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Biomedical subjects

M C Gebhardt

Publications and source records attributed to M C Gebhardt.

At least 37 records · Page 2Linked to original sources
PubMed2000

Chondroblastoma of bone.

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.

Adolescent↗
PubMed1999

Extraskeletal myxoid chondrosarcoma of the knee.

Extraskeletal myxoid chondrosarcoma is an uncommon neoplasm, accounting for less than 2% of all soft tissue sarcomas. It affects adult males with a median age in the fifth decade at the time of diagnosis. The tumor usually arises in the deep soft tissues, especially in the lower extremities. Patients present with a gradually enlarging mass that may or may not be associated with pain. This report describes a 25-year-old man who initially presented with a 4- to 5-year history of right knee pain and an enlarging mass in the right knee. Evaluation revealed a cartilaginous neoplasm with no evidence of metastatic disease. The tumor was widely excised and an allograft reconstruction was performed. The patient was closely followed with an eventual above the knee amputation for recurrent myxoid chondrosarcoma. At 34 months, retroperitoneal metastases were noted on abdominal CT. The patient underwent a left radical nephrectomy, renal vein thrombectomy and enucleation of the mass in the right kidney, distal pancreatectomy, and splenectomy. The patient received postoperative chemotherapy. Forty-eight months after initial diagnosis, the patient was found to have recurrent abdominal and retroperitoneal lesions. At 64 months, the patient died from complications of extraskeletal myxoid chondrosarcoma.

Abdominal Neoplasms↗
PubMed1999

Tumor reconstruction.

This article discusses opinions for reconstruction of bony defects created by tumor resections. The literature is reviewed, and the results of different reconstruction methods from the Massachusetts General and Children's Hospitals' database are discussed. The authors' treatment goals and algorithms are reviewed as well as the rationale behind them.

Algorithms↗
PubMed1999

Decreasing length of hospital stay in treatment of osteoid osteoma.

Ninety-eight operative procedures were performed for treatment of osteoid osteoma since 1978 at the authors' institution. During these years there was a progressive decrease in the length of hospital stay, decreasing from a mean of 6.8 days between 1978 and 1980 to 2.6 days between 1994 and 1996. Factors that influenced the length of stay after a surgical procedure include patient age, lesion location, choice of procedure, and surgeon. However, the decline in length of stay with time is independent of these factors, and antedates the era of managed care. Increased reliance on more conservative surgical procedures has markedly diminished the length of hospital stay required in the care of these patients.

Adolescent↗
PubMed1999

Chondrosarcoma of bone: an assessment of outcome.

BACKGROUND: The data on 227 patients who had been managed for a chondrosarcoma at one institution were reviewed to determine the nature of the lesions, the predictors of outcome, and whether there were any ways to change the treatment approaches to improve the results. METHODS: The patients were followed for a mean duration of six years (range, three to twenty-five years). The mean age of the patients was forty-seven years (range, nine to eighty-four years). The most prevalent sites of the tumors were the femur (seventy-eight), the pelvis (fifty-one), and the humerus (thirty-nine). The tumors were divided into two groups according to histological grade. Eighty-six tumors (sixteen atypical enchondromas and seventy grade-1 chondrosarcomas) that were locally destructive but were associated with a low likelihood of metastasis were considered to be low-grade. The remaining 141 lesions, which were locally destructive, potentially metastatic, and capable of causing death, were thought to be high-grade. One hundred and three of these 141 lesions were grade 2, and thirty-eight were grade 3 (eighteen of the thirty-eight were grade 3 only, and twenty were both grade 3 and dedifferentiated). Two hundred and twenty-four patients were managed with resection and a limb-sparing procedure; the remaining three patients had an amputation. Postoperative adjuvant radiation was used for fifty-six patients; chemotherapy, for thirty-five; and both radiation and chemotherapy, for nineteen. Flow cytometric patterns were analyzed for 105 patients. RESULTS: The patients who had a high-grade tumor were older than those who had a low-grade tumor (mean age [and standard deviation], 50+/-17.0 years compared with 40+/-15.9 years; p < 0.001). Pathological fracture, metastasis, local recurrence, and death were more prevalent in the group that had a high-grade lesion (p < 0.001). Predictors of metastasis and death in that group of patients included local recurrence, a pelvic location of the tumor, a tumor that was more than 100 cubic centimeters in size, a ploidic abnormality (aneuploidy coupled with a high mean DNA index), a histological grade of 3, and a dedifferentiated type of tumor (p < 0.001). CONCLUSIONS: Although the data are suggestive, with the numbers available for study we could not detect a significant difference in the rates of pulmonary metastasis and death between the patients who had a grade-3 lesion and those who had a grade-3 lesion that was also dedifferentiated. However, the interval between diagnosis and death was 32+/-22.8 months for the patients who had a grade-3 lesion compared with 5+/-3.7 months for those who had a grade-3 lesion that was also dedifferentiated (p < 0.001). Overall, patients who had had a resection with wide margins (margins extending outside the reactive zone) had a longer duration of survival than did those who had had a so-called marginal resection (margins extending outside the tumor but within the reactive zone) or an intralesional resection (margins within the lesion) (p < 0.04). Adjunctive chemotherapy or radiation, or both (which, it must be noted, was used, without a protocol, in a relatively small number of patients), after an intralesional resection, for recurrent disease, or for distant metastasis did not appear to alter the outcome.

Adolescent↗
PubMed1998

Actin organization associated with the expression of multidrug resistant phenotype in osteosarcoma cells and the effect of actin depolymerization on drug resistance.

We have previously reported that P-glycoprotein (Pgp)-overexpressing multidrug resistant (MDR) osteosarcoma cells were functionally more differentiated than their parent cells. The present study showed that in the parent cells, the actin filaments were sparsely distributed or were diffusely spread throughout the cytoplasm, whereas the MDR osteosarcoma cells exhibited a remarkable increase in well-organized actin stress fibers. Furthermore, dihydrocytochalasin B, a specific inhibitor of actin polymerization, dramatically disrupted this network of stress fibers, increased the intracellular accumulation of doxorubicin (DOX) and modified the resistance against DOX. These results indicate that the organization of actin filaments associated with cellular differentiation may be involved in the expression of Pgp function in the MDR osteosarcoma cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Individualizing management of aggressive fibromatoses.

PURPOSE: To examine prognostic indicators in aggressive fibromatoses that may be used to optimize case-specific management strategy. METHODS AND MATERIALS: One hundred and seven fibromatoses presenting between 1971 and 1992 were analyzed. The following treatment modalities were utilized: (a) surgery alone for 51 tumors; (b) radiation alone for 15 tumors; and (c) radiation and surgery (combined modality) for 41 tumors. Outcome analysis was based on 5-year actuarial local control rates. RESULTS: Control rates among surgery, radiation therapy, and combined modality groups were 69%, 93%, and 72%. Multivariate analysis identified age < 18 years, recurrent disease, positive surgical margins, and treatment with surgery alone as predictors for failure. Patients treated with surgery alone had control rates of 50% (3 of 6) for gross residual, 56% for microscopically positive margins, and 77% for negative margins. Radiation and surgery resulted in rates of 59% for gross residual, 78% for microscopically positive margins, and 100% (6 of 6) for negative margins. For recurrent vs. primary tumors, control was achieved in 48% vs. 77%, 90% vs. 100% (5 of 5), and 67% vs. 79% in the Surgery, Radiation, and Combined modality Groups, respectively. Patients presenting with multiple disease sites tended to have aggressive disease. A radiation dose-control relation to > 60 Gy was seen in patients with unresected or gross residual disease. Of the patients, 23 with disease involving the plantar region had a control rate of 62%, with significantly worse outcomes in children. CONCLUSIONS: These results are consistent with those found in the relevant literature. They support primary resection with negative margins when feasible. Radiation is a highly effective alternative in situations where surgery would result in major functional or cosmetic defects. When negative surgical margins are not achieved in recurrent tumors, radiation is recommended. Perioperative radiation should be considered in other high-risk groups (recurrent disease, positive margins, and plantar tumors in young patients). Doses of 60-65 Gy for gross disease and 50-60 Gy for microscopic residual are recommended. Observation may be considered for primary tumors with disease remaining in situ when they are located such that progression would not cause significant morbidity. Although plantar lesions in children may represent a group at high risk for recurrence or aggressive behavior, the greater potential for radiation-induced morbidity in this group must also temper its use. Given the inconsistent nature and treatment response of this tumor, it is fundamental that treatment recommendations should be made based on the risk:benefit analysis for the individual patient, dependent on tumor characteristics and location, as well as patient characteristics and preferences.

Adolescent↗
PubMed1998

Role of glutathione in cisplatin resistance in osteosarcoma cell lines.

This study was designed to examine whether and how glutathione and catalase increase the resistance of osteosarcoma cells to the toxicity of cisplatin. Eight osteosarcoma cell lines were exposed to varying concentrations of cisplatin, and a [3H]thymidine incorporation study then estimated their drug sensitivity. Cells were pretreated with aminotriazole and buthionine sulfoximine to depress catalase and glutathione activities and then entered into the same protocol to assess their sensitivity to cisplatin. Intracytoplasmic levels of catalase and glutathione were measured before and after the treatments. Cisplatin-glutathione conjugates were created to examine how glutathione might depress the toxicity of cisplatin. Although the cell lines differed in the magnitude of their response to cisplatin, there was a statistical correlation between intrinsic glutathione content and cisplatin resistance. Pretreatment with aminotriazole reduced catalase activity by 84% but did not change the sensitivity to cisplatin. Depletion of glutathione activity by 70% increased the sensitivity of the cells to the cytotoxicity of cisplatin. In addition, cisplatin was detoxified following conjugation with glutathione. The increased sensitization to cisplatin toxicity caused by the depletion of glutathione and cisplatin detoxification after the in vitro reaction of glutathione to cisplatin indicated that the formation of the glutathione-cisplatin conjugate was an important mechanism in the cellular resistance to cisplatin. These data also demonstrated that catalase activity did not contribute to resistance to cisplatin and suggested that H2O2-induced oxidative stress did not significantly contribute to the cytotoxicity of cisplatin in osteosarcoma cells.

Adenosine Triphosphate↗
PubMed1998

Diagnosis and treatment of unicameral and aneurysmal bone cysts in children.

Bone cysts are commonly encountered clinical problems in the pediatric age group. The most common types of cysts are the unicameral and aneurysmal bone cysts. These benign lesions vary in their aggressiveness, clinical behavior and treatment. Both of these lesions are poorly understood in terms of their etiology, but effective treatment exists. These lesions represent a source of great consternation to both clinicians and families, for they weaken the bone and may be confused with malignant lesions. This review will focus on the two most commonly encountered cystic lesions in the pediatric population.

Bone Cysts, Aneurysmal↗
PubMed1998

Combination chemotherapy using vinblastine and methotrexate for the treatment of progressive desmoid tumor in children.

PURPOSE: We report the treatment of 10 children for progressive desmoid tumor not amenable to standard surgical or radiation therapy with the use of vinblastine (VBL) and methotrexate (MTX). PATIENTS AND METHODS: Ten patients aged 6.4 to 18 years with primary (two patients) or recurrent (eight patients) desmoid tumor were treated with VBL and MTX for 2 to 35 months. Patients with recurrent tumors had been previously treated with surgical resection with (two patients) or without (five patients) radiation therapy or with radiation therapy alone (one patient). No patient had previously received cytotoxic chemotherapy. The tumor response was assessed at routine intervals by physical examination and magnetic resonance imaging (MRI). RESULTS: Five patients had clinical evidence of response to therapy with complete resolution (three patients) or partial resolution (two patients) of physical examination and radiographic abnormalities. Three patients had stable disease during 10 to 35 months of treatment. Two of these patients had progressive disease 9 and 37 months after treatment stopped; one patient had no progression 16 months after therapy. Two additional patients with stable disease had chemotherapy discontinued after 2 and 3 months. Common side effects included mild alopecia and myelosuppression and moderate nausea and vomiting. In patients with responding tumors, MRI showed decreased tumor size and, in two patients, changes consistent with fibrosis and decreased cellularity of the tumor. CONCLUSION: Combination chemotherapy with VBL and MTX appears to control desmoid tumor without significant acute or long-term morbidity in most children. This may allow for further growth and development in these patients, which may decrease the morbidity of subsequent definitive therapy.

Adolescent↗
PubMed1998

Reconstruction of the distal aspect of the radius with use of an osteoarticular allograft after excision of a skeletal tumor.

Twenty-four patients had reconstruction of the distal aspect of the radius with use of an osteoarticular allograft, between 1974 and 1992, after excision of a giant-cell tumor (twenty patients), a desmoplastic fibroma (two patients), a chondrosarcoma (one patient), or an angiosarcoma (one patient). Nine giant-cell tumors were recurrent lesions, and eleven were extracompartmental primary lesions that had extended through the cortex or subchondral bone. The average age of the patients was 31.5 years (range, fifteen to sixty-one years); thirteen patients were female and eleven were male. Seventeen lesions involved the right wrist and seven involved the left wrist. The reconstruction was performed through a dorsoradial incision with use of a size-matched, preserved, fresh-frozen, distal radial allograft. All procedures included internal fixation and reconstruction of the radiocarpal ligaments. All patients were followed for a minimum of two years (average, 10.9 years; range, 2.1 to 22.3 years). At the time of follow-up, two patients -- one who had a giant-cell tumor and one who had a desmoplastic fibroma -- had a local recurrence. Eight patients needed a revision of the osteoarticular allograft, at an average of 8.1 years (range, 0.8 to 17.8 years) after the initial reconstruction. Seven of these patients had an arthrodesis and one had an amputation. The reason for the revision was a fracture of the allograft in four patients, recurrence of the tumor in one, pain in two, and volar dislocation of the carpus in one. There were fourteen other complications, including ulnocarpal impaction necessitating excision of the distal aspect of the ulna (four), painful hardware necessitating removal (four), rupture of the extensor pollicis longus tendon necessitating transfer of the extensor indicis proprius (two), fracture of the allograft necessitating open reduction and internal fixation (two), volar dislocation of the carpus necessitating closed reduction (one), and a ganglion of the dorsal aspect of the wrist necessitating excision (one). Of the sixteen patients in whom the osteoarticular allograft survived, three did not have pain, nine had pain in association with strenuous activities, and four had pain in association with moderate activities. Three patients reported no functional limitation, nine had limitation in the ability to perform strenuous activities, and four had limitation in the ability to perform moderate activities. The average range of motion of the wrist was 36 degrees of dorsiflexion, 21 degrees of volar flexion, 16 degrees of radial deviation, 15 degrees of ulnar deviation, 58 degrees of supination, and 72 degrees of pronation. Reconstruction of the distal aspect of the radius with use of an osteoarticular allograft was associated with a low rate of recurrence of the tumor, a moderately high rate of revision, little pain in association with common activities, good function, and a moderate range of motion. Osteoarticular allografts are an option for reconstruction of the distal aspect of the radius after excision of a malignant tumor or a recurrent or locally invasive benign lesion.

Adolescent↗
PubMed1998

Percutaneous radiofrequency coagulation of osteoid osteoma compared with operative treatment.

Osteoid osteoma, a benign bone tumor, has traditionally been treated with operative excision. A recently developed method for percutaneous ablation of the tumor has been proposed as an alternative to operative treatment. The relative outcomes of the two approaches to treatment have not previously been compared, to our knowledge. The rates of recurrence and of persistent symptoms were compared in a consecutive series of eighty-seven patients who were managed with operative excision and thirty-eight patients who were managed with percutaneous ablation with radiofrequency. Patients who had a spinal lesion were excluded. The minimum duration of follow-up was two years. There was a recurrence, defined as the need for subsequent intervention, after operative treatment in six (9 per cent) of sixty-eight patients who had been managed for a primary lesion and in two of nineteen who had been managed for a recurrent lesion. The average length of the hospital stay was 4.7 days for the patients who had a primary lesion and 5.1 days for those who had a recurrent lesion. There was a recurrence after percutaneous treatment in four (12 per cent) of thirty-three patients who had been managed for a primary lesion and in none of five who had been managed for a recurrent lesion. The average length of the hospital stay was 0.2 day for these thirty-eight patients. With the numbers available, we could detect no significant difference between the two treatments with regard to the rate of recurrence. The rate of persistent symptoms (that is, symptoms that did not necessitate additional treatment) was greater than the rate of recurrence. According to responses to a questionnaire, eight (30 per cent) of twenty-seven patients had persistent symptoms after operative treatment and six (23 per cent) of twenty-six patients had persistent symptoms after percutaneous treatment with radiofrequency. Two patients had complications after operative excision, necessitating a total of five additional operations. There were no complications associated with the percutaneous method. The results of the present study suggest that percutaneous ablation with radiofrequency is essentially equivalent to operative excision for the treatment of an osteoid osteoma in an extremity. The percutaneous method is preferred for the treatment of extraspinal osteoid osteoma because it generally does not necessitate hospitalization, it has not been associated with complications, and it is associated with a rapid convalescence.

Adult↗
PubMed1997

Expression of transforming growth factor-beta (TGF-beta) isoforms in osteosarcomas: TGF-beta3 is related to disease progression.

BACKGROUND: Transforming growth factor-beta (TGF-beta) is a multipotent growth factor affecting development, homeostasis, and tissue repair. In addition, increased expression of TGF-beta has been reported in different malignancies, suggesting a role for this growth factor in tumorigenesis. METHODS: Using immunohistochemistry, the expression, prevalence, and distribution of TGF-beta isoforms were evaluated in 25 high grade human osteosarcomas. The Cox proportional hazards models and Kaplan-Meier curves were calculated correlating disease free survival with TGF-beta expression. RESULTS: Expression of one or more TGF-beta isoforms was found in all the osteosarcomas. Immunoreactivity for TGF-beta1 and TGF-beta3 generally was stronger than for TGF-beta2. The cytoplasm of the tumor cells showed stronger staining than their surrounding extracellular stroma. Most notably, osteoclasts showed strong to intense staining for all three isoforms. In 11 of 25 specimens angiogenic activity was noted with staining of multiple small vessels in the tumor stroma. Expression of TGF-beta3, but not of TGF-beta2 or TGF-beta1, related to disease progression, such that there was a statistically significant decrease in the disease free interval as the immunoreactivity for TGF-beta3 increased. CONCLUSIONS: All osteosarcomas expressed TGF-beta in the cytoplasm of the tumor cells as well as in their extracellular stroma. The presence of TGF-beta in the endothelial and perivascular layers of small vessels in the tumor stroma suggests angiogenic activity of this growth factor. The expression of TGF-beta3 was correlated strongly with disease progression (P = 0.027). These data suggest that increased expression of TGF-beta isoforms, especially TGF-beta3, may play a role in osteosarcoma progression.

Adolescent↗
PubMed1997

Effect of timing of postoperative chemotherapy on survival of dogs with osteosarcoma.

BACKGROUND: After excision of primary tumors, initiation of chemotherapy for micrometastases is often delayed for 2 to 4 weeks to permit patient recovery and early healing of the surgical wound. However, studies using murine tumors have indicated that removal of a primary tumor may cause increased cell proliferation within micrometastases during the first 7 to 10 days after surgery, potentially rendering the micrometastases more susceptible to chemotherapy. Clinical trials assessing the value of early postoperative initiation of chemotherapy for human breast carcinoma have yielded conflicting results. Osteosarcoma of dogs is a naturally occurring model for human tumors likely to have micrometastases at the time of diagnosis. METHODS: Before surgery, 102 dogs with osteosarcoma were randomized to receive cisplatin and doxorubicin chemotherapy beginning either 2 days or 10 days after amputation. Survival analysis was performed for each treatment group and for a historic control group comprised of 162 dogs treated by amputation alone. RESULTS: Median survival times for dogs treated by amputation alone and for dogs receiving chemotherapy beginning 2 or 10 days after surgery were 5.5, 11.5, and 11.0 months, respectively. Survival was significantly longer for each of the two groups of dogs receiving chemotherapy than for control dogs (P < 0.0001). There was no significant difference in survival between treatment groups (P = 0.727). CONCLUSIONS: These results do not disprove the theory that removal of a primary tumor alters the growth kinetics of metastases, but do imply that there is no substantial advantage to early postoperative initiation of adjuvant chemotherapy for spontaneous tumors of large species.

Amputation, Surgical↗
PubMed1997

Childhood soft tissue sarcoma: a 20-year experience.

PURPOSE: To evaluate the disease-free and overall survival of pediatric patients with nonrhabdomyosarcoma soft-tissue sarcomas. METHODS: We retrospectively analyzed the records of 67 pediatric patients with a diagnosis of nonrhabdomyosarcoma soft tissue sarcoma treated with curative intent between 1970 and 1992. Median follow-up time for the 52 survivors was 120 months (range, 7 to 277 months). Fifty-nine patients received external beam radiotherapy, in a median dose of 5400 cGy (range, 1800 to 6660 cGy.) All patients underwent an initial surgical procedure. Eighteen patients had gross residual disease, and 15 had gross total excision with microscopic residual disease or positive margins. Adjuvant chemotherapy was administered to 44 patients (65%). RESULTS: The actuarial 10-year freedom from progression or recurrence and overall survival rates were 76% and 75%, and the 20-year rates were the same. Of 18 patients with gross residual disease, 9 (50%) had local progression and 6 died of local-only disease. By contrast, only one patient with microscopic residual disease who received postoperative radiotherapy had a local recurrence. The disease-free survival rate also correlated with histologic grade. CONCLUSIONS: As with adult soft tissue sarcomas, gross residual disease predicts local failure. Our results suggest that pediatric patients with soft tissue sarcomas treated with surgery and postoperative radiotherapy generally have a favorable overall survival rate.

Adolescent↗