Challenges with anti-PD1 agents in brain metastases management of NSCLC patients: a case report

Immunotherapy is dramatically changing the therapeutic landscape of advanced Non Small Cell Lung Cancer (NSCLC), with unprecedented results compared with chemotherapy. However, this novel treatment approach poses several novel challenges, including optimal treatment duration, coexistence with other conventional therapies (radiotherapy, targeted therapies, and chemotherapy), and activity in special populations, including patients with brain metastases (BMs). Traditionally, central nervous system (CNS) has been considered an immune-privileged organ, although recent evidences suggest a potential role of the immune system as exploitable target for cancer immunotherapy. Here we present a case of a non-squamous NSCLC patient with a rapid and long-lasting response to the anti-PD1 agent Nivolumab with a remarkable activity in the CNS, without previous brain irradiation

Recurrent primary leiomyosarcoma of the seminal vesicle treated with curative radiotherapy.

A case of locally recurrent leiomyosarcoma of the left seminal vesicle, previously surgically resected, is described in a 65-year-old man. The patient underwent curative radiation therapy (61 Gy/33 fractions). Initially, he experienced a complete response after irradiation, but 15 months after treatment, progressive disease was recorded both in lung and bone, without evidence of local recurrence. The lack of efficient systemic therapies leads to a poor prognosis in this disease; clinical outcome in this patient seems to suggest the utility of radiotherapy in the very rare scenario of locally recurrent seminal vesicle leiomyosarcoma. Bangladesh Journal of Medical Science Vol.18(1) 2019 p.156-15

Baseline neutrophilia, derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), and outcome in non small cell lung cancer (NSCLC) treated with Nivolumab or Docetaxel

Nivolumab is a novel therapeutic option in NSCLC, associated with a significant survival gain compared with Docetaxel. However, predictive biomarkers are lacking. The presence of systemic inflammation has been correlated with poor outcome in many cancer types. We aimed to evaluate whether there is a correlation between some indicators of inflammation and response to Nivolumab or Docetaxel in pre-treated NSCLCs. Data of 62 patients receiving Nivolumab or Docetaxel were analyzed. Baseline neutrophilia and thrombocytosis were not associated with response. High dNLR was associated with no response to Nivolumab, but not with Docetaxel, whereas high PLR correlated with low treatment response in both groups. Among refractory patients, a higher incidence of thrombocytosis, neutrophilia, high PLR, and high dNLR levels were observed compared with the overall population. This is one of the first reports in this field and suggests that indicators of inflammation might be included together with other predictive biomarkers in the baseline evaluation of patients candidate for immunotherapy

Computer-assisted morphometry of the peripheral nervous system. A diagnostic tool.

A formal systematization of the set of procedures required in peripheral nerve morphometry has been implemented in a computer program, in an attempt to provide an easy-to-handle diagnostic tool in current neuropathological practice. The hardware is composed of an IBM-PC compatible computer and a graphic tablet. Programs are written in BASIC and run in computers compatible with the MS-DOS operating system. The flow of operative steps involved in the morphometric study is controlled by the software. Sequential measurements are also tested for congruence. Nerve fibre measurements are stored in pluri-dimensional matrices for subsequent statistical calculations, i.e. evaluation of size-frequency distribution of nerve fibres and correlation analysis between nerve fibre subcomponents. Stereological estimates of the parenchymal components are also derived. The increase in accuracy achieved using area instead of diameter measurements is stressed. Compared to "dedicated" machines such personal computer-assisted systems exhibit substantial advantages in terms of low cost and flexibility

Differenziazione cellulare e capacita' metastatica. Uno studio morfometrico sulle metastasi polmonari delle linee F1 ed F10 del melanoma B16 di topo

E' stato condotto uno studio morfometrico sulle linee cellulari F1 ed F10 del melanoma murino B16 che ha evidenziato interessanti correlazioni tra la differenziazione cellulare, valutata a livello ultrastrutturale, e la capacita' metastatic

A morphometric comparison of subcellular structures between primary breast tumors and their nodal metastases.

A morphometric study of subcellular structures in human primary breast tumors (of the ductal infiltrating type) and their synchronous lymph node metastases was carried out using planimetry and stereology. Each primary neoplasm was compared separately with its axillary metastatic growth in order to detect differences in the quantitative estimates of their subcellular components. A set of 24 morphometric parameters was used to quantitatively describe each neoplastic cell profile. Although some subcellular parameters showed significant differences between the cells of a primary tumor and its metastases, no parameter was found to be consistently altered in all cases. No consistent increase or decrease in the values of the affected parameters was observed in the metastases. More than being due to the expression of a biologically variant (more-or-less differentiated) metastatic phenotype, the differences in stereologic parameters detected in metastatic cells appear to reflect the existence of different functional states of the same cell type

Morphometric changes in sympathetic nerve fibres in diabetes.

A morphometric study was carried out on electron micrographs of lumbar sympathetic nerve fibres surgically removed from 12 patients with arteriosclerosis obliterans: 4 diabetics, 4 non-diabetics and 4 subjects with glucose intolerance. In patients with diabetes and glucose intolerance a significant decrease in the percent area fraction of unmyelinated axons and an increase in the percent area fraction of the endoneurial space were demonstrated

A New Approach for Impedance Tracking of Piezoelectric Vibration Energy Harvesters Based on a Zeta Converter

Piezoelectric energy harvesters (PEHs) are a reduced, but fundamental, source of power for embedded, remote, and no-grid connected electrical systems. Some key limits, such as low power density, poor conversion efficiency, high internal impedance, and AC output, can be partially overcome by matching their internal electrical impedance to that of the applied resistance load. However, the applied resistance load can vary significantly in time, since it depends on the vibration frequency and the working temperature. Hence, a real-time tracking of the applied impedance load should be done to always harvest the maximum energy from the PEH. This paper faces the above problem by presenting an active control able to track and follow in time the optimal working point of a PEH. It exploits a non-conventional AC–DC converter, which integrates a single-stage DC–DC Zeta converter and a full-bridge active rectifier, controlled by a dedicated algorithm based on pulse-width modulation (PWM) with maximum power point tracking (MPPT). A prototype of the proposed converter, based on discrete components, was created and experimentally tested by applying a sudden variation of the resistance load, aimed to emulate a change in the excitation frequency from 30 to 70 Hz and a change in the operating temperature from 25 to 50 °C. Results showed the effectiveness of the proposed approach, which allowed to match the optimal load after 0.38 s for a ΔR of 47 kΩ and after 0.15 s for a ΔR of 18 kΩ

Metastatic capacity and differentiation in murine melanoma cell lines. A morphometric study.

A morphometric analysis was carried out on electron micrographs of cells of the F1 (low metastatic capacity) and F10 (high metastatic capacity) variant sublines of the murine B16 melanoma, both in in-vitro cultures and in lung-metastatic nodules developed after the intravenous injection of neoplastic cells in syngeneic C57 black male mice. A group of 28 morphometric parameters was derived to describe quantitatively each neoplastic cell profile. No qualitative difference was observed between the two cell lines. The quantitative expression of subcellular organelles was dissimilar in the two sublines, being consistently characterized, both in in-vitro cultured cells and in lung-metastatic colonies, by a significant decrease in the mean values of parameters related to melanosomes in the high metastatic capacity cell line (B16-F10). Moreover, in in-vitro cultured cells, indices describing heterochromatin masses and cytoplasmic membranous compartments displayed statistically significant differences between the two sublines. In this experimental system, an inverse relationship between metastatic capacity and differentiation is detected, since cells with a more aggressive metastatic behavior exhibit a decreased degree of differentiation