Role of transvaginal ultrasound in evaluation of ureteral involvement in deep infiltrating endometriosis.

OBJECTIVE: To assess whether routine examination of the ureters on transvaginal sonography (TVS) can identify reliably potential silent ureteral involvement by endometriosis and should therefore be recommended in all patients with deep infiltrating endometriosis (DIE). METHODS: This was a prospective study of 200 consecutive patients scheduled for surgery for DIE, evaluated between January 2012 and December 2014 at a tertiary endometriosis center at Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. Routine TVS, abdominal ultrasound and gynecological examination were performed within 3 months before surgery, and patient history, signs and symptoms were recorded. Surgical and histological findings were compared with the preoperative ultrasonographic diagnosis. The main outcome of interest was the presence of ureteral dilatation or hydronephrosis caused by endometriosis. RESULTS: Of 200 patients with DIE, associated ureteral dilatation was diagnosed on TVS in 13 (6.5%) cases. Ureteral involvement was confirmed intraoperatively in all 13 cases by detection of ureteral dilatation caused by endometriotic tissue surrounding the ureter and causing stenosis. Of the 13 patients with ureteral dilatation, renal ultrasound detected six (46.2%) cases of hydronephrosis. Mean duration of visualization and study of dilated ureters was 5 min (range, 3-9 min). Ureteric diameter was ≥ 6 mm in all cases of ureteral dilatation, with a median diameter of 6.9 mm (range, 6-18 mm). Both ureters were identified on TVS in all 200 patients with DIE. CONCLUSIONS: Our study confirms a relatively high incidence of ureteral involvement in patients with DIE. TVS appears to be a reliable tool for the diagnosis of ureteral involvement and, additionally, it allows the detection of both the level and degree of obstruction. Our findings confirm that TVS examination is an accurate non-invasive diagnostic tool for the detection of ureteral involvement by endometriosis. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Bleeding profile and endometrial safety of continuous combined regimens 1 mg 17beta-estradiol/trimegestone versus 1 or 2 mg 17beta-estradiol/norethisterone acetate in postmenopausal women.

OBJECTIVE: To compare the bleeding profile and endometrial safety of continuous combined 1 mg 17beta-estradiol (17beta-E2) and 0.125 mg trimegestone (TMG) with those of two continuous combined 17beta-E2 and norethisterone acetate (NETA) regimens. STUDY DESIGN: This was a double-blind, randomized, multicenter study conducted in 12 European countries and Israel over a 2-year period. Healthy postmenopausal women with an intact uterus were given either 1 mg 17beta-E2/0.125 mg TMG, 2 mg 17beta-E2/1 mg NETA or 1 mg 17beta-E2/0.5 mg NETA for up to 26 cycles, each of 28 days. RESULTS: The percentage of amenorrheic women was greater in most cycles up to cycle 13 in the 1 mg 17beta-E2/0.125 mg TMG group than in the comparator groups. The mean number of bleeding days was similar in the 1 mg 17beta-E2/0.125 mg TMG and the 1 mg 17beta-E2/0.5 mg NETA groups, but greater in the 2 mg 17beta-E2/1 mg NETA group. No endometrial hyperplasia was observed for any group. CONCLUSION: Continuous combined 1 mg 17beta-E2/0.125 mg TMG exhibits a more favorable bleeding profile than 1 mg 17beta-E2/0.5 mg NETA up to 1 year, while providing an adequate protective effect on the endometrium.

Antimitotic effects of usnic acid on different biological systems.

Usnic acid is a biosynthesis product characteristic of several epiphytic lichens such as Evernia, Cladonia and Parmelia. Usnic acid has several interesting biological properties. It is an antibiotic and it also seems to exert an antimitotic action. It has even been postulated that usnic acid can play a role as an environmental indicator, since its concentration varies according to the presence of toxic agents. A series of tests have been run on different biological systems such as fungi, yeasts, plant cells and neoplastic human cell cultures in order to make a general evaluation of the properties of usnic acid and to highlight any analogy between its effects on phylogenetically distant organisms. The results obtained confirm some of the already known properties of usnic acid and identify concentration ranges that are active against cells from different organisms. Furthermore, at low concentrations, the acid displays a capacity to stimulate cell metabolism in some of the biological systems tested.

Effects of interferon-beta on steroid receptors, prostaglandins and enzymatic activities in human endometrial cancer.

Steroid receptors, prostaglandin output and enzymatic activities were determined in explants derived from human endometrium exposed to natural interferon-beta (IFN-beta). Receptors and cell metabolism were evaluated before culturing the tissue fragments and after a 3-day treatment with varying concentrations of IFN-beta. Total steroid receptor levels were unchanged when explants were set up, but there was a redistribution of both estrogen and progesterone receptors (ER and PR). A decrease in cytoplasmic receptors corresponded to an increase in receptor molecules within the nucleus. Treatment with low concentrations of IFN-beta caused a significant enhancement (p < 0.05) of ER and PR in neoplastic endometrium. In basal conditions the ratio between prostaglandin F2 alpha (Pgf2 alpha) and prostaglandin E2 (PgE2) was higher in normal than in neoplastic endometrium. The addition of low concentrations of IFN-beta to the culture medium determined a significant increase (p < 0.02) in PgF2 alpha and a parallel increase in the above ratio in neoplastic tissue, while no variation was found in normal endometrium. Analysis of the results concerning the variations in hormone-related enzymatic activities due to IFN-B revealed a significant increase (p < 0.05) in 17 beta-hydroxy-steroid-dehydrogenase (17 beta-HSD) activity. The data presented here indicate that treatment with IFN-beta modifies those biological characteristics of neoplastic cells which are involved in hormone-responsiveness.

Interferon-beta increases the sensitivity of endometrial cancer cells to cell-mediated cytotoxicity.

Established monolayer cell lines derived from human endometrial carcinoma (Ishikawa and HEC-50) were sensitive to the cytotoxic activity of peripheral blood lymphocytes (PBLs). The percentages of hormone-responsive Ishikawa cells lysed by the cytotoxic activity of lymphocytes were 45.7 +/- 4.3 (mean +/- SE), 31.5 +/- 4.1, and 20.1 +/- 1.6, at effector/target (E/T) ratios of 50:1, 25:1, and 12:1, respectively. Values of 44.7 +/- 5.4%, 29.4 +/- 4.6%, and 20 +/- 4.9% were obtained when non-hormone-responsive HEC-50 cells were used as targets at the same E/T ratio. The percentages of epithelial and stromal cells, isolated from human endometrial cancer, lysed by the cytotoxic activity of lymphocytes were 40 +/- 5.4 and 25.2 +/- 3.8, respectively, at an E/T ratio of 25:1. The addition of interferon-beta (IFN-beta) to the culture increased tumor target cell sensitivity to the lytic activity of untreated PBL. The increase produced by 10 IU/ml of IFN-beta ranged between 0.60- and 0.89-fold (P < 0.01 Student's t test, two-tailed, unpaired) in Ishikawa cells and between 0.37- and 0.72-fold P < 0.05) in HEC-50 cells. Higher concentrations of IFN-beta (100 and 1000 IU/ml) were less effective in increasing the sensitivity of the target cells. There was no significant increase in the cytotoxic activity of lymphocytes treated with IFN-beta whereas cytotoxic activity toward untreated tumor target cells increased when lymphocytes were treated with IFN-alpha. The effects of IFN-beta were also evaluated using epithelial and stromal cells derived from human endometrial cancer. It was found that IFN-beta at low concentrations (10 IU/ml) significantly increased the sensitivity of both epithelial and stromal cells, by 48 and 73%, respectively. Our data indicate that Ishikawa, HEC-50, epithelial, and stromal cells may provide a useful experimental model for studying the effects of immunomodulant agents such as IFN-beta in hormone-related tumors. IFN-beta increases endometrial target cell sensitivity, rather than the lytic activity of lymphocytes.

Natural interferon-beta treatment and steroid hormone receptors in primary endometrial cancer.

Forty-three patients with primary endometrial carcinoma were treated with natural interferon-beta (IFN-beta) at two different dose levels (2 x 10(6) IU or 6 x 10(6) IU im 3 times/week for 1 week). IFN-beta increased receptors for estrogens (ER) and progesterone (PR) in a high percentage of the 40 evaluable patients, without modifying the receptor affinity. The ER and PR enhancement, which was simultaneous in at least 50% of patients, and the increase of over 100 fmol/mg protein observed in some cases suggest that IFN-beta exerts a profound influence on receptor expression and, probably, on the hormone sensitivity of the tumor.

Steroid hormones and gonadotropins in a case of ovarian endometriosis associated with virilization.

The clinical course, the hormone secretion, the testosterone receptors and the enzymatic activities related to androgen metabolism in a 56-year-old postmenopausal woman with a history of virilization and ovarian endometrioma are reported. Unexpectedly, at the time of examination, no evidence of biochemical hyperandrogenism was obtained. The uncommon association of virilization and ovarian endometrioma simulating a functioning tumor of the ovary is discussed.

Hormone receptors and enzymatic activities in human endometrial adenocarcinoma.

The hormone sensitivity of endometrial carcinoma is related to the presence of steroid hormone receptors. The determination of progesterone receptors has been proposed in order to predict clinical prognosis and to aid treatment selection. The integrity of the hormone receptor system and postreceptoral events in tumors is essential to endocrine therapy response. Nevertheless, although hormone receptors are present in a large number of endometrial carcinomas, only 30% of cases respond to hormone therapy. In some neoplasms the receptors can be present, but not functioning, or else neoplastic transformation could have induced alterations in processes after hormone-receptor interaction.

Hormone receptor status in human endometrial adenocarcinoma.

Steroid receptor levels were determined in 196 samples of endometrial adenocarcinoma: cytosol estradiol receptors (ERc) were measured in 171 samples, cytosol progesterone receptors (PRc) in all samples; nuclear estradiol receptors (ERn) and nuclear progesterone receptors (PRn) in 68 samples; total estradiol receptors (ERt = ERc plus ERn) and total progesterone receptors (PRt = PRc plus PRn) were measured in 68 samples. The ERc levels were 88.2 +/- 8.9 (mean +/- SEM) and ERn were 94.4 +/- 15.6 fmol/mg protein; PRc levels were 197.9 +/- 25.9 and PRn 178.3 +/- 55.9 fmol/mg protein. The ERt levels were 162.6 +/- 23.2 and PRt 249.8 +/- 75.7 fmol/mg protein. The presence of PRc was related to the ERc levels according to the cut-off used. Estradiol receptors (ER) and progesterone receptors (PR) were present in the cytoplasmic and nuclear fractions in 60.2% and 36.8% of cases, respectively. The simultaneous presence of both ERt and PRt was observed only in 27.9% of cases. In the normal endometrium ERc and PRc were negatively correlated (r = -0.525, P less than 0.005), whereas in endometrial adenocarcinoma the correlation was positive (r = 0.491, P less than 0.001). In contrast with the normal endometrium the correlation between ERc and ERn was positive (r = 0.582, P less than 0.001) in tumor tissue. In neoplastic tissue Scatchard analysis showed a single class of specific ERc sites with a dissociation constant (Kd) of 1.39 +/- 0.8 X 10(-9) mol/l, one tenth of that found in the normal premenopausal endometrium. Qualitative and quantitative analysis of the receptor status showed that in 30% to 40% of cases studied the behavior of the neoplastic cell was similar to that found in the normal endometrial cell. In a 4-year follow-up of patients affected by endometrial adenocarcinoma there is better survival in the groups of patients with a simultaneous presence of ERt and PRt than in the group with their absence.

Androgen binding in human fetal amnion.

Human fetal amnion cytosol obtained at term is able to bind specifically [3H]testosterone. The cytosol (105,000 g supernatant) from human amnion was used after a 30 min treatment with dextran-coated charcoal and incubated with increasing concentrations of [3H]testosterone, [3H]dihydrotestosterone, [3H]methyltrienolone for 2 h at 4 degrees C and for 16 h at 15 degrees C. To avoid any possible contamination of sex hormone binding globulin we used a Sepharose 4B column. Scatchard plot analysis of the data after incubation at 4 degrees C for 2 h showed that the amnion possesses high affinity (Kd = 0.62 +/- 0.20 nM) and low capacity (95.0 +/- 21.1 fmol/mg protein) binding sites for [3H]testosterone. After incubation at 15 degrees C for 16 h, we obtained a high affinity (Kd = 0.29 +/- 0.14 nM), low capacity (49.5 +/- 12.8 fmol/mg protein) and a low affinity (Kd = 5.55 +/- 2.55 nM), high capacity (181.7 +/- 20.8 fmol/mg protein) binding sites for [3H]testosterone. The values of Kd, calculated from Scatchard plot analysis were 1.03 +/- 0.7 nM with 20.2 +/- 10.4 fmol/mg protein and 1.97 +/- 1.06 nM with 55.6 +/- 15.9 fmol/mg protein for [3H]methyltrienolone and [3H]dihydrotestosterone respectively. These findings suggest that human fetal amnion cytosol at term contains a specific binding protein for androgens.