Adjuvant treatment of colorectal cancer in the elderly : where do we come from and where are we going?

Objective: Colorectal cancer is the third most commonly reported cancer in the world and about 50% of patients are diagnosed over the age of 70 years. The authors discuss age-related changes in organ function, comorbidities and frailty in the elderly, and their impact on chemotherapy toxicity. Methods: The authors review data from observational studies and subgroup analyses of randomized clinical trials on adjuvant chemotherapy in elderly colorectal cancer patients. Results: Several large population-based studies suggest that adjuvant chemotherapy is offered less frequently to elderly patients, although in recent years the prescription patterns tended to significantly increase. In fact, data from retrospective analyses of randomized trials indicate that elderly stage III colorectal cancer patients may get similar clinical advantage from adjuvant treatment with fluoropyrimidines, although major comorbidities may substantially limit life expectancy and minimize the survival benefits. The use of oxaliplatin-based regimens needs to take into account the individual risk/benefit profile due to lack of unequivocal evidence of positive literature data. Conclusions: Adjuvant chemotherapy of colorectal cancer should be investigated by prospective trials specifically designed for the elderly. Fit elderly patients should be offered standard adjuvant treatments, while modified schedule, attenuated doses or even treatment omission can be offered to more frail patients

Gate-source distance scaling effects in H-terminated diamond MESFETs

In this paper, an analysis of gate-source and gate-drain scaling effects in MESFETs fabricated on hydrogen-terminated single-crystal diamond films is reported. The experimental results show that a decrease in gate-source spacing can improve the device performance by increasing the device output current density and its transconductance. On the contrary, the gate--drain distance produces less pronounced effects on device performance. Breakdown voltage, knee voltage, and threshold voltage variations due to changes in gate-source and drain-source distances have also been investigated. The obtained results can be used as a design guideline for the layout optimization of H-terminated diamond-based MESFETs

A 3-dimensional interdigitated electrode geometry for the enhancement of charge collection efficiency in diamond detectors

In this work, a single crystal CVD diamond film with a novel three-dimensional (3D) interdigitated electrode geometry has been fabricated with the reactive ion etching (RIE) technique in order to increase the charge collection efficiency (CCE) with respect to that obtained by standard superficial electrodes. The geometrical arrangement of the electric field lines due to the 3D patterning of the electrodes results in a shorter travel path for the excess charge carriers, thus contributing to a more efficient charge collection mechanism. The CCE of the device was mapped by means of the ion beam induced charge (IBIC) technique. A 1MeV proton microbeam was raster-scanned over the active area of the diamond detector under different bias voltage conditions, enabling to probe the charge transport properties of the detector up to a depth of 8 ìm below the sample surface. The experimental results, supported by the numerical simulations, show a significant improvement in the 3D detector performance (i.e. CCE, energy resolution, extension of the active area) if compared with the results obtained by standard surface metallic electrodes

Bevacizumab treatment in the elderly patient with metastatic colorectal cancer

Metastatic colorectal cancer (mCRC), like many cancers, is primarily a disease of elderly people. Despite this prevalence, such patients are often excluded from randomized trials or represent a minority of enrolled patients. Moreover, the criteria for establishing benefit or side effects of treatment strategies in this population are uncertain and not well recognized. Bevacizumab improves the outcome of mCRC when used in combination with standard first-line and second-line chemotherapy and beyond the first disease progression when given with a chemotherapy backbone different from that used in the precedent line. The particular toxicity profile of this antiangiogenesis agent (in particular hypertension, thromboembolic events, hemorrhage, and renal failure) may discourage its use in elderly patients with comorbidities. Data from subgroup analyses of randomized trials and the results of recent cohort studies suggest a significant benefit from the addition of bevacizumab to standard chemotherapy for elderly patients comparable with that observed in younger patients, except for the increased risk for thromboembolic events. Age alone should not be a barrier to use of bevacizumab, and further research with a more complete geriatric assessment should investigate the role of bevacizumab in elderly patients with mCRC to avoid undertreatment of this patient population due to a historical conservative approach

Gender influence on professional satisfaction and gender issue perception among young oncologists. A survey of the Young Oncologists Working Group of the Italian Association of Medical Oncology (AIOM)

Background The professional gender gap is increasingly recognised in oncology. We explored gender issues perception and gender influence on professional satisfaction/gratification among young Italian oncologists. Methods Italian oncologists aged ≤40 years and members of the Italian Association of Medical Oncology were invited to participate in an online survey addressing workload/burnout, satisfaction in professional abilities and relations, relevant factors for professional gratification, and gender barriers. ‡ 2 test for general association or ‡ 2 test for trend was used to analyse the data. Results 201 young oncologists participated in the survey: 67% female, 71% aged 30-40 years, 41% still in training and 82% without children. Women and men were equally poorly satisfied by the relations with people occupying superior hierarchical positions. There was heterogeneity between women and men in current (p=0.011) and expected future (p=0.007) satisfaction in professional abilities: women were more satisfied by current empathy and relations with colleagues and were more confident in their future managerial and team leader skills. The most important elements for professional gratification indicated by all participants were, in general, work-life balance (36%) and intellectual stimulation/research (32%); specifically for women, work-life balance (48%) and intellectual stimulation/research (20%); and specifically for men, career (29%) and social prestige/recognition (26%). Heterogeneity within the same gender emerged. For example, the elements indicated by men as the most important were intellectual stimulation/research (39%) and work-life balance (21%) in general, versus social prestige/recognition (24%) and career (24%), respectively, specifically for men (p<0.0001). More women versus men perceived gender issue as an actual problem (60% vs 38%, p=0.03); men underestimated gender barriers to women's career (p=0.011). Conclusions Satisfaction in professional abilities varied by gender. Work-life balance is important for both women and men. Stereotypes about gender issues may be present. Gender issue is an actual problem for young oncologists, mostly perceived by women

Endothelial cells from umbilical cord of women affected by gestational diabetes: A suitable in vitro model to study mechanisms of early vascular senescence in diabetes

Human umbilical cord endothelial cells (HUVECs) obtained from women affected by gestational diabetes (GD-HUVECs) display durable pro-atherogenic modifications and might be considered a valid in vitro model for studying chronic hyperglycemia effects on early endothelial senescence. Here, we demonstrated that GD- compared to C-HUVECs (controls) exhibited oxidative stress, altered both mitochondrial membrane potential and antioxidant response, significant increase of senescent cells characterized by a reduced NAD-dependent deacetylase sirtuin-1 (SIRT1) activity together with an increase in cyclin-dependent kinase inhibitor-2A (P16), cyclin-dependent kinase inhibitor-1 (P21), and tumor protein p53 (P53) acetylation. This was associated with the p300 activation, and its silencing significantly reduced the GD-HUVECs increased protein levels of P300 and Ac-P53 thus indicating a persistent endothelial senescence via SIRT1/P300/P53/P21 pathway. Overall, our data suggest that GD-HUVECs can represent an “endothelial hyperglycemic memory” model to investigate in vitro the early endothelium senescence in cells chronically exposed to hyperglycemia in vivo

Pharmacogenomic evaluation of single nucleotide polymorphisms associated with oxaliplatin-induced peripheral neuropathy: a preliminary study

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Whole exome sequencing analysis of urine trans-renal tumour DNA in metastatic colorectal cancer patients

Background The analysis of circulating free tumour DNA (ctDNA) in blood, commonly referred as liquid biopsy, is being used to characterise patients with solid cancers. Tumour-specific genetic variants can also be present in DNA isolated from other body fluids, such as urine. Unlike blood, urine sampling is non-invasive, can be self-performed, and allows recurrent longitudinal monitoring. The features of tumour DNA that clears from the glomerular filtration barrier, named trans-renal tumour DNA (trtDNA), are largely unexplored. Patients and methods Specimens were collected from 24 patients with KRAS or BRAF mutant metastatic colorectal cancer (mCRC). Driver mutations were assessed by droplet digital PCR (ddPCR) in ctDNA from plasma and trtDNA from urine. Whole exome sequencing (WES) was performed in DNA isolated from tissue, plasma and urine. Results Out of the 24 CRC cases, only four had sufficient DNA to allow WES analyses in urine and plasma. We found that tumour alterations primarily reside in low molecular weight fragments (less than 112\u2009bp). In patients whose trtDNA was more than 2.69% of the urine derived DNA, cancer-specific molecular alterations, mutational signatures and copy number profiles identified in urine DNA are comparable with those detected in plasma ctDNA. Conclusions With current technologies, WES analysis of trtDNA is feasible in a small fraction of mCRC patients. Tumour-related genetic information is mainly present in low molecular weight DNA fragments. Although the limited amounts of trtDNA poses analytical challenges, enrichment of low molecular weight DNAs and optimised computational tools can improve the detection of tumour-specific genetic information in urine

S-band hybrid amplifiers based on hydrogenated diamond FETs

The first realizations of S-band hybrid amplifiers based on hydrogenated-diamond (H-diamond) FETs are reported. As test vehicles of the adopted H-diamond technology at microwave frequencies, two designs are proposed: one, oriented to low-noise amplification, the other, oriented to high-power operation. The two amplifying stages are so devised as to be cascaded into a two-stage amplifier. The activities performed, from the technological steps to characterization, modelling, design and realization are illustrated. Measured performance demonstrates, for the low-noise stage, a noise figure between 7 and 8 dB in the 2–2.5 GHz bandwidth, associated with a transducer gain between 5 and 8 dB. The OIP3 at 2 GHz is 21 dBm. As to the power-oriented stage, its transducer gain is 5–6 dB in the 2–2.5 GHz bandwidth. The 1-dB output compression point at 2 GHz is 20 dBm whereas the OIP3 is 33 dBm. Cascading the measured S-parameters of the two stages yields a transducer gain of 15 ± 1.2 dB in the 2–3 GHz bandwidth