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Biomedical subjects

M Campanacci

Publications and source records attributed to M Campanacci.

At least 37 records · Page 2Linked to original sources
PubMed1995

The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit.

The c-MET oncogene encodes the receptor for the Hepatocyte Growth Factor/Scatter Factor (HGF), a cytokine that stimulates the invasive growth of normal and neoplastic cells. The Met/HGF receptor is expressed by epithelial cells and its ligand by cells of mesenchymal origin. Receptor-ligand interaction occurs via a paracrine circuit. We studied the expression of the Met/HGF receptor and of its ligand in mesenchymal human tumours by examining 39 clinical samples of bone tumours. The Met/HGF receptor was not detectable in the majority of bone tumours, as expected from their mesenchymal origin. Notably, the receptor was overexpressed in 60% of the osteosarcomas examined. In 12 osteosarcoma cell lines the Met/HGF receptor was overexpressed, phosphorylated by HGF stimulation and fully functional. HGF was detected in two out of seven clinical specimens of osteosarcoma. The ligand and the receptor are co-expressed in two clonal osteosarcoma cell lines. In these lines the Met/HGF receptor was constitutively phosphorylated; phosphorylation was suppressed by suramin treatment, a known blocker of autocrine loops. These data suggest that activation of the Met/HGF receptor by a paracrine or an autocrine mechanism might play a role in the particularly aggressive behaviour of osteosarcomas.

Bone Neoplasms↗
PubMed1995

Clinical relevance of Ki-67 expression in bone tumors.

BACKGROUND: The availability of Ki-67 monoclonal antibody has opened new possibilities for an extensive analysis of cell kinetics in human neoplasms. Ki-67 antibody reveals a nuclear antigen that is expressed in proliferating but not in quiescent cells. Although the reliability of Ki-67 immunostaining has been evaluated in different tumor types, little information has been reported on bone neoplasms. METHODS: Cell proliferation, as determined by Ki-67 expression, was measured by immunofluorescence on representative cytospins obtained from 205 patients with bone tumors. In each sample, the percentage of Ki-67-positive cells was quantified on at least 500 cells and expressed as Ki-67 labeling index (LI). RESULTS: Ki-67 LI was lower in benign and low grade lesions as compared with high grade malignant lesions. A correlation between Ki-67 LI and histologic grade was observed in osteosarcoma and chondrosarcoma. In osteosarcoma, among the 43 primary lesions included in this study, 30 patients, all treated with the same regimen of chemotherapy and limb-salvage surgery, were selected to establish the prognostic significance of cell proliferation. The Ki-67 labeling was higher in patients with a good histologic response to chemotherapy. However, at a 24-month follow-up, a worse prognosis was associated with a higher proliferative activity, whereas no correspondence was found between the histologic response to preoperative chemotherapy and the disease free survival, suggesting that in high grade osteosarcoma the biologic aggressiveness expressed by high levels of Ki-67 LI may be clinically more relevant than the responsiveness to antineoplastic agents. CONCLUSIONS: In bone tumors, the level of Ki-67 expression correlates with the level of malignancy and is diagnostically and prognostically useful.

Adolescent↗
PubMed1995

Multicentric giant cell tumor of skeleton.

A case of multicentric metachronous GCT was presented. The clinical and radiographic features of multicentric GCT as reported in the literature and in the present case were discussed. The multiple bone involvement made therapeutic assessment difficult. The surgical stage as well as the location of each lesion were important in planning surgery.

Adult↗
PubMed1995

Analysis of P-glycoprotein expression in osteosarcoma.

Current treatment of high-grade osteosarcoma combines surgical removal of the lesion with chemotherapy. In this study we evaluated whether the expression of P-glycoprotein, a protein closely associated with multidrug resistance, may be helpful in identifying the patients whose tumours will be further resistant to specific agents. By using multidrug-resistant osteosarcoma cell lines as standards, the expression of P-glycoprotein was evaluated in 105 cases of primary and metastatic osteosarcoma by semiquantitative immunofluorescence. Overexpression of the protein was shown in 23% of primary and in 50% of metastatic lesions. In 38 cases, homogeneously treated and followed-up for at least 24 months, overexpression of P-glycoprotein appeared to be associated with a higher relapse rate and with a trend toward a worse outcome. These data support the role of P-glycoprotein in the response to chemotherapy and its involvement in the determination of the outcome of osteosarcoma patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

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↗
PubMed1995

[Neoadjuvant treatment of Ewing's sarcoma: results obtained in 122 patients treated with a 6-drug chemotherapeutic protocol (vincristine, adriamycin, cyclophosphamide, dactinomycin, ifosfamide and etoposide)].

From January 1988 to October 1991, one hundred and twelve patients with non metastatic Ewing's sarcoma of bone were treated with a 6 drugs neoadjuvant chemotherapy protocol (IOR/Ew2) in which, to the four drugs usually used in the treatment of this tumor (vincristine, adriamycin, cyclophosphamide and dactinomycin), Ifosfamide and VP-16 were added. The local treatment consisted of radiation therapy in 52 cases, a surgical treatment was performed in 27 cases and in the remaining 33 cases both the previous treatments were used. At a mean follow-up of 4.5 years (3-6.5), 62 patients (55.3%) remained continuously free of disease and 50 relapsed: 41 with metastases, 8 with mestastases and local recurrence and 1 with local recurrence alone. These results do not differ from the ones obtained in our Institution in 98 patients treated between 1983 and 1988 with a neoadjuvant protocol (IOR/Ew1) in which only VCR, ADM, CTX and actD were used (3 year CDFS: IOR/Ew2 = 60.7%-IOR/Ew1 = 55.1%). In IOR/Ew2 a higher DFS rate was observed in the patients with tumor located in the axile bones in comparison with that obtained in the previous study (IOR/Ew2 = 48.6%, IOR Ew1 = 25.6%). Despite the fact that these results came from a not-randomized study, the authors conclude that the addition of Ifosfamide and VP-16 to the four drugs standard regimen do not improve the outcome of patients with Ewing's sarcoma of bone, with the possible exception of the patients with tumor located in the axile bones. This data should be confirmed in further and larger studies.

Adolescent↗
PubMed1994

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↗
PubMed1994

Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma.

PURPOSE AND METHODS: To assess patients with high-grade osteosarcoma treated at our institution for various prognostic factors for the development of local recurrence of disease. Follow-up data were available for all patients and the mean follow-up duration was 65 months in surviving patients. RESULTS: There were 28 local recurrences in this study (7%). Of these, only three patients (11%) were alive at the most recent follow-up point, 28, 53, and 54 months after local recurrence. None of 59 patients who were treated primarily with a radical amputation and none of 10 who underwent a rotationplasty developed local recurrence. Four of 48 patients (8%) who had wide amputations, one of whom had an intralesional amputation, and 23 of 237 (10%) who had limb-salvage surgery developed locally recurrent disease. Of 237 patients who underwent limb-sparing resection, three prognostic factors for local control were identified. The strongest association with local recurrence was chemotherapy response (P < .0001), followed closely by surgical margins (P = .0001). Older patients were more likely to have locally recurrent disease (P = .033), with each decade of life older than the first decade having a relative risk of 1.5 times greater per decade (SE = 0.16; 95% confidence interval, 0.034 to .0650). Factors that were not associated with local recurrence included sex, date of diagnosis, and anatomic site of disease. CONCLUSION: Chemotherapy-induced tumor necrosis and surgical margins are important prognostic factors for local control of patients with osteosarcoma.

Adolescent↗
PubMed1994

Effect of electromagnetic fields on patients undergoing massive bone graft following bone tumor resection. A double blind study.

Massive bone allograft after tumor resection has been used for over 20 years. Many factors negatively influence the healing of the junction between the allograft and the host bone, resulting in a low healing rate and lengthy time to union. This study evaluated whether pulsing electromagnetic field stimulation could be advantageously used in these patients. A double blind prospective randomized study was designed. Eighty three host graft junctions in 47 patients were considered. The overall host graft junction healing rate was the same (67%) in both control and active stimulated patients. Although not statistically significant, a positive effect of pulsing electromagnetic fields was observed for those host graft junctions with a cortico-cortical contact between allograft and host bone. When adjuvant postoperative chemotherapy was not employed, a definite effect of pulsing electromagnetic field stimulation was observed: the healing time decreased from 9.4 months in the control group to 6.7 months in the active stimulated group (p < 0.001). This effect would have been lost if chemotherapy was employed. There was also no advantage in supplement with iliac crest autografts at the host graft junction site if chemotherapy was used. Factors that significantly influenced the host graft junction healing rate were: chemotherapy; type of allograft host bone contact; quality of host graft junction; and, in intercalary allografts, use of the osteosynthesis device. No difference was observed between control and active groups for patient survival or number of local or distal tumor recurrences.

Adolescent↗
PubMed1994

Modular uncemented prosthetic reconstruction after resection of tumours of the distal femur.

We report the use of the uncemented Kotz modular femur and tibia reconstruction system after 95 distal femoral resections performed from 1983 to 1989. The average follow-up was 51 months; 62 patients had at least 36 months' follow-up and 36 at least 60 months. Complications required reoperation in 55%. The postoperative infection rate was 5% for primary cases, 6% for revision cases, and 43% for revision of previously infected cases. The polyethylene bushes failed in 42% of cases at an average of 64 months postoperatively. Stem breakage occurred in 6% and was associated with the use of narrow stems and extensive quadriceps excision. The radiological results were excellent or good in most cases and were related to the initial screw fixation, but not to age, chemotherapy, length of resection or size of stem. The clinical results were excellent or good in 75%, failure usually being associated with a complication, especially infection.

Adolescent↗
PubMed1993

Solid variant of aneurysmal bone cyst.

BACKGROUND AND METHODS: Of the 200 cases of ABC in the Rizzoli Institute files, 15 had solid features on both gross and histologic examination. Inasmuch as fibrous proliferation with giant cell and bone production along with fibromyxoid areas and small aneurysmal spaces were found in the solid parts of the aneurysmal bone cyst, a grossly solid and radiographically osteolytic bone lesion with these microscopic features was called a solid aneurysmal bone cyst. Some authors call the same lesion extragnathic giant cell reparative granuloma. RESULTS: Sixty percent of the patients were female. The metaphysis was the preferred location in the long bones (8/11). Radiographic appearance was not specific, and sometimes a malignant lesion was very difficult to rule out. In seven patients, the lesion was considered radiographically "aggressive." Intralesional excision (curettage) in 12 patients and marginal resection in 3 patients with diaphyseal location was effective in controlling the lesion. No recurrence was detected after a mean follow-up of 59 months. CONCLUSIONS: High proliferative activity of the benign-appearing proliferative spindle cells, often with fairly abundant mitoses, associated with benign giant cells and immature bone production are the features of this pseudosarcomatous hyperplastic lesion. It is sometimes is mistaken for a malignant tumor.

Adolescent↗
PubMed1993

Osteosarcoma. Low-grade intraosseous-type osteosarcoma, histologically resembling parosteal osteosarcoma, fibrous dysplasia, and desmoplastic fibroma.

BACKGROUND: Low-grade intraosseous osteosarcoma is a rare variety of osteosarcoma and it is difficult to recognize. METHODS: A series of 10 patients with low-grade intraosseous osteosarcoma is reported. These patients were identified from the Istituto Rizzoli files, which includes approximately 1000 cases of osteosarcoma. Clinical data and radiographic and histologic features were studied. RESULTS: The radiographic appearance confirmed malignancy in five patients and suggested it in two. A benign lesion was diagnosed in three patients. Three lesions resembled parosteal osteosarcoma, two appeared similar to fibrous dysplasia, and two had features of desmoplastic fibroma. A mixed histologic pattern was found in three other tumors. Recurrence after intralesional excision in all patients indicated the aggressive nature of this lesion. The development of metastases in two patients and progression in the grade of malignancy in one of these highlighted the malignant nature of the tumor. CONCLUSIONS: The correct diagnosis would permit adequate treatment with wide surgical margins.

Adolescent↗
PubMed1993

Osteoblastoma-like osteosarcoma. The Rizzoli Institute experience.

A series of 11 osteosarcomas that histologically resembles osteoblastoma was reviewed. The ages of the seven males and four females ranged from 19 to 47 yr (average 29). In six patients the roentgenograms showed cortical destruction and poorly defined borders on the lesion; this roentgenographic presentation was suggestive of malignancy. Histologically, the tumor permeation of the surrounding host tissue allowed us to differentiate osteoblastoma-like osteosarcoma from osteoblastoma. The differential diagnosis can be very difficult or even impossible on a small biopsy. The first diagnosis was considered benign in nine of our cases. Osteoblastoma-like osteosarcoma is a rare variety of osteosarcoma (1.1% of all osteosarcoma). It is a low-grade malignant lesion in which recurrence is the rule when adequate surgical margins were not achieved (five patients). Two of these patients died from tumors after inadequate surgical treatment of the primary tumor as well as of the recurrences. The six patients who were treated with wide surgical margins were alive without recurrence. One of them had lung metastasis, twice, treated with wide-wedge resection. Osteoblastoma-like osteosarcoma is a low-grade variety of osteosarcoma with characteristic histopathologic features. It needs to be recognized by the pathologist to achieve the right treatment which is wide surgical procedure.

Adult↗
PubMed1993

The role of surgical therapy in patients with nonmetastatic Ewing's sarcoma of the limbs.

Of 131 patients with primary Ewing's sarcoma (ES) with extremity locations, treated between April 1972 and May 1987, 13 had amputation; 56 had a local resection with 31 (55%) requiring radiation therapy (RT) as an adjuvant to local therapy. Sixty-two of 131 patients (47%) had RT only. Local recurrences were reported in 5% of patients treated with surgery alone, 1% of the group treated with surgery and radiation therapy, 24% of patients treated with radiation therapy alone (46% for cesium-radiation therapy, and 12% with cobalt-radiation therapy).

Adolescent↗
PubMed1992

Adriamycin binding assay: a valuable chemosensitivity test in human osteosarcoma.

The reliability of a simple method evaluating the pattern of subcellular binding of Adriamycin (Adriamycin binding assay, ABA) as an index of sensitivity was demonstrated in different primary cultures and in sensitive and resistant cell lines of human osteosarcoma. After exposure to Adriamycin (10 micrograms/ml for 30 min at 37 degrees C), living sensitive cells showed selective intranuclear uptake of the drug, whereas in resistant cells no distinct subcellular distribution was observed. The binding pattern of Adriamycin in sensitive and in highly resistant cells was inversely related to the expression of P-glycoprotein. However, low levels of resistance in vitro, not detectable by increased levels of expression of P-glycoprotein, were revealed by ABA. The use of ABA in combination with the estimate of P-glycoprotein expression is recommended in clinical practice as an accurate means for predicting the sensitivity of osteosarcoma to Adriamycin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Evaluation of osteonectin as a diagnostic marker of osteogenic bone tumors.

Osteonectin (ON), a 32,000-kd glycoprotein involved in the early steps of mineralization of skeletal tissue, is a recognized differentiation marker of normal osteogenic cells. The expression of ON was evaluated in vitro and in tissue sections by the polyclonal antibody bON II. In different cell cultures immunocytochemistry and molecular biology displayed a nonspecific reaction for the antibody, which showed itself to be useless for the in vitro identification of cells of the osteoblastic lineage. The diagnostic use of bON II antibody was investigated by immunohistochemistry on a series of osteogenic and nonosteogenic bone tumors. A strongly positive stain of the entire neoplastic component of osteosarcoma and osteoblastoma and a weaker stain of the mononuclear component of giant cell tumor and chondroblastoma were observed. On the other hand, stains for chondrosarcoma, Ewing's sarcoma, fibrosarcoma, malignant fibrous histiocytoma, and brown tumor from hyperparathyroidism were entirely negative. Our results indicate that ON may be helpful in the histologic diagnosis of bone tumors, particularly in differentiating small cell osteosarcoma from other small round cell tumors.

Biomarkers, Tumor↗
PubMed1992

Surgical approach to soft tissue sarcomas of the extremities.

Authors emphasize the primary role of surgery in the treatment of soft tissue sarcoma, confirming the recent acquisition that conservative surgery and adjuvant therapy yield results comparable to those of more extensive surgery. Subsequently, the authors delineate the general guidelines in the surgical treatment of soft tissue sarcoma, depending on the anatomic location of the tumor, and point out the main goals: first to provide local control of the tumor, and second to preserve as much function as possible without jeopardizing the adequacy of the procedure.

Extremities↗