1. How to Assess and Manage Strictures, Abscesses, and Phlegmons in the Complicated Crohn’s Disease Patient
David A Schwartz, MD
Associate Professor of Medicine
Director, IBD Center
Vanderbilt University
Raymond Cross, MD, MS
Associate Professor of Medicine
Director, IBD Program
University of Maryland School of Medicine

2. Case Presentation #1
17 year old woman with obstructing ileal CD with upper tract involvement has been hospitalized twice for treatment of partial SBO
Treated with oral 5-ASA and three courses of steroids
Imaging demonstrates 5 cm stricture with wall enhancement, mesenteric adenopathy and proximal dilation

3. Findings at Colonoscopy – Stricture in TI with Ulceration

4. Should You Consider Escalation of Medical Treatment in this Case?

5. Inflammatory vs. Fibrotic Stricture
Inflammation is present
Mucosal hyperenhancement
Mesenteric fat stranding
Mesenteric hypervascularity (“comb sign”)
Fibrosis is present
Abnormally thickened wall without signs of active inflammation
“…dilation of the proximal intestine strongly suggests a fixed, chronic obstruction”
Liu, YB, et al. Abdom Imaging 2006
Kirsner’s Inflammatory Bowel Diseases 6th Edition 2004

6. Pre-Stenotic Dilation is Associated with Increased Fibrosis and Inflammation
Adler, J. et al. Inflamm Bowel Dis 2012

7. “Pure” Inflammatory and Fibrotic Strictures are Rare in Clinical Practice
Adler, J. et al. Inflamm Bowel Dis 2012

8. Response to Medical Treatment for Complicated Crohn’s Disease
Samimi, R., et al Inflamm Bowel Dis

9. Most Patients Require Surgery after Treatment for Complicated CD
Post operative complication rate 32% in
patients exposed to anti-TNF
(years)
Samimi, R., et al Inflamm Bowel Dis

10. Is There Any Downside in Attempting Medical Treatment for Complicated Crohn’s Disease?

11. Clinical Factors Predicting Postoperative Complications
CD patients operated on between (n=343)
566 operations and 1,008 anastomoses
Intraabdominal septic complication in 13%
Predictors
Low albumin (<3.0 g/dl)
Preoperative steroids
Abscess at laparotomy
Fistula at laparotomy
If all 4 present, risk 50%!
If 0 factors present, risk 5%
Yamamoto, T et al. Dis Colon Rectum 2000

12. Does Pre-Operative Anti-TNF Use Increase the Risk of Postoperative Complications?

13. Author
Year
Type of Procedure
# of Patients/# exposed to Anti TNF
Findings
Tay, GS
2003
Resection or plasty
100/14
↓ complications
Marchal
2004
Resection
79/40
No effect
Colombel
Resection, plasty or bypass
270/52
Kunitake
2008
Abdominal surgery
413/101
Appau
389/60
↑ complications
Nasir
2010
Surgery with “suture or staple line”
377/119
Canedo
2011
225/65
El-Hussuna
2012
417/32
Waterman
473/195
Krane
2013
518/142

14. Risk Associated with Anti-TNF in CD Patients Undergoing Surgery
325 surgeries in 211 CD patients at UMB between
All abdominal surgeries were included
At least one resection (n=211)
Diverting stoma (n=117)
Emergent (n=39)
150 had anti-TNF ≤ 8 weeks before surgery
97% were within standard maintenance intervals
43% of biologic patients with perianal disease compared to 27% of controls
Syed, A., et al. Am J Gastroenterol 2013

15. Adverse Postoperative Outcomes
All complications were defined as those within 30 days from the date of surgery or discharge
Intra-abdominal septic complication: abdomino-pelvic abscess, peritonitis, or anastomotic leak
Surgical site complication: intra-abdominal septic complication, wound dehiscence, local fistula, or wound infection
Infectious complication: any wound infection, abdomino-pelvic abscess, peritonitis, sepsis, pneumonia, or other major infection
Syed, A., et al. Am J Gastroenterol 2013

16. Anti-TNF Use is Associated with an Increased Risk of Complications
Outcome
Anti-TNF vs. no anti-TNF OR (95% CI)
IASC
2.01 ( )
Surgical site complications
1.96 ( )
All infectious complications
2.43 ( )
Any major complication
1.85 ( )
Syed, A., et al. Am J Gastroenterol 2013

17. Anti-TNF are Associated with an Increased Risk of Complications in CD
Meta-analysis (n=4,659 patients)
18 studies
Patients with CD using pre-op anti-TNF had an increase in:
Postop infectious complications (OR 1.93)
Total complications (OR 2.19)
UC patients using pre-op anti-TNF did not have increased risk of complications
Narula, N et al. Aliment Pharmacol Ther 2013

18. Steps to Decrease Postoperative Complications in CD
Treat septic complications
Improve nutrition
Decrease or eliminate corticosteroids
Do not start anti-TNF or hold dose(s) if surgery is imminent

19. Both you and the patient agree to pursue surgery instead of medical therapy 1. Proximal dilation suggests more severe fibrosis 2. Medical therapy unlikely to result in durable response 3. Anti-TNF therapy is associated with postoperative complications 4. Stricture is short

20. 45 yo Male with Intra-Abdominal Abscess
45 yo male presents with history ileocolic resection 10 years before. No maintenance medication post-op.
Presents now with 3 month history of abdominal pain after eating. 20# wt loss during this time.
FH: positive for Crohn’s
PE: Some RLQ tenderness and possible fullness…
Colonoscopy and Imaging show…..

21. Stricture at anastomosis
Severe right-sided colitis

22. CTE

23. How do you manage this patient?

24. Long-Term Course of Crohn’s Disease
100 90
Probability of remaining free of complications 80 70 60
Penetrating
Cumulative probability (%) 50 40 30
Stricturing 20 10 24 48 72 96
120
144
168
192
216
240
Months
N = 2002 patients with Crohn’s disease since diagnosis of the disease Cosnes J et al. Inflamm Bowel Dis. 2002;8:244–250.

25. How Do You Evaluate and Treat a Patient with an Intraabominal Abscess?
Cross sectional imaging with positive oral contrast
Intravenous antibiotics with coverage against gram – and anaerobic bacteria

26. How Do You Evaluate and Treat a Patient with an Intraabominal Abscess?
Drainage
Percutaneous if possible
Open if septic and/or abscess not amenable to perc drainage
Avoid steroids!
Reduce dose if possible
Hold immune suppressants and biologics in short term
Nutritional Support
Bowel rest initially
TPN

27. Initial Management
Abscess needs to be drained especially if > 3 cm. (poor penetration of antibiotics)
Perc drainage successful in 77% of the time in largest study. 1
1-Golfieri et al. Tech Coloproct 2006

28. Drainage is achieved…. Now what?
Continue antibiotics
Wait for patient to be afebrile for hours and re-image
If wbc remains elevated and /or fever persists re-interrogate the drain
Consider scope (if one has not been done recently to help guide treatment)

29. Decisions to make at this point?
TPN vs. resuming diet
Early surgery (with diverting stoma) vs. trial of medical treatment

30. TPN vs. Diet
Retrospective report of the use of short-term TPN in pts with penetrating disease
78 pts given pre-op nutritional treatment (median 23 days) and weaned off steroids, immunosuppressives1
Need for stoma was only 8%
major complications 5%
1- Zerbib, APT 2010

31. Perioperative TPN in Surgical Patients
Malnourished Veterans undergoing laparotomy or noncardiac thoracotomy (n=395)
TPN group received TPN for 7-15 days prior to surgery and 3 days after
Severely malnourished Veterans who received TPN
Fewer infectious complications than controls (5 vs. 43%, p=0.03)
The Veterans Total Parenteral Nutrition Cooperative Study Group N Engl J Med 1991

32. Early Surgery vs. Attempt at Medical Treatment
1st determine if abscess related to stricture /fistula and if stricture is fibrotic vs. inflammatory
If stricture is present (especially if fibrotic) treatment is largely surgical
No prospective trial to look specifically at internal fistulas.
In general, internal fistulas less likely to respond to anti-TNF treatment.
Parsi, Am J Gastro 2004

33. Early Surgery vs. Attempt at Medical Treatment
In general, if fistula present chance of non-surgical success is low
Sahai et al. found in retrospective study of 27 pts with intra-abd abscess that associated fistulas was associated with need for surgery within 30 days despite drainage1
Golfieri et al. found in a study of 70 patients that all failures of perc drainage were associated with a fistula to the bowel 2
1-Sahai et al. Am J Gastro 1997
2-Golfieri et al. Tech Coloproct 2006

34. Medical vs. Surgical Treatment of IAA
Retrospective review of 95 patients from Mayo Clinic ( )
55 underwent percutaneous drainage (PD)
More likely female, older, longer disease duration, and active ileal disease
12 (22%) underwent PD as an outpatient
9/40 (23%) had high severity of illness and 9/40 (23%) had multiple abscesses in surgical group
Median follow up 3.5 years
Perianal disease and active ileal disease positively and anti-TNF negatively associated with recurrence
Nguyen, D. L. et al. (2012). Clin Gastroenterol Hepatol.

35. Cumulative Probability of Abscess Recurrence in Medically vs
Cumulative Probability of Abscess Recurrence in Medically vs. Surgically Treated Patients
2/3 of patients had recurrence in
first 30 days
Source: Clinical Gastroenterology and Hepatology 2012; 10: (DOI: /j.cgh )
Copyright © 2012 AGA Institute Terms and Conditions

36. Most Patients Require Surgery after Treatment for Complicated CD
Post operative complication rate 32% in
patients exposed to anti-TNF
(years)
Samimi, R., et al Inflamm Bowel Dis

37. Clinical Factors Predicting Postoperative Complications
CD patients operated on between (n=343)
566 operations and 1,008 anastomoses
Intraabdominal septic complication in 13%
Predictors
Low albumin (<3.0 g/dl)
Preoperative steroids
Abscess at laparotomy
Fistula at laparotomy
If all 4 present, risk 50%!
If 0 factors present, risk 5%
Yamamoto, T et al. Dis Colon Rectum 2000

38. Anti-TNF Use is Associated with an Increased Risk of Complications
Outcome
Anti-TNF vs. no anti-TNF OR (95% CI)
IASC
2.01 ( )
Surgical site complications
1.96 ( )
All infectious complications
2.43 ( )
Any major complication
1.85 ( )
Syed, A., et al. Am J Gastroenterol 2013

39. Pros and Cons of Medical Treatment for Intraabdominal Abscess
Largest study from Mayo Clinic shows equivalent outcomes compared to surgery
May delay or prevent surgery
Decrease length of stay
Cons:
Use of anti-TNF may be associated with increased post-op complications
May delay inevitable
May “handicap” anti-TNF agents as disease is at an irreversible stage
Patients failing aggressive therapy unlikely to respond

40. Recommendations
Initial treatment should be antibiotics and percutaneous drainage
Consider bowel rest and nutritional support as bridge to surgery especially if malnourished
Surgery should be recommended in patients with
Medically refractory disease prior to IAA
Stricture associated with abscess
Consider post-op anti-TNF in patients undergoing surgery
In other patients, consider medical treatment after discussion of risks and benefits

41. Extra Slides

42. What is the natural history of CD after ileocolonic resection and primary anastomosis?

43. Natural History of CD After Surgery
Rutgeerts P, et al. Gastroenterology. 1990

44. Rutgeert’s Endoscopic Score

45. Symptomatic Recurrence Based on Degree of Endoscopic Activity
Rutgeerts P, et al. Gastroenterology. 1990

46. How Do We Manage CD Patients After Surgery?
Can we predict who is more likely to have recurrence?
How should patients be followed?
When should colonoscopy be performed?
Which medications should be given?
How should endoscopic recurrence be managed?

47. Risk Factors Associated with Postoperative CD Recurrence
Patient Related
Smoking
Younger age at diagnosis
Disease-Related
Perforating > fibrostenotic
Disease duration < 10 years
Ileocolitis > ileitis > colitis
Disease refractory to medical therapy
Surgery-Related
Ileocolonic anastomosis > ileal > ileostomy
Kirsner’s Inflammatory Bowel Diseases 6th edition 2004

48. 5-ASA, Nitroimidazoles, AZA/6-MP
Summary of Postop RCTs
5-ASA, Nitroimidazoles, AZA/6-MP
Postoperative Prevention RCTs
Clinical Recurrence
Endoscopic recurrence
Placebo
25% – 77%
53% - 79%
5 ASA
24% - 58%
63% - 66%
Budesonide
19% - 32%
52% - 57%
Nitroimidazole
7% - 8%
52% - 54%
AZA/6MP
34% – 50%
42 – 44%
Regueiro M. Inflamm Bowel Dis. 2009

49. IFX Reduces Post-operative Recurrence after Intestinal Resection
Endoscopic Recurrence: endoscopic scores of i2, i3, or i4
Regueiro, M., et al. Gastroenterology. 2009

50. Why not wait until after disease has recurred endoscopically to start treatment?

51. Rates of Mucosal Healing are Decreased with Delays in Starting Treatment

52. Risk of Post-Op Recurrence
Low
Moderate
High
No Meds
6MP or AZA ± metronidazole
Anti-TNF
Colonoscopy 6-12 months post-op
Colonoscopy 6-12 months post-op
No Recurrence
Recurrence
No Recurrence
Recurrence
Colonoscopy every 1-3 yrs
Immunomodulator or anti-TNF
Colonoscopy every 1-3 yrs
 anti-TNF or Δ biologics
Long-standing CD, 1st surgery, Stricture <10 cm
<10yrs CD, Stricture >=10 cm or inflammatory CD
Penetrating disease, > 2 surgeries
Regueiro, M. Inflamm Bowel Dis. 2009