PMID- 28938468
OWN - NLM
STAT- MEDLINE
DCOM- 20171031
LR  - 20180518
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 102
IP  - 10
DP  - 2017 Oct 1
TI  - Long-Term Natural Course of Small Nonfunctional Pancreatic Neuroendocrine Tumors 
      in MEN1-Results From the Dutch MEN1 Study Group.
PG  - 3795-3805
LID - 10.1210/jc.2017-00372 [doi]
AB  - BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) are highly prevalent in 
      patients with multiple endocrine neoplasia type 1 (MEN1), and metastatic disease 
      is an important cause of MEN1-related mortality. Especially small nonfunctional 
      (NF) pNETs pose a challenge to the treating physician and more information is 
      needed regarding their natural course. We assessed long-term natural history of 
      small NF-pNETs and its modifiers in the Dutch MEN1 population. PATIENTS AND 
      METHODS: Retrospective longitudinal observational cohort study of patients with 
      small (<2 cm) NF-pNETs from the Dutch national MEN1 database, which includes >90% 
      of the Dutch MEN1 population. Modifiers of long-term natural course were analyzed 
      using linear mixed-models analysis. RESULTS: Growth rate of the 115 included 
      small NF-pNETs from 99 patients was slow (0.4 mm/y; 95% confidence interval, 0.15 
      to 0.59). Seventy percent of the tumors was stable and a subgroup of 30% of the 
      tumors was growing (1.6 mm/y; 95% confidence interval, 1.1 to 2.0). No 
      differences in clinical characteristics were identified between growing and 
      stable tumors. Within the subgroup of growing tumors, germline missense mutations 
      were significantly associated with accelerated growth compared with nonsense and 
      frameshift mutations. CONCLUSION: The majority of small NF-pNETs are stable at 
      long-term follow-up, irrespective of the underlying MEN1 genotype. A subgroup of 
      tumors is slowly growing but cannot be identified on clinical grounds. In this 
      subgroup, tumors with missense mutations exhibited faster growth. Additional 
      events appear necessary for pNETs to progress. Future studies should be aimed at 
      identifying these molecular driving events, which could be used as potential 
      biomarkers.
CI  - Copyright (c) 2017 Endocrine Society
FAU - Pieterman, Carolina R C
AU  - Pieterman CRC
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, 3508 GA 
      Utrecht, The Netherlands.
FAU - de Laat, Joanne M
AU  - de Laat JM
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, 3508 GA 
      Utrecht, The Netherlands.
FAU - Twisk, Jos W R
AU  - Twisk JWR
AD  - Department of Clinical Epidemiology and Biostatistics, VU University Medical 
      Center, 1007 MB Amsterdam, The Netherlands.
AD  - Department of Health Sciences, VU University, 1007 MB Amsterdam, The Netherlands.
FAU - van Leeuwaarde, Rachel S
AU  - van Leeuwaarde RS
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, 3508 GA 
      Utrecht, The Netherlands.
FAU - de Herder, Wouter W
AU  - de Herder WW
AD  - Department of Internal Medicine, Erasmus Medical Center, 3000 CA Rotterdam, The 
      Netherlands.
FAU - Dreijerink, Koen M A
AU  - Dreijerink KMA
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, 3508 GA 
      Utrecht, The Netherlands.
FAU - Hermus, Ad R M M
AU  - Hermus ARMM
AD  - Department of Endocrinology, Radboud University Medical Center, 6500 HB Nijmegen, 
      The Netherlands.
FAU - Dekkers, Olaf M
AU  - Dekkers OM
AD  - Departments of Endocrinology and Metabolism and Clinical Epidemiology, Leiden 
      University Medical Center, 2300 RC Leiden, The Netherlands.
FAU - van der Horst-Schrivers, Anouk N A
AU  - van der Horst-Schrivers ANA
AD  - Department of Endocrinology, University of Groningen, University Medical Center 
      Groningen, 9700 RB Groningen, The Netherlands.
FAU - Drent, Madeleine L
AU  - Drent ML
AD  - Department of Internal Medicine, Section of Endocrinology, VU University Medical 
      Center, 1007 MB Amsterdam, The Netherlands.
FAU - Bisschop, Peter H
AU  - Bisschop PH
AD  - Department of Endocrinology and Metabolism, Academic Medical Center, 1100 DD 
      Amsterdam, The Netherlands.
FAU - Havekes, Bastiaan
AU  - Havekes B
AD  - Department of Internal Medicine, Division of Endocrinology, Maastricht University 
      Medical Center, 6202 AZ Maastricht, The Netherlands.
FAU - Borel Rinkes, Inne H M
AU  - Borel Rinkes IHM
AD  - Department of Endocrine Surgical Oncology, University Medical Center Utrecht, 
      3508 GA Utrecht, The Netherlands.
FAU - Vriens, Menno R
AU  - Vriens MR
AD  - Department of Endocrine Surgical Oncology, University Medical Center Utrecht, 
      3508 GA Utrecht, The Netherlands.
FAU - Valk, Gerlof D
AU  - Valk GD
AD  - Department of Endocrine Oncology, University Medical Center Utrecht, 3508 GA 
      Utrecht, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - Non functioning pancreatic endocrine tumor
SB  - IM
MH  - Adult
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/complications/diagnosis/*pathology
MH  - Neuroendocrine Tumors/complications/diagnosis/*pathology
MH  - Pancreatic Neoplasms/complications/diagnosis/*pathology
MH  - Prognosis
MH  - Retrospective Studies
MH  - Time Factors
MH  - *Tumor Burden
MH  - Young Adult
EDAT- 2017/09/25 06:00
MHDA- 2017/11/01 06:00
CRDT- 2017/09/23 06:00
PHST- 2017/02/08 00:00 [received]
PHST- 2017/08/01 00:00 [accepted]
PHST- 2017/09/25 06:00 [pubmed]
PHST- 2017/11/01 06:00 [medline]
PHST- 2017/09/23 06:00 [entrez]
AID - 4064262 [pii]
AID - 10.1210/jc.2017-00372 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2017 Oct 1;102(10):3795-3805. doi: 
      10.1210/jc.2017-00372.