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Biomedical subjects

P Bacchini

Publications and source records attributed to P Bacchini.

At least 37 records · Page 2Linked to original sources

Analysis of 12q13-15 genes in parosteal osteosarcoma.

The region q13-15 of chromosome 12 frequently is altered in human sarcomas, and several genes, such as SAS, CDK4, and MDM2, have been found to be amplified in bone and soft tissue sarcomas. These genes and their products were studied by quantitative polymerase chain reaction and immunohistochemical analysis in 25 parosteal osteosarcoma samples (22 Grades I or II, three dedifferentiated) to evaluate if the possible alterations detected of the genes on chromosome 12 could have a role in the development of this rare bone tumor. Immunohistochemical analysis was performed on formalin fixed, paraffin embedded tumor sections to evaluate CDK4 and MDM2 protein expression. To measure the degree of SAS and CDK4 gene amplification, quantitative polymerase chain reaction was done on deoxyribonucleic acid derived from the same samples. The results showed that CDK4 protein was expressed in 92% of the cases. Strong and uniform CDK4 and MDM2 immunoreactivity was found respectively in three of three and two of three dedifferentiated parosteal osteosarcomas. SAS and CDK4 genes were found to be amplified fourfold in two Grade II tumors and in one dedifferentiated tumor. These findings, which should be investigated further, might suggest a possible role of the chromosome 12 genes in the pathogenesis of parosteal osteosarcoma.

Bone Neoplasms↗

Prognostic factors in nonmetastatic Ewing's sarcoma of bone treated with adjuvant chemotherapy: analysis of 359 patients at the Istituto Ortopedico Rizzoli.

PURPOSE: The identification of prognostic factors in patients with nonmetastatic Ewing's sarcoma could allow the use of risk-adapted therapeutic strategies of treatment. PATIENTS AND METHODS: Data on 359 patients with nonmetastatic Ewing's sarcoma of bone treated at a single institution between January 1979 and April 1995 were retrospectively considered. The influence of clinical, hematologic, therapeutic, and histologic parameters on event-free survival was assessed. RESULTS: By univariate analysis, the following features were found to be associated with a poor prognosis: male sex (P <.02), age older than 12 years (P <.006), fever (P <.0001), anemia (P <.0025), high serum lactate dehydrogenase (LDH) level (P <.0001), axial location (P <.04), radiation therapy only for local control (P <.009), type of chemotherapy regimen (P <.0001), and poor chemotherapy-induced necrosis (P <.001). After multivariate analysis, the adverse independent prognostic factors were male sex (P <.04), age older than 12 years (P <.001), fever (P <.0002), anemia (P <.02), high serum LDH level (P <.0003), axial location (P <.02), and type of chemotherapy regimen (P <.0003). When the multivariate analysis was restricted to surgically treated patients, the adverse independent prognostic factors were poor chemotherapy-induced necrosis (P <.0001), fever (P <.015), anemia (P <.02), and high serum LDH level (P <.025). CONCLUSION: The prognosis in cases of nonmetastatic Ewing's sarcoma is influenced by many different clinical and hematologic variables, all of which are to be considered when patients are being stratified according to the risk of relapse. In surgically treated patients, the most important prognostic factor is chemotherapy-induced necrosis.

Adolescent↗

Neoadjuvant chemotherapy for peripheral malignant neuroectodermal tumor of bone: recent experience at the istituto rizzoli.

PURPOSE: The results achieved in 44 patients with nonmetastatic peripheral neuroectodermal tumor (PNET) of bone treated with neoadjuvant chemotherapy are reported. PATIENTS AND METHODS: A six-drug regimen of chemotherapy (vincristine, doxorubicin, dactinomycin, cyclophosphamide, ifosfamide, and etoposide) was administered to all patients. Local treatment consisted of surgery in 20 patients, surgery followed by radiotherapy in 13, and radiotherapy only in 11. RESULTS: At a mean follow-up of 4.5 years (range, 2 to 7 years), 23 patients (52%) remain event-free, 20 have relapsed (45%), and one has died of chemotherapy-related toxicity. The 5-year event-free survival and overall survival were 54.2% and 62.7%, respectively. To assess the prognostic significance of neural differentiation in the family of Ewing's sarcoma, these results have been compared with the outcomes of 138 concomitant patients with typical Ewing's sarcoma (TES) who were treated according to the same protocol. Of these, 103 (75%) remained continuously event-free, 34 (24%) relapsed, and one died of chemotherapy-related toxicity. It follows that PNET patients treated with this chemotherapy regimen have a significantly worse prognosis than typical ES patients (5-year event-free survival, 54.2% v 70.6%, P <.012; 5-year overall survival, 62.7% v 78.3%, P <.002). CONCLUSION: The authors conclude that studies into new adjuvant therapy for Ewing's sarcoma modulated according to risk of relapse should also consider neural differentiation as a risk factor.

Adolescent↗

Extraabdominal desmoid tumor. A study of 83 cases.

One hundred three patients with extraabdominal desmoid tumor were treated between 1970 and 1996 at the authors' institution. Among these, 15 patients were lost to followup and five were excluded because they had less than 1-year followup. The remaining 83 patients were followed up for a mean of 11.2 years. Thirty-seven (44.6%) patients experienced local recurrence on average 1.8 years after treatment. There was no difference in the incidence of recurrence between the two groups treated with surgery only (45.3%) or with adjuvant radiation therapy administered after inadequate surgical resection of the tumor margins (41.2%). Recurrence was not related to age, gender, and site. None of the 83 patients died of the disease. For recurrent but stable lesions, clinical observation alone may be considered.

Adolescent↗

Synovial sarcoma: identification of low and high risk groups.

BACKGROUND: Synovial sarcoma, one of the most common soft tissue sarcomas that occur in adolescents and young adults, is generally viewed and treated as a high grade sarcoma. However, the authors' own experience and some previous studies have indicated that it has a wide spectrum of biologic behavior and that low and high risk subgroups of patients with synovial sarcoma can be identified. METHODS: A total of 121 consecutive patients with synovial sarcoma (including 66 males and 55 females ages 9-74 years), treated primarily or secondarily at 2 large referral centers for musculoskeletal tumors, were included in a statistical analysis conducted to identify independent prognostic factors. RESULTS: There were local recurrences in 38 patients (31%), usually after inadequate primary surgery outside the referral centers; 64 patients (54%) developed metastasis, primarily to the lungs. The estimated 5-, 10-, and 15-year survival rates were 60%, 50%, and 45%, respectively (the mean follow-up for surviving patients was 9.8 years, with a range of 1-30 years). In multivariate analysis, independent risk factors for local recurrence included larger tumor size and primary surgical resection outside the referral center. Independent risk factors for metastasis were older patient age, tumor with poor histologic differentiation, and tumor necrosis. For tumor-related death, the independent risk factors were older patient age, tumor with poor histologic differentiation, and larger tumor size. Local recurrence was associated with a 3.66-fold increased risk of tumor-related death. A low risk group (patient age <25 years, tumor size <5 cm, and no histologic evidence of poorly differentiated tumor) with 88% overall disease free survival was identified, as was a high risk group (patient age > or = 25 years, tumor size > or = 5 cm, and poorly differentiated tumor) with 18% overall disease free survival (P < 0.001). CONCLUSIONS: The identification of low and high risk synovial sarcoma patients indicates that synovial sarcomas are not uniformly high grade tumors. It also indicates that treatment strategies should be modified for these risk groups. Adequate primary surgery is essential to both local control and outcome for synovial sarcoma patients.

Adolescent↗

Bizarre parosteal osteochondromatous proliferation of bone.

A 47-year-old man presented with a painless mass of 7 months' duration, on the plantar aspect of the great toe of the right foot. Radiographs and CT images initially suggested an osteochondroma arising from the proximal phalanx of the great toe but there was no continuity between the medullary canal of the phalanx and the lesion. The mass was excised and a histological diagnosis of bizarre parosteal osteochondromatous proliferation of bone (Nora's disease) was made. The aggressive growth of this lesion may clinically suggest a neoplasm. Histological features, however, are those of a reactive lesion.

Bone Neoplasms↗

Giant cell reparative granuloma of the phalanx of the hand with aggressive radiographic features.

This report describes a giant cell (reparative) granuloma in the proximal phalanx of the third finger of the right hand in a 52-year-old man. Radiographically it showed aggressive features with bony permeation, breaking of the cortex, and soft tissue extension. These features suggested a malignant lesion. Histology was characteristic of giant cell reparative granuloma. This lesion, along with aneurysmal bone cyst and giant cell tumor in the small bones of hand and foot, occasionally may show aggressive features mimicking a malignant lesion.

Biopsy↗

Classification of bone tumors.

The classification of bone tumors relies on the cytologic features and products of tumor cells. This classification is reproducible and accepted by pathologists, oncologic surgeons and oncologists. Chondrogenic tumors are the second largest group of bone tumors. Their histologic pattern suggests a relationship to hyaline cartilage. Exostoses, or osteochondromas, represent about 1/3 of chondrogenic lesions. Chondromas are hyaline cartilage tumors which can be found centrally or subperiosteally; they may contain some calcifications and/or ossifications. Chondroblastomas are tumors whose cells produce, at least focally, a matrix similar to hyaline cartilage. Histology of chondromyxoid fibromas shows large or small areas where proliferating cells produce a matrix resembling the hyaline cartilage. Chondosarcomas are tumors whose malignant cells produce a cartilaginous matrix. Most of them occur in previously normal bones; they are classified as conventional or primary chondrosarcomas. Secondary chondrosarcomas result from the malignant transformation of a benign cartilaginous lesion less commonly enchondromas and most commonly osteocartilaginous exostoses, or osteochondromas. Less common variants include dedifferentiated, mesenchymal and clear cell chondrosarcomas. Osteogenic tumors are the third largest group of bone tumors, with osteosarcomas being the most frequent type. The most important criterion for a tumor to be considered an osteosarcoma is that the malignant tumor cells must produce a recognizable osteoid matrix, at least focally. Osteosarcomas are divided into three groups: osteoblastic, chondroblastic and fibroblastic, according to the dominant histologic feature. Osteosarcomas can be multifocal, synchronous or metachronous; they are also classified by the histologic grade of malignancy. Pathologically low grade lesions, which are clinically indolent, are generally known as low grade central and parosteal osteosarcomas.

Bone Neoplasms↗

Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin.

PURPOSE: In osteosarcoma of the extremity, a strong correlation between chemotherapy-induced necrosis and prognosis has been reported. The aim of this study was to investigate the possible factors that influence histologic response to primary chemotherapy. PATIENTS AND METHODS: In 272 patients with high-grade osteosarcoma of the extremity preoperatively treated with high-dose methotrexate (HDMTX), cisplatin (CDP), and doxorubicin (ADM), the histologic response to chemotherapy was evaluated and graded as complete (no viable tumor cells) or incomplete (persistence of viable tumor cells). Several factors, such as metastatic disease to the lung at diagnosis, sex, age, site and tumor volume, histologic subtype, serum alkaline phosphatase, lactate dehydrogenase (LDH), and methotrexate (MTX) pharmacokinetics were investigated to test their predictive significance on histologic response. RESULTS: Fifty-one patients with localized disease (20.6%) and none of the 25 patients with metastatic disease at presentation had a complete histologic response (P = .006). After multivariate analysis, performed on patients with localized disease only, MTX serum peak (> or = 700 micromol/L) and histologic subtype were proven to be significant predictive factors of histologic response. A complete response was seen in 28.8% of patients with 700 micromol/L or greater MTX serum levels and in 9.9% of those patients with lower levels (P = .001). The chondroblastic subtype was less responsive (6.1% of complete response), compared with the osteoblastic (16.3%), fibroblastic (33.3%), and telangiectatic (42.3%). CONCLUSION: Patients with metastatic osteosarcoma and localized chondroblastic osteosarcoma have a reduced chemosensitivity to primary chemotherapy with MTX, CDP, and ADM. MTX serum peak significantly influences tumor necrosis. A dose adaptation of MTX is recommended to obtain a serum peak of 700 micromol/L or greater when MTX is infused in 6 hours.

Adolescent↗

Osteosarcoma of the bones of the foot--an easily misdiagnosed malignant tumor.

OBJECTIVE: To evaluate the frequency of osteosarcoma involving the foot and determine the clinical outcome of affected patients. MATERIAL AND METHODS: We retrospectively reviewed the cases of osteosarcoma encountered between 1911 and 1992 at the Rizzoli Orthopedic Institute. In particular, we analyzed whether common clinical, radiographic, or histologic features could lead to a correct diagnosis of osteosarcoma of the foot. RESULTS: The bones of the foot were the primary site of osteosarcomas in 12 cases--0.6% of the entire series of such tumors at our institution during the study period. The mean age of the patients was 33 years. Initial symptoms were usually pain and swelling. Late diagnosis was common; the mean time interval between the first symptoms and diagnosis was 28 months. Misdiagnoses occurred in 6 of the 12 cases (50%): osteoblastoma, chondroblastoma, chondrosarcoma, osteoid osteoma, desmoid fibroma, and osteomyelitis were, respectively, the initial diagnoses. Histologically, 5 of the 12 tumors (42%) were low-grade lesions. Four of the seven patients with a high-grade tumor died of metastatic disease after a mean survival of 50 months. Eight patients are alive with no evidence of disease after a mean follow-up of 162 months. CONCLUSION: When a painful swelling in a bone of the foot is observed, even if numerous benign conditions (such as fractures, infections, or benign bone tumors) are far more likely to occur, osteosarcoma must be ruled out to avoid delays in the treatment. Osteosarcomas of the foot may easily be misdiagnosed, especially because they almost always occur in adults, in contrast to osteosarcomas in general. High-grade tumors of the foot are as aggressive as other osteosarcomas and should be managed accordingly--with use of a safe-margins surgical procedure and chemotherapy.

Adolescent↗

Prognostic significance of cyclin expression in human osteosarcoma.

To evaluate the distribution of cyclin protein expression, in relation to cell proliferation rate and clinical behavior, an immunohistochemical study was performed on 92 tumor samples of patients with high grade osteosarcoma (OS). A large cyclin A- and cyclin E-positive fraction was found respectively in 59% and 47% of the osteosarcomas, while immunostaining for cyclin D1 was weak or absent in most tumor samples. A positive, statistically significant correlation was found between A and E cyclins and Ki67 expression (p<0.001). Disease-free survival (DFS) analysis included 69 of the 92 patients. A significantly higher probability of metastasis was seen in patients lacking cyclin D1 compared to those in which cyclin D1 was positive (p<0.01). Conversely, patients with >40% of cyclin A-positive cells relapsed more frequently than those with <40% of cyclin A-positive cells (p<0.05). The multivariate analysis demonstrated that cyclin A had a lower predective risk in terms of disease-free survival as opposed to the loss of cyclin D1 that is considered a powerful prognostic factor.

Biopsy↗

Genetic imbalances in 67 synovial sarcomas evaluated by comparative genomic hybridization.

We used comparative genomic hybridization (CGH) to evaluate DNA sequence copy number changes in 67 synovial sarcomas of both monophasic and biphasic histological subtypes. Changes (mean among aberrant cases: 4.7 aberrations/tumor; range: 1-17), affecting most often entire chromosomes or chromosome arms, were detected in 37 sarcomas (55%). Gains and losses were distributed equally, but different chromosomes were affected with variable frequencies. The most frequent aberrations, each detected in 9-11 of 67 tumors, were gain of 8q and gain at 12q (12q14-15 and 12q23-qter), loss of 13q21-31, and loss of 3p. Other frequent changes (in 7 or 8 cases) included gains at 2p, 1q24-31, and 17q22-qter, and losses at 3cen-q23 and 10q21. High-level amplifications were seen in 7 cases. A total of 16 regions were detected. Two of them, 8p12-qter and 21q21-qter, seen in 4 and 2 tumors, respectively, were recurrent. No aberrations specific to histological subtype were identified. However, genetic changes in the monophasic tumors were more complex and numerous (mean among aberrant cases: 5.3 aberrations/tumor; range: 1-17) than in the biphasic tumors (mean: 2.5 aberrations/tumor; range: 1-5), and high-level amplifications occurred more frequently. All but 1 of the sarcomas showing high-level amplification were of the monophasic subtype. These findings may reflect differences in the pathogenesis and biological behavior of both histological subtypes of synovial sarcoma.

Adolescent↗

Altered G1 phase regulation in osteosarcoma.

Alterations in the normal cell cycle lead to abnormal cell proliferation and to tumor development. To explore the role of the cyclin D/Cdk4 complex and the retinoblastoma protein (pRb) in the growth and spread of osteoblastic osteosarcoma (OS), 40 tumor samples were selected. In 17 of these cases, lung metastases occurred during follow-up. Expression of pRb, cyclin D1 and its catalytic subunit, Cdk4, was studied by immunohistochemistry and immunoblotting. As controls, non-neoplastic tissues surrounding the tumor were used. The expression level and pattern were compared to clinical outcome. Cdk4 was over-expressed in 80% of OS, independently of clinical outcome, and showed an intense and uniform distribution in tumor cells compared to normal cells. However, co-immunoprecipitation of Cdk4 with cyclin D1 revealed low levels of cyclin D/Cdk4 complex; 20 of 40 OS examined had a negative or minimal immunostaining for active pRb. The probability of relapse was significantly higher in pRb-negative than in the -positive patients (p < 0.05). The ratio of unphosphorylated/hyperphosphorylated pRb was lower in relapsed patients than in patients with no evident disease, though the difference was not statistically significant. High levels of pRb/cyclin D1 were found in all samples exhibiting functional pRb expression. Our results show that G1 phase deregulation is involved in formation and development of OS. The expression levels of both pRb and cyclin D1 had a clear correlation with clinical outcome, suggesting that these parameters could be used as prognostic markers.

Bone Neoplasms↗

Chondrosarcoma as a complicating factor in Paget's disease of bone.

A 65-year-old male patient with an 8-year history of poliostotic Paget's disease complained of shoulder pain that started 6 months prior to admission. An extensive lytic area was identified in the right proximal humerus along with Paget's disease. There was cortical destruction and a soft tissue mass. Following an incisional biopsy, a diagnosis of grade 2 chondrosarcoma associated with Paget's disease was made. The histologic identification of chondrosarcoma associated with Paget's disease is rare. However, the presence of a calcified matrix in a destructive lesion associated with Paget's disease should alert the radiologist and the pathologist to the possibility of a chondromatous differentiation taking place in the sarcoma associated with Paget's disease. The histologic evaluation of the lesion will form the basis for the diagnosis.

Aged↗

Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing's sarcoma of the extremities.

PURPOSE: This study was performed to assess the prognostic value of the proposed histopathologic method to evaluate the response of the primary tumor to preoperative chemotherapy in Ewing's sarcoma. PATIENTS AND METHODS: The response to chemotherapy was evaluated from the specimens of 118 Ewing's sarcoma patients, who were preoperatively treated by chemotherapy alone. Responses were graded I to III (macroscopic viable tumor, microscopic viable tumor, and no viable tumor cells, respectively). Follow-up data were available for all patients, with a mean follow-up duration of 86 months (range, 30 to 158). RESULTS: A statistically highly significant difference was observed in outcome among the three groups of patients. For patients with total necrosis (grade III response), the estimated 5-year disease-free survival rate was 95%, in contrast to 68% for grade II responders and 34% for grade III responders (P < .0001). This difference was also confirmed when any single group was compared with the other groups. Among the parameters tested, patient age and the size of tumor had some prognostic value. CONCLUSION: The proposed histopathologic grading, to evaluate the effect of chemotherapy on the primary tumor, had the strongest correlation to clinical outcome. This method could therefore be used to identify patients with a high risk of recurrent disease. These patients could be randomized to receive alternative postoperative treatments to investigate whether more aggressive therapies will improve outcome.

Adolescent↗