1. Endoscopy in IBD: Endoscopy in IBD: Appropriate Indications and Response to Findings
Thomas Ullman, M.D.
Associate Professor of Medicine
The Mount Sinai School of Medicine
New York, NY

2. Team Hope/Team Euro Orange All the Way

3. Uses of Endoscopy in IBD
Diagnosis
Disease extent
Assessment of Activity/Healing
Stricture evaluation and dilation
Dysplasia Surveillance
Diagnose/Control Bleeding
Pouch Evaluation
Endoscopic Ultrasound

4. Uses of Endoscopy in IBD
Diagnosis
Disease extent
Assessment of Activity/Healing
Stricture evaluation and dilation
Dysplasia Surveillance
Diagnose/Control Bleeding
Pouch Evaluation
Endoscopic Ultrasound
VCE

5. Ileocolonoscopy for Diagnosis and Activity in Small Bowel Crohn’s Disease
STRENGTHS
Technically easy
Reliability
Accuracy
Acceptable to most Crohn’s patients
WEAKNESSES
High cost
Less-than ideal safety profile

6. Endoscopy for Diagnosis
Still the Gold Standard for UC and Crohn’s ileocolitis or colitis diagnosis
Silver standard for Crohn’s small bowel diagnosis (when TI or distal ileum involved)

7. Sensitivity for SB CD Solem, GIE, 2008
* P > 0.05 CE compared with other SB modalities
** P > 0.05 CE compared with other SB modalities
(trending toward significant for SBFT)
Solem, GIE, 2008

8. Specificity for SB CD Solem, GIE, 2008
* P < 0.05 CE compared with other SB modalities
**P > 0.05 CE compared with other SB modalities (trending
toward significant for CTE and SBFT)

9. Activity

10. Ileocolonoscopy: Activity Index
CDEIS, Mary et al, Gut 1989
Aim: “Elaborate and validate a CDEIS”
Authors forgot that a “simple” index would be preferable

11. CDEIS, 1989 9 Possible Mucosal Lesions Pseudopolyp Healed ulceration
Frank erythema
Frankly swollen mucosa
Aphthoid ulceration
Superficial or shallow ulceration
Deep ulceration
Non ulcerated stenosis
Ulcerated stenosis
Measured across 5 segments: rectum, left/sig, transverse, right, ileum
Constructed and compared against a global physicians assesment (10 cm Likiert scale)

12. Results High degree of correlation (r=0.81-0.96)
High degree of reproducibility
High degree of annoyance of use
CDEIS= 12 x # segments with deep ulcerations +
6 x # segments with superficial ulcerations + Average surface area involved in cm +
Average surface area with ulcerations in cm +
3 x presence of non-ulcerated stenosis +
3 x presence of ulcerated stenosis
Mary et al, Gut 1989

13. There’s Something About Mary (1998)
“Unless, of course, somebody comes up with 6-Minute Abs. Then you're in trouble, huh?”
Attempt to come up with “6 minute abs” for CDEIS

14. “Simple” Endoscopic Score for Crohn’s Disease SES-CD, 2004
Same 5 segments
4 variables per segment, all 0-3 score 1 2 3
Size of ulcers
None
Aphthous
Large
(0.5-2 cm)
Very large (>2 cm)
Ulcerated surface
<10%
10-30%
>30%
Affected surface
Unaffected segment
<50%
50-75%
>75%
Narrowings
Single, can be passed
Multiple, can be passed
Cannot be passed
Daperno, et al, GI Endoscopy, 2004

15. Prognosis

16. Rutgeerts P, et al. Gastroenterology. 1990;99:956-963
Actuarial analysis of symptomatic recurrence in patients stratified according to severity of endoscopic lesions
Rutgeerts et al have reported a correlation between endoscopic Crohn’s disease recurrence and future clinical and surgical relapses. Specifically, they reported that an endoscopic score of i0 or i1 correlated with a low risk of endoscopic progression and had clinical recurrence rates of less than 10% over 10years
Endoscopic scores of i2 correlated with clinical recurrence rates of 20%over 5 years. Scores of i3 and i4 correlated with clinical recurrence rates of 50%-100% and a high likelihood of re-operation.
Rutgeerts P, et al. Gastroenterology. 1990;99:
Dubinsky 16

17. Endoscopic activity associated with prolonged remission in follow up of “Top-Down” study
Baert, Gastroenterology 2010

18. Fewer abdominal surgeries with endoscopic healing independent of treatment arm in a series of patients receiving IFX
Schnitzler, IBD 2009

19. Curatio PowerPoint Template
4/21/2017 7:25 AM
Endoscopic Healing Associated Inversely Associated with Colectomy Rate in UC
1.00
0.98
Proportion of UC Patients Not Colectomized
0.96
0.94
0.92
Key Point:
Mucosal healing was recently shown to correlated with reduced future colectomy rate in patients with UC.
Background:
• Frøslie et al. examined the impact of mucosal healing on subsequent disease course in 740 IBD patients (n=227 with Crohn's disease, n=513 with UC).
• Clinical and endoscopic examinations were performed at baseline and repeated after 1 and 5 years of treatment with various therapies, which included 5-ASA agents, steroids, antibiotics, or azathioprine.
•Among patients with UC, mucosal healing was associated with a lower risk of future colectomy (P = 0.02)
Reference:
Frøslie KF, Jahnsen J, Moum BA, and the IBSEN Group. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133(2):
0.90 1 2 3 4 5 6 7 8
Time in Years After 1-Year Visit
* Oral 5-ASA, topical 5-ASA, sulfasalazine, antibiotics, corticosteroids, azathioprine, and/or metronidazole
Froslie KF et al, Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort, Copyright (2007), with permission from the American Gastroenterological Association. 19 19

20. Dysplasia Surveillance

21. Current ACG Surveillance Guidelines 2010 (Secondary Prevention)
Who: left-sided or pan-UC more than 8-10 years (exception: PSC and UC- start immediately)
Technique: random biopsies every 10 cm of mucosa; at least 33 biopsies; extra focus on nodules, masses, strictures
How often: q 6 months-2 years
Outcome (reviewed by second pathologist):
High-grade dysplasia: colectomy
Low-grade dysplasia: consider colectomy
Indefinite dysplasia: increase surveillance?
Atypia or indeterminate: treatment of active disease, repeat colonoscopy and biopsies
Kornbluth and Sachar, Ulcerative colitis practice guidelines (update). Am J Gastroenterol, 2010.
David T. Rubin, MD 2007 21

22. British Society Guidelines 2010
Suggest Chromoscopy, Incorporate Inflammation
Screening colonoscopy at 10 years (preferably in remission, pancolonic dye-spray)
Lower Risk
Extensive colitis with NO ACTIVE endoscopic/histological inflammation
OR left-sided colitis
OR Crohn’s colitis of <50% colon
Intermediate Risk
Extensive colitis with MILD ACTIVE
endoscopic/histological inflammation
OR post-inflammatory polyps
OR family history CRC in FDR aged 50+
Higher Risk
Extensive colitis with MODERATE/SEVERE ACTIVE endoscopic/histological inflammation
OR stricture in past 5 years
OR dysplasia in past 5 years declining surgery
OR PSC / transplant for PSC
OR family history CRC in FDR aged <50
5 Years
3 Years
1 Year
Fact check:
Figure 2, taken from Gut_guidelines reference, pg 670—PERMISSION NEEDED
Biopsy Protocol
Pancolonic dye spraying with targeted biopsy of abnormal areas is recommended, otherwise 2–4 random biopsies from
every 10 cm of the colorectum should be taken
Other Considerations
Patient preference, multiple post-inflammatory polyps, age and comorbidity, accuracy and completeness of examination
FDR, first-degree relative; PSC, primary sclerosing cholangitis
Cairns SR et al. Gut. 2010;56:666. 22

23. The algorithm shown here is a suggested strategy for addressing initial dysplasia status. In this strategy, colectomy is recommended if flat LGD, HGD, or cancer is found, although the issue of surgery for LGD is controversial. In the case of IND, the colonoscopy should be repeated within 3 to 6 months. If the findings are negative for dysplasia, the surveillance schedule can be continued as planned.8

24. Problems with the Current Surveillance Guidelines
No prospective evidence of mortality benefit (or even CRC benefit)
Low rates of observer agreement in histopathologic interpretation
No risk stratification based on multiple variables (e.g. inflammation and PSC, etc.)
No adjustment for improved technology or understanding of natural history
Uncertainty around when to perform surgery (LGD)

25. The Limitations of Random Biopsies
Surface area of colorectum: cm2
Surface area of biopsy forceps: mm2
Recommended “at least 33 biopsies”
Percent surface area with this approach: %-0.1%
Sadahiro S. et al. Cancer.1991.
Rubin CE, et al. Gastroenterol
Kornbluth and Sachar. Am J Gastroenterol

27. Prospective Studies Comparing Chromoendoscopy to White Light
Author N Method Increased Yield
Kiesslich et al (2003) 165 MB 3-fold (lesions)
Hurlstone et al (2004) 162 IC 4-fold (lesions)
Rutter et al (2004) 100 IC 4.5-fold (lesions)
Hurlstone et al (2005) 700 IC 3-fold (lesions)
Kiesslich et al (2007) 161 MB and EM 4.75-fold (lesions)
Marion et al (2008) 102 MB 1.5 fold (patients) 27 27

28. But Does Detecting “More Dysplasia” Matter? (How Much Are We Missing?)
Mount Sinai Surveillance Database
1183 dysplasia surveillance examinations of patients with extensive UC
# of cases with CRC without prior dysplasia?
1 (0.085%)
The old system wasn’t all that bad
Ullman, ACG 2007 28

29. Needed with Advanced Endoscopic Techniques
Longitudinal studies
Agreement of end-points worth achieving
Dysplasia Yield?
Cancers?
Cancer mortality/morbidity?
Cost?
Intervals between colonoscopies?

30. Modern Guide to LGD Management (2013)
Expert review of pathology slides
Discussion with patient re: possibility of synchronous cancer (0-20%)
Consultation with a colorectal surgeon
Repeat colonoscopy
Excellent Prep
High Def or Chromo
CLEAR THE COLON OR REMOVE THE COLON
Surgery for incomplete lesion removal
Repeat colonoscopy in 3-6 months for complete removal or no lesion identified
Surgery if non-targeted biopsies positive for dysplasia

31. Is the Curve Changing with Surveillance?
Eaden et al. Gut 48:526, Ullman, et al. CGH 6:1225, 2008

32. Has Colitis-Related CRC Declined in Importance?
SMR
95% CI
Copenhagen, Denmark1
1.05
Olmsted, MN, USA2
1.1
1. Winther, CGH 2004;2:1088–1095
2. Jess, Gastro 2006;130:1039–1046

33. Thank You