Biomedical subjects

Bruno Fuchs

Publications and source records attributed to Bruno Fuchs.

14 recordsLinked to original sources

PubMed2004

Vascular endothelial growth factor expression is up-regulated by EWS-ETS oncoproteins and Sp1 and may represent an independent predictor of survival in Ewing's sarcoma.

PURPOSE: Tumor markers ideally allow monitoring and prediction of disease progression. In Ewing's sarcoma, a devastating childhood cancer, only a few reliable prognostic markers have been identified. To this end, we analyzed the expression of four tumor-promoting proteins, cyclin D1, HER2/Neu, Mdm2, and vascular endothelial growth factor (VEGF), in Ewing's sarcoma. EXPERIMENTAL DESIGN AND RESULTS: Thirty-one tissue samples from patients with Ewing's sarcoma were stained with antibodies against cyclin D1, HER2/Neu, Mdm2, or VEGF. Whereas no significant expression of HER2/Neu and Mdm2 was detected, positive cyclin D1 and VEGF staining was observed in 42% and 55% of all tumors, respectively. Importantly, VEGF expression was found to be an independent negative predictor of survival in Ewing's sarcoma patients, whereas cyclin D1 expression did not correlate with survival in these patients. Consistently, the Ewing's sarcoma-specific EWS-ETS oncoproteins were capable of activating both the cyclin D1 and VEGF promoters in transient transfections of tissue culture cells. Furthermore, this activation was enhanced by coexpression of the Sp1 transcription factor. Using a mammalian two-hybrid system, some evidence was obtained that this may involve a physical interaction between EWS-ETS and Sp1 proteins. CONCLUSIONS: Our data reveal that VEGF may serve as a prognostic marker in Ewing's sarcoma patients and provide a molecular mechanism by which VEGF and cyclin D1 expression is up-regulated in approximately half of all Ewing's sarcomas.

Antigens, Protozoan↗

PubMed2004

Long-term results of segmental prosthesis fixation by extracortical bone-bridging and ingrowth.

BACKGROUND: The technique of extracortical bone-bridging and ingrowth fixation with a porous coating over the shoulder region of the implant and augmentation by autogenous bone-grafting was introduced to improve the longevity of implant fixation. The potential advantages of this technique are that new-bone formation across the bone-prosthesis junction may share stress and may prevent osteolysis by sealing off this critical region against the infiltration of wear particles. The objectives of this study were to examine the prevalence of stem-loosening with use of the extracortical bone-bridging and ingrowth technique, the amount of bone formation over the porous-coated region of this prosthesis, and the characteristics of bone formation over the porous-coated region and adjacent bone. METHODS: Forty-three patients who had prosthetic reconstruction with the extracortical bone-bridging and ingrowth technique from 1976 to 1990 were included in this retrospective study. The mean length of follow-up was 9.7 years (range, two to twenty-one years). All but one patient were managed with autogenous bone graft; five, with allograft and autograft; and one, with allograft only. Extracortical bone formation was measured over a 2-cm length of the porous-coated region of the prosthesis in four zones (the medial and lateral aspects on anteroposterior radiographs and the anterior and posterior aspects on lateral radiographs) and was reported as the percentage of the total length (8 cm) covered by extracortical bone with a thickness of >1 mm. The Spearman rank coefficient was used to assess the correlation between pairs of continuous variables. RESULTS: The final average percentage of the porous-coated region that was covered by extracortical bone formation was 76% +/- 34% for all patients and anatomical sites of reconstruction. Use of bone cement was associated with less bone formation (p = 0.04), and this value remained lower at the final measurement (p = 0.06). One stem had aseptic loosening, but no sign of osteolysis was found. The radiographic appearance of the bone formation had stabilized at two years of follow-up. All patients with allograft augmentation had greater bone formation. The amount of extracortical bone formation did not differ in relation to the type of porous coating, anatomical sites, pathological disorder, sex or age of the patient, or length of reconstruction. CONCLUSIONS: As shown by the low prevalence of stem-loosening (two of fifty-six stems or one of forty-three patients), the use of the extracortical bone-bridging and ingrowth fixation technique is associated with improved stem fixation in segmental bone-replacement prostheses applied for limb salvage. In the demanding biomechanical environment and with the risk of stress and particle-related bone resorption, the extracortical bone-bridging and ingrowth fixation is an attractive method to provide long-lasting implant fixation.

Adolescent↗

PubMed2003

Complications in long-term survivors of Ewing sarcoma.

BACKGROUND: Multimodality treatment has dramatically improved the outcome of patients with Ewing sarcoma. However, there appears to be little information concerning treatment-related complications in patients who are long-term survivors. METHODS: Forty-one patients with Ewing sarcoma who were treated between 1960-1980 and who survived the disease by at least 20 years were included in the current study. In a retrospective analysis, all complications related to the multimodality treatment of Ewing sarcoma were assessed. RESULTS: The patient group was comprised of 17 men and 24 women, with a mean age at the time of presentation of 16.8 years (range, 5-51 years). Approximately 20% of the lesions were located in the pelvis. All but 9 patients (78%) received chemotherapy as part of their treatment. The overall follow-up period averaged 25 years (range, 20-36 years). All except 1 patient were alive at the time of final follow-up, with the latter patient dying of radiation-induced secondary malignancy after 33 years. Only 17 patients (41%) were found to be free of any complication. These included metastases, local recurrence, secondary malignancies, pathologic fractures, and radiation-associated and chemotherapy-associated morbidities. CONCLUSIONS: Although the patients in the current study were treated successfully in terms of surviving an aggressive tumor, the high complication rate in this group of long-term survivors is noteworthy and indicates that long-term follow-up should be mandatory.

Adolescent↗

PubMed2003

Upregulation of the matrix metalloproteinase-1 gene by the Ewing's sarcoma associated EWS-ER81 and EWS-Fli-1 oncoproteins, c-Jun and p300.

The mechanisms of action of Ewing's sarcoma (EWS) associated EWS-ETS oncoproteins have largely remained unresolved. Here, we analyzed how two EWS-ETS proteins, EWS-ER81 and EWS-Fli-1, in vitro activate the matrix metalloproteinase (MMP)-1 promoter that is upregulated in a subset of EWSs. EWS-ER81 and EWS-Fli-1 interact with and thereby activate the MMP-1 promoter, which is potentiated by the cofactor p300 and the proto-oncoprotein c-Jun. Further, EWS-ER81 binds to c-Jun in vitro and in vivo. The interaction between c-Jun, p300 and EWS-ER81 or EWS-Fli-1 may also be relevant to the regulation of other yet-to-be-identified genes that are responsible for EWS formation.

Base Sequence↗

PubMed2003

Femoral osteotomy and iliac graft vascularization for femoral head osteonecrosis.

The objective of this study was to determine the long-term clinical and radiologic outcomes of patients with osteonecrosis treated by a combination of intertrochanteric osteotomy and pedicled iliac bone block transfer. Between 1978 and 1986, 41 patients (52 hips) with a mean age of 33 years were operated on for Ficat Stages II and III disease. Thirty-three patients (44 hips) were assessed clinically and radiologically at a mean followup of 13.5 years (range, 5-20 years). Fifteen hips (15 of 44; 34%; 13 patients) had conversion surgery to a total hip arthroplasty because of progressive arthritis or collapse, or both. Six patients died and two were lost to followup. Preoperatively, the patients with failed revascularization had significantly more pain and decreased gait function than patients without failure. In the patients without failure, postoperative pain sensation and gait function improved significantly. However, flexion became restricted mainly because of progressive degeneration of the hip. Radiographically, 31% of the hips (nine hips; six patients) had severe arthritis, 59% (17 hips; 12 patients) had moderate arthritis, and only three hips (two patients) had mild arthritis. Ninety percent of patients without hip failures (26 of 29 hips; 18 patients) considered the functional outcome, including pain relief and gait function, to be successful. Despite the subjective success, this surgery could not restore normal hip anatomy, and arthritis progressed with time. Intertrochanteric osteotomy and vascularized iliac bone block transfer should be considered only in young symptomatic patients with good preoperative clinical function and Ficat Stage II disease.

Adolescent↗

PubMed2003

Pathologic fracture as a complication in the treatment of Ewing's sarcoma.

The purpose of the current study was to define the outcome of patients with Ewing's sarcoma who sustained a fracture either at initial presentation or subsequent to multimodal treatment, and to identify parameters that may influence the treatment of these patients. The age of the 21 males and 14 females who sustained a fracture during the treatment for Ewing's sarcoma averaged 15 years (range, 4-30 years) at diagnosis. Fourteen patients presented with a pathologic fracture, whereas 21 patients had a fracture develop subsequent to the initial treatment at a mean of 4 years (range, 1-19 years). The femur was the most common location (50%). At a mean followup of 10 years (range, 1-33 years), 21 of 35 patients (60%) were alive and free of disease. There was no local recurrence, but there was one postradiation sarcoma associated with the fracture. Comparing the followup of patients who sustained the fracture at presentation with the followup of patients who subsequently had a fracture, no statistically significant difference was found (117 months versus 124 months). Overall, pathologic fracture in association with Ewing's sarcoma does not seem to be a negative prognostic parameter with respect to survival in this series. Therefore, a fracture at presentation may not mandate amputation. However, it occurs frequently subsequent to initial multimodal treatment because of delayed fracture healing. Because conservative or minimal osteosynthesis have high failure rates, more aggressive resection and reconstruction have to be considered carefully.

Adolescent↗

PubMed2003

Functional outcome of patients with rotationplasty about the knee.

Rotationplasty is a surgical procedure designed to achieve a durable reconstruction after the resection of tumors about the knee. However, because of the recent advances with expandable prostheses, rotationplasty has been less popular in the skeletally immature patient, particularly in the United States. We assessed the functional outcome of patients who had rotationplasty to allow better comparison with other operative techniques in this patient population. Seven patients, who were operated on at our institution at an average age of 9.4 years (range, 5-14 years), had a followup of at least 4 years and were evaluated in the Motion Analysis Laboratory. The gait analysis included kinetic, kinematic and temporal-distance parameters to evaluate the patient's functional performance. The data also were compared with measurements of a population of 25 able-bodied subjects and with four subjects with distal above-knee amputation. All patients had the ability to weightbear fully. All patients ambulated without assistive devices. Gait analysis of patients with rotationplasty revealed only slight asymmetry regarding stride duration, stride length, cadence, velocity and stance-swing ratio compared with healthy subjects. Although the gait was similar to subjects with distal above-knee amputation, knee motion was superior in patients who had rotationplasty. Rotationplasty offers a durable reconstruction. Rotationplasty allows the patient to actively control the knee, which results in a coordinated gait pattern, which is similar to the gait of the able-bodied population, and better than in subjects with distal-knee amputation.

Activities of Daily Living↗

PubMed2003

Ewing's sarcoma and the development of secondary malignancies.

The multimodality treatment approach for patients with Ewing's sarcoma during the last decades has dramatically improved patient long-term survival. With improved survival, late consequences and morbidity associated with treatment have become apparent. Among the morbidity associated with treatment is the increased risk of development of secondary malignancies. Therefore, the purpose of the current study was to define the outcome of patients who had secondary malignancy develop subsequent to the diagnosis and treatment of Ewing's sarcoma. Of the 397 patients treated for Ewing's sarcoma at our institution during the past 25 years, 26 patients (6.5%) had 29 secondary malignancies develop. The mean age of the 13 males and 13 females averaged 16 years (range, 6-51 years), and the interval from the diagnosis of the Ewing's sarcoma to the development of the secondary malignancy averaged 9.5 years (range, 1-32.5 years). The secondary malignancies included eight hematopoietic cancers, 12 sarcomas, and nine carcinomas. Although carcinomas most likely represent the general risk of developing cancer in the healthy population, the sarcomas were caused by radiation therapy and the hematopoietic tumors caused by chemotherapy. The latter occurred at a mean latent period of 4.8 years (range, 1.7-12.9 years), and the sarcomas occurred after a mean of 10.9 years (range, 1.5-32.5 years). At the mean followup of 15 years (range, 2-33 years) from diagnosis of Ewing's sarcoma and at a mean followup of 5 years (range, 0.5-28 years) from diagnosis of the second malignancy, 14 patients are alive (43%); however, patients with either sarcomas or hematopoietic secondary malignancies had not only a significantly shorter interval from secondary malignancy to followup (3.3 and 1.2 years, respectively, versus 7.3 years), but also a more dismal prognosis (eight of 12 or six of eight patients died, respectively, versus one of nine). Although the risk of having secondary malignancy develop after the treatment of a Ewing's sarcoma may be only slightly greater than the risk compared with other childhood cancers, patients with hematopoietic and radiation-induced secondary malignancies have a detrimental prognosis. Patients with Ewing's sarcoma need to be followed up carefully and frequently.

Adolescent↗

PubMed2002

The human homolog of yeast SEP1 is a novel candidate tumor suppressor gene in osteogenic sarcoma.

The hSEP1 gene is the human homolog of yeast SEP1. Yeast SEP1 is a multifunctional gene that regulates a variety of nuclear and cytoplasmic functions including homologous recombination, meiosis, telomere maintenance, RNA metabolism and microtubule assembly. The function of hSEP1 is not known. We show loss or reduced expression of hSEP1 messenger RNA (mRNA) in three of four primary osteogenic sarcoma (OGS)-derived cell lines and in eight of nine OGS biopsy specimen. In addition, we find a heterozygous missense mutation (Valine(1484)>Alanine) at a conserved amino acid in the primary OGS-derived cell line U2OS. Importantly, we identified a homozygous missense mutation involving a CG-dinucleotide leading to a change in a conserved amino acid, aspartic acid(1137) >asparagine, in the primary OGS-derived cell line, TE85. hSEP1 mRNA expression was nearly undetectable in TE85 and low in U2OS cell lines. None of these mutations were identified in 20 normal samples consisting of bone, cartilage and fibroblast. The hSEP1 gene is located in chromosome 3 at 3q25-26.1 between markers D3S1309 and D3S1569. An adjacent locus defined by the polymorphic markers D3S1212 and D3S1245 has previously been reported to undergo loss of heterozygosity (LOH) at a >70% frequency in OGS and claimed to harbor an important tumor suppressor gene in osteosarcoma. The homozygous mutation in the hSEP1 mRNA in TE85 cell line suggest that this gene itself is subject to LOH. Taken together, these results suggest that hSEP1 acts as a tumor suppressor gene in OGS.

Base Sequence↗

PubMed2002

Combined posterior pelvis and lumbar spine resection for sarcoma.

The oncologic outcome in the treatment of pelvic sarcomas is not comparable with that in the extremity. Particular problems arise when the tumor involves the posterior pelvis and the sacrum or even the lower lumbar spine. Because of the difficulty in achieving local control and the major functional deficits after extensive surgery, some authors suggest conservative, nonsurgical treatment for these patients. The purpose of the current study was to analyze the oncologic outcome of patients who were treated for a pelvic sarcoma necessitating resection of the ilium, part of the sacrum and part of the lower spine, which is defined as extended hemipelvectomy. Between 1979 and 1999, 11 males and seven females with a mean age of 34.5 years (range, 14-67 years) had an extended hemipelvectomy for a sarcoma of the posterior pelvis. The tumors included seven osteogenic sarcomas, six chondrosarcomas, and five fibrosarcomas: 13 were classified as high-grade lesions. The mean size of the tumor was 11 x 9 x 6 cm. In 11 patients, a hemivertebrectomy of L5 and in seven patients of L4 combined with L5 was done to achieve an adequate margin. In four patients, the resection was followed by reconstruction with a vascularized fibula or autograft. At a mean followup of 56 months (range, 3-220 months), 12 of 18 patients were alive and without disease. Six patients died; four of these patients had metastasis to the lung at presentation. The two remaining patients died of complications of adjuvant treatment. The authors conclude from this small series of patients that an aggressive surgical resection for localized, nonmetastatic, high-grade sarcomas of the posterior pelvis may be justified to provide local control and improve survival.

Adolescent↗

PubMed2002

Iliofemoral arthrodesis and pseudarthrosis: a long-term functional outcome evaluation.

Reconstruction after the resection of pelvic tumors is a major challenge. It depends on many factors such as age, activity level, type of tumor, its adjuvant treatment, and the extent of the disease. The purpose of the current study was to analyze the functional and oncologic outcomes of patients who had an iliofemoral arthrodesis after resection of a pelvic sarcoma. Between 1981 and 1999, 20 males and 12 females with a mean age of 39.9 years (range, 10-71 years) had an iliofemoral arthrodesis, either as a solid fusion or primary pseudarthrosis, at one institution. The functional outcome was evaluated using the Musculoskeletal Tumor Society and the Toronto Extremity Salvage scores. At a mean followup of 97 months (range, 14-226 months), 15 of 32 patients were alive, all without disease. The radiographic union rate was 86%. The mean overall Musculoskeletal Tumor Society and Toronto Extremity Salvage scores were 64% and 48%, respectively. Patients with a primary solid fusion did functionally better compared with patients who had pseudarthrosis (Toronto Extremity Salvage Score, 76%; Musculoskeletal Tumor Society Score, 71% versus Toronto Extremity Salvage Score, 52%; Musculoskeletal Tumor Society Score, 25%). Biomechanical analysis showed that the loss of motion in the hip is well-compensated. The authors conclude from this series that iliofemoral reconstruction after resection of a pelvic sarcoma provides acceptable and durable long-term results, not only from the oncologic, but also from the functional perspective.

Adolescent↗

PubMed2002

Bowel and bladder function after major sacral resection.

Major sacral resection generally is reserved for patients with malignant lesions. Because of the uncommon nature of these diseases, little is known about outcomes of surgical treatment. The current authors describe the retrospective analysis of bowel and bladder function in patients having major sacral resection at their institution during a 10-year period. Fifty-three patients were identified. In patients who had unilateral sacrectomy, in whom the contralateral sacral nerves were preserved, normal bowel and bladder function was retained in 87% and 89%, respectively. In patients who had bilateral S2-S5 nerve roots sacrificed, all had abnormal bowel and bladder function. In patients who had bilateral S3-S5 resection, normal bowel and bladder function was retained in 40% and 25%, respectively. In patients who had bilateral S4-S5 resection, with preservation of the S3 nerves bilaterally, normal bowel and bladder function was retained in 100% and 69%, respectively. In patients who had asymmetric sacral resections, with preservation of at least one S3 nerve root, normal bowel and bladder function was retained in 67% and 60%, respectively. These results show that unilateral resection of sacral roots or preservation of at least one S3 root in bilateral resection preserves bowel and bladder function in the majority of patients.

Adolescent↗

PubMed2002

Etiology of osteosarcoma.

Although the prognosis and quality of life of patients with osteosarcoma were improved significantly during the past decades, the pathogenesis and etiology of this disease remain obscure. Significant interest and effort in this cancer led to the identification of numerous etiologic agents. Several chemical agents such as beryllium, viruses such as FBJ, subsequently found to contain the src-oncogene, and radiation were shown to be potent inducers of osteosarcoma. Paget's disease, electrical burn, or trauma all are thought to be other factors that may contribute to the pathogenesis. More recently, patients with hereditary diseases such as Rothmund-Thomson syndrome, Bloom syndrome, and Li-Fraumeni syndrome were found to have an increased risk of having osteosarcoma develop. During the past few years, the molecular analysis brought a wealth of new information with numerous genes that were associated with osteosarcoma and its clinical disease progression. They can be categorized into self-sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue evasion and metastasis. Although the understanding of these processes in osteosarcoma still is incomplete, it may have the potential to significantly affect the patient care in the future.

Animals↗

PubMed2002

Relationship between surgical margins and local recurrence in sarcomas of the spine.

The combination of improved resection, stabilization, and fusion techniques allows for more aggressive removal of malignant spinal tumors with acceptable mortality and morbidity. Thirty consecutive patients with primary sarcomas of the mobile spine, who were operated on at the authors' institution from January 1970 to December 2000, were included in the current study. Demographic information, tumor location, type of resection, resection margins, local recurrence, and overall survival data were retrieved and analyzed. Treatment consisted of en bloc resection in 12 patients (40%) and piecemeal resections in 18 patients (60%). The resection was classified as wide in seven patients (23.3%), marginal in three patients (10%), and intralesional in 20 patients (66.7%). Pathology reports showed tumor-free resection margins in 12 patients (40%). In the remaining 18 patients (60%), resection margins were positive and resulted in a fivefold increase in the risk of a local recurrence. Ninety-two percent of the patients with local recurrence died of sequelae associated with the local recurrence. Primary sarcomas of the mobile spine in certain cases, can be removed completely with tumor-free resection margins. En bloc resection with tumor-free margins provides substantial improvement in overall survival.

Adolescent↗