Neoadjuvant chemotherapy: an alternative option of treatment for locally advanced cervical cancer.

Although the incidence of cervical cancer has declined in both North America and Europe, it still represents the second most common cancer in women and the fifth most common malignancy worldwide. Most patients in the developed countries present with disease either confined to the cervix or with limited extension beyond it. Historically, the standard treatment was usually radiotherapy or radical hysterectomy with node dissection. In 1999, five randomized clinical trials performed by the Gynecologic Oncology Group, the Radiation Therapy Oncology Group and the Southwest Oncology Group have demonstrated a significant outcome advantage when cisplatin-based chemotherapy was administered during radiation in patients with cervical cancer. In the current review, we will analyze the role of neoadjuvant chemotherapy followed by radiotherapy and surgery as an alternative option treatment to the standard chemoradiation for locally advanced cervical cancer (stage Ib2 or larger).

Antimicrobial prophylaxis in vaginal gynecologic surgery: a prospective randomized study comparing amoxicillin-clavulanic acid with cefazolin.

The aim of this prospective, randomized study was to compare amoxicillin-clavulanic acid with cefazolin as ultra-short term prophylaxis in vaginal gynecologic surgery. It was conducted at the Department of Obstetrics and Gynecology, University of Bari. Patients were randomly allocated to receive amoxicillin-clavulanic acid (2.2 g) [Group A] or cefazolin (2 g) [Group B] as a single dose 30 minutes before surgery. Each patient was assessed daily until discharge to evidence febrile status and the presence of infections at the operative site, urinary tract and respiratory tract. In the amoxicillin-clavulanic acid (Group A) and cefazolin (Group B) groups, overall 88 and 90 patients, respectively, were evaluable for prophylactic efficacy at hospital discharge. Infectious complications were infrequent in both arms, with febrile morbidity occurring in 4 (4.5%) and 16 (8.9%) patients respectively in the amoxicillin-clavulanic acid and cefazolin groups (p=0.016). Urinary tract infections were higher but not significantly in the amoxicillin-clavulanic acid group (6.8% versus 4.4 %), whereas asymptomatic bacteriuria was detected in 2.2% of the patients in both groups. There was no respiratory tract infection or septic death in either group. It is concluded that ultra-short term prophylaxis with both amoxicillin-clavulanic acid and cefazolin is safe and effective in elective vaginal gynecologic surgery.

[Polycystic ovary syndrome: from physiopathology to therapy]. / La sindrome dell' ovaio policistico: dalla patogenesi alla terapia.

Polycystic ovary syndrome (PCOS) is still a complex and heterogeneous disorder that presents a challenge for clinical investigators. It is the most common endocrine and metabolic disorder of reproductive-aged women that presents with varied symptoms such as hyperinsulinemia, anovulatory dysfunction, hirsutism, obesity and elevated incidence of cardiac problems. For these reasons, this syndrome is considered by some physicians as an endocrine and for others as a metabolic syndrome. This article will focus on the disorder of the PCOS. It will be based on an understanding of the physiopathology in order to present therapeutic recommendations.

[A randomized study comparing amoxicillin-clavulanic acid with cefazolin as antimicrobial prophylaxis in laparotomic gynecologic surgery]. / Studio randomizzato che paragona l'acido amoxicillino-clavulanico alla cefazolina come profilassi antimicrobica nella chirurgia ginecologica per via laparotomica.

AIM: The aim of this paper was to compare amoxicillin-clavulanic acid with cefazolin as ultra-short term prophylaxis in laparotomic gynecologic surgery. METHODS: A prospective randomized study was conducted to compare 2 antimicrobial regimens in the surgical prophylaxis of laparotomic surgery. Patients were randomly allocated to receive amoxicillin-clavulanic acid (2.2 g, group A) or cefazolin (2 g, group B) as a single dose 30 min before surgery. Each patient was assessed daily until discharge to evidence febrile status and the presence of infections at the operative site, urinary tract and respiratory tract. RESULTS: In the amoxicillin-clavulanic acid (group A) and cefazolin (group B) groups, overall 346 and 352 patients, respectively, were evaluable for prophylactic efficacy at hospital discharge. Infectious complications were infrequent in both arms. Febrile morbidity occurred in 21 (6.1%) and 26 (7.4%) patients respectively in the amoxicillin-clavulanic acid and cefazolin groups. Wound infection and urinary tract infection were also higher, but not significantly in the cefazolin group (1.1% versus 0.5% and 2.5% versus 2%, respectively). There was one respiratory tract infection (0.2%) in group B and no septic death in either groups. CONCLUSIONS: Ultra-short term prophylaxis with both amoxicillin-clavulanic acid and cefazolin is safe in elective laparotomic gynecologic surgery.

Modulation of endometrial redox balance during the menstrual cycle: relation with sex hormones.

This study aimed to evaluate the effects of changes in sex hormones occurring during the menstrual cycle on the redox balance and lipid peroxidation in normal human endometrial cells. Forty women, ages 21-41 yr, who were admitted to the Department of Gynecology and Obstetrics of the University of Bari for routine checkups or were treated for benign uterine disease, underwent endometrial biopsy and venipuncture. On the basis of histological examination, patients were allocated as follows: 10 in the early proliferative phase, 12 in the late proliferative phase, 8 in the early secretory phase, and 10 in the late secretory phase. LH, FSH (immunoradiometric essay), estradiol (E2), and progesterone (P(4)) (RIA) were determined in plasma samples. On the endometrial specimens, total glutathione (GSH), oxidized GSH (GSSG), malondialdehyde, and GSH peroxidase activity (GSH-Px) were determined. Significant cycle-dependent changes in endometrial GSH-Px (P < 0.0001), GSH (P < 0.001), and GSSG as a percentage of GSH (P < 0.0001) were observed. Malondialdehyde did not show significant differences. A linear regression model correlating sex hormone changes with redox indexes was performed. A significant positive correlation was observed between E2 and GSH-Px (r = 0.74; P = 0.0001), E2 and GSSG, as percentage of total (r = 0.84; P < 0.0001); a negative correlation was found between E2 and GSH (r = -0.57; P = 0.0001). No significant correlation was found between P(4) or FSH and oxidative balance. LH was found to be correlated with GSH-Px (r = 0.66; P = 0.0001) and GSSG as percentage of GSH (r = 0.5; P < 0.001). We conclude that the hormonal pattern is involved in maintaining the optimal redox balance in endometrium, mainly through modulation of GSH level and metabolism.

Successful establishment of pregnancy by superovulation and intrauterine insemination with sperm recovered by a modified Hotchkiss procedure from a patient with retrograde ejaculation.

OBJECTIVE: To improve the quality of the sperm recovered from the bladder in a patient with retrograde ejaculation who already had failed to conceive after several attempts at IUI with sperm recovered by conventional techniques. SETTING: University Hospital. PATIENTS: A couple with male infertility due to retrograde ejaculation caused by the Zielke operation, a spinal fixation procedure performed to correct severe kyphoscoliosis. INTERVENTION: Superovulation and IUI of sperm recovered from the bladder using a modified Hotchkiss procedure involving the introduction into the bladder of Earle's balanced salt solution (EBSS) buffered with Hepes in sufficient quantity to bring the urinary pH and osmolarity to those of fresh ejaculate. MAIN OUTCOME MEASURES: Urine pH and osmolarity at baseline and after dilution with EBSS buffered with HEPES. Concentration, motility, and progression score of the sperm recovered from the bladder. RESULTS: Good sperm samples were achieved. Pregnancy was established when IUI was performed in association with superovulation induction. CONCLUSIONS: Determination of urine pH and osmolarity appears to be a useful method for choosing the ideal sperm recovery procedure. The modified Hotchkiss procedure described seems to be a promising alternative method for recovering sperm for artificial insemination.

Diagnostic inadequacy of dilatation and curettage.

OBJECTIVE: To assess the diagnostic inadequacy of dilatation and curettage (D&C) by comparing histologic findings with this technique with those obtained after hysterectomy. DESIGN: Retrospective clinical study. SETTING: University-affiliated hospital. PATIENT(S): Three hundred ninety-seven patients with abnormal uterine bleeding who underwent D&C and, within 2 months, hysterectomy because of histologic findings or persistence of symptoms. MAIN OUTCOME MEASURE(S): Comparison of histologic findings on D&C with those obtained after hysterectomy. RESULT(S): In 248 of 397 patients (62.5%), D&C failed to detect intrauterine disorders subsequently found at hysterectomy; the sensitivity was 46%, the specificity was 100.0%, the positive predictive value was 100.0%, and the negative predictive value was 7.1%. CONCLUSION(S): Dilatation and curettage is an inadequate diagnostic and therapeutic tool for all uterine disorders; this technique missed 62.5% of major intrauterine disorders, and all endometrial disorders were still present in the removed uterus.

Comparison between nafarelin and leuprolide acetate for in vitro fertilization: preliminary clinical study.

OBJECTIVE: To evaluate the clinical effect of two different biochemical GnRH agonists (GnRH-a), nafarelin acetate and leuprolide acetate (LA), as adjunct to induction of ovulation in patients for IVF. DESIGN: Twenty-four women were assigned randomly to either nafarelin acetate or LA during IVF cycles. SETTING: University-affiliated clinics. PATIENTS: Infertile women undergoing IVF cycles in an academic research environment. INTERVENTIONS: Intranasal nafarelin at a dosage of 200 micrograms twice daily or LA at a dose of 1 mg/d SC was administered. Blood samples were collected on day 21 of previous cycle, days 2 and 8, and before hCG injection. MAIN OUTCOME MEASURE: Patient response as indicated by follicular phase serum levels of E2, FSH, and LH. RESULTS: Hormone profiles on cycle day 2 showed no statistical difference between both GnRH-a groups in FSH levels and a slight statistical difference for E2 levels. Patient response as demonstrated by follicular phase of E2, FSH, and LH measured on cycle day 8 and the day of hCG injection showed no statistically significant difference in both groups. Furthermore, the mean number of follicles, eggs retrieved, egg quality, fertilization rate, and number of embryos transferred and frozen were similar. The cycle cancellation rate and pregnancy rate per stimulation start were also not statistically different between the two groups. CONCLUSION: The study shows the comparable efficacy of these two drugs in controlled ovarian hyperstimulation (COH) protocols. The easy administration of nafarelin with prompt nasal absorption and the readily achieved blood level made nafarelin an option for use in COH in assisted reproductive technology.

Uterine cavity assessment in infertile women: comparison of transvaginal sonography and hysteroscopy.

OBJECTIVES: To evaluate the diagnostic accuracy of transvaginal sonography (TVS) in detecting uterine cavity abnormalities in infertile patients, with reference to hysteroscopy as the gold standard method. STUDY DESIGN: At the Institute of Obstetrics and Gynaecology, University of Bari, 134 infertile women were investigated with both TVS and hysteroscopy. In all cases endometrial biopsy was performed. Sensitivity, specificity, and positive and negative predictive values were calculated for TVS, considering hysteroscopic diagnosis as the gold standard. Statistical analysis was performed by using McNemar test. RESULTS: There was one failed insertion of hysteroscope. Hysteroscopy diagnosed pathological findings in 58 out of 133 cases (44%). TVS was in agreement with 50 of the 58 (86%) of the pathological findings diagnosed at hysteroscopy. As a test for the detection of uterine cavity abnormalities, TVS in comparison with hysteroscopy had 84.5% sensitivity and 98.7% specificity, 98.0% positive predictive value and 89.2% negative predictive value. CONCLUSIONS: TVS is able to diagnose polyps, septum and submucous fibroids with quite significant accuracy, while hysteroscopy is indicated for their confirmation and removal. Thus, hysteroscopy provides both diagnostic and therapeutic capabilities, but TVS permits to proceed directly to operative hysteroscopy avoiding the need for a separate diagnostic procedure.

Valuation of some markers in the malignant neoplastic pathology of the female genital tract.

The Authors studied the presence of some markers in different gynaecological tumours, by radioimmunoassay. Beta-HCG, 1-alfa-FP, CA 125, GICA and TPA were assayed in 76 patients. Eight of the patients were affected by CIN III, 38 presented a cervical carcinoma (10 at stage I, 14 at stage II, 10 at stage III, 4 at stage IV); 14 patients had an endometrial adenocarcinoma (3 at stage I, 7 at stage II, 2 at stage III and II at stage IV); 12 cases consisted of an ovarian carcinoma with 2 patients at stage I, 5 at stage II and 5 at stage III; 2 patients had a peritoneal diffusion, whereas two women presented a vulvar carcinoma; the control group was formed by 10 patients with no malignant or benign pathology. The results show that tumoral markers, studied in the blood of patients affected by malignant gynaecological tumours, represent a great advantage in the evaluation of both the response to the therapy and of an eventual remission or tumoral recurrence.

Lymphocyte subpopulations in patients with cervical cancer.

The evaluation of the immunological aspects in cervical cancer has been a point of major interest in the past few years. Data found in literature are, however, often confusing. In order to identify changes in cell mediated immunoresponse in these malignancies, we have studied the lymphocyte subpopulations from peripheral blood samples in women with FIGO intraepithelial + IB stages vs a control group. The analysis of our results show evidence of an increase in the number of natural killer cells even in intraepithelial tumors. The activation of the immunological system from the very early stage is probably in response to viral antigens in the neoplastic cells and/or soluble factors produced by the tumor.

[Current findings on the endometrium and human reproduction]. / Attuali aspetti su endometrio e riproduzione umana.

Human endometrium is a very complex system that plays a critical role during implantation process. Several reports focused the attention on the adequate proliferative phase, particularly on mitotic and angiogenetic pathway. The growth factors and angiogenetic factors involved during the different phases of menstrual cycle are discussed and attention is drawn on the interaction between embryo and endometrium through metalloproteinases and integrins during implantation.

[Heterotopic ovarian pregnancy after in-vitro fertilization and embryo transfer and contralateral tubal pregnancy after gamete intrafallopian transfer]. / Gravidanza eterotopica ovarica dopo fertilizzazione in vitro ed embryo transfer e gravidanza tubarica controlaterale dopo trasferimento intratubarico dei gameti.

One case of ovarian ectopic pregnancy associated with twin intrauterine viable pregnancy after IVF-ET, and one case of contralateral tubal ectopic pregnancy after GIFT performed with normal fallopian tubes, are reported. The possible pathogenesis and management are discussed.

[Gonadal function after chemotherapy for acute lymphoblastic leukemia]. / La funzione gonadica dopo chemioterapia per leucemia linfoblastica acuta.

Object of this study was to verify long term effects on gonadal function in pre- and pubertal patients affected by acute lymphoblastic leukemia (ALL). The population examined was represented by 15 patients, 10 males and 5 females, who came to our Unit after a period of time ranging from 4.5 to 6.2 years. All the patients underwent combined chemotherapy without alkylating agents, such as cyclophosfamide and citosine arabinoside, and intrathecally radiotherapy for a mean period of two years. All the patients were off-therapy and without symptoms of relapse except for one case. The examination of the male and female gonadal function was done on the basis of hormonal assay, ultrasonographic examinations, Tanner's determination of the pubertal development, monitoring of the ovulation and seminal fluid evaluation. The clinical results obtained showed an absence of negative effects both on the gonadal function and on pubertal development. Combined chemotherapy for ALL during pre- and pubertal stage without alkylating agents does not alter the normal gonadal function during the following ten years. Prospective studies will establish the risk of partial follicular atresia and the incidence of premature gonadal failure.

[The correlation between idiopathic leukocytospermia, embryo quality and outcome in the FIVET and ICSI procedures]. / Correlazione tra leucocitospermia idiopatica, qualità embrionaria ed outcome delle procedure FIVET ed ICSI.

BACKGROUND: An adverse effect of leukocytospermia in seminal fluid on motility and fertilizing power of spermatozoa has been described. This detrimental effect could be mediated by radical oxygen species (ROS). Recently, a direct effect on nuclear DNA of sperm induced by ROS has been described, although the chance of fertilization did not seem altered during ICSI procedure. Aim of this prospective case-control study was to compare the outcome of results in term of fertilization rate and embryo quality in patients with and without idiopathic leukocytospermia during IVF and ICSI cycles. METHODS: Seventy-two patients selected for a program of IVF and ICSI were admitted in the study. Fourty-two patients underwent IVF procedure, 14 with idiopathic leukocytospermia and 28 without, and thirty underwent ICSI procedure, 16 with leukocytospermia and 14 without leukocytospermia. RESULTS: Statistical significant differences on cleavage rate of embryos between leukocytospermia and control group in IVF cycles were observed. In ICSI procedure a low fertilization, cleavage rate and percentage of good embyros in the presence of leukocytospermia were evidenced. CONCLUSIONS: The presence of a significant number of leukocytes in semen, even in idiopathic condition, could affect the results of IVF and ICSI procedure. An adverse effect of lipoperoxidation process of plasma membrane and damage of nuclear chromatin of sperm, as result of leukocyte contamination could be hypothesized and future studies needed in order to verify the role of ROS on sperm functions.

Hormone replacement therapy on ovarian and uterine cancer risk and cancer survivors: how shall we do no harm?

This article will focus on the results of the Women's Health Initiative on the effects of hormone replacement therapy on coronary heart disease, stroke, venous thromboembolism, breast cancer, and colorectal cancer. Data from other relevant trials, including the most recent data on ovarian and uterine cancer risk and on gynecologic cancer patients, are also discussed to provide some guidelines on prescribing hormone replacement therapy in clinical practice, particularly in gynecologic cancer survivors.

Diagnosis of endometrial hyperplasia in women with abnormal uterine bleeding.

BACKGROUND: Reliability of hysteroscopy in diagnosing endometrial hyperplasia in women with abnormal uterine bleeding. METHODS: Out of 105 patients with abnormal uterine bleeding 47 showed structural abnormalities. Comparative analysis between hysteroscopic and histological results in 58 women without gross abnormalities has been performed in order to verify sensitivity and specificity of hysteroscopy in the diagnosis of endometrial hyperplasia. RESULTS: Specificity of hysteroscopy in diagnosing endometrial hyperplasia was 84.7% while sensitivity resulted to be 80%. CONCLUSIONS: Women with abnormal uterine bleeding and normal uterine cavity has a low rate (3.4%) of false negative endometrial hyperplasia. On the contrary findings of endometrial hyperplasia at hysteroscopy has a high incidence of false positive (25.8%). In conclusion, abnormal uterine bleeding could cause an increased thickness in endometrium, appearing as hyperplasia on hysteroscopic examination.

Polycystic ovary syndrome: relationship between insulin sensitivity, sex hormone levels and ovarian stromal blood flow.

Polycystic ovary syndrome (PCOS) is the most common cause of menstrual disorders, and is characterized by chronic anovulation, hyperandrogenism and infertility. In recent years, it has become apparent that PCOS is also associated with hyperinsulinemia that is probably central to the pathogenesis of PCOS. As a peculiar vascular pattern has been reported to be present in PCOS, the aim of this study was to investigate intraovarian stromal vascularization in PCOS patients and its possible correlation with sex hormones, gonadotropins and insulin levels. Twenty-eight oligomenorrheic or amenorrheic patients with PCOS and 14 eumenorrheic women with a PCOS-like ovarian pattern undergoing endocrine screening and ultrasound color Doppler intraovarian blood flow were recruited to the study. Ten healthy women with regular menses represented the control group. Hormonal assays (follicle-stimulating hormone (FSH), luteinizing hormone (LH), androstenedione, testosterone, sex hormone-binding globulin (SHBG) and estradiol), oral glucose tolerance test (OGTT), baseline and glucose-induced insulin levels, and transvaginal ultrasonographic and color Doppler analysis (pulsatility index (PI), resistance index (RI) and velocity (Vmax) of ovarian stromal flow) were performed in all participants in the early proliferative phase. Endocrine values showed significant differences in PCOS patients compared with PCOS-like women and controls, while PI and RI indices were significantly higher in controls. PCOS patients were divided into hyperinsulinemic (n = 16) and normoinsulinemic (n = 12). Androstenedione was significantly higher (p < 0.01) in the hyperinsulinemic than in the normoinsulinemic patients and controls, while SHBG was significantly (p < 0.01) lower in the hyperinsulinemic group. Analysis of color Doppler intraovarian vascularization showed a significantly lower RI and a higher Vmax in the hyperinsulinemic subjects than in the normoinsulinemic PCOS patients and controls. An increased stromal blood flow was observed in the PCOS and PCOS-like patients by transvaginal color Doppler evaluation, but this technique is not able to differentiate these two similar ovarian patterns. However, hyperinsulinemic PCOS patients had an increased vascularity of the ovarian stroma. A strong correlation between hyperinsulinemia, hyperandrogenism and low SHBG levels was evidenced, and a hyperinsulinemia-induced mechanism for ovarian stromal angiogenesis is discussed.