Impact and Clinical Predictors of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors

Abstract

Background:The optimal surgical management of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) is still controversial. Here, we evaluated the impact of lymph node status on postoperative recurrence in patients with NF-PNET and the potential of preoperative variables for predicting lymph node metastasis (LNM).Methods:In this mono-institutional retrospective cohort study conducted in 100 consecutive patients who underwent NF-PNET resection between January 2004 and December 2014, we evaluated risk factors for survival using the Kaplan–Meier method and the Cox regression model. Predictors of LNM were evaluated using the logistic regression model, and the power of predictive models was evaluated using receiver operating characteristic curve analysis.Results:Five-year disease-free survival of resected NF-PNET was 64.1%. LNM was independently associated with postoperative recurrence (hazard ratio = 3.995, P = 0.003). Multivariate analysis revealed tumor grade as an independent factor associated with LNM (G2 vs. G1: odds ratio [OR] =6.287, P = 0.008; G3 vs. G1: OR = 12.407, P = 0.001). When tumor grade was excluded, radiological tumor diameter >2.5 cm (OR = 5.430, P = 0.013) and presence of symptoms (OR = 3.366, P = 0.039) were significantly associated with LNM. Compared to neoplasms with radiological diameter >2.5 cm (32.1%), tumors ≤2.5 cm had an obviously lower risk of LNM (7.7%), indicating the reliability of this parameter in predicting LNM (area under the curve, 0.693). Incidentally discovered NF-PNETs ≤2.5 cm were associated with a low-risk of LNM and excellent survival.Conclusions:LNM is significantly associated with postoperative recurrence. Radiological tumor diameter is a reliable predictor of LNM in NF-PNETs. Our results indicate that lymphadenectomy in small (≤2.5 cm) NF-PNETs is not routinely necessary.

Pancreatic neuroendocrine tumors: Preoperative factors that predict lymph node metastases to guide operative strategy

“…In studies that include patients with distant metastases, some groups have found that lymph node metastases are not associated with overall survival; however, this is not a universal finding [6,21,22]. Beyond overall survival, however, multiple studies, including the present one, have found that lymph node metastases are related to disease-related survival which includes the event of recurrence, RFS, disease-free survival, time to liver recurrence, and disease-specific survival [17,[19][20][21]28,30]. Thus, lymph node status is an important predictor of patient outcomes.…”

“…Other investigators have explored and reported on the lymph node positivity rates or progression rates at distinct size intervals: <1 cm 15%, <1.5 cm 13%, <2 cm 8-12%, <2.5 cm 8%, <3 cm 37% [20,23,28,29,31,34]. In the current study, a tumor size of !2 cm was associated with presence of lymph node positivity in 35% of patients, yet for tumors <2 cm, the lymph node positivity rate was 6%.…”

“…In addition, tumor location in the pancreatic head or uncinate was found to be another factor prognostic for lymph node metastases, a finding that again has not been universally consistent across studies [28,29]. Other factors that have been attributed to presence of lymph node metastases include high grade, presence of calcification on preoperative imaging, presence of distant metastases, and tumor size [8,18,20,[28][29][30][31]. Of these criteria, much focus has been on the utility of tumor size in guiding management.…”

“…Without definitive treatment guidelines, one must weigh multiple factors in determining the treatment approach, one of which is lymph node status. Preoperative factors predictive of lymph node involvement are not well defined, and data on the prognostic value of lymph node metastases in PanNETs have been conflicting [6,8,[17][18][19][20][21][22][23]. Thus, we sought to determine factors associated with presence of nodal metastases and to evaluate whether nodal metastases were associated with recurrence-free survival (RFS) in an institutional cohort of patients who underwent resection of PanNET over a recent 15-year period.…”

Surgery management for sporadic small (≤2 cm), non-functioning pancreatic neuroendocrine tumors: A consensus statement by the Chinese Study Group for Neuroendocrine Tumors (CSNET)

“…Nevertheless, a Chinese study reported that lymphadenectomy in small (≤2.5 cm) NF-PNETs is not routinely necessary, for the reason that incidentally discovered NF-pNETs ≤2.5 cm were associated with a low-risk of lymph nodal metastases (7.7%) and excellent survival (51). Another large population, including total of 1854 patients with NF-pNETs ≤2 cm, based on NCDB data from the United States showed that, among tumors ≤0.5 cm, 33% presented with regional lymph nodal metastases and 11% with distant metastases.…”