Tobias KraussAlfonso Massimiliano FerraraThera P. LinksUlrich WellnerIrina BancosAndrey KvachenyukKarina Villar Gómez De Las HerasMarina Y. YukinaRoman PetrovGarrett BullivantLaura Von DueckerSwati JadhavUrsula PloeckingerStaffan WelinCamilla Schalin-JänttiOliver GimmMarija PfeiferJoanne NgeowKornelia Hasse-LazarGabriela SansóXiaoping QiM. Umit UgurluRene E. DiazNelson WohllkMariola PeczkowskaJens AberleDelmar M. LourençoMaria A.A. PereiraMaria C.B.V. FragosoAna O. HoffMadson Q. AlmeidaAlice H.D. ViolanteAna R.P. QuiduteZhewei ZhangMònica RecasensLuis Robles DíazTada KunavisarutTaweesak WannachaleeSirinart SirinvaravongEric JonaschSimona Grozinsky-GlasbergMerav FraenkelDmitry BeltsevichViacheslav I. EgorovDirk BauschMatthias SchottNikolaus TilingGianmaria PennelliStefan ZschiedrichRoland DärrJuri RufTimm DeneckeKarl Heinrich LinkStefania ZovatoErnst Von DobschuetzSvetlana YaremchukHolger AmthauerOzer MakayAttila PatocsMartin K. WalzTobias B. HuberJochen SeufertPer HellmanRaymond H. KimEkaterina KuchinskayaFrancesca SchiaviAngelica MalinocNicole ReischBarbara JarzabMarta BarontiniAndrzej JanuszewiczNalini ShahWilliam F. YoungGiuseppe OpocherCharis EngHartmut P.H. NeumannBirke BauschThe Second Affiliated Hospital Zhejiang University School of MedicineEndocrinology Research CentreIstituto Oncologico Veneto IOV - IRCCSInstytut Kardiologii im. Prymasa Tysiaclecia Stefana Kardynała WyszynskiegoV. P. Komisarenko Institute of Endocrinology and Metabolism of the Ukraine Academy of Medical SciencesMaria Sklodowska-Curie Institute – Oncology CenterTaussig Cancer CenterLudwig-Maximilians-Universität MünchenUniversität HamburgMarmara ÜniversitesiCharité – Universitätsmedizin BerlinUniversität Freiburg im BreisgauHeinrich Heine UniversitätSemmelweis EgyetemUniverzitetni Klinični Center LjubljanaUniversidade Federal do CearaHospital de Ninos Ricardo GutierrezUniversity of TorontoAkademiska SjukhusetUniversity of Texas MD Anderson Cancer CenterHospital Universitari de Girona Dr. Josep TruetaUniversidad de ChileUniversität zu LübeckFaculty of Medicine, Siriraj Hospital, Mahidol UniversityLinköpings universitetOntario Cancer Institute University of TorontoUniversidade de Sao Paulo - USPHospital del SalvadorUniversity of Groningen, University Medical Center GroningenMayo ClinicNanyang Technological UniversityUniversitätsklinikum Hamburg-Eppendorf und Medizinische FakultätHospital Universitario 12 de OctubreHelsingin YliopistoKing Edward Memorial Hospital IndiaUniversità degli Studi di PadovaHadassah University Medical CentreUniversidade Federal do Rio de JaneiroDivision of Endocrine SurgeryCentral ServicesBakhrushin Brothers Moscow City HospitalAsklepios Paulinen KlinikHuyssens Foundation ClinicsWenzhou Medical University2019-08-232019-08-232018-09-01Endocrine-Related Cancer. Vol.25, No.9 (2018), 783-79314796821135100882-s2.0-85050883238https://repository.li.mahidol.ac.th/handle/20.500.14594/45073© 2018 Society for Endocrinology Published by Bioscientifica Ltd. Printed in Great Britain. 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 2cm; P<0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P=0.001). All metastatic tumors were ≥2.8cm. 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 ≥2.8cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8cm vs ≥2.8cm (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 2.8cm 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1530/ERC-18-0100