Biomedical subjects

Francesco Raspagliesi

Publications and source records attributed to Francesco Raspagliesi.

14 recordsLinked to original sources

PubMed2006

Clinical and pathological prognostic factors in squamous cell carcinoma of the vulva.

OBJECTIVE: The objective of this study was the prognostic analysis of clinicopathologic variables related to primary tumor and to lymph node metastases. METHODS: We retrospectively analyzed 389 cases of squamous cell carcinoma of the vulva. The following variables were studied: patients' age, diameter and location of the tumor, clinical tumor characteristics, depth of invasion, grade, lymphovascular space involvement (LVSI) and lymph node status. In the subset of 110 node positive patients, we evaluated number of positive nodes, laterality, extension of node dissection, lymph node chains involved, presence of extracapsular spread and rate of lymph node replacement. All variables with P value < 0.2 by the univariate analysis were successively subjected to multivariate analysis (Cox proportional hazard model). RESULTS: Among all the tumor-related variables age, clinical tumor characteristics, LVSI and lymph node status were found to be statistically significant predictors of survival for the log-rank test. On the basis of multivariate analysis, the nodal status was the most significant independent prognostic factor (hazard rate [HR]: 2.06; confidence interval [CI] 95%: 1.57-12.07) followed by LVSI (HR: 3.47; CI95%: 1.85-7.85). The independent prognostic factors among the variables relative to positive nodes were the percentage of nodal replacement (HR: 6.99; CI95%: 3.51-16.14) and the extracapsular spread (HR: 4.88; CI95%: 2.96-10.14). CONCLUSIONS: Lymph node status and nodal features, such as extracapsular spread and nodal replacement rate, were shown to be independent factors. These factors should be considered to identify high risk patients and in planning further adjuvant therapy.

Adult↗

PubMed2006

Type II versus Type III nerve-sparing radical hysterectomy: comparison of lower urinary tract dysfunctions.

OBJECTIVES: According to our previous experience, Type III Nerve-sparing Radical hysterectomy (NSRH) for cervical cancer presented an acceptable urologic morbidity, without compromising radicality. The aim of this study was to compare Type NSRH with other types of RH in terms of incidence of early bladder dysfunctions and perioperative complications. METHODS: One hundred and ten patients with cervical cancer were submitted to Type II RH (group 1), Type III NSRH (group 2) and Type III RH (group 3). We assessed the postoperative early bladder function and complications. The follow-up period was 3 months. RESULTS: Group 1 had a significantly shorter duration of the surgery, minor mean blood loss and shorter mean length of postoperative stay when compared to groups 2 and 3. No intraoperative complications were reported in either of the groups. The groups did not differ significantly in terms of GIII/IV morbidity (group 1 = 10%, group 2 = 10% and group 3 = 15%, chi(2), P value: 0.65). Not even they differed in terms of urologic GI-IV morbidity (group 1 = 13%, group 2 = 15% and group 3 = 10%, chi(2), P value = 0.88). Groups 1 and 2 presented a prompt recover of bladder function, significantly different from that of group 3. There was a significant difference between the groups regarding the number of patients discharged with self-catheterism (group 1 = 0; group 2 and group 3 = 11; chi(2), P value << 0.05). CONCLUSIONS: The Type III NSRH seems to be comparable to Type II RH and superior to Type III RH in terms of early bladder dysfunctions.

Adult↗

PubMed2005

Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: a randomized clinical trial.

BACKGROUND: The role of systematic aortic and pelvic lymphadenectomy in patients with optimally debulked advanced ovarian cancer is unclear and has not been addressed by randomized studies. We conducted a randomized clinical trial to determine whether systematic aortic and pelvic lymphadenectomy improves progression-free and overall survival compared with resection of bulky nodes only. METHODS: From January 1991 through May 2003, 427 eligible patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB-C and IV epithelial ovarian carcinoma were randomly assigned to undergo systematic pelvic and para-aortic lymphadenectomy (n = 216) or resection of bulky nodes only (n = 211). Progression-free survival and overall survival were analyzed using a log-rank statistic and a Cox multivariable regression analysis. All statistical tests were two-sided. RESULTS: After a median follow-up of 68.4 months, 292 events (i.e., recurrences or deaths) were observed, and 202 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for first event was statistically significantly lower in the systematic lymphadenectomy arm (hazard ratio [HR] = .75, 95% confidence interval [CI] = 0.59 to 0.94; P = .01) than in the no-lymphadenectomy arm, corresponding to 5-year progression-free survival rates of 31.2 and 21.6% in the systematic lymphadenectomy and control arms, respectively (difference = 9.6%, 95% CI = 1.5% to 21.6%), and to median progression-free survival of 29.4 and 22.4 months, respectively (difference = 7 months, 95% CI = 1.0 to 14.4 months). The risk of death was similar in both arms (HR = 0.97, 95% CI = 0.74 to 1.29; P = .85), corresponding to 5-year overall survival rates of 48.5 and 47%, respectively (difference = 1.5%, 95% CI = -8.4% to 10.6%), and to median overall survival of 58.7 and 56.3 months, respectively (difference = 2.4 months, 95% CI = -11.8 to 21.0 months). Median operating time was longer, and the percentage of patients requiring blood transfusions was higher in the systematic lymphadenectomy arm than in the no-lymphadenectomy arm (300 versus 210 minutes, P<.001, and 72% versus 59%; P = .006, respectively). CONCLUSION: Systematic lymphadenectomy improves progression-free but not overall survival in women with optimally debulked advanced ovarian carcinoma.

Adult↗

PubMed2004

Gene expression profiling of advanced ovarian cancer: characterization of a molecular signature involving fibroblast growth factor 2.

Epithelial ovarian cancer (EOC) is the gynecological disease with the highest death rate. We applied an automatic class discovery procedure based on gene expression profiling to stages III-IV tumors to search for molecular signatures associated with the biological properties and progression of EOC. Using a complementary DNA microarray containing 4451 cancer-related, sequence-verified features, we identified a subset of EOC characterized by the expression of numerous genes related to the extracellular matrix (ECM) and its remodeling, along with elements of the fibroblast growth factor 2 (FGF2) signaling pathway. A total of 10 genes were validated by quantitative real-time polymerase chain reaction, and coexpression of FGF2 and fibroblast growth factor receptor 4 in tumor cells was revealed by immunohistochemistry, confirming the reliability of gene expression by cDNA microarray. Since the functional relationships among these genes clearly suggested involvement of the identified molecular signature in processes related to epithelial-stromal interactions and/or epithelial-mesenchymal cellular plasticity, we applied supervised learning analysis on ovarian-derived cell lines showing distinct cellular phenotypes in culture. This procedure enabled construction of a gene classifier able to discriminate mesenchymal-like from epithelial-like cells. Genes overexpressed in mesenchymal-like cells proved to match the FGF2 signaling and ECM molecular signature, as identified by unsupervised class discovery on advanced tumor samples. In vitro functional analysis of the cell plasticity classifier was carried out using two isogenic and immortalized cell lines derived from ovarian surface epithelium and displaying mesenchymal and epithelial morphology, respectively. The results indicated the autocrine, but not intracrine stimulation of mesenchymal conversion and cohort/scatter migration of cells by FGF2, suggesting a central role for FGF2 signaling in the maintenance of cellular plasticity of ovary-derived cells throughout the carcinogenesis process. These findings raise mechanistic hypotheses on EOC pathogenesis and progression that might provide a rational underpinning for new therapeutic modalities.

Cell Line, Tumor↗

PubMed2004

CD95-mediated apoptosis is impaired at receptor level by cellular FLICE-inhibitory protein (long form) in wild-type p53 human ovarian carcinoma.

PURPOSE: Ovarian carcinoma is a highly lethal malignancy that often becomes resistant to chemotherapy. Alterations in apoptotic signals and p53 status contribute to drug resistance, and CD95-mediated apoptosis is also deficient in resistant cells. We analyzed the mechanism of resistance to CD95-mediated apoptosis in ovarian carcinoma cell lines differing in p53 status. EXPERIMENTAL DESIGN: CD95-mediated apoptosis was induced by agonistic anti-CD95 antibody, and the apoptotic cascade was monitored with biochemical and functional assays. RESULTS: CD95-mediated apoptosis was blocked in human ovarian cancer cells. In cell lines with wild-type p53, treatment with the protein synthesis inhibitor cycloheximide (CHX) together with anti-CD95 overcame the resistance, suggesting the presence of a labile inhibiting protein. Indeed, the labile protein cellular FLICE-inhibitory protein long form (c-FLIP(L)) was found to block caspase-8 recruitment to the death-inducing signaling complex (DISC), and sensitization of cells by CHX was due to c-FLIP(L) down-modulation at the DISC level. Down-regulation of c-FLIP(L) with antisense oligonucleotides increased CD95-mediated apoptosis as in cells sensitized by CHX, demonstrating the direct involvement of c-FLIP(L) in apoptosis resistance. Removal of c-FLIP(L) block at DISC level allowed full activation of the mitochondrial pathway and, eventually, apoptosis in wild-type p53 cells, whereas in cells with mutated p53, c-FLIP(L) involvement in CD95-mediated apoptosis resistance appeared to be irrelevant. Immunohistochemical analysis of an ovarian tumor tissue array revealed c-FLIP(L) expression in samples with no p53 accumulation (P = 0.034), and a significant (P = 0.037) inverse relationship between c-FLIP(L) and p53 expression levels was also observed in 27 epithelial ovarian cancer specimens with known p53 status. CONCLUSION: The inhibitory protein c-FLIP(L) is involved in resistance to CD95-mediated apoptosis in ovarian carcinoma cells with wild-type p53.

Apoptosis↗

PubMed2004

Paclitaxel 175 or 225 mg per meters squared with carboplatin in advanced ovarian cancer: a randomized trial.

PURPOSE: To analyze the effect of different doses of paclitaxel with fixed doses of carboplatin in the treatment of ovarian cancer. PATIENTS AND METHODS: Patients with histologically confirmed epithelial ovarian cancer, International Federation of Gynecology and Obstetrics stages IIB to IV, were eligible for this randomized, multicenter study. Women were randomly assigned to treatment with (1) carboplatin at the dose (in milligrams) corresponding to the following formula: target area under the free carboplatin plasma concentration versus time curve (AUC) = 6 x (glomerular filtration rate + 25) mg/m(2) (AUC6) plus paclitaxel 175 mg/m(2) for six cycles every 21 days or (2) carboplatin AUC6 plus paclitaxel 225 mg/m(2) for six cycles every 21 days. A total of 502 women entered the study. RESULTS: Pathologic complete response was documented in 132 patients (63.8%) in the 175 mg/m(2) group and in 127 cases (55.7%) in the 225 mg/m(2) group (chi(2) P =.090). The 4-year progression-free survival rate was 41.5% (SE = 3.5) in the 175-mg group and 39.2% (SE = 3.5) in the 225-mg group. The corresponding 4-year survival rates were 46.2% (based on 115 deaths) and 47.3% (based on 113 deaths), respectively. CONCLUSION: This randomized trial suggests that paclitaxel 175 mg/m(2) plus carboplatin AUC6 is the schedule with a more favorable profile than paclitaxel 225 mg/m(2) plus carboplatin AUC6.

Adolescent↗

PubMed2004

Hysteroscopic injection of tracers in sentinel node detection of endometrial cancer: a feasibility study.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of sentinel lymph node (SLN) detection in endometrial cancer patients with hysteroscopic injection of tracers. Study design Eighteen patients with endometrial adenocarcinoma were submitted to hysteroscopic injection of technetium-99m-labeled colloids and blue-dye subendometrially around the lesion followed by lymphoscintigraphic scans. The SLN was detected by direct visualization of blue-dye marked nodes and by a radio-guided surgery (RGS). RESULTS: Seventeen hysteroscopic procedures were satisfactory regarding the visualization of the uterine cavity. The compliance to the procedure was acceptable in 15 cases, with no severe complication. A hysterectomy and bilateral salpingo-oophorectomy were performed in all cases, and pelvic lymphadenectomy in 14 cases. The RGS detected a total of 45 SLN with a mean of 3 SLN/patient (range 2 to 4). Blue-dye uptake was observed in 6 (33%) cases. No case presented blue-dye uptake and radioactive-colloid negativity. CONCLUSION: The results seem promising for further controlled studies.

Adenocarcinoma↗

PubMed2004

Nerve-sparing radical hysterectomy: a surgical technique for preserving the autonomic hypogastric nerve.

OBJECTIVES: Recently, a nerve-sparing radical hysterectomy has been proposed for cervical cancer to reduce morbidity. The aim of this study is (i) to describe the surgical anatomy of the autonomic nervous system, (ii) to describe a new nerve-sparing technique for Piver III radical hysterectomy (RH) using the CUSA, in which greater attention was paid to the autonomic nervous pathway, and (iii) to assess the feasibility and the impact of this nerve-sparing technique on the incidence of early bladder dysfunctions. METHODS: Twenty-three patients with cervical cancer were submitted to nerve-sparing Piver III RH with pelvic lymphadenectomy. Postoperative assessment of bladder function consisted draining the bladder for 3 days using Foley catheterization. Then, we started draining the bladder every 3 h with a no. 10 French catheter to register the onset of spontaneous voiding and to assess the postvoid residual urine volume (PVR). RESULTS: The nerve-sparing technique were performed satisfactorily in all cases. The mean operating time was 219 min (range: 150-270). The mean blood loss was 489 ml (range: 200-800). The average period of hospitalization was 10 days (range: 5-16). Two (9%) patients were discharged with self-catheterization, and one of them recovered the ability to void her bladder spontaneously by the time of her first visit to the outpatient clinic. CONCLUSIONS: This nerve-sparing RH technique using the CUSA proved feasible, with promising results in terms of preventing early bladder dysfunction. The average time between surgery and the onset of spontaneous voiding was acceptable. Further prospective controlled studies are needed to confirm our data.

Adult↗

PubMed2004

Gemcitabine combined with oxaliplatin (GEMOX) as second-line chemotherapy in patients with advanced ovarian cancer refractory or resistant to platinum and taxane.

OBJECTIVES: The aim of this multicenter feasibility study was to determine the toxicity profile and antitumor activity of the gemcitabine plus oxaliplatin combination as second-line treatment in platinum plus paclitaxel resistant/refractory advanced ovarian cancer. METHODS: Twenty patients received a 30-60-min infusion of gemcitabine a week for 2 weeks, followed by 120-180 min infusion of oxaliplatin every 3 weeks. The doses used were 1,000 and 130 mg/m(2), respectively. Seventeen cases (85% of the total) were platinum resistant and 3 (15%) were platinum refractory. RESULTS: Grade 3/4 thrombocytopenia occurred in 14/20 of cases (70%); there were no symptomatic cases. 2 patients required platelet transfusion and 8 patients received hydrocortisone. The dose- limiting toxicity was thrombocytopenia. Combined grade 3/4 neutropenia was observed in 8/20 (40%) of cases (no sepsis was registered). Five patients were treated with recombinant erythropoietin because of grade 3 anemia and 4 cases received G-CSF prophylactically from the first cycle. The overall response rate of the combination in terms of antitumor activity was 26% (95% CI = 9-51%). CONCLUSION: A combination of gemcitabine and oxaliplatin using this schedule gave rise to a moderate/severe toxicity profile and would be feasible only if growth factors were used and/or gemcitabine were administered at lower doses. The antitumor activity of the combination was insufficient reward for the resultant toxicity profile. However, equivalent to that of other drugs used in platinum refractory and resistant patients.

Adult↗

PubMed2003

Microinvasive squamous cell cervical carcinoma.

Several histologic tumor-related features are the key factors for further treatment planning in microinvasive cervical cancer (MIC) after conization. To better define the indications for conservative treatment of MIC we conducted a literature review for prognostic factors for MIC and we carried out a prospective observational study evaluating most important pathologic factors and the relationships between tumor and edges of the cone and incidence of recurrences. In our experience seven recurrences were observed. Two distinct groups of patients were identified with a clearance lower or higher of 10 and 8 mm for apical and lateral margin respectively. Depth of infiltration and even lymph-vascular involvement have been confirmed as the most important histologic parameters to be evaluated. Apical and lateral clearance of the tumor are significantly correlated with the recurrence rate. If an adequate lateral border of healthy tissue is present on the specimen, conization may be considered as definitive treatment of MIC.

Carcinoma, Squamous Cell↗

PubMed2003

Management of peritoneal surface component of ovarian cancer.

Primary surgery followed by systemic platinum-based chemotherapy is the cornerstone of management for ovarian cancer. However, the majority of patients have an advanced disease (stage III/IV) at the time of diagnosis rendering the optimal primary cytoreduction feasible in only a small percentage of cases. A large tumor bulk limits the success of subsequent antiblastic therapy. There are two alternatives to overcome this unfavorable situation: (1) employment of ultra-radical interventions such as peritonectomy procedures, to increase the optimal cytoreduction rate; or (2) neoadjuvant chemotherapy. Whether such strategies would have an influence on the final outcome of patients is an issue to be defined in further prospective randomized studies. For second-line therapies no consensus regarding treatment has emerged. When previous effective drug combinations fail, there is virtually no chance of inducing a significant response with second-line treatment. The combination of secondary CRS and intraperitoneal hyperthermic perfusion constitutes a feasible and potential option for this subset of patients based on phase II studies. A randomized trial will be conducted to test the effectiveness of this strategy in patients with cisplatin-resistant disease. The indication for second-line treatment is macroscopic residual or relapse within 6 months after the completion of first line chemotherapy.

Adult↗

PubMed2002

Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study.

PURPOSE: Neoadjuvant chemotherapy (NACT) and radical surgery (RS) have emerged as a possible alternative to conventional radiation therapy (RT) in locally advanced cervical carcinoma. In 1990, a phase III trial was undertaken to verify such a hypothesis in terms of survival and treatment-related morbidity. PATIENTS AND METHODS: Patients with squamous cell, International Federation of Gynecology and Obstetrics stage IB2 to III cervical cancer were eligible for the study. They received cisplatin-based NACT followed by RS (type III to V radical hysterectomy plus systematic pelvic lymphadenectomy) (arm A) or external-beam RT (45 to 50 Gy) followed by brachyradiotherapy (20 to 30 Gy) (arm B). RESULTS: Of 441 patients randomly assigned to NACT+RS or RT, eligibility was confirmed in 210 and 199 patients, respectively. Treatment was administered according to protocol in 76% of arm A patients and 72% of arm B patients. Adjuvant treatment was delivered in 48 operated patients (29%). There was no evidence for any significant excess of severe morbidity in one of the two arms. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 58.9% and 55.4% for arm A and 44.5% and 41.3% for arm B (P =.007 and P =.02), respectively. Subgroup survival analysis shows OS and PFS rates of 64.7% and 59.7% (stage IB2-IIB, NACT+RS), 46.4% and 46.7% (stage IB2-IIB, RT) (P =.005 andP =.02), 41.6% and 41.9% (stage III, NCAT+RS), 36.7% and 36.4% (stage III, RT) (P =.36 and P =.29), respectively. Treatment had a significant impact on OS and PFS. CONCLUSION: Although significant only for the stage IB2 to IIB group, a survival benefit seems to be associated with the NACT+RS compared with conventional RT.

Adult↗

PubMedDate not supplied

Gonadoblastoma in androgen insensitivity syndrome: a case report.

We report a case of androgen insensitivity syndrome (AIS) characterized by malignant degeneration of the testes consisting of gonadoblastoma and dysgerminoma. AIS is a rare inherited form of male pseudohermaphroditism that can manifest as a normal female phenotype without müllerian derivatives and absence of the upper third of the vagina. A 32-year-old white 46,XY female with AIS underwent removal of the dysgenetic gonads at the Gynecological Oncology Department of the Istituto Nazionale Tumori, Milan, Italy. We investigated cytogenetic alterations, hormonal levels and the presence of neoplasia in the dysgenetic gonads. Histological analysis revealed a gonadoblastoma mixed with dysgerminoma in the left gonad and a pure dysgerminoma in the right gonad. The patient's hormonal status matched that of a male. Second-look laparotomy after chemotherapy showed a complete pathological response. AIS should be suspected in phenotypically female patients with primary amenorrhea; surgical removal of the gonads is mandatory to avoid malignant degeneration.

Adult↗

PubMedDate not supplied

Nerve-sparing radical hysterectomy: a pilot study.

Nerve-sparing radical hysterectomy has increasingly been used for cervical cancer, with less morbidity. We aimed with this study: i) to describe an alternative technique of nerve-sparing radical Piver III hysterectomy, using the CUSA, in which attention was given to the uterosacral ligament and cardinal ligament; ii) to evaluate the feasibility of this new nerve-sparing technique; iii) to describe the surgical anatomy of the autonomic nervous system; iv) to assess the early incidence of bladder dysfunction. Twelve consecutive patients with local-regional advanced cervical cancer were enrolled in the study on nerve-sparing radical hysterectomy with extended pelvic lymphadenectomy. The mean age was 44 years (range, 30-59), mean body mass index was 24 kg/m2 (range, 18-30), mean operating time was 217 mins (range, 195-240), and mean blood loss was 437 cc (range, 200-750). The average hospitalization time was 9 days (range, 5-15 days). Two patients presented pathologically positive parametrium. Two of 12 (17%) patients were discharged with self-catheterism. In the first outpatient follow-up, 1 patient had recovered spontaneous voiding. The nerve-sparing technique with CUSA can be an option to reduce radical hysterectomy-related morbidity. The technique proved to be feasible, with promising results in terms of preventing bladder dysfunction. An elevated body mass index and large tumors can impair the performance of the technique. Further studies clarifying neuroanatomy and neurophysiology of autonomic nervous structures, as well as a prospective controlled trial on nerve-sparing radical hysterectomy should be carried out to confirm our data.

Adult↗