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Biomedical subjects

B Fisher

Publications and source records attributed to B Fisher.

At least 253 records · Page 14Linked to original sources
PubMed1985

Biologic considerations regarding the one and two step procedures in the management of patients with invasive carcinoma of the breast.

Investigation of the biologic significance of delay between biopsy and mastectomy was performed upon women with invasive carcinoma of the breast in protocol four of the NSABP. Since the period of delay was two weeks or less in approximately 75 per cent, no comment concerning the possible effects of longer periods can be made. Life table analyses failed to reveal any difference in ten year survival rates between patients undergoing radical mastectomy management by the one and two step procedures. Similarly, no difference in adjusted ten year survival rate was observed between women managed by the two step procedure who did or did not have residual tumor identified in the mastectomy specimen after the first step or biopsy. Importantly, the clinical or pathologic stages, sizes of tumor or histologic grades were similar in women managed by the one and two step procedures minimizing selection bias. The material used also allowed for study of the possible causative role of biopsy of the breast on the development of sinus histiocytosis in regional axillary lymph nodes. No difference in degree or types of this nodal reaction could be discerned in the lymph nodes of the mastectomy specimens obtained from patients who had undergone the one and two step procedures. This finding indicates that nodal sinus histiocytosis is indeed related to the neoplastic process, albeit in an undefined manner, rather than the trauma of biopsy per se as has been suggested. These results do not invalidate the use of the one step procedure in the management of patients with carcinoma of the breast. Indeed, it is highly likely that it will be commonly used now that breast-conserving operations appear to represent a viable alternative modality for the primary surgical treatment of carcinoma of the breast. Yet, it is apparent that the one step procedure will be performed for technical and practical rather than biologic reasons.

Actuarial Analysis↗
PubMed1984

Pathologic findings from the National Surgical Adjuvant Breast Project (Protocol No. 4). XI. Bilateral breast cancer.

Sixty-six confirmed instances of clinically metachronous second breast cancers were encountered over a 10-year period in 1578 women with invasive breast cancer enrolled in Protocol 4 of the National Surgical Adjuvant Breast Project (NSABP). Seven of the second cancers were in situ, yielding an incidence of 3.7% invasive and 0.5% noninvasive cancers. Except for a peak of 1.75% in the second postoperative year, the annual incidence based on patients at risk was constant and less than 1%. Ninety-three percent of the second cancers occurred within 7 years and 80% within 5 years following mastectomy for the initial primary. All of the second cancers were regarded as being primarily of mammary origin exhibiting either: (1) an in situ component; (2) dissimilar but well-recognized patterns of primary breast cancers; or (3) the appearance of scar cancer, a recently described morphologic feature characteristically observed in some primary breast cancers. A search for factors that might be predictive of bilaterality was performed. Thirty-eight pathologic and eight clinical factors were assessed, including family history. Although the latter was 1.5 to 2 times more frequent in patients with bilateral disease, this estimate was not statistically significant. On the other hand, a statistically significant association with bilateral disease was found when the initial tumor measured more than 2.0 cm, was associated with invasive cancer or proliferative fibrocystic disease, nipple involvement, absent nodal sinus histiocytosis, lobular carcinoma in situ in the vicinity of the dominant mass, or was of the lobular invasive or tubular types. However, the degree of risk of these discriminants was no greater than 2 to 3:1. Despite the clinical scrutiny imposed by the NSABP protocol second tumors measured only 1 cm less than the first, measuring on average 2.4 cm, which reflects the difficulty attendant on the clinical detection of so-called early breast cancers. Yet, no significant difference in pathologic nodal status was noted between the first and second cancers or that of patients with unilateral disease. Furthermore, there was no difference in survival rate between patients who developed a second cancer and those with unilateral disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Clinical trials for the evaluation of cancer therapy.

One of the great advances of the last 50 years has been the introduction of prospective randomized controlled trials into clinical medicine. Those efforts apply the scientific method to clinical problem solving and provide the mechanism for obtaining answers to important clinical and biologic questions that can be obtained in no other way. When properly employed, clinical trials supply definitive information relative to the worth of therapies prior to their widespread use on populations as a whole. They are sophisticated endeavors requiring the interactions of clinicians, investigators, and statisticians as equal partners in a common effort that requires discipline as rigid as that of a laboratory experiment. There are three types or phases of clinical trials conducted on cancer patients; each is directed toward supplying answers to different questions. Phase I trials determine safe dose levels and/or schedules of drugs in humans. They may be aimed at using known drugs in combinations heretofore not tried or at determining the tolerably toxic dose of drugs that have shown benefit in animal models. Efficacy is not a defined goal of Phase I trials. Utilizing schedules and dosages and incorporating limitations discovered in Phase I trials, studies are next conducted that are aimed at determining therapeutic efficacy; i.e., Phase II trials. They are performed on patients of the same tumor type and measurable disease (usually Stage IV). In neither Phase I or II trials is randomization a feature. With demonstration of at least some efficacy in a Phase II trial, a therapy becomes a candidate for full-scale testing and comparison with a currently "standard" therapy in a Phase III trial. This report presents an overview of some of Stages I and II cancer. Comments will be made relative to their rationale, design, conduct, and statistical requirements, as well as ethical considerations, with the hope that more of the current generation of physicians will become aware of their importance and will be stimulated to participate in such endeavors. This overview is not meant for the statistician or for the sophisticate who is well versed in the vast literature that is accumulating in this area. Comments are primarily based upon experiences derived from the clinical trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) for a quarter of a century. Where appropriate, breast cancer will serve as a model for the discussion.

Clinical Trials as Topic↗
PubMed1984

The relationship of depth of penetration and tumor size to the number of positive nodes in Dukes C colorectal cancer.

This study examines the interrelationships of depth of penetration, tumor size, and the number of positive nodes in Dukes C colorectal cancer. The results indicated that depth of tumor penetration was related to both tumor size and the number of positive regional lymph nodes. Tumors with positive nodes which failed to penetrate the muscularis propria (C1) were smaller, and were associated with fewer positive nodes than were tumors penetrating all coats of the bowel (C2). Although tumor penetration was related to tumor size and the number of positive nodes, no correlation was evident between tumor size and the number of positive nodes within the C1 and C2 patient subsets. The data underscore the biological significance of depth of tumor penetration and militate against tumor size as a prognostic discriminant in patients with colorectal cancer. The findings represent a contradiction to the prevailing biological concepts relative to the behavior of solid tumors as reflected in the TNM classification scheme.

Colonic Neoplasms↗
PubMed1984

Pathologic findings from the National Surgical Adjuvant Project for Breast Cancers (protocol no. 4). X. Discriminants for tenth year treatment failure.

A search for prognostic discriminants of treatment failure in the tenth postmastectomy year was undertaken in 614 patients enrolled in protocol no. 4 of the National Surgical Adjuvant Project for Breast Cancers treated by radical mastectomy. Exploratory analyses of 38 pathologic and 6 clinical features disclosed 16 and 13 variables significantly related to nodal status and treatment failure, respectively. However, multivariate analyses with life tables adjusted or controlled for nodal status revealed that patients whose tumors measured less than 2 cm had a more favorable clinical course. All of the characteristics were also explored when patients were stratified according to numbers of nodal metastases, the most significant prognostic discriminant for disease-free survival in the tenth year. A germinal center predominance lymph node pattern and high histologic grade according to our conventional grading method were observed to adversely influence disease-free survival in patients with negative nodes. A strong trend in this manner was also observed with tumors greater than or equal to 2 cm and types 3 and 5 scar cancers. Histologic grade and tumor size were significantly recognized as discriminatory in patients with 4+ nodes but no factors were significantly observed in the group of patients with 1 to 3 positive nodes. A possible explanation for this inconsistency is discussed. For the most part, these factors were also encountered by us previously at the 5-year postoperative period. Only the presence of 13+ nodal metastases and types 3 and 5 scar cancers and cancers without scar appeared to discriminate success or failure between the fifth and tenth year. It is therefore concluded that nodal category, germinal center predominance, histologic grade, and tumor size, in the contexts noted, represent strong prognostic discriminants exerting a rather constant influence on disease-free survival at least to the tenth postmastectomy period. The prognostic value of categorizing those patients with 4+ positive nodes into subgroups with 4 to 6, 7 to 12 and 13+ is reaffirmed. The actual disease-free survival of patients in the tenth year was not strikingly different from that observed previously by us at 5 years in this cohort.

Breast↗
PubMed1984

The efficacy of bone scanning in the follow-up of patients with operable breast cancer.

A considerable fraction of first metastases in breast cancer patients are found in the skeletal system. Consequently, to improve the probability of detecting bone lesions, protocols of the National Surgical Adjuvant Breast and Bowel Project (NSABP) have required radionuclide scans every six months for the first three postoperative years and yearly thereafter. The present study was conducted to evaluate the worth of 7984 bone scans performed prior to documentation of first treatment failure on 2 697 stage II (positive node) patients entered into NSABP clinical trial B-09. At the time of evaluation, there were 779 patients with a treatment failure, 163 (20.9%) of whom had their recurrence limited to bone. At most, 52 (0.6%) of the total number of screening scans were efficacious in detecting lesions in asymptomatic patients. As a result of this minimal benefit from routine scans, it was recommended that they be conducted less frequently. In presently ongoing NSABP studies, asymptomatic patients having tumors with positive axillary nodes receive scans at yearly intervals for the first three years. Future NSABP trials will require follow-up bone scans only as indicated by symptoms.

Adult↗
PubMed1984

The prognostic significance of preoperative carcinoembryonic antigen levels in colorectal cancer. Results from NSABP (National Surgical Adjuvant Breast and Bowel Project) clinical trials.

This analysis explores the prognostic significance of preoperative carcinoembryonic antigen (CEA) levels in patients with colorectal cancer. The data were derived from 945 patients entered into two randomized prospective clinical trials of the National Surgical Adjuvant Breast and Bowel Project. A strong correlation was evident between preoperative CEA level and Dukes class. The mean CEA progressively increased with each Dukes category and the mean value for each of the four classes was significantly different. This relationship was prevalent whether the data were analyzed for all colorectal lesions regardless of location or specifically for right-sided colon tumors. The prognostic function of preoperative CEA level was independent of the number of positive histologic nodes. Preoperative CEA level correlated with the degree of lumen encirclement by tumor. Tumors that did not encircle more than one half the lumen were associated with significantly lower preoperative CEA levels than those that did. The presence or absence of lumen obstruction was unrelated to the preoperative CEA level. The relative risk of developing a treatment failure was associated with preoperative CEA, in both Dukes B and C patients, demonstrating that the prognostic significance of preoperative CEA was independent of Dukes class.

Carcinoembryonic Antigen↗
PubMed1984

Delayed effect of radiation therapy with or without chemotherapy on ovarian function in women with Hodgkin's disease.

In this retrospective investigation of 51 female patients with Hodgkin's disease, the age of the patient at the time of primary treatment and the extent of radiation therapy were the two most important factors determining post-therapy ovarian function. Favourable indicators of ovarian preservation included young age, especially premenarchal , at the time of primary therapy, and irradiation confined to above the pelvic brim, whereas, age over 40 and irradiation below the pelvic brim predicted high probability of ovarian failure. Overall, 55 per cent of female patients under the age of 50 treated with chemotherapy alone or with radiation therapy above the pelvic brim retained normal ovarian function. The stage of disease at presentation and the post-therapy status of disease had no apparent effect on subsequent menstrual function.

Adolescent↗
PubMed1984

Master indenture: capital financing for health care systems.

The master indenture enables members of multiinstitutional health care systems to finance capital programs and expansions by borrowing on the basis of systemwide revenues and assets. Participation in a master indenture financing may be structured in two ways. In a restricted group, only the parent organization issues notes, and only the parent is directly liable for the debt. To ensure that each member's revenues flow to the parent, the latter must have sole member status and be permitted to approve subsidiaries' debts, budgets, amendments to articles and bylaws of incorporation, and selection of trustees. Each entity's articles and bylaws must permit it to support the system members' common charitable purpose. In contrast, members of an obligated group have direct joint and several liability for master indenture notes. If one subsidiary misses a payment, the parent can call for payment from other obligated group members. Limitations on a member's obligation to support system debt in case of insolvency or bankruptcy may be included in the master indenture provisions. Whichever structure is selected, the amount of debt that can be incurred is based on the institutions' combined financial statements. The master indenture thus allows financially weak institutions to benefit from the credit strengths of stranger system members and permits the parent organization to control members' access to capital markets.

Capital Financing↗
PubMed1984

Relation of estrogen and its receptor to rat liver growth and regeneration.

A variety of hormones have been implicated in the process of liver regeneration. Despite the demonstration of specific estrogen receptors (ER) in mammalian liver and the identification of responses to estrogen which occur in liver, there has been little or no investigation of the relation of that hormone or its receptor to liver regeneration or liver growth. This report provides information which indicates: (a) the effect of 17 beta-estradiol on the mass of both intact and regenerating rat liver; (b) the percentage of hepatocytes in neonatal and adult normal intact livers which contain ER, i.e., the estrogen receptor index (ERI); (c) changes in ERI and in nuclear ER occurring in that cell population following partial hepatectomy (PH) and/or 17 beta-estradiol administration; and (d) the temporal relation of the changes in ER with those related to DNA synthesis and liver regeneration and to liver growth. Approximately 55 to 60% of parenchymal cells from intact livers in adult rats were found to contain ER which was entirely located in the cytoplasm. No nuclear ER was evident in such cells. By 1 hr, and subsequently following 17 beta-estradiol administration to such animals, there resulted a depletion in the number of ER-containing cells and the identification of nuclear ER. These changes were followed by the onset of increased DNA synthesis and an increase in liver weight (p less than 0.001). Subsequent to 70% PH, a similar series of events occurred in liver remnants. Not only was there a decrease in the ERI from 60% at the time of PH to 40% 3 hr later and 30% after 72 hr, there was a decrease in cytosol ER as well. Accompanying the decrease was an increase in the number of cells with nuclear ER. By 24 hr post-PH, 29% of the cells with ER displayed that receptor in their nuclei. At that time, DNA synthesis was at its peak, and liver regeneration was taking place. When 17 beta-estradiol was administered at the time of PH, there was a more rapid onset of translocation of ER to the nuclei of parenchymal cells. At PH, when 17 beta-estradiol was given, no cells displayed nuclear ER. One hr later, 18% of cells with ER had nuclear ER, in contrast to the finding that only 3% of cells had nuclear ER 1 hr post-PH when 17 beta-estradiol was not administered. Regeneration was greater (59 versus 73%; p = 0.003) when animals received 17 beta-estradiol prior to PH.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update.

The current findings completely affirm the validity of our original observations indicating the appropriateness of grouping primary breast cancer patients into those with negative, 1 to 3, or greater than or equal to 4 positive nodes. Results, however, reveal that there is a risk in combining all patients with greater than or equal to 4 positive nodes into a single group. Since there was a 25% greater disease-free survival and an 18% greater survival in those with 4 to 6 than in those with greater than or equal to 13 positive axillary nodes, such a unification may provide misleading information regarding patient prognosis, as well as the worth of a therapeutic regimen when compared with another from a putatively similar patient population. Of particular interest were findings relating the conditional probability, i.e., the hazard rate, of a treatment failure or death each year during the 5-year period following operation to nodal involvement with tumor. Whereas the hazard rate for those with negative, or 1 to 3 positive nodes, was relatively low and constant, in those with greater than or equal to 4 positive nodes the risk in the early years was much greater, but by the fifth year it was similar to that occurring when 1-3 nodes were involved, and not much different from negative node patients. The same pattern existed whether 4 to 6 or greater than or equal to 13 nodes were positive. When the current findings are considered relative to other factors with predictive import, it is concluded that nodal status still remains the primary prognostic discriminant.

Axilla↗
PubMed1983

Fluoresceinated estrone binding by cells from human breast cancers obtained by needle aspiration.

Despite widespread use there are disadvantages associated with biochemical methods for ER determination. Since there is increasing emphasis on earlier detection of primary breast cancers there is clearly a need for a method which requires only small numbers of tumor cells. A variety of other clinical situations exist in which the availability of a technic that could supply information regarding tumor ER from a small cell population would be helpful. This report presents our experience with 17-fluoresceinated estrone (17-FE) binding for detecting the proportion of estrone binding cells in samples obtained by fine-needle aspiration of tumors prior to their removal. The findings from the aspirated cells employing 17-FE were compared with results obtained from aliquots of the same tumors following their removal using both cytochemical (17-FE) and biochemical (3H-estradiol binding) methods for ER determination. When biochemically determined ER values (fmol/mg cytosol protein) were compared to the proportion of fluorescent cells observed either in cells from needle aspirates prior to tumor removal or in cells from the removed tumor there was no direct quantitative relationship. That lack of correlation is to be expected and does not indicate that one or the other method is inappropriate. It was found, however, that 100% of tumors having ER levels greater than or equal to 10 fmol had greater than or equal to 10% marker positive cells. Fifty-four percent of tumors with a negative or borderline (less than 10 fmol) ER level had less than 10% marker positive cells. The less satisfactory correlation in biochemically ER negative tumors may be related to false negative biochemical determinations. The better correlation between results from the biochemical method and those with 17-FE binding using needle aspirates than between the former and the latter when cells from fragments of removed tumor were used for cytochemical analysis, and the lack of concordance in 17-FE binding by the two cell suspensions (from needle aspirates and from parts of the removed tumor) may be related to the heterogeneity of the cellular composition of a tumor as regards ER content and consequently to the methods of sampling. The authors' experience in this and previous studies using 17-FE for determination of the proportion of putatively ER positive cells indicate that the method is worthy of further evaluation and consideration for experimental and clinical use.

Adult↗