Obviously, there are still a lot of questions to be answered before MSCs can be fully accepted as a novel and safe therapy for fistulizing Crohn’s disease. 10. 1. Introduction Crohn’s disease (CD) is a complex disorder of uncertain etiology characterized by chronic recurrent inflammation of the bowel. The disease incidence in North America ranged from 3.1 to Haloperidol D4 20.2 cases per 100,000 persons per year in published epidemiological studies [1, 2]. Perianal fistulas occur in about 20% of patients with CD and are almost always classified as complex fistulas [3]. Parks et al. classified fistulas based on their anatomy of origin, route, and external opening into superficial, intersphincteric, transsphincteric, suprasphincteric, or extrasphincteric [4]. The American Gastroenterology Association (AGA) divided fistulas into simple and complex fistulas based on number of external opening, location, and associated Haloperidol D4 complications. Both are useful and common classification methods when referring to CD perianal fistula disease. The ideal outcome from treatment of these fistulas is usually complete closure with prevention of contamination and abscess formation. However, intensive medical and surgical therapy has only success rates ranging from 30 to 80%. In view of incomplete fistula closure, treatment strategies have shifted from remedy to reduction of fistula drainage and quality life improvement until more effective therapies become available. 2. Conventional and Biological Medical Treatments Antibiotics, immunosuppressive drugs such as thiopurines, oral tacrolimus, and anti-TNF alpha’s role in the management of fistulizing CD have been reported with variable success rates when used as single brokers or in combination (see Table 1). Antibiotics use in uncontrolled studies of fistulizing CD report symptom reduction but fail to result in fistula closure [5, 6]. There was no significant difference between antibiotics and placebo in achieving complete fistula closure or/and improvement of fistula in a small sampled, randomized, double blinded, placebo-control study [7]. Effectiveness of thiopurines, including 6-metacaptopirine and azathioprine, studied by Pearson et al., has been investigated in a meta-analysis of 5 controlled trials reporting complete fistula closure or reduction in fistula drainage in 54% of patients [8]. Multiple studies and randomized controlled trials showed that anti-TNF alpha treatments including infliximab, adalimumab, and certolizumab are superior to placebo in induction treatment and maintenance therapy for perianal fistulas Haloperidol D4 in CD [9C14]. However, development of antibodies against these brokers has been reported and can result in loss of clinical response Haloperidol D4 [15]. In addition, anti-TNF agents have been associated with opportunistic infections, serum sickness-like reaction, autoimmune disorders, and sepsis [16]. In a randomized control trial, although oral tacrolimus was effective in closure of 50% of CD fistulas, there was no difference in complete closure of all fistulas when compared to placebo [17]. Table 1 Summary of conventional and biological medical treatments of fistulizing CD and reported outcomes. = 0.002, = 0.02, resp.)ACCENT II study [10] infliximab versus placeboMaintenance of complete closure of draining fistula; 36% versus 19% (= 0.009) ?AdalimumabCHARM study [12] adalimumab versus placeboComplete fistula healing at 56?wks; 33% versus 13% ( 0.05)ADHERE study [13]23% fistula remission, 41% fistula improvement ?Certolizumab pegolSchreiber et al. [14] an RCT; certolizumab pegol versus placeboComplete closure at 26 weeks; 36% versus 17% (= 0.038) Open in a separate window 3. Surgical Options Fistulotomy with sphincterotomy is the favored management for simple fistulas that results in high remedy rates without fecal incontinence in non-CD fistulas. In CD fistulas with any Rabbit polyclonal to GST degree of diarrhea, seton placement, advancement flaps, and ligation of the intersphincteric fistula tract (LIFT) are surgical options that have higher recurrence rates in an attempt to avoid fistulotomy with sphincterotomy that could result in incontinence. Seton placement for chronic drainage does not remedy fistulas but limits recurring perianal sepsis and is the standard surgical option for CD fistulas that is meant to improve quality of life in patients living with chronic disease [18C22]. Advancement flaps have healing rates from 60 to 70% but have increased complications over seton drains [18, 23, 24]. Data regarding effectiveness of the LIFT procedure in CD patients are lacking [25C27]. Best practice guidelines recommend seton placement as the favored technique to allow continuous drainage [28, 29]. Current combined medical and surgical management is reported to have better Haloperidol D4 outcomes in the treatment of perianal fistulas in CD [30C32]..