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Original Investigation
October 31, 2018

Prognostic Role of Lymph Node Positivity and Number of Lymph Nodes Needed for Accurately Staging Small-Bowel Neuroendocrine Tumors

Author Affiliations
  • 1Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
  • 2Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus
  • 3Department of Surgery, Stanford University Medical Center, Stanford, California
  • 4Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
  • 5Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
  • 6Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor
  • 7Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison
  • 8Department of Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri
JAMA Surg. 2019;154(2):134-140. doi:10.1001/jamasurg.2018.3865
Key Points

Questions  Is lymph node positivity associated with disease recurrence in patients with small-bowel neuroendocrine tumors, and how many lymph nodes are needed to accurately stage patients undergoing curative resection?

Findings  This case series involving 199 patients who underwent curative-intent resection of a primary small-bowel neuroendocrine tumor found that lymph node positivity alone was not associated with disease recurrence; rather, a threshold of 4 positive lymph nodes was needed to see earlier disease recurrence. Retrieval of 8 or more total lymph nodes accurately discriminates recurrence-free survival in patients with 4 or more, 1 to 3, or 0 positive lymph nodes.

Meaning  Having 4 or more positive lymph nodes is associated with earlier disease recurrence, and a minimum of 8 lymph nodes are needed to stage patients with small-bowel neuroendocrine tumors.

Abstract

Importance  Little information is available regarding the minimum number of lymph nodes needed to accurately stage patients when performing a mesenteric lymphadenectomy for small-bowel neuroendocrine tumors.

Objectives  To determine the prognostic role of lymph node positivity and the ideal number of lymph nodes for accurately staging patients with small-bowel neuroendocrine tumors.

Design, Setting, and Participants  This case series from the US Neuroendocrine Tumor Study Group, a collaboration among8 US-based, academic tertiary care referral centers, obtained demographic, perioperative, and pathologic data from the group’s database, Social Security Death Index, and publicly available obituaries. All patients in these institutions with small-bowel neuroendocrine tumors who underwent curative-intent surgical resection of a primary tumor between January 1, 2000, and December 31, 2015, were included (n = 199). Patients with duodenal or ampullary tumors, other nonneuroendocrine concurrent malignant neoplasms, mortality of fewer than 30 days after the surgical procedure, and distant metastatic disease were excluded. Data analysis was conducted from September 1, 2017, to December 1, 2017.

Main Outcomes and Measures  Primary study outcome was recurrence-free survival. Hypothesis was generated after data collection and data entry into the US Neuroendocrine Tumor Study Group database.

Results  Of the 199 patients included, 112 (56.3%) were male and 87 (43.7%) female with a mean (SD) age of 60.3 (12.5) years and a mean (SD) body mass index of 29.5 (6.0). One hundred fifty-four patients (77.4%) had lymph node–positive disease. No difference in 3-year recurrence-free survival was found between patients with lymph node–positive and lymph node–negative disease. Patients with 4 positive lymph nodes had a worse 3-year recurrence-free survival compared with those with 1 to 3 or 0 positive lymph nodes (81.6% vs 91.4% vs 92.1%; P = .01). When examining patients with fewer than 8 resected lymph nodes, no difference in 3-year recurrence-free survival was observed among patients with 4 or more, 1 to 3, or 0 positive lymph nodes (100% vs 93.8% vs 91.7%; P = .87). Retrieval of 8 or more lymph nodes, however, accurately discriminated patients with 4 or more, 1 to 3, or 0 positive lymph nodes (3-year recurrence-free survival: 79.9% vs 89.6% vs 92.9%; P = .05).

Conclusions and Relevance  The findings from this study suggest that, for patients undergoing curative-intent resection of small-bowel neuroendocrine tumors, accurate lymph node staging requires a minimum of 8 lymph nodes for examination, and 4 or more positive lymph nodes are associated with decreased 3-year recurrence-free survival compared with 1 to 3 or 0 positive lymph nodes; a thorough regional lymphadenectomy may be critical for accurate staging and management of this disease.

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