Luca Fuso

Università degli Studi di Brescia, Brescia, Lombardy, Italy

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Publications (21)89.13 Total impact

  • Article: Prognostic Factors and Clinical Outcome of Patients With Recurrent Early-Stage Epithelial Ovarian Cancer: An Italian Multicenter Retrospective Study.
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    ABSTRACT: OBJECTIVE: The objective of this study was to assess the clinical outcome of patients with recurrent early-stage ovarian cancer. METHODS: The hospital records of 87 patients were reviewed. The median follow-up of survivors from recurrence was 87.6 months. RESULTS: The 25%, 50%, and 75% quantiles of time to recurrence were 15, 25, and 44 months, respectively. The pelvis was the most common site of failure (39.1%), followed by abdomen (18.3%) and retroperitoneal nodes (18.3%). Treatment at recurrence consisted of chemotherapy in 46 patients, surgery plus chemotherapy in 29, surgery in 3, surgery plus radiotherapy in 2, and other therapies in 7. A macroscopically complete cytoreduction was obtained in 29 (85.2%) of the 34 patients who underwent secondary surgery. Five- and 7-year survival rates after recurrence were 34.3% and 29.6%. By log-rank test, survival after recurrence was related to patient age (≤60 vs >60 years; P = 0.001), time to recurrence (>15 vs ≤15 months; P = 0.049), site of recurrence (retroperitoneum vs pelvis vs other; P = 0.004), and surgery at recurrence (yes vs not; P = 0.001), but not to substage, histotype, grade, prior adjuvant chemotherapy, examination that detected recurrence, and chemotherapy at recurrence. On multivariate analysis, patient age (hazard ratio, 1.836; 95% confidence interval, 1.060-3.180) and surgical treatment at recurrence (hazard ratio, 1.972; 95% confidence interval, 1.084-3.587) were independent prognostic variables for survival after recurrence. CONCLUSIONS: Patient age and surgery at recurrence were independent prognostic variables for patients with recurrent early-stage ovarian cancer. When feasible, salvage surgery appears to give a survival advantage in this clinical setting.
    International Journal of Gynecological Cancer 01/2013; · 1.65 Impact Factor
  • Article: Analysis of Treatment Failures and Survival of Patients With Uterine Papillary Serous Carcinoma: A Cooperation Task Force (CTF) Study.
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    ABSTRACT: To assess the pattern of failures and the survival of patients with uterine papillary serous carcinoma (UPSC). The hospital records of 119 women with UPSC were reviewed. Surgery was the initial therapy for all the cases. The median follow-up of survivors was 133 months (range, 3-216 months). Postoperative treatment was used in 98 patients (82.4%). Adjuvant treatment was radiotherapy in 25 women, chemotherapy in 61 women, and chemotherapy plus radiotherapy in 12 women. Tumor recurred in 44 (37.0%) of the 119 patients, after a median time of 15.1 months. Relapse was symptomatic in 15 patients (34.1%), and recurrent disease involved peritoneum or distant sites in 26 (66.7%) of the 39 patients for whom the site of failure was known. Five- and 10-year survival rates were 61.8% and 54.6%, respectively. Survival was related to disease stage (P < 0.0001). Among patients with advanced tumor, 5-year survival was lower in women who had macroscopic residual disease after surgery than in those who had not (15.4% vs 37.5%; P = 0.08). Distant failures were higher in women with histologically proven positive nodes than in those with negative nodes (28.6% vs 9.1%; P = 0.048). There was a trend to better survival for patients with stage I to stage II disease who underwent chemotherapy when compared with those who did not. Uterine papillary serous carcinoma has an aggressive clinical behavior with a great tendency to recur especially in peritoneal and distant sites. Tumor stage is a strong prognostic factor, whereas the role of adjuvant treatment is still uncertain.
    International Journal of Gynecological Cancer 09/2012; 22(8):1355-60. · 1.65 Impact Factor
  • Article: Could different follow-up modalities play a role in the diagnosis of asymptomatic endometrial cancer relapses?: an Italian multicentric retrospective analysis.
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    ABSTRACT: To determine current practice and to assess the value of routine follow-up procedures for endometrial cancer surveillance. To discuss whether such procedures are feasible and effective to identify asymptomatic recurrences and describe the pattern of relapse detected by procedures. The records of 282 consecutive women with recurrent endometrial cancer treated from 1986 to 2005 were retrospectively collected in 8 Italian institutions. Primary disease, clinical history, and recurrence features and data were analyzed. Thirty-five (12.4%) of 282 patients had recurrence in vaginal vault, 51 patients (18.0%) had recurrence in central pelvis, 14 patients (4.9%) had recurrence in pelvic wall, and 39 patients (13.8%) had recurrence in lymph nodes. One-hundred twenty-eight patients (45.3%) showed a distant relapse, whereas 15 patients (5.3%) developed both distant relapse and local relapse. The site of relapse influenced survival because the patients with vaginal vault recurrences lived significantly longer than the patients with recurrences in other sites. Eighty (28.4%) of the 282 patients became symptomatic and anticipated the scheduled visit, 37 (13.1 %) of the patients reported their symptoms during the follow-up meeting, and 165 (58.5 %) of the patients were asymptomatic and the diagnostic path was introduced by a planned visit or examination. Among the asymptomatic patients, the first procedure that led to further examinations was clinical visit alone for 60 (36.4%) of 165 patients, imaging for 103 patients (62.4%), and cytologic examination for 2 patients (1.2%). Symptoms at recurrence can predict survival: patients with an asymptomatic recurrence had a median survival time from relapse of 35 months versus 13 months if they had a symptomatic repetition (P = 0.0001). Follow-up after endometrial cancer treatment varies in Italy. In this retrospective study, women with asymptomatic recurrence have shown a better clinical outcome compared with those with symptomatic relapse. The optimal approach is actually unknown, and guidelines comparing follow-up protocols have not been established. Prospective cost-effectiveness studies are needed.
    International Journal of Gynecological Cancer 06/2012; 22(6):1013-9. · 1.65 Impact Factor
  • Article: Variation in gynecological oncology follow-up practice: attributable to cancer centers or to patient characteristics? A Piedmont Regional Oncology Network Study.
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    ABSTRACT: Although guidelines recommend minimalist follow-up, there is wide variability in gynecological oncology practice. The aims of this study were to describe between-center differences in the follow-up of endometrial, ovarian, and uterine cervical cancer; to identify the determinants of test prescription; to estimate the related costs; and to assess the weight of center habits and patient characteristics as sources of unexplained variability. The medical records of patients treated between August 2004 and July 2005 for gynecological malignancies and followed up for the detection of recurrent disease were retrospectively collected from 29 centers of the Piedmont Oncology Network. Multivariate multilevel analyses were performed to study the determinants of test prescription and costs. Analyses were performed on 351 patients (median follow-up: 578 days). The unexplained variability in computed tomography prescriptions (26%), ultrasound prescriptions (17%), and total cost of follow-up (15%) can be attributed to center habits, independenty of the clinical characteristics of the patients. Much of the unexplained variability in the follow-up for gynecological malignancies is attributable to different habits of centers belonging to a cancer network. These results prompted us to design a multicenter randomized controlled trial to compare minimalist versus intensive follow-up programs in endometrial cancer.
    Tumori. 09/2011; 97(5):551-8.
  • Article: Angiogenesis and molecular markers in advanced epithelial ovarian cancer: a retrospective study.
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    ABSTRACT: The role of molecular markers in ovarian cancer is still a matter of debate. Angiogenesis is a necessary condition for tumor growth. Hypoxia induces angiogenesis, and cyclooxygenase-2 (COX-2), p53 and HER2 are involved in cancer proliferation and angiogenesis regulation. The aims of this study were to evaluate the relationship between intratumoral microvessel density (IMD) and the expression of molecular markers that affect angiogenesis (COX-2, p53 and HER2) in advanced epithelial ovarian cancer (EOC), to analyze their prognostic and predictive value and their association with clinicopathological features, such as serum hemoglobin level at diagnosis (Hb). Immunohistochemical staining with CD34 (for IMD), COX-2, p53 and HER2 antibodies was performed in 113 patients with advanced EOC who had undergone primary surgery. Clinicopathological data were collected and statistical analyses were performed. Neither IMD, COX-2 nor HER2 had any predictive or prognostic value in EOC. A relationship that approached statistical significance was found between p53 expression and a complete response to treatment (p=0.05). p53 expression and tumor grade were inversely associated (p=0.012). Hb<12g/dl had predictive value (p=0.02). In our series IMD, COX-2 and HER2 had neither prognostic nor predictive value in advanced EOC. p53 and Hb may be predictive factors. The results and clinical usefulness of immunohistochemistry are controversial. Further evaluations are required to determine whether the serum levels of molecular markers correlate with the results of immunohistochemical assays and whether they offer any prognostic and/or predictive value. Targeted therapy remains the ultimate goal of these studies.
    Gynecologic Oncology 08/2011; 123(2):301-7. · 3.89 Impact Factor
  • Article: Analysis of vitamin D receptor expression and clinical correlations in patients with ovarian cancer.
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    ABSTRACT: Although the antiproliferative and differentiating properties of vitamin D have been demonstrated, its effects on cancer cells are variable. Little is known about vitamin D receptor (VDR) levels in patients with ovarian cancer. In this population we sought to determine correlations between VDR expression, clinical parameters and treatment outcome. We analyzed VDR content in platelets of healthy women and of a cohort of patients with ovarian tumors and we evaluated possible correlations with clinical parameters, tumor characterization (stage, histology, nuclear grading, ascites), response to therapy and survival. Moreover receptor expression was evaluated immunohistochemically on tissue samples. VDR levels were markedly lower in healthy women when compared with the pathological group. In the latter a significant increase in receptor expression was observed in malignancies compared with benign cases. No correlation existed between VDR expression and clinicopathological parameters, although we observed an advantage on survival if patients had a higher level of VDR expression in platelets. A cytoplasmic localization of the protein was observed by immunohistochemistry in ovarian cancer cells. Vitamin D receptor status measured in platelets differs significantly between healthy and pathological groups, increasing with malignancy, and there is a trend towards longer overall survival for tumors showing higher VDR levels. These data suggest that platelet VDR content could be used as a pathological marker. The meaning of this increased VDR expression in platelets needs further investigation and it is possibly linked to an inflammatory response.
    Gynecologic Oncology 10/2010; 119(1):121-4. · 3.89 Impact Factor
  • Article: Gemcitabine and vinorelbine combination in platinum-sensitive recurrent ovarian cancer.
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    ABSTRACT: Most patients with ovarian cancer are candidates for second-line or salvage treatments often for prolonged periods. Patients with platinum-sensitive disease can benefit from a platinum retreatment with a likelihood of response dependents on the treatment-free interval. Alternative agents and combination chemotherapy are potential therapeutic approaches. At our institution, we carried out a phase II trial to evaluate feasibility, efficacy, and toxicity of gemcitabine and vinorelbine combination in recurrent ovarian carcinoma. The aim of the present study was to evaluate the role of this combination in patients with platinum-sensitive disease. Patients with platinum-sensitive disease recurring after 1 or more lines of platinum-based chemotherapy were included. Vinorelbine at 25 mg/m followed by gemcitabine at 1000 mg/m was administered intravenously on days 1 and 8 every 3 weeks. Response Evaluation Criteria in Solid Tumors and cancer antigen 125 test (CA-125 Kinetics [Rustin criteria]) were adopted to classify responses. Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria. Thirty-nine patients were eligible. Platinum-free interval (PFI) was 6 to 12 months in 13 patients (33.3%; PFI 6-12) and more than 12 months in 26 patients (66.7%; PFI > 12). The overall response rate was 48.7%, with 6 complete responses. Median response duration was 38 weeks. The response rate was 23% in PFI 6-12 and 62% in PFI >12. The most frequently observed toxicity was hematological, with 23% of the patients having grade 3 or 4 neutropenia. Gemcitabine and vinorelbine combination is effective and well tolerated in recurrent platinum-sensitive ovarian cancer. It may represent an option in the management of these patients because the chronic nature of the disease.
    International Journal of Gynecological Cancer 12/2009; 19(9):1529-34. · 1.65 Impact Factor
  • Article: Are surveillance procedures of clinical benefit for patients treated for ovarian cancer?: A retrospective Italian multicentric study.
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    ABSTRACT: The aim of this retrospective investigation was to assess the pattern of failures of 412 patients with recurrent ovarian cancer followed up with different surveillance protocols.Time to recurrence was less than 6 months in 98 women (23.8%), 6 to 12 months in 102 women (24.7%), and more than 12 months in 212 women (51.5%). Symptoms at relapse were referred by 81 women (19.7%). Among the 331 asymptomatic patients, the surveillance procedure that raised the suspect of recurrent disease was clinical examination in 49 (14.8%), imaging technique in 90 (27.2%), serum CA 125 in 77 (23.3%), and both serum CA 125 and imaging technique in 115 (34.7%). At univariate analysis, survival from initial diagnosis was related to stage (P = 0.004), residual disease after initial surgery (P < 0.0001), time to recurrence (P < 0.0001), site of relapse (P = 0.04), and treatment at recurrence (P < 0.0001), and survival after recurrence was related to stage (P = 0.01), residual disease (P < 0.0001), time to recurrence (P < 0.0001), and treatment at recurrence (P < 0.0001). Conversely, symptoms at recurrence had no prognostic relevance. Cox proportional hazards model showed that residual disease and time to recurrence were the only independent prognostic variables for both survival from initial diagnosis (P < 0.0001) and survival after recurrence (P < 0.0001). In conclusion, there was no survival difference between asymptomatic and symptomatic patients at the time of relapse, and therefore, the diagnostic anticipation allowed by a scheduled follow-up protocol did not seem to improve the clinical outcome of patients who ultimately developed recurrent disease.
    International Journal of Gynecological Cancer 04/2009; 19(3):367-74. · 1.65 Impact Factor
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    Article: Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues.
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    ABSTRACT: Gene expression profiles were studied by microarray analysis in 2 sets of archival breast cancer tissues from patients with distinct clinical outcome. Seventy-seven differentially expressed genes were identified when comparing 30 cases with relapse and 30 cases without relapse within 72 months from surgery. These genes had a specific ontological distribution and some of them have been linked to breast cancer in previous studies: AIB1, the two keratin genes KRT5 and KRT15, RAF1, WIF1 and MSH6. Seven out of 77 differentially expressed genes were selected and analyzed by qRT-PCR in 127 cases of breast cancer. The expression levels of 6 upregulated genes (CKMT1B, DDX21, PRKDC, PTPN1, SLPI, YWHAE) showed a significant association to both disease-free and overall survival. Multivariate analysis using the significant factors (i.e., estrogen receptor and lymph node status) as covariates confirmed the association with survival. There was no correlation between the expression level of these genes and other clinical parameters. In contrast, SERPINA3, the only downregulated gene examined, was not associated with survival, but correlated with steroid receptor status. An indirect validation of our genes was provided by calculating their association with survival in 3 publicly available microarray datasets. CKMT1B expression was an independent prognostic marker in all 3 datasets, whereas other genes confirmed their association with disease-free survival in at least 1 dataset. This work provides a novel set of genes that could be used as independent prognostic markers and potential drug targets for breast cancer.
    International Journal of Cancer 07/2008; 123(6):1327-38. · 5.44 Impact Factor
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    Article: Influence of estrogens and antiestrogens on the expression of selected hormone-responsive genes.
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    ABSTRACT: Estrogen exerts a primary regulatory role on a wide variety of physiological processes in different tissues and organs. Agonistic ad antagonistic compounds are widely used in human health and, therefore, a deep understanding of their mechanisms of action at the molecular level is mandatory. The effect of 17beta-estradiol and three antiestrogenic drugs, comprising two selective estrogen receptor modulator (SERM, 4-OH-tamoxifen, Raloxifene) and the pure antiestrogen ICI 182,780, on genome-wide gene expression levels was evaluated in breast carcinoma cell lines by DNA microarray analysis. Different clusters of genes, showing specific coregulation patterns, were found. First, several groups of genes displaying temporal-specific up- or down-regulation were characterized. Second, clusters of genes responding to different antiestrogenic drugs in either antagonstic or agonistic fashion, were found. Genes responding specifically to antiestrogens, but not to estrogen, were also identified. In addition, each individual compound exhibited a very specific gene regulation. Bioinformatic analysis was applied to the regulatory sequences of different groups of genes and confirmed that specific pathways and secondary responses are activated at each temporal point and in response to different compounds. Our results underline the complexity of genomic responses to estrogen in breast cancer cells and strongly suggest that the molecular characterization of estrogen agonists and antagonists used in human therapy should be carefully studied.
    Maturitas 05/2007; 57(1):50-5. · 2.77 Impact Factor
  • Article: Constitutional high expression of an APC mRNA isoform in a subset of attenuated familial adenomatous polyposis patients.
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    ABSTRACT: Familial adenomatous polyposis is an inherited condition associated with hundreds to thousands of colorectal adenomas conferring a very high risk of cancer at a young age. In addition to "classical" form, there is also an attenuated polyposis, with fewer than 100 polyps and a delayed age of cancer onset. Both classical and attenuated polyposis are characterized by a relevant phenotypic heterogeneity. The disease has been linked to constitutive mutations of either APC tumor suppressor gene, or less frequently, MYH base-excision repair gene. However, the genetic cause remains undetected in up to 70-80% of patients with the attenuated form. This analysis was performed on 26 polyposis patients with the attenuated phenotype. All patients had formerly proven to be negative for APC truncating mutations that typically represent the majority of APC gene alterations. We evaluated the APC mRNA constitutional level by real-time quantitative reverse transcription polymerase chain reaction (PCR). Eleven patients (42%) showed an anomalous APC transcription level. One patient with reduced mRNA was a carrier of a whole APC gene deletion. In seven out of the ten remaining cases, we found the increased expression of an APC mRNA isoform resulting from exon 10/15 connection and giving rise to a stable truncated peptide. Mutations neither in the invariant splice sites nor in the known transcription regulatory signals were found. Our results support the notion that in attenuated polyposis patients, a detailed investigation of APC transcription can allow detection of rare alterations. Although functional data are required, the isoform we observed might have some pathogenic role, accounting for the heterogeneous phenotype that characterizes the polyposis syndrome.
    Journal of Molecular Medicine 04/2007; 85(3):305-12. · 4.67 Impact Factor
  • Article: Progesterone receptor and human epidermal growth factor receptor 2 status: an independent influence on the efficacy of endocrine therapy in breast cancer?
    Journal of Clinical Oncology 04/2006; 24(9):1481-2; author reply 1482. · 18.37 Impact Factor
  • Article: Attitudes of Italian gynaecologists towards prophylactic oophorectomy at hysterectomy for non-malignant conditions.
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    ABSTRACT: To compare the attitudes of Italian oncologic gynaecologists towards prophylactic oophorectomy at hysterectomy for a non-neoplastic reason. A four-item two-part questionnaire was submitted to 170 gynaecologists attending a national conference on gynaecologic oncology. About 92% of gynaecologists reported they would perform prophylactic oophorectomy in women over 50 years, but only 14% said they would in patients aged 45-50; a family history of cancer emerged as a major decision-making criterion for performing oophorectomy in the younger set of patients. Our brief survey confirms the wide variability in attitudes among gynaecologists towards performing prophylactic oophorectomy at hysterectomy for a non-neoplastic pathology in women aged 40-50.
    European Journal of Obstetrics & Gynecology and Reproductive Biology 02/2006; 124(1):82-7. · 1.97 Impact Factor
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    Article: Laparoscopic treatment of endometrial cancer: feasibility and results.
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    ABSTRACT: The aim of this study was to compare laparoscopic and abdominal approach in the treatment of endometrial cancer in our department. From January 1999 to November 2002, 77 patients underwent surgery for stages I-III endometrial cancer. The first group of 36 patients had abdominal hysterectomy as well as salpingo-oophorectomy, with or without lymphadenectomy. The remaining 41 patients received laparoscopic assisted vaginal hysterectomy as well as salpingo-oophorectomy, with or without lymphadenectomy. In this retrospective study, we have compared the surgical results, the short- and long-term morbidity and the outcome of the two patient groups. Body mass index (BMI) was significantly higher in the laparoscopic group (27.3 versus 24.6; p=0.009). The average time for surgery was significantly longer for the laparoscopic group (143.6 min versus 109.7 min; p=0.0001), but lymphadenectomy was performed in more patients (63.4% versus 25%; p=0.001). Postoperative hospital stay was significantly longer in patients undergoing the abdominal approach (4.59 days versus 3.18 days; p<0.0001). No blood transfusions were performed and the rates of complications were similar in the two groups. No differences were found in recurrence and survival rate. In our experience, laparoscopic and abdominal surgery can achieve similar results in the treatment of endometrial cancer. In our series, even with the BMI and the number of lymphadenectomies being higher in the laparoscopic group, the rates of complications were similar in the two groups.
    European Journal of Obstetrics & Gynecology and Reproductive Biology 02/2006; 124(2):232-6. · 1.97 Impact Factor
  • Article: Pretreatment serum hemoglobin level as a predictive factor of response to neoadjuvant chemotherapy in patients with locally advanced squamous cervical carcinoma: a preliminary report.
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    ABSTRACT: The aim of this study was to evaluate the predictive value of pretreatment serum hemoglobin level (Hb) together with a series of clinical and pathological variables available before neoadjuvant chemotherapy in locally advanced squamous cervical cancer. The influence on response to neoadjuvant chemotherapy of a series of pretreatment clinico-pathological features: hemoglobin level at diagnosis, age, parity, menopausal status, body mass index, clinical stage, tumor diameter, and nuclear grading were analyzed on 73 patients with locally advanced cervical cancer treated with platinum-based neoadjuvant chemotherapy followed by radical surgery. The relationships between pretreatment variables and response to chemotherapy were assessed in univariate and multivariate settings. A univariate and multivariate logistic regression model was adapted to predict an "optimal" response (pathological complete response or more than 50% reduction in tumoral diameter) or "sub-optimal" response (<50% reduction in tumoral diameter). Seventy-three patients-clinical stage: Ib2: 29 (39.7%) IIa: 22 (30.1%) IIb: 22 (30.1%)-received 3 cycles of platinum-based neoadjuvant chemotherapy followed by type III radical hysterectomy. A complete response to neoadjuvant chemotherapy was significantly associated with higher level of pretreatment hemoglobin (mean 14.0 mg/dl) compared to patients with > or =50% response (12.7 mg/dl) or <50% (11.9 mg/dl) (P = 0.002). At multivariate analysis, Hb level was found to be the most powerful and significantly related factor to response to neoadjuvant chemotherapy. A hemoglobin threshold of 12 mg/dl was able to distinguish between patients-with > or =12 mg/dl-at higher probability to respond to neoadjuvant chemotherapy from the ones at lower probability (hemoglobin level under 12 mg/dl). Patients with a complete response to chemotherapy had a 100% survival compared to 93.1% and 53.8% for patients with responses > or =50% and <50% respectively (P = 0.0001). Patients with a pretreatment hemoglobin level of > or =12 mg/dl showed a survival of 87% compared to 63% for patients with a lower hemoglobin level (P = 0.008). Pretreatment Hb level showed a prognostic and independent predictive value for response to neoadjuvant chemotherapy in locally advanced cervical cancer. In our preliminary report, performed on a limited sample, a threshold of 12 mg/dl seems to be helpful to distinguish between "optimal" and "non-optimal" response.
    Gynecologic Oncology 12/2005; 99(3 Suppl 1):S187-91. · 3.89 Impact Factor
  • Article: Endometrial carcinosarcomas have a different prognosis and pattern of spread compared to high-risk epithelial endometrial cancer.
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    ABSTRACT: The endometrial origin of uterine carcinosarcoma has recently been well established. The current study investigates whether uterine carcinosarcomas can be included in protocols on high-risk endometrial cancer, given the similarities in biologic behavior of both entities. Pathological and surgical notes of patients diagnosed with grade 3 endometrioid, carcinosarcoma, serous and clear cell endometrial cancer subtypes were retrospectively analyzed with special attention to the spread pattern of the different subtypes. Information on site of relapse and time to recurrence was obtained. We traced 146 patients of which 9 patients were ineligible. Histological subtypes of the remaining 137 patients were as follows: 50 (37%) grade 3 endometrioid carcinoma, 54 (39%) serous or clear cell carcinoma (non-endometrioid carcinoma), and 33 (24%) carcinosarcomas. Distribution of early stage disease (I and II) was 67, 46, and 78% for grade 3 endometrioid, non-endometrioid, and carcinosarcoma, respectively. Although we could not trace differences in hematogenic and transperitoneal spread among the three subtypes, non-endometrioid and carcinosarcomas were more likely to spread to pelvic and paraaortic lymph nodes (P < 0.01). Using univariate analysis, both stage (P < 0.006, Wald statistic) and histological type appear to determine the outcome, whereas lymphovascular space infiltration (P < 0.25) and age (P < 0.07) were not significantly different between the three histological subtypes. Cox Regression multivariate analysis on 127 women suffering from the three histological subtypes suggested that both stage III-IV disease (P < 0.00001) and histological type (carcinosarcoma) (P < 0.003) were of prognostic significance [hazard ratio (CI 95%) were, respectively, 3.8 (2.1-7.0) and 3.2 (1.7-5.9)]. Analyzing cases limited to stage I-II endometrial cancer, 24/28 (86%) grade 3 endometrioid, 18/24 (75%) non-endometrioid, and 11/25 (44%) carcinosarcomas survived, suggesting a worse outcome for endometrial carcinosarcoma when compared to the other subtypes (P < 0.008, Log Rank). A higher incidence of pulmonary metastases explained the worse outcome for early stage carcinosarcoma (P < 0.006), whereas the incidence of liver metastasis, transperitoneal spread, or recurrences in lymph nodes or vagina were comparable between the three pathologic subtypes. Although endometrial carcinosarcoma originates from epithelial cancer, the intrinsic more aggressive tumor biology suggests that this subtype should not be incorporated in studies on high-risk epithelial endometrial cancer.
    Gynecologic Oncology 09/2005; 98(2):274-80. · 3.89 Impact Factor
  • Article: Relationship between time interval from primary surgery to the start of taxane- plus platinum-based chemotherapy and clinical outcome of patients with advanced epithelial ovarian cancer: results of a multicenter retrospective Italian study.
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    ABSTRACT: To assess whether the interval from primary surgery to the start of taxane- plus platinum-based chemotherapy has any impact on the clinical outcome of advanced ovarian cancer patients. The study was conducted on 313 patients who underwent surgery followed by taxane- plus platinum-based chemotherapy. The median follow-up of survivors was 30.7 months (range, 6 to 109 months). The 25%, 50%, and 75% quantiles of intervals from surgery to the start of chemotherapy were 11, 21, and 31 days, respectively. After the sixth cycle, 102 patients achieved a pathologic complete response at second-look surgery and 98 obtained a clinical complete response but were not submitted to second-look surgery. Taking into consideration the best assessed response, a complete (either clinical or pathologic) response was found in 200 patients. Residual disease (< or = 1 v > 1 cm; P < .0001) and ascites (absent v present; P = .003) were independent predictive factors for achieving a complete response, whereas residual disease (P = .001) and stage (IIc to III v IV; P = .04) were independent prognostic variables for survival. Conversely, statistical analyses failed to detect significant differences in complete response rates and survival among patients with an interval from surgery to chemotherapy shorter than 11 days, 12 to 21 days, 22 to 31 days, and longer than 31 days. The interval from surgery to the start of taxane- plus platinum-based chemotherapy seems to have neither a predictive value for response to treatment nor a prognostic relevance for survival of advanced ovarian cancer patients.
    Journal of Clinical Oncology 03/2005; 23(4):751-8. · 18.37 Impact Factor
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    Article: Pretreatment serum hemoglobin level and a preliminary investigation of intratumoral microvessel density in advanced ovarian cancer.
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    ABSTRACT: The primary aim of this study was to evaluate the prognostic and predictive value of pretreatment serum hemoglobin level (Hb) in advanced ovarian cancer; second aim was to perform a preliminary investigation of intratumoral microvessel density (IMD). The influence on survival and response to treatment of several clinico-pathological features, including Hb, was analyzed in 72 patients with advanced ovarian cancer. IMD was assessed in tumor specimens of 25 of the 72 patients to compare three different endothelial markers: anti-FactorVIII, anti-CD31 and anti-CD34. In this subgroup of patients, a preliminary analysis of the prognostic and predictive value of IMD, and its relationship with Hb and other clinico-pathological features, was performed. Hb >or= 12 g/dl was significantly associated with a better overall survival in univariate analysis (P = 0.0181) and was the only independent prognostic variable in multivariate analysis (P = 0.0160). Hb was directly related to progression-free survival (P = 0.0240) and complete response to treatment (P = 0.016). In the preliminary investigation of IMD, mean microvessel count did not show any significant difference among the three endothelial markers used, but anti-CD34 revealed a more consistent staining reaction. The relationship between IMD and complete response to treatment was found near to statistical significance (P = 0.05); Hb and IMD were inversely related (r = -0.47; P = 0.045). Hb has a prognostic and predictive value in advanced ovarian cancer. In our preliminary study, which was performed on a limited number of patients, we found anti-CD34 to be an optimal marker for IMD determination, IMD to be a possible predictive factor of complete response to treatment, and IMD and Hb to be inversely related.
    Gynecologic Oncology 12/2004; 95(2):323-9. · 3.89 Impact Factor
  • Article: Personal use of HRT by postmenopausal women doctors and doctors' wives in the north of Italy.
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    ABSTRACT: This study aimed to describe the prevalence of hormone replacement therapy (HRT) use by women doctors and doctors' wives in northern Italy, to explore the relationship between their personal characteristics and HRT use, and to gather information about the use of alternative remedies. A questionnaire was mailed to all physicians born between 1935 and 1955 included in the database of the Medical Register of Turin County (Northern Italy). The questions were meant to explore medical, behavioral, and professional characteristics; personal use of HRT; reasons for and against HRT use; side effects and use of other therapies. 56.5% of postmenopausal women who completed the questionnaire had used HRTand 68.3% of them were current users. The median duration of HRT use was 3.7 years. Only 18.5% of the women had used HRT for 5 years or more; in this case, HRT was started significantly earlier than in the other groups. More than 50% had taken oral HRT, while 39% had used patches; estrogens only had been taken by 21.9%. HRT users had a significantly lower basal body mass index and more vasomotor and dystrophic symptoms at menopause onset compared with non-HRT users. More women on HRT were in good physical health and had an active sex life. Previous breast cancer and family history of cardiovascular diseases were inversely associated with HRT use. The main reason for not taking HRT or stopping it was fear of breast cancer (43.7% and 34.8%, respectively); irregular bleeding and weight gain were also frequently reported as a reason for HRT (30% and 22%). Overall, 22% of women had used alternative drugs to alleviate menopausal symptoms or prevent menopause-related diseases, mainly tibolone (21% among never HRT users and 2% among HRT users; p = 0.015) and phytoestrogens. The prevalence and duration of use of HRT by Italian physicians is consistent with the available data from other Western countries, and is much higher than in the general population. This is in contrast with the very low prevalence of use in the general population and may lead, in the near future, to a larger use of HRT in Italy.
    Gynecological Endocrinology 04/2004; 18(3):165-74. · 1.58 Impact Factor
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    Article: Angiopoietin-2 expression in breast cancer correlates with lymph node invasion and short survival.
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    ABSTRACT: Angiogenic factors produced by tumor cells are essential for tumor growth and metastasis. In our study, the expression of Angiopoietin-1 (ANG1) and Angiopoietin-2 (ANG2) mRNA in archival human breast cancer tumor samples and in 6 breast cancer cell lines was investigated. Total RNA from biopsies of 38 breast cancer patients was extracted and ANG1 and ANG2 mRNA expression was measured by means of quantitative real-time RT-PCR (Taqman). Matching data with available clinicopathologic and biochemical data revealed a significant association between ANG2 expression and axillary lymph node invasion. Univariate and multivariate survival analysis, by means of Kaplan-Meier method and Cox's proportional hazards model, showed significant and independent association between ANG2 mRNA level and both disease-free (p < 0.0001) and overall survival (p < 0.0003). An important fact is that, notwithstanding the small number of cases examined, this association was confirmed also in the group of lymph node-negative patients (DFS, p < 0.003; OS, p < 0.020). Immunohistochemical analysis demonstrated that Ang2 is expressed by both tumor cells and endothelial elements. Expression in tumor cells was confirmed by studying a panel of human breast carcinoma cell lines in culture by RT-PCR. In ZR75.1 and T47D cells, expression of ANG2 mRNA was increased up to 10-fold by treatment with estrogen within 24 hr. Although preliminary, these data suggest a possible role of ANG2 as a prognostic factor for primary breast cancer.
    International Journal of Cancer 02/2003; 103(4):466-74. · 5.44 Impact Factor