Regional lymphadenectomy is indicated in the surgical treatment of pancreatic neuroendocrine tumors (PNETs)

Abstract

Objective: To explore the prognostic importance and preoperative predictors of lymph node metastasis in an effort to guide surgical decision making in patients with pancreatic neuroendocrine tumors (PNETs).

Background: PNETs are uncommon, and the natural history of the disease is not well described. As a result, there remains controversy regarding the optimal management of regional lymph nodes during resection of the primary tumor.

Methods: A retrospective review of a prospectively maintained database of patients who underwent surgery for locoregional PNET between 1994 and 2012 was performed. Logistic regression was used to identify predictors of nodal metastasis. Overall survival and disease-free survival were calculated using Kaplan-Meier method. Results were expressed as P values and odds ratio estimates, with 95% confidence intervals.

Results: One hundred thirty-six patients were identified, of whom 50 (38%) patients had nodal metastasis. The frequency of lymph node metastasis was higher for larger tumors [> 1.5 cm (odds ratio [OR] = 4.7)], tumors of the head as compared with body-tail of the pancreas (OR = 2.8), tumors with Ki-67 greater than 20% (OR = 6.7), and tumors with lymph vascular invasion (OR = 3.6) (P < 0.05). Median disease-free survival was lower for patients with nodal metastases (4.5 vs 14.6 years, P < 0.0001).

Conclusions: Lymph node metastasis is predictive of poor outcomes in patients with PNETs. Preoperative variables are not able to reliably predict patients where the probability of lymph node involvement was less than 12%. These data support inclusion of regional lymphadenectomy in patients undergoing pancreatic resections for PNET.

Conflict of interest statement

Disclosures:

There are no relevant conflicts of interest for this manuscript. Statistical support was provided by the Biostatistics Core, Siteman Comprehensive Cancer Center, and NCI Cancer Center Support Grant P30 CA091842. Salary support was provided for YH by the Washington University Surgical Oncology Training Grant (5T32CA00962124).

Figures

Figure 1

Logistic regression, probability of lymph node metastasis Ki-67 > 20, LVI, tumor in the head vs. body-tail and size > 1.5 cm, were found to be associated with increase in probability of lymph node metastasis (P values= 0.008, 0.008, 0.004 and 0.002 respectively).

Figure 2

Showing relationship between lymph nodes status of patients with PNET and (A) tumor size, (B) Tumor location, (C) lymphovascular invasion, and (D) Ki-67 proliferative index.

Figure 2

Showing relationship between lymph nodes status of patients with PNET and (A) tumor size, (B) Tumor location, (C) lymphovascular invasion, and (D) Ki-67 proliferative index.

Figure 2

Showing relationship between lymph nodes status of patients with PNET and (A) tumor size, (B) Tumor location, (C) lymphovascular invasion, and (D) Ki-67 proliferative index.

Figure 2

Showing relationship between lymph nodes status of patients with PNET and (A) tumor size, (B) Tumor location, (C) lymphovascular invasion, and (D) Ki-67 proliferative index.

Figure 3

A probability plot for N stage > 0 versus tumor size for both tumors in the head and body-tail of the pancreas was generated. The smallest tumors in the pancreatic head have a probability that is very unlikely to be less 20% of having node metastasis; the lower bound of the CI is slightly below 20%. In tumors located at the body-tail the smallest tumors also have an estimated probability of node metastasis close to 20% with 8.8% lower bound of 95% CI.

Figure 4

Kaplan-Meier model of disease-free survival for patients with PNET, comparing patients with positive and negative lymph node metastasis (Log-Rank =0.0004).

Figure 5

Kaplan-Meier model of overall survival for patients with PNET comparing patients with positive and negative surgical margins (Log-Rank= 0.007).