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Long term outcomes of lymph node dissection in small non-functional pancreatic neuroendocrine tumors in a large multi-center cohort
Louisa Bolm1, Martina Nebbia1, Natalie Petruch1, Carlos Fernandez-del Castillo1, Jian Y. Zheng2, Alessandra Pulvirenti3, Ammar A. Javed4, Andrew L. Warshaw1, Vikram Deshpande5, Motaz Qadan1, Keith Lillemoe1, Alice Wei3, Amer H. Zureikat2, Jin He4, Cristina R. Ferrone1
1Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, United States, 2Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States, 3Department of Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York, United States, 4Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, United States, 5Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, United States

Introduction: The role of lymph node dissection in small (<3cm) non-functional pancreatic neuroendocrine tumors (pNET) is unlikely to be studied in a prospective randomized clinical trial. By combining data from 4 high volume centers we compared the disease-free survival (DFS) and overall survival (OS) of patients who underwent parenchyma-sparing resections (PSR) to patients who underwent formal oncologic resections (OR).

Patients and Methods: Retrospective review of prospectively collected clinicopathologic data of patients undergoing surgical resection between 2000-2021 was collected from four high volume institutions. Patients undergoing PSR (enucleation and central pancreatectomy) were compared to patients with OR (pancreaticoduodenectomy, distal pancreatectomy). Statistical testing was performed by Chi-squared test and t test, median OS estimates with Kaplan Meier method and multivariate analysis with cox proportional hazard model.

Results: Of the 1742 patients with small PNETs, 1521 (87.2%) underwent OR, 121 (6.1%) had an enucleation and 100 (5.7%) had a central pancreatectomy. The median age was 58 years and 52.1% were female with a median tumor size of 2.5 cm. After case-control matching for tumor size, 221 patients in each group were matched. Patients with PSR were more likely to undergo minimally invasive operations (32.6% vs. 13.6%, p<0.001), had less intraoperative blood loss (209ml vs. 511ml, p<0.001) and shorter operative times (180min vs. 330min, p<0.001) than patients undergoing OR. While the median number of lymph nodes harvested was lower for PSR (n=1 vs. n=10, p<0.001), the median number of positive lymph nodes was equivalent to OR (n=1 vs. n=1, p=0.808). Postoperative morbidity was similar for both groups (38.5% vs. 48.2%, p=0.090), however subset analysis demonstrates the highest morbidity for central pancreatectomies (56.6%, p=0.003). Long-term median DFS (190m vs. 195m, p=0.505) and OS (189m vs. 190m, p=0.172) were comparable.
Of the 1742 resected patients 136 had no lymph nodes resected. These patients experienced less blood loss, shorter operation times (p<0.001), and lower postoperative complication rates as compared to patients undergoing lymphadenectomy (39.7% vs. 56.9%, p=0.008). Median DFS (191m vs. 215m, p=0.837) and OS (200m vs. 176m, p=0.827) were similar for patients with no lymph nodes resected and patients with negative lymph nodes (N0) after lymphadenectomy.

Conclusion: Parenchyma- and lymph node-sparing resections can be safely performed in patients with small non-functional pNETs without suspicious lymph nodes on preoperative imaging. Oncological resections and lymphadenectomy are associated with higher blood loss, longer operative times and higher complication rates for similar long-term oncological outcomes. Parenchyma- and lymph node-sparing resections should be considered for patients with small non-functional pNETs at low risk of lymph node involvement.

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