Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

Autor: Krauss T; Department of RadiologyMedical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Ferrara AM; Familial Cancer Clinic and OncoendocrinologyVeneto Institute of Oncology IOV- IRCCS, Padua, Italy., Links TP; Department of EndocrinologyUniversity of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Wellner U; Department of SurgeryUniversity of Luebeck, Luebeck, Germany., Bancos I; Division of EndocrinologyDiabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, USA., Kvachenyuk A; Institute of Endocrinology and MetabolismNAMS of Ukraine, Kiev, Ukraine., Villar Gómez de Las Heras K; Central ServicesServicio de Salud de Castilla-La Mancha (SESCAM), Toledo, Spain., Yukina MY; Department of SurgeryEndocrinology Research Center, Moscow, Russia., Petrov R; Department of SurgeryBakhrushin Brothers Moscow City Hospital, Moscow, Russia., Bullivant G; Princess Margaret Cancer CenterUniversity Health Network, Toronto, Ontario, Canada., von Duecker L; Department of Medicine IVFaculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany., Jadhav S; Department of EndocrinologyKEM Hospital, Mumbai, India., Ploeckinger U; Interdisciplinary Center of Metabolism: EndocrinologyDiabetes and Metabolism, Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany., Welin S; Department of Endocrine OncologyUppsala University Hospital, Uppsala, Sweden., Schalin-Jäntti C; EndocrinologyAbdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Gimm O; Department of Clinical and Experimental MedicineDepartment of Surgery, University of Linköping, Linköping, Sweden., Pfeifer M; Department of EndocrinologyUniversity Medical Center, Ljubljana, Slovenia., Ngeow J; Cancer Genetics ServiceDivision of Medical Oncology, National Cancer Center Singapore and Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore., Hasse-Lazar K; Department of Endocrine Oncology and Nuclear MedicineCenter of Oncology, MSC Memorial Institute, Gliwice, Poland., Sansó G; Centro de Investigaciones Endocrinológicas 'Dr Cesar Bergada' (CEDIE)Hospital de Niños Ricardo Gutiérrez, CABA, Buenos Aires, Argentina., Qi X; Department of Oncologic and Urologic Surgerythe 117th PLA Hospital, Wenzhou Medical University, Hangzhou, Peoples Republic of China., Ugurlu MU; Department of General SurgeryBreast and Endocrine Surgery Unit, Marmara University School of Medicine, Istanbul, Turkey., Diaz RE; Endocrine SectionHospital del Salvador, Santiago de Chile, Chile., Wohllk N; Department of MedicineEndocrine Section, Hospital del Salvador, University of Chile, Santiago de Chile, Chile., Peczkowska M; Department of HypertensionInstitute of Cardiology, Warsaw, Poland., Aberle J; 3rd Department of MedicineUniversity Medical Center Hamburg-Eppendorf, Hamburg, Germany., Lourenço DM Jr; Serviço de EndocrinologiaHospital das Clínicas (HCFMUSP) and Instituto do Cancer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Pereira MAA; Serviço de EndocrinologiaHospital das Clinicas (HCFMUSP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Fragoso MCBV; Serviço de EndocrinologiaHospital das Clínicas (HCFMUSP) and Instituto do Cancer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Hoff AO; Serviço de EndocrinologiaHospital das Clínicas (HCFMUSP) and Instituto do Cancer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Almeida MQ; Serviço de EndocrinologiaHospital das Clínicas (HCFMUSP) and Instituto do Cancer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil., Violante AHD; Department of Internal Medicine-EndocrinologyFaculty of medicine-Hospital Universitario Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil., Quidute ARP; Department of Physiology and PharmacologyDrug Research and Development Center (NPDM), Faculty of Medicine, Federal University of Ceará (UFC), Fortaleza, Brazil., Zhang Z; Department of Urology2nd Hospital of Zhejiang University, School of Medicine, Hangzhou, China., Recasens M; Hospital Universitari de GironaGerencia Territorial Girona, Institut Català de la Salut, Girona, Spain., Díaz LR; Unidad de Tumores DigestivosServicio de Oncología Médica, Hospital Universitario 12 de Octubre, Madrid, Spain., Kunavisarut T; Division of Endocrinology and metabolismSiriraj Hospital, Mahidol University, Bangkok, Thailand., Wannachalee T; Division of Endocrinology and metabolismSiriraj Hospital, Mahidol University, Bangkok, Thailand., Sirinvaravong S; Division of Endocrinology and metabolismSiriraj Hospital, Mahidol University, Bangkok, Thailand., Jonasch E; Department of Genitourinary Medical OncologyDivision of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Grozinsky-Glasberg S; Neuroendocrine Tumor DivisionEndocrinology & Metabolism Service, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel., Fraenkel M; Neuroendocrine Tumor DivisionEndocrinology & Metabolism Service, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel., Beltsevich D; Department of SurgeryEndocrinology Research Center, Moscow, Russia., Egorov VI; Department of SurgeryBakhrushin Brothers Moscow City Hospital, Moscow, Russia., Bausch D; Department of SurgeryUniversity of Luebeck, Luebeck, Germany., Schott M; Department of EndocrinologyHeinrich-Heine-University, Düsseldorf, Germany., Tiling N; Interdisciplinary Center of Metabolism: EndocrinologyDiabetes and Metabolism, Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany., Pennelli G; Department of Medicine (DIMED)Surgical Pathology Unit, University of Padua, Padua, Italy., Zschiedrich S; Department of Medicine IVFaculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany., Därr R; Department of Medicine IVFaculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany.; Department of Cardiology and Angiology IHeart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Ruf J; Department of Nuclear MedicineFaculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany., Denecke T; Department of RadiologyCampus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin, Germany., Link KH; Department of SurgeryAsklepios-Paulinen Klinik, Wiesbaden, Germany., Zovato S; Familial Cancer Clinic and OncoendocrinologyVeneto Institute of Oncology IOV- IRCCS, Padua, Italy., von Dobschuetz E; Section of Endocrine SurgeryReinbek Hospital, Academic Teaching Hospital University of Hamburg, Reinbek, Germany., Yaremchuk S; Institute of Endocrinology and MetabolismNAMS of Ukraine, Kiev, Ukraine., Amthauer H; Department of Clinical Nuclear MedicineCharité - Universitätsmedizin Berlin, Berlin, Germany., Makay Ö; Department of General SurgeryDivision of Endocrine Surgery, Izmir, Turkey., Patocs A; 2nd Department of Medicine and Molecular Medicine Research GroupHungarian Academy of Sciences, Semmelweis-University, Budapest, Hungary., Walz MK; Department of SurgeryHuyssens Foundation Clinics, Essen, Germany., Huber TB; 3rd Department of MedicineUniversity Medical Center Hamburg-Eppendorf, Hamburg, Germany., Seufert J; Department of Medicine IIFaculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany., Hellman P; Department of Surgical SciencesUppsala University, University Hospital, Uppsala, Sweden., Kim RH; Department of MedicineUniversity of Toronto, University Healthy Network & Mount Sinai Hospital, The Fred A Litwin Family Center in Genetic Medicine, Toronto, Ontario, Canada., Kuchinskaya E; Department of Clinical Genetics and Department of Clinical and Experimental MedicineLinköping University, Linköping, Sweden., Schiavi F; Familial Cancer Clinic and OncoendocrinologyVeneto Institute of Oncology IOV- IRCCS, Padua, Italy., Malinoc A; Department of Medicine IVFaculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany., Reisch N; Department of EndocrinologyLudwigs-Maximilians-University of Munich, Munich, Germany., Jarzab B; Department of Endocrine Oncology and Nuclear MedicineCenter of Oncology, MSC Memorial Institute, Gliwice, Poland., Barontini M; Centro de Investigaciones Endocrinológicas 'Dr Cesar Bergada' (CEDIE)Hospital de Niños Ricardo Gutiérrez, CABA, Buenos Aires, Argentina., Januszewicz A; Department of HypertensionInstitute of Cardiology, Warsaw, Poland., Shah N; Department of EndocrinologyKEM Hospital, Mumbai, India., Young WF Jr; Division of EndocrinologyDiabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, USA., Opocher G; Scientific DirectionVeneto Institute of Oncology IOV-IRCCS, Padua, Italy., Eng C; Genomic Medicine InstituteLerner Research Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA., Neumann HPH; Section for Preventive MedicineFaculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany., Bausch B; Department of Medicine IIFaculty of Medicine, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany birke.bausch@uniklinik-freiburg.de.
Jazyk: angličtina
Zdroj: Endocrine-related cancer [Endocr Relat Cancer] 2018 Sep; Vol. 25 (9), pp. 783-793. Date of Electronic Publication: 2018 May 10.
DOI: 10.1530/ERC-18-0100
Abstrakt: Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P  < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P  = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8 cm vs ≥2.8 cm (94% vs 85% by 10 years; P  = 0.020; 80% vs 50% at 10 years; P  = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.
(© 2018 Society for Endocrinology.)
Databáze: MEDLINE