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Biomedical subjects

D Winchester

Publications and source records attributed to D Winchester.

8 recordsLinked to original sources
PubMed2001

Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma.

PURPOSE: To define patterns of care for the local therapy of stage I and II breast cancer and to identify factors used to select patients for breast-conserving therapy (BCT). PATIENTS AND METHODS: A convenience sample of 16,643 patients with stage I and II breast cancer treated in 1994 was obtained from hospital-based tumor registries. Histologic variables were determined from original pathology reports. RESULTS: BCT was performed in 42.6% of patients. Multivariate analysis demonstrated that living in the Northeast United States (odds ratio [OR], 2.48; 95% confidence interval [CI], 2.16 to 2.84), having a clinical T1 tumor (OR, 2.51; 95% CI, 2.27 to 2.78), and having a tumor without an extensive intraductal component (OR, 2.07; 95% CI, 1.81 to 2.37) were the strongest predictors of breast-conserving surgery. Radiation therapy was given to 86% of patients who had breast-conserving surgery. Age less than 70 years was the most significant predictor of receiving radiation (OR, 2.11; 95% CI, 1.77 to 2.25). Tumor variables did not correlate with the use of radiation, but favorable tumor characteristics were associated with the use of breast-conserving surgery. CONCLUSION: Despite strong evidence supporting the use of BCT, the majority of women continue to be treated with mastectomy. Predictors of the use of BCT do not correspond to those suggested in guidelines.

Adult↗
PubMed1998

BAG-1, a negative regulator of Hsp70 chaperone activity, uncouples nucleotide hydrolysis from substrate release.

Molecular chaperones influence the process of protein folding and, under conditions of stress, recognize non-native proteins to ensure that misfolded proteins neither appear nor accumulate. BAG-1, identified as an Hsp70 associated protein, was shown to have the unique properties of a negative regulator of Hsp70. Here, we demonstrate that BAG-1 inhibits the in vitro protein refolding activity of Hsp70 by forming stable ternary complexes with non-native substrates that do not release even in the presence of nucleotide and the co-chaperone, Hdj-1. However, the substrate in the BAG-1-containing ternary complex does not aggregate and remains in a soluble intermediate folded state, indistinguishable from the refolding-competent substrate-Hsp70 complex. BAG-1 neither inhibits the Hsp70 ATPase, nor has the properties of a nucleotide exchange factor; instead, it stimulates ATPase activity, similar to that observed for Hdj-1, but with opposite consequences. In the presence of BAG-1, the conformation of Hsp70 is altered such that the substrate binding domain becomes less accessible to protease digestion, even in the presence of nucleotide and Hdj-1. These results suggest a mechanistic basis for BAG-1 as a negative regulator of the Hsp70-Hdj-1 chaperone cycle.

Adenosine Triphosphatases↗
PubMed1993

Cancer of the stomach. A patient care study by the American College of Surgeons.

OBJECTIVE: The major purpose of this study was to document the modes of presentation, diagnostic methods, clinical management, and outcome of gastric cancer as reported by tumor registries of US hospitals and cancer programs approved by the American College of Surgeons. SUMMARY BACKGROUND DATA: Gastric cancer continues to diminish in the US, but the stage of disease and survival outcome after surgical resection is unchanged despite increased availability and sophistication of diagnostic techniques. This is in contrast to the marked improvement in survival outcome in Japanese and other Eastern series over the last decades. Possible reasons for the improved Japanese results have been earlier detection secondary to active diagnostic surveillance of the population and widespread adoption of aggressive surgical resection emphasizing wide-field node (R2) dissection. Although selected US centers using the Japanese approach report better survival data, the approach has not been widely adapted by US treatment centers. METHODS: Tumor registries at American College of Surgeons (ACS) approved hospitals were mailed a study protocol in 1987. They were instructed to review 25 consecutive patients with gastric cancer treated in 1982 (long-term study) and 25 patients treated in 1987 (short-term study). A detailed protocol included significant history, diagnostic results, staging, pathology findings, and treatment results. The data forms on 18,365 patients were returned and analyzed (11,264 patients in the long-term study and 7101 patients in the short-term study). RESULTS: Of 18,365 patients, 63% were males. The median ages were 68.4 years in males and 71.9 years in females. There was a history of gastric ulcer in 25.5% of the patients. Lesion location was upper third in 31%, middle third in 14%, distal third in 26%, and entire stomach in 10% of patients (and the site was unknown in 19%). Gastric resection was performed for 80% of upper third cancers and 85% of distal third cancers; 50% of patients with total gastric involvement had gastric resection. The extent of gastric resection varied according to location. For lower third lesions, subtotal gastrectomy was done in 55% of the cases, extended resection in 21%, and total gastrectomy in 6%. For proximal lesions, 29% had subtotal, 4.6% had total, and 41% had extended gastrectomies (including esophagus), and 13.6% had dissection of celiac nodes. The operative mortality rate was 7.2%. Staging (American Joint Committee on Cancer [AJCC]) was as follows: I, 17%; II, 17%; III, 36%; and IV, 31%. The overall survival rate reflecting deaths from all causes was 14% among 10,891 patients diagnosed in 1982, and it was 19% in patients having resection. The disease specific survival rate was 26%. The survival rate after resection was 19% and 21% for lower and mid third cancers, 10% for upper third cancers, and 4% if the entire stomach was involved. The stage-related survival rates were 50% (stage I), 29% (stage II), 13% (stage III), and 3% (stage IV). Among patients with pathologically clear margins, the survival rate was 35% versus 13% in those with microscopically involved margins, and it was 3% in those with grossly involved margins. CONCLUSION: This report of gastric cancer treatment by American College of Surgeons approved institutions in the US provides an overview of the disease as commonly treated throughout the US. Although the results are less favorable than those reported by centers with large institutional experiences with this disease and are inferior to those of the Japanese and other Eastern centers, they suggest potential for increasing survival by upstaging through earlier diagnosis and using resectional techniques demonstrated to more adequately control local regional disease.

Adult↗
PubMed1993

Popliteal venous aneurysms.

Popliteal venous aneurysms are rarely reported but represent a potentially life-threatening condition requiring accurate diagnosis and surgical resection. Newer techniques including magnetic resonance imaging, computed tomography, and color flow duplex imaging offer new noninvasive methods to define popliteal fossa venous abnormalities. Excision of the aneurysm with venous reconstruction removes the embolic source and maintains prograde venous flow. A posterior surgical approach to the popliteal fossa is recommended to facilitate exposure. Early control of venous outflow is needed to avoid thromboembolism. This report describes the diagnosis and treatment of popliteal venous aneurysms in three patients with a review of the English-language literature.

Adolescent↗
PubMed1990

Results of a national survey of characteristics of hospital tumor conferences.

A descriptive survey of hospital tumor conferences, which are also referred to as tumor boards, was conducted by the National Cancer Institute in collaboration with the American College of Surgeons and Roswell Park Memorial Institute. The survey was done to assess the involvement of the tumor conference in the care of the patient with cancer and to lay the groundwork for additional studies of the conference. The data from the descriptive survey are based on questionnaires sent to 1,700 hospitals in the United States. The questionnaires requested information about frequency, attendance, composition, role of the chairman, agenda and other variables that relate to the format and purpose of the conference. From the results, we conclude that tumor conferences are an accepted and established institution for the multidisciplinary care of patients with cancer. They are a major source of consultation and education for physicians and for other professionals involved in oncology. Tumor conferences are conducted in a wide spectrum of hospitals and related institutions that vary in size and function.

Clinical Protocols↗
PubMed1987

Adult soft tissue sarcomas. A pattern of care survey of the American College of Surgeons.

A nationwide survey of the clinical presentation, pathology, and management of soft tissue sarcomas in adults was carried out under the auspices of the Commission on Cancer of the American College of Surgeons. Two separate 2-year periods were used to allow assessment of changes in patterns of care. Data were obtained from 504 hospitals in 1977-1978 (2355 patients) and 645 institutions in 1983-1984 (3457 patients). Pretreatment findings of interest included some evidence of physician delay in diagnosis, overuse of excisional biopsy as opposed to the generally preferred approach of incisional biopsy, a low rate of usage of the American Joint Committee for Cancer Staging (AJCSS) system, and major reliance on CT for pretreatment patient evaluation. Operation was the primary treatment, with or without adjuvant therapies, in approximately three fourths of the patients. The other one fourth were primarily patients with distant metastasis at the time of diagnosis. Some increase in multimodal therapy did occur in the second period but the rate of amputation was low (approximately 10%) in both periods studied. Survival curves support the prognostic validity of the AJCCS system and the value of complete resection of soft tissue sarcomas. Adverse prognostic factors included positive surgical margins, large tumors, retroperitoneal or mediastinal primary sites, some histologic types, and the perceived need for adjuvant therapy. Patients receiving adjuvant radiation or chemotherapy had less favorable survival data than those treated by operation alone due to criteria used for selecting patients for these therapies. Approximately one half of the treatment failures in the 1977-1978 series were locoregional, whereas 18% were limited to lung metastasis. Salvage therapy for these two forms of treatment failure yielded 61% and 21% 5-year survival rates.

Adult↗