Julie Perinel1, Gennaro Nappo2, Alessandro Zerbi3, Charlotte M Heidsma4, Elisabeth J M Nieveen van Dijkum4, Ho Seong Han5, Yoo-Seok Yoon5, Sohei Satoi6, Ihsan Ekin Demir7, Helmut Friess7, Yogesh Vashist8, Jakob Izbicki9, Alexandra Charlotte Muller10, Beat Gloor10, Marta Sandini11, Luca Gianotti11, Fabien Subtil12, Mustapha Adham13. 1. Department of Digestive Surgery, E. Herriot Hospital, Hospices Civils de Lyon, Lyon Sud Faculty of Medicine, UCBL1, Lyon, France. Electronic address: julie.perinel@chu-lyon.fr. 2. Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS Rozzano, Milan, Italy. 3. Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy. 4. Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, The Netherlands. 5. Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Republic of Korea. 6. Department of Surgery, Kansai Medical University, Osaka, Japan; Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO. 7. Department of Surgery, Technical University Munich Faculty of Medicine, Munchen, Germany. 8. Medias Klinikum, Centre for Surgical Oncology, Burghausen, Germany. 9. General, Visceral, and Thoracic Surgery Department, Clinic University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 10. University Hospital Bern Inselspital Bern, Switzerland. 11. School of Medicine and Surgery, University of Milano-Bicocca and Department of Surgery, San Gerardo Hospital, Monza, Italy. 12. UCBLUMR CNRS 5558 - LBBE, Service de Biostatistiques, Hospices Civils de Lyon, France. 13. Department of Digestive Surgery, E. Herriot Hospital, Hospices Civils de Lyon, Lyon Sud Faculty of Medicine, UCBL1, Lyon, France.
Abstract
BACKGROUND: Although the correlation between tumor size and aggressiveness is clearly established in sporadic nonfunctional pancreatic neuroendocrine tumors, the management of tumors ≤2 cm remains debated. In recent guidelines, the cut-off size to operate ranged from 1 to 2 cm. The aim of this retrospective study was to report the rate of lymph nodes metastases in resected sporadic nonfunctional pancreatic neuroendocrine tumors, according to tumor size and, second, to identify risk factors of lymph node metastases and disease-free survival. METHODS: Resected sporadic nonfunctional pancreatic neuroendocrine tumors from 9 international expert centers were included (1999-2017). Functional pancreatic neuroendocrine tumors, genetic syndromes, and R2 resection were excluded. Aggressiveness was defined as microvascular invasion, perineural invasion, lymph node metastases, G3 grading, distant metastases, and/or recurrence. RESULTS: Overall, 495 resected sporadic nonfunctional pancreatic neuroendocrine tumors were included. For tumors up to 5 cm, the risk of lymph node metastases was increased by 1.73 for every 1 cm increase in size (odds ratio = 1.73; 95% confidence interval = 1.46-2.03). Tumor size >2 cm (P < .001), perineural invasion (P = .002), microvascular invasion (P < .001), and distant metastases (P = .008) were independently associated with lymph node metastases. Tumor size >2 cm (P = .003), R1 status (P = .004), lymph node metastases (P < .001), and World Health Organization grade 3 (P = .002) were independently associated with disease-free survival. Aggressiveness rate was 13.1% in tumors ≤1 cm and 29% in tumors between 1.1 and 2 cm. CONCLUSION: In resected sporadic nonfunctional pancreatic neuroendocrine tumors, the risk of lymph node metastases is correlated to tumor size. Considering that sporadic nonfunctional pancreatic neuroendocrine tumors between 1.1 and 2 cm had a higher risk of lymph node metastases and recurrence compared to tumors ≤1 cm, the decision to perform surgery in this subgroup of patients should be individualized in surgically fit patients.
BACKGROUND: Although the correlation between tumor size and aggressiveness is clearly established in sporadic nonfunctional pancreatic neuroendocrine tumors, the management of tumors ≤2 cm remains debated. In recent guidelines, the cut-off size to operate ranged from 1 to 2 cm. The aim of this retrospective study was to report the rate of lymph nodes metastases in resected sporadic nonfunctional pancreatic neuroendocrine tumors, according to tumor size and, second, to identify risk factors of lymph node metastases and disease-free survival. METHODS: Resected sporadic nonfunctional pancreatic neuroendocrine tumors from 9 international expert centers were included (1999-2017). Functional pancreatic neuroendocrine tumors, genetic syndromes, and R2 resection were excluded. Aggressiveness was defined as microvascular invasion, perineural invasion, lymph node metastases, G3 grading, distant metastases, and/or recurrence. RESULTS: Overall, 495 resected sporadic nonfunctional pancreatic neuroendocrine tumors were included. For tumors up to 5 cm, the risk of lymph node metastases was increased by 1.73 for every 1 cm increase in size (odds ratio = 1.73; 95% confidence interval = 1.46-2.03). Tumor size >2 cm (P < .001), perineural invasion (P = .002), microvascular invasion (P < .001), and distant metastases (P = .008) were independently associated with lymph node metastases. Tumor size >2 cm (P = .003), R1 status (P = .004), lymph node metastases (P < .001), and World Health Organization grade 3 (P = .002) were independently associated with disease-free survival. Aggressiveness rate was 13.1% in tumors ≤1 cm and 29% in tumors between 1.1 and 2 cm. CONCLUSION: In resected sporadic nonfunctional pancreatic neuroendocrine tumors, the risk of lymph node metastases is correlated to tumor size. Considering that sporadic nonfunctional pancreatic neuroendocrine tumors between 1.1 and 2 cm had a higher risk of lymph node metastases and recurrence compared to tumors ≤1 cm, the decision to perform surgery in this subgroup of patients should be individualized in surgically fit patients.