Management of MEN1 Related Nonfunctioning Pancreatic NETs: A Shifting Paradigm: Results From the DutchMEN1 Study Group

Sjoerd Nell, Helena M. Verkooijen, Carolina R. C. Pieterman, Wouter W. de Herder, Ad R. Hermus, Olaf M. Dekkers, Anouk N. van der Horst-Schrivers, Madeleine L. Drent, Peter H. Bisschop, Bas Havekes, Inne H. M. Borel Rinkes, Menno R. Vriens, Gerlof D. Valk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objective: 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. Background: MEN1 leads to multiple early-onset NF-pNETs. The evidence base for guiding the difficult decision who and when to operate is meager. Methods: 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. Results: 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. Conclusions: 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.
Original languageEnglish
Pages (from-to)1155-1160
Number of pages6
JournalAnnals of Surgery
Issue number6
Publication statusPublished - 1 Jun 2018


  • multiple endocrine neoplasia type 1
  • oncology
  • pancreatic neuroendocrine tumors
  • surgery
  • survival
  • GTE


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