Natural killer cell activity in endometriosis: correlation between serum estradiol levels and cytotoxicity.

OBJECTIVE: To evaluate the correlation between natural killer cell activity and serum estradiol (E2) levels in patients with different stages of endometriosis. METHODS: Natural killer cell activity of peripheral blood lymphocytes and serum E2 levels were evaluated in 73 women who underwent laparoscopy for pelvic pain, infertility, and benign adnexal masses. RESULTS: The 33 patients (45%) with endometriosis showed a significant decrease in natural killer cell activity in relationship to an increase in disease stage (correlation coefficient r = -0.83, P < .001). A significant inverse relationship was observed between cytotoxicity and serum E2 levels (correlation coefficient r = -0.89, P < .001). CONCLUSION: The relationship between natural killer cell activity and serum E2 levels suggests that an immunoendocrine interaction plays an important role in the progression of endometriosis.

Endometrioid carcinoma arising in endometriosis. Case report.

Malignant transformation arising in endometriosis has been reported in some cases. Following Sampson's criteria, about 0.7%-1% of all cases of endometriosis undergo malignant transformation and the ovary is the most frequent site. A case is reported of a patient with endometriosis which, after 10 years, grew into ovarian endometrioid carcinoma. The relationship between endometriosis and cancer suggests a radical treatment of endometriosis and a careful assessment of postmenopausal woman presenting reactivation signs.

Immuno-biologic integration for therapeutic approach in ovarian carcinoma.

The "in vitro" cell growth of 14 ovarian carcinomas was evaluated and related with the clinical-pathologic stage (FIGO) and grade of histologic differentiation of disease, with the patients' immunological pattern and with the relapse and survival rates. We identified 4 different patterns of "in vitro" cell growth (P1, P2, P3 and P4). Their correlation with the clinical-pathologic stages of disease as well as with the recurrence and survival rates was strong: 75% of recurrences in pattern P3 and 100% in pattern P4, while tumours with patterns P1 and P2 did not relapse. Similar results were obtained for survival, in fact 2 of the 3 patients who died from disease had cell growth pattern P4, and the other a P3. A significant correlation was found with basal natural killer cell activity of peripheral blood lymphocytes too: in patients with P1 neoplasia the basal NK cell activity was significantly higher (p < 0.05) while it was significantly lower (p < 0.05) in patients with P4 neoplasia in comparison with the others. We conclude that the "in vitro" biological behaviour of ovarian neoplasia can be regarded as prognostic factors even if patients' basal NK activity represents the most significant prognostic element, directly related to the recurrence rate (p = 0.002).

Lymphocyte subset in HPV infection.

The outcome of HPV infection and its progression to neoplastic disease may be conditioned by the immune status of patients. In the present study we observed the systemic lymphocyte subset, with particular regard to NK cells and NK activity in 7 patients with HPV infection. The lymphocyte phenotypes in peripheral blood were studied using a panel of monoclonal antibodies, while NK activity was evaluated as percentage of lysis of K 562 target cells. We noticed a significant decrease of basal NK activity especially in patients with HPV 16-18 infection (p less than 0.001), without any difference in the absolute number of these cells.

Improvement of decreased natural killer cell activity in cervical cancer patients by active lipids (AL 721).

In the present study we observed the absolute number of NK cells and the NK activity in 10 patients with cervical cancer. NK activity was determined before and after stimulation with Active Lipids. We reported a significant decrease of basal NK activity, but after AL stimulation NK activity was increased with statistical significance. Therefore our findings show that the reduction of NK activity in neoplastic patients is not an irreversible phenomenon since it can be restored by "in vitro" AL administration. This is important for the adoptive immunotherapy by which we could give LAK cells to the patients.

Endometrioid carcinoma of the ovary. Retrospective study.

From 1985 to 1991, 9 patients with endometrioid carcinoma of the ovary were treated and followed at the University of Ancona, Department of Gynecology and Obstetrics. Four patients (44.4%) had Stage I disease, 1 (11.1%) Stage II, 1 (11.1%) Stage III and 3 (33.3%) Stage IV. Six patients (66.6%) had grade 2 of the disease and 3 (33.3%) grade 3. Two of the patients (22.2%) had synchronous endometrial carcinoma while 3 had histologic evidence of endometriosis at the time of presentation. All the patients received treatment of combination of surgery, polychemotherapy, hormone and/or immunotherapy. The overall survival rate after a median follow up of 26.6 months was 66.6%. A high survival (100%) was observed for patients with associated endometriosis.

Decrease of cellular growth potential in "in vitro" culture of amnions with premature rupture of membranes.

The "in vitro" cellular growth of 8 amniotic membranes from preterm deliveries with premature rupture of membrane (PROM) in absence of risk factors as cervical or vaginal infection (microbiologic negativity), cervical incontinence and other mechanical factors, was compared with cellular growth of 9 amnions from preterm deliveries without PROM. Amniotic membranes were set up in the Eagle basal medium with Earle salts and heat-inactivated fetal bovine serum (10%), gentamicin 50 micrograms/ml and amphotericin B 0.5 micrograms/ml. The results suggested that the growth potential of the cells (epithelial cells and fibroblasts) obtained from amnions with PROM was lower than that of cells obtained from amnions without PROM. We postulated that the premature rupture of membranes in patients without risk factors for PROM, would be conditioned by an intrinsic decrease of cellular growth potential.

Induction of ovulation with pulsatile gonadotropin releasing hormone (GnRH) in anovulatory women.

In this study we employed pulsatile GnRH therapy in different anovulatory disorders to test its real efficacy on ovulation induction. Ten adult women, 25-35 years old with primary or secondary infertility, underwent our study; all women showed anovulatory disorders such as Secondary Amenorrhea (n. 4), PCOD (n. 3) or Oligomenorrhea resistant to Clomiphene Citrate (n. 3). Pulsatile gonadotropin releasing hormone (GnRH) was given intravenously via automatic micropump, with a pulse interval of 90' and a pulse dose of 5 mcg/day. Ovulation was achieved in 7 cases (70%), whereas the failure of therapy was observed in 3 patients (30%), all affected by PCOD. The mean duration of follicular phase was 15 days and the ovulatory cycles did not need the luteal phase support. The maximum length of infusional therapy was 20 days with a low incidence of adverse side effects such as phlebitis; only in one patient a mild ovarian hyperstimulation was observed. Our results confirm that infusional pulsatile GnRH therapy is a very important tool to ovulation induction and it is more successful in primary or secondary amenorrhea and in hypothalamic disorders than in PCOD.

Natural killer cell activity and progression-free survival in ovarian cancer.

A longitudinal evaluation of the natural killer (NK) cell activity of peripheral blood lymphocytes was performed in 17 patients with advanced ovarian cancer (treated surgically and with subsequent multiagent chemotherapy) for a median follow-up period of 32 months. At the time of primary treatment, the mean value of NK cell activity was significantly lower in patients who then had disease progression (p < 0.05) than in patients with progression-free survival. During the follow-up period, no significant modifications of the NK cell activity were observed; only at the time of clinical disease progression did the NK cell activity show a significant reduction. We conclude that the NK cell activity is a potentially important prognostic factor.

[Prognostic significance of diagnostic delay in carcinoma of the endometrium: our experience]. / Valore prognostico del ritardo diagnostico nel carcinoma dell'endometrio: nostra esperienza.

Although endometrial carcinoma is characterized by a precocious symptomatology, in 28.4-22.6% of cases at the time of diagnosis it is found to be at clinical stage higher than I. In the present study the diagnostic delay is related to the stage of disease. Our data suggest that diagnostic delay can cause a higher risk of advanced-stage disease; all the cases of stage III and IV disease, in fact, were diagnosed after more than 7 months. Diagnostic delay was also directly related to depth of myometrial invasion; the mean diagnostic delay was significantly shorter in patients with stage I disease and superficial myometrial invasion (3.92 vs 8.76 months) (p < 0.001). Therefore, diagnostic delay is directly related to well-established prognostic variables as well as to clinical stage and depth of myometrial invasion.

Lymphocyte subset and NK activity in cervical intra-epithelial neoplasia.

We have studied the systemic T-lymphocyte subset and, in particular, the natural-killer (NK) activity in 23 patients with cervical intra-epithelial neoplasia (CIN), and 11 controls (a history of normal cervical PAP smears and colposcopy patterns). The lymphocyte phenotypes were studied using a panel of monoclonal antibodies, and NK activity was evaluated as the percentage lysis of K 562 target cells. In patients with CIN we found a significant decrease in NK activity (p = 0.002) which was directly correlated with the grade of CIN, with no alterations in the absolute number of NK cells.

Bipolar Electrodes in the Treatment of Ectopic Pregnancy

During operative laparoscopy in the management of the ectopic pregnancy, conservative treatment consisting of linear salpingotomy and extraction of trophoblast must be carried out systematically. Until recently, tubal incision was performed with monopolar delivery systems. Bipolar electrosurgery has been used for many years, but is limited to coagulation. We applied bipolar technology in the conservative treatment of ectopic pregnancy. The instrument we used for the salpingotomy consisted of disposable Bilap needle or hook electrodes with shaft diameter of 5 mm and working length 33 cm. The trophoblast was extracted with a hydrodissection pump provided with 10- or 5-mm probes without irrigation holes. The electrodes were connected to an electrosurgical generator with maximum cutting power of 70 W. This system offers cutting in bipolar applications that are designed to eliminate current passing through tissues other than those selected. The conductive electrodes are closely spaced, reducing the energy requirements and power delivered to the surrounding tissue. The operative procedure was performed in 12 women. We had no persistent trophoblastic proliferation, and no patient required additional treatment.

[Transvaginal echography in the evaluation of the grade of myometrial invasion in locally advanced endometrial carcinoma]. / L'ecografia transvaginale nella valutazione del grado di invasione miometriale nel carcinoma endometriale localmente avanzato.

Neoplastic myometrial invasion is an important prognostic factor in local advanced endometrial carcinoma, conditioning therapeutic choice. In 34 patients with stage I and II endometrial carcinoma, the depth of myometrial invasion was evaluated by transvaginal sonography (TVS). In comparison with pathological findings, TVS showed an overall accuracy of 82.3% with a sensitivity of 82.6% and a specificity of 81.8%. The principal error was related to the underestimation of the lesion: negative predictive value of 49.2% vs positive predictive value of 90.4%. In conclusion, TVS is an accurate imaging method for staging of local advanced endometrial carcinoma.

[Homologous intrauterine insemination: our experience]. / Inseminazione intrauterina omologa: nostra esperienza.

Sixty-five couples with male infertility or unexplained infertility or infertility due to cervical factor underwent 156 cycles of homologue intrauterine insemination. The overall pregnancy rate was 16.5% with 2.4 mean value of insemination cycles for each couple. The highest pregnancy rate was observed in cases of cervical factor infertility. The mean age of patients who had pregnancy was 30 years (overall mean value 34 years) and the mean time of sterility was 3 years (overall mean value 4.4 years).

Lymphocytes subset in hyperandrogenic women with polycystic ovarian disease.

The correlation between the sex steroids and the immune system is already known but the relationships between testosterone, progesterone, estradiol, cortisol and the immune system are still controversial. The Authors have studied lymphocytes subset in ten women with polycystic ovarian disease (PCOD); it was observed: 1) a decrease of T8 in 64% and of natural killer activity (NK) in 60% of patients, and an increase of T4/T8 ratio in 55%; 2) a significant negative correlation between androstenedione and testosterone (P less than 0.05); 3) a significant positive correlation between the decreased T8 lymphocytes and NK cells and the increase of testosterone and androstenedione serum values. The data suggest that in PCOD a correlation between endocrine and immune system exists and the androgens can affect the lymphocyte subset.

Natural killer cell activity in patients with gynecologic malignancies: correlation with histologic grading and stage of disease.

Basal natural killer (NK) cell activity in peripheral blood lymphocytes (PBLs) of 29 patients with gynecologic malignancy and 10 healthy controls was performed using K 562 cell line. A significant decrease of NK cell activity was observed in patients with gynecologic malignancy (p = 0.003). The NK cell activity of patients with poorly differentiated tumor or with stage IV of disease was significantly reduced with respect to patients at any other lower grade or earlier stage. We conclude that in patients with gynecologic malignancies there is a decrease of basal NK cell activity of PBLs, which is more significant in cases of distant tumor dissemination or poorly differentiated tumor (p less than 0.001).