Alexandra G Lopez-Aguiar1, Mohammad Y Zaidi1, Eliza W Beal2, Mary Dillhoff2, John G D Cannon3, George A Poultsides3, Zaheer S Kanji4, Flavio G Rocha4, Paula Marincola Smith5, Kamran Idrees5, Megan Beems6, Clifford S Cho6, Alexander V Fisher7, Sharon M Weber7, Bradley A Krasnick8, Ryan C Fields8, Kenneth Cardona1, Shishir K Maithel9. 1. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA. 2. Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. 3. Department of Surgery, Stanford University Medical Center, Stanford, CA, USA. 4. Department of Surgery, Virginia Mason Medical Center, Seattle, WA, USA. 5. Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. 6. Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA. 7. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 8. Department of Surgery, Washington University School of Medicine, St Louis, MO, USA. 9. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA. smaithe@emory.edu.
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.
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.
Authors: Adriana C Gamboa; Yuan Liu; Rachel M Lee; Mohammad Y Zaidi; Charles A Staley; Maria C Russell; Kenneth Cardona; Patrick S Sullivan; Shishir K Maithel Journal: J Surg Oncol Date: 2019-08-26 Impact factor: 3.454
Authors: Masayuki Tanaka; Max Heckler; André L Mihaljevic; Pascal Probst; Ulla Klaiber; Ulrike Heger; Simon Schimmack; Markus W Büchler; Thilo Hackert Journal: Ann Surg Oncol Date: 2020-07-27 Impact factor: 5.344
Authors: Kota Sahara; Diamantis I Tsilimigras; Rittal Mehta; Amika Moro; Anghela Z Paredes; Alexandra G Lopez-Aguiar; Flavio Rocha; Zaheer Kanji; Sharon Weber; Alexander Fisher; Ryan Fields; Bradley A Krasnick; Kamran Idrees; Paula M Smith; George A Poultsides; Eleftherios Makris; Cliff Cho; Megan Beems; Mary Dillhoff; Shishir K Maithel; Itaru Endo; Timothy M Pawlik Journal: Ann Surg Oncol Date: 2019-12-14 Impact factor: 5.344
Authors: Ugo Marchese; Martin Gaillard; Anna Pellat; Stylianos Tzedakis; Einas Abou Ali; Anthony Dohan; Maxime Barat; Philippe Soyer; David Fuks; Romain Coriat Journal: Cancers (Basel) Date: 2022-01-15 Impact factor: 6.639