- Email: [email protected]
Surgisis Fistula Plug: The United States Experience
Surgisis Fistula Plug: The United States Experience Michael F. McGee, MD and Bradley Champagne, MD Anorectal fistulae are a heterogeneous group of disorders that can cause significant pain, social impairment, hygienic problems, and, rarely, sepsis. Surgery is the mainstay of treatment for anorectal fistulae, yet no one procedure is universally efficacious and safe. Simple fistulae can often be treated by simple fistulotomy, but complex fistulae present a more complicated scenario— effective surgical treatment options are compromised by increased risk of incontinence. Likewise, safe treatment alternatives have low risk of postoperative incontinence but low success rates. The Surgisis AFP appears to be an effective and safe treatment alternative for complex fistula, including Crohn’s fistula, based on initial reports. Semin Colon Rectal Surg 20:43-47 © 2009 Published by Elsevier Inc.
A
lthough anorectal fistulae are commonly encountered, treatment of this condition remains one of the most challenging and controversial topics in colorectal surgery. Perianal fistulous disease is responsible for a range of clinical effects ranging from minor pain and social hygienic embarrassment to frank sepsis and has vast implications in patient quality of life. Management of anorectal fistulae is encumbered by several individualized factors such as etiology, location, type, duration, as well as previously performed procedures and preoperative assessments of sphincter function. Surgery is the mainstay of treatment for anorectal fistulae,1 with the ultimate goal of draining local sepsis, eradicating the fistulous tract, and avoiding recurrence while preserving native sphincter function.2
Traditional Treatment of Anorectal Fistulae Since Parks and colleagues classified anorectal fistulae in 1976, surgical treatment has been predicated upon several points of conventional surgical wisdom.3 After drainage of acute abscess and sepsis, traditional surgical treatment begins with identification of internal and external openings of the fistulous tract.1 Over 90% of anorectal fistulae result from cryptoglandular abscess originating from the crypts of Morgagni,4,5 and most internal openings of the fistula reside around the anal glands surrounding the dentate line. Fistulae will then course on one of the four following paths: inter-
Case Medical Center, Cleveland, Ohio. Address reprint requests to: Bradley Champagne, MD, Case Medical Center, Surgery, 11100 Euclid Avenue, Cleveland, OH 44106. E-mail: Brad. [email protected]
1043-1489/09/$-see front matter © 2009 Published by Elsevier Inc. doi:10.1053/j.scrs.2008.10.008
sphincteric (45%), transphincteric (30%), suprasphincteric (20%), or extrasphincteric (5%) before finally arriving at a perianal external opening.3 Occasionally, small fistulae will be limited to submucosal planes. In addition to cryptoglandular fistulae, Crohn’s disease and iatrogenic surgical fistulae (eg, ileal pouch and rectovaginal fistulae) are other causes of fistulae that require specialized treatments. Following drainage of acute sepsis and identification of the fistula tract’s internal and external openings, a curative surgical procedure is typically performed. Unfortunately, no single surgical approach adequately addresses all types of anorectal fistulae.6 Countless surgical techniques have been described to treat anorectal fistulae depending on the location, severity, chronicity of the fistula, as well as a host of functional characteristics related to each patient. Traditionally, well-drained, low-lying simple intersphincteric fistulae are treated with simple fistulotomy. Fistulotomy is the centuries-old “gold standard”6 that involves laying open the fistula tract in entirety.1 Overall fistula recurrence following fistulotomy ranges from 0% to 21%, with high, although widely variable, rates of resultant incontinence (0%-82%).7-9 Anterior fistulae present a therapeutically challenging subgroup and convey higher rates of postfistulotomy incontinence due to the natural anatomical attenuation of the external sphincter muscle and perineal body, especially in women.4,5 For fistulae that traverse longer distances of sphincter, such as proximal high transphincteric, fistulotomy conveys high rates of postoperative incontinence and alternative surgical treatments are necessary. For these “complex” fistulae, cutting setons are used to slowly divide fistulous tissue tracts on the leading edge of the seton, while allowing healing to occur on the trailing edge, whereby preserving sphincter continuity and theoretically preserving sphincter function. Success rates 43
44 for cutting setons range from 82% to 100%; however, longterm incontinence rates can exceed 30%. In light of unacceptably high rates of long-term incontinence, several alternative treatments have been developed.10-12 Endoanal advancement flaps are attractive options employed to treat complex fistula. Following adequate drainage and identification of the fistulous tract, mucosal advancement flaps are raised adjacent to the internal opening to provide tissue coverage of tract opening and subsequently allow the tract to heal and close. A variety of techniques exist, and in experienced hands, have low recurrence rates (0%-36%) and tolerable incontinence rates ranging from 0% to 12.5%.13-15 Not all anorectal fistulae patients are candidates for mucosal flap advancement. Very high fistulae, for example, are technically challenging to treat with mucosal advancement flaps. Additionally, anal stenosis, active proctitis, and inflammatory bowel disease are relative contraindications due to high complication and failure rates.16 Last, success rates for mucosal advancement flap surgery outcomes are highly variable, likely indicating the importance of a surgeon’s expertise with these exacting procedures. In the era of minimally invasive surgery and the notion that “less is more,” recent introduction of synthetic biological materials has brought a bevy of new techniques to treat anorectal fistulae. A variety of Food and Drug Administration approved fibrin-based glue materials have been used to treat difficult fistulae. Fibrin glue injection through the fistula tract offers a minimally invasive and expeditious treatment whereby sparing sphincter division. Early success rates for difficult fistula rates approach 60%-70%17-23; however, long-term fistula recurrence approaches 69%-100%.21,24,25 Fibrin glue extravasation from within the fistula tract and failure to identify and completely fill all branches of the tract with glue are the putative explanations for long-term failure.26 Nonetheless, the noninvasive and safe treatment profile of fibrin glue renders it a reasonable first-line treatment despite the high failure rate.24 Similar glue experiences have been reported substituting polymerized bovine serum albumin and glutaraldehyde (BioGlue Surgical Adhesive; CryoLife, Inc, Kennesaw, GA).27 The controversy associated with fistula treatment techniques is rooted within the balance of the therapeutic index— highly efficacious techniques, such as fistulotomy, have unfavorably high rates of incontinence. Unfortunately, safer techniques, such as fibrin glue and advancement flaps, sacrifice fistula recurrence for lower rates of postoperative incontinence.
The Surgisis Anal Fistula Plug (AFP) In 2005, a biosynthetic plug of material was introduced by Cook Surgical for treatment of anorectal fistula. The plug is a configuration of their Food and Drug Administration approved material, Surgisis, which is derived from lyophilized porcine small intestinal submucosa. Surgisis is manufactured into sheets of varying size and thickness and has been applied to a host of surgical indications. Hernia repair (inguinal, ven-
M.F. McGee and B. Champagne tral, paraesophageal), urethral sling, and stapler line reinforcement with Surgisis are reported applications.28-31 The xenograft is resistant to infection, produces no giant cell foreign body reaction, and becomes repopulated with native host cell tissues within 12 weeks.32,33 The fistula plug technique, which tunnels the plug inside the fistula tract, avoids sphincter division and subsequently avoids sphincter dysfunction and incontinence. The device is pulled through the fistula tract and secured with a suture, whereby avoiding sphincter division, preserving innate function.34 The procedure offers immediate mechanical occlusion of the tract, and over the next 12 weeks, inflammatory cells imbibe through the plug matrix and gradually heal the tract with native host tissue. The conical shape of the plug provides mechanical stability and helps prevent extrusion. The fistula plug was designed to ameliorate postoperative incontinence for high-risk fistulae, such as fistulae with high internal openings, anterior fistulae, or those that transverse significant portions of sphincter muscle. Initial reports of the fistula plug are favorable, most notably in high-risk fistulae where conventional treatment with fistulotomy, cutting setons, and mucosal advancement flaps were ineffective or caused unacceptably high incontinence rates. Johnson et al published their initial series of 25 patients with high transphincteric or deeper cryptoglandular fistulae prospectively assigned to undergo treatment with fibrin glue (n ⫽ 10) or fistula plug (n ⫽ 15).34 Superficial (ie, mucosal), low transphincteric, and Crohn’s’ fistulae were excluded from the study. At an average follow-up of approximately 3 months, fistula plug closure of anorectal fistula was successful in 87% of the fistula plug cohort, whereas fibrin glue closure was successful in 40% of the fibrin glue cohort (P ⬍ 0.05). Long-term follow-up data were republished in 2006 by Champagne and coworkers, which included the original fistula plug cohort for a total study population of 46 patients.35 At 2 years follow-up (range, 6 months-24 months), the fistula plug had an 83% successful closure rate. Of patients failing closure, 87.5% failed in the first postoperative month, and 57% of failures involved mechanical extrusion of the plug from the fistulous tract. Complicated horseshoe fistulae were the second most common cause of failure (50%). One criticism of the study, however, was lack of steadfast anatomical definition of “high” fistula.36 Additionally, no assessment was made regarding postoperative incontinence. Subsequent studies from other institutions have validated the same efficacy of the fistula plug experience. In 2007, van Koperen and coworkers reported on patients (n ⫽ 17) with “difficult” high perianal fistulae, defined as those coursing through the upper 2/3 of the external sphincter complex.36 In this two-institution study, 12 of 17 (70.6%) were reoperative patients, two had human immunodeficiency virus, one had Crohn’s disease, and the remainder of the study had anal stenosis, anal fibrosis, and irregular hemorrhoidal tissue thought to complicate repair. Repair averaged only 25 minutes per patient, and no postoperative complications were encountered. In this complicated reoperative cohort, 41% (7 of 17) of fistulae were healed at a mean follow-up of 7 months (range, 3 months-9 months). In 7 of 10 patients failing fistula
Surgisis fistula plug plug therapy, the primary cause of failure was plug extrusion. Although the success rate was nearly half of similar reports, the authors were careful to qualify that these difficult patients were therapy resistant and had no other remaining treatment options absent of chronic seton placement or diverting stoma. The authors felt that in this difficult population, results were encouraging. Ellis retrospectively reported his fistula plug experience (n ⫽ 19) compared to a historical group receiving either mucosal or anodermal advancement flap (n ⫽ 95).6 At a median follow-up of 10 (range, 6-22) months, fistula plug success rate was 88%, while the advancement flap success rate was 67.4% (P ⬎ 0.05). The underpowered study is hindered by its retrospective nature and dissimilarity between groups. Additionally, 30% of the fistula plug group had Crohn’s disease, while such patients were excluded from the advancement flap group. Anorectal fistulae in the setting of Crohn’s disease require special consideration apart from cryptoglandular disease due to the traditionally high likelihood of fistula recurrence. Simple Crohn’s fistulae can be treated with fistulotomy; however, most Crohn’s fistulae are complex and require complicated advancement flaps, which convey high rates of failure and incontinence. Historically, proctectomy has been ultimately required in 2%-12% of patients with perianal Crohn’s fistulae.37-39 O’Connor and coworkers reported the prospective case series (n ⫽ 20) of complex Crohn’s fistulae with a median follow-up of 10 (range, 3-24) months.40 The fistula plug successfully closed all perianal fistulous Crohn’s disease for 16 of 20 patients (80%). Of 20 patients, 7 (35%) had multiple fistula tracts for 36 individual fistulae within the study population. Of the 36 total fistulae, 30 (83%) were successfully closed. Subset analysis associated singular fistula tracts with successful closure, and multiple fistula tracts with failed closure (P ⬍ 0.01), as all patients with singular fistula tracts healed completely. Of patients with multiple fistula tracts, success was achieved in only three of seven (43%) patients.
The Anal Fistula Plug Consensus Conference Based on the encouraging results of the fistula plug, a consensus conference was held to develop uniformity of opinion from surgeons with considerable experience in the use of the device.41 Despite favorable initial reports, there has been no level I evidence of actual benefit, and controversy exists regarding indications and technique. Based on the limited preliminary data and expert opinion, the panel felt that transphincteric fistulae the ideal indication for plug, acknowledging that longer tracts appear more amenable to plug closure than shorter tracts. Contraindications to using the AFP are listed in Table 1. Several technical factors were debated among panelists and a few conclusions can be gleaned from the proceedings. Preoperative bowel preparation has not been studied and therefore is left to the discretion of the individual surgeon. A single dose of systemic preoperative antibiotics was recom-
45 Table 1 Relative Contraindications of the Surgisis Fistula Plug Conventional uncomplicated intersphincteric fistulae Rationale: Success approaches 100% with standard fistulotomy and minimal morbidity, and the cost/failure rate of the plug is inappropriately high Recto-vaginal fistula Rationale: Low anticipated success rates with short tract Fistula with persistent abscess cavity or suggestion of Infection Rationale: Uncontrolled sepsis will impair incorporation of plug material and inhibit host tissue ingrowth Allergy to porcine products Inability to completely identify internal and external openings
mended. The panel stressed the importance of identifying all internal/external openings and encouraged irrigating the tract with either saline or hydrogen peroxide to assist with identification. The panel recommended avoiding curettage, debridement, or brushing of the fistula tract for concern of enlarging the orifice, whereby enabling plug extrusion. Likewise, the panel rejected using the plug in the setting of acute sepsis or inflammation and deferred to seton drainage for a period of 6-12 weeks until evidence of acute inflammation subsided and all sepsis was drained. As most reported failures involved mechanical extrusion of the plug, the consensus panel emphasized the importance of proper plug placement and fixation. A suture was recommended to pull the narrow end of the plug through the internal opening to the external opening of the fistula until securely snug. Excess plug material should be trimmed flush at both the internal and the external openings. The plug should be secured to the internal sphincter at the level of the internal opening with braided absorbable suture. Fixation at the external opening was discouraged, to avoid creating a closed loop undrained tract. Postoperative management was devoid of rigorous scientific data and deferred to experience and opinion. The panel did not agree on any specific dietary restrictions; however, it did unanimously agree on avoiding strenuous activity for 14 postoperative days.
Ongoing Studies for the Anal Fistula Plug Despite encouraging initial reports, additional studies are needed to concretely define the role of the fistula plug in anorectal fistulae. As noted in the AFP consensus conference, a paucity of supportive level 1 evidence exists regarding the AFP and ongoing prospective randomized studies are underway to substantiate the encouraging early results. The contemporary body of literature supporting the AFP consists of a subjectively defined, heterogeneous group of fistulae with overall encouraging outcomes; future studies will more accurately classify location and type of fistula to better understand and subsequently predict efficacy of this device. Furthermore, the effects of various technical factors, such as fixation techniques, tract debridement, sphincter incorporation, and
46 perioperative antibiotic administration, need to be better assayed. Last, the role of various postoperative regimens, such as dietary modification, bowel preparation, and stool-altering agents (eg, supplemental fiber and loperamide), needs to be defined. As with any new technology or device, physician reimbursement schedules and coding often lag behind use until widespread efficacy is proven to third-party payers. Currently, AFP placement alone is not a reimbursable procedure. The increasing application of the procedure has led to the assignment of a tracking or “T” code as a means to better quantify its usage. This facilitates the adoption of a recognized billable CPT code to help justify the cost of the device. Once the reimbursement schedule is determined and the true costs of the AFP procedure are determined, economic costbenefit analyses will ultimately be required to compare AFP performance with other traditional forms of fistula repair.
Conclusions The Surgisis AFP appears to be an effective and safe treatment alternative for complex anorectal fistula, including Crohn’s fistula, based on initial reports. Future work should seek prospective randomized studies to more conclusively determine the future role of the AFP and better determine the indications and contraindications, as well as technical concerns related to implantation and fixation. Last, the economic implications of the device need to be compared to traditional low-cost techniques in separate cost-benefit analyses.
References 1. Williams JG, Farrands PA, Williams AB, et al: The treatment of anal fistula: ACPGBI position statement. Colorectal Dis 9:18-50, 2007 (suppl 4) 2. Gurer A, Ozlem N, Gokakin AK, et al: A novel material in Seton treatment of fistula-in-ano. Am J Surg 193:794-796, 2007 3. Parks AG, Gordon PH, Hardcastle JD: A classification of fistula-in-ano. Br J Surg 63:1-12, 1976 4. Bastawrous A, Cintron J: Anorectal abscess and fistula, in Therapy JC (ed): Current Surgical. Philadelphia, PA, Elsevier Mosby, 2004 5. Lowney J, Fleshman J: Benign disorders of the anorectum, in Zinner M, Ashley S (eds): Maingot’s Abdominal Operations. New York, NY, McGraw-Hill Companies, 2007 6. Ellis CN: Bioprosthetic plugs for complex anal fistulas: An early experience. J Surg Educ 64:36-40, 2007 7. Westerterp M, Volkers NA, Poolman RW, et al: Anal fistulotomy between Skylla and Charybdis. Colorectal Dis 5:549-551, 2003 8. Ho YH, Tan M, Chui CH, et al: Randomized controlled trial of primary fistulotomy with drainage alone for perianal abscesses. Dis Colon Rectum 40:1435-1438, 1997 9. Cox SW, Senagore AJ, Luchtefeld MA, et al: Outcome after incision and drainage with fistulotomy for ischiorectal abscess. Am Surg 63:686689, 1997 10. Dziki A, Bartos M: Seton treatment of anal fistula: Experience with a new modification. Eur J Surg Acta Chir 164:543-548, 1998 11. Christensen A, Nilas L, Christiansen J: Treatment of transsphincteric anal fistulas by the Seton technique. Dis Colon Rectum 29:454-455, 1986 12. Ustynoski K, Rosen L, Stasik J, et al: Horseshoe abscess fistula. Seton treatment. Dis Colon Rectum 33:602-605, 1990 13. Lewis P, Bartolo DC: Treatment of trans-sphincteric fistulae by full thickness anorectal advancement flaps. Br J Surg 77:1187-1189, 1990
M.F. McGee and B. Champagne 14. Sonoda T, Hull T, Piedmonte MR, et al: Outcomes of primary repair of anorectal and rectovaginal fistulas using the endorectal advancement flap. Dis Colon Rectum 45:1622-1628, 2002 15. Miller GV, Finan PJ: Flap advancement and core fistulectomy for complex rectal fistula. Br J Surg 85:108-110, 1998 16. Ozuner G, Hull TL, Cartmill J, et al: Long-term analysis of the use of transanal rectal advancement flaps for complicated anorectal/vaginal fistulas. Dis Colon Rectum 39:10-14, 1996 17. Cintron JR, Park JJ, Orsay CP, et al: Repair of fistulas-in-ano using fibrin adhesive: Long-term follow-up. Dis Colon Rectum 43:944-949; discussion:949-950, 2000 18. Lindsey I, Smilgin-Humphreys MM, Cunningham C, et al: A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula. Dis Colon Rectum 45:1608-1615, 2002 19. Venkatesh KS, Ramanujam P: Fibrin glue application in the treatment of recurrent anorectal fistulas. Dis Colon Rectum 42:1136-1139, 1999 20. Patrlj L, Kocman B, Martinac M, et al: Fibrin glue-antibiotic mixture in the treatment of anal fistulae: Experience with 69 cases. Dig Surg 17: 77-80, 2000 21. Buchanan GN, Bartram CI, Phillips RK, et al: Efficacy of fibrin sealant in the management of complex anal fistula: A prospective trial. Dis Colon Rectum 46:1167-1174, 2003 22. Zmora O, Mizrahi N, Rotholtz N, et al: Fibrin glue sealing in the treatment of perineal fistulas. Dis Colon Rectum 46:584-589, 2003 23. Abel ME, Chiu YS, Russell TR, et al: Autologous fibrin glue in the treatment of rectovaginal and complex fistulas. Dis Colon Rectum 36: 447-449, 1993 24. Loungnarath R, Dietz DW, Mutch MG, et al: Fibrin glue treatment of complex anal fistulas has low success rate. Dis Colon Rectum 47:432436, 2004 25. Hammond TM, Grahn MF, Lunniss PJ: Fibrin glue in the management of anal fistulae. Colorectal Dis 6:308-319, 2004 26. Ellis CN, Clark S: Fibrin glue as an adjunct to flap repair of anal fistulas: A randomized, controlled study. Dis Colon Rectum 49:1736-1740, 2006 27. de la Portilla F, Rada R, Leon E, et al: Evaluation of the use of BioGlue in the treatment of high anal fistulas: Preliminary results of a pilot study. Dis Colon Rectum 50:218-222, 2007 28. Edelman DS: Laparoscopic herniorrhaphy with porcine small intestinal submucosa: A preliminary study. JSLS 6:203-205, 2002 29. Oelschlager BK, Barreca M, Chang L, et al: The use of small intestine submucosa in the repair of paraesophageal hernias: Initial observations of a new technique. Am J Surg 186:4-8, 2003 30. Rahman NU, Minor TX, Deng D, et al: Combined external urethral bulking and artificial urinary sphincter for urethral atrophy and stress urinary incontinence. BJU Int 95:824-826, 2005 31. Pinheiro JS, Correa JL, Cohen RV, et al: Staple line reinforcement with new biomaterial increased burst strength pressure: An animal study. Surgery for obesity and related diseases. Surg Obes Relate Dis 2:397-9, discussion 400, 2006 32. Badylak SF: The extracellular matrix as a scaffold for tissue reconstruction. Semin Cell Dev Biol 13:377-383, 2002 33. Badylak S: Small intestinal submucosa (SIS): A biomaterial conductive to smart tissue remodeling, in Bell E (ed): Tissue Engineering: Current Perspectives. Cambridge, Burkhauser Publishing, 1993, pp 179-189 34. Johnson EK, Gaw JU, Armstrong DN: Efficacy of anal fistula plug vs. fibrin glue in closure of anorectal fistulas. Dis Colon Rectum 49:371376, 2006 35. Champagne BJ, O’Connor LM, Ferguson M, et al: Efficacy of anal fistula plug in closure of cryptoglandular fistulas: Long-term follow-up. Dis Colon Rectum 49:1817-1821, 2006 36. van Koperen PJ, D’Hoore A, Wolthuis AM, et al: Anal fistula plug for closure of difficult anorectal fistula: A prospective study. Dis Colon Rectum 50:2168-2172, 2007 37. Morrison JG, Gathright JB Jr, Ray JE, et al: Surgical management of anorectal fistulas in Crohn’s disease. Dis Colon Rectum 32:492-496, 1989
Surgisis fistula plug 38. Williams JG, Rothenberger DA, Nemer FD, et al: Fistula-in-ano in Crohn’s disease. Results of aggressive surgical treatment. Dis Colon Rectum 34:378-384, 1991 39. Marks CG, Ritchie JK, Lockhart-Mummery HE: Anal fistulas in Crohn’s disease. Br J Surg 68:525-527, 1981
47 40. O’Connor L, Champagne BJ, Ferguson MA, et al: Efficacy of anal fistula plug in closure of Crohn’s anorectal fistulas. Dis Colon Rectum 49: 1569-1573, 2006 41. The Surgisis AFP anal fistula plug: Report of a consensus conference. Colorectal Dis 10:17-20, 2008
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lthough anorectal fistulae are commonly encountered, treatment of this condition remains one of the most challenging and controversial topics in colorectal surgery. Perianal fistulous disease is responsible for a range of clinical effects ranging from minor pain and social hygienic embarrassment to frank sepsis and has vast implications in patient quality of life. Management of anorectal fistulae is encumbered by several individualized factors such as etiology, location, type, duration, as well as previously performed procedures and preoperative assessments of sphincter function. Surgery is the mainstay of treatment for anorectal fistulae,1 with the ultimate goal of draining local sepsis, eradicating the fistulous tract, and avoiding recurrence while preserving native sphincter function.2
Traditional Treatment of Anorectal Fistulae Since Parks and colleagues classified anorectal fistulae in 1976, surgical treatment has been predicated upon several points of conventional surgical wisdom.3 After drainage of acute abscess and sepsis, traditional surgical treatment begins with identification of internal and external openings of the fistulous tract.1 Over 90% of anorectal fistulae result from cryptoglandular abscess originating from the crypts of Morgagni,4,5 and most internal openings of the fistula reside around the anal glands surrounding the dentate line. Fistulae will then course on one of the four following paths: inter-
Case Medical Center, Cleveland, Ohio. Address reprint requests to: Bradley Champagne, MD, Case Medical Center, Surgery, 11100 Euclid Avenue, Cleveland, OH 44106. E-mail: Brad. [email protected]
1043-1489/09/$-see front matter © 2009 Published by Elsevier Inc. doi:10.1053/j.scrs.2008.10.008
sphincteric (45%), transphincteric (30%), suprasphincteric (20%), or extrasphincteric (5%) before finally arriving at a perianal external opening.3 Occasionally, small fistulae will be limited to submucosal planes. In addition to cryptoglandular fistulae, Crohn’s disease and iatrogenic surgical fistulae (eg, ileal pouch and rectovaginal fistulae) are other causes of fistulae that require specialized treatments. Following drainage of acute sepsis and identification of the fistula tract’s internal and external openings, a curative surgical procedure is typically performed. Unfortunately, no single surgical approach adequately addresses all types of anorectal fistulae.6 Countless surgical techniques have been described to treat anorectal fistulae depending on the location, severity, chronicity of the fistula, as well as a host of functional characteristics related to each patient. Traditionally, well-drained, low-lying simple intersphincteric fistulae are treated with simple fistulotomy. Fistulotomy is the centuries-old “gold standard”6 that involves laying open the fistula tract in entirety.1 Overall fistula recurrence following fistulotomy ranges from 0% to 21%, with high, although widely variable, rates of resultant incontinence (0%-82%).7-9 Anterior fistulae present a therapeutically challenging subgroup and convey higher rates of postfistulotomy incontinence due to the natural anatomical attenuation of the external sphincter muscle and perineal body, especially in women.4,5 For fistulae that traverse longer distances of sphincter, such as proximal high transphincteric, fistulotomy conveys high rates of postoperative incontinence and alternative surgical treatments are necessary. For these “complex” fistulae, cutting setons are used to slowly divide fistulous tissue tracts on the leading edge of the seton, while allowing healing to occur on the trailing edge, whereby preserving sphincter continuity and theoretically preserving sphincter function. Success rates 43
44 for cutting setons range from 82% to 100%; however, longterm incontinence rates can exceed 30%. In light of unacceptably high rates of long-term incontinence, several alternative treatments have been developed.10-12 Endoanal advancement flaps are attractive options employed to treat complex fistula. Following adequate drainage and identification of the fistulous tract, mucosal advancement flaps are raised adjacent to the internal opening to provide tissue coverage of tract opening and subsequently allow the tract to heal and close. A variety of techniques exist, and in experienced hands, have low recurrence rates (0%-36%) and tolerable incontinence rates ranging from 0% to 12.5%.13-15 Not all anorectal fistulae patients are candidates for mucosal flap advancement. Very high fistulae, for example, are technically challenging to treat with mucosal advancement flaps. Additionally, anal stenosis, active proctitis, and inflammatory bowel disease are relative contraindications due to high complication and failure rates.16 Last, success rates for mucosal advancement flap surgery outcomes are highly variable, likely indicating the importance of a surgeon’s expertise with these exacting procedures. In the era of minimally invasive surgery and the notion that “less is more,” recent introduction of synthetic biological materials has brought a bevy of new techniques to treat anorectal fistulae. A variety of Food and Drug Administration approved fibrin-based glue materials have been used to treat difficult fistulae. Fibrin glue injection through the fistula tract offers a minimally invasive and expeditious treatment whereby sparing sphincter division. Early success rates for difficult fistula rates approach 60%-70%17-23; however, long-term fistula recurrence approaches 69%-100%.21,24,25 Fibrin glue extravasation from within the fistula tract and failure to identify and completely fill all branches of the tract with glue are the putative explanations for long-term failure.26 Nonetheless, the noninvasive and safe treatment profile of fibrin glue renders it a reasonable first-line treatment despite the high failure rate.24 Similar glue experiences have been reported substituting polymerized bovine serum albumin and glutaraldehyde (BioGlue Surgical Adhesive; CryoLife, Inc, Kennesaw, GA).27 The controversy associated with fistula treatment techniques is rooted within the balance of the therapeutic index— highly efficacious techniques, such as fistulotomy, have unfavorably high rates of incontinence. Unfortunately, safer techniques, such as fibrin glue and advancement flaps, sacrifice fistula recurrence for lower rates of postoperative incontinence.
The Surgisis Anal Fistula Plug (AFP) In 2005, a biosynthetic plug of material was introduced by Cook Surgical for treatment of anorectal fistula. The plug is a configuration of their Food and Drug Administration approved material, Surgisis, which is derived from lyophilized porcine small intestinal submucosa. Surgisis is manufactured into sheets of varying size and thickness and has been applied to a host of surgical indications. Hernia repair (inguinal, ven-
M.F. McGee and B. Champagne tral, paraesophageal), urethral sling, and stapler line reinforcement with Surgisis are reported applications.28-31 The xenograft is resistant to infection, produces no giant cell foreign body reaction, and becomes repopulated with native host cell tissues within 12 weeks.32,33 The fistula plug technique, which tunnels the plug inside the fistula tract, avoids sphincter division and subsequently avoids sphincter dysfunction and incontinence. The device is pulled through the fistula tract and secured with a suture, whereby avoiding sphincter division, preserving innate function.34 The procedure offers immediate mechanical occlusion of the tract, and over the next 12 weeks, inflammatory cells imbibe through the plug matrix and gradually heal the tract with native host tissue. The conical shape of the plug provides mechanical stability and helps prevent extrusion. The fistula plug was designed to ameliorate postoperative incontinence for high-risk fistulae, such as fistulae with high internal openings, anterior fistulae, or those that transverse significant portions of sphincter muscle. Initial reports of the fistula plug are favorable, most notably in high-risk fistulae where conventional treatment with fistulotomy, cutting setons, and mucosal advancement flaps were ineffective or caused unacceptably high incontinence rates. Johnson et al published their initial series of 25 patients with high transphincteric or deeper cryptoglandular fistulae prospectively assigned to undergo treatment with fibrin glue (n ⫽ 10) or fistula plug (n ⫽ 15).34 Superficial (ie, mucosal), low transphincteric, and Crohn’s’ fistulae were excluded from the study. At an average follow-up of approximately 3 months, fistula plug closure of anorectal fistula was successful in 87% of the fistula plug cohort, whereas fibrin glue closure was successful in 40% of the fibrin glue cohort (P ⬍ 0.05). Long-term follow-up data were republished in 2006 by Champagne and coworkers, which included the original fistula plug cohort for a total study population of 46 patients.35 At 2 years follow-up (range, 6 months-24 months), the fistula plug had an 83% successful closure rate. Of patients failing closure, 87.5% failed in the first postoperative month, and 57% of failures involved mechanical extrusion of the plug from the fistulous tract. Complicated horseshoe fistulae were the second most common cause of failure (50%). One criticism of the study, however, was lack of steadfast anatomical definition of “high” fistula.36 Additionally, no assessment was made regarding postoperative incontinence. Subsequent studies from other institutions have validated the same efficacy of the fistula plug experience. In 2007, van Koperen and coworkers reported on patients (n ⫽ 17) with “difficult” high perianal fistulae, defined as those coursing through the upper 2/3 of the external sphincter complex.36 In this two-institution study, 12 of 17 (70.6%) were reoperative patients, two had human immunodeficiency virus, one had Crohn’s disease, and the remainder of the study had anal stenosis, anal fibrosis, and irregular hemorrhoidal tissue thought to complicate repair. Repair averaged only 25 minutes per patient, and no postoperative complications were encountered. In this complicated reoperative cohort, 41% (7 of 17) of fistulae were healed at a mean follow-up of 7 months (range, 3 months-9 months). In 7 of 10 patients failing fistula
Surgisis fistula plug plug therapy, the primary cause of failure was plug extrusion. Although the success rate was nearly half of similar reports, the authors were careful to qualify that these difficult patients were therapy resistant and had no other remaining treatment options absent of chronic seton placement or diverting stoma. The authors felt that in this difficult population, results were encouraging. Ellis retrospectively reported his fistula plug experience (n ⫽ 19) compared to a historical group receiving either mucosal or anodermal advancement flap (n ⫽ 95).6 At a median follow-up of 10 (range, 6-22) months, fistula plug success rate was 88%, while the advancement flap success rate was 67.4% (P ⬎ 0.05). The underpowered study is hindered by its retrospective nature and dissimilarity between groups. Additionally, 30% of the fistula plug group had Crohn’s disease, while such patients were excluded from the advancement flap group. Anorectal fistulae in the setting of Crohn’s disease require special consideration apart from cryptoglandular disease due to the traditionally high likelihood of fistula recurrence. Simple Crohn’s fistulae can be treated with fistulotomy; however, most Crohn’s fistulae are complex and require complicated advancement flaps, which convey high rates of failure and incontinence. Historically, proctectomy has been ultimately required in 2%-12% of patients with perianal Crohn’s fistulae.37-39 O’Connor and coworkers reported the prospective case series (n ⫽ 20) of complex Crohn’s fistulae with a median follow-up of 10 (range, 3-24) months.40 The fistula plug successfully closed all perianal fistulous Crohn’s disease for 16 of 20 patients (80%). Of 20 patients, 7 (35%) had multiple fistula tracts for 36 individual fistulae within the study population. Of the 36 total fistulae, 30 (83%) were successfully closed. Subset analysis associated singular fistula tracts with successful closure, and multiple fistula tracts with failed closure (P ⬍ 0.01), as all patients with singular fistula tracts healed completely. Of patients with multiple fistula tracts, success was achieved in only three of seven (43%) patients.
The Anal Fistula Plug Consensus Conference Based on the encouraging results of the fistula plug, a consensus conference was held to develop uniformity of opinion from surgeons with considerable experience in the use of the device.41 Despite favorable initial reports, there has been no level I evidence of actual benefit, and controversy exists regarding indications and technique. Based on the limited preliminary data and expert opinion, the panel felt that transphincteric fistulae the ideal indication for plug, acknowledging that longer tracts appear more amenable to plug closure than shorter tracts. Contraindications to using the AFP are listed in Table 1. Several technical factors were debated among panelists and a few conclusions can be gleaned from the proceedings. Preoperative bowel preparation has not been studied and therefore is left to the discretion of the individual surgeon. A single dose of systemic preoperative antibiotics was recom-
45 Table 1 Relative Contraindications of the Surgisis Fistula Plug Conventional uncomplicated intersphincteric fistulae Rationale: Success approaches 100% with standard fistulotomy and minimal morbidity, and the cost/failure rate of the plug is inappropriately high Recto-vaginal fistula Rationale: Low anticipated success rates with short tract Fistula with persistent abscess cavity or suggestion of Infection Rationale: Uncontrolled sepsis will impair incorporation of plug material and inhibit host tissue ingrowth Allergy to porcine products Inability to completely identify internal and external openings
mended. The panel stressed the importance of identifying all internal/external openings and encouraged irrigating the tract with either saline or hydrogen peroxide to assist with identification. The panel recommended avoiding curettage, debridement, or brushing of the fistula tract for concern of enlarging the orifice, whereby enabling plug extrusion. Likewise, the panel rejected using the plug in the setting of acute sepsis or inflammation and deferred to seton drainage for a period of 6-12 weeks until evidence of acute inflammation subsided and all sepsis was drained. As most reported failures involved mechanical extrusion of the plug, the consensus panel emphasized the importance of proper plug placement and fixation. A suture was recommended to pull the narrow end of the plug through the internal opening to the external opening of the fistula until securely snug. Excess plug material should be trimmed flush at both the internal and the external openings. The plug should be secured to the internal sphincter at the level of the internal opening with braided absorbable suture. Fixation at the external opening was discouraged, to avoid creating a closed loop undrained tract. Postoperative management was devoid of rigorous scientific data and deferred to experience and opinion. The panel did not agree on any specific dietary restrictions; however, it did unanimously agree on avoiding strenuous activity for 14 postoperative days.
Ongoing Studies for the Anal Fistula Plug Despite encouraging initial reports, additional studies are needed to concretely define the role of the fistula plug in anorectal fistulae. As noted in the AFP consensus conference, a paucity of supportive level 1 evidence exists regarding the AFP and ongoing prospective randomized studies are underway to substantiate the encouraging early results. The contemporary body of literature supporting the AFP consists of a subjectively defined, heterogeneous group of fistulae with overall encouraging outcomes; future studies will more accurately classify location and type of fistula to better understand and subsequently predict efficacy of this device. Furthermore, the effects of various technical factors, such as fixation techniques, tract debridement, sphincter incorporation, and
46 perioperative antibiotic administration, need to be better assayed. Last, the role of various postoperative regimens, such as dietary modification, bowel preparation, and stool-altering agents (eg, supplemental fiber and loperamide), needs to be defined. As with any new technology or device, physician reimbursement schedules and coding often lag behind use until widespread efficacy is proven to third-party payers. Currently, AFP placement alone is not a reimbursable procedure. The increasing application of the procedure has led to the assignment of a tracking or “T” code as a means to better quantify its usage. This facilitates the adoption of a recognized billable CPT code to help justify the cost of the device. Once the reimbursement schedule is determined and the true costs of the AFP procedure are determined, economic costbenefit analyses will ultimately be required to compare AFP performance with other traditional forms of fistula repair.
Conclusions The Surgisis AFP appears to be an effective and safe treatment alternative for complex anorectal fistula, including Crohn’s fistula, based on initial reports. Future work should seek prospective randomized studies to more conclusively determine the future role of the AFP and better determine the indications and contraindications, as well as technical concerns related to implantation and fixation. Last, the economic implications of the device need to be compared to traditional low-cost techniques in separate cost-benefit analyses.
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