Serrated polyposis syndrome (SPS) carries an elevated colorectal cancer (CRC) risk. Serrated lesions involving the appendix (SLAs) are relatively frequent in SPS but remain challenging to treat. Endoscopic mucosal resection and endoscopic submucosal dissection are hampered by limited visualization of the deep appendiceal margin, resulting in a high risk of incomplete resection and perforation. Endoscopic full-thickness resection (EFTR) improves R0 rates but typically cannot achieve complete removal of the appendix and carries a substantial risk of post-procedural appendicitis, likely due to impaired appendiceal drainage. Meanwhile, standard laparoscopic appendectomy may leave residual peri-orificial serrated mucosa. A laparoscopic appendectomy extended to the cecum can theoretically ensure wider margins, but defining an adequate lateral boundary without jeopardizing the ileocecal valve is difficult, often leading to ileocecal resection. In summary, no current strategy reliably combines complete resection, anatomical preservation and procedural safety for SLAs in patients with SPS.

We propose a laparoscopic–endoscopic cooperative surgery (LECS) approach combining, in a single session, an endoscopic full-thickness resection performed with an over-the-scope full-thickness resection device and a laparoscopic appendectomy. Endoscopic delineation and full-thickness excision of the serrated lesion allow a radical resection while preserving ileocecal anatomy. The subsequent complete removal of the appendix prevents post-EFTR appendicitis.

Among 1,936 patients undergoing colonoscopy within the CRC screening program of Friuli Venezia Giulia (2021–2025), 18 (1:108) met the 2019 World Health Organization criteria for SPS. 7 of these patients (39%) had a SLA and underwent LECS. All achieved en bloc full-thickness resection with R0 margins. Median postoperative stay was 3 days, and no postoperative complications were observed. In 3 patients (43%), histology revealed an additional serrated lesion within the laparoscopically resected appendiceal stump, concomitant to the SLA treated, suggesting that endoscopic removal alone would not have achieved complete eradication of the disease.

In SPS patients, SLAs remain difficult to manage with standard endoscopic or surgical approaches. Our results show that a LECS strategy enables safe and radical full-thickness resection while preserving ileocecal anatomy and eliminating the risk of post-EFTR appendicitis through complete appendiceal removal. Histology revealed additional serrated lesions within the surgicallly resected appendix in 3 patients, underscoring the multifocal nature of appendiceal involvement in SPS and the diagnostic and therapeutic value of complete appendectomy, and reinforcing the concept that the appendix represents a blind spot in the endoscopic surveillance of SPS. Therefore, LECS proved safe and effective for the complete resection of appendiceal and periappendiceal serrated lesions in SPS. These findings support considering LECS as a promising therapeutic option for SLAs in this setting.