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Davide Donati

Publications and source records attributed to Davide Donati.

13 recordsLinked to original sources
PubMed2004

Bone reconstruction of large defects using bone marrow derived autologous stem cells.

Bone is a tissue that has the ability to heal itself when fractured. Occasionally, a critical defect can be formed when part of the bone is lost or excised, in this case the bone fails to heal and requires bone reconstruction to prevent a non-union defect. Autogenous cancellous bone is the current gold standard treatment in bone loss. Because the amount of autogenous cancellous bone that can be harvested is limited, the expanding need for bone reconstruction is paired by the growth of interest in the discipline of tissue engineering. Labs worldwide are working to provide the right carrier and the right set of cells that, once retransplanted, will ensure bone repair. Several investigators have focused their attention on a subset of autologous non-hematopoietic stem/progenitor cells contained in the adult bone marrow stroma, referred to as stromal stem cells (SSC), as the appropriate cells to be transplanted. The use of autologous cells is facilitated by less stringent ethical and regulatory issues and does not require the patient to be immunologically suppressed. In pre-clinical and clinical protocols of critical defects in which SSC are employed, two approaches are mainly used: in the first, SSC are derived from bone marrow and directly introduced at the lesion site, in the second, SSC are derived from several sites and are expanded ex vivo before being implanted. Both approaches, equally correct in principle, will have to demonstrate, with definitive evidence of their efficacy, their capability of solving a critical clinical problem such as non-union. In this report we outline the difficulties of working with SSC.

Bone Marrow↗
PubMed2004

Hemangioendothelioma of the spine.

A review of the patient files from our institution's oncology department showed that between 1950 and 2000, 11 patients were diagnosed with hemangioendothelioma of the spine, a rare, low-grade malignant vascular tumor. After reevaluation of the diagnoses by orthopaedic oncologists and pathologists, three patients were excluded; therefore eight patients formed the study group. The eight lesions were located in the thoracic (three) or lumbar spine (five, one in each vertebral level). Computed tomography scans revealed expansile lytic process. All lesions involved the vertebral body, but only one was diffuse with spinous process involvement. Treatment included: external beam irradiation alone (one patient), curettage and external beam irradiation (one patient), laminectomy and external beam irradiation (two patients), anterior resection only (two patients), and anterior resection with postoperative external beam irradiation (two patients). Patients without spinal stabilization had chronic low back pain; no patient with spinal stabilization had such pain. One patient who had surgical resection and radiation therapy had a radiation-induced sarcoma develop after 4 years. One patient who was treated with radiation therapy alone had a metastatic lung lesion develop. No other patient had tumor recurrence or progression. Therefore, patients with hemangioendothelioma of the spine may be treated with radiation therapy alone, surgery alone, or a combination thereof. However, because the number of patients in the current series was small, no definitive recommendations regarding treatment may be made. Resection of large lesions and stabilization of vertebral collapse may decrease back pain.

Adult↗
PubMed2004

Role of surgery in local treatment of Ewing's sarcoma of the extremities in patients undergoing adjuvant and neoadjuvant chemotherapy.

Although more and more patients with Ewing's sarcoma of bone (ESB) are being treated by surgery, the relative role of surgery and radiotherapy in the local treatment of this tumor has yet to be determined. Because the outcome of ESB may differ according to the anatomical site of the tumor, results reported in the literature, which generally refer to series with tumors located in all sites, may be selection biased. Therefore, we have retrospectively evaluated patients with ESB exclusively in the extremity and locally treated by surgery or radiotherapy. Two hundred and sixty-eight patients treated at Rizzoli 1979-1996 for non-metastatic ES of the extremities were assessed. Chemotherapy was administered according to four sequentially activated protocols. One hundred and thirty-six patients were treated by surgery, 70 by surgery and radiotherapy, and 60 patients by radiotherapy. Two patients underwent only chemotherapy. The follow-up range was 5-23 years (mean 13 years). One hundred and fifty-two patients remained continuously free of disease, 108 relapsed, 2 died of chemotherapy toxicity and 6 developed a second malignancy. The 5-year event-free survival (EFS) and overall survival (OS) were respectively 62 and 69%. Although patients of all groups were matched for possible risk factors, the rates of 5-year EFS and local control were significantly lower in patients treated with radiotherapy compared to patients treated by surgery or surgery and radiotherapy (48% vs 66%, p=0.002; 80% vs 94%, p=0.0001). Furthermore, in group 3 there were 6 secondary malignancies. Our results indicate that surgery should always be considered in the local treatment of ES of the extremities. Postoperative radiation therapy must be added in case of inadequate surgical margins.

Adolescent↗
PubMed2003

Neoadjuvant chemotherapy for high-grade central osteosarcoma of the extremity. Histologic response to preoperative chemotherapy correlates with histologic subtype of the tumor.

BACKGROUND: In primary central high-grade osteosarcoma, a number of distinct subtypes have been identified, but little is known about the response to chemotherapy. METHODS: The authors investigated whether the subtypes correlated with histologic response to chemotherapy in 1058 patients with osteosarcoma of the extremities who were treated with neoadjuvant chemotherapy over the last 20 years. The tumors were classified as osteoblastic (70%), chondroblastic (13%), fibroblastic (9%), and telangiectatic (6%). At diagnosis, 911 patients had localized disease and 147 had resectable lung metastases. RESULTS: The response to preoperative chemotherapy was good (90% or more tumor necrosis) in 59% of patients and poor (< 90% tumor necrosis) in 41% of patients. The rate of good responses was significantly higher (P = 0.0001) in the fibroblastic (83%) and telangiectatic (80%) tumors and significantly lower in chondroblastic tumors (43%). Prognosis was significantly correlated with the histologic subtypes. The 5-year overall survival rate was significantly higher (P = 0.0001) in fibroblastic (83%) and telangiectatic (75%) tumors than in osteoblastic (62%) and chondroblastic (60%) tumors. In all subtypes, except for the chondroblastic subtype, the 5-year overall survival rate was significantly higher (P = 0.0001) in good responders P = 0.0001 (68%) than in poor responders (52%). CONCLUSIONS: The authors concluded that the histologic subtype of primary central high-grade osteosarcoma of the extremity was strictly correlated with histologic response to chemotherapy and probably, as a consequence, also with prognosis. Further studies are needed to establish whether these results justify a specific therapeutic approach based on the histologic subtype of the tumor.

Adolescent↗
PubMed2003

Platelet-derived growth factors enhance proliferation of human stromal stem cells.

Studies on new procedures for bone reconstruction suggest that autologous cells seeded on a resorbable scaffold can improve the treatment of bone defects. It is important to develop culture conditions for ex vivo expansion of stromal stem cells (SSC) that do not compromise their self-renewing and differentiation capability. Bone marrow SSC and platelet gel (PG) obtained by platelet-rich plasma provide an invaluable source for autologous progenitor cells and growth factors for bone reconstruction. In this study the effect of platelet-rich plasma (PRP) released by PG on SSC proliferation and differentiation was investigated. MTT assay was used to investigate the effect of PRP on proliferation: results showed that PRP induced SSC proliferation. The effect was dose dependent and 10% PRP is sufficient to induce a marked cell proliferation. Untreated cells served as controls. Upon treatment with 10% PRP, cells entered logarithmic growth. Removal of PRP restored the characteristic proliferation rate. Because SSC can gradually lose their capability to differentiate along the chondrogenic and osteogenic lineage during subculture in vitro, we tested whether 10% PRP treatment affected SSC ability to mineralize. SSC were first exposed to 10% PRP for five passages, at passage 6 PRP was washed away and plated cells were treated with dexamethasone (DEX). DEX induced a three-fold increase in the number of alkaline phosphatase positive cells and induced mineralization that is consistent with the differentiation of osteochondroprogenitor cells. In conclusion, 10% PRP promotes SSC proliferation; cells expanded with 10% PRP can mineralize the extracellular matrix once PRP is withdrawn.

Adolescent↗
PubMed2003

Nonmetastatic osteosarcoma of the extremity with pathologic fracture at presentation: local and systemic control by amputation or limb salvage after preoperative chemotherapy.

To determine whether a pathologic fracture in osteosarcoma of long bones has prognostic importance, and limb salvage can be safely performed in such cases, we reviewed the surgical treatment and oncologic results in 46 patients with nonmetastatic osteosarcoma of the extremity and pathologic fracture at presentation who had been treated in our Institution with neoadjuvant chemotherapy, between 1983 and 1999. Neoadjuvant chemotherapy was given according to 6 consecutive protocols. Surgery consisted of limb salvage (34 patients), amputation (11 patients) and rotationplasty (1 patient). The average follow-up was 11 (3-20) years. 28 patients remained continuously disease-free, 17 patients relapsed and 1 died of chemotherapy-related toxicity. Despite the high rate of limb salvage, only 2 local failures occurred, 1 after amputation and 1 after limb salvage. The 5-year disease-free survival and overall survival rates were 59% and 65%, respectively, with no differences between amputated and resected patients. These results are similar to those obtained in 689 contemporary patients having an osteosarcoma without a pathologic fracture treated in our Institution, and using the same protocols for chemotherapy. We conclude that with neoadjuvant chemotherapy, osteosarcoma patients presenting with a pathologic fracture can be surgically treated like those with no fracture, and that limb salvage procedures do not increase the risk of local recurrence or death of these patients.

Adolescent↗
PubMed2003

Multimodal therapy for the treatment of nonmetastatic Ewing sarcoma of pelvis.

The purpose of this study was to evaluate the outcome of patients with Ewing sarcoma (ES) of the pelvis, attempting to identify prognostic factors to select patients for more aggressive treatment. Seventy-seven patients with nonmetastatic ES of the pelvis were treated at Rizzoli Institute between 1979 and 1996. Four different protocols of chemotherapy were used successively. Two protocols consisted of VACAc, and two of VACAc plus ifosfamide and etoposide. Local treatment consisted of surgery in 5 patients, radiotherapy in 60, and surgery followed by radiotherapy in 12. Mean follow-up was 11 years (range 5-25 years). Thirty-three patients remained continuously free of disease; 43 relapsed (24 due to metastases and 19 to local recurrence and metastases); 1 died of treatment-related complications. The 5- and 10-year event-free survival rates were 45% and 44%, respectively, and the 5- and 10-year overall survival rates were 48 and 44. These results are significantly worse than the ones achieved in 329 contemporary patients with extrapelvic lesions treated with the same protocols of chemotherapy (5- and 10-year event-free survival = 46% vs. 64% and 44% vs. 69%). Thus, despite associated chemotherapy, the outcome of ES localized in the pelvis remains poor, and new innovative methods for the treatment of this tumor are needed.

Adolescent↗
PubMed2003

Neoadjuvant chemotherapy for osteosarcoma of the extremity: intensification of preoperative treatment does not increase the rate of good histologic response to the primary tumor or improve the final outcome.

PURPOSE: The aim of this study was to compare the results in terms of histologic response to primary chemotherapy of two sequential studies in osteosarcoma patients preoperatively treated with methotrexate, doxorubicin, cisplatin, and ifosfamide, given at different doses. PATIENTS AND METHODS: Between January 1993 and March 1995, 171 patients with osteosarcoma of the extremity were treated according to a protocol of neoadjuvant chemotherapy with preoperative methotrexate, cisplatin, doxorubicin, and ifosfamide. From April 1995 to December 1999, 196 osteosarcoma patients were preoperatively treated with the same drugs at higher doses. Postoperatively, patients received the same treatment in both studies used, but poor responders (tumor necrosis <95%) had more cycles of treatment than good responders. RESULTS: Comparing the two chemotherapy regimens, there were no significant differences in terms of good histologic response to chemotherapy (69% vs. 62%), 5-year event-free survival (60% vs. 65%), 5-year overall survival (74% vs. 80%), and rate of local recurrence (6% vs. 4%). The 5-year event-free survival was significantly related to the serum level of alkaline phosphatase before treatment (77% for patients with normal values vs. 46% for patients with high values) and the degree of histologic response to preoperative chemotherapy (69% for good responders vs. 54% for poor responders). CONCLUSIONS: Increasing the doses of preoperative chemotherapy does not improve the rate of good histologic response and survival in osteosarcoma of the extremity. The degree of necrosis induced by preoperative treatment probably reflects an innate sensitivity to chemotherapy, which is not altered by increasing drug doses.

Adolescent↗
PubMed2002

Proximal femur reconstruction by an allograft prosthesis composite.

Twenty-seven patients who had resection of the proximal femur for bone tumors and reconstruction with an allograft prosthesis composite are reported. In most of the patients, the prosthesis was a long-stem revision type, cemented in the allograft and uncemented in the femoral shaft. The abductor muscles and iliopsoas were sutured to the corresponding tendons on the allograft. Implant-related complications and functional results were evaluated and are reported. Twenty-two patients achieved a minimum followup of 36 months (range, 36-126 months; average, 58 months). The implant was removed in two patients (one for infection, one for intraoperative fracture of the allograft). One patient experienced nonunion, whereas in the remaining 24 patients, the allograft eventually united to the host bone. A frequent late complication (17 patients) was fracture of the greater trochanter of the allograft. In the whole series, only four new operations were done for implant-related complications. In 22 patients who could be evaluated, the functional evaluation according to the Musculoskeletal Tumor Society System was excellent in 16 (73%) patients, good in four (18%), and fair in two (9%). These results compare favorably with those of megaprostheses for tumor resection of the proximal femur, where a Trendelenburg gait almost always is present.

Adolescent↗
PubMed2002

Seven BMPs and all their receptors are simultaneously expressed in osteosarcoma cells.

Members of the bone morphogenetic protein (BMP) family and their receptors (BMPRs and activin receptors-ActRs) promote the development of bones with a fine regulation of their expression. Mutations in BMPs or BMPRs cause several diseases, as shown in knockout mice, such as skeletal defects, familial primary pulmonary hypertension and neoplasias. Osteosarcoma is the most frequent primary malignant tumor of bone. Due to their importance in bone development, BMPs, BMPRs and ActRs could also play a role in osteosarcoma growth and development. Previous data have shown that the overexpression of the BMPR-II was related to poor prognosis in malignant and metastatic bone tumors. We evaluate by reverse transcription-linked polymerase chain reaction analysis (RT-PCR) the expression pattern of BMPs, BMPRs and ActRs in five different human osteosarcoma cell lines (MG63, G292, HOS, SaOS and U2). Moreover, we performed the mutational screening of the complete BMPR-II mRNA by automated sequencing of the correspondent cDNA to evaluate the presence of point mutations in osteosarcoma cell lines. All the osteosarcoma cell lines studied simultaneously expressed the BMPs, BMPRs and ActRs investigated. No mutations were detected in the BMPR-II cDNA. Our results suggest the presence of a mechanism involving the simultaneous activation of the BMPs and their receptors in osteosarcoma cell lines.

Activin Receptors↗
PubMedDate not supplied

Prognostic significance of serum alkaline phosphatase in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: recent experience at Rizzoli Institute.

In 560 patients with high-grade osteosarcoma of the extremity treated with 5 different protocols of neoadjuvant chemotherapy at a single institution between 1983 and 1995, the pre-treatment serum alkaline phosphatase (SAP) was examined to evaluate whether the enzyme levels had a clinical value in predicting the course of the disease. SAP was normal in 302 (54%) patients and high in 258 (46%). High levels of SAP was observed significantly and independently more frequently in male patients over 14-years-old, and in tumours larger than 150 ml and of osteoblastic subtypes. The 5-year event-free survival (EFS) and overall survival (OS) for all patients were respectively 60 and 68%. With multivariate analysis only two factors were independently correlated with the 5-year EFS: SAP levels (p=0.002) and the grade of chemotherapy-induced necrosis (p=0.0001). The authors conclude that in planning randomized clinical trials of neoadjuvant treatment for osteosarcoma, patients should be stratified according to SAP levels, and that when tailoring the aggressiveness of postoperative chemotherapy to the risk of relapse, in addition to the histologic response to preoperative treatment, the SAP levels should also be considered.

Adolescent↗
PubMedDate not supplied

Recovery of stromal stem cells in bone sarcoma patients after chemotherapy: implication for cell-based therapy in bone defect reconstruction.

Bone sarcomas, such as osteosarcoma (OS) or Ewing sarcoma (ES), frequently arise in the intramedullary region of long bones. Patients affected by bone sarcomas are treated with preoperative aggressive chemotherapy immediately after diagnosis. After chemotherapy, patients undergo surgery that frequently entails the excision of wide bone segments. If a large segment of the bone is lost (defined as a critical defect) the patient undergoes bone reconstruction. Because bone marrow derived stromal stem cells (SSC) offer great promise for cell-based regenerative medicine in bone reconstruction, we investigated whether SSC could be isolated from chemotherapy-treated bone sarcoma patients. We also investigated whether chemotherapy modified SSC differentiation capability. We studied 9 SSC derived from OS and ES patients that had undergone chemotherapy and 5 SSC derived from bone sarcoma patients that had not undergone chemotherapy. SSC could be obtained from all the patients analyzed regardless of whether the patients received chemotherapy or not. Our results also showed that post-chemotherapy SSC can be cultured and expanded ex vivo, these cells retained the ability to differentiate toward the osteogenic lineage in vitro. In conclusion, our results support that SSC cells can be obtained from bone sarcoma patients that undergo chemotherapy and suggest that SSC can be used for cell-based bone reconstruction techniques in bone sarcoma patients treated with preoperative chemotherapy.

Adolescent↗