Treatment strategies of the borderline ovarian tumors.

The present study was undertaken to establish the role of surgical procedures, histologic type, and stage of the tumor on the survival rate of patients with borderline ovarian tumors in a 5 to 15 years of follow-up. Data reported in the literature have shown the low malignancy of this cancer and that only the stage, but not the pathological diagnosis, is significantly influencing the survival rate of the patients. After 5 years, the survival rate of patients with tumors of stage I to stage II is 98.2% (n=567) and 81.4% (n=46), respectively, with no statistical difference. After 5 years, survival rate between tumors of stage I to stage III is 98.2% (n=567) and 79.1% (n=96), respectively (p< 0.05). The data shows that for borderline ovarian tumors, a minimally invasive surgery is warranted.

Immunologically mediated abortion (IMA).

Roughly 20% of all clinical pregnancies evolve into "spontaneous abortions". The causes of spontaneous abortion have been determined in under 60% of the total and comprise genetic, infectious, hormonal and immunological factors. In some cases the immune tolerance mechanism may be impaired and the foetus immunologically rejected (IMA, immunologically mediated abortion). The immunological mechanism implicated depends on the time in which pregnancy loss takes place. During preimplantation and up to the end of implantation (13th day) the cell-mediated immune mechanism (potential alloimmune etiologies) is responsible for early abortion. This mechanism involves immunocompetent decidual cells (eGL, endometrial granulated lymphocytes) already present during pre-decidualization (late luteal phase) and their production of soluble factors or cytokines. Once the implantation process is over, after blastocyst penetration of the stroma and the decidual reaction of uterine tissue, IMA could be caused by cell-mediated and humoral mechanism (anti-paternal cytotoxic antibodies or autoantibody etiology), by the production of paternal anti major histocompatibility complex antibodies, or even by an autoimmune disorder leading to the production of autoantibodies (antiphospholipid antibodies, antinuclear antibodies or polyclonal B cell activation). The diagnostic work-up adopted to select IMA patients is crucial and includes primary (karyotype of both partners, toxo-test, hysterosalpingography, endometrial biopsy, thyroid function tests, serum hprolactin, luteal phase dating) and secondary (full hemochromocytometric test, search for LE cells, lupus anticoagulant, anticardiolipin, antinuclear antibodies, Rheumatoid factor, blood complement VDRL) investigations. Therapeutical approaches vary. If autoimmune disorders are demonstrated therapies with different combinations of corticosteroids, aspirin and heparin or intravenous immunoglobulin are administered. Otherwise, therapy with paternal or donor peripheral blood mononuclear cells should be instituted.

Dysfunctional uterine bleeding (DUB).

Cyclic or irregular uterine bleeding is common in perimenarchal and perimenopausal women with or without endometrial hyperplasia. The disturbance often requires surgical treatment because of its negative effects on both blood loss and abnormal endometrial growth including the development of endometrial cancer. The endometrium is often overstimulated during the perimenopausal period when estrogen/progesterone production is unbalanced. A therapeutical approach with gonadotropin-releasing hormone agonist (GnRHa) was proposed in a depot formulation (Zoladex) that induces a sustained and reversible ovarian suppression. To avoid the risk of osteoporosis and to obtain adequate endometrial proliferation and differentiation during ovarian suppression, transdermal 17-beta-estradiol and oral progestin were administered. Results of 20 cases versus 20 controls showed a reduction of metrorrhagia, a normalization of hemoglobin plasma concentration, and an adequate proliferation and secretory differentiation of the endometrium of patients with abnormal endometrial growth. Abnormal uterine bleeding is mainly due to uterine fibrosis and an inadequate estrogen and/or progesterone production or to a disordered estrogen transport from blood into the endometrium. In premenopausal women, endometrial hyperplasia may be part of a continuum that is ultimately manifested in the histological and biological pattern of endometrial carcinoma. The regression of endometrial hyperplasia obtained by using the therapeutic regimen mentioned above represents a preventive measure for endometrial cancer. Finally the normalization of blood loss offers a good medical alternative to surgery for patients with DUB.

Reproductive failure due to spontaneous abortion and recurrent miscarriage.

The epidemiology, aetiology, diagnosis and clinical management of spontaneous and recurrent abortion and of the failure of embryo implantation are discussed in a retrospective overview of the major studies conducted since 1975 identified through a Medline search. Infertile women who experienced spontaneous single (32%) and recurrent (0.5%) abortion as well as those who became pregnant after induction of ovulation with gonadotrophins (abortion rate 17-31%) and those who underwent assisted fertilization programmes (abortion rate 18-34%) are considered. Causes and treatments are here reported. Medical treatments for immunologically mediated abortion (IMA) are based on prednisolone, heparin, aspirin and intravenous immunoglobulin. Efficacy of the medical treatment of patients with a history of IMA has yet to be completely demonstrated. Genetic disorders are possible causes of both failure in implantation and early abortion; this cause is more prominent with advanced age and currently cannot be treated. Endocrine factors may also be responsible for miscarriage, and correction of hormone abnormalities is discussed. Infections, endometriosis and psychological factors are other possible important causes of embryo loss without specific widely accepted treatments. Prominent areas of research are the identification of genetic preimplantation abnormalities, and pharmacological intervention for abnormal spontaneous uterine contractility. The data here reported are encouraging, but the efficacy of different treatments is still not convincing. The information available is sufficient to develop new diagnostic and therapeutic tools to evaluate their efficacy in reducing spontaneous abortion at an early stage.

Adhesion formation after laparoscopic myomectomy.

STUDY OBJECTIVE: To determine the frequency of adhesion formation after myomectomy performed by operative laparoscopy or laparotomy. DESIGN: Case-control study. Setting. Academic women's hospital. PATIENTS: Thirty-two premenopausal women scheduled for myomectomy by one of two techniques. INTERVENTIONS: Surgical removal of myomata. MEASUREMENTS AND MAIN RESULTS: Of the 32 women, 16 underwent laparotomy and 16 laparoscopy. Second-look laparoscopy was performed in 28 patients, at which time adhesions were lysed. Compared with laparotomy, laparoscopy resulted in adhesions in significantly fewer patients, and in significantly lower scores when adhesions were detected. CONCLUSION: Laparoscopic removal of uterine myomata is associated with fewer adhesions than removal by laparotomy.

Targeted drug delivery in gynaecology: the first uterine pass effect.

The objective was to verify the hypothesis of a 'first uterine pass effect' or direct preferential vagina-to-uterus transport, suggested by the evidence of higher than expected uterine tissue concentrations after vaginal administration of progesterone; we used a human ex-vivo uterine perfusion model. A mixture of tritiated (3H) and unlabelled progesterone was applied to the cuff of vaginal tissue remaining attached to the cervix after hysterectomy. At the end of the perfusion period (up to 12 h), 3H and 14C radioactivity was measured in samples of uterine tissue. Tritiated water and [14C]dextran were tested to determine the extent of non-specific vagina-to-uterus transport (leaks). Finally, sections of uterine tissue exposed only to [3H]progesterone were prepared for autoradiography. By 4-5 h after application progesterone had diffused to the entire uterus and had reached a steady state; 4 h after application, progesterone concentrations reached 185 +/- 155 and 254 +/- 305 ng/100 mg of endometrial and myometrial tissue respectively. Endometrial extraction of progesterone was higher when the experiment was performed on uteri obtained during the luteal phase (280 +/- 156 ng/100 mg of endometrial tissue) than those removed during the proliferative phase of the menstrual cycle (74 +/- 28 ng/100 mg of endometrial tissue). These data demonstrate that a 'first uterine pass effect' occurs when drugs are delivered vaginally, thereby providing an explanation for the unexpectedly high uterine concentrations relative to the low serum concentration observed after vaginal administration. Hence, the vaginal route permits targeted drug delivery to the uterus, thereby maximizing the desired effects while minimizing the potential for adverse systemic effects.

The efficacy of drugs in the management of endometriosis.

STUDY OBJECTIVE: To establish the crude effects of danazol and gonadotropin-releasing hormone (GnRH) analogs in the management of endometriosis. DESIGN: Prospective case-control study. SETTING: Unit of the Pathophysiology of Reproduction outpatient department. PATIENTS: Two groups of 110 women each with endometriosis (American Fertility Society score 1-3) who received danazol and GnRH analogs, and a control group who did not receive any drugs. INTERVENTIONS: Women in the treatment groups received danazol 200 mg every 8 hours for 6 months, or a different GnRH agonist at standard dosages for 6 months. Laparoscopy was performed twice, at the time of diagnosis and just before the end of treatment (or no therapy for controls). Surgical treatment of the implants was performed at the second laparoscopy. MEASUREMENTS AND MAIN RESULTS: Samples of both eutopic and ectopic endometrium were collected during both laparoscopies. Both danazol and GnRH agonists were useful in reducing the AFS scores to inactive endometriotic implants, and there were no significant differences between the effects (p <0.001). Fibrosis was found after 6 months of observation in the implants in one control woman (0.9%), in 20 patients (18.2%) treated with danazol (p <0.001 vs controls), and in 4 patients (3.6%) treated with GnRH agonists (NS vs controls). A correlation between a clinical diagnosis of AFS score zero and histologic features of fibrosis in the ectopic specimens after therapies was observed in 28% of women, with poor agreement (k = 0.07). CONCLUSIONS: Fibrosis, which represent the absence of endometrial cells within the specimens of endometriotic lesions or eutopic endometrium, did not appear in eutopic endometria but it was found in some endometriotic implants. Danazol and GnRH agonists reduced the clinical AFS scores of endometriosis, but their histologic effects in completely and permanently eliminating endometriotic implants were unacceptable.

The Financial Impact of Laparoscopy versus Laparotomy in the Treatment of Uterine Leiomyomata

To compare the efficiency of two surgical techniques to remove uterine myomata, 120 premenopausal women were included in this case control study based on the criteria of no previous operations, size of leiomyoma, and age. Sixty patients were treated by laparoscopy (group 1) and 60 by laparotomy (group 2). The hospital stay for group 1 was shorter than that for group 2 (3.53 ± 1.33 and 7.98 ± 2.05 days, p <0.001). The rate of total complications (body temperature >38° C, hemoglobin <8.5 g/100 ml, infiltration of abdominal sutures, dysuria, reduction in blood platelets) was 13% in group 1 versus 53% in group 2 (p <0.001). The mean cost for each surgical treatment was $628.71 and $652.40, respectively. The mean entire cost (surgery plus hospital stay) was $1357.23 and $2298.90, respectively (p <0.001). The savings were detectable after 9 and 52 operations, respectively, whether including all expenditures or only the cost of surgery. The cost saving of the entire treatment for 60 operations was $56,500.12.