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Background: We sought to define the diagnostic yield and concordance rates between endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) and surgical pathology specimen following resection of pancreatic neuroendocrine tumors (pNET) less than 2 cm. Methods: Patients with a pNET less than 2 cm who underwent EUS-FNA were identified using a multi-institutional international database. Tumor differentiation, and Ki-67 index, as determined through EUS-FNA were examined and concordance rates between EUS-FNA and the surgical pathology were assessed. Results: Among 628 patients with a pNET less than 2 cm, 57.2% of patients had an EUS-FNA performed. Patients who underwent EUS had slightly smaller size tumors (1.3 vs 1.4 cm), and the pNETs were less likely to be functional (15.3% vs 26.8%) or symptomatic (48.5% vs 56.5%) (both P

Contains fulltext : 245221.pdf (Publisher’s version ) (Open Access) BACKGROUND: Metastasized pancreatic neuroendocrine tumors are the leading cause of death in patients with multiple endocrine neoplasia type 1. Aside from tumor size, prognostic factors of pancreatic neuroendocrine tumors are largely unknown. The present study aimed to assess whether the prognosis of patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors differs from those with resected multiple endocrine neoplasia type 1-related insulinomas and assessed factors associated with prognosis. METHODS: Patients who underwent resection of a multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors between 1990 and 2016 were identified in 2 databases: the DutchMEN Study Group and the International MEN1 Insulinoma Study Group databases. Cox regression was performed to compare liver metastases-free survival of patients with a nonfunctioning pancreatic neuroendocrine tumors versus those with an insulinoma and to identify factors associated with liver metastases-free survival. RESULTS: Out of 153 patients with multiple endocrine neoplasia type 1, 61 underwent resection for a nonfunctioning pancreatic neuroendocrine tumor and 92 for an insulinoma. Of the patients with resected lymph nodes, 56% (18/32) of nonfunctioning pancreatic neuroendocrine tumors had lymph node metastases compared to 10% (4/41) of insulinomas (P = .001). Estimated 10-year liver metastases-free survival was 63% (95% confidence interval 42%-76%) for nonfunctioning pancreatic neuroendocrine tumors and 87% (72%-91%) for insulinomas. After adjustment for size, World Health Organization tumor grade, and age, nonfunctioning pancreatic neuroendocrine tumors had an increased risk for liver metastases or death (hazard ratio 3.04 [1.47-6.30]). In pancreatic neuroendocrine tumors ≥2 cm, nonfunctioning pancreatic neuroendocrine tumors (2.99 [1.22-7.33]) and World Health Organization grade 2 (2.95 [1.02-8.50]) were associated with liver metastases-free survival. CONCLUSION: Patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors had a significantly lower liver metastases-free survival than patients with insulinomas. Postoperative counseling and follow-up regimens should be tumor type specific and at least consider size and World Health Organization grade.

Background: Pancreatoduodenectomy (PD) or distal pancreatectomy (DP) are common procedures for patients with a pancreatic neuroendocrine tumor (pNET). Nevertheless, certain patients may benefit from a pancreas-preserving resection such as enucleation (EN). The aim of this study was to define the indications and differences in long-term outcomes among patients undergoing EN and PD/DP. Methods: Patients undergoing resection of a pNET between 1992 and 2016 were identified. Indications and outcomes were evaluated, and propensity score matching (PSM) analysis was performed to compare long-term outcomes between patients who underwent EN versus PD/DP. Results: Among 1034 patients, 143 (13.8%) underwent EN, 304 (29.4%) PD, and 587 (56.8%) DP. Indications for EN were small size (1.5 cm, IQR:1.0–1.9), functional tumors (58.0%) that were mainly insulinomas (51.7%). After PSM (n = 109 per group), incidence of postoperative pancreatic fistula (POPF) grade B/C was higher after EN (24.5%) compared with PD/DP (14.0%) (p = 0.049). Median recurrence-free survival (RFS) was comparable among patients who underwent EN (47 months, 95% CI:23–71) versus PD/DP (37 months, 95% CI: 33–47, p = 0.480). Conclusion: Comparable long-term outcomes were noted among patients who underwent EN versus PD/DP for pNET. The incidence of clinically significant POPF was higher after EN.

Background: Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. Risk stratification with preoperatively available parameters could guide decision-making in multidisciplinary treatment concepts. C-reactive Protein (CRP) is linked to inferior survival in several malignancies. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs. Methods: A retrospective multicenter study with national exploration and international validation. CRP and other factors associated with overall survival (OS) were evaluated by multivariable cox-regression to create a clinical risk score (CRS). Predictive values regarding OS, disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by time-dependent receiver-operating characteristics. Results: Overall, 364 patients were included. Median CRP was significantly higher in patients &gt, 60 years, G3, and large tumors. In multivariable analysis, CRP was the strongest preoperative factor for OS in both cohorts. In the combined cohort, CRP (cut-off &ge, 0.2mg/dL, hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size &ge, 3.0cm (HR:1.83) showed a significant association with OS. A CRS incorporating these variables was associated with postoperative histological grading, T category, nodal positivity, and 90-day morbidity/mortality. Time-dependent area-under-the-curve at 60 months for OS, DSS, and RFS was 69%, 77%, and 67%, respectively (all p &lt, 0.001), and the inclusion of grading further improved the predictive potential (75%, 84%, and 78%, respectively). Conclusions: CRP is a significant marker of unfavorable oncological characteristics in panNENs. The proposed internationally validated CRS predicts histological features and patient survival.

In this case report, we describe a 40-year-old patient with a large grade 2 pancreatic neuroendocrine tumour (pNET) with spleen metastasis. Albeit radical resection, he developed liver metastasis after 2 years, for which he underwent radio frequency ablation and embolization, and was treated successfully with different subsequent lines of systemic therapy. Eight years after the initial diagnosis, he was admitted for symptomatic and refractory hypercalcaemia, due to calcitriol synthesis by the liver metastasis. After tumour load reduction by hemihepatectomy, there was an initial normalization of hypercalcaemia, until it recurred after 18 months. In this period, the liver metastasis had progressed despite chemo- and immunotherapy. Patient underwent an additional extend hemihepatectomy, from which he recovered well with normalization of calcium levels. This case illustrates the hormonal plasticity of pNETs and shows how prolonged survival can be achieved for metastatic pNET by multimodality approach.

Simple Summary Approximately 30% of patients with a pancreatic neuroendocrine tumor (pNET) will develop metastases. Curative-intent treatment largely involves resection. Identifying patients with early recurrence (ER) following resection might help tailor adjuvant therapies and the surveillance intensity. The aim of this retrospective study was to determine an evidence-based cut-off value for ER, and to explore risk factors associated with ER. ER was identified 18 months after surgery. Tumor size (OR 1.20, 95% CI 1.05–1.37, p = 0.007) and positive lymph nodes (OR 4.69, 95%CI 1.41–15.58, p = 0.01) were independently associated with ER. Patients with ER had lower post-recurrence free survival and overall survival than patients with late recurrence. These data support intensive follow-up shortly after surgery, and adjuvant therapy may help improve survival in pNET patients with ER after surgery. Abstract Background: Identifying patients at risk for early recurrence (ER) following resection for pancreatic neuroendocrine tumors (pNETs) might help to tailor adjuvant therapies and surveillance intensity in the post-operative setting. Methods: Patients undergoing surgical resection for pNETs between 1998–2018 were identified using a multi-institutional database. Using a minimum p-value approach, optimal cut-off value of recurrence-free survival (RFS) was determined based on the difference in post-recurrence survival (PRS). Risk factors for early recurrence were identified. Results: Among 807 patients who underwent curative-intent resection for pNETs, the optimal length of RFS to define ER was identified at 18 months (lowest p-value of 0.019). Median RFS was 11.0 months (95% 8.5–12.60) among ER patients (n = 49) versus 41.0 months (95% CI: 35.0–45.9) among non-ER patients (n = 77). Median PRS was worse among ER patients compared with non-ER patients (42.6 months vs. 81.5 months, p = 0.04). On multivariable analysis, tumor size (OR: 1.20, 95% CI: 1.05–1.37, p = 0.007) and positive lymph nodes (OR: 4.69, 95% CI: 1.41–15.58, p = 0.01) were independently associated with ER. Conclusion: An evidence-based cut-off value for ER after surgery for pNET was defined at 18 months. These data emphasized the importance of close follow-up in the first two years after surgery.

Background and objectives Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatis (NASH) may occur after pancreatic resection due to exocrine pancreatic insufficiency (EPI). Patients with long-term survival, such as after pancreatic neuroendocrine tumor (pNET) resection, are at risk of NAFLD/NASH. We aimed to determine the incidence and risk factors for new onset NAFLD/NASH and EPI after pNET resection. Methods Retrospective monocenter cohort study. Patients who underwent pNET resection (1992-2016) were assessed for new onset NAFLD/NASH and EPI. Postoperative NAFLD/NASH was determined by a blinded abdominal radiologist, who compared pre- and postoperative imaging. Results Out of 235 patients with pNET, a total of 112 patients underwent resection and were included with a median follow-up of 54 months. New onset NAFLD/NASH occurred in 20% and EPI in 49% of patients. Multivariate analysis showed that the only risk factor for new onset NAFLD/NASH was recurrent disease (OR 4.4, 95% CI 1.1-16.8, P = 0.031), but not EPI (OR 0.94, 95% CI 0.3-2.8, P = 0.911). The only risk factor for EPI was pancreatoduodenectomy (OR 4.3, 95% CI 1.4-13.7, P = 0.012). Conclusions New onset NAFLD/NASH is occasionally found after pNET resection, especially in patients with recurrent disease, but is not related to EPI.