Transcript Natural History of Dysplasia

How Should We be Assessing and
Documenting Endoscopies in IBD:
Incorporating Standard Scoring
Systems into Patient Care
Gary R Lichtenstein, MD
Director, Center for IBD
University of Pennsylvania School of Medicine
Hospital of the University of PA
Philadelphia, PA
Uses of Endoscopy in IBD
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Diagnosis
Disease extent
Prognostication
Assessment of Activity/Healing
Stricture evaluation and dilation
Dysplasia Surveillance
Diagnose/Control Bleeding
Pouch Evaluation
Endoscopic Ultrasound
Video Capsule Endoscopy
I. Mucosal Healing
 UC and Crohn’s disease characterized by
the presence of gut inflammation
accompanied by areas of ulceration
 Mucosal healing is becoming increasingly
important in the clinical management of UC
and Crohn’s disease, as well as being used
as an end point in clinical trials.
 Achieving mucosal healing has unequivocally
been associated with better outcomes, and
for these reasons, it has become an
important treatment goal.
I. Mucosal Healing
 Multiple methods to score endoscopic disease
activity in both UC and Crohn’s disease.
 Those used most frequently or that have been
validated:
• Mayo Endoscopic Score
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Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
Crohn’s Disease Endoscopic Index of Severity (CDEIS),
Simple Endoscopic Score for Crohn’s Disease (SES-CD),
Rutgeerts Postoperative Endoscopic Index for Crohn’s
disease.
II. Definition of Mucosal Healing
 Mucosal healing in the context of IBD refers
to the endoscopic assessment of disease
activity.
 Simply stated, mucosal healing should imply
the absence of ulceration and erosions.
 There is currently no validated definition of
mucosal healing in IBD.
III. Inflammation in UC
 The pattern of inflammation in UC is
associated with several mucosal changes,
initially
 vascular congestion,
 erythema, and
 granularity.
 As inflammation becomes more severe,
 friability (bleeding to light touch),
 spontaneous bleeding, and
 erosions and
 ulcers develop.
What Is the Definition
of Mucosal Healing?
AGA Consensus on Efficacy
End Points: Endoscopic Healing
in Ulcerative Colitis
“Absence of friability, blood, erosions, and
ulcers in all visualized segments are the
required components of genuine
endoscopic healing.”
D’Haens G et al. Gastroenterology 2007;132(2):763–86.
Mucosal Healing in Ulcerative Colitis
•
Disease:
TheofIssues
What is the definition
mucosal healing?
– Depends on finding a scoring system of your choice
– some studies allow erythema and friability in the
definition of mucosal healing 1
Many different endoscopic indices for UC have been
used in clinical trials, only one UCEIS - validated in
prospective studies; this creates problems when comparing
trials.
Mucosal Abnormalities in
Crohn’s Disease
The SB has limited ways to demonstrate injury:
Mucosal Disruption
 Erosions
 Ulcers
Erythema
Villous Blunting
Strictures
These findings are easily captured by
capsule endoscopy, but are not pathognomonic
of IBD.
Hypothesis
Erythema and Villous Blunting
Aphthous Ulcers
VCE +
Superficial Ulceration
Serpiginous or Linear Ulcers
Cobblestone Appearance
Rad +
Transmural Inflammation
Strictures, Fistulas
Carucci LR et al: GI Clinics NA 31:93-117, 2002
What Is the Definition of
Mucosal Healing in Crohn’s Disease?
•
CDEIS: Deep ulceration, superficial ulceration, and inflammation1
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–
–
–
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Complex (many variables and scores range from 0 to 44)
Experience is required
Difficult to use in clinical practice
No validated definition of mucosal healing
SES-CD: Ulcers, inflammation, and narrowing2
– Validated in only 1 study
– Scores range from 0 to 60
– No validated definition of mucosal healing
•
Rutgeerts Score: Aphthoid lesions, inflammation, ulcers, nodules,
and narrowing3
– Only applicable to postoperative recurrence
– No endpoint for endoscopic remission in the trials
CDAI = Crohn’s Disease Activity Index; SES-CD = Simple Endoscopic Score for Crohn's Disease.
1. Mary JY et al. Gut. 1989;30:983-989; 2. Daperno M et al. Gastroenterology. 2002;122:A216;
3. Rutgeerts P et al. Gastroenterology. 1990;99:956-963.
Limitations of Endoscopic Scores of
Bowel Lesions in Crohn’s Disease?
• No validated endpoints for:
– Endoscopic response
– Endoscopic remission
• Complete mucosal healing = total disappearance
of all ulcers
• Does the mucosal activity reflect transmural damage?
– No controlled studies have evaluated endoscopic score
correlation with the entire thickness of the intestinal wall
• What is the spontaneous variation of endoscopic
activity in Crohn’s disease?
– Study of the placebo effect
Limitations of Endoscopic Scores of
Bowel Lesions in Crohn’s Disease?
• Does not access small bowel other than
terminal ileum
• Makes assumption that changes to the lesions
in terminal ileum reflect what transpires in
remainder of the small bowel
Actual Endoscopic Indices
• Ulcerative Colitis
– Mayo Score
– UCIEIS
• Crohn’s Disease
– UCEIS
– SES-CD
– Rutgeerts Score
UC Endoscopic Indices
Table Source- Walsh A, et al. Gastrointest. Endoscopy Clin. N. Am. 2014; 24: 367–378
Mayo Scoring System1
for Assessment of UC Activity
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Stool frequency:
•
Rectal bleeding:
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Endoscopic findings:
•
0 = Normal number of stools for this patient
1 = 1 to 2 stools more than normal
2 = 3 to 4 stools more than normal
3 = 5 or more stools more than normal
0 = None
1 = Streaks of blood with stool less than half the time
2 = Obvious blood with stool most of the time
3 = Blood alone passes
0 = Normal or inactive disease
1 = Mild disease (redness, decreased vascular
pattern visible, friability)
2 = Moderate disease (redness, no vascular
pattern visible, friability, erosions)
3 = Severe disease (bleeding, ulceration)
Physician’s global assessment of disease activity: 0 (normal) to 3 (severe)
1. Schroeder KW, et al. N Engl J Med. 1987;317(26):1625-1629.
Mayo Score: Practical Points
 Overlap in the features of the different levels
of this endoscopic index, which causes high
interobserver variation.
 The most troublesome component of this
index is friability, as this is subjective and
leads to inconsistent results.1
 This inconsistency has lead to an adaptation
of the index to remove friability. 2,3
1.) D’Haens G, et al Gastroenterology2012;143(6):1461–9.
2.) Kamm MA, et al. Gastroenterology2007;132(1):66–75.
3.) Lichtenstein GR, et al Clinical Gastroenterol Hepatol. 2007; 2007;5: 95–102.
Mayo Score: Practical Points
 The value of this index is its widespread use
in clinical trials.
 Mucosal healing – 0 or 1- or a deceases from
the subscores of 2 or 3.1
 In Active Ulcerative Colitis Trials, patients with
a post-treatment Mayo score of grade 1 were
no more likely to undergo a colectomy than
those with a score of 0. 1
1.) Rutgeerts P , et al N Engl J Med 2005;353(23):2462–76.
UCEIS for Assessment of UC Activity
Table Source- Walsh A, et al. Gastrointest. Endoscopy Clin. N. Am. 2014; 24: 367–378
UCEIS: Practical Points
• In practical terms, the most severely affected part
of the mucosa is scored.
• Limitations– Thresholds for remission and mild, moderate,
and severe disease have yet to be set.
– The extent to which full colonoscopy may
influence the score compared with the flexible
sigmoidoscopy on which it was based, has only
started to be evaluated .1
1- Thia KT et al, Inflamm Bowel Dis. 2011;17(6):1257–64.
UCEIS: Practical Points
• Knowledge of symptoms does not materially influence the
score, and a comparison with the Mayo Clinic endoscopy
subscore shows that the UCEIS is less subject to
variation by a central reader.
• UCEIS is simple enough to use in clinical practice and
should achieve its goal of reducing variation in
endoscopic assessment of activity between observers.
• Patients admitted with acute severe colitis with a score of
7 or 8 (out of 8) on admission predicted an inadequate
response to intravenous steroids and the need for rescue
therapy with cyclosporine or infliximab1.
• Easy for in office use
1.) Conte CJ, et al. Gastroenterology 2013; 144(5): S-102.
Crohn’s Disease: Endoscopy
Table Source- Walsh A, et al. Gastrointest. Endoscopy Clin. N. Am. 2014; 24: 367–378
Crohn’s Disease Endoscopic Index of Severity
 Prospectively developed instrument constructed to
detect changes in disease activity1.
 Examines 4 endoscopic variables
 In each of the following locations: rectum, sigmoid
and left colon, transverse colon, and right colon
and ileum
 CDEIS scores range from 0 to 44.
Mary JY, et al. Gut 1989;30(7): 983–9.
Crohn’s Disease Endoscopic Index of Severity
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CDEIS Evaluates:
• Deep ulcerations: score 0 if absent or 12
if present.
• Superficial ulcerations: score 0 if absent or
6 if present.
• Length of ulcerated mucosa (0-10cm):
score 0 to 10 according to length in
centimeters
• Length of diseased mucosa (0-10cm):
score 0 to 10 according to length in
centimeters.
Crohn’s Disease Endoscopic Index of Severity
 The numbers are added up in each
segment and divided by the number of
segments evaluated.
 An additional 3 points is given if an
ulcerated stenosis is present, and a
further 3 points if a nonulcerated
stenosis is present.
Mary JY, et al. Gut 1989;30(7): 983–9.
Crohn’s Disease Endoscopic Index of Severity
Table Source- Walsh A, et al. Gastrointest. Endoscopy Clin. N. Am. 2014; 24: 367–378
Crohn’s Disease Endoscopic Index of Severity
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CDEIS Definitions:
• Endoscopic remission (minor or no lesions) is
defined as a CDEIS score less than or equal to
6 or less than or equal to 7
• Complete endoscopic remission (mucosal
healing, i.e., no lesions at all or scarred lesions
only) is defined as a CDEIS score less than or
equal to 3 or less than or equal to 4.
• Endoscopic response is a decrease from
baseline CDEIS score of at least 4 or 5
points. .
Mary JY, et al. Gut 1989;30(7): 983–9.
Crohn’s Disease Endoscopic Index of Severity
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Critque:
• It is the standard index and it is reproducible.
• It is complex
• Requires training and experience
• To estimate ulcerated or disease mucosal surface
areas
• To distinguish between superficial and deep
ulcerations.
• It is cumbersome to use in clinical practice.
Mary JY, et al. Gut 1989;30(7): 983–9.
Simplified Endoscopic Score for Crohn’s Disease
Daperno M, et al. Gastrointest Endoscopy 2004; 60: 505-512.
Crohn’s Disease Endoscopic Index of Severity
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Critque:
• The SES-CD correlates well with the CDEIS
• Correlation coefficient (r=0.920)
• Interobserver reliability (kappa- 0.791-1.000)
• Easy to use
• Less complex than the CDEIS
• No cutoff values have been determined for this
• Mucosal healing not defined.
Daperno M, et al. Gastrointest Endoscopy 2004; 60: 505-512.
The Natural Course of Postop CD
Recurrence is clinically silent initially
Histologic
Within
1 week
Endoscopic
Radiologic
70-90%
by 1 yr
Tissue
damage
Clinical
30% 3 yr
60% 5 yr
Surgery
[1] D’Haens G, Geboes K, Peeters M, et al. Gastroenterology 1998;114:262-267.
[2] Olaison G, S medh K, Sjodahl R. Gut 1992;33:331-335.
[3] Rutgeerts P, Geboes K, Vantrappen G, et al Gastroenterology 1990;99:956-983.
[4] Sachar DB. Med Clin North Am 1990;74:183-188.
Surgical
50% by 5 yrs
Endoscopic Recurrence Score
• i0:
no lesions
• i1:
< 5 aphthous lesions
• i2:
> 5 aphthous lesions with normal intervening
mucosa
• i3:
diffuse aphthous ileitis with diffusely inflamed
mucosa
• i4:
diffuse inflammation with large ulcers,
nodules, and/or narrowing
Rutgeerts P, Geboes K, Vantrappen G, et al Gastroenterology 1990;99:956-983.
>70% of Pts Have i2,3,4 Recurrence 1 Year
after Surgery – Rutgeerts et al Gastro 1990
i1
i0 and i1 remission
-low likelihood of
progression
i,3
i4
i2,i3,i4 recurrence
Likely progression
to another surgery
Actuarial Rate of Symptomatic
Recurrence
Those individuals with grade 3 and 4 lesions at one year postoperatively during
colonoscopy were more likely to have symptomatic recurrences earlier than
% symptom free survival
those with individuals with grade 1 and 2 lesions.
1.0
Grade 0 and
Grade 1
0.8
0.6
Grade 2
0.4
0.2
Grade 4
Grade 3
0
0
1
2
3
4
5
6
Rutgeerts P, Geboes K, Vantrappen G, et al Gastroenterology 1990;99:956-983.
7
8
9
10
POCER Study: Postoperative Crohn’s Disease
Endoscopic Recurrence
Methods: Multicentre RCT
No Endoscopy
(“Standard”)
Randomization
All patients: Metronidazole: 0-3
months
Low risk: No further treatment
High risk: Thiopurine or adalimumab if thiopurine intolerant
RISK Stratification:
Low or High
(High risk: smoker,
≥ second operation,
perforating disease)
SURGERY:
Curative resection
2/3 of
patients
Endoscopic
Intervention
(“Active”)
6 Month
Colonoscopy
Step up Rx if ≥ i2 on
Rutgeerts scale
De Cruz P, et al. Presented at DDW; May 21 2013. Abstract 925J.
18 Month Colonoscopy
Risk driven best drug
therapy
1/3 of
patients
POCER Study: Postoperative Crohn’s Disease
Endoscopic Recurrence
Results:
32% dropout rate; no difference between both study arms
174 randomized: 122 Active/ 52 Standard
Rutgeerts ≤ i2 at 18 months
Active Care (n=122)
62/122 (51%)
Standard Care (n=52)
17/52 (33%)
Adalimumab Immediately Postop (n=28)
16/28 (57%)
Adalimumab Initiated if i≥2 at 6 Months (n=32)
13/32 (41%)
P= 0.028
P = 0.2
6-month (short-term) endoscopic recurrence: ADA better than thiopurine in high-risk patients
(P=0.028)
Stepping up at 6 months if ≥i2 brought 39% into endoscopic remission at 18 months
Remission at 6 months colonoscopy, 39% endoscopic recurrence at 18 months
Conclusions regarding postoperative recurrence of Crohn’s:
Treatment according to risk of recurrence at 6 month colonoscopy, is superior to drug therapy
alone
Step-up with anti-TNF therapy, based on colonoscopy findings at 6 months, is a viable strategy in
high-risk patients
De Cruz P, et al. Presented at DDW; May 21, 2013. Abstract 925J.
CONCLUSION

The colonoscopic assessment of mucosal
inflammation and healing is important for
assessment of patients with UC and CD
 All clinicians should try to achieve mucosal healing
in patients with IBD
 Multiple endoscopic indices for UC exist but only
one, the UCEIS is validated
 The CDEIS and SES-CD are validated in CD
 The Rutgeerts postoperative endoscopic index is
useful for predicting the clinical course in patients
with ileocecal CD undergoing ileocecal resections