Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network

Management of Asymptomatic Sporadic Nonfunctioning Pancreatic Neuroendocrine Neoplasms (ASPEN) <= 2 cm: Study Protocol for a Prospective Observational Study

Introduction: The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN <2 cm of diameter. Several retrospective series demonstrated that a non-operative management is safe and feasible, but no prospective studies are available. Aim of the ASPEN study is to evaluate the optimal management of asymptomatic NF-PanNEN ≤2 cm comparing active surveillance and surgery. Methods: ASPEN is a prospective international observational multicentric cohort study supported by ENETS. The study is registered in ClinicalTrials.gov with the identification code NCT03084770. Based on the incidence of NF-PanNEN the number of expected patients to be enrolled in the ASPEN study is 1,000 during the study period (2017–2022). Primary endpoint is disease/progression-free survival, defined as the time from study enrolment to the first evidence of progression (active surveillance group) or recurrence of disease (surgery group) or death from disease. Inclusion criteria are: age >18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at 68Gallium DOTATOC-PET scan. Conclusion: The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach

Long-Term Pancreatic Functional Impairment after Surgery for Neuroendocrine Neoplasms

Radical surgery represents the only curative treatment for pancreatic neuroendocrine neoplasms (PanNEN). The aim of this study was to evaluate the postoperative onset of diabetes mellitus (DM) and/or pancreatic exocrine insufficiency (PEI) in surgically treated PanNEN. Consecutive PanNEN patients, without preoperative DM, who underwent partial pancreatic resection, were included. After a median follow-up of 72 months, overall 68/276 patients (24%) developed DM. Patients who developed DM were significantly older (p = 0.002) and they had a higher body mass index (BMI) (p &lt; 0.0001) than those who did not; they were more frequently male (p = 0.017) and with nonfunctioning neoplasms (p = 0.019). BMI &gt; 25 Kg/m2 was the only independent predictor of DM (p = 0.001). Overall, 118/276 patients (43%) developed a PEI, which was significantly more frequent after pancreaticoduodenectomy (p &lt; 0.0001) and in patients with T3-T4 tumors (p = 0.001). Pancreaticoduodenectomy was the only independent predictor of PEI (p &lt; 0.0001). Overall, 54 patients (20%) developed disease progression. Patients with and without DM had similar progression free survival (PFS), whereas patients without PEI had better five-year-PFS (p = 0.002), although this association was not confirmed in multivariate analysis. The risk of DM and PEI after surgery for PanNEN is relatively high but it does not affect PFS. BMI and pancreatic head resection are independent predictors of DM and PEI, respectively

Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network

Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology

Neuroendocrine carcinomas (NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors

The size of well differentiated pancreatic neuroendocrine tumors correlates with Ki67 proliferative index and is not associated with age

Background: Concerns exist about a conservative management of well-differentiated nonfunctioning small pancreatic neuroendocrine tumors (NF-PanNET) in young patients and when preoperative Ki67 proliferative index is &gt;= 3%.Aim: To evaluate an association between age, tumor size and grading in patients with sporadic NF-PanNET who underwent curative resection.Methods: Patients who underwent surgery for sporadic NF-PanNET (excluding G3) were retrospectively analyzed. Linear regression analysis was performed to evaluate a possible correlation between continuous variables, whereas multiple logistic regression analysis was performed for determining predictors of NF-PanNET-G2.Results: Overall, 235 patients with NF-PanNET-G1/G2 were included. The median largest radiological diameter was 25 mm. Age correlated neither with tumor size (P = 0.675) nor with Ki67 index (P = 0.376). On multivariate linear regression analysis, factors independently associated with Ki67 index were NF-PanNET size (P = 0.031), perineural invasion (P = 0.004), microvascular invasion (P = 0.001) and necrosis (P = 0.009). The most accurate NF-PanNET size for predicting NF-PanNET-G2 was 25 mm. On multivariate analysis, a NF-PanNET size &gt;25 mm was independently associated with the risk of having a PanNET-G2 (P = 0.025).Conclusion: No correlations exist between age and NF-PanNET size or proliferative index. Therefore, an a priori aggressive attitude is not justified in young patients with small NF-PanNET, as a long-life expectancy is probably unlikely to increase the risk of malignant transformation. (C) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Is the Real Prevalence of Pancreatic Neuroendocrine Tumors Underestimated? A Retrospective Study on a Large Series of Pancreatic Specimens

The annual incidence of pancreatic neuroendocrine tumors (PanNET) has been estimated to be around 0.8/100,000 inhabitants. The aim of this study was to determine the frequency of incidental histological diagnosis of PanNET in pancreatic specimen evaluation for a purpose other other than PanNET diagnosis