MITO END-3: efficacy of avelumab immunotherapy according to molecular profiling in first-line endometrial cancer therapy.

BACKGROUND: Immunotherapy combined with chemotherapy significantly improves progression-free survival (PFS) compared to first-line chemotherapy alone in advanced endometrial cancer (EC), with a much larger effect size in microsatellite instability-high (MSI-H) cases. New biomarkers might help to select patients who may have benefit among those with a microsatellite-stable (MSS) tumor. PATIENTS AND METHODS: In a pre-planned translational analysis of the MITO END-3 trial, we assessed the significance of genomic abnormalities in patients randomized to standard carboplatin/paclitaxel without or with avelumab. RESULTS: Out of 125 randomized patients, 109 had samples eligible for next-generation sequencing analysis, and 102 had MSI tested. According to The Cancer Genome Atlas (TCGA), there were 29 cases with MSI-H, 26 with MSS TP53 wild type (wt), 47 with MSS TP53 mutated (mut), and 1 case with POLE mutation. Four mutated genes were present in >30% of cases: TP53, PIK3CA, ARID1A, and PTEN. Eleven patients (10%) had a BRCA1/2 mutation (five in MSI-H and six in MSS). High tumor mutational burden (≥10 muts/Mb) was observed in all MSI-H patients, in 4 out of 47 MSS/TP53 mut, and no case in the MSS/TP53 wt category. The effect of avelumab on PFS significantly varied according to TCGA categories, being favorable in MSI-H and worst in MSS/TP53 mut (P interaction = 0.003); a similar non-significant trend was seen in survival analysis. ARID1A and PTEN also showed a statistically significant interaction with treatment effect, which was better in the presence of the mutation (ARID1A P interaction = 0.01; PTEN P interaction = 0.002). CONCLUSION: The MITO END-3 trial results suggest that TP53 mutation is associated with a poor effect of avelumab, while mutations of PTEN and ARID1A are related to a positive effect of the drug in patients with advanced EC.

Circulating myomiRNAs as biomarkers in patients with Cushing's syndrome.

PURPOSE: Impairment of skeletal muscle mass and strength affects 40-70% of patients with active Cushing's syndrome (CS). Glucocorticoid excess sustains muscle atrophy and weakness, while muscle-specific microRNAs (myomiRs) level changes were associated with muscle organization and function perturbation. The aim of the current study is to explore changes in circulating myomiRs in CS patients compared to healthy controls and their involvement in IGFI/PI3K/Akt/mTOR pathway regulation in skeletal muscle. METHODS: C2C12, mouse myocytes, were exposed to hydrocortisone (HC), and atrophy-related gene expression was investigated by RT-qPCR, WB and IF to assess HC-mediated atrophic signalling. miRNAs were evaluated in HC-treated C2C12 by PCR Arrays. MyomiRs significantly overexpressed in C2C12 were investigated in 37 CS patients and 24 healthy controls serum by RT-qPCR. The anti-anabolic role of circulating miRNAs significantly upregulated in CS patients was explored in C2C12 by investigating the IGFI/PI3K/Akt/mTOR pathway regulation. RESULTS: HC induced higher expression of atrophy-related genes, miR-133a-3p, miR-122-5p and miR-200b-3p in C2C12 compared to untreated cells. Conversely, the anabolic IGFI/PI3K/Akt/mTOR signalling was reduced and this effect was mediated by miR-133a-3p. In CS patients miR-133a-3p and miR-200b-3p revealed higher circulating levels (p < 0.0001, respectively) compared to controls. ROC curves for miR-133a-3p (AUC 0.823, p < 0.0001) and miR-200b-3p (AUC 0.850, p < 0.0001) demonstrated that both myomiRs represent potential biomarkers to discriminate between CS and healthy subjects. Pearson's correlation analysis revealed that circulating levels of miR-133a-3p are directly correlated with 24 h urinary-free cortisol level (r = 0.468, p = 0.004) in CS patients. CONCLUSIONS: HC induces atrophic signals by miR-133a-3p overexpression in mouse myocytes and humans. Circulating miR-133a-3p is promising biomarkers of hypercortisolism.

Long-term high-dose L-arginine supplementation in patients with vasculogenic erectile dysfunction: a multicentre, double-blind, randomized, placebo-controlled clinical trial.

PURPOSE: The current randomized, double-blind, placebo-controlled clinical trial addressed the effects on penile erectile function of relatively high daily oral doses (6 g/day) of L-ARG for 3 months (N = 51) compared to placebo (N = 47), in patients with vasculogenic ED, with comparison between mild-moderate and severe vasculogenic ED. METHODS: The outcome measures included IIEF-6 score and cavernous arteries peak systolic flow velocity (PSV) at dynamic penile duplex ultrasonography (PDU). RESULTS: L-ARG supplementation for 3 months significantly increased IIEF-6 score in the overall cohort (p < 0.0001) and in subgroups of patients with mild-moderate (p < 0.0001) and severe (p = 0.007) vasculogenic ED; PSV was significantly increased in the overall cohort (p < 0.0001) and in patients with mild-moderate (p < 0.0001), but not severe vasculogenic ED. At study completion, 74% of patients improved ED degree category, although only 24% of patients, mainly belonging to the baseline category of mild ED, reached IIEF-6 scores compatible with absence of ED; moreover, 20% of patients, exclusively belonging to the baseline category of mild-moderate vasculogenic ED, reached PSV values compatible with absence of ED. CONCLUSION: The results of the current study demonstrated that supplementation with relatively high doses of L-ARG as a single compound for 3 months significantly improved penile erectile function, assessed by both IIEF-6 score and PSV at dynamic PDU in patients with mild-moderate, and improved IIEF-6 score, but not PSV, in patients with severe vasculogenic ED, therefore suggesting that L-ARG might be an alternative treatment in mild-moderate vasculogenic ED patients experiencing adverse effects or with contraindications for chronic treatment with PDE5i compounds.

Monolithic AlGaAs second-harmonic nanoantennas: erratum.

Figure 1(b) in [V. F. Gili et al, Opt. Express24, 15965 (2016)10.1364/OE.24.015965] is corrupted and is corrected in this erratum.

A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer.

BACKGROUND: HER2-positive (+) breast cancers, defined by HER2 overexpression and/or amplification, are often addicted to HER2 to maintain their malignant phenotype. Yet, some HER2+ tumors do not benefit from anti-HER2 therapy. We hypothesize that HER2 amplification levels and PI3K pathway activation are key determinants of response to HER2-targeted treatments without chemotherapy. PATIENTS AND METHODS: Baseline HER2+ tumors from patients treated with neoadjuvant lapatinib plus trastuzumab [with endocrine therapy for estrogen receptor (ER)+ tumors] in TBCRC006 (NCT00548184) were evaluated in a central laboratory for HER2 amplification by fluorescence in situ hybridization (FISH) (n = 56). HER2 copy number (CN) and FISH ratios, and PI3K pathway status, defined by PIK3CA mutations or PTEN levels by immunohistochemistry were available for 41 tumors. Results were correlated with pathologic complete response (pCR; no residual invasive tumor in breast). RESULTS: Thirteen of the 56 patients (23%) achieved pCR. None of the 11 patients with HER2 ratio <4 and/or CN <10 achieved pCR, whereas 13/45 patients (29%) with HER2 ratio ≥4 and/or CN ≥10 attained pCR (P = 0.0513). Of the 18 patients with tumors expressing high PTEN or wild-type (WT) PIK3CA (intact PI3K pathway), 7 (39%) achieved pCR, compared with 1/23 (4%) with PI3K pathway alterations (P = 0.0133). Seven of the 16 patients (44%) with HER2 ratio ≥4 and intact PI3K pathway achieved pCR, whereas only 1/25 (4%) patients not meeting these criteria achieved pCR (P = 0.0031). CONCLUSIONS: Our findings suggest that there is a clinical subtype in breast cancer with high HER2 amplification and intact PI3K pathway that is especially sensitive to HER2-targeted therapies without chemotherapy. A combination of HER2 FISH ratio and PI3K pathway status warrants validation to identify patients who may be treated with HER2-targeted therapy without chemotherapy.

Self-tuning of second-harmonic generation in GaAs nanowires enabled by nonlinear absorption.

We investigate the effects of nonlinear absorption of the pump beam on second-harmonic generation in GaAs nanowires. Our model includes nonlinear absorption of the pump and allows obtaining a self-consistent solution of the nonlinear Maxwell equations. First, we observe that SHG conversion efficiency can be limited from two-photon absorption and generated free-carriers depending on the pump intensity. Second, we show a method to modulate the SHG response by varying the pump beam intensity. We find that varying the pump intensity from 1 GW/cm2 up to 15 GW/cm2 can red-shift the SH peak wavelength up to 5 nm and modulate the conversion efficiency at a fixed pump wavelength up to 60%. Our results enable new applications of dielectric nanoresonators for nonlinear applications such as harmonic generation, optical switching, and all-optical ultrafast modulation.

Imaging tests in staging and surveillance of non-metastatic breast cancer: changes in routine clinical practice and cost implications.

BACKGROUND: Although guidelines do not recommend computerised tomography (CT), positron emission tomography (PET) or magnetic resonance imaging (MRI) for the staging or follow-up of asymptomatic patients with non-metastatic breast cancer, they are often requested in routine clinical practice. The aim of this study was to determine the staging and follow-up patterns, and relative costs in a large population of breast cancer patients living and treated in a Southern Italian region. METHODS: We analysed the clinical computerised information recorded by 567 primary-care physicians assisting about 650 000 inhabitants in the Campania region. Patients with non-metastatic breast cancer were identified and divided into calendar years from 2001 to 2010. The number of diagnostic tests prescribed per 100 patients (N/Pts) and the mean cost per patient was determined 3 months before diagnosis and up to 1 year after diagnosis. Costs are expressed in constant 2011 euros. RESULTS: We identified 4680 newly diagnosed cases of asymptomatic non-metastatic breast cancer. N/Pts increased significantly (P<0.0001) from 2001 to 2010. The mean number of prescribed mammograms, bone scans, abdominal ultrasound and chest X-rays ('routine tests'), and costs was unchanged. However, the number of CT, PET scans and MRI ('new tests')prescriptions almost quadrupled and the mean cost per patient related to these procedures significantly increased from [euro ]357 in 2001 to [euro ]830 in 2010 (P<0.0001). CONCLUSIONS: New test prescriptions and relative costs significantly and steadily increased throughout the study period. At present there is no evidence that the delivery of new tests to asymptomatic patients improves breast cancer outcome. Well-designed clinical trials are urgently needed to shed light on the impact of these tests on clinical outcome and overall survival.

Polarization properties of second-harmonic generation in AlGaAs optical nanoantennas.

Manipulating light at the nanoscale by means of dielectric nanoantennas recently received renewed attention thanks to the development of key enabling fabrication tools in semiconductor technology, combined with the extremely low losses exhibited by dielectrics in the optical regime. Nanostructures based on III-V type semiconductors, characterized by an intrinsic broken symmetry down to a single elementary cell, has already demonstrated remarkable nonlinear conversion efficiencies at scales well below the operating wavelength. In this Letter, we thoroughly investigate the emission properties of second-harmonic generation (SHG) in AlGaAs monolithic nanoantennas. Our findings point toward the pivotal role of volume susceptibility in SHG, further unraveling the physics behind the nonlinear processes in these systems. The extremely high SHG efficiency attained, together with the control over the polarized emission in these nanoantennas, constitute key ingredients for the development of tunable nonlinear metasurfaces.

Controlling second-harmonic generation at the nanoscale with monolithic AlGaAs-on-AlOx antennas.

We review recent achievements in the field of nanoscale nonlinear AlGaAs photonics based on all-dielectric optical antennas. After discussing the motivation and main technological challenges for the development of an AlGaAs monolithic platform for χ (2) nonlinear nanophotonics, we present numerical and experimental investigations of the second-order nonlinear response and physical reasons for high efficiency of second-order nonlinear interactions in the AlGaAs nano-antennas. In particular, we emphasize the role of the dipolar resonances at the fundamental frequency and the multipolar resonances at the second harmonic wavelength. We also discuss second-harmonic generation directionality and show possible strategies to engineer the radiation pattern of nonlinear antennas.

Monolithic AlGaAs second-harmonic nanoantennas.

We demonstrate monolithic aluminum gallium arsenide (AlGaAs) optical nanoantennas. Using a selective oxidation technique, we fabricated epitaxial semiconductor nanocylinders on an aluminum oxide substrate. Second harmonic generation from AlGaAs nanocylinders of 400 nm height and varying radius pumped with femtosecond pulses delivered at 1554-nm wavelength has been measured, revealing a peak conversion efficiency exceeding 10-5 for nanocylinders with an optimized geometry.

Tumor characteristics and prognosis in familial breast cancer.

BACKGROUND: Approximately 5-10% of breast cancers are hereditary and their biology and prognosis appear to differ from those of sporadic breast cancers. In this study we compared the biological features and clinical characteristics of non metastatic breast cancer in patients with BRCA mutations versus patients with a family history suggesting hereditary breast cancer but without BRCA mutations (BRCA wild type) versus patients with sporadic disease, and correlated these findings with clinical outcome. METHODS: We retrieved the clinical and biological data of 33 BRCA-positive, 66 BRCA-wild type and 1826 sporadic breast cancer patients contained in a single institution clinical database between 1980 and 2012. Specifically, we recorded age, tumor size, nodal status, treatment type, pattern of relapse, second primary incidence, outcome (disease-free survival and overall survival), and biological features (estrogen receptor [ER], progesterone receptor [PgR], tumor grade, proliferation and c-erbB2 status). Median follow-up was 70 months. RESULTS: BRCA-positive patients were significantly younger than sporadic breast cancer patients, and less likely to be ER-, PgR- or c-erbB2-positive than women with BRCA-wild type or sporadic breast cancer. Tumor size and grade, nodal status and proliferation did not differ among the three groups. Rates of radical mastectomy were 58, 42 and 37%, and those of conservative surgery were 42, 58 and 63% in women with BRCA-positive, BRCA-wild type and sporadic breast cancer (p = 0.03), respectively. The incidence of contralateral breast cancer was 12, 14 and 0% (p <0.0001) and the incidence of second primary tumors (non breast) was 9, 1 and 2% (p <0.0001) in BRCA-positive, BRCA-wild type and sporadic breast cancer, respectively. Median disease-free survival in years was 29 in BRCA-wild type, 19 in BRCA-positive and 14 in sporadic breast cancer patients (log-rank = 0.007). Median overall survival in years was not reached for BRCA-wild type, 19 for BRCA-positive and 13 for sporadic breast cancer patients (log-rank <0.0001). At multivariate analyses only BRCA-wild type status was related to a significant improvement in overall survival versus the sporadic breast cancer group (HR = 0,51; 95% CI (0,28-0,93) p = 0.028). CONCLUSIONS: The biology and outcome of breast cancer differ between patients with BRCA mutations, patients with a family history but no BRCA mutations and patients with sporadic breast cancer.

Adenomyosis: a systematic review of medical treatment.

Adenomyosis is a heterogeneous gynaecologic condition with a range of clinical presentations, the most common being heavy menstrual bleeding and dysmenorrhoea; however, patients can also be asymptomatic. Several studies support the theory that adenomyosis results from invasion of the endometrium into the myometrium, causing alterations in the junctional zone. These changes are commonly seen on imaging studies, such as transvaginal ultrasound and magnetic resonance imaging. The aim of this review is to discuss the medical approach to the management of adenomyosis symptoms, including pain and abnormal uterine bleeding. The standard treatment of adenomyosis is hysterectomy, but there is no medical therapy to treat the symptoms of adenomyosis while still allowing patients to conceive. Medical therapies using suppressive hormonal treatments, such as continuous use of oral contraceptive pills, high-dose progestins, selective oestrogen receptor modulators, selective progesterone receptor modulators, the levonorgestrel-releasing intrauterine device, aromatase inhibitors, danazol, and gonadotrophin receptor hormone agonists can temporarily induce regression of adenomyosis and improve the symptoms.

Evaluation of an enhanced recovery protocol after pancreaticoduodenectomy in elderly patients.

BACKGROUND: Recent evidence has shown that enhanced recovery after surgery (ERAS) protocols decrease hospital stay following pancreaticoduodenectomy (PD). The aims of this study were to assess the feasibility and to evaluate the effect of introducing ERAS principles after PD in elderly patients. METHODS: Patients ≥75 years were defined as elderly. Comparison of postoperative outcome was performed between 22 elderly patients who underwent ERAS (elderly ERAS + patients) and a historical cohort of 66 elderly patients who underwent standard protocols (elderly ERAS-patients). RESULTS: The lowest adherence with ERAS among elderly patients was observed for starting a solid food diet within POD 4 (n = 7) and early drains removal (n = 2). The highest adherence was observed for post-operative glycemic control (n = 21), epidural analgesia (n = 21), mobilization (n = 20) and naso-gastric removal in POD 0 (n = 20). Post-operative outcomes did not differ between elderly ERAS+ and elderly ERAS- patients. In patients with an uneventful postoperative course, the median intention to discharge was earlier in elderly ERAS + patients as compared to the elderly ERAS- patients (4 days versus 8 days, P < 0.001). CONCLUSION: An ERAS protocol following PD seems to be feasible and safe among elderly although it is not associated with improved postoperative outcomes.

Enhanced second-harmonic generation from magnetic resonance in AlGaAs nanoantennas.

We designed AlGaAs-on-aluminium-oxide all-dielectric nanoantennas with magnetic dipole resonance at near-infrared wavelengths. These devices, shaped as cylinders of 400nm height and different radii, offer a few crucial advantages with respect to the silicon-on-insulator platform for operation around 1.55µm wavelength: absence of two-photon absorption, high χ((2)) nonlinearity, and the perspective of a monolithic integration with a laser. We analyzed volume χ((2)) nonlinear effects associated to a magnetic dipole resonance in these nanoantennas, and we predict second-harmonic generation exceeding 10(-3) efficiency with 1GW/cm(2) of pump intensity.

The comprehensiveness of the ESHRE/ESGE classification of female genital tract congenital anomalies: a systematic review of cases not classified by the AFS system.

STUDY QUESTION: How comprehensive is the recently published European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) classification system of female genital anomalies? SUMMARY ANSWER: The ESHRE/ESGE classification provides a comprehensive description and categorization of almost all of the currently known anomalies that could not be classified properly with the American Fertility Society (AFS) system. WHAT IS KNOWN ALREADY: Until now, the more accepted classification system, namely that of the AFS, is associated with serious limitations in effective categorization of female genital anomalies. Many cases published in the literature could not be properly classified using the AFS system, yet a clear and accurate classification is a prerequisite for treatment. STUDY DESIGN, SIZE AND DURATION: The CONUTA (CONgenital UTerine Anomalies) ESHRE/ESGE group conducted a systematic review of the literature to examine if those types of anomalies that could not be properly classified with the AFS system could be effectively classified with the use of the new ESHRE/ESGE system. An electronic literature search through Medline, Embase and Cochrane library was carried out from January 1988 to January 2014. Three participants independently screened, selected articles of potential interest and finally extracted data from all the included studies. Any disagreement was discussed and resolved after consultation with a fourth reviewer and the results were assessed independently and approved by all members of the CONUTA group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 143 articles assessed in detail, 120 were finally selected reporting 140 cases that could not properly fit into a specific class of the AFS system. Those 140 cases were clustered in 39 different types of anomalies. MAIN RESULTS AND THE ROLE OF CHANCE: The congenital anomaly involved a single organ in 12 (30.8%) out of the 39 types of anomalies, while multiple organs and/or segments of Müllerian ducts (complex anomaly) were involved in 27 (69.2%) types. Uterus was the organ most frequently involved (30/39: 76.9%), followed by cervix (26/39: 66.7%) and vagina (23/39: 59%). In all 39 types, the ESHRE/ESGE classification system provided a comprehensive description of each single or complex anomaly. A precise categorization was reached in 38 out of 39 types studied. Only one case of a bizarre uterine anomaly, with no clear embryological defect, could not be categorized and thus was placed in Class 6 (un-classified) of the ESHRE/ESGE system. LIMITATIONS, REASONS FOR CAUTION: The review of the literature was thorough but we cannot rule out the possibility that other defects exist which will also require testing in the new ESHRE/ESGE system. These anomalies, however, must be rare. WIDER IMPLICATIONS OF THE FINDINGS: The comprehensiveness of the ESHRE/ESGE classification adds objective scientific validity to its use. This may, therefore, promote its further dissemination and acceptance, which will have a positive outcome in clinical care and research. STUDY FUNDING/COMPETING INTERESTS: None.

Levodopa/carbidopa intestinal gel infusion in advanced Parkinson's disease: a 7-year experience.

BACKGROUND AND PURPOSE: Levodopa/carbidopa intestinal gel (LCIG) infusion is nowadays becoming an established therapeutic option for advanced Parkinson's disease (PD) patients with fluctuating symptoms unresponsive to conventional oral treatment. As the implementation of LCIG therapy is increasing, there is a need for safety and efficacy data from current clinical practice. METHODS: All PD patients treated with LCIG at our centre over a 7-year period were analysed to determine the duration of treatment, retention rate, reasons for discontinuation, LCIG efficacy in motor complications, modifications of concomitant therapy and adverse events. RESULTS: Of the 59 patients, seven subjects (12%) died of causes unrelated to LCIG infusion and 11 patients (19%) discontinued therapy prior to the cut-off date. Duodopa improved motor complications and over 90% of patients reported an improvement in their quality of life, autonomy and clinical global status. The most common adverse events were dislocation and kinking of the intestinal tube. CONCLUSIONS: LCIG infusion is effective for the long-term treatment of advanced PD patients and exerts a positive and clinically significant effect on motor complications with a relatively low dropout rate.

Benefit of supplements in functional dyspepsia after treatment of Helicobacter pylori.

AIM: Functional dyspepsia, though benign, leads to deterioration of the quality of life and high costs for healthcare systems. The optimal therapy for functional dyspepsia is still to be defined because of its multifactorial pathogenesis. In an open multicentric study of patients with functional dyspepsia, we prospectively evaluated the benefit of treatment with a food supplement composed of sodium alginate, carbonate calcium, pineapple, papaya, ginger, α-galactosidase and fennel (Perdiges, Bioten Snc, Turin, Italy). METHODS: Ninety-one consecutive patients were included, suffering from functional dyspepsia, who had been previously submitted to therapy to eradicate the infection from Helicobacter pylori (H. pylori) and were waiting to perform the Urea Breath Test (UBT). The primary goal was to establish the percentage of patients who continued to abstain from proton pump inhibitors (PPI) as they waited to carry out the UBT, differentiating between patients who were treated (N.=55) with Perdiges and those who were not (N.=36). Our secondary goal was to document the differences within the 2 groups in terms of symptoms perceived between the start and end of the observation period. The wellness reported, during or in absence of treatment with Perdiges, was evaluated by the use of the VAS scale (Visual Analogical Scale) completed before the start of the treatment and after 30 days. RESULTS: All the patients treated with Perdiges (55/55, 100%) and 31/36 (86.1%) patients who were not (P=0.008) continued to abstain from PPI in the period awaiting the UBT. The VAS scale of those who took Perdiges improved on average by 1.78 points versus a worsening of 0.08 points of those who did not take it (P<0.0001). Furthermore, while among those who took Perdiges there was a statistically significant improvement (P<0.0001) in the VAS scale, between the baseline and the end of treatment, a worsening of 0.08 points (P=0.78) was noticed among the patients who did not take it. CONCLUSION: Perdiges is significantly effective in the period following treatment to eradicate the infection from H. pylori in patients with functional dyspepsia. This allows to reduce the need to use antisecretive drugs. Further randomised studies, with wide ranging case histories, must assess its long-term efficacy.

Aprepitant and granisetron for the prophylaxis of radiotherapy-induced nausea and vomiting after moderately emetogenic radiotherapy for bone metastases: a prospective pilot study.

PURPOSE: We evaluated the novel combination of aprepitant and granisetron for the prophylaxis of radiotherapy-induced nausea and vomiting (rinv) among patients receiving moderately-emetogenic radiotherapy for thoracolumbar bone metastases. METHODS: In this single-centre two-arm nonrandomized prospective pilot study, patients undergoing single-fraction radiotherapy (8 Gy) received aprepitant 125 mg and granisetron 2 mg on the day of radiotherapy and aprepitant 80 mg on each of the first 2 days after the day of radiotherapy. Patients undergoing multiple-fraction radiotherapy (20 Gy in 5 fractions) received aprepitant 125 mg on day 1 of radiotherapy, aprepitant 80 mg on days 3 and 5 of radiotherapy, and granisetron 2 mg on every day of radiotherapy. Symptoms and total medication intake were recorded daily during the acute phase (day 1 of radiotherapy until the first day after the last day of radiotherapy), and the delayed phase (days 2-10 after the last day of radiotherapy). Control of vomiting, retching, and nausea was defined as no symptoms and no use of rescue medication. RESULTS: Control rates for single-fraction patients (n = 13) were 100% for acute nausea, 62% for delayed nausea, 100% for acute vomiting and retching, and 85% for delayed vomiting and retching. Control rates for multiple-fraction patients (n = 6) were 67% for acute nausea, 83% for delayed nausea, 67% for acute vomiting and retching, and 83% for delayed vomiting and retching. No grade 3 or 4 toxicities attributable to the study intervention were observed. CONCLUSIONS: The combination of aprepitant and granisetron was safe and efficacious for the prophylaxis of rinv after both single- and multiple-fraction moderately emetogenic radiotherapy for thoracolumbar bone metastases. Our results require confirmation in a larger population.

Endoscopic ultrasound in the 2013 preoperative evaluation of gastric cancer.

The capacity of endoscopic ultrasound (EUS) to distinguish the different wall layers of the gastrointestinal (GI) tract and the possibility to obtain samples of suspicious lesions or lymph nodes by means of EUS-guided fine-needle aspiration (EUS-FNA), make EUS an ideal staging modality for GI cancers. After an endoscopic and histological diagnosis of gastric cancer (GC), an accurate preoperative evaluation is essential to choose the correct management decision, because for this malignancy various and radically different stage-oriented therapies can be performed. Even if EUS is inserted in the last guidelines for the management of GC as an essential pretherapeutic staging modality, in the literature the reported accuracy, the imaging features and the performances of the technique are variable. In this review, we synthesize the current status and the imaging findings of EUS when describing and staging GC, with a particular attention to the early GC that represents till today a diagnostic and therapeutic challenge. Currently, the EUS study is mandatory for the preoperative staging, to assess with a good accuracy the tumor depth of wall invasion, the presence of suspicious lymph-nodes and of ascites (predictive of peritoneal involvement). The main limitations for a correct EUS staging remain some features of the lesion or its localization, so more attention should be paid when these characteristics are present.

Settleable atmospheric particulate matter affects the swimming performance and aerobic metabolic rate of Nile tilapia (Oreochromis niloticus).

Atmospheric particulate matter (APM) produced by the steel industry comprises a complex mixture of particles that includes a wide variety of metals and metallic nanoparticles. These particles settle out onto areas surrounding the industries. There is evidence that this 'settleable' APM (SePM) may cause air-to-water cross-contamination with significant effects on aquatic biota. Recent investigations have reported sublethal impacts on the gill structure and blood oxygen-carrying capacity of fishes, which raises the hypothesis that there will be consequences for gas exchange capacity and ability to support aerobic activities. Therefore, we investigated the effects of an environmentally relevant level of SePM contamination on swimming performance and associated aerobic metabolic rates in Nile tilapia, Oreochromis niloticus. Short-term exposure (96 h) to SePM reduced critical swimming speed, energetic efficiency of aerobic swimming, standard metabolic rate, maximum metabolic rate, and aerobic scope. The compromised swimming performance could have adverse ecological effects by limiting foraging ability, predator evasion, territorial protection, and migration. The impairments to aerobic capacity could also affect overall fish performance by influencing long-term energy balance and allocation to growth and reproduction. Thus, despite being sublethal, SePM contamination is considerably debilitating, and if its limiting effects are not compensated for in the longer term, this may reduce the survival and fitness of fish populations.