ABSTRACT
PURPOSE: The scapula is a relatively common site for chondrosarcoma to develop in contrary to the clavicle, which is rarely affected by these tumors. The aim of this study is to determine the functional and oncological outcome for patients treated operatively for scapular or clavicular chondrosarcoma. METHODS: In this single-center retrospective study, we included a sample of 20 patients that received the diagnosis of a primary chondrosarcoma of the scapula or clavicle. Of the surviving patients, the functional function was assessed using the DASH and the PROMIS Physical Function-Upper Extremity. Patients were longitudinally tracked for their oncological outcome. RESULTS: All patients were followed for at least 2 years or until death. The mean age of the cohort was 47 years. Eighteen patients suffered from a chondrosarcoma of the scapula, and in 2 patients, the tumor was located in the clavicle. Metastasis, local recurrence and a higher tumor grade were all associated with a decreased overall survival. For the patients with a chondrosarcoma of the scapula, the average DASH score was 16 ± 16 and the mean PROMIS Physical Function-Upper Extremity score was 48 ± 10. Patients with both an intact rotator cuff and glenoid had a better physical function. CONCLUSIONS: Upper extremity function after (partial) scapulectomy varied depending on whether the glenoid was spared and whether a functioning shoulder abductor remained. When the resection spared these structures, then excellent functional outcomes were reported. Oncologic outcomes depended upon the grade of the tumor and whether local recurrence and metastases occurred.
Subject(s)
Bone Neoplasms/surgery , Chondrosarcoma/surgery , Clavicle/surgery , Scapula/surgery , Adult , Aged , Bone Neoplasms/diagnosis , Bone Neoplasms/mortality , Chondrosarcoma/diagnosis , Chondrosarcoma/mortality , Female , Follow-Up Studies , Humans , Limb Salvage , Male , Middle Aged , Range of Motion, Articular , Retrospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
Liposarcoma is an uncommon connective tissue tumor arising from lipoblast cells. The lesion is located in body soft parts and rarely arises from the bones. The tumors are variable in presentation ranging from benign well-differentiated tumors to myxoid and round cell-dedifferentiated and pleomorphic forms which can present with metastases. The lesions are most often treated by surgical resection. Chemotherapy and radiation may be added to the treatment of the more malignant variants with some success.
Subject(s)
Liposarcoma/diagnosis , Soft Tissue Neoplasms/diagnosis , Humans , Liposarcoma/therapy , Soft Tissue Neoplasms/therapy , Survival AnalysisABSTRACT
'Schwannomas are unusual benign tumors which arise from the surface of neural elements of the body or within the brain. They do not as a rule metastasize but may cause sometimes severe local problems on the nerves, blood vessels and adjacent bone. The tumors arise from the Sheath of Schwann, a structure on the surface of a nerve. The lesions may expand and cause considerable damage to adjacent tissues. They do not arise within bone since there are no Sheaths of Schwann within the osseous tissue but may cause local damage to the bony cortex and sometimes fractures. Rarely the lesions may metastasize and cause patients' death. The treatment is usually local resection, and most often is successful although may cause damage to the adjacent nerve.
Subject(s)
Neurilemmoma , Soft Tissue Neoplasms , Humans , Neurilemmoma/pathology , Neurilemmoma/therapy , Rare Diseases , Soft Tissue Neoplasms/pathology , Soft Tissue Neoplasms/therapyABSTRACT
A presentation defining the nature, characteristics, causation, treatment and outcome of patients with lesions formerly known as malignant fibrous histiocytoma and now as pleomorphic spindle cell sarcoma is clearly a very difficult subject. Many authors do not believe that the tumor exists and instead describe them as forms of fibrosarcomas, fibromyxoid lesions, dedifferentiated chondrosarcomas or even leiomyosarcomas. The reasons for this confusion are presumably related to the fact that the malignant pleomorphic spindle cell sarcoma does not seem to be a distinct type of lesion with specific histologic and genetic characteristics. Instead, the tumor has at least four separate histologic variations and no specific gene signature and in fact does not seem to be either familial or ethnic in presentation. In view of the fact that the tumor was traditionally the most frequently encountered malignant soft-tissue neoplasm, the world of orthopedic oncology is clearly distressed by the problems that these patients have and is joined by the radiation oncologists and chemotherapists in seeking new solutions.
Subject(s)
Sarcoma/pathology , Soft Tissue Neoplasms/pathology , Adult , Age Factors , Aged , Combined Modality Therapy , Female , Giant Cells/pathology , Histiocytoma, Malignant Fibrous/classification , Histiocytoma, Malignant Fibrous/pathology , Humans , Male , Middle Aged , Neoplasm Grading , Retrospective Studies , Sarcoma/classification , Sarcoma/therapy , Soft Tissue Neoplasms/classification , Soft Tissue Neoplasms/therapy , Survival Rate , Terminology as TopicABSTRACT
Gaucher disease is an uncommon autosomal recessive disorder characterized by lysosomal storage of glucosyl ceramide, a material released during cell degradation. Patients with Gaucher disease often have significant hematologic, bone structural, and visceral problems which sometimes greatly affect their health and life style. Based on some extraordinary scientific discoveries over the past 45 years, a treatment system has evolved which consists of administration of an enzyme, which destroys the lysosome-stored material and to some extent restores the patients to good health. There are still some problems for these patients; however, and the purpose of the study is to define some of the clinical, sociologic, and psychologic problems with a specially designed questionnaire. Questionnaire data was collected for 128 patients from two institutions with complete anonymity, and the information compared against data from a National Health Interview Survey. The results show that many of the patients still have fairly extensive problems, which could possibly be helped by some alterations in treatment protocols.
Subject(s)
Gaucher Disease/complications , Adolescent , Adult , Aged , Aged, 80 and over , Bone Diseases/etiology , Child , Child, Preschool , Female , Gaucher Disease/genetics , Gaucher Disease/psychology , Gaucher Disease/therapy , Heart Diseases/etiology , Hematologic Diseases/etiology , Humans , Joint Diseases/etiology , Lung Diseases/etiology , Male , Middle Aged , Pregnancy , Pregnancy Complications/etiology , Surveys and Questionnaires , United StatesABSTRACT
Twenty-seven patients developed infection following bulk allograft transplantation and were treated with resection of the allograft, placement of an antibiotic-impregnated polymethylmethacrylate (PMMA) spacer, and intravenous antibiotics. Overall, the infection was eradicated in 14 (52%) of 27 patients. Of the 11 patients who did not undergo allograft reimplantation, 5 underwent amputations for persistent infection in the presence of the spacer and 4 had a retained spacer at most recent follow-up. No significant correlation was noted between successful eradication of the infection and age, sex, diagnosis, adjuvant therapy, acute or chronic infection, number of operative procedures, type of allograft procedure, duration of antibiotics, or type of organism. Although deep infection of allograft transplantations continues to result in a high rate of failure, this method of management results in successful limb salvage in almost half of the patients.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Bone Transplantation/adverse effects , Drug Delivery Systems , Postoperative Complications/drug therapy , Adolescent , Adult , Bone Cements/therapeutic use , Bone Neoplasms/surgery , Comorbidity , Female , Humans , Male , Middle Aged , Polymethyl Methacrylate/therapeutic use , Postoperative Complications/microbiology , Regression Analysis , Retrospective Studies , Transplantation, HomologousABSTRACT
Radiofrequency (RF) treatment has been used for a variety of malignant and benign conditions. However, treatment of a bone malignancy has yet to be reported. The authors present a 21-year old woman with multifocal epithelioid hemangioendothelioma (EH) treated by a combination of surgical excision, chemotherapy and four RF ablations. Follow-up radiographs of the RF-treated sites reveal no evidence of recurrent disease 71, 58, 49 and 33 months, respectively, after treatment.
Subject(s)
Bone Neoplasms/therapy , Hemangioendothelioma, Epithelioid/therapy , Adult , Antineoplastic Agents/therapeutic use , Catheter Ablation , Combined Modality Therapy , Female , Foot Bones , Humans , Interferon-alpha/therapeutic use , Leg BonesABSTRACT
The diagnosis and grading of bone tumors remains a challenging problem. We studied the relationship between histologic grade and cytofluorometric cellular DNA and RNA content in 108 primary bone tumors. The data included DNA ploidy, mean DNA content (MDC), S-phase fraction (SPF), mean RNA content (MRC) and RNA/DNA ratio (RDR; MRC/MDC) which represents the RNA content normalized for the DNA content. Benign tumors had a diploid stem line with low MDC (mean; 1.04), low SPF (0.9), high MRC (2.41) and high RDR (2.31). Giant cell tumors of bone, which are locally aggressive benign tumors, showed diploidy with relatively higher MDC (1.07, p < 0.01) and SPF (2.6, p < 0.01) and lower MRC (1.81, p < 0.01) and RDR (1.69, p < 0.01). Similar results were obtained in low-grade sarcomas. In high-grade sarcomas, the data depended on the histologic findings. Pleomorphic sarcomas such as osteosarcomas revealed aneuploidy with remarkably higher MDC (1.70 in osteosarcomas, p < 0.01) and SPF (6.5, p < 0.01), but lower RDR (1.70, p < 0.01). In contrast, small cell sarcomas, such as Ewing's sarcomas, showed diploidy with low MDC (1.11 in Ewing's sarcomas, N.S.) and SPF (2.5, p < 0.01) and extremely low RDR (1.34, p < 0.01). The RDR value was higher in well-differentiated tumors than in primitive tumors, rendering it useful in grading bone tumors with a diploid stem line. By combining the RDR value with the MDC value, 96% of diploid sarcomas could be distinguished from benign tumors. These results indicate that cellular DNA and RNA content analysis may be of value in assessing the malignant potential of diploid as well as aneuploid bone sarcomas.
Subject(s)
Bone Neoplasms/genetics , DNA, Neoplasm/analysis , RNA, Neoplasm/analysis , Bone Neoplasms/classification , Bone Neoplasms/pathology , Diploidy , Flow Cytometry/methods , Giant Cell Tumor of Bone/classification , Giant Cell Tumor of Bone/genetics , Giant Cell Tumor of Bone/pathology , Humans , Neoplasm Staging , Osteosarcoma/classification , Osteosarcoma/genetics , Osteosarcoma/pathologyABSTRACT
Two hundred lower extremity osteoarticular allografts (in 200 patients) performed for aggressive or malignant bone tumors between 1976 and 1997 included 124 grafts of the distal femur, 46 of the proximal tibia, and 30 of the proximal femur. Seventy-four patients did not receive chemotherapy, and 126 received either adjuvant or neoadjuvant therapy. The diagnoses, mean ages, and length of followup were different for the two groups because most of the patients in the chemotherapy group had osteosarcoma, whereas the largest number in the control group had chondrosarcoma or parosteal osteosarcoma. The extent of the surgery was essentially the same for both patient groups, as is reflected by a low recurrence rate (7% for the control and 6% for the chemotherapy group). A statistical comparison of the various parameters showed that the infection, fracture, and amputation rates were the same, but the nonunion rate was markedly increased in the patients who received chemotherapy (32% versus 12%). Cox regression and Kaplan-Meier studies showed that chemotherapy had a significant effect on outcome, with the success rates for the two groups being quite different (72% versus 56%). The results for the distal femur showed a greater effect than for either the proximal tibia or the proximal femur. Analysis of these data suggest the distal femur is perhaps the most prone to healing problems, possibly based in part on the extent of the surgery. A final study supports the concept that the results improved in later years, suggesting a modification or application of the drugs used, better selection of patients, and improvements in surgical technique.
Subject(s)
Bone Neoplasms/surgery , Bone Transplantation , Chondrosarcoma/surgery , Osteosarcoma/surgery , Adolescent , Adult , Aged , Bone Neoplasms/drug therapy , Chemotherapy, Adjuvant , Child , Chondrosarcoma/drug therapy , Female , Femur/transplantation , Humans , Male , Middle Aged , Osteosarcoma/drug therapy , Plastic Surgery Procedures , Tibia/transplantation , Transplantation, HomologousABSTRACT
The following report describes two consecutive brothers from a nonimmigrant family, with no identifiable predisposing factors, who presented with osteosarcomas of their distal femurs, one at the age of 18 years and the other at the age of 21 years. Until a cost-effective program is developed to screen for osteosarcoma, a detailed family history should be obtained from every new patient with osteosarcoma and parents should be urged to schedule early evaluations of siblings with complaints of painful extremities. Increased frequency of cytogenetic studies to screen for genetic abnormalities in patients with osteosarcoma is recommended to help elucidate the cause of osteosarcoma.
Subject(s)
Femoral Neoplasms/genetics , Osteosarcoma/genetics , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Arthroplasty, Replacement, Knee , Cytogenetics , Fatal Outcome , Femoral Neoplasms/surgery , Humans , Magnetic Resonance Imaging , Male , Mass Screening , Neoadjuvant Therapy , Osteosarcoma/secondary , Osteosarcoma/surgery , Tomography, X-Ray ComputedABSTRACT
A retrospective review of patients with allograft fractures was done at the authors' institution. Between 1974 and 1998, 185 of 1046 (17.7%) structural allografts fractured in 183 patients at a mean of 3.2 years after transplantation. Initial allograft fixation included internal fixation with plates and screws in 181 patients. Patients with grafts that were longer than the average length (15.5 cm) tended to have worse results. Adjuvant therapy had no effect on fracture rate. Seventy-three patients with fractures had other allograft complications. Infection and nonunion with allograft fracture significantly worsened the outcome. The incidence of fracture in the patients with osteoarticular and arthrodesis transplants was significantly higher than those patients who had intercalary and composite reconstructions. Treatment of the allograft fractures included open reduction and internal fixation in 41 patients, reconstruction with a new allograft in 38, allograft-prosthesis composite in five, oncologic prosthesis in 19, amputation in 15, arthroscopic removal of loose bodies in three, resurfacing of fractured osteoarticular allograft surfaces in 39, allograft removal and cement spacer placement in 15. Twenty patients did not receive treatment. Eight of the fractures in patients who were not treated healed spontaneously. Outcomes were judged as excellent in nine patients (4.9%), good in 72 patients (38.9%), fair in 17 patients (9.2%), and in 85 patients (45.9%) the allograft reconstruction failed.
Subject(s)
Bone Transplantation/adverse effects , Fractures, Bone/etiology , Adult , Amputation, Surgical , Arthrodesis/adverse effects , Arthroscopy , Bone Cements/therapeutic use , Bone Neoplasms/surgery , Bone Plates/adverse effects , Bone Screws/adverse effects , Bone Transplantation/pathology , Chemotherapy, Adjuvant , Female , Fracture Fixation , Fractures, Bone/surgery , Humans , Incidence , Internal Fixators/adverse effects , Joint Loose Bodies/surgery , Joints/surgery , Male , Prostheses and Implants , Radiotherapy, Adjuvant , Retrospective Studies , Surgical Wound Infection/etiology , Transplantation, Homologous , Treatment Outcome , Wound HealingABSTRACT
Nonunion of allograft-host junction after bone transplantation is not uncommon, and its treatment frequently is problematic. To improve the understanding of these nonunions, a retrospective review was performed of 163 nonunions in 945 patients who underwent allograft transplantation (17.3%) for various benign and malignant tumors at the authors' institution between 1974 and 1997. Of these 945 patients, 558 did not receive adjuvant therapy. Chemotherapy was administered to 354 patients and only 33 patients received radiation therapy alone. Seventy-one patients had radiation treatment and chemotherapy. Of the 163 patients who had nonunion develop at the allograft-host junction, there were 269 reoperations performed on the involved extremity. In 108 patients, treatment was successful resulting in union of the allograft-host junction. Forty-nine patients did not respond to multiple surgical treatment attempts. The greater the number of surgical procedures, the worse the outcome. The rate of nonunions increased to 27% for the patients who received chemotherapy as compared with 11% for the patients who did not receive chemotherapy. The order of allografts from highest rate of nonunion to lowest was as follows: alloarthrodesis, intercalary, osteoarticular, and alloprosthesis. Infection and fracture rates were higher in the patients with nonunions as compared with the patients without nonunions.
Subject(s)
Bone Transplantation/physiology , Bone and Bones/surgery , Adolescent , Adult , Age Factors , Aged , Arthrodesis , Bone Neoplasms/drug therapy , Bone Neoplasms/radiotherapy , Bone Neoplasms/surgery , Bone and Bones/physiopathology , Chemotherapy, Adjuvant , Chi-Square Distribution , Child , Child, Preschool , Chondrosarcoma/surgery , Female , Follow-Up Studies , Fractures, Bone/etiology , Giant Cell Tumor of Bone/surgery , Graft Survival , Humans , Joints/surgery , Male , Middle Aged , Osteosarcoma/surgery , Proportional Hazards Models , Radiotherapy, Adjuvant , Reoperation , Retrospective Studies , Sarcoma, Ewing/surgery , Surgical Wound Infection/etiology , Transplantation, Homologous , Treatment Outcome , Wound HealingABSTRACT
This report describes a chondromyxoid fibroma which developed in the distal part of the second metacarpal of a 12-year-old girl. The tumor is rare, perhaps the rarest of all bone tumors, and the occurrence in a metacarpal of a young female is extraordinarily uncommon.
Subject(s)
Bone Neoplasms/pathology , Fibroma/pathology , Metacarpus/pathology , Bone Neoplasms/diagnostic imaging , Child , Female , Fibroma/diagnostic imaging , Humans , Metacarpus/diagnostic imaging , RadiographyABSTRACT
BACKGROUND: There is little information on the natural history or treatment of osteochondromas arising from the distal aspect of either the tibia or the fibula. It is believed that there is a risk of deformation of the ankle if these exostoses are left untreated or if the physis or neurovascular structures are injured during operative intervention. METHODS: We reviewed the records of twenty-three patients who had been treated for osteochondroma of the distal aspect of the tibia or fibula between 1980 and 1996. Four of the patients had hereditary multiple cartilaginous exostoses. There were seventeen male and six female patients, and the average age at the time of presentation was sixteen years (range, eight to forty-eight years). RESULTS: Preoperative radiographs showed evidence of plastic deformation of the fibula in eleven patients who had a large osteochondroma. Four patients elected not to have an operation. The tumor was excised in nineteen patients. Postoperatively, all nineteen patients had a Musculoskeletal Tumor Society score of 100 percent for function of the lower extremity with pain-free symmetrical and unrestricted motion of the ankle at the latest follow-up examination. Partial remodeling of the tibia and fibula gradually diminished the asymmetry of the ankles in all nineteen operatively managed patients; however, the remodeling was most complete in the younger patients. Pronation deformities of the ankle did not change after excision of the tumor. Complications of operative treatment included four recurrences (only three of which were symptomatic), one sural neuroma, one superficial wound infection, and one instance of growth arrest of the distal aspects of the tibia and fibula. CONCLUSIONS: Osteochondromas of the distal and lateral aspects of the tibia were more often symptomatic than those of the distal aspect of the fibula; they most commonly occurred in the second decade of life with ankle pain, a palpable mass, and unrestricted ankle motion. Untreated or partially excised lesions in skeletally immature patients may become larger and cause plastic deformation of the tibia and fibula and a pronation deformity of the ankle. Ideally, operative intervention should be delayed until skeletal maturity, but, in symptomatic patients, partial excision preserving the physis may be necessary for the relief of symptoms and the prevention of progressive ankle deformity. However, partial excision is associated with a high rate of recurrence, so a close follow-up is required. Skeletally mature patients who are symptomatic may require excision of the tumor.
Subject(s)
Bone Neoplasms/surgery , Fibula/surgery , Osteochondroma/surgery , Tibia/surgery , Adolescent , Adult , Bone Neoplasms/diagnostic imaging , Child , Female , Fibula/diagnostic imaging , Follow-Up Studies , Humans , Male , Middle Aged , Osteochondroma/diagnostic imaging , Postoperative Complications/epidemiology , Radiography , Tibia/diagnostic imagingABSTRACT
We reviewed the results of 19 patients with hemipelvic allograft reconstructions after periacetabular tumor resection at Massachusetts General Hospital from 1977 to 1996. Histological diagnosis showed chondrosarcoma (in 7 patients), osteosarcoma in 5, and other tumors in 7. Seventeen patients were continuously disease-free for 12-228 months (mean, 57 months). One patient died of sepsis caused by wound infection after surgery for local recurrence. Results of evaluation (by the Mankin scale) in the 19 patients were: excellent in 1, good in 6, fair in 5, and failure in 7. Of the 19 patients, 5 (28%) had wound infection, and 3 patients had local recurrence. Allograft fracture was observed in 1 patient. Allograft and bipolar prosthesis were used in 11 patients, and migration of the bipolar prosthesis was observed in 4 of these patients. In 7 patients the femoral head was preserved; 2 patients received total hip arthroplasty because of osteoarthrosis in the hip joint or collapsed allograft. Migration of the bipolar prosthesis, with eventual osteoathrosis in the hip joint was also observed. However, hemipelvic allograft was thought to be an alternative useful reconstruction method despite the unresolved problems of loosening, dislocation, and breakage of the custom-made prosthetic hemipelvis.
Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip , Bone Neoplasms/surgery , Pelvic Bones/surgery , Acetabulum/diagnostic imaging , Adult , Bone Neoplasms/diagnostic imaging , Chondrosarcoma/diagnostic imaging , Chondrosarcoma/surgery , Female , Follow-Up Studies , Giant Cell Tumor of Bone/diagnostic imaging , Giant Cell Tumor of Bone/surgery , Humans , Male , Middle Aged , Osteosarcoma/diagnostic imaging , Osteosarcoma/surgery , Pelvic Bones/diagnostic imaging , Postoperative Complications/diagnostic imaging , Radiography , Sarcoma, Ewing/diagnostic imaging , Sarcoma, Ewing/surgeryABSTRACT
BACKGROUND: Chondroblastoma of bone is a rare lesion, and few large series have been reported. The purpose of this paper is to report forty-seven cases treated by one group of surgeons and to identify factors associated with more aggressive tumor behavior. METHODS: Seventy-three patients with chondroblastoma of bone were treated between 1977 and 1998. We were able to obtain historical data, imaging studies, histological findings, and adequate personal or telephone follow-up to determine the outcome for forty-seven patients. RESULTS: The lesions were distributed widely in the skeleton, but most were in the epiphyses or apophyses of the long bones, especially the proximal part of the tibia (eleven tumors) and the proximal part of the humerus (ten tumors). The principal presenting symptoms were pain and limitation of movement. The treatment consisted of a variety of procedures, but the majority of the patients had intralesional curettage and packing with allograft or autograft bone chips or polymethylmethacrylate. Most of the patients had an excellent functional result, although in three osteoarthritis developed in the adjacent joint. Seven patients (15 percent) had a local recurrence; three of them had a second recurrence and one, a third recurrence. One patient died of widespread metastases, and another who had metastases to multiple sites was alive and disease-free after aggressive treatment of the metastatic lesions. CONCLUSIONS: While the size of the lesion, the age and gender of the patient, the status of the growth plate, and an aneurysmal-bone-cyst component to the tumor had no significant effect on the recurrence rate, lesions around the hip (the proximal part of the femur, the greater trochanter, and the pelvis) accounted for the majority (five) of the seven recurrent tumors and one of the two metastatic lesions.
Subject(s)
Bone Neoplasms/surgery , Chondroblastoma/surgery , Adolescent , Adult , Bone Neoplasms/epidemiology , Child , Chondroblastoma/epidemiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Postoperative Complications/epidemiologyABSTRACT
BACKGROUND: There are two general categories of drug resistance: acquired and intrinsic. The mechanisms involved in acquired drug resistance have been extensively studied, and several mechanisms have been described. However, the mechanisms responsible for intrinsic drug resistance have not been elucidated, to our knowledge. The purpose of the present study was to investigate the cytological and biochemical differences between acquired and intrinsic drug resistance in osteosarcoma cells. METHODS: We previously isolated a clonal cell line (MOS/ADR1) to study acquired resistance in osteosarcoma by exposure of parental murine osteosarcoma cells (MOS) to doxorubicin. In the present study, we cloned a new, intrinsically resistant cell line (MOS/IR1) by single-cell culture of MOS cells and we investigated the differences in cell phenotype and the mechanisms of resistance in both of these resistant clones. RESULTS: The MOS/ADR1 and MOS/IR1 cells were sevenfold and fivefold more resistant to doxorubicin than the parental murine osteosarcoma cells. Morphologically, the MOS/ADR1 cell line was composed of polygonal cells, whereas the MOS/IR1 cell line consisted of plump spindle cells with long cytoplasmic processes. The MOS/IR1 cells showed a much lower level of alkaline phosphatase activity than did the MOS/ ADR1 and MOS cells. There were no substantial differences in the cellular DNA content or the doubling time among these three lines. Overexpression of the P-glycoprotein involved in the function of an energy-dependent drug-efflux pump was detected in the MOS/ADR1 cells but not in the MOS/ IR1 cells. After the cells were incubated with doxorubicin for one hour, the two resistant lines had less accumulation of the drug than did the parent line (p < 0.05). The addition of a P-glycoprotein antagonist, verapamil, or the depletion of cellular adenosine triphosphate resulted in a marked increase in the accumulation of doxorubicin in the MOS/ADR1 cells (p < 0.05) but not in the MOS/ IR1 cells. The MOS/ADR1 cells were found to exhibit cross-resistance only to substrates for P-glycoprotein (such as doxorubicin, vincristine, and etoposide), whereas the MOS/IR1 cells were resistant to all of the drugs studied (including cisplatin and methotrexate). The degree of drug resistance in the MOS/IR1 cells was found to be associated with the molecular weight of the drugs (p < 0.05). Permeabilization of the plasma membrane by saponin increased both the accumulation of doxorubicin (p < 0.05) and the cytotoxic activity of this drug in all lines, but the effects were most pronounced in the MOS/IR1 cells. CONCLUSIONS: Taken together, this data suggests that reduced drug accumulation in the MOS/IR1 cells may be due to the effect of decreased permeability of the plasma membrane on the transport of drugs from the extracellular environment into the cytosol of the cell and that this may be the mechanism responsible for intrinsic resistance to multiple drugs in the MOS/IR1 cell line. CLINICAL RELEVANCE: Current drug treatment for human osteosarcoma may include multiple chemotherapeutic agents, such as doxorubicin, cisplatin, and methotrexate. These drugs exhibit different cytotoxic actions and, thus, the mechanisms of resistance to individual drugs vary. Clinical resistance to multidrug chemotherapy may be observed in tumors that recur after repetitive chemotherapy and in previously untreated tumors. In the former group, a tumor cell may express multidrug resistance by combining several different mechanisms due to its exposure to various drugs. In the latter group, however, this is not likely. Decreased intracellular drug accumulation due to reduced permeability of the plasma membrane, found in the MOS/IR1 cells, is one possible mechanism and may explain the intrinsic resistance to multidrug chemotherapy for the treatment of osteosarcoma. Further study regarding the resistance mechanism in the MOS/IR1 cells may help to overcome the intrinsic drug resistance in oste
Subject(s)
Bone Neoplasms/drug therapy , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Osteosarcoma/drug therapy , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Adenosine Triphosphate/antagonists & inhibitors , Alkaline Phosphatase/analysis , Animals , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Agents/therapeutic use , Biological Transport, Active/drug effects , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Calcium Channel Blockers/therapeutic use , Cell Division , Cell Membrane Permeability/drug effects , Clone Cells , Cross Reactions , Cytoplasm/ultrastructure , DNA, Neoplasm/analysis , Doxorubicin/therapeutic use , Gene Expression Regulation, Neoplastic , Humans , Mice , Molecular Weight , Osteosarcoma/genetics , Osteosarcoma/metabolism , Osteosarcoma/pathology , Phenotype , Saponins/therapeutic use , Tumor Cells, Cultured , Verapamil/therapeutic useABSTRACT
Massive structural allografts used for replacement of bone defects after removal of bone tumors have several complications, including fracture, infection, and nonunion. To decrease the rate of infection, irradiation of selected allografts before their implantation was performed. This study evaluated the complications in patients with these irradiated grafts. Twenty-four patients were identified who had received allografts from 1987 through 1991 that were irradiated before implantation. The dosage of radiation was between 10 kGy and 30 kGy. The mean length of followup of the patients was 5 years (range, 2-9 years). These grafts were compared with a control group of grafts that were not irradiated but were implanted during the same time and used for similar diagnostic problems with defects of similar size. The outcomes of the groups differed significantly only in the incidence of allograft fracture. These findings indicate that high-dose irradiation to bone allografts is associated with a higher rate of fracture than are similar reconstructions using nonirradiated allografts.
Subject(s)
Bone Neoplasms/surgery , Bone Transplantation , Bone and Bones/radiation effects , Fractures, Bone/etiology , Postoperative Complications , Adolescent , Adult , Child , Chondrosarcoma/surgery , Female , Humans , Male , Middle Aged , Osteosarcoma/surgery , Radiation , Transplantation, Homologous , TransplantsABSTRACT
The adverse effects of osteoarthritis on the quality of life for tens of millions of people and on the costs of health care and economic productivity make it a major health problem that will increase in incidence and impact with the aging of the population. Although in most patients the cause of osteoarthritis remains unknown and no cure has been identified, appropriate diagnosis and treatment, including education of the patients, can minimize symptoms and help patients maintain active and productive lives. Accomplishing this aim requires that physicians have an understanding of the pathophysiology of joint degeneration and the relationships between joint degeneration and the clinical syndrome of osteoarthritis. Although much remains to be learned about the development and progression of the joint degeneration responsible for osteoarthritis, it is clear that the loss of articular cartilage results from disruption of the structural integrity of the articular cartilage coupled with or caused by an imbalance in the anabolic and catabolic activity of the tissue. The progression of joint degeneration varies considerably among patients. In some individuals the joint degenerates rapidly; in others the degenerative changes progress slowly over decades and in others the disease may remain stable. In rare patients, the joint degenerative changes spontaneously improve. Although joint degeneration is the underlying cause of the symptoms of osteoarthritis, including joint pain and loss of joint function, not all patients with joint degeneration have symptoms of osteoarthritis. Future therapeutic approaches may include disease-modifying drugs and surgical procedures that correct mechanical abnormalities, debride joints, and replace degenerated articular cartilage with implants that stimulate restoration of a cartilaginous joint surface. Development of methods to detect and monitor subtle changes in cartilage metabolism and identify the joint changes that precede loss of articular cartilage may make it possible to detect the earliest signs of osteoarthritis, when therapeutic interventions have the greatest potential for preventing progression of the disease.