Genova 24 novembre 2012 La storia naturale delle recidive post- operatorie della malattia di Crohn giovanni russo GL IBD U.O.C. gastroenterologia asl 5 spezzino

POST-OPERATIVE RECURRENCE SURGERY IS AN ALMOST INEVITABLE EVENT IN CD BUT IS NOT CURATIVE: POST-OPERATIVE RECURRENCE FOLLOW A PREDICTABLE AND SEQUENTIAL COURSE 1 YEAR after resection: 60-80% of patients have new lesions at the neo-terminal ileum (endoscopic recurrence), 10-20% will develop symptoms (clinical recurrence) 5% will need further intestinal resection (surgical recurrence) 10 YEARS after resection 50% of patients will clinical recurrence 35% will need reoperation. Ferrante, et al gastroenterology 2006

PRESYMPTOMATIC PHASE: why the ileal mucosa is so vulnerable to recurrent lesions? a)Perineural inflammatory changes in the section margins b)Bacteria c)Luminal contents d)Bile acids e)The break in the mucosa of the suture f)Reflux of colonic contents g)The organization of the mucosal immune cells Greenstein, GUT 1998

RUTGEERTS SCORE (gastroenterology 1990) ENDOSCOPIC HEALING OR RECURRENCE IN THE NEOTERMINAL ILEUM AFTER SURGERY IN CD 0 no lesions 1 <5 apthous lesions 2 >5 apthous lesions with normal mucosa between the lesions 3 Diffuse apthous ileitis with diffusely inflamed mucosa 4 Diffuse inflammation, already with larger ulcers, nodules, and/or narrowing

PREDICTABILITY The severity and extent of tissue recurrence predicts the time of the clinical relapse : REGUEIRO, GASTROENTEROLOGY ) patients without lesions or presenting with only a few aphtous ulcers at ileocolonoscopy at 1 year are not at risk for early symptomatic relapse 2) more than half of the patients presenting with diffuse aphtous or ulcerative ileitis will have symptomatic relapse within 1 to 3 years after operation 3) patients with ulcers confined to the immediate perianastomotic region are probably prone to develop a fibrotic stricture

PREDICTOR FACTORS 1)SEVERITY OF ENDOSCOPIC LESIONS one year after surgery is the strongest predictor of the subsequent clinical course RIGBY, GUT ) age at onset of disease 3) age at the time of surgery (40 years) 4) gender (female) 5) family history of CD 6) smoking habits 7) duration of disease before surgery 8) indication for surgery 9) length of resected bowel and anastomotic technique 10) presence of granuloma in the surgical specimen 11) disease involvement at the line of resection 12) need of blood transfusions 13) post operative prophylactic treatment

ECCO GUIDELINES PREDICTING POST-OP RECURRENCE ECCO Statement 8A The following are considered predictors of early post- operative recurrence after ileocolonic resection: 1)smoking, 2)prior intestinal surgery 3)penetrating disease behaviour, 4)perianal location 5)extensive small bowel resection 6)absence of prophylactic treatment is associated with a higher risk of relapse.

IMAGING AND POST-OP RECURRENCE ECCO Statement 8D (2010) Radiology and imaging (US, MR, and CT) are being evaluated as independent diagnostic methods for post- operative recurrence. SBCE performed 6 or 12 months after surgery appears of comparable sensitivity, specificity and positive and negative predictive values as ileocolonoscopy in diagnosing post-operative recurrence. The value of MR or CT enterography, or SBCE to diagnose post- operative recurrence in the ileum or jejunum has not been systematically studied.

SURGICAL TIMING Disease duration before surgery seems to affect the post-operative course. A short disease duration before surgery ( 3 years). Margagnoni, Papi et al Minerva gastroenterol 2011

RISK FACTORS: BEHAVIOR OF DISEASE PERFORATING GROUP: Time to first reoperation was 4.7 years (acute free perforation, subacute perforation with abscess and chronic perforation with fistula); in this group time to second reoperation averaged 2.3 years. Second operation was in 64% of the patients with ileitis and 77% with ileocolitis. RIGBY, GUT 2009 NON-PERFORATING GROUP: Time to first reoperation was 8.8 years (intestinal obstruction, medical intractibility, hemorrhage, and toxic dilatation without perforation); in this group time to second reoperation was 5.2 years

BEHAVIOR OF DISEASE The pattern of CD remains unchanged after surgery in comparison with the preoperative situation Perforating disease tend to the develop the same complications and will have early recurrent symptoms Fibrostenosis disease will be more indolent after resection RUTGEERTS, ADVANCED THERAPY OF IBD,2011

RISK FACTORS:LOCATION Highest rate of recurrence are found after resection for ileocolitis or ileitis with ileocolonic anastomosis. Reoperation rates range from 40% at 5 years and 65% at 15 years Lower rates are found after colonic resection with colo- colonic anastomosis. Reoperation rates range between 20% at 5 years and 30% at 15 years The rate of symptomatic recurrence proximal to an ileostomy is lowest CD recurs also in the ileum after right colonic resection with ileocolonic anastomosis when the ileum was not diseased before surgery GRIFFITHS, GUT 2001

RISK FACTORS: SMOKING STATUS 6-YEAR RECURRENCE FREE-RATE AFTER SURGERY: 60% FOR NONSMOKERS 40% FOR EX-SMOKERS 25% FOR SMOKERS (COTTONE, GASTROENTEROLOGY 1994) THE NEED FOR REPEATED SURGERY AFTER 5 AND 10 YEARS: 20% and 40% IN NONSMOKERS 35% and 70% IN SMOKERS the risk is very high in female smokers with small bowel disease (SUTHERLAND, GASTROENTEROLOGY 1990)

PREVENTION Prevention of post-operative recurrence is a central problem in the management of CD. Among the various drugs evaluated, mesalazine, metronidazole and ornidazole, azathioprine, infliximab and adalimumab have been shown to be effective

SURGERY In conclusion, surgery alone is an excellent treatment for patients with isolated ileo-caecal CD and guarantees a good clinical outcome in approximately 50% of patients by 10 years after operation. Surgery, therefore, continues to play an important role in ileo-caecal CD and should therefore not be considered only a failure of medical treatment.

MORBO DI CROHN DEL COLON - FISIOPATOLOGIA DISTRIBUZIONE ANATOMICA Bocca % Esofago <1 % Stomaco-duodeno % Intestino tenue % Colon+tenue % Colon % Retto e regione perianale 20 % %

MORBO DI CROHN DEL COLON - FISIOPATOLOGIA PRESENTAZIONE CLINICA Colite limitata a tratti di colon 30% Colite diffusa, estesa all’ileo (ileocolite) 40% Colite diffusa, estesa al retto-ano 30 %

post-operative prophylactic treatment with mesalazine has no impact on the long term recurrence rate. patients receiving or not receiving mesalazine prophylaxis after surgery have the same probability of experiencing a moderate to severe clinical recurrence requiring steroids within 10 years after resection, and have the same probability of developing refractory or complicated disease requirinig re-operation

SURGERY Surgery is an excellent treatment for patients with isolated ileo-caecal CD and guarantees a good clinical outcome in approximately 50% of patients by 10 years after operation. Surgery, therefore, continues to play an important role in ileo- caecal CD and should therefore not be considered only a failure of medical treatment.

EPIDEMIOLOGIA INCIDENZA 4:100000/ANNO PREVALENZA 54:100000

CLINICAL R. is defined as the re- appearance of symptoms requiring treatment in the presence of well documented endoscopic and/or radiologic recurrence. SURGICAL R. is defined as the need for re-operation for refractory or complicated disease. RECURRENCE