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Colonoscopy with at least 30 biopsies should be the procedure of

choice in UC surveillancechoice in UC surveillanceAsher Kornbluth , MD

The Henry D. Janowitz Division of Gastroenterologygy

The Mount Sinai Medical Center

Routine colonoscopy with >30 biopsies should remain the standard:

Wh t th i ?What are the issues?• How good is conventional (white light)

colonoscopy in visualizing dysplasia?• How can we enhance dysplasia detectionHow can we enhance dysplasia detection

yield with white light colonoscopy?• What is the natural history of lesions found

only with chromoendoscopy?• What are the practical issues concerning

chromoendoscopy?

Dysplasia is visible with white light colonoscopy: St. Marks Group 1988-

20022002• Retrospective review of neoplasia• 525 patients, 2204 surveillance exams• Random biopsies “non targeted” as well as• Random biopsies non-targeted as well as

“targeted” biopsies of macroscopic lesions• 110 dysplastic lesions in 56 patients• In 89% of patients in whom dysplasia was• In 89% of patients in whom dysplasia was

found, it was visible to the endoscopist

Dysplasia is visible with white light colonoscopy: University of Chicago,

1994 20021994-2002• Retrospective review of neoplasia

622 patients, 1339 surveillance exams• Random biopsies “non-targeted” as well as

“targeted” biopsies of macroscopic lesions• 73 dysplastic lesions in 46 patients

I 78% f i i h d l i• In 78% of patients in whom dysplasia was found it was visible to the endoscopist

Dysplasia is visible with white light colonoscopy: Univ. of Pennlight colonoscopy: Univ. of Penn• Review of 48 patients found to have

dysplasia during routine surveillance colonoscopy py

• 1997-2004; 1997 introduction of newer generation of video colonoscopes (non-zoom)

• 88% of dysplasia found was visible to the endoscopist

Is chromo necessary?



colonoscopy in visualization?• How can we enhance dysplasia detectionHow can we enhance dysplasia detection



chromoendoscopy?

“Interval cancer” detection with routine colonoscopy: The 30 year St. Marks

surveillance600 i• 600 patients– 2627 colonoscopies, 5932 patient years f/u– 30 colorectal cancers found

• Only 4 cancers occurred in less than a 1• Only 4 cancers occurred in less than a 1 year interval

• 9 additional cancers if interval was longer than 1 yeara yea

• Median interval between a normal exam and cancer = 1.5 years

How can we enhance dysplasia detection yield with white light colonoscopy:

Are Are Gastroenterologists Taking Enough Gastroenterologists Taking Enough g g gg g gBiopsies?Biopsies?

Survey of 298 British gastroenterologists# of Biopsies % of GI’s0 5 70-5 76-10 5011-15 3116-20 1016 20 10>20 2

Eaden, GI Endoscopy, 2000

How can we enhance dysplasia detection yield with white light colonoscopy: An

internet study

• If a polyp is identified and completely removed, do you perform biopsy of the mucosa surrounding the polyp?

• 54 % of private practice physicians biopsy the adjacent mucosa (vs. 94% of “IBD experts”)

Farraye F, GIE 2007: 66: 519

How can we enhance dysplasia detection yield with white light colonoscopy: Is longer

and slower better?

Toruner, Inflamm Bowel Dis 2005;11:428

Longer procedure time, and slower withdrawal time is associated with increased detection rate of flat dysplasia



colonoscopy in visualization?• How can we enhance dysplasia detectionHow can we enhance dysplasia detection



chromoendoscopy?

Does finding a dysplastic lesion by chromo predict outcomes?

• Kiesslich (zoom scope)• Kiesslich (zoom scope)– No follow-up

• Kiesslich (confocal laser endomicroscopy)– No follow-upNo follow-up

• Hurlstone (zoom scope)– No follow-up

• RutterRutter – No follow-up

• Marion – Follow-up with colectomy specimens

Chromoendoscopy for UC Surveillance: Patient Demographics: Mt. Sinaig p

• 102 enrolled: 79 UC, 23 CC

• Median duration of disease 21.5 years

• All enrolled in surveillance programs

• 39% had previous dysplasia– LGD 38, HGD 2

– IND 10 patientsMarion J, et al.AJG,2008;103:2342

Follow-up of chromo positive patients: What does the total proctocolectomy

specimen show?specimen show?

Marion J, et al.AJG,2008;103:2342

Total proctocolectomy in chromo positive patients found no cancers

Series of chromoendoscopy in UC surveillance: Problems

• All published series were from “IBD endoscopists” at tertiary centers

H i did h “ i ”• How many patients did they “practice” on before starting their series?

Th t di ’t bli d d• These studies weren’t blinded

• Publication bias?



colonoscopy in visualizing dysplasia?• How can we enhance dysplasia detectionHow can we enhance dysplasia detection



chromoendoscopy?

“Politics is the art of the possible”

Winston Churchill

“Medicine, like politics is the art of the possible”

Henry D. Janowitz, MDy ,

Chromoendoscopy for UC surveillance: Practical considerations

• How will all gastroenterologists be trained---spray technique and pit pattern interpretation?

• What is the learning curve?

• What are the additional costs---time and money?

Conclusions

Conclusions: routine UC surveillance colonoscopy (for now)py ( )

• Frequent surveillance exams----recognize need for improved detection in patients at high risk: prior dysplasia, PSCg p y p ,

• Biopsy throughout the colon, meticulous exam for irregular “flat” lesions

• Slower withdrawal times• Watch for upcoming chromo- patient long

term follow up data

Thank you

Determination of Mucosal Healing is Not Necessary in the Management of

Patients with Ulcerative ColitisPatients with Ulcerative ColitisAsher Kornbluth, MD

The Mount Sinai Medical CenterNew York, NY

Does Surveillance Colonoscopy Improve Mortality?

Mucosal Healing in UC: The IssuesIssues

• What is the definition of mucosal healing ?• Is it necessary to monitor disease activity?• How does it relate to clinical outcomes in• How does it relate to clinical outcomes in

clinical trials?• Does it predict future outcomes?• Then why look for mucosal healing?• Then why look for mucosal healing?

What is the definition of mucosal healing ?

• Baron score: 4 point scale based on rigid proctoscopy– Scores related to bleeding only and notScores related to bleeding only and not

ulceration• Powell-Tuck score: 3 point scale, part of a

22 point overall score– Related to friability/bleeding

What is the definition of mucosal healing ?healing ?

• Rachmilewitz: 12 point score – Granularity, “vulnerability”,

“damage”mucus,fibrin, exudate, erosions and g , , ,ulcers

• Sigmoidoscopic Index (Hanauer): 5 variables

h f i bili l i / l i– Erythema,friability,granularity/ulceration,mucopus, loss of vascular pattern

What is the definition of mucosal healing ? The Mayo Scorehealing ? The Mayo Score

• Essentially based on the (proctoscopic) Baron Score– 0 = Normal or inactive disease0 Normal or inactive disease– 1 = Mild disease (erythema, decreased vascular

pattern, mild friability)– 2 = Moderate disease (marked erythema, lack

f l tt f i bilit i )of vascular pattern, friability, erosions)– 3 = Severe disease (spontaneous bleeding,

ulceration)

Proctoscopy as per Baron, et al, 19641964

• Essentially a diagnostic procedure to 10-15 pcm

• Beyond 15 cm, it’s no longer diagnostic, it’s punitive and sadistic

AGA Consensus on Efficacy End Points: Endoscopic HealingPoints: Endoscopic Healing

•

“Absence of friability, blood, erosions, d l i ll i li dand ulcers in all visualized segments

are the required components of genuine endoscopic healing.”

ACT 1 and ACT 2: Landmark RCTs for Infliximab in UC,

NEJM 2005NEJM 2005

ACT 1 and ACT 2: Landmark RCTs for Infliximab in UCRCTs for Infliximab in UC

• Clinical Remission • Week 8 = 37 % • Week 30 = 30%

“Mucosal Healing”Week 8 = 62 % !!Week 30 = 48 % !!

ACT 1 and ACT 2: Landmark RCTs for Infliximab in UCRCTs for Infliximab in UC

• Clinical Remission • Week 8 = 37 % • Week 30 = 30%• Week 30 = 30%

• “Mucosal Healing”W k 8 62 % !!• Week 8 = 62 % !!

• Week 30 = 48 % !!

How can “Mucosal Healing” occur so much more frequently

h li i l i ithan clinical remission

• “Mucosal remission” defined as a endoscopic score of 0 or 1endoscopic score of 0 or 1

• 0 = normal mucosa• 1= includes:

– erythemaerythema– decreased vascular pattern – mild friability

How can “Mucosal Healing” occur so much more frequently than clinical

remissionremission• Because it can look

like this

And this…

And this:

N b f UC li i l i l iNumber of UC clinical trials in which individual patient clinical and endoscopic outcomes were p

correlated

Does Mucosal Healing Predict Future Outcomes: Dysplasia and

CCancer• Rutter, St. Marks: Multivariate analysis---

Microscopic, but not macroscopic i fl ti di t d l iinflammation predicted neoplasia

• Rubin, U. of Chicago: Correlated histologic inflammation with neoplasia

• Gupta Mt Sinai: Correlated histologic• Gupta, Mt. Sinai: Correlated histologic grade with development of neoplasia

So why not define Mucosal Healing as Histologic Healing?Healing as Histologic Healing?

• Variable interobserver agreement

• Need for additional cost risk of biopsies• Need for additional cost, risk of biopsies

• No standardization for site, number, frequency and depth of biopsyfrequency and depth of biopsy

Number of UC clinical trials in which individual patient clinical and histologic outcomes were

correlatedcorrelated

Histologic Assessment of Healing----Pick your choice from

h f ll i T blthe following Table

AGA Consensus on Efficacy End Points: Histologic AssessmentPoints: Histologic Assessment

• “The authors do not recommend that histologic remission be used as the primary end point for a therapeutic trial in patients p p pwith UC.”

Do patients want mucosal healing?

• Oh doctor, can you please look inside me one more time (for endoscopic healing) ?

• Oh doctor, when you’re looking inside me, can you take one more little pinch of me for one of your biopsies (for histologic healing)?

How can we, the practicing gastroenterologist assess for

l h li ?mucosal healing?

Ambulatory Endoscopy Centers

A Bigger Ambulatory Endoscopy Center (Texas, of course)Center (Texas, of course)

New York State: Office Endoscopy roomEndoscopy room

New York City: Traffic Endoscopy

Scopeforlife.com

Ileocolonoscopy in IBD• UC and endoscopic differential diagnoses

– UC vs CD and other colitides– UC plus

• Pouches– Ileoanal J PouchIleoanal J Pouch– Koch Pouch

• The neo-TI• Strictures

d• Lumps and Bumps• Bad Things

Is all UC, UC?

• UC and some myths re indeterminate colitis

– Rectal sparing can’t be assessed onRectal sparing can t be assessed on topical tx

– Endoscopic skip areas may be selective healingC bbl i i UC– Cobblestoning may appear in severe UC as in CD

UC and “Skip Areas” may be selective healing, and NOT Crohn’s

DiDisease

Rectum Transverse Cecum

“Cobblestoning” in UC

• Cobblestones represent the intersection of horizontal and vertical ulcerations

• May be seen with severely ulcerated UC

• Therefore is not specific for CD in the• Therefore is not specific for CD in the absence of other CD-features

“Cobblestoning” in UC

“Segmental Colitis”

• Reported by referring physician as scattered distal aphthous ulcers

• Biopsies consistent• Biopsies consistent with lymphoid hyperplasia

• Simple dx = Phosphate based prepPhosphate based prep

UC Ddx: SRUS

• Rectal bleeding• Sense of constipation

or tenesmusUsual hx of (surreptitous

manual disimpaction)May not be an ulcer and

may not be solitaryPathognomonic

histology

Known UC, Plus• Recognize change g g

in pattern of symptoms

• Severe flare of UC l lalmost always

involves bleeding• Consider NSAIDs,

infectiousinfectious, ischemic, hypercoagulability

Colitis Ddx: Diverticular colitis• Typically confined to

sigmoid colon in region of diverticuli

• Mucosal inflammatory• Mucosal inflammatory changes with mucopurulent exudate

• Usually mistaken for CD li i dCD colitis and worsen quickly with steroids

• Treat with antibiotics

Inside pouches

The Ileoanal Anastomotic Pouch:AKA

• IAAPIAAP• J Pouch• Restorative Proctocolectomy• Surgical Techniques include:g q

– Stapled anastamosis– Hand-Sewn anastamosis– Hand-sewn anastamosis with hand sewn

micromucosectomymicromucosectomy– Surgeons can debate merits of these for hours;

we’ll move on….

Pouchitis• Symptoms of colitis all over again• Often with constitutional symptoms and

extraintestinal manifestations• More common in patients with:

High pre op ANCA titers– High pre-op ANCA titers– Non-smokers– PSC– Pre-op EIMSPre op EIMS

• Diagnosis cannot be made solely based on symptoms (at least not initially) and must be supported by endoscopic findings

The Ileoanal Pouch: The cuff, pouch and afferent limb

Rectal Cuff

Pouch Body

Afferent Limb

Pouchitis: No different than colitic appearancespp

Severe pouchitis

Pouch Pouch

Suture line

Efferent limb

Efferent Afferent limb

limb

Cuffitis

• Residual “cuff” of rectal mucosa distal to anastamosis

• May develop symptoms of “proctitis” primarily bleeding

• Also at (low) risk of dysplasia

The Continent Ileostomy: aka, The Koch Pouch

• Replaced by the J pouch in 1980s• Abdominal wall continent small bowel

stoma created with internal “nipple valve”pp• Patient empties the internal Koch pouch by

self-intubation with Foley catheter• Chief problem = gradual slippage of the

valve leading to inability to empty pouchvalve leading to inability to empty pouch• SBO

Koch Pouchitis

Strictures, aka,Luminal narrowingg

Luminal narrowing: Pseudopolypoid

• Soft, but may entirely obscure lumen

• May be entirely asymptomaticasymptomatic

• May pose diagnostic challenge when surveillance indicated

• Often long segment and g gnot easily amenable to endoscopic dilation

Ileocolic anastamotic strictures• Usually concentric at

it f t l dsite of a stapled anastamosis

• May be entirely asymptomatic despite very narrow lumen

• If symptomatic, usually easily treated with balloon dilation

The ulcerated Crohn’s stricture• Colonic or small bowel• Colonic or small bowel• Symptoms may be

inflammatory or obstructive

• Should be treatedShould be treated medically, aggressively

• Very high risk perforation if dilation attempted in setting of acute i fl iinflammation

The ulcerated UC stricture

• Always in setting of clinically severe colitis

• Treatment is aggressive medical therapymedical therapy

• SHOULD NOT BE DILATED

• May heal with fibrosis, posing surveillance p gdifficulties

The neo-terminal ileum, and why does it matter?

Assessing the neo-TI: The Rutgeerts Score

• Ileocolonoscopy at 3-6 months can predict endoscopic and clinical recurrence rates for the following 3 yearsg y

• May help guide selection of patients for post-op maintenance

• Predicts responses to post-op maintenance therapy

The Neo-TI: The Rutgeerts Score

Rutgeerts 0 Rutgeerts 1 Rutgeerts 2Rutgeerts 0 Rutgeerts 1 Rutgeerts 2

Normal ileal mucosa

< 5 aphthous ulcers

> 5 aphthous ulcers, normal intervening mucosa

The Neo-TI: The Rutgeerts Score

Rutgeerts 3 Rutgeerts 4

Ulceration w/o normal intervening mucosa

Severe ulceration with nodules, cobblestoning or stricture

Lumps and Bumps:Tread cautiously and humblyy y

Small and Subtle?

Multiple but discrete?

Large and Clumped?

Nearly flat and carpeted?

Seeing Bad Things

Severe UC: Do you really need to go that far? Couldn’t you pull out in time?

• 37 y.o woman severe37 y.o woman severe UC symptoms despite maximal topical therapy

• Flex sig with severe inflammation to 30 cm w/o transition

• Is more proximal visualization

?necessary?• Next day: fever, upper

abdominal pain, much less diarrhea

The “What the *#@! Is That”SignSign

• Surveillance pouchoscopy 3 days earlier

• “A difficult exam”• A difficult exam• Post- procedure fever

and bleeding• Would have liked to

see mucosa notsee mucosa, not muscle

Bad things: Digital anal stricture dilations

• Even finger dilations of anal strictures require caution

Crohn’s disease– Crohn s disease – Ileoanal pouches– Hartmann pouches

• Symptoms of difficulty emptying—difficulty emptyingself-disimpaction may have created false tract

Attempts at passage of Crohn’s stricture at 25 cm

• Ulcerated stricture in CD

• Consider carefully indication forindication for colonoscopy:– Dilation?

Surveillance?– Surveillance?– Assess disease

severity and extent?

Creeping Fat in CD: An Endoscopic View

• Yes, Mrs. Soprano, we completed the colonoscopy a little sooner than usual, but

l fplease excuse me for a moment while I call a surgeon

A d t tt i• And get my matters in order

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