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Showing papers by "Francesco Boccardo published in 2012"


Journal ArticleDOI
TL;DR: In this article, the diagnostic approach and the medical and surgical therapy for both primary and secondary lymphedema are discussed. But, the focus of this review was not on the diagnosis and treatment of the secondary lymphatic malformation.

98 citations


Journal ArticleDOI
TL;DR: An association between a decreased mortality risk and enterolactone levels ≥10 nmol/l was found in respect to both all-cause and breast cancer-specific mortality, providing further evidence that mammalian lignans might play an important role in reducing all- Cause and cancer- specific mortality of the patients operated on for breast cancer.
Abstract: We previously demonstrated that high serum enterolactone levels are associated with a reduced incidence of breast cancer in healthy women. The present study was aimed at investigating whether a similar association might be found between serum enterolactone levels and the mortality of women with early breast cancer. The levels of enterolactone in cryopreserved serum aliquots obtained from 300 patients, operated on for breast cancer, were measured using a time-resolved fluoro-immunoassay. Levels were analyzed in respect to the risk of mortality following surgery. Cox proportional hazard regression models were used to check for prognostic features, to estimate hazard ratios for group comparisons and to test for the interaction on mortality hazards between the variables and enterolactone concentrations. The Fine and Gray competing risk proportional hazard regression model was used to predict the probabilities of breast cancer-related and breast cancer-unrelated mortalities. At a median follow-up time of 23 years (range 0.6-26.1), 180 patients died, 112 of whom died due to breast cancer-related events. An association between a decreased mortality risk and enterolactone levels ≥ 10 nmol/l was found in respect to both all-cause and breast cancer-specific mortality. The difference in mortality hazards was statistically significant, but it appeared to decrease and to lose significance after the first 10 years, though competing risk analysis showed that breast cancer-related mortality risk remained constantly lower in those patients with higher enterolactone levels. Our findings are consistent with those of most recent literature and provide further evidence that mammalian lignans might play an important role in reducing all-cause and cancer-specific mortality of the patients operated on for breast cancer.

46 citations


Journal ArticleDOI
TL;DR: The findings show that POSTN might represent a novel prognostic marker for PCa, and stromal and epithelial POSTN expression were significantly increased in tumor tissues.
Abstract: Background The purpose of the present study was to evaluate the prognostic value of POSTN expression following prostatectomy.

40 citations


Journal ArticleDOI
TL;DR: How it is important to integrate diagnostic and clinical findings to better understand how to properly identify risk patients for lymphatic injuries and, therefore, when it is useful and proper to do prevention is demonstrated.
Abstract: The problem of prevention of lymphatic complications in surgery is extremely important if we think about the frequency of both early complications such as lymphorrhea, lymphocele, wound dehiscence and infections and late complications such as lymphangitis and lymphedema. Nowadays, it is possible to identify risk patients and prevent these lesions or treat them at an early stage. This report helps to demonstrate how it is important to integrate diagnostic and clinical findings to better understand how to properly identify risk patients for lymphatic injuries and, therefore, when it is useful and proper to do prevention. Authors report their experiences in the prevention and treatment of lymphatic injuries after surgical operations and trauma. After an accurate diagnostic approach, prevention is based on different technical procedures among which microsurgical procedures. It is very important to follow-up the patient not only clinically but also by lymphoscintigraphy. A protocol of prevention of secondary limb lymphedema was proposed and it includes, from the diagnostic point of view, lymphoscintigraphy and, as concerns therapy, it recognizes also a role to early microsurgery. It is necessary to accurately follow-up the patient who has undergone an operation at risk for the appearance of lymphatic complications and, even better, to assess clinically and by lymphoscintigraphy the patient before surgical operation.

22 citations


Journal ArticleDOI
TL;DR: Improved understanding of normal and pathologic processes and their underlying pathomechanisms could lead to more successful approaches in classification, treatment, and even prevention of cancer and a whole host of other diseases.
Abstract: Recent discoveries in molecular lymphology, developmental biology, and tumor biology in the context of long-standing concepts and observations on development, growth, and neoplasia implicate overlapping pathways, processes, and clinical manifestations in developmental disorders and cancer metastasis. Highlighted in this review are some of what is known (and speculated) about the genes, proteins, and signaling pathways and processes involved in lymphatic/blood vascular development in comparison to those involved in cancer progression and spread. Clues and conundra from clinical disorders that mix these processes and mute them, including embryonic rests, multicentric nests of displaced cells, uncontrolled/invasive “benign” proliferation and lymphogenous/hematogenous “spread”, represent a fine line between normal development and growth, dysplasia, benign and malignant neoplasia, and “metastasis”. Improved understanding of these normal and pathologic processes and their underlying pathomechanisms, e.g., stem cell origin and bidirectional epithelial-mesenchymal transition, could lead to more successful approaches in classification, treatment, and even prevention of cancer and a whole host of other diseases.

12 citations


Journal Article
TL;DR: The observation that the expression of several genes, including B-cell lymphoma-2 (BCL2), myelocytomatosis oncogene (MYC), caspases, is modulated midly-to-moderately, after 4OHT addition suggests that this combined approach in the clinical setting should be further investigated through appropriate trials.
Abstract: BACKGROUND Bicalutamide (BIC) is an alternative treatment to castration for advanced prostate cancer. Breast events are common adverse effects which can be effectively prevented by the concurrent administration of tamoxifen, a selective estrogen receptor modulator. MATERIALS AND METHODS We investigated the effects of BIC, 4-hydroxy Tamoxifen (4OHT), the active metabolite of tamoxifen, and their combination on the expression of a panel of genes implicated in prostate cancer development and progression in LNCaP cells stimulated with dihydrotestosterone. RESULTS Our findings confirm the anti-proliferative activity of BIC on LNCaP cell growth but also show the down-regulating function of this anti-androgen on the expression of genes involved in tumor proliferation and invasion [cyclins, caspases, epidermal growth factor (EGF)]. The combination with 4OHT exerts a synergistic effect on the downregulation of some genes involved in prostate cancer progression. CONCLUSION The observation that the expression of several genes [such as B-cell lymphoma-2 (BCL2), myelocytomatosis oncogene (MYC), caspases] is modulated midly-to-moderately, after 4OHT addition suggests that this combined approach in the clinical setting should be further investigated through appropriate trials.

9 citations



Journal ArticleDOI
TL;DR: Changes in NM scaffolding are strongly associated with the clinical outcome of patients following radical prostatectomy, suggesting a specific role for these proteins in PCa progression.
Abstract: Purpose The aim of the study was to correlate nuclear matrix (NM) protein expression profiles with the risk of PSA progression or death in early prostate cancer (PCa).

8 citations


Journal ArticleDOI
TL;DR: Geena is a new tool that aims at automating some of the fundamental steps involved in the analysis of m/z and abundance data from MALDI/TOF MS experiments, based on original algorithms based on heuristic and original algorithms.
Abstract: Motivations. Mass spectrometry (MS), one of the most recent high-throughput technologies, produces a high volume of data. Many tools exist for MS data management, but little is available for the automation of related procedures. Geena is a new tool that aims at automating some of the fundamental steps involved in the analysis of m/z and abundance data from MALDI/TOF MS experiments. Geena was developed by taking into account the following assumptions: a. in each spectrum, molecules are present in the form of different isotopic abundances that can besummed together to give a total abundance value; b. often, experimental data have to be normalized against an internal standard in order to obtain (semi) quantitative results; c. experimental data can be affected by background noise. The selection of signals above a modulated threshold built on the spectra profile may be useful; d. the analysis of sample replicates yields multiple spectra which are different because of marginal errors/changes in the experimental phase only. An average spectrum representative of the sample may be defined by aligning these spectra along the m/z axis and computing mean intensity values from the corresponding abundances. e. In order to compare single or average spectra obtained from different samples the alignment along the m/z axis is required. Methods. Geena was written in PHP and partially, for spectra alignment, in perl. Both input and output are managed in simple text files, usually having tab or comma delimited values. Such formats can easily be consumed by MS Excel or any other data management system. Data may be stored on the server in a mySQL database. The processing method is mainly heuristic and it is based on original algorithms. It includes the following steps: a) preprocessing of spectra replicates, which consists in isotopic peaks joining, normalization, and peak selection; b) computing average spectra for replicated analysis of samples; c) alignment of average spectra. Results. Geena is a public web server. The input consists in MALDI/TOF MS spectra. The data file is usually uploaded to the server and removed as soon as it has been used. It may include data from many samples, for each of which more spectra replicates can be provided. The output consists both in the averaged spectra from replicates and in the alignment of averaged spectra. The alignment is shown in the results page, while all results are available for downloading from the same page and sent by email, if a valid address is provided. Many parameters are defined. The analysis range is specified by indicating the lower and upper m/z values. The presence of a normalization peak and its corresponding m/z value must be specified in order to normalize data. The threshold for peak selection is specified by providing abundance threshold values for the upper and lower limits of the analysis range. Further Intermediate thresholds may be specified, in which case a broken line is built by linear interpolation. An alternative method, that is based on data background estimation, is being added to Geena. Isotopic peaks of the same molecule are identified on the basis of the maximum allowed delta between them, i.e. the maximum deviation from expected values to consider a signal as an isotopic abundance of a given peak, and of the maximum number of isotopic replicates. In order to compute average spectra for a given sample, the maximum delta for aligning replicates, i.e. the maximum allowed deviation along the m/z axis between two signals belonging to replicates of the same sample to align them, and the minimum number of signals in replicates, that defines the minimum number of replicates that should contain a signal to include it in the average spectrum, can be specified. Similarly, the maximum delta for aligning average spectra and the minimum number of signals in average spectra can be specified to support alignment of average spectra. The method has been used for the analysis of long-term cryopreserved sera [1]. Availability http://bioinformatics.istge.it/geena/ References 1. Mangerini R, Romano P et al. (2011) The application of atmospheric pressure MALDI to the analysis of long-term cryopreserved serum peptidome. Analytical Biochemistry 417: 174-181.

3 citations


Journal ArticleDOI
TL;DR: This preliminary analysis of Italian pts enrolled in the EAP provides real world safety data and suggests a good safety profile of cabazitaxel even in heavily pretreated pts, which is in agreement with Italian experience in TROPIC.
Abstract: 253 Background: A significant number of docetaxel (D) refractory mCRPC patients (pts) have a life expectancy of > 15 months and ask for additional efficacious treatments. In the phase 3 TROPIC trial treatment of mCRPC patients with CbzP who progressed during or after docetaxel resulted in a statistically significant overall survival benefit compared with mitoxantrone / prednisone (Lancet 2010). This survival benefit supported establishment of a global early access program (EAP), allowing pts with mCRPC to have access to the drug prior to its commercial availability. Here we describe preliminary safety results from the EAP in Italy. Methods: We report here the data of the first 16 mCRPC patients (out of the 123 enrolled by 19 Italian centers until Sept 2011 in EAP) treated with Cbz (25mg/m2 Q3W) plus P(10mg bid). Results: Pts were median age 73.5 years (>75 years 38%), ECOG PS-0 81.3% and had received a median of 7 prior cycles of D (median cumulative D dose 562.5mg). Median time from last D dose to inclus...

3 citations


Journal ArticleDOI
G. Gravis, Karim Fizazi1, F. Joly Lobbedez, Stéphane Oudard  +459 moreInstitutions (95)
TL;DR: Combining docetaxel and ADT improves PFS over ADT alone in pts with HSMPC, however, no difference in OS was observed between the two arms.

Journal ArticleDOI
TL;DR: Benefits observed in the TROPIC study supported a global EAP to allow pts with mCRPC to have an early access to CbzP and provide confirmatory data in daily clinical practice.
Abstract: e15185 Background: A significant percentage of mCRPC pts, who have progressed on D therapy, have a long life expectancy and are candidates for additional treatments. In TROPIC trial pts who progres...