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POST OPERATIVE CROHN’S
DISEASE
ShankarZanwar
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 lesion
i1 <5 aphthous lesions
i2 >5 aphthous lesions with N mucosa b/n lesions or skip areas or
lesions confined to I/C anastomosis
i3 Diffuse aphthous ulcers with diffuse inflamed mucosa
i4 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 assesment
Castiglione, 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 recommendCT 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 cost
Koilakou, 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 useful
Doherty, 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 year
A 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
antiTNF therapy over placebo, in endoscopic
and clincal recurrence prevention
 Majority of studies did not show any recurrence
with maintenance on antiTNF 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 group
Reinisch, Gut, 2010
 AntiTNF
 Significant difference when compared with AZA
or ASA
 Most potent drug class to treat POR
A Buisson, Digestive and Liver Dis, 2012
Protocol AZA
 TPMT –
< 6 – avoidAZA
6-10 – 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

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POST-OPERATIVE CROHN'S DISEASE MANAGEMENT

  • 2. Surgery in Crohn’s Disease  Indications  Intrabdominal abscess  Medically intractable fistula  Fibrotic stricture with obstructive symptoms  Toxic megacolon  Intractable hemorrhage  Cancer
  • 3. Predictors of surgery A Goel, A Dutta, A Chacko, IJG, 2008
  • 4.  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
  • 6. Sanjay Bandopadhyay, API Med update 2012
  • 8.  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
  • 9. 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
  • 10.  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.
  • 11.  Endoscopic - Endoscopic score Definition - Rutgeerts classification i0 No lesion i1 <5 aphthous lesions i2 >5 aphthous lesions with N mucosa b/n lesions or skip areas or lesions confined to I/C anastomosis i3 Diffuse aphthous ulcers with diffuse inflamed mucosa i4 Diffuse inflammation with large ulcers, nodules and/or narrowing Rutgeerts,Gastroenterology 1990
  • 12. 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
  • 13. 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
  • 14. 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 assesment Castiglione, IBD, 2008
  • 15. CT scan  CT enterography – most distinguishing features –  Comb sign  Bowel wall thickening  Stratification  Anastomotic stenosis  Sn and Sp – 88% and 97%  ECCO doesnot recommendCT as alternative to endoscopy – d/t ionising radiation. Soyer P, Radiology, 2010
  • 16. 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 cost Koilakou, IBD 2010
  • 17. 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
  • 18. 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
  • 19.  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
  • 21.  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
  • 22. 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 useful Doherty, Alim Pharmaco , 2010
  • 23. 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
  • 24. 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
  • 26.  Metanalysis – Modest clinical benefit over placebo with AZA  15 % more effective than ASA or placebo in preventing POR – NNT – 7 for 1 year A 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
  • 28.  A number of studies have proven superiority of antiTNF therapy over placebo, in endoscopic and clincal recurrence prevention  Majority of studies did not show any recurrence with maintenance on antiTNF therapy  These should be considered treatment of choice in patient with highest risk of recurrence.
  • 29. 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 group Reinisch, Gut, 2010
  • 30.  AntiTNF  Significant difference when compared with AZA or ASA  Most potent drug class to treat POR A Buisson, Digestive and Liver Dis, 2012
  • 31.
  • 32. Protocol AZA  TPMT – < 6 – avoidAZA 6-10 – 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