Effect of mode of delivery on vertical human papillomavirus transmission - A meta-analysis.

A systematic review of the literature has been conducted (last update March 2014) for clinical studies reporting the prevalence of human papillomavirus (HPV) in the offspring of HPV-infected women in association to their mode of delivery. A meta-analysis was carried out according to the identification of concordant neonatal to maternal HPV types. Overall eight studies were included in the meta-analysis. Our pooled results, showed that caesarean section is associated with significantly lower rates of HPV transmission than vaginal birth (14.9% vs. 28.2%, risk ratio or RR: 0.515, 95% confidence interval or CI: 0.34-0.78). The number of caesarean sections needed to prevent one case of perinatal infection (number needed to treat or NNT) would be 7.5. As a conclusion it should be noted that caesarean section decreases the risk for perinatal HPV transmission by approximately 46%. Perinatal transmission still occurs in approximately 15% of the children born by caesarean section.

Effectiveness of sublingual use of 400 mcg prostaglandin E1 for first trimester surgical abortion according to parity: a retrospective study.

AIM: The aim of this paper was to evaluate the effectiveness of sublingual use of misoprostol in women undergoing first trimester surgical abortion. Special consideration was given in a sub-group analysis according to parity. METHODS: A retrospective study was conducted, enrolling patients during 2006-2009. Pregnancies less than 12 weeks of gestation were exclusively included. Our sample was divided in: group 1, in which we included women who had received 400 mcg of misoprostol sublingually two hours before surgical abortion and group 2, with no use of misoprostol. Cervical dilatation and estimated blood loss (EBL) were compared between the two groups. Moreover, a sub-group analysis of the former parameters was made separately in nulliparous and multiparous women. RESULTS: Out of 79 patients included, 48 (60.75%) received misoprostol, while 31 (39.25%) did not. Cervical dilatation was significantly higher in group 1 (6.4±2.1 mm vs. 4.7±1.7 mm in group 2, P=0.001), while EBL was significantly lower in the same group (105.0±22.1 mL vs. 120.3±24.2 mL for group 2, P=0.005). Concerning the sub-analysis, cervical dilatation was significantly increased and EBL was significantly lower in multiparous receiving misoprostol comparing with those who did not (P=0.001 and P=0.002, respectively). However, the same parameters did not differ significantly between the two sub-groups of nulliparous women. CONCLUSION: Sublingual administration of 400mcg misoprostol is effective concerning cervical ripening and EBL in women undergoing first trimester surgical abortion. According to the results of the present clinical trial prostaglandin E1 is more effective in multiparous group of women.

Neonatal outcomes of late preterm deliveries with pre-eclampsia.

AIM: The aim of the study was to examine the impact of pre-eclampsia on neonatal outcomes of late preterm deliveries. METHODS: A retrospective study was conducted, enrolling pregnancies delivered between 34 0/7 and 36 6/7 weeks of gestation during the period 2004-2007 in a large tertiary center. Pregnancies were divided in group 1, including those complicated with pre-eclampsia and group 2, including normotensive cases. Epidemiological characteristics, mode of delivery and complications contributing in late preterm delivery were initially studied. Neonatal morbidity parameters of our interest included mean Apgar score in the 1st and 5th minute, admission to Neonatal Intensive Care Unit (NICU) and need for emergency intubation. Intrauterine growth retardation (IUGR), low birth weight (LBW) and very LBW (VLBW), respiratory distress syndrome (RDS), hypoglycemia, NICU infection, abnormal cerebral ultrasonographic findings and duration of NICU residence were also compared between the two groups. RESULTS: Out of 363 late preterm pregnancies, 29 (8%) were delivered because of pre-eclampsia. Mean gestational week and birth weight were significantly lower in group 1. The rate of elective caesarean section was also significantly higher in this group. The same observation was made concerning rates of IUGR, LBW and VLBW neonates. Furthermore, incidence of NICU admission and hypoglycemia were significantly higher in the group of infants born by pre-eclamptic mothers. Incidence of RDS and cerebral echo pathology were also higher, but without significant difference when compared to group 2. CONCLUSION: Neonatal adverse outcomes were increased in late preterm infants of pre-eclamptic women in comparison with those of normotensive women.

Conservative management of young patients with endometrial highly-differentiated adenocarcinoma.

Endometrial cancer is uncommon in young women. However, almost 5% of patients are younger than 40 years old. Progestins such as medroxyprogesterone acetate (MPA) and megestrol acetate (MA), have been used as a fertility-sparing approach in this group of patients, with different dose regimens of cyclic (14 days every month) or continuous therapy successfully used. According to the present data, the overall response rate was 73% in a median time of 4 months (range 1-15 months). Endometrial biopsy every 3 months was the common approach to evaluate the patient's response during the treatment. The relapse rate was 36% in a median follow-up time of 22 months (range 6-73 months). Overall, 40% of patients who responded to the treatment successfully, conceived. Half of the patients used assisted reproductive technology to achieve an immediate pregnancy. Although, there are no definite recommendations concerning the conservative management of young patients with early stage endometrial cancer, progestin agents may be used in a selected group of patients for fertility-sparing reasons. After childbearing is completed, hysterectomy remains the standard treatment.

Parity affects pregnancy outcomes in women 35 and older.

PURPOSE OF INVESTIGATION: The objective of the study was to examine the impact of parity on pregnancy outcomes in women 35 years and older. METHODS: The study was a retrospective cohort of singleton pregnancies of women aged > or = 35 years old during the period 2004-2008. Women were divided in two groups: group 1 included primigravidas and group 2 those with at least one past labor. Epidemiological characteristics, obstetric and neonatal outcomes were analyzed using the t test and chi-square test. RESULTS: 816 out of 5834 (14%) cases involved women aging > or = 35 years, 234 (28.7%) of which were nulliparous and 582 (61.3%) multiparous. Rate of cesarean section was 2.4 fold higher for primigravidas (p < .0001). Fetal distress, prolonged labor and Neonate Intensive Care Unity (NICU) admission were also significantly higher in group 1. CONCLUSION: Adverse pregnancy outcomes were increased in primigravidas of 35 years and older compared to multigravidas of the same age.

Time trends of female breast cancer mortality in Greece during 1980-2005: a population based study.

BACKGROUND: Changes in female breast cancer mortality trends have been observed in recent years in western countries. The aim of the present study was to analyse breast cancer mortality in Greece, between 1980 and 2005. METHODS: Time trends of breast cancer mortality were calculated per 100,000 women in the whole female population of Greece, in different age groups, and in different areas of the country. Mortality data and population age distribution were provided by the National Statistical Service of Greece. RESULTS: Overall, female breast cancer mortality in Greece had an increasing trend during 1980-2005. Subgroup analysis according to age showed that this increase was confined to women older than 70 years. In contrast, a mild decrease was noted after the mid-1990s in women 40-69 years old. There were no notable regional differences in breast cancer mortality. CONCLUSIONS: The increasing trend of breast cancer mortality in women aged 70 years and older could be attributed to limited use of secondary prevention methods and rare administration of systemic cytotoxic chemotherapy in these women. In contrast, implementation of these strategies could explain the recent reduction of breast cancer mortality in younger age groups.

Long-term follow-up after cervical cancer treatment and subsequent successful surrogate pregnancy.

Preservation of fertility is a major concern for premenopausal women after diagnosis of cervical cancer. Successful surrogate pregnancy after treatment for cervical cancer has very rarely been reported. In the present report, a case of successful surrogate pregnancy after radical hysterectomy, lymphadenectomy and ovarian transposition for cervical cancer, followed by radiation therapy, is presented. After stimulation of the transposed ovaries using the short gonadotrophin-releasing hormone (GnRH) analogue protocol, four oocytes were retrieved transabdominally from the genetic mother. IVF followed and two embryos were transferred to the surrogate mother, leading to an uneventful singleton pregnancy, and ultimately normal vaginal delivery of a healthy female infant at term. The unique aspect in this case is the long-lasting favourable outcome for both genetic mother and child, observed during 8.5 years of follow-up, the longest follow-up period reported to date in such cases.

Hormone therapy for postmenopausal breast cancer survivors: a survey among obstetrician-gynaecologists.

PURPOSE OF INVESTIGATION: To investigate the attitude of Greek obstetrician-gynaecologists towards prescription of hormone therapy to postmenopausal breast cancer survivors. METHODS: An anonymous questionnaire was sent to members of the Hellenic Society of Obstetrics and Gynaecology with a hypothetical case and a series of relevant questions. RESULTS: Three hundred valid answers were received. Hormone therapy would be prescribed to a breast cancer survivor by only 8%; 80% of these would prefer tibolone. In contrast, 92% would not prescribe hormone therapy; 97% would do so due to the risk of disease recurrence; 70% would not prescribe any alternative therapy, 21% would prescribe CNS-active compounds and 7% SERMs. CONCLUSIONS: The vast majority of Greek obstetrician-gynaecologists would not prescribe hormone therapy for menopausal symptoms in breast cancer survivors due to the theoretical risk of disease recurrence. Among those who would not prescribe hormone therapy, 21% would opt to CNS-active compounds.

A rare case of renal cell carcinoma metastasizing to the uterine cervix.

Metastatic tumors to the uterine cervix originating from malignancies in other organs are very rare. A case of a 45-year-old white woman presenting with vaginal bleeding, due to renal cell carcinoma metastasizing to the cervix, is reported. The patient had been treated four years and five months earlier due to two primary malignancies: colon adenocarcinoma and renal cell carcinoma. After D&C, microscopic examination and immunohistochemical staining showed that the tumor was metastatic, originating from the renal cell carcinoma. Radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node resection followed, and postoperatively the patient received targeted therapy with sutinib malate. The possibility of metastasis from another primary should be considered in the differential diagnosis of tumors of the uterine cervix in order to plan optimal management.

ERBB2 (HER2) protein expression in uterine sarcomas.

PURPOSE: Multiple clinical trials in recent years have shown that breast cancer patients with primary tumors overexpressing ERBB2 can be effectively treated with specific forms of modern anti-ERBB2-targeted therapy. The aim of the present study was to analyze the expression of the ERBB2 (HER2) protein in uterine sarcomas, in order to investigate the possibility of applying this treatment modality in uterine sarcomas. METHODS: The expression of ERBB2 has been analyzed immunohistochemically in formalin-fixed paraffin-embedded primary uterine sarcomas (n = 11). RESULTS: Using a semi-quantitative immunohistochemical score, we found that ERBB2 expression was very weak in the majority of tumors, with only three sarcomas showing moderate ERBB2 expression. Published studies evaluating the same issue in small numbers of uterine sarcomas reached similar findings. CONCLUSION: Overall, ERBB2 expression appears to be weak in uterine sarcomas. However, targeted treatment might still be feasible in a subgroup of patients with uterine sarcomas overexpressing ERBB2.

Virilizing ovarian hilus (Leydig) cell tumor with concurrent contralateral hilus cell hyperplasia: a rare diagnosis.

Ovarian hilus or Leydig cell tumor and ovarian hilus cell hyperplasia are rare clinical entities, causing virilization in both pre- and postmenopausal women. Differentiation between these two conditions is not always straightforward; the former is usually unilateral appearing as a single, grossly visible, circumscribed mass of hilus cells, while the latter is usually bilateral, appearing as diffuse microscopic aggregates of hilus cells. We report herein an extremely rare case of ovarian hilus or Leydig cell tumor, presenting concurrently with contralateral ovarian hilus cell hyperplasia in a postmenopausal woman with virilization. To the best of our knowledge, only four such cases have been previously reported in the literature. Ovarian hilus cell tumors and hilus hyperplasia almost always have benign biological behavior, thus making bilateral salpingo-oophorectomy an appropriate and sufficient therapeutic approach.

KIT protein expression in uterine sarcomas: an immunohistochemical study and review of the literature.

PURPOSE: The aim of the present study was to investigate the possibility of treating uterine sarcomas with imatinib mesylate. Imatinib mesylate, a selective tyrosine kinase inhibitor, is very efficient against mesenchymal tumors of the gastrointestinal tract, known as GISTs. Imatinib mesylate acts against a tyrosine kinase encoded by the KIT gene in GISTs, and is more effective in tumors expressing this protein. METHODS: Expression of KIT was analyzed immunohistochemically (n = 12) in formalin-fixed paraffin-embedded primary uterine sarcomas. RESULTS: Using a semi-quantitative immunohistochemical score we found that KIT expression was very weak in the majority of tumors, while none of the uterine sarcomas tested showed strong expression. Overall, published studies addressing this issue in small series of uterine sarcomas yielded similar results. CONCLUSION: Current data suggest that it is unlikely that imatinib mesylate could be used effectively as a single agent in patients with uterine sarcomas.

Primary ovarian angiosarcoma--review of the literature and report of a case with coexisting chylothorax.

BACKGROUND: Primary ovarian angiosarcoma is a very rare gynaecologic malignancy with poor prognosis and uncertain, up-to-date, treatment options. Its exact diagnosis is challenging for surgeons and difficult for pathologists. There are only a few cases reported in the international literature. CASE: We report a case of primary pure ovarian angiosarcoma with coexisting chylothorax which is, to the best of our knowledge, the first reported case. An extensive review of the literature analyzing all clinical and pathological parameters related to this condition is presented. RESULT: In spite of all therapeutic efforts, surgical and medical, prognosis of ovarian angiosarcoma remains very poor in most cases. CONCLUSION: Primary ovarian angiosarcoma is a rare and aggressive malignancy. The report of such cases is interesting in order to exchange knowledge and experience, and possibly to further improve our diagnostic and therapeutic capabilities.

Self-sampling versus physician-sampling for human papillomavirus testing.

We evaluated the detection of human papillomavirus (HPV) infection using two sampling methods of cervical exfoliated cells, consisting of self-sampling of vaginal cells and cervical sampling performed by the physician. Women included were 379 patients of the general population attending outpatient clinics in Northern Greece for routine cytological cervical dysplasia screening. HPV DNA detection was similar with both sampling techniques. The HPV prevalences in self-collected samples were 4.7% and 3.7% in the physician-collected samples (P>0.05). The Kappa statistic for HPV DNA agreement between the two methods was 0.54 (95% Confidence interval = 0.33-0.75). Self-sampling of cervico-vaginal exfoliated cells could be used as an alternative option to test for HPV infection.

Methylenetetrahydrofolate reductase polymorphism C677T is not associated to the risk of cervical dysplasia.

The aim of the study was to explore a possible association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and cervical neoplasia. A total of 229 women were subjected to cytologic and colposcopic evaluation. Ninety-one of them were found to be normal, and served as the control group, while the other 138 of them had present or past histologically proven cervical pathology (patients group). All patients and controls were investigated for the MTHFR C677T polymorphism. Statistical analysis between the groups of cases with cervical intraepithelial neoplasia or invasive cervical cancer and the control group did not reveal any statistically significant difference in the frequency of the MTHFR C677T polymorphism.

Epidemiology of human papillomavirus infection in Greek asymptomatic women.

In an attempt to estimate the prevalence of human papilloma virus (HPV) positivity among asymptomatic, cytologically normal Greek women, and the possible associations between HPV infection and other demographic, sexual, behavioural and sociological parameters, we undertook an epidemiological study of 226 clinically normal women from an outpatient gynaecological clinic in Northern Greece. The polymerase chain reaction was used for detection of HPV DNA and dot blot hybridization analysis for HPV typing (only for the high-risk types 16 and 18). Eighty-two of the 226 women examined (36.3%) were positive for HPV DNA, 6.6% (15/226) were positive for HPV-16 DNA and only 1.3% (3/226) were positive for HPV-18 DNA. From all epidemiological correlates, age and residence showed a negative correlation with risk of HPV infection, whereas use of contraceptive intrauterine device, class II or III result of the last Papanicolaou cytological examination, history of painful inflammatory disease of inner genitals and frequent washing of the genital area, particularly during the menstrual period, were positively correlated with increased risk of HPV infection. No association was found between HPV DNA positivity and other well-known risk factors for cervical cancer, confirming the observations of other authors that sexual behaviour, a significant risk factor for cervical cancer, is not inevitably correlated with risk of HPV infection.

p53 codon 72 polymorphism and risk of intra-epithelial and invasive cervical neoplasia in Greek women.

In 1998, Storey and co-workers suggested that individuals homozygous for arginine (Arg) at codon 72 of the p53 gene are about seven times more susceptible to human papillomavirus (HPV)-related carcinogenesis than heterozygotes. Since then, several studies from Northern Europe, Japan and the USA have failed to demonstrate a similar correlation. By contrast, a study in Brazil as well as one recent study in Italian and Swedish populations showed strong positive associations. We examined the frequency of p53 codon 72 polymorphism in samples from both invasive and intra-epithelial cervical neoplasias (CIN), and compared them with samples from healthy controls. All 88 samples came from women with a Greek ethnic background. Tissue specimens were collected from archival material with histologically diagnosed low-grade CIN (LGCIN), high-grade CIN (HGCIN) or cervical cancer (CxCa). As a control, we used cellular material newly collected by cytobrush from the cervices of 30 healthy women with normal cytological and colposcopical examinations. p53 Arg homozygosity (Arg/Arg) alone was associated with four-, six- or eight-fold increased risks for LGCIN, HGCIN or invasive cancer, respectively. The frequency of the p53Arg/Arg genotype and of the proline (Pro) allele showed significant linear trends according to the degree of severity of the lesion (P = 0.0007 and P = 0.0009, respectively). Exclusion of the ten HPV16/18-negative cases did not substantially alter the Arg/Arg frequency among the groups nor the significant linear trend. Our results confirm the initial findings of Storey and co-workers, as well as the data of the Brazilian and the recent European study, but do not accord with those of the other aforementioned studies. Variations in ethnic background, laboratory performance, verification of the HPV status, definition of controls, and sample size are the most plausible explanations for this controversy. In all our samples, the distribution of the p53 alleles fits the Hardy-Weinberg equilibrium and the 0.48 frequency of the Pro allele in our controls accords well with the percentages previously reported for different ethnic groups as characteristic of the assumed north-south cline. Some authors assert that the discrepancy in the results could not be attributed to differences in the methods; however, the Brazilian study emphasized the effect of inter-laboratory variation in detecting the association between p53 polymorphism and cervical cancer. Regarding the control group, our samples were only from women with a cytologically and colposcopically benign cervical epithelium. We think that simply choosing 'normal volunteers' for collecting control DNA blood samples without knowing the status of their cervical epithelium is indeed a possible source of bias. Finally, it is very unlikely that loss of heterozygosity at the p53 locus could be a factor interfering with the allelotype distribution. Our present small study results, which suggest a biologically relevant association, provide strong evidence that homozygous arginine at codon 72 of p53 may confer a higher susceptibility to HPV-associated intra-epithelial and invasive cervical neoplasia.

P53 codon 72 polymorphism and correlation with ovarian and endometrial cancer in Greek women.

The polymorphism of codon 72 in the p53 tumour suppressor gene has been associated in the last decade with the risk of developing various neoplasias. An influence of this polymorphism on ovarian and endometrial cancer has also been suggested. We examined the genotype frequency of this polymorphism in archival samples from 56 patients with endometrial neoplasias and 51 patients with ovarian neoplasias. Cervical smears from 30 healthy, human papillomavirus (HPV)-negative women with normal cytology and colposcopy, served as control sample. Women with ovarian neoplasias, especially adenocarcinomas, had Arg/Arg more often than healthy controls [odds ratio (OR) 4.16 at P = 0.0058]. No statistically significant difference was found between women with endometrial cancer and controls. Differentiation of ovarian tumours did not appear to be associated in a statistically significant manner with the genotype, whereas a positive linear trend of Arg/Arg towards poor differentiation was noted in endometrial malignancies (mainly endometrioid adenocarcinomas). Our results suggest that homozygous arginine at codon 72 of p53 may represent a risk factor for developing ovarian malignancies and may affect the differentiation of endometrial cancer. Further studies need to be carried out in order to establish the clinical use of this polymorphism for risk assessment and possibly outcome prediction of ovarian and endometrial neoplasias.

Cervical human papillomavirus infection in women attending gynaecological outpatient clinics in northern Greece.

Human papillomavirus (HPV) is the necessary cause for the development of invasive cervical cancer. Identification of HPV determinants may contribute to the targeting of high-risk groups for cervical cancer. The study was aimed at estimating HPV prevalence and its determinants among 1296 women attending six gynaecological outpatient clinics in northern Greece. Information was available through personal interview and the study of cervical exfoliated cells. HPV DNA was detected by reverse line-blot polymerase chain reaction using the L1 primers PGMY09/11. The overall HPV prevalence was 2.5%. After controlling for potential confounders, the two independent risk factors associated with an increased prevalence were young age and parity. The prevalence odds ratio (POR) for those younger than 27 years against those older than 42 years was 5.31 (95% confidence interval (CI)=1.53-18.44) and the POR for nulliparous women compared with women with two or more children was 4.15 (95% CI=1.35-12.76). HPV was present in 10 of 12 women with low-grade cervical intraepithelial lesions (CIN) (83.3%) and in 3 of 4 with high-grade CIN (75%). The prevalence of genital HPV infections in the study population was among the lowest ever reported internationally.

Methods of prenatal determination of fetal maturity based on differentiation of the fetal skin during the last weeks of pregnancy.

During the process of 'maturation' of the fetal skin, detachment of the layer of vernix caseosa takes place from the fetal epidermis into the amniotic fluid, in the course of the last weeks of pregnancy. This results in: (a) a change of the cytological image of the amniotic fluid followed by a considerable increase in the proportion of the keratinized epidermic cells, (b) a simultaneous increase in the turbidity of the amniotic fluid and (c) a parallel increase in the quantity of sediment which remains after centrifugation of the amniotic fluid. The data presented in this paper, measured in 87 samples of amniotic fluid from normal, eutrophic, uncomplicated pregnancies, indicate the difference between the values of the various parameters before and after the main detachment of the vernix caseosa. Since the fetal skin is the organ reflecting most accurately the general status of the fetal maturity at the end of pregnancy, we consider that an overall examination of findings from the amniotic fluid indicating the condition of the fetal skin supplies us with reliable results for making a prenatal prediction of the maturity status of the fetus.