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Biomedical subjects

D S Springfield

Publications and source records attributed to D S Springfield.

At least 19 recordsLinked to original sources

Pulmonary function tests after whole-lung irradiation and doxorubicin in patients with osteogenic sarcoma.

PURPOSE: Because of the scarcity of information regarding long-term follow-up of pulmonary function after whole-lung irradiation, a prospective study was started at the University of Florida in 1979 to evaluate pulmonary function after treatment with whole-lung irradiation and doxorubicin in patients with osteogenic sarcoma. PATIENTS AND METHODS: Between 1979 and 1984, 57 osteogenic sarcoma patients with no evidence of metastatic disease at diagnosis received adjuvant therapy consisting of whole-lung irradiation (with the heart shielded) followed by Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH). The whole-lung irradiation schema was 1,600 cGy in 10 fractions with 8-MV x-rays via anterior and posterior fields. This was followed by five cycles of Adriamycin for a total dose of 450 mg/m2. Pulmonary function tests (PFTs) consisting of spirometry, lung volumes, and diffusing capacity were obtained before the whole-lung irradiation, at 6 and 12 months after irradiation, and at yearly intervals thereafter. RESULTS: At the time of analysis, 28 of the 57 patients were available for study, with a mean follow-up of 42 months (range, 6 to 77 months). Follow-up pulmonary function testing revealed decreased forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV1) during the first 6 to 12 months after whole-lung irradiation. These values returned to baseline during the second-year posttherapy and remained at baseline throughout the remainder of the follow-up period. Changes in lung volumes demonstrated a similar early trend, with significant decreases in total lung capacity (TLC) and functional residual capacity (FRC) at 6 to 12 months. These changes, however, did not improve significantly during the remainder of the follow-up period. Diffusing capacity of the lungs for carbon monoxide (DLCO) also reached a nadir at 6 to 12 months after whole-lung irradiation, with resolution by 2 years and maintenance of at least baseline values for the remainder of the follow-up period. CONCLUSIONS: Treatment with whole-lung irradiation and Adriamycin, as given in this study, caused no significant sequelae, as demonstrated by pulmonary function testing during the mean follow-up period of 42 months, although a mild, transient restrictive ventilatory defect occurred at 6 to 12 months after treatment.

Adolescent

Metastatic disease of the femur.

Metastatic involvement of the femur is a common clinical problem and accounts for the third highest incidence after the spine and pelvis. These patients are confronted with the possibility of losing the ability to ambulate during their remaining months. However, with improved prosthetic implants and internal fixation devices, most patients can resume their previous activities after operative treatment of their femoral fractures.

Bone Nails

Current status of allografting for bone tumors.

Over the past 20 years the Orthopaedic Oncology Unit of the Massachusetts General Hospital has performed over 660 massive cadaveric allograft transplantations, mostly for patients with bone tumors. The overall success rate for such procedures is around 80%, with most of the failures occurring in the first 3 years as a result of fracture (19%), nonunion (14%), and infection (10%). With longer follow up, late occurring osteoarthritis has been noted in approximately 17% of those patients at risk, suggesting that the articular surface begins to "wear" at 5 years. Some problems remain with the procedure, and more study of such aspects as the immune mechanism, cryopreservation of cartilage, maintaining the status and safety of the bone banking system, and improving the techniques of surgery ultimately may lead to a more uniform and predictable success rate.

Adolescent

Fresh and frozen articular cartilage allografts.

Fresh and frozen cartilage allografts both function well to relieve joint pain due to cartilage injury. Fresh cartilage allografts appear to remain alive for many months and are most applicable to small injuries such as osteochondritis dissecans, traumatic defects, and osteonecrosis. Frozen cartilage allografts have been used mostly for treatment of bone tumors which most often involve the subchondral and the metaphyseal areas of the long bones, particularly around the knee and hip. Frozen cartilage allografts appear to survive well and maintain joint space for several years. Deterioration of either type of graft does not appear to result in joint pain, making these grafts useful for long periods of time.

Adaptation, Physiological

Autogenous bone grafts: nonvascular and vascular.

Nonvascularized autogenous bone grafts have been used for at least 150 years. Vascularized bone grafts were first done only 17 years ago. We now know that bone grafts act through osteoconductive and osteoinductive mechanisms to produce new bone. Autogenous bone grafts remain the gold standard against which allografts and artificial graft materials should be measured.

Bone Transplantation

Late follow-up of a short-term intensive regimen for Ewing's sarcoma.

Twenty-two patients received a short-term intensive regimen for Ewing's sarcoma between November 1977 and December 1981. The regimen consisted of vincristine (1.5 mg/m2) on day 1, and doxorubicin HCl (75 mg/m2) plus cyclophosphamide (1,000 mg/m2) on day 2. Six cycles were given at 28-day intervals. Local irradiation was started shortly after cycle 2. Eight patients with lesions of expendable bones also underwent surgery as part of the treatment to the primary site, 4 at the end of chemotherapy and 4 at diagnosis. The 5-year event-free survival rate was 45% for all patients and 48% for those with localized disease at diagnosis. Two patients died of treatment-related toxicity. The most common form of failure was distant metastases, indicating that finding a better systemic treatment remains the problem in eradicating Ewing's sarcoma.

Adolescent

In vitro assay of nuclear uptake of doxorubicin hydrochloride in osteosarcoma cells of dogs.

A rapid, simple chemosensitivity assay, assessing tumor cell nuclear uptake of doxorubicin hydrochloride, was evaluated in 16 dogs with appendicular osteosarcoma. Doxorubicin was administered to dogs in 5 biweekly treatments, and surgical resection was performed after the second or third treatment. The chemosensitivity assay was performed on biopsy specimens from all dogs before chemotherapy. It was repeated on tissue from resected tumors, and tumors were evaluated histologically to determine the degree of necrosis resulting from chemotherapy. Disease-free and total survival time correlated significantly (P less than 0.05 in both cases) with the degree of postchemotherapy necrosis of the primary tumors. Significant correlation was not apparent between the percentage of tumor cells with nuclear uptake of doxorubicin (in either biopsy or resection samples) and disease-free or total survival time. The percentage of cells with nuclear uptake of doxorubicin in surgically resected tumors correlated significantly (P less than 0.05) with percentage of necrosis.

Animals

Flow cytometric studies of human osteosarcoma.

A number of recent studies have emphasized the potential value of flow cytometry as a "marker" to assess the malignity and therefore to help predict the biologic behavior of neoplasms, including bone tumors. Using propidium iodide and a home-built flow cytometer, the authors have studied the DNA distribution in 95 patients with osteosarcoma and determined the percentage of cells in diploidy, S-phase, tetraploidy, and aneuploidy. Using these values and a derived one, mean DNA concentration, it was possible to demonstrate the extent of the abnormalities observed in this group of neoplasms and show their severity as compared with the normal pattern. When the data are compared against disease-free survival and total survival, correlations were noted that, although weak, suggested that some patterns were predictive of increased risk of metastasis and death. The effect of treatment could also be assessed by evaluating the pattern before and after chemotherapy and correlating these with survival. It seems likely that with some improvement in technology, flow cytometry will be of value in the future in assessing the prognosis for osteosarcoma and predicting whether treatment has been effective.

Adolescent

The use of bone allografts for limb salvage in high-grade extremity osteosarcoma.

Limb preservation is increasingly being employed in the local treatment of high-grade extremity osteosarcoma. Bone allografts used to reconstruct the bony defects following tumor resection offer many advantages, including joint reconstruction and incorporation of the graft to the host bone in these relatively young patients. The results of 53 patients 30 years of age or younger were assessed to determine functional outcome. Fresh-frozen allografts were employed as osteoarticular grafts, allograft-arthrodeses, allograft-prosthesis composites, or intercalary grafts. Follow-up intervals averaged 25 months (range, two to 63 months). Life-table analysis showed that the probability of a satisfactory functional result was 73% if local tumor recurrences were excluded. Complications included 16 infections, six fractures, 12 nonunions, and six unstable joints. There were five local recurrences. Eighteen grafts ultimately failed, and in six patients, this resulted in an above-knee amputation. An additional five received a second graft. The functional "end results" of the 38 patients with two or more years of follow-up examinations were 70% satisfactory in those without a local recurrence. There was no statistically significant difference in functional outcome or local or distant relapse in those patients receiving preoperative chemotherapy. The authors conclude that allografts can be used for limb reconstruction in patients with high-grade osteosarcoma who receive aggressive adjuvant chemotherapy. The functional results are comparable to other methods of reconstruction, and once incorporated by the host, offer the advantage of longevity, compared with metallic implants.

Adolescent

Rotationplasty as a reconstructive operation after tumor resection.

Reconstruction in the skeletally immature patient following resection of osteosarcoma about the knee is a challenging problem. Salvaging of the limb with allogeneic or prosthetic replacement results in a shortened limb with functional limitations. Arthrodesis yields a stiff and shortened limb. The so-called growing prosthesis has a high complication rate and is still unproven. However, rotationplasty has been successfully used as a reconstructive technique following resection of these types of tumors in the skeletally immature patient. A limb with normal sensation and proprioceptions, adequate range of motion, and without leg-length discrepancies, functional limitations, or painful neuroma is to be expected. Although a prosthesis must be worn, these patients are active and participate in unrestricted physical activity. Cosmetic acceptance has not been a problem and complications are minimal. Thus, rotationplasty requires only a single operation and results in a highly functional limb.

Adolescent

Spontaneous necrosis in osteosarcoma.

The percentage of necrosis in a primary osteosarcoma after the patient has received preoperative chemotherapy is prognostic and is usually used to select subsequent chemotherapy. However, the percentage of necrosis that occurs spontaneously, without preoperative chemotherapy, has not been adequately studied. The examination of histologic macrosections of 76 osteosarcomas from patients who had not received preoperative treatment and of 20 patients who had received preoperative chemotherapy revealed a significant difference in the percentage of necrosis. There was minimal spontaneous necrosis, but necrosis after preoperative chemotherapy was usually extensive. The larger the tumor, the greater the percentage of spontaneous necrosis; however, size did not correlate with the percentage of necrosis with preoperative chemotherapy. Survival among those patients who did not receive preoperative treatment correlated with the size and percentage of necrosis. Necrosis in an osteosarcoma in a patient who has received preoperative chemotherapy can be considered the result of chemotherapy and not a spontaneous event.

Adolescent

High-risk Ewing's sarcoma: end-intensification using autologous bone marrow transplantation.

Because of retrospective analysis showing survival to be related to primary tumor size, in February 1982 a study to test this hypothesis prospectively was begun at the University of Florida. Patients with primary tumors 8 cm or less in maximum diameter and no metastases received adjuvant chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, and dactinomycin plus radiotherapy or surgery (standard-risk protocol). All others received a similar regimen followed by end-intensification with high-dose melphalan and autologous bone marrow transplantation (Protocol HR-2). Because of poor results of HR-2, another high-risk protocol (HR-3) was initiated in January 1985. Patients on HR-3 received 2 cycles of chemotherapy containing vincristine, cyclophosphamide, and doxorubicin followed by local radiation therapy and maintenance chemotherapy. At the end of this therapy, autologous bone marrow transplantation (ABMT) was performed, using a preparatory regimen of total body irradiation and intensive chemotherapy. The 2-year disease-free survival rate was 70% for the standard-risk protocol, 20% for HR-2, and 80% for HR-3. The follow-up on HR-3 is still short, but the results are promising enough to warrant further clinical trials.

Antineoplastic Combined Chemotherapy Protocols