Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients

INTRODUCTION: Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients. METHODS: We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group). RESULTS: In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019). CONCLUSION: We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment

Non-sutureless minimally invasive aortic valve replacement: mini-sternotomy versus mini-thoracotomy: a series of 1130 patients

OBJECTIVES: Aortic valve replacement through conventional sternotomy still represents the gold-standard surgical approach for aortic valve disease. However, given the increasing number of patients with comorbidities, strategies that can improve operative results are always sought. Minimally invasive aortic valve surgery, although related to a steep learning curve, might be associated with improved post- operative outcomes. The main aim of this study was to assess whether significant differences exist in terms of operative and early results between a mini-sternotomy and a right mini-thoracotomy approach for isolated aortic valve replacement without sutureless technologies. METHODS: This is an observational retrospective multicentre study from nine Italian cardiac centres that analyses prospectively collected data of patients who underwent isolated minimally invasive aortic valve replacement between January 2010 and December 2014. Two approaches are considered (mini-sternotomy and mini-thoracotomy) and compared in terms of operative and early outcomes. RESULTS: After interrogation of the centralized database, a total of 1130 patients were retrieved (854 mini-sternotomy and 276 mini-thoracotomy). Patients in the mini-sternotomy group had a higher risk profile. There was no difference in terms of early mortality; cardiopulmonary bypass and cross-clamp time did not differ significantly between the groups; and a significantly higher number of reoperations for bleeding was observed in the right mini-thoracotomy group. CONCLUSIONS: Both mini-sternotomy and mini-thoracotomy could be performed safely, with low mortality and postoperative morbidity. The mini-thoracotomy approach was associated with a significantly higher rate of reoperation for bleeding. Uptake among cardiac centres was low. Sutureless technologies could potentially increase surgical volume by simplifying the mini-thoracotomy procedure

Bisphosphonate-associated jaws osteonecrosis: an important complication of oncology treatment

Os bisfosfonatos são um grupo de medicamentos utilizados no tratamento de doenças malignas metastáticas e em outras doenças ósseas como osteoporose e doença de Paget. A despeito dos seus benefícios, uma importante complicação denominada de osteonecrose dos maxilares vem sendo observada nos pacientes usuários crônicos dos bisfosfonatos que se caracteriza clinicamente por exposições ósseas na região maxilofacial persistente, acompanhadas de osteomielite, geralmente sintomáticas e cujo tratamento é complexo. Este estudo tem por objetivo revisar a literatura sobre a osteonecrose associada ao uso dos bisfosfonatos, em especial, em oncologia, no período de 2003 a 2008. Serão apresentados e discutidos os fatores de risco, aspectos etiopatogênicos, clínicos, imagenológicos, terapêuticos e preventivos desta doença. Devido à dificuldade de tratamento da osteonecrose associada aos bisfosfonatos, o foco deve ser a prevenção, sendo o ideal a eliminação de quadros infecciosos orais antes da terapia com os bisfosfonatos ter sido iniciada e minimizar traumas em boca após o uso destes medicamentos.Bisphosphonates are drugs used in the treatment of malignant metastatic diseases and in other bone lesions such as osteoporosis and Paget´s disease. Besides their benefits, jaw osteonecrosis, an important side effect, has been observed in long-term users of these drugs. Jaw osteonecrosis is clinically characterized by prolonged maxillary and mandible bone exposure accompanied by osteomyelitis. These lesions are usually symptomatic and difficult to treat. This study has the objective of reviewing publications from 2003 to 2008 about bisphosphonate-associated jaw osteonecrosis, in particular in relation to oncology. Risk factors, and etiopathological, clinical, radiographic, therapeutic, and preventive aspects of this condition are presented and discussed. Due to the difficulty to treat this disease, the focus must be prevention, with the ideal therapy being the elimination of oral infections before treatment with bisphosphonates is initiated thereby attempting to minimize possible traumas to the mouth with the use of these medications

Right anterior mini-thoracotomy vs. conventional sternotomy for aortic valve replacement: A propensity-matched comparison

Background: Right anterior mini-thoracotomy (MIAVR) is a promising technique for aortic valve replacement. We aimed at comparing its outcomes with those obtained in a propensity-matched group of patients undergoing sternotomy at our two high-volume centers. Methods: Main clinical and operative data of patients undergoing aortic valve replacement between January 2010 and May 2016 were retrospectively collected. A total of 678 patients were treated with a standard full sternotomy approach, while MIAVR was performed in 502. Propensity score matching identified 363 patients per each group. Results: In-hospital mortality was not significantly different between the propensity-matched groups (1.7% in MIAVR patients vs. 2.2% in conventional sternotomy patients; P=0.79). No significant difference in the incidence of major post-operative complications was observed. Post-operative ventilation times (median 7, range 5-12 hours in MIAVR patients vs. median 7, range 5-12 in conventional sternotomy patients; P=0.72) were not significantly different between the two groups. Cardiopulmonary bypass time (61.0±21.0 vs. 65.9±24.7 min in conventional sternotomy group; P &lt; 0.01) and aortic cross-clamping time (48.3±16.7 vs. 53.2±19.6 min in full sternotomy group; P &lt; 0.01) were shorter in MIAVR group. EuroSCORE (OR 1.52, 95% CI, 1.12-2.06; P &lt; 0.01) was found to be the only independent predictor of intra-hospital mortality in the whole propensity-matched population. Conclusions: Our experience shows that mini-access isolated aortic valve surgery is a reproducible, safe and effective procedure with similar outcomes and no longer operative times compared to conventional sternotomy

Minimally invasive mitral valve surgery: State-of-the-art and our experience

The minimally invasive approach is becoming the standard-of-care for surgery of the mitral valve. As any less invasive strategy, it entails an increased surgical complexity. Standard-of-care mitral repair using the totally videoscopic approach is indeed reproducible; however, few specific data on patients with complex mitral valve disease are available in the published literature. The purpose of the present paper is to provide an overview of the current state-of-the-art in minimally invasive cardiac surgery, and a summary of recent evidence on the topic, with particular regard to the surgical techniques and comparisons with conventional surgery. The experience of the GVM Care and Research network in the field is also briefly reported

An observational retrospective analysis of the main metastatic site and corresponding locoregional treatment as a prognostic factor in metastatic gastric cancer

Despite novel drugs, the prognosis for patients with metastatic gastric cancer remains poor. In rare instances, locoregional therapies are used in addition to standard chemotherapy in patients with oligometastatic involvement. This type of approach has not been supported by solid published evidence. The aim of the present retrospective study was to assess the prognostic impact of factors such as metastatic site, tumour histology and locoregional treatment in patients with metastatic gastric cancer. A total of 184 patients with metastatic gastric or gastroesophageal junction adenocarcinoma who received at least one line of palliative therapy with doublet or triplet chemotherapy were enrolled in the current analysis. Median overall survival (OS) was 8.32 months (95% CI, 7.02-9.41) and median progression-free survival (PFS) was 4.16 months (95% CI, 3.24-5.08). Lung metastases vs. other sites of metastatic involvement [hazard ratio (HR), 0.27; P=0.0133] and intestinal histology (HR, 0.48; P=0.08) were significantly associated with an improved OS. Improved PFS was also observed (HR, 0.49; P=0.10 and HR, 0.72; P=0.08 for lung metastases and intestinal histology, respectively). Second line chemotherapy and locoregional treatment of metastases (surgery or radiotherapy) were associated with improved OS (HR, 0.52; P<0.0001 and HR, 0.35; P<0.0001, respectively). Multivariate analysis confirmed an independent prognostic role for OS only for locoregional treatment, second line treatment and intestinal histology. The present results suggested that the presence of lung metastases alone was not a relevant prognostic factor and was influenced by the availability of further lines of treatment or by locoregional treatments. Locoregional treatments in patients with oligometastatic disease should be offered as they allow prolonged survival in patients with otherwise relatively short life expectancy

Evidence for a large-magnitude Holocene eruption of Mount Rittmann (Antarctica): A volcanological reconstruction using the marine tephra record

In Antarctica, the near-source exposures of volcanic eruption deposits are often limited as they are not well preserved in the dynamic glacial environment, thus making volcanological reconstructions of explosive eruptions extremely challenging. Fortunately, pyroclastic deposits from explosive eruptions are preserved in Southern Ocean sediments surrounding Antarctica, and the tephrostratigraphy of these sequences offers crucial volcanological information including the timing and tempo of past eruptions, their magnitude, and eruption dynamics. Here we report the results of a tephrostratigraphy and tephrochronology study focused on four sediment cores recovered from the Wood Bay area in the western Ross Sea, Antarctica. In all these sedimentary sequences, we found a well-stratified primary tephra of considerable thickness, up to 80 cm, hereafter named the Aviator Tephra (AVT). According to the characteristics of the tephra deposit and its distribution, the AVT was associated with an eruption of considerable intensity, potentially representing one of the largest Holocene eruptions recorded in Antarctica. Based on the major and trace element geochemistry and the mineral assemblage of the tephra, Mount Rittmann was identified as the source of the AVT. A Holocene age of ∼11 ka was determined by radiocarbon dating organic material within the sediments and 40Ar-39Ar dating of alkali-feldspar crystals included in the tephra. Eruption dynamics were initially dominated by hydromagmatic magma fragmentation conditions producing a sustained, relatively wet and ash-rich eruptive cloud. The eruption then evolved into a highly energetic, relatively dry magmatic Plinian eruption. The last phase was characterized by renewed efficient magma-water interaction and/or collapse of the eruptive column producing pyroclastic density currents and associated co-ignimbritic plumes. The distal tephra deposits might be linked to the widespread lag breccia layer previously identified on the rim of the Mount Rittmann caldera which share the same geochemical composition. Diatoms found in the sediments surrounding the AVT and the primary characteristics of the tephra indicate that the Wood Bay area was open sea at the time of the eruption, which is much earlier than previously thought. AVT is also an excellent tephrostratigraphic marker for the Wood Bay area, in the Ross Sea, and a useful marker for future synchronization of continental ice and marine archives in the region

XM02 is superior to placebo and equivalent to Neupogen™ in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy

Abstract Background Recombinant granulocyte colony-stimulating factors (G-CSFs) such as Filgrastim are used to treat chemotherapy-induced neutropenia. We investigated a new G-CSF, XM02, and compared it to Neupogen™ after myelotoxic chemotherapy in breast cancer (BC) patients. Methods A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were randomised to treatment with daily injections (subcutaneous 5 μg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of XM02 (n = 140), Neupogen™ (n = 136) or placebo (n = 72). The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1. Results The mean DSN in cycle 1 was 1.1, 1.1, and 3.9 days in the XM02, Neupogen™, and placebo group, respectively. Superiority of XM02 over placebo and equivalence of XM02 with Neupogen™ could be demonstrated. Toxicities were similar between XM02 and Neupogen™. Conclusion XM02 was superior to placebo and equivalent to Neupogen™ in reducing DSN after myelotoxic chemotherapy. Trial Registration Current Controlled Trials ISRCTN02270769</p

Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front-line with paediatric-inspired regimens: A retrospective multicentre Campus ALL study

Within the Campus ALL network we analyzed the incidence, characteristics, treatment and outcome of a central nervous system (CNS) relapse in 1035 consecutive adult acute lymphoblastic leukemia (ALL) patients treated frontline with pediatric-inspired protocols between 2009 and 2020. Seventy-one patients (6.8%) experienced a CNS recurrence, more frequently in T- (28/278; 10%) than in B-ALL (43/757; 5.7%) (p&nbsp;= 0.017). An early CNS relapse—&lt; 12 months from diagnosis—was observed in 41 patients. In multivariate analysis, risk factors for early CNS relapse included T-cell phenotype (p&nbsp;=&nbsp;&lt;0.001), hyperleucocytosis &gt;100 × 109/L (p&lt;0.001) and male gender (p&nbsp;= 0.015). Treatment was heterogeneous, including chemotherapy, radiotherapy, intrathecal therapy and novel agents. A complete remission (CR) was obtained in 39 patients (55%) with no differences among strategies. After CR, 26 patients underwent an allogenic transplant, with a significant overall survival benefit compared to non-transplanted patients (p&nbsp;= 0.012). After a median observation of 8 months from CNS relapse, 23 patients (32%) were alive. In multivariate analysis, the time to CNS relapse was the strongest predictor of a lower 2-year post-relapse survival (p&lt;0.001). In conclusion, in adult ALL the outcome after a CNS relapse remains very poor. Effective CNS prophylaxis remains the best approach and allogenic transplant should be pursued when possible

Charge separation relative to the reaction plane in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}}= 2.76 TeV

Measurements of charge dependent azimuthal correlations with the ALICE detector at the LHC are reported for Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV. Two- and three-particle charge-dependent azimuthal correlations in the pseudo-rapidity range $|\eta| < 0.8$ are presented as a function of the collision centrality, particle separation in pseudo-rapidity, and transverse momentum. A clear signal compatible with a charge-dependent separation relative to the reaction plane is observed, which shows little or no collision energy dependence when compared to measurements at RHIC energies. This provides a new insight for understanding the nature of the charge dependent azimuthal correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286