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Biomedical subjects

M C Gebhardt

Publications and source records attributed to M C Gebhardt.

At least 91 records · Page 5Linked to original sources

Allograft reconstructions of the shoulder after bone tumor resections.

Large skeletal defects resulting from tumor resections about the shoulder create reconstructive challenges for the orthopedic surgeon. Bone allografts offer several advantages compared with other reconstructive techniques, and functional outcomes are generally satisfactory. They may be used either as osteoarticular grafts, intercalated segments to create an arthrodesis, or in combination with standard proximal humerus metallic implants. Patient expectations and specific oncologic factors must be considered when selecting the optimal method of reconstruction.

Arthrodesis↗

Osteoarticular allografts for reconstruction in the proximal part of the humerus after excision of a musculoskeletal tumor.

An osteoarticular allograft was used to replace the proximal end of the humerus in twenty patients who had had a wide excision of a bone tumor. Three patients needed a second allograft because the first became infected. All patients were followed for at least two years except for two patients who died. The functional results and complications of the twenty-three index procedures were evaluated. Function was excellent in one patient, good in eleven, fair in one, and poor in five. The allografts had advantages compared with other options for reconstruction (for example, prosthetic implants); these included restoration of the length of the bone, replacement of the articular surface, and sites for reattachment of the deltoid muscle and rotator cuff. We concluded that the complications do not preclude use of this procedure.

Adolescent↗

Tumors about the knee in children.

Tumors are rare causes of knee symptoms in children but must be considered in the differential diagnosis of pediatric knee pain in order to avoid errors in treatment that could result in loss of limb or even life. Experience with 199 bone and soft-tissue tumors about the knee in children are reviewed. The majority of lesions were benign bone tumors (n = 101), with osteocartilaginous exostoses, nonossifying fibromas, and chondroblastomas predominating. Malignant bone tumors (n = 59) were less frequent, and osteosarcoma (n = 48) was by far the most common sarcoma. Soft-tissue lesions (n = 31) were much less frequent and included rhabdomyosarcoma, synovial sarcoma, fibrosarcoma, and desmoid tumors. A careful history, physical examination, and review of roentgenograms are essential to avoid errors in diagnosis. Malignant tumors require roentgenograms and laboratory studies in sequence to stage the patient. A properly performed biopsy established the diagnosis in most instances. Popliteal cysts, stress fractures, infection, myositis ossificans, histiocytosis, and other lesions can mimic tumors and delay correct diagnosis.

Adolescent↗

Fractures of allografts. Frequency, treatment, and end-results.

One of the major complications of implantation of a massive frozen cadaveric allograft in the treatment of a tumor is fracture of the allograft. To determine the incidence, risk factors, appropriate management, and results of treatment of this complication, the records of the Orthopaedic Oncology Unit of the Massachusetts General Hospital were reviewed. Forty-three patients were identified in whom a tumor had been treated with an allograft that had subsequently fractured. The over-all incidence of fracture was almost 16 per cent. When the several risk factors (age and sex of the patient, stage and site of the lesion, and so on) for the forty-three patients who had a fracture were compared with those for the rest of the series, the only correlation was the incidence of non-union at the site of the host-donor junction, which was significantly higher in the patients who had a fracture. The mean time to fracture was 28.6 months after the operation. Three types of fractures occurred: Type I (two patients), rapid dissolution of the graft; Type II (twenty-two patients), fracture of the shaft, which was observed more frequently in male patients and which occurred a mean of 27.6 months after the operation; and Type III (nineteen patients), fragmentation of the joint, which usually occurred later (a mean of 31.6 months postoperatively) and was found more frequently in female patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Growth factor production by sarcoma cells in primary culture.

Cell lines derived from human sarcomas have been previously shown to produce a protein growth factor which, similar to platelet-derived growth factor (PDGF), can induce competence for mitosis in fibroblasts. Whether this factor production is an important feature of sarcomas in vivo or simply an artefact caused by long-term culture conditions is unclear, however. We demonstrated growth factor activity in conditioned medium from six of 11 primary sarcoma cultures, utilizing flow cytometric analysis of DNA to monitor the presence of sarcoma cells in cultures. Cells isolated from control tissues failed to show a similar mitotic effect.

Cells, Cultured↗

Timing of chemotherapy and surgery in a murine osteosarcoma model.

The sequential use of chemotherapy and surgery in the treatment of osteosarcoma developed in an empirical fashion without the benefit of investigations in animal models. The MGH-OGS murine osteosarcoma is a transplantable tumor that resembles the human disease with respect to histology, local invasiveness, metastatic characteristics, tumor ploidy, and its response to chemotherapy. We have used this tumor model to investigate the efficacy of preoperative, perioperative, and postoperative chemotherapy on the development of pulmonary metastases in three different experimental protocols. In each experimental design, perioperative chemotherapy demonstrated a significant advantage in preventing systemic relapse.

Animals↗

Kinetic effects of adriamycin and bleomycin on two osteosarcoma models.

Although chemotherapeutic drugs are frequently administered to patients with osteosarcoma, there has been little research into the effect of cytotoxic drugs on osteosarcoma cell biology. The effect of two drugs (Adriamycin and bleomycin) on cell cycle kinetics was investigated in vitro in an established line of human osteosarcoma cells and in vivo using the Dunn osteosarcoma model. The cell cycle changes were consistent with G2 arrest for both drugs in vivo and in vitro. The alteration in cell cycle distribution was correlated with inhibition of 3H-thymidine incorporation in vitro. In vivo, the greater change in cell cycle distribution caused by Adriamycin was reflected in the increased inhibition of tumor growth found with this drug.

Animals↗

Evaluation of fluorescein diacetate for flow cytometric determination of cell viability in orthopaedic research.

Accurate estimation of cellular viability is important both in research and in aspects of orthopaedic clinical practice. We have been interested in the potential for flow cytometric application of fluorescein diacetate (FDA) in evaluating chondrocyte survival following cryopreservation of osteochondral allografts as well as in the assessment of sarcoma necrosis following preoperative chemotherapy. In order to evaluate the suitability of this method for cell viability assays, this study compared FDA with more traditional methodology (trypan blue, clonigenic assay, metabolic activity analysis, measurement of DNA synthesis, and histological assessment of necrosis). Both chondrocytes and sarcoma cells were exposed to various experimental injuries prior to viability analysis. Although it is evident from these experiments that FDA accurately reflects cell survival after physical injury, it underestimates the effect of chemotherapy on cell reproductive potential in vitro. However, FDA is highly correlated with histological assessment of tumor viability after chemotherapy in vivo. It is apparent that the methodology chosen for determination of viability should be appropriate for the type of experimental injury and should analyze the cell function (i.e., metabolic activity or reproductive capacity) that is appropriate for the experimental model.

Animals↗

Treatment of the patient with stage M0 soft tissue sarcoma.

During the period 1971 to 1985, 220 patients with soft tissue sarcoma of the extremities, torso, and head-neck region were managed by radiation and resectional surgery at the Massachusetts General Hospital (MGH). Actuarial 5-year local control and disease-free survival rates were 86% and 70%, respectively. The success rate improved during this time period. Namely, the local control rates for 1971 to 1975, 1976 to 1980, and 1981 to 1985 were 81%, 81%, and 94%, respectively. For the same time periods, the 5-year disease-free survival rates were 64%, 70%, and 76%. One hundred thirty-one patients were treated with postoperative radiation, and 89 with preoperative radiation. In the most recent 5-year period, the local control rates were 91% and 97% for the two groups (number of patients being 50 and 57 in the post- and preoperative groups, respectively). Treatment by preoperative radiation appears to have a major advantage for patients with very large sarcomas, ie, greater than 15 cm in maximum dimension. None of our patients with local control of grade 1 sarcoma have developed distant metastasis (DM). In contrast, among patients with grade 2 or 3 sarcomas, there is a relentless and progressive increase in the frequency of DM with size of the primary lesion, namely, 6% at less than or equal to 2.5 cm, congruent to 60% at 15 to 20 cm, and congruent to 80% at greater than 20 cm.

Combined Modality Therapy↗

Infection in bone allografts. Incidence, nature, and treatment.

Of 283 patients who had a massive allograft of bone, an infection developed in thirty-three (11.7 per cent). To assess the frequency and identify the co-morbid and predisposing factors of this devastating complication, we compared demographic data for the infected and non-infected patients. Comparison of mean age, type of graft, anatomical site of the procedure, and stage of the tumor yielded no significant differences. Multiple-regression analysis of a subgroup of eighty-two patients who had a distal femoral graft showed a correlation between infection and factors that are associated with more extensive surgery (more loss of bone, soft tissue, or skin) or with multiple operations. Approximately 30 per cent of the patients who had an infected allograft had no co-morbid or predisposing factors that could be statistically correlated with an increased risk for infection. Gram-positive organisms were the most common cause of infection, with twelve infections (36 per cent) being due to Staphylococcus epidermidis. Six patients had a single gram-negative organism and nine had mixed flora. The final result in the thirty-three patients who had an infected allograft was poor compared with that of the over-all series and of the uninfected patients. Twenty-seven infected allografts (82 per cent) were considered to be failures of treatment because amputation of the limb or resection of the graft was required to control the infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Reconstruction for defects of the proximal part of the femur using allograft arthroplasty.

One of the most difficult problems in orthopaedic oncology is reconstruction after resection of a tumor of the proximal end of the femur. In order to achieve a wide margin about a primary or secondary malignant neoplasm of bone, it is often necessary to resect not only the hip joint and fifteen or more centimeters of the proximal part of the femur, but also the surrounding envelope of soft tissue. In some patients, little is left but the sciatic and femoral nerves and vessels. Since 1971, we have done reconstructions in forty-four patients, using an allograft and an implant or else an osteoarticular graft alone to replace the proximal end of the femur. Twenty-eight of these reconstructions were performed in patients who had had a malignant tumor and were followed for two to fifteen years postoperatively. Fifteen of the patients had only an osteoarticular graft, and thirteen had an allograft and a prosthesis (nine Austin Moore, two bipolar, and two long-stem total hip replacements). The average length of the femoral segment was 18.4 centimeters; the longest one measured thirty-one centimeters. Using an evaluation system of functional end-results that includes failures as a result of recurrence of the tumor, we recorded approximately 70 per cent excellent and good results for both groups. When the two failures that were due to recurrence of the tumor were omitted from the statistics (in order to evaluate the allograft procedure more fully), the successful results increased to about 80 per cent. In general, the patients who had an osteoarticular reconstruction fared less well than did those who had an allograft and a prosthesis, but the series were not quite comparable. The major complications were metastases in nine patients (five of whom died), infection in five, and fracture of the allograft in six. Restoration of the reconstruction was possible for most of the patients who had a problem that was not related to the tumor, and only one patient required an amputation for recurrent tumor. Despite the many difficulties, we think that an allograft, with or without a prosthetic implant, should be given primary consideration as a means of reconstruction of the limb when resection of a tumor necessitates resection of a long segment of the proximal end of the femur.

Adult↗

The use of flow cytometry as a diagnostic aid in the management of soft-tissue tumors.

The diagnosis and staging of soft-tissue tumors is a complex problem, and even the experienced pathologist sometimes finds it difficult to determine whether a particular lesion is benign or malignant and whether a sarcoma is high or low grade. However, this information is essential in planning treatment. Flow cytometric analysis of nuclear DNA is a method to determine the number of cells that are in the process of replicating or dividing (S or G2, or M phase), since these cells have abnormal concentrations of DNA (DNA aneuploidy). Previous studies from our laboratory have established the relative value of this technique as an adjunct in the staging of primary bone tumors. In the past four years, 146 soft-tissue lesions have been evaluated by flow cytometry, using propidium iodide staining of isolated cells that were obtained in the fresh state. The tumors were forty-two benign neoplasms, ten lesions of synovial origin, thirty desmoids (aggressive but not malignant), and sixty-four sarcomas ranging in grade from 1 to 3 on a 3-point scale. The over-all values for flow cytometry showed that a number of factors correlated well with the grade of the tumor, but the best correlations were with the mean concentration of DNA (a calculated average for concentrations of DNA for the various types of cells in the lesion), the total percentage of cells in S-phase plus the G2 and M-phases (called percentage of replicating and dividing cells), and the presence or absence of DNA aneuploidy.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Intra-articular entrapment of the median nerve after elbow dislocation in children.

Two cases of intra-articular median nerve entrapment after reduction of elbow dislocations in children are described. The diagnosis of median nerve entrapment is often delayed. A proximal median nerve deficit, limited passive elbow motion, and an associated medial epicondyle avulsion after reduction of a child's posterior elbow dislocation should alert the surgeon to the possibility of nerve entrapment. Optimal management of this problem consists of early surgical exploration and nerve release.

Adolescent↗

The treatment of adamantinoma of the tibia by wide resection and allograft bone transplantation.

Since 1975, nine patients who had adamantinoma of the tibia were treated by the orthopaedic oncology service of the Massachusetts General Hospital and the Children's Hospital, Boston, Massachusetts. All patients were followed for two years or more or until a relapse occurred (mean length of follow-up, 5.3 years). Five of the patients were female and four were male; their ages ranged from fourteen to fifty-six years (mean, 19.1 years). The treatment consisted of staging, wide surgical resection of the tumor, and insertion of a segment of intercalary bone allograft (eight patients) or an osteoarticular segment (one patient). All grafts were fixed with compression plates and screws. All but two of the allografts had united at both the proximal and the distal host-donor junction site by twelve months. None of the patients had a local recurrence but pulmonary metastases developed in one. Four of the patients had complications that affected the final result. The functional results were excellent in five patients, good in one, fair in one, and a failure in two. Seven of the nine patients were asymptomatic and fully functional at the time of writing; only one needed a brace to walk. On the basis of this experience we recommend wide resection and implantation of an intercalary allograft in the treatment of adamantinoma of the tibia.

Adolescent↗

Methods of banking bone and cartilage for allograft transplantation.

Storage of bone for use as allograft has become an important endeavor because banked bone is becoming increasingly useful and popular as a substitute for, or as a supplement to, autograft bone. Methods have been developed for safe and reliable bone banking, including standard criteria for acceptable donors, proven techniques of retrieval of tissue, and appropriate storage facilities and conditions. In contrast, cartilage banking is still an investigative procedure, but current research may provide more effective approaches to maintaining viable cells during freezer storage of osteochondral allografts.

Animals↗

The use of frozen cadaveric allografts in the management of patients with bone tumors of the extremities.

Since 1971, 314 frozen osteoarticular and intercalary cadaveric allografts have been implanted primarily in the management of patients with aggressive or malignant tumors of bone. The procedure, although arduous and sometimes resulting in complications, was successful in preserving the limb and restoring function to the part in over 70 per cent of the patients. Key to the system is the maintenance of a high-quality procurement and banking program.

Adolescent↗