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.
