Established EUS-guided therapeutic interventions.

Over the three last decades, endosonography ultrasound (EUS) has evolved from a diagnostic tool to an interventional modality through cumulative advances in experience, knowledge, equipment, and devices. EUS-guided therapeutic procedures appear feasible and safe when performed in highly-experienced centers. This review covers the technical aspects, indications, and results of the most commonly performed procedures. Celiac plexus neurolysis and collection drainages are now well-established techniques and considered to be first-line treatments. Biliary and pancreatic EUS-guided drainages are, conversely, more challenging, and there is currently insufficient clinical evidence documenting their superiority over established practice. Well-designed prospective trials are thus needed in order to accurately assess this modality's risks and long-term outcomes compared to radiological or surgical techniques.

Impact of mucosal healing on long-term outcomes in ulcerative colitis treated with infliximab: a multicenter experience.

BACKGROUND: Mucosal healing can be achieved with infliximab (IFX). AIM: To assess the impact of mucosal healing on long-term outcomes in patients with ulcerative colitis (UC) when treated with infliximab (IFX) beyond 1 year. METHODS: All consecutive adult patients with refractory UC receiving maintenance treatment with IFX in five French referral centres were analysed retrospectively. Only patients who had endoscopic evaluation between 6 and 52 weeks following IFX initiation were included. According to their Mayo endoscopic sub-score, patients were categorised into mucosal healing (sub-score: 0-1) and no mucosal healing (2-3). Outcome measures were colectomy and IFX failure defined by drug withdrawal due to secondary failure among primary responders. RESULTS: Of the 63 patients (30 women; median age: 38 years), 30 (48%) achieved mucosal healing. The median follow-up duration was 27 (3-79) months. Colectomy-free survival rates at 12, 24 and 36 months were, respectively, 100%, 96% and 96% in patients with mucosal healing. The corresponding figures were, respectively, 80%, 65% and 65% in patients without mucosal healing (P = 0.004). By multivariate analysis, mucosal healing was the only factor associated with colectomy-free survival, with an odds ratio of 18.01 (95%CI: 1.58-204.92). IFX failure-free survival rates at 12, 24 and 36 months were, respectively, 76%, 69% and 64% in patients with mucosal healing, and 44%, 25% and 21% in those without mucosal healing (P = 0.003). CONCLUSION: Patients with refractory UC who achieved mucosal healing after IFX initiation had better long-term outcomes, with significantly less colectomy and less IFX failure.

Review article: the natural history of postoperative Crohn's disease recurrence.

BACKGROUND: Surgical resection of the diseased bowel in Crohn's disease is unfortunately not curative, and postoperative recurrence remains a problem in these patients. AIM: To review the rates of and risk factors for clinical and endoscopic recurrence in population-based studies, referral centres and randomised controlled trials. METHODS: We searched MEDLINE (source PUBMED, 1966 to September, 2011). RESULTS: In randomised controlled trials, clinical recurrence in the first year after surgery occurred in 10-38% of patients, whereas endoscopic recurrence in the first year was reported in 35-85% of patients. In population-based studies, approximately half of patients experienced clinical recurrence at 10 years. In referral centres, 48-93% of the patients had endoscopic lesions (Rutgeerts' score ≥1) in the neoterminal ileum within 1 year after surgery, whereas 20-37% had symptoms suggestive of clinical recurrence. Three years after surgery, the endoscopic postoperative recurrence rate increased to 85-100%, and symptomatic recurrence occurred in 34-86% of patients. Smoking is the strongest risk factor for postoperative recurrence, increasing by twofold, the risk of clinical recurrence. Prior intestinal resection, penetrating behaviour, perianal disease and extensive bowel disease (>50 cm) are established risk factors for postoperative recurrence. Risk factors for postoperative recurrence remain poorly defined in population-based cohorts. CONCLUSION: Endoscopic and clinical postoperative recurrence remains common in patients with Crohn's disease, and the identification of risk factors may allow targeted strategies to reduce this recurrence rate.

Inflammatory bowel disease and hepatitis B and C.

The risk of viral B and C hepatitis has long been considered to be increased in patients with inflammatory bowel disease (IBD). Blood transfusion and surgery have been identified as the two main risk factors, suggesting nosocomial transmission could be involved. However, recent epidemiologic surveys have found that prevalence in IBD patients is similar to or even lower than that in the general population. Part of the explanation of these recent data may lie in the application of protective measures against viral infection (hepatitis B virus [HBV] vaccination and hepatitis C virus [HCV]-free blood transfusions). Sometimes fatal viral reactivations have been reported in patients on immunosuppressive therapy. Two periods can be distinguished: a) during therapy, a rise in viremia associated with a decrease of immune-mediated hepatic lesions; b) after cessation of therapy, an immune rebound with a destruction of virus-infected hepatocytes. For HBV, preemptive strategy consisting of an antiviral analog is efficient in chronic HBs antigen carriers. For HCV, the impact of immunosuppressive drugs on the natural history is unclear. Most studies report improved comfort although no biopsies were performed before and after immunosuppressive treatment. Physicians managing IBD patients should be aware of the need for screening and institute preventive measures against B and C hepatitis.

Adalimumab for Crohn's disease with intolerance or lost response to infliximab: a 3-year single-centre experience.

BACKGROUND: Adalimumab is effective in inducing clinical remission in patients with Crohn's disease who lost response or became intolerant to infliximab. AIM: To evaluate long-term efficacy and safety of adalimumab as a second line therapy in luminal and fistulizing Crohn's disease. METHODS: We report our single-centre experience in 53 patients. We evaluated maintenance of clinical response defined as the absence of adverse events leading to drug withdrawal, no major abdominal surgery and no loss of clinical response in initial responders. Major abdominal surgery, steroid sparing, complete fistula closure and safety were also assessed. RESULTS: The probability of maintaining clinical response was 77.2%, 67.8% and 50.8% at 26, 52 and 130 weeks respectively. The probability of remaining major abdominal surgery-free was 82.3% at 26, 52 and 130 weeks. Complete fistula closure occurred in six of 10 patients, and eight of 10 patients were able to taper steroid therapy. Adverse events occurred in 31 patients (58.5%) leading to adalimumab withdrawal in nine patients (17%). CONCLUSION: Adalimumab therapy may be effective in the long term in both luminal and fistulizing Crohn's disease in infliximab-failure patients, half of patients maintaining clinical response and potentially avoiding major abdominal surgery in 80% of cases.

[Helminths and inflammatory bowel diseases]. / Helminthes et maladies inflammatoires chroniques intestinales.

The current etiologic model of inflammatory bowel diseases proposes a genetically predisposed host responding to a variety of environmental triggers by exhibiting an abnormal immune response to normal luminal flora. Crohn's disease is common in highly industrialized western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms. From this observation grew the hygiene hypothesis, which states that our failure to be exposed to previously common infectious agents alters the immune repertoire established in childhood. Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis. Crohn's disease involves over reactive T-helper (Th1) pathways, and helminths blunt Th1 responses, inducing production of Th2 cytokines. Helminths also induce regulatory T cells to maintain host mucosal homeostasis. Thus, there is an immunological basis to expect that exposure to helminths such as Trichuris suis will prove beneficial in Crohn's disease. Exposure to helminths may be effective in treating inflammatory bowel diseases and was well tolerated, according to the results of few studies. Its long-term safety remains unknown.

Long-term outcome of adalimumab therapy for ulcerative colitis with intolerance or lost response to infliximab: a single-centre experience.

BACKGROUND: Adalimumab may be effective in inducing remission in patients with mild-to-moderate ulcerative colitis who had secondary failure to infliximab. AIM: To evaluate long-term efficacy and safety of adalimumab in patients with ulcerative colitis who previously responded to infliximab, and then lost response or became intolerant. METHODS: We report our single-centre experience in 13 patients. The patients received a loading dose of 160 mg of adalimumab subcutaneously in week 0, followed by 80 mg at week 2 and then 40 mg every other week starting at week 4. The primary efficacy measure was the proportion of patients on adalimumab therapy during the study. RESULTS: Median duration of follow-up was 42 weeks (range, 10-100). The mean number of adalimumab infusions was 21 (range, 5-50). The probability of maintaining adalimumab was 92.3%, 84.6%, 60.6% and 32.5% at 1, 3, 6 and 23 months respectively. Six of 13 patients (46.2%) underwent colectomy during the study. No serious toxicities occurred in the study. CONCLUSION: Adalimumab is well-tolerated and may be effective in maintaining clinical remission in a subgroup of patients with ulcerative colitis and lost response or intolerance to infliximab, potentially avoiding colectomy in about half of the patients.