Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer.

BACKGROUND: Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established. METHODS: We performed immunohistochemical analysis of 186 frozen specimens from advanced-stage ovarian carcinomas to assess the distribution of tumor-infiltrating T cells and conducted outcome analyses. Molecular analyses were performed in some tumors by real-time polymerase chain reaction. RESULTS: CD3+ tumor-infiltrating T cells were detected within tumor-cell islets (intratumoral T cells) in 102 of the 186 tumors (54.8 percent); they were undetectable in 72 tumors (38.7 percent); the remaining 12 tumors (6.5 percent) could not be evaluated. There were significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons). The five-year overall survival rate was 38.0 percent among patients whose tumors contained T cells and 4.5 percent among patients whose tumors contained no T cells in islets. Significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons) were also seen among 74 patients with a complete clinical response after debulking and platinum-based chemotherapy: the five-year overall survival rate was 73.9 percent among patients whose tumors contained T cells and 11.9 percent among patients whose tumors contained no T cells in islets. The presence of intratumoral T cells independently correlated with delayed recurrence or delayed death in multivariate analysis and was associated with increased expression of interferon-gamma, interleukin-2, and lymphocyte-attracting chemokines within the tumor. The absence of intratumoral T cells was associated with increased levels of vascular endothelial growth factor. CONCLUSIONS: The presence of intratumoral T cells correlates with improved clinical outcome in advanced ovarian carcinoma.

Isolated premature pubarche: ultrasonographic and color Doppler analysis--a longitudinal study.

Twenty-seven girls with premature pubarche were studied by ultrasonographic and color Doppler analyses to determine the incidence of polycystic ovaries (PCO), to longitudinally assess their evolution, and to search for any hormonal correlation. The girls were submitted to auxological, clinical, and hormonal evaluation, and 21-hydroxylase deficiency was ruled out by an ACTH test. Furthermore, the girls underwent ultrasonographic and color Doppler ovarian and uterine analyses. Among girls with premature pubarche, the prevalence of PCO was 41%. Advanced skeletal maturation, tall stature, and increased hair distribution were constant in these patients. In patients with ultrasonographic and color Doppler evidence of PCO, the ovarian volume, the number of small-sized subcapsular follicles, the stromal echogenicity, and the ovarian stromal vascularization progressively increased during the study. In the whole studied population, ovarian volume correlated with the number of small-sized follicles (r = 0.719; P < 0.0001). Furthermore, a slight and inverse correlation has been found between ovarian volume and ovarian stromal artery pulsatility index (r = -536; P = 0.048). In conclusion, we affirm that PCO are greatly represented among girls with premature pubarche and progressively evolve.

Hormone therapy and ophthalmic artery blood flow changes in women with primary open-angle glaucoma.

OBJECTIVE: To compare the effects of hormone therapy (HT) on plasma viscosity and Doppler flow parameters in normal, healthy, postmenopausal women and in women with normal-tension and chronic, open-angle glaucoma. DESIGN: Eight postmenopausal women with glaucoma (group I) and 15 controls (group II) were given HT. The duration of the study was 6 months, and the women were examined in basal condition and at the end of the treatment. All women underwent ultrasonographic evaluation of pelvic organs and color Doppler analysis of uterine, internal carotid, and ophthalmic arteries. Also, plasma viscosity was assayed. RESULTS: The ultrasonographic analysis showed that none of the women presented with irregular endometrial echoes, polyps, or intracavitary fluid. In addition, endometrial thickness never exceeded the normal range (5 mm). Plasma viscosity and Doppler parameters significantly improved during therapy. However, the ophthalmic artery mean improvements of pulsatility index (-43% v -28%; P = 0.001), peak systolic blood flow velocity (+35% v +24%; P = 0.026), and time-averaged maximum velocity (+44% v +32%; P = 0.031) were significantly more evident in the control group than in the glaucoma group. CONCLUSIONS: Although, in people with glaucoma, vasospasm can increase the risk of visual loss by inducing a retrobulbar blood flow reduction, HT seems to beneficially affect the ocular vascularization.

Tibolone, oral or transdermal hormone replacement and colour Doppler analysis: a prospective, randomised pilot study.

OBJECTIVE: To compare the plasma thromboxane, the plasma viscosity and the Doppler flow modifications induced by tibolone and by oral or transdermal continuous combined hormone replacement therapy. METHODS: Forty-two post-menopausal patients underwent either on: oral daily treatment with tibolone (2.5 mg) (Group I; n= 14); or continuous oral administration of 0.625 mg conjugated equine estrogens + medroxyprogesterone 5 mg per day (Group II; n = 14 ); or continuous estradiol transdermal supplementation, at a dose of 50 microg per day, + medroxyprogesterone 5 mg per day (Group III; n = 14 ). The duration of the study was 6 months and the patients were submitted to transvaginal ultrasonographic evaluation of pelvic organs; Doppler analysis of the uterine, internal carotid and ophthalmic arteries; thromboxane and plasma viscosity assays in basal condition, and at 1, 3 and 6 months from the beginning of the study. RESULTS: Although the endometrial thickness increased significantly, there were no cases in which it exceeded the normal range (< or = 5 mm). In all the three groups, the pulsatility index of the uterine, internal carotid and ophthalmic arteries significantly decreased during the therapy showing a reduced impedance since the first month of treatment. Similar variations were observed for the peak systolic blood flow velocity of the internal carotid and ophthalmic arteries. Hormone replacement therapy and tibolone induced a deep, significant and rapid decrease in plasma thromboxane and plasma viscosity levels. CONCLUSIONS: Hormone replacement therapy and tibolone seem to have beneficial effects on vascular and hemorrheological parameters.

Time since menopause does not affect plasma viscosity, plasma thromboxane levels and Doppler findings.

OBJECTIVES: To evaluate whether the use of transdermal hormone replacement therapy (HRT), in women within 5 years of menopause compared with women who were postmenopausal for > 5 years, would significantly influence thromboxane B2 levels, plasma viscosity and Doppler flow parameters at the level of the uterine, internal carotid, ophthalmic and bladder wall arteries. METHODS: Thirty-five normal-weight (body mass index > 19 and < 25 kg/m(2)) postmenopausal women (age 54.6 +/- 3.9 years, mean +/- standard deviation) participated in the study and were divided into two groups (Group I: n = 19, time since menopause < 5 years; and Group II: n = 16, time since menopause > 5 years). Patients were treated with a continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate every 2 months. They were studied at baseline and after 6 months (in the estrogen-only phase of the cycle). RESULTS: Results showed a beneficial effect of hormone substitution after 6 months of therapy. Baseline plasma viscosity was similar in both groups, and decreased significantly after therapy in both Group I (-17.5%) and Group II (-15.6%). Plasma levels of thromboxane B(2) were similar at baseline and diminished equally in Group I and Group II (-85.6% and -85.2%, respectively) after treatment. Doppler assessment of the pulsatility index at the level of uterine, internal carotid, ophthalmic and bladder wall arteries showed no differences between groups at baseline and revealed a significant reduction of vascular impedance at the end of the treatment in both groups. CONCLUSIONS: Time since menopause does not affect the potential hemodynamic benefits of HRT in normal-weight women.

Adjuvant L-arginine treatment in controlled ovarian hyperstimulation: a double-blind, randomized study.

BACKGROUND: Enhanced vascularization appears to be important for follicular selection and maturation in both spontaneous and stimulated IVF cycles. Nitric oxide, formed in vivo from L-arginine, may play a key role in follicular maturation and ovulation. METHODS: To evaluate the role of L-arginine supplementation in controlled ovarian hyperstimulation, 37 IVF patients were divided into two groups according to ovarian stimulation protocols: group I, GnRH agonist plus pure (p)FSH plus oral L-arginine (n = 18); and group II, GnRH agonist plus pFSH plus placebo (n = 19). Hormonal, ultrasonographic and Doppler evaluations were performed, and plasma and follicular fluid nitrite/nitrate concentrations were monitored. RESULTS: Thirty-two patients completed the study. In group I (n = 16), plasma L-arginine concentrations increased from (basal) 87 +/- 12 micromol to 279 +/- 31 micromol (P = 0.002) on the day of beta-HCG administration. In this group, pFSH treatment was shorter (P = 0.039) than in group II (n = 16). The number of the follicles > or =17mm was lower (P = 0.038) in group I than group II. The "good quality" embryos were fewer in number (P = 0.034) and pregnancy rate, both per patient (P = 0.024) and per embryo transfer (P = 0.019), was lower in group I. In the L-arginine group, an increased follicular fluid concentration of nitrite/nitrate was observed. On day 8 of the cycle, elevated plasma estradiol levels were associated with decreased blood flow resistances of perifollicular arteries. Follicular fluid concentrations of nitrite/nitrate were inversely correlated with embryo quality (r = -0.613; P = 0.005) and perifollicular artery pulsatility index (r = -0.609; P = 0.021). CONCLUSIONS: L-Arginine supplementation may be detrimental to embryo quality and pregnancy rate during controlled ovarian hyperstimulation cycles.

Polycystic ovaries in childhood: a common finding in daughters of PCOS patients. A pilot study.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a controversial endocrine pathology and, recently, it has been suggested that the condition is hereditary. The aim of this study was to prospectively determine in daughters of patients with PCOS, by ultrasonographic (US) and colour Doppler analyses, the incidence of polycystic ovaries and search any correlation with specific hormonal parameters. METHODS: Fifteen prepubertal offspring (Group I) of patients with PCOS and 10 normal control prepubertal girls (Group II) were submitted to clinical, auxological, and basal hormonal assay. In addition all patients were submitted to US and colour Doppler ovarian and uterine evaluation. RESULTS: Among Group I girls the prevalence of polycystic ovaries was 93%, whereas no subjects among Group II had polycystic ovaries. The ovarian volume (2.76 +/- 1.21 ml versus 0.87 +/- 0.46 ml; P < 0.001) and the number of small sized follicles (5.36 +/- 2.2 versus 0.75 +/- 0.92; P < 0.001) were significantly higher in Group I than Group II patients. In addition, a normal stromal score and an absent stromal vascularization was observed in the control group. The hormone levels did not differ between the two groups. CONCLUSION: In conclusion we speculate that polycystic ovaries in childhood may be considered a sign of genetic predisposition to PCOS and that environmental factors may express the adult clinical and hormonal presentation of the syndrome.