Colon on Cancer er Survei eilla llance nce & Chemop oprev - - PowerPoint PPT Presentation

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Oct 11, 2023 575 likes •877 views

Colon on Cancer er Survei eilla llance nce & Chemop oprev reven entio tion n in IBD William am Tremaine ne, , MD Maxine ne & Jack Zarrow Professor Mayo Clini nic What at is the risk k of colon on Canc ncer er in the

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SLIDE 1

Colon

  • n Cancer

er Survei eilla llance nce & Chemop

  • prev

reven entio tion n in IBD

William am Tremaine ne, , MD Maxine ne & Jack Zarrow Professor Mayo Clini nic

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SLIDE 2

What at is the risk k of colon

  • n Canc

ncer er in the U.S. Popula latio ion? n?

U.S. . 148,810 10 cases / year 49,960 0 deaths / year 148K per year / 307 million

  • n = 0.048%

Colorecta rectal cancer er rates 10 times higher:

  • N. Americ

ica, a, W. Europe e VS Afric rica, a, Asia

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SLIDE 3

What is the Risk of Colon Cancer in Patients with IBD?

Best data from Manitoba Population based Reporting is a legal requirement 6027 IBD patients in database 5529 matched controls Follow-up to 41.7 years for UC

Bernstein CN Cancer 2001; 91(4): 854-92

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SLIDE 4

What is the Risk of Colon Cancer in Patients with IBD?

  • 1% of all cases of colorectal ca
  • ccur in IBD patients

nevertheless…

  • IBD patients are one of the

highest risk groups for colorectal ca.

Choi PM Gut 1994; 35: 950-4

slide-5
SLIDE 5

What is the Risk of Colon Cancer in Patients with IBD?

Ulcerative Colitis Increased Relative Risk = 2.75 Crohn’s Disease Increased Relative Risk = 2.64

(Crohn’s: small bowel ca IRR = 17.4)

Bernstein CN Cancer 201; 91(4): 854-92

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SLIDE 6

Do UC and Crohn’s Have Similar Risks for Colon Ca?

Yes

  • Both depend on the extent

t and durati tion n of colorecta rectal diseas ase

  • The more extensive

e and longer the diseas ease, , the more the risk

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SLIDE 7

Colorectal Ca in IBD Variables

  • Exten

ent

  • Durati

tion

  • Family history

ry of Colorec ectal tal Ca

  • More severe

e inflamm ammati tion

  • n
  • Primary

mary Scleros

  • sing

g Cholangi giti tis

  • Early age at onset

Chambers WM Brit J Surg 2005; 92: 928-36

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SLIDE 8

Colorectal Ca in IBD Variables

  • Exten

ent: t: Longsta tandi nding g UC

– Pan

Pan-colonic

  • lonic risk: 19 times

es higher

– Left-sided

ided risk : 4 times higher er

Chambers WM Brit J Surg 2005; 92: 928-36

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SLIDE 9

Colorectal Ca in IBD Variables

  • Exten

ent

  • Durati

tion

– For extens

ensiv ive ulcer erat ativ ive e colit itis is

  • Afte

ter r 20 years rs 8 %

  • Afte

ter 30 years 18 %

Eaden JA Gut 2001 48: 526-35

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SLIDE 10

Colorectal Ca in IBD Variables

  • Duration

ation

  • Extent

ent

  • Family history

ry of Colorec ectal tal Ca

– 147 UC cases

es, 150 controls rols

– Cancer

er in 1st

st Degree

e relativ ives: es:

  • 14.3

.3% % cases; s; 6.7% % controls ls

– Odds

ds ratio

  • is 2.33,

3, p=0.03 03

Nuako KW Gastroenterology 1998; 115: 1079-83

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SLIDE 11

Colorectal Ca in IBD Variables

  • Durati

tion

  • n
  • Extent
  • Family history of Colorect

ectal al Ca

  • More severe

e inflamm ammati tion

  • n

– St Marks, London

  • n

– Case

e (68) : Control rol (136) ) study udy

– Inflam

lammat ation ion sever erit ity & cancer er risk

– Odds

ds Ratio

  • 4.7,

7, p<0.001 01

Rutter M Gastroenterology 2004; 126: 451-59

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SLIDE 12

Colorectal Ca in IBD Variables

  • Durati

tion

  • n
  • Extent
  • Family history of Colorect

ectal al Ca

  • More severe

e inflammati tion

  • Primary

mary Scleros

  • sing

g Cholangi giti tis

– Meta-analy

analysis is, 11 studies dies

– Risk of colon

n Ca in PSC + UC

– Odds

ds ratio

  • 4.09 95%

% CI [2.89, 89, 5.76] 6]

Soetikno RM Gastrointes Endos 2002; 56: 48-54

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SLIDE 13

Colorectal Ca in IBD Variables

  • Duration
  • Extent
  • Family history of Colorectal Ca
  • More severe inflammation
  • Primary Sclerosing Cholangitis
  • Early age at onset

– Sweden.

. 91 p pt with UC + colorec ectal tal CA

– For each 10 year increase

se in age at onset

– Cance

cer r risk decrea rease sed by half

  • Odds

s Ratio 0.51 95%CI CI [0.4 .46, , 0.56]

Ekbom A NEJM 1990; 323: 1228-1233

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SLIDE 14

Predictive and Protective Factors for CRC in UC

Velayos FS Gastroenterology 2006; 130: 1941-9

Variable OR 95% CI

p value

Pseudopolyps 2.5 1.4-4.6 <.05 1 or 2 colonoscopies 0.4 0.2-0.7 <.05 Smoking 0.5 0.2-0.9 <.05 Steroid use > 1 yr 0.4 0.2-0.8 <.05 Aspirin 0.3 0.1-0.8 <.05 NSAIDS 0.1 .03-.05 <.05 5-ASA for 1-5 years 0.4 0.2-0.8 <.05

188 cases (UC+CRC) and 188 controls UC

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SLIDE 15

5-ASA Effect on Colorectal Ca and Dysplasia in UC: Meta-analysis

1.0

Lower risk Higher risk

Any Cancer or dysplasia Adjusted odds ratio

10 25 43 102 102 18 76 11 54

Number in each study P=0.39 Velayos FS Am J Gastro 2005; 100: 1345-53

10 .01

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SLIDE 16

5-ASA Effect on Colorectal Ca and Dysplasia in UC: Meta-analysis

Tang J Dig Dis Sci August 25, 2009. epub Medication Dose

# Cases

#Control s

Odds Ratio P value Mesalamine None 3 1 <4.5 kg 14 15 0.311 >4.5kg 1 14 0.024 0.047 Folic Acid None 15 12 Ever 3 18 0.11 0.002

18 UC = Ca matched with 30 UC controls

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SLIDE 17

Immune Modulator Effect on Colorectal Ca and Dysplasia in UC

Author Year

Drug # Patients

Rx Time Outcome Matula 2005 6-MP 315 8 years No Effect Rutter 2004 AZA/ 6-MP 68 8 years Non- significant Lashner 1989 15 98 > 1 year No Effect

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SLIDE 18

Ursodeoxycholic Acid: Prevention

  • f Colon Neoplasia in UC +PSC

Urso Placebo Year

10 5 1

Probability

.1 1.0 .5

Pardi DE Gastro 2003; 124: 889-893 52 patients UCDA

28-20 mg/kg/day

P=0.034

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SLIDE 19

High Dose Urso for PSC

  • UCDA 28-20 mg/kg/day 76 pt
  • Placebo 74 pt
  • Liver biopsy prior to Rx & after 5 years
  • Study terminated after 6 years—futility
  • Risk 2.1x greater with UCDA for:

– Death, transplant, minimal listing criteria

  • P=0.038

Lindor KD Hepatology May 20, 2009 epub versus

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SLIDE 20

Do Biologics Reduce the Risk of Colon Ca in IBD?

  • Plausible
  • Not much data so far

– 1 recent study

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SLIDE 21

Colectomy Rates After Rx with Infliximab vs Placebo

  • ACT-1, ACT-2, and extension study
  • 728 patients; 87% with 52 wk follow-up

– Infliximab 484 pt; Placebo 244 pt.

  • Colectomy: 10% Infliximab, 17% placebo

– P=0.02

  • Colorectal Ca: Infliximab 1, Placebo 0
  • Colon Dysplasia: Infliximab 2, Placebo 1

Sandborn WJ Gastroenterology 2009 epub

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SLIDE 22

Colonoscopic Surveillance for Dysplasia in IBD

  • Initial screening after 8-10 years
  • > 33 biopsies for 90% sensitivity
  • 4 quadrant random biopsies each 10 cm
  • If initial exam is negative, repeat each 1-2

years

  • For PSC begin screening at the time of

diagnosis, repeat yearly

Itzkowitz SH. Inflam Bowel Dis 2005; 11: 314-21

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SLIDE 23

Chromoendoscopy Targeted Biopsies

5 10 15 20 25 Random Non-Dye Dye Non-Dye + Dye

Marion JF Am J Gastro 2008; 103: 2342-9

102 patients Each had: Standard exam Targeted biopsies

Methylene blue %

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SLIDE 24

Colectomy for Colon Cancer Risk in IBD: Indications

Absolute

  • Flat high-grade dysplasia
  • Multifocal flat low-grade dysplasia
  • Flat dysplasia plus PSC
  • Adenoma-like polyp, DALM, that can’t be

removed endoscopically

Zisman TL, Rubin DT. World J Gastro 2008; 14(7): 2662-9

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SLIDE 25

Colectomy for Colon Cancer Risk in IBD: Indications

Controversial

  • Pan-colonic Disease for > 8-10 years
  • Unifocal flat low-grade dysplasia
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SLIDE 26

Cancer Prevention and Surveillance in IBD: Summary

Prevention

  • Minimize inflammation

Surveillance

  • Target high risk patients
  • Surveillance colonoscopy