Review Article

Medical-surgical Combined Approach in Perianal Fistulizing Crohn's Disease (CD): Doing it Together

Author(s): Kapil Sahnan*, Samuel O Adegbola, Ana Fareleira, Ailsa Hart and Janindra Warusavitarne

Volume 20, Issue 13, 2019

Page: [1373 - 1383] Pages: 11

DOI: 10.2174/1389450120666190520103454

Price: $65

Abstract

Fistulising perianal Crohn’s disease (pCD) is an aggressive phenotype, and patients not only suffer from perianal manifestations but also a worsening course for their luminal disease. This article describes the 6 key steps clinicians need to consider when managing patients with pCD which include; (i) ensuring a prompt diagnosis, (ii) multi-disciplinary management, (iii) psychological support, (iv) using multimodal medical and surgical treatment strategies, (v) continually monitoring and optimising therapy and (vi) ensuring that patients have a way of accessing care if required. Patients with fistulising pCD often have an unpredictable disease course and complete remission can be elusive. As such, a considered and nuanced approach is essential keeping the wider multi-disciplinary team and the patient involved in all decision making.

Keywords: Crohn's disease, perianal, surgery, medical therapy, luminal disease, optimising therapy.

Graphical Abstract
[1]
Tarrant KM, Barclay ML, Frampton CMA, Gearry RB. Perianal disease predicts changes in Crohn’s disease phenotype-results of a population-based study of inflammatory bowel disease phenotype. Am J Gastroenterol 2008; 103(12): 3082-93.
[http://dx.doi.org/10.1111/j.1572-0241.2008.02212.x] [PMID: 19086959]
[2]
Keighley MR, Allan RN. Current status and influence of operation on perianal Crohn’s disease. Int J Colorectal Dis 1986; 1(2): 104-7.
[http://dx.doi.org/10.1007/BF01648416] [PMID: 3611935]
[3]
Adegbola SO, Pisani A, Sahnan K, et al. Medical and surgical management of perianal Crohn’s disease. Ann Gastroenterol 2018; 31(2): 129-39.
[http://dx.doi.org/10.20524/aog.2018.0236] [PMID: 29507460]
[4]
Kotze PG, Shen B, Lightner A, et al. Modern management of perianal fistulas in Crohn’s disease: future directions. Gut 2018; 67(6): 1181-94.
[http://dx.doi.org/10.1136/gutjnl-2017-314918] [PMID: 29331943]
[5]
Hellers G, Bergstrand O, Ewerth S, Holmström B. Occurrence and outcome after primary treatment of anal fistulae in Crohn’s disease. Gut 1980; 21(6): 525-7.
[http://dx.doi.org/10.1136/gut.21.6.525] [PMID: 7429313]
[6]
Riss S, Schwameis K, Mittlböck M, et al. Sexual function and quality of life after surgical treatment for anal fistulas in Crohn’s disease. Tech Coloproctol 2013; 17(1): 89-94.
[http://dx.doi.org/10.1007/s10151-012-0890-x] [PMID: 22956209]
[7]
Adegbola S, Dibley L, Sahnan K, et al. N002 A qualitative exploration into experiences of living with Crohn’s anal fistula. J Crohn’s Colitis 2018; 12((supplement_1)): S568-9.
[http://dx.doi.org/10.1093/ecco-jcc/jjx180.1016]
[8]
Norton C, Dibley LB, Bassett P. Faecal incontinence in inflammatory bowel disease: associations and effect on quality of life. J Crohn’s Colitis 2013; 7(8): e302-11.
[http://dx.doi.org/10.1016/j.crohns.2012.11.004] [PMID: 23228710]
[9]
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(8): 750-5.
[http://dx.doi.org/10.1111/codi.13668] [PMID: 28371062]
[10]
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; (May): 1-6.
[http://dx.doi.org/10.1093/ecco-jcc/jjy071] [PMID: 29800373]
[11]
Sahnan K, Tozer PJ, Adegbola SO, et al. Developing a core outcome set for fistulising perianal Crohn’s disease. Gut 2018; 01136.
[http://dx.doi.org/doi:10.1136/gutjnl-2017-315503]
[12]
Singh S, Ding NS, Mathis KL, et al. Systematic review with meta-analysis: faecal diversion for management of perianal Crohn’s disease. Aliment Pharmacol Ther 2015; 42(7): 783-92.
[http://dx.doi.org/10.1111/apt.13356] [PMID: 26264359]
[13]
Sahnan K, Adegbola SO, Tozer PJ, Watfah J, Phillips RK. Perianal abscess. BMJ 2017; 356(8): j475.
[http://dx.doi.org/10.1136/bmj.j475] [PMID: 28223268]
[14]
Castaño-Milla C, Chaparro M, Saro C, et al. Effectiveness of adalimumab in perianal fistulas in crohn’s disease patients naive to anti-TNF therapy. J Clin Gastroenterol 2015; 49(1): 34-40.
[http://dx.doi.org/10.1097/MCG.0000000000000169] [PMID: 25485513]
[15]
Eglinton TW, Barclay ML, Gearry RB, Frizelle FA. The spectrum of perianal Crohn’s disease in a population-based cohort. Dis Colon Rectum 2012; 55(7): 773-7.
[http://dx.doi.org/10.1097/DCR.0b013e31825228b0] [PMID: 22706129]
[16]
Beaugerie L, Seksik P, Nion-Larmurier I, Gendre J-P, Cosnes J. Predictors of Crohn’s disease. Gastroenterology 2006; 130(3): 650-6.
[http://dx.doi.org/10.1053/j.gastro.2005.12.019] [PMID: 16530505]
[17]
Vavricka SR, Spigaglia SM, Rogler G, et al. Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease. Inflamm Bowel Dis 2012; 18(3): 496-505.
[http://dx.doi.org/10.1002/ibd.21719] [PMID: 21509908]
[18]
Schoepfer AM, Dehlavi M-A, Fournier N, et al. Diagnostic delay in Crohn’s disease is associated with a complicated disease course and increased operation rate. Am J Gastroenterol 2013; 108(11): 1744-53.
[http://dx.doi.org/10.1038/ajg.2013.248] [PMID: 23978953]
[19]
D’Haens G, Baert F, van Assche G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: An open randomised trial. Lancet 2008; 371(9613): 660-7.
[http://dx.doi.org/10.1016/S0140-6736(08)60304-9] [PMID: 18295023]
[20]
Pearce L, Newton K, Smith SR, et al. Multicentre observational study of outcomes after drainage of acute perianal abscess. Br J Surg 2016; 103(8): 1063-8.
[http://dx.doi.org/10.1002/bjs.10154] [PMID: 27061287]
[21]
Sahnan K, Askari A, Adegbola SO, et al. Natural history of anorectal sepsis. Br J Surg 2017; 104(13): 1857-65.
[http://dx.doi.org/10.1002/bjs.10614] [PMID: 28857130]
[22]
Lee MJ, Heywood N, Sagar PM, Brown SR, Fearnhead NS. Surgical management of fistulating perianal Crohn’s disease: a UK survey. Colorectal Dis 2017; 19(3): 266-73.
[http://dx.doi.org/10.1111/codi.13462] [PMID: 27423057]
[23]
Gecse KB, Bemelman W, Kamm MA, et al. A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn’s disease. Gut 2014; 63(9): 1381-92.
[http://dx.doi.org/10.1136/gutjnl-2013-306709] [PMID: 24951257]
[24]
Sahnan K, Adegbola SO, Tozer PJ, et al. Improving the understanding of perianal crohn fistula through 3d modeling. Ann Surg 2018; 267(6): e105-7.
[http://dx.doi.org/10.1097/SLA.0000000000002629] [PMID: 29232211]
[25]
Sahnan K, Adegbola SO, Tozer PJ, et al. Innovation in the imaging perianal fistula: a step towards personalised medicine. Therap Adv Gastroenterol 2018; 24(11): 1756284818775060.
[http://dx.doi.org/10.1177/1756284818775060] [PMID: 29854001]
[26]
Zhang CK, Hewett J, Hemming J, et al. The influence of depression on quality of life in patients with inflammatory bowel disease. Inflamm Bowel Dis 2013; 19(8): 1732-9.
[http://dx.doi.org/10.1097/MIB.0b013e318281f395] [PMID: 23669400]
[27]
Mahadev S, Young JM, Selby W, Solomon MJ. Self-reported depressive symptoms and suicidal feelings in perianal Crohn’s disease. Colorectal Dis 2012; 14(3): 331-5.
[http://dx.doi.org/10.1111/j.1463-1318.2011.02613.x] [PMID: 21689304]
[28]
Adegbola S, Dibley L, Sahnan K, et al. N001 Developing a quality of life score for Crohn’s anal fistula (CAF-QoL). J Crohn’s Colitis 2018; 12((supplement_1): S568-8.
[http://dx.doi.org/doi:10.1093/ecco-jcc/jjx180.1015]
[29]
Yassin N, Al-Hassi H, Ansari T, et al. PTU-200 Why do crohn’s and idiopathic anal fistulae persist? Gut 2015; 64((Suppl 1)): A151-1.
[http://dx.doi.org/10.1136/gutjnl-2015-309861.315]
[30]
Gionchetti P, Dignass A, Danese S, et al. 3rd European evidence-based consensus on the diagnosis and management of crohn’s disease 2016: part 2: surgical management and special situations. J Crohn’s Colitis 2017; 11(2): 135-49.
[http://dx.doi.org/10.1093/ecco-jcc/jjw169] [PMID: 27660342]
[31]
Kawalec P, Mikrut A, Wiśniewska N, Pilc A. Tumor necrosis factor-α antibodies (infliximab, adalimumab and certolizumab) in Crohn’s disease: systematic review and meta-analysis. Arch Med Sci 2013; 9(5): 765-79.
[http://dx.doi.org/10.5114/aoms.2013.38670] [PMID: 24273556]
[32]
Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004; 350(9): 876-85.
[http://dx.doi.org/10.1056/NEJMoa030815] [PMID: 14985485]
[33]
Lichtenstein GR, Yan S, Bala M, Blank M, Sands BE. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn’s disease. Gastroenterology 2005; 128(4): 862-9.
[http://dx.doi.org/10.1053/j.gastro.2005.01.048] [PMID: 15825070]
[34]
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(1): 52-65.
[http://dx.doi.org/10.1053/j.gastro.2006.11.041] [PMID: 17241859]
[35]
Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med 2007; 357(3): 239-50.
[http://dx.doi.org/10.1056/NEJMoa062897] [PMID: 17634459]
[36]
Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med 2007; 357(3): 228-38.
[http://dx.doi.org/10.1056/NEJMoa067594] [PMID: 17634458]
[37]
Schreiber S, Lawrance IC, Thomsen OØ, et al. Randomised clinical trial: certolizumab pegol for fistulas in Crohn’s disease - subgroup results from a placebo-controlled study. Aliment Pharmacol Ther 2011; 33(2): 185-93.
[http://dx.doi.org/10.1111/j.1365-2036.2010.04509.x] [PMID: 21083671]
[38]
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(8): 975-81. .e1, 4.
[http://dx.doi.org/10.1016/j.cgh.2012.12.042] [PMID: 23376316]
[39]
Colombel J-F, Feagan BG, Sandborn WJ, Van Assche G, Robinson AM. Therapeutic drug monitoring of biologics for inflammatory bowel disease. Inflamm Bowel Dis 2012; 18(2): 349-58.
[http://dx.doi.org/10.1002/ibd.21831] [PMID: 22021134]
[40]
Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 2013; 369(8): 711-21.
[http://dx.doi.org/10.1056/NEJMoa1215739] [PMID: 23964933]
[41]
Feagan B, Schwartz D, Danese S, et al. Vedolizumab for the treatment of fistulising Crohn’s disease: An exploratory analysis of data from GEMINI 2. J Crohn’s Colitis 2015; 9: S333-4.
[http://dx.doi.org/10.1093/ecco-jcc/jju027.626]
[42]
Sands BE, Blank MA, Diamond RH, Barrett JP, Van Deventer SJ. Maintenance infliximab does not result in increased abscess development in fistulizing Crohn’s disease: results from the ACCENT II study. Aliment Pharmacol Ther 2006; 23(8): 1127-36.
[http://dx.doi.org/10.1111/j.1365-2036.2006.02878.x] [PMID: 16611273]
[43]
Khorrami S, Ginard D, Marín-Jiménez I, et al. Ustekinumab for the Treatment of Refractory Crohnʼs Disease. Inflamm Bowel Dis 2016; 22(7): 1662-9.
[http://dx.doi.org/10.1097/MIB.0000000000000842] [PMID: 27306072]
[44]
Ma C, Fedorak RN, Kaplan GG, et al. Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn’s disease: real world experience from a multicentre cohort. Aliment Pharmacol Ther 2017; 45(9): 1232-43.
[http://dx.doi.org/10.1111/apt.14016] [PMID: 28252210]
[45]
Targan SR, Hanauer SB, van Deventer SJH, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med 1997; 337(15): 1029-35.
[http://dx.doi.org/10.1056/NEJM199710093371502] [PMID: 9321530]
[46]
Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002; 359(9317): 1541-9.
[http://dx.doi.org/10.1016/S0140-6736(02)08512-4] [PMID: 12047962]
[47]
Schreiber S, Rutgeerts P, Fedorak RN, et al. A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn’s disease. Gastroenterology 2005; 129(3): 807-18.
[http://dx.doi.org/10.1053/j.gastro.2005.06.064] [PMID: 16143120]
[48]
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(2): 323-33.
[http://dx.doi.org/10.1053/j.gastro.2005.11.030] [PMID: 16472588]
[49]
Sandborn WJ, Hanauer SB, Rutgeerts P, et al. Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial. Gut 2007; 56(9): 1232-9.
[http://dx.doi.org/10.1136/gut.2006.106781] [PMID: 17299059]
[50]
Colombel J-F, 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(1): 52-65.
[http://dx.doi.org/10.1053/j.gastro.2006.11.041] [PMID: 17241859]
[51]
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): 829-38.
[http://dx.doi.org/10.7326/0003-4819-146-12-200706190-00159] [PMID: 17470824]
[52]
Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 2010; 362(15): 1383-95.
[http://dx.doi.org/10.1056/NEJMoa0904492] [PMID: 20393175]
[53]
Sandborn WJ, Schreiber S, Feagan BG, et al. Certolizumab pegol for active Crohn’s disease: a placebo-controlled, randomized trial. Clin Gastroenterol Hepatol 2011; 9(8): 670-678.e3.
[http://dx.doi.org/10.1016/j.cgh.2011.04.031] [PMID: 21642014]
[54]
Adegbola SO, Sahnan K, Warusavitarne J, Hart A, Tozer P. Anti-TNF therapy in Crohn’s disease. Int J Mol Sci 2018; 19(8): E2244.
[http://dx.doi.org/10.3390/ijms19082244] [PMID: 30065229]
[55]
Graf W, Andersson M, Åkerlund J-E, Börjesson L. Long-term outcome after surgery for Crohn’s anal fistula. Colorectal Dis 2016; 18(1): 80-5.
[http://dx.doi.org/10.1111/codi.13106] [PMID: 26338142]
[56]
Adegbola SO, Sahnan K, Pellino G, et al. Short-term efficacy and safety of three novel sphincter-sparing techniques for anal fistulae: a systematic review. Tech Coloproctol 2017; 21(10): 775-82.
[http://dx.doi.org/10.1007/s10151-017-1699-4] [PMID: 29080959]
[57]
Wong S, Solomon M, Crowe P, Ooi K. Cure, continence and quality of life after treatment for fistula-in-ano. ANZ J Surg 2008; 78(8): 675-82.
[http://dx.doi.org/10.1111/j.1445-2197.2008.04616.x] [PMID: 18796027]
[58]
Sahnan K, Tozer PJ, Adegbola SO, et al. Developing a core outcome set for fistulising perianal Crohn’s disease. Gut 2019; 68(2): 226-38.
[http://dx.doi.org/10.1093/ecco-jcc/jjx180.103]
[59]
Cirocchi R, Farinella E, La Mura F, et al. Fibrin glue in the treatment of anal fistula: a systematic review. Ann Surg Innov Res 2009; 3(1): 12.
[http://dx.doi.org/10.1186/1750-1164-3-12] [PMID: 19912660]
[60]
Senéjoux A, Siproudhis L, Abramowitz L, et al. Fistula plug in fistulising ano-perineal Crohn’s Disease: A randomised controlled trial. J Crohn’s Colitis 2016; 10(2): 141-8.
[http://dx.doi.org/10.1093/ecco-jcc/jjv162] [PMID: 26351393]
[61]
Datta I, Johnston C, Baxter NN. A systematic review of the anal fistula plug for patients with crohnʼs and non-crohnʼs related fistula-in-ano. Dis Colon Rectum 2012; 55(3): 351-8.
[http://dx.doi.org/10.1097/DCR.0b013e318239d1e4] [PMID: 22469804]
[62]
Taxonera C, Schwartz DA, García-Olmo D. Emerging treatments for complex perianal fistula in Crohn’s disease. World J Gastroenterol 2009; 15(34): 4263-72.
[http://dx.doi.org/10.3748/wjg.15.4263] [PMID: 19750568]
[63]
Soltani A, Kaiser AM. Endorectal advancement flap for cryptoglandular or Crohn’s fistula-in-ano. Dis Colon Rectum 2010; 53(4): 486-95.
[http://dx.doi.org/10.1007/DCR.0b013e3181ce8b01] [PMID: 20305451]
[64]
Ky AJ, Sylla P, Steinhagen R, et al. Collagen fistula plug for the treatment of anal fistulas. Dis Colon Rectum 2008; 51(6): 838-43.
[http://dx.doi.org/10.1007/s10350-007-9191-2] [PMID: 18330649]
[65]
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(1): 59-62.e2.
[http://dx.doi.org/10.1053/j.gastro.2017.04.001] [PMID: 28400193]
[66]
Garcia-Olmo D, Herreros D, Pascual I, et al. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum 2009; 52(1): 79-86.
[http://dx.doi.org/10.1007/DCR.0b013e3181973487] [PMID: 19273960]
[67]
Pellino G, Selvaggi F. Surgical treatment of perianal fistulizing Crohn’s disease: From lay-open to cell-based therapy--an overview. Sci World J 2014; 2014: 146281.
[http://dx.doi.org/10.1155/2014/146281] [PMID: 25431776]
[68]
Mizrahi N, Wexner SD, Zmora O, et al. Endorectal advancement flap: are there predictors of failure? Dis Colon Rectum 2002; 45(12): 1616-21.
[http://dx.doi.org/10.1007/s10350-004-7248-z] [PMID: 12473884]
[69]
Göttgens KWA, Smeets RR, Stassen LPS, et al. Treatment of Crohn’s disease-related high perianal fistulas combining the mucosa advancement flap with platelet-rich plasma: a pilot study. Tech Coloproctol 2015; 19(8): 455-9.
[http://dx.doi.org/10.1007/s10151-015-1311-8] [PMID: 25975971]
[70]
Soltani A, Kaiser AM. Endorectal advancement flap for cryptoglandular or Crohn’s fistula-in-ano. Dis Colon Rectum 2010; 53(4): 486-95.
[http://dx.doi.org/10.1007/DCR.0b013e3181ce8b01] [PMID: 20305451]
[71]
Gingold DS. Murrell Z a, Fleshner PR. A prospective evaluation of the ligation of the intersphincteric tract procedure for complex anal fistula in patients with crohn disease. Ann Surg 2013; 00(00): 1-5.
[http://dx.doi.org/10.1097/SLA.0000000000000479] [PMID: 24374520]
[72]
Kamiński JP, Zaghiyan K, Fleshner P. Increasing experience of LIFT procedure for patients with Crohn’s disease: what have we learned?. Color Dis 2017.
[http://dx.doi.org/10.1111/codi.13668]
[73]
Lee WY, Park KJ, Cho YB, et al. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn’s fistula. Stem Cells 2013; 31(11): 2575-81.
[http://dx.doi.org/10.1002/stem.1357] [PMID: 23404825]
[74]
Ciccocioppo R, Bernardo ME, Sgarella A, et al. Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn’s disease. Gut 2011; 60(6): 788-98.
[http://dx.doi.org/10.1136/gut.2010.214841] [PMID: 21257987]
[75]
de la Portilla F, Alba F, García-Olmo D, Herrerías JM, González FX, Galindo A. Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn’s disease: results from a multicenter phase I/IIa clinical trial. Int J Colorectal Dis 2013; 28(3): 313-23.
[http://dx.doi.org/10.1007/s00384-012-1581-9] [PMID: 23053677]
[76]
Molendijk I, Bonsing BA, Roelofs H, et al. Allogeneic bone marrow-derived mesenchymal stromal cells promote healing of refractory perianal fistulas in patients with Crohn’s disease. Gastroenterology 2015; 149(4): 918-27.e6.
[http://dx.doi.org/10.1053/j.gastro.2015.06.014] [PMID: 26116801]
[77]
García-Olmo D, García-Arranz M, Herreros D, et al. A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 2005; 48(7): 1416-23.
[http://dx.doi.org/10.1007/s10350-005-0052-6] [PMID: 15933795]
[78]
Cho YB, Lee WY, Park KJ, et al. Autologous adipose tissue-derived stem cells for the treatment of Crohn’s fistula: A phase I clinical study. Cell Transplant 2013; 22(2): 279-85.
[http://dx.doi.org/10.3727/096368912X656045] [PMID: 23006344]
[79]
Panés J, García-Olmo D, Van Assche G, et al. 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): 1281-90.
[http://dx.doi.org/10.1016/S0140-6736(16)31203-X] [PMID: 27477896]
[80]
Gu J, Valente MA, Remzi FH, Stocchi L. Factors affecting the fate of faecal diversion in patients with perianal Crohn’s disease. Colorectal Dis 2015; 17(1): 66-72.
[http://dx.doi.org/10.1111/codi.12796] [PMID: 25306934]
[81]
Kasparek MS, Glatzle J, Temeltcheva T, et al. Long-term quality of life in patients with Crohn’s disease and perianal fistulas: influence of fecal diversion. Dis Colon Rectum 2007; 50(12): 2067-74.
[http://dx.doi.org/10.1007/s10350-007-9006-5] [PMID: 17680311]
[82]
Yamamoto T, Bain IM, Allan RN, Keighley MR. Persistent perineal sinus after proctocolectomy for Crohn’s disease. Dis Colon Rectum 1999; 42(1): 96-101.
[http://dx.doi.org/10.1007/BF02235190] [PMID: 10211527]
[83]
Lewis RT, Maron DJ. Efficacy and complications of surgery for Crohn’s disease. Gastroenterol Hepatol (N Y) 2010; 6(9): 587-96.
[PMID: 21088749]
[84]
Bermejo F, Guerra I, Algaba A, López-Sanromán A. Pharmacological approach to the management of crohn’s disease patients with perianal disease. Drugs 2018; 78(1): 1-18.
[http://dx.doi.org/10.1007/s40265-017-0842-x] [PMID: 29139091]
[85]
Guerra I, Bermejo F. Management of inflammatory bowel disease in poor responders to infliximab. Clin Exp Gastroenterol 2014; 7: 359-67.
[http://dx.doi.org/10.2147/CEG.S45297] [PMID: 25258548]
[86]
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(7): 933-40.
[http://dx.doi.org/10.1111/apt.13970] [PMID: 28211593]
[87]
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(5): 549-55.
[http://dx.doi.org/10.1093/ecco-jcc/jjw182] [PMID: 28453755]
[88]
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(2): 98-103.
[http://dx.doi.org/10.1097/00054725-200303000-00003] [PMID: 12769443]
[89]
Point-of-care and home faecal calprotectin tests for monitoring treatment response in inflammatory bowel disease Guidance and guidelines NICE.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy