Retrieved human allografts : a clinicopathological study.

BACKGROUND: We studied seventy-three massive preserved human allografts, retrieved from two to 156 months after implantation, to provide insight into the mechanisms of their repair. METHODS: The specimens were studied with radiographic and histological techniques that permitted time-related quantitative analysis of the reparative mechanisms of union, cortical repair, soft-tissue attachment, fracture, and characteristics of the allograft-cement interface and the articular cartilage. RESULTS: Union at cortical-cortical junctions occurred slowly (approximately twelve months) by host-derived external callus that bridged the junction and filled the gap between abutting cortices. The bone in the gap did not undergo stress-oriented remodeling even after many years, and, when the union was intentionally disrupted, failure occurred at the cement line that marked the allograft-host junction. Repair of the necrotic graft matrix was both external and internal. External repair consisted of the apposition of a thin seam of host bone on the outer surface of the graft, coating about 40% of the surface at one year and 80% at two years. Internal repair was confined to the ends and the periphery of the cortices and penetrated so slowly that only 15% to 20% of the graft was repaired by five years, after which deeper repair seldom occurred. Graft fractures in specimens retrieved soon after fracture showed only necrotic bone adjacent to the fracture site, whereas those retrieved after fracture-healing showed a marked increase in internal repair of the bone about the fracture site. When bone cement had been used to fix a prosthesis, there was no evidence of bone resorption or loosening of the device. The osteoarticular specimens showed no survival of chondrocytes in the articular cartilage. However, the architecture of the acellular cartilage was well preserved after two to three years and occasionally after as many as five years. Late degenerative changes in the articular cartilage coincided with subchondral revascularization and fragmentation, and the articulating surfaces became covered by a pannus of fibrovascular reparative tissue. Degenerative changes in articular cartilage occurred earlier and were more advanced in specimens retrieved from patients with an unstable joint than in those retrieved from patients with a stable joint. CONCLUSIONS: Repair of massive human allografts is an indolent process that follows a fairly predictable course during the first few years and is influenced by other biological activities, such as fracture repair, supplementary autografting, and tumor recurrence.

Megavoltage radiotherapy for aneurysmal bone cysts.

PURPOSE: An aneurysmal bone cyst (ABC) is a rapidly expansile and destructive benign tumor of bone that is usually treated by curettage and bone graft, with or without adjuvant treatment. For recurrent tumors, or tumors for which surgery would result in significant functional morbidity, does radiotherapy (RT) provide a safe and effective alternative for local control? PATIENTS AND METHODS: Nine patients with histologically diagnosed aneurysmal bone cysts without other associated benign or malignant tumors were treated at the University of Florida with megavoltage RT between February 1964 and June 1992. The patients received local radiotherapy doses between 20 and 60 Gy, with 6 patients receiving 26--30 Gy. In 6 patients the diagnosis was made by biopsy alone; 3 underwent intralesional curettage before RT. Minimum follow-up was 20 months; 7 of 9 patients (77%) had follow-up greater than 11 years. RESULTS: No patient experienced a local recurrence (median follow-up, 17 years). One patient required stabilization of the cervical spine 10 months after RT because of dorsal kyphosis from vertebral body collapse. No other significant side effects were experienced, and no patients developed secondary malignancies. Four patients were lost to follow-up: at 20 months, 11.5 years, 17 years, and 20 years after the initiation of treatment, none with any evidence of local recurrence. All of the patients who had significant pain before RT had relief of their symptoms within 2 weeks of completion of therapy. CONCLUSIONS: Using modern-day RT, patients with recurrent or inoperable aneurysmal bone cysts can be treated effectively (with minimal toxicity) using a prescribed tumor dose of 26--30 Gy.

An abbreviated history of orthopaedic oncology in North America.

Orthopaedic oncology in North America has its roots in European medicine of the 1800s where sarcomas were first classified on the basis of their gross characteristics (1804) and amended on the basis of their histologic features (1867). Surgical treatment, local excision, with unacceptable mortality led to amputation in the 1870s and remained so until limb-sparing resection was cautiously embarked on in the mid-1900s. Nonsurgical adjuvant therapy was first devised in the 1880s (as Coley's toxins) but remained largely ineffective until the advent of chemotherapy in the 1970s. The combination of these techniques in the past 30 years, and the vastly improved staging and reconstructive techniques has led to the current preponderance of limb-salvaging surgery and greatly improved survival rates. The application of these treatments has been enhanced by the development of orthopaedic oncology fellowships, orthopaedic oncology societies, and federally funded regional cancer centers and multidisciplinary teams to treat patients with sarcomas.

Revision surgery in dermatofibrosarcoma protuberans of the trunk and extremities.

AIMS: Dermatofibrosarcoma protuberans is a rare condition which is frequently misdiagnosed at presentation, resulting in a high incidence of local recurrence due to inadequate resection. The archives of the Department of Orthopaedics at the University of Florida were analysed to investigate the natural history and results of treatment for this tumour. METHODS: Between 1975 and 1996, 35 cases of DFSP were treated at the University of Florida. Of these, one was treated primarily, five were treated for local recurrence, 17 had tumour bed excisions following inadequate primary excisions elsewhere and 12 had tumour bed excisions following inadequate resection of local recurrences elsewhere. The data were analysed to assess the impact of age, gender, duration of symptoms, tumour site and size, surgical margin, number of operations and adjuvant treatments on survival and local recurrence outcomes. RESULTS: Complete follow-up was available for 34 patients. Mean follow-up was 58 months (range 12-144 months). Thirty-three patients remain alive and disease-free. One patient died of unrelated causes. The margins obtained were wide in 28 patients, marginal in six and intralesional in one. Of the seven patients with inadequate surgical margins, four received adjuvant radiation therapy and remain disease-free. No patient with an adequate margin developed a local recurrence, but there were three local recurrences in the patients with an inadequate margin who did not receive adjuvant radiation therapy (local recurrence rate: 8%). No patient developed lymphatic or distant metastasis. Local recurrences were more likely to be classified Stage IB (17/17) than primary tumours (1/18) (P<0.001). Local recurrence was more likely where the surgical margin was less than 2.5 cm from the lesion. CONCLUSIONS: Dermatofibrosarcoma protuberans is a low-grade tumour that has a high potential for local recurrence unless it can be completely excised. The overall rate of local recurrence in referred patients in this series was 20/35 cases (57%). All occurred after inadequate margins at previous surgery in other institutions. Revision surgery in these patients showed a local recurrence rate of 8%. To avoid extensive surgery for recurrences, initial treatment should be by wide excision incorporating the underlying deep fascia and a cuff of 2.5-3 cm of normal skin tissue. Radiation therapy provides a useful adjunct where adequate margins cannot be obtained.

Long-term followup of patients with autogenous resection arthrodesis of the knee.

Arthrodesis of the knee may be indicated for the reconstruction after resection of tumor around the knee. Since the introduction of this technique, resection arthrodesis using segmental autogenous grafts has been the principal method of reconstruction. From August 1967 to February 1985, 73 patients underwent resection arthrodesis using autogenous grafts. All procedures were performed for malignant or potentially malignant lesions. Ten-year followup was available on 40 patients. The reconstructive procedure was performed using an intramedullary rod and hemicortical femoral or tibial grafts with a single autogenous nonvascularized fibula or with dual nonvascularized fibulae. Despite a high surgical complication rate, the majority of patients achieved successful limb salvage. Independent ambulation was achieved by 86% of the patients. A Musculoskeletal Tumor Society functional evaluation in 32 available patients at a mean of 17 years showed the majority of patients functioning satisfactorily. Long-term followup of these patients shows continued durability of the reconstruction and a persistent high level of function and patient satisfaction. Resection arthrodesis using massive autogenous grafts should continue to be in the armamentarium of the orthopaedic oncologist.

Local host response in osteosarcoma after chemotherapy referred to radiographs, CT, tumour necrosis and patient survival.

PURPOSE: The necrotic effect of chemotherapy on primary osteosarcoma has been shown to be predictive of the final outcome. Little attention has been paid to the local response of the host (LHR), which reflects the tumour-host relationship. DESIGN: A four-step grading system was developed based on distinct histological patterns of the LHR around the lesion. These responses were correlated with the chemotherapy-induced necrosis or chemosensitivity and analysed in an attempt to ascertain their influence on the patient prognosis. The ability of conventional radiographs and computed tomography to measure LHR was studied. METHODS: The grading system was applied to macroslides of specimens obtained from 72 patients with stage II B primary osteosarcoma in various limbs after wide resection and complete courses of pre- and postoperative chemotherapy who were treated between 1985 and 1991 with a median follow-up of 5 years and 9 months. The histological specimens were blindly reviewed by two pathologists and two experienced musculoskeletal oncologists to assign a grade of response. The results were correlated with tumour necrosis, patient survival and response features on conventional radiographs and CT images. RESULTS: Significant correlation was found between LHR and tumour necrosis or chemosensitivity (r=0.55) and between LHR and CT response (r=0.56). There was no correlation between LHR and the findings on conventional radiographs. A grade 4 LHR was predictive of long-term survival. CONCLUSIONS: The LHR to preoperative chemotherapy has a prognostic influence on patient survival and can be predicted by CT.

[CT-controlled thermocoagulation of osteoid osteoma in comparison with traditional methods]. / Die CT-gesteuerte Thermokoagulation des Osteoidosteoms im Vergleich zu traditionellen Verfahren.

QUESTION: What are the advantages of CT-guided radiofrequency ablation in comparison to traditional techniques? METHODS: 91 patients with Osteoid Osteoma were analyzed. 15 patients were treated by a wide excision removing a bone block. 26 patients had a marginal resection removing the entire nidus. 36 patients had intralesional margins by curettage or high speed burr technique. Four patients were treated percutaneously by CT-guided drilling technique. 10 patients were treated with the new CT-guided radiofrequency ablation technique. RESULTS: Patients treated by a wide excisional margin had an average procedural length of 2 hours 45 minutes and an average hospital stay of 5 days. Cost figures totaled $13,826. One patient in this group required a bone graft. All patients had a non weight bearing status for six weeks and were limited for ten weeks on average. After marginal resections procedure length was 3 hours. Patients required an hospital stay of 3 days and cost data showed an amount of $10,857.28. 2 patients requiring bone grafts. All patients required post op casting, crutches or braces. Intralesional resection showed a procedure length of 2 hours 40 minutes with an hospital stay of 5 days. Cost figures showed an amount of $10,992. Recovery time was on average of 7 weeks. A cast was applied to three patients post op and one patient did require bone grafting due to the resulting defect. The percutaneous CT-guided burr ablation technique took 2 1/2 hours and the patients required overnight hospital stays for pain control. The costs added to $8589.80. One patient developed a non displaced fracture. For the new CT-guided Radiofrequency ablation technique the average time was 2 hours 10 minutes. Only one patient required an overnight hospital stay. Average total costs for these patients were $6583.66. 1 week post procedure all patients were free of symptoms and resumed full weight bearing. There has been no evidence of recurrence and all patients were symptom free at last contact. CONCLUSION: CT-guided radiofrequency ablation allows the orthopaedic surgeon to heal osteoid osteoma with minimal trauma, functional restrictions and costs.

The staging and surgery of musculoskeletal neoplasms.

This review has outlined the surgical staging of benign and malignant musculoskeletal neoplasms. Based on their unique natural history, these neoplasms behave in a predictable fashion. The surgical staging system assigns progressively higher degrees of risks to the neoplasms based on their surgical grade, their anatomic location, and the presence or absence of metastases. The staging system articulates well with preoperative planning, defining the margins needed for local tumor control. Because surgery distorts most of the imaging modalities available, all clinical staging studies must be completed before surgical intervention. As more data accrue as to the importance of DNA ploidy, genetic markers, and other characteristics, it is likely they will play an important role in the diagnosis and treatment of musculoskeletal neoplasms in the future.

Immunologic responses in human recipients of osseous and osteochondral allografts.

A multiinstitutional study was carried out to evaluate immunologic responses for human recipients of massive frozen (-80 degrees C) osseous and osteochondral allografts. Allografts were used to reconstruct skeletal defects associated with a variety of traumatic degenerative and neoplastic disorders. Serum samples were obtained before surgery and from 1 month to 4 years after surgery. Sera were tested by microcytotoxicity against T cells from 60 donors for human leukocyte antigen Class I antibodies and against beta 2-microglobulin treated B cells from 40 donors for human leukocyte antigen Class II antibodies. Panels were selected to represent the majority of known human leukocyte antigen specificities. Of the 84 cases evaluated, 62 (74%) received blood transfusions and 28 of 44 (64%) female recipients had been previously pregnant. Sensitization before transplant was shown in 33 of 84 (39%) patients. After grafting, 49 of 84 (58%) recipients showed evidence of sensitization to Class I antigens and 46 of 84 (55%) recipients showed evidence to sensitization to Class II antigens. Overall sensitization was 67%.

Allograft-prosthesis composite versus megaprosthesis in proximal femoral reconstruction.

A review of 33 patients who underwent proximal femoral resection for primary bone tumor and reconstruction with an allograft-prosthesis composite or a megaprosthesis is presented to consider the relative merits of the 2 procedures. Clinical function, reconstruction survival, and associated complications were analyzed. Eighteen composites in 16 patients and 18 megaprosthesis in 17 patients were analyzed. Infection in the composite group and instability in the megaprosthesis group were the common causes of failure and removal of reconstructions. The average functional evaluation in 14 surviving patients with composites was 87% of normal. In 10 surviving patients with megaprostheses, the average function was 80% when complications were avoided. Survival analysis of the patients with reconstructions showed a 10 year survival of 76% for the patients with composites and 58% for those with megaprostheses. Both composite and megaprosthetic reconstruction of the proximal femur seem to function equally well from the perspective of function and survival because no statistically significant difference could be shown by this review.

Multicentric giant cell tumor of bone.

Giant cell tumor of bone accounts for 4% to 5% of primary bone tumors in the United States. Multicentric giant cell tumors occur in < 1% of all patients with giant cell tumors, and only 43 patients with multicentric giant cell tumor have been reported on in the literature. This series presents 3 additional cases of multicentric giant cell tumor, includes updated data for 2 patients previously reported on in the literature, and reviews 24 cases previously reported on in detail in the literature. The mechanism by which giant cell tumor involves multiple locations is not known. Multicentric giant cell tumor, in contrast to unifocal giant cell tumor, has a tendency to involve the hands, feet, and metaphysis/diaphysis of long bones and to occur in a slightly younger population. In 15 of the 29 patients reviewed, a second lesion did not develop for > 2 years after their initial presentation. Eighteen of those 29 patients had > 2 sites of tumor involvement, 1 of whom had 11 lesions. Two of the 5 patients in the authors' series presented with a spectrum of disease activity, with latent, active, and aggressive lesions present throughout the observation period.

Surgical considerations in a diagnostic imaging evaluation of musculoskeletal masses.

The management of patients with soft-tissue masses necessitates careful assessment and appropriate use of investigational tools to obtain a diagnosis. The interaction among surgeons, radiologists, and pathologists allows adequate staging of soft-tissue tumors and better planning of the definitive treatment. The ability of MR imaging to maximize contrast between normal and tumor tissues in any desired plane makes it usually the best cross-sectional imaging modality in the preoperative staging of soft-tissue masses.

A comparison of the amount of vascularity in pagetic and normal human bone.

The lower extremity of a patient with Paget's disease of the proximal femur was infused with contrast medium after hemipelvectomy. Cross sectional specimens were computer analyzed to compare quantitatively the microvascularity of the proximal femoral pagetic bone to the distal femoral normal bone. The pagetic bone contained nearly six times more contrast per cross sectional area (28%) than the normal bone (5%).

Radiation therapy for giant cell tumor of bone.

PURPOSE: Giant cell tumor of bone is usually treated with surgical curettage. For recurrent tumors, tumors that are inoperable because of location, and tumors that would require amputation or another radical procedure limiting function, does radiotherapy provide an alternative for local control? METHODS AND MATERIALS: Sixteen patients with histologically confirmed, giant cell tumor of bone were treated at the University of Florida with irradiation between March 1973 and September 1988. Minimum follow-up was 32 months; 63% of the patients had follow-up for at least 5 years, 44% for greater than 10 years. All sites received doses of 35 Gy or more, and all were treated with megavoltage irradiation. RESULTS: In 12 (75%) of 16 patients, the tumor was controlled locally with irradiation. The four failures occurred at 8, 13, 13, and 25 months following initiation of treatment. Surgical salvage was successful in all four failures for an overall local control rate of 100%. One patient developed pulmonary metastasis 1 month after surgical salvage and is alive without evidence of disease after multiple courses of chemotherapy, surgical resection, and whole-lung irradiation. All patients tolerated the treatment well with no severe or chronic complications. No secondary soft-tissue sarcomas have occurred within the irradiated areas. CONCLUSION: Giant cell tumor of bone is not a radioresistant tumor as once believed, and complications seen with modern treatment regimens are minor.

A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system.

The need for a standardized system of end result reporting of various surgical alternatives after limb salvaging and ablative procedures for musculoskeletal tumors was clearly recognized during the first International Symposium on Limb Salvage (ISOLS) in 1981. During the ensuing four biannual symposia, there has been an ongoing developmental experience with a system extensively field tested in 1989 by the Musculoskeletal Tumor Society (MSTS). This system of functional evaluation has been adopted by the MSTS and ISOLS for their joint studies and program presentation. In brief, the system assigns numerical values (0-5) for each of six categories: pain, and function and emotional acceptance in upper and lower extremities; supports, and walking and gait in the lower extremity; and hand positioning, and dexterity and lifting ability in the upper extremity. Demographic information and a patient satisfaction component is included. A numerical score and percent rating is calculated to allow for comparison of results. The system has been field tested in 220 patients with low (+/-) interobserver variability. It was well accepted by the participants, and its usage is recommended by the MSTS to facilitate valid comparative end result studies of musculoskeletal tumor reconstructions.

Osteonectin in osteosarcomas: a marker for differential diagnosis and/or prognosis?

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.

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.

Local growth and the prognosis of osteosarcoma.

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.