R2 정상완

Introduction  Perianal fistulas : ¼ of Crohn’s disease (CD)  physical and psychologic morbidity with a long-term risk of proctectomy  metronidazole, ciprofloxacin, 6-MP/azathioprine, cyclosporine, tacrolimus  Anti-TNF a agents (infliximab ), ACCENT II trial  superior in terms of fistula closure, fistula improvement, reduction in hospitalizations  fistula tracks persist with varying degrees of residual inflammation  recurrent fistulas and pelvic abscesses  Surgery  multiple procedures are often required with the risk of sphincter damage and fecal incontinence.

Introduction  Fibrin glue  activation of thrombin to form a fibrin clot  mechanically seals the fistula tract.  clot undergoes gradual fibrinolysis while promoting tissue-healing processes to obliterate permanently the fistula tract.  a simple procedure for the treatment of perianal fistulas, but the experience in CD is still scarce  We here report the results of the first controlled trial of fibrin glue in the treatment of perianal CD fistulas.

Methods  multicenter, open-label, randomized, controlled trial  at 12 sites (11 in France and 1 in Belgium)  November 2003 and September 2005  Exclusion  Treatment with an anti-TNF a agent or with cyclosporine or tacrolimus within the last 3 months  Presence of a perianal abscess defined as a cavity of more than 3 mm in diameter  Presence of anal or rectal stenosis  Surgery during the previous month (except seton removal)  Previous fibrin glue injection  Pregnancy.

Methods  Inclusion  ≥18 years old  CD confirmed by endoscopy and histology.  CDAI < 250  ≥ 1 perianal fistula (between anus or low rectum and per perineum, vulva or vagina), draining for ≥ 2 months  Setons, were removed at the time of inclusion.  Azathioprine, 6-MP, MTX, or thalidomide at stable dose for ≥ 3 months  Aminosalicylates at a stable dose for ≥ 1 month.  Oral corticosteroids at stable dose for ≥ 2 weeks

Methods - Methods - Study Treatment  By either a surgeon or a proctologist  Under anesthetic in gynecological position, a dilator was positioned in the anal canal, and the fistula tract was probed via the external openings.  The fibrin glue : a combination of human fibrinogen, factor XIII,plasminogen, thrombin and of bovine aprotinin  The glue was slowly discharged until glue was seen at the internal opening, to obtain a complete obstruction of the fistula tracts  Complex fistulas : with multiple tracts, fistulas with a large ulcer (5 mm) at the internal opening, and fistulas with ano- or rectovaginal tract.

Methods - Methods - Follow-up  Visits at weeks 4, 8, and 16.  Draining : from 0 (no draining) to 5 (passage of stools).  Perianal pain : from 0 (none) to 3 (severe).  Clinical remission : the absence of any draining by fistula openings, the absence of perianal pain, and the absence of perianal abscess.  Primary end point : clinical remission at week 8.  Secondary end points : clinical response at weeks 4 and 8 ( 50% of the fistula tracts without any draining by the external openings, the occurrence of perianal abcess, and adverse events)

Result

Primary end point

Secondary end points  Clinical improvement  at week 4 : 13 of the 32 (41%) in the fibrin glue group 11 of the 37 (30%) in the observation group  at week 8 : 16 of the 32 (50%) in the fibrin glue group 12 of 34 (35%) in the observation group  A perianal abscess  1 of the fibrin glue group vs 3 of the observation group.  Among the 31 patients of the observation group not in clinical remission at week 8, 20 were eligible and accepted to crossover to fibrin glue injection. Ten of the 19 patients (53%) examined at week 16 were in clinical remission.

Conclusion  Fibrin glue injection is a simple, effective, and well- tolerated therapeutic option for patients with Crohn’s disease and perianal fistula tracts.