المؤلفون: Klein Haneveld, Mirthe J, van Treijen, Mark J C, Pieterman, Carolina R C, Dekkers, Olaf M, van de Ven, Annenienke, de Herder, Wouter W, Zandee, Wouter T, Drent, Madeleine L, Bisschop, Peter H, Havekes, Bas, Vriens, Menno R, Verrijn Stuart, Annemarie A, Valk, Gerlof D, van Leeuwaarde, Rachel S

المصدر: Klein Haneveld , M J , van Treijen , M J C , Pieterman , C R C , Dekkers , O M , van de Ven , A , de Herder , W W , Zandee , W T , Drent , M L , Bisschop , P H , Havekes , B , Vriens , M R , Verrijn Stuart , A A , Valk , G D & van Leeuwaarde , R S 2021 , ' Initiating Pancreatic Neuroendocrine Tumor (pNET) Screening in Young MEN1 Patients : Results From the DutchMEN Study Group ' , Journal ....

مصطلحات موضوعية: Adolescent, Adult, Age of Onset, Aged, Child, Preschool, Databases, Factual, Diagnostic Imaging, Early Detection of Cancer/methods, Female, Follow-Up Studies, Humans, Male, Middle Aged, Multiple Endocrine Neoplasia Type 1/physiopathology, Netherlands/epidemiology, Neuroendocrine Tumors/diagnosis, Pancreatic Neoplasms/diagnosis, Prognosis, Retrospective Studies, Survival Rate, Tumor Burden, Young Adult, ENDOCRINE NEOPLASIA TYPE-1, INTERVAL-CENSORED-DATA, surveillance, multiple endocrine neoplasia type 1, age-related penetrance, pancreatic NET

الوصف: CONTEXT: Nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the optimal age to initiate screening for pNETs is under debate. OBJECTIVE: The aim of this work is to assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients. METHODS: Pancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size ≥ 20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease. RESULTS: Five of 350 patients developed clinically relevant NF-pNETs before age 18 years, 2 of whom subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET-free survival were found for sex, time frame, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5%, and 5% risk of having developed a clinically relevant tumor are 9.5 (6.5-12.7), 13.5 (10.2-16.9), and 17.8 years (14.3-21.4), respectively. CONCLUSION: Analyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13 to 14 years is justified. The psychological and medical burden of screening at a young age should be considered.

الإتاحة: https://doi.org/10.1210/clinem/dgab569Test
https://cris.maastrichtuniversity.nl/en/publications/b4e76abf-f1e2-4a83-99e7-5808d22c1cdcTest

المؤلفون: van den Broek, Medard F. M., de Laat, Joanne M., van Leeuwaarde, Rachel S., van de Ven, Annenienke C., de Herder, Wouter W., Dekkers, Olaf M., Drent, Madeleine L., Kerstens, Michiel N., Bisschop, Peter H., Havekes, Bas, Hackeng, Wenzel M., Brosens, Lodewijk A. A., Vriens, Menno R., Buikhuisen, Wieneke A., Valk, Gerlof D.

المصدر: van den Broek , M F M , de Laat , J M , van Leeuwaarde , R S , van de Ven , A C , de Herder , W W , Dekkers , O M , Drent , M L , Kerstens , M N , Bisschop , P H , Havekes , B , Hackeng , W M , Brosens , L A A , Vriens , M R , Buikhuisen , W A & Valk , G D 2021 , ' The Management of Neuroendocrine Tumors of the Lung in MEN1 : Results From the ....

مصطلحات موضوعية: multiple endocrine neoplasia type 1, lung NET, tumor growth, survival, surveillance

الوصف: Introduction: Multiple endocrine neoplasia type 1 (MEN1)-related neuroendocrine tumors (NETs) of the lung are mostly indolent, with a good prognosis. Nevertheless, cases of aggressive lung NET do occur, and therefore the management of individual patients is challenging. Aim: To assess tumor growth and the survival of patients with MEN1-related lung NETs at long-term follow-up. Methods: The population-based Dutch MEN1 Study Group database (n=446) was used to identify lung NETs by histopathological and radiological examinations. Tumor diameter was assessed. Linear mixed models and the Kaplan-Meier method were used for analyzing tumor growth and survival. Molecular analyses were performed on a lung NET showing particularly aggressive behavior. Results: In 102 patients (22.9% of the total MEN1 cohort), 164 lesions suspected of lung NETs were identified and followed for a median of 6.6 years. Tumor diameter increased 6.0% per year. The overall 15-year survival rate was 78.0% (95% confidence interval: 64.6-94.2%) without lung NET-related death. No prognostic factors for tumor growth or survival could be identified. A somatic c.3127A>G (p.Met1043Val) PIK3CA driver mutation was found in a case of rapid growing lung NET after 6 years of indolent disease, presumably explaining the sudden change in course. Conclusion: MEN1-related lung NETs are slow growing and have a good prognosis. No accurate risk factors for tumor growth could be identified. Lung NET screening should therefore be based on well-informed, shared decision-making, balancing between the low absolute risk of an aggressive tumor in individuals and the potential harms of frequent thoracic imaging.

الإتاحة: https://doi.org/10.1210/clinem/dgaa800Test
https://cris.maastrichtuniversity.nl/en/publications/f2729f47-2bda-472a-9895-d178115c21dcTest

المؤلفون: Buitenwerf, Edward, Osinga, Thamara E, Timmers, Henri J L M, Lenders, Jacques W M, Feelders, Richard A, Eekhoff, Elisabeth M W, Haak, Harm R, Corssmit, Eleonora P M, Bisschop, Peter H L T, Valk, Gerlof D, GrooteVeldman, Ronald, Dullaart, Robin P F, Links, Thera P, Voogd, Magiel F, Wietasch, Götz J K G, Kerstens, Michiel N

المصدر: Buitenwerf , E , Osinga , T E , Timmers , H J L M , Lenders , J W M , Feelders , R A , Eekhoff , E M W , Haak , H R , Corssmit , E P M , Bisschop , P H L T , Valk , G D , GrooteVeldman , R , Dullaart , R P F , Links , T P , Voogd , M F , Wietasch , G J K G , Kerstens , M N & PRESCRIPT-investigators 2020 , ' Efficacy of α-blockers on hemodynamic control during ....

مصطلحات موضوعية: pheochromocytoma, sympathetic paraganglioma, alpha-adrenergic receptor blocker, hemodynamic instability, MEAN ARTERIAL-PRESSURE, INTRAOPERATIVE HYPOTENSION, PERIOPERATIVE MANAGEMENT, PREOPERATIVE MANAGEMENT, CLINICAL-PRACTICE, BLOOD-PRESSURE, SURGERY, PARAGANGLIOMA, BLOCKADE, ASSOCIATION

الوصف: CONTEXT: Pretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL). OBJECTIVE: To determine which type of α-adrenergic receptor blocker provides the best efficacy. DESIGN: Randomized controlled open-label trial (PRESCRIPT; ClinicalTrials.gov NCT01379898). SETTING: Multicenter study including 9 centers in The Netherlands. PATIENTS: 134 patients with non-metastatic PPGL. INTERVENTION: phenoxybenzamine or doxazosin starting 2-3 weeks before surgery using a blood pressure targeted titration schedule. Intraoperative hemodynamic management was standardized. MAIN OUTCOME MEASURES: Primary efficacy endpoint was the cumulative intraoperative time outside the blood pressure target range (i.e., SBP >160 mmHg or MAP <60 mmHg) expressed as a percentage of total surgical procedure time. Secondary efficacy endpoint was the value on a hemodynamic instability score. RESULTS: Median cumulative time outside blood pressure targets was 11.1% [IQR: 4.3-20.6] in the phenoxybenzamine group compared to 12.2% [5.3-20.2] in the doxazosin group (P=0.75, r=0.03). The hemodynamic instability score was 38.0 [28.8-58.0] and 50.0 [35.3-63.8] in the phenoxybenzamine and doxazosin group, respectively (P=0.02, r=0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P=0.68). There was no mortality after 30 days. CONCLUSIONS: The duration of blood pressure outside the target range during resection of a PPGL was not different after preoperative treatment with either phenoxybenzamine or doxazosin. Phenoxybenzamine was more effective in preventing intraoperative hemodynamic instability, but it could not be established whether this was associated with a better clinical outcome.

الإتاحة: https://doi.org/10.1210/clinem/dgz188Test
https://cris.maastrichtuniversity.nl/en/publications/40870d58-65f6-468d-a915-8217aad779cfTest

المؤلفون: van Beek, Dirk-Jan, Nell, Sjoerd, Pieterman, Carolina R. C., de Herder, Wouter W., van de Ven, Annenienke C., Dekkers, Olaf M., van der Horst-Schrivers, Anouk N., Drent, Madeleine L., Bisschop, Peter H., Havekes, Bas, Rinkes, Inne H. M. Borel, Vriens, Menno R., Valk, Gerlof D.

المصدر: van Beek , D-J , Nell , S , Pieterman , C R C , de Herder , W W , van de Ven , A C , Dekkers , O M , van der Horst-Schrivers , A N , Drent , M L , Bisschop , P H , Havekes , B , Rinkes , I H M B , Vriens , M R & Valk , G D 2019 , ' Prognostic factors and survival in MEN1 patients with gastrinomas : Results from the DutchMEN study group (DMSG) ' , Journal of Surgical Oncology , vol. 120 ....

مصطلحات موضوعية: multiple endocrine neoplasia type 1, neuroendocrine tumor, oncology, Zollinger-Ellison syndrome, ENDOCRINE NEOPLASIA TYPE-1, ZOLLINGER-ELLISON-SYNDROME, PANCREATIC NEUROENDOCRINE TUMORS, NATURAL-HISTORY, GUIDELINES, MANAGEMENT, DIAGNOSIS, SURGERY

الوصف: Background and objectives Gastrinomas are the most prevalent functioning neuroendocrine tumors (NET) in multiple endocrine neoplasia type 1 (MEN1). Guidelines suggest medical therapy in most patients, but surgery may be considered in a subgroup. Currently, factors to guide management are necessary. This population-based cohort study assessed prognostic factors of survival in patients with MEN1-related gastrinomas. Methods Patients with MEN1 having gastrinomas were identified in the Dutch MEN1 database from 1990 to 2014 based on fasting serum gastrin (FSG) levels and/or pathology. Predictors of overall survival were assessed using Cox regression. Results Sixty-three patients with gastrinoma (16% of the MEN1 population) were identified. Five- and 10-year overall survival rates were 83% and 65%, respectively. Prognostic factors associated with overall survival were initial FSG levels >= 20x upper limit of normal (ULN) (hazard ratio [HR], 6.2 [95% confidence interval, 1.7-23.0]), pancreatic NET >= 2 cm (HR 4.5; [1.5-13.1]), synchronous liver metastases (HR 8.9; [2.1-36.7]), gastroduodenoscopy suspicious for gastric NETs (HR 12.7; [1.4-115.6]), and multiple concurrent NETs (HR 5.9; [1.2-27.7]). Conclusion Life expectancy of patients with MEN1 gastrinoma is reduced. FSG levels and pancreatic NETs >= 2 cm are prognostic factors. FSG levels might guide surveillance intensity, step-up to additional diagnostics, or provide arguments in selecting patients who might benefit from surgery.

الإتاحة: https://doi.org/10.1002/jso.25667Test
https://cris.maastrichtuniversity.nl/en/publications/5875072a-269e-4e63-a6b2-23d32f363320Test

المؤلفون: van Leeuwaarde, Rachel S., Pieterman, Carolina R. C., Bleiker, Eveline M. A., Dekkers, Olaf M., van der Horst-Schrivers, Anouk N., Hermus, Ad R., de Herder, Wouter W., Drent, Madeleine L., Bisschop, Peter H., Havekes, Bas, Vriens, Menno R., Valk, Gerlof D.

المصدر: van Leeuwaarde , R S , Pieterman , C R C , Bleiker , E M A , Dekkers , O M , van der Horst-Schrivers , A N , Hermus , A R , de Herder , W W , Drent , M L , Bisschop , P H , Havekes , B , Vriens , M R & Valk , G D 2018 , ' High Fear of Disease Occurrence Is Associated With Low Quality of Life in Patients With Multiple Endocrine Neoplasia Type 1: Results From the Dutch MEN1 Study Group ' , Journal of Clinical ....

مصطلحات موضوعية: CANCER RECURRENCE, BREAST-CANCER, OF-LIFE, SURVIVORS, TUMORS, DISTRESS, DEATH

الوصف: Objective: Multiple endocrine neoplasia type 1 (MEN1) is a hereditary disease characterized by a high risk of developing primary hyperparathyroidism, duodenopancreatic neuroendocrine tumors, and pituitary tumors (PITs). It is unclear if having MEN1 leads to psychological distress because of fear of disease occurrence (FDO), thereby potentially affecting quality of life. Design: A cross-sectional study was performed using the Dutch MEN1 cohort. All patients received the Cancer Worry Scale (a score >= 14 reflects high FDO), the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), and questions on sociodemographic and medical history. Results: A total of 227 of 285 (80%) eligible patients with MEN1 completed the questionnaire. The mean (+/- standard deviation) age was 47 6 15 years. Overall, patients experienced an FDO of 15.1 +/- 4.7, with 58% of patients having a score >= 14. This is higher than reported in previous studies assessing fear of cancer recurrence in different cancer populations (31% to 52%). Adjusted for age and sex, the FDO score was negatively associated with almost all SF-36 subscales. In multivariable analysis, the diagnosis of a PIT, a pancreatic neuroendocrine tumor, and not being employed were associated with FDO (P < 0.05). Patients had higher FDO scores for their family members than for themselves. Conclusion: The majority of patients with MEN1 have FDO for themselves and even more for their relatives. This psychological distress is associated with a lower health-related quality of life. Therefore, in the medical care for MEN1, emphasis should also be placed on FDO and quality of life.

الإتاحة: https://doi.org/10.1210/jc.2018-00259Test
https://cris.maastrichtuniversity.nl/en/publications/02530806-b0a6-4db5-b04e-891259c7dd2aTest

المؤلفون: Demirdas, Serwet, van Spronsen, Francjan J., Hollak, Carla E. M., van der Lee, J. Hanneke, Bisschop, Peter H., Vaz, Fred M., ter Horst, Nienke M., Rubio-Gozalbo, M. Estela, Bosch, Annet M.

المصدر: Demirdas , S , van Spronsen , F J , Hollak , C E M , van der Lee , J H , Bisschop , P H , Vaz , F M , ter Horst , N M , Rubio-Gozalbo , M E & Bosch , A M 2018 , ' Response to the Letter to the Editor Regarding "Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria" ' , Annals of Nutrition and Metabolism , vol. 72 , no. 1 , pp. 80-81 . https://doi.org/10.1159/000486185Test

مصطلحات موضوعية: FRACTURES

الإتاحة: https://doi.org/10.1159/000486185Test
https://cris.maastrichtuniversity.nl/en/publications/9cb97897-4cf4-4aad-bf0b-4b32d20ecfebTest

المؤلفون: Demirdas, Serwet, van Spronsen, Francjan J., Hollak, Carla E. M., van der Lee, J. Hanneke, Bisschop, Peter H., Vaz, Fred M., ter Horst, Nienke M., Rubio-Gozalbo, M. Estela, Bosch, Annet M.

المصدر: Demirdas , S , van Spronsen , F J , Hollak , C E M , van der Lee , J H , Bisschop , P H , Vaz , F M , ter Horst , N M , Rubio-Gozalbo , M E & Bosch , A M 2017 , ' Micronutrients, Essential Fatty Acids and Bone Health in Phenylketonuria ' , Annals of Nutrition and Metabolism , vol. 70 , no. 2 , pp. 111-121 . https://doi.org/10.1159/000465529Test

مصطلحات موضوعية: Phenylketonuria, Micronutrients, Essential fatty acids, Bone mineral density, Phenylalanine, Osteopenia, Osteoporosis, YOUNG-ADULTS, VITAMIN-D, SELENIUM, CHILDREN, DIET, PKU, SUPPLEMENTATION, METAANALYSIS, ADOLESCENTS

الوصف: Introduction: In phenylketonuria (PKU), a natural protein-restricted dietary treatment prevents severe cognitive impairment. Nutrient deficiencies may occur due to strict diet. This study is aimed at evaluating the dietary intake and blood concentrations of micronutrients and essential fatty acids (FA), bone mineral density (BMD) and fracture history in patients on long-term dietary treatment. Methods: Sixty early diagnosed Dutch patients (aged 1-39 years) were included in a multi-center cross-sectional study. Their dietary intake, blood concentrations of micronutrients, FA, fracture history and BMD were assessed. Results: Selenium dietary intake and serum concentrations were low in 14 and 46% of patients, respectively. The serum 25-OH vitamin D2 + D3 concentration was low in 14% of patients while 20% of patients had a low vitamin D intake. Zinc serum concentrations were below normal in 14% of patients, despite adequate intake. Folic acid serum concentrations and intake were elevated. Despite safe total protein and fat intake, arginine plasma concentrations and erythrocyte eicosapentaenoic acid were below reference values in 19 and 6% of patients, respectively. Low BMD (Z-score

الإتاحة: https://doi.org/10.1159/000465529Test
https://cris.maastrichtuniversity.nl/en/publications/b8fdea60-b139-4ab6-859a-f90dc9e704c9Test

المؤلفون: van Leeuwaarde, Rachel S., Dreijerink, Koen M., Ausems, Margreet G., Beijers, Hanneke J., Dekkers, Olaf M., de Herder, Wouter W., van der Horst-Schrivers, Anouk N., Drent, Madeleine L., Bisschop, Peter H., Havekes, Bas, Peeters, Petra H. M., Pijnappel, Ruud M., Vriens, Menno R., Valk, Gerlof D.

المصدر: van Leeuwaarde , R S , Dreijerink , K M , Ausems , M G , Beijers , H J , Dekkers , O M , de Herder , W W , van der Horst-Schrivers , A N , Drent , M L , Bisschop , P H , Havekes , B , Peeters , P H M , Pijnappel , R M , Vriens , M R & Valk , G D 2017 , ' MEN1-Dependent Breast Cancer : Indication for Early Screening? Results From the Dutch MEN1 Study Group ' , Journal of Clinical Endocrinology & Metabolism ....

مصطلحات موضوعية: ENDOCRINE NEOPLASIA TYPE-1, BRCA2 MUTATION CARRIERS, SELECTION BIAS, RISK, BENEFITS, SMOKING, HARMS, NONCARRIERS, PENETRANCE, MORTALITY

الوصف: Objective: Multiple endocrine neoplasia type 1 (MEN1) is associated with an early-onset elevated breast cancer risk. This finding potentially has implications for breast cancer screening for women with MEN1, and therefore it is necessary to assess whether other risk factors are involved to identify those at greatest risk. Design: A cross-sectional case control study was performed using the Dutch MEN1 cohort, including >90% of the adult Dutch MEN1 population. All women with a confirmed MEN1 mutation received a questionnaire regarding cancer family history and breast cancer-related endocrine and general cancer risk factors. Results: A total of 138 of 165 (84%) eligible women with MEN1 completed the questionnaire. Eleven of the 138 women had breast cancer. Another 34 relatives with breast cancer were identified in the families of the included women, of whom 11 were obligate MEN1 carriers, 14 had no MEN1 mutation, and 9 had an unknown MEN1 status. The median age at breast cancer diagnosis of women with MEN1 (n = 22) was 45 years (range, 30 to 80 years), in comparison with 57.5 years (range, 40 to 85 years) in female relatives without MEN1 (n = 14; P = 0.03) and 61.2 years in the Dutch reference population. Known endocrine risk factors and general risk factors were not different for women with and without breast cancer. Conclusion: The increased breast cancer risk in MEN1 carriers was not related to other known breast cancer risk factors or familial cancer history, and therefore breast cancer surveillance from the age of 40 years for all women with MEN1 is justifiable.

الإتاحة: https://doi.org/10.1210/jc.2016-3690Test
https://cris.maastrichtuniversity.nl/en/publications/b2d94e72-4a3a-41f1-a751-607a099be067Test

المؤلفون: van Leeuwaarde, Rachel S., van Nesselrooij, Bernadette P. M., Hermus, Ad R., Dekkers, Olaf M., de Herder, Wouter W., van der Horst-Schrivers, Anouk N., Drent, Madeleine L., Bisschop, Peter H., Havekes, Bas, Vriens, Menno R., de Laat, Joanne M., Pieterman, Carolina R. C., Valk, Gerlof D.

المصدر: van Leeuwaarde , R S , van Nesselrooij , B P M , Hermus , A R , Dekkers , O M , de Herder , W W , van der Horst-Schrivers , A N , Drent , M L , Bisschop , P H , Havekes , B , Vriens , M R , de Laat , J M , Pieterman , C R C & Valk , G D 2016 , ' Impact of Delay in Diagnosis in Outcomes in MEN1: Results From the Dutch MEN1 Study Group ' , Journal of Clinical Endocrinology & Metabolism , ....

الوصف: Objective: Identifying a germline mutation in the multiple endocrine neoplasia type 1 (MEN1) gene in an index case has consequences for a whole family. Eligible family members should be offered genetic counseling and MEN1 mutation testing. Subsequently, clinical screening of mutation carriers according to the guidelines should be initiated. We assessed whether there is a lag time from MEN1 diagnosis of the index case to MEN1 diagnosis of family members. In addition, we determined whether this lag time was associated with an increased morbidity and mortality risk. Design: A cohort study was performed using the Dutch MEN1 database, including >90% of the Dutch MEN1 population >16 years of age (n = 393). Results: Fifty-eight MEN1 families were identified, of whom 57 were index cases and 247 were non-index cases (n = 304). The median lag time in MEN1 diagnosis of family members was 3.5 (range, 0-30) years. At the time of MEN1 diagnosis, 30 (12.1%) non-index cases had a duodeno-pancreatic neuroendocrine tumor, of whom 20% had metastases with a mean lag time of 10.9 years, in comparison with 7.1 years without metastases. Twenty-five (10.1%) non-index cases had a pituitary tumor, of whom 80% had a microadenoma and 20% had a macroadenoma, with mean lag times of 7.2 and 10.6 years, respectively. Ninety-five (38.4%) non-index cases had a primary hyperparathyroidism with a mean lag time of 9.5 years in comparison with seven patients without a primary hyperparathyroidism with a mean lag time of 3 years (P = .005). Ten non-index cases died because of a MEN1-related cause that developed during or before the lag time. Conclusion: There is a clinically relevant delay in MEN1 diagnosis in families because of a lag time between the diagnosis of an index case and the rest of the family. More emphasis should be placed on the conduct of proper counseling and genetic testing in all eligible family members.

الإتاحة: https://doi.org/10.1210/jc.2015-3766Test
https://cris.maastrichtuniversity.nl/en/publications/b8bc352b-1c62-49c4-a3c1-6ea0a692ce93Test

المؤلفون: de Laat, Joanne M., van der Luijt, Rob B., Pieterman, Carolina R. C., Oostveen, Maria P., Hermus, Ad R., Dekkers, Olaf M., de Herder, Wouter W., van der Horst-Schrivers, Anouk N., Drent, Madeleine L., Bisschop, Peter H., Havekes, Bas, Vriens, Menno R., Valk, Gerlof D.

المصدر: de Laat , J M , van der Luijt , R B , Pieterman , C R C , Oostveen , M P , Hermus , A R , Dekkers , O M , de Herder , W W , van der Horst-Schrivers , A N , Drent , M L , Bisschop , P H , Havekes , B , Vriens , M R & Valk , G D 2016 , ' MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients ' , BMC Medicine , vol. 14 . https://doi.org/10.1186/s12916-016-0708-1Test

مصطلحات موضوعية: MEN1, Diagnosis, Survival

الوصف: Background: Multiple Endocrine Neoplasia type 1 (MEN1) is diagnosed when two out of the three primary MEN1-associated endocrine tumors occur in a patient. Up to 10-30 % of those patients have no mutation in the MEN1 gene. It is unclear if the phenotype and course of the disease of mutation-negative patients is comparable with mutation-positive patients and if these patients have true MEN1. The present study aims to describe and compare the clinical course of MEN1 mutation-negative patients with two out of the three main MEN1 manifestations and mutation-positive patients during long-term follow-up. Methods: This is a cohort study performed using the Dutch MEN1 database, including > 90 % of the Dutch MEN1 population. Results: A total of 293 (90.7 %) mutation-positive and 30 (9.3 %) mutation-negative MEN1 patients were included. Median age of developing the first main MEN1 manifestation was higher in mutation-negative patients (46 vs. 33 years) (P = 0.007). Mutation-negative patients did not develop a third main MEN1 manifestation in the course of follow-up compared to 48.3 % of mutation-positive patients (P <0.001). Median survival in mutation-positive patients was estimated at 73.0 years (95 % CI, 69.5-76.5) compared to 87.0 years (95 % CI not available) in mutation-negative patients (P = 0.001). Conclusions: Mutation-positive and mutation-negative MEN1 patients have a different phenotype and clinical course. Mutation-negative patients develop MEN1 manifestations at higher age and have a life expectancy comparable with the general population. The apparent differences in clinical course suggest that MEN1 mutation-negative patients do not have true MEN1, but another MEN1-like syndrome or sporadic co-incidence of two neuro-endocrine tumors.

الإتاحة: https://doi.org/10.1186/s12916-016-0708-1Test
https://cris.maastrichtuniversity.nl/en/publications/bcf13a96-5e90-420e-8517-8c88f3f9328cTest