Multimodal treatment of perianal fistulas in Crohn's disease: seton versus anti-TNF versus advancement plasty (PISA): study protocol for a randomized controlled trial.

BACKGROUND: Currently there is no guideline for the treatment of patients with Crohn's disease and high perianal fistulas. Most patients receive anti-TNF medication, but no long-term results of this expensive medication have been described, nor has its efficiency been compared to surgical strategies. With this study, we hope to provide treatment consensus for daily clinical practice with reduction in costs. METHODS/DESIGN: This is a multicentre, randomized controlled trial. Patients with Crohn's disease who are over 18 years of age, with newly diagnosed or recurrent active high perianal fistulas, with one internal opening and no anti-TNF usage in the past three months will be considered. Patients with proctitis, recto-vaginal fistulas or anal stenosis will be excluded. Prior to randomisation, an MRI and ileocolonoscopy are required. All treatment will start with seton placement and a course of antibiotics. Patients will then be randomised to: (1) chronic seton drainage (with oral 6-mercaptopurine (6MP)) for one year, (2) anti-TNF medication (with 6MP) for one year (seton removal after six weeks) or (3) advancement plasty after eight weeks of seton drainage (under four months anti-TNF and 6MP for one year). The primary outcome parameter is the number of patients needing fistula-related re-intervention(s). Secondary outcomes are the number of patients with closed fistulas (based on an evaluated MRI score) after 18 months, disease activity, quality of life and costs. DISCUSSION: The PISA trial is a multicentre, randomised controlled trial of patients with Crohn's disease and high perianal fistulas. With the comparison of three generally accepted treatment strategies, we will be able to comment on the efficiency of the various treatment strategies, with respect to several long-term outcome parameters. TRIAL REGISTRATION: Nederlands Trial Register identifier: NTR4137 (registered on 23 August 2013).

Strategies to improve clinical research in surgery through international collaboration.

More than 235 million patients undergo surgery every year worldwide, but less than 1% are enrolled in surgical clinical trials--few of which are international collaborations. Several levels of action are needed to improve this situation. International research collaborations in surgery between developed and developing countries could encourage capacity building and quality improvement, and mutually enhance care for patients with surgical disorders. Low-income and middle-income countries increasingly report much the same range of surgical diseases as do high-income countries (eg, cancer, cardiovascular disease, and the surgical sequelae of metabolic syndrome); collaboration is therefore of mutual interest. Large multinational trials that cross cultures and levels of socioeconomic development might have faster results and wider applicability than do single-country trials. Surgeons educated in research methods, and aided by research networks and trial centres, are needed to foster these international collaborations. Barriers to collaboration could be overcome by adoption of global strategies for regulation, health insurance, ethical approval, and indemnity coverage for doctors.