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Lymph Nodes and Survival in Pancreatic Neuroendocrine Tumors

Geoffrey W. Krampitz, MD; Jeffrey A. Norton, MD; George A. Poultsides, MD; Brendan C. Visser, MD; Lixian Sun, MS; Robert T. Jensen, MD
Arch Surg. 2012;147(9):820-827. doi:10.1001/archsurg.2012.1261.
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Hypothesis  Lymph node metastases decrease survival in patients with pancreatic neuroendocrine tumors (pNETs).

Design  Prospective database searches.

Setting  National Institutes of Health (NIH) and Stanford University Hospital (SUH).

Patients  A total of 326 patients underwent surgical exploration for pNETs at the NIH (n = 216) and SUH (n = 110).

Main Outcome Measures  Overall survival, disease-related survival, and time to development of liver metastases.

Results  Forty patients (12.3%) underwent enucleation and 305 (93.6%) underwent resection. Of the patients who underwent resection, 117 (35.9%) had partial pancreatectomy and 30 (9.2%) had a Whipple procedure. Forty-one patients also had liver resections, 21 had wedge resections, and 20 had lobectomies. Mean follow-up was 8.1 years (range, 0.3-28.6 years). The 10-year overall survival for patients with no metastases or lymph node metastases only was similar at 80%. As expected, patients with liver metastases had a significantly decreased 10-year survival of 30% (P < .001). The time to development of liver metastases was significantly reduced for patients with lymph node metastases alone compared with those with none (P < .001). For the NIH cohort with longer follow-up, disease-related survival was significantly different for those patients with no metastases, lymph node metastases alone, and liver metastases (P < .001). Extent of lymph node involvement in this subgroup showed that disease-related survival decreased as a function of the number of lymph nodes involved (P = .004).

Conclusions  As expected, liver metastases decrease survival of patients with pNETs. Patients with lymph node metastases alone have a shorter time to the development of liver metastases that is dependent on the number of lymph nodes involved. With sufficient long-term follow-up, lymph node metastases decrease disease-related survival. Careful evaluation of number and extent of lymph node involvement is warranted in all surgical procedures for pNETs.

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Figure. Kaplan-Meier plots. A, Overall survival; B and C, time to development of liver metastases; and D and E, disease-related survival. For National Institutes of Health (NIH) and Stanford University Hospital patients (N = 326), overall survival was not significantly different between patients with lymph node involvement and those without metastases (A). As a result, we analyzed the time to development of liver metastases and found a significant difference (P < .001) between the 2 groups (B). This difference in time to development of liver metastases was related to the number of lymph nodes involved (P < .001) (C). Because of the longer follow-up time for the NIH cohort (n = 216), we performed an analysis of disease-related survival on this subgroup (D) and found significant differences among patients with no metastases, lymph node metastases only, and liver metastases (P < .001). We then looked at the extent of lymph node involvement in the subgroup analysis (E) and found that disease-related survival decreases as a function of the number of lymph nodes involved with tumor (P = .004).

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