Biomedical subjects
Publications and source records attributed to W F Enneking.
We have analysed 63 patients who had stage II osteosarcoma of the distal femur (32) or proximal tibia (31) to determine the patterns of disease-free and overall survival in relation to local growth. All had neoadjuvant chemotherapy. The extent of local growth predicts both types of survival in these tumours.
Seventy-five osteosarcomas at various grades of histologic differentiation were investigated for evidence of osteonectin. According to the results of the study, osteonectin was present in all osteosarcomas. An association between the intensity of the osteonectin antibody reaction and prognosis could not be established. Evidence of osteonectin was also found in other bone tumors. Osteonectin is therefore unsuitable for differential diagnosis, cannot be regarded as a bone specific protein and has not prognostic value.
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.
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.
Radiographic and histological studies of sixteen massive retrieved human allografts were carried out after the allografts had been in situ for four to sixty-five months. The studies demonstrated that union between the allograft and the host took place slowly at cortical-cortical junctions by the formation of an external callus derived from the cortex of the host, and it took place more rapidly at cancellous-cancellous junctions by internal callus advancing from the host into the allograft. Internal repair took place very slowly, was confined to the superficial surface and the ends of the graft, and had involved only 20 per cent of the graft by five years. The deep unrepaired portions of the graft retained their architecture, and where bone cement had been used to fix a prosthetic stem or an intramedullary rod to the allograft, there was no evidence of resorption of bone or loosening of the device. Soft tissues of the host became attached to the graft by deposition of a thin seam of new bone on the surface of the graft. A previous fracture of two grafts had healed before the time of retrieval. Analysis of the articular cartilage revealed no evidence that any chondrocytes had survived, even when the graft had been cryoprotected before it was preserved by freezing. The necrotic cartilage functioned well for as long as five years, and as it degenerated, it was covered by a pannus of fibrovascular reparative tissue. Two allografts that had been removed because of rejection were surrounded by an envelope of chronic inflammatory tissue that prevented union, adherence of soft tissue, and internal repair. Internal repair was more advanced about sites of fracture and adjacent to recurrent tumors than in other portions of the graft. These findings suggest that large frozen allografts in humans are osteoconductive rather than osteoinductive.
Twenty-nine patients (thirty sites) who had histologically confirmed aggressive fibromatosis were treated with radical courses of radiation at the University of Florida between March 1975 and February 1986. The minimum length of follow-up was two years; 76 per cent of the patients were followed for more than five years. Twenty-seven sites received doses of at least 5000 centigrays (one centigray equals one rad). Twelve patients were treated twice a day. Fourteen sites were treated with radiation postoperatively for known or presumed microscopic quantities of residual aggressive fibromatosis; in eleven, the disease was locally controlled. Sixteen sites were treated postoperatively for known grossly apparent residual disease; in fourteen, the disease was locally controlled. Over-all, aggressive fibromatosis was controlled in twenty-five (83 per cent) of the thirty sites. The six-year actuarial rate of local control was 79 per cent. The five local recurrences occurred at four, eleven, thirty-four, sixty-one, and sixty-eight months after the initiation of radiation therapy. Two of the five failures occurred in the high-dose radiation field in patients who were treated for grossly apparent disease. The remaining three failures occurred at the margin of the irradiated field in patients who were treated for assumed microscopic quantities of residual disease. There was no apparent difference in local control between patients who were treated for primary (previously untreated) aggressive fibromatosis and those who were treated after one or more recurrences. Comparison of the results of radiation therapy with published data on operative treatment shows that local control substantially improves with postoperative radiation therapy when operative margins are less than wide.(ABSTRACT TRUNCATED AT 250 WORDS)
Between May 1978 and January 1987, 58 adult patients with previously untreated sarcomas of the trunk and extremities were treated with preoperative irradiation and surgery at the University of Florida. All patients had a minimum of 2 years of follow-up; 24 had a minimum of 5 years of follow-up. The preoperative dose was usually 5040 cGy, with 120-125 cGy per fraction delivered twice daily. Operations were performed 2 to 6 weeks after radiation therapy. Eight patients received adjuvant chemotherapy. The tumors were high grade in 52 (90%), measured greater than 10 cm in 45 (78%), and were extracompartmental in 49 (84%). The surgical margins were wide in 17, marginal in 31, and intralesional in 10 patients. A functional extremity was preserved in 47 of 54 patients who would have required an amputation had they been treated by operation alone. Five of 58 patients (9%) developed local failure; in three, the failure occurred outside of the irradiated volume. Survival rates (product-limit method) at 5 years according to grade and size of lesion were as follows: low grade, 100%; high grade, 10 cm or less in largest diameter, 68%; high grade, 11-20 cm, 39%. Data are insufficient for a 5-year analysis of high-grade lesions greater than 20 cm; to date, there are no 5-year survivors in these patients. Moderate and severe wound complications occurred in 16%. There were four pathological fractures in 52 long bones at risk.
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We analyzed the cases of twenty-three patients who had Stage-IIB osteosarcoma and skip metastasis to determine the rates of disease-free and long-term survival. The regimens of preoperative and postoperative chemotherapy varied. The patterns of relapse and long-term survival were studied in relation to the skip lesions, and these patterns were compared with those of 224 patients who had Stage-II osteosarcoma but no skip lesion. Of the twenty-three patients who had a skip lesion, twenty-two had either a local recurrence or a distant metastasis; twenty-two patients died, and one remained disease-free at thirty-eight months. Kaplan-Meier analysis showed significant differences in the rates of local recurrence and distant metastasis (Mantel-Cox test statistic, p less than 0.0001) and in the over-all survival (Mantel-Cox test statistic, p less than 0.0001) between the patients who had and those who did not have skip metastasis. The cases of fourteen patients who had skip metastasis from a lesion in the distal end of the femur were compared with those of eighty-seven patients who had a similarly situated primary lesion but no skip metastasis. The difference was significant, although less so than when lesions in all anatomical sites were analyzed. The follow-up data indicated that the use of adjuvant chemotherapy did not improve the poor prognosis of patients who had skip metastasis. Therefore, we regard a skip lesion, along with regional lymphatic metastasis or metastasis to a distant organ, as another criterion for considering an osteosarcoma to be Stage III.
The malignant transformation of enchondromas in patients with Ollier's Disease is a well known occurrence although few studies have prospectively followed patients with this disease and reviewed the frequency of this process. When malignant degeneration occurs, usually only one focus is noted even though others potentially may be involved. This paper represents a case report in which two separate locations of chondrosarcoma were found. Discussion includes chondrosarcomatous transformation of enchondromas, radiographic findings in this transformation, and treatment of multicentric chondrosarcomas in a patient with Ollier's Disease.
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Optimal conditions for diagnosis and, hence, rational treatment planning require the integration of a comprehensive history, physical examination, and screening radiographic studies to formulate a working differential diagnosis. From this the appropriate laboratory and radiographic staging studies can be selected to narrow the differential diagnosis, obtain precise, surgically oriented anatomic localization of the lesion, and identify any distant disease. Only after this information is obtained can a biopsy be performed with the least risk of compromising subsequent treatment and the greatest accuracy in surgical staging. This is done most easily when the radiographic staging studies and biopsy are under the direction of the surgeon responsible for the definitive surgical procedure.
The effect of inadvertent tumor violation with visually evident wound contamination during the surgical resection of musculoskeletal neoplasms is unknown. In an attempt to assess the significance of wound contamination by tumor tissue, the incidence of local recurrence in 28 cases of known wound contamination was determined. The influence of immediate lavage, re-excision, subsequent surgical margin, and the use of adjuvant chemotherapy and/or radiation therapy upon local recurrence was assessed. Achieving a wide surgical margin by immediate re-excision after contamination gave a significantly lower incidence of recurrence than those with lesser final margins (P less than 0.01). The use of postoperative adjuvant chemotherapy or irradiation resulted in a lower recurrence rate, but the difference between those with and without adjuvant treatment had statistically less significance than the surgical margin on the incidence of local recurrence (P less than 0.2). The risk of local recurrence after contamination was not influenced by the histologic grade of the tumor.
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.
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Fifty-three patients who had a high-grade osteosarcoma had either a limb-salvage resection or an amputation. They all received adjuvant therapy that consisted of administration of Adriamycin (doxorubicin) and whole-lung irradiation. At the time of follow-up, the surgical margin was assessed by examination of the surgical specimen. Each patient was followed for at least three years or until death. The data suggested that a wide surgical margin is adequate to control a primary osteosarcoma. When a wide surgical margin can be used and a functional limb can be salvaged, an amputation probably is not required.