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Biomedical subjects

N Wilking

Publications and source records attributed to N Wilking.

At least 55 records · Page 3Linked to original sources
PubMed1992

Immunocytochemical analysis of receptors for estrogen and progesterone in fine needle aspirates from anal epidermoid carcinoma.

Fifteen patients with anal epidermoid carcinoma were examined with percutaneous or transanorectal fine needle aspiration (FNA) cytology. Aspirates from all patients allowed cytologic verification of the diagnosis. Estrogen receptor (ER) and progesterone receptor (PgR) were analyzed using an immunohistochemical technique well adapted for steroid receptor analysis in hormone-dependent carcinomas. Neither ER nor PgR could be detected in any of the aspirates. This finding is somewhat unexpected since there is a strong female predominance in this tumor type. However, our findings do not negate that sex steroid hormones may indirectly play a role in the tumorigenesis of anal epidermoid carcinoma.

Adult↗
PubMed1992

Analogues of LHRH versus orchidectomy: comparison of economic costs for castration in advanced prostate cancer.

Analogues of luteinising hormone releasing hormone (LHRH) have recently been introduced as an alternative to surgical orchidectomy in prostate cancer, but there has been concern about the economic costs of long-term treatment. The paper presents a comparison of costs for LHRH analogues versus orchidectomy in patients with advanced prostate cancer. The cost for the surgical procedure was estimated using data on patients treated with orchidectomy in Stockholm County, Sweden, during 1981-86. Estimates of costs for treatment with a depot LHRH analogue was based on observed treatment times among patients with symptomatic prostate cancer in a British randomised clinical trial of medical castration versus surgical orchidectomy. The average cost for orchidectomy was estimated at 2,580 pounds i.e. 7-31% less than for treatment with a depot LHRH analogue (2,760 pounds-3,380 pounds) assuming a mean treatment time in the range 19-23 months. The most cost-effective policy for castration was found to be initial treatment with an LHRH analogue followed by deferred orchidectomy after about 2 years among long-term responders. This policy would obviate the need for surgery in about 85% of the patients and the average cost (1,900 pounds) would be about 26% lower compared to that of a policy of primary orchidectomy in all patients.

Antineoplastic Agents↗
PubMed1992

Serum steroids and prolactin during and after major surgical trauma.

Serum levels of cortisol, dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A-4), 17-alfa-hydroxy-progesterone (17 OHP), testosterone (T, only in males), unconjugated (E1) and total estrone (tE1 greater than 85% estrone sulfate) were studied in six male and two female patients before, during and up to 30 days after aortic graft surgery. All steroids except 17 OHP decreased following induction of anesthesia but, except for testosterone, rose again during surgery to preoperative levels or slightly above. Extremely high peak values for E1 and tE1 and a less pronounced peak for cortisol were noted on postoperative day 2; after that, the levels of these steroids returned to normal. The levels of 17-OHP, DHA and DHAS decreased after surgery and were below preoperative values from postoperative day 4 to day 16 or (DHAS) day 30. In males, 17 OHP showed a pronounced peak 30 min after initiation of surgery, but decreased after that to below preoperative values. Testosterone levels decreased further during surgery and remained very low until postoperative day 16. Major surgical trauma has a rapid, profound and long-lasting effect on gonadal activity, as judged from decreased testosterone levels, while the effect on adrenal steroids is less pronounced. Adrenal delta 4 and delta 5-steroids showed different patterns in the postoperative period, indicating differences in their regulation. The highly elevated estrogen levels on postoperative day 2 probably reflect either transiently elevated peripheral aromatization or decreased estrogen metabolism rather than increased levels of substrate steroids (A-4). The biological significance of this remains to be elucidated.

17-alpha-Hydroxyprogesterone↗
PubMed1992

Prognostic significance of axillary nodal status in primary breast cancer in relation to the number of resected nodes. Stockholm Breast Cancer Study Group.

The prognostic significance of the number of metastatic axillary lymph nodes in relation to the number of identified nodes among 1,622 patients with operable breast cancer was assessed. We present a Cox's analysis of the prognostic significance of nodal status in relation to loco-regional recurrence, axillary recurrence, distant metastasis and death due to breast cancer respectively. As expected, the relative risks were generally higher for patients with nodal involvement, particularly those with 4 or more positive nodes or with few examined nodes. However, among those with more than 4 positive nodes the risk of distant metastases and death due to breast cancer was about the same irrespective of the number of nodes examined.

Antineoplastic Agents↗
PubMed1992

Analysis of hormone receptors and proliferation fraction in fine-needle aspirates from primary breast carcinomas during chemotherapy or tamoxifen treatment.

Twelve postmenopausal women (54-93 years) with primary breast carcinoma were treated with tamoxifen due to infirmity or refusal to undergo surgery. Seven premenopausal patients (32-50 years) were given preoperative chemotherapy because of large tumors or inflammatory carcinoma. Fine-needle aspiration biopsy was used to procure tumor cells for diagnosis, hormone receptor determination and analysis of proliferation fraction. Aspirations were repeated every 3 months in the tamoxifen group and each month in patients receiving chemotherapy. Two patients who responded to tamoxifen had tumors with more than 75% estrogen receptor positive cells. A decreased proliferation fraction was observed in two tumors responding to tamoxifen. Eight patients, all with estrogen receptor positive tumors, had stable disease. Progressive disease was observed in two patients with less than 25% receptor positive cells. In these tumors the percentage of proliferating cells remained high during therapy. Objective response was recorded for six patients treated with chemotherapy. The clinical response was reflected in a decreased proliferation fraction. No correlation was observed between response and percentage of proliferating cells in the untreated tumor. The results suggest that analysis of tumor cell characteristics such as hormone receptor content and proliferation fraction can be used to predict and monitor response to endocrine treatment and chemotherapy in breast carcinomas.

Adult↗
PubMed1992

Randomized trial of adjuvant tamoxifen in node negative postmenopausal breast cancer. Stockholm Breast Cancer Study Group.

The paper presents long-term results of a randomized trial of adjuvant tamoxifen (40 mg daily for 2 or 5 years) versus surgery alone including 1,347 postmenopausal patients with histologically negative axillary nodes and a tumour diameter less than or equal to 30 mm. Data on the estrogen receptor status of the primary tumour were available in 1,136 patients (84%). At a median follow-up of 7 years (range 1.7-13.0 years) there was a significant prolongation of the recurrence-free survival among those allocated to tamoxifen (p less than 0.01), significantly fewer deaths due to breast cancer (p = 0.02) and a trend towards improved overall survival (p = 0.11). The treatment benefit was restricted to patients with ER-positive tumours. There was no significant reduction of breast cancer recurrences in the tamoxifen group among patients whose tumours were classified as ER-negative. The results support and extend previous studies in showing a long-term benefit of tamoxifen in postmenopausal breast cancer patients with node-negative, estrogen receptor positive disease.

Breast Neoplasms↗
PubMed1992

The DNA profile of breast cancer in situ.

The nuclear DNA content of 46 mammary adenocarcinomas in situ was measured by means of image cytometry in 4-microns-thick Feulgen-stained histological sections. Aneuploidy was found in 23 cases (50%), whereas the other 23 cases exhibited a diploid DNA distribution pattern. Intraductal carcinoma, the most common subtype in the present study, was found to be aneuploid in 19 cases (63%), with the comedo variant showing aneuploidy in as many as 10 of 11 cases (91%). In contrast, lobular and papillary carcinoma in situ exhibited only 17% and 0% aneuploidy, respectively. The percentages of aneuploid and diploid DNA profiles of the in situ lesions in the present study are almost identical to those observed in invasive breast adenocarcinoma. This indicates that the DNA distribution pattern characteristic for an individual breast adenocarcinoma is already established at the in situ stage, i.e., it occurs before invasiveness and does not progress from a euploid to an aneuploid pattern. In clinical routines DNA ploidy measurements may be of help to distinguish between e.g., hyperplasias and in situ lesions and may also indicate in which direction the malignancy potential of in situ lesions will develop.

Adult↗
PubMed1991

Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy.

Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Effects of tamoxifen on the female genital tract.

Tamoxifen is a widely used drug in medical oncology, mainly for treatment of breast cancer, but also for second line treatment of endometrial cancer. We recently reported an increased incidence of endometrial cancer associated with long-term adjuvant tamoxifen. This observation, previous reports of stimulatory effects of tamoxifen in the female genital tract, and experimental data are in accordance with a mainly estrogenic effect of tamoxifen in these tissues. An increased incidence of endometrial cancer may limit the usefulness of tamoxifen for benign indications. For adjuvant treatment of early breast cancer, however, the improvement of both recurrence-free survival and overall survival probably outweighs the increased frequency of uterine tumors. However, the possibility of growth stimulation of tumor subclones should be considered when tamoxifen is used in the treatment of endometrial cancer.

Adjuvants, Pharmaceutic↗
PubMed1991

Adjuvant tamoxifen in early-stage breast cancer: effects on intercurrent morbidity and mortality.

Intercurrent mortality and the pattern of inpatient hospital care was studied among 1,846 postmenopausal patients included in the Stockholm randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no adjuvant endocrine therapy. The median follow-up time was 54 months (range, 2 to 123 months). The patients were matched to the Swedish National Registry of Causes of Death and a computerized register covering about 95% of all hospital admissions in Stockholm County. There was no significant difference in the pattern of intercurrent mortality among the tamoxifen and control patients. The total number of hospital admissions was similar in both groups, but the tamoxifen patients were admitted significantly less frequently because of immunologic diseases (relative risk [RR] = 0.4; 95% confidence interval [CI], 0.2 to 0.9). Admissions because of thrombotic diseases were slightly, but not significantly, more frequent among the tamoxifen patients (RR = 1.2; 95% [CI], 0.6 to 2.3). The risk of hospital stay for benign gynecologic diseases other than prolapse or uterine bleeding was increased in the tamoxifen group (RR = 3.2; 95% CI, 1.2 to 8.6). No significant differences were found for diseases related to arteriosclerosis or osteoporosis. The study confirms and extends previous reports, which have shown that tamoxifen has few and usually mild side effects. However, the current results should be judged cautiously because of the relatively short median follow-up time (4.5 years) and the limitation of data in detecting morbidity that does not necessarily result in hospitalization.

Aged↗
PubMed1990

Randomized trial of adjuvant tamoxifen combined with postoperative radiation therapy or adjuvant chemotherapy in postmenopausal breast cancer.

From 1976 to 1984, 427 postmenopausal women with high-risk breast cancer (pN + or pT greater than 30 mm) were randomized between postoperative radiation therapy (RT), radiation therapy plus tamoxifen (RT-TAM), adjuvant chemotherapy (CT), or chemotherapy plus tamoxifen (CT-TAM). Surgery was a modified radical mastectomy in all cases. The radiation therapy was given with high-voltage techniques and included the chest wall and regional nodes. The dose was 4600 cGy/4 1/2 weeks. Tamoxifen was given at a dose of 40 mg daily for 2 years. The adjuvant chemotherapy consisted of 12 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (or chlorambucil, methotrexate, and 5-fluorouracil [LMF] for patients entered before 1978). At a median follow-up time of 6 1/2 years the recurrence-free survival was significantly better for patients allocated to radiation therapy compared to chemotherapy and for patients allocated to tamoxifen compared to no adjuvant endocrine treatment (P less than 0.01). At 10 years the recurrence-free survival for patients in the RT-TAM, RT, CT-TAM, and CT groups was 63%, 57%, 47%, and 31%, respectively. A significant reduction of treatment failures with tamoxifen was only observed among patients with estrogen receptor-positive tumors. The overall survival difference in favor of patients allocated to radiation therapy or tamoxifen was not significant: the respective survival percentage at 10 years in the RT-TAM, RT, CT-TAM, and CT group was 65%, 62%, 52%, and 50%. The results indicate that postoperative radiation therapy continues to play an important role in the primary management of postmenopausal women with high-risk breast cancer and that the addition of tamoxifen may further improve the results among ER-positive patients.

Aged↗
PubMed1990

Sex steroids in human brain tumors and breast cancer.

The concentrations of three sex steroids, estradiol, progesterone and testosterone, were analyzed by radioimmunoassay after celite chromatography in brain tumor and breast cancer tissues. The concentrations in malignant gliomas and breast cancers showed interindividual variations, especially evident with regard to estradiol. High estradiol concentrations were recorded in two patients with malignant astrocytoma. The concentrations of 1.00 pg/mg and 3.32 pg/mg were 10 to 30 times as high as in normal female brain. In five of ten astrocytomas the estradiol concentration was higher than the lowest breast cancer value. The distribution of progesterone seemed more even, and the level was significantly lower in brain tumors and breast cancers as compared with female brain, perhaps indicating an increased metabolism. Testosterone levels were somewhat higher in brain tumors, as compared with breast cancers, but not different from values in brain tissue. There were no significant age or sex correlation or differences in the concentrations of steroids in the brain tumors. The results suggest that manipulation of sex steroid metabolism in malignant brain tumors can be of beneficial therapeutic value as has been shown for breast cancer and prostatic carcinoma.

Adolescent↗
PubMed1989

Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers.

The frequency of new primary cancers was studied in 1846 postmenopausal patients included in a randomised trial of tamoxifen as an adjunct to primary surgery for early breast cancer. The median follow-up was 4.5 years (range 0.5-10.5 years). The number of new cancers in the tamoxifen group (n = 57) did not differ significantly from that in the control group (n = 70). However, in tamoxifen patients second breast cancers occurred less often and endometrial cancer occurred more often than in the controls. The increase in endometrial cancers was probably related to the agonistic oestrogenic effects of tamoxifen and was most pronounced in those treated for over 2 years.

Adenocarcinoma↗
PubMed1989

Steroid receptor levels in breast cancer. Relationships with age and menopausal status.

The paper presents descriptive data concerning relationships between age, menopausal status and steroid receptor content in primary breast carcinoma. The study was based on 2,329 women with primary breast carcinoma diagnosed in Stockholm county during 1980-1983. Oestrogen (ER) and progesterone receptor (PgR) content was determined using the isoelectric focusing technique. All analyses were done in one laboratory. There was a gradual increase in mean ER values with age. Premenopausal patients had lower mean ER values than peri- and postmenopausal patients of the same age. In contrast, PgR levels were similar in different age-groups. This could be a result of an insufficient stimulation of the tumour cells via the ER pathway. It is also possible that the PgR stimulation is maximal already at ER values below those found in old patients. It is concluded that steroid receptor content measured with commonly used ligand assays may reflect both biological properties of the tumour cells as well as influences by nontumoural factors, e.g. the endogenous levels of sex hormones.

Adult↗