POST OPERATIVE CROHN’S DISEASE Shankar Zanwar
POST OPERATIVE CROHN’S DISEASE
Shankar Zanwar
Surgery in Crohn’s Disease
Indications Intrabdominal abscess
Medically intractable fistula
Fibrotic stricture with obstructive symptoms
Toxic megacolon
Intractable hemorrhage
Cancer
Predictors of surgery
A Goel, A Dutta, A Chacko, IJG, 2008
Incidence – ~75% have some surgery by 20 years
of diagnosis
Depending on medical culture – Within 3 years of Δ – 25 – 45 % Of these 30% - reintervention within 5 yrs And 1/3rd require 3rd intervention
Cosnes, Gastroenterology, 2011
Indian scenario
Sanjay Bandopadhyay, API Med update 2012
Sanjay Bandopadhyay, API Med update 2012
Mathew Philip, IJG, 2008
Strictures Treatment - Surgical/ endoscopic
Study by Scimeca –balloon safe in long term and long term benefit achieved
Study, n=27, 66.7% responded dilatation avoided surgery atleast for 7 years Non responders – surgery needed in 1.6 years
Blomberg, Endoscopy 1991
Recurrence of Crohns after surgery
Upto 90% have endoscopic recurrence with in 1 year
Site – neoterminal ileum, just above the I-C anastomosis
Of these ~30% manifest at 3 year, 50% at 5 years and 60% at 10 years
Ng SC, Am J Gastro, 2008
Risk of recurrence is perforating disease > stricturising
Simillis, Am J Gastro, 2008
Recurrence can be seen as early as 1 week post op, bowel continuity predisposes
Progression displays natural history – Aphthous ulcer stellate fistula/stricutre
Definition of recurrence – histologically, endoscopically and clinically.
Endoscopic - Endoscopic score
Definition - Rutgeerts classification
i0 No lesioni1 <5 aphthous lesionsi2 >5 aphthous lesions with N mucosa b/n lesions or
skip areas or lesions confined to I/C anastomosisi3 Diffuse aphthous ulcers with diffuse inflamed mucosai4 Diffuse inflammation with large ulcers, nodules
and/or narrowing
Rutgeerts, Gastroenterology 1990
Rutgeerts score
Prognosis – i0/i1 low risk – 80-85% asymptomatic for
3 years after surgery Recurrence at 3 years – 5 %
i3/i4 – only 10% asymptomatic after 3 years
Recurrence at 3 yrs - i2, i3 and i4 – 20, 40 and 90%
Blum, Inflam. B D 2009
Post operative surviallance
Endoscopy - ileoscopy Recommended as gold standard by ECCO
guidelines Recommended after 6 -12 months of surgery
Cottone, Gastroenterology, 2006 Capsule (WCE)
Sn and Sp for POR (≥ Rutgeerts i2), 50-79% and 94-100%
Considered as emerging alternative Risk impaction in strictures
Bourreille A, Gut, 2006
Imaging
USG Sn and Sp – 77-81% and 86-94%.
Oral contrast enhance USG (SICUS) – Sn – 86%, Sp – 96% - with BWT cut-off – 5mm
SICUS – as accurate as ileoscopy –but little higher false positive rate
Useful non invasive tool for initial assesmentCastiglione, IBD, 2008
CT scan
CT enterography – most distinguishing features – Comb sign Bowel wall thickening Stratification Anastomotic stenosis
Sn and Sp – 88% and 97%
ECCO doesnot recommend CT as alternative to endoscopy – d/t ionising radiation.
Soyer P, Radiology, 2010
MRI
Classification of findings MR -0 – No abnormality MR 1 – minimal mucosal changes MR 2 – diffuse aphthoid iletis MR 3 – Severe recurrence – trans and extramural changes
Compared with Rutgeerts – Kappa value – 0.67
MR & MR3 – Sn & Sp – 89 & 100% for i3 & i4
Emerging non invasive tool, lmtd access and costKoilakou, IBD 2010
Biomarkers Fecal calprotectin(FC) and Fecal lactoferrin(FL)
Cut-offs for POR – FC - >50 U, FL.7.5 U(μg/g)
Increase to 2X ULN – disease flare
Both were better than CRP in POR prediction, better sensitivity
But other studies showed ↑ level despite POR
Since they have low specificity, ECCO – does not recommend their routine use
A Buisson, Digestive and Liver Dis, 2012
Predictors of post operative recurrence
Patient related Tobacco smoking – OR – 2.5 @ 10y of POR Female > male
Disease related Prior surgery Penetrating and perforating disease Young age Shorter duration prior of disease b/f surgery (<10y) Use of steroids Multisite disease Family history
Jana Hashash, Expert Review Gastro-hep, 2012
Surgery related Inconclusive
Surgical margins Perioperative complications Need of BTs Presence and number of granulomas
Type of anastomosis Least with stappled – end to end anastomosis Higher with – hand sewn e-to-e.
Yamamoto, Scand J Gastro, 1999
Prevention ASA
Metanalysis (n=1282), 11 RCTs – mesalamine has only modest, at all benefit in POR
Mesalamine – may have only slight efficacy in prevention of POR
Jana Hashash, Expert Review Gastro-hep, 2012
Sulphasalazine has no benefit in preventing POR (Metanalysis)
Ewe, Digestion, 1989
Probiotics Study, using 12 billion Lactobacillus
rhamnosus, (n=45) out come not superior to placebo
Similar results with Lactobacillus johnsonii Symbiotics of 4 probiotics and 4 prebiotics VSL#3
Metanalysis – Pre-pro-biotics not usefulDoherty, Alim Pharmaco , 2010
Antibiotics Rutgeerts – metronidazole – 20mg.kg.d within 7 days of
surgery vs placebo 1 year recurrence – 4% vs 25% But effect not lasted for 2 and 3 yrs
Rutgeerts, Gastroenterology, 1999
Other study – ornidazole – 1 g/d vs placebo Recurrence @ 1 yr – 7.9 vs 35% p =0.004
Rutgeerts, Gastroenterology, 2005
Higher side effects – neuropathy in long term Rx, higher chances of non-complaince
Conclusion – Effective > placebo, but not sustained beyond 1 yr
Steroids
RCTs of budesonide vs placebo N= 129 Duration – 12 months Response – 52 vs 58%, p>0.05
Steroids don not have any preventive role in POR prevention
Ewe, Eur J Gastro Hepa, 1999
Thiopurines – Azathioprine/6-MP
Metanalysis – Modest clinical benefit over placebo with AZA 15 % more effective than ASA or placebo
in preventing POR – NNT – 7 for 1 yearA Buisson, Digestive and Liver Dis, 2012
Conclusion – Azathioprine and 6-MP had better recurrence prevention chances than placebo or ASA but have greater withdrawal rates d/t side effects
Anti- TNF therapy
A number of studies have proven superiority of anti TNF therapy over placebo, in endoscopic and clincal recurrence prevention
Majority of studies did not show any recurrence with maintenance on anti TNF therapy
These should be considered treatment of choice in patient with highest risk of recurrence.
Treatment
Azathioprine Studies have shown benefit of AZA over
ASA or placebo, lower rates of endoscopic lesions (30% vs 60%).
Useful in the moderate risk groupReinisch, Gut, 2010
Anti TNF Significant difference when compared
with AZA or ASA
Most potent drug class to treat PORA Buisson, Digestive and Liver Dis, 2012
Protocol AZA
TPMT – < 6 – avoid AZA6-10 – 1.0 mg/kg/d> 10 – 2.0 mg/kg/d
6- TGN - level, 230 – 260 U in RBCs – 62% remission rate compared to 36% those with lower
Shunting – 6MMP:6TGN - >10 unlikey to benefit – add allopurinol
Thank You