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

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Endo

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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

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Pati

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with

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ucos

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ealin

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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