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J S Wunder

Publications and source records attributed to J S Wunder.

49 records · Page 3Linked to original sources
PubMed1998

The histological response to chemotherapy as a predictor of the oncological outcome of operative treatment of Ewing sarcoma.

Seventy-four patients who had a Ewing sarcoma of bone were managed with preoperative and postoperative chemotherapy and operative resection, with or without postoperative irradiation. The primary objectives of the study were to determine the histological response to preoperative chemotherapy in terms of the percentage of tumor necrosis and to assess the relationship between the histological response and the oncological outcome. The minimum duration of follow-up of the surviving patients who were continuously free of disease was five years. Sections of each operative specimen were examined, and the histological response to chemotherapy was graded semiquantitatively. Grade I indicated necrosis of 50 per cent of the tumor or less; grade II, necrosis of more than 50 per cent but less than 90 per cent; grade III, necrosis of 90 to 99 per cent; and grade IV, necrosis of 100 per cent of the tumor. Of the seventy-four tumors, forty-four (59 per cent) were exquisitely sensitive to chemotherapy and had complete (grade-IV) or nearly complete (grade-III) necrosis. In contrast, fourteen tumors (19 per cent) had little or no response to chemotherapy (grade I) and sixteen (22 per cent) had a moderate degree of necrosis (grade II). The histological response to preoperative chemotherapy (p = 0.0001), followed by the size of the tumor (p = 0.001), were the most important predictors of event-free survival. At five years, the rate of event-free survival was zero of fourteen patients who had had a grade-I response, six of sixteen who had had a grade-II response, and thirty-seven (84 per cent) of forty-four who had had a grade-III or IV response. The risk of local recurrence was most strongly associated with the operative margins; there were only four local recurrences (6 per cent) after sixty-seven resections with negative margins. Local recurrence may also have been influenced by the histological response and the use of local radiation. There were no local recurrences after operative treatment of six tumors that had been associated with pathological fracture. The histological response to preoperative chemotherapy and the size of the primary tumor are the most important clinical predictors of the outcome of operative treatment of non-metastatic Ewing sarcoma. These indicators should be used to identify patients who are at high risk for metastasis as such patients may be candidates for more intensive or novel therapies.

Adolescent↗
PubMed1998

MR imaging of primary lymphoma of bone: variability of T2-weighted signal intensity.

OBJECTIVE: The purpose of this study was to investigate the MR imaging characteristics of primary lymphoma of bone. MATERIALS AND METHODS: Records of 27 patients with histologic and clinical evidence of primary lymphoma of bone were retrospectively reviewed. Nineteen of these patients underwent MR imaging before surgical biopsy and initiation of therapy. Fifteen of the 19 patients underwent conventional spin-echo T1- and T2-weighted imaging, and the other four patients underwent T1-weighted and fast spin-echo T2-weighted imaging with fat saturation. MR images were separately and independently reviewed by two observers for signal intensity characteristics and homogeneity on T1- and T2-weighted sequences. Signal intensity characteristics were correlated with semiquantitative histopathologic assessments of tumor fibrosis, maturity of fibrosis, and vascularity. RESULTS: T1-weighted signal intensity ranged from isointense to hypointense relative to muscle for all lesions. Twelve of 19 cases showed heterogeneity of signal intensity on T2-weighted images. Predominant tumor T2-weighted signal intensities relative to fat for the 19 patients were assessed as hypointense (observer 1, n = 3; observer 2, n = 1), isointense (observer 1, n = 10; observer 2, n = 11), and hyperintense (observer 1, n = 6; observer 2, n = 7). No correlation among intralesional fibrosis, maturity of fibrosis, or intralesional vascularity and T2-weighted signal intensity characteristics was found. CONCLUSION: T2-weighted MR imaging characteristics of primary lymphoma of bone vary and do not seem to be a simple reflection of histologic findings of intralesional vascularity or fibrosis.

Adipose Tissue↗
PubMed1998

Hindquarter amputation for pelvic tumors. The importance of patient selection.

Twenty-two patients underwent hindquarter amputation with curative intent for malignant or locally aggressive tumors of the pelvis (21 cases) or proximal thigh (one case). In all cases, the ilium was resected, and in seven cases an osteotomy of the sacrum was done to achieve negative surgical margins. Only six wounds healed without complications. The worst wound problems occurred in patients requiring ligation of the common iliac vessels and in those requiring a sacral osteotomy. Twelve patients have died of disease, two are alive with extensive pulmonary metastases, and one remains well after excision of a local tumor recurrence. Thirteen of 14 patients with high grade sarcoma had metastases develop, compared with only one of eight patients with low grade sarcoma. Eight patients (all with high grade sarcoma) died within 1 year of surgery. Seven patients have remained disease free at a mean of 39 months after surgery. Given the poor prognosis and high morbidity after amputation in high grade sarcoma, the authors think that consideration should be given to pursuing nonoperative management in patients with large, high grade sarcomas and significant medical extension to the sacroiliac joint or sacrum.

Adolescent↗
PubMed1998

Bone sarcoma diagnosed at the time of reconstructive hip surgery.

OBJECTIVE: To describe the clinical course of a group of patients in whom sarcoma of the proximal femur was diagnosed at the time of reconstructive hip surgery. DESIGN: A retrospective case series. SETTING: Final management of all patients took place at a tertiary care centre. PATIENTS AND INTERVENTIONS: Six consecutive patients with sarcoma of the proximal femur diagnosed at the time of reconstructive hip surgery. The mistaken diagnoses made before surgery were benign tumour (2 patients), avascular necrosis (2 patients), subtrochanteric fracture due to metastasis (1 patient) and granuloma from a loose hip implant (1 patient). The final diagnosis was osteosarcoma in 3 patients and chondrosarcoma in 3. Three patients with high-grade sarcoma received neoadjuvant chemotherapy followed by femoral or pelvic resection, or both, and reconstruction. Two patients with chondrosarcoma underwent wide excision of the tumour with allograft or modular implant reconstruction. One patient with widespread metastasis received only palliative chemotherapy. MAIN OUTCOME MEASURES: Overall survival with respect to oncologic and functional results of treatment. RESULTS: Two patients (1 who received only palliative chemotherapy) died after 5 and 21 months' followup, respectively. Average follow-up for the remaining 4 patients was 65.2 months (range from 51 to 75 months). They were disease free at latest follow-up. One patient required amputation for septic complications related to the reconstruction. CONCLUSIONS: Limb salvage surgery for sarcoma of the proximal femur is challenging when the diagnosis is made at the time of reconstructive surgery rather than through an appropriately planned biopsy. However, this series suggests that limb preservation is feasible and that hindquarter amputation is not the only solution.

Adult↗
PubMed1997

The impact of residual disease on local recurrence in patients treated by initial unplanned resection for soft tissue sarcoma of the extremity.

BACKGROUND AND OBJECTIVES: "Unplanned excision" in soft tissue sarcoma (STS) is defined as the gross removal of tumor without preoperative staging or consideration of the need for removal of normal tissue around the tumor. This study evaluated whether unplanned excision in patients with extremity STS would have an impact on local relapse (LR), even if reexcision of the tumor bed was undertaken. METHOD: Two hundred thirty-nine (239) patients with primary, extremity STS treated with limb salvage surgery were included in this study. Of the 239, 78% were treated with surgery and irradiation. Forty-seven tumors were low-grade and 192 high grade. Mean tumor diameter was 7.5 cm. Twenty had local recurrences and 64 relapsed systemically. RESULTS: Only margin and prior surgery were significant in univariate analysis (P < 0.05, log-rank test). The Cox multivariate analysis revealed that both margin of resection (P < 0.001) and the status of the local tumor site (P < 0.05) at definitive surgery were significant predictors of local relapse. CONCLUSIONS: These results suggest that the presence of microscopic disease in the reexcised specimen following unplanned resection is a risk factor for local disease recurrence.

Adolescent↗
PubMed1997

Chondroblastoma with multiple distant soft tissue metastases.

A case of metachronous distant soft tissue metastases from a primary rib chondroblastoma, occurring in a 60-year-old man 17 years following resection of the initial lesion, is described. Metastatic chondroblastomas are very rare and almost always involve the lungs. Discussed herein are the clinical, radiologic, and pathologic findings of this unusual case with comparison of our findings to other reports of metastasizing chondroblastomas.

Bone Neoplasms↗
PubMed1997

Allograft reconstruction of the acetabulum after resection of stage-IIB sarcoma. Intermediate-term results.

Seventeen consecutive patients were managed with an allograft reconstruction of the pelvis (including the acetabulum) following resection of a stage-IIB bone sarcoma during a twelve-year period. The initial diagnosis was chondrosarcoma in nine patients, osteosarcoma in six, Ewing sarcoma in one, and leiomyosarcoma in one. All patients who had osteosarcoma or Ewing sarcoma received chemotherapy preoperatively and postoperatively. Fifteen patients were managed with an allograft-total hip prosthesis composite. Two patients initially were managed with an osteoarticular allograft without a prosthesis, but one had a subsequent revision to an allograft-implant composite. Four patients died with an intact allograft reconstruction. Eight patients survived with an intact allograft reconstruction, and they were followed for at least four years (mean, seven years; maximum, fourteen years). All but one was able to walk in the community with one or two canes at the time of the latest follow-up. There was a high rate of local recurrence, which occurred in three of the seventeen patients, and of infection, which developed in two patients. The five patients had a subsequent hindquarter amputation or removal of the allograft. The mean functional score (and standard deviation), according to the rating system of the Musculoskeletal Tumor Society, was 65 +/- 21.16 per cent (median, 70 per cent; range, 13 to 87 per cent) for the thirteen patients who were thus evaluated. Preservation of the limb and reconstruction with an allograft may be considered as an alternative to hindquarter amputation in carefully selected patients who have a bone sarcoma involving the acetabulum. However, patients who have a high-grade bone sarcoma must be warned that there is a substantial risk of local recurrence or infection. In the present series, more than half of the patients either died or had failure of the reconstruction.

Acetabulum↗
PubMed1995

The effect of intramedullary cement on intercalary allograft reconstruction of bone defects after tumour resection: a pilot study.

OBJECTIVE: A pilot study to evaluate the surgical and functional results of resection and reconstruction of diaphyseal bone tumours with cemented and uncemented intercalary allografts. DESIGN: A retrospective case series. SETTING: A quaternary care unit within a teaching hospital. PATIENTS: Twenty-two patients with diaphyseal bone tumours treated between 1988 and 1992, with mean follow-up of 38 months (range from 20 to 70 months). INTERVENTIONS: Diagnostic biopsy in all patients. Preoperative and postoperative chemotherapy in patients with high-grade sarcoma. En-bloc excision of all tumours. Reconstruction of the defect with cemented (15 patients) or uncemented (7 patients) intercalary allografts. MAIN OUTCOME MEASURES: Nonunion at one or both osteosynthesis sites, death from systemic disease, amputation. RESULTS: Six of the 22 patients died of systemic disease with the graft intact, and 3 subsequently had amputation for either local recurrence (2 patients) or failure of free tissue transfer (1 patient), leaving 13 patients alive with the allograft in situ at an average of 36 months (range from 24 to 64 months). There were no revision procedures to remove or replace the original allograft. Five patients had nonunion at one or more osteosynthesis sites on plain radiographs 9 months after resection. Four patients with nonunion were in the cemented group of 13 patients available for assessment at 9 months, and 1 was in the uncemented group of 5 patients available for assessment at 9 months. There were two graft fractures, both in the uncemented group. CONCLUSION: The results of this pilot study offer guarded support for the use of pressurized cement in allografts prior to reconstruction of intercalary defects.

Adolescent↗
PubMed1993

Expression of the multidrug resistance gene in osteosarcoma: a pilot study.

Resistance to combination chemotherapy remains a challenge in the treatment of osteosarcoma yet has not been studied extensively in this tumour. One mechanism of multiple drug resistance is increased expression of the multidrug resistance gene (mdr1). The level of mdr1 messenger RNA (mRNA) expression has been found to correlate with the degree of drug resistance in a number of tumour cell lines in vitro, which suggests that it also may be useful as a predictor of similar resistance in vivo. Using a highly sensitive assay based on the polymerase chain reaction to measure the amount of mdr1 mRNA, we detected various levels of mdr1 expression in 18 osteosarcoma specimens from 15 patients with resectable nonmetastatic osteosarcoma. At follow-up at a minimum of 30 months later, a trend toward a worse outcome was observed in patients with tumours exhibiting high levels of mdr1 expression. The results of this pilot study suggest that a larger scale prospective investigation of the effect of mdr1 gene expression on outcome in osteosarcoma is warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Analysis of alterations in the retinoblastoma gene and tumor grade in bone and soft-tissue sarcomas.

We examined 43 sporadic bone and soft-tissue sarcomas for molecular genetic alterations affecting the retinoblastoma susceptibility gene Rb-1 (also known as RB1). The gene was altered in 6 of 14 sporadic osteosarcomas and in 5 of 29 other bone and soft-tissue sarcomas. Rb-1 messenger RNA (mRNA) transcripts were detected in normal tissues and benign lipomas, but they were absent or altered in each of the 19 sarcomas we examined. To examine the association of deletions in the Rb-1 gene with tumor grade, we correlated the DNA alterations in the Rb-1 gene with clinical data for 36 patients. The Rb-1 gene was altered in 40% of high-grade bone and soft-tissue tumors, but not in low-grade bone tumors and in only one low-grade, soft-tissue sarcoma. Overall, 10 of 25 high-grade sarcomas had detectable alterations of the Rb-1 gene compared with only 1 of 11 low-grade tumors.

Bone Neoplasms↗
PubMed1990

Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction.

The resistance of tumor cells to chemotherapeutic drugs is a major obstacle to successful cancer chemotherapy. In human cells, expression of the MDR1 gene, encoding a transmembrane efflux pump (P-glycoprotein), leads to decreased intracellular accumulation and resistance to a variety of lipophilic drugs (multidrug resistance; MDR). The levels of MDR in cell lines selected in vitro have been shown to correlate with the steady-state levels of MDR1 mRNA and P-glycoprotein. In cells with a severalfold increase in cellular drug resistance, MDR1 expression levels are close to the limits of detection by conventional assays. MDR1 expression has been frequently observed in human tumors after chemotherapy and in some but not all types of clinically refractory tumors untreated with chemotherapeutic drugs. We have devised a highly sensitive, specific, and quantitative protocol for measuring the levels of MDR1 mRNA in clinical samples, based on the polymerase chain reaction. We have used this assay to measure MDR1 gene expression in MDR cell lines and greater than 300 normal tissues, tumor-derived cell lines, and clinical specimens of untreated tumors of the types in which MDR1 expression was rarely observed by standard assays. Low levels of MDR1 expression were found by polymerase chain reaction in most solid tumors and leukemias tested. The frequency of samples without detectable MDR1 expression varied among different types of tumors; MDR1-negative samples were most common among tumor types known to be relatively responsive to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

An atypical presentation of Paget's disease in an immunocompromised individual. A case report.

Paget's disease of bone is a localized disorder of bony resorption. The mechanism underlying the development of the disease remains controversial. There is substantial evidence suggesting a genetic basis for Paget's disease in some patients. A viral etiology of Paget's disease has been advocated. A further hypothesis implicating an immunological mechanism for this disease is based on growing evidence reviewed in the text. The presented case showed clinical and X-ray features typical of a very aggressive form of Paget's disease. We hypothesize that the extreme local aggressiveness of this case was secondary to the patient's concomitant immunosuppression due to an extended therapy following renal transplant.

Humans↗