Mario Campanacci

Giant cell tumor of bone.

True giant-cell tumors are quite rare. Solitary bone cysts occur with about the same frequency, while sarcomata of bone are found five times as often as either. We agree with Geschickter and Copeland that. there is a close clinical kinship between giant-cell tumor and solitary bone cyst., and tlsat they probably have a common origin. Giant-cell tumors are neoplasms and as such can be expected to recur in sites of incomplete extirpation. Moreover, they may undergo malignant changes, either through trauma or as a result of inadequate treatment. The number and size of the giant cells, together with the number of nuclei pet cell, furnish the best criterion for determining the prognosis. The small, sparsely nucleated giant cells with a tendency for collection of many cells in each high-powered field indicate more activity and rapid growth. These tumors have a greater tendency to recur or become malignant. X-irradiation should be reserved for those lesions inaccessible to surgery. The danger of incomplete cures, recurrence, and of an overdosage of roentgen rays are not as important as the hazard of late sarcomatous changes. Resection of the involved portion of a bone where feasible is the treatment of choice. The distal portion of the radius can be sipplanted successfully by use Proximal end of the fibula. The femoral condyle can be replaced by a section from the ilium. If resection is not practical, the next best method of treatment is thorough curettage, with or without cauterization, together with multiple bone grafts or chips to fill the cavity. The most important single factor in this method applies to the treatment of solitary bone cyst as well as giant-cell tumor: this is thorough curettage, breaking through and destroying the limiting wall and thus opening into the normal cancellous bone of the shaft. Bone chips or grafts should he inserted when large defects are created. The so-called giant-cell variants in most instances are probably separate and distinct pathological lesions resembling this tumor only through the presence of giant cells.Of 327 patients who had a giant-cell tumor of bone and were seen at the Istituto Rizzoli, 293 were treated at the Institute, and 280 of these were followed for two to forty-four years. The distribution according to sex and age of the patient and site of the tumor was similar to the distributions in major reports of large series. The tumor usually involved the metaphysis and the epiphysis, but was occasionally limited to the metaphysis, and in only 2 per cent of the patients was it adjacent to an open growth plate. The tumor on occasion invaded the articular space, also involving the ligaments and the synovial membrane. Extension to an adjacent bone through the joint occurred in 5 per cent of the tumors. Our radiographic grading, which is roughly comparable with the staging system of Enneking et al., was Grade I in 4 per cent, II in 74 per cent, and III in 22 per cent of 266 patients before treatment. A pathological fracture was apparent on the first radiograph in 9 per cent of the patients. In the 280 patients with adequate follow-up, 331 surgical procedures were performed. The rate of local recurrence was 27 per cent in the 151 intralesional procedures, 8 per cent in the 122 marginal excisions, and zero in the fifty-eight wide or radical procedures. These results did not correlate with the radiographic grade of the lesion. Of the fifty-one local recurrences that were seen after treatment at our institution, 90 per cent appeared in the first three years after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone and soft tissue tumors

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Expression of P-Glycoprotein in High-Grade Osteosarcomas in Relation to Clinical Outcome

BACKGROUND Increased levels of P-glycoprotein occur in some osteosarcomas. In this study we determined the relation between P-glycoprotein status and outcome in patients with high-grade osteosarcoma. METHODS P-glycoprotein status was determined immunohistochemically in specimens of osteosarcoma of the extremities (stage II) from 92 patients who were treated with surgery and chemotherapy. The P-glycoprotein status was analyzed in relation to the length of event-free survival. RESULTS The presence of increased levels of P-glycoprotein in the osteosarcoma was significantly associated with a decreased probability of remaining event-free after diagnosis (P = 0.002). In a multivariate analysis, P-glycoprotein status (P = 0.001) and the extent of tumor necrosis after preoperative chemotherapy (P = 0.04) were independent predictors of clinical outcome. The risk of adverse events was increased substantially (rate ratio, 3.37; 95 percent confidence interval, 1.60 to 7.10) among patients with increased levels of P-glycoprotein in tumor cells, as compared with patients who did not have increased levels of P-glycoprotein in tumor cells. CONCLUSIONS In patients with high-grade osteosarcoma treated with surgery and chemotherapy, the presence of increased levels of P-glycoprotein in tumor cells is associated with a significantly increased risk of adverse events and is independent of the extent of necrosis after preoperative chemotherapy.

Long-Term Outcome for Patients With Nonmetastatic Osteosarcoma of the Extremity Treated at the Istituto Ortopedico Rizzoli According to the Istituto Ortopedico Rizzoli/Osteosarcoma-2 Protocol: An Updated Report

PURPOSE To provide an estimate of long-term prognosis for patients with osteosarcoma of the extremity treated in a single institution with neoadjuvant chemotherapy and observed for at least 10 years. PATIENTS AND METHODS Patients with nonmetastatic osteosarcoma of the extremity were preoperatively treated with high-dose methotrexate, cisplatin, and doxorubicin (ADM). Postoperatively, good responders (90% or more tumor necrosis) received the same three drugs used before surgery, whereas poor responders (less than 90% tumor necrosis) received ifosfamide and etoposide in addition to those three drugs. RESULTS For the 164 patients who entered the study between September 1986 and December 1989, surgery was a limb salvage in 136 cases (82%) and a good histologic response was observed in 117 patients (71%). At a follow-up ranging from 10 to 13 years (median, 11.5 years), 101 patients (61%) remained continuously free of disease, 61 relapsed, and two died of ADM-induced cardiotoxicity. There were no differences in prognosis between good and poor responding patients. ADM-induced cardiotoxicity (six patients), male infertility (10 of the 12 assessable patients), and second malignancies (seven patients) were the major complications of chemotherapy. Despite the large number of limb salvages performed, only four local recurrences (2.4%) were registered. CONCLUSION With an aggressive neoadjuvant chemotherapy, it is possible to cure more than 60% of patients with nonmetastatic osteosarcoma of the extremity and amputation may be avoided in more than 80% of them. Because local or systemic relapses, myocardiopathies, and second malignancies are possible even 5 years or more after the beginning of treatment, a long-term follow-up is recommended for these patients.

Unicameral and aneurysmal bone cysts

Unicameral and aneurysmal bone cysts are considered tumorlike conditions of unclear origin. The diagnosis of unicameral bone cysts is almost always based on the radiographic appearance, whereas aneurysmal bone cyst imaging may sometimes mimic a sarcomatous lesion. Several pathogenetic hypotheses [correction of hypothesis] reported in literature have been described. Classifications have been proposed to detect the activity of the cysts and to predict the prognostic behavior. The results observed with different options of treatment have been discussed.

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.

Histologic evaluation of necrosis in osteosarcoma induced by chemotherapy regional mapping of viable and nonviable tumor

The predominant sites of viable and nonviable tumor were determined in the primary lesions of 50 patients with osteosarcoma after initial treatment with preoperative chemotherapy. The degree of tumor destruction was classified as good, fair, and poor and a map of the sites revealing viable and nonviable tumor was constructed. The study revealed several preferential sites where viable tumor was likely to persist: soft tissues, cortex, subcortex, ligaments, and areas in contact with cartilage (growth plate and/or articular cartilage). Localized areas of hemorrhage and necrosis, designated “lacunae,” were noted within the tumor. They were frequently surrounded by bundles of viable tumor and appeared to correlate with open surgical biopsies. Factors responsible for this phenomenon and the persistence of viable tumor are discussed. The findings have important implications in the design of surgical treatment and in the use of needle biopsies to determine the effects of preoperative treatment. Cancer 56: 1515‐1521, 1985.

Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for osteosarcoma of the extremities the istituto rizzoli experience in 127 patients treated preoperatively with intravenous methotrexate (high versus moderate doses) and intraarterial cisplatin

Between March 1983 and June 1986 127 patients with localized osteosarcoma of the extremity were treated with neoadjuvant chemotherapy. Preoperative chemotherapy consisted of two cycles of methotrexate (MTX) (high or moderate doses) followed by 6 days by cisplatin (CDP). Surgery was an amputation or a rotation plasty, or a limb salvage. Necrosis was good in 52% of cases, fair in 36%, and poor in 12%. Postoperative chemotherapy consisted of Adriamycin (doxorubicin [ADM]) and bleomycin (BCD) for poor responders; and ADM, MTX, and CDP for fair responders. Good responders were treated as fair responders or with only MTX and CDP. At a 47‐month follow‐up, 66 patients remained continuously disease free and 61 patients developed metastases. Six of these patients had also a local recurrence. According to the grade of necrosis, the cumulative disease‐free probability at 5 years was 67% for good responders, 42% for fair responders, and for poor responders 10% at 45 months. According to the doses of MTX, survival at 5 years was 58% for patients who received high doses and 42% for patients treated with moderate doses. No differences in the rate of survivors were observed between amputated patients and patients treated with limb salvage. The authors conclude that (1) a limb salvage procedure is possible in about 70% of cases and as safe as demolitive surgery, if adequate surgical margins are achieved; (2) good responders have a better prognosis than fair and poor responders if postoperative chemotherapy is sufficiently prolonged and also includes ADM; (3) a different postoperative chemotherapy for poor responders did not improve their prognosis; and (4) a multidrug regimen using high doses of MTX is probably more effective than moderate doses.

Long‐term results in 144 localized Ewing's sarcoma patients treated with combined therapy

The results of 144 previously untreated cases of primary Ewings sarcoma of bone are reported with a minimum follow‐up of 5 years. This series was treated between 1972 and 1982 at Istituto Ortopedico Rizzoli with a combined therapy. The local control of the disease consisted of amputation (ten cases), resection followed by radiation therapy (35‐45 Gy) (48 cases) and radiation therapy alone (40‐60 Gy) (86 cases). Adjuvant chemotherapy, rigorously standardized, was performed according two different protocols: the first (85 cases treated in the period 1972–1978) consisted of vincristine (VCR) Adriamycin (doxorubicin) (ADM), and cyclophosphamide (EDX); the second (59 cases treated in the period 1979‐1982) of VCR, ADM, EDX and dactinomycin (DACT). At a follow‐up of 5 to 16 years (median, 9), 59 patients (41%) are continuously disease‐free (CDF), 81 (56%) developed metastatic disease and/or local recurrence, and four (3%) had a second malignancy. Three factors seem to be correlated to prognosis: the site of the initial lesion (only 23% of the pelvic lesions are represented in the CDF group versus 46% of the other locations); the chemotherapy protocol (32% of the cases in the first protocol are CDF versus 54% in the second); the type of local treatment (60% of the patients treated with amputation or resection plus radiotherapy versus 28% of those treated with radiation therapy alone are CDF). A local recurrence was observed in 24% of the patients (8% in the group locally treated with surgery or surgery plus radiation therapy versus 36% in the group treated with radiation therapy alone). These data suggest that even though adjuvant chemotherapy can improve the long‐term results in localized Ewings sarcoma patients, this disease still represents, in a high percentage of cases, a lethal process whose final prognosis widely depends on the local control of the lesion. Due to the questionable effect of the radiation therapy alone in controlling the primary lesion and its important side effects, the role of surgery in treating Ewings sarcoma of bone should be extended.

Mesenchymal chondrosarcoma of bone and soft tissues

Mesenchymal chondrosarcoma of bone and soft tissues treated at the Istituto Ortopedico Rizzoli are reviewed. The skeletal locations were prominent in five cases. Only two cases were in the soft tissues. Radiographic picture in the bone shows an aggressive osteolysis, with soft tissues invasion. Histologic picture is the same in bone and soft tissues, and is highly distinctive: islands of well‐differentiated chondrosarcoma embedded in undifferentiated mesenchymal cells with high malignancy characteristics. The cases showed a poor prognosis, and no patient survived more than four years.