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Biomedical subjects

M Mercuri

Publications and source records attributed to M Mercuri.

At least 19 recordsLinked to original sources

Histologically verified lung metastases in benign giant cell tumours--14 cases from a single institution.

From 1975 to 1997, 649 cases of benign giant cell tumours of the bone were treated at the Istituto Rizzoli. Fourteen patients (2.1%) experienced lung metastases after a mean of 35.2 months. The time interval between the diagnosis and the appearance of the lung metastases ranged from 3 months to 11.9 years. Metastasectomy was performed in all patients. Histologically, the metastases were identical to the primary bone lesions. Two patients with unresectable multiple metastases received additional chemotherapy. After a follow-up of 70 months (range: 8.2 to 185 months), all patients are alive. Ten patients showed no evidence of disease, one of these after a second resection of metastases, and four patients presented stable disease with multiple lung metastases. Local recurrence of the bone lesion occurred in seven patients before or simultaneously to the metastases. In contrast to previous reports, we could not detect a predominance of the distal radius, but all of the patients had a stage III tumour according to the Enneking criteria of benign lesions. We conclude that even metastatic benign giant cell tumours have an excellent prognosis after adequate resection. No prognostic factors despite high-grade lesions were detectable.

Adolescent↗

Pattern of relapse in 290 patients with nonmetastatic Ewing's sarcoma family tumors treated at a single institution with adjuvant and neoadjuvant chemotherapy between 1972 and 1999.

AIMS: Evaluation of pattern of recurrences of 290 patients with an Ewing's sarcoma family tumor (ESFT), who relapsed after adjuvant or neoadjuvant chemotherapy. METHODS: Retrospective analysis at a median follow-up of 16.6 years (range: 5-32) from the primary therapy. RESULTS: There were 378 recurrences, treated by surgery, and/or chemotherapy, radiotherapy, or only palliative treatments. At the last control 18 patients were alive and free of disease 2.5 to 20 years (median 12.1 year) from the last treatment, 4 were alive with uncontrolled disease, 2 died of second line chemotherapy-related toxicity, and 266 died of the tumor 4 months to 20.5 years from the first relapse (median 3.2 years). The 5-year event free survival after the last relapse and overall survival were 5.1 and 7.9%, respectively, and resulted significantly correlated with the time of first relapse, the site of first metastases, the treatment performed after relapse (all patients presently free of disease had been treated by surgery alone or combined with a second line chemotherapy) and for patients treated with neoadjuvant chemotherapy and locally by surgery, with the histologic response to preoperative chemotherapy. CONCLUSIONS: We confirm that the post-relapse outcome of patients with ESFT who relapse after conventional treatment is very poor. Nonetheless specific subgroups of patients may be cured even after 2 or 3 relapses: patients who relapse 2 or more years after primary treatment, patients who relapse with only lung metastases, and patients whose recurrences can be surgically treated.

Adolescent↗

Molecular alterations of monophasic synovial sarcoma: loss of chromosome 3p does not alter RASSF1 and MLH1 transcriptional activity.

Differential diagnosis of monophasic synovial sarcoma requires the detection of specific biological markers. In this study we evaluated the presence of molecular alterations in 15 monophasic synovial sarcomas. Multiple changes affecting chromosome arms were detected by CGH-array in all microdissected cases available, and an association between gain or loss of specific regions harbouring cancer progression-associated genes and aneuploid status was found. The most frequent alteration was loss of 3p including 3p21.3-p23 region that, however, did not involve the promoter regions of the corresponding genes, RASSF1 and MLH1. Using Real-Time PCR, mRNA levels of both resulted moderately high compared to normal tissue; however, the weak to absent protein expression suggests RASSF1 and MLH1 post-transcription deregulation. Moreover, immunohistochemical analysis revealed that both mesenchymal and epithelial antigens were present in diploid tumours. These findings confirm the genetic complexity of monophasic synovial sarcoma and underline the need to integrate different analyses for a better knowledge of this tumour, essential to investigate new diagnostic and prognostic markers.

Adaptor Proteins, Signal Transducing↗

Radiofrequency thermoablation of primary non-spinal osteoid osteoma: optimization of the procedure.

Osteoid osteoma is a small benign tumor that requires treatment due to the intense pain it causes. Surgical therapy has been the ablative technique of choice after a failure of medical therapy. Recently, numerous less invasive, alternative procedures have been proposed: drill trepanation with or without ethanol injections, cryoablation, and thermoablation with laser or radiofrequency. The aim of this review is to retrospectively assess the effect of radiofrequency (RF) thermoablation in the treatment of primary non-spinal osteoid osteoma. From June 2001 to July 2003, we treated 106 patients affected by osteoid osteoma with RF thermoablation. Five patients with spinal osteoid osteoma and four with a previously treated osteoma were excluded from the study. In this paper, we assess the results obtained in a selected group of 97 primary non-spinal osteoid osteoma. The lesions were predominantly in the metaphysics of the femur. Central nidus calcifications were frequent and there was no prevalence for which side they occurred. Primary success was achieved in 82 patients (85%), while we obtained secondary success in 15 patients (15%). In two patients (2%), pain persisted between the two treatments and failed to be resolved, even after the second treatment; therefore, surgical excision was performed and complete resolution was obtained. No complications were reported. In conclusion, our results confirm that the treatment of choice for non-spinal osteoid osteoma is RF thermoablation, offering several advantages over ablative techniques.

Adolescent↗

Osteoarticular allograft reconstruction of the distal radius after bone tumour resection.

Resection of the distal end of the radius is indicated in the treatment of locally aggressive primary benign and malignant bone tumours. The aim of this study was to evaluate the technique of osteoarticular allograft reconstruction of this bone defect. We analysed 12 patients retrospectively with a minimum follow-up of 2 years (range 26-145 months, median 52 months). Three patients had a malignant tumour and nine had a giant cell tumour. The patients ages ranged from 13 to 65 years. The mean resected length of the radius was 6.6 (range 4-14)cm. Non-union of the osteotomy line was diagnosed 6 months after surgery in one case and needed bone grafting. Distal radio-ulnar joint instability was observed in eight cases. Subchondral bone alterations and joint narrowing were present in all cases but were painful in only one patient. The mean range of motion was 51 degrees of flexion and 37 degrees of extension.

Adolescent↗

Surgical treatment and outcome of conventional pelvic chondrosarcoma.

We reviewed 124 patients with a conventional pelvic chondrosarcoma who had been treated over a period of 20 years. We recorded the type of tumour (central or peripheral), type of operation (limb salvage surgery or hemipelvectomy), the grade of tumour, local recurrence and/or metastases, in order to identify the factors which might influence survival. More satisfactory surgical margins were achieved for central tumours or in those patients treated by hemipelvectomy. However, grade 1 tumours, whatever the course, did not develop metastases or cause death, while grade 3 tumours had the worst outcome and prognosis. Central, high-grade tumours require aggressive surgical treatment in order to achieve adequate surgical margins, particularly in those lesions located close to the sacroiliac joint. By contrast, grade 1 peripheral chondrosarcomas may be treated with contaminated margins in order to reduce operative morbidity, but without reducing survival.

Bone Neoplasms↗

Osteoid osteoma simulating an osteocartilaginous exostosis.

We describe a case of osteoid osteoma in the tibia of a 3-year-old patient who presented with a clinical and radiographic picture that suggested an exostosis. The formation of osteoid osteoma with a radiographic picture similar to that of osteophytes or exostosis has been previously documented only rarely. The authors hypothesize that the exostosis-like formation observed was actually the calcification of soft tissues that formed after the intense periosteal inflammatory reaction caused by the osteoid osteoma. As a result of its peculiar clinical and radiographic presentation, diagnosis of this lesion was delayed. Being located close to the medial growth plate of the tibia, it caused lengthening of the limb with a pronounced valgus deviation of the knee. An excisional biopsy provided histological evidence, clinical resolution and immediate pain relief, but incomplete resolution of the valgus deformity of the knee.

Bone Neoplasms↗

Surgery for lung metastases in Ewing's sarcoma of bone.

The addition of chemotherapy and radiotherapy to local treatment for Ewing's sarcoma of bone (ES) significantly bettered its prognosis. Nonetheless, although with no signs of local recurrence some patients still relapse with lung metastases. These patients are generally treated with non-surgical procedures. The few reports in literature on surgical resection of metachronous pulmonary metastases do not allow any conclusions. This study aims to report the results achieved in 24 Ewing's sarcoma patients who relapsed only with lung metastases, and no local recurrence, treated with surgery at the authors' institution.

Adolescent↗

Osteosarcoma of the pelvis.

AIMS: To describe the outcomes of a large number of patients with pelvic osteosarcoma, and to define the guidelines for appropriate treatment. METHODS: We reviewed 60 consecutive patients with primary pelvic high-grade osteosarcoma. The tumour involved the whole hemipelvis in 15 cases, while the most common location was the iliac wing in 29 cases (48.3%): 25 of these adjacent to or passing the sacroiliac joint. RESULTS: Thirty patients underwent surgery; there were 16 hindquarter amputations and 14 internal hemipelvectomies. All the patients who presented with metastasis died of their disease. In 18 cases wide margins were achieved, however, eight patients experienced local recurrence. Of the series, only eight patients are still alive. CONCLUSION: The use of intense chemotherapy and surgical wide margin, hardly seems to achieve local control, however, tumour necrosis was correlated with positive prognosis. When internal hemipelvectomy it is not safe enough, amputation must be considered, particularly for cases with sacrifice of the sciatic nerve roots or for older patients where a shorter surgical procedure can be less risky.

Adolescent↗

Experience of the Rizzoli Institute in radiofrequency thermal ablation of musculoskeletal lesions.

Thermal ablation with radiofrequency (RF) is gaining increasing attention for the treatment of musculoskeletal lesions. This treatment offers several advantages compared to other methods: reduced invasiveness, low cost, and short hospitalisation time. In June 2001 we began using RF thermal ablation on osteoid osteomas (OO) in the appendicular and axial skeleton. Later, we also treated local benign and/or malignant tumors, some surgical recurrences, and some secondary localizations. Altogether we have performed over 270 procedures, mainly on OO. The experience we have gained has led us to think that the indication for this treatment can be extended to other thermosensitive lesions.

Bone Neoplasms↗

Proteases and interleukin-6 gene analysis in 92 giant cell tumors of bone.

BACKGROUND: Giant cell tumor of bone (GCT) is a benign tumor with a significant tendency to recur locally and rarely to produce pulmonary metastases. It is characterized by the presence of multinucleated osteoclast-like giant cells together with mononuclear spindle-shaped cells. Few prognostic markers have been reported to predict the clinical outcome of GCT patients, so is very important to find the factor that can be implicated in its potential aggressiveness. PATIENTS AND METHODS: Different groups of GCT patients were selected for this study, including patients without evidence of disease and patients who recurred locally or with lung metastasis. The total of 92 tumor samples also included the specimens of the local recurrences and the lung metastases. By using immunohistochemistry and real-time quantitative polymerase chain reaction techniques, the genetic and proteic analyses were performed on the urokinase-type plasminogen activator (u-PA), its receptor (u-PAR) and its inhibitor (PAI-1), which have been described to be frequently implicated in the process of degradation of the extracellular matrix during the metastatic process. Interleukin-6 (IL-6), a cytokine released by GCT cells, which stimulates resorption of bone, was also analyzed. RESULTS: IL-6, u-PA, u-PAR and PAI 1 genes were found amplified, respectively, in 7%, 5%, 8% and 12% of total cases (92). In particular, the percentages of amplified genes were higher in the GCT cells that gave rise to metastases (12 cases) and in the samples of lung metastases (nine cases) compared with the disease-free group of patients (60 cases). CONCLUSIONS: These results suggest a possible association of these factors with a higher biological aggressiveness of GCT. Morever, it appears that increased expression of the IL-6, u-PA, u-PAR and PAI1 proteins might not depend on mutation of the corresponding genes.

Biomarkers, Tumor↗

Tissue and serum loss of metalloproteinase inhibitors in high grade soft tissue sarcomas.

The activity of matrix metalloproteinases (MMPs) in degrading extracellular matrix is controlled by activation of pro-enzymes and inhibition of MMP tissue inhibitors (TIMPs). To assess proteolytic cascade imbalance in malignancy progression, the enzymatic activity of MMP2 and MMP9 and the expression and serum level of their inhibitors, TIMP2 and TIMP1 respectively, was evaluated in selected patients with high-risk soft tissue sarcoma (STS). Gelatinase activity and inhibitor expression was evaluated on 69 biopsies by zymography and immunohistochemistry. TIMP1 and TIMP2 serum concentration was tested in 53 STS patients and in 56 controls using a sandwich enzyme immunoassay. Clinical and biological variables were related to clinical outcome of the patients. A significant gelatinolytic activity was seen in a high percentage of STS. TIMP expression was weak or negative in the majority of samples. The difference between disease-free (p=0.001) and overall survival (p=0.007) curves based on TIMP2 immunoreactivity was statistically significant. TIMP plasma concentration of 53 STS revealed significantly lower levels compared to those of 56 controls (p=0.0001). In conclusion, low levels of negative regulators of proteolysis may be related to tumor biological aggressiveness and used to select patients with poor prognosis to improve cure.

Adolescent↗

Knee arthrodesis with a temporary spacer performed in malignant tumor around the knee.

The issue of utilizing a temporary cement spacer after a knee resection arthrodesis of a highly malignant bone tumor is discussed. In our experience, this is the first type of reconstruction performed in the early days of the limb salvage. Now, after more than 12 years of follow-up based on the results of 84 patients, the usefulness and mechanical performance of this type of reconstruction are considered. Of these patients, 45 died of disease. Wound complications were present in 31% of the patients and led to amputation in 7 and healing failure in 6. Mechanical complications occurred in 39%, but radiographic analysis of the implant showed 32 cases (38%) with an inadequate spacer. Only 9 patients are still walking on the original reconstruction, 6 of them uncomplicated (the remaining 3 had rod migrations and shortening). The survival curve showed no statistical difference between the two groups (adequate vs inadequate spacer). In 33 patients who are still alive and retain their limb, the final functional results were excellent in 6, good in 8, fair in 14, and poor in 5. This type of reconstruction can still be considered in developing countries, or when a definitive arthrodesis is planned where there is a lack of a bone source (children, no bone bank). In our institution, reconstruction with cement is still suggested for patients with a large tumor around the knee, when the quadriceps is completely sacrificed, and the patient prognosis is markedly unfavorable.

Adolescent↗

Neoadjuvant chemotherapy for Ewing's tumour of bone: recent experience at the Rizzoli Orthopaedic Institute.

The results achieved in 157 patients with non-metastatic Ewing's sarcoma of the bone treated at a single institution between 1991 and 1997 according to a new protocol (REN-3) are reported. Induction chemotherapy consisted of two cycles of 'VAC': vincristine (V), doxorubicin (A), cyclophosphamide (C) alternated with one cycle of 'VIAc': V, ifosfamide (I), actinomycin (Ac). After local treatment, patients received three more cycles of VAC, two of VIAc, three cycles of I plus etoposide (E) and two cycles with V, C and Ac. Local treatment was surgery in 53% of patients, surgery+radiotherapy in 25% and radiotherapy only in 22%. With a follow-up ranging between 4 and 10 years (mean: 7 years), 110 patients (70%) remained continuously event-free, 2 patients died of toxicity and 45 patients relapsed: 33 due to metastases and 12 due to local recurrence always associated with metastases. The 5-year event-free survival (EFS) and overall survival (OS) were 71.0 and 76.5% respectively. These results are significantly better that the ones achieved in our previous three studies in which a three-drug VAC regimen (REA-1), and 4-drug VACAc regimen (REA-2 and REN-1) was used, and in our most recent study (REN-2) which was based on a six-drug regimen as in the present study, but where I and Ac were used only after the local treatment. However, since REN-3 surgery was used in a significantly larger number of patients, we cannot say whether the better outcome of this study was due to the use of a six-drug regimen with an early delivery of ifosfamide and actinomycin, or to the wider use of surgery as local treatment or both.

Adolescent↗

Allograft arthrodesis treatment of bone tumors: a two-center study.

The current study consists of an outcome review of a consecutive series of 92 patients with knee arthrodesis using an allograft, done for malignant or aggressive tumors in two centers on different continents during a period of 18 years (mean followup, 5 +/- 4 years). The data were compiled by creating a computerized file using the information provided by both centers. Seventy-five of the patients (81%) had high-grade nonmetastatic tumors (Stage II), mostly osteosarcoma. In addition seven (8%) had metastases at outset (Stage III) and the remaining 10 (11%) had benign disease, mostly giant cell tumor or revision procedures for failed allograft or total joint replacement. Seventy-two patients (78%) had distal femoral lesions (78%) whereas the proximal tibia was the site of the tumor in 20 patients (22%). The average age of the patients was 23 +/- 16 years; 51 were males and 41 were females. Tumor complications were a major problem for patients in the series. Thirty-four percent of the patients died, 47% had metastases develop, and 9% had a local recurrence. Allograft complications included an infection rate of 20%, a fracture rate of 25%, and a nonunion rate of 44%. Repeat surgery was required for more than 50% of the patients with 26 requiring one additional operation, 11 requiring two, and 10 requiring three or more operations. Nineteen of the patients required an amputation (20%), only four of which were for recurrent tumor. When these data were compared with data for a control series of 880 patients with allografts other than allograft arthrodeses, the complications were greater and the outcome less successful, suggesting that other approaches should be considered unless there are special indications for this procedure.

Adult↗

High dose ifosfamide in combination with high dose methotrexate, adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: preliminary results of an Italian Sarcoma Group/Scandinavian Sarcoma Group pilot study.

With the intention of starting an international protocol between Italy and Scandinavia on neoadjuvant treatment of extremity osteosarcoma using the four active drugs at maximum doses (doxorubicin 75 mg/m2 pre-operatively, and 90 mg/m2 post-operatively, cisplatin 120 mg/m2, methotrexate 12 g/m2, and ifosfamide 15 g/m2), a single center (the Rizzoli institute) performed a pilot study to closely monitor toxicity, safety, and tumor necrosis. Only 7 patients (10%) had a reduced number of the scheduled cycles. A total of 1,050 of the expected 1,076 cycles (98%) were administered. Delays and dose reduction were minimal, leading to a mean received dose intensity of 89%. Limb salvage surgery was performed in 59 cases (87%), with 6 amputations and 3 rotation plasties. Chemotherapy-induced necrosis higher than 95% was observed in 38 patients (56%). Eleven patients had total necrosis (16%). At a median follow-up of 60 months (range 50-65 months), 53 patients (73%) were continuously disease-free. Six of the relapsed patients were rescued with further treatments leading to an overall survival of 87%. Hematological toxicity was remarkable despite the use of G-CSF and hospitalization due to febrile neutropenia occurred in 25 patients (37%). Platelet transfusions were required in 77 of the 194 episodes of grade 4 thrombocytopenia, but no case of major bleeding was observed. Red blood cell transfusions were necessary in all patients (in 15 cases perioperatively only). Non-hematological toxicity comprised grade 1-2 nephrotoxicity in 3 cases, CNS toxicity in 2 cases, and dilata- tive cardiopathy leading to heart transplantation in 1 case. In conclusion, the pilot study was feasible in the vast majority of cases with toxicity not superior to that of the previous protocols where chemotherapy was given in lower doses. The rate of limb salvage procedures, event-free survival and overall survival seemed to be higher than in previous protocols. On the basis of this study, in March 1997 the Italian and Scandinavian Sarcoma Groups started a new protocol for osteosarcoma of the extremities.

Adolescent↗

Radiological study of 12 high-grade surface osteosarcomas.

OBJECTIVE: The purpose of our study was to report the imaging characteristics of 12 high-grade surface osteosarcomas, diagnosed, staged, treated and followed up in a single institution. DESIGN AND PATIENTS: There were 3 females and 9 males ranging in age from 15 to 34 years (mean 20 years). The radiological documents (plain films in all patients, CT scans in 8 and MR images in 6) were reviewed and compared with the histological findings. RESULTS: Disease sites were the femur (7), tibia (4) and fibula (1). Tumor size varied from 6 to 17 cm. The cortex appeared normal in two patients, thick in seven and/or thin in five. The tumor showed dense ossification in all except in one case where ossification was slight. Minimal marrow involvement was visible in two cases on CT/MRI. Only one case exhibited a satellite nodule in a previous biopsy tract. Two cases radiologically mimicked periosteal osteosarcoma. CONCLUSION: High-grade surface osteosarcomas are often characterized by the presence of an ossified mass contiguous with and originating from the cortical bone with no or minimal marrow involvement.

Adolescent↗