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How to Assess and Manage Strictures, Abscesses, and Phlegmons in the
Complicated Crohn’s Disease Patient
David A Schwartz, MDAssociate Professor of Medicine
Director, IBD CenterVanderbilt University
Raymond Cross, MD, MSAssociate Professor of Medicine
Director, IBD ProgramUniversity of Maryland School of
Medicine
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
Findings at Colonoscopy – Stricture in TI with Ulceration
Should You Consider Escalation of Medical Treatment in this Case?
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 2006Kirsner’s Inflammatory Bowel Diseases 6th Edition 2004
Pre-Stenotic Dilation is Associated with Increased Fibrosis and
Inflammation
No Dilation Dilation0
0.5
1
1.5
2
2.5
3
3.5
4
Fibrosis Inflammation
Adler, J. et al. Inflamm Bowel Dis 2012
“Pure” Inflammatory and Fibrotic Strictures are Rare in Clinical Practice
Adler, J. et al. Inflamm Bowel Dis 2012
Response to Medical Treatment for Complicated Crohn’s Disease
30 days 90 days 180 days0%
10%20%30%40%50%60%70%80%90%
100%
Complete Partial None
Days Since Initiation of Medical Therapy
Resp
onse
Rat
e
n= 11 17 24 13 15 19 10 8 10
Samimi, R., et al. 2010. Inflamm Bowel Dis
Most Patients Require Surgery after Treatment for Complicated CD
Samimi, R., et al. 2010. Inflamm Bowel Dishttp://onlinelibrary.wiley.com/doi/10.1002/ibd.21160/full#fig2
Post operative complication rate 32% in patients exposed to anti-TNF
(years)
Is There Any Downside in Attempting Medical Treatment for
Complicated Crohn’s Disease?
Clinical Factors Predicting Postoperative Complications
• CD patients operated on between 1980-1997 (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
Does Pre-Operative Anti-TNF Use Increase the Risk of Postoperative
Complications?
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 2004 Resection, plasty or bypass
270/52 No effect
Kunitake 2008 Abdominal surgery
413/101 No effect
Appau 2008 Resection 389/60 ↑ complications
Nasir 2010 Surgery with “suture or staple line”
377/119 No effect
Canedo 2011 Resection 225/65 No effect
El-Hussuna 2012 Resection 417/32 No effect
Waterman 2012 Abdominal surgery
473/195 ↑ complications
Krane 2013 Resection 518/142 No effect
Risk Associated with Anti-TNF in CD Patients Undergoing Surgery
• 325 surgeries in 211 CD patients at UMB between 2004-2011• 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
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
Anti-TNF Use is Associated with an Increased Risk of Complications
Outcome Anti-TNF vs. no anti-TNF OR (95% CI)
IASC 2.01 (0.85-4.74)
Surgical site complications 1.96 (1.02-3.77)
All infectious complications 2.43 (1.18-5.03)
Any major complication 1.85 (0.89-3.83)
Syed, A., et al. Am J Gastroenterol 2013
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
Steps to Decrease Postoperative Complications in CD
1. Treat septic complications2. Improve nutrition3. Decrease or eliminate corticosteroids4. Do not start anti-TNF or hold dose(s) if
surgery is imminent
Both you and the patient agree to pursue surgery instead of medical therapy
1. Proximal dilation suggests more severe fibrosis2. Medical therapy unlikely to result in durable response 3. Anti-TNF therapy is associated with postoperative complications4. Stricture is short
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…..
• Severe right-sided colitis
• Stricture at anastomosis
CTE
How do you manage this patient?
Long-Term Course of Crohn’s Disease
N = 2002 patients with Crohn’s disease since diagnosis of the disease Cosnes J et al. Inflamm Bowel Dis. 2002;8:244–250.
Cu
mu
lati
ve p
rob
abil
ity
(%)
Months
Probability of remaining free of complications
0 24 48 72 96 120 168 192 216 240144
100
90
80
70
60
50
40
30
20
10
0
Penetrating
Stricturing
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
• 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
How Do You Evaluate and Treat a Patient with an Intraabominal Abscess?
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
Drainage is achieved…. Now what?
• Continue antibiotics• Wait for patient to be afebrile for 48-72 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)
• Decisions to make at this point?–TPN vs. resuming diet–Early surgery (with diverting stoma)
vs. trial of medical treatment
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
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
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.
External Internal0
20406080 69
13
Response Rate to IFX
Response Rate%
Parsi, Am J Gastro 2004
• 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
Early Surgery vs. Attempt at Medical Treatment
1-Sahai et al. Am J Gastro 19972-Golfieri et al. Tech Coloproct 2006
Medical vs. Surgical Treatment of IAA
• Retrospective review of 95 patients from Mayo Clinic (1999-2006)
• 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 recurrenceNguyen, D. L. et al. (2012). Clin Gastroenterol Hepatol.
Source: Clinical Gastroenterology and Hepatology 2012; 10:400-404 (DOI:10.1016/j.cgh.2011.11.023 )
Copyright © 2012 AGA Institute Terms and Conditions
Cumulative Probability of Abscess Recurrence in Medically vs. Surgically Treated Patients
2/3 of patients had recurrence infirst 30 days
Most Patients Require Surgery after Treatment for Complicated CD
Samimi, R., et al. 2010. Inflamm Bowel Dishttp://onlinelibrary.wiley.com/doi/10.1002/ibd.21160/full#fig2
Post operative complication rate 32% in patients exposed to anti-TNF
(years)
Clinical Factors Predicting Postoperative Complications
• CD patients operated on between 1980-1997 (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
Anti-TNF Use is Associated with an Increased Risk of Complications
Outcome Anti-TNF vs. no anti-TNF OR (95% CI)
IASC 2.01 (0.85-4.74)
Surgical site complications 1.96 (1.02-3.77)
All infectious complications 2.43 (1.18-5.03)
Any major complication 1.85 (0.89-3.83)
Syed, A., et al. Am J Gastroenterol 2013
Pros and Cons of Medical Treatment for Intraabdominal Abscess
• Pros:– 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
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
Extra Slides
What is the natural history of CD after ileocolonic resection and
primary anastomosis?
Natural History of CD After Surgery
1 2 3 4 5 6 7 80
102030405060708090
100
Survival without en-doscopic lesionsSurvival without symptomsSurvival without surgery
Years
Prob
abili
ty o
f Rec
urre
nce
Rutgeerts P, et al. Gastroenterology. 1990
Rutgeert’s Endoscopic Score
i0
i4
i1
i3
i2
Symptomatic Recurrence Based on Degree of Endoscopic Activity
0 1 2 3 4 5 6 7 80
0.2
0.4
0.6
0.8
1
1.2
i0+i1i2i3i4
Years
Prob
abili
ty o
f Rec
urre
nce
Rutgeerts P, et al. Gastroenterology. 1990
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?
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
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%
Summary of Postop RCTs5-ASA, Nitroimidazoles, AZA/6-MP
Regueiro M. Inflamm Bowel Dis. 2009
IFX Reduces Post-operative Recurrence after Intestinal Resection
Placebo IFX0
10
20
30
40
50
60
70
80
90
100
Endo
scop
ic R
ecur
renc
e Ra
te
Regueiro, M., et al. Gastroenterology. 2009
Endoscopic Recurrence: endoscopic scores of i2, i3, or i4
Why not wait until after disease has recurred endoscopically to
start treatment?
Rates of Mucosal Healing are Decreased with Delays in Starting
Treatment
Series10
20
40
60
80
100
120SorrentinoRegueiroYoshidaFernandez-BlancoMantzarisYamamotoRegueiro2Mantzaris2Sorrentino2SONICACCENT 1MUSICEXTEND
Prop
ortio
n of
Pati
ents
with
M
ucos
al H
ealin
g
Risk of Post-Op Recurrence
LowLow ModerateModerate HighHigh
No MedsNo Meds
Colonoscopy 6-12 months post-op
Colonoscopy 6-12 months post-op
No Recurrence
No Recurrence
6MP or AZA ± metronidazole
6MP or AZA ± metronidazole
Anti-TNFAnti-TNF
Colonoscopy 6-12 months post-op
Colonoscopy 6-12 months post-op
No Recurrence
No Recurrence
Colonoscopy every 1-3 yrs
Colonoscopy every 1-3 yrs
Immunomodulator or anti-TNF
Immunomodulator or anti-TNF
Colonoscopy every 1-3 yrs
Colonoscopy every 1-3 yrs
anti-TNF or Δ biologics
anti-TNF or Δ biologics
Recurrence Recurrence
Long-standing CD, 1st surgery, Stricture <10 cm<10yrs CD, Stricture >=10 cm or inflammatory CDPenetrating disease, > 2 surgeries
Regueiro, M. Inflamm Bowel Dis. 2009