Genova 24 novembre 2012

La storia naturale delle recidive post-

operatorie della malattia di Crohn

giovanni russoGL IBD

U.O.C. gastroenterologiaasl 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 2009

1) 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 FACTORS1) SEVERITY OF ENDOSCOPIC LESIONS one year after

surgery is the strongest predictor of the subsequent clinical course

RIGBY, GUT 20092) 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 GUIDELINESPREDICTING POST-OP RECURRENCE

ECCO Statement 8AThe 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 RECURRENCEECCO 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) is associated with a post-operative course without clinical recurrence significantly longer than that of patients with longer 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