIDDK NIH HHS
• National Institutes of Health
• Crohn’s and Colitis Foundation
• Rainin Foundation
• Helmsley Charitable Trust

• Colorectal surgery
• Laparoscopic surgery
• Neuromuscular blockade reversal
• Sugammadex

Chronic inflammatory bowel disease (IBD) is a condition with multifactorial pathophysiology. To date, there is no permanent cure and the disease is primarily managed by immunosuppressive drugs; long-term use promotes serious side effects including increased risk malignancies. The current study aimed to target neutrophil-myeloperoxidase, a key contributor to the pathogenesis of IBD, through the use of AZD3241that inhibits extracellular myeloperoxidase. Experimental colitis was induced in C57BL/6 male mice by 2% dextran sodium sulfate in drinking water ad libitum over 9 days. Mice received either normal drinking water and peanut butter (control), 2% DSS in drinking water and peanut butter or 2% DSS in drinking water and AZD3241 (30 mg/kg) dispersed in peanut butter daily for 9 days. Administered AZD3241 attenuated body weight loss (10% p<0.05) and improved clinical score (9 fold p<0.05; a score comprising the time-dependent assessment of stool consistency and extent of rectal bleeding), loss of colonic crypts (p<0.001), preserved surface epithelium (p<0.001) and enhanced expression of the transcription factor Nrf-2 (regulator of antioxidants) and enhanced expression of the downstream antioxidant response element haeoxygenase-1 (HO-1) in the colon tissue. Also, the concentration of fecal hemoglobin and the myeloperoxidase specific oxidative damage biomarker 3-chlorotyrosine in the colon were significantly decreased in the presence of AZD3241. This latter result was consistent with AZD3241 inhibiting MPO activity in vitro. Overall, AZD3241 ameliorated the course and severity of experimental colitis through ameliorating MPO derived tissue damage and could be considered a potential therapeutic option, subject to further validation in chronic IBD models.

• dextran sodium sulfate
• host tissue damage
• inflammatory bowel disease
• neutrophil-myeloperoxidase
• pharmacologic inhibitor

• Fecal calprotectin
• Ileal pouch anal anastomosis
• Pouchitis
• Total proctocolectomy
• Ulcerative colitis

• IPAA
• carp
• ileoanal pouch
• pouchitis
• prebiotic
• probiotic
• prophylaxis
• surveillance

Fecal calprotectin (FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases (IBD). Many different methods of assessment have been developed and different cut-offs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome (IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn’s disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.

• Fecal calprotectin
• Inflammatory bowel diseases
• Crohn’s disease
• Ulcerative colitis
• Irritable bowel syndrome

• Biomarkers/analysis
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/drug therapy
• Colon/diagnostic imaging
• Colon/pathology
• Colonoscopy
• Crohn Disease/diagnosis
• Crohn Disease/drug therapy
• Diagnosis, Differential
• Feces/chemistry
• Gastrointestinal Agents/therapeutic use
• Humans
• Intestinal Mucosa/diagnostic imaging
• Intestinal Mucosa/pathology
• Irritable Bowel Syndrome/diagnosis
• Leukocyte L1 Antigen Complex/analysis
• Predictive Value of Tests
• Recurrence
• Reproducibility of Results
• Severity of Illness Index
• Treatment Outcome

• Biomarker
• C-reactive protein
• Crohn's disease
• Fecal calprotectin
• Inflammatory bowel disease
• Ulcerative colitis

• Bowel resection
• Endoscopy
• Inflammatory bowel disease
• Pediatrics
• Stool tests

• Biomarker
• Fecal calprotectin
• Inflammatory bowel disease
• Mucosal healing

• Biomarkers/analysis
• Feces/chemistry
• Humans
• Inflammation/diagnosis
• Inflammation/pathology
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/physiopathology
• Intestinal Mucosa/pathology
• Leukocyte L1 Antigen Complex/analysis
• Predictive Value of Tests
• Recurrence
• Reproducibility of Results

• Canadian Institutes of Health Research

The role of fecal lactoferrin and calprotectin has been extensively studied in many areas of inflammatory bowel disease (IBD) patients’ management. The post-operative setting in both Crohn’s disease (CD) and ulcerative colitis (UC) patients has been less investigated although few promising results come from small, cross-sectional studies. Therefore, the current post-operative management still requires endoscopy 6-12 mo after intestinal resection for CD in order to exclude endoscopic recurrence and plan the therapeutic strategy. In patients who underwent restorative proctocolectomy, endoscopy is required whenever symptoms includes the possibility of pouchitis. There is emerging evidence that fecal calprotectin and lactoferrin are useful surrogate markers of inflammation in the post-operative setting, they correlate with the presence and severity of endoscopic recurrence according to Rutgeerts’ score and possibly predict the subsequent clinical recurrence and response to therapy in CD patients. Similarly, fecal markers show a good correlation with the presence of pouchitis, as confirmed by endoscopy in operated UC patients. Fecal calprotectin seems to be able to predict the short-term development of pouchitis in asymptomatic patients and to vary according to response to medical treatment. The possibility of both fecal markers to used in the routine clinical practice for monitoring IBD patients in the post-operative setting should be confirmed in multicentric clinical trial with large sample set. An algorithm that can predict the optimal use and timing of fecal markers testing, the effective need and timing of endoscopy and the cost-effectiveness of these as a strategy of care would be of great interest.

• Calprotectin
• Lactoferrin
• Fecal markers
• Inflammatory bowel disease
• Post-operative
• Surgery
• Crohn’s disease
• Ulcerative colitis

Inflammatory bowel disease (IBD) and irritable bowel syndrome share many symptoms. While irritable bowel syndrome is a functional bowel disorder for which no specific treatment is available, the range of effective therapies for IBD is evolving rapidly. Accurate diagnosis of IBD is therefore essential. Clinical assessment, together with various imaging modalities and endoscopy, has been the mainstay of diagnosis for many years. Fecal biomarkers of gastrointestinal inflammation have appeared in the past decade, of which calprotectin, a neutrophil cytosolic protein, has been studied the most. Crohn’s disease and ulcerative colitis are chronic remitting and relapsing diseases, and objective assessment of disease activity and response to treatment are important. This review focuses on the use of fecal calprotectin measurements in the diagnosis and monitoring of patients with IBD.

• Crohn’s disease
• calprotectin
• inflammation
• inflammatory bowel disease
• ulcerative colitis

• Autologous intestinal reconstruction procedures
• Hirschsprung disease
• Intestinal failure
• Intestinal transplantation
• Short bowel syndrome

• fecal calprotectin
• ileal pouch-anal anastomosis
• matrix metalloprotease-9
• pouchitis
• ulcerative colitis

• Crohn’s disease
• fecal markers
• monitoring
• ulcerative colitis

• Crohn’s disease
• calprotectin
• inflammation
• inflammatory bowel disease
• lactoferrin
• ulcerative colitis

• Anti-TNF-α therapy
• Complex perianal fistulas
• Pediatric Crohn's disease
• Perianal Crohn's disease
• Seton drainage

• Hirschsprung disease
• Restorative proctocolectomy
• Total colonic aganglionosis

• Colonic Pouches
• Follow-Up Studies
• Hirschsprung Disease/surgery
• Humans
• Infant
• Infant, Newborn
• Male
• Patient Satisfaction/statistics & numerical data
• Postoperative Complications
• Proctocolectomy, Restorative/methods
• Retrospective Studies
• Treatment Outcome

In recent years the use of faecal and serologic biomarkers has been evaluated in the diagnosis and management of inflammatory bowel disease (IBD). Faecal calprotectin (FC) has been proposed as a surrogate marker for intestinal inflammation; elevated concentrations in IBD patients have been confirmed in numerous studies. Already available rapid calprotectin tests help to differentiate between IBD and irritable bowel syndrome. Faecal calprotectin greatly correlates with endoscopic activity scales and reflects the mucosal healing; thus in patients in clinical remission high levels of it correlate with increased risk of disease relapse in the following 12 months. Adapting the calprotectin assay as a screening test before colonoscopy enables a significant reduction in endoscopic procedures. ANCA/ASCA antibodies have been used in IBD diagnosis and to distinguish CD from ulcerative colitis (UC). Lactoferrin and S100A12 protein were also used to assess the disease activity. This review aims to present the actual potential of biomarker assays for faster diagnosis of IBD and their ability to monitor the disease course, predict exacerbations and improve the way IBD is managed.

• biomarkers
• calprotectin
• inflammatory bowel disease
• serology

The inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are chronic relapsing, remitting disorders. Diagnosis, along with assessment of disease activity and prognosis present challenges to managing clinicians. Faecal biomarkers, such as faecal calprotectin, are a non-invasive method which can be used to aid these decisions. Calprotectin is a calcium and zinc binding protein found in the cytosol of human neutrophils and macrophages. It is released extracellularly in times of cell stress or damage and can be detected within faeces and thus can be used as a sensitive marker of intestinal inflammation. Faecal calprotectin has been shown to be useful in the diagnosis of IBD, correlates with mucosal disease activity and can help to predict response to treatment or relapse. With growing evidence supporting its use, over the last decade this faecal biomarker has significantly changed the way IBD is managed.

• Faecal calprotectin
• Inflammatory bowel disease
• Crohn’s disease
• Ulcerative colitis
• Faecal biomarker

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.

• Children
• Matrix metalloproteinase 3
• Tissue inhibitor of matrix metalloproteinase 3
• Matrix metalloproteinase 7
• Pouchitis
• Ulcerative colitis