Smoking in inflammatory bowel diseases: Good, bad or ugly?

Smoking is an important environmental factor in inflammatory bowel disease (IBD), having different effects in ulcerative colitis (UC) and Crohn’s disease (CD). A recent meta-analysis partially confirmed previous findings that smoking was found to be protective against ulcerative colitis and, after onset of the disease, might improve its course, decreasing the need for colectomy. However, smoking increases the risk of developing Crohn’s disease and worsens its course, increasing the need for steroids, immunosuppressants and re-operations. Smoking cessation aggravates ulcerative colitis and improves Crohn’s disease. Data are however, largely conflictive as well as the potential mechanisms involved in this dual relationship are still unknown. In this review article, the authors review the role of smoking in inflammatory bowel diseases

Factors affecting pouch-related outcomes after restorative proctocolectomy.

PURPOSES: Restorative proctocolectomy (RPC) with ileal pouch anal anastomosis (IPAA) is the procedure of choice for patients with familial adenomatous polyposis (FAP) and ulcerative colitis (UC) despite morbidities that can lead to pouch failure. We aimed to identify factors associated with pouch-related morbidities. METHODS: A retrospective analysis of patients who underwent RPC with IPAA was performed. To investigate the factors associated with pouch-related morbidities, patients' preoperative demographic and clinical factors, and intraoperative factors were included in the analysis. RESULTS: A total of 49 patients with UC, FAP, and colorectal cancer were included. Twenty patients (40.8%) experienced leakage-related, functional, and/or pouchitis-related morbidities. Patients with American Society of Anesthesiologists (ASA) grade 2 or 3 had a higher risk of functional morbidity than those with grade 1. Intraoperative blood loss exceeding 300.0 mL was associated with an increased risk of pouchitis-related morbidity. CONCLUSIONS: Our study demonstrated associations of higher ASA grade and increased intraoperative blood loss with poor functional outcomes and pouchitis, respectively.ope

A comprehensive review of inflammatory bowel disease focusing on surgical management

The two main diseases of inflammatory bowel disease are Crohn's disease and ulcerative colitis. The pathogenesis of inflammatory disease is that abnormal intestinal inflammations occur in genetically susceptible individuals according to various environmental factors. The consequent process results in inflammatory bowel disease. Medical treatment consists of the induction of remission in the acute phase of the disease and the maintenance of remission. Patients with Crohn's disease finally need surgical treatment in 70% of the cases. The main surgical options for Crohn's disease are divided into two surgical procedures. The first is strictureplasty, which can prevent short bowel syndrome. The second is resection of the involved intestinal segment. Simultaneous medico-surgical treatment can be a good treatment strategy. Ulcerative colitis is a diffuse nonspecific inflammatory disease that involves the colon and the rectum. Patients with ulcerative colitis need surgical treatment in 30% of the cases despite proper medical treatment. The reasons for surgical treatment are various, from life-threatening complications to growth retardation. The total proctocolectomy (TPC) with an ileal pouch anal anastomosis (IPAA) is the most common procedure for the surgical treatment of ulcerative colitis. Medical treatment for ulcerative colitis after a TPC with an IPAA is usually not necessary.ope

Differentielle Induzierung der Ausschüttung pro- und anti-inflammatorischer Zytokine durch verschiedene probiotische Bakterien

Das Ziel der vorliegenden Arbeit war, zu untersuchen, ob periphere mononukleäre Blutzellen (PBMNC) durch Zelltrümmer oder Zellextrakte verschiedener Probiotika-Stämme zur Ausschüttung pro- und anti-inflammatorischer Zytokine stimuliert werden können und ob dieser Effekt für alle untersuchten Probiotikaspezies ähnlich oder speziesspezifisch unterschiedlich ist. Drei Stämme von Bifidobakterien, vier Stämme aus der Familie der Lakto¬bakterien und E. coli Nissle wurden mittels Ultraschall zerstört und durch Zentrifugation in Zelltrümmer und Zellextrakte aufgetrennt. PBMNC von gesunden Blutspendern wurden nach dem Dichtegradienten aufgetrennt und für 36 h entweder mit den Zelltrümmern oder dem Zellextrakt der einzelnen Probiotika-Spezies in Konzentrationen von 102 bis 108 CFU/ml inkubiert. Die Überstände wurden abgenommen und mittels ELISA Interleukin (IL)-10, Interleukin (IL)-1β und Tumornekrosefaktor (TNF)-α gemessen. Abhängig von der Familie der Probiotika zeigten die einzelnen Stämme unterschiedliche Stimulationsmuster. Mit Ausnahme von L. casei wies der Zellextrakt von Bifidobakterien und Laktobakterien eine geringere Stimulationskapazität auf als die Zelltrümmer. Hingegen zeigten Zellextrakt und Zelltrümmer von E. coli Nissle vergleichbare und insgesamt signifikant größere Stimulationskapazitäten als Bifidobakterien und Lakto¬bakterien. Die höchste relative Stimulationskapazität für das anti-inflammatorische Zytokin IL-10 zeigte E. coli Nissle. Die Inkubation probiotischer Spezies, die sich in klinischen Untersuchungen entzündlicher Darmerkrankungen als erfolgversprechend erwiesen haben, mit immunkompetenten Zellen führt zu speziesspezifischen Reaktionen. Es konnte eine hohe IL-10-Ausschüttung nach Stimulation mit Zelltrümmern von Bifidobakterien und E. coli Nissle nachgewiesen werden. Diese Ergebnisse stimmen überein mit positiven Effekten von Bifidobakterien und E. coli Nissle in klinischen Studien zu chronisch entzündlichen Darmerkrankungen im Vergleich zu negativen Ergebnissen in Verbindung mit Laktobakterien

Clinical and laboratory studies of the bacterial pathogenesis and management of Pouchitis

20-50% of patients develop pouchitis following restorative proctocolectomy for ulcerative colitis (UC). Pre-pouch ileitis (PPI) also develops in some of these patients. Bacteria are implicated in the pathogenesis of pouchitis and antibiotics are the mainstay of treatment. Studies were performed to examine the role of bacteria in the pathogenesis of this disease and to develop new treatment. Further studies examined the prevalence and implications of PPI and the efficacy and complications associated with maintenance antibiotic therapy. 16s rRNA sequencing demonstrated an increase in Proteobacteria and a reduction in Bacteroidetes in the UC compared with the familial adenomatous polyposis (FAP) cohort, but only limited differences between the UC non-pouchitis and pouchitis groups. We were unable to identify an individual species or phylotype specifically associated with pouchitis. Treatment with elemental diet produced a symptomatic improvement in 71% of chronic pouchitis patients but none entered clinical remission. Patients with PPI were identified, the prevalence, symptoms and short term outcomes of this group were studied. PPI was identified in 5.7% of patients with UC. All patients had associated pouchitis but not all were symptomatic. PPI was not associated with reclassification to Crohn’s disease. A subgroup of patients with symptomatic pre-pouch ileitis were treated with combination antibiotic therapy and 86% entered remission. Faecal samples from patients with antibiotic resistant pouchitis were grown on agar and sensitivity patterns identified. Following guided antibiotic therapy 80% of patients entered remission. Stool analysis also identified the presence of extended spectrum beta-lactamase (ESBL) resistant coliforms in 35% of patients with chronic pouchitis. Not all were symptomatic. PPI was associated with an increased risk of ESBL. Patients treated with maintenance antibiotic therapy were identified. Pre-pouch ileitis was associated with an increased risk of relapse. Reported side effects were rare and treatment was associated with an improved quality of life

Studies of the aetiopathogenesis of pouchitis

The ileal pouch offers a unique opportunity to study the inter-relationships between the gut microbiota, barrier function and host immune responses. Intestinal dendritic cells (DC) are pivotal in the maintenance of gut immune homeostasis. Impaired barrier function due to altered cell to cell junctions, enables interactions between the microbiota and host immune responses prior to the onset of inflammation and epithelial damage. The role of innate immune factors in pouchitis remains unclear. We performed cross sectional and longitudinal studies of patients following restorative proctocolectomy and assessed DC and tight junction protein (TJP) characteristics in the ileal pouch. Increased expression of the “pore-forming” claudin 2 was an early event in the development of pouch inflammation and aberrant DC expression of gut homing markers was characterised in the ileum and ileal pouch of ulcerative colitis patients without inflammation. DC phenotype in pouchitis suggested an activated innate immune response to microbial signals. Intestinal immune responses may be manipulated by modification of the gut microbiota. An emerging approach is transplantation of the entire “organ” of the gut microbiota. Effects of faecal microbiota transplantation (FMT) on recipient microbiota and immune responses in inflammatory bowel diseases are unknown. A single nasogastrically delivered FMT from a healthy donor to patients with chronic pouchitis, resulted in some shift in the composition of the microbiota, with specific changes in the abundance of species suggestive of a “healthier” pouch microbiota. However, microbiota engraftment success varied greatly between recipients and regardless of engraftment success, FMT did not result in immunological response or clinical efficacy. In conclusion, aberrant DC and TJP characteristics are associated with inflammation of the ileal pouch. Manipulation of the microbiota by FMT may be one means of modifying DC and TJP expression in the ileal pouch. However, these factors were not influenced by a single nasogastrically delivered FMT.Open Acces

Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model.

BACKGROUND: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients' quality of life. The burden for the NHS is substantial. OBJECTIVES: To evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities. DATA SOURCES: Peer-reviewed publications, European Public Assessment Reports and manufacturers' submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals. REVIEW METHODS: A systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model. RESULTS: Ten randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade(®), Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira(®), AbbVie) or golimumab (GOL) (Simponi(®), MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8-32 and 32-52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8-32 weeks and GOL 50 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32-52 weeks was significant. The greatest effects were associated with GOL (at 8-32 weeks) and ADA (at 32-52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained. LIMITATIONS: The health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review. CONCLUSIONS: Adult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006883. FUNDING: The National Institute for Health Research Health Technology Assessment programme