Resection of At‐Risk Mesenteric Lymph Nodes Is Associated with Improved Survival in Patients with Small Bowel Neuroendocrine Tumors

Abstract

Background Neuroendocrine tumors of the small intestine commonly metastasize to regional lymph nodes (LNs). Single-institution reports suggest that removal of LNs improves outcome, but comprehensive data are lacking. We hypothesized that the extent of lymphadenectomy reported in a large administrative database would be associated with overall survival for jejunal and ileal neuroendocrine tumors. Methods A search of the Surveillance Epidemiology and End Results database was performed for patients with jejunal and ileal neuroendocrine tumors from 1977 to 2004. Descriptive patient characteristics were collected to include age at diagnosis, sex, race, grade, primary tumor size, LN status, number of LNs resected, presence of distant metastasis, and the type of operation. Statistical analyses were limited to patients with only one primary tumor to exclude patients with other malignancies. Univariate and multivariate analyses were performed to analyze the number of LNs resected and the LN ratio (number of positive LNs/total number of LNs removed) to determine the effect on cancer-specific survival. Results Altogether, 1,364 patients were included in this analysis. Removal of any LNs was associated with improved cancer-specific survival when compared to patients with no LN removal reported (p = 0.0027) on univariate analysis. Among those who had any LNs removed, a median of eight LNs were identified in resection specimens with a median LN ratio of 0.29 (range 0–1). On multivariate analysis (adjusting for age and tumor size), patients with ≤7 LNs removed experienced better cancer-specific survival than those with B7 LNs removed (median survival not reached vs. 140 months): hazard ratio and 95 % confidence interval were 0.573 (0.402, 0.817) (p = 0.002). Conclusions This review of a large number of surgical patients demonstrates that regional mesenteric lymphadenectomy in conjunction with resection of the primary tumor is associated with improved survival of patients with small bowel neuroendocrine tumors.

Lymphatic vessels regulate immune microenvironments in human and murine melanoma

“…In our case, LN metastasis may be a route of systemic dissemination, as tumor cells move through collecting lymphatic vessels remaining in subcutaneous tissue (37) and eventually re-enter circulation via the thoracic duct (17). While direct evidence for lymphatic vessel-mediated systemic spread is lacking and the efficacy of sentinel LN resection as a means of preventing metastatic spread is controversial (46,47), these data indicate that lymphatic vessels contribute to a more metastatic phenotype within primary tumor microenvironments. In fact, impaired local inflammation that results from loss of lymphatic vessels may itself alter metastatic phenotype, as immune cells play an important role in directing tumor cell exit via hematogenous vasculature through secretion of matrix metalloproteinases, growth factors, and chemokines (48).…”

Update on Surgical Management of Small Bowel Neuroendocrine Tumors

“…Patients with stage I-III si-NENs should undergo curative resection with lymphadenectomy across mesenteric vessels with respect to vasculature of the residual bowel (88, 89) 2. 5-And 10-year OS is 100% for stages I and II, and >95% and 80%, respectively, for stage III (20,90) 3. For tumours located in terminal ileum, a right hemicolectomy may be necessary (88) 4.…”

“…Dissection of at least eight (10,14,20) or 12 (23) lymph nodes has a positive impact on survival. A recent metaanalysis showed that among patients with metastatic disease, palliative resection of the primary tumor conferred a survival benefit (24).…”

“…Optimal lymphadenectomy may be really challenging, especially when there is coexistence of mesenteric fibrosis or large lymph node metastases of the superior mesenteric artery (SMA) (21). Optimal enterectomy with optimal lymphadenectomy is vital for improving survival and preventing recurrence (6,20,22). Therefore, it is advisable that such operations be conducted at specialized centers with relevant expertise treating a large number of patients.…”

“…Systemic lymph node dissection along with enterectomy may improve survival and rate of complications (20). Optimal lymphadenectomy may be really challenging, especially when there is coexistence of mesenteric fibrosis or large lymph node metastases of the superior mesenteric artery (SMA) (21).…”