title: Management of MEN1 Related Nonfunctioning Pancreatic NETs: A Shifting Paradigm: Results From the DutchMEN1 Study Group.
abstract: To assess if surgery for Multiple Endocrine Neoplasia type 1 (MEN1) related nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) is effective for improving overall survival and preventing liver metastasis.
  
  
  
  MEN1 leads to multiple early-onset NF-pNETs. The evidence base for guiding the difficult decision who and when to operate is meager.
  
  
  
  MEN1 patients diagnosed with NF-pNETs between 1990 and 2014 were selected from the DutchMEN1 Study Group database, including > 90% of the Dutch MEN1 population. The effect of surgery was estimated using time-dependent Cox analysis with propensity score restriction and adjustment.
  
  
  
  Of the 152 patients, 53 underwent surgery and 99 were managed by watchful waiting. In the surgery group, tumors were larger and faster-growing, patients were younger, more often male, and were more often treated in centers that operated more frequently. Surgery for NF-pNETs was not associated with a significantly lower risk of liver metastases or death, [adjusted hazard ratio (HR) = 0.73 (0.25-2.11)]. Adjusted HR's after stratification by tumor size were: NF-pNETs <2 cm = 2.04 (0.31-13.59) and NF-pNETs 2-3 cm = 1.38 (0.09-20.31). Five out of the 6 patients with NF-pNETs >3 cm managed by watchful waiting developed liver metastases or died compared with 6 out of the 16 patients who underwent surgery.
  
  
  
  MEN1 patients with NF-pNETs <2 cm can be managed by watchful waiting, hereby avoiding major surgery without loss of oncological safety. The beneficial effect of a surgery in NF-pNETs 2 to 3 cm requires further research. In patients with NF-pNETs >3 cm, watchful waiting seems not advisable.
authors.affiliation: Department of Endocrine Surgical Oncology and Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Nell
authors.affiliation: Imaging Division, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Verkooijen
authors.affiliation: Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Carolina R C
authors.initials: CRC
authors.lastname: Pieterman
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
authors.affiliation: Department of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ad R
authors.initials: AR
authors.lastname: Hermus
authors.affiliation: Departments of Endocrinology and Metabolism and Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anouk N
authors.initials: AN
authors.lastname: van der Horst-Schrivers
authors.affiliation: Department of Internal Medicine, Section of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Madeleine L
authors.initials: ML
authors.lastname: Drent
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Bisschop
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Havekes
authors.affiliation: Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Inne H M
authors.initials: IHM
authors.lastname: Borel Rinkes
authors.affiliation: Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Menno R
authors.initials: MR
authors.lastname: Vriens
authors.affiliation: Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Gerlof D
authors.initials: GD
authors.lastname: Valk
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000517:prevention & control / Q000556:secondary; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000150:complications / Q000473:pathology / Q000601:surgery*; D010190:Pancreatic Neoplasms / Q000150:complications / Q000473:pathology / Q000601:surgery*; D016016:Proportional Hazards Models; D057832:Watchful Waiting