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Regional Lymphadenectomy Is Indicated in the Surgical Treatment of Pancreatic Neuroendocrine Tumors (PNETs)

Hashim, Yassar M. MD*; Trinkaus, Kathryn M. PhD; Linehan, David C. MD*; Strasberg, Steven S. MD*; Fields, Ryan C. MD*; Cao, Dengfeng MD, PhD; Hawkins, William G. MD*

doi: 10.1097/SLA.0000000000000348

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.

Pancreatic neuroendocrine tumors are uncommon, and the significance of lymph node metastasis remains uncertain. The optimal surgical approach for pancreatic neuroendocrine tumor (PNET) is controversial. Our data demonstrate that small tumors frequently metastasize to lymph nodes and that lymph node status is strongly associated with recurrence. We recommend en bloc regional lymphadenectomy with resection of a primary PNET.

*Department of Surgery and the Alvin J. Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO

Division of Biostatistics, Washington University School of Medicine, St. Louis, MO; and

Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, and Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital, Beijing, China.

Reprints: William G. Hawkins, MD, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8109, Saint Louis, MO, 63110. E-mail:

Disclosure: 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 Y. H. by the Washington University Surgical Oncology Training grant (5T32CA00962124). The authors declare no conflicts of interest.

© 2014 by Lippincott Williams & Wilkins.