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Biomedical subjects

L E Wold

Publications and source records attributed to L E Wold.

At least 55 records · Page 3Linked to original sources
PubMed1993

Prognostic significance of spontaneous tumour necrosis in osteosarcoma.

Preoperative chemotherapy is an integral part of the management of osteosarcoma, and the extent of tumour necrosis found at operation is an important prognostic variable. Knowledge about spontaneous, pretherapy necrosis is difficult to obtain but provides important quantitative information about the necrotic effect of chemotherapy. Using three different methods, we studied spontaneous tumour necrosis in 20 localized intramedullary osteosarcomas of the distal femur diagnosed between 1963 and 1972. All patients received surgical treatment only. All six patients with spontaneous necrosis involving more than 20% of tumour died. Five of 14 patients with necrosis amounting to less than 20% were long-term, disease-free survivors. The extent of necrosis was independent of tumour size. Two semiquantitative methods of evaluation were easily applied and reproducible. Spontaneous necrosis in untreated osteosarcomas occurs frequently; extensive necrosis may indicate a rapid clinical course. Tumour necrosis can be quantified reliably in clinical work.

Adolescent↗
PubMed1993

A 50-year experience of male breast cancer: is outcome changing?

During the period 1933-1983, 124 men (median age 62.5 years, range 33-86 years) were treated for breast carcinoma. Median length of follow-up was 6.7 years and was complete for 93% of patients. Presenting complaints were most frequently a mass (95%) or pain (31%) while physical examination revealed the tumour to be central in 95% of patients with nipple or skin retraction in 36% and associated gynaecomastia in 12%. Twenty-seven per cent of the patients had a positive family history of breast cancer, 6% noted previous breast trauma and 7% had prior chest wall irradiation. Mean tumour size was 2.5 cm, and the pathological stage was 0 in 3%, I in 17%, II in 22%, III in 35%, IV in 11%, and unknown in 12%. Ninety-four per cent were ductal carcinoma. Histological grading of tumours was 2% grade 1, 10% grade 2, 33% grade 3 and 48% grade 4. Ninety-two per cent of patients underwent mastectomy (41% radical, 39% modified radical and 12% simple), while adjuvant irradiation was used in 44% and chemotherapy in 9%. Median disease-free patient survival was 5 years (36% of patients developed tumour recurrence). Median overall patient survival was 6.3 years (57% at 5 years and 31% at 10 years). Tumour size (P < 0.05), pathological stage (P < 0.04), and tumour grade (P = 0.007) were adverse factors for recurrence, while pathological stage (P < 0.02), tumour size (P < 0.03), pain (P < 0.05) and age (P < 0.02) were associated with a decreased survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

DNA ploidy and percent S-phase as prognostic factors in node-positive breast cancer: results from patients enrolled in two prospective randomized trials.

PURPOSE AND METHODS: To help clarify the clinical utility of flow-cytometric parameters, we performed flow cytometry on archival paraffin-embedded primary breast cancers from 502 patients treated on two adjuvant chemotherapy protocols performed by the North Central Cancer Treatment Group (NCCTG) and Mayo Clinic. DNA ploidy and percent S-phase (%S) were examined in univariate and Cox model multivariate analyses along with tumor size, menopausal and estrogen receptor status, Quetelet's index (QI), number of positive nodes and nodes examined, and Fisher and nuclear grades. RESULTS: Ploidy analysis showed that 40% of tumors were DNA diploid and 60% were DNA nondiploid (12% tetraploid and 48% aneuploid). There was no difference in relapse-free survival (RFS) (P = .82) or overall survival (OS) (P = .78) between the ploidy groups. Tetraploid patients had the longest RFS and OS of any group, but this did not achieve statistical significance. The %S was computed in 98% of cases and the medians were 9.0% for all patients, 6.4% for diploid patients, and 11.7% for nondiploid patients (P < .0001). By use of a %S greater than 12.3 as a prognostic variable in a univariate analysis, there was a significant difference in the RFS (P = .02) and OS (P = .007) of patients with low- versus high-proliferative tumors. However, when the %S was adjusted for clinical characteristics in the multivariate analysis, it was not a significant factor for RFS (P = .23) or OS (P = .36). CONCLUSION: These results indicate that DNA content and %S measurements by flow cytometry are not clinically useful independent prognostic factors in women with resected node-positive breast cancer administered adjuvant chemotherapy.

Adult↗
PubMed1993

Ewing sarcoma of the pelvis. Clinicopathological features and treatment.

The results of treatment in twenty-seven patients who had a Ewing sarcoma of the pelvis were reviewed. Six patients had had metastatic disease at the time of the diagnosis. The three-year actuarial survival of these patients was 17 per cent (95 per cent confidence interval, 8 to 52 per cent). Of the twenty-one remaining patients, thirteen had received chemotherapy and radiation therapy to the primary lesion and eight had had chemotherapy and operative resection, with or without radiation therapy. The actuarial five-year over-all survival was 25 per cent (95 per cent confidence interval, 6 to 51 per cent) in the group that had had radiation without a resection and 75 per cent (95 per cent confidence interval, 31 to 93 per cent) in the group that had had a resection (p < 0.005, log-rank method). The actuarial over-all five-year survival was 45 per cent (23 to 65 per cent) for all patients who had had localized disease when first seen. Actuarial local failure analysis (the censoring of patients who died without evidence of local failure before the two-year follow-up examination) revealed a rate of local failure of 44 per cent (14 to 79 per cent) in the group that had been treated with chemotherapy and radiation alone compared with 13 per cent (0 to 53 per cent) in the patients who had had a resection, but this difference was not significant (p > 0.25, log-rank method).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Extensive osteolysis around an aseptic, stable, uncemented total knee replacement.

Extensive osteolysis occurred around an aseptic, well-fixed, stable, uncemented total knee prosthesis. At the time of revision, tibial polyethylene wear and minimal metal-on-metal contact were present. A hypertrophic synovium-like membrane abutted bone in regions of osteolysis. Examination of this membrane revealed polyethylene-wear debris and significant levels of chromium, cobalt, and titanium. Wear debris--polyethylene, metal, or a combination of both--may be responsible for the osteolytic process in this case.

Bone Cements↗
PubMed1993

Soft-tissue sarcomas. Future perspectives.

Although the previous outlook for patients with soft-tissue tumors was poor, in recent years advances have been made in earlier recognition and management of soft-tissue sarcomas. Advances include improved clinical pathologic correlation and clinical staging, as well as improved concept of what constitutes adequate surgical management. In addition, recent advances in surgical adjuvant treatment programs promise better results. Moreover, a better understanding of the biology of cancer and the development of sophisticated techniques of molecular biology should lead to more effective treatment.

Adjuvants, Immunologic↗
PubMed1993

Osteogenic melanoma. A rare variant of malignant melanoma.

Osteogenic melanoma is a rare variant of malignant melanoma; only eight cases have been reported. To characterize this unusual neoplasm further, we present four new cases. Two patients were men and two were women (average age, 56 years; range, 47-78 years). All tumors arose from acral lentiginous melanomas. Three were subungual finger lesions and one was on the sole of the foot. All four had been previously diagnosed as or were suspected to have been primary osseous lesions. The vertical growth components were high-grade, amelanotic sarcomatoid malignancies with abundant osteoid matrix. Two tumors also had chondroblastic differentiation. Cells with epithelioid features, including prominent eosinophilic nucleoli, were discernible in every tumor. Regional lymph node metastases in two cases retained osteocartilaginous differentiation, whereas metastatic cells in another case were purely epithelioid. Tumor cells in every case were immunoreactive for S-100 protein and vimentin, and non-reactive for cytokeratin. Two tumors also expressed HMB-45. Melanosomes were identified ultrastructurally in every tumor. Follow-up information was available on every patient. Three developed regional lymph node metastases and are currently alive and well after 14, 39, and 101 months. The fourth patient died of metastatic uterine carcinoma 20 months postoperatively. The differential diagnosis of osteogenic melanoma includes osteosarcoma as well as atypical fibro-osseous proliferations. Clinico-pathologic features that support a diagnosis of osteogenic melanoma include junctional activity, absence of primary bony involvement, regional nodal metastases, immunoreactivity for S-100 protein and/or HMB-45, lack of cytokeratin reactivity, and ultrastructural identification of melanosomes.

Aged↗
PubMed1992

Pattern of p53 gene mutations in breast cancers of women of the midwestern United States.

BACKGROUND: Mutation in the p53 gene is the most common genetic lesion in human cancers. The pattern of mutation in the p53 gene differs among cancers and may be a useful epidemiological tool for identification of factors contributing to carcinogenesis. PURPOSE: Our purpose was to determine if the pattern of p53 mutation in breast carcinomas in our population of women residing in the midwestern region of the United States is similar to the pattern of p53 mutation in breast cancers in patients from other regions of the United States and Europe and in other epithelial tumors. METHODS: With a technique we recently developed for the analysis of p53 mutations in genomic DNA from tumor cell clusters in touch preparations of solid tumors, we sequenced exons 5-9 and adjacent splice junctions of the gene in 44 breast cancers. Cells from each tumor were also stained with three monoclonal antibodies which recognize different epitopes of the p53 protein. RESULTS: We detected p53 mutations in 14 (32.6%) of 44 breast carcinomas. Only half of the mutations were missense changes. The other half included five microdeletions (three producing frame-shifts), one single-base substitution generating a stop codon, and one single-base substitution generating a splice junction abnormality. Nuclear expression of p53 antigen was present in eight of 44 cancers, including six with hemizygous missense mutations in the p53 gene. CONCLUSIONS: The pattern of p53 mutations in our breast cancer population differs from that reported in breast cancer populations by other investigators in which most p53 mutations were missense. Among 14 mutations in our population, at least five drastically altered the structure of p53, suggesting that a recessive mechanism of inactivation of the p53 gene may be more common than in other populations. IMPLICATIONS: Differences in the pattern of p53 mutation in breast cancers in Midwestern women and in breast cancers in other populations may reflect selection bias or small sample sizes currently available. However, our data are compatible with the possibility that an endogenous or exogenous factor influences p53 carcinogenesis in some women with breast cancer in the Midwest to a greater extent than in other regions of the United States and Europe.

Adult↗
PubMed1992

Phyllodes tumor: clinicopathologic review of 60 patients and flow cytometric analysis in 30 patients.

We reviewed 66 phyllodes tumors of the breast from 60 patients. Our patients included 59 women and one man ranging in age from 16 to 72 years. Fifty patients presented for primary treatment of newly diagnosed breast masses, nine presented with recurrent tumors, and one presented with soft tissue metastases 9 years after bilateral subcutaneous mastectomies and multiple chest wall recurrences of phyllodes tumor. After 0.3 to 53.2 years (mean, 15.5 years) of follow-up, 26 (43.3%) patients are free of disease without recurrence, 26 (43.3%) patients are dead of other (17 patients) or unknown (nine patients) causes, four (6.7%) patients had locally recurrent tumor 0.7 to 2.9 years after lumpectomy and are free of disease 3 months to 12 years after re-excision or simple mastectomy, two (3.3%) patients are lost to follow-up, and two (3.3%) patients died with metastatic disease 1.8 and 7 years after diagnosis. Histologic features and flow cytometric analysis showed no correlation with outcome. Fifty-six breast tumors were biphasic and nine were purely stromal tumors. Twenty-six (47%) biphasic tumors showed stromal overgrowth. Tumor margins were pushing in 20 (39%) and infiltrative in 29 (61%) of 49 evaluable cases. Twenty-one tumors were highly cellular and 17 showed cytologic atypia. Necrosis was identified in 16 tumors. Mitotic rates ranged from 0/10 high-power fields to 48/10 high-power fields. Twenty-four diploid, six aneuploid, three tetraploid, and one polyploid tumor were identified by flow cytometry. S-phase fractions tended to be higher in nondiploid tumors. Neither DNA content nor S-phase fraction correlated with outcome. Our results indicate that most mammary phyllodes tumors, including purely stromal tumors, behave as low-grade, nonmetastasizing neoplasms. Neither histologic evaluation nor DNA content provides reliable clues concerning the natural history of an individual tumor.

Adolescent↗
PubMed1991

DNA content flow cytometry as a prognostic factor for node-positive breast cancer. The role of multiparameter ploidy analysis and specimen sonication.

The DNA content was analyzed in paraffin-embedded material from 167 patients with node-positive breast cancer to learn whether specimen sonication and multiparameter ploidy analysis (MPPA) (using DNA content and light scatter) could improve the strength of ploidy as a prognostic variable. Sonicated specimens were found to have fewer aggregates, a lower percentage of cells in S-phase (%S) and G2M phase than the corresponding nonsonicated specimens. The results using MPPA predicted the prognosis better because they allowed detection of small aneuploid peaks in histograms classified as diploid or tetraploid using DNA content alone. Ploidy was a significant univariate factor, and patients with tetraploid tumors had the best survival. In the multivariate analysis, if other routine factors were examined preferentially, ploidy and %S did not provide additional prognostic information for survival. This study of paraffin-embedded breast cancers suggested that sonication and MPPA may improve the ploidy analysis in certain cases and that tetraploidy may be a favorable ploidy pattern in this group.

Breast Neoplasms↗
PubMed1991

Direct sequencing from touch preparations of human carcinomas: analysis of p53 mutations in breast carcinomas.

A new technique for characterizing somatic mutations in very small samples of cellularly heterogeneous human cancer tissue was developed and tested using mutations in the p53 gene in breast carcinomas as a model system. The technique combines touch preparation of specimens to obtain homogeneous clusters of carcinoma cells free of normal cells with a nested pair of polymerase chain reaction (PCR) amplifications of DNA to increase the amount of target gene sequence sufficiently to permit direct sequencing of the p53 gene. Touch preparations of fresh or previously frozen tissue from human adenocarcinomas derived from several organs were stained, and clusters of 10-50 malignant cells were transferred by pipette into microfuge tubes for PCR amplification. Exons 5-9 of the p53 gene, which contain the major mutational hot spots associated with most human cancers, were sequenced by the following steps: 1) two rounds of PCR amplification using DNA Taq polymerase and two sets of oligonucleotide primers, the second set being nested within the segment amplified by the first set and having attached T7 and SP6 phage promoter sequences, 2) transcription of the amplified DNA sequences with T7 and SP6 RNA polymerases, and 3) dideoxy sequencing of single-stranded RNA transcripts with reverse transcriptase and with additional oligonucleotide primers to achieve specificity for this unique region of the genome. The utility of this approach is illustrated by our success in detecting and analyzing point mutations in cell clusters from four of 11 primary adenocarcinomas of the human breast.

Adenocarcinoma↗
PubMed1991

Survival and management considerations in postirradiation osteosarcoma and Paget's osteosarcoma.

Postirradiation and Paget's osteosarcomas are high-grade malignancies. The five-year survival was only 10% in recent experience at the author's institution. Progressive pain is an important clinical feature in both conditions. Careful roentgenographic studies demonstrate cortical destruction and a soft-tissue mass in virtually all patients. Metastasis was present in 25% of both groups of patients at presentation. In contrast to previous series, more than 80% of the patients with postirradiation osteosarcoma had had irradiation for malignant entities and more than 70% had been treated with modern radiotherapy regimens (cobalt-60 or linear accelerator). Twice as many patients with postirradiation osteosarcoma were evaluated and treated in the 1980s than in the previous decade. The initial indication for irradiation often was carcinoma of the breast, uterus, or cervix, or lymphoma. Two-thirds of the patients had progressive disease that was not controllable within six months after diagnosis. Early detection may be the only effective means of improving survival with postirradiation or Paget's osteosarcoma. These patients require lifelong follow-up evaluations.

Bone Neoplasms↗
PubMed1989

Randomized trial to evaluate the addition of tamoxifen to cyclophosphamide, 5-fluorouracil, prednisone adjuvant therapy in premenopausal women with node-positive breast cancer.

A randomized clinical trial was performed to determine if the addition of hormonal therapy with tamoxifen to a combination chemotherapy regimen was superior to the chemotherapy alone for adjuvant treatment of premenopausal women after mastectomy for node-positive breast cancer. The chemotherapy regimen utilized consisted of cyclophosphamide (C), 5-fluorouracil (F), and prednisone (P), and the doses employed were: C, 150 mg/m2 IV days 1 to 5; F, 300 mg/m2 IV days 1 to 5; and P, 10 mg orally three times daily on days 1 to 7. A total of ten courses of therapy, given every 6 weeks, was planned. Tamoxifen (T) was given at a dose of 10 mg twice daily and was stopped 6 weeks after the last course of CFP. Four hundred patients are fully eligible and evaluable. With a median observation time of 5.3 years, the proportion of recurrences on each arm were: CFP, 95 of 202 (47%); CFPT, 77 of 198 (39%). The relapse-free survival distribution for CFPT was superior to that for CFP, at a borderline level of significance (two-sided P = 0.06). When significant prognostic factors were considered in covariate analysis, CFPT was not significantly better than CFP (P = 0.43). This marked change in level was due to imbalance in several factors not considered in stratification. Currently, 31% of CFP and 25% of CFPT patients have died, and although there is a slight separation of the survival curves in favor of CFPT, the difference is not significant (P = 0.21). Analysis within receptor subsets also showed no significant advantage for the addition of tamoxifen. This study does not establish a significant advantage for the concurrent administration of tamoxifen with the CFP regimen. It does, however, clearly demonstrate the importance of examination of clinically important prognostic factors, even those not utilized in stratification, and consideration of these factors in covariate analysis if imbalances are present.

Adult↗
PubMed1989

Steroid receptors and giant cell tumor of bone.

The cell of origin and giant cell tumor remains unknown, but on the basis of most experimental evidence it is probably a mesenchymal cell showing some macrophage characteristics. The clinical features which have led people to suggest that this tumor may be a steroid receptor positive lesion are tenuous at best. Early histochemical data suggesting a presence of estrogen and progesterone receptors in giant cell tumor have not been substantiated by further studies. Immunohistochemical techniques have not identified estrogen receptors in giant cell tumor. Multiple biochemical techniques have failed to identify clinically significant levels of estrogen or progesterone receptors in giant cell tumor.

Bone Neoplasms↗