Patterns of Lymph Node Metastasis and Optimal Surgical Strategy in Small (≤20 mm) Gastroenteropancreatic Neuroendocrine Tumors

Abstract

BackgroundRegional lymph node metastasis (LNM) is crucial for planning additional lymphadenectomy, and is directly correlated with poor prognosis in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the patterns of LNM for small (≤20 mm) GEP-NETs remain unclear. This population-based study aimed at evaluating LNM patterns and identifying optimal surgical strategies from the standpoint of lymph node dissemination.MethodsThis retrospective cohort study retrieved data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database for 17,308 patients diagnosed as having localized well-differentiated GEP-NETs ≤ 20 mm between January 1, 2004, and December 31, 2017. The patterns of LNM were characterized in 6,622 patients who underwent extended resection for adequate lymph node harvest.ResultsOf 6,622 patients with localized small GEP-NETs in the current study, 2,380 (36%) presented with LNM after regional lymphadenectomy. Nodal involvement was observed in approximately 7.4%, 49.1%, 13.6%, 53.7%, 13.8%, 7.8%, and 15.4% of gastric (g-), small intestinal (si-), appendiceal (a-), colonic (c-), rectal (r-), non-functional pancreatic (nfp-), and functional pancreatic (fp-) NETs ≤ 20 mm. Patients with younger age, larger tumor size, and muscularis invasion were more likely to present with LNM. Additional lymphadenectomy conferred a significant survival advantage in NETs (≤10 mm: HR, 0.47; 95% CI, 0.33–0.66; p < 0.001; 11–20 mm: HR, 0.54; 95% CI, 0.34–0.85; p = 0.008) and fp-NETs ≤ 20 mm (HR, 0.08; 95% CI, 0.02–0.36; p = 0.001), as well as g-NETs (HR, 0.39; 95% CI, 0.16–0.96; p = 0.041) and c-NETs of 11–20 mm (HR, 0.07; 95% CI, 0.01–0.48; p = 0.007). Survival benefits of additional lymphadenectomy were not found in a-NETs, r-NETs, and nfp-NETs with a small size.ConclusionsGiven the increased risk for nodal metastasis, primary tumor resection with regional lymphadenectomy is a potential optimal surgical strategy for si-NETs and fp-NETs ≤ 20 mm, as well as g-NETs and c-NETs of 11–20 mm. Local resection is an appropriate and reliable surgical approach for a-NETs, r-NETs, and nfp-NETs ≤ 20 mm.

Incidence, survival, and prognostic factors for patients with gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms: a SEER population-based study

“…Patient data of gastrointestinal MiNENs and NETs from 2000 to 2019 were obtained from the SEER database according to the International Classification of Diseases for Oncology, the Third Edition (ICD-O-3, the site codes: stomach C16.0–16.9, small intestine C17.0–17.9, appendix C18.1, colon C18.0 and 18.2–18.9, rectum C19.9 and 20.9) (Cai et al 2022 ).…”

“…The following inclusion criteria were used: (1) tumor histological type: MiNENs (SEER histology code: 8244/3)(Song et al 2022 ), and NETs (SEER histology codes: 8013/3, 8041/3, 8150/3–8157/3, 8240/3, 8241/3, 8242/3, 8243/3, 8246/3, 8249/3) (Cai et al 2022 ; Shah et al 2019 ; Miao et al 2018 ); (2) confirmation of MiNENs and NETs diagnosis histologically or microscopically. The following were the exclusion criteria: (1) survival time was unknown; (2) incomplete clinical and pathological data.…”

Treatment of localized well-differentiated rectal neuroendocrine tumors: A focused review

“…In a recent analysis of data from 370 rectal NETs measuring ≤20 mm, the lymph node metastasis rate was 40.3% for rectal NETs measuring 11-20 mm and 30.8% for T1 alone. [35] An analysis of 199 cases from Italy showed that a tumor diameter ≥11.5 mm (odds ratio [OR]: 54.9) and vascular invasion (OR: 51.3) were independent risks for lymph node metastasis. [36] Accordingly, tumors measuring >10 mm in diameter have a reasonably high rate of lymph node metastasis.…”

Incidence, survival, and prognostic factors for patients with gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms: a SEER population-based study

“…Patient data of gastrointestinal MiNENs and NETs from 2000 to 2019 were obtained from the SEER database according to the International Classi cation of Diseases for Oncology, the Third Edition (ICD-O-3, the site codes: stomach C16.0-16.9, small intestine C17.0-17.9, <link rid="Sec12"><link rid="Sec13"> <link rid="Sec17"><link rid="Sec18"><link rid="Sec19">appendix</link></link></link></link></link> C18.1, colon C18.0 and 18.2-18.9, rectum C19.9 and 20.9) (Cai et al 2022).…”