Increased blood cadmium levels were not associated with increased fracture risk but with increased total mortality in women: the Malmö Diet and Cancer Study.

This study aimed to investigate if high levels of blood cadmium at baseline were associated with increased fracture risk during follow-up in middle-aged women. No increased fracture risk was observed during follow-up, but women with higher levels of cadmium had an increased overall mortality. INTRODUCTION: Exposure to high levels of cadmium has been associated with an increased fracture risk. The aim was to investigate a perceived association between low levels of blood cadmium (B-Cd) at baseline and risk of first incident fracture. METHODS: From the population-based Malmö Diet and Cancer Study Cardiovascular cohort, 2920 middle-aged women with available background questionnaire and B-Cd measurements were included. Women were divided into quartiles (Q) according to their cadmium levels (Cd-Q1 <0.18 µg/L, Cd-Q2 0.18-0.28 µg/L, Cd-Q3 0.28-0.51 µg/L, and Cd-Q4 >0.51 µg/L). National registries were analysed for prospective risk of fractures or death. Associations between B-Cd and fracture risk were assessed by survival analysis (Cox regression analysis). RESULTS: In total, 998 first incident fractures occurred in women during a follow-up lasting 20.2 years (median) (12.5-21.2 years) (25th-75th percentile). Women in Cd-Q4 were more often current smokers than in Cd-Q1 78.4 vs. 3.3% (p < 0.001) and the number of cigarettes smoked per day correlated with B-Cd (r = 0.49; p < 0.001). The risk of fracture was not associated with baseline B-Cd in adjusted models. The hazard ratio (HR) Cd-Q4 vs. Cd-Q1 was 1.06 (95% confidence interval (CI) 0.89-1.27). In the multivariate Cox regression, independent variables for increased fracture risk were history of gastric ulcer and increasing age, whereas increasing body mass index (BMI) lowered fracture risk. Overall mortality was significantly higher for women with high B-Cd, HR 2.06 (95% CI 1.57-2.69). CONCLUSIONS: Higher blood levels of cadmium did not increase fracture risk in middle-aged women but reduced overall survival.

Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register study-On behalf of the Swedish Gynecological Cancer Group.

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI ≥ 50% (risk ratio [RR] = 4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI ≥ 50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not.

Low-dose oral combination of 17beta-estradiol and norethisterone acetate in postmenopausal women decreases factor VII, fibrinogen, antithrombin and plasminogen activator inhibitor-1.

OBJECTIVE: Controversies still persist concerning hormone replacement therapy (HRT) and its effects upon blood coagulation and fibrinolysis. This study was carried out to evaluate possible effects of continuously administered low-dose 17beta-estradiol (E2) and norethisterone acetate (NETA) on coagulation and fibrinolytic factors. METHODS: We conducted a randomized double-blind, placebo-controlled, 1-year study in 120 healthy postmenopausal women. The three groups consisted of a placebo group (n = 40), a group receiving oral continuous combined E2 1 mg and NETA 0.25 mg (n = 40) and a group receiving oral continuous combined E2 1 mg and NETA 0.5 mg (n = 40). RESULTS: The two low doses of E2-NETA induced significantly lower plasma levels of factor VII, fibrinogen, antithrombin and plasminogen activator inhibitor-1 (PAI-1), compared with placebo treatmen CONCLUSIONS: Low-dose E2 (1 mg) in combination with NETA resulted in favorable changes of factor VII activity and fibrinogen, compared with placebo. The lower plasma levels of PAI-1 may lead to increased fibrinolytic activity. These findings suggest a decreased risk of developing coronary heart disease. Antithrombin activity was also reduced, which may increase the risk of developing venous thromboembolism. The clinical significance of the lower levels of these factors remains to be clarified.

Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1).

The plasminogen activating system is involved in tumor growth and metastasis by degradation of extracellular matrix, and modulation of cell adhesion and migration. Benign and well-differentiated malignant ovarian tumors present as cystic lesions with preserved glandular morphology, whereas poorly differentiated tumors and metastases are solid with characteristic absence of glandular morphology. We analyzed the mRNAs for urokinase plasminogen activator (uPA), its receptor (uPAR), and inhibitor (PAI-1) in serous ovarian tumors by in situ hybridization and by densitometric scanning of Northern blots prepared from tissue extracts. The mRNA expressing cells in the in situ hybridization sections were evaluated and counted by two different observers. The number of mRNA expressing cells for uPA, uPAR and PAI-1 were all significantly increased in solid as compared with cystic malignant tumors. The increased expression of all three mRNA species was mainly located in the stroma of poorly differentiated tumors and metastases. Apart from being expressed in the stroma of these tumors, uPAR mRNA was also expressed by tumor cells located along the stromal/epithelial boarder. In addition, the tumor tissue content of uPA, uPAR and PAI-1 mRNAs as measured by Northern blots were higher in the solid as compared with the cystic tumors. Increased expression of uPA, uPAR and PAI-1 genes in the solid tumors suggest a correlation with a more aggressive phenotype.

Transvaginal ultrasonographic findings in the uterus and the endometrium: low prevalence of leiomyoma in a random sample of women age 25-40 years.

BACKGROUND: In articles and textbooks the prevalence of uterine leiomyomas is said to be 20-25% in women over the age of 30. The aim of this study was to investigate the rate of uterine leiomyoma, the thickness and the texture of the endometrium, and the size of the uterus in a random sample of asymptomatic women 25-40 years old. METHODS: A random sample of women 25-40 years old was offered a transvaginal ultrasonographic examination and 335 (72%) accepted the invitation. RESULTS: In 18 women uterine leiomyomas were detected, i.e. 5.4% (95% CI 3.0-7.8%). The prevalence of leiomyomas increased with age, being 3.3% (95% CI 0.7-6.0%) in the 25-32 years age group and 7.8% (95% CI 3.6-12.0%) in the 33-40 age group. The size of the uterus correlated to parity, age and height. In women on combined oral contraceptives the size of the uterus was smaller than in women with natural cycles. The size of the uterus did not correlate to body mass index, cycle day or smoking habits. The endometrium increased in thickness and had in most cases a triple line appearance during the proliferative phase until day 15, whereafter it was unchanged in thickness throughout the secretory phase and hyperechogenic in appearance. CONCLUSIONS: This study confirms earlier studies on the endometrium based on selected populations. The size of the uterus increased with parity, age and height, and was smaller in combined oral contraceptive users. The prevalence figures for uterine leiomyomas in textbooks are not confirmed.

Transvaginal sonographic ovarian findings in a random sample of women 25-40 years old.

OBJECTIVE: To investigate the occurrence rate of adnexal lesions in premenopausal women. METHODS: A random sample of women 25-40 years old was invited to undergo a transvaginal ultrasound examination, and 335 women were examined. The criteria used to define an adnexal lesion were either a cystic lesion with its largest diameter of at least 25 mm within the pelvic region, or the appearance of solid parts in any lesion regardless of size. RESULTS: Adnexal lesions were found in 26/335 cases, (7.8%) (95% confidence interval (CI), +/- 2.9%). The occurrence rate of ovarian cysts was 22/335 (6.6%) (95% CI, +/- 2.7%). There were no differences between the women with or without ovarian cysts related to age, smoking habits, parity or body mass index. At follow-up 3 months later, 18 of the 22 (82%) cysts had disappeared (95% CI, +/- 16%). Women using progesterone contraception (either oral contraception or an intrauterine device with levonorgestrel) had a significantly higher relative risk of 2.7 (95% CI, 1.1-6.9) of functional cysts as compared to women with natural cycles. Polycystic ovaries were found in 10.2% (95% CI, +/- 4.2%) of the women not using any hormonal contraception. The mean volumes of the polycystic ovaries were significantly larger compared to those in natural cycles. CONCLUSION: Adnexal lesions are common in asymptomatic women in the age group 25-40 years, but four out of five ovarian cysts disappeared spontaneously after 3 months. The ultrasound appearance of the cyst, the woman's family history and her own feelings must be considered if a persisting cyst is to be surgically removed or followed by repeated transvaginal ultrasound.

High tissue content of urokinase plasminogen activator (u-PA) is associated with high stromal expression of u-PA mRNA in poorly differentiated serous ovarian carcinoma.

Urokinase plasminogen activator (u-PA) plays a pivotal role in tissue degradation during tumor spread and metastasis. We have quantitated u-PA in tissue homogenates of 31 serous ovarian tumors and localized u-PA and its mRNA in tissue sections of 26 serous ovarian tumors. The content of u-PA was higher in malignant than in benign tumors, with the highest levels being found in poorly differentiated cancers. In tissue sections, the u-PA mRNA was hybridized with a radiolabeled RNA probe. Signals were almost exclusively found in the epithelium in benign and borderline tumors and in well-differentiated cancers. Poorly differentiated tumors and metastases exhibited prominent stromal expression of u-PA mRNA, whereas epithelial expression was weak or absent. Immuno-histochemical staining co-localized u-PA antigen with its mRNA in the epithelium of benign and borderline tumors and in well-differentiated cancers. Poorly differentiated malignant tumors showed extensive immunostaining in the epithelium in addition to stromal staining. The u-PA mRNA-expressing and u-PA-immunostained cells in the stroma were not tumor cells since no cells in the stroma were positive for cytokeratin. Poorly differentiated tumors had increased numbers of stromal macrophages (CD68), and they co-localized with some of the u-PA-positive cells. The presence of u-PA antigen and the absence of u-PA mRNA in tumor epithelium of poorly differentiated tumors and metastases together with the presence of u-PA mRNA in the stroma suggests production in stromal cells and subsequent binding to receptor sites in tumor cells.

The hypereosinophilic syndrome. Report of a case with successful medical treatment following cardiac biopsy.

Together with pronounced blood eosinophilia an endomyocardial biopsy is the method of choice in diagnosing and assessing the severity of the systemic disorder hypereosinophilic syndrome (HES). Eosinophilia is not uncommon in several connective tissue diseases which may share clinical manifestations with HES. We report a case of HES, investigated and followed up with cardiac biopsies. A missing right radial artery pulsation gave rise to several differential diagnostic considerations.