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Biomedical subjects

A Gadducci

Publications and source records attributed to A Gadducci.

At least 37 records · Page 2Linked to original sources
PubMed2000

Intraperitoneal versus intravenous cisplatin in combination with intravenous cyclophosphamide and epidoxorubicin in optimally cytoreduced advanced epithelial ovarian cancer: a randomized trial of the Gruppo Oncologico Nord-Ovest.

Intraperitoneal chemotherapy has a strong biological and pharmacological rationale in the treatment of ovarian cancer. From 1989 to 1996 the present study included 113 patients with FIGO stage II-IV ovarian cancer with residual disease less than 2 cm who were randomly allocated to receive 50 mg/m(2) intraperitoneal cisplatin (CDDP) plus 60 mg/m(2) intravenous epidoxorubicin (EPIDOX) and 600 mg/m(2) intravenous cyclophosphamide (CTX) (ipPEC arm) or 50 mg/m(2) intravenous CDDP plus 60 mg/m(2) intravenous EPIDOX and 600 mg/m(2) intravenous CTX (ivPEC arm). Chemotherapy was repeated every 4 weeks for six cycles. Treatment protocol was changed in 22 patients, 2 from the iv arm (who received single-agent carboplatin) and 20 from the ip arm (who were crossed to systemic chemotherapy, ivPEC, or single-agent carboplatin). At the end of chemotherapy, a second-look was performed in 33 of the 54 patients from the ip arm and in 34 of the 57 patients from the systemic arm. The pathologic complete response rate was 41% of all entered patients and 69% of patients submitted to second-look. No significant difference in pathologic response rate as well as in hematologic and nonhematologic toxicities was seen between the two arms. Up to September 1998, 72 patients showed a disease recurrence (33 treated with ipPEC and 39 treated with ivPEC), 55 died (22 ipPEC and 30 ivPEC), and 10 were lost to follow-up (6 ipPEC and 4 ivPEC). Median progression-free survival was 42 and 25 months for ipPEC and ivPEC, respectively (p = 0.13). Median overall survival was 67 and 51 months for ipPEC and ivPEC, respectively (p = 0.14). In conclusion, besides confirming that intraperitoneal chemotherapy is feasible with acceptable toxicity but with poor compliance in community hospitals, this trial showed that intraperitoneal CDDP compared with intravenous CDDP in combination with EPIDOX and CTX obtained a slight (not significant) improvement in progression-free survival and overall survival of optimally cytoreduced advanced ovarian cancer patients.

Adult↗
PubMed2000

Complete salvage surgical cytoreduction improves further survival of patients with late recurrent ovarian cancer.

OBJECTIVE: The aim of this study was to assess the clinical benefit of salvage surgical cytoreduction in patients with late recurrent ovarian cancer. METHODS: Thirty patients with recurrent ovarian cancer who underwent salvage surgical cytoreduction were retrospectively reviewed. All had been initially treated by primary surgery and platinum-based chemotherapy and had a period of clinical remission of at least 6 months. Median time to recurrence was 17.5 months (range, 6-76 months). RESULTS: A macroscopically complete salvage cytoreduction was obtained in 17 (56.7%) patients, whereas 8 patients were left with macroscopic residual disease <2 cm and 5 patients with a larger residuum. Logistic regression showed that the probability of achieving a complete cytoreduction was significantly related to the residual disease after initial surgery (<2 cm versus >2 cm, P = 0.0027, odds ratio = 36.000, 95% confidence interval = 3. 473-373.176), but not to FIGO stage, tumor grade, histologic type, patient age at recurrence, and time to recurrence. In the whole series median survival following salvage surgery was 21 months. Survival was significantly longer in patients who were completely cytoreduced compared to those who were not (median: 37 months versus 19 months, P = 0.04). Moreover, survival was significantly related to time to recurrence (>17.5 months versus <17.5 months, median: 25 months versus 15 months, P = 0.039), number of recurrence sites (single versus multiple, median: 40 months versus 19 months, P = 0. 009), and residual disease after initial surgery (<2 cm versus >2 cm, median: 37 months versus 19 months, P = 0.01), but not to patient age, recurrence site with the largest size, FIGO stage, tumor grade, and histologic type. CONCLUSIONS: The present data seem to show that complete salvage surgical cytoreduction significantly improves further survival of ovarian cancer patients who recur at least 6 months after the completion of primary therapy.

Adult↗
PubMed2000

Serum markers as prognostic factors in epithelial ovarian cancer: an overview.

A comprehensive review of the literature and the authors' personal experience on serum determination of tumour markers in epithelial ovarian cancer can be summarised as follows: CA 125 is the most reliable marker for monitoring the course of epithelial ovarian cancer; CA 125 assay is not an adequate screening test for this malignancy but it can represent an useful adjunct to clinical examination and ultrasound in the differential diagnosis of ovarian masses in postmenopausal women; Serial measurements of CA 125 are useful in monitoring the response to chemotherapy and follow-up. In patients with preoperative positive CA 125 assay, the concomitant determination of other tumour markers does not add further information when compared to CA 125 alone. Conversely in patients with preoperative negative assay the measurement of one or more of other antigens could be of clinical relevance.

Biomarkers, Tumor↗
PubMed1999

Assessment of the prognostic relevance of serum anti-p53 antibodies in epithelial ovarian cancer.

The objective of this study was to assess the prognostic relevance of preoperative serum anti-p53 antibodies in epithelial ovarian cancer. These autoantibodies were detected with a new generation enzyme-linked immunosorbent assay in blood samples preoperatively drawn from 86 patients with this malignancy. Serum anti-p53 antibodies were found in 3 (10.0%) of the 30 patients with stage I-II and 15 (26.8%) of the 56 patients with stage III-IV epithelial ovarian cancer (P = 0.09). We assessed in detail 44 patients with stage III-IV disease who underwent six cycles of first-line platinum-based chemotherapy. A pathological complete response at second-look was achieved by none of the 15 patients with serum anti-p53 antibodies compared to 24.1% of the 29 patients without autoantibodies (P = 0.09). However, the preoperative serum anti-p53 antibody status had no prognostic relevance for progression-free survival and survival. In conclusion, the assessment of preoperative serum anti-p53 antibodies seems to have a limited clinical value in the management of patients with advanced epithelial ovarian cancer.

Autoantibodies↗
PubMed1999

Benign ovarian fibroma associated with free peritoneal fluid and elevated serum CA 125 levels.

This paper reports the clinical case of a patient with ovarian neoplasia, ascites effusion, and elevated serum CA 125 levels (411 U/ml). This condition simulated a malignant pathology on the grounds of preoperative diagnostic examinations. Surgical investigation diagnosed an ovarian fibroma and ascites. Ascites was resolved rapidly and the serum CA 125 levels decreased after surgical neoplasia removal. An ovarian neoplasia associated with ascites effusion and elevated serum CA 125 levels (also in the presence of suspect ecographic and tomographic features) do not necessarily imply a malignant neoplasia.

Ascites↗
PubMed1998

Analysis of failures after negative second-look in patients with advanced ovarian cancer: an Italian multicenter study.

This multicenter retrospective study is based on 192 patients with advanced ovarian cancer in pathological complete response at second-look surgery. Ninety-four (48.9%) patients developed recurrent disease after a median time of 18 months (range, 4-89 months) from surgical reassessment. The recurrence involved the pelvis in 45 (47.9%) cases, the abdomen in 42 (44.7%), the retroperitoneal lymph nodes in 13 (13.8%), and distant sites in 20 (21.2%). On the whole series, 5- and 7-year disease-free survival rates after negative second-look were 47.4 and 44.5%, respectively. By log-rank test the disease-free survival rate was related to FIGO stage (P = 0.008), tumor grade (P = 0.0021), size of residual disease after initial surgery (P = 0.0038), and type of second-look (laparoscopy vs laparotomy, P = 0.0061), but not to histological type and first-line chemotherapy. Cox proportional hazard model showed that tumor grade, size of residual disease, and type of second-look were independent prognostic variables for disease-free survival. The risk ratio of relapse was 2.386 (95% CI, 1.140-4.990) for grade 2 and 3.118 (95% CI, 1.515-6.416) for grade 3 compared to grade 1 disease. For patients with residual disease 1-2 cm and > 2 cm the risk ratio was, respectively, 1.877 (95% CI, 1.117-3.156) and 2.156 (95% CI, 1.324-3.511) compared to patients with residual disease < 1 cm. The risk ratio was 1.826 (95% CI, 1.121-2.973) for patients who were submitted to a laparoscopic second-look compared to those who underwent a laparotomic reassessment. Poorly differentiated grade and large residual disease after initial surgery are the strongest prognostic variables for recurrence after a negative second-look.

Adult↗
PubMed1998

Serum macrophage colony-stimulating factor (M-CSF) levels in patients with epithelial ovarian cancer.

The preoperative macrophage colony-stimulating factor (M-CSF) levels were measured in serum samples from 56 patients with epithelial ovarian cancer and 68 patients with benign ovarian disease who had undergone laparotomy. M-CSF values were significantly higher in the former (median, range: 2.18, 0.70-10.00 ng/ml versus 1.19, 0.17-5.54 ng/ml, P < 0.0001), and were not significantly related to stage, histology, grade of differentiation, age, and residual disease after first surgery. M-CSF concentrations were also measured in 163 serum samples drawn from patients with stage III-IV epithelial ovarian cancer at different times since the first surgery. M-CSF values were higher in the 81 samples from patients with clinically evident disease than in the 82 samples from patients with no clinical evidence of disease (median, range: 2.13, 0.60-10.00 ng/ml versus 1.05, 0.40-10.00 ng/ml, P < 0.0001). M-CSF levels before second-look laparotomy were similar in the 18 patients who showed persistent disease at surgical reevaluation and in the 11 patients who achieved pathological complete response (median, range: 1.26, 0.70-3.27 ng/ml versus 0.94, 0.46-4.23 ng/ml, P = NS). M-CSF concentrations were raised (> or = 1.70 ng/ml) only in 1 (14.3%) of the 7 samples from patients with clinically evident disease and serum CA125 < 35 U/ml, and only in 5 (38.5%) of the 13 samples from patients with positive second-look findings and serum CA125 < 35 U/ml. In conclusion, serum M-CSF levels correlated with the clinical status of disease in patients with epithelial ovarian cancer. However, the concomitant determination of serum M-CSF seems to add little to the CA125 assay alone in the monitoring of patients with this malignancy.

Adult↗
PubMed1998

An analysis of approaches to the management of endometrial cancer in North America: a CTF study.

OBJECTIVE: The aim of this study was to define the clinical-therapeutical approach to endometrial cancer now being followed in some of the most important centers of reference for gynecological cancer in North America by means of a questionnaire. STUDY DESIGN: The questionnaire focused on four principal areas: (1) surgical staging and therapy; (2) adjuvant treatment; (3) treatment modifications; and (4) management of advanced stages (FIGO III-IV). RESULTS: There were 48 evaluable responses (77%) received by the end of December 1994 which were considered for this analysis. Lymphadenectomy is utilized routinely in 26/48 centers (54.2%) and in selective clinical-pathological conditions in another 21/48 centers (43.5%). In the majority of centers (31/48; 64.6%) radical surgery is utilized for selected indications such as cervical involvement. Only 3/48 (6.2%) centers consider the vaginal approach totally inappropriate. The great majority (40/48; 83.3%) of the centers considered postsurgical adjuvant therapy to be necessary in FIGO Stage Ic. Brachytherapy is routinely performed in 3 centers (6.2%) in postsurgical management of Stage I endometrial cancer, while the majority of the centers (31/48; 64.6%) perform brachytherapy of the vaginal vault in certain clinical-pathological conditions. A wide variety of treatments are used for advanced stages (FIGO III-IV). CONCLUSIONS: It emerges that some controversial aspects exist on endometrial cancer treatment, and these conflicting data need a large-scale multicenter randomized clinical trial.

Adult↗
PubMed1998

Evaluation of FHIT gene alterations in ovarian cancer.

The FHIT gene, recently cloned and mapped on chromosome 3p14.2, has frequently been found to be abnormal in several established cancer cell lines and primary tumours. As alterations of chromosome 3p are common events in ovarian cancers with breakpoint sites at 3p14.2, we decided to investigate the role of FHIT in human ovarian tumorigenesis. Fifty-four primary ovarian carcinomas were studied by reverse transcription of FHIT mRNA followed by polymerase chain reaction (PCR) amplification and sequencing of products. The same tumours and matched normal tissues were also investigated for loss of heterozygosity using three microsatellite markers located inside the gene. We found an abnormal transcript of the FHIT gene in two cases (4%) and allelic losses in eight cases (15%). Twelve (22%) of the 54 tumours investigated belonged to young patients with a family history of breast/ovarian cancer. In none of these cases was the FHITgene found to be altered. Our results indicate that FHITplays a role in a small proportion of ovarian carcinomas.

Acid Anhydride Hydrolases↗
PubMed1998

Expression and secretion of inhibin and activin in normal and neoplastic uterine tissues. High levels of serum activin A in women with endometrial and cervical carcinoma.

Inhibins and activins are growth factors belonging to the transforming growth factor-beta) family and are known to influence cell proliferation and differentiation. Because transforming growth factor-beta is involved in physiological and tumoral changes of uterine tissues, the present study aimed to evaluate whether human normal and neoplastic endometrial and cervical epithelial cells express and secrete inhibin A, inhibin B, and activin A. To test this hypothesis, different approaches were used. By RT-PCR, the expression of specific messenger RNAs (mRNAs) for the inhibin alpha, activin betaA and betaB subunits, and activin receptor type II and type IIB was investigated: 1) in primary cultures of endometrial (stroma and epithelium) or cervical (epithelium) cells from healthy women; and 2) in specimens of endometrial or cervical carcinoma. To demonstrate a possible secretion of the proteins, dimeric inhibin A, inhibin B, and activin A were measured in culture medium of normal epithelial or stromal endometrial cells and in uterine washing fluid of healthy women or patients with endometrial adenocarcinoma. Levels of the proteins were also measured in serum of women with endometrial or cervical carcinoma. Cultured endometrial stromal or epithelial cells and epithelial cervical cells expressed inhibin alpha, activin betaA and betaB, and activin receptor type II and type IIB mRNAs. The same finding was obtained in specimens of endometrial or cervical carcinomas. Dimeric inhibin A, inhibin B, and activin A were measured in culture medium of both endometrial and cervical cells. In particular, resulting activin A levels were significantly higher in epithelial than in stromal cultured endometrial cells (P < 0.01). Dimeric proteins were also detected in the washing fluid of the uterine cavities of healthy women (controls) and with endometrial adenocarcinoma, in which higher activin A levels were found (P < 0.01 vs. controls). Women with endometrial carcinoma showed serum activin A levels significantly higher than healthy controls (P < 0.01), which significantly decreased after surgical removal of endometrial or cervical tumors (P < 0.01). The present study, for the first time, showed that inhibin A, inhibin B, and activin A, as well as activin receptors, are expressed in normal and neoplastic human uterine tissues. A secretion of activin A from tumoral cells into systemic circulation is suggested by the observation that the high levels in serum of patients with endometrial or cervical carcinoma decreased after the surgical removal of the tumor.

Activin Receptors↗
PubMed1997

Intraperitoneal carboplatin with or without interferon-alpha in advanced ovarian cancer patients with minimal residual disease at second look: a prospective randomized trial of 111 patients. G.O.N.O. Gruppo Oncologic Nord Ovest.

From June 1990 to October 1994, 111 advanced ovarian cancer patients with minimal (less than 2 cm) residual disease after platinum-based front-line chemotherapy and second-look laparotomy entered a cooperative randomized study aimed at evaluating the effectiveness and the toxicity of the addition of interferon-alpha2 to carboplatin, both intraperitoneally (ip) administered. Patients were randomized to receive either 3 courses of ip Carboplatin 400 mg/m2 Day 1 q 28 days (54 pts) (CBDCA) or ip interferon-alpha 25 x 10(6) U Day 1 + ip carboplatin 400 mg/m2 Day 2 q 28 days (57 pts) (CBDCA + IFN). Patients treated with interferon experienced more severe (WHO grade 3-4) leukopenia (28% vs 17.1%) and anemia (14% vs 4.2%). Fever (P = 0.000) and flu-like syndrome (P = 0.02) were significantly more frequent in the combination arm. No difference in gastroenteric, neurologic, or renal toxicity was observed. At a median follow-up time of 13 months (range 1-72) 71 patients showed a disease progression (31 CBDCA, 40 CBDCA + IFN) and 44 patients died (21 CBDCA, 23 CBDCA + IFN). Median progression-free survival was 11 months in the CBDCA group and 10 months in the CBDCA + IFN arm. Median survival was 22 and 29 months in CBDCA and CBDCA + IFN arm, respectively. In conclusion, intraperitoneal interferon-alpha does not seem to improve the results achievable with intraperitoneal carboplatin in this subset of patients, while the toxicity and the costs of the combination are consistently higher than with chemotherapy alone.

Adult↗
PubMed1997

Preoperative D-dimer plasma assay is not a predictor of clinical outcome for patients with advanced ovarian cancer.

D-dimer (DD) plasma levels are significantly higher in patients with ovarian cancer than in those with benign ovarian masses. The aim of this paper is to assess whether preoperative DD plasma assay has a prognostic relevance for 35 patients with advanced ovarian cancer receiving platinum-based chemotherapy. Preoperative DD levels ranged from 162 to 3720 ng/ml. The 25, 50, and 75% quartiles of DD levels were 1600, 1894, and 2069 ng/ml, respectively. Preoperative DD levels correlated neither with the common clinicopathological prognostic variables nor with the disease status at the end of first-line chemotherapy. Survival was related to residual disease after initial surgery (> or =2 cm vs <2 cm, P = 0.003), but not to preoperative DD levels. In conclusion, the present data seem to show that preoperative DD plasma assay is not a predictor of clinical outcome for patients with advanced ovarian cancer.

Adult↗
PubMed1997

Carcinosarcoma of the uterus: a clinicopathological multicenter CTF study.

The purpose of this paper is to retrospectively analyze the clinical and pathological data of 118 cases of uterine carcinosarcoma. Prognostic factors and management were evaluated. chi 2 and log-rank tests were performed. Surgical stage at time of surgery was the most important prognostic factor (P < 0.0001); in stage I-II disease depth of myometrial invasion and lymphatic/vascular space involvement were significantly related to outcome, whereas other factors were not useful. In stage I-II patients postoperative radiation did not improve 5-year disease-free survival. Survival curves in patients with advanced disease treated with cisplatin-containing regimens or with doxorubicin (without cisplatin)-containing regimens were overlapping.

Adult↗
PubMed1997

p53 alterations are predictive of chemoresistance and aggressiveness in ovarian carcinomas: a molecular and immunohistochemical study.

Chemotherapeutic management of ovarian cancers is a difficult task as these neoplasms show significant differences in chemosensitivity, even if they share identical clinicopathological features. The present study was undertaken to investigate the prognostic and predictive role of p53 alterations in ovarian cancer. To this end, using different technical approaches, i.e. genetic and immunohistochemical analyses, we analysed a series of 68 ovarian neoplasms including 15 low malignant potential (LMP) tumours and 53 invasive carcinomas. We never observed p53 abnormalities in LMP tumours. p53 alterations were present only in invasive ovarian carcinomas, and they were detected much more frequently in tumours characterized by high histological grade (P = 0.01) and advanced-stage disease (P = 0.006 and P = 0.05 for gene mutations and protein expression respectively). For 33 patients with invasive ovarian cancer, information was available concerning response to cisplatin-based chemotherapy. A strong correlation (P = 0.001) has emerged between p53 alterations and response to chemotherapy; only one (14%) of seven patients who had a pathological complete response to antiblastic drugs showed p53 aberrations, whereas 18 (82%) of 22 cases with partial response and all of the four non-responsive patients scored positive for p53 abnormalities. We also observed that patients with p53 mutations had a significantly shorter progression-free survival than patients with p53-negative tumours (P = 0.05). Taken together, our results strongly suggest that in epithelial ovarian malignancies tumours showing p53 aberrations are significantly less sensitive to chemotherapy and more aggressive than those with functional p53. Thus, a routine analysis of this gene could have profound implications for the treatment of ovarian cancer.

Antineoplastic Agents↗
PubMed1997

Serum CA125 assay at the time of relapse has no prognostic relevance in patients undergoing chemotherapy for recurrent ovarian cancer: a multicenter Italian study.

The present retrospective study assessed the prognostic value of serum CA125 assay at relapse in 73 patients with recurrent epithelial ovarian cancer. At the time of relapse, serum CA125 levels ranged from 7 to 7000 U ml-1. The 25%, 50% and 75% quantiles of CA125 levels were 76, 178 and 339 U ml-1, respectively. Antigen values were >35 U ml-1 in 67 (91.8%) of the 73 patients. Median time to recurrence was 16 months (range, 4-62 months). Serum CA125 levels at relapse were not related to site of recurrence, time to recurrence, FIGO stage, histologic type, tumor grade and residual disease after initial surgery. Sixty patients received salvage chemotherapy at relapse. In these patients survival after recurrence was significantly related to time to recurrence (< or = 6 months vs < 6 months, P = 0.0371; < or =12 months vs >12 months, P = 0.0014; < or =16 months vs >16 months, P = 0.0001), but not to CA125 level at relapse (at any cut-off value for the antigen: 35, 76, 178 and 339 U ml-1), site of recurrence, FIGO stage, histologic type, tumor grade and residual disease after initial surgery. In conclusion, time to recurrence was the only variable predictive of further survival in patients undergoing salvage chemotherapy for recurrent ovarian cancer, whereas serum CA125 level at relapse had no prognostic relevance.

Journal Article↗