PubMed Health⌕ Search

Biomedical subjects

J S Wunder

Publications and source records attributed to J S Wunder.

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

Functional and oncological outcome of acetabular reconstruction for the treatment of metastatic disease.

BACKGROUND: Metastatic disease of the acetabulum can be painful and disabling. Operative intervention is indicated for patients who fail to respond adequately to nonoperative treatment. We evaluated the functional and oncological outcome of acetabular reconstruction after curettage for the treatment of refractory symptomatic acetabular metastases. METHODS: Fifty-five patients with metastatic disease of the acetabulum were treated with operative acetabular reconstruction combined with a total hip replacement. The most common primary tumor was carcinoma of the breast (eighteen patients), followed by carcinoma of the kidney (seven patients) and carcinoma of the prostate (seven patients). Forty (73 percent) of the patients presented with multiple skeletal metastases, and eighteen (33 percent) had associated visceral metastases. Twenty-eight (51 percent) had severe pain requiring continuous use of narcotics, twenty-four (44 percent) had moderate pain requiring periodic use of narcotics, and the remaining three (5 percent) had mild pain requiring use of non-narcotic analgesics. Eighteen (33 percent) of the patients could not walk, twenty-three (42 percent) needed a walker or crutches, twelve (22 percent) used a single cane, and two (4 percent) walked without assistive devices. Intralesional curettage of the tumor was performed in all of the patients. Fifty-four of the hips were reconstructed with a protrusio cup and one, with a hemipelvis endoprosthesis. Large defects were reinforced with cement and pin or screw fixation (the modified Harrington technique), which allowed transmission of weight-bearing forces to the remaining intact pelvis. Thirty-six acetabular reconstructions were performed with antegrade pins or cannulated screws; fifteen, with long retrograde screws; and four, with cement. RESULTS: The median period of survival was nine months. Patients with visceral metastases had a median period of survival of three months compared with twelve months for patients without visceral metastases (p < 0.001). Patients with breast cancer presented later in the disease process (p < 0.004) and lived longer than did those with other carcinomas (p < 0.004). Forty-five patients were evaluated three months after reconstruction. Thirty-four (76 percent) of them had relief of pain as determined by decreased use of narcotics. Nine of the eighteen patients who could not walk preoperatively regained the ability to walk. Fourteen of the seventeen patients who originally were able to walk in the community retained that ability. Thirty-three patients were available for evaluation at six months. Twenty-five (76 percent) still had relief of pain, and nineteen (58 percent) were able to walk and function in the community. Overall, fourteen (25 percent) of the fifty-five patients had moderate local progression of the disease, and five of these patients had failure of the fixation. Fourteen early complications developed in twelve (22 percent) of the patients. One patient (2 percent) died perioperatively. CONCLUSIONS: Patients who have acetabular metastases that are refractory to radiation and chemotherapy have a short life expectancy. The early, gratifying results of reconstruction validate the role of operative treatment as a short-term palliative procedure. Protrusio acetabular cups presumably compensate for deficiencies of the medial wall, while cement and pin fixation can be used effectively to reconstruct large defects in the acetabular column and dome. The low rate of fixation failure supports the biomechanical principles of the reconstruction. Generally, the reconstructions are sufficiently durable to exceed the life expectancy of the patients.

Acetabulum↗
PubMed1999

Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor).

Aggressive fibromatosis (also called desmoid tumor) occurs as a sporadic lesion or as part of Familial Adenomatous Polyposis, which is caused by germ line mutations in the Adenomatous polyposis Coli (APC) gene. APC is involved in the regulation of the cellular level of beta-catenin, which is a mediator in Wnt signaling. Mutational analysis of the beta-catenin and APC genes was performed in 42 sporadic aggressive fibromatoses. Nine tumors had mutations in APC, and 22 had a point mutation in beta-catenin at either codon 45 or codon 41 (producing a stabilized beta-catenin protein product). Immunohistochemistry showed an elevated beta-catenin protein level in all tumors, regardless of mutational status. Beta-catenin localized to the nucleus, and was not tyrosine phosphorylated in the six tumors in which this was tested. The demonstration of mutations in two mediators in the Wnt-APC-beta-catenin pathway implicates beta-catenin stabilization as the key factor in the pathogenesis of aggressive fibromatosis. This is the first demonstration of somatic beta-catenin mutations in a locally invasive, but non metastatic lesion composed of spindle cells, illustrating the importance of beta-catenin stabilization in a variety of cell types and neoplastic processes. Moreover, this tumor has one of the highest reported frequencies of beta-catenin mutations of any tumor type.

Base Sequence↗
PubMed1999

Co-amplification and overexpression of CDK4, SAS and MDM2 occurs frequently in human parosteal osteosarcomas.

Amplification of genes in the 12q13-15 region occurs frequently in several malignancies including osteosarcoma. The products of these amplified genes are thought to provide cancer cells with a selective growth advantage; however, the specific gene(s) driving this amplicon is unknown. We have previously shown that the SAS gene is amplified in most parosteal osteosarcomas. In this study we analysed additional putative growth regulatory genes in this chromosomal region in 24 primary osteosarcoma specimens. CDK4 and SAS were coamplified in 6/6 parosteal tumors, and MDM2 was also amplified in 4/5 parosteal cases. In comparison, amplification occurred in only 2/16 classical intramedullary osteosarcomas and involved the SAS gene. Each amplified gene had a correspondingly elevated mRNA level. Four high grade intramedullary tumors had elevated mRNA expression of SAS, but did not exhibit gene amplification. Gene amplification/overexpression was not associated with metastatic disease and did not change markedly with tumor progression, as evidenced by analysis of sequential tumor specimens from eight patients. Three other genes in the 12q13-15 region (CDK2, WNT1 and WNT10b) were not amplified in any of the tumors. The different patterns of gene amplification and overexpression of CDK4, SAS and MDM2 in parosteal and intramedullary osteosarcomas may help explain the disparity in the biological behaviour of these two types of osteosarcoma.

Cyclin-Dependent Kinase 4↗
PubMed1999

Comparison between a 2- and 3-grade system in predicting metastatic-free survival in extremity soft-tissue sarcoma.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine whether a histologic grading system consisting of 2 or 3 categories had better discrimination for predicting metastasis-free survival in extremity soft-tissue sarcoma. METHODS: One hundred thirty patients with nonmetastatic soft-tissue sarcoma were identified and the histologic grade (3-grade system) for each tumor was determined. For the 2-grade system, grade was determined by collapsing 3 grades into 2. The Kaplan-Meier method was used to estimate disease free survival. RESULTS: By use of a 3-grade system, grade 2 tumors showed a 5.2-fold and grade 3 tumors a 9-fold increased risk of systemic relapse when compared with grade 1 tumors. When grade 2 and 3 tumors were combined, they had a 2.6-fold increased risk of systemic relapse compared with grade 1 tumors. When grade 1 and 2 tumors were combined, grade 3 tumors had an 8.4-fold risk of relapse. After data were controlled for size and depth of tumor, each increase in grade in the 3-grade system showed a successive 2.3-fold increase in risk of systemic relapse. CONCLUSIONS: A 3-grade system may be more appropriate for predicting systemic relapse than 2 grades. A prospective study is required to confirm this.

Adolescent↗
PubMed1999

Expression of osteocalcin and its transcriptional regulators core-binding factor alpha 1 and MSX2 in osteoid-forming tumours.

Osteosarcoma, fibrous dysplasia, and myositis ossificans contain osteoid-producing cells that are not necessarily morphologically typical osteoblasts. Nevertheless, these pathologic cells may share differentiation steps with osteoblasts at the molecular level. Osteocalcin, a bone-specific extracellular matrix protein, is a marker of mature osteoblasts. Osteocalcin is upregulated by the transcription factor core-binding factor alpha 1, which is responsible for commitment to the osteoblastic lineage, and is downregulated by MSX2, a homeobox-containing transcription factor expressed during the early proliferative phase of osteoblast differentiation. Semiquantitative reverse transcription-polymerase chain reaction was used to compare expression levels of osteocalcin, core-binding factor alpha 1, and MSX2 in 34 osteosarcoma, five fibrous dysplasia, and five myositis ossificans specimens, as well as in seven normal cortical bone samples. Despite normal or elevated levels of core-binding factor alpha-1 expression in most specimens, osteocalcin expression was low or undetectable in most cases of osteosarcoma (25 of 34) and myositis ossificans (4 of 5). Single-strand conformation polymorphism and sequencing did not identify any mutations in the DNA-binding domain of core-binding factor alpha 1. However, a high level of MSX2 expression was demonstrated in these lesions, which may inhibit osteocalcin transcription. The presence of moderate levels of osteocalcin in fibrous dysplasia may contribute to the characteristic disconnected appearance of trabeculae in that entity because osteocalcin is a negative regulator of bone formation.

Bone Neoplasms↗
PubMed1999

Intradermal injection of autologous dermal fibroblasts improves wound healing in irradiated skin.

BACKGROUND: Despite its well-recognized benefits in the management of several solid tumors, the use of radiotherapy prior to surgery is associated with a high incidence of significant surgical wound healing complications. Radiation-induced damage to dermal fibroblasts has been proposed as an important cause. We hypothesized that the introduction of normal, unirradiated fibroblasts into previously irradiated skin would enhance healing of the subsequent surgical wound. MATERIALS AND METHODS: Four groups of wounds were examined in female Wistar rats: (1) unirradiated skin (n = 10), (2) irradiated skin injected with tissue culture medium alone (n = 17), (3) irradiated skin injected with autologous dermal fibroblasts (n = 17), and (4) irradiated skin injected with irradiated autologous dermal fibroblasts (n = 7). Wounds were evaluated biomechanically and histologically. RESULTS: The biomechanical values of breaking load, ultimate tensile strength, elastic modulus, and toughness were significantly greater in the irradiated wounds injected with fibroblasts than those injected with medium only. These cell-injected wounds did not perform as well biomechanically as those in unirradiated skin. Irradiating the cells prior to injection resulted in biomechanical results no better than those in medium-injected wounds. CONCLUSIONS: These results demonstrate that injection of normal, unirradiated fibroblasts significantly improves healing of the irradiated surgical wound. These cells are likely better able to respond to the proliferative, migratory, and synthetic demands of the wound healing environment, as injection of irradiated cells has an equivalent effect on healing as injection of medium alone.

Animals↗
PubMed1999

Functional outcome in amputation versus limb sparing of patients with lower extremity sarcoma: a matched case-control study.

OBJECTIVE: To quantify the differences in physical disability and handicap experienced by patients with lower extremity sarcoma who required amputation for their primary tumor as compared with those treated by limb-sparing surgery. DESIGN: Matched case-control study. Twelve patients with amputation were matched with 24 patients treated by limb-sparing surgery on the following variables: age, gender, length of follow-up, bone versus soft-tissue tumor, anatomic site, and treatment with adjuvant chemotherapy. PATIENTS: Patients who underwent above-knee amputation (AKA) or below-knee amputation (BKA) for primary soft-tissue or bone sarcoma, who had not developed local or systemic recurrence, and who had been followed up for at least 1 year since surgery. MAIN OUTCOME MEASURES: The Toronto Extremity Salvage Score (TESS), a measure of physical disability; the Shortform-36 (SF-36), a generic health status measure; and the Reintegration to Normal Living (RNL), a measure of handicap. RESULTS: Mean TESS score for the patients with amputations was 74.5 versus 85.1 for the limb-sparing patients. (p = .15). Only the physical function subscale of the SF-36 showed statistically significant differences, with means of 45 and 71.1 for the amputation versus limb-sparing groups, respectively (p = .03). The RNL for the amputation group was 84.4 versus 97 for the limb-sparing group (p = .05). Seven of the 12 patients with amputations experienced ongoing difficulty with the soft tissues overlying their stumps. CONCLUSIONS: There was a trend toward increased disability for those in the amputation group versus those in the limb-sparing group, with the amputation group showing significantly higher levels of handicap. These data suggest that the differences in disability between amputation and limb-sparing patients are smaller than anticipated. The differences may be more notable in measuring handicap.

Adult↗
PubMed1999

Gender issues in patients with extremity soft-tissue sarcoma: a pilot study.

Soft-tissue sarcoma (STS) affects men and women with equal frequency and commonly presents as an asymptomatic mass in patients 40 to 50 years of age. Recent study has identified physical, emotional, and psychological factors associated with a diagnosis of malignancy, but the tissues affecting the STS patient population may differ from those of more common cancers due to physical disability secondary to treatment. Research to date has not dealt specifically with gender differences in the reaction and adaptation to the cancer diagnosis. This pilot study was designed to evaluate the treatment experiences of five males and five females treated with surgery and radiation for STS of the thigh and followed posttreatment for at least 2 years. The open-ended interview was used to collect data, which was then subjected to a constant comparative analysis technique. The STS patients shared many concerns of cancer patients, with additional physical complaints. Physical symptoms were common to men and women, but women adapted more easily with explanation. Women feared losing life, family role, and relationships. Along with men, they also feared the losses of limb and career. For women, support included faith and sharing stories with others, whereas men preferred to deal with their illnesses individually and concealed emotions from loved ones. The perception of disease time frame was also distinct, with men adopting a fatalistic attitude and regarding their disease as an isolated episode. Women believed their condition was ongoing. Women need repeated information from several sources along with reassurance and increased social support, whereas men prefer the minimum of social support, requiring instead independence and extra attention to physical limitations. These results can improve STS patient treatment by increasing awareness in the patient, family, and medical team of the psychosocial issues that can be expected to arise.

Adaptation, Psychological↗
PubMed1999

EWS-FLI1 and EWS-ERG gene fusions are associated with similar clinical phenotypes in Ewing's sarcoma.

PURPOSE: There are a variety of solid tumors in which alternative chromosomal translocations generate related fusion products. In alveolar rhabdomyosarcoma and synovial sarcoma, these variant fusions have been found to have major clinical significance. We investigated whether the two alternative gene fusion products, EWS-FLI1 and EWS-ERG, define different clinical subsets within the Ewing's sarcoma family of tumors. PATIENTS AND METHODS: We selected 30 cases of Ewing's sarcoma with the EWS-ERG gene fusion and 106 cases with the EWS-FLI1 fusion. Clinical data were obtained for each case and compared with the molecular diagnostic findings. RESULTS: There were no significant clinical differences observed between the two groups in age of diagnosis, sex, metastasis at diagnosis, primary site, event-free survival, or overall survival. CONCLUSION: Differences in the C-terminal partner in the Ewing's sarcoma family gene fusions are not associated with significant phenotypic differences.

Adolescent↗
PubMed1999

Treatment of giant-cell tumors of long bones with curettage and bone-grafting.

BACKGROUND: The use of curettage, phenol, and cement is accepted by most experts as the best treatment for giant-cell tumor of bone. The present study was performed to evaluate whether equivalent results could be obtained with curettage with use of a high-speed burr and reconstruction of the resulting defect with autogenous bone graft with or without allograft bone. METHODS: The prospectively collected records of patients who had a giant-cell tumor of a long bone were reviewed to determine the rate of local recurrence after treatment with curettage with use of a high-speed burr and reconstruction with autogenous bone graft with or without allograft bone. All of the patients were followed clinically and radiographically, and a biopsy was performed if there were any suspicious changes. RESULTS: Fifty-nine patients met the criteria for inclusion in the study. According to the grading system of Campanacci et al., two patients (3 percent) had a grade-I tumor, twenty-nine (49 percent) had a grade-II tumor, and twenty-eight (47 percent) had a grade-III tumor. Seventeen patients (29 percent) had a pathological fracture at the time of presentation. The mean duration of follow-up was eighty months (range, twenty-eight to 132 months). Seven patients (12 percent) had a local recurrence. Six of these seven were disease-free at the latest follow-up examination after at least one additional treatment with curettage or soft-tissue resection (one patient). One patient had resection and reconstruction with a prosthesis after a massive local recurrence and pulmonary metastases. CONCLUSIONS: Despite the high rates of recurrence reported in the literature after treatment of giant-cell tumor with curettage and bone-grafting, the results of the present study suggest that the risk of local recurrence after curettage with a high-speed burr and reconstruction with autogenous graft with or without allograft bone is similar to that observed after use of cement and other adjuvant treatment. It is likely that the adequacy of the removal of the tumor rather than the use of adjuvant modalities is what determines the risk of recurrence.

Adolescent↗
PubMed1999

Doxorubicin-cisplatin chemotherapy for high-grade nonosteogenic sarcoma of bone. Comparison of treatment and control groups.

OBJECTIVE: To evaluate the role of chemotherapy with a combination of doxorubicin (adriamycin) and cisplatin in high-grade, nonosteogenic, non-Ewing's sarcoma (non-OSA) of bone. DESIGN: A case series comparison with a literature-derived control group. SETTING: A university-affiliated tertiary care centre. PATIENTS: Thirty patients with a diagnosis of non-OSA. Of these, 8 had low-grade disease (grade 1 or 2) and 22 had high-grade disease (grade 3). Eleven of the 22 with high-grade disease had malignant fibrous histiocytoma. Seventeen patients with nonmetastatic high-grade non-OSA were compared with a literature cohort of 37 patients who met the eligibility criteria of nonmetastatic, high-grade non-OSA treated with surgery, with or without radiotherapy. The mean follow-up was 25.2 months. INTERVENTIONS: Eight patients with low-grade tumour underwent surgery alone; 22 patients with high-grade tumour underwent surgery and 6 courses of adriamycin (75 mg/m2 every 3 weeks) and cisplatin (100 mg/m2 every 3 weeks). MAIN OUTCOME MEASURES: Disease-free survival and overall survival in those with high-grade tumours treated with or without chemotherapy. RESULTS: Of 8 patients who had low-grade tumours and underwent surgery alone, 3 had systemic relapse. Of the 22 having high-grade tumours, 4 did not receive chemotherapy because of age and comorbid conditions. Of the other 18, 13 received 3 courses of chemotherapy preoperatively and 3 courses postoperatively, 4 received all 6 courses postoperatively and 1 received all chemotherapy preoperatively to treat metastatic disease. In the 17-patient cohort used for comparison with the literature control group, disease-free survival was 57% at a mean follow-up of 25.6 months and overall survival was 57% at a mean follow-up of 30.1 months. In the control group, disease-free survival was 16% at a mean follow-up of 20.9 months and overall survival was 26% at a mean follow-up of 29.9 months. These differences are significant: p = 0.0000, chi 2 = 41.61 for disease-free survival and p = 0.0000, chi 2 = 46.49 for overall survival. CONCLUSIONS: The findings of this study support the use of adjuvant chemotherapy in patients with high-grade non-OSA, in whom malignant fibrous histiocytoma was the predominant histologic subtype.

Adolescent↗
PubMed1998

MR imaging of symptomatic osteochondromas with pathological correlation.

OBJECTIVE: To demonstrate the value of MR imaging in the diagnosis and differentiation of the various symptomatic complications of osteochondromas, providing pathological correlation with emphasis on the usefulness of MR imaging as a single imaging modality in these patients. DESIGN: We retrospectively reviewed all MR examinations of clinically symptomatic osteochondromas (30 patients) performed at our institution between March 1990 and October 1997. PATIENTS: Thirty patients had clinically symptomatic osteochondromas during the study period. Twenty patients were male and 10 were female. There were five cases of multiple osteochondromatosis. Pathological correlation was available in 24 patients. RESULTS AND CONCLUSION: Symptomatic complications included fracture (7%), osseous deformity limiting range of motion (23%), vascular injury (7%), neurological compromise (10%), bursa formation (27%) and malignant transformation (27%). MR imaging was able to diagnose or suggest the etiology for the clinical symptomatology in all cases, demonstrating that it is an ideal imaging modality in the diagnostic evaluation of symptomatic complications of osteochondromas and often avoids the need for further imaging.

Adolescent↗
PubMed1998

Distal ulnar tumours. Results of management by en bloc resection in nine patients and review of the literature.

A variety of reconstructive procedures have been suggested for stabilizing the ulnar shaft following resection of the distal ulna for tumour. We present the results of a series of nine distal ulnar tumour resections in which four different stabilization techniques were employed. We based our results on an evaluation of function, pain, motion, strength and instability. We obtained good or excellent results in seven patients treated with a soft tissue stabilization of the ulnar stump. One patient did not undergo any stabilization procedure and scored fair in our system. A further patient who required a radiocarpal arthrodesis also had an inferior result. These results suggest that soft tissue stabilization of the ulnar stump should be performed whenever possible.

Adult↗
PubMed1998

Capsular replacement with synthetic mesh: effectiveness in preventing postoperative dislocation after wide resection of proximal femoral tumors and prosthetic reconstruction.

We describe a surgical technique for replacing the hip joint capsule using synthetic mesh after oncological resections of the proximal femur that resulted in gross intraoperative instability of the prosthetic reconstruction. The results of its use in 13 patients, 6 of whom also had pelvic resections, are described. These patients were selected from a total group of 88 patients undergoing proximal femoral replacement, 75 of whom did not require capsular replacement (none of these 75 patients have experienced dislocation). In the group requiring capsular reconstruction, 1 of 4 patients with bipolar hemiarthroplasty and 4 of 9 patients with total hip replacements experienced dislocation after operation. Of the dislocated total hip replacements, 1 remains chronically dislocated, and 3 were successfully stabilized by open reduction with further capsular augmentation. Given that the resections involved removal of most of the soft tissues stabilizing the hip joint, we believe that the technique of capsular reconstruction is useful in this difficult group of patients.

Adult↗
PubMed1998

Function after subtotal scapulectomy for neoplasm of bone and soft tissue.

We describe the functional results in 14 patients (7 men, 7 women) after subtotal scapulectomy for primary bone and soft-tissue tumours at a specialist musculoskeletal oncology unit. Eight had chondrosarcomas, two Ewing's sarcomas, one aggressive fibromatosis and three soft-tissue sarcomas. The mean follow-up was 52 months (6 to 120). Analysis of residual symptoms and of range and strength of movement by physicians used the Musculoskeletal Tumour Society rating scale (MSTS). Physical disability was measured by the patients using the Toronto Extremity Salvage Score (TESS). All 14 patients are still alive, two with systemic disease. Nine had more than 80% of their scapula resected but the glenohumeral joint was preserved in all cases. Eight had full movement and another two achieved 90 degrees of flexion. The mean functional results were good to excellent in all except three patients (mean MSTS = 71.6 and TESS = 79.9). Two of these three patients had considerable pain as a result of brachial neuropathy. Scapulectomy gives an excellent functional result if the glenohumeral joint is preserved. The rotator cuff could be removed without a severe functional deficit provided that the deltoid was reattached to the scapular remnant and the trapezius.

Adolescent↗