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

Issued Date

2018-09-01

Resource Type

Article

ISSN

14796821
13510088

DOI

10.1530/ERC-18-0100

Other identifier(s)

2-s2.0-85050883238

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Endocrine-Related Cancer. Vol.25, No.9 (2018), 783-793

Suggested Citation

Tobias Krauss, Alfonso Massimiliano Ferrara, Thera P. Links, Ulrich Wellner, Irina Bancos, Andrey Kvachenyuk, Karina Villar Gómez De Las Heras, Marina Y. Yukina, Roman Petrov, Garrett Bullivant, Laura Von Duecker, Swati Jadhav, Ursula Ploeckinger, Staffan Welin, Camilla Schalin-Jäntti, Oliver Gimm, Marija Pfeifer, Joanne Ngeow, Kornelia Hasse-Lazar, Gabriela Sansó, Xiaoping Qi, M. Umit Ugurlu, Rene E. Diaz, Nelson Wohllk, Mariola Peczkowska, Jens Aberle, Delmar M. Lourenço, Maria A.A. Pereira, Maria C.B.V. Fragoso, Ana O. Hoff, Madson Q. Almeida, Alice H.D. Violante, Ana R.P. Quidute, Zhewei Zhang, Mònica Recasens, Luis Robles Díaz, Tada Kunavisarut, Taweesak Wannachalee, Sirinart Sirinvaravong, Eric Jonasch, Simona Grozinsky-Glasberg, Merav Fraenkel, Dmitry Beltsevich, Viacheslav I. Egorov, Dirk Bausch, Matthias Schott, Nikolaus Tiling, Gianmaria Pennelli, Stefan Zschiedrich, Roland Därr, Juri Ruf, Timm Denecke, Karl Heinrich Link, Stefania Zovato, Ernst Von Dobschuetz, Svetlana Yaremchuk, Holger Amthauer, Ozer Makay, Attila Patocs, Martin K. Walz, Tobias B. Huber, Jochen Seufert, Per Hellman, Raymond H. Kim, Ekaterina Kuchinskaya, Francesca Schiavi, Angelica Malinoc, Nicole Reisch, Barbara Jarzab, Marta Barontini, Andrzej Januszewicz, Nalini Shah, William F. Young, Giuseppe Opocher, Charis Eng, Hartmut P.H. Neumann, Birke Bausch Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors. Endocrine-Related Cancer. Vol.25, No.9 (2018), 783-793. doi:10.1530/ERC-18-0100 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45073

Research Projects

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Thesis

Title

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

Author(s)

Tobias Krauss
 Alfonso Massimiliano Ferrara
 Thera P. Links
 Ulrich Wellner
 Irina Bancos
 Andrey Kvachenyuk
 Karina Villar Gómez De Las Heras
 Marina Y. Yukina
 Roman Petrov
 Garrett Bullivant
 Laura Von Duecker
 Swati Jadhav
 Ursula Ploeckinger
 Staffan Welin
 Camilla Schalin-Jäntti
 Oliver Gimm
 Marija Pfeifer
 Joanne Ngeow
 Kornelia Hasse-Lazar
 Gabriela Sansó
 Xiaoping Qi
 M. Umit Ugurlu
 Rene E. Diaz
 Nelson Wohllk
 Mariola Peczkowska
 Jens Aberle
 Delmar M. Lourenço
 Maria A.A. Pereira
 Maria C.B.V. Fragoso
 Ana O. Hoff
 Madson Q. Almeida
 Alice H.D. Violante
 Ana R.P. Quidute
 Zhewei Zhang
 Mònica Recasens
 Luis Robles Díaz
 Tada Kunavisarut
 Taweesak Wannachalee
 Sirinart Sirinvaravong
 Eric Jonasch
 Simona Grozinsky-Glasberg
 Merav Fraenkel
 Dmitry Beltsevich
 Viacheslav I. Egorov
 Dirk Bausch
 Matthias Schott
 Nikolaus Tiling
 Gianmaria Pennelli
 Stefan Zschiedrich
 Roland Därr
 Juri Ruf
 Timm Denecke
 Karl Heinrich Link
 Stefania Zovato
 Ernst Von Dobschuetz
 Svetlana Yaremchuk
 Holger Amthauer
 Ozer Makay
 Attila Patocs
 Martin K. Walz
 Tobias B. Huber
 Jochen Seufert
 Per Hellman
 Raymond H. Kim
 Ekaterina Kuchinskaya
 Francesca Schiavi
 Angelica Malinoc
 Nicole Reisch
 Barbara Jarzab
 Marta Barontini
 Andrzej Januszewicz
 Nalini Shah
 William F. Young
 Giuseppe Opocher
 Charis Eng
 Hartmut P.H. Neumann
 Birke Bausch

Other Contributor(s)

The Second Affiliated Hospital Zhejiang University School of Medicine
 Endocrinology Research Centre
 Istituto Oncologico Veneto IOV - IRCCS
 Instytut Kardiologii im. Prymasa Tysiaclecia Stefana Kardynała Wyszynskiego
 V. P. Komisarenko Institute of Endocrinology and Metabolism of the Ukraine Academy of Medical Sciences
 Maria Sklodowska-Curie Institute – Oncology Center
 Taussig Cancer Center
 Ludwig-Maximilians-Universität München
 Universität Hamburg
 Marmara Üniversitesi
 Charité – Universitätsmedizin Berlin
 Universität Freiburg im Breisgau
 Heinrich Heine Universität
 Semmelweis Egyetem
 Univerzitetni Klinični Center Ljubljana
 Universidade Federal do Ceara
 Hospital de Ninos Ricardo Gutierrez
 University of Toronto
 Akademiska Sjukhuset
 University of Texas MD Anderson Cancer Center
 Hospital Universitari de Girona Dr. Josep Trueta
 Universidad de Chile
 Universität zu Lübeck
 Faculty of Medicine, Siriraj Hospital, Mahidol University
 Linköpings universitet
 Ontario Cancer Institute University of Toronto
 Universidade de Sao Paulo - USP
 Hospital del Salvador
 University of Groningen, University Medical Center Groningen
 Mayo Clinic
 Nanyang Technological University
 Universitätsklinikum Hamburg-Eppendorf und Medizinische Fakultät
 Hospital Universitario 12 de Octubre
 Helsingin Yliopisto
 King Edward Memorial Hospital India
 Università degli Studi di Padova
 Hadassah University Medical Centre
 Universidade Federal do Rio de Janeiro
 Division of Endocrine Surgery
 Central Services
 Bakhrushin Brothers Moscow City Hospital
 Asklepios Paulinen Klinik
 Huyssens Foundation Clinics
 Wenzhou Medical University

Abstract

© 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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/45073

Collections

Scopus 2018