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Biomedical subjects

Giovanni Scambia

Publications and source records attributed to Giovanni Scambia.

At least 19 recordsLinked to original sources
PubMed2007

Lymph node involvement in locally advanced cervical cancer patients administered preoperative chemoradiation versus chemotherapy.

BACKGROUND: A retrospective study was planned in 127 locally advanced cervical cancer (LACC) to investigate: (1) the rate and pattern of metastatic lymph node involvement in patients administered preoperative chemoradiation (CT/RT) versus neoadjuvant chemotherapy (NACT), and (2) the profile of clinico-pathological parameters predictive of metastatic lymph node involvement in these two clinical settings. Finally, we investigated whether the pathologically assessed status of lower pelvic nodes (LPN) was able to predict the pathologically assessed status of upper pelvic nodes (UPN) and parametrium in cases administered CT/RT. METHODS: Patients were selected including LACC patients who were administered concomitant CT/RT (n = 87) or NACT (n = 40), before radical surgery. RESULTS: Metastatic pelvic lymph node involvement was significantly lower in cases administered CT/RT (11.5%) compared to cases administered NACT (30.0%) (P value = 0.009). In the CT/RT group, only MRI-assessed pelvic node status (both at staging and post-treatment evaluation) was associated with pathologic pelvic node status. In patients administered CT/RT, the status of LPN appeared associated with the status of UPN. CONCLUSIONS: (1) Preoperative CT/RT treatment is associated with a lower rate of pelvic node disease in LACC patients compared to NACT; (2) there is no association between the preoperative extent of residual cervical disease after CT/RT and pathologically assessed pelvic node status; (3) the pathological status of LPN is predictive of the pathological status of UPN and parametrium.

Adult↗
PubMed2007

Serous ovarian carcinoma recurring as a heterologous carcinosarcoma.

Only two cases of recurrence of heterologous carcinosarcoma from adenocarcinoma of the ovary have been documented in the published literature. We report a case of serous ovarian carcinoma recurring as a heterologous carcinosarcoma. The immunohistochemical analysis of several biological parameters in primary ovarian adenocarcinoma and recurrent carcinosarcoma has been also performed.

Carcinosarcoma↗
PubMed2006

Ovarian serous carcinoma presenting with mediastinal lymphadenopathy 20 months before the intraabdominal mass: role of immunohistochemistry.

INTRODUCTION: Metastatic involvement of the mediastinal lymph nodes is an extremely uncommon finding in epithelial ovarian cancers. CASE REPORT: A 63-year-old woman was admitted to hospital for dyspnoea due to an anterior mediastinal mass. The surgical biopsy showed a 6-cm metastatic lymph node with a papillary pattern, scattered psammomas and immunoreactivity for WT1, Cytokeratin 7, EMA and negative for E-cadherin, GCFDP-15, Thyroglobulin, Cytokeratin 20, Cytokeratin 5/6, CEA, Vimentin, Calretinin, TTF1. After 20 months a follow-up CT identified an ovarian mass with the same histological pattern and immunoreactivity of the mediastinal nodule. RESULTS: Immunohistochemistry, especially WT1, is useful in assessing the ovarian origin of an unusual metastasis particularly if it is the first presentation of the disease.

Diagnosis, Differential↗
PubMed2006

Expression of class III beta tubulin in cervical cancer patients administered preoperative radiochemotherapy: correlation with response to treatment and clinical outcome.

OBJECTIVES: Alterations of the beta subunit of tubulin have been reported to be predictive of resistance to radiation and antitubulin agents in several solid tumors. The aim of the study was to investigate the clinical role of beta III tubulin expression as prognostic factor for survival and as a predictive parameter of response to preoperative radiochemotherapy in a single institutional series of locally advanced cervical cancer (LACC) patients. METHODS: The study included 98 LACC patients admitted to the Gynecologic Oncology Unit, Catholic University of Rome and Campobasso between January 1998 and January 2005. Immunohistochemistry was performed by using the polyclonal rabbit anti-beta III tubulin antibody (Covance, Princeton, NJ, USA). The value of 10% immunostained tumor cells was arbitrarily chosen as cut-off value to distinguish cases with high versus low beta III tubulin content. RESULTS: In the whole series, beta III tubulin immunoreaction was detectable in 66/98 cases (67.3%), and the percentage of positively stained cells ranged from 0 to 100% (median=10%). The percentages of cases with high beta III tubulin expression were shown not to be differently distributed according to clinico-pathological characteristics. There was no statistically significant difference in the distribution of cases with high beta III tubulin expression according to clinical and pathological response to treatment. During the follow-up period, recurrence and death of disease occurred in 15 and 13 cases, respectively. There was no difference in disease-free and overall survival in cases with high versus low beta III tubulin expression. CONCLUSIONS: The assessment of class III beta tubulin status seems of little usefulness in order to identify LACC patients with poor chance of response to concomitant radiochemotherapy and unfavorable prognosis.

Adult↗
PubMed2006

Impact of pattern of recurrence on clinical outcome of ovarian cancer patients: clinical considerations.

Recurrence of disease represents a clinical challenge in ovarian cancer patients. The aim of this study was to analyse the distribution and pattern of recurrence and their association with clinical outcome in a large series of ovarian cancer patients. This study was conducted on 328 primary untreated ovarian cancer patients. For each relapse, information on date of clinical/instrumental recurrence, and pattern of disease presentation were retrieved. In stage III-IV cases (n = 270), diffuse abdominal carcinomatosis occurred in 62.1% of cases, while recurrences presented as a single lesion or multiple nodules occurred in 9.9% and 26.7% of cases, respectively. Pattern of recurrence as carcinomatosis was shown to be associated with unfavourable outcome even when stratified according to platinum free interval (PFI) duration. In multivariate analysis, pattern of recurrence and PFI duration retained an independent prognostic role for post-relapse survival. Duration of PFI and type of recurrence may independently influence post-relapse survival in ovarian cancer patients.

Adult↗
PubMed2006

Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial.

BACKGROUND: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III trial comparing carboplatin plus paclitaxel to carboplatin plus pegylated liposomal doxorubicin in first-line chemotherapy of patients with ovarian cancer. Due to the paucity of published phase I data on the 3-weekly experimental schedule used, an early safety analysis was planned. METHODS: Patients with ovarian cancer (stage Ic-IV), aged < 75 years, ECOG performance status <or= 2, were randomized to carboplatin AUC 5 plus paclitaxel 175 mg/m2, every 3 weeks or to carboplatin AUC 5 plus pegylated liposomal doxorubicin 30 mg/m2, every 3 weeks. Treatment was planned for 6 cycles. Toxicity was coded according to the NCI-CTC version 2.0. RESULTS: The pre-planned safety analysis was performed in July 2004. Data from the first 50 patients treated with carboplatin plus pegylated liposomal doxorubicin were evaluated. Median age was 60 years (range 34-75). Forty-three patients (86%) completed 6 cycles. Two thirds of the patients had at least one cycle delayed due to toxicity, but 63% of the cycles were administered on time. In most cases the reason for chemotherapy delay was neutropenia or other hematological toxicity. No delay due to palmar-plantar erythrodysesthesia (PPE) was recorded. No toxic death was recorded. Reported hematological toxicities were: grade (G) 3 anemia 16%, G3/G4 neutropenia 36% and 10% respectively, G3/4 thrombocytopenia 22% and 4% respectively. Non-haematological toxicity was infrequent: pulmonary G1 6%, heart rhythm G1 4%, liver toxicity G1 6%, G2 4% and G3 2%. Complete hair loss was reported in 6% of patients, and G1 neuropathy in 2%. PPE was recorded in 14% of the cases (G1 10%, G2 2%, G3 2%). CONCLUSION: This safety analysis shows that the adopted schedule of carboplatin plus pegylated liposomal doxorubicin given every 3 weeks is feasible as first line treatment in ovarian cancer patients, although 37% of the cycles were delayed due to haematological toxicity. Toxicities that are common with standard combination of carboplatin plus paclitaxel (neurotoxicity and hair loss) are infrequent with this experimental schedule, and skin toxicity appears manageable.

Adult↗
PubMed2006

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.

Adult↗
PubMed2006

Recurrence in skeletal muscle from squamous cell carcinoma of the uterine cervix: a case report and review of the literature.

BACKGROUND: The occurrence of skeletal muscle metastases is a very rare event. Only two cases of late skeletal muscle recurrence from cervical cancer have been documented until now. CASE PRESENTATION: A 38-year old patient, submitted to radical hysterectomy and pelvic lymphadenectomy for a squamous FIGO stage IB1 cervical carcinoma, presented after 76 months with a palpable, and painless swelling on the left hemithorax. MRI showed a nodule located in the context of the intercostal muscles. Pathology revealed the presence of metastasis of squamous cell carcinoma of similar morphology as the primary. On the basis of FDG-PET findings, which excluded other sites of disease, surgical excision of the lesion was performed. The patient was triaged to chemotherapy plus external radiotherapy. CONCLUSION: A case of skeletal muscle recurrence from cervical cancer after a very long interval from primary diagnosis is reported. Muscular pain or weakness, or just a palpable mass in a patient with a history of cancer has always to raise the suspicion of muscle metastasis.

Adult↗
PubMed2006

A laparoscopy-based score to predict surgical outcome in patients with advanced ovarian carcinoma: a pilot study.

BACKGROUND: Our objective was to set up a more objective quantitative laparoscopy-based model in predicting the chances of optimal cytoreductive surgery in advanced ovarian cancer patients. METHODS: Sixty-four advanced ovarian cancer patients were submitted to both laparoscopy and standard longitudinal laparotomy sequentially, to define the chances of optimal debulking surgery (residual disease < or = 1 cm). Three patients could not be evaluated by laparoscopy because of the presence of multiple and tenacious adherences. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each laparoscopic parameter. On the basis of the statistical probability of each factor to predict surgical outcome, seven laparoscopic features were selected for inclusion in the final model. Each parameter was assigned a numerical score based on the strength of statistical association, and a total predictive index value was tabulated for each patient. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict surgical outcome. RESULTS: After debulking surgery, 41 (67.2%) of 61 patients were left with optimal residual disease. The presence of omental cake, peritoneal carcinosis, diaphragmatic carcinosis, mesenteric retraction, bowel and/or stomach infiltration, and liver metastases satisfied the basic inclusion criteria and were assigned a final predictive index value of 2. In the final model, a predictive index score > or = 8 identified patients undergoing suboptimal surgery with a specificity of 100%. The positive predictive value was 100%, and the negative predictive value was 70%. CONCLUSIONS: The reliability of laparoscopy in assessing the chance of optimal cytoreduction can be improved by using a simple scoring system.

Female↗
PubMed2006

Novel BRCA1 and BRCA2 germline mutations and assessment of mutation spectrum and prevalence in Italian breast and/or ovarian cancer families.

Familial aggregations of breast/ovarian cancer cases frequently depend on BRCA1/2 pathogenic mutations. Here we counselled 120 Italian breast/ovarian cancer families and selected 73 probands for BRCA1/2 mutation screening. Through this analysis we defined the prevalence of BRCA1/2 pathogenic mutations occurring in Italian breast/ovarian cancer families, enlarged the spectrum of Italian BRCA1/2 mutations by 15% and report on the identification of 13 novel variants, including two deleterious truncating mutations and two potentially pathogenic missense mutations, on the BRCA1 and BRCA2 genes. Finally in hereditary breast cancer families with three or more female breast cancer cases we observed a low mutation prevalence and a significant association with BRCA2 mutations.

BRCA1 Protein↗
PubMed2006

Anemia in patients with locally advanced cervical carcinoma administered preoperative radiochemotherapy: association with pathological response to treatment and clinical outcome.

OBJECTIVE: The aim of this study was to investigate the role of anemia at presentation (basal HB) and during treatment (nadir HB) as predictor of pathological response, as well as disease-free (DFS) and overall survival (OS) in LACC patients undergoing chemoradiation followed by radical surgery. METHODS: 114 consecutive LACC patients were accrued at the Gynecologic Oncology Unit, Catholic University, Rome and at the Department of Oncology, Catholic University of Campobasso, Italy. Neoadjuvant treatment included chemotherapy with cisplatin (20 mg/m2) and 5-fluorouracil (1000 mg/m2, 24-h infusion) (both on days 1-4 and 27-30) and external radiotherapy to the whole pelvic region (22 fractions, 1.8 Gy/day, totaling 39.6 Gy). Clinical responders underwent radical surgery. Hemoglobin levels were recorded and expressed in gram per literx10(-2) (g/dl). The value of 10 g/dl was arbitrarily chosen as cut-off value. RESULTS: In cases showing high basal HB status, the percentage of pathological response was significantly higher than in patients showing low HB status (76.3% versus 46.7%) (P value=0.027). When logistic regression was applied, only advanced stage remained associated with a poor chance of response to treatment. Cases with low basal HB status had a shorter DFS and OS than cases with a high HB status (P value=0.0001 and 0.0022, respectively). Similar results were obtained when analyzing nadir HB status. In multivariate analysis, high basal HB status, and advanced stage, retained an independent negative prognostic role for DFS and OS. CONCLUSIONS: Anemia identifies LACC patients administered preoperative radiochemotherapy, who are at higher risk of recurrence and death of disease.

Adult↗
PubMed2006

Advanced vulvar carcinoma: is it worth operating? A perioperative management protocol for radical and reconstructive surgery.

OBJECTIVE: The aim of this study was to characterize the means whereby the results could be improved and the morbidity and side-effects minimized, of radical and extensive surgery performed together with plastic reconstruction, in the treatment of locally advanced and relapsed vulvar carcinoma. METHODS: Between May 2000 and November 2004, twenty-three patients with locally advanced or relapsed vulvar carcinoma underwent major radical or extended vulvectomy, requiring reconstructive surgery. A consistent protocol for the perioperative management of these patients, including precautionary measures to reduce the rate of early complications, was introduced in the second study period (from November 2003) to verify the benefit on surgical outcome. RESULTS: An analysis of the medical reports showed an improvement in the median time of the postoperative course and related morbidity as a consequence of a strict application of the management protocol, with consequent decrease of early complications. CONCLUSIONS: Reconstructive surgery, which broadens the spectrum of available operative therapy in primary and locally recurrent vulvar cancer, is characterized by a high complication rate. The application of a strict perioperative protocol could reduce the number and the clinical impact of such complications.

Aged↗
PubMed2006

Class III beta-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients.

PURPOSE: Overexpression of beta III tubulin has been involved in paclitaxel resistance in several experimental models. We investigated the role of beta III tubulin as predictor of clinical outcome in ovarian cancer patients given platinum/paclitaxel treatment. We also investigated whether beta III tubulin expression could be modified after the selective pressure represented by chemotherapy in vivo. EXPERIMENTAL DESIGN: The study was designed to include a series of consecutive ovarian cancer patients with unresectable disease at time of first surgery, who underwent interval debulking surgery with pathologic assessment of response to treatment with platinum/paclitaxel chemotherapy. Immunostaining was done on formalin-fixed, paraffin-embedded tissue sections from pretreatment and posttreatment tissue biopsies by using the polyclonal rabbit anti-class III beta-tubulin antibody. RESULTS: beta III Tubulin immunoreaction was observed in 51 of 62 (82.2%) cases. beta III Tubulin positivity was neither associated with clinicopathologic variables nor with pathologic response to chemotherapy. Significantly lower percentages of beta III tubulin positivity were observed in posttreatment (range, 5-80%; median, 20%) versus pretreatment (range 10-100%; median, 40%) tissue biopsies (P = 0.0011). Cases with high beta III tubulin expression showed a worse overall survival with respect to cases with low beta III tubulin expression (median overall survival, 25 versus 46 months; P = 0.002). Multivariate analysis showed that high content of beta III tubulin remains independently associated with a worse prognosis. CONCLUSIONS: Assessment of beta III tubulin could be useful to identify poor prognosis ovarian cancer patients candidates to more aggressive and/or targeted therapy.

Aged↗
PubMed2006

Celecoxib up-regulates the expression of the zeta chain of T cell receptor complex in tumor-infiltrating lymphocytes in human cervical cancer.

PURPOSE: We evaluated the effects of celecoxib treatment on tumor-infiltrating lymphocyte (TIL) subsets [CD3(+), CD4(+),CD8(+), CD25(+), and T cell receptor (TCR)-zeta-expressing cells] and tryptase-positive mast cells in cervical tumors. Circulating levels of cytokines [interleukin (IL)-1beta, IL-10, tumor necrosis factor-alpha, IL-6, and IL-12] and angiogenesis-modulating factors (vascular endothelial growth factor and endostatin) have also been analyzed. EXPERIMENTAL DESIGN: Cervical tumor biopsies and blood samples were obtained at the time of diagnosis and after 10 days of celecoxib treatment (400 mg b.i.d., at 8:00 a.m. and 8:00 p.m.) in 27 cases. Immunohistochemistry and ELISA assays were used to assess the expression of biological factors in tumor tissue and circulating levels of cytokines and angiogenic molecules. RESULTS: We showed a statistically significant increase in the percentage of TIL expressing the TCR-zeta chain after celecoxib treatment: indeed, in cases exposed to celecoxib, the percentage of TCR-zeta(+) cells ranged from 5.0 to 50.0 (median, 22.5) with respect to baseline expression (range, 3.0-50.0; median, 10.0; P = 0.0016). There was no significant treatment-related difference in the percentage of CD3(+), CD4(+), CD8(+), and CD25(+) TIL as well as in tryptase-positive cells. IL-12 levels were significantly reduced in posttreatment samples with respect to baseline levels (P = 0.002). We also found a reduction in the circulating levels of vascular endothelial growth factor, and a statistically significant increase of serum endostatin levels (P = 0.035). CONCLUSIONS: We reported the first evidence in humans that celecoxib restores zeta expression by TIL in primary cervical tumors, suggesting that a positive modulation of immune function may serve as an additional mechanism supporting the antitumor effect of this class of drugs.

Adult↗
PubMed2006

Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features.

Several hematopoietic growth factors, including interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1), promote the differentiation of tolerogenic dendritic cells (DCs). Hepatocyte growth factor (HGF) is a pleiotropic cytokine whose effects on human DC differentiation and function have not been investigated. Monocytes cultured with HGF (HGFMo) differentiated into accessory cells with DC-like morphology, released low amounts of IL-12p70 and up-regulated IL-10 both at the mRNA and at the protein level. Upon activation with HGFMo, allogeneic CD4+CD25- T cells expressed the T regulatory (Treg)-associated transcription factor FoxP3, proliferated poorly, and released high levels of IL-10. Interestingly, blockade of surface immunoglobulin-like transcript 3 (ILT3) on HGFMo or neutralization of secreted IL-10 translated into partial restoration of T-cell proliferation. Secondary stimulation of HGFMo-primed CD4+ T cells with immunogenic DCs differentiated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 from monocytes of the same donor resulted in measurable T-cell proliferation. HGFMo-primed CD4+ T cells significantly inhibited the proliferation of naive CD4+CD25- T cells in a cell-contact-dependent manner. Finally, DNA microarray analysis revealed a unique gene-expression profile of HGF-activated monocytes. Collectively, our findings point to a novel role for HGF in the regulation of monocyte/DC functions that might be exploited therapeutically.

CD4-Positive T-Lymphocytes↗
PubMed2006

Endometrial cancer arising in both horns of didelphys uterus in a Down's syndrome woman.

BACKGROUND: There are only few reports of endometrial cancer arising in patients with uterine malformations. Down's syndrome is characterized by a reduced risk of solid tumors, and there are no reports about its correlation with uterine malformations. CASE: An endometrial adenocarcinoma arising in both horns of a didelphys uterus of a Down's syndrome woman. CONCLUSION: Uterine malformations and genetical disorders may cause a delayed diagnosis of gynecological cancers. Gynecological examination in asymptomatic patients and differential diagnosis in abnormal uterine bleeding patients should be considered.

Adult↗