The Treatment Of Anal Fistulas With Biologically Derived Products: Is Innovation Better Than Conventional Surgical Treatment? An Update

New technical approaches involving biologically derived products have been applied in the treatment for anal fistulas in order to avoid the risk of fecal incontinence. The aim of this review was to evaluate the scientific evidence present in the literature regarding these techniques. Trials comparing surgery (fistulotomy, advancement mucosal flap closure and placement of seton) versus fibrin glue, fistula plug or acellular dermal matrix were considered. In fibrin glue versus traditional surgical treatment the healing rate was higher in the surgery group, and the recurrence rate was lower in the traditional surgery group, but these results were not statistically relevant. In acellular dermal matrix (ADM) versus traditional surgical treatment the recurrence rate of fistulas was significantly lower in the ADM group, but non-significant differences were recorded in incontinence and anal deformity. Our review shows that there are no significant advantages of the new techniques involving biologically derived products. Further randomized controlled trials are needed. © 2012 Springer-Verlag Italia.173259273Sainio, P., Fistula-in-ano in a defined population. Incidence and epidemiological aspects (1984) Ann Chir Gynaecol, 73, pp. 219-224. , 6508203 1:STN:280:DyaL2M%2FntVylsQ%3D%3DZanotti, C., Martinez-Puente, C., Pascual, I., Pascual, M., Herreros, D., Garcia-Olmo, D., An assessment of the incidence of fistula-in-ano in four countries of the European Union (2007) Int J Colorectal Dis, 22, pp. 1459-1462. , 17554546 10.1007/s00384-007-0334-7Eisenhammer, S., The anorectal fistulous abscess and fistula (1966) Dis Colon Rectum, 9, pp. 91-106. , 5908774 10.1007/BF02617307 1:STN:280:DyaF287gslGmtg%3D%3DKhubchandani, M., Comparison of results of treatment of fistula-in-ano (1984) J R Soc Med, 77, pp. 369-371. , 6726753 1:STN:280:DyaL2c3hs1Wquw%3D%3DParks, A.G., Gordon, P.H., Hardcastle, J.D., A classification of fistula-in-ano (1976) Br J Surg, 63, pp. 1-12. , 1267867 10.1002/bjs.1800630102 1:STN:280:DyaE287osFegtg%3D%3DMalouf, A.J., Buchanan, G.N., Carapeti, E.A., A prospective audit of fistula-in-ano at St. Mark's hospital (2002) Colorectal Dis, 4, pp. 13-19. , 12780648 10.1046/j.1463-1318.2002.00277.xMarks, C.G., Ritchie, J.K., Anal fistulas at St Mark's Hospital (1977) Br J Surg, 64, pp. 84-91. , 890252 10.1002/bjs.1800640203 1:STN:280:DyaE2s3ktlaitg%3D%3DSileri, P., Franceschilli, L., Angelucci, G.P., Ligation of the intersphincteric fistula tract (LIFT) to treat anal fistula: Early results from a prospective observational study (2011) Tech Coloproctol, 15, pp. 413-416. , 22076690 10.1007/s10151-011-0779-0 1:STN:280:DC%2BC38%2FjsV2ltg%3D%3DCintron, J.R., Park, J.J., Orsay, C.P., Repair of fistulas-in-ano using fibrin adhesive: Long-term follow-up (2000) Dis Colon Rectum, 43, pp. 944-949. , 10910240 10.1007/BF02237355 1:STN:280:DC%2BD3czmsFKisg%3D%3D discussion 949-950De Parades, V., Far, H.S., Etienney, I., Zeitoun, J.D., Atienza, P., Bauer, P., Seton drainage and fibrin glue injection for complex anal fistulas (2010) Colorectal Dis, 12, pp. 459-463. , 19210300 10.1111/j.1463-1318.2009.01811.xRoig, J.V., Garcia-Armengol, J., Jordan, J.C., Moro, D., Garcia-Granero, E., Alos, R., Fistulectomy and sphincteric reconstruction for complex cryptoglandular fistulas (2010) Colorectal Dis, 12, pp. E145-E152. , 19604292 1:STN:280:DC%2BC3cjhtVyltg%3D%3DUribe, N., Millan, M., Minguez, M., Clinical and manometric results of endorectal advancement flaps for complex anal fistula (2007) Int J Colorectal Dis, 22, pp. 259-264. , 16896993 10.1007/s00384-006-0172-zRothenberger, D.A., Christenson, C.E., Balcos, E.G., Endorectal advancement flap for treatment of simple rectovaginal fistula (1982) Dis Colon Rectum, 25, pp. 297-300. , 7083973 10.1007/BF02553599 1:STN:280:DyaL383htVWisA%3D%3DCirocchi, R., Farinella, E., La Mura, F., Fibrin glue in the treatment of anal fistula: A systematic review (2009) Ann Surg Innov Res, 3, p. 12. , 19912660 10.1186/1750-1164-3-12Ellis, C.N., Rostas, J.W., Greiner, F.G., Long-term outcomes with the use of bioprosthetic plugs for the management of complex anal fistulas (2010) Dis Colon Rectum, 53, pp. 798-802. , 20389214 10.1007/DCR.0b013e3181d43b7dWang, J.Y., Garcia-Aguilar, J., Sternberg, J.A., Abel, M.E., Varma, M.G., Treatment of transsphincteric anal fistulas: Are fistula plugs an acceptable alternative? (2009) Dis Colon Rectum, 52, pp. 692-697. , 19404076 10.1007/DCR.0b013e31819d473fJohnson, E.K., Gaw, J.U., Armstrong, D.N., Efficacy of anal fistula plug vs. fibrin glue in closure of anorectal fistulas (2006) Dis Colon Rectum, 49, pp. 371-376. , 16421664 10.1007/s10350-005-0288-1Garcia-Olmo, D., Garcia-Arranz, M., Herreros, D., Expanded adipose-derived stem cells for the treatment of complex perianal fistula including Crohn's disease (2008) Expert Opin Biol Ther, 8, pp. 1417-1423. , 18694359 10.1517/14712598.8.9.1417 1:CAS:528:DC%2BD1cXpslart7w%3DGarcia-Olmo, D., Herreros, D., Pascual, I., Expanded adipose-derived stem cells for the treatment of complex perianal fistula: A phase II clinical trial (2009) Dis Colon Rectum, 52, pp. 79-86. , 19273960 10.1007/DCR.0b013e3181973487Garcia-Aguilar, J., Belmonte, C., Wong, W.D., Goldberg, S.M., Madoff, R.D., Anal fistula surgery. Factors associated with recurrence and incontinence (1996) Dis Colon Rectum, 39, pp. 723-729. , 8674361 10.1007/BF02054434 1:STN:280:DyaK283ptVGmtQ%3D%3DUribe Quintana, N., Aguado Perez, M., Minguez Perez, M., Impact of endorectal advancement flaps in fecal incontinence (2009) Circ Esp, 86, pp. 224-229. , 10.1016/j.ciresp.2009.03.005Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement (2009) PLoS Med, 6, p. 1000097. , 19621072 10.1371/journal.pmed.1000097Chapman, A.L., Morgan, L.C., Gartlehner, G., Semi-automating the manual literature search for systematic reviews increases efficiency (2010) Health Info Libr J, 27, pp. 22-27. , 20402801 10.1111/j.1471-1842.2009.00865.xHiggins, J.G., (2011) Cochrane Handbook for Systematic Reviews of Interventions, , ed Collaboration TCLiberati, A., Altman, D.G., Tetzlaff, J., The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration (2009) PLoS Med, 6, p. 1000100. , 19621070 10.1371/journal.pmed.1000100Greenland, S., Robins, J.M., Estimation of a common effect parameter from sparse follow-up data (1985) Biometrics, 41, pp. 55-68. , 4005387 10.2307/2530643 1:STN:280:DyaL2M3is1OgtQ%3D%3DMantel, N., Haenszel, W., Statistical aspects of the analysis of data from retrospective studies of disease (1959) J Natl Cancer Inst, 22, pp. 719-748. , 13655060 1:STN:280:DyaG1M%2FosVOhtQ%3D%3DFriedman, H.P., Goldberg, J.D., Meta-analysis: An introduction and point of view (1996) Hepatology, 23, pp. 917-928. , 8666350 10.1002/hep.510230437 1:STN:280:DyaK283jtVWhsg%3D%3DSIGN Guidelines, , http://www.sign.ac.uk/guidelines/fulltext/50/checklist3, Accessed: March 20, 2009Rangel, S.J., Kelsey, J., Colby, C.E., Anderson, J., Moss, R.L., Development of a quality assessment scale for retrospective clinical studies in pediatric surgery (2003) J Pediatr Surg, 38, pp. 390-396. , 12632355 10.1053/jpsu.2003.50114 discussion 390-396Chalmers, T.C., Smith Jr., H., Blackburn, B., A method for assessing the quality of a randomized control trial (1981) Control Clin Trials, 2, pp. 31-49. , 7261638 10.1016/0197-2456(81)90056-8 1:STN:280:DyaL3M3lvFOktA%3D%3DJadad, A.R., Moore, R.A., Carroll, D., Jenkinson, C., Reynolds, D.J., Gavaghan, D.J., McQuay, H.J., Assessing the quality of reports of randomized clinical trials: Is blinding necessary? (1996) Control Clin Trials, 17, pp. 1-12. , 8721797 10.1016/0197-2456(95)00134-4 1:STN:280:DyaK28zgvVCmug%3D%3DSiddiqui, M.R., Sajid, M.S., Qureshi, S., Cheek, E., Baig, M.K., Elective laparoscopic sigmoid resection for diverticular disease has fewer complications than conventional surgery: A meta-analysis (2010) Am J Surg, 200, pp. 144-161. , 20637347 10.1016/j.amjsurg.2009.08.021Christoforidis, D., Pieh, M.C., Madoff, R.D., Mellgren, A.F., Treatment of transsphincteric anal fistulas by endorectal advancement flap or collagen fistula plug: A comparative study (2009) Dis Colon Rectum, 52, pp. 18-22. , 19273951 10.1007/DCR.0b013e31819756acChung, W., Kazemi, P., Ko, D., Anal fistula plug and fibrin glue versus conventional treatment in repair of complex anal fistulas (2009) Am J Surg, 197, pp. 604-608. , 19393353 10.1016/j.amjsurg.2008.12.013 1:CAS:528:DC%2BD1MXltVCkurs%3DHuang, H.-G., Chu, H., Lu, M., Chang, Z.-S., Ai, E.-H.-T., Fan, K., Randomized controlled trial of minimally invasive surgery using acellular dermal matrix for complex anorectal fistula (2010) World J Gastroenterol, 16, pp. 3279-3286Altomare, D.F., Greco, V.J., Tricomi, N., Seton or glue for trans-sphincteric anal fistulae: A prospective randomized crossover clinical trial (2011) Colorectal Dis, 13, pp. 82-86. , 19832873 10.1111/j.1463-1318.2009.02056.x 1:STN:280: DC%2BC3M%2Fmt1egtw%3D%3DEllis, C.N., Clark, S., Fibrin glue as an adjunct to flap repair of anal fistulas: A randomized, controlled study (2006) Dis Colon Rectum, 49, pp. 1736-1740. , 17053867 10.1007/s10350-006-0718-8Lindsey, I., Smilgin-Humphreys, M.M., Cunningham, C., Mortensen, N.J., George, B.D., A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula (2002) Dis Colon Rectum, 45, pp. 1608-1615. , 12473883 10.1007/s10350-004-7247-0Singer, M., Cintron, J., Nelson, R., Treatment of fistulas-in-ano with fibrin sealant in combination with intra-adhesive antibiotics and/or surgical closure of the internal fistula opening (2005) Dis Colon Rectum, 48, pp. 799-808. , 15785883 10.1007/s10350-004-0898-zVan Koperen, P.J., Bemelman, W.A., Gerhards, M.F., The anal fistula plug treatment compared with the mucosal advancement flap for cryptoglandular high transsphincteric perianal fistula: A double-blinded multicenter randomized trial (2011) Dis Colon Rectum, 54, pp. 387-393. , 21383557 10.1007/DCR.0b013e318206043eSenejoux, A., Fistules anales: Obturer ou non? de quelle façon? (2011) Colon Rectum, 5, p. 303. , 10.1007/s11725-011-0344-zDe La Portilla, F., Rada, R., Jimenez-Rodriguez, R., Diaz-Pavon, J.M., Sanchez-Gil, J.M., Evaluation of a new synthetic plug in the treatment of anal fistulas: Results of a pilot study (2011) Dis Colon Rectum, 54, pp. 1419-1422. , 21979188 10.1097/DCR.0b013e31822c4d59Haim, N., Neufeld, D., Ziv, Y., Long-term results of fibrin glue treatment for cryptogenic perianal fistulas: A multicenter study (2011) Dis Colon Rectum, 54, pp. 1279-1283. , 21904143 10.1097/DCR.0b013e318223c894(2010) Estudio Multicéntrico Descriptivo de Seguimiento Prospectivo Del Tratamiento de Las Fístulas Anales Con Adhesivo de Fibrina, , Aparicio Rodríguez Ò Universitat Autònoma de BarcelonaSchwandner, O., Stadler, F., Dietl, O., Wirsching, R.P., Fuerst, A., Initial experience on efficacy in closure of cryptoglandular and Crohn's transsphincteric fistulas by the use of the anal fistula plug (2008) Int J Colorectal Dis, 23, pp. 319-324. , 18038233 10.1007/s00384-007-0398-4 1:STN:280:DC%2BD1c%2FltFKrtA%3D%3DSong, W.L., Wang, Z.J., Zheng, Y., Yang, X.Q., Peng, Y.P., An anorectal fistula treatment with acellular extracellular matrix: A new technique (2008) World J Gastroenterol, 14, pp. 4791-4794. , 18720541 10.3748/wjg.14.4791Van Koperen, P.J., Wind, J., Bemelman, W.A., Slors, J.F., Fibrin glue and transanal rectal advancement flap for high transsphincteric perianal fistulasIs there any advantage? (2008) Int J Colorectal Dis, 23, pp. 697-701. , 18322659 10.1007/s00384-008-0460-xVan Koperen, P.J., Bemelman, W.A., Bossuyt, P.M., The anal fistula plug versus the mucosal advancement flap for the treatment of anorectal fistula (PLUG trial) (2008) BMC Surg, 8, p. 11. , 18573198 10.1186/1471-2482-8-11Ortiz, H., Marzo, M., De Miguel, M., Ciga, M.A., Oteiza, F., Armendariz, P., Length of follow-up after fistulotomy and fistulectomy associated with endorectal advancement flap repair for fistula in ano (2008) Br J Surg, 95, pp. 484-487. , 18161890 10.1002/bjs.6023 1:STN:280:DC%2BD1c7mslOktA%3D%3DHammond, T.M., Grahn, M.F., Lunniss, P.J., Fibrin glue in the management of anal fistulae (2004) Colorectal Dis, 6, pp. 308-319. , 15335361 10.1111/j.1463-1318.2004.00676.x 1:STN:280: DC%2BD2cvjtVGktg%3D%3DSwinscoe, M.T., Ventakasubramaniam, A.K., Jayne, D.G., Fibrin glue for fistula-in-ano: The evidence reviewed (2005) Tech Coloproctol, 9, pp. 89-94. , 16007368 10.1007/s10151-005-0204-7 1:STN:280:DC%2BD2MnhsVaktg%3D%3DMalik, A.I., Nelson, R.L., Surgical management of anal fistulae: A systematic review (2008) Colorectal Dis, 10, pp. 420-430. , 18479308 10.1111/j.1463-1318.2008.01483.x 1:STN:280: DC%2BD1czhslegug%3D%3DDeeba, S., Aziz, O., Sains, P.S., Darzi, A., Fistula-in-ano: Advances in treatment (2008) Am J Surg, 196, pp. 95-99. , 18466873 10.1016/j.amjsurg.2007.12.047Jacob, T.J., Perakath, B., Keighley, M.R., Surgical intervention for anorectal fistula (2010) Cochrane Database Syst Rev, pp. CD006319Rizzo, J.A., Naig, A.L., Johnson, E.K., Anorectal abscess and fistula-in-ano: Evidence-based management (2010) Surg Clin North Am, 90, pp. 45-68. , 20109632 10.1016/j.suc.2009.10.001Cirocchi, R., Santoro, A., Trastulli, S., Meta-analysis of fibrin glue versus surgery for treatment of fistula-in-ano (2010) Ann Ital Chir, 81, pp. 349-356. , 21294388Shawki, S., Wexner, S.D., Idiopathic fistula-in-ano (2011) World J Gastroenterol, 17, pp. 3277-3285. , 21876614 10.3748/wjg.v17.i28.3277O'Riordan, J.M.D., Johnston, C., Baxter, N.N., A Systematic Review of the Anal Fistula Plug for Patients with Crohn's and Non-Crohn's Related Fistula-in-Ano (2012) Dis Colon Rectum, 55, pp. 351-358. , 22469804 10.1097/DCR.0b013e318239d1e4GRADE, , http://ims.cochrane.org/gradeproJurczak, F., Laridon, J.Y., Raffaitin, P., Redon, Y., Pousset, J.P., Long-term follow-up of the treatment of high anal fistulas using fibrin glue (2009) J Chir, 146, pp. 382-386. , 10.1016/j.jchir.2009.08.019 1:STN:280:DC%2BD1MnpslKmtQ%3D%3DBuchanan, G.N., Bartram, C.I., Phillips, R.K., Efficacy of fibrin sealant in the management of complex anal fistula: A prospective trial (2003) Dis Colon Rectum, 46, pp. 1167-1174. , 12972959 10.1007/s10350-004-6708-9Naldini, G., Cerullo, G., Mascagni, D., Hiding intersphincteric and transsphincteric sepsis in a novel pathological approach to chronic anal fissure (2011) Surg Innov, 19, pp. 33-36. , 21742658 10.1177/1553350611410990Hamadani, A., Haigh, P.I., Liu, I.L., Abbas, M.A., Who is at risk for developing chronic anal fistula or recurrent anal sepsis after initial perianal abscess? (2009) Dis Colon Rectum, 52, pp. 217-221. , 19279415 10.1007/DCR.0b013e31819a5c52Johnson, W.R., Druitt, D.M., Masterton, J.P., Anterior rectal advancement flap in the repair of benign rectoprostatic fistula (1981) Aust N Z J Surg, 51, pp. 383-385. , 6944064 10.1111/j.1445-2197.1981.tb04976.x 1:STN:280:DyaL3M3otFCgtg%3D%3DSaad, M.N., Khoo, C.T., Lochaitis, A.S., A simple technique for repair of urethral fistulae by Y-V advancement (1980) Br J Plast Surg, 33, pp. 410-412. , 7000213 10.1016/0007-1226(80)90104-6 1:STN:280:DyaL3M%2FktVCisA%3D%3DSun, M.R., Smith, M.P., Kane, R.A., Current techniques in imaging of fistula in ano: Three-dimensional endoanal ultrasound and magnetic resonance imaging (2008) Semin Ultrasound CT MR, 29, pp. 454-471. , 19166042 10.1053/j.sult.2008.10.006Abel, M.E., Chiu, Y.S., Russell, T.R., Volpe, P.A., Autologous fibrin glue in the treatment of rectovaginal and complex fistulas (1993) Dis Colon Rectum, 36, pp. 447-449. , 8482163 10.1007/BF02050009 1:STN:280:DyaK3s3ksFKjtg%3D%3DLoungnarath, R., Dietz, D.W., Mutch, M.G., Birnbaum, E.H., Kodner, I.J., Fleshman, J.W., Fibrin glue treatment of complex anal fistulas has low success rate (2004) Dis Colon Rectum, 47, pp. 432-436. , 14978618 10.1007/s10350-003-0076-8Sentovich, S.M., Fibrin glue for anal fistulas: Long-term results (2003) Dis Colon Rectum, 46, pp. 498-502. , 12682544 10.1007/s10350-004-6589-yTinay, O.E., El-Bakry, A.A., Treatment of chronic fistula-in-ano using commercial fibrin glue (2003) Saudi Med J, 24, pp. 1116-1117. , 14578981Venkatesh, K.S., Ramanujam, P., Fibrin glue application in the treatment of recurrent anorectal fistulas (1999) Dis Colon Rectum, 42, pp. 1136-1139. , 10496552 10.1007/BF02238564 1:STN:280:DyaK1MvisVyksw%3D%3DChan, S., McCullough, J., Schizas, A., Initial experience of treating anal fistula with the Surgisis anal fistula plug (2012) Tech Coloproctol, 16, pp. 201-206. , 22527917 10.1007/s10151-012-0810-0 1:STN:280:DC%2BC38rns1Sgsw%3D%3DHjortrup, A., Moesgaard, F., Kjaergard, J., Fibrin adhesive in the treatment of perineal fistulas (1991) Dis Colon Rectum, 34, pp. 752-754. , 1914738 10.1007/BF02051064 1:STN:280:DyaK38%2Fgs12kug%3D%3DPigot, F.S., (2003) Fistules Anales et Colle Biologique. Le Courrier de Colo-proctologie, , http://wwwsnfcporg/data/Modulegestiondecontenu/02-bibliotheque4:2-4Adams, T., Yang, J., Kondylis, L.A., Kondylis, P.D., Long-term outlook after successful fibrin glue ablation of cryptoglandular transsphincteric fistula-in-ano (2008) Dis Colon Rectum, 51, pp. 1488-1490. , 18612689 10.1007/s10350-008-9405-2Garg, P., Song, J., Bhatia, A., Kalia, H., Menon, G.R., The efficacy of anal fistula plug in fistula-in-ano: A systematic review (2010) Colorectal Dis, 12, pp. 965-970. , 19438881 10.1111/j.1463-1318.2009.01933.x 1:STN:280: DC%2BC3M7gtVKlsA%3D%3DLawes, D.A., Efron, J.E., Abbas, M., Heppell, J., Young-Fadok, T.M., Early experience with the bioabsorbable anal fistula plug (2008) World J Surg, 32, pp. 1157-1159. , 18373120 10.1007/s00268-008-9504-1 1:STN:280:DC%2BD1czit1Sjtw%3D%3DSafar, B., Jobanputra, S., Sands, D., Weiss, E.G., Nogueras, J.J., Wexner, S.D., Anal fistula plug: Initial experience and outcomes (2009) Dis Colon Rectum, 52, pp. 248-252. , 19279419 10.1007/DCR.0b013e31819c96acAmerican Gastroenterological Association medical position statement: Perianal Crohn's disease (2003) Gastroenterology, 125, pp. 1503-1507Dover, N.H., (2012) Wentworth-Douglass Hospital-Radiology, , http://www.wdhospital.com/body.cfm?id=445, Wentworth-Douglass Hospital CA, Dover, NH Wentworth-Douglass Hospital, 789 Central Avenue, Dover, NH 03820Santoro, G.A., Wieczorek, A.P., Dietz, H.P., State of the art: An integrated approach to pelvic floor ultrasonography (2011) Ultrasound Obstet Gynecol, 37, pp. 381-396. , 20814874 10.1002/uog.8816 1:STN:280:DC%2BC3M3ovFWlug%3D%3DSeddon, M.E., Marshall, M.N., Campbell, S.M., Roland, M.O., Systematic review of studies of quality of clinical care in general practice in the UK, Australia and New Zealand (2001) Qual Health Care, 10, pp. 152-158. , 11533422 10.1136/qhc.0100152 1:STN:280:DC%2BD3MvptFejtg%3D%3