- Email: [email protected]
Surgical therapy of perianal Crohn's disease
Digestive and Liver Disease 39 (2007) 988–992
Mini-Symposium
Surgical therapy of perianal Crohn’s disease B. Singh a , B.D. George b , N.J. McC Mortensen b,∗ b
a Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, United Kingdom Department of Colorectal Surgery, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
Received 24 July 2007; accepted 24 July 2007 Available online 27 August 2007
Abstract The surgical management of perianal Crohn’s disease is complex with a wide range of operations being described. The initial emergency treatment is to drain any source of underlying sepsis. A loose seton drainage or a defunctioning stoma can then be used as a ‘bridge’ to definitive treatment allowing both adequate assessment of the condition and preventing further sepsis. The likelihood of success of any surgical repair must be weighed against the risk of faecal incontinence. Improved results of a local surgical repair are seen with optimal surgical and medical management of perianal Crohn’s disease. © 2007 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Damage limitation; Local repair; Perianal Crohn’s disease; Proctectomy; Sepsis
Anal Crohn’s disease (CD) affects approximately 33% of patients with CD. It is more common with distal intestinal disease and may cause considerable morbidity. Optimal management depends on thorough disease assessment, typically colonoscopy, small bowel radiology, MRI and examination under anaesthesia. This review considers the place of surgery in the light of recent advancements in medical therapy. The large list of operative procedures for perianal CD highlights the difficulty surgeons have in managing this group of patients. The relatively benign nature of some perianal conditions and the potential for major surgical complications, such as incontinence and unhealed wounds, has resulted in the traditional view that surgery be avoided as much as possible in perianal CD [1]. Keighley and Allan [2], for example, reported that in patients with a low anal fistula, treated by simple laying-open of the tract, there was poor healing in 8% of patients, and even of more concern was that 50% of patients reported postoperative incontinence. Surgical treatment includes resection of intestinal disease, a defunctioning stoma, local surgical repair or, in extreme cases, a proctectomy [3].
1. Emergency treatment of sepsis The commonest acute presentation of perianal CD is an underlying abscess which necessitates immediate incision and drainage [4,5]. Some surgeons favour leaving a drain (Mushroom or Malecot catheter) although there is little evidence that use of a drain alters the ultimate outcome [6]. The principles of surgery are to achieve adequate drainage of sepsis and to avoid sphincter damage. A course of perioperative antibiotics is advisable particularly if associated with cellulites. The most commonly used antibiotics are metronidazole and ciprofloxacin. A seton drain can be inserted at this initial presentation if a fistula tract is easily identified. In cases where an underlying abscess is not obvious use of intraoperative endoanal ultrasound may be helpful [7]. Furthermore serial endoanal ultrasound examinations also allow the surgeon to determine healing response to medical treatment [8]. Alternatively the extent and location of a perianal collection can be identified with a MRI scan [9] (Fig. 1).
2. Damage limitation ∗
Corresponding author. Tel.: +44 1865 220926; fax: +44 1865 221274. E-mail address: [email protected] (N.J. McC Mortensen).
Once any focus of sepsis has been drained the next stage involves stabilisation to allow adequate assessment of the
1590-8658/$30 © 2007 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2007.07.157
B. Singh et al. / Digestive and Liver Disease 39 (2007) 988–992
Fig. 1. A MRI scan showing an underlying abscess in a patient with perianal CD.
extent of perianal CD. We refer to this as the ‘bridging period’, which is also a period of damage limitation. The two commonest strategies employed are a loose (drainage) seton or a defunctioning stoma. The aim of seton drainage is to prevent further abscess formation, drain underlying sepsis and to avoid division of sphincter muscle. The commonest material used for a seton is an inert substance, such as silastic or ethibond (Fig. 2). Results suggest that outcomes using seton drainage are unaffected by rectal involvement and furthermore there is a minimal effect on incontinence [10–12]. Therefore seton drainage of Crohn’s fistulae is a safe option before attempting a more definitive surgical procedure. Whilst a seton can be left indefinitely the long-term results show recurrence in 83% of cases following removal [13]. If there is extensive perianal disease or disease progression despite initial abscess drainage then an alternative procedure is formation of a stoma. A defunctioning stoma may also allow control of sepsis prior to a proctectomy as well as
989
allowing patients to come to terms with a permanent stoma. In addition a defunctioning stoma also creates a favourable environment in which to perform a local perianal repair. A laparoscopic approach is now favoured because it is minimally invasive and also allows the opportunity to assess for intestinal disease [14]. Zelas and Jagelman [15] reported a loop ileostomy resulted in an initial clinical improvement in 96% of cases. However, recurrence developed in 26% of cases despite the presence of the ileostomy. This has been attributed to the fact that a loop ileostomy only partially defunctions the bowel. However, a split ileostomy improved perianal disease in only 69% of cases [16]. Edwards et al. [17] found that 15 (83%) out of 18 patients had remission of their perianal CD after being defunctioned. However, closure of the stoma was undertaken in only four patients with two developing relapse. Furthermore the study did not resolve the question of whether a split ileostomy results in a better prognosis than a loop ileostomy. Yamamoto et al. [18] also found that despite a clinical response of 81% in patients with perianal CD, defunctioned with a loop ileostomy or loop colostomy, only 10% of patients had their stoma reversed. Galandiuk et al. [19] looked at factors which predicted the need for a permanent stoma. They noted that the risk for stoma was highest for patients with colonic Crohn’s disease and an anal stricture. Furthermore as the number of surgical procedures increased there was also an increase in permanent stoma formation.
3. Definitive surgery The place of definitive surgery for perianal CD is controversial and is usually only applicable to fissures or fistulae (Table 1). Conservative surgeons emphasise the observed healing of many fistulae with no treatment or medical therapy and the risks of surgery, particularly delayed wound healing and incontinence. More aggressive surgeons report satisfactory healing rates with surgical intervention particularly in the absence of sepsis and proctitis. The results of local definitive surgery are better in the absence of proctitis and sepsis. 3.1. Resection of proximal disease
Fig. 2. Silastic seton in a high ano-vaginal fistula.
Proximal intestinal CD may require resection due to an abscess, stricture formation, perforation or fistulating disease. Studies by Bergstrand et al. [20] and Heuman et al. [21] both showed that resection of intestinal disease led to improvement of perianal CD. Wolff et al. [22] also noted a reduced incidence of perianal CD but only if all of the proximal disease had been excised and there was no recurrence of disease. However, not all studies have shown a beneficial effect of proximal resection [23]. Therefore proximal bowel resection should only be performed for complicated CD and not as treatment per se for perianal CD.
990
B. Singh et al. / Digestive and Liver Disease 39 (2007) 988–992
Table 1 Specific treatment of perianal Crohn’s disease lesions [67] Condition
Treatment
Skin tags
Rarely require specific treatment. A reflection of underlying disease activity
Fissures
First line: pharmacological management (GTN paste, calcium channel antagonists, botulinum toxin) Second line: (proctitis) medical treatment ±Anal dilatation [68] (No proctitis) lateral internal sphincterotomy
Haemorrhoids
Surgical treatment should be avoided [50,51]
Ulcers
Medical management, including local injection of steroids [69]. Rarely require proctectomy, especially with proctitis
Anal stricture
Asymptomatic: no treatment Symptomatic: dilatation (if repeated dilatations required consider proctectomy especially if proctitis [52])
Abscess/fistula
Sepsis: drainage Bridging treatment: seton (rarely stoma) Specific treatment: 6-Mercaptopurine/azathioprine, anti-TNF␣ strategies and seton drainage Fistulotomy Flap repair (no proctitis) Proctectomy (proctitis)
3.2. Fistula This is the commonest presentation in the elective setting. However, the management of perianal fistulae is highlighted by the extensive range of surgical operations. These range from simple fistulotomy, either as a primary procedure or following staged seton drainage, to the use of flaps and interposition grafts. In some cases a repair is undertaken once a defunctioning stoma is raised thereby allowing an optimal environment for success. The failure rate of each procedure must be carefully balanced against its long-term effect on faecal incontinence. Operative management of fistulae depends on whether they are low or high/complex. In the former, success rates range from 73 to 94% by simple fistulotomy with minimal effects on continence [24–29]. Furthermore healing rates are improved in the absence of rectal disease. High/complex fistulae can be managed with a combination of seton drainage and staged fistulotomy again with poor results in the presence of rectal disease [5,12,30,31]. Whilst healing rates are not comparable to low fistulae the advantage of a long-term seton is a minimal effect on continence [32]. Alternatively a mucosal advancement flap can be used following resolution of underlying sepsis by initial seton drainage or in the presence of a defunctioning stoma [33]. More recently a combined surgical and medical approach has been shown to be extremely effective for the treatment of complex fistulae. This approach involves seton placement, infliximab and maintenance medical therapy [34–36]. Results have shown complete healing in 47–67% of cases [34,37]. In
these studies infliximab is administered systemically but an alternative approach is local injection of infliximab. Poggioli et al. described a course of six local injections of infliximab at four weekly intervals in patients with complex perianal CD fistulae [38]. In patients where there was no initial response treatment was extended up to 12 injections. Infliximab was administered at the internal opening and along the fistula tract. Healing was observed in 67% of cases. This treatment may avoid the systemic side effects on infliximab. A rectal mucosal advancement flap repair avoids the problem of open wounds as well as the poor healing that may occur in the presence of perianal sepsis. Furthermore it avoids the problem of dividing the sphincter mechanism and rendering patients incontinent. It can be used to repair both perianal and recto-vaginal fistulae. Results suggest an initial healing rate of 64–89% but recurrence in up to 50% [39–41]. Factors which are associated with flap failure include Crohn’s colitis [39], active small bowel CD [40] and proctitis [42]. Therefore in the presence of rectal disease the safest option is seton drainage and medical management to treat the proctitis. Alternative strategies to treat perianal fistulae are a dermalisland flap [43], a cutaneous advancement flap [44], a sleeve advancement flap [45] or a gracilis muscle transposition [46]. Options to repair recto-vaginal fistulae are similar to those used in perianal fistulae and include the anocutaneous flap [47], rectal advancement flap and a vaginal flap [48]. These may be performed as a single procedure or part of a staged procedure in which the initial procedure is a defunctioning stoma. 3.3. Other perianal CD conditions Symptomatic fissures which remain unhealed after appropriate medical therapy may be treated by lateral internal sphincterotomy [49]. Surgery is best avoided in the case of haemorrhoids as there is a risk for stricture formation and perianal sepsis [50,51]. In contrast anal strictures can be managed by repeated anal dilatations but failing conservative management may require proctectomy [52]. Surgical treatment is summarised in Table 1. 3.4. Proctectomy In instances where perianal disease has failed both medical management and local surgical treatment an option is proctectomy. This seems the appropriate treatment in the presence of extensive perianal disease and rectal involvement. The reported incidence for proctectomy is 12–20% [12,29,53,54]. However, a complication of proctectomy or proctocolectomy is poor wound healing and perineal sinus. The incidence of the latter is reduced if a stoma is raised prior to proctocolectomy [55]. To reduce the incidence of poor wound healing, following proctectomy, a gracilis transposition flap can be used [56] or a transverse rectus abdominis myocutaneous (TRAM) flap [57]. Whilst a low Hartmann’s procedure is an attractive compromise operation [58] there
B. Singh et al. / Digestive and Liver Disease 39 (2007) 988–992
is still approximately a 50% incidence of sepsis from the excluded rectal stump requiring a completion proctectomy [59]. 3.5. Novel surgical treatments Novel treatments include laser [60,61] and adhesive treatments. The use of fibrin adhesive glue for the treatment of fistulae seems an attractive idea. However, results are less successful for CD fistulae than for cryptogenic fistulae [62]. Similarly use of factor XIII was unsuccessful in treating such fistulae [63]. Variations to fibrin glue include human granulocyte colony-stimulating factor [64] and autologous mesenchymal adult stem cells. The latter are harvested from adipose tissue and initial studies have shown a complete response in 75% of patients with complex perianal CD fistulae [65]. More recently the use of an anal plug, incorporating porcine intestinal submucosa, has been used in the treatment of patients with an anal fistula. However, the long-term results in patients with perianal CD fistulae are awaited [66].
4. Conclusion Despite the common occurrence of this condition, which may be the only manifestation of CD, there is little evidencebased practice. The scope of treatment ranges from medical to surgical but often requiring a combined approach. In many cases medical strategies can lead to remission but there are side effects associated with long-term treatment. In contrast the benefit of a surgical solution must be weighed against any deterioration in continence. Therefore management of perianal CD relies on accurate evaluation of the condition and optimal results are seen with combined surgical and medical management.
Conflict of interest statement None declared.
References [1] Alexander-Williams J, Buchmann P. Perianal Crohn’s disease. World J Surg 1980;4:203–8. [2] Keighley MR, Allan RN. Current status and influence of operation on perianal Crohn’s disease. Int J Colorectal Dis 1986;1:104–7. [3] Frizelle FA, Santoro GA, Pemberton JH. The management of perianal Crohn’s disease. Int J Colorectal Dis 1996;11:227–37. [4] Fry RD, Shemesh EI, Kodner IJ, Timmcke A. Techniques and results in the management of anal and perianal Crohn’s disease. Surg Gynecol Obstet 1989;168:42–8. [5] Sangwan YP, Schoetz DJ, Murray JJ, Roberts PL, Coller JA. Perianal Crohn’s disease. Results of local surgical treatment. Dis Colon Rectum 1996;39:529–35. [6] Pritchard TJ, Schoetz DJ, Roberts PL, Murray JJ, Coller JA, Veidenheimer MC. Perirectal abscess in Crohn’s disease. Drainage and outcome. Dis Colon Rectum 1990;33:933–7.
991
[7] Solomon MJ. Fistulae and abscesses in symptomatic perianal Crohn’s disease. Int J Colorectal Dis 1996;11:222–6. [8] Schwartz DA, White CM, Wise PE, Herline AJ. Use of endoscopic ultrasound to guide combination medical and surgical therapy for patients with Crohn’s perianal fistulas. Inflamm Bowel Dis 2005;11:727–32. [9] Haggett PJ, Moore NR, Shearman JD, Travis SP, Jewell DP, Mortensen NJ. Pelvic and perineal complications of Crohn’s disease: assessment using magnetic resonance imaging. Gut 1995;36:407–10. [10] White RA, Eisenstat TE, Rubin RJ, Salvati EP. Seton management of complex anorectal fistulas in patients with Crohn’s disease. Dis Colon Rectum 1990;33:587–9. [11] Pearl RK, Andrews JR, Orsay CP, Weisman RI, Prasad ML, Nelson RL, et al. Role of the seton in the management of anorectal fistulas. Dis Colon Rectum 1993;36:573–7 [discussion 7-9]. [12] Williams JG, MacLeod CA, Rothenberger DA, Goldberg SM. Seton treatment of high anal fistulae. Br J Surg 1991;78:1159–61. [13] Buchanan GN, Owen HA, Torkington J, Lunniss PJ, Nicholls RJ, Cohen CR. Long-term outcome following loose-seton technique for external sphincter preservation in complex anal fistula. Br J Surg 2004;91:476–80. [14] Liu J, Bruch HP, Farke S, Nolde J, Schwandner O. Stoma formation for fecal diversion: a plea for the laparoscopic approach. Tech Coloproctol 2005;9:9–14 [discussion]. [15] Zelas P, Jagelman DG. Loop ileostomy in the management of Crohn’s colitis in the debilitated patient. Ann Surg 1980;191:164–8. [16] Harper PH, Kettlewell MG, Lee EC. The effect of split ileostomy on perianal Crohn’s disease. Br J Surg 1982;69:608–10. [17] Edwards CM, George BD, Jewell DP, Warren BF, Mortensen NJ, Kettlewell MG. Role of a defunctioning stoma in the management of large bowel Crohn’s disease. Br J Surg 2000;87:1063–6. [18] Yamamoto T, Allan RN, Keighley MR. Effect of fecal diversion alone on perianal Crohn’s disease. World J Surg 2000;24:1258–62 [discussion 62-3]. [19] Galandiuk S, Kimberling J, Al-Mishlab TG, Stromberg AJ. Perianal Crohn disease: predictors of need for permanent diversion. Ann Surg 2005;241:796–801 [discussion 2]. [20] Bergstrand O, Ewerth S, Hellers G, Holmstrom B, Ullman J, Wallberg P. Outcome following treatment of anal fistulae in Crohn’s disease. Acta Chir Scand Suppl 1980;500:43–4. [21] Heuman R, Bolin T, Sjodahl R, Tagesson C. The incidence and course of perianal complications and arthralgia after intestinal resection with restoration of continuity for Crohn’s disease. Br J Surg 1981;68:528–30. [22] Wolff BG, Culp CE, Beart RW, Ilstrup DM, Ready RL. Anorectal Crohn’s disease. A long-term perspective. Dis Colon Rectum 1985;28:709–11. [23] Marks CG, Ritchie JK, Lockhart-Mummery HE. Anal fistulas in Crohn’s disease. Br J Surg 1981;68:525–7. [24] Morrison JG, Gathright JB, Ray JE, Ferrari BT, Hicks TC, Timmcke AE. Surgical management of anorectal fistulas in Crohn’s disease. Dis Colon Rectum 1989;32:492–6. [25] Levien DH, Surrell J, Mazier WP. Surgical treatment of anorectal fistula in patients with Crohn’s disease. Surg Gynecol Obstet 1989;169:133–6. [26] Scott HJ, Northover JM. Evaluation of surgery for perianal Crohn’s fistulas. Dis Colon Rectum 1996;39:1039–43. [27] Platell C, Mackay J, Collopy B, Fink R, Ryan P, Woods R. Anal pathology in patients with Crohn’s disease. Aust N Z J Surg 1996;66:5–9. [28] Fuhrman GM, Larach SW. Experience with perirectal fistulas in patients with Crohn’s disease. Dis Colon Rectum 1989;32:847–8. [29] Williams JG, Rothenberger DA, Nemer FD, Goldberg SM. Fistula-inano in Crohn’s disease. Results of aggressive surgical treatment. Dis Colon Rectum 1991;34:378–84. [30] Halme L, Sainio AP. Factors related to frequency, type, and outcome of anal fistulas in Crohn’s disease. Dis Colon Rectum 1995;38:55–9. [31] Nordgren S, Fasth S, Hulten L. Anal fistulas in Crohn’s disease: incidence and outcome of surgical treatment. Int J Colorectal Dis 1992;7:214–8.
992
B. Singh et al. / Digestive and Liver Disease 39 (2007) 988–992
[32] Thornton M, Solomon MJ. Long-term indwelling seton for complex anal fistulas in Crohn’s disease. Dis Colon Rectum 2005;48:459–63. [33] van der Hagen SJ, Baeten CG, Soeters PB, Beets-Tan RG, Russel MG, van Gemert WG. Staged mucosal advancement flap for the treatment of complex anal fistulas: pretreatment with noncutting setons and in case of recurrent multiple abscesses a diverting stoma. Colorectal Dis 2005;7:513–8. [34] Topstad DR, Panaccione R, Heine JA, Johnson DRE, MacLean AR, Donald Buie W. Combined seton placement, infliximab infusion, and maintenance immunosuppressives improve healing rate in fistulizing anorectal Crohn’s disease: a single center experience. Dis Colon Rectum 2003;46:577–83. [35] Regueiro M, Mardini H. Treatment of perianal fistulizing Crohn’s disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis 2003;9:98–103. [36] Hyder SA, Travis SPL, Jewell DP, Mortensen NJ, George BD. Fistulating anal Crohn’s disease: results of combined surgical and infliximab treatment. Dis Colon Rectum 2006. [37] Talbot C, Sagar PM, Johnston MJ, Finan PJ, Burke D. Infliximab in the surgical management of complex fistulating anal Crohn’s disease. Colorectal Dis 2005;7:164–8. [38] Poggioli G, Laureti S, Pierangeli F, Rizzello F, Ugolini F, Gionchetti P, et al. Local injection of infliximab for the treatment of perianal Crohn’s disease. Dis Colon Rectum 2005;48:768–74. [39] Makowiec F, Jehle EC, Becker HD, Starlinger M. Clinical course after transanal advancement flap repair of perianal fistula in patients with Crohn’s disease. Br J Surg 1995;82:603–6. [40] Joo JS, Weiss EG, Nogueras JJ, Wexner SD. Endorectal advancement flap in perianal Crohn’s disease. Am Surg 1998;64:147–50. [41] Hyman N. Endoanal advancement flap repair for complex anorectal fistulas. Am J Surg 1999;178:337–40. [42] Jones IT, Fazio VW, Jagelman DG. The use of transanal rectal advancement flaps in the management of fistulas involving the anorectum. Dis Colon Rectum 1987;30:919–23. [43] Nelson RL, Cintron J, Abcarian H. Dermal island-flap anoplasty for transsphincteric fistula-in-ano: assessment of treatment failures. Dis Colon Rectum 2000;43:681–4. [44] Robertson WG, Mangione JS. Cutaneous advancement flap closure: alternative method for treatment of complicated anal fistulas. Dis Colon Rectum 1998;41:884–6 [discussion 6-7]. [45] Marchesa P, Hull TL, Fazio VW. Advancement sleeve flaps for treatment of severe perianal Crohn’s disease. Br J Surg 1998;85:1695–8. [46] Zmora O, Tulchinsky H, Gur E, Goldman G, Klausner JM, Rabau M. Gracilis muscle transposition for fistulas between the rectum and urethra or vagina. Dis Colon Rectum 2006. [47] Hesterberg R, Schmidt WU, Muller F, Roher HD. Treatment of anovaginal fistulas with an anocutaneous flap in patients with Crohn’s disease. Int J Colorectal Dis 1993;8:51–4. [48] Sher ME, Bauer JJ, Gelernt I. Surgical repair of rectovaginal fistulas in patients with Crohn’s disease: transvaginal approach. Dis Colon Rectum 1991;34:641–8. [49] Fleshner PR, Schoetz DJ, Roberts PL, Murray JJ, Coller JA, Veidenheimer MC. Anal fissure in Crohn’s disease: a plea for aggressive management. Dis Colon Rectum 1995;38:1137–43. [50] Wolkomir AF, Luchtefeld MA. Surgery for symptomatic hemorrhoids and anal fissures in Crohn’s disease. Dis Colon Rectum 1993;36:545–7.
[51] Jeffery PJ, Parks AG, Ritchie JK. Treatment of haemorrhoids in patients with inflammatory bowel disease. Lancet 1977;1:1084–5. [52] Linares L, Moreira LF, Andrews H, Allan RN, Alexander-Williams J, Keighley MR. Natural history and treatment of anorectal strictures complicating Crohn’s disease. Br J Surg 1988;75:653–5. [53] Basu A, Wexner SD. Perianal Crohn’s disease. Curr Treat Options Gastroenterol 2002;5:197–206. [54] Faucheron JL, Saint-Marc O, Guibert L, Parc R. Long-term seton drainage for high anal fistulas in Crohn’s disease – a sphincter-saving operation? Dis Colon Rectum 1996;39:208–11. [55] Yamamoto T, Bain IM, Allan RN, Keighley MR. Persistent perineal sinus after proctocolectomy for Crohn’s disease. Dis Colon Rectum 1999;42:96–101. [56] Rius J, Nessim A, Nogueras JJ, Wexner SD. Gracilis transposition in complicated perianal fistula and unhealed perineal wounds in Crohn’s disease. Eur J Surg 2000;166:218–22. [57] Oomen JW, Spauwen PH, Bleichrodt RP, van Goor H. Guideline proposal to reconstructive surgery for complex perineal sinus or rectal fistula. Int J Colorectal Dis 2006. [58] Sher ME, Bauer JJ, Gorphine S, Gelernt I. Low Hartmann’s procedure for severe anorectal Crohn’s disease. Dis Colon Rectum 1992;35:975–80. [59] Guillem JG, Roberts PL, Murray JJ, Coller JA, Veidenheimer MC, Schoetz DJ. Factors predictive of persistent or recurrent Crohn’s disease in excluded rectal segments. Dis Colon Rectum 1992;35: 768–72. [60] Bodzin JH. Laser ablation of complex perianal fistulas preserves continence and is a rectum-sparing alternative in Crohn’s disease patients. Am Surg 1998;64:627–31 [discussion 32]. [61] Moy J, Bodzin J. Carbon dioxide laser ablation of perianal fistulas in patients with Crohn’s disease: experience with 27 patients. Am J Surg 2006;191:424–7. [62] Lindsey I, Smilgin-Humphreys MM, Cunningham C, Mortensen NJ, George BD. A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula. Dis Colon Rectum 2002;45: 1608–15. [63] Oshitani N, Nakamura S, Matsumoto T, Kobayashi K, Kitano A. Treatment of Crohn’s disease fistulas with coagulation factor XIII. Lancet 1996;347:119–20. [64] Vaughan D, Drumm B. Treatment of fistulas with granulocyte colonystimulating factor in a patient with Crohn’s disease. N Engl J Med 1999;340:239–40. [65] Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA. A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 2005;48:1416–23. [66] Johnson EK, Gaw JU, Armstrong DN. Efficacy of anal fistula plug vs. fibrin glue in closure of anorectal fistulas. Dis Colon Rectum 2006;49:371–6. [67] Singh B, Mc CMNJ, Jewell DP, George B. Perianal Crohn’s disease. Br J Surg 2004;91:801–14. [68] Allan A, Keighley MR. Management of perianal Crohn’s disease. World J Surg 1988;12:198–202. [69] Hughes LE, Donaldson DR, Williams JG, Taylor BA, Young HL. Local depot methylprednisolone injection for painful anal Crohn’s disease. Gastroenterology 1988;94:709–11.
Mini-Symposium
Surgical therapy of perianal Crohn’s disease B. Singh a , B.D. George b , N.J. McC Mortensen b,∗ b
a Nuffield Department of Surgery, John Radcliffe Hospital, Oxford, United Kingdom Department of Colorectal Surgery, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom
Received 24 July 2007; accepted 24 July 2007 Available online 27 August 2007
Abstract The surgical management of perianal Crohn’s disease is complex with a wide range of operations being described. The initial emergency treatment is to drain any source of underlying sepsis. A loose seton drainage or a defunctioning stoma can then be used as a ‘bridge’ to definitive treatment allowing both adequate assessment of the condition and preventing further sepsis. The likelihood of success of any surgical repair must be weighed against the risk of faecal incontinence. Improved results of a local surgical repair are seen with optimal surgical and medical management of perianal Crohn’s disease. © 2007 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Damage limitation; Local repair; Perianal Crohn’s disease; Proctectomy; Sepsis
Anal Crohn’s disease (CD) affects approximately 33% of patients with CD. It is more common with distal intestinal disease and may cause considerable morbidity. Optimal management depends on thorough disease assessment, typically colonoscopy, small bowel radiology, MRI and examination under anaesthesia. This review considers the place of surgery in the light of recent advancements in medical therapy. The large list of operative procedures for perianal CD highlights the difficulty surgeons have in managing this group of patients. The relatively benign nature of some perianal conditions and the potential for major surgical complications, such as incontinence and unhealed wounds, has resulted in the traditional view that surgery be avoided as much as possible in perianal CD [1]. Keighley and Allan [2], for example, reported that in patients with a low anal fistula, treated by simple laying-open of the tract, there was poor healing in 8% of patients, and even of more concern was that 50% of patients reported postoperative incontinence. Surgical treatment includes resection of intestinal disease, a defunctioning stoma, local surgical repair or, in extreme cases, a proctectomy [3].
1. Emergency treatment of sepsis The commonest acute presentation of perianal CD is an underlying abscess which necessitates immediate incision and drainage [4,5]. Some surgeons favour leaving a drain (Mushroom or Malecot catheter) although there is little evidence that use of a drain alters the ultimate outcome [6]. The principles of surgery are to achieve adequate drainage of sepsis and to avoid sphincter damage. A course of perioperative antibiotics is advisable particularly if associated with cellulites. The most commonly used antibiotics are metronidazole and ciprofloxacin. A seton drain can be inserted at this initial presentation if a fistula tract is easily identified. In cases where an underlying abscess is not obvious use of intraoperative endoanal ultrasound may be helpful [7]. Furthermore serial endoanal ultrasound examinations also allow the surgeon to determine healing response to medical treatment [8]. Alternatively the extent and location of a perianal collection can be identified with a MRI scan [9] (Fig. 1).
2. Damage limitation ∗
Corresponding author. Tel.: +44 1865 220926; fax: +44 1865 221274. E-mail address: [email protected] (N.J. McC Mortensen).
Once any focus of sepsis has been drained the next stage involves stabilisation to allow adequate assessment of the
1590-8658/$30 © 2007 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2007.07.157
B. Singh et al. / Digestive and Liver Disease 39 (2007) 988–992
Fig. 1. A MRI scan showing an underlying abscess in a patient with perianal CD.
extent of perianal CD. We refer to this as the ‘bridging period’, which is also a period of damage limitation. The two commonest strategies employed are a loose (drainage) seton or a defunctioning stoma. The aim of seton drainage is to prevent further abscess formation, drain underlying sepsis and to avoid division of sphincter muscle. The commonest material used for a seton is an inert substance, such as silastic or ethibond (Fig. 2). Results suggest that outcomes using seton drainage are unaffected by rectal involvement and furthermore there is a minimal effect on incontinence [10–12]. Therefore seton drainage of Crohn’s fistulae is a safe option before attempting a more definitive surgical procedure. Whilst a seton can be left indefinitely the long-term results show recurrence in 83% of cases following removal [13]. If there is extensive perianal disease or disease progression despite initial abscess drainage then an alternative procedure is formation of a stoma. A defunctioning stoma may also allow control of sepsis prior to a proctectomy as well as
989
allowing patients to come to terms with a permanent stoma. In addition a defunctioning stoma also creates a favourable environment in which to perform a local perianal repair. A laparoscopic approach is now favoured because it is minimally invasive and also allows the opportunity to assess for intestinal disease [14]. Zelas and Jagelman [15] reported a loop ileostomy resulted in an initial clinical improvement in 96% of cases. However, recurrence developed in 26% of cases despite the presence of the ileostomy. This has been attributed to the fact that a loop ileostomy only partially defunctions the bowel. However, a split ileostomy improved perianal disease in only 69% of cases [16]. Edwards et al. [17] found that 15 (83%) out of 18 patients had remission of their perianal CD after being defunctioned. However, closure of the stoma was undertaken in only four patients with two developing relapse. Furthermore the study did not resolve the question of whether a split ileostomy results in a better prognosis than a loop ileostomy. Yamamoto et al. [18] also found that despite a clinical response of 81% in patients with perianal CD, defunctioned with a loop ileostomy or loop colostomy, only 10% of patients had their stoma reversed. Galandiuk et al. [19] looked at factors which predicted the need for a permanent stoma. They noted that the risk for stoma was highest for patients with colonic Crohn’s disease and an anal stricture. Furthermore as the number of surgical procedures increased there was also an increase in permanent stoma formation.
3. Definitive surgery The place of definitive surgery for perianal CD is controversial and is usually only applicable to fissures or fistulae (Table 1). Conservative surgeons emphasise the observed healing of many fistulae with no treatment or medical therapy and the risks of surgery, particularly delayed wound healing and incontinence. More aggressive surgeons report satisfactory healing rates with surgical intervention particularly in the absence of sepsis and proctitis. The results of local definitive surgery are better in the absence of proctitis and sepsis. 3.1. Resection of proximal disease
Fig. 2. Silastic seton in a high ano-vaginal fistula.
Proximal intestinal CD may require resection due to an abscess, stricture formation, perforation or fistulating disease. Studies by Bergstrand et al. [20] and Heuman et al. [21] both showed that resection of intestinal disease led to improvement of perianal CD. Wolff et al. [22] also noted a reduced incidence of perianal CD but only if all of the proximal disease had been excised and there was no recurrence of disease. However, not all studies have shown a beneficial effect of proximal resection [23]. Therefore proximal bowel resection should only be performed for complicated CD and not as treatment per se for perianal CD.
990
B. Singh et al. / Digestive and Liver Disease 39 (2007) 988–992
Table 1 Specific treatment of perianal Crohn’s disease lesions [67] Condition
Treatment
Skin tags
Rarely require specific treatment. A reflection of underlying disease activity
Fissures
First line: pharmacological management (GTN paste, calcium channel antagonists, botulinum toxin) Second line: (proctitis) medical treatment ±Anal dilatation [68] (No proctitis) lateral internal sphincterotomy
Haemorrhoids
Surgical treatment should be avoided [50,51]
Ulcers
Medical management, including local injection of steroids [69]. Rarely require proctectomy, especially with proctitis
Anal stricture
Asymptomatic: no treatment Symptomatic: dilatation (if repeated dilatations required consider proctectomy especially if proctitis [52])
Abscess/fistula
Sepsis: drainage Bridging treatment: seton (rarely stoma) Specific treatment: 6-Mercaptopurine/azathioprine, anti-TNF␣ strategies and seton drainage Fistulotomy Flap repair (no proctitis) Proctectomy (proctitis)
3.2. Fistula This is the commonest presentation in the elective setting. However, the management of perianal fistulae is highlighted by the extensive range of surgical operations. These range from simple fistulotomy, either as a primary procedure or following staged seton drainage, to the use of flaps and interposition grafts. In some cases a repair is undertaken once a defunctioning stoma is raised thereby allowing an optimal environment for success. The failure rate of each procedure must be carefully balanced against its long-term effect on faecal incontinence. Operative management of fistulae depends on whether they are low or high/complex. In the former, success rates range from 73 to 94% by simple fistulotomy with minimal effects on continence [24–29]. Furthermore healing rates are improved in the absence of rectal disease. High/complex fistulae can be managed with a combination of seton drainage and staged fistulotomy again with poor results in the presence of rectal disease [5,12,30,31]. Whilst healing rates are not comparable to low fistulae the advantage of a long-term seton is a minimal effect on continence [32]. Alternatively a mucosal advancement flap can be used following resolution of underlying sepsis by initial seton drainage or in the presence of a defunctioning stoma [33]. More recently a combined surgical and medical approach has been shown to be extremely effective for the treatment of complex fistulae. This approach involves seton placement, infliximab and maintenance medical therapy [34–36]. Results have shown complete healing in 47–67% of cases [34,37]. In
these studies infliximab is administered systemically but an alternative approach is local injection of infliximab. Poggioli et al. described a course of six local injections of infliximab at four weekly intervals in patients with complex perianal CD fistulae [38]. In patients where there was no initial response treatment was extended up to 12 injections. Infliximab was administered at the internal opening and along the fistula tract. Healing was observed in 67% of cases. This treatment may avoid the systemic side effects on infliximab. A rectal mucosal advancement flap repair avoids the problem of open wounds as well as the poor healing that may occur in the presence of perianal sepsis. Furthermore it avoids the problem of dividing the sphincter mechanism and rendering patients incontinent. It can be used to repair both perianal and recto-vaginal fistulae. Results suggest an initial healing rate of 64–89% but recurrence in up to 50% [39–41]. Factors which are associated with flap failure include Crohn’s colitis [39], active small bowel CD [40] and proctitis [42]. Therefore in the presence of rectal disease the safest option is seton drainage and medical management to treat the proctitis. Alternative strategies to treat perianal fistulae are a dermalisland flap [43], a cutaneous advancement flap [44], a sleeve advancement flap [45] or a gracilis muscle transposition [46]. Options to repair recto-vaginal fistulae are similar to those used in perianal fistulae and include the anocutaneous flap [47], rectal advancement flap and a vaginal flap [48]. These may be performed as a single procedure or part of a staged procedure in which the initial procedure is a defunctioning stoma. 3.3. Other perianal CD conditions Symptomatic fissures which remain unhealed after appropriate medical therapy may be treated by lateral internal sphincterotomy [49]. Surgery is best avoided in the case of haemorrhoids as there is a risk for stricture formation and perianal sepsis [50,51]. In contrast anal strictures can be managed by repeated anal dilatations but failing conservative management may require proctectomy [52]. Surgical treatment is summarised in Table 1. 3.4. Proctectomy In instances where perianal disease has failed both medical management and local surgical treatment an option is proctectomy. This seems the appropriate treatment in the presence of extensive perianal disease and rectal involvement. The reported incidence for proctectomy is 12–20% [12,29,53,54]. However, a complication of proctectomy or proctocolectomy is poor wound healing and perineal sinus. The incidence of the latter is reduced if a stoma is raised prior to proctocolectomy [55]. To reduce the incidence of poor wound healing, following proctectomy, a gracilis transposition flap can be used [56] or a transverse rectus abdominis myocutaneous (TRAM) flap [57]. Whilst a low Hartmann’s procedure is an attractive compromise operation [58] there
B. Singh et al. / Digestive and Liver Disease 39 (2007) 988–992
is still approximately a 50% incidence of sepsis from the excluded rectal stump requiring a completion proctectomy [59]. 3.5. Novel surgical treatments Novel treatments include laser [60,61] and adhesive treatments. The use of fibrin adhesive glue for the treatment of fistulae seems an attractive idea. However, results are less successful for CD fistulae than for cryptogenic fistulae [62]. Similarly use of factor XIII was unsuccessful in treating such fistulae [63]. Variations to fibrin glue include human granulocyte colony-stimulating factor [64] and autologous mesenchymal adult stem cells. The latter are harvested from adipose tissue and initial studies have shown a complete response in 75% of patients with complex perianal CD fistulae [65]. More recently the use of an anal plug, incorporating porcine intestinal submucosa, has been used in the treatment of patients with an anal fistula. However, the long-term results in patients with perianal CD fistulae are awaited [66].
4. Conclusion Despite the common occurrence of this condition, which may be the only manifestation of CD, there is little evidencebased practice. The scope of treatment ranges from medical to surgical but often requiring a combined approach. In many cases medical strategies can lead to remission but there are side effects associated with long-term treatment. In contrast the benefit of a surgical solution must be weighed against any deterioration in continence. Therefore management of perianal CD relies on accurate evaluation of the condition and optimal results are seen with combined surgical and medical management.
Conflict of interest statement None declared.
References [1] Alexander-Williams J, Buchmann P. Perianal Crohn’s disease. World J Surg 1980;4:203–8. [2] Keighley MR, Allan RN. Current status and influence of operation on perianal Crohn’s disease. Int J Colorectal Dis 1986;1:104–7. [3] Frizelle FA, Santoro GA, Pemberton JH. The management of perianal Crohn’s disease. Int J Colorectal Dis 1996;11:227–37. [4] Fry RD, Shemesh EI, Kodner IJ, Timmcke A. Techniques and results in the management of anal and perianal Crohn’s disease. Surg Gynecol Obstet 1989;168:42–8. [5] Sangwan YP, Schoetz DJ, Murray JJ, Roberts PL, Coller JA. Perianal Crohn’s disease. Results of local surgical treatment. Dis Colon Rectum 1996;39:529–35. [6] Pritchard TJ, Schoetz DJ, Roberts PL, Murray JJ, Coller JA, Veidenheimer MC. Perirectal abscess in Crohn’s disease. Drainage and outcome. Dis Colon Rectum 1990;33:933–7.
991
[7] Solomon MJ. Fistulae and abscesses in symptomatic perianal Crohn’s disease. Int J Colorectal Dis 1996;11:222–6. [8] Schwartz DA, White CM, Wise PE, Herline AJ. Use of endoscopic ultrasound to guide combination medical and surgical therapy for patients with Crohn’s perianal fistulas. Inflamm Bowel Dis 2005;11:727–32. [9] Haggett PJ, Moore NR, Shearman JD, Travis SP, Jewell DP, Mortensen NJ. Pelvic and perineal complications of Crohn’s disease: assessment using magnetic resonance imaging. Gut 1995;36:407–10. [10] White RA, Eisenstat TE, Rubin RJ, Salvati EP. Seton management of complex anorectal fistulas in patients with Crohn’s disease. Dis Colon Rectum 1990;33:587–9. [11] Pearl RK, Andrews JR, Orsay CP, Weisman RI, Prasad ML, Nelson RL, et al. Role of the seton in the management of anorectal fistulas. Dis Colon Rectum 1993;36:573–7 [discussion 7-9]. [12] Williams JG, MacLeod CA, Rothenberger DA, Goldberg SM. Seton treatment of high anal fistulae. Br J Surg 1991;78:1159–61. [13] Buchanan GN, Owen HA, Torkington J, Lunniss PJ, Nicholls RJ, Cohen CR. Long-term outcome following loose-seton technique for external sphincter preservation in complex anal fistula. Br J Surg 2004;91:476–80. [14] Liu J, Bruch HP, Farke S, Nolde J, Schwandner O. Stoma formation for fecal diversion: a plea for the laparoscopic approach. Tech Coloproctol 2005;9:9–14 [discussion]. [15] Zelas P, Jagelman DG. Loop ileostomy in the management of Crohn’s colitis in the debilitated patient. Ann Surg 1980;191:164–8. [16] Harper PH, Kettlewell MG, Lee EC. The effect of split ileostomy on perianal Crohn’s disease. Br J Surg 1982;69:608–10. [17] Edwards CM, George BD, Jewell DP, Warren BF, Mortensen NJ, Kettlewell MG. Role of a defunctioning stoma in the management of large bowel Crohn’s disease. Br J Surg 2000;87:1063–6. [18] Yamamoto T, Allan RN, Keighley MR. Effect of fecal diversion alone on perianal Crohn’s disease. World J Surg 2000;24:1258–62 [discussion 62-3]. [19] Galandiuk S, Kimberling J, Al-Mishlab TG, Stromberg AJ. Perianal Crohn disease: predictors of need for permanent diversion. Ann Surg 2005;241:796–801 [discussion 2]. [20] Bergstrand O, Ewerth S, Hellers G, Holmstrom B, Ullman J, Wallberg P. Outcome following treatment of anal fistulae in Crohn’s disease. Acta Chir Scand Suppl 1980;500:43–4. [21] Heuman R, Bolin T, Sjodahl R, Tagesson C. The incidence and course of perianal complications and arthralgia after intestinal resection with restoration of continuity for Crohn’s disease. Br J Surg 1981;68:528–30. [22] Wolff BG, Culp CE, Beart RW, Ilstrup DM, Ready RL. Anorectal Crohn’s disease. A long-term perspective. Dis Colon Rectum 1985;28:709–11. [23] Marks CG, Ritchie JK, Lockhart-Mummery HE. Anal fistulas in Crohn’s disease. Br J Surg 1981;68:525–7. [24] Morrison JG, Gathright JB, Ray JE, Ferrari BT, Hicks TC, Timmcke AE. Surgical management of anorectal fistulas in Crohn’s disease. Dis Colon Rectum 1989;32:492–6. [25] Levien DH, Surrell J, Mazier WP. Surgical treatment of anorectal fistula in patients with Crohn’s disease. Surg Gynecol Obstet 1989;169:133–6. [26] Scott HJ, Northover JM. Evaluation of surgery for perianal Crohn’s fistulas. Dis Colon Rectum 1996;39:1039–43. [27] Platell C, Mackay J, Collopy B, Fink R, Ryan P, Woods R. Anal pathology in patients with Crohn’s disease. Aust N Z J Surg 1996;66:5–9. [28] Fuhrman GM, Larach SW. Experience with perirectal fistulas in patients with Crohn’s disease. Dis Colon Rectum 1989;32:847–8. [29] Williams JG, Rothenberger DA, Nemer FD, Goldberg SM. Fistula-inano in Crohn’s disease. Results of aggressive surgical treatment. Dis Colon Rectum 1991;34:378–84. [30] Halme L, Sainio AP. Factors related to frequency, type, and outcome of anal fistulas in Crohn’s disease. Dis Colon Rectum 1995;38:55–9. [31] Nordgren S, Fasth S, Hulten L. Anal fistulas in Crohn’s disease: incidence and outcome of surgical treatment. Int J Colorectal Dis 1992;7:214–8.
992
B. Singh et al. / Digestive and Liver Disease 39 (2007) 988–992
[32] Thornton M, Solomon MJ. Long-term indwelling seton for complex anal fistulas in Crohn’s disease. Dis Colon Rectum 2005;48:459–63. [33] van der Hagen SJ, Baeten CG, Soeters PB, Beets-Tan RG, Russel MG, van Gemert WG. Staged mucosal advancement flap for the treatment of complex anal fistulas: pretreatment with noncutting setons and in case of recurrent multiple abscesses a diverting stoma. Colorectal Dis 2005;7:513–8. [34] Topstad DR, Panaccione R, Heine JA, Johnson DRE, MacLean AR, Donald Buie W. Combined seton placement, infliximab infusion, and maintenance immunosuppressives improve healing rate in fistulizing anorectal Crohn’s disease: a single center experience. Dis Colon Rectum 2003;46:577–83. [35] Regueiro M, Mardini H. Treatment of perianal fistulizing Crohn’s disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis 2003;9:98–103. [36] Hyder SA, Travis SPL, Jewell DP, Mortensen NJ, George BD. Fistulating anal Crohn’s disease: results of combined surgical and infliximab treatment. Dis Colon Rectum 2006. [37] Talbot C, Sagar PM, Johnston MJ, Finan PJ, Burke D. Infliximab in the surgical management of complex fistulating anal Crohn’s disease. Colorectal Dis 2005;7:164–8. [38] Poggioli G, Laureti S, Pierangeli F, Rizzello F, Ugolini F, Gionchetti P, et al. Local injection of infliximab for the treatment of perianal Crohn’s disease. Dis Colon Rectum 2005;48:768–74. [39] Makowiec F, Jehle EC, Becker HD, Starlinger M. Clinical course after transanal advancement flap repair of perianal fistula in patients with Crohn’s disease. Br J Surg 1995;82:603–6. [40] Joo JS, Weiss EG, Nogueras JJ, Wexner SD. Endorectal advancement flap in perianal Crohn’s disease. Am Surg 1998;64:147–50. [41] Hyman N. Endoanal advancement flap repair for complex anorectal fistulas. Am J Surg 1999;178:337–40. [42] Jones IT, Fazio VW, Jagelman DG. The use of transanal rectal advancement flaps in the management of fistulas involving the anorectum. Dis Colon Rectum 1987;30:919–23. [43] Nelson RL, Cintron J, Abcarian H. Dermal island-flap anoplasty for transsphincteric fistula-in-ano: assessment of treatment failures. Dis Colon Rectum 2000;43:681–4. [44] Robertson WG, Mangione JS. Cutaneous advancement flap closure: alternative method for treatment of complicated anal fistulas. Dis Colon Rectum 1998;41:884–6 [discussion 6-7]. [45] Marchesa P, Hull TL, Fazio VW. Advancement sleeve flaps for treatment of severe perianal Crohn’s disease. Br J Surg 1998;85:1695–8. [46] Zmora O, Tulchinsky H, Gur E, Goldman G, Klausner JM, Rabau M. Gracilis muscle transposition for fistulas between the rectum and urethra or vagina. Dis Colon Rectum 2006. [47] Hesterberg R, Schmidt WU, Muller F, Roher HD. Treatment of anovaginal fistulas with an anocutaneous flap in patients with Crohn’s disease. Int J Colorectal Dis 1993;8:51–4. [48] Sher ME, Bauer JJ, Gelernt I. Surgical repair of rectovaginal fistulas in patients with Crohn’s disease: transvaginal approach. Dis Colon Rectum 1991;34:641–8. [49] Fleshner PR, Schoetz DJ, Roberts PL, Murray JJ, Coller JA, Veidenheimer MC. Anal fissure in Crohn’s disease: a plea for aggressive management. Dis Colon Rectum 1995;38:1137–43. [50] Wolkomir AF, Luchtefeld MA. Surgery for symptomatic hemorrhoids and anal fissures in Crohn’s disease. Dis Colon Rectum 1993;36:545–7.
[51] Jeffery PJ, Parks AG, Ritchie JK. Treatment of haemorrhoids in patients with inflammatory bowel disease. Lancet 1977;1:1084–5. [52] Linares L, Moreira LF, Andrews H, Allan RN, Alexander-Williams J, Keighley MR. Natural history and treatment of anorectal strictures complicating Crohn’s disease. Br J Surg 1988;75:653–5. [53] Basu A, Wexner SD. Perianal Crohn’s disease. Curr Treat Options Gastroenterol 2002;5:197–206. [54] Faucheron JL, Saint-Marc O, Guibert L, Parc R. Long-term seton drainage for high anal fistulas in Crohn’s disease – a sphincter-saving operation? Dis Colon Rectum 1996;39:208–11. [55] Yamamoto T, Bain IM, Allan RN, Keighley MR. Persistent perineal sinus after proctocolectomy for Crohn’s disease. Dis Colon Rectum 1999;42:96–101. [56] Rius J, Nessim A, Nogueras JJ, Wexner SD. Gracilis transposition in complicated perianal fistula and unhealed perineal wounds in Crohn’s disease. Eur J Surg 2000;166:218–22. [57] Oomen JW, Spauwen PH, Bleichrodt RP, van Goor H. Guideline proposal to reconstructive surgery for complex perineal sinus or rectal fistula. Int J Colorectal Dis 2006. [58] Sher ME, Bauer JJ, Gorphine S, Gelernt I. Low Hartmann’s procedure for severe anorectal Crohn’s disease. Dis Colon Rectum 1992;35:975–80. [59] Guillem JG, Roberts PL, Murray JJ, Coller JA, Veidenheimer MC, Schoetz DJ. Factors predictive of persistent or recurrent Crohn’s disease in excluded rectal segments. Dis Colon Rectum 1992;35: 768–72. [60] Bodzin JH. Laser ablation of complex perianal fistulas preserves continence and is a rectum-sparing alternative in Crohn’s disease patients. Am Surg 1998;64:627–31 [discussion 32]. [61] Moy J, Bodzin J. Carbon dioxide laser ablation of perianal fistulas in patients with Crohn’s disease: experience with 27 patients. Am J Surg 2006;191:424–7. [62] Lindsey I, Smilgin-Humphreys MM, Cunningham C, Mortensen NJ, George BD. A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula. Dis Colon Rectum 2002;45: 1608–15. [63] Oshitani N, Nakamura S, Matsumoto T, Kobayashi K, Kitano A. Treatment of Crohn’s disease fistulas with coagulation factor XIII. Lancet 1996;347:119–20. [64] Vaughan D, Drumm B. Treatment of fistulas with granulocyte colonystimulating factor in a patient with Crohn’s disease. N Engl J Med 1999;340:239–40. [65] Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA. A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 2005;48:1416–23. [66] Johnson EK, Gaw JU, Armstrong DN. Efficacy of anal fistula plug vs. fibrin glue in closure of anorectal fistulas. Dis Colon Rectum 2006;49:371–6. [67] Singh B, Mc CMNJ, Jewell DP, George B. Perianal Crohn’s disease. Br J Surg 2004;91:801–14. [68] Allan A, Keighley MR. Management of perianal Crohn’s disease. World J Surg 1988;12:198–202. [69] Hughes LE, Donaldson DR, Williams JG, Taylor BA, Young HL. Local depot methylprednisolone injection for painful anal Crohn’s disease. Gastroenterology 1988;94:709–11.