printing supported by . Visit Chiesi at Stand B2.10 WEDNESDAY, SEPTEMBER 5TH 2012 P4619 Serum thioredoxin-1 as a diagnostic marker for malignant peritoneal mesothelioma Chiharu Tabata1, Takayuki Terada1, Rie Tabata2, Takashi Nakano1.... more
printing supported by . Visit Chiesi at Stand B2.10 WEDNESDAY, SEPTEMBER 5TH 2012 P4619 Serum thioredoxin-1 as a diagnostic marker for malignant peritoneal mesothelioma Chiharu Tabata1, Takayuki Terada1, Rie Tabata2, Takashi Nakano1. 1Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinimiya, Japan; 2Department of Internal Medicine, Hyogo Prefectural Tsukaguchi Hospital, Amagasaki, Japan Background: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intra-peritoneal chemotherapy. Therefore, diagnosing DMPM early is very important. Reactive oxygen species (ROS) play an important role in asbestos toxicity, which is associated with the pathogenesis of DMPM growing. Thioredoxin-1 (TRX) is a small redox-active protein that demonstrates anti-oxidative activity associated with tumor growth. Here, we investigated the serum lev...
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Introduction Coronavirus disease 2019 (COVID-19) has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian... more
Introduction Coronavirus disease 2019 (COVID-19) has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak impacted on access to cancer diagnosis and treatment for LC pts compared to pre-pandemic time. Methods Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared to the same period in 2019. Differences between the two years were analyzed using chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Results A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 vs 1637, p=0.09). Newly LC pts in 2020 were more likely to be diagnosed with stage IV disease (p<0.01) and to be current smokers (p<0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% vs -3.2%) compared to the other months included. More LC pts referred to low/medium volume hospital in 2020 compared to 2019 (p=0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (p=0.94), symptoms onset and cytohistological diagnosis (p=0.92), symptoms onset and treatment start (p=0.40), treatment start and first radiological revaluation (p=0.36). Conclusions Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.
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Introduction: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggressive clinical course and poor prognosis. No reliable prognostic markers have been validated to date; thus, the definition of a specific NEC... more
Introduction: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggressive clinical course and poor prognosis. No reliable prognostic markers have been validated to date; thus, the definition of a specific NEC prognostic algorithm represents a clinical need. This study aimed to analyze a large NEC case series to validate the specific prognostic factors identified in previous studies on gastro-entero-pancreatic and lung NECs and to assess if further prognostic parameters can be isolated. Methods: A pooled analysis of four NEC retrospective studies was performed to evaluate the prognostic role of Ki-67 cut-off, the overall survival (OS) according to primary cancer site, and further prognostic parameters using multivariable Cox proportional hazards model and machine learning random survival forest (RSF). Results: 422 NECs were analyzed. The most represented tumor site was the colorectum (n = 156, 37%), followed by the lungs (n = 111, 26%), gastroesophageal sit...
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BACKGROUND In EBV-related nasopharyngeal carcinoma (NPC), quantitative determination of circulating EBV-DNA (cEBV-DNA) can potentially be applied as disease marker. The aim of the study was to investigate if the clinical utility of... more
BACKGROUND In EBV-related nasopharyngeal carcinoma (NPC), quantitative determination of circulating EBV-DNA (cEBV-DNA) can potentially be applied as disease marker. The aim of the study was to investigate if the clinical utility of cEBV-DNA is established in clinical practice guidelines and if recommendations are provided to standardize the quantitative cEBV-DNA determination. METHODS A systematic literature search for NPC guidelines published since 2011 was performed. Information for cEBV-DNA detection method and use in clinical practice was synthesized in consecutive steps of increasing simplification. RESULTS From 570 titles and abstracts identified by the search, 16 guidelines were included. The selected documents were further clustered as either being based on a systematic literature revision to generate recommendations (4/16) or not (12/16). cEBV-DNA was evaluated in only one guideline based on a systematic revision and in 8 guidelines without systematic revision. Half of available guidelines provide recommendation for its clinical use. Methodological issues on cEBV-DNA determination are discussed by 31% of guidelines, without providing any recommendation on method standardization. CONCLUSIONS Due to its prognostic value, cEBV-DNA is suggested in the pre-treatment work-up and in the follow-up. Guideline producers need to take into more consideration methodological aspects impacting the actual reliability and generalizability of laboratory results.
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To develop a CT texture-based model able to predict epidermal growth factor receptor (EGFR)-mutated, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinomas and distinguish them from wild-type tumors on pre-treatment CT scans.... more
To develop a CT texture-based model able to predict epidermal growth factor receptor (EGFR)-mutated, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinomas and distinguish them from wild-type tumors on pre-treatment CT scans. Texture analysis was performed using proprietary software TexRAD (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT scans of 84 patients with metastatic primary lung adenocarcinoma. Textural features were quantified using the filtration-histogram approach with different spatial scale filters on a single 5-mm-thick central slice considered representative of the whole tumor. In order to deal with class imbalance regarding mutational status percentages in our population, the dataset was optimized using the synthetic minority over-sampling technique (SMOTE) and correlations with textural features were investigated using a generalized boosted regression model (GBM) with a nested cross-validation approach (performance averaged over 1000 resampling episodes). ALK rearrangements, EGFR mutations and wild-type tumors were observed in 19, 28 and 37 patients, respectively, in the original dataset. The balanced dataset was composed of 171 observations. Among the 29 original texture variables, 17 were employed for model building. Skewness on unfiltered images and on fine texture was the most important features. EGFR-mutated tumors showed the highest skewness while ALK-rearranged tumors had the lowest values with wild-type tumors showing intermediate values. The average accuracy of the model calculated on the independent nested validation set was 81.76% (95% CI 81.45–82.06). Texture analysis, in particular skewness values, could be promising for noninvasive characterization of lung adenocarcinoma with respect to EGFR and ALK mutations.
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e12504Background: Aromatase-inhibitors (AIs) decrease the bone mineral density (BMD) and increase the risk of clinical fractures but the mechanism underlying the increased fracture risk (FR) is not fully elucidated. In healthy post... more
e12504Background: Aromatase-inhibitors (AIs) decrease the bone mineral density (BMD) and increase the risk of clinical fractures but the mechanism underlying the increased fracture risk (FR) is not fully elucidated. In healthy post menopausal women obesity is associated with lower FR due the protective effect of elevated estrogen levels. However this mechanism cannot be extended to AI treated pts since estrogens are deeply inhibited. We designed a cross sectional study to explore the effect of Fat body mass (FBM) on the risk of morphometric vertebral fracture (VF) in postmenopausal estrogen receptor positive breast carcinoma (BC) submitted to adjuvant AI therapy. Methods: From October 2013 to May 2017 315 EBC patients (pts) were recruited. All pts underwent a dual-energy X-ray absorptiometry (DXA) for the assessment of BMD, morphometric evaluation of VFs and body composition at baseline and after at least one year of AI therapy. Results: 187 pts were AI naive and 128 AI treated, and the prevalence of VFs ...
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Research Interests: Medicine, Humans, Female, Male, Lung, and 15 moreClinical Sciences, Aged, Middle Aged, Epidermal Growth Factor, Carcinoma, Adult, Prognosis, Disease Progression, Antineoplastic Agents, Adenocarcinoma, Progression Free Survival, Gefitinib, Disease Free Survival, Neoplasm metastasis, and lung neoplasms
Research Interests: Medicine and Mesothelioma
Research Interests: Computed Tomography, Chemotherapy, Medicine, Multivariate Analysis, Lung Cancer, and 15 moreHumans, Female, Male, Clinical Sciences, Cisplatin, Aged, Middle Aged, Observer Variation, Adult, Antineoplastic Agents, Predictive value of tests, Contrast Media, Adenocarcinoma, Neoplasm staging, and lung neoplasms
Small cell lung cancer (SCLC) represents about 13%–15% of all lung cancers. It has a particularly unfavorable prognosis and in about 70% of cases occurs in the advanced stage (extended disease). Three phase III studies tested the... more
Small cell lung cancer (SCLC) represents about 13%–15% of all lung cancers. It has a particularly unfavorable prognosis and in about 70% of cases occurs in the advanced stage (extended disease). Three phase III studies tested the combination of immunotherapy (atezolizumab, durvalumab with or without tremelimumab, and pembrolizumab) with double platinum chemotherapy, with practice-changing results. However, despite the high tumor mutational load and the chronic pro-inflammatory state induced by prolonged exposure to cigarette smoke, the benefit observed with immunotherapy is very modest and most patients experience disease recurrence. Unfortunately, biological, clinical, or molecular factors that can predict this risk have not yet been identified. Thanks to these clinically meaningful steps forward, SCLC is no longer considered an “orphan” disease. Innovative treatment strategies and combinations are currently under investigation to further improve the expected prognosis of patients ...
Many small molecules and monoclonal antibodies blocking the activity of Epidermal Growth factor receptor (EGFR) have been developed and have shown clinical activity in patients with non-small cell lung cancer (NSCLC), pancreatic cancer,... more
Many small molecules and monoclonal antibodies blocking the activity of Epidermal Growth factor receptor (EGFR) have been developed and have shown clinical activity in patients with non-small cell lung cancer (NSCLC), pancreatic cancer, and colorectal cancer (CRC), and are in clinical development for a range of other solid tumors. The toxicity profile of such agents is characterized by a typical pattern of cutaneous reactions. In this paper we reviewed the current available data regarding the clinical significance of skin reaction due to EGFR targeted agents. We show that skin toxicity can be considered as predictive marker of response to such drugs and that it is not disease specific; however its potential prognostic value is still to be proven. Copyright © 2009 Monica Giovannini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is...
Background: Oral premalignant lesions (OPLs) represent the most common oral precancerous conditions. One of the major challenges in this field is the identification of OPLs at higher risk for oral squamous cell cancer (OSCC) development,... more
Background: Oral premalignant lesions (OPLs) represent the most common oral precancerous conditions. One of the major challenges in this field is the identification of OPLs at higher risk for oral squamous cell cancer (OSCC) development, by discovering molecular pathways deregulated in the early steps of malignant transformation. Analysis of deregulated levels of single genes and pathways has been successfully applied to head and neck squamous cell cancers (HNSCC) and OSCC with prognostic/predictive implications. Exploiting the availability of gene expression profile and clinical follow-up information of a well-characterized cohort of OPL patients, we aim to dissect tissue OPL gene expression to identify molecular clusters/signatures associated with oral cancer free survival (OCFS). Materials and methods: The gene expression data of 86 OPL patients were challenged with: an HNSCC specific 6 molecular subtypes model (Immune related: HPV related, Defense Response and Immunoreactive; Me...
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Background: Little information is available concerning prognostic factors for bronchopulmonary large cell neuroendocrine carcinomas (BP-LCNECs) and even less is known about combined LCNECs (Co-LCNECs). We investigated whether an... more
Background: Little information is available concerning prognostic factors for bronchopulmonary large cell neuroendocrine carcinomas (BP-LCNECs) and even less is known about combined LCNECs (Co-LCNECs). We investigated whether an integrated morphological, immunohistochemical, and molecular approach could be used for their prognostic evaluation. Methods: Morphological (including combined features), proliferative (mitotic count/Ki-67 index), immunohistochemical (napsin A, p40, TTF-1, CD44, OTP, SSTR2A, SSTR5, mASH1, p53, RB1, and MDM2), and genomic (TP53, RB1, ATM, JAK2, KRAS, and STK11) findings were analyzed in BP-LCNECs from 5 Italian centers, and correlated with overall survival (OS). The Ki-67 index was expressed as the percentage of positive cells in hot spots as indicated in the WHO 2019 Digestive System Tumors and, for Co-LCNECs, the Ki-67 index was evaluated only in the LCNEC component. Results: A total of 111 LCNECs were distinguished into 70 pure LCNECs, 35 Co-LCNECs (27 wit...
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Background: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to... more
Background: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy. Methods: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b+ tumor-associated-neutrophils (TAN) and CD3+ T cells. Bioinformatics analysis of UBC datasets and gene expression analysis of UBC cell lines were additionally performed. Results: Basal type BC contained a significantly higher density of CD66b+ TAN compared to the luminal type. This finding was validated on TCGA, GSE32894 and GSE124305 datasets by computing a neutrophil signature. Of note, basal-type MIBC display a significantly higher level of chemokines (CKs) attracting neutrophils. Moreover, pro-inflammatory stimuli significantly up-regulate CXCL1, CXCL2 and CXCL8 in 5637 and RT4 UBC cell lines and induce neut...
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e20612 Background: Acquired T790M EGFR mutation (mut) is not predictable by any clinical-pathological feature. The best time point for T790M mut detection by liquid or tissue biopsy is currently undefined. Methods: This is an... more
e20612 Background: Acquired T790M EGFR mutation (mut) is not predictable by any clinical-pathological feature. The best time point for T790M mut detection by liquid or tissue biopsy is currently undefined. Methods: This is an observational study at 6 Italian Centers enrolling EGFR mutant NSCLC patients (pts) progressing after first/second generation EGFR TKI, between 2014 and 2018. The primary endpoint of the study was to compare clinical features in acquired T790M+ compared with T790M- cases. The secondary endpoint was to assess different progression (PD) patterns between the two groups. We also explored the PD pattern at the time of cfDNA negativity and subsequent positivity, in a subgroup of pts receiving serial liquid biopsies. Statistical analysis was performed by the Chi-square test to correlate clinical features with T790M status, and by the Kaplan-Meier estimator to evaluate median progression free (mPFS) and overall survival (mOS). Multiple logistic regression and log-rank ...
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To investigate the role of conventional radiotherapy (RT) and stereotactic body radiotherapy (SBRT) in patients with epidermal growth factor (EGFR)-mutant or anaplastic lymphoma kinase (ALK) rearrangement-positive metastatic non-small... more
To investigate the role of conventional radiotherapy (RT) and stereotactic body radiotherapy (SBRT) in patients with epidermal growth factor (EGFR)-mutant or anaplastic lymphoma kinase (ALK) rearrangement-positive metastatic non-small cell lung cancer (NSCLC). Fifty patients with EGFR-mutated or ALK rearrangement-positive NSCLC were treated at our Institution. Radiotherapy was delivered before, after or concomitantly with tyrosine kinase inhibitors (TKIs). Acute toxicities and overall survival (OS) were assessed. Radiotherapy was performed within 30 days before TKI, concomitantly with TKI and within 30 days after TKI in eight (16%), 33 (66%) and 9 (18%) cases, respectively. The median duration of TKI therapy in the whole series was 11.9 months. The median OS was 19.3 months and 1- and 2-year OS was 71.5% and 36.5%, respectively. The group treated with SBRT had a significant benefit in terms of OS (p=0.043). Only two grade 3 toxicities were reported. RT concomitantly or close to TKI ...
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Second line treatment of recurrent or progressive glioblastoma multiforme (GBM) is not standardized. Anti-angiogenic strategies with tyrosine-kinase inhibitors have been tested with conflicting results. We tested the association of... more
Second line treatment of recurrent or progressive glioblastoma multiforme (GBM) is not standardized. Anti-angiogenic strategies with tyrosine-kinase inhibitors have been tested with conflicting results. We tested the association of sunitinib (S) plus irinotecan (CPT-11) in a phase II trial in terms of response rate (RR) and 6-months progression-free survival (6-PFS). We also reviewed the clinical evidence from all the trials with S in this setting published to date and summarized it in a meta-analysis. Patients with GBM recurrent or progressive after surgery and standard chemo-radiotherapy were treated with S 37.5 mg/day for 14 days + CPT-11 125 mg/sqm every 14 days in a Simon's two-stage phase II study. A summary data meta-analysis was performed to establish the 6-PFS in patients with ascertained histological diagnosis of GBM treated with sunitinib. Six patients were enrolled in the stage I of the trial and only one had a stable disease. The overall response rate was 17% and 6-...
Androgen receptor is the major driver of and testosterone the natural growth factor of prostate cancer (PC). Studies exploring the relationship among circulating testosterone levels, PC aggressiveness, and patient prognosis showed... more
Androgen receptor is the major driver of and testosterone the natural growth factor of prostate cancer (PC). Studies exploring the relationship among circulating testosterone levels, PC aggressiveness, and patient prognosis showed contradictory results. We performed a comprehensive literature search for studies reporting the independent relationship between serum testosterone and prognosis of PC patients. Meta-analyses using random effects models were conducted to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). We identified 25 articles that evaluated the prognostic value of testosterone in early-stage PC (8 studies), in advanced PC either before (4 studies) or during androgen deprivation therapy (ADT) (5 studies), and in castration-resistant PC (8 studies). In early PC, serum testosterone level was not prognostic in terms of overall survival (HR = 1.03; 95% CI, 0.99-1.08; P = .19) and biochemical recurrence (HR = 0.99; 95% CI, 0.87-1.13; P = .93). In advance...
Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial... more
Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial clinical impact. Due to its antioxidant properties, N-acetylcysteine (NAC) has a recognized hepatoprotective effect and this provides the rationale for testing NAC in the management of trabectedin-induced hepatotoxicity. Patients with recurrent or metastatic soft tissue sarcoma, consecutively observed at our institution, who were considered eligible to trabectedin, received concomitant NAC if they had impaired hepatic or renal function at baseline or developed hepatotoxicity during treatment. The study aim was to retrospectively explore trabectedin administration in terms of number of cycles, mean dose, and dose intensity (DI) in patients who received NAC as compared with those who did not. Secondary end points were progression-free survival (PFS) and over...
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Essential hypertension is a complex clinical condition, characterized by multiple and concomitant abnormal activation of different regulatory and contra-regulatory pathophysiological mechanisms, leading to sustained increase of blood... more
Essential hypertension is a complex clinical condition, characterized by multiple and concomitant abnormal activation of different regulatory and contra-regulatory pathophysiological mechanisms, leading to sustained increase of blood pressure (BP) levels. Asymptomatic rise of BP may, indeed, promote development and progression of hypertension-related organ damage, which in turn, increases the risk of major cardiovascular and cerebrovascular events. A progressive and independent relationship has been demonstrated between high BP levels and increased cardiovascular risk, even in the high-to-normal range. Conversely, evidence from randomized controlled clinical trials have independently shown that lowering BP to the recommended targets reduces individual cardiovascular risk, thus improving event-free survival and reducing the incidence of hypertension-related cardiovascular events. Despite these benefits, overall rates of BP control remain poor, worldwide. Currently available guideline...
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The effects of long-term replacement therapy of adrenal insufficiency (AI) are still a matter of controversy. In fact, the established glucocorticoid replacement regimens do not completely reproduce the endogenous hormonal production and... more
The effects of long-term replacement therapy of adrenal insufficiency (AI) are still a matter of controversy. In fact, the established glucocorticoid replacement regimens do not completely reproduce the endogenous hormonal production and the monitoring of AI treatment may be a challenge for the lack of reliable clinical and biochemical markers. Consequently, several AI patients are frequently exposed to relative glucocorticoid excess potentially leading to develop chronic complications, such as diabetes mellitus, dyslipidemia, hypertension and fragility fractures with consequent impaired QoL and increased mortality risk. This review deals with the pathophysiological and clinical aspects concerning the over-replacement therapy of primary and secondary AI.
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Lung adenocarcinoma can transform to small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. This phenomenon has repeatedly been described in several case reports and small patient series. The... more
Lung adenocarcinoma can transform to small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. This phenomenon has repeatedly been described in several case reports and small patient series. The characteristics and treatment outcomes of this population, however, have not been comprehensively reported. We performed a systematic review of the published literature to obtain explorative information on the clinical and pathological features and prognosis of the reported cases. Twenty-five eligible publications were identified, contributing to 39 patients. The median time from initial diagnosis of lung adenocarcinoma to the transformation to SCLC (ttSCLC) was 19months (range 1-61months). The median survival after SCLC diagnosis was 6months. Female gender was significantly associated with longer ttSCLC at the multivariable analysis. Smoking status seemed to be associated with worse prognosis after the diagnosis of SCLC. In this series of published cases, the transformation to a SCLC phenotype after an initial diagnosis of lung adenocarcinoma following TKI therapy appeared to be a late phenomenon. The prognosis after SCLC diagnosis is poor and current treatment strategies derived from primary SCLC seem to be largely inefficacious. New therapies are needed in the management of transformed SCLC.
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The administration of abiraterone acetate (abiraterone) leads to an adrenocorticotropic hormone (ACTH)-driven increase in mineralocorticoid hormones, requiring glucocorticoid supplementation that may stimulate the growth of prostate... more
The administration of abiraterone acetate (abiraterone) leads to an adrenocorticotropic hormone (ACTH)-driven increase in mineralocorticoid hormones, requiring glucocorticoid supplementation that may stimulate the growth of prostate cancer (PCa). Amiloride is a drug that selectively reduces the aldosterone-sensitive Na+/K+ exchange and could be effective in the management of mineralocorticoid excess syndrome (MCES). The efficacy of amiloride + hydrochlorothiazide (HCT) in the clinical management of abiraterone-induced MCES was assessed in 5 consecutive patients with castration-resistant PCa (CRPC). Then, using the in vitro experimental model of PCa cell lines, the possible effects of drugs usually used in the clinical management of CRPC patients on PCa cell viability were investigated. Amiloride/HCT led to a complete disappearance of all clinical and biochemical signs of abiraterone-induced MCES in the 5 treated patients. The in vitro study showed that abiraterone treatment signific...
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Topoisomerase II alpha (TOP2A) and Thymidylate Synthase (TS) are known prognostic parameters in several tumors and also predictors of efficacy of anthracyclines, topoisomerase inhibitors and fluoropirimidines, respectively. Expression of... more
Topoisomerase II alpha (TOP2A) and Thymidylate Synthase (TS) are known prognostic parameters in several tumors and also predictors of efficacy of anthracyclines, topoisomerase inhibitors and fluoropirimidines, respectively. Expression of TOP2A and TS mRNA was assessed in 98 patients with adrenocortical carcinoma (ACC) and protein expression was assessed by immunohistochemistry in a subset of 39 tumors. Ninety-two patients were radically resected for stage II-III disease and 38 of them received adjuvant mitotane. Twenty-six patients with metastatic disease received the EDP-M (Etoposide, Doxorubicin, Adriamycin, Cisplatin plus mitotane). TOP2A and TS expression in ACC tissue was directly correlated with the clinical data. Both markers were not associated with either disease free survival (DFS) or overall survival (OS) in multivariate analyses and failed to be associated to mitotane efficacy. Disease response or stabilization to EDP-M treatment was observed in 12/17 (71%) and 1/9 (11%)...
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The impact of long-term adjuvant therapy with aromatase inhibitors (AIs) on vertebral fracture (VF) risk is still unclear. In this cross-sectional study, we explored the prevalence and determinants of VFs in breast cancer (BC) patients... more
The impact of long-term adjuvant therapy with aromatase inhibitors (AIs) on vertebral fracture (VF) risk is still unclear. In this cross-sectional study, we explored the prevalence and determinants of VFs in breast cancer (BC) patients before and during AI therapy. Each woman underwent a dual-energy X-ray absorptiometry (DXA) to evaluate bone mineral density (BMD) and identify VFs by a quantitative morphometric approach. Blood samples were collected to measure serum hormone and calcium levels. We consecutively included 263 postmenopausal women with hormone receptor-positive early BC. One-hundred-sixty-nine women were AI-naïve, and 94 were AI-treated. AI-treated patients had lower BMD at total hip (p=0.01) and lumbar spine (p=0.03), higher serum vitamin D (p&amp;amp;amp;amp;lt;0.001) and parathyroid hormone (p=0.006) values as compared to AI-naïve patients. The prevalence of VFs was 18.9% in AI-naïve patients, and 31.2% in those assessed during AI therapy (odds ratio 1.90, 95% CI 1.1-3.5, p=0.03). In AI-naïve patients, VFs were associated with older age (p=0.002) and lower BMD values at femoral neck (p=0.04) and total hip (p=0.007), whereas VFs occurred without association with any parameter analyzed in AI-treated patients. In AI-treated group, the prevalence of VFs was not significantly different between patients with osteoporosis and those with normal BMD (36.7% vs. 20.0%; p=0.31). In women with early BC, AI therapy is associated with high prevalence of radiological VFs, which were shown to be independent of BMD values during the adjuvant treatment. These findings may be clinically relevant since they may lead to a change in management of AI-induced skeletal fragility. Specifically, the results of this study provide a rationale for performing a morphometric evaluation of VFs in all women undergoing treatment with AIs.
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In case of undiagnosed pleural effusions, it is necessary to conduct thoracentesis with pleural fluid (PF) cytology. Yet, sensitivity of PF cytology is widely variable as a result of sample size, experience and preparation method. The aim... more
In case of undiagnosed pleural effusions, it is necessary to conduct thoracentesis with pleural fluid (PF) cytology. Yet, sensitivity of PF cytology is widely variable as a result of sample size, experience and preparation method. The aim of this study was to assess whether pleural fluid (PF) cytology is correlated to visceral or parietal pleural invasion as assessed by thoracoscopy in metastatic pleural effusions. All records of patients with pleural effusion were reviewed. The inclusion criteria were as follows: PF cytology, reported appearance of macroscopic pleural invasion during thoracoscopy and malignant diagnosis. Patients with mesothelioma were excluded. Finally, 287 patients who met all criteria were selected. According to the thoracoscopy findings, the extend of the disease on the pleura was analyzed in relation to the PF cytology. In this study, 160 patients (55.7%) had a positive PF cytology (Group A) while 127 (44.3%) recorded negative PF cytology (Group B). From Group...