• Sjoerd Nell, Helena M Verkooijen, PietermanCarolina R CCRCDepartment of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Wouter W de Herder, Ad R Hermus, Olaf M Dekkers, Anouk N van der Horst-Schrivers, Madeleine L Drent, Peter H Bisschop, Bas Havekes, Borel RinkesInne H MIHMDepartment of Endocrine Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands., Menno R Vriens, and Gerlof D Valk.
• Department of Endocrine Surgical Oncology and Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
• Ann. Surg. 2018 Jun 1; 267 (6): 1155-1160.

ObjectiveTo 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.BackgroundMEN1 leads to multiple early-onset NF-pNETs. The evidence base for guiding the difficult decision who and when to operate is meager.MethodsMEN1 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.ResultsOf 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.ConclusionsMEN1 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.

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