[Variations in the x-ray examination technique. 2].
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Humans↗
Biomedical subjects
B Lindahl
Publications and source records attributed to B Lindahl.
A prospective population-based management program including primary surgery and postoperative risk assessment by means of DNA ploidy and histopathology. Adjuvant radiotherapy is not necessary for the majority of patients with FIGO stage I-II endometrial cancer.
A management program for FIGO stage I-II nonserous, nonclear-cell adenocarcinomas was evaluated. Histopathology and DNA ploidy were used to estimate postoperatively the risk of progression or death of disease and to tailor treatment. The patient material was a population-based consecutive cohort of all women with endometrial cancer in the Southern Swedish Health Care Region diagnosed between June 1993 and June 1996 (n = 553). Of these, 335 were eligible for the management program. Patients estimated to be at low risk were treated by surgery only, while high-risk patients also received vaginal brachytherapy. A large low-risk group consisting of 84% (n = 283) of the patients with an estimated disease-specific 5-year survival of 96% (95% CI = 93-98%) was identified. The high-risk group (n = 52, 16%) showed a worse outcome with an 80% 5-year disease-specific survival (95% CI = 65-89%). The difference in survival between the groups was highly significant (P < 0.0001). Half of the progressions were distant in the high-risk group. Although there is a clear indication for adjuvant therapy for this group, locoregional radiotherapy could be expected to fail in cases with distant progression. Thus, effective systemic treatments need to be developed. Low-risk patients, constituting the majority (84%) of the patients, can be safely treated by surgery only.
Adenocarcinoma↗
Disaccordance between estimation of endometrial thickness as measured by transvaginal ultrasound compared with hysteroscopy and directed biopsy in breast cancer patients treated with tamoxifen.
OBJECTIVE: To estimate endometrial thickness by transvaginal ultrasound technique (TVU) in patients treated with tamoxifen; and to compare the results with hysteroscopy and directed biopsy, and to relate the findings to curettage material. METHODS: Fifty-four women, over 50 years of age at the time of their primary breast cancer operation and scheduled for adjuvant treatment of tamoxifen, were investigated. If the endometrium measured 8 mm or more (35 patients) hysteroscopy and directed biopsy was performed. RESULTS: In the 35 patients, hysteroscopy and curretage revealed polyps in 18 cases (51.4%), proliferation in 1 case (2.9%) and atrophy in 16 cases (45.7%). In 54.3% (19 cases) of the patients the histopathological finding was a polyp or benign proliferation of the endometrium in agreement with the thickened endometrium seen with TVU. In the remaining 45.7% (16 cases) of the patients a thickened endometrium by transvaginal ultrasound was false positive as the hysteroscopic and subsequent histopathological diagnosis only showed atrofia of the uterine endometrium. CONCLUSIONS: In almost half of the patients the TVU gave a misleading picture concerning the condition of the endometrium. Changes in the myometrium and related connective tissue could be misinterpreted by the ultrasound technique as changes in the endometrium. These results may confirm the theory that stimulation and changes by antiestrogenic treatment of the uterine tissue is not only restricted to the endometrium. In patients with thickened endometrium measured by TVU, a dilatation and curettage is not sufficient, as TVU has not the ability to differentiate between endometrial polyps and myometrial changes. A hysteroscopy and directed biopsy could therefore be performed.
Adult↗
5-year survival rate in endometrial carcinoma stage I-II related to steroid receptor concentration, degree of differentiation, age and myometrial invasion.
Three hundred and twenty-seven patients with endometrial carcinoma stage I-II were all followed for at least 5 years. The estradiol receptor concentrations were measured in 298 tumors. In 272 cases the progesterone receptor concentrations were measured as well. Both receptors were significant prognostic factors measured as 5 year survival rate. In a Cox regression test stage, degree of differentiation, myometrial invasion and age remained as independent significant factors. Progesterone receptor concentrations were almost significant in a two-sided test including all degrees of differentiation but were significant (p = 0.04) when only poorly differentiated tumors were included. Thus PgR concentrations were used only on poorly differentiated tumors. The patients could be divided into a high risk group (deep myometrial invasion), an intermediate risk group (poorly differentiated carcinomas without deep myometrial invasion but with a low progesterone receptor concentration) and a low risk group (the remaining) with 5 year survival rated of 61%, 80% and 96% respectively.
Adult↗
Spontaneous endometrial hyperplasia. The prognostic significance of steroid receptor concentration. A two year follow-up of patients treated with abrasio only.
The steroid receptor concentrations were measured in 63 patients. The patients were part of a prospective randomized study and were treated with abrasio only. With respect to Cystic Glandular Hyperplasia (43 patients) 16 out of 25 with PgR values less than 10,000 (fmol/mg DNA) were normalized compared to only 4/14 with higher PgR conc (p = 0.03). No limit could be identified regarding patients with Adenomatous Hyperplasia and Atypical Hyperplasia (29 patients). Consequently patients with CGH and a high PgR concentration are recommended for high dose gestagen therapy.
DNA↗
Endometrial hyperplasia following estrogen treatment without the addition of gestagen. A follow-up study after withdrawal of estrogens.
From December 1980 to February 1991 24 patients with endometrial hyperplasia after estrogen treatment were followed-up at the Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden. All were referred for post-menopausal bleeding. They were followed-up with abrasio three and nine months after the initial diagnosis. Seven patients demonstrated cystic glandular hyperplasia (CGH), six adenomatous hyperplasia (AD) and eleven atypical hyperplasia (AT). In the CGH-group five revealed atrophic endometria and one developed into endometrial carcinoma. In the AD-group two patients refused follow-up, four had atrophic endometria, in the AT-group five developed atrophia, one refused follow-up, one developed CGH, while three developed carcinoma. All four carcinomas in the series developed within the first three months of follow-up. The frequency of carcinomatous development was much higher for exogen estrogen induced hyperplasias compared to earlier findings for endogenously estrogen-induced endometrial hyperplasias. It is recommended that non-opposed estrogen treatment should be used in rare circumstances under close follow-up and that patients developing endometrial hyperplasias are followed-up until the hyperplastic changes have disappeared.
Endometrial Hyperplasia↗
Flow cytometrical DNA measurements in endometrial hyperplasias. A prospective follow-up study after abrasio only or additional high-dose gestagen treatment.
As part of a prospective study on endometrial hyperplasias the DNA content in individual cells was measured by flow cytometry in 109, 35 and 12 cases of cystic glandular, adenomatous and atypical hyperplasias respectively. About 20% of all types of hyperplastic endometria revealed a non-diploid DNA index compared to 6% in normal endometria and 29% in well differentiated carcinomas. Increasing severity of hyperplasia was accompanied by increased proliferative activity as reflected by increased S-phase-and (S + G2)-fractions. The findings emphasise a previous suggestion that all types of hyperplasias are predecessors to endometrial carcinomas. Examination after 3 months following abrasio alone or in combination with high-dose gestagen treatment revealed a still high frequency of non-diploid cells. This was the case in endometria without histologic signs of hyperplasia as well as in those still demonstrating hyperplastic changes. Hypothetically chromosomal aberrations could be the main reason for the development of hyperplasias.
Adenoma↗
Endometrial hyperplasia. Clinico-pathological considerations of a prospective randomised study after abrasio only or high-dose gestagen treatment. Results of 2 years follow-up of 292 patients.
Endometrial hyperplasia has since long been proposed to be a predecessor to endometrial carcinoma. In this prospective randomised study one group was treated with abrasio only at regular intervals to follow the natural course. In this group 96/176 were normalised after a 2 year follow-up and 3 patients developed cancer. The frequency of normalised patients after abrasio only (55%) resembles that of cyclic low-dose gestagen treatment. In the other patient group treated with Medroxy progesterone acetate 500 mg i.m. twice weekly for 3 months and then followed for 2 years, 86/89 normalised and none developed cancer.
Antineoplastic Agents↗
Flow cytometrical DNA- and clinical parameters in the prediction of prognosis in stage I-II endometrial carcinoma.
In almost all studies regarding flow cytometry and endometrial carcinoma, the DNA factors used are stronger prognostic parameters than the clinical factors previously used. Number of sub-populations and/or percentage of cells in S-phase are mostly used to select those tumors with the worst prognosis. In this study, reporting the 2 year follow-up of 245 patients (222 followed for more than 2 years), we claim that the DNA-index is a stronger prognostic tool than other DNA parameters, but also that the range of myometrial invasion is a stronger predictor than all other parameters including the DNA. Range of myometrial invasion and DNA index are used to form one high-risk group, consisting of 22% of the patients with a relapse rate of 38%, and one low-risk group, consisting of 47% of the patients with a relapse rate of 4%.
DNA, Neoplasm↗
Endometrial hyperplasia: a prospective randomized study of histopathology, tissue steroid receptors and plasma steroids after abrasio, with or without high dose gestagen treatment.
274 patients with spontaneous endometrial hyperplasias were randomized into two groups: one treated with only abrasio, and another with additional 500 mg medroxyprogesterone acetate (MPA) twice weekly for 3 months. Total disappearance of all types of hyperplasias was seen following MPA treatment, whereas with only abrasio about 60% were removed suggesting that MPA does not have to be generally given to eliminate endometrial hyperplasias. Quantitative determinations of tissue steroid receptors and plasma steroids do not seem to be useful for the selection of patients in need of gestagen treatment.
Androstenedione↗
Enzyme immunoassay of progesterone receptor in cancerous and normal endometrial tissue. A comparison with dextran coated charcoal method.
Enzyme immunoassay (EIA) was compared with the dextran-coated charcoal method and Scatchard analysis for the measurement of progesterone receptor (PgR) in cancerous and normal endometrial samples. A highly significant correlation was obtained between the two assays in both types of tissue (rs = 0.77 and 0.91, respectively; p less than 0.001). The measurable amount of PgR was usually higher with EIA (mean increase 90 and 100 per cent, respectively). EIA is suggested to be a suitable method for PgR measurement in endometrial tissue (normal and cancerous) and can also be used for analysis of PgR in the nuclear fraction.
Biomarkers, Tumor↗
Flow cytometric DNA analysis of normal and cancerous human endometrium and cytological-histopathological correlations.
The DNA content in individual cells from 112 histopathologically normal endometria and from 222 malignant endometrial tumors was measured using flow cytometry. In the normal endometrial cases only single DNA peaks were found, all in the diploid region, and the range of DNA index values was used for defining the limits for diploid tumor cases. In most cases with aneuploid cell populations, an additional peak was found in the normal diploid region. However, combined cytological and histopathological analysis showed that a majority of these diploid cells were to be considered as tumor cells. Aneuploid cell populations were found in 43% of malignant endometria; in the remaining endometrial carcinomas, the flow cytometrical findings showed no differences compared to those of benign tissue. Flow cytometry in this respect did not prove useful as a diagnostic screening method. Ploidy aberrations were correlated to histopathology. Aneuploidy was more common (62%) in poorly differentiated tumors than in highly/moderately differentiated tumors (29%). Two or more aneuploid cell populations were found in 6% of the cases. No difference in aneuploidy was found between FIGO stage I and II (36% and 34%), but aneuploidy was more frequent in stage IV (86%). In normal endometria the fraction of cells with DNA content corresponding to S-phase (S-fraction) was 9.7% on average in the proliferative phase and 6.2% in the secretory phase. In well and moderately differentiated diploid tumors the S-fraction was about the same (8.8% and 9.2%), but in poorly differentiated tumors it was significantly higher (12-16.5%).
Adenocarcinoma↗
Prognostic value of flow cytometrical DNA measurements in stage I-II endometrial carcinoma: correlations with steroid receptor concentration, tumor myometrial invasion, and degree of differentiation.
The prognostic value of flow cytometric DNA measurements of individual tumor cells was studied in 166 patients with endometrial carcinoma stage I-II. Follow-up time was 1-46 months and 110 patients were followed for more than 2 years. Three different ways of estimating DNA ploidy were evaluated, and the use of normal endometria in defining diploidy was considered the best. DNA-ploidy had a much more marked prognostic value in terms of 2-year recurrence-free survival than other known prognostic parameters, such as degree of differentiation, range of myometrial invasion and estradiol and progesterone receptor concentrations. The proliferative activity as determined by DNA flow cytometrical analysis was not correlated with prognosis.
Aneuploidy↗
Permanent alterations induced in plasma prolactin and estrogen receptor concentration in benign and malignant tissue of women who started oral contraceptive use at an early age.
In 65 young women undergoing curettage for benign uterine disorders a significant relationship was found between early oral contraceptive use (starting age less than 25 years) and a high ratio of ln plasma prolactin versus ln estrogen receptor concentration of the uterine mucosae (p less than 0.047, Mann-Whitneys U-test). Year of birth, age at menarche, age at first full term pregnancy, parity, menstrual cycle phase and duration of oral contraceptive use could not explain the results. Because similar results have previously been found for breast cancer patients using plasma prolactin and breast tumour estrogen receptor concentration, the findings indicate that early oral contraceptive use permanently alters plasma prolactin levels and estrogen receptor concentration, both in benign uterine tissue and in malignant breast tumours.
Adult↗
Relapse of endometrial carcinoma related to steroid receptor concentration, staging, histologic grading and myometrial invasion.
Estradiol and progesterone receptor concentrations were positively correlated to the stage of the disease and to the grade of the tumors, but not to myometrial invasion. Myometrial invasion of more than the inner third and degree of differentiation are both important prognostic factors. By combining low estradiol receptor concentration and the degree of myometrial invasion in poorly differentiated adenocarcinomas, stage I-II, it was possible to identify a group of patients containing a high percentage of relapses. This group consisted of 60% of all patients with poorly differentiated carcinoma stage I-II, who had a relapse rate of almost 50%, and were thus suitable for aggressive initial treatment.
Adult↗
Improved method for assay of estradiol and progesterone receptors with special reference to breast cancer.
Isoelectric focusing of estradiol receptor (ER) and multiple point dextran-coated charcoal (DCC) technique for progesterone receptor (PgR) were adapted for assay of both receptors in the same cytosol sample. Technical improvements and increased recovery of receptors were achieved. 1.0 fmol/ml cytosol of ER may be detected; sensitivity of PgR was 5-10 fmol/ml cytosol. Quantitation of ER was made in 414 (95%) out of 434 consecutive breast cancers. Inclusion of isoelectric focusing records showing only qualitative indication for presence of ER resulted in 98% ER containing tumours, supporting the aspect that strictly ER negative tumours are a rarity. Implications for therapy in disseminated disease are discussed.
Animals↗
Correlation between estradiol-17 beta and progesterone cytosol receptor concentration, histologic differentiation and 3H-thymidine incorporation in endometrial carcinoma.
Women treated with estrogen exhibit a higher risk of developing endometrial cancer. steroid hormones exert their effects on target tissue through specific cytosol receptor protein. Knowledge of this steroid receptor concentration in endometrial carcinoma might facilitate the treatment of recurrences. We have compared the concentrations of endometrial estrogen and progesterone cytosol receptors with the histologic grade of endometrial carcinoma as well as the rate of 3H-thymidine incorporation. We found a significant difference in receptor concentration between well-moderately differentiated tumours and poorly differentiated ones. No correlation was found between 3H-thymidine incorporation rate and differentiation. A positive correlation between thymidine incorporation rate and progesterone receptor concentration was noticed. The concentration of receptors varies within a wide range of each group of differentiation; thus 23% and 4% of the poorly differentiated tumours had higher concentration of estradiol and progesterone receptors respectively than the median values for well differentiated tumours.
Cytosol↗
Identification of high-risk groups in endometrial carcinoma stage I-II. A combination of DNA- and steroid receptor-measurements identifies early deaths from the disease.
BACKGROUND: Treatment of endometrial carcinoma has not improved during the last decades, due to the already good results. Such therapy has been a compromise, strong enough to cure some of those in need of harder treatment, but weak enough not to cause too severe side-effects. One way of solving the problem of overtreatment is to identify those in real need of a harder regimen. Generally, the histopathologic picture and the depth of myometrial invasion of the tumour have been used. However, this often means a too large high-risk group, often exceeding 50% of the patients. METHODS: Steroid receptor concentrations and later DNA-measurements have been increasingly used to identify high-risk groups not, however, in combination. In 156 patients with endometrial carcinoma, both estradiol receptor concentration and flow cytometrically estimated DNA content were measured on all patients and the patients were followed-up for over five years. RESULTS: By using the number of DNA-populations (ploidy) we could identify a small high-risk group (28%) with a death frequency of 35%. This small group could be further divided, by using the estradiol receptor concentration, into an extremely small high-high-risk group (11%) consisting of 17 patients of whom 9 died from the disease within 5 years, almost all of the deaths occurring within 2 years. CONCLUSION: Thus histopathology was reduced to merely identifying cancer but DNA- and estradiol receptor measurements in combination could identify an extremely small high-risk group, with almost all deaths occurring within 2 years.
Adult↗