Citation for published version (APA): de Groof, E. J. (2017). Surgery and medical therapy in Crohn s disease: Improving treatment strategies

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1 UvA-DARE (Digital Academic Repository) Surgery and medical therapy in Crohn s disease de Groof, E.J. Link to publication Citation for published version (APA): de Groof, E. J. (2017). Surgery and medical therapy in Crohn s disease: Improving treatment strategies General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 17 Mar 2019

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4 Inflammatory bowel disease Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract usually affecting patients at a young age. Patients are either diagnosed with Crohn s disease (CD) or ulcerative colitis (UC). CD can affect any part of the gastrointestinal tract and is characterized by transmural inflammation, while UC is confined to the colon and rectum with more superficial inflammation. Both UC and CD are reported to have a substantial impact on quality of life (QoL). Prevalence and incidence In the past two decades, prevalence and incidence rates of IBD have changed throughout the world. IBD used to be more common in industrialised countries in Europe and North-America and was relatively rare in Asia, Africa, and Latin-America. The highest reported prevalence rates for IBD were in Europe (UC, 505 per 100,000 persons; CD, 322 per 100,000 persons) and North America (UC, 249 per 100,000 persons; CD, 319 per 100,000 persons). 1 Multidisciplinary treatment Most IBD patients are initially treated with medical therapy. However, intestinal resection is ultimately required in approximately 75% of patients with CD and up to 35% of patients with UC during the course of their disease. 2 Established indications for surgery in IBD include therapy refractory disease, unacceptable medical therapy side-effects and, in patients with CD, a perforation or obstruction. Procedures depend on the localization and extension of the disease and vary from ileocecal resections for localised disease in CD to restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for extensive therapy refractory UC. Ileocecal Crohn s disease Ileocecal resection versus infliximab Patients with CD of the terminal ileum are nowadays treated according to the step-up approach. This traditional pyramid step up approach has not been changed for years, starting with prednisolone for induction after which maintenance treatment with an 11

5 immunomodulator, e.g. azathioprine or mercaptopurine, can be initiated. 3 If necessary treatment can be escalated to anti-tnf, which was introduced in Ileocolic resection for localised terminal ileitis is a common procedure in CD patients with a stenosis of the ileum or medical therapy refractory disease. However, surgery is still generally considered as last resort when all medical options failed. Single port laparoscopic surgery for IBD Multi-port laparoscopic surgery for IBD was first reported in the early 1990s. 4 Since then experience has evolved and more complex laparoscopic procedures were performed for both CD and UC. There is an abundance of literature claiming that laparoscopic small and large bowel resections are safe and efficacious. Therefore, laparoscopy is considered to be an important surgical tool in the minimally invasive treatment of IBD patients. Single-incision laparoscopic resection in colorectal surgery was first described in 2008 and is considered a feasible and safe procedure. 5, 6 Perianal Crohn s disease In population-based estimates CD patients have a lifetime risk of fistula development ranging from 14% to 38%. 7 Perianal fistulising disease is associated with local pain, discharge, and considerable morbidity rates (including sphincter and perineal tissue destruction) resulting in a negative impact on quality of life. Unfortunately spontaneous fistula closure rates are low, with estimates from 6% to 13%. 8, 9 The impact on health care resources is enormous due to multiple surgical interventions and costly medication. Classification Two classification systems of perianal fistulas are used: the Park s and the American Gastroenterology Association (AGA) classification. 10 The Parks classification defines four types of perianal fistulas in relation to the external sphincter: intersphincteric, transsphincteric, suprasphincteric and extrasphincteric. The most common fistulas are the intersphincteric and the transsphincteric. A more clinical classification with a distinction between simple and complex fistulas was proposed by the AGA. The Parks classification is superior from a surgical point of view. However, since this system can be complicated 12

6 in daily practice a distinction between simple and complex can be a better option, especially in a multidisciplinary setting. Treatment of perianal fistulas Management of perianal fistulas requires the availability of specialist imaging techniques and detailed understanding of perianal anatomy and pathology, especially in complex fistulas. Treatment of perianal fistulas has changed since the introduction of biologicals, towards more non-surgical treatment. 8 There are several treatment options for complex high fistulas (involvement of upper two-thirds of external sphincter). Complete closure and fibrosis of the fistula tract can be achieved either via surgical approach or with medical treatment. Medical therapy The administration of medical therapy in Crohn s perianal fistulas aims at reduction of symptoms and eventually closure, with improvement of QoL. Prevention of recurrent abscess formation is of crucial importance. There are several medical treatment options. Symptom alleviation may be achieved with medical therapy, however definite closure of perianal fistulas is rare and, unfortunately, overall recurrence rates are high. With the introduction of anti-tnf agents (infliximab and adalimumab), the treatment for Crohn s fistulas has changed from almost exclusively surgical to placing a much larger emphasis on medical therapy. Since the results of two large trials, assessing the 8, 11 benefit of anti-tnf medication, almost all patients receive this medication. Surgical therapy The majority of patients with perianal fistulas requires surgical treatment during the course of their disease. Primary treatment goals of surgical treatment are abscess drainage and prevention of recurrent abscesses by remaining patency of the tract. On the long term, fistula closure and preservation of continence are more important. Several techniques are available, depending on the characteristics of the fistula. Until several decades ago, the most frequently used treatment approach for complex perianal fistulas has been surgical seton placement for chronic drainage of the tract. A seton maintains patency of the tract and eliminates the accumulation of pus which prevents the recurrent formation of tracts and abscesses, with subsequent low re-intervention rates (10-20%). 12 However, the seton has been reported to negatively influence QoL. Another disadvantage of this technique is that the fistula will not close with the seton 13

7 in situ. It remains unclear when the seton can be removed and whether the tract heals after removal. Another surgical treatment option is closure of the internal fistula opening by creating an advancement plasty (figure 1 and 2). This is usually done after primary seton drainage for several weeks. In a recent systematic review, the success rate of endorectal advancement plasty for Crohn s fistulas was 64%. These results seem quite promising, although almost 10% faecal incontinence was described and re-interventions were needed in almost 50% of the patients. 13 Fig 1 and 2: Endorectal advancement flap procedure steps. Proctectomy in IBD In some patients with severe (colo)rectal CD or UC, a completion proctectomy may be indicated. Epidemiological studies revealed that rectal resection is necessary in up to 20% of Crohn s patients with perianal fistulas. 14 In these patients, perineal wound healing is frequently disturbed and creates a major problem for these patients. In CD, failed primary perineal wound healing is reported in > 50% of the patients, whereas this is less frequently reported in ulcerative colitis (UC) Known perineal complications are persistent perineal sepsis with presacral abscess formation or development of a persistent sinus, both of which are difficult to manage Since complete lymph node dissection according to oncological principles is not necessary in IBD, close rectal dissection has been proposed. This technique was first described by Lee and Downing in It has been hypothesised that close rectal dissection could improve healing and reduce infectious complications by leaving the rectal mesentery in situ to minimise the pelvic dead space when compared to total mesorectal excision. 14

8 The mesorectum is mainly composed of adipose tissue. Adipose tissue has been implicated in CD, as one of the hallmarks of CD is the wrapping of mesenteric adipose tissue around the intestine, known as creeping fat. 26, 27 Although creeping fat is generally considered to be pathological, only scant literature is available regarding its composition and function. 15

9 References 1. Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012; 142:46-54 e42; quiz e Rungoe C, Langholz E, Andersson M, et al. Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study Gut 2014; 63: Dignass A, Van Assche G, Lindsay JO, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn s disease: Current management. J Crohns Colitis 2010; 4: Peters WR. Laparoscopic total proctocolectomy with creation of ileostomy for ulcerative colitis: report of two cases. J Laparoendosc Surg 1992; 2: Remzi FH, Kirat HT, Kaouk JH, et al. Single-port laparoscopy in colorectal surgery. Colorectal Dis 2008; 10: Bucher P, Pugin F, Morel P. Single port access laparoscopic right hemicolectomy. Int J Colorectal Dis 2008; 23: Hellers G, Bergstrand O, Ewerth S, et al. Occurrence and outcome after primary treatment of anal fistulae in Crohn s disease. Gut 1980; 21: 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: Present DH, Korelitz BI, Wisch N, et al. Treatment of Crohn s disease with 6-mercaptopurine. A long-term, randomised, double-blind study. N Engl J Med 1980; 302: Parks AG, Gordon PH, Hardcastle JD. A classification of fistula-in-ano. Br J Surg 1976; 63: 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: Buchanan GN, Owen HA, Torkington J, et al. Long-term outcome following loose-seton technique for external sphincter preservation in complex anal fistula. Br J Surg 2004; 91: Soltani A, Kaiser AM. Endorectal advancement flap for cryptoglandular or Crohn s fistulain-ano. Dis Colon Rectum 2010; 53: Singh S, Ding NS, Mathis KL, et al. Systematic review with meta-analysis: faecal diversion for management of perianal Crohn s disease. Alimentary Pharmacology & Therapeutics 2015; 42: Irvin TT, Goligher JC. A controlled clinical trial of three different methods of perineal wound management following excision of the rectum. Br J Surg 1975; 62: Corman ML, Veidenheimer MC, Coller JA, et al. Perineal wound healing after proctectomy for inflammatory bowel disease. Dis Colon Rectum 1978; 21: Oakley JR, Fazio VW, Jagelman DG, et al. Management of the perineal wound after rectal excision for ulcerative colitis. Dis Colon Rectum 1985; 28: Baudot P, Keighley MR, Alexander-Williams J. Perineal wound healing after proctectomy for carcinoma and inflammatory disease. Br J Surg 1980; 67: Schlegel N, Kim M, Reibetanz J, et al. Sphincter-sparing intersphincteric rectal resection as an alternative to proctectomy in long-standing fistulizing and stenotic Crohn s proctitis? Int J Colorectal Dis 2015; 30:

10 20. Yamamoto T, Bain IM, Allan RN, et al. Persistent perineal sinus after proctocolectomy for Crohn s disease. Dis Colon Rectum 1999; 42: Rius J, Nessim A, Nogueras JJ, et al. Gracilis transposition in complicated perianal fistula and unhealed perineal wounds in Crohn s disease. Eur J Surg 2000; 166: Collie MH, Potter MA, Bartolo DC. Myocutaneous flaps promote perineal healing in inflammatory bowel disease. Br J Surg 2005; 92: Adam, Shorthouse. Perineal wound morbidity following proctectomy for inflammatory bowel disease (IBD). Colorectal Dis 2000; 2: Yamamoto T, Mylonakis E, Keighley MR. Omentoplasty for persistent perineal sinus after proctectomy for Crohn s disease. Am J Surg 2001; 181: Lee EC, Dowling BL. Perimuscular excision of the rectum for Crohn s disease and ulcerative colitis. A conservation technique. Br J Surg 1972; 59: Desreumaux P, Ernst O, Geboes K, et al. Inflammatory alterations in mesenteric adipose tissue in Crohn s disease. Gastroenterology 1999; 117: Peyrin-Biroulet L, Chamaillard M, Gonzalez F, et al. Mesenteric fat in Crohn s disease: a pathogenetic hallmark or an innocent bystander? Gut 2007; 56: