Small-bowel surveillance and therapeutic polypectomy are key components in the management of Peutz–Jeghers syndrome (PJS). We aimed to evaluate the real-world performance of double balloon enteroscopy (DBE) in patients with PJS who had undergone prior small-bowel mapping with magnetic resonance enterography (MRE) and/or computed tomography enterography (CTE), but not capsule endoscopy due to contraindications.

We retrospectively reviewed consecutive PJS patients who underwent their first enteroscopy at our center between January 2022 and December 2024. All included patients had prior small-bowel mapping with MRE or CTE but were not eligible for capsule endoscopy due to known strictures, multiple prior laparotomies or previous episodes of intussusception. Data on epidemiology, imaging characteristics, enteroscopic approach, therapeutic yield, complications, and the number of procedures required for complete polyp eradication were collected. Discrepancies between imaging and enteroscopy regarding polyp number, size, and dominant location were recorded.

Sixteen patients were enrolled (11 males; mean age 39 ± 13 years). The mean age at PJS diagnosis was 17 ± 7 years. A de novo mutation was identified in 9/16 (56%) who were diagnosed following an episode of intussusception or bleeding. A history of laparotomy was present in 12/16 (75%). Prior mapping identified no polyps >15 mm in 3/16 (18.8%), 1–5 polyps in 12/16 (75%), and >5 polyps in 1/16 (6.2%). Enteroscopy was performed via an antegrade approach in 14/16 (87.5%) and retrograde in 2/16 (12.5%); laparoscopic-assisted DBE was required in 3/16 (18.8%). At least one polyp was removed in all patients. The median number of polyps removed during the initial procedure was 2 (range 1–7), with a median largest polyp size of 40 mm (15–70 mm). Standard endoscopic mucosal resection was performed in 14/16 (87.5%), while  surgical resection was required in two cases.  A single post-procedural bleeding event (6.25%) was recorded. Complete eradication of all identified polyps required a median of one enteroscopy (range 1–4). Among patients requiring multiple sessions, the median interval to complete eradication was 25 months (range 3–39). Imaging underestimated polyp burden in 9/16 patients (56.3%) and polyp size in 7/16 (43.7%), while discrepancies in dominant polyp location occurred in 3/16 (18.8%).

Double balloon enteroscopy is a highly effective and safe therapeutic modality for small-bowel polyp management in PJS, achieving complete polyp eradication with minimal complications. When Cross-sectional imaging is the sole surveillance modality the polyp burden can occasionally be underestimated, highlighting the essential role of enteroscopy for accurate assessment and comprehensive treatment planning in PJS.