# Utility of Random Biopsies in Inflammatory Bowel Disease

> **NIH NIH U01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $2,410,980

## Abstract

PROJECT SUMMARY
Patients with long standing inflammatory bowel diseases (IBD) have an increased risk of colorectal cancer
(CRC) as a consequence of chronic inflammation. To reduce morbidity and mortality from IBD-related CRC,
surveillance for precancerous dysplasia with colonoscopy is recommended every 1-3 years beginning 8-10
years after diagnosis for most patients with IBD. However, the most effective way to perform dysplasia
surveillance has not been definitively established. IBD-associated precancerous dysplastic lesions may
represent a field effect from chronic inflammation and are difficult to see with standard definition white light
colonoscopy. Fortunately, the advent of high-definition white light colonoscopy (HDWLC) improved our ability
to visualize and remove precancerous dysplastic lesions. Nonetheless, the historical practice of collecting four
untargeted random mucosal biopsies every 10 cm throughout the colon continues to be widely employed for
patients with IBD. The rationale is that random biopsies may help detect these difficult to see precancerous
lesions. However, the recommendations for this practice are based on uncontrolled observations and ex-vivo
studies of resected specimen. In the one small randomized clinical trial to test the efficacy of random biopsies,
the rate of dysplasia detection was numerically higher in the patients only getting targeted biopsies. This has
led to equipoise regarding random biopsies. The proposed Utility of Random Biopsies in Inflammatory Bowel
Disease (URBI) trial will be a multicenter pragmatic randomized clinical trial among 1642 patients to definitively
assess whether a limited biopsy strategy obtaining only two random biopsies from two locations is non-inferior
to the practice of obtaining four random biopsies every 10cm throughout the colon among patients with IBD
undergoing dysplasia surveillance with HDWLC. The primary outcome will be the average number of dysplastic
and sessile serrated adenoma lesions detected per colonoscopy.
The URBI trial will also present an opportunity to study the biology of colitis-associated dysplasia. Dysplasia is
graded as absent, low-grade (LGD) or high-grade (HGD). Indefinite for dysplasia (IFD) is used when there is
uncertainty whether or not there is LGD. Better understanding the biology of the dysplasia sequence could
improve pathologic classification and minimizing the need for the IFD category. Yet, little research has been
done to understand the progression of inflammation to dysplasia or the molecular characteristics of IFD using
modern omics technologies. We will utilize spatial transcriptomics and an integrative analytic approach to
inform the biologic progression from inflammation to HGD, including the biology of IFD. The biopsy samples
and linked clinical data collected in the URBI trial will provide an ideal resource to study the molecular biology
of colitis-associated dysplasia and IFD. Thus, the URBI trial will establish best practices for IB...

## Key facts

- **NIH application ID:** 10855624
- **Project number:** 1U01DK138901-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** KLAUS H KAESTNER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,410,980
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10855624

## Citation

> US National Institutes of Health, RePORTER application 10855624, Utility of Random Biopsies in Inflammatory Bowel Disease (1U01DK138901-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10855624. Licensed CC0.

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