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Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness., Materials and Methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index <5 in Crohn's disease (CD) and Patient Simple Clinical Colitis Activity index <3 in ulcerative colitis (UC)., Results: Two-hundred forty-six patients (147 CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone ≥1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p < .0001 in both groups). Faecal-calprotectin decreased in CD (p < .0001) and in UC (p = .001), whereas CRP decreased in CD (p = .002) but not in UC (p = .11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48)., Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

Background: Real-life long-term data on infliximab treatment in ulcerative colitis are limited., Aim: To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined., Methods: A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant., Results: Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy., Conclusions: Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy., (© 2016 John Wiley & Sons Ltd.)

Objective: The medical treatment of ulcerative colitis (UC) has seen a change towards a more active attitude during recent years, including both the use of more traditional drugs as well as new biological substances. In this epidemiological study we have evaluated the results of modern treatment of UC in a population-based cohort of patients including all age groups, with regard to relapse rate, colectomy and IBD-associated mortality., Material and Methods: Patients diagnosed with UC in the Uppsala health care region in the middle of Sweden during 2005-2009 were included in the study. Out of 524 patients, 491 (93%) could be followed for five full years or until death., Results: Nineteen patients (3.9%) had died and two of these deaths could be attributed to UC (one postoperative death and one colonic carcinoma). The following drugs were used by the patients during the study period: 5-ASA (91%), systemic steroids (66%), immunomodulators (IMM), mainly thiopurines (26%) and anti-TNF (11%). During the observation period, 74% experienced at least one relapse and 5.3% were subjected to colectomy. Among patients <17 years at diagnosis, colectomy was performed in two (4.8%)., Conclusions: Five years after diagnosis of ulcerative colitis, 5.3% had been subjected to colectomy and two patients (0.38%) had died because of the disease.

The immunosurveillance theory argues that the immune system recognizes tumour-specific antigens expressed by transformed cells, which results in the destruction of cancer precursors before they become clinically manifest. As a model for the development of cancer, we set out to study premalignant lesions and immune responses in sentinel lymph nodes from patients with long-standing ulcerative colitis and progression of mucosal dysplasia. Mesenteric lymph nodes draining dysplastic and normal intestinal segments were identified by sentinel node technique during surgery in 13 patients with ulcerative colitis who were subjected to colectomy because of intestinal dysplasia. T cells were extracted from the lymph nodes and analysed by flow cytometry, and lymphocyte proliferation assays were set up in the presence of extracts from dysplastic and normal intestinal mucosa. Increase in CD4/CD8 ratio was observed in sentinel lymph nodes draining dysplastic epithelium compared to normal mucosa. The increase in CD4(+) T cells in relation to CD8(+) T cells correlated with the degree of dysplasia reflected by a significant increase in the ratio against low-grade dysplasia compared to indefinite dysplastic lesions. The T-cell response was specific to antigens from dysplastic epithelial lining as seen in proliferation assays. The observation suggests an important surveillance role for the immune system against premalignant intestinal lesions in patients with long-standing ulcerative colitis.

Patients with collagenous colitis have watery diarrhea and histopathologically thickened collagen layer with discrete signs of mucosal inflammation. Vascular endothelial growth factor (VEGF) is a potent angiogenic, mitogenic, permeability, and fibrosis enhancing peptide and it was studied by segmental perfusion and immunohistochemistry in patients and controls. The concentrations of VEGF were significantly increased in perfusates from both the descending colon and the rectum in patients compared to controls but this difference was not found in serum. Immunohistochemical staining showed expression of VEGF within colon epithelial cells, inflammatory cells, and fibroblasts in the lamina propria. The intensity of staining in the surface epithelium was not different between patients and controls but in the lamina propria the intensity was significantly higher among controls. Patients with collagenous colitis have increased colorectal mucosal secretion of VEGF, which may lead to albumin leakage and promote fibrosis with deposition of collagen.

Objectives: Collagenous colitis (CC), a condition of unknown ethiology and pathophysiology, is characterized by watery diarrhea and increased amounts of collagen in the colonic mucosa. Basic fibroblast growth factor (bFGF) is a potent multifunctional growth factor that stimulates proliferation and differentiation of fibroblasts that was recently detected in high intraluminal concentrations in patients with ulcerative colitis. In this study we examined the secretion and expression of bFGF in the colorectal mucosa of patients with CC., Methods: Ten CC patients and 10 control patients underwent colonoscope-based segmental perfusion of the descending colon and rectum. The concentrations of bFGF in perfusate and serum were determined by immunochemical methods, and the expression of bFGF was analyzed immunohistochemically in biopsy samples from colonic mucosa., Results: The median concentrations of bFGF in perfusates from the descending colon and rectum were increased 4-fold in CC patients compared with control patients. The median concentration of bFGF in serum was not significantly different in patients and controls. Immunohistochemical staining of bFGF was located in the colorectal epithelial cells and in exsudate on the luminal side of these cells. In the lamina propria, inflammatory cells and fibroblasts contained bFGF. There were no differences in the intensity of bFGF staining in surface epithelium or lamina propria between patients and controls., Conclusions: Local investigation of the colorectal mucosa seems to be crucial when studying the pathophysiology of CC. Increased colorectal mucosal secretion of bFGF in patients with CC may promote differentiation of fibroblasts and thereby lead to increased subepithelial collagen deposition.

The local release of human neutrophil lipocalin, considered to be highly specific for neutrophil granulocyte activation, and interleukin-8 and tumor necrosis factor-alpha were studied in 11 patients with distal ulcerative colitis and proctitis before and during treatment with steroid enemas. A rectal perfusion technique for sampling and specific immunoassays for analysis were used. In responders (N = 8) the concentrations of all proteins decreased during the study. There was a close correlation between human neutrophil lipocalin concentrations and treatment response. Tumor necrosis factor-alpha showed an initial decline in concentrations irrespective of treatment outcome and preceded the decline of human neutrophil lipocalin and interleukin-8. We conclude that decreased neutrophil degranulation is correlated with treatment outcome. Furthermore, an important role of tumor necrosis factor-alpha in the process of stimulating neutrophil activation and degranulation in ulcerative colitis is suggested.

There is an increased influx of activated eosinophils to the intestinal mucosa in active ulcerative colitis, and an increased release of eosinophil-derived proteins, such as ECP, has also been observed. These findings indicate that eosinophils may contribute to tissue damage and intestinal inflammation in this disease. The relative importance of different chemotactic factors and the impact of steroid treatment on their effect in active ulcerative colitis are not known. We measured the eosinophil chemotactic activity in perfusion fluids from 11 patients with ulcerative colitis before and after steroid treatment and from 7 control patients. The effect of neutralizing antibodies to IL-5 and -8, RANTES, eotaxin, MCP-3, TNF-alpha, GM-CSF was investigated. The chemotactic activity was higher in perfusion fluids from patients than from controls (P = 0.0043). Anti-IL-5 (P = 0.005) and -TNF-alpha (P = 0.017) inhibited the activity in perfusion fluids obtained before treatment. Steroid treatment prevented the effect of all antibodies but had no significant effect on the chemotactic activity. The chemotactic activity correlated with the levels of eosinophil granule proteins in the perfusion fluids. In conclusion, in ulcerative colitis, eosinophils are attracted to the intestinal tissue by chemotactic factors, of which IL-5 and TNF-alpha may be the most prominent steroid-sensitive ones. The steroid-insensitive chemotactic activities remain unidentified.

Objective: The pathophysiological role of neutrophil and eosinophil granulocytes in relation to steroid enema treatment was studied in patients with distal ulcerative colitis and proctitis., Methods: The rectal release of the neutrophil (myeloperoxidase, MPO), and eosinophil (eosinophilic cationic protein, ECP and eosinophil peroxidase, EPO) granule constituents were measured in 11 patients using intraluminal segmental perfusion of the rectum. The released amounts of MPO, ECP, and EPO in the perfusion fluids were determined by radioimmunoassays before and during prednisolone enema treatment and related to clinical, endoscopical, and histopathological data in addition to treatment outcome., Results: Clinical activity and particularly endoscopic activity correlated well with intraluminal MPO concentrations both before and during treatment. At the end of the study, eight of 11 patients fulfilled predefined response criteria; all responding patients had significant decrease of MPO concentrations (p < 0.01). This decline of MPO concentration was seen after 7 days of treatment (p < 0.05) in the response group and often occurred before clinical improvement. There was a nonsignificant trend toward a decrease in the concentrations of ECP and EPO at the end of treatment in responders.

Background: Restorative proctocolectomy is considered to be the procedure of choice in the operative treatment of ulcerative colitis. The aim of this study was to evaluate the functional outcome following operation and to identify possible predictive factors., Methods: Some 168 patients (median age 32 years, 102 men) with ulcerative colitis underwent restorative proctocolectomy. The functional outcome was evaluated by a symptom index created from a questionnaire at a median of 29 (13-123) months of follow-up. The records of these patients were reviewed, and preoperative, peroperative and postoperative variables were registered and related to outcome., Results: The response rate to the questionnaire was 155 (92 per cent) of 168. The symptom index was related to patients' overall assessment of outcome. In spite of a perceived good result many patients experienced a number of symptoms. Age over 50 years (P < 0.01), presence of extraintestinal manifestations (P < 0.05) and late complications, such as anastomotic stricture (P < 0.05), pouchitis (P < 0.01) and anal pain (P < 0.05), were related to a less favourable outcome., Conclusion: While preoperative data may help in selecting patients suitable for restorative proctocolectomy, prevention of late complications seems most important in improving the functional outcome.

Background: Basic fibroblast growth factor (bFGF) promotes angiogenesis and several other biologic processes, including proliferation of mesenchymal cells and tumor progression. We investigated whether bFGF could be detected in the intraluminal secretion of the small intestine, sigmoid colon, and rectum in healthy individuals and in patients with ulcerative colitis., Methods: We used endoscopic perfusion techniques to obtain samples from well-defined intestinal segments. The perfusion fluid concentrations of bFGF, biochemical markers of inflammation, myeloperoxidase (MPO), interleukin-6 (IL-6), and permeability (albumin) were determined with immunochemical methods., Results: In the perfusion fluids the albumin concentration, which reflects passive diffusion, was less than 1% of the plasma concentration, whereas the intestinal concentration of bFGF was similar to that in plasma. Among healthy subjects the concentration of bFGF was eightfold higher in the jejunum and twofold higher in the rectum than in the sigmoid colon. The perfusion fluid from colorectal segments in patients with ulcerative colitis had a significantly higher mean concentration of bFGF than that from healthy individuals; an almost 10-fold difference was found in rectal segments. There were strong correlations between the concentration of bFGF and the concentrations of MPO and IL-6., Conclusions: The high concentrations of bFGF in the intestinal perfusion fluid reflect either a local synthesis or an active secretion of bFGF within the mucosa. The bFGF concentration differs in intestinal anatomic location and increases significantly in patients with ulcerative colitis in close relationship with biochemical markers of inflammation and permeability.