Indication of prophylactic vaccines as a tool for secondary prevention in HPV-linked disease.

PURPOSE: To determine whether quadrivalent HPV vaccination is effective in reducing recurrent disease in women with a previous history of HPV disease. METHODS: All women under 45 years of age treated for HPV-linked disease and with negative HPV test, cytology and colposcopy 3 months after treatment were enrolled. Women were randomly assigned into two groups: a group that received HPV vaccine post treatment and a group that was only submitted to follow-up. Follow-up was performed every 6 months for a duration of at least 3 years. Kaplan-Meier curve was used to estimate the overall disease-free survival during the follow-up period. Statistical analysis was performed by Fisher's exact test. RESULTS: From November 2013 to October 2014, we enrolled a total of 178 women at Careggi University Hospital in Florence and at Azienda USL in Massa Carrara. 12 out of 89 patients in the non-vaccination group recurred (13.5%), while 3 out of 89 patients in the vaccination group recurred (3.4%). The Kaplan-Meier curves showed a statistically difference in the log rank test (p = 0.0147) for the overall disease-free survival in the study groups during follow-up. The rate of recurrence was significantly higher in the non-vaccination group, with a p = 0.0279 by Fisher exact test. CONCLUSION: The introduction of anti-HPV vaccination during the follow-up post treatment for HPV-linked disease is recommended to reduce the risk of recurrence. The clinical implication of this could be very important to influence post-treatment management of HPV disease.

Over-Expression of the LH Receptor Increases Distant Metastases in an Endometrial Cancer Mouse Model.

OBJECTIVE: The aim of the present study was to define the role of luteinizing hormone receptor (LH-R) expression in endometrial cancer (EC), using preclinical mouse models, to further transfer these data to the clinical setting. MATERIALS AND METHODS: The role of LH-R over-expression was studied using EC cells (Hec1A, e.g., cells with low endogenous LH-R expression) transfected with the LH-R (Hec1A-LH-R). In vitro cell proliferation was measured through the WST-1 assay, whereas cell invasion was measured trough the matrigel assay. The effects of LH-R over-expression in vivo were analyzed in an appropriately developed preclinical mouse model of EC, which mimicked postmenopausal conditions. The model consisted in an orthotopic xenograft of Hec1A cells into immunodeficient mice treated daily with recombinant LH, to assure high levels of LH. RESULTS: In vitro data indicated that LH-R over-expression increased Hec1A invasiveness. In vivo results showed that tumors arising from Hec1A-LH-R cells injection displayed a higher local invasion and a higher number of distant metastases, mainly in the lung, compared to tumors obtained from the injection of Hec1A cells. LH withdrawal strongly inhibited local and distant metastatic spread of tumors, especially those arising from Hec1A-LH-R cells. CONCLUSION: The over-expression of the LH-R increases the ability of EC cells to undergo local invasion and metastatic spread. This occurs in the presence of high LH serum concentrations.

[Cigarette smoking in pregnancy: observational prospective study in three towns of Tuscany Region (Central Italy)]. / Fumo di sigaretta in gravidanza: studio osservazionale prospettico in tre città della Toscana.

OBJECTIVE: to assess the prevalence of smoking in pregnancy and its changes after childbirth, and the characteristics associated with a greater likelihood of smoking during pregnancy in a sample of women attending three university hospitals in Tuscany (Central Italy). DESIGN: observational prospective multicentric study. SETTING AND PARTICIPANTS: 1,036 women in ninth month of pregnancy were enrolled at the teaching hospitals of Careggi (Firenze), Pisa and Siena. Women filled a standardized, self-administered questionnaire at enrolment. A second questionnaire was administered by phone to the smoking, ex-smoking and abstinent-during-pregnancy women one year after the delivery. RESULTS: 60.5% of women was never smoker, 17.4% was ex-smoker, 14% of women stopped smoking during pregnancy, and 8.4% were current smokers. Smoking in pregnancy was significantly associated with being younger than 31 years old (OR 1.75; 95%CI 1.01-1.84) and unmarried (OR 1.75; 95%CI 1.10- 2.78), having a low school degree (OR 2.31; 95%CI 1.58-3.36) and a smoking partner (OR 3.03; 95%CI 2.32-3.96). The absolute risk of smoking during pregnancy was 42%. One year after delivery, 44%of women who stopped smoking in pregnancy relapsed. CONCLUSIONS: a not negligible percentage of women residents in Tuscany Region smokes during pregnancy. Relapses after delivery are high. Even if recently in Italy a smoke free legislation was implemented, the study shows a low attention toward passive smoking during pregnancy. Smoking cessation interventions specifically tailored for pregnant women and relapses prevention need to be implemented in Tuscany by all health care professionals who care for women during pregnancy and after delivery.

Mini-laparotomy versus vaginal surgery for class II-III obese patients with early-stage endometrial cancer.

AIM: To compare minilaparotomic and vaginal surgery in selected obese patients with early-stage endometrial cancer at high surgical risk. PATIENTS AND METHODS: Data of 37 consecutive class II-III obese patients submitted to minilaparotomic surgery were retrospectively reviewed. Thirty-seven women matched for demographic characteristics, BMI and stage of disease submitted to vaginal surgery in the same period comprised the control group. RESULTS: No difference was observed concerning intra- and postoperative data among the two groups. The patients who were submitted to general anesthesia exhibited a larger use of supplemental drugs for pain control (p>0.01), a higher incidence of thromboembolic events (p>0.005) and a longer hospitalization (p>0.02). No statistical difference was observed in terms of pattern of recurrence, disease-free survival and overall survival between the two groups of patients. CONCLUSION: Obese patients with endometrial cancer unfit for vaginal surgery can be safely managed through mini-laparotomy with the same surgical and oncological outcomes.

The effect of the hormonal milieu of pregnancy on deep infiltrating endometriosis: serial ultrasound assessment of changes in size and pattern of deep endometriotic lesions.

BACKGROUND: Deep infiltrating endometriosis (DIE) is associated with severe painful symptoms and represents a complex management challenge. OBJECTIVE: To analyse the effect of pregnancy on deep infiltrating lesions and related symptomatology. STUDY DESIGN: As part of a longitudinal study performed over the past 3 years to determine the efficacy of hormonal treatment in treating women with DIE, we identified three cases of advanced pelvic endometriosis, all with DIE (deep recto-vaginal and recto-sigmoid involvement) where patients achieved spontaneous pregnancies. They were followed up by transvaginal ultrasound (TV-US). The main outcome measures were analysis of the size and echographic pattern of deep infiltrating lesions of endometriosis and evaluation of clinical symptoms during pregnancy. RESULTS: We observed modifications in lesion size and pattern. In the two patients observed in the third trimester, the lesions were more homogeneous with less evident limits of nodules and band-like echoes, less fibrotic-like. All patients showed complete resolution of symptoms during pregnancy. CONCLUSIONS: The hormonal environment produced by pregnancy might determine significant modifications of endometriotic lesions and reduce painful symptoms. As surgery for DIE is difficult, complex and can lead to major complications, the achievement of a pregnancy-specific hormonal state, through pregnancy or hormonal treatment, may be a valid option in selected cases.

Ovarian surgery for bilateral endometriomas influences age at menopause.

BACKGROUND: Questions remain as to whether surgical excision of ovarian endometriomas might cause damage to ovarian function. To test the hypothesis that ovarian surgery for endometrioma compromises ovarian function and accelerates ovarian failure. METHODS: In a tertiary university Clinic, longitudinal prospective cohort study. Patients who underwent laparoscopy for endometriosis between March 1993 and November 2007 were assessed for inclusion in the study. A prospective follow-up at 3, 6 and 12 months then yearly was conducted. Evolution of menstrual pattern, symptoms and reproductive outcomes were investigated. RESULTS: From over the 14-year period, 302 patients were included in the study. The mean age (±SD) of patients was 32.6 ± 5.6 years; the median duration of follow-up was 8.5 years (range 2-17 years). Menopause was documented in 43 women (14.3%) at a mean age of 45.3 ± 4.3 years (range 32-52 years). Women previously submitted to bilateral cystectomy were younger at menopause than those with monolateral endometrioma (42.1 ± 5.1 years versus 47.1 ± 3.5 years, P = 0.003). Premature ovarian failure (POF) was observed in 7 of 43 (16.3%) menopausal patients; the majority (4, 57.1%) after bilateral cystectomy. The relationship between the preoperative ovarian endometriomas total diameter and menopausal age was significant in case of surgery for bilateral endometriomas (R(2) = 0.754, P = 0.002). CONCLUSIONS: Patients who had been operated on for bilateral endometriomas have an increased risk of POF. Ovarian parenchyma loss at the time of surgery seems related to cyst diameter. In the case of unilateral ovarian endometrioma, the contralateral intact ovary might adequately compensate.

Impact of endometriosis on in vitro fertilization and embryo transfer cycles in young women: a stage-dependent interference.

OBJECTIVE: Endometriosis is a frequent indication for in vitro fertilization and embryo transfer (IVF-ET). Its influence on IVF-ET cycles remains controversial. We evaluated the impact of the severity of endometriosis on IVF-ET cycles in young women. DESIGN: Retrospective cohort study. SETTING: Academic tertiary referral centre. SAMPLE AND METHODS: In a retrospective cohort analysis, 164 IVF-ET cycles in 148 women with endometriosis-associated infertility were analyzed. Eighty cycles performed during the same period on 72 consecutive women with tubal infertility were considered as controls. All patients were younger than 35 years old. MAIN OUTCOME MEASURES: Response to controlled ovarian hyperstimulation (COH), number of oocytes retrieved, fertilization, implantation and pregnancy rate (PR). RESULTS: Clinical PR was lower in the group with endometriosis (all stages) in comparison with the tubal factor group. Higher total gonadotropin requirements, lower response to COH and lower oocyte yield were also found in the endometriosis group. Stage-stratified analysis showed a lower fertilization rate in stage I-II (52.6% stage I-II, 70.5% stage III-IV and 71.9% tubal factor). In stage III-IV endometriosis there was a higher cycle cancellation rate, a reduced response to COH and a lower PR compared with both the stage I-II and the tubal infertility groups (PR 9.7, 25 and 26.1%, respectively). CONCLUSIONS: Stage III-IV was strongly associated with poor IVF outcome. A decreased fertilization rate in stage I-II might be a cause of subfertility in these women, owing to a hostile environment caused by the disease.

Long-term follow-up after laparoscopic treatment for endometriosis: multivariate analysis of predictive factors for recurrence of endometriotic lesions and pain.

OBJECTIVE: To investigate factors that might influence the recurrence of both painful symptoms and endometriotic lesions following laparoscopic treatment of endometriosis. STUDY DESIGN: Retrospective cohort study in a University teaching hospital. We reviewed data from patients referred for laparoscopy between March 1993 and November 2007. We selected women who were followed up throughout Transvaginal-ultrasound (TV-US) after a first conservative laparoscopy for endometriosis. After laparoscopy, all patients were followed up according to an internal protocol: a standard gynaecologic examination, the assessment of painful symptoms and a TV-US scan that were repeated at 3, 6, and 12 months, and subsequently on a yearly basis. Sixteen factors were assessed by univariable and multivariable Cox proportional hazards models to evaluate their associations with recurrence of endometriotic lesions and pain related-endometriosis. RESULTS: 401 women were enrolled. A total of 154 (38.4%) experienced moderate or severe pain after laparoscopy; endometriotic lesions were observed by TV-US in 74 (18.4%) patients. In the multivariable model, age at menarche, severity of chronic pelvic pain (CPP) and dysmenorrhoea prior to surgery were significant risk factors for recurrence/occurrence of pain. Age at the first laparoscopy, stage of disease, pre-operative severity of CPP, and pregnancy were predictive factors of the recurrence for such lesions. CONCLUSION: The severity of CPP prior to the first laparoscopy showed the only significant factor in the overall prediction of recurrence of pain and endometriotic lesions. Patients with severe CPP at the time of their first surgery might represent a sub-group of women with a more aggressive form of endometriosis.

Quantitative variation analysis of fetal DNA in maternal plasma samples collected before and after amniocentesis.

AIMS: The aim of this study was to evaluate possible procedure-related variations in the levels of cell-free fetal DNA (fDNA) in maternal plasma of women undergoing genetic amniocentesis. MATERIALS AND METHODS: Blood samples were collected at 16-18 weeks' gestation from 33 pregnant women attending the Fetal Medicine Unit for genetic amniocentesis. For each woman, two blood samples were obtained: the first immediately before amniocentesis and the second one 15 min after the procedure. A real-time quantitative polymerase chain reaction assay, using primers for SRY and beta-globin genes, was used to assess fDNA concentrations in maternal plasma. A Wilcoxon signed-rank test was used for statistical analysis. RESULTS: The karyotype on cultured amniocytes showed that 15 out of 33 women had a male fetus. Real-time quantitative polymerase chain reaction results, on maternal plasma sample pairs from known male pregnancies, showed no significant variations of fDNA correlated to amniocentesis (P=0.394). CONCLUSIONS: Our preliminary study suggests that amniocentesis, although invasive, could be associated with minimal, if any, disruption at the fetal-maternal interface, as revealed by the lack of substantial modifications of fDNA levels in maternal circulation.

DNA ploidy is stronger than lymph node metastasis as prognostic factor in cervical carcinoma: 10-year results of a prospective study.

INTRODUCTION: To improve the outcome of patients with cervical cancer, a more accurate prognostic assessment is essential. The aim of this study was to evaluate the role of tumor DNA ploidy as an independent prognostic factor in cervical carcinoma. Furthermore, we investigated whether the presence of lymph node metastasis may have a different clinical impact according to ploidy status. METHODS: In a long-term prospective study, DNA ploidy was evaluated by flow cytometry from fresh tumor samples from 136 patients with cervical cancer who underwent surgery. Ploidy, lymph node metastasis, and other classical parameters were analyzed in relation to the length of disease-specific survival. Treatment modalities did not differ between patients with diploid tumors and patients with aneuploid tumors. RESULTS: DNA aneuploidy was found in 52 patients (38.2%). Patients with DNA-aneuploid tumors had a significantly reduced disease-specific survival (P = 0.003). Overall, the 10-year survival probability was 54% for patients with DNA-aneuploid tumors and 80% for patients with DNA-diploid tumors. Among 64 patients with International Federation of Gynecologists and Obstetricians stage I disease, the 10-year survival rates were 38.7% for the patients with DNA-aneuploid tumors and 86.3% for those with DNA-diploid tumors (P = 0.003). Overall, diploid tumors with lymph node metastasis did significantly better than aneuploid tumors with lymph node metastasis (P = 0.05). Among the patients with International Federation of Gynecologists and Obstetricians stage I disease, there was a highly significant difference between patients with diploid node-positive tumors and patients with aneuploid node-positive tumors, with no deaths from the disease in the former group in contrast with the worst outcome in the latter group (P = 0.005). By multivariate analysis, pathologic tumor stage, lymph vascular invasion, and tumor ploidy were significant and independent parameters, whereas lymph node metastasis yielded no independent information. CONCLUSIONS: DNA ploidy was an independent prognostic factor in cervical carcinoma. Presence of lymph node metastasis may not always have the same impact on survival but may vary according to DNA ploidy of the primary tumor.

Techniques of laparoscopic myomectomy.

Myomectomy is one of the commonest gynaecological operations. Laparoscopic myomectomy has emerged over the last two decades as a possible alternative to the traditional laparotomy. Most studies have revealed that the laparoscopic procedure is at least as safe as the open procedure as to the rate of complications and may retain relevant advantages in terms of shorter admission and recovery times. Currently laparoscopic myomectomy is still a challenging operation that requires a well-trained surgical team, adequate instrumentation and accurate patient selection; the increasing slant of gynaecologists towards laparoscopic techniques, along with the advances in surgical instrumentation and suturing materials, will hopefully contribute to keep laparoscopic myomectomy no longer confined to tertiary care centres.

Levonorgestrel-releasing intrauterine system (LNG-IUS) as an effective treatment option for endometrial hyperplasia: a 15-year follow-up study.

The levonorgestrel-releasing intrauterine system may represent an effective treatment option in >85% of endometrial hyperplasia cases, but histologic regression during and/or at the end of treatment does not assure stable recovery. We recommend periodic endometrial samplings for at least the first 2 years of follow-up and long-term clinical surveillance thereafter.

Use of a No. 11 blade scalpel and reusable blunt trocar to establish pneumoperitoneum: description of a safe and inexpensive technique.

First access is crucial in laparoscopic surgery because of its potentially life-threatening complications. A number of procedures using a variety of instruments have been previously described; however, the safest approach remains uncertain. Herein, we describe a simple and inexpensive method for direct trocar insertion using reusable instruments that was developed over 10 years in a series of 4721 consecutive gynecologic laparoscopic procedures. Observed data revealed that the technique is feasible, rapidly performed, and safe, with a likely cost savings, using a small set of reusable instruments. This procedure should be compared with other access methods in randomized studies to confirm the observed advantages.

Effects of epidural and systemic maternal analgesia in term infants: the NoPiL study.

The aim of the No Pain in Labour (NoPiL) study was to evaluate the stress and clinical outcome of infants vaginally born without maternal analgesia and after maternal epidural or systemic analgesia. We studied 120 healthy term infants, 41 in the no analgesia group, 38 in the epidural analgesia group, and 41 in the systemic analgesia group. Cortisol, beta-endorphin, oxidative stress markers (ie: total hydroperoxide (TH) and advanced oxidation protein products (AOPP)), interleukin-1beta (IL-1beta), and interleukin-8 (IL-8) cytokines were measured in arterial cord blood samples. Infants in the 3 groups had similar Apgar score, cord blood pH and occurrence of hypoglycaemia, hyperbilirubinemia, and respiratory depression. Cortisol and endorphin plasma levels did not differ in the groups, nor did TH and AOPP values. IL-1beta and IL-8 cytokine were higher in infants born after maternal epidural analgesia than in other groups. Short-term outcome and stress were similar in infants vaginally born without maternal analgesia and after epidural and systemic analgesia. The possible implications of the highest interleukin levels in the epidural analgesia group deserve further study.

Large-muscle endometriosis involving the adductor tight compartment: case report.

Extrapelvic endometriosis is an uncommon condition but can involve nearly every organ, resulting in a wide range of clinical manifestations. Herein, we describe the case of a 45-year-old woman not a candidate for hormonal therapy who had cyclic pain in the left thigh associated with progressive impairment of walking ability. Clinical, instrumental, and laboratory data supported the diagnosis of endometriosis involving the adductor muscles compartment associated with ovarian endometriomas. Laparoscopic bilateral salpingo-oophorectomy and local wide excision in collaboration with an experienced orthopedic oncologist were performed, and definitive histologic analysis confirmed the diagnosis of endometriosis. The patient was pain-free at 6-month follow-up and demonstrated substantial improvement in ambulation and quality of life. Large-muscle endometriosis is a rare entity that can compromise musculoskeletal integrity and decrease quality of life. In this case, surgical excision in collaboration with an orthopedic oncologist was the cornerstone of treatment.

Method of delivery and intraventricular haemorrhage in extremely preterm infants.

OBJECTIVES: It has been reported that caesarean delivery (CD) protects against intraventricular haemorrhage (IVH) in the extremely preterm infant, but it is not known whether this effect involve the more severe grades of IVH. Thus, our aim was to confirm the correlation between the occurrence of IVH and the mode of delivery, and to evaluate this correlation for each grade of IVH. METHODS: All infants with gestational age (GA) ≤ 28 weeks admitted to the neonatal intensive care unit of a tertiary hospital were studied for each grade IVH and major complications rate. RESULT: We found that vaginally born infants had a higher rate of each grade of IVH, but the increase was statistically significant only for grade 3 IVH (18% vs. 2%, p < 0.0001) and all grades IVH (45% vs. 20%, p < 0.0001). Multivariate analysis demonstrated that CD (RR: 0.42, 95% CI 0.28-0.63), birth weight ≥ 800 g (RR: 0.48, 95% CI 0.32-0.73), 27-28 weeks of GA (RR: 0.38, 95% CI 0.25-0.60) and antenatal steroids (0.66, 95% CI 0.22-0.46) decrease independently the risk of developing IVH. CONCLUSIONS: Our study demonstrates that CD decreases the risk of developing IVH in extremely preterm infants including the most severe grades of IVH.

Preoperative assessment of HER-2/neu status in breast carcinoma: the role of quantitative real-time PCR on core-biopsy specimens.

OBJECTIVES: Knowledge of HER-2/neu status is mandatory to identify breast cancer patients amenable to trastuzumab treatment. We evaluated the diagnostic performance of quantitative real-time polymerase chain reaction (qRT-PCR) in the preoperative determination of HER-2/neu status in breast cancer, using core biopsy material. METHODS: In a prospective series, qRT-PCR was performed on fresh core biopsy specimens taken preoperatively in 87 patients with breast carcinoma. Cases with qRT-PCR ratio > or = 2.0 were considered to have HER-2/neu amplification. The results of RT-PCR analysis were compared with those of the standard immunohistochemistry (IHC) and Fluorescence in situ hybridization (FISH) methods. Cases with IHC 3+ or with IHC 2+ and FISH showing amplification were considered HER-2/neu positive. All other cases were considered HER-2/neu negative. RESULTS: qRT-PCR showed HER-2/neu amplification in 13 cases (14.9%), while the standard IHC-FISH combined approach identified 17 HER-2/neu-positive cases (19.5%). Overall, there was concordance between methods in 83 of 87 patients (95.4%). The Spearman's rho correlation coefficient was 0.851; p<0.001. The diagnostic performance for preoperative diagnosis of HER-2/neu status using RT-PCR on core biopsy specimens as compared to standard approach was as follows: sensitivity 76.5%; specificity 100%; positive predictive value 100%; negative predictive value 94.6%. CONCLUSIONS: Quantitative RT-PCR determination of HER-2/neu status from core biopsy specimens provided results comparable to those given by the standard IHC and FISH methods. The use of qRT-PCR on core biopsy material may represent a very useful and easy tool to enhance early identification of HER-2/neu-positive breast cancer patients who, possibly can benefit from trastuzumab treatment.

Levonorgestrel-releasing intrauterine system alone as primary treatment in young women with early endometrial cancer: case report.

Young women with polycystic ovary syndrome (PCOS) are at increased risk of endometrial adenocarcinoma (EAC) through chronic unopposed estrogen production. We describe the first case, to our knowledge, of grade 1 endometrioid EAC arising in the context of complex atypical endometrial hyperplasia in a 26-year-old woman with thrombophilia and PCOS who wished to retain fertility potential and was treated using a levonorgestrel-releasing intrauterine system alone. At first follow-up biopsy, a single focus of complex hyperplasia without atypia was documented. All specimens sampled during subsequent follow-up demonstrated inactive endometrium with pseudodecidual changes, and no ultrasonographic or magnetic resonance (MR) images exhibiting myometrial invasion or endoabdominal spread were observed. This successful outcome suggests that insertion of a levonorgestrel-releasing intrauterine system is a treatment option in selected young women with early-stage EAC who are not candidates for systemic therapy and who wish to maintain fertility potential. Close histologic follow-up is required, and immediate surgery is mandatory if endometrial cancer persists.

The efficacy and safety of continuous intravenous administration of remifentanil for birth pain relief: an open study of 205 parturients.

In an observational study, we prospectively evaluated the efficacy and safety of remifentanil in 205 parturients. Remifentanil was administered as a continuous infusion. The initial infusion of 0.025 microg x kg(-1) x min(-1) was increased in a stepwise manner to a maximum dose of 0.15 microg x kg(-1) x min(-1). Maternal pain, other maternal and fetal variables, side effects, and satisfaction were recorded. The mean (+/-sd) visual analog score before the start of the infusion was 9.4 +/- 1.2 cm and decreased to 5.1 +/- 0.4 cm after 5 min and 3.6 +/- 1.5 cm after 30 min. The maternal side effects were minimal and no fetal or neonatal side effects were noted.