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

Lopez‐Aguiar, Alexandra G.; Zaidi, Mohammad Y.; Beal, Eliza W.; Dillhoff, Mary; Cannon, John G.D.; Poultsides, George A.; Kanji, Zaheer; Rocha, Flavio G.; Smith, Paula Marincola; Idrees, Kamran; Beems, Megan; Cho, Clifford S.; Fisher, Alan E.; Weber, Sharon M.; Krasnick, Bradley A.; Fields, Ryan C.; Cardona, Kenneth; Maithel, Shishir K.

doi:10.1245/s10434-019-07367-y

Cited by 40 publications

(31 citation statements)

References 30 publications

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“…As lymph node metastases have demonstrated a negative prognostic role across most neuroendocrine tumor sites, including pancreas, and small bowel, various other studies have sought to predict nodal positivity with pre‐operatively available clinicopathologic variables to guide patient management . Our group recently demonstrated that for pancreatic neuroendocrine tumors, node positivity is associated with a worse 5‐year recurrence‐free survival with a minimum of seven lymph nodes required for adequate staging . Similarly, small bowel neuroendocrine tumors have demonstrated aggressive behavior, and guidelines recommend radical resection for all tumors with routine lymphadenectomy .…”

Section: Discussionmentioning

confidence: 99%

“…21 Our group recently demonstrated that for pancreatic neuroendocrine tumors, node positivity is associated with a worse 5-year recurrence-free survival with a minimum of seven lymph nodes required for adequate staging. 22 Similarly, small bowel neuroendocrine tumors have demonstrated aggressive behavior, and guidelines recommend radical resection for all tumors with routine lymphadenectomy. 23,24 Conversely, the role of lymphadenectomy for duodenal neuroendocrine tumors remains ill-defined and although regional nodal involvement may be common with increasing tumor size, the predictive value of lymph node metastases on long-term outcomes has not been proven.…”

Section: Discussionmentioning

confidence: 99%

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A novel preoperative risk score to predict lymph node positivity for rectal neuroendocrine tumors: An NCDB analysis to guide operative technique

Gamboa

Liu

Lee

et al. 2019

Journal of Surgical Oncology

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Background/Objective Staging and type of resection for rectal neuroendocrine tumors (R‐NETS) relies on preoperative identification of lymph node (LN) involvement. Study objective was to develop a Preoperative Rectal Stratification Score (PReSS) for LN‐positivity and to assess the association of PReSS with overall survival (OS). Methods All patients in the National Cancer Database (2004‐2014) with non‐metastatic/nonfunctional R‐NETS were included. Tumor size was divided into three categories (<1, 1‐2, and ≥2 cm). Results Among 383 patients, median age was 57 years, 52% were male (n = 200), median tumor size was 1.4 cm, 43% had positive LNs (n = 163). On univariate analysis, age > 60, poorly differentiated grade, depth of invasion past submucosa, and size >1 cm were associated with LN positivity. On multivariable analysis, depth of invasion past submucosa, and increasing tumor size >1 cm remained associated with LN positivity. As these can be determined preoperatively, incidence of LN positivity was determined for each combination of tumor size and depth of invasion. Each variable was assigned a score to create a PReSS of four groups (0‐3) associated with an increasing rate of LN‐positivity (PReSS group 0: 11%, 1: 38%, 2: 50%, 3: 78%, P < .01). PReSS correlated with 10‐year OS (PReSS 0: 90%; 1: 81%; 2: 59%; 3: 41%). Conclusion For R‐NETS, depth of invasion and tumor size predict LN positivity and both can be obtained preoperatively. PReSS incorporates both variables and stratifies tumors into four risk groups of progressively increasing LN positivity and should be used to guide surgical approach.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A novel preoperative risk score to predict lymph node positivity for rectal neuroendocrine tumors: An NCDB analysis to guide operative technique

Gamboa

Liu

Lee

et al. 2019

Journal of Surgical Oncology

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“…In addition, data from the current study demonstrated that an increase in the number of LNs evaluated was associated with a concomitant increase in the number of LNM detected. Specifically, removing >8 LNs was associated with a higher therapeutic index compared with harvesting seven or fewer LNs (index difference of more than 10), suggesting that eight LNs is the appropriate goal of LND threshold …”

Section: Discussionmentioning

confidence: 98%

Therapeutic index of lymphadenectomy among patients with pancreatic neuroendocrine tumors: A multi‐institutional analysis

Sahara

Tsilimigras

et al. 2019

Journal of Surgical Oncology

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Background: The benefit derived from lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) based on clinicopathological characteristics remains unclear.Methods: Patients undergoing surgery for pNET between 1997 and 2016 were identified using a multi-institutional dataset. The therapeutic index of LND relative to patient characteristics was calculated.Results: Among 647 patients, the median number of lymph nodes (LNs) evaluated was 10 (interquartile range: 4-16) and approximately one quarter of patients had lymph node metastasis (LNM) (N = 159, 24.6%). Among patients with LNM, 5-year recurrence-free survival was 56.0%, reflecting a therapeutic index value of 13.8. The therapeutic index was highest among patients with a moderately/poorly-differentiated pNET (21.5), Ki-67 ≥ 3% (20.1), tumor size ≥2.0 cm (20.0), and tumor location at the head of the pancreas (20.0). Patients with ≥8 LNs evaluated had a higher therapeutic index than patients who had 1 to 7 LNs evaluated (≥8: 17.9 vs 1-7: 7.5; difference of index: 11.4).Conclusion: LND was mostly beneficial among patients with pNETs >2 cm, Ki-67 ≥ 3%, and lesions located at the pancreatic head as identification of LNM was most common among individuals with these tumor characteristics. Evaluation of ≥8 LNs was associated with a higher likelihood of identifying LNM as well as a higher therapeutic index, and therefore this number of LNs should be considered the goal. K E Y W O R D S lymphadenectomy, pancreatic neuroendocrine tumor, therapeutic index Lu Wu, Kota Sahara, and Diamantis I. Tsilimigras contributed equally to this work.

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“…Patients undergoing surgery for PanNET have lymph-node metastasis (pN+) in 26-37% of cases (32,36,37). While the association of nodal metastasis with overall survival remains controversial, several studies have now demonstrated the correlate of pN+ with recurrence (6,9,16,32,(36)(37)(38). Patients with lymph nodal involvement have a ×5 risk of recurrence following curative resection and a reduced 5-year disease-free survival (DFS) from 86-97% to 60-70% compared to patients with no nodal involvement (36,37).…”

Section: Lymph-node Statusmentioning

confidence: 99%

“…On preoperative cross-sectional imaging, the finding of enlarged lymph nodes that might appear hypervascular is strongly suggestive of nodal involvement (36). The use of 68Ga-DOTATATE PET/CT for baseline staging can show a pathological uptake in abdominal retroperitoneal nodal sites with higher accuracy than CT scans (18,37). Although survival benefit of extended lymphadenectomy has not been proved, formal surgical resection (pancreaticoduodenectomy or distal pancreatectomy) with regional lymphadenectomy should be performed in PanNET at increased risk of nodal disease to allow an accurate pathological staging (6,19,36).…”

Section: Lymph-node Statusmentioning

confidence: 99%

Clinical and Molecular Risk Factors for Recurrence Following Radical Surgery of Well-Differentiated Pancreatic Neuroendocrine Tumors

et al. 2020

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Well-differentiated pancreatic neuroendocrine tumors are increasingly diagnosed neoplasms. For localized disease, surgery is the first-line therapy and is curative in most cases. However, although recurrence is a rare event, it can still occur up to 10 years from surgery, worsening the prognosis. Many clinical and pathological factors have been associated with recurrence; however, it is currently unclear how to accurately discern patients at risk for relapse of disease from those that should be considered cured. In this review, we focus on clinical, pathological, and molecular factors associated with recurrence and discuss available prediction tools to assess the risk of recurrence following surgery.

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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

Cited by 40 publications

References 30 publications

A novel preoperative risk score to predict lymph node positivity for rectal neuroendocrine tumors: An NCDB analysis to guide operative technique

A novel preoperative risk score to predict lymph node positivity for rectal neuroendocrine tumors: An NCDB analysis to guide operative technique

Therapeutic index of lymphadenectomy among patients with pancreatic neuroendocrine tumors: A multi‐institutional analysis

Clinical and Molecular Risk Factors for Recurrence Following Radical Surgery of Well-Differentiated Pancreatic Neuroendocrine Tumors

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