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Defining the Role of Lymphadenectomy for Pancreatic Neuroendocrine Tumors: An Eight-Institution Study of 695 Patients from the US Neuroendocrine Tumor Study Group

  • Alexandra G. Lopez-Aguiar
  • Mohammad Y. Zaidi
  • Eliza W. Beal
  • Mary Dillhoff
  • John G. D. Cannon
  • George A. Poultsides
  • Zaheer S. Kanji
  • Flavio G. Rocha
  • Paula Marincola Smith
  • Kamran Idrees
  • Megan Beems
  • Clifford S. Cho
  • Alexander V. Fisher
  • Sharon M. Weber
  • Bradley A. Krasnick
  • Ryan C. Fields
  • Kenneth Cardona
  • Shishir K. MaithelEmail author
Endocrine Tumors

Abstract

Background

Preoperative factors that reliably predict lymph node (LN) metastases in pancreatic neuroendocrine tumors (PanNETs) are unclear. The number of LNs needed to accurately stage PanNETs has not been defined.

Methods

Patients who underwent curative-intent resection of non-functional PanNETs at eight institutions from 2000 to 2016 were analyzed. Preoperative factors associated with LN metastases were identified. A procedure-specific target for LN retrieval to accurately stage patients was determined.

Results

Of 695 patients who underwent resection, 33% of tumors were proximal (head/uncinate) and 67% were distal (neck/body/tail). Twenty-six percent of patients (n = 158) had LN-positive disease, which was associated with a worse 5-year recurrence-free survival (RFS; 60% vs. 86%; p < 0.001). The increasing number of positive LNs was not associated with worse RFS. Preoperative factors associated with positive LNs included tumor size ≥ 2 cm (odds ratio [OR] 6.6; p < 0.001), proximal location (OR 2.5; p < 0.001), moderate versus well-differentiation (OR 2.1; p = 0.006), and Ki-67 ≥ 3% (OR 3.1; p < 0.001). LN metastases were also present in tumors without these risk factors: < 2 cm (9%), distal location (19%), well-differentiated (23%), and Ki-67 < 3% (16%). Median LN retrieval was 13 for pancreatoduodenectomy (PD), but only 9 for distal pancreatectomy (DP). Given that PD routinely includes a complete regional lymphadenectomy, a minimum number of LNs to accurately stage patients was not identified. However, for DP, removal of less than seven LNs failed to discriminate 5-year RFS between LN-positive and LN-negative patients (less than seven LNs: 72% vs. 83%, p = 0.198; seven or more LNs: 67% vs. 86%; p = 0.002).

Conclusions

Tumor size ≥ 2 cm, proximal location, moderate differentiation, and Ki-67 ≥ 3% are preoperative factors that predict LN positivity in resected non-functional PanNETs. Given the 9–23% incidence of LN metastases in patients without such risk factors, routine regional lymphadenectomy should be considered. PD inherently includes sufficient LN retrieval, while DP should aim to remove seven or more LNs for accurate staging.

Notes

Funding

Funding was provided in part by the Katz Foundation.

Disclosures

This work was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1TR000454 and TL1TR000456. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Alexandra G. Lopez-Aguiar
    • 1
  • Mohammad Y. Zaidi
    • 1
  • Eliza W. Beal
    • 2
  • Mary Dillhoff
    • 2
  • John G. D. Cannon
    • 3
  • George A. Poultsides
    • 3
  • Zaheer S. Kanji
    • 4
  • Flavio G. Rocha
    • 4
  • Paula Marincola Smith
    • 5
  • Kamran Idrees
    • 5
  • Megan Beems
    • 6
  • Clifford S. Cho
    • 6
  • Alexander V. Fisher
    • 7
  • Sharon M. Weber
    • 7
  • Bradley A. Krasnick
    • 8
  • Ryan C. Fields
    • 8
  • Kenneth Cardona
    • 1
  • Shishir K. Maithel
    • 1
    Email author
  1. 1.Division of Surgical Oncology, Department of Surgery, Winship Cancer InstituteEmory UniversityAtlantaUSA
  2. 2.Division of Surgical OncologyThe Ohio State University Comprehensive Cancer CenterColumbusUSA
  3. 3.Department of SurgeryStanford University Medical CenterStanfordUSA
  4. 4.Department of SurgeryVirginia Mason Medical CenterSeattleUSA
  5. 5.Division of Surgical Oncology, Department of SurgeryVanderbilt University Medical CenterNashvilleUSA
  6. 6.Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of SurgeryUniversity of MichiganAnn ArborUSA
  7. 7.Department of SurgeryUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  8. 8.Department of SurgeryWashington University School of MedicineSt LouisUSA

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