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