The Essential Role of a Multidisciplinary Approach in Inflammatory Bowel Diseases: Combined Medical-Surgical Treatment in Complex Perianal Fistulas in CD

Jeroen Geldof; Nusrat Iqbal; Janindra Warusavitarne; Ailsa Hart

doi:10.1055/s-0041-1740035

Clinics in Colon and Rectal Surgery, Table of Contents

Clin Colon Rectal Surg 2022; 35(01): 021-031
DOI: 10.1055/s-0041-1740035

Review Article

The Essential Role of a Multidisciplinary Approach in Inflammatory Bowel Diseases: Combined Medical-Surgical Treatment in Complex Perianal Fistulas in CD

Jeroen Geldof

¹IBD Unit, St. Mark's Hospital, Harrow, United Kingdom

²Gastroenterology Department, University Hospital Ghent, Ghent, Belgium

,

Nusrat Iqbal

³Robin Phillips Fistula Research Unit, St. Mark's Hospital, Harrow, United Kingdom

,

Janindra Warusavitarne

³Robin Phillips Fistula Research Unit, St. Mark's Hospital, Harrow, United Kingdom

,

Ailsa Hart

¹IBD Unit, St. Mark's Hospital, Harrow, United Kingdom

³Robin Phillips Fistula Research Unit, St. Mark's Hospital, Harrow, United Kingdom

› Author Affiliations

Abstract

Perianal fistulizing Crohn's disease (PFCD) represents a challenging and complex disease phenotype. Patients typically suffer a more severe disease course than those without perianal complications and are often managing debilitating symptoms. Etiology is understood to be multifactorial, with genetic predisposition, microbiological insult, aberrant immunity, and mechanical factors all implicated. As a result, multimodal treatment strategies must be employed to achieve disease control and fistula closure. This requires the complimentary involvement of medical and surgical disciplines in order to ensure thorough assessment and treatment tailored to the individual scenario and patient goals. The aim of this article is to describe an overview of the various treatment strategies available for PFCD, focusing on how a synergistic approach is required to ensure maximal chances of success.

Keywords

Crohn's disease - PFCD - perianal fistula - multidisciplinary treatment

Full Text

References

References
1 Kotze PG, Shen B, Lightner A. et al. Modern management of perianal fistulas in Crohn's disease: future directions. Gut 2018; 67 (06) 1181-1194
2 Luglio G, Cassese G, Amendola A, Rispo A, Maione F, De Palma GD. Novel approaches to ileocolic and perianal fistulising Crohn's disease. Gastroenterol Res Pract 2018; 2018: 3159543
3 Gecse KB, Sebastian S, Hertogh Gd. et al. Results of the fifth scientific workshop of the ecco [ii]: clinical aspects of perianal fistulising Crohn's disease-the unmet needs. J Crohn's Colitis 2016; 10 (07) 758-765
4 Panés J, Rimola J. Perianal fistulizing Crohn's disease: pathogenesis, diagnosis and therapy. Nat Rev Gastroenterol Hepatol 2017; 14 (11) 652-664
5 Lopez N, Ramamoorthy S, Sandborn WJ. Recent advances in the management of perianal fistulizing Crohn's disease: lessons for the clinic. Expert Rev Gastroenterol Hepatol 2019; 13 (06) 563-577
6 Steinhart AH, Panaccione R, Targownik L. et al. Clinical practice guideline for the medical management of perianal fistulizing Crohn's disease: the Toronto consensus. Inflamm Bowel Dis 2019; 25 (01) 1-13
7 Yassin NA, Askari A, Warusavitarne J. et al. Systematic review: the combined surgical and medical treatment of fistulising perianal Crohn's disease. Aliment Pharmacol Ther 2014; 40 (07) 741-749
8 Papamichael K, Cheifetz AS. Defining and predicting deep remission in patients with perianal fistulizing Crohn's disease on anti-tumor necrosis factor therapy. World J Gastroenterol 2017; 23 (34) 6197-6200
9 Gold SL, Cohen-Mekelburg S, Schneider Y, Steinlauf A. Perianal fistulas in patients with Crohn's disease, part 1: current medical management. Gastroenterol Hepatol (N Y) 2018; 14 (08) 470-481
10 Park SH, Aniwan S, Scott Harmsen W. et al. Update on the natural course of fistulizing perianal Crohn's disease in a population-based cohort. Inflamm Bowel Dis 2019; 25 (06) 1054-1060
11 Schwartz DA, Ghazi LJ, Regueiro M. et al; Crohn's & Colitis Foundation of America, Inc. Guidelines for the multidisciplinary management of Crohn's perianal fistulas: summary statement. Inflamm Bowel Dis 2015; 21 (04) 723-730
12 Spinelli A, Armuzzi A, Ciccocioppo R. et al. Management of patients with complex perianal fistulas in Crohn's disease: optimal patient flow in the Italian clinical reality. Dig Liver Dis 2020; 52 (05) 506-515
13 Schwartz DA, Loftus Jr EV, Tremaine WJ. et al. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Gastroenterology 2002; 122 (04) 875-880
14 Tozer PJ, Lung P, Lobo AJ. et al; of ENiGMA Collaboration. Review article: pathogenesis of Crohn's perianal fistula-understanding factors impacting on success and failure of treatment strategies. Aliment Pharmacol Ther 2018; 48 (03) 260-269
15 Khan KJ, Ullman TA, Ford AC. et al. Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol 2011; 106 (04) 661-673
16 Su JW, Ma JJ, Zhang HJ. Use of antibiotics in patients with Crohn's disease: a systematic review and meta-analysis. J Dig Dis 2015; 16 (02) 58-66
17 Thia KT, Mahadevan U, Feagan BG. et al. Ciprofloxacin or metronidazole for the treatment of perianal fistulas in patients with Crohn's disease: a randomized, double-blind, placebo-controlled pilot study. Inflamm Bowel Dis 2009; 15 (01) 17-24
18 Adegbola SO, Pisani A, Sahnan K, Tozer P, Ellul P, Warusavitarne J. Medical and surgical management of perianal Crohn's disease. Ann Gastroenterol 2018; 31 (02) 129-139
19 Torres J, Bonovas S, Doherty G. et al. ECCO guidelines on therapeutics in Crohn's disease: medical treatment. J Crohn's Colitis 2020; 14 (01) 4-22
20 Pearson DC, May GR, Fick GH, Sutherland LR. Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. Ann Intern Med 1995; 123 (02) 132-142
21 Chande N, Townsend CM, Parker CE, MacDonald JK. Azathioprine or 6-mercaptopurine for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2016; 10 (10) CD000545
22 Sandborn WJ, Present DH, Isaacs KL. et al. Tacrolimus for the treatment of fistulas in patients with Crohn's disease: a randomized, placebo-controlled trial. Gastroenterology 2003; 125 (02) 380-388
23 Egan LJ, Sandborn WJ, Tremaine WJ. Clinical outcome following treatment of refractory inflammatory and fistulizing Crohn's disease with intravenous cyclosporine. Am J Gastroenterol 1998; 93 (03) 442-448
24 Present DH, Rutgeerts P, Targan S. et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 1999; 340 (18) 1398-1405
25 Sands BE, Anderson FH, Bernstein CN. et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med 2004; 350 (09) 876-885
26 Davidov Y, Ungar B, Bar-Yoseph H. et al. Association of induction infliximab levels with clinical response in perianal Crohn's disease. J Crohn's Colitis 2017; 11 (05) 549-555
27 Yarur AJ, Kanagala V, Stein DJ. et al. Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn's disease. Aliment Pharmacol Ther 2017; 45 (07) 933-940
28 Hanauer SB, Sandborn WJ, Rutgeerts P. et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology 2006; 130 (02) 323-333 , quiz 591
29 Sandborn WJ, Rutgeerts P, Enns R. et al. Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial. Ann Intern Med 2007; 146 (12) 829-838
30 Colombel JF, Sandborn WJ, Rutgeerts P. et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology 2007; 132 (01) 52-65
31 Colombel JF, Schwartz DA, Sandborn WJ. et al. Adalimumab for the treatment of fistulas in patients with Crohn's disease. Gut 2009; 58 (07) 940-948
32 Lichtiger S, Binion DG, Wolf DC. et al. The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn's disease who failed prior infliximab therapy. Aliment Pharmacol Ther 2010; 32 (10) 1228-1239
33 Strik A, Lowenberg M, Buskens CJ. et al. Higher anti-TNF serum levels are associated with perianal fistula closure in Crohn's disease patients. Scand J Gastroenterol 2019; 54 (04) 453-458
34 Schreiber S, Lawrance IC, Thomsen OØ, Hanauer SB, Bloomfield R, Sandborn WJ. Randomised clinical trial: certolizumab pegol for fistulas in Crohn's disease - subgroup results from a placebo-controlled study. Aliment Pharmacol Ther 2011; 33 (02) 185-193
35 Vavricka SR, Spasojevic M, Rogler G. et al; Swiss IBDnet. Long-term efficacy and safety of certolizumab pegol in an unselected Crohn's disease population: the FACTS III survey. Dig Dis 2017; 35 (05) 423-432
36 Feagan BG, Schwartz D, Danese S. et al. Efficacy of vedolizumab in fistulising Crohn's disease: exploratory analyses of data from GEMINI 2. J Crohn's Colitis 2018; 12 (05) 621-626
37 Schwartz DA, Peyrin-Biroulet L, Lasch K, Adsul S, Danese S. Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn's Disease: ENTERPRISE Study. Clin Gastroenterol Hepatol 2021; S1542-3565 (21) 01042-01049
38 Sands BE, Gasink C, Jacobstein D. et al. Fistula healing in pivotal studies of ustekinumab in Crohn's disease. Present DDW 2017 Gastroenterol 2017; 152: S185
39 Kotze PG, Ma C, Almutairdi A, Panaccione R. Clinical utility of ustekinumab in Crohn's disease. J Inflamm Res 2018; 11: 35-47
40 Biron C, Seksik P, Nachury M. et al. DOP74 efficacy of ustekinumab in perianal Crohn's disease: the BioLAP multi-centre observational study. J Crohn's Colitis 2019; 13 (Suppl. 01) S074-S075
41 Dejaco C, Harrer M, Waldhoer T, Miehsler W, Vogelsang H, Reinisch W. Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn's disease. Aliment Pharmacol Ther 2003; 18 (11-12): 1113-1120
42 West RL, van der Woude CJ, Hansen BE. et al. Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn's disease with infliximab: a double-blind placebo-controlled study. Aliment Pharmacol Ther 2004; 20 (11-12): 1329-1336
43 Dewint P, Hansen BE, Verhey E. et al. Adalimumab combined with ciprofloxacin is superior to adalimumab monotherapy in perianal fistula closure in Crohn's disease: a randomised, double-blind, placebo controlled trial (ADAFI). Gut 2014; 63 (02) 292-299
44 Sun XL, Chen SY, Tao SS, Qiao LC, Chen HJ, Yang BL. Optimized timing of using infliximab in perianal fistulizing Crohn's disease. World J Gastroenterol 2020; 26 (14) 1554-1563
45 Kwapisz L, Raffals LE, Bruining DH. et al. Combination biologic therapy in inflammatory bowel disease: experience from a tertiary care center. Clin Gastroenterol Hepatol 2021; 19 (03) 616-617
46 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 (02) 98-103
47 Tanaka S, Matsuo K, Sasaki T. et al. Clinical advantages of combined seton placement and infliximab maintenance therapy for perianal fistulizing Crohn's disease: when and how were the seton drains removed?. Hepatogastroenterology 2010; 57 (97) 3-7
48 Bouguen G, Siproudhis L, Gizard E. et al. Long-term outcome of perianal fistulizing Crohn's disease treated with infliximab. Clin Gastroenterol Hepatol 2013; 11 (08) 975-81.e1 , 4
49 Ibraheim H, Giacomini C, Kassam Z, Dazzi F, Powell N. Advances in mesenchymal stromal cell therapy in the management of Crohn's disease. Expert Rev Gastroenterol Hepatol 2018; 12 (02) 141-153
50 Lightner AL, Wang Z, Zubair AC, Dozois EJ. A systematic review and meta-analysis of mesenchymal stem cell injections for the treatment of perianal Crohn's disease: progress made and future directions. Dis Colon Rectum 2018; 61 (05) 629-640
51 Dietz AB, Dozois EJ, Fletcher JG. et al. Autologous mesenchymal stem cells, applied in a bioabsorbable matrix, for treatment of perianal fistulas in patients with Crohn's disease. Gastroenterology 2017; 153 (01) 59-62.e2
52 Panés J, García-Olmo D, Van Assche G. et al; ADMIRE CD Study Group Collaborators. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial. Lancet 2016; 388 (10051): 1281-1290
53 Panés J, García-Olmo D, Van Assche G. et al; ADMIRE CD Study Group Collaborators. Long-term efficacy and safety of stem cell therapy (Cx601) for complex perianal fistulas in patients with Crohn's disease. Gastroenterology 2018; 154 (05) 1334-1342.e4
54 NICE. Darvadstrocel for treating complex perianal fistulas in Crohn's disease (TA556). National Institute for Health and Care Excellence; 2018: 1-19
55 Adamina M, Bonovas S, Raine T. et al. ECCO guidelines on therapeutics in Crohn's disease: surgical treatment. J Crohn's Colitis 2020; 14 (02) 155-168
56 Gecse KB, Bemelman W, Kamm MA. et al; World Gastroenterology Organization, International Organisation for Inflammatory Bowel Diseases IOIBD, European Society of Coloproctology and Robarts Clinical Trials, World Gastroenterology Organization International Organisation for Inflammatory Bowel Diseases IOIBD European Society of Coloproctology and Robarts Clinical Trials. A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn's disease. Gut 2014; 63 (09) 1381-1392
57 Soltani A, Kaiser AM. Endorectal advancement flap for cryptoglandular or Crohn's fistula-in-ano. Dis Colon Rectum 2010; 53 (04) 486-495
58 Stellingwerf ME, van Praag EM, Tozer PJ, Bemelman WA, Buskens CJ. Systematic review and meta-analysis of endorectal advancement flap and ligation of the intersphincteric fistula tract for cryptoglandular and Crohn's high perianal fistulas. BJS Open 2019; 3 (03) 231-241
59 Rojanasakul A, Pattanaarun J, Sahakitrungruang C, Tantiphlachiva K. Total anal sphincter saving technique for fistula-in-ano; the ligation of intersphincteric fistula tract. J Med Assoc Thai 2007; 90 (03) 581-586
60 Mujukian A, Truong A, Fleshner P, Zaghiyan K. Long-term healing after complex anal fistula repair in patients with Crohn's disease. Tech Coloproctol 2020; 24 (08) 833-841
61 Gingold DS, Murrell ZA, Fleshner PR. A prospective evaluation of the ligation of the intersphincteric tract procedure for complex anal fistula in patients with Crohn's disease. Ann Surg 2014; 260 (06) 1057-1061
62 van Praag EM, Stellingwerf ME, van der Bilt JDW, Bemelman WA, Gecse KB, Buskens CJ. Ligation of the intersphincteric fistula tract and endorectal advancement flap for high perianal fistulas in Crohn's disease: a retrospective cohort study. J Crohn's Colitis 2020; 14 (06) 757-763
63 Kamiński JP, Zaghiyan K, Fleshner P. Increasing experience of ligation of the intersphincteric fistula tract for patients with Crohn's disease: what have we learned?. Colorectal Dis 2017; 19 (08) 750-755
64 Meinero P, Mori L. Video-assisted anal fistula treatment (VAAFT): a novel sphincter-saving procedure for treating complex anal fistulas. Tech Coloproctol 2011; 15 (04) 417-422
65 Schwandner O. Video-assisted anal fistula treatment (VAAFT) combined with advancement flap repair in Crohn's disease. Tech Coloproctol 2013; 17 (02) 221-225
66 Adegbola SO, Sahnan K, Tozer PJ. et al. Symptom amelioration in Crohn's perianal fistulas using video assisted anal fistula treatment (VAAFT). J Crohn's Colitis 2018; 12 (09) 1067-1072
67 Giamundo P, Esercizio L, Geraci M, Tibaldi L, Valente M. Fistula-tract Laser Closure (FiLaC™): long-term results and new operative strategies. Tech Coloproctol 2015; 19 (08) 449-453
68 Wilhelm A, Fiebig A, Krawczak M. Five years of experience with the FiLaC™ laser for fistula-in-ano management: long-term follow-up from a single institution. Tech Coloproctol 2017; 21 (04) 269-276
69 Senéjoux A, Siproudhis L, Abramowitz L. et al; Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif [GETAID]. Fistula plug in fistulising ano-perineal Crohn's disease: a randomised controlled trial. J Crohn's Colitis 2016; 10 (02) 141-148
70 Grimaud JC, Munoz-Bongrand N, Siproudhis L. et al; Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif. Fibrin glue is effective healing perianal fistulas in patients with Crohn's disease. Gastroenterology 2010; 138 (07) 2275-2281 , 2281.e1
71 Vidon M, Munoz-Bongrand N, Lambert J. et al. Long-term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease. Colorectal Dis 2021; 23 (04) 894-900
72 Ferrante M, Siproudhis L, Poggioli G. et al. P801 treatment patterns of complex perianal fistula in Crohn's disease in five European countries: the PREFACE study, a retrospective chart review. J Crohn's Colitis 2020; 14 (Suppl. 01) S628-S628
73 Iqbal N, Twum-Barima C, Reza L, Warusavitarne J, Tozer P, Hart A. P007 joint medical-surgical assessment in inflammatory bowel disease (IBD) clinics: are patients satisfied?. Colorectal Dis 2020; 22 (S3): 9-57