Concurrent versus sequential adjuvant chemo-endocrine therapy in hormone-receptor positive early stage breast cancer patients: a systematic review and meta-analysis.

BACKGROUND: Although in clinical practice adjuvant chemotherapy (CT) and endocrine therapy (ET) are administered sequentially in patients with hormone-receptor positive breast cancer, the optimal timing, i.e. concurrent or sequential administration, of these treatments has been scarcely investigated. To better clarify this issue we conducted a systematic review and meta-analysis of randomized studies comparing these two modalities of administrations in terms of disease-free survival (DFS) and overall survival (OS). METHODS: Relevant studies were identified by searching PubMed, Web of Knowledge and the proceedings of the major conferences with no date restriction up to March 2016. The summary risk estimates (pooled hazard ratio [HR] and 95% confidence intervals [CI]) for DFS and OS were calculated using random effect models (DerSimonian and Laird method). RESULTS: A total of three randomized studies were eligible including 2021 breast cancer patients. Overall, 755 DFS events were observed, 365 in the sequential arm and 390 in the concomitant arm, with a pooled HR of 0.95 (95% CI = 0.76 to 1.18, P = 0.643). No association between timing of treatment and OS was observed (HR = 0.95; 95% CI = 0.80 to 1.12, P = 0.529). CONCLUSION: Our pooled analysis showed no association between the timing of administration of adjuvant CT and ET and DFS and OS in breast cancer patients candidates for both adjuvant treatments. Because of the small number of published trials, the lack of data on the timing with modern adjuvant treatments, i.e. taxane-containing CT and aromatase inhibitors, this topic remain still controversial and requires further studies to be clarified.

Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies.

BACKGROUND: The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS). METHODS: A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models. RESULTS: A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P < 0.001), yet with significant heterogeneity (I(2) = 47.1%, Pheterogeneity = 0.026). In eight studies reporting amenorrhea rates 1 year after chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P < 0.001) without heterogeneity (I(2) = 0.0%, Pheterogeneity = 0.936). In five studies reporting pregnancies, more patients treated with LHRHa achieved pregnancy (33 versus 19 women; OR 1.83, 95% CI 1.02-3.28, P = 0.041; I(2) = 0.0%, Pheterogeneity = 0.629). In three studies reporting DFS, no difference was observed (HR 1.00, 95% CI 0.49-2.04, P = 0.939; I(2) = 68.0%, Pheterogeneity = 0.044). CONCLUSION: Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis.

Discharging fused silica optics occluded by an electrostatic drive.

Charge accumulation on test masses is a potentially limiting noise source for gravitational-wave interferometers, and may occur due to exposure to an electrostatic drive (ESD) in modern test mass suspensions. We verify that an ESD can cause charge accumulation on a fused silica test mass at a rate of 8 × 10(-16) C/cm(2)/h. We also demonstrate a charge mitigation system consisting of a stream of nitrogen ionized by copper feedthrough pins at 3750 VAC. We demonstrate that the system can neutralize positive and negative charge from 10(-11) C/cm(2) to 3 × 10(-14) C/cm(2) in under 2 h.

Note: discharging fused silica test masses with ionized nitrogen.

We have developed a technique for discharging fused silica test masses in a gravitational-wave interferometer with nitrogen ionized by an electron beam. The electrons are produced from a heated filament by thermionic emission in a low-pressure region to avoid contamination and burnout. Some electrons then pass through a small aperture and ionize nitrogen in a higher-pressure region, and this ionized gas is pumped across the test mass surface, neutralizing both polarities of charge. The discharge rate varies exponentially with charge density and filament current, quadratically with filament potential, and has an optimal working pressure of ∼8 mT. Adapting the technique to larger test mass chambers is also discussed.

SV40 associated miRNAs are not detectable in mesotheliomas.

BACKGROUND: Simian virus-40 (SV40) is a DNA tumour virus that was introduced into the human population with contaminated poliovirus vaccine, and its role in mesothelioma is widely debated. PCR based testing has been called into question, as false positives can be because of cross-reactivity with related viruses, or to laboratory contamination. The Institute of Medicine has recommended the development of more sensitive and specific tests to resolve this controversy. METHODS: We have characterized highly sensitive RT-PCR based assays that are specific for SV40-encoded microRNAs (miRNAs), as an alternative to current testing methods. RESULTS: Using this sensitive and specific detection method, we were unable to identify SV40 miRNA expression in human malignant pleural mesothelioma (MM) samples. CONCLUSION: Our work indicates that SV40 miRNAs are not likely to contribute to mesothelioma tumourogenesis, but highlights the value of this approach when compared with the relatively unspecific current testing methods.

Minimally invasive versus traditional chest surgical approach in patients with reduced renal function.

AIM: All surgical access approaches to the chest wall cause a different degree of muscle damage and freeing of substances as myogloblin into the bloodstream thus compromising kidney function. The aim of this study was to evaluate the potential kidney damage in relation to entity of muscle lesions caused by the different surgical approaches. METHODS: The hematic levels of creatine phosphokinase (CPK), myoglobin, lactate dehydrogenase (LDH), creatinine as well as the amount of the diuresis at different intervals of time were taken of 66 patients who underwent a thoracic surgical operation with diverse surgical access approaches. RESULTS: Surgery determines muscle substances to be freed into the bloodstream. Myoglo-blin levels resulted to be correlated to those of CPK (r=0.83; P<0.00005). Although serum levels of myogloblin are not determined as a routine procedure, high levels of CPK must induce to dose myogloblin. The amount of muscle substances freed depend on the width of the surgical access (r=0.7; P<0.00005) and not upon extension (r=0.36; P=0.18) or duration of surgery. (r=0.4; P=0.093). CONCLUSION: In patients with a reduced renal function or affected by kidney failure a minimally invasive or thoracoscopic approach is indicated whenever possible in order to reduce the amount of myogloblin in the bloodstream.

Developing an optical chopper-modulated capacitive probe for measuring surface charge.

Gravitational-wave observatories such as Laser Interferometer Gravitational-Wave Observatory (LIGO) use suspended optics in a Michelson interferometer configuration to measure strains in space between 10 Hz and 3 kHz. One potential noise source in this frequency range is the buildup and motion of surface charge on the optics, which can generate fluctuating electric fields, interfere with position control, and reduce reflectance by attracting dust to the optical surface. We have developed a capacitive probe to measure the magnitude and relaxation time of surface charge deposited on smaller test optics in high vacuum ( approximately 10(-5) Torr). Our device modulates capacitance with a tuning-fork optical chopper between probe and sample, chosen for vacuum compatibility and minimal cost. We have found that the probe has a resolution of (3.5+/-0.5)x10(5) e(-)cm(2) in air, on the order of charging levels that could contribute noise to Advanced LIGO, and sufficient for measuring relaxation times on test optics.

Frequency of musculoskeletal conditions among patients referred to Italian tertiary rheumatological centers.

OBJECTIVE: To describe the occurrence of different rheumatic diseases and to examine the characteristics of patients referred to six Italian rheumatological units. To compare these data with those from other countries. METHODS: Six Italian rheumatological tertiary referral centers participated in the study. Diagnoses of in- and outpatients aged over 16 years were classified according to the International Classification of Diseases, ninth revision. RESULTS: Three thousand, five hundred and thirty-seven patients with mean age 56 +/- 14.8 years, of which 2604 (73.6%) were women, were studied. Inflammatory joint and spine diseases were diagnosed in 40.4%, connective tissue diseases in 14.4%, degenerative joint and spine diseases in 21.4%, soft tissue rheumatisms in 18.5%, and metabolic bone diseases in 5.3%. There was a significant difference among centers in the frequency of most diagnoses: non-academic centers cared for more patients with arthritis and connective tissue diseases and for less patients with degenerative diseases, soft tissue rheumatisms and metabolic bone diseases. Connective tissue diseases were constantly seen more often in Italian centers, whereas soft tissue rheumatisms were seen more often abroad. CONCLUSION: Our data emphasize the great variability of the diagnostic case-mix in different centers from the same country, an observation that raises some concerns of the results of descriptive multicenter studies. Studies on the breakdown of diagnoses made in rheumatological centers could be helpful to determine the burden of rheumatic diseases on the health system, and for the planning of health interventions by both the national rheumatological societies and health authorities.

Incidence of pleural mesothelioma in Liguria Region, Italy (1996-2002).

In this study, incidence of pleural malignant mesothelioma (PMM) in the Liguria Region (Italy) (approximately 1.6 million inhabitants), in the presence of asbestos exposure was investigated. New PMM cases recorded by the Mesothelioma Registry of Liguria, from 1996 to 2002 and interviews reported on a standardised questionnaire were analysed according to demographical and etiological characteristics. Nine hundred and forty five PMM cases were recorded (757 males and 188 females); the age standardised (European population) incidence rates per 100,000 were 8.51 and 1.43, respectively. The rates among the four provinces ranged between 1.18 and 13.7 for males and 0.68 and 1.44 for females. The questionnaire was evaluated for 786 PMM cases (or next-of-kin). Higher incidence rates were reported in the provinces with larger industrial and harbour areas, including shipyards (construction and repair), dockyards, building activities, chemical and heavy industrial activities. Asbestos exposure was unlikely or unknown for 57.5% females and 15% males. A major role of environmental asbestos exposure in the etiology of PMM is hypothesised for females and for a minor proportion of males.

Oncological research overview in the European Union. A 5-year survey.

This study evaluates the distribution of papers published by European Union (EU) authors in oncological journals from 1996 to 2000, and compares the results with those of a previous study carried out in 1995. The impact of oncological research in the EU is compared with that of the United States (US) and the world, and research trends are highlighted through an analysis of keywords. Data on articles published in oncological journals (ISI Subject Category=ONCOLOGY) selected from Current Contents/Life Science and Current Contents/Clinical Medicine (1996-2000) on the weekly diskette version were downloaded. Mean Impact Factor (IF), source country population and gross domestic product (GDP) were analysed. A special-purpose software to determine the most commonly used keywords was utilised. From 1996 to 2000, 66021 papers were published in the world in oncological journals: 35.5% came from the EU (UK, Italy, Germany, France and The Netherlands ranking the highest) and 38.8% from the US. The total number of EU papers increased from 4063 in 1995 to 4843 in 2000. Compared with the previous study, no important changes were seen, with the top five countries in 1995 maintaining their ranking in 2000. However, some small countries (Denmark, Norway and Ireland) fared worse in 2000, while others (France, Germany and Greece) improved their position. The mean IF for the EU papers was 2.9 compared with 4.0 in the US. The mean IF increased for all of the nations. In particular, while France and Germany showed a very positive performance trend in their respective IFs, countries such as Norway, Denmark and Italy showed less improvement. The analysis of keywords appearing in articles written in 2000 showed that the leading fields of research were breast cancer in the diseases category of keywords, cisplatin and platinum compounds in the drugs category, radiotherapy in the treatment category and apoptosis in the experimental studies category. Variety in the use of keywords should be avoided, and journal editors should encourage their standardisation.

[Diabetes and bleeding in thoracic surgery]. / Diabete e sanguinamento in toraco-chirurgia.

BACKGROUND: The aim of this study is to assess the influence of diabetes over early postoperative bleeding in thoracic surgical patients. In fact, diabetes leads to hypercoagulation as well as to an alteration of microvessels that could have a negative effect on the retraction and vasoconstriction of the damaged microvessel before hemostasis coagulation phase. METHODS: Data referring to 193 typical pneumonectomies associated with extensive removal of mediastinic nodes, 19 performed in diabetic patients have been retrospectively analysed. RESULTS: Any statistically significant difference between the two groups was found. CONCLUSIONS: More studies would be necessary to confirm our conclusions, on more extensive series of patients with more severe diabetic disease, as well as on non-thoracic surgical patients, in order to avoid the consequences of the early and sudden negative pressure on wounds, that in thoracic patients could hide the effects of less evident factors.

Assessing oncological productivity. is one method sufficient?

This work analyses the distribution of oncological papers published in 1995 by authors from the European Union (EU) in any journal of all the Subject Categories of the Science Citation Index compiled by ISI (Institute for Scientific Information, Philadelphia, USA) and is based on the country of origin of all of the contributors. The study compares the results with those of a previous study dealing with publications in journals of the ISI Oncology Category based on the country of origin of the corresponding author. The aim of the study was to compare two different methods used to evaluate research productivity in order to understand the extent to which the results are influenced by the methodology adopted. Data on the number of published papers for each country, ratio between the number of occurrences of papers and country population and gross domestic product (GDP), and mean Impact Factors (IF ) were compared. While findings on the number of published papers (United Kingdom (UK), Germany and France ranking best), source country population (Sweden, Denmark and the Netherlands ranking best) and gross domestic product (Sweden, Finland and the Netherlands ranking best) showed no important changes, the mean IF value result was, for some countries, very different from the previous study. In particular, while Germany, Belgium, Portugal and France fared well, Norway, Sweden, Austria and Spain showed poorer results. Some hypotheses are advanced, and care in the scientometric interpretation of data is urged. An analysis of the journals in which EU authors published their articles was also carried out and the main SCI categories to which the journals belong are reported. As was expected, many categories other than oncology were represented (biochemistry, haematology, pathology, etc.).

Histological subtypes of Hodgkin's disease in the setting of HIV infection.

The relative incidence of Hodgkin's disease (HD) has been found to have increased approximately seven times in HIV-infected patients. We analyzed the histological distribution of HIV-associated HD with the aim of clarifying purported difference(s) from de novo HD. References on HIV/AIDS-associated HD were retrieved from the most complete databases. Nineteen articles were the subject of our analysis. Seventeen of them reported data on the histological type of HIV/AIDS-associated HD patients; the route of infection and age of the patients were also considered when available. According to the Peto's methodology, histological types were compared with those from two large studies in the United States on de novo HD: 3,245 cases from the Surveillance, Epidemiology, and End Results (SEER) and 1,140 from Stanford University. The analysis of the two groups showed statistically significant differences (p<0.001) in the percentage of all histological types and odds ratios (OR) of the pooled effect of 0.4 (95% CI: 0.3-0.6) for lymphocyte predominance (LP), 0.3 (95% CI: 0.2-0.4) for nodular sclerosis (NS), 3.2 (95% CI: 2.6-3.8) for mixed cellularity (MC), and 6.3 (95% CI: 4.5-8.8) for lymphocyte depletion (LD). Comparison with the Stanford University series yielded similar results. Whilst retrospective and based on a limited number of cases, our data confirm a higher incidence of unfavorable histological subtypes in HIV-infected patients and show a reduction in the observed cases of good prognosis subtypes. Prospective studies, with careful histological observations, are required to better evaluate the characteristics of the LP subtype in the special setting of HIV infection.

Observation of B --> K(+/-) pi(0) and B --> (K)0 pi(0), and evidence for B --> pi(+)pi(-).

We have studied charmless hadronic decays of B mesons into two-body final states with kaons and pions and observe three new processes with the following branching fractions: beta(B-->pi(+)pi(-)) = (4.3(+1. 6)(-1.4)+/-0.5)x10(-6), beta(B-->K(0)pi(0)) = (14.6(+5.9+2.4)(-5.1-3. 3))x10(-6), and beta(B-->K(+)/-pi(0)) = (11.6(+3.0+1.4)(-2.7-1.3))x10(-6). We also update our previous measurements for the decays B-->K(+)/-pi(-/+) and B+/--->K(0)pi(+/-).

Two-body B meson decays to eta and eta('): observation of B --> eta K*.

In a sample of 19 x 10(6) produced B mesons, we have observed the decays B-->eta K(*) and improved our previous measurements of B-->eta'K. The branching fractions we measure for these decay modes are B(B+-->eta K(*+)) = (26.4(+9.6)(-8.2)+/-3.3)x10(-6), B(B(0)-->eta K(*0)) = (13.8(+5.5)(-4.6)+/-1.6)x10(-6), B(B(+)-->eta'K(+) = (80(+10)(-9)+/-7)x10(-6), and B(B(0)-->eta'K0) = (89(+18)(-16)+/-9)x10(-6). We have searched with comparable sensitivity for related decays and report upper limits for these branching fractions.