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Abstract
Background and aim: Colonoscopic surveillance is recommended in patients with longstanding inflammatory bowel disease (IBD) as they are at increased risk of colorectal cancer (CRC). Non-invasive surveillance may improve compliance and access. Multi-target stool DNA (MT-sDNA) has been validated for screening of sporadic CRC but has not been assessed in IBD. Our aim was to assess the performance of a MT-sDNA test in a real-life surveillance setting of patients with longstanding IBD.
Material and methods: A total of 192 IBD patients enrolled from two prospective cohorts submitted an EDTA buffered stool sample and underwent chromo- or white light colonoscopy. Stools were assayed for methylated BMP3 & NDRG4, mutant KRAS and β-actin by a laboratory blinded to clinical data.
Results: The multitarget-sDNA panel was positive in 2/2 CRC and 5/15 low-grade dysplasia (LGD) < 1 cm in diameter. Sensitivities were 100% (95% CI 16–100%) for CRC and 33% (95% CI 13–61%) for LGD lesions <1 cm, with specificities of 87% (95% CI 81–91%) and 93% (95% CI 88–96%), respectively. The estimated number of patients needed to screen to detect a single CRC was 96 (95% CI 93–99%) and was 28 (95% CI 22–34%) to detect any colorectal neoplasia (CRN).
Conclusion: The MT-sDNA panel detected CRC in IBD. Sensitivity for sub-centimeter colorectal neoplasms in IBD patients appears similar to that observed in the general population. The test may be a valuable tool for detection of malignancy during structured surveillance of long-term IBD in a first line hospital setting.
Acknowledgments
We thank: Anita Tollisen, Unger-Vetlesen Institute, Department of Internal Medicine, Lovisenberg Hospital, Lovisenberggt.17, 0456 Oslo, Norway; Lars Gustav Lyckander, Department of Pathology, Akershus University Hospital, Sykehusveien 25, 1474 Lørenskog; Thomas deLange, Department of Gastroenterology, Vestre Viken Baerum hospital, Sogneprest Munthe-kaas vei 100, 1346 Gjettum and Members of the Inflammatory Bowel South-East Norway (IBSEN) Study Group: Marte Lie Høivik, Iril Monstad and Camilla Solberg, Oslo University Hospital, Oslo; Jørgen Jahnsen, Akershus University Hospital, Lørenskog; Øistein Hovde, Innlandet Hospital, Gjøvik; Ole Høie, Sørlandet Hospital, Arendal; Gert Huppertz Hauss and Tomm Bernklev, Telemark Hospital, Skien; Magne Henriksen and Eva Gunther, Østfold Hospital, Moss/Fredrikstad and Njaal Stray, Diakonhjemmet Hospital, Oslo for participating in this study. Exact Sciences (Madison, Wisconsin, USA) who performed stool DNA assays and Graham P. Lidgard, Hatim T. Allawi, and Tamara Sander at Exact for their technical assistance. Unger-Vetlesen Institute (Oslo, Norway) for their logistic support.
Disclosure statement
Dr. Klepp is an employee at Lovisenberg Diakonale Hospital which has funded the study.
Mayo Clinic has entered into an intellectual property development agreement with Exact Sciences, under which Drs. Kisiel and Ahlquist, could receive royalties.
The additional authors have no conflicts of interest to disclose.