Pathology Reporting in Neuroendocrine Neoplasms of the Digestive System: Everything You Always Wanted to Know but Were Too Afraid to Ask

During the 5th NIKE (Neuroendocrine tumors Innovation in Knowledge and Education) meeting, held in Naples, Italy, in May 2019, discussions centered on the understanding of pathology reports of gastroenetropancreactic neuroendocrine neoplasms. In particular, the main problem concerned the difficulty that clinicians experience in extrapolating relevant information from neuroendocrine tumor pathology reports. During the meeting, participants were asked to identify and rate issues which they have encountered, for which the input of an expert pathologist would have been appreciated. This article is a collection of the most rated questions and relative answers, focusing on three main topics: 1) morphology and classification; 2) Ki67 and grading; 3) immunohistochemistry. Patient management should be based on multidisciplinary decisions, taking into account clinical and pathology-related features with clear comprehension between all health care professionals. Indeed, pathologists require clinical details and laboratory findings when relevant, while clinicians require concise and standardized reports. In keeping with this last statement, the minimum requirements in pathology datasets are provided in this paper and should be a baseline for all neuroendocrine tumor professionals

Emerging therapies in pheochromocytoma and paraganglioma: Immune checkpoint inhibitors in the starting blocks

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respec-tively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progres-sive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology

Integrated motor drives: state of the art and future trends

With increased need for high power density, high efficiency and high temperature capabilities in Aerospace and Automotive applications, Integrated Motor Drives (IMD) offers a potential solution. However, close physical integration of the converter and the machine may also lead to an increase in components temperature. This requires careful mechanical, structural and thermal analysis; and design of the IMD system. This paper reviews existing IMD technologies and their thermal effects on the IMD system. The effects of the power electronics (PE) position on the IMD system and its respective thermal management concepts are also investigated. The challenges faced in designing and manufacturing of an IMD along with the mechanical and structural impacts of close physical integration is also discussed and potential solutions are provided. Potential converter topologies for an IMD like the Matrix converter, 2-level Bridge, 3-level NPC and Multiphase full bridge converters are also reviewed. Wide band gap devices like SiC and GaN and their packaging in power modules for IMDs are also discussed. Power modules components and packaging technologies are also presented

Integral-resonant control for stand-alone voltage source inverters

This study deals with a newly-conceived voltage control method for three-phase four-leg voltage source inverters (VSIs) which are being required in autonomous power generating units devoted to supply both three-phase and single-phase electrical loads in four-wire electric power distribution systems. To deal with VSI operating conditions providing three-phase voltage supply of both unbalanced loads and non-linear loads, an integral + resonant (I + R) voltage control structure is discussed and experimentally verified by means of a 25 kVA rated power converter prototype. It is shown that the proposed voltage control allows simplifying the overall control configuration, achieving zero-overhead power factor regulation and fast compensation of load unbalances. Further to that, a complete current limiting strategy is described and tested under different load conditions

High-Speed Electric Drive for Exhaust Gas Energy Recovery Applications

High-speed electric drives play an important role in the field of power generating units on board vehicles and aircrafts. This paper deals with the solutions for developing the direct coupled electric drive to be used in combination with a radial turbo-expander for exhaust energy recovery in automotive applications. The descriptions of prototypal realization of both the axial-flux permanent-magnet (PM) generator and the three-level boost-rectifier converter, which results as the preferred topology for the controlled rectifier, are given. The high rotational speed of the direct-driven PM generator results in high electric fundamental frequency also, which is challenging for the electric drive control issues. Results of the electric drive prototype experimental activity are finally presented

Three-Phase Z-Source Power Supply Design

Z-source converter configurations make it possible to overcome intrinsic limits present in conventional ac–dc and dc–ac converters. A typical three-phase inverter cannot supply output voltages greater than the voltages at its input; in the same manner, a typical three-phase boost rectifier cannot supply output voltages lower than input voltages. Using Z-source topology permits overcoming both these limits. In fact, a Z-source boost rectifier can theoretically either step-up or step-down the output voltage to any desired value starting from the conventional three-phase diode bridge rectifier output voltage level. In addition, it presents intrinsic immunity to shoot-through states, resulting in improved reliability of the entire system. In this study, attention is focused on the mathematical modelling of a three-phase Z-source boost rectifier for power factor correction power supply applications; using such a topology as first-stage converter allows designing the second-stage converters with the same voltage constraints of single-phase units

The safety of available treatments options for neuroendocrine tumors

Neuroendocrine neoplasms (NEN) represent a heterogeneous group of malignancies generally characterized by low proliferation and indolent course. However, about half of the newly diagnosed cases are metastatic and require long-term systemic therapies. Areas covered: This review revises the literature to summarize the current knowledge upon safety of all systemic treatment options available. Thirty three different clinical studies have been considered, including 4 on somatostatin analogues (SSA), 5 on targeted therapies, 10 on peptide receptor radionuclide therapy (PRRT), and 14 on chemotherapy. Expert opinion: SSA are safe and well tolerated without any relevant severe adverse event and very low treatment discontinuation rate. Targeted therapies show a satisfying safety profile. Most adverse events are grade 1-2 and easy manageable with dose reduction or temporary interruption. PRRT is manageable and safe with a low rate of grade 3-4 adverse events. However, severe renal and hematologic toxicity may occur. Chemotherapy is usually considered after previous therapeutic lines. Therefore, these subjects are more susceptible to experience adverse events due to cumulative toxicities or poor performance status. The available systemic treatment options are generally well tolerated and suitable for long-term administration. Cumulative toxicity should be taken in account for the definition of therapeutic sequence