Kira Oleinikov1,2, Inbal Uri1,2, Harold Jacob2,3, Julia Epshtein2,3, Ariel Benson2,3, Simona Ben-Haim2,4,5, Karine Atlan2,6, Ilanit Tal1,2, Amichay Meirovitz2,7, Ofra Maimon2,7, Naama Lev-Cohain2,8, Haggi Mazeh2,9, Benjamin Glaser1,2, David J Gross1,2, Simona Grozinsky-Glasberg10,11. 1. Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 2. ENETS Center of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 3. Advanced Endoscopy Unit, Department of Gastroenterology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 4. Department of Nuclear Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 5. Institute of Nuclear Medicine, University College Hospitals, NHS Trust, London, UK. 6. Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 7. Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 8. Department of Radiology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 9. Department of Surgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 10. Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. simonag@hadassah.org.il. 11. ENETS Center of Excellence, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. simonag@hadassah.org.il.
Abstract
PURPOSE: The decreased life expectancy of MEN-1 patients is mainly related to pancreatic neuroendocrine tumors (pNETs). At best, limited data is available on the natural history of MEN-1-associated pNETs, as these tumors are rare and have a wide range of biologic behavior. Our study aims to explore the clinical course of patients with MEN-1-associated pNETs and the long-term outcomes. METHODS: This longitudinal study was conducted on the MEN-1 cohort treated at our referral center over a 22-year period (1996-2018). Relevant clinical data were retrospectively analysed. RESULTS: Among the 33 MEN-1 patients included in our study, pNETs were identified in 21 subjects with a penetrance of 48% by the age of 50. Non-functioning and functioning pNETs were diagnosed in sixteen (76%) and five (24%) patients, respectively. Two-thirds of the patients had multifocal tumors. The median number of pancreatic macroscopic lesions per individual was 4.0 ± 3.9 (range 1-8) with a mean size of 1.3 ± 2.1 cm (range 0.5-10). The metastatic rate according to the dominant pNET lesion reached 100%, 62% and 6% for tumors sized > 4 cm, 2.1-4 cm, and 1-2 cm, respectively. Over the study period, one or more therapeutic interventions for pNETs were required in 20 out of the 21 patients. pNET-related metastatic complication was the main cause of death within this MEN-1 cohort. The overall survival rate for the pNETs patients was 86% during a mean follow-up period of 8.0 ± 4.6 years. CONCLUSIONS: In our MEN-1 cohort, non-functioning pNETs were the most frequent type of pancreaticoduodenal tumor, and the tumor size correlated with the risks of metastasis and death. Increased awareness, early diagnosis, and a multidisciplinary approach may improve the associated morbidity and mortality in these patients.
PURPOSE: The decreased life expectancy of MEN-1patients is mainly related to pancreatic neuroendocrine tumors (pNETs). At best, limited data is available on the natural history of MEN-1-associated pNETs, as these tumors are rare and have a wide range of biologic behavior. Our study aims to explore the clinical course of patients with MEN-1-associated pNETs and the long-term outcomes. METHODS: This longitudinal study was conducted on the MEN-1 cohort treated at our referral center over a 22-year period (1996-2018). Relevant clinical data were retrospectively analysed. RESULTS: Among the 33 MEN-1patients included in our study, pNETs were identified in 21 subjects with a penetrance of 48% by the age of 50. Non-functioning and functioning pNETs were diagnosed in sixteen (76%) and five (24%) patients, respectively. Two-thirds of the patients had multifocal tumors. The median number of pancreatic macroscopic lesions per individual was 4.0 ± 3.9 (range 1-8) with a mean size of 1.3 ± 2.1 cm (range 0.5-10). The metastatic rate according to the dominant pNET lesion reached 100%, 62% and 6% for tumors sized > 4 cm, 2.1-4 cm, and 1-2 cm, respectively. Over the study period, one or more therapeutic interventions for pNETs were required in 20 out of the 21 patients. pNET-related metastatic complication was the main cause of death within this MEN-1 cohort. The overall survival rate for the pNETspatients was 86% during a mean follow-up period of 8.0 ± 4.6 years. CONCLUSIONS: In our MEN-1 cohort, non-functioning pNETs were the most frequent type of pancreaticoduodenal tumor, and the tumor size correlated with the risks of metastasis and death. Increased awareness, early diagnosis, and a multidisciplinary approach may improve the associated morbidity and mortality in these patients.
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