Capsule endoscopy for small-bowel surveillance in Lynch syndrome patients: a 20-year cohort experience

Aims Lynch syndrome (LS) is an autosomal dominant hereditary disease caused by germline mutations in the DNA mismatch repair (path_MMR) genes. LS carriers harbor a high risk of developing early-onset gastrointestinal (GI) and extra-GI malignancies, including small-bowel (SB) cancer for which a consensus recommendation for screening is lacking [1], as recent evidence failed to demonstrate a clear benefit of SB cancer screening with capsule endoscopy (CE) [2]. Accordingly, our study aims to assess the effectiveness of SB cancer surveillance with CE in a large cohort of LS patients.

Methods We retrospectively included asymptomatic LS patients undergoing SB cancer surveillance with CE in two academic centers over 20 years (2003-2023). The diagnostic yield (DY) of CE for SB adenomas/adenocarcinomas was assessed, as well as patients’ demographic and path_MMR distribution. Videos were interpreted by expert readers (>1000 lifetime capsules).

Results 57 LS patients (31 females, 26 males) with different path_MMR distribution underwent 81 CE procedures. One patient was excluded from analysis for gastric CE retention.

The median age at the first CE examination was 55.5 years (56 patients; interquartile range [IQR] 41–64).

In the first screening round, CE detected 4 SB adenocarcinomas (2 in the jejunum and 2 in the ileum) and 4 SB polyps (2 in the ascending duodenum, 10 mm; 2 in the jejunum, 15 mm). The duodenal polyps were subsequently removed by device-assisted enteroscopy (DAE) (histology: tubular adenomas with low-grade dysplasia), whereas both jejunal polyps were considered CE false positives after negative DAE and magnetic resonance enterography (MRE). Therefore, the positive predictive value of CE was 75%, with a DY for histology-confirmed pathology of 10.7%.

16 patients underwent follow-up CE. Of these patients, 3 had a previous positive examination (2 with duodenal polyps and 1 with adenocarcinoma) in the first CE round. In the second-round examination, performed at a median interval of 27 months (IQR 15.5–42.25), all CE were negative (DY 0%). Third- and fourth-round CE examinations have been performed so far in 6 (median interval 22.5 months) and 2 patients (median interval 21 months), respectively: one suspected jejunal polyp (size 10 mm) in the third round was considered CE false positive after negative DAE and MRE (DY 0%). The overall median follow-up time in patients repeating CE (regardless of the number of rounds) was 42 months (IQR 22.25–59.5). No significant differences in the path_MMR distribution were found.

Conclusions Assuming all normal procedures were true negative (long follow-up, confirmatory tests), CE was effective in diagnosing SB malignancy in a large cohort of asymptomatic LS patients albeit with a considerable amount of false positives, requiring complementary imaging confirmation. Prospective studies are required to establish the potential role of standardized SB cancer surveillance protocols, considering the 0% DY of CE in follow-up procedures.

Publication History

Article published online:
15 April 2024

• References

• 1 Cortegoso Valdivia P, Deding U, Bjørsum-Meyer T. et al. Surveillance of the small-bowel by capsule endoscopy in Lynch syndrome – A systematic review with meta-analysis. Dig Liver Dis 2023; S1590-8658 (23) 00780-6 (online ahead of print)
• 2 Pennazio M, Rondonotti E, Despott EJ. et al. Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2022. Endoscopy 2023; 55: 58-95