BackgroundSurgical resection is the only potentially curative treatment for pancreatic neuroendocrine tumors. The choice for the type of procedure is influenced by the expected oncological benefit and the anticipated risk of procedure-specific complications. Few studies have focused on complications in these patients. This cohort study aimed to assess complications and risk factors after resections of pancreatic neuroendocrine tumors.MethodsPatients undergoing resection of a pancreatic neuroendocrine tumor were identified within 2 centers of excellence. Complications were assessed according to the Clavien-Dindo classification and the comprehensive complication index. Logistic regression was performed to compare surgical procedures with adjustment for potential confounders (Clavien-Dindo ≥3).ResultsThe cohort comprised 123 patients, including 12 enucleations, 50 distal pancreatectomies, 51 pancreatoduodenectomies, and 10 total/combined pancreatectomies. Mortality was 0.8%, a severe complication occurred in 41.5%, and the failure-to-rescue rate was 2.0%. The median comprehensive complication index was 22.6 (0–100); the comprehensive complication index increased after more extensive resections. After adjustment, a pancreatoduodenectomy, as compared to a distal pancreatectomy, increased the risk for a severe complication (odds ratio 3.13 [95% confidence interval 1.32–7.41]). Of the patients with multiple endocrine neoplasia type 1 or von Hippel-Lindau, 51.9% developed a severe complication vs 38.5% with sporadic disease. After major resections, morbidity was significantly higher in patients with multiple endocrine neoplasia type 1/von Hippel-Lindau (comprehensive complication index 45.1 vs 28.9, P = .029).ConclusionSurgery for pancreatic neuroendocrine tumors is associated with a high rate of complications but low failure-to-rescue in centers of excellence. Complications are procedure-specific. Major resections in patients with multiple endocrine neoplasia type 1/von Hippel-Lindau appear to increase the risk of complications.
Objective: To study the feasibility and impact of a nationwide training program in minimally invasive distal pancreatectomy (MIDP). Summary of Background Data: Superior outcomes of MIDP compared with open distal pancreatectomy have been reported. In the Netherlands (2005 to 2013) only 10% of distal pancreatectomies were in a minimally invasive fashion and 85% of surgeons welcomed MIDP training. The feasibility and impact of a nationwide training program is unknown. Methods: From 2014 to 2015, 32 pancreatic surgeons from 17 centers participated in a nationwide training program in MIDP, including detailed technique description, video training, and proctoring on-site. Outcomes of MIDP before training (2005–2013) were compared with outcomes after training (2014–2015). Results: In total, 201 patients were included; 71 underwent MIDP in 9 years before training versus 130 in 22 months after training (7-fold increase, P < 0.001). The conversion rate (38% [n = 27] vs 8% [n = 11], P < 0.001) and blood loss were lower after training and more pancreatic adenocarcinomas were resected (7 [10%] vs 28 [22%], P = 0.03), with comparable R0-resection rates (4/7 [57%] vs 19/28 [68%], P = 0.67). Clavien-Dindo score ≥III complications (15 [21%] vs 19 [15%], P = 0.24) and pancreatic fistulas (20 [28%] vs 41 [32%], P = 0.62) were not significantly different. Length of hospital stay was shorter after training (9 [7–12] vs 7 [5–8] days, P < 0.001). Thirty-day mortality was 3% vs 0% (P = 0.12). Conclusion: A nationwide MIDP training program was feasible and followed by a steep increase in the use of MIDP, also in patients with pancreatic cancer, and decreased conversion rates. Future studies should determine whether such a training program is applicable in other settings.
Epigenetic changes contribute to pancreatic neuroendocrine tumor (PanNET) development. Hypermethylation of promoter DNA as a cause of tumor suppressor gene silencing is a well-established oncogenic mechanism that is potentially reversible and therefore an interesting therapeutic target. Multiple endocrine neoplasia type 1 (MEN1) is the most frequent cause of inherited PanNETs. The aim of this study was to determine promoter methylation profiles in MEN1-related PanNETs.Methylation-specific multiplex ligation-dependent probe amplification was used to assess promoter methylation of 56 tumor suppressor genes in MEN1-related (n = 61) and sporadic (n = 34) PanNETs. Differences in cumulative methylation index (CMI), individual methylation percentages and frequency of promoter hypermethylation between subgroups were analyzed.We found promoter methylation of a large number of potential tumor suppressor genes. CMI (median CMI: 912 vs 876, P = 0.207) was the same in MEN1-related and sporadic PanNETs. We found higher methylation percentages of CASP8 in MEN1-related PanNETs (median: 59% vs 16.5%, P = 0.002). In MEN1-related non-functioning PanNETs, the CMI was higher in larger PanNETs (>2 cm) (median: 969.5 vs 838.5; P = 0.021) and in PanNETs with liver metastases (median: 1036 vs 869; P = 0.013). Hypermethylation of MGMT2 was more frequent in non-functioning PanNETs compared to insulinomas (median: 44.7% vs 8.3%; P = 0.022). Hypermethylation of the Von Hippel-Lindau gene promoter was observed in one MEN1-related PanNET and was associated with loss of protein expression.Promoter hypermethylation is a frequent event in MEN1-related and sporadic PanNETs. Targeting DNA methylation could be of therapeutic value in MEN1 patients with advanced PanNETs.
