Leuprolide acetate as a salvage-therapy in relapsed epithelial ovarian cancer.

A large number of studies have been conducted in patients affected by epithelial ovarian cancer to assess the potential utility of a variety of different regimens in patients who have relapsed after primary surgery and adjuvant chemotherapy. In this open prospective study, 32 patients with ovarian cancer of epithelial histology who had relapsed after platinum-based line chemotherapy and had exhausted all standard treatments, received Leuprolide acetate depot 3.75 mg, intramuscularly once a month until tumor progression. Four patients (12.5%) had clinical and/or radiological partial response; remission was then maintained for a mean duration of 8.7 months (range 6-11 months) before new progression occurred. Five patients (15.6%) remained stable for a mean time of 5.2 months (range 4-6 months) and 23 patients (71.9%) continued to progress following therapy and have since died by tumor with a median survival of 3.6 months after initiation of the protocol. Treatment is well-tolerated and no toxicity has been noted. These data stress the significant activity of Leuprolide acetate as a salvage therapy in patients with relapsed advanced epithelial ovarian cancer after previous platinum-based chemotherapies.

Simplified ondansetron regimens for antiemetic prophylaxis in cisplatin-based chemotherapy of ovarian cancer.

In past years prevention of emesis and nausea induced by antiblastics has been based on extremely heterogeneous protocols with little efficacy. However, by the use of selective antagonists of serotonin S3 receptors there has been a remarkable improvement in the control of side effects. Among these antagonists ondansetron has been till now the most studied. The dosage protocols with which it has usually been employed establish an i.v. administration of the drug of 1 mg/h for 24 hours or the repetition of ondansetron 0.15 mg/kg x 2 every 2-4 hours after the end of chemotherapy. In our study, carried out from September 1991 till September 1992, 21 patients affected by ovarian carcinoma and treated by cisplatin chemotherapy protocols were evaluated (for a total of 63 cycles). Ten patients were under first line adjuvant chemotherapy treatment, whereas 11 patients were in relapse and had already undergone previous antiblastic treatments with serious side effects. In 18 out of 21 patients cyclophosphamide which has a strong emetic factor was associated with cisplatin. According to the total quantity of cisplatin contained in each cycle (in all < or =/> 100 mg) we used ondansetron in two different dosages simplified and shortened in time. They have been illustrated with particular details in the text. The control of nausea and vomiting during the first 24 hours was similar to the controls obtained in other studies in which ondansetron was administered according to the "traditional schemes".(ABSTRACT TRUNCATED AT 250 WORDS)

Variations of lymphocyte sub-populations in vulvar condylomata during therapy with beta-interferon.

Several experiences induced us to consider genital HPV infection as an expression of a local immunodeficiency. The aim of our study was to research the effect of immunotherapy on the lymphocyte subpopulations and Langerhans cells in vulvar condyloma. Twenty women with persistent vulvar condylomata, treated with 2,000,000 IU/die of beta-interferon for 15 days, were submitted to vulvar biopsy before and 2-5 months after medical treatment. The frozen sections obtained were assayed with the following monoclonal antibodies: OKT4 (T helper lymphocytes), OKT8 (T suppressor lymphocytes), OKB7 (B lymphocytes) and S-100 protein (Langerhans cells). Using a morphometric evaluation, the average number of both intraepithelial and stromal lymphocyte subsets and of the intraepithelial Langerhans cells was assessed. In all the biopsies preceding the medical treatment we found a low number of T helper lymphocytes both in the epithelium and stroma, with inversion of T4/T8 lymphocyte ratio and rare presence of Langerhans cells. In patients with a good therapeutic response (50-100% of condyloma reduction) we observed an increase in intraepithelial T4 lymphocytes and a decrease in both intraepithelial and stromal T8 lymphocytes. In cases with persistent disease after therapy, the histological pattern was similar to that observed in the first biopsy, with the exception of a significant increase in the average number of Langerhans cells. Our data correlate the clinical response to the immunotherapy with the histology of lymphocyte subsets in the vulvar condylomata. The increase in Langerhans cells observed in patients with negative response may be interpreted with a probable inability of these cells to promote the immune reaction.

Depth of myometrial invasion in endometrial cancer: preoperative assessment by transvaginal ultrasonography and magnetic resonance imaging.

Depth of myometrial invasion in endometrial cancer correlates with pelvic lymph node metastases and tumor recurrence. Thirty patients diagnosed as having FIGO stage I endometrial carcinoma on the basis of D&C were evaluated preoperatively by magnetic resonance imaging (MRI); 14 cases of the same group were also evaluated by transvaginal ultrasound. The degree of invasion evaluated by MRI and transvaginal sonography was compared to the pathological specimens. MRI was successful in evaluating myometrial invasion in 2.5 of 30 cases (accuracy 83%, sensitivity 87%, specificity 78%, positive predictive value 82%, negative predictive value 84%). Evaluation with transvaginal sonography was accurate in 11 of 14 cases (accuracy 78%, sensitivity 80% specificity 77%, positive predictive value 87%, negative predictive value 66%).

Variations of lymphocyte sub-populations in vulvar condylomata during therapy with beta-interferon.

Several experiences induced us to consider genital HPV infection as an expression of a local immunodeficiency. The aim of our study was to research the effect of immunotherapy on the lymphocyte subpopulations and Langerhans cells in vulvar condyloma. Twenty women with persistent vulvar condylomata, treated with 2,000,000 IU/die of beta-interferon for 15 days, were submitted to vulvar biopsy before and 2-5 months after medical treatment. The frozen sections obtained were assayed with the following monoclonal antibodies: OKT 4 (T helper lymphocytes), OKT 8 (T suppressor lymphocytes), OKB 7 (B lymphocytes) and S-100 protein (Langerhans cells). Using a morphometric evaluation, the average number of both intraepithelial and stromal lymphocyte subsets and of the intraepithelial Langerhans cells was assessed. In all the biopsies preceeding the medical treatment we found a low number of T helper lymphocytes both in the epithelium and stroma, with inversion of T4/T8 lymphocyte ratio and rare presence of Langerhans cells. In patients with a good therapeutic response (50-100% of condyloma reduction) we observed an increase in intraepithelial T4 lymphocytes and a decrease in both intraepithelial and stromal T8 lymphocytes. In cases with persistent disease after therapy, the histological pattern was similar to that observed in the first biopsy, with the exception of a significant increase in the average number of Langerhans cells. Our data correlate the clinical response to the immunotherapy with the histology of lymphocyte subsets in the vulvar condylomata. The increase in Langerhans cells observed in patients with negative response may be interpreted with a probable inability of these cells to promote the immune reaction.

A randomized comparative study for the clinical evaluation of hormone replacement by transdermal and oral routes.

During a six-month randomized study involving 460 post-menopausal women, transdermal estradiol has proved to be as effective as oral conjugated equine estrogens in the control of menopausal symptoms and to produce similar estrogenic effects on the endometrium. The group of patients treated with transdermal estradiol showed better compliance and had fewer drop-outs. Moreover, the quality and duration of menstrual bleeding were considered more physiological in the transdermal estradiol group than in the orally treated patients. The trial was carried out with the co-operation of 17 Italian University Centres, under the supervision of Ciba-Geigy Italy S.p.A. Medical Department.

Ontogeny of human lymphocytes. Two-color fluorescence analysis of circulating lymphocyte subsets in fetuses in the second trimester of pregnancy.

By using monoclonal antibodies, two-color immunofluorescence techniques and flow cytometry, we evaluated the surface marker phenotypes of lymphocyte subsets in cord blood samples from fetuses in the second trimester of pregnancy. The results indicate that cells of the T-, B- and NK-cell lineages as well as precursor cells can be detected in fetal blood at 18-20 weeks of gestation. At this stage of development, variable proportions of T and B lymphocytes express surface molecules, such as the CD1, CD10, CD38, CD45RA, indicative of a precursor or 'naive' state; on the other hand, the CD57 molecule is not detectable on the membrane of NK and T cells, and the RO isoform of the CD45 leukocyte antigen is synthesized by a low percentage of T cells. We suggest that the observed phenotypic peculiarities of the lymphoid cells might be related to the easy induction of tolerance that occurs in the early ontogenetic stages of the immune system.

Procoagulant activity of mononuclear phagocytes from different anatomical sites in patients with gynecological malignancies.

Mononuclear phagocytes exhibit complex interactions with cancer cells and might contribute to fibrin formation associated with malignancy through the production of procoagulant activity (PCA). We have studied the PCA of peritoneal macrophages in 8 patients with advanced (stages III or IV) ovarian cancer and of macrophages from regional lymph nodes in 14 patients with limited (stages I or II) uterine cancer; peritoneal and lymph-node macrophages from patients with benign gynecological tumors were used as reference cell populations. In all patients, PCA of blood monocytes was also studied. Peritoneal and lymph-node macrophages obtained from patients with ovarian and uterine cancer, respectively, expressed far higher levels of basal PCA than the corresponding cell populations from patients with benign tumors (p less than 0.001). PCA of blood mononuclear cells from patients with ovarian, but not with uterine cancer, was significantly higher (p less than 0.001) than that of control cells. High levels of D-dimer, a specific product derived from plasmin-induced degradation of stabilized fibrin, were found in all ascitic fluids and in all plasma samples but one from patients with ovarian cancer. In contrast, all controls and all uterine cancer patients but one had normal plasma D-dimer. Our findings suggest that local activation of host macrophages for PCA production might contribute to fibrin formation within the tumoral mass. In advanced cancer, blood monocytes may also be activated to produce PCA and thus contribute to activation of intravascular coagulation and, possibly, to thrombo-embolic complications frequently associated with disseminated malignancy.

Endocervical adenocarcinoma. Immunohistochemical characterization.

The presence of cytokeratins, IgA, alphafetoprotein (AFP), beta-Human Chorionic Gonadotropin (HCG), Carcinoembryonic antigen (CEA) and Epithelial Membrane Antigen (EMA) were immunohistochemically researched with a PAP method in 19 cases of endocervical adenocarcinoma. AFP and HCG were always absent, while the low and median molecular weight cytokeratins were present in 18 case (95%). These findings confirm the hypothesis of the tumoral histogenesis from the reserve cell of the endocervical epithelium. In 11 case (60%) there was a strong positivity of IgA in the lymphocytes surrounding the tumor nests, in the neoplastic cells and in the endoglandular secretion: this may represent a sign of an immune response of the patients to the tumoral antigens. CEA was present in 8 cases and EMA in 12 cases, with a unique expression: CEA positive cases showed no evidence of EMA and case with EMA positive cells were negative for the presence of CEA. Only in one case CEA and EMA were contemporaneously present. The possible interpretation of these findings is discussed.

Effectiveness of defibrotide for prophylaxis of deep venous thrombosis in gynecological surgery: a double-blind, placebo-controlled clinical trial.

Defibrotide, a new antithrombotic compound without anticoagulant activity, has been tested for prevention of deep venous thrombosis (DVT) in patients undergoing gynecological surgery (mainly hysterectomy). Eighty-nine women (mean age 48.5) were randomly allocated to defibrotide (44 patients) or placebo (45 patients). 800 mg defibrotide was given daily (200 mg intravenously 4 times a day), starting on the day before operation and then for the next 7 days. DVT were detected by the conventional 125I-fibrinogen test. The two groups were homogeneous for known risk factors (age, varicosities, obesity, neoplasia and previous thromboembolic episodes). The results showed a statistically significant reduction of DVT incidence in patients on defibrotide, as compared with those on placebo: 4/44 = 9% vs. 13/45 = 28.8% (p less than 0.05). There were no side effects, including hemorrhagic complications. The numbers of units transfused were comparable for the 2 groups. In conclusion, the trial shows that defibrotide is an effective and safe drug for the prevention of DVT in gynecological surgery.

Adenosine deaminase activity in peripheral lymphocytes of patients with gynaecologic malignancies.

Peripheral lymphocyte adenosine deaminase (ADA) activity was assessed in a group of 31 patients with gynaecologic malignancies (19 with carcinoma of the portio, 7 with endometrial adenocarcinoma, 3 with ovarian cancer, 1 with adenocarcinoma of the cervix, 1 with liposarcoma myxoide). 30 female subjects, aged 30 to 70 years, were studied as the control group. Lymphocyte ADA activity in the 31 patients ranged from 0 to 7 U/10(7) cells with a mean of 2.3 U/10(7) cells (normal values: range 2-5 U/10(7) cells; mean 2.8 U/10(7) cells). In cases where the enzyme was absent or far below the controls, a faster evolution of the disease was observed. We would point out that lymphocyte ADA activity in the patients under investigations shows a broad range of variability. Our preliminary observations would suggest that lymphocyte ADA assessment in a larger series of cancer patients may add further prognostic informations.

[2-Br-alpha-ergocryptine in the treatment of amenorrhea-galactorrhea syndromes and in inhibition of puerperal lactation. Effect on secretion of prolactin and pituitary gonadotropin]. / La 2-Br-alpha-ergocriptina nel trattamento delle sindromi di amenorrea-galattorrea e nella inibizione della lattazione puerperale. Effetto sulla secrezione prolattinica e gonadotropa ipofisaria

PIP: 11 patients suffering from amenorrhea-galactorrhea, and 26 puerperas for whom lactation was not indicated were treated with 2-Br-alpha-ergocryptine. The drug led to a regression of galactorrhea, and to normal menstrual cycles in all patients, except in one who was suffering from hypophyseal adenoma. Lactation was effectively inhibited in all 26 puerperas after only a few days of treatment. Results showed that 2-Br-alpha-ergocryptine has a powerful inhibitory action on the hypophyseal secretion of prolactin, both during puerperium and in nonpuerperal conditions.^ieng