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 MedicineNew York, NY

Team Hope/Team EuroTeam Hope/Team EuroOrange All the WayOrange All the Way

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

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

Ileocolonoscopy for Diagnosis and ActivityIleocolonoscopy for Diagnosis and Activityin Small Bowel Crohn’s Diseasein Small Bowel Crohn’s Disease

• STRENGTHSSTRENGTHS– Technically easyTechnically easy– ReliabilityReliability– AccuracyAccuracy– Acceptable to most Crohn’s patientsAcceptable to most Crohn’s patients

• WEAKNESSESWEAKNESSES– High costHigh cost– Less-than ideal safety profileLess-than ideal safety profile

Endoscopy for DiagnosisEndoscopy 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)

Sensitivity for SB CD

8274

83

6575

67

86

59

0%

20%

40%

60%

80%

100%

CDActive*

CDPresent**

CTEIleoscopyCESBFT

* 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

Specificity for SB CD

90100

53

94 88100

62

94

0%

20%

40%

60%

80%

100%

CDActive*

CDPresent**

CTEIleoscopyCESBFT

* 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)

Solem, GIE, 2008

Activity

Ileocolonoscopy: Activity IndexIleocolonoscopy: Activity Index

• CDEIS, Mary et al, Gut 1989CDEIS, Mary et al, Gut 1989– Aim: “Elaborate and validate a CDEIS”Aim: “Elaborate and validate a CDEIS”– Authors forgot that a “simple” index would be Authors forgot that a “simple” index would be

preferablepreferable

CDEIS, 1989CDEIS, 1989

9 Possible Mucosal Lesions9 Possible Mucosal Lesions1.1. PseudopolypPseudopolyp2.2. Healed ulcerationHealed ulceration3.3. Frank erythemaFrank erythema4.4. Frankly swollen mucosaFrankly swollen mucosa5.5. Aphthoid ulcerationAphthoid ulceration6.6. Superficial or shallow ulcerationSuperficial or shallow ulceration7.7. Deep ulcerationDeep ulceration8.8. Non ulcerated stenosisNon ulcerated stenosis9.9. Ulcerated stenosisUlcerated stenosisMeasured across Measured across 5 segments5 segments: rectum, left/sig, transverse, : rectum, left/sig, transverse,

right, ileumright, ileumConstructed and compared against a Constructed and compared against a global physicians global physicians

assesmentassesment (10 cm Likiert scale) (10 cm Likiert scale)

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 stenosisMary et al, Gut 1989Mary et al, Gut 1989

There’s Something About Mary There’s Something About Mary (1998)(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

“Simple” Endoscopic Score for Crohn’s DiseaseSES-CD, 2004

• Same 5 segments• 4 variables per segment, all 0-3 score

0 1 2 3

Size of ulcers

None Aphthous Large

(0.5-2 cm)

Very large (>2 cm)

Ulcerated surface

None <10% 10-30% >30%

Affected surface

Unaffected segment

<50% 50-75% >75%

Narrowings None Single, can be passed

Multiple, can be passed

Cannot be passed

Daperno, et al, GI Endoscopy, 2004Daperno, et al, GI Endoscopy, 2004

Prognosis

Actuarial analysis of symptomatic recurrence in patients stratified according

to severity of endoscopic lesions

Rutgeerts P, et al. Gastroenterology. 1990;99:956-963

Endoscopic activity associated with prolonged remission in follow up of

“Top-Down” study

Baert, Gastroenterology 2010

Fewer abdominal surgeries with Fewer abdominal surgeries with endoscopic healing endoscopic healing independentindependent of of treatment arm in a series of patients treatment arm in a series of patients

receiving IFXreceiving IFX

Schnitzler, IBD 2009

Froslie KF et al, Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort, 412-422.

Copyright (2007), with permission from the American Gastroenterological Association.

Endoscopic Healing Associated Inversely Endoscopic Healing Associated Inversely Associated with Colectomy Rate in UCAssociated with Colectomy Rate in UC

Pro

po

rtio

n o

f U

C P

atie

nts

N

ot

Co

lect

om

ized

0.90

0.92

0.96

0.98

1.00

0 1 4 5 6 8

0.94

32 7

Time in Years After 1-Year Visit* Oral 5-ASA, topical 5-ASA, sulfasalazine, antibiotics, corticosteroids, azathioprine, and/or metronidazole

Dysplasia Surveillance

Current ACG Surveillance Guidelines 2010Current ACG Surveillance Guidelines 2010(Secondary Prevention)(Secondary Prevention)

• Who:Who: left-sided or pan-UC more than 8-10 years (exception: PSC and UC- start immediately)

• Technique:Technique: random biopsies every 10 cm of mucosa; at least 33 biopsies; extra focus on nodules, masses, strictures

• How often: How often: q 6 months-2 years

• Outcome (reviewed by second pathologist): 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.

Cairns SR et al. Gut. 2010;56:666.

Screening colonoscopy at 10 years(preferably in remission, pancolonic dye-spray)

Lower RiskExtensive colitis with NO ACTIVE

endoscopic/histological inflammation

OR left-sided colitisOR Crohn’s colitis of <50% colon

Intermediate RiskExtensive colitis with MILD ACTIVE

endoscopic/histological inflammation

OR post-inflammatory polypsOR family history CRC in FDR aged 50+

Higher RiskExtensive colitis with MODERATE/SEVERE

ACTIVE endoscopic/histological inflammation

OR stricture in past 5 yearsOR dysplasia in past 5 years declining surgeryOR PSC / transplant for PSCOR family history CRC in FDR aged <50

5 Years 3 Years 1 Year

FDR, first-degree relative; PSC, primary sclerosing cholangitis

Biopsy ProtocolPancolonic dye spraying with targeted biopsy of abnormalareas is recommended, otherwise 2–4 random biopsies fromevery 10 cm of the colorectum should be taken

Other ConsiderationsPatient preference, multiple post-inflammatory polyps,age and comorbidity, accuracy and completeness of examination

British Society Guidelines 2010British Society Guidelines 2010Suggest Chromoscopy, Incorporate InflammationSuggest Chromoscopy, Incorporate Inflammation

Problems with the Current Problems with the Current Surveillance GuidelinesSurveillance 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)

The Limitations of Random The Limitations of Random BiopsiesBiopsies

• Surface area of colorectum: 1578.1 + 301.0 cm2

• Surface area of biopsy forceps: 2.2-5 mm2

• Recommended “at least 33 biopsies”

• Percent surface area with this approach: 0.05%-

0.1%

Sadahiro S. et al. Cancer.1991.Rubin CE, et al. Gastroenterol. 1992.

Kornbluth and Sachar. Am J Gastroenterol. 2010.

Prospective Studies Comparing Prospective Studies Comparing Chromoendoscopy to White LightChromoendoscopy to White Light

AuthorAuthor NN MethodMethod Increased YieldIncreased YieldKiesslich et al (2003)Kiesslich et al (2003) 165165 MBMB 3-fold (lesions)3-fold (lesions)Hurlstone et al (2004)Hurlstone et al (2004) 162162 ICIC 4-fold (lesions)4-fold (lesions)Rutter et al (2004)Rutter et al (2004) 100100 ICIC 4.5-fold (lesions)4.5-fold (lesions)Hurlstone et al (2005)Hurlstone et al (2005) 700700 ICIC 3-fold (lesions)3-fold (lesions)Kiesslich et al (2007)Kiesslich et al (2007) 161161 MB and EMMB and EM 4.75-fold (lesions)4.75-fold (lesions)Marion et al (2008)Marion et al (2008) 102102 MBMB 1.5 fold (patients)1.5 fold (patients)

But Does Detecting “More Dysplasia” But Does Detecting “More Dysplasia” Matter?Matter?

(How Much Are We Missing?)(How Much Are We Missing?)

• Mount Sinai Surveillance DatabaseMount Sinai Surveillance Database

• 1183 dysplasia surveillance examinations of 1183 dysplasia surveillance examinations of patients with extensive UCpatients with extensive UC

• # of cases with CRC without prior # of cases with CRC without prior dysplasia?dysplasia?

• 1 (0.085%)1 (0.085%)

• The old system wasn’t all that badThe old system wasn’t all that bad

Ullman, ACG 2007

Needed with Advanced Endoscopic Techniques

• Longitudinal studies

• Agreement of end-points worth achieving

– Dysplasia Yield?

– Cancers?

– Cancer mortality/morbidity?

– Cost?

– Intervals between colonoscopies?

Modern Guide to LGD Management (2013)

1. Expert review of pathology slides 2. Discussion with patient re: possibility of synchronous cancer (0-

20%)3. Consultation with a colorectal surgeon4. Repeat colonoscopy

1. Excellent Prep2. High Def or Chromo

5. CLEAR THE COLON OR REMOVE THE COLON1. Surgery for incomplete lesion removal2. Repeat colonoscopy in 3-6 months for complete removal or no

lesion identified3. Surgery if non-targeted biopsies positive for dysplasia

Is the Curve Changing with Is the Curve Changing with Surveillance?Surveillance?

20.015.010.05.00.0

Years After Entry

1.0

0.8

0.6

0.4

0.2

0.0

Pro

gre

ssi

on

Progression to Advanced Neoplasia

NoD

IND

LGD

Eaden et al. Gut 48:526, 2001Eaden et al. Gut 48:526, 2001 Ullman, et al. CGH 6:1225, 2008 Ullman, et al. CGH 6:1225, 2008

Has Colitis-Related CRC Has Colitis-Related CRC Declined in Importance?Declined in Importance?

SMRSMR 95% CI95% CI

Copenhagen, Denmark1 1.05 0.56-1.79

Olmsted, MN, USA2 1.1 0.4-2.4

1. Winther, CGH 2004;2:1088–1095

2. Jess, Gastro 2006;130:1039–1046

Thank YouThank You