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Biomedical subjects

S Ferrari

Publications and source records attributed to S Ferrari.

At least 433 records · Page 24Linked to original sources
PubMedDate not supplied

Delay in diagnosis of high-grade osteosarcoma of the extremities. Has it any effect on the stage of disease?

In 965 patients with high-grade osteosarcoma of the extremities, we investigated the correlation between diagnostic delay and the stage of the tumor at presentation. The mean interval between the onset of first symptoms and the final diagnosis was significantly shorter in patients with metastatic disease than in patients with localized disease at the time of the diagnosis. The difference was due to a late presentation of patients with localized disease to the physician and not to delays in performing radiologic examinations or in referring patients to a specialized hospital for biopsy and treatment. We conclude that in high-grade osteosarcoma of the extremity the shorter interval between onset of symptoms and diagnosis observed in patients with disseminated disease at the time of the diagnosis reflects a more aggressive behavior of tumors that are metastatic at presentation.

Adolescent↗
PubMedDate not supplied

Nonmetastatic osteosarcoma of the extremity: results of a neoadjuvant chemotherapy protocol (IOR/OS-3) with high-dose methotrexate, intraarterial or intravenous cisplatin, doxorubicin, and salvage chemotherapy based on histologic tumor response.

AIMS AND BACKGROUND: From 1986 to 1989, a study for the treatment of nonmetastatic osteosarcoma of the extremity (IOR/OS-2) was carried out at the Rizzoli Institute. The cumulative dose of doxorubicin delivered was 480 mg/m2, and severe heart failure developed in 5 (3%) of the 164 treated patients. The specific aim of the subsequent study was to assess the efficacy of a protocol, similar to IOR/OS-2, but with a reduced cumulative dose of doxorubicin (390 mg/m2). Additional aims were to assess the role of the route of infusion (intraarterial or intravenous) of cisplatin on histologic response of the primary tumor and the use of ifosfamide as salvage chemotherapy in poor responders. METHODS: The new chemotherapy regimen (IOR/OS-3) was comprised of a preoperative phase with methotrexate (10 g/m2), cisplatin (120 mg/m2 intraarterially or intravenously), and doxorubicin (60 mg/m2). After surgery, the same drugs were administered, with the addition of ifosfamide (10 g/m2) in patients who had a poor histologic response to primary chemotherapy. RESULTS: Ninety-five patients entered the study. The rate of good histologic response was 64% with intraarterial cisplatin and 43% with intravenous cisplatin (P = 0.05). The 8-year event-free survival and overall survival were 54% and 61%, respectively, with no significant difference according to the histologic response. No cases of clinical doxorubicin-induced cardiopathy were recorded. Event-free and overall survival did not significantly differ from those achieved with IOR/OS-2 (8-year disease-free and overall survival, respectively 63% and 72%). CONCLUSIONS: The reduction in the doxorubicin cumulative dose avoided episodes of cardiotoxicity, without consequences on the efficacy of treatment. The addition of ifosfamide was an effective "salvage" therapy for poor responders. A better histologic response with intraarterial cisplatin was observed, but owing to the availability of an effective salvage therapy for poor responders, the advantages in terms of histologic response did not compensate for the cost and discomfort for the patients of this modality of infusion of cisplatin.

Adolescent↗
PubMedDate not supplied

Neoadjuvant chemotherapy for osteosarcoma of the extremity in patients in the fourth and fifth decade of life.

From January 1986 to March 1993, 29 patients aged between 40 and 60 years with primary high grade osteosarcoma of the extremity were treated at Rizzoli Institute with neoadjuvant chemotherapy. Before surgery patients received cisplatin and adriamycin. Postoperatively, patients with a good histologic response received the same two drugs preoperatively used, while in case of poor response ifosfamide and etoposide were added to cisplatin and adriamycin. Twenty-five patients (86%) were surgically treated with a limb salvage, whereas 4 patients (14%) were amputated. With a median follow-up of 8 years (5-12), the 8-year event-free survival was 57% and the 8-year overall survival was 62%. No chemotherapy-related deaths were recorded and toxicity was manageable. These results are significantly better than those achieved in 24 patients of the same age, treated at Rizzoli Institute between 1975 and 1985 only with surgery (87% of amputation and 17% of 8-year event-free and overall survival) and indicate an advantage for the use of neo-adjuvant chemotherapy also in patients with high grade osteosarcoma of the extremity older than 40 years.

Adult↗
PubMedDate not supplied

Prognostic significance of serum LDH in Ewing's sarcoma of bone.

The pretreatment serum lactic dehydrogenase (SLDH) levels of 618 patients with Ewing's sarcoma of the extremities (136 metastatic at presentation and 482 localized) were analyzed to evaluate whether the enzyme level had a clinical value in predicting the course of the disease. The percentage of patients with increased SLDH was significantly higher in the metastatic group than in the group of patients with localized disease (68% vs 32%; P<0.0001). In the latter group treated with neoadjuvant chemotherapy the 5-year disease-free survival rate was significantly higher in patients with normal pretreatment SLDH than in those with high levels (65% vs 41%; P<0.0001). The time to relapse was significantly shorter for patients with elevated SLDH than in patients with normal values of the enzyme. The site of the tumor was significantly related with the stage of the disease, and for patients with localized disease, with the disease survival rate, at the multivariate analyses site of the tumor and SLDH levels were independently related with the stage of disease and with prognosis. These data demonstrate that in Ewing's sarcoma of bone pretreatment SLDH have a prognostic value and should be considered in the comparison of the results achieved with different therapies and in planning new randomized clinical therapeutic trials.

Adolescent↗
PubMedDate not supplied

Neoadjuvant chemotherapy for osteosarcoma of the extremities with synchronous lung metastases: treatment with cisplatin, adriamycin and high dose of methotrexate and ifosfamide.

We report on the clinical course and outcome of 28 patients, treated at The Istituti Ortopedici Rizzoli between 1995 and 1997 for osteosarcoma of the extremities metastatic to the lung at presentation. The treatment for these patients was the following: primary chemotherapy with cisplatin, adriamycin and high dose of methotrexate and ifosfamide followed by simultaneous resection of primary and metastatic lesions (when feasible), and further chemotherapy. After primary chemotherapy, lung metastases disappeared in 6 patients, whereas metastases in 3 remained surgically unresectable. These 9 patients received surgical treatment of the primary tumor only. In the remaining 19 patients, after chemotherapy, a simultaneous resection of the primary and metastatic tumor was performed. The resection of metastatic lesions was complete in 18 cases and incomplete in one. Three of the 4 patients who did not achieve a tumor-free status died in a few months and one is still alive with uncontrolled disease. With a median follow-up of 32 months (19-43) of the 24 patients who achieved remission, 12 (55%) remained continuously free of disease, 11 relapsed with new metastases and 1 died of chemotherapy-related toxicity. The 2-year DFS and OS were 36% and 53% respectively. These results are much worse than those achieved in 114 contemporary patients with localised disease (2-year DFS: 81%) treated in the same period and they are superimposible to the results achieved in 23 patients previously treated with the same protocol, but with standard dose of ifosfamide (2-year DFS: 32%). However, it must be underlined that, as regards prognosis, patients with metastatic disease at presentation are a hetero-geneous group. The DFS was significantly higher for patients with only one or two metastatic lesions than for patients with 3 or more lesions (2 year DFS: 78% vs. 28%). In 12 of the 19 patients who had a complete simultaneous resection of the primary and metastatic tumor, a strong correlation between the degree of necrosis of the primary and metastatic lesions was found. We conclude that in patients with osteosarcoma of the extremity with lung metastases at presentation: a) the combination of aggressive chemotherapy with simultaneous resection of primary and metastatic tumors works very well only for those patients who present with one or two metastatic nodules whereas for patients with 3 or more pulmonary metastases the prognosis is very poor; b) within the 4-drug regimen used in this study, the increment of ifosfamide dose from 10 g/m2 to 15 g/m2 for cycle does not improve prognosis; c) the strong correlation found between the histologic response of the primary tumor and metastases supports the strategy, largely used nowadays in the neoadjuvant treatment of osteosarcoma, of tailoring postoperative chemo-therapy on the basis of the primary tumor histologic response to preoperative chemotherapy.

Adolescent↗
PubMedDate not supplied

Cell cycle status and apoptosis of hematopoietic progenitor cells released into the peripheral blood after taxanes and granulocyte colony-stimulating factor in breast cancer patients.

Paclitaxel and its analogue docetaxel show a significant antitumor activity, particularly evident in breast cancer. Paclitaxel has also been proved to be effective as a peripheral blood progenitor cell (CPC) mobilizing agent. To optimize the use of active, disease-specific drugs as CPC priming, we have evaluated the effects of either paclitaxel or docetaxel both at standard dosages and followed by granulocyte colony-stimulating factor (G-CSF), on circulating CPC release and function in 18 patients with advanced breast cancer who had failed previous anthracycline-based regimens. The reported differences in biological behaviour between bone marrow and blood-derived hematopoietic progenitor cells and the ability of both paclitaxel and docetaxel to induce apoptosis, prompted us to simultaneously evaluate the cell cycle perturbations induced on CD34+ cells. Median CD34+ peaks were 24 microl (range: 10-58) in the paclitaxel-treated patients and 39 microl (range: 17-91), respectively, in the patients who received docetaxel. After paclitaxel, the percentage of CD34+ cells in S-phase was low (bromodeoxyuridine, BrdU, labelling index = 3.4+/-2%) with a concomitant presence of early apoptotic cells (8.1+/-3%). On the contrary, after docetaxel, the percentage of CD34+ cells in S-phase was higher (BrdU labelling index = 14.5+/-4%, p<0.05 vs. paclitaxel), while early apoptotic cells were detected at a similar rate (8. 6+/-3%, p = n.s. vs. paclitaxel). In conclusion, when used at standard dosages, with respect to paclitaxel + G-CSF, docetaxel + G-CSF is a more satisfactory tool to mobilize CPC and to induce them into the cell cycle. These data should be taken into account when combinations of docetaxel with other agents are explored as CPC mobilizing regimens for autografting.

Adult↗
PubMedDate not supplied

Left ventricular function in colon cancer patients receiving adjuvant fluoro-folate chemotherapy: an echocardiographic study.

Cardiotoxicity has been reported with increasing frequency after 5-FU administration. Since 5-FU-based regimens are increasingly used as adjuvant treatment for resected colon cancer patients, this carries a potential increased risk of cardiotoxicity. In the present study, we evaluated if fluoro-folate chemotherapy has any effect on left ventricular (LV) diastolic function in resected colon cancer. Twenty-five resected colon cancer patients receiving adjuvant fluoro-folate chemotherapy, were prospectively studied. Both digitized M-mode and Doppler echocardiography were performed, in order to investigate different aspects of LV diastolic function. None of the studied parameters was influenced by chemotherapy administration. Indeed, values recorded at the end of the 6-month treatment and 6 months later were not statistically different from baseline values. This study suggests that the use of fluoro-folate chemotherapy in otherwise normal subjects carries a very low risk of severe cardiotoxicity.

Aged↗
PubMedDate not supplied

Local and systemic control for osteosarcoma of the extremity treated with neoadjuvant chemotherapy and limb salvage surgery: the Rizzoli experience.

Five-hundred and twenty-six patients with non-metastatic osteosarcoma of the extremities treated at Istituto Ortopedico Rizzoli from 1983 to 1995 with neoadjuvant chemotherapy and limb salvage, were retrospectively studied to evaluate the rate of local and systemic control. At a mean follow-up of 9.5 years (3-17), 320 patients remained continuously free of disease and 206 relapsed. The 5-year disease-free survival and overall survival were 64% and 70% respectively. In patients who relapsed, there were 31 local recurrences (6%). The rate of local failures was significantly higher in the 79 patients with inadequate surgical margins (marginal, intralesional, and contaminated margins) than in the 486 patients with wide surgical margins (2.6% vs. 25.0%; P<0.0001). Twenty-nine of the 31 patients (94%) with local recurrence also had metastases and died of the tumor. In comparison with patients who only had a systemic relapse, patients with local recurrences had a higher rate of metastases located in bones (41% vs. 7%; P<0.001), and a worse post-relapse outcome (5-year overall survival: 6% vs. 24%; P<0.04). We concluded that in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: i) limb salvages procedures do not compromise the outcome of patients, provided the achievement of adequate surgical margins; ii) local recurrences are a marker either of the inadequacy of local treatment or of the high local and systemic aggressiveness of the tumor.

Adolescent↗
PubMedDate not supplied

Ewing's sarcoma of bone: relation between clinical characteristics and staging.

Patients with metastatic Ewing's sarcoma of bone have a poor prognosis. A relation between clinical characteristics and presence of metastatic disease at diagnosis in patients with Ewing's sarcoma of bone was investigated. Data from 618 patients [136 (22%) with metastases at diagnosis] registered at the authors' institution between April 1972 and December 1997 were collected. The distribution of several clinical and hematologic parameters in patients with metastases and those without metastases was analyzed, and clinical risk factors of metastatic disease at presentation were analyzed by means of multivariate logistic regression analysis. All the variables significant at the univariate analysis (age, fever, site, volume, lactic dehydrogenase, anemia, and interval between onset of symptoms and diagnosis) were considered in the multivariate analysis. Pelvic location of the tumor, high level of lactic dehydrogenase, presence of fever, an interval between onset of symptoms and diagnosis less than 3 months, and age older than 12 years were found to be risk factors of clinically evident metastatic disease. In the subset of patients with no risk factors the rate of metastatic disease at presentation was only 4%; in case of contemporary presence of two factors it was 23%, although it was almost double (44%) if three or four factors were present. Only six patients were positive for five factors and all of them had metastases at presentation. The parameters identified are clinical markers of Ewing's sarcoma having a particularly aggressive metastatic behavior.

Adolescent↗
PubMedDate not supplied

Relationship between dose-intensity of treatment and outcome for patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy.

One hundred and forty-four patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy at the authors' institution between 1986 and 1989 were retrospectively analyzed to evaluate the relationship between the dose-intensity of chemotherapy actually received (RDI) and the prognosis. Preoperative chemotherapy consisted of high-dose methotrexate i.v., cisplatin i.a., and doxorubicin i.v. After surgery "good responder" patients (90% or more tumor necrosis) had a 31-weeks of chemotherapy with the same drugs, while "poor responder" patients (less than 90% tumor necrosis) received a 40 weeks treatment with ifosfamide and etoposide added to the three drugs used preoperatively. Due to delays and dose-reductions, only 17 patients (12%) received the treatment exactly as scheduled by the protocol, 66 (46%) received a dose-intensity between 90 and 99%, and 61 (42%) a dose-intensity between 63 and 89%. At a follow-up ranging between 10 and 13 years, 97 patients (67%) remained continuously free of disease, 45 relapsed, and two died of doxorubicin-induced cardiopathy. The continuous disease-free survival (CDFS) was not related to patients' gender and age, tumor histology, site and size, serum value of alkaline phosphatase, type of surgery and histologic response to chemotherapy. According to the RDI, CDFS resulted significantly higher for those 81 patients who received 90% or more of the scheduled dose-intensity than for those 61 who had less than 90% of the scheduled dose-intensity (76.5% v.s. 57.3%; p<0.02). These results seem to suggest that in neoadjuvant treatment of osteosarcoma the dose-intensity of chemotherapy is crucial for outcome, therefore every effort should be made to avoid reductions of doses and/or delays in performing the cycles of chemotherapy.

Adolescent↗
PubMedDate not supplied

[Topotecan: a new field of use].

Topotecan, a semi-synthetic derivative of the alkaloid camptothecin is an antitumor drug that like other camptothecin derivatives, targets DNA topoisomerase I, an enzyme that is present in cells in concentration relatively independent of the stage in the cell cycle. Topotecan stabilizes the complex formed between topoisomerase I and DNA, leading to DNA strand breakage and cell death. In accordance with preclinical studies, clinical efficacy of topotecan was documented in ovarian carcinoma, in small cell lung cancer and in childhood solid tumors. Myelosuppression is the dose-limiting toxicity and nonhematologic side effects are generally mild. The activity of topotecan against a number of hematological malignancies is now increasingly exploited as well as its role in high-dose chemotherapy programs with stem cell support. In both lymphoblastic and myeloid acute leukemias, topotecan has been widely utilised both as single agent or associated to other cytostatic drugs with proven efficacy in these diseases. Most of the published phase II studies demonstrated that heavily pre-treated, relapsing patients achieve a high percentage of overall responses with manageable toxicity. In myelodisplastic syndromes and acute myelomonocitic leukemias a recently published study shows positive results for the combination of topotecan and cytarabin. Topotecan seems to preferentially affect the abnormal cytogenetic clones and in patients achieving a complete response, a conversion from an aneuploid to a diploid karyotipe was documented. In non-Hodgkin lymphomas, several schedules have been tested in the phase I setting. When utilized alone and at very low dosage, the drug yielded 15% of objective responses and a lack of extrahematologic toxicity. Of particular interest seems to be the association of topotecan with taxanes that needs to be supported by growth factors. In multiple myeloma Topotecan has been utilized as single agent in heavily pre-treated patients. The obtained results show good activity and again myelosuppression as preminent toxicity. The use of topotecan in high-dose chemotherapy regimens for multiple myeloma has been proposed. The utilization of topotecan in high-dose chemotherapy is one of the newer and more interesting applications. Solid tumors (i.e. ovarian cancer and small cell lung cancer) are actually investigated by many authors, who have indicated that this drug can be used preferentially as a part of diversified programs containing overlimit dosages of different cytostatics. Furthermore, topotecan demonstrated to be an effective drug to mobilize CD34+ cells for autografting. A general conclusion is that topotecan is an interesting addition to the actual chemotherapy scenario, both because of its mechanism of action and its toxicity profile. The present review of the new possibility of utilization, give us the idea that topotecan has activity in several hematologic neoplasias; further investigations in these diseases (i.e., induction treatment, combination chemotherapy) are then warranted. The broad spectrum of antitumor activity and the characteristics of toxicity make it also interesting for use in both the circulating progenitor cell mobilization and in the consolidation phase of high-dose chemotherapy programs.

Antineoplastic Agents↗
PubMedDate not supplied

[Relations between serum apha-antitrypsin level and neoplasms].

Alpha1-antitrypsin levels were determined in patients with bronchopneumopathies and in others with various forms of neoplasia. No relationship between levels and disease was noted in the first group, whereas a marked increase in values was observed in the second, particularly in the case of subjects with lung cancer. The interestiang aspects of this finding are discussed.

Breast Neoplasms↗
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[Ewing's sarcoma of the bone. Anatomoclinical study of 424 cases].

The clinic-epidemiologic and prognostic features of 424 cases of Ewing sarcoma observed at "Rizzoli" Institute between 1972-1990 are reported. The incidence of the tumor was higher in the second decade of life with slight predominance in the male sex. The primary lesion was especially localized in the extremity and the ratio lower/upper extremity was 5/1. We did not find, in contrast with other Authors, differences in height or in incidence of congenital malformations when compared to controls. The pain was the first common symptom at debut (90%) followed by swelling (50%) and fever (40%). Diagnosis was made 5.5 months after the first symptom and the delay was due to wrong diagnosis at debut in 3/4 of the patients. Laboratory tests showed anemia in about half of the patients and increased value of ESR (60%) and LDH (40%). Seventy-one of the patients were metastatic at presentation, none of these patients were still living after three years. At a median follow-up of 9 years 43% of the patients with localized disease, treated with adjuvant and neo-adjuvant chemotherapy remained continuously disease free, 53% developed metastatic disease and/or local recurrences and 2% had a second malignancy. In 24% of the patients metastases and/or local recurrences appeared three years after the beginning of treatment. Better prognosis was observed in female patients, without fever at diagnosis, with tumor localized at extremities and with normal value of hemoglobin, ERS and LDH. Regarding the type of treatment, better results were obtained by surgery of the primary tumor and by chemotherapy with four drugs (vincristine, cyclophosphamide, adriamycin dactinomycin) in comparison to radiotherapy of the primary tumor and chemotherapy with three drugs (vincristine, cyclophosphamide, adriamycin).

Adolescent↗
PubMedDate not supplied

The prognostic value of serum alkaline phosphatase in osteosarcoma of the limbs.

The values for serum alkaline phosphatase were evaluated in 340 patients affected with osteosarcoma of the limbs. The percentage of patients with high values for the enzyme at the onset of disease was significantly higher in the 69 cases who presented with metastases at the time of diagnosis, as compared to the 271 cases in which the neoplasm still appeared to be localized (81% vs 62%: p less than 0.001). In this last group of patients, treated with neoadjuvant chemotherapy, an evident relationship between values for alkaline phosphatase and prognosis was demonstrated. The percentage of patients who developed metastases was in fact 22% in the group with normal serum values for the enzyme at the onset of the disease and 40% for the patients with high values of the same (P less than 0.001). These data confirm the prognostic value for serum alkaline phosphatase in osteosarcoma, which should be taken into consideration when planning chemotherapy and in classifying patients for randomized therapeutic studies.

Adolescent↗
PubMedDate not supplied

[Three cases of congenital cutaneous candidosis].

We report three cases of term newborns with Congenital Cutaneous Candidosis (CCC) occured in a ten months period. Two of these showed respiratory distress that require mechanical ventilation and the administration of exogenous surfactant in one case. All the three cases recovered after therapy with fluconazole. Early onset of severe respiratory distress may require intubation and mechanical ventilation, and systemic involvement requires systemic antimichotic therapy. We did not find any predisposing factors of such a rare disease, in spite of the occurrence of three cases in a short period of time.

Candidiasis, Cutaneous↗
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Plasma osteocalcin levels in liver cirrhosis.

Osteocalcin, a recently identified protein, is produced by osteoblasts in the bone tissue. Its plasma level is a good marker of bone metabolism and is reduced in the presence of 'osteodystrophia', commonly found in cholostatic liver diseases. We assayed plasma osteocalcin levels in 20 cirrhotic patients and compared the values with those of 22 healthy controls. In the same patients we also measured the liver function, clotting and mineral metabolism indexes and calcitonin plasma levels. Osteocalcin levels were significantly lower in liver disease patients than in controls (5.53 ng/ml S.D. 2.57 vs 7.79 ng/ml S.D. 2.23; p less than 0.01) and calcitonin plasma levels were much higher in cirrhotics (130.18 pg/ml S.D. 212.30 vs 28.9 pg/ml S.D. 13.09; p less than 0.05). We think that the low osteocalcin levels observed in cirrhotics may be a consequence of "hepatic osteodystrophy" due to low vitamin D and calcium plasma levels.

Adult↗