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Biomedical subjects

C Rose

Publications and source records attributed to C Rose.

At least 271 records · Page 15Linked to original sources
PubMed1987

Combined treatment of advanced malignant melanoma with coumarin and cimetidine. A phase II study.

Immunostimulant therapy with coumarin and cimetidine was evaluated in 17 patients with advanced malignant melanoma. Induction therapy with coumarin 100 mg daily was given for 8 weeks, whereupon cimetidine 1000 mg daily was added. No patients had been previously treated with cytotoxic drugs, and all patients had a good performance status. In 16 patients progressive disease was observed, and only 1 patient experienced no change in condition, lasting 30 weeks. We conclude that treatment with this schedule of coumarin and cimetidine is without effect in advanced malignant melanoma.

Adult↗
PubMed1987

Stage and pattern of metastases in patients with breast cancer.

This study compares the pattern of metastases in 228 patients with initial stage I and 635 patients with initial stage II breast cancer. All these patients had recurrence within a median time of follow-up of 4.9 years (range 2.0-7.0 years). All patients were initially mastectomized, and staging was based on histopathological evaluation of mastectomy specimens. Patients with stage II disease received postoperative radiotherapy; 67% also received systemic adjuvant therapy. Locoregional recurrences were the most common sites of recurrence in stage I, whereas distant metastases occurred more often in stage II patients. Stage II patients had a significantly higher number of metastatic sites than stage I patients. Among patients with a single site of recurrence the frequency of local or regional recurrence was 62% in stage I patients compared to 16% in stage II patients. When correcting for this difference, which was ascribed to the effect of radiotherapy, the number and the distribution of metastatic sites were almost equal in stage I and II patients. The anatomical distribution of metastatic sites in different periods after mastectomy was almost the same in stage I and stage II patients; extraregional lymph node metastases, however, occurred earlier in stage II than in stage I patients. The recurrence-free interval, the survival after recurrence (SAR), and the overall survival were all significantly shorter for stage II than for stage I patients. The reduced SAR for patients with stage II disease hints that tumours of higher stages have a higher rate of progression. The progression time, however, was of the same duration in patients with initial stage I and II breast cancer. The prognostic significance of the classification of patients with breast cancer according to stage does not seem to discriminate tumours with different biological properties with regard to the rate as well as the pattern of dissemination. Postmastectomy follow-up of patients with stage I and II disease should therefore, follow the same guide-lines. Since the anatomical distribution of metastases was the same in different periods after mastectomy, the screening for recurrent disease should not be directed towards any specific sites in certain periods after initial diagnosis.

Adult↗
PubMed1987

Prognostic factors in primary mucinous breast carcinoma.

Two hundred seven mucinous breast carcinomas were morphologically classified into two different groups: pure mucinous carcinomas consisting only of areas with small epithelial islands of solid tumor floating in abundant extracellular mucin, and mixed carcinomas where the tumor contains large areas of mucin, as well as areas with infiltrating carcinoma devoid of extracellular mucin. Of the 207 tumors, 95 were of the pure type and 112 of the mixed type. The pure and mixed carcinomas differed significantly with respect to a number of prognostic factors, the most important of which was lymph node status. Patients with pure mucinous carcinomas had significantly fewer lymph node metastases at the time of primary operation (P = 0.0001) and a significantly longer recurrence-free survival (P = 0.03) than patients with mixed carcinomas. Patients with mixed carcinomas closely resembled patients with infiltrating ductal carcinomas not otherwise specified (NOS) with respect to both lymph node status and recurrence-free survival. In multivariate analysis, the single most important factor for predicting recurrence-free survival among the 207 patients was lymph node status. However, of 94 pure carcinomas, only 6 had lymph node metastases at the time of mastectomy. A detailed morphologic analysis demonstrated that two of these six cases were incorrectly diagnosed as being pure mucinous carcinomas--they were actually of the mixed type. In another two of these cases, the metastases originated from a co-existent infiltrating ductal carcinoma. Thus, metastases to the regional lymph nodes were observed in only two cases of pure mucinous carcinomas. It is concluded that the biologic behavior of the pure mucinous carcinomas differs from that of both the mixed carcinomas and infiltrating ductal carcinomas NOS. Thus, a new definition is suggested, in which a mucinous carcinoma is classified as such only if it is a pure carcinoma, and mixed mucinous carcinomas are classified according to the component without extracellular mucin production.

Adenocarcinoma, Mucinous↗
PubMed1987

Evidence of a castration-mediated effect of adjuvant cytotoxic chemotherapy in premenopausal breast cancer.

This prospective randomized trial, conducted by the Danish Breast Cancer Cooperative Group, is the largest study, so far, of adjuvant chemotherapy in premenopausal breast cancer. The trial is unique in that it is nationwide and based on a nonselected population of patients, and is the only adjuvant trial studying the effect of cyclophosphamide monotherapy. After total mastectomy with axillary node sampling, followed by local radiotherapy, 1,032 pre- and perimenopausal women with operable breast cancer were randomized to observation alone, or to adjuvant chemotherapy for 1 year with either cyclophosphamide monotherapy or with a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). As of January 1987, median follow-up was 68 months. From early on both cyclophosphamide alone and CMF were found to improve recurrence-free survival (RFS) significantly and to a similar degree (P = .0001). However, an overall survival advantage did not become evident until 5 years after the start of treatment. So far, this advantage appears to be more pronounced in CMF (P = .0065) than in cyclophosphamide-only patients (P = .08). Thus, the study confirms the findings of the National Surgical Adjuvant Breast Project (NSABP) and Milan trials that adjuvant chemotherapy prolongs the survival of premenopausal women with early breast cancer. A retrospective analysis revealed that, in contrast with CMF, cyclophosphamide alone did not improve RFS significantly in subsets of patients without amenorrhea, with estrogen-receptor (ER) negative tumors, and with tumors of low histological differentiation. Assuming that cyclophosphamide alone is a less tumoricidal treatment than CMF, these findings suggest that the effect of adjuvant cytotoxic chemotherapy is mediated partly through chemical castration, and partly through a purely cytotoxic effect.

Adult↗
PubMed1986

Detection of surface antigens defined by monoclonal antibodies in primary mucinous breast carcinomas. Relation to prognostic factors and recurrence-free survival.

Three monoclonal antibodies, 67D11, 115H10 and 115C2, raised against human milk fat globule membranes, have been applied to 207 primary mucinous breast carcinomas. The tumours reacted positively in 18% (67D11), 54% (115H10), and 20% (115C2) of the cases. The detected epitopes (MAM-3a (67D11), MAM-3b (115H10), and MAM-3c (115C2)) have formerly been shown to be markers of differentiation in infiltrating ductal carcinomas. In the present group of mucinous breast carcinomas, statistically significant correlation to high risk factors, such as occurrence of primary lymph node metastases, large tumour size, and local invasion of the tumour into overlying skin or deep fascie, were found. Furthermore, the antigen expression was less marked in pure mucinous carcinomas as compared to carcinomas also presenting with non-mucinous tumour areas. Thus, especially the antigen MAM-3b, is more frequently present in mixed tumours, in large tumours, in tumours with local invasion, and in tumours with primary lymph node metastases. However, no association could be demonstrated between expression of MAM-3b and recurrence-free survival. Mucinous carcinomas of the breast apparently differ from other carcinomas not only with respect to morphology, but also in their pattern of antigenic expression in relation to other prognostic factors.

Adenocarcinoma, Mucinous↗
PubMed1986

Metastatic pattern and response to endocrine therapy in human breast cancer.

The effect of endocrine therapy in 465 postmenopausal patients with advanced breast cancer who entered four consecutive, randomized trials has been related to the site of the metastases. Patients received either tamoxifen (T) alone or T in combination with medroxyprogesterone acetate, diethylstilbestrol, halotestin, or aminoglutethimide. The overall response rate was 40%. Responses were most frequently seen in patients with metastases in soft tissue, and the duration of response to endocrine therapy in these patients was longer than for those with metastases in bone or viscera (p less than 0.00001). In addition, the response rate was inversely correlated with the number of main metastatic sites in patients with soft tissue metastases, whereas the response rate was not associated with the number of metastatic sites in patients with metastases in bone and viscera. Survival after first recurrence was significantly longer in responding patients with soft tissue lesions compared to those with recurrence in bone or viscera. In contrast, survival after first recurrence was identical in patients with nonresponding disease, irrespective of dominant site of metastases. The outcome of endocrine therapy depends partially upon the dominant site of metastases. This may reflect a difference in biological characteristics of human breast cancer tumor cells that metastasize to different sites.

Aminoglutethimide↗
PubMed1986

Fine needle aspiration and Tru-Cut biopsy in the diagnosis of soft tissue metastases in breast cancer.

Soft tissue is a common site of the first recurrence in patients with breast cancer, and soft tissue lesions are often used to assess the efficacy of systemic therapy. It is therefore desirable to obtain histological/cytological verification of such lesions. It is our experience that FNA and TCB in psycho-social respects are superior to a surgical biopsy. Using a surgical biopsy as the key-diagnosis we have compared the diagnostic value of Fine-Needle Aspiration (FNA), Tru-Cut Biopsy (TCB) and clinical evaluation. The FNA was found to be significantly better than TCB in establishing the diagnosis. The diagnostic specificity and sensitivity for FNA was 1.0 and 0.65, while the corresponding figures for TCB and the clinical diagnosis were 1.0 and 0.36 and 0.76 and 0.33, respectively. Since no false positive results were obtained by use of FNA, this procedure seems to be a sufficient diagnostic procedure. However, in case of a negative outcome of the FNA, the diagnosis must be obtained by a surgical biopsy.

Adult↗
PubMed1986

A clinical trial of Fluosol DA 20% in advanced squamous cell carcinoma of the head and neck.

Fluosol DA 20% (Fluosol) enhances the response of several rodent tumors to radiation and oxygen. This is a Phase I/II study of Fluosol and oxygen breathing in the radiation treatment of advanced squamous cell carcinoma of the head and neck. Fifteen patients with Stage III/IV tumors entered and completed this trial. Patients received 1.8 Gy/fraction to 45 Gy, at which time the spinal cord was shielded and gross disease was carried to 68-72 Gy. 8 ml/kg (11 patients) or 9 ml/kg (4 patients) Fluosol was infused prior to the first fraction each week for the first 5 weeks. All patients inspired 100% oxygen before and during the initial 25 fractions. The infusions were well-tolerated. Four acute reactions that responded to diphenhydramine or steroids were observed in the 75 infusions. 8/15 patients exhibited liver function abnormalities of 2-3X normal which fell after therapy was discontinued. Normal mucosal reactions were enhanced despite the 1.8 Gy fraction size. 10/15 patients required at least one treatment break: the mean dose achieved before the break was 35 Gy. Tumor clearance was also accelerated. Thirteen patients had primary tumor clearance, but one had a local recurrence. Ten had primary and nodal clearance and 2/3 with nodal persistence had salvage surgery with fibrosis only at pathologic review. One patient, locally controlled, developed distant metastases. Thus, 10/15 patients are NED, but followup time is short.

Carcinoma, Squamous Cell↗
PubMed1986

Sequential multi-agent chemotherapy and whole abdominal irradiation for stage III ovarian carcinoma.

Modern therapy for stage III ovarian carcinoma patients usually involves one or more laparotomies with maximal resection of tumor, and intensive multi-agent chemotherapy. However, with long-term follow-up only 10-15% of patients remain free of disease. In the hope of improving outcome, we have treated 17 women with sequential multimodality therapy, including initial surgical resection (if possible), cyclophosphamide-adriamycin +/- cis-platinum, second-look surgery, and whole abdominal irradiation. Seven patients are currently alive without disease, with median follow-up of 52 months since initiation of radiation and 60 months since initiation of chemotherapy. Disease-free survival correlated with residual tumor at the start of radiotherapy: none (4/4); microscopic, less than or equal to 5 mm (3/4); greater than 5 mm or no surgery (0/9). Survival also correlated with tumor grade: grade 1 (2/2); grade 2 (2/3); grade 3 (3/11). Hematological tolerance of radiotherapy was dependent upon the number of chemotherapy cycles: ten of 11 patients receiving less than or equal to eight cycles completed radiotherapy without excessive delay, compared with only one of five receiving greater than eight cycles. There were no treatment-related deaths and only one patient required laparotomy for bowel obstruction. We conclude that intensive multimodal treatment may be tolerated moderately well if the amount of chemotherapy is limited, and that further studies are justified.

Adult↗
PubMed1986

Prognostic usefulness of estrogen receptor immunocytochemical assays for human breast cancer.

Breast cancers of postmenopausal patients at high risk for recurrence participating in an adjuvant therapy protocol were independently assayed for estrogen receptor by conventional dextran-coated charcoal steroid binding assays and by immunocytochemistry (ER-ICA) to compare the two assays and to assess the prognostic usefulness of ER-ICA. The ER-ICA was based on a monoclonal antibody to the estrogen receptor and was applied to lightly fixed, frozen sections of the cancers. Excellent agreement was found between the two estrogen receptor methods. It was found that a combination of the distribution of ER-ICA stained cells and the overall staining intensity gave a statistically significant correlation with the quantitative estrogen receptor dextran-coated charcoal steroid binding assay value. In addition, the overall appraisal of the lesion as ER-ICA positive or negative as well as the ER-ICA staining intensity and proportion of ER-ICA stained cancer cells related to patient disease-free interval and survival, independent of patient lymph node involvement. This relationship of ER-ICA status to prognosis appeared not to relate only to responses to adjuvant tamoxifen treatment since it also was observed with patients who did not receive the antiestrogen.

Breast Neoplasms↗
PubMed1986

Major operative trauma increases peripheral amino acid release during the steady-state infusion of total parenteral nutrition in man.

The effect of major operative trauma on skeletal muscle metabolism was examined in nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acids/m2/day) for 5 days before and 4 days after an operation. Compared with the preoperative state, 72 hours after the operation there was a significant rise in arterial levels of glucagon, cortisol, norepinephrine, and inactive triiodothyronine and a drop in concentrations of insulin, active triiodothyronine, and amino acids. Forearm blood flow increased, as well as the efflux from forearm muscle of lactate, taurine, serine, glycine, valine, methionine, isoleucine, leucine, phenylalanine, lysine, arginine, and total amino acid nitrogen (440%). This loss of muscle protein after trauma is associated with increased muscle proteolysis, as measured by increased urinary 3-methylhistidine excretion (83%), and accounts for increased nitrogen loss (54%) from the body. Increased activity of the sympathetic nervous system is manifested by increased levels of epinephrine and norepinephrine, a relative lack of insulin, and increased levels of glucagon. This hormonal milieu plays an important role in the production of hypoaminoacidemia, increased efflux of amino acids and lactate from muscle, and negative nitrogen balance observed in these traumatized patients.

Aged↗
PubMed1986

Insulin decreases muscle protein loss after operative trauma in man.

Seventy-two hours after major operative trauma, nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acid/m2/day) showed a negative nitrogen balance, increased muscle catabolism, as measured by 3-methylhistidine excretion, increased amino acid efflux from muscle, and decreased circulating levels of insulin. When 5 U of insulin/hr were added to the infusate, arterial insulin levels rose significantly from 39.7 +/- 4.1 microU/ml to approximately the pretrauma levels (74.6 +/- 7.7 microU/ml). Despite this normalization of insulin levels, excretion of nitrogen and 3-methylhistidine and the efflux of amino acids from forearm muscle fell but did not return to pretraumatic levels, suggesting some insulin resistance. Visceral gluconeogenesis from amino acids appeared to decrease, since insulin infusion decreased the efflux of alanine from skeletal muscle with no change in its arterial level. Insulin also significantly reduced the efflux of isoleucine, tyrosine, phenylalanine, glutamine, and total amino acid nitrogen from forearm muscle. These findings, along with the partial reduction in the excretion of 3-methylhistidine and nitrogen, suggest that insulin, in combination with infused calories and protein, decreases the loss of muscle protein after trauma.

Aged↗
PubMed1986

Combined endocrine treatment of postmenopausal patients with advanced breast cancer. A randomized trial of tamoxifen vs. tamoxifen plus aminoglutethimide and hydrocortisone.

The therapeutic efficacy of combined endocrine therapy with tamoxifen, aminoglutethimide and hydrocortisone (T+AG+H) was evaluated against treatment with tamoxifen (T) alone in 210 patients above 65 years of age with metastatic breast cancer. The treatment results have been assessed for the 166 fully evaluable patients and were the following for the T and T+AG+H groups, respectively: PD: 31 and 35%; NC: 35 and 37%; PR: 13 and 16%; and CR: 21 and 12%. The overall treatment results are not statistically different (p = 0.35) and the 95% C.L. of the difference of the response rates are -8% to +20%. The median duration of remission was approximately 24 months in both treatment groups (p = 0.31). The time to treatment failure was comparable with median values of 10 and 8 months in the T and the T+AG+H groups respectively (p = 0.17). Toxicity was more frequent and severe in the combined treatment group and could in most instances be attributed to treatment with AG+H. In conclusion, the simultaneous use of T and AG and H does not seem to improve the therapeutic results in postmenopausal patients with advanced breast cancer.

Aged↗
PubMed1986

Steroid hormone receptors as prognostic indicators in primary breast cancer.

Recurrence-free survival (RFS) has been evaluated with regard to estrogen and progesterone receptor (ER and PgR) status for 145 postmenopausal women with primary breast cancer at high risk for recurrent disease. All patients received only local-regional therapy as an adjuvant therapy (DBCG protocol 77-c patients). ER+ patients had a significantly longer RFS than ER-patients. This difference was apparent using a cut-off level of 10 fmol/mg cytosol protein to distinguish between ER+ and ER-patients. There was no apparent difference in patients with high (greater than = 100 fmol/mg cytosol protein) ER levels vs. those with intermediate (10-99 fmol/mg cytosol protein) levels, indicating that the prognostic value of ER determinations in the natural course of the disease resides in a qualitative rather than a quantitative distinction among patients. No difference in RFS was found patients when patient were subdivided according to PgR status. The clinical applicability of the ER-ICA assay method for ER determinations is demonstrated in a subset of patients, some of whom received adjuvant endocrine therapy.

Actuarial Analysis↗
PubMed1986

Adjuvant tamoxifen in postmenopausal high-risk breast cancer patients: present status of Danish Breast Cancer Cooperative Group trials.

The aim of the present study was to analyze the efficacy of adjuvant tamoxifen (TAM) in postmenopausal patients with high-risk breast cancer. The primary surgical treatment was total mastectomy with axillary sampling. There were 1,650 eligible patients; 829 were randomized to receive postoperative radiotherapy (RT) and 821, to receive RT + TAM (10 mg three times daily for 1 yr). The 2 groups were identical with respect to age, tumor size, number of positive lymph nodes, degree of anaplasia, and estrogen and progesterone receptor content. Overall recurrence-free survival at 6 years was 39% in the RT group, compared to 48% in the RT + TAM group (P = 0.0008), but there was no significant difference in survival (P = 0.14). From retrospective analyses of recurrence-free survival according to prognostic variables, it appears that 4 subgroups of patients benefited from adjuvant TAM: those less than 69 years of age, those with 4 or more positive nodes, those with grade I-II tumors, and those with high estrogen receptor values (greater than 100 fmol/mg cytosol protein).

Aged↗
PubMed1986

Oestrogen and progesterone receptor determinations in breast cancer: technology and biology.

Our present state of knowledge regarding oestrogen and progesterone receptors (ER and PgR, respectively) has led to changes in treatment strategies: patients without receptors in their tumour tissues cannot be expected to respond to endocrine therapy; furthermore, groups of patients with specifically good or poor prognoses can be selected. Treatment of the disease is now starting to be rational rather than empirical. However, it is imperative that we achieve a greater level of understanding before we can predict with high probabilities which patients will benefit from endocrine therapy. Only through a coordinated effort by many centres can we hope to attain this goal. In such collaboration several factors must be considered if reproducible conclusions with respect to results from receptor assays are to be reached: sampling of the tumour biopsy for analysis, potential differences in assay procedures which may affect results and the composition of the population studied. Differences between centres in any of these aspects may affect the study conclusions. The causes of and direction of possible biases due to these factors will be discussed here. Approximately 90% of all patients with primary breast cancer have been registered in the national Danish Breast Cancer Cooperative Group (DBCG) project. ER and PgR determinations have been performed on tumour tissue from approximately 30% of these patients in a single laboratory. The results of these analyses are presented here for 3735 patients in relation to age, menopausal status, tumour size, grade of anaplasia, lymph node involvement and parity. Approximately 30% of these patients have been in DBCG protocols in which no adjuvant systemic therapy has been administered. Because of this large number of cases, the recurrence-free survival of the untreated disease in relation to receptor status can be reliably analysed. Both ER status and PgR status were found to be significant prognostic variables for premenopausal women under 50 years of age. In contrast, in the postmenopausal women neither ER nor PgR status was a significant prognostic factor in the low risk group (tumour less than 5 cm, no lymph node involvement). In high risk, postmenopausal women, however, ER status is a significant prognostic factor for recurrence-free survival and it appears to be independent of lymph node status.

Adult↗