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

被引：52

作者：

Krauss, Tobias ^{[1
]}

Ferrara, Alfonso Massimiliano ^{[2
]}

Links, Thera P. ^{[3
]}

Wellner, Ulrich ^{[4
]}

Bancoss, Irina ^{[5
]}

Kvachenyuk, Andrey ^{[6
]}

Gomez de las Heras, Karim Villar ^{[7
]}

Yukina, Marina Y. ^{[8
]}

Petrov, Roman ^{[9
]}

Bullivant, Garrett ^{[10
]}

von Duecker, Laura ^{[11
]}

Jadhav, Swati ^{[12
]}

Ploeckinger, Ursula ^{[13
]}

Welin, Staffan ^{[14
]}

Schalin-Jantti, Camilla ^{[15
,16
]}

Gimm, Oliver ^{[17
]}

Pfeifer, Marija ^{[18
]}

Ngeow, Joanne ^{[19
,20
]}

Hasse-Lazar, Kornelia ^{[21
]}

Sanso, Gabriela ^{[22
]}

Qi, Xiaoping ^{[23
]}

Ugurlu, M. Umit ^{[24
]}

Diaz, Rene E. ^{[25
]}

Wohllk, Nelson ^{[26
]}

Peczkowska, Mariola ^{[27
]}

Aberle, Jens ^{[28
]}

Lourenco Jr, Delmar M. ^{[29
,30
]}

Pereira, Maria A. A. ^{[31
]}

Fragoso, Maria C. B., V ^{[29
,30
]}

Hoff, Ana O. ^{[29
,30
]}

Almeida, Madson Q. ^{[29
,30
]}

Violante, Alice H. D. ^{[32
]}

Ouidute, Ana R. P. ^{[33
]}

Zhang, Zhewei ^{[34
]}

Recasens, Monica ^{[35
]}

Robles Diaz, Luis ^{[36
]}

Kunavisarut, Tada ^{[37
]}

Wannachalee, Taweesak ^{[37
]}

Sirinvaravong, Sirinart ^{[37
]}

Jonasch, Eric ^{[38
]}

Grozinsky-Glasberg, Simona ^{[39
]}

Fraenkel, Merav ^{[39
]}

Beltsevich, Dmitry ^{[8
]}

Egorov, Viacheslav, I ^{[9
]}

Bausch, Dirk ^{[4
]}

Schott, Matthias ^{[40
]}

Tiling, Nikolaus ^{[13
]}

Pennelli, Gianmaria ^{[41
]}

Zschiedrich, Stefan ^{[11
]}

Daerr, Roland ^{[11
,42
]}

机构：

[1] Univ Freiburg, Med Ctr, Fac Med, Dept Radiol, Freiburg, Germany

[2] IRCCS, Veneto Inst Oncol IOV, Familial Canc Clin & Oncoendocrinol, Padua, Italy

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands

[4] Univ Lubeck, Dept Surg, Lubeck, Germany

[5] Mayo Clin, Div Endocrinol Diabet Metab &Nutr, Rochester, MN USA

[6] NAMS Ukraine, Inst Endocrinol & Metab, Kiev, Ukraine

[7] Serv Salud Castilla La Mancha SESCAM, Cent Serv, Toledo, Spain

[8] Endocrinol Res Ctr, Dept Surg, Moscow, Russia

[9] Bakhrushin Bros Moscow City Hosp, Dept Surg, Moscow, Russia

[10] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[11] Albert Ludwigs Univ, Fac Med, Dept Med 4, Freiburg, Germany

[12] King Edward Mem Hosp, Dept Endocrinol, Bombay, Maharashtra, India

[13] Charite Univ Med Berlin, Interdisciplinary Ctr Metab Endocrinol Diabet & M, Campus Virchow Klinikum, Berlin, Germany

[14] Uppsala Univ Hosp, Dept Endocrine Oncol, Uppsala, Sweden

[15] Univ Helsinki, Abdominal Ctr, Endocrinol, Helsinki, Finland

[16] Helsinki Univ Hosp, Helsinki, Finland

[17] Univ Linkoping, Dept Clin & Expt Med, Dept Surg, Linkoping, Sweden

[18] Univ Med Ctr, Dept Endocrinol, Ljubljana, Slovenia

[19] Nanyang Technol Univ, Natl Canc Ctr Singapore, Canc Genet Serv, Div Med Oncol, Singapore, Singapore

[20] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore

[21] MSC Mem Inst, Ctr Oncol, Dept Endocrine Oncol & Nucl Med, Gliwice, Poland

[22] Hosp Ninos Dr Ricardo Gutierrez, Ctr Invest Endocrinol Dr Cesar Bergada CEDIE, Buenos Aires, DF, Argentina

[23] Wenzhou Med Univ, PLA Hosp 117, Dept Oncol & Urol Surg, Hangzhou, Zhejiang, Peoples R China

[24] Marmara Univ, Dept Gen Surg, Breast & Endocrine Surg Unit, Sch Med, Istanbul, Turkey

[25] Hosp Salvador, Endocrine Sect, Santiago, Chile

[26] Univ Chile, Hosp Salvador, Dept Med, Endocrine Sect, Santiago, Chile

[27] Inst Cardiol, Dept Hypertens, Warsaw, Poland

[28] Univ Med Ctr Hamburg Eppendorf, Dept Med 3, Hamburg, Germany

[29] Univ Sao Paulo, Serv Endocrinol, Hosp Clin HCFMUSP, Sao Paulo, Brazil

[30] Univ Sao Paulo, ICESP, Fac Med, Sao Paulo, Brazil

[31] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Serv Endocrinol, Sao Paulo, Brazil

[32] Univ Fed Rio de Janeiro, Dept Internal Med Endocrinol, Fac Med, Hosp Univ Clementino Fraga Filho, Rio De Janeiro, Brazil

[33] Fed Univ Ceara UFC, Fac Med, Dept Physiol & Pharmacol, Drug Res & Dev Ctr NPDM, Fortaleza, Ceara, Brazil

[34] Zhejiang Univ, Sch Med, Dept Urol, Hosp 2, Hangzhou, Zhejiang, Peoples R China

[35] Hosp Univ Girona, Inst Catala Salut, Gerencia Terr Girona, Girona, Spain

[36] Hosp Univ 12 Octubre, Serv Oncol Med, Unidad Tumores Digest, Madrid, Spain

[37] Mahidol Univ, Siriraj Hosp, Div Endocrinol & Metab, Bangkok, Thailand

[38] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Div Canc Med, Houston, TX 77030 USA

[39] Hadassah Hebrew Univ, Dept Med, Endocrinol & Metab Serv, Neuroendocrine Tumor Div,Med Ctr, Jerusalem, Israel

[40] Heinrich Heine Univ, Dept Endocrinol, Dusseldorf, Germany

[41] Univ Padua, Dept Med DIMED, Surg Pathol Unit, Padua, Italy

[42] Univ Freiburg, Heart Ctr Freiburg Univ, Fac Med, Dept Cardiol & Angiol 1, Freiburg, Germany

[43] Albert Ludwigs Univ, Fac Med, Dept Nucl Med, Freiburg, Germany

[44] Charite Univ Med Berlin, Dept Radiol, Campus Virchow Klinikum, Berlin, Germany

[45] Asklepios Paulinen Klin, Dept Surg, Wiesbaden, Germany

[46] Acad Teaching Hosp Univ Hamburg, Reinbek Hosp, Sect Endocrine Surg, Reinbek, Germany

[47] Charite Univ Med Berlin, Dept Clin Nucl Med, Berlin, Germany

[48] Dept Gen Surg, Div Endocrine Surg, Izmir, Turkey

[49] Semmelweis Univ, Hungarian Acad Sci, Dept Med 2, Budapest, Hungary

[50] Semmelweis Univ, Hungarian Acad Sci, Mol Med Res Grp, Budapest, Hungary

来源：

关键词：

PanNET; von Hippel-Lindau disease; survival; management recommendations; CLINICAL-FEATURES; JAPANESE PATIENTS; GA-68-DOTATOC; SURVEILLANCE; INVOLVEMENT; CRITERIA; PET/CT;

D O I：

10.1530/ERC-18-0100

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：783 / 793

页数：11

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