High frequency of early colorectal cancer in inflammatory bowel disease M W M D Lutgens, F P Vleggaar, M E I Schipper, P C F Stokkers, C J van der Woude, D W Hommes, D J de Jong, G Dijkstra, A A van Bodegraven, B Oldenburg and M Samsom GUT 2008;57:1246–1251 R3. Hwang Seung Joon

Background (1) ▪ IBD-associated CRC IBD Patients : At increased risk of developing CRC Ulcerative colitis : Cumulative risks of 2%, 8%, 18% after 10, 20, 30 years of disease (Eaden et al, The risk of colorectal cancer in ulcerative colitis: a meta- analysis. Gut 2001) Crohn’s disease : Increased standardised incidence ratio of 1.9 for CRC (Jess T et al, Increased risk of intestinal cancer in Crohn’s disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol 2005)

Background (2) ▪ IBD associated CRC Colonic surveillance for IBD Patients : American Gastroenterological Association (AGA) : British Society for Gastroenterology (BSG)  Crohn’s disease, Extensive ulcerative colitis : After 8–10 years  Lt. sided ulcerative colitis : After 15–20 years Objectives : To assess the time intervals between the occurrence of IBD & CRC : To evaluate how often IBD-associated CRC occurred before the first surveillance colonoscopy is advised

Materials & Methods (1) ▪ Study population PALGA database (Dutch National Database of Pathology)  1990, Jan. ~ 2006, June (n=149), Retrospective study  In all Dutch university medical centers for synchronous or metachronous diagnoses of IBD & CRC ▪ Data collection Chart review  Type of IBD, Sex, Age at Dx. of IBD, Age at Dx. of CRC, Date of Dx. of IBD, Date of o/s of Sx. attributable to IBD, Date of Dx. of CRC, Maximum extent of disease as seen on colonoscopy, Maximum histological extent of disease, Tumor location, Tumor stage, History of colonic surgery or surgery during f/u, History of 5-aminosalicylic acid (5-ASA) medication, Concomitant primary sclerosing cholangitis (PSC)

Materials & Methods (2) ▪ AGA and BSG colonic surveillance guidelines for patients with IBD -Differences between the AGA & BSG ▪ BSG ▪ :With pancolitis, a colonoscopy should be conducted every 3 years in the second decade of disease, every 2 years in the third decade, and yearly by the fourth decade of disease (cf. AGA : Every 1-2 years) : Regular surveillance should begin after 8–10 years (from onset of symptoms) for pancolitis and after 15–20 years for left-sided disease (cf. AGA : After 15 years of left-sided colitis)

Materials & Methods (3) ▪ Statistical analysis -Calculations were made of the percentages of patients : CRC before 8 or 15 years of disease duration for extensive or left- sided colitis, respectively : CRC before 10 or 20 years of disease duration for extensive or left- sided colitis, respectively : In Crohn’s colitis : Only compared with the 8 and 10 year intervals -With SPSS for Windows software version

Results

Patient’s Characteristics ▪ Patients

Initial Cause of of diagnosis of colorectal cancer (CRC) ▪ Colorectal cancers (1) ▪ 166 carcinomas were identified in 149 Pts ▪ Multiple synchronous primary colorectal cancers : 9% of patients (n=14)

Location of colorectal cancer ▪ Colorectal cancers (2) ▪ Most cancers (51%) : Located in the Lt. colon, mainly rectum (27%) & Sigmoid colon (24%) ▪ No difference between UC & CD concerning Lt. or Rt. sided tumor location (p=0.89)

Tumor Stage ▪ Colorectal cancers (3)

Time Intervals betwwen IBD & CRC ▪ Intervals between IBD & CRC (1) Time interval Starting point of surveillance at 8 years disease duration Starting point of surveillance at 10 years disease duration left-sided colitis who developed CRC before 15 or 20 years disease duration

Analysis of IBD-CRC in different subgroup ▪ Intervals between IBD & CRC (2)

Discussions (1) Substantial part of all IBD-associated CRC occur before colonic surveillance should start according to BSG and AGA guidelines ▪ AGA surveillance guidelines : Based on expert’s opinion ▪ BSG surveillance guidelines : Based on Meta-analysis of 19 studies  IBD-associated CRC risks of 2%, 8% and 18% for the respective disease durations of 10, 20 and 30 years  “CRC is rarely encountered when disease duration is less than 8–10 years”  73 of 394 colorectal cancers (19%) found in 16 of the 19 studies  Not taken into account in the BSG guidelines d/t ▪ Possibility for sporadic CRC ▪ Cost-effectiveness

Discussions (2) Medical History ▪ Possible antineoplastic effect of 5-ASA treatment (Velayos FS et al. Effect of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and metaanalysis of observational studies. Am J Gastroenterol 2005)  119 out of 139 (10 cases unknown) patients (86%) have used a 5-ASA preparation  All these patients developed CRC Are CRCs diagnosed within 10 yrs of o/s of IBD sporadic?  Median age of patients when CRC was diagnosed did not differ between the ‘‘early’’ and ‘‘late’’ carcinoma groups (47 years (21–83) vs 49 years (28–85))  Almost all (38 of 41) ‘‘early’’ tumors were found in mucosa that was or had been inflamed endoscopically and/or histologically

Discussions (3) Onset of IBD-associated symptoms, instead of the actual diagnosis, may provide a better estimation of years at risk  Can be recall bias  Date of onset of IBD-associated symptoms : Equal to the actual date of diagnosing IBD in little over a half of patients (52%) : Differed by < 1 year in 74% Proposal  Structure of current surveillance guidelines after a fixed period of time seems to be somewhat rigid  Consider other risk factors ex) Severity of disease, Early age of onset of IBD, Family history of CRC, Pseudopolyps, Biomarkers, etc.

Conclusions ■ Diagnosis of colorectal cancer is delayed or missed in a substantial number of patients (17–28%) when conducting surveillance strictly according to formal guidelines