Colorectal serrated lesions (CSLs) are increasingly recognized as important precursors of colorectal cancer, accounting for up to a quarter of cases. Recent advances include the 2019 WHO classification, which categorizes CSLs into sessile serrated lesions (SSL), SSL with dysplasia (SSLD), traditional serrated adenomas (TSA), and unclassified serrated adenomas. Although piecemeal resection is widely used, larger CSLs may harbor unexpected dysplasia and carry a higher risk of metachronous neoplasia, underscoring the importance of achieving accurate histological evaluation. Endoscopic submucosal dissection (ESD) enables en bloc resection and precise pathological assessment, but its technical difficulty and risk profile are influenced by factors such as lesion size, location, and submucosal fibrosis. This study aimed to clarify the association between CSLs and submucosal fibrosis, and to determine how fibrosis affects therapeutic outcomes in colorectal ESD.

This retrospective cohort study reviewed consecutive colorectal ESD procedures performed at Kyoto Prefectural University of Medicine from January 2020 to November 2024. To align with the 2019 WHO classification, only lesions measuring ≥20 mm was included. Indications followed Japanese ESD guidelines, with serrated lesions treated when SSLs were ≥30 mm or when lesions ≥20 mm were suspected to be SSLD or TSA based on magnified endoscopic evaluation. Lesions were classified histologically as CSLs—including SSL, TSA, SSLD, and unclassified serrated adenomas—or as adenomas/T1 cancers. Data on patient and lesion characteristics, fibrosis status, and therapeutic outcomes were collected. Submucosal fibrosis was graded endoscopically. ESD outcomes included procedure time, en bloc and R0 resection, and adverse events such as perforation or delayed bleeding. The primary outcome was the frequency of any or severe fibrosis in CSLs compared with adenomas/T1 cancers. Logistic regression analyses identified predictors of fibrosis, severe fibrosis, and prolonged procedure time (>90 min), with lesion size categorized as <40 or ≥40 mm.

Among 445 colorectal ESD cases, 72 were CSLs (16.2%) and 373 were adenoma + T1 cancers. Submucosal fibrosis was present in 46.3% of all lesions, and severe fibrosis in 16.4%. CSLs showed significantly lower rates of fibrosis than adenoma + T1 cancers (34.7% vs 48.5%, p=0.04) and lower severe fibrosis (6.9% vs 18.2%, p=0.03). CSLs were more common in females (61.1% vs 41.0%, p<0.01), predominantly right-sided (73.6%), and more frequently non-polypoid (95.8% vs 77.7%, p<0.01). Mean procedure time was shorter for CSLs (53.0±25.6 min vs 67.1±44.2 min, p<0.01). In multivariate analysis, serrated histology independently reduced the risk of fibrosis (OR 0.58, 95% CI 0.33–0.99; p=0.04), while lesion size ≥40 mm increased it (OR 2.03, 95% CI 1.30–3.20; p<0.01); rectal location lowered risk (OR 0.40, 95% CI 0.22–0.70; p<0.01). Severe fibrosis was associated with lesion size ≥40 mm (OR 2.45, 95% CI 1.40–4.27; p<0.01) and polypoid morphology (OR 3.42, 95% CI 1.92–6.06; p<0.01). Prolonged procedure time ≥90 min was linked to lesion size ≥40 mm (OR 25.00), fibrosis (OR 3.73), and severe fibrosis (OR 5.14). Among five CSLs with severe fibrosis, R0 resection was achieved in 60%.

This study investigated serrated histology as a predictor of reduced submucosal fibrosis in colorectal ESD. These results may aid therapeutic decision-making. ESD should be considered for lesions ≥40 mm or those with polypoid morphology, as characteristics were associated with a higher risk of severe submucosal fibrosis.