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P Picci

Publications and source records attributed to P Picci.

At least 19 recordsLinked to original sources

Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome.

BACKGROUND: Increased levels of P-glycoprotein occur in some osteosarcomas. In this study we determined the relation between P-glycoprotein status and outcome in patients with high-grade osteosarcoma. METHODS: P-glycoprotein status was determined immunohistochemically in specimens of osteosarcoma of the extremities (stage II) from 92 patients who were treated with surgery and chemotherapy. The P-glycoprotein status was analyzed in relation to the length of event-free survival. RESULTS: The presence of increased levels of P-glycoprotein in the osteosarcoma was significantly associated with a decreased probability of remaining event-free after diagnosis (P = 0.002). In a multivariate analysis, P-glycoprotein status (P = 0.001) and the extent of tumor necrosis after preoperative chemotherapy (P = 0.04) were independent predictors of clinical outcome. The risk of adverse events was increased substantially (rate ratio, 3.37; 95 percent confidence interval, 1.60 to 7.10) among patients with increased levels of P-glycoprotein in tumor cells, as compared with patients who did not have increased levels of P-glycoprotein in tumor cells. CONCLUSIONS: In patients with high-grade osteosarcoma treated with surgery and chemotherapy, the presence of increased levels of P-glycoprotein in tumor cells is associated with a significantly increased risk of adverse events and is independent of the extent of necrosis after preoperative chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem

Dedifferentiated chondrosarcoma.

We reviewed 74 cases of dedifferentiated central and peripheral chondrosarcoma. Histologically these tumours consist of an underlying cartilaginous component (either benign or malignant) juxtaposed to a high-grade non-cartilaginous component, with a typically abrupt transition between the two tissue types. The non-cartilaginous component may constitute a very small or a very large proportion of the tumour, so diagnosis often requires histological evaluation of the entire tumour. The diagnosis is often suspected on the basis of the clinical course and careful evaluation of the radiographic characteristics. Central dedifferentiated chondrosarcoma can be classified radiographically into three types. In type I (36 cases in our review) the radiographic features are the same as those of a central chondrosarcoma, with the addition of a region with very aggressive radiographic features. Type 2 lesions (20 cases) resemble the underlying benign enchondroma but also have destructive changes and/or a large soft tissue mass. Type 3 lesions (8 cases) are not distinctive radiographically and present as a very high grade destructive lesion of bone. These cases are diagnosed following biopsy or tumour resection. The prognosis of these tumours is extremely poor, with 13% overall 5-year survival in this series. Improved survival was found in those cases where diagnosis was prompt and surgical treatment with a wide or radical margin was attained. No benefit was found from the use of adjuvant chemotherapy or radiotherapy. Thus, early recognition of the characteristic radiographic features, adequate histological sampling, and wide or radical surgical margins are necessary for satisfactory management of this highly malignant variant of chondrosarcoma.

Adult

Metachronous pulmonary metastases resection in patients with Ewing's sarcoma initially treated with adjuvant or neoadjuvant chemotherapy.

55 patients with Ewing's sarcoma of bone, treated at our Institution with adjuvant or neoadjuvant chemotherapy between 1972 and 1990, relapsed with pulmonary metastases alone. 12 of these patients--selected according to their long disease-free interval before relapse, monolaterality of the lesions, small numbers of metastatic nodules, resectability and refusal to undergo further chemotherapic treatments--were treated with surgical resection of the metastatic lesions and with no additional radio- or chemotherapy. At a follow-up ranging between 3 and 14 years (mean 9 years), 5 of these 12 patients (42%), were continuously free of disease, whereas the remaining 7 patients died with uncontrolled disease 12-39 months (mean 22 months) after thoracotomy. These results seem to indicate that an aggressive surgical approach should be considered for a selected group of Ewing's sarcoma patients who relapse with only lung metastases.

Adolescent

Changing pattern of relapse in osteosarcoma of the extremities treated with adjuvant and neoadjuvant chemotherapy.

In 551 patients with osteosarcoma of the extremities treated between 1980 and 1991 in our Institution with surgery only (35 cases), surgery combined with adjuvant chemotherapy (147 cases) or neoadjuvant chemotherapy (369 cases) the relapse patterns were analyzed. Adjuvant chemotherapy was performed according to 2 different protocols and neoadjuvant chemotherapy according to 3 different protocols successively activated. In the 252 patients who relapsed, the interval between initial treatment and first relapse was significantly longer in the group treated with adjuvant and neoadjuvant chemotherapy (18.1 and 21.3 mo) than in the group treated with surgery only (5.4 mo). For patients treated with neoadjuvant chemotherapy, a longer interval was seen in the most effective regimen of neoadjuvant chemotherapy (25 mo). No significant differences were seen among the 3 groups, according to the site of first metastasis, although in patients treated with the most effective neoadjuvant regimen there was a higher incidence of bone metastasis. In patients who relapsed with pulmonary metastases the average number of nodules seen by standard X-rays, as well as CT scans, was significantly higher in patients treated with surgery only (3.6) than in patients treated with adjuvant or neoadjuvant chemotherapy (2.5 and 2.6 nodules). We conclude that these changes in metastatic pattern in patients treated with adjuvant and neoadjuvant chemotherapy are important, because they may encourage the use of salvage therapy with thoracotomy in a larger number of patients. Prolongation of time relapsed after more effective regimens of adjuvant and neoadjuvant chemotherapy should be considered when evaluating the preliminary results of new chemotherapy protocols.

Adult

[Treatment of metastatic osteosarcoma with verapamil, cyclosporine and chemotherapy. A case report].

Studies on the use of revertants to overcome MDR have aroused a great interest even if they failed to prove their actual usefulness. A case of 10 years and 6 months old boy is described. He suffered from osteoblastic osteosarcoma and underwent chemotherapy following CNR-NEO3 protocol, wide surgical resection and postoperative chemotherapy. Nineteen months after diagnosis he underwent the removal of a little subpleural nodule in the right lung. Forty-five days later, in the same site, a large local metastasis was observed together with many others secondaries localizations spred in both lungs. Because of the rapid evolution they were considered not suitable for surgical treatment. A cyclosporine and verapamil treatment in association with adryamicin and etoposide was begun with the aim overcoming multidrug resistance. Five treatments were provided. ECG monitoring during verapamil infusion did not show any trouble; mielotoxicity was mild, with no need of transfusions. A lung CT scan at the end of the therapy demonstrated an important decrease of the subpleural metastasis and the vanishing of lung nodules. Another surgical intervention was provided together with 2 postoperative chemotherapy treatments. Twenty-six months later no sign of the disease was observed. Association of verapamil and cyclosporine with chemotherapy allowed to get a good clinical response with a very low toxicity, in a critical situation in which chemotherapy alone did not seem to offer any real possibility.

Bone Neoplasms

Cytokeratin expression and distribution in adamantinoma of the long bones and osteofibrous dysplasia of tibia and fibula. An immunohistochemical study correlated to histogenesis.

Twenty-four cases of adamantinoma and 24 cases of osteofibrous dysplasia of the long bones were studied to evaluate the expression and distribution of cytokeratin (CK) subtypes in relation to histogenesis and differentiation. The immunohistochemical study was performed on tissue fixed in buffered formalin and embedded in paraffin wax utilizing antibodies to vimentin, factor VIII, epithelial membrane antigen and cytokeratins of different molecular weights. In all cases the vimentin antibody marked positively in stroma, endothelium and osteoblasts, while factor VIII expression was confined to endothelial cells. In 71% of adamantinomas, vimentin showed strong immunoreactivity in the tumour cells of nests and tubules. CKAE1/AE3 and CK19 were strongly expressed in all morphological patterns of adamantinoma emphasizing their epithelial origin, while the antibodies to CK8 and CK18 showed a high percentage of negative responses. In osteofibrous dysplasia the epithelial-like component was much smaller than in adamantinoma and was present in scattered islands composed of a few cell positive for CKAE1/AE3 and CK19 and negative for other keratins. These results suggest that these two lesions are of a similar histogenesis.

Ameloblastoma

Treatment recommendations for osteosarcoma and adult soft tissue sarcomas.

During the past 20 years, dramatic improvements have been obtained in the treatment of localised osteosarcoma of the extremities, both in the rates of disease-free survival and in quality of life. Twenty years ago 80 to 90% of the patients died, in spite of mutilating surgery, but now about 75% survive and avoid the necessity of amputation. This is due to the introduction of very effective combined treatments, mostly also using preoperative chemotherapy. One of the major issues is that of intensive preoperative chemotherapy, which improves both limb salvage and survival. A multidisciplinary approach is necessary to obtain good results. When the role of adjuvant or neoadjuvant chemotherapy is not accurately defined for soft tissue sarcomas, particular emphasis is given to the staging of the diseases and to the important role of local treatment in the survival of these patients. A combination of radiation therapy and surgery is strongly recommended.

Antineoplastic Agents

Osteosarcoma of the extremity metastatic at presentation: results achieved in 26 patients treated with combined therapy (primary chemotherapy followed by simultaneous resection of the primary and metastatic lesions).

From September 1986 to December 1989, 26 selected patients with high-grade osteosarcoma of the extremities metastatic at presentation were treated with primary chemotherapy (high doses of methotrexate, -cisplatinum and adriamycin) followed by surgery. Twenty-one cases underwent resections of the primary and metastatic tumor at the same time; owing to the disappearance of lung metastases after preoperative chemotherapy in 3 cases, only the primary tumor was operated on. Due to progression of the disease in 2 patients, no surgery was performed. Histologic examination of the resected specimen was performed to evaluate the percentage of necrosis produced by chemotherapy on the primary and metastatic tumor. After surgery, the patients received further chemotherapy with the same drugs used preoperatively plus ifosfamide and VP-16. The histologic response of the primary tumor was good (> 90% tumor necrosis) in 25% of the cases; in the resected metastatic nodules, 23% had good responses. A discrepancy between the histologic response of the primary and secondary tumor was observed in only 15% of the cases. These results seem to confirm the validity of the strategy (widely used today in the neoadjuvant treatment of non-metastatic osteosarcoma) of changing the postoperative treatment when the histologic response of the primary tumor is poor. At an average follow-up of 3.5 years, only 6 patients remained disease-free; 19 patients relapsed and 1 patient died for adriamycin cardiotoxicity. Of the 19 relapsed patients, 16 died and 3 are still alive but with uncontrolled disease. These results are much worse than those obtained in 144 cases of non-metastatic osteosarcoma of the extremities treated in the same period with the same preoperative chemotherapy (77% with good response in the primary tumor and 78% with continuous disease-free survival). The data suggest that a very effective neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities gives disappointing results in osteosarcoma of the extremities which is metastatic at presentation.

Adolescent

Effect of intra-arterial versus intravenous cisplatin in addition to systemic adriamycin and high-dose methotrexate on histologic tumor response of osteosarcoma of the extremities.

In neoadjuvant treatment of osteosarcoma of the extremities intra-arterial (IA) instead of intravenous (IV) administration of cisplatinum (CDDP) has been advocated to improve local response and consequently increase the percentage of limb salvages and the cure rate. Since the major local advantages from the IA use of CDDP have been recently questioned, a comparative prospective study was performed at the Rizzoli Institute between July 1990 and September 1991. Preoperative chemotherapy consisted of two cycles of high-dose methotrexate (HDMTX), followed 6 days later by CDDP and adriamycin (ADM), HDMTX and ADM were delivered intravenously while CDDP was delivered according to previous randomization, either intra-arterially or intravenously. Of the 79 patients who entered the study 40 received CDDP IA and 39 CDDP IV. The percentage of clinical and radiological response of the tumor as well as the percentage of limb salvage procedures performed was the same in the two groups. However the rate of good histological response (tumor necrosis greater than 90%) was significantly higher in the group of patients who received IA CDDP than in the patients who received the drug intravenously (77.5% vs 46%: p less than 0.01). No differences in terms of local or systemic side effects were found in the two groups. A longer follow-up is necessary to establish if this improved good response rate achieved with IA CDDP will lead to an improved cure rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Limb sparing versus amputation in osteosarcoma. Correlation between local control, surgical margins and tumor necrosis: Istituto Rizzoli experience.

Three hundred fifty-five patients with osteosarcoma were surgically managed at the Istituto Ortopedico Rizzoli between 1983 and 1988. Three hundred two patients performed two cycles of neoadjuvant chemotherapy according to two different protocols consecutively activated; the remaining 53 patients were immediately operated on without neoadjuvant treatment. Follow-up ranged from 19 to 88 months, with a mean of 51 months. Demolitive surgery was performed in 116 patients (33%), while conservative in 239 patients (67%). A radical margin was achieved only in patients undergoing amputations: no radical surgical margins were achieved by local resection: 174 resected patients (73%) had wide margins, while 34 (14%) had marginal margins; 20 patients had contaminated margins and 11 patients (5%) had intralesional margins. Wide or marginal margins were achieved in 208 (87%) of the patients managed by local resection. Local recurrence was identified in 24 of 355 patients (7%). Incidence of local recurrence is strictly related to surgical margin, but above all, to tumor necrosis induced by neoadjuvant chemotherapy. In fact, neoadjuvant chemotherapy makes limb salvage feasible in the majority of cases without increasing the risk of local recurrence: in the group of patients immediately operated on without neoadjuvant chemotherapy, the incidence of local recurrence is dramatically high even when the surgical margins are adequate.

Adolescent

Primary chemotherapy and delayed surgery for osteosarcoma of the extremities with synchronous metastases.

From September 1986 to September 1989 11 patients affected by osteosarcoma of the extremities with synchronous metastases were treated with two cycles of high-dose methotrexate i.v., cisplatin i.a. and adriamycin i.v. followed by simultaneous resection of the primary and metastatic tumor. A complete histological examination of the resected specimens was always performed to evaluate the percentage of necrosis produced by chemotherapy on both the primary and metastatic tumor. After surgery the patients received 3 more cycles of the same drugs as used preoperatively plus ifosfamide. The histological response of the primary tumor was 'good' (90% or more tumor necrosis) in 4 patients and 'poor' (less than 90% of tumor necrosis) in 7, while in the 34 metastatic nodules the resulting necrosis was good in 8 and poor in 26. A good correlation between the histological response in the primary and metastatic tumor was observed, particularly for poor responders (91% of poor responses also in metastatic nodules). At an average follow-up of 42 months, only 3 patients are alive, 2 disease-free, and one with uncontrolled disease. These data suggest that the prognosis of osteosarcoma of the extremities with synchronous metastases remains poor, even with a very aggressive treatment. Our results also seem to confirm the validity of the present strategy in the treatment of non-metastatic osteosarcoma: introducing new drugs post-operatively in poor responding patients can allow a better treatment of microscopic disease and can improve the prognosis for these patients.

Adolescent

Expression of MDR1 and GST-pi in human soft tissue sarcomas: relation to drug resistance and biological aggressiveness.

Human soft tissue sarcomas (HSTS) in adults are a family of mesenchymal tumors characterized by high biological aggressiveness and general refractoriness to chemotherapy. A series of 36 HSTS, 24 untreated and 12 homogeneously treated with a presurgical chemotherapeutic regimen consisting of doxorubicin (intra-arterial) and iphosphamide (intra-vein), was analyzed for expression of MDR1 and the glutathione-S-transferase-pi (GST-pi) gene in order to identify molecular phenomena which may be implicated in the chemoresistance displayed by these tumors. The MDR1 gene was expressed in a greater percentage of drug-treated tumors and at higher levels than in untreated ones. By contrast, chemotherapeutic treatment has no effect on GST-pi mRNA expression. The GST-pi expression level (EL) was much higher in the HSTS with biologically aggressive features. In fact, significant correlations were observed between GST-pi and histologic grade (p = 0.01); aneuploidy (p less than 0.01); and histone H3 EL (p = 0.01), suggesting a possible causal relationship between GST-pi activity and biological aggressiveness in HSTS.

Adult

Osteosarcoma and other cancers of bone.

Because of great improvements in survival and reduction in amputations in patients with osteosarcoma, investigators in the various fields involved in diagnosis and care of these patients are making greater efforts to contribute to better knowledge of the disease and the effects of treatment. Recent developments include basic studies on genetic abnormalities, evaluation of the role of modern imaging in predicting chemo-induced tumor necrosis and in defining tumor margins, and research into new agents, with new combinations and schedules for increasing prognosis and reducing side effects. Major efforts are also being made by surgeons in the difficult field of reconstruction after bone resections.

Acetylmuramyl-Alanyl-Isoglutamine

Osteoblastoma of the spine.

Osteoid osteomas and osteoblastomas have similar histologic characteristics, although their clinical course in the spine may be significantly different. At the authors' institution, spinal osteoblastomas constituted 46% (30/65) of all osteoblastomas treated. Sixteen of the lesions occurred in the lumbar spine (53%), eight in the thoracic spine, and six in the cervical spine. In all regions of the spine, the posterior elements and pedicles were more frequently involved than the vertebral body. Twenty patients had pain or other symptoms for more than 12 months before diagnosis. Six of eight patients had thoracic lesions that demonstrated neurologic involvement. Twelve patients presented with painful scoliosis. Fourteen patients had lesions with well-circumscribed margins confined within the vertebral structure (Enneking Stage 2), and 16 had ill-defined margins with soft-tissue extension (Enneking Stage 3). Well-defined lesions were treated with curettage, with excellent results in 12 of 14 patients. The more extensive lesions were treated by intralesional excision (15/16) and adjuvant radiation therapy (9/16).

Adolescent

Tumours of the patella.

We report 15 cases of primary tumours and pseudotumours of the patella. The radiographic features and the surgical treatment of the different histological types are described in relation to Enneking's surgical staging and data derived from the literature.

Adolescent

Clear cell chondrosarcoma of bone. A report of 8 cases.

We report 8 cases of clear cell chondrosarcoma from 350 cases of chondrosarcoma (2.2%) seen at Istituto Rizzoli. The lesion is always low grade in nature and occurs in an epiphyseal location, usually in the proximal femur or humerus. This relatively inaccessible location may hinder the exact diagnosis. Wide resection is the treatment of choice, although 3 of our patients underwent intralesional or marginal procedures. At present all patients are free of disease. However, a longer followup is essential because of the slow-growing nature of this sarcoma.

Adult