Organizzazione sanitaria e workflow nella gestione del paziente cronico: analisi e confronto tra usual care e telemonitoraggio nel progetto europeo CIP "Renewing Health"

Tesi svolta in collaborazione con il Consorzio Arsenàl.IT, nell'ambito del Progetto Europeo "RENEWING HEALTH" (CIP 2007-2013), che studia il telemonitoraggio per pazienti cronici (malattie cardiovascolari, diabete, BPCO). Nella tesi si analizzano i processi, le organizzazioni e i workflow esistenti nel modello della sanità attuale (usual care) e le modalità con cui essi si modificano introducendo nel sistema un servizio di telemonitoraggio. Lo scopo finale è quello di valutare l'impatto organizzativo del telemonitoraggio sulla gestione del paziente cronico e le organizzazioni sanitarie che lo assistono. Lo standard adottato per modellare i workflow e i patient flow è il linguaggio UML (diagrammi dei casi d'uso e diagrammi di attività). Le informazioni sono state raccolte presso le Aziende Sanitarie del Veneto che partecipano al progetto Renewing Healthope

Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients

Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients

Cyclo-oxygenase-2 (Cox-2) expression and resistance to platinum versus platinum/paclitaxel containing chemotherapy in advanced ovarian cancer

BACKGROUND: Cyclo-oxygenase-2 (COX-2), the key enzyme in the conversion of arachidonic acid to prostaglandins, is involved in critical steps of tumor onset and progression, and is a strong predictor of chemotherapy resistance and poor outcome in advanced ovarian cancer. To our knowledge, no data has been reported until now about the association between COX-2 status and response to different chemotherapy regimens. METHODS: A retrospective study was performed to investigate the association of COX-2 with outcome and response to platinum versus platinum/paclitaxel in 68 primary ovarian cancer. COX-2 immunoreaction was performed on paraffin-embedded sections by using rabbit polyclonal antiserum against COX-2. RESULTS: In the overall series, COX-2 positivity was found in a statistically significant higher percentage of not responding cases than in patients responding to chemotherapy (n = 15/21; 71.4% versus n = 17/47; 36.1%; p value = 0.0072). A higher percentage of COX-2 positivity was found in patients unresponsive (n = 11/13; 84.6%) versus patients responsive to platinum-based chemotherapy (n = 9/26; 34.6%). In cases administered platinum/paclitaxel, COX-2 positivity was found in 4 out of 8 (50%) of un responsive versus 8 out of 21 (38.1%) of responsive cases. Logistic regression analysis of parameters likely to affect response to treatment resulted in a p value = 0.17 for the interaction COX-2/type of treatment. CONCLUSION: Although these findings need to be confirmed in a larger series, our study suggests a possible indication that there is a difference in the influence of COX-2 on response depending on treatment regimen

Pegylated liposomal doxorubicin in the management of ovarian cancer

Among the pharmaceutical options available for treatment of ovarian cancer, much attention has been progressively focused on pegylated liposomal doxorubicin (PLD), whose unique formulation, which entraps conventional doxorubicin in a bilayer lipidic sphere surrounded by a polyethylene glycol layer, prolongs the persistence of the drug in the circulation and potentiates intratumor drug accumulation. These properties enable this drug to sustain its very favorable toxicity profile and to be used safely in combination with other drugs. PLD has been already approved for treatment of advanced ovarian cancer patients failing first-line platinum-based treatment. Moreover, phase III trials have been already completed, and results are eagerly awaited, which hopefully will expand the range of PLD clinical application in this neoplasia both in front-line treatment, and in the salvage setting in combination with other drugs. Moreover, attempts are continuing to enable this drug to be combined with novel cytotoxic drugs and target-based agents. This review aims at summarizing the available evidence and the new perspectives for the clinical role of PLD in the management of patients with epithelial ovarian cancer

Immunoradiometric and immunohistochemical analysis of Cathepsin D in ovarian cancer: lack of association with clinical outcome.

The aim of this study was to analyse the clinical significance of Cathepsin D (Cath D) content as determined by an immunoradiometric assay in a series of primary untreated ovarian cancers from 162 patients. In addition, immunohistochemical analysis of Cath D was also performed on a subset of 86 tumours. Cath D levels were distributed in an asymmetrical way and were skewed towards the lower values (median value 20.8 pmol mg(-1) protein, range 2.0-99.0 pmol mg(-1) protein). No correlation was found between Cath D levels and clinicopathological parameters. However, the percentage of Cath D positivity was significantly higher in oestrogen receptor-positive (57%) compared with oestrogen receptor-negative (36%) cases (P= 0.01). The percentage of Cath D-positive staining was not significantly different for both epithelial (27%) and stromal components (40%). Immunoradiometrically detected Cath D levels were not different according to Cath D stromal immunostaining (P= 0.18), while higher Cath D levels were measured in Cath D-positive than in Cath D-negative tumour epithelial cells (P = 0.027). Survival analysis was conducted on 161 primary untreated ovarian cancer patients. The 5-year overall survival rate was 57% and 55% in Cath D-positive and Cath D-negative patients respectively (P = 0.69). As far as time to progression was concerned, there was no significant difference in the survival rate of patients with either high or low Cath D content (P = 0.56). Similar results have been obtained in the subset of patients in which Cath D was analysed by immunohistochemistry. In conclusion, Cath D measurement in tumour extracts appears to have a limited usefulness in improving the prognostic characterization of ovarian cancer patients

Nm23 expression in endometrial and cervical cancer: inverse correlation with lymph node involvement and myometrial invasion.

The expression of nm23 has been shown to correlate in some solid tumours with their metastatic potential and to be associated with a favourable prognosis in human breast cancer and melanoma. In breast and ovarian cancer nm23 expression is also correlated with lymph node involvement. We analysed the expression of nm23-H1 and -H2 in normal endometrium and in endometrial and cervical cancer by both Northern and Western blotting. Cellular localisation of Nm23-H1 was visualised by immunohistochemistry mostly in the cytoplasm. Both isoforms of Nm23 were present in all the samples analysed, and a clear direct correlation between Nm23-H1 and -H2 levels was evident. Median nm23-H2 levels were higher than than -H1 levels in both tissues. Cervical cancer patients with lymph node involvement were shown to have significantly lower protein levels of Nm23 (P < 0.007 for H1 and P < 0.009 for H2), and a similar trend was also evident in endometrial cancer. Furthermore, the degree of myometrial invasion in endometrial cancer patients was also inversely correlated with Nm23-H1 levels of expression (P < 0.003). Nm23 level may therefore be taken into consideration as a new marker in the prognostic characterisation and in the treatment planning of uterine tumour patients