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Biomedical subjects

A Gadducci

Publications and source records attributed to A Gadducci.

At least 127 records · Page 7Linked to original sources

The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer.

CYFRA 21-1 assay, which detects serum fragments of cytokeratin 19, has been widely assessed as a serum marker of several malignancies. Preoperative serum CYFRA 21-1 levels were retrospectively measured in 60 patients with ovarian cancer and in 59 control patients with benign ovarian disease. CYFRA 21-1 levels were also serially measured in 90 serum samples drawn from patients with advanced (FIGO stage III-IV) ovarian cancer followed after surgery and chemotherapy. Preoperative serum CYFRA 21-1 levels were higher in patients with ovarian cancer compared with controls (median, range = 2.6, 0.1-51.4 ng/ml versus 0.4, 0.0-3.6 ng/ml, P < 0.0001), and among the former, antigen values were higher in the 39 patients with advanced-stage than in the 21 patients with early (FIGO stage I-II) disease (P < 0.0001). In advanced ovarian cancer patients, the 25%, 50%, and 75% quantiles of preoperative CYFRA 21-1 levels were 1.9, 4.8 and 14.4 ng/ml, respectively. Preoperative CYFRA 21-1 levels were lower in the 11 patients who achieved a pathologic complete response at second-look compared with those who had clinically or surgically detectable persistent disease after first-line chemotherapy (median, range 1.9, 0.6-9.2 ng/ml versus 10.2, 0.1-51.4 ng/ml, P = 0.007). The pathologic complete response rate was significantly greater in patients with low preoperative CYFRA 21-1 levels compared with those with elevated CYFRA 21-1 levels at any cut-off limit for the antigen (1.9, 4.8 and 14.4 ng/ml). However, Cox regression analysis failed to detect a significant association between preoperative CYFRA 21-1 assay and survival. As for the follow-up of advanced ovarian cancer patients, CYFRA 21-1 levels were higher in the 42 samples drawn from patients with clinically detectable disease compared with the 48 specimens collected from patients with no clinical evidence of disease (median, range = 1.15, 0.3-40.7 ng/ml versus 0.4, 0.1-9.1 ng/ml, P < 0.0001). In conclusion, preoperative serum CYFRA 21-1 assay appears to be predictive of response to chemotherapy, but not prognostic of survival, for patients with advanced ovarian cancer. Moreover, the serial measurement of CYFRA 21-1 levels might have a potential clinical relevance for the assessment of disease status in patients followed after surgery and chemotherapy.

Adult↗

Factors influencing survival in endometrial cancer relapsing patients: a Cooperation Task Force (CTF) study.

The purpose of this study was to identify patterns of relapse and to determine the outcome of salvage treatment and the factors influencing survival of endometrial cancer relapsing patients. One thousand six hundred and six endometrial cancer (stages I to IV) patients treated at five Italian institutions were retrospectively reviewed. Of these, 209 (13%) subjects had recurred; the site of relapse was vagina in 35 cases (16.7%), pelvis in 67 (32.1%), and distant locations in 107 (51.2%). Most of the patients relapsed within 24 months: 45% (94) recurred within 1 year, 20.6% (43) between 1 and 2 years. Adjuvant radiotherapy (RT) seemed to reduce the percentage of pelvic recurrence in high risk early stages (IB-IIA) subjects and a higher proportion of patients failed at a distant site when postoperative external-beam pelvic RT was given. However survival curves were not statistically different in the two groups for stage IB endometrial cancer patients. Five and 10-year survival rates of patients with recurrent disease was 26% and 22%, respectively. Relapse of endometrial cancer is often early and at distant sites. Survival rate was related to site of relapse, disease-free interval, and postoperative treatment as independent prognostic variables. The site of relapse is the most important predictor of survival of patients with recurrent disease.

Adult↗

Preoperative serum E-cadherin assay in patients with ovarian carcinoma.

E-cadherin is a 120-kDa transmembrane glycoprotein involved in the calcium dependent adhesion of epithelial cells. Soluble E-cadherin fragment levels have been found to be significantly elevated in patients with different malignancies when compared to healthy controls (Katayama M. et al. Br. J. Cancer 69, 580-585, 1994). The aim of this paper was to assess the clinical relevance of preoperative serum E-cadherin assay in patients with ovarian carcinoma. E-cadherin was measured with a solid phase enzyme immunoassay based on a sandwich method using two mouse monoclonal anti-human E-cadherin antibodies. Preoperative serum E-cadherin levels were higher in 55 patients with ovarian carcinoma than in 31 patients with benign ovarian disease as controls, even though the difference did not reach the statistical significance (median value, range: 6615 ng/ml, 444-26,092 ng/ml versus 5531 ng/ml, 1548-12668 ng/ml, p = 0.063). However, the subset of the 36 patients with FIGO stage III-IV ovarian carcinoma had significantly higher antigen levels (median value, range: 7205 ng/ml, 444-26,092 ng/ml) when compared to controls (p = 0.039). Among patients with advanced ovarian carcinoma, preoperative serum E-cadherin correlated neither with the common clinico-pathological prognostic variables nor with the response to chemotherapy and survival. Our data seem to show that the preoperative serum E-cadherin assay does not offer useful clinical information for the management of patients with ovarian carcinoma.

Adult↗

Serum preoperative vascular endothelial growth factor (VEGF) in epithelial ovarian cancer: relationship with prognostic variables and clinical outcome.

Substantial experimental and clinical evidence links tumor growth, progression and metastatic potential with neoangiogenesis. This process is modulated by several angiogenic growth factors, such as vascular endothelial growth factor (VEGF). Little data are currently available on serum VEGF levels in cancer patients. In the present retrospective investigation preoperative serum VEGF was higher in 53 patients with epithelial ovarian cancer than in 25 patients with benign ovarian disease as controls (median, range: 229.7, 23.5-1807.5 pg/ml versus 140.3, 14.7-1038.7 pg/ml, p = 0.034). With regard to FIGO stage, antigen values were significantly elevated in stage III-IV (p = 0.027) but not in stage I-II ovarian cancer patients when compared to controls. In patients with advanced disease preoperative serum VEGE was significantly related to the presence of ascites (p = 0.013), but not to common prognostic variables, response to chemotherapy and survival. In conclusion, preoperative serum VEGF assay reflects tumor progression and ascites generation in epithelial ovarian cancer, but it seems to have a limited predictive and prognostic value in patients with advanced disease.

Adult↗

Combination of cisplatin, epirubicin, and cyclophosphamide (PEC regimen) in advanced or recurrent endometrial cancer: a retrospective clinical study.

The combination of cisplatin (50 mg/m2), epirubicin (60 mg/m2), and cyclophosphamide (600 mg/m2) (PEC regimen) was given every 4 weeks to 19 patients with advanced (n.2) or recurrent (n.17) endometrial cancer. The median number of cycles delivered to each patient was 5 (range, 2-8). All patients were evaluable for toxicity and 16 for response. Two (12.5%) patients experienced a complete response and 5 (31.2%) had a partial response, for an overall objective response rate of 43.7%. The median duration of objective response was 10 months (range, 3-28 months). Median survival was 10 months (range, 3-68+ months) in the whole series. According to response to chemotherapy, median survival was 12 months (range, 3-68+ months) for responders and 9 months (range, 6-17 months) for nonresponders. Hematologic toxicity was relatively frequent but it could be easily managed, and significant nonhematologic toxicities were not found except for nausea and vomiting. In conclusion, PEC regimen has a good activity in advanced or recurrent endometrial cancer, but the short duration of responses limits the impact of the treatment on survival time.

Aged↗

Surgical cytoreduction during second-look laparotomy in patients with advanced ovarian cancer.

BACKGROUND: The impact of surgical cytoreduction performed during second-look on the survival of patients with advanced ovarian cancer is still under debate. MATERIALS AND METHODS: The present retrospective investigation assessed 81 patients with advanced ovarian cancer who underwent second-look laparotomy after initial cytoreductive surgery and six cycles of platinum-based chemotherapy. RESULTS: At the beginning of the second-look, 31 patients were in pathological complete response, 7 had microscopic residual disease, 22 had macroscopic residual disease < 2 cm and 21 had a larger residuum. Twenty-two (51.2%) of the 43 patients with macroscopic disease underwent surgical cytoreduction during the second-look: 11 patients were completely cytoreduced, whereas 11 were debulked from residuum > 2 cm to macroscopic residuum < 2 cm. Patients with microscopic residual disease after the second-look had improved survival when compared to those with macroscopic residuum after re-exploration (median survival, 43 months versus 19.5 months, p = 0.002). Among the former, no difference in survival was detected between the patients who had microscopic disease at the beginning of the second-look and those who were surgically cytoreduced to microscopic disease. Moreover, the patients with macroscopic residuum < 2 cm after the second-look had a better survival than those with a larger residuum after re-exploration (median survival, 24 months versus 10 months, p = 0.0001). Among the former, no difference in survival was seen between the patients who had residual disease < 2 cm at the beginning of the second-look and those who were surgically cytoreduced to < 2 cm. However, ovarian cancer recurred in all the patients with small or large macroscopic residuum after the second-look. CONCLUSION: The complete resection of macroscopic persistent tumor seems to give ovarian cancer patients the highest likelihood of long-term survival and should represent the goal of surgical cytoreduction during second-look laparotomy.

Antineoplastic Combined Chemotherapy Protocols↗

An intensive follow-up does not change survival of patients with clinical stage I endometrial cancer.

BACKGROUND: The clinical benefit of an intensive follow-up protocol in endometrial cancer patients is still uncertain. MATERIALS AND METHODS: One hundred and thirty-three patients underwent initial abdominal surgery for clinical stage I endometrial cancer between January 1988 and December 1997 and were periodically followed-up until April 1999 or until death. After surgery, 89 patients received postoperative adjuvant treatment. Periodical surveillance included physical examination, vaginal smear and abdominal-pelvic ultrasound every 3-4 months for the first 2 years from surgery, every 6 months for the next 3 years and yearly thereafter. Chest X-ray was performed every 6 months for the first 2 years, every year for the next 3 years and with individually increasing intervals afterwards. An abdominal-pelvic CT scan was carried out yearly for 5 years. RESULTS: Twenty-four patients (18.0%) developed recurrent disease after a median time of 17.5 months (range, 6-64 months). Five-year actuarial disease-free survival was 81.2% in the whole series, and in detail 94.2% in the subset of patients with FIGO stage Ia grade 1 or 2 endometrioid adenocarcinoma, or stage Ib grade 1 endometrioid adenocarcinoma (low-risk), compared to 76.0 (p = 0.0472) in the subset of patients with stage Ia grade 3 endometrioid adenocarcinoma, stage Ib grade 2 or 3 endometrioid adenocarcinoma, stage equal to or greater than Ic endometrioid adenocarcinoma any grade, and aggressive histologies (high-risk). The site of recurrent disease was local in 6 (25.0%) patients, distant in 17 (70.8%), and local plus distant in 1 (4.2%). Eleven (45.8%) recurrences were symptomatic and 13 (54.2%) were asymptomatic. The median survival after recurrence was 10 months. Survival was longer in patients who relapsed after 17.5 months from initial surgery when compared to those who relapsed earlier (p = 0.02). Conversely, survival after recurrence was not related to patient characteristics at diagnosis, such as FIGO stage, tumor grade, myometrial invasion, histologic type, and lymph node status. It is noteworthy that survival was similar in asymptomatic women, in whom the relapse was occasionally detected by follow-up examinations, and in symptomatic ones. CONCLUSION: An intensive surveillance protocol seems to have no significant impact on the outcome of patients with clinical stage I endometrial cancer. Simplified follow-up programs tailored for patient subsets with different recurrence risk are required.

Actuarial Analysis↗

p53 status is neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen.

BACKGROUND: The aim of this study was to assess the relationship between p53 status and the clinical outcome of patients with advanced ovarian cancer treated with a paclitaxel-based regimen. PATIENTS AND METHODS: The investigation was conducted on 38 patients with FIGO stage III-IV ovarian cancer from whom tumor tissue samples for p53 protein immunostaining were obtained during initial cytoreductive surgery. All these patients subsequently received six cycles of first-line combination chemotherapy with paclitaxel 175 mg/m2 (3-hour infusion) plus carboplatin AUC 6 with or without epidoxorubicin 75 mg/m2. RESULTS: Positive p53 immunostaining was detected in tissue samples collected from 24 (63.2%) ovarian cancers. A clinical complete response was obtained in 14 (58.3%) of the 24 patients with positive p53 immunostaining compared to 9 (64.3%) of the 14 patients with negative p53 immunostaining (p = 0.717). A pathological complete response was found in 6 (25.0%) of the former compared to 4 (28.6%) of the latter (p = 0.956). Similarly, survival did not correlate with p53 status (p = 0.1271). DISCUSSION: p53 status seems to be neither a predictive nor a prognostic variable in patients with advanced ovarian cancer treated with a paclitaxel-based regimen. These results are consistent with experimental data showing that paclitaxel cytotoxicity in ovarian cancer is likely to be mediated by a p53-independent pathway.

Adult↗

Malnutrition and cachexia in ovarian cancer patients: pathophysiology and management.

In ovarian cancer patients the poor nutritional status and cachexia are caused by the metabolic effects of the enlarging tumor masses and bowel obstruction. These patients may have a high resting energy expenditure due to increase in Cori cycle activity, glucose and triglyceride-fatty acid cycling and gluconeogenesis. Biochemical mediators of cachexia include cytokines, such as tumor necrosis factor and interleukin-6, and tumor-produced catabolic factors, such as lipid-mobilizing factor, proteolysis-inducing factor, and anemia-inducing factor. Mechanisms involved in the pathogenesis of obstruction may include extrinsic occlusion of the bowel due to pelvic, mesenteric omental masses, or intestinal motility disorders due to infilor tration of the mesentery or bowel muscle and nerves. The relief of malnutrition and cachexia may be attempted through nutritional support, pharmacological approach (megestrol acetate, cyclooxygenase inhibitors) and palliative treatment of bowel obstruction. Very few agents have been demonstrated to have true anticachectic activity, so future research should be addressed to the identification of drugs able to block the activity of tumor-produced catabolic factors. The decision regarding optimum management of bowel obstruction should be individualized. Krebs' and Goplerud's score (based on age, nutritional status, tumor status, ascites, previous chemotherapy and irradiation) seems to offer reliable eligibility criteria for those patients who can benefit from surgery.

Adrenergic beta-Antagonists↗

Neoadjuvant chemotherapy and concurrent chemoradiation in the treatment of advanced cervical cancer.

The role of chemotherapy in the management of advanced cervical cancer has been long debated. Whereas some phase II trials have shown promising results with neoadjuvant chemotherapy followed by irradiation, most phase III trials failed to demonstrate any benefit with this sequential treatment in terms of loco-regional control and survival, mainly because chemotherapy could cause accelerated tumor clonogen resistant cell repopulation The data on cisplatin-based neoadjuvant chemotherapy before surgery appear to be more promising. This treatment modality can increase the operability rate and reduce the incidence of positive nodes and other pathological risk factors. However, very few randomized trials comparing cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy versus conventional irradiation treatment are currently available, whilst data about long-term survival of chemo-surgical-treated patients are scanty. Recently five prospective randomized trials compared concurrent cisplatin-based chemotherapy and irradiation versus hydroxyurea plus irradiation or irradiation alone. All showed a significant improvement in the outcome of patients treated with concurrent cisplatin-based chemoradiation. Based on these data, the National Cancer Institute released a Clinical Announcement stating that concurrent cisplatin-based chemoradiation should be the new standard of therapy for high-risk early stage and locally advanced cervical cancer. The introduction of taxanes in both neoadjuvant chemotherapy followed by radical hysterectomy and concurrent chemoradiation could further improve the results of these two treatment modalities. A multicenter randomized trial comparing chemo-surgical treatment with concurrent chemoradiation is warranted to better define the optimum therapeutic strategy for patients with advanced cervical cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment options in patients with recurrent ovarian cancer.

The majority of patients with advanced ovarian cancer need a second-line treatment for recurrent disease after surgical cytoreduction and first-line chemotherapy. In these patients, treatment planning is mainly dependent on the platinum-free-interval. The patients may be distinguished as platinum-refractory (progression under platinum-based therapy), platinum-resistant (relapse within 6 months), or platinum-sensitive (relapse after 6 months). Patients with platinum-refractory or -resistant disease should be encouraged to enter clinical trials. Alternatively, these patients could receive tamoxifen or a non-platinum single-agent therapy. Since response rate and duration to different single-agents are similar, patient convenience, toxicities from prior treatment, side-effects and costs play a role in the drug selection for salvage chemotherapy. Patients with platinum-sensitive disease should receive carboplatin based or carboplatin-plus paclitaxel-based regimens. Secondary surgical cytoreduction may have a role in highly selected patients with good performance status, with long disease-free interval and without extra-abdominal or liver metastases.

Female↗

CA 195: a new monoclonal antibody-defined Lea blood group-related tumor marker in patients with epithelial ovarian cancer.

The levels of CA 125 (reference values [RV]s = 35 U/mL and 65 U/mL), CA 19.9 (RV = 40 U/mL), CA 50 (RV = 20 U/mL) and CA 195 (RVs = 10.5 U/mL and 15 U/mL) were measured in blood samples collected before laparotomy from 71 patients with ovarian carcinoma and 204 patients with benign ovarian pathology as controls. CA 125 levels greater than 35 U/mL were observed in 53/61 patients with non-mucinous carcinomas and in 6/10 with mucinous ones, while antigen levels above 65 U/mL were detected in 50/61 patients with non-mucinous malignancies and in 6/10 with mucinous ones; therefore mucinous tumors expressed this antigen less frequently than non-mucinous ones. Elevated CA 19.9 levels were found in 15/61 patients with non-mucinous malignancies and in 8/10 with mucinous ones. Raised CA 50 levels were observed in 13/50 patients with non-mucinous cancers and in 7/8 with mucinous ones. CA 195 values were greater than 10.5 U/mL and 15 U/mL respectively in 20.0% and in 15.0% of 40 patients with non-mucinous tumors, while antigen levels were above 10.5 U/mL and 15 U/mL respectively in 75.0% and 62.5% of 8 patients with mucinous carcinomas. Therefore, CA 19.9, CA 50 and CA 195 highly correlated with mucinous histotype. The results of CA 195 and CA 19.9 determinations were very similar because of the closely related: structures of the two epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Cisplatin nephrotoxicity: effects on fractional excretion of sodium and enzymuria].

The effects (in five therapeutic cycles) of Cisplatin on urinary enzyme excretion (specific markers of tubular damage), fractional excretion of sodium, fractional reabsorption of phosphate, serum Creatinine and creatinine Clearance were assessed in 17 female patients with ovarian carcinoma. An immediate reduction of sodium fractional excretion was observed: this appears a more sensible Cisplatin-nephrotoxicity marker than serum Creatinine and creatinine Clearance. No significant variations were noted in fractional reabsorption of phosphate or urinary Lysozyme and Beta-2-microglobulin but there was a significant increase of other urinary enzymes, confirming the potential nephrotoxicity of DDP treatment.

Adenocarcinoma↗

The serum concentrations of TAG-72 antigen measured with CA 72-4 IRMA in patients with ovarian carcinoma. Preliminary data.

The Authors assayed CA 125 (cut-off value: 65 and 35 U/ml), CA 19.9 (cut-off value: 40 U/ml) and CA 72.4 (cut-off value 3.8 U/ml) immunoreactivity in blood samples drawn before surgery in 34 patients with ovarian carcinoma and in 47 patients with benign ovarian pathology. With a cut-off value of 65 U/ml, CA 125 had a sensitivity (SE) for ovarian carcinoma of 85.3%, a specificity (SP) of 89.4%, a diagnostic accuracy (DA) of 87.7%; with a cut-off value of 35 U/ml CA 125 had a SE of 88.2%, a SP of 66.0%, a DA of 75.3%; CA 19.9 had a SE of 20.6%, a SP of 70.2%, a DA of 49.4%; CA 72.4 had a SE of 64.7%, a SP of 93.6%, a DA of 81.5%. CA 125 was expressed by all ovarian carcinoma histotypes. CA 72.4 seems to have a high correlation with mucinous histotype, analogously to CA 19.9. However CA 72.4 seems to be preferable to CA 19.9 for its greater sensitivity and specificity.

Antigens, Neoplasm↗

The trend of serum CA125 levels during the first three courses of chemotherapy as a predictor of second-look findings in patients with ovarian carcinoma.

The serum CA125 levels were monitored monthly in a group of 20 patients with ovarian carcinoma undergoing a six-month chemotherapy cycle. None of the 8 patients with serum CA125 levels higher than 65 U/ml before the third course of chemotherapy had negative second-look findings at the end of chemotherapy. Conversely, no evidence of disease at surgical re-evaluation was found in 9 out of 12 (75%) patients with antigen levels lower than 65 U/ml before the third chemotherapy course; on the other hand, none of the 4 patients of this group in whom serum CA125 values fell below 65 U/ml only after the third course, achieved a complete surgical response. Among the 9 patients in whom second-look surgery documented a complete response, 8 had CA125 levels below 35 U/ml and one had CA125 values above 35 U/ml but lower than 65 U/ml at the three-month check-point. These data suggest that the trend of serum CA125 levels during the first three courses of chemotherapy is a strong predictor of second-look findings in patients with ovarian carcinoma at the completion of treatment.

Antigens, Tumor-Associated, Carbohydrate↗