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Biomedical subjects

F Bertoni

Publications and source records attributed to F Bertoni.

At least 109 records · Page 6Linked to original sources
PubMed1997

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↗
PubMed1997

Osteogenic sarcoma of the extremity with detectable lung metastases at presentation. Results of treatment of 23 patients with chemotherapy followed by simultaneous resection of primary and metastatic lesions.

BACKGROUND: In the past 20 years, it has been demonstrated that the combination of surgery and chemotherapy improves the prognosis for patients with osteosarcoma of the extremity without detectable metastases at presentation. By contrast, the efficacy of chemotherapy coupled with aggressive surgery has not yet been well established for patients with metastatic disease at diagnosis. The current study evaluates the efficacy of chemotherapy associated with simultaneous surgery of primary and metastatic lesions in patients presenting with osteosarcoma of the extremity with lung metastases. METHODS: Patients with lung metastases originating from an osteosarcoma of the extremity received chemotherapy (high dose methotrexate, cisplatin, doxorubicin, and ifosfamide) followed by simultaneous resection of primary and metastatic lesions and additional chemotherapy. RESULTS: Between January 1993 and June 1995, 23 patients entered the study. After primary chemotherapy, lung metastases disappeared in three patients, whereas in four patients they remained surgically unresectable. All seven patients received surgical treatment of the primary tumor only. In the remaining 16 patients, a simultaneous resection of the primary and metastatic tumors was performed after chemotherapy. The resection of metastatic lesions resulted in a complete remission in 15 patients and an incomplete remission in 1 patient. All five patients who never achieved tumor free status died within a few months. Of the 18 patients who achieved radiologic remission at a 30-month follow-up (range, 14-50 months), 10 (55.5%) remained continuously free of disease, 7 relapsed with new metastases, and 1 died of toxicity. In 13 of the 18 patients who underwent a complete simultaneous resection of the primary and the metastatic lesions, or whose pulmonary metastases disappeared after chemotherapy, a strong correlation was found between degree of necrosis of the primary tumor and of the metastatic tumor. CONCLUSIONS: In patients presenting with osteosarcoma of the extremity with lung metastases, the combination of aggressive chemotherapy with simultaneous resection of the primary and metastatic lesions improves traditionally negative outcomes. The strong correlation found between the histologic response of the primary and metastatic tumors supports the strategy, largely used currently in the neoadjuvant treatment of osteosarcoma, of tailoring postoperative chemotherapy on the basis of the histologic response of the primary tumor to preoperative chemotherapy.

Adolescent↗
PubMed1997

Prognostic determinants in supraglottic carcinoma: univariate and Cox regression analysis.

BACKGROUND: A series of 281 consecutive patients affected by supraglottic cancer and treated with surgery alone or with surgery followed by radiotherapy between 1983 and 1989 was reviewed to identify significant prognostic determinants. METHODS: Fifty-one variables (related to host, tumor, and treatment) were tested by univariate and multivariate analysis performed on absolute and determinate survival. RESULTS: The final model of the multivariate analysis for absolute survival included the following covariates listed in order of higher relative risk of death: extracapsular spread, involvement of the medial wall of the pyriform sinus, thyroid cartilage invasion, metachronous tumor, anesthesiologic risk according to the American Society of Anesthesiologists classification (chi 2 = 71.28 with 6 d.f., p < .00001). The definitive model for determinate survival included: extracapsular spread, involvement of the medial wall of the pyriform sinus, extralaryngeal soft tissue invasion, and thyroid cartilage invasion (chi 2 = 82.74 with 5 d.f., p < .0001). CONCLUSIONS: Extracapsular spread was the most important factor affecting the prognosis of patients with supraglottic carcinoma. A second important finding was that T and N category did not emerge as a significant independent prognostic predictor at multivariate analysis. The negative impact on absolute survival of physical status and metachronous tumor could be the expression of the influence of concomitant diseases on survival. These observations concur to reinforce the concept that the current TNM classification is rather inadequate in predicting the prognosis of patients with supraglottic carcinoma when the aforementioned variables are considered.

Adult↗
PubMed1997

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↗
PubMed1997

Clinical relevance of bcl-2(MBR)/J(H) rearrangement detected by polymerase chain reaction in the peripheral blood of patients with follicular lymphoma.

We evaluated the prognostic role of peripheral blood polymerase chain reaction (PCR) assay for detection of the bcl-2(MBR)/J(H) rearrangement in 59 patients with follicular lymphoma (FL) treated at our centre since 1989. Thirty-five (59%) patients were bcl-2/J(H) positive and 24 (41%) were negative in the peripheral blood at diagnosis. Peripheral blood bcl-2/J(H) rearrangement detection at diagnosis had no relation to overall survival (OS) and time to progression (TTP). Peripheral blood PCR assay was performed post treatment in 17 patients who were bcl-2/J(H) positive at diagnosis. Fourteen of the patients (82%, 95% CI 56-96%) became bcl-2/J(H) negative. Nine of these patients were further analysed during follow-up and, after several months, circulating cells carrying the bcl-2/J(H) rearrangement reappeared in five of the nine patients. Peripheral blood clearance of bcl-2/J(H)-positive cells was correlated with better overall survival (log-rank P < 0.05) but not with TTP. Our data confirmed that bcl-2(MBR)/J(H) rearrangement detection by PCR at diagnosis is not a prognostic factor in follicular lymphoma. In our series, clearance of circulating bcl-2/J(H)-positive cells appeared to correlate with better overall survival. Post-treatment examination of the peripheral blood by PCR may have clinical relevance for prediction of the survival pattern of the patients.

Genes, bcl-2↗
PubMed1997

Immunoglobulin heavy chain diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process.

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement. DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences. Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen. The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.

Amino Acid Sequence↗
PubMed1997

Malignant giant cell tumor of the tendon sheaths and joints (malignant pigmented villonodular synovitis).

Malignant pigmented villonodular synovitis (PVNS) is a rare lesion whose existence may be debatable. We studied eight cases that we consider to be examples of malignant PVNS. The three male and five female patients were aged 12 to 79 years. The knee was involved in three cases; the ankle in two; and the cheek, dorsum of the foot, and thigh in one each. Four patients had swelling for 6 months to 17 years before presentation. Three cases of malignant PVNS were secondary, arising in patients in whom PVNS had been documented previously, and five cases were primary, with histologic features similar to those of the secondary ones. Important histologic features of malignancy were (a) a nodular, solid infiltrative pattern of the lesion; (b) large, plump, round or oval cells with deep eosino philic cytoplasm and indistinct borders; (c) large nuclei with prominent nucleoli; and (d) necrotic areas. Atypical mitoses were occasionally seen. Four patients died with pulmonary metastasis (two also had metastasis to inguinal lymph nodes). Four patients are alive from 3 1/2 to 5 years after the last surgical treatment. The malignant nature of this lesion, the histologic architecture similar to that of PVNS, and the fibrohistiocytic appearance of the cells suggest that malignant PVNS is an entity.

Adult↗
PubMed1997

Neoadjuvant chemotherapy for osseous malignant fibrous histiocytoma of the extremity: results in 18 cases and comparison with 112 contemporary osteosarcoma patients treated with the same chemotherapy regimen.

Eighteen patients with high grade malignant fibrous histiocytoma (MFH) of bone and 112 patients with high grade osteosarcoma (OS) of the extremity were treated with neoadjuvant chemotherapy comprised of methotrexate, cisplatinum, doxorubicin and ifosfamide. For the 18 patients with MFH, surgery involved amputation in 2 cases and limb salvage in 16 (89%); the 112 osteosarcoma patients had amputation in 8 cases and limb salvage procedure in 104 cases (93%). The rate of good histologic response to preoperative chemotherapy (90% or more tumor necrosis) was significantly higher in patients with osteosarcoma than in patients with MFH (74% vs 28%; p < 0.003). However, at a median follow-up of 38 months (range 25-61), the 3-year event-free survival (EFS) did not differ in the two groups (MFH 77.8%, OS 70.5%; p = ns). In patients with MFH, no local recurrences were registered, whereas in the osteosarcoma group there were 6 local relapses (5.%). The effectiveness of neoadjuvant chemotherapy in the treatment of osteosarcoma has been assessed during the last 15 years. The results of the present study seem to indicate that, in spite of a usually poor histologic response to preoperative treatment, neoadjuvant chemotherapy is very effective also in MFH of bone.

Adolescent↗
PubMed1997

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↗
PubMed1997

Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma.

The purpose of this paper is to report the clinical characteristics and treatment outcome following different therapeutic approaches in a large series of patients with primary low-grade MALT lymphoma of the stomach. A total of ninety-three patients (median age 63 years) were reviewed. The patients were treated by different modalities (local treatment alone, combined treatment, chemotherapy, antibiotics alone); seven patients refused any treatment. The antibiotic-treated group of patients was prospectively followed with regular endoscopic biopsies, and their responses were histologically evaluated. The 5-years projected overall survival is 82% (95% C.I.; 67%-91%) in the series as a whole. Second tumors were observed in 21.5% of the patients in this series (95% CI 14%v to 31%). There was no apparent difference in overall survival and event-free survival between patients who received different treatments. In the antibiotic-treated group histologic regression of MALT lymphoma was documented in 67% of patients (95% CI 51% to 80%). In conclusion the indolent nature of the disease justifies a conservative approach. The use of antibiotics as first-line therapy may avert or at least postpone the indication for surgical resection in the majority of patients.

Adult↗
PubMed1996

En bloc resections of bone tumors of the thoracolumbar spine. A preliminary report on 29 patients.

STUDY DESIGN: Twenty-nine patients with primary bone tumors and solitary metastases of the thoracolumbar spine treated with en bloc resection are reviewed retrospectively. OBJECTIVE: To demonstrate the possibility to apply in the spine the same principles of surgical oncology adopted for primary bone tumors of the limbs. SUMMARY OF BACKGROUND DATA: The surgical oncologic staging systems currently applied in limb tumor surgery are difficult to apply to spinal tumors. The anatomic conditions make extralesional surgery difficult or impossible, which has restrained a more common use of resection surgery in the spine. Focus is put on a new surgical staging system and en bloc vertebral resection. METHODS: Twenty-five primary malignant and aggressive benign bone tumors and four solitary metastases were treated. The patients were submitted to oncologic and surgical staging for surgical planning. The primary tumors were classified according to Enneking system: three Stage IA, six Stage IB, eight Stage IIB, eight Stage 3 benign. Staging according to the Weinstein-Boriani-Biagini system was also done. Thirteen lesions involved the vertebral body; nine lesions developed in the posterior arch, or part of it, and seven lesions occupied part of the body and part of the arch. A careful anesthesiologic evaluation was performed as well as a continuous intraoperative on-line monitoring of the vital parameters. The en bloc resections (multisegmental in five patients) were performed in 10 thoracic, in 16 lumbar, in two thoracolumbar lesions, and in one lumbosacral lesion. Reconstruction was performed, aiming to replace the resected columns. The specimens were submitted to histologic study of the margins. All the patients were followed, and their status was defined on clinical and imaging studies. RESULTS: In 20 patients, a wide margin was achieved, in eight a marginal margin, in one an intralesional margin. The margin was contaminated in seven patients. Surgical time was 3-21 hours (average, 12 hours). No patient died during surgery or from surgical complications. Three mechanical failures of the implants required additional surgery. One deep infection arose. The only neurologic problems observed were related to the nerve roots sectioned for oncologic purpose. No local recurrence was found at follow-up evaluation after 6-134 months (average, 30 months). CONCLUSIONS: En bloc resection can be performed in selected tumors of the spine; the indication to such major surgery must be based on the oncologic stage, and the procedure must be carefully planned. For this purpose, the Weinstein-Boriani-Biagini system could be a helpful tool. Long-term results must be weighed before a definitive statement of the indications can be made.

Adolescent↗
PubMed1996

Multidrug resistance and malignancy in human osteosarcoma.

In osteosarcoma, resistance to chemotherapy and metastatic spread are the most important mechanisms responsible for the failure of current multimodal therapeutic programs. We have shown previously that overexpression of the MDR1 gene product P-glycoprotein is the most important predictor of an adverse clinical course in patients with osteosarcoma. treated with chemotherapy. In this study, we analyzed the relationship between P-glycoprotein expression and local aggressiveness and systemic dissemination of multidrug-resistant (MDR) human osteosarcoma cells. Compared to parental sensitive cells, MDR cells showed a decreased tumorigenicity,and metastatic ability in athymic mice, together with a reduced migratory and invasive ability and a lower homotypic adhesion ability in vitro, suggesting that P-glycoprotein overexpression is associated with a less malignant phenotype. These experimental observations were confirmed by clinical data. In fact, the time of appearance of lung metastases in a series of osteosarcoma patients treated with chemotherapy was significantly shorter in the group of cases with no expression of P-glycoprotein in the primary lesion compared to the group with P-glycoprotein overexpression. Moreover, the incidence of P-glycoprotein overexpression was found to be higher among patients with localized disease at the clinical onset than in patients with evidence of metastasis at the time of diagnosis. These data indicate that, in osteosarcoma, the MDR phenotype is not associated with a more aggressive behavior both in vitro and in clinical settings, suggesting that the previously shown association of the MDR phenotype with a worse outcome in osteosarcoma is not related to a higher metastatic ability of cells with P-glycoprotein overexpression but is more likely due to their lack of responsiveness to cytotoxic drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Immunostaining of the p30/32MIC2 antigen and molecular detection of EWS rearrangements for the diagnosis of Ewing's sarcoma and peripheral neuroectodermal tumor.

The identification of Ewing's sarcoma (ES) and peripheral neuroectodermal tumor (PNET) among other small round cell tumors (SRCTs) is a critical issue in musculoskeletal pathology because of the lack of clearly distinctive morphological features. In this study, the authors have compared advantages and limits of two procedures that were recently suggested as additional tools for the identification of ES/PNET, the analysis of p30/32MIC2 antigen by immunohistochemistry, and the evaluation of the fusion products of two specific chromosomal aberrations, the t(11;22)(q24;q12) and the t(21;22)(q22;q12), by reverse transcriptase-polymerase chain reaction (RT-PCR). The authors have analyzed the expression of p30/32MIC2 in 28 cell lines and in 90 tumor samples. p30/32MIC2 was highly expressed in ES/PNET but was also present in all the other cell types. The broad spectrum of positivity for p30/32MIC2 in SRCTs of bone was substantially confirmed by the analysis of tissue samples. In the same material, the authors have evaluated the presence of t(11;22) or t(21;22) transcripts (EWS/FLI-1 and EWS/ERG, respectively) by RT-PCR. These transcripts were found in all the cell lines and tissue samples of ES/PNET, but not in other tumors. The authors' results question the use of p30/32MIC2 immunostaining alone for the identification of ES/PNET and suggest the adoption of RT-PCR as an advantageous alternative. Molecular diagnosis of ES/PNET by RT-PCR is highly specific and can be applied to small amounts of tissue. Moreover, RNA extracted from paraffin-embedded specimens was shown to be suitable for RT-PCR analysis, thus enabling analysis of archival material.

Adolescent↗