Search PubMed⌕ Search

Biomedical subjects

B Fisher

Publications and source records attributed to B Fisher.

At least 307 records · Page 17Linked to original sources

Pathologic findings from the National Surgical Adjuvant Breast Project (Protocol no. 4). VI. Discriminants for five-year treatment failure.

Thirty-six pathologic and six clinical characteristics observed in 581 patients enrolled in protocol no. 4 of the National Surgical Adjuvant Breast Project were treated by radical mastectomy and were correlated with five-year treatment failure. The cases were initially stratified according to pathologic nodal status, the most important discriminant in breast cancer. The presence of tumor necrosis, poor tumor differentiation (histologic grade 3) and a tumor size > 4 cm were found by multivariate analyses to influence treatment failure in patients without nodal metastases. Prognosis was usually worse in individuals whose tumors exhibited all of these features than in those in whom only one or two could be detected. Although the sample size was small, life-table analysis also disclosed a highly significant relationship between treatment failure and a germinal center predominance pattern in regional nodes in this subset of patients. Except for this latter, these same discriminants were similarly noted to affect treatment failure in those patients with four or more nodal metastases but not those with only 1--3 positive nodes. A possible explanation for this inconsistency among nodal categories is discussed. Nevertheless, it is concluded that these rather easily measured pathologic parameters represent important discriminants for the prognosis and the design of treatment schemes and subsequent protocols for patients with breast cancer, particularly those without regional nodal metastasis. The findings amplify the importance of intrinsic tumor characteristics as well as possibly host factors in accounting for the clinical behavior of patients with breast cancer.

Breast↗

Correlation of estrogen receptor and pathologic characteristics of invasive breast cancer.

Estrogen receptor (ER) status was correlated with a large number of pathological and clinical characteristics of 178 invasive breast cancers. Positive ER was found to be significantly associated with high nuclear and low histologic grades, absence of tumor necrosis, presence of marked tumor elastosis, and older patients. These pathologic parameters enumerated are either directly or indirectly related to tumor differentiation suggesting that ER represents another index of this latter. Multivariate analyses disclosed that both age and tumor differentiation are associated with the ER status. Well-differentiated tumors were more frequently ER+ in older women. Inclusion of an estimate of tumor necrosis as well as patient age appears to allow for further discrimination of ER status in poorly differentiated lesions. Considerations relative to ER and tumor differentiation provide a possible explanation for the dichotomy of response to adjuvant chemotherapy observed in pre and postmenopausal women.

Adult↗

Pathologic findings from the National Surgical Adjuvant Breast Project (protocol no. 4). VI. Invasive papillary cancer.

Although papillary forms of intraductal cancer are a common component of amny mammary cancers, invasive papillary cancer of the breast is relatively rare. Only 35 examples were encountered in the specimens obtained from 1603 women participating in a prospective randomized study of invasive mammary cancer. Contingency-table analysis disclosed that invasive papillary cancer, as opposed to the non-papillary histologic types, is significantly more likely to show circumscription, cytoplasmic oxyphilia, microcalcification, intermediate histologic grade, moderate or marked mucin and an intraductal component of papillary type. Although patients who have invasive papillary cancer are frequently judged by clinical criteria to have regional nodal metastases, in pathologic analysis these metastases are not commonly found and, if present, involve fewer than four nodes. There is a significant frequency of marked sinus histiocytosis in regional nodes. The lesion occurs with a significantly high frequency among non-Caucasian and postmenopausal women. Only three patients with invasive papillary cancer experienced treatment failure after five years of observation. Life-table probabilities showed that the treatment failure rate was significantly lower for the group of patients who had any other histologic type, and in this regard invasive papillary cancer was similar to the tubular and mucinous varieties. Although apocrine metaplasia, fibrous supporting stalks and cellular differentiation have been espoused as important criteria distinguishing intraductal papi-loma from intraductal cancer, these features were also not uncommonly observed in the examples of invasive papillary cancer studied. It is concluded that invasive papillary cancer represents a unique histologic type of invasive mammary cancer attendant with a favorable prognosis.

Breast Neoplasms↗

Diagnosis of invasive aspergillosis by passive hemagglutination assay of antibody.

Sheep red cells treated with concanavalin A and sensitized with a partially purified aspergillus antigen were used to detect antibody to Aspergillus by passive hemagglutination (PHA). Sera from eight patients with aspergillomas or allergic aspergillosis had PHA titers of greater than or equal to 1:800 and antibody detectable by immunodiffusion (ID). Of 122 hospitalized cancer patients without invasive aspergillosis, 118 had titers of less than or equal to 1:80, 86 of < 1:10, two of 1:160, and two of 1:320. None had antibody by ID. Antibody was detectable by PHA in sera from 12 of 14 healthy microbiology laboratory workers. Of 55 cancer patients who had sera available for testing within two weeks before diagnosis of invasive aspergillosis, 18 patients seroconverted: 13 by both PHA and ID, two by PHA alone, and three by ID alone. PHA titers rose from < 1:10 to between 1:40 and 1:1,280. In immunosuppressed patients who were at risk of developing invasive aspergillosis, the appearance of antibody correlated with the diagnosis of invasive aspergillosis.

Antibodies, Fungal↗

Cellular cytotoxicity in tumor-bearing mice after transfer of normal or tumor-sensitized lymphoid cells.

The present investigations are a continuation of those indicating that the administration to normal inbred C3HeB/-FeJ mice of syngeneic tumor-sensitized cells or cells from F344 Mai rats (xenogeneic) sensitized to mouse tumor imparted "information" that resulted in the production of tumor-specific cytotoxic cells by recipients. Current findings revealed that normal but not tumor-sensitized spleen cells when transferred to syngeneic tumor-bearing recipients enhanced the cytotoxicity ofrom F344 Mai rats (xenogeneic) sensitized to mouse tumor imparted "information" that resulted in the production of tumor-specific cytotoxic cells by recipients. Current findings revealed that normal but not tumor-sensitized spleen cells when transferred to syngeneic tumor-bearing recipients enhanced the cytotoxicity of lymphoid cells in the recipients. This enhanced cytotoxicity was specific for the immunizing tumor. Inoculation of normal or tumor-sensitized lymph node cells failed to produce such an effect. Our present and previous findings suggested that in the presence of a tumor, uncommitted cells that reside in the spleen and that are available for recruitment and "instruction" may become depleted, whereas no comparable deficit may exist in cells that are capable of information transfer.

Animals↗

Cellular cytotoxicity and serum inhibition in normal mice following transfer of syngeneic tumor-sensitized cells.

Investigations were performed to elucidate changes in normal syngeneic recipients after they received tumor-sensitized cells. Transfer of regional or nonregional lymph node cells or spleen cells from tumor-bearing inbred C3HeB/FeJ mice to normal syngeneic recipients caused the recipients to produced bone marrow, which mediated in vitro cytolysis of immunizing tumor target cells. This finding was not entirely limited to transfer of lymphoid cells. The transfer of myeloid cells, granulocytes, and cultured macrophages from tumor-bearing mice also produced cytotoxic cells. The extent of cytotoxicity following cell transfer was related to the duration of tumor growth in cell donors, to the degree of cytotoxicity, and to the number of cells transferred. Both the iv and ip routes were equally effective. Treatment of cells before transfer with trypsin or pronase, mitomycin C, or sublethal irradiation failed to prevent development of cytotoxicity in cells of the recipient, whereas freeze-thawing abolished this event. Serum from the cell recipient could inhibit the cytotoxicity demonstrated by lymphoid cells derived from the recipient or from a tumor-bearing animal. The findings indicate that "information" transferred to normal animals not previously exposed to a tumor results in production of tumor-specific cytotoxic cells in these animals.

Animals↗

Further observations on the inhibition of tumor growth by C. parvum with cyclophosphamide. VII. Effect of treatment prior to primary tumor removal on the growth of distant tumor.

The present investigations were directed toward determining whether primary tumor manipulation prior to its removal is advantageous for the control of metastases and survival. Studies were carried out to ascertain whether 1) there is justification for delaying surgical removal of a primary tumor to permit preoperative administration of cyclophosphamide (CY) and/or C. parvum (CP) and 2) there is an advantage to administering the immunotherapy directly into a primary tumor. After operation, in all investigations, systemic CP and CY was used. Despite the putative similarity of animals, tumors and treatment regimens there was marked variation in response of tumors to therapy. No benefit was derived from administering preoperative immunotherapy alone. When operation was delayed to employ systemic immuno-chemotherapy, a slight improvement in the control of distant tumor was noted. The employment of preoperative intratumor immunotherapy led to a greater prolongation of survival and more inhibition of distant tumor growth than did immediate primary tumor removal or the use of preoperative systemic immunotherapy. The results suggest that there may be an advantage to delaying removal of a primary tumor so that it may be employed in therapeutic strategies directed toward control of metastatic disease.

Animals↗

1-phenylalanine mustard (L-PAM) in the management of premenopausal patients with primary breast cancer: lack of association of disease-free survival with depression of ovarian function. National Surgical Adjuvant Project for Breast and Bowel Cancers.

Breast cancer patients participating in a prospective randomized clinical trial who were less than or equal to 49 years of age, had positive axillary nodes, and who received prolonged 1-phenylalanine mustard (L-PAM) as an adjuvant to mastectomy continue (after 4 years) to demonstrate a significantly greater disease-free survival (p = .007) than do patients who received placebo. Benefit was achieved in patients who were less than or equal to 39 years as well as those who were 40-49 years of age. Those in the younger age group showed a greater improvement in disease-free survival at 4 years relative to their controls (32% vs. 69%; p = .01) than did those in the older age group (48% vs. 61%; p = .09). When patients were examined relative to their nodal status, a highly favorable effect was found to have been achieved with L-PAM in those with 1-3 positive nodes (54% vs. 86%; p = .006). Results indicate that both age groups were benefited. When considered over time, they demonstrate that a relatively greater effect was achieved in the younger women. While L-PAM failed to significantly alter the disease-free survival of those with greater than or equal to 4 positive nodes a slightly better effect was achieved in the group less than or equal to 39 years. Since adjuvant chemotherapy has been found to be more effective in premenopausal than postmenopausal women, it has been presumed that decreased ovarian function, as a result of the chemotherapy, is responsible for the findings. To support or repudiate that concept, information regarding serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), as well as menstrual function, has been obtained from women receiving L-PAM or L-PAM plus 5-FU therapy. In contrast to findings relative to disease-free survival, ovarian function and menses were most affected in patients 40-49 years of age. Amenorrhea occurred in 73% of patients in that age group and in only 22% of those less than or equal to 39 years (p less than .001). Similarly, a significant increase in LH and FSH and a decrease in E2, all indicative of ovarian suppression, was observed only in the older group of patients. Thus, it is concluded that while ovarian suppression may account for some of the adjuvant chemotherapeutic effect in premenopausal women, the dichotomy of findings in younger and older premenopausal women relative to therapeutic response and ovarian function indicates that other factors could be responsible.

Adult↗

The significance of concordance in mammographic interpretations.

Twenty-eight women participating in a screening program had a breast cancer diagnosed subsequent to the report of a negative mammogram which was read by only one of a group of radiologists. Fourteen occurred prior to a scheduled routine screening visit (interval cancers) and 14 were detected during such an examination. The negative mammograms from the 28 cancer patients, together with those from 120 women without cancer (controls) were independently reviewed by each member of a panel of three radiologists. Forty-six percent of the cancer cases and 5.8% of the controls were interpreted as positive by two or more of the radiologists. These findings suggest that agreement among several independent reviewers enchances the value and accuracy of mamography by reducing the number of false negative interpretations.

Breast Neoplasms↗

Benign prostatic hyperplasia in an XX man.

A sixty-nine-year-old white phenotypic male who was being investigated for a myeloproliferative disorder, was found to have an XX karyotype in all cells examined in bone marrow, lymphocytes, and skin fibroblast cultures. Despite essentially no testosterone in the plasma, he also suffered from severe prostatic hyperplasia, a finding not reported previously in patients with this genotype. While endocrine studies showed normal follicle-stimulating hormone, the luteinizing hormone level was twice the upper limit of normal and estrogens were in the normal female range. Except for complete absence of Leydig cells, testicular histology resembled that usually found in Klinefelter syndrome. The patient died of the combined effects of the myeloproliferative disease and urinary tract obstruction. The mechanism of occurrence of the sex chromosome anomaly as well as the cause and implication of the unusual finding of prostatic hyperplasia are discussed.

Aged↗