Composite non-clinical interventions for a safe cesarean section rate reduction: results of a pre-post interventional study.

OBJECTIVE: To evaluate the impact on cesarean section (CS) rate with of a program of multiple non-clinical interventions targeted at health-care professional within a hospital maternity ward. MATERIALS AND METHODS: Retrospective quasi-experimental pre-post intervention study with an historical control group conducted in a second-level teaching hospital. All women who gave birth in the period 2014 to 2018 were included. A series of multiple non-clinical interventions including a dedicated team of obstetricians for delivery room and antenatal counseling, monthly internal audits and physician education by local opinion leader were prospectively introduced from September 2016. The primary outcome of the study was the CS rate. The incidences of operative vaginal delivery, 3rd-/4th-degree perineal tears and further maternal and neonatal complications were considered as secondary outcomes. RESULTS: The CS rate dropped from 33.05 to 26.06% after starting the interventions (p < 0.01); in particular, the cumulative rate of CS performed during labor decreased significantly from 19.46 to 14.11% (p < 0.01). CS reduction was still statistically significant after multivariate correction (OR = 0.66, CI.95 = 0.57-0.76, p < 0.01). Results further showed an increased prevalence of 3rd-degree perineal tears (0.97% versus 2.24%, p < 0.01), present also after correcting for possible confounding factors (OR = 2.36, CI.95 = 1.48-3.76, p < 0.01). No differences were found in the rate of vaginal-operative births and further maternal complications, while the composite neonatal outcome was found to be improved (OR = 0.73, CI.95 = 0.57-0.93, p = 0.010). CONCLUSIONS: The introduction of multiple non-clinical interventions can significantly reduce the CS rate. However, beside an improvement in neonatal composite outcome, a potential increase in high-degree perineal tears should be taken in account.

Importance of Transvaginal Elastography in the Diagnosis of Uterine Fibroids and Adenomyosis.

PURPOSE: To evaluate normal uterine tissue with special regard to age and the presence of uterine fibroids and adenomyosis with transvaginal elastography. MATERIALS AND METHODS: In a prospective study elastographic data of the uterus were obtained in 206 unselected women with transvaginal ultrasound. Women who presented without any uterine pathology in ultrasonography were included in a control group, women with uterine fibroids in a uterine fibroid group, and women with adenomyosis in an adenomyosis group. In the control group strain values were measured at two regions of interest (ROIs) placed one upon the other in the anterior inferior uterine segment during a cycle of compression. The maximum strain ratio (ROI1 / ROI2) was stored as the "age index". In all groups strain values were measured at two ROIs placed side by side in a uterine fibroid (uterine fibroid group) or adenomyosis (adenomyosis group) or healthy homogeneous tissue (control group) and adjacent healthy tissue. Maximum strain ratios (ROI3 / ROI4) were stored as the "lesion index". RESULTS: The "age index" was significantly negatively correlated with the age of the women (r = -0.49, p < 0.001). The median "lesion indices" were significantly (p < 0.001) different between the uterine fibroid, adenomyosis and control groups. Median "lesion indices" were 2.65, 0.44 and 1.19, respectively. CONCLUSION: The "age index" shows that normal uterine tissue has a certain age-dependent stiffness that increases with age. The "lesion index" allows for the assessment of the presence of a uterine fibroid or adenomyosis and helps to differentiate between both focal findings. Thus the use of elastography in addition to conventional ultrasound could help to diagnose uterine focal lesions and may be useful in preoperative planning.

First generation prophylactic HPV vaccines: the state of the art.

A chronic infection with "high risk" human papillomavirus (HPV) is as an obligated step in the development of cervical dysplasia and cancer and, less frequently, other types of cancers. It has been suggested to be responsible for an estimated 100% of cases of cervical cancer, 90% of anal cancers, 40% of vulvar, vaginal and penile cancers and very likely about 18% of oropharyngeal cancers. Furthermore, infection with "low risk" HPV types is responsible for some benign conditions such as genital warts and recurrent respiratory papillomatosis. Even if it is only very rarely a causative factor leading to cancer, these benign diseases have a high socio-economic impact. HPV vaccination has been shown to be viable method in the prevention of HPV-related pathologies. Currently, there are two vaccine formulas belonging to the very low particles (VLPs) first generation vaccines. The first is the bivalent vaccine Cervarix®, which is active against high risk HPV 16 and 18. The second is the quadrivalent vaccine Gardasil®, which is active against high risk HPV 16 and 18, as well as against the low risk HPV types 6, 11. In this paper, we will discuss typical HPV-related pathologies, the effectiveness of these two first generation vaccines, existing advices, potential side effects and limits as well as new directions for HPV-vaccines implementation.

Second trimester amniotic fluid retinol in patients developing preeclampsia.

BACKGROUND: Retinol (ROH) is an essential micronutrient required for normal fetal development and an essential molecule for antioxidant processes. OBJECTIVE: To investigate the putative role of ROH as a marker of preeclampsia in early second trimester amniotic fluid (AF). MATERIALS AND METHODS: Case-control study comparing the concentration of ROH and other antioxidants such as uric acid, vitamin E and malondialdehyde (MDA) in second trimester AF in patients that later developed preeclampsia with normal pregnancies. RESULTS: The concentration of ROH in amniotic fluids of women that later developed preeclampsia was significantly higher than those of uncomplicated pregnancies (66.72 µg/l (49.00-70.56) vs. 44.4 µg/l (31.9-51.17), p < 0.05). No statistical significant difference was found in uric acid, vitamin E and MDA concentration. In the multivariate logistic regression, concentrations of ROH in amniotic fluids directly correlate with the risk of developing preeclampsia (OR 1.13, IC 0.01-1.26, p < 0.05). CONCLUSIONS: Second trimester AF ROH concentration was significantly higher in pregnancies that developed preeclampsia compared to normal pregnancies.

Quantitative elastography of the cervix for predicting labor induction success.

PURPOSE: To evaluate the role of quantitative elastography of the cervix in the prediction of successful labor induction compared to the Bishop score (BS) and ultrasound cervical length (CL). MATERIALS AND METHODS: A prospective pilot study was conducted between July 2010 and June 2011 in patients without preterm membrane rupture undergoing labor induction with vaginal prostaglandins. Before starting induction, the BS, functional CL and cervical tissue strain (TS) were assessed. TS assessment was performed twice using the Tissue Doppler Imaging (TDI) software. Diagnostic accuracy was evaluated for the prediction of the following endpoints: active labor achievement (success vs. failure, time interval < 24 h and < 48 h), vaginal delivery (success vs. failure, time interval < 36 h and < 72 h) and total amount of prostaglandins used for labor induction (< 6 mg and < 12 mg). RESULTS: We analyzed 77 patients with a mean gestational age of 39.7 ± 1.5 weeks of gestation and a mean strain of 0.75 ± 0.17. The TS significantly predicted a failure of labor induction, which occurred in 4 cases, both in mono- and multivariate analysis, independently of the functional cervical length (TS 0.6 ± 0.1). No correlation was found between the TS and other outcomes. The Bishop score and functional cervical length were found to predict only an early response to labor induction (time to active labor < 24 h, time to vaginal delivery < 36 h and PG usage < 6 mg). The diagnostic accuracy was slightly but not significantly improved if both TS and CL were considered. CONCLUSION: Preliminary data show the possible usefulness of quantitative cervical elastography in the prediction of labor induction failure.

Quantitative elastography of the uterine cervix as a predictor of preterm delivery.

OBJECTIVE: To evaluate the correlation between preterm delivery before 37 weeks of gestation and ultrasound elastography strain measurement of cervical stiffness. STUDY DESIGN: In this prospective study, 182 pregnant women were examined vaginally by ultrasound elastography from a mid-sagittal plane. Cervical length was measured and strain was calculated in four regions of interest on the anterior cervical lip. First, the software was validated by intraobserver variability. Second, strain and strain ratios were calculated with adjusted software presets and correlated to the outcome of spontaneous preterm delivery (sPTD). RESULT: A total of 8928 regions of interest (ROIs) and 6696 ratios were evaluated. The median gestational age at examination was 26 ± 6.1 weeks. A median maternal age of 33 ± 5.6 and a medial parity of 1 ± 0.9 were observed. Intra-Class-Correlation values in validation phase ranged from 0.893 to 0.967. The prevalence of sPTD was 11.9%. Strain ratio Rselective was identified as the best predictor of preterm delivery. Rselective values >0.89 were associated with preterm delivery with a sensitivity of 0.59 and a specificity of 0.86 (odds ratio=1.474 for an increase of 0.1 in Rselective; P=0.002). CONCLUSION: Ultrasound elastography strain measurement of cervical stiffness is correlated with the predictability of preterm delivery.

Quantitative elastography for cervical stiffness assessment during pregnancy.

AIM: Feasibility and reliability of tissue Doppler imaging-(TDI-) based elastography for cervical quantitative stiffness assessment during all three trimesters of pregnancy were evaluated. MATERIALS AND METHODS: Prospective case-control study including seventy-four patients collected between the 12th and 42nd weeks of gestation. The tissue strain (TS) was measured by two independent operators as natural strain. Intra- and interoperator intraclass correlation coefficient (ICC) agreements were evaluated. RESULTS: TS measurement was always feasible and exhibited a high performance in terms of reliability (intraoperator ICC-agreement=0.93; interoperator ICC agreement=0.89 and 0.93 for a single measurement and for the average of two measurements, resp.). Cervical TS showed also a significant correlation with gestational age, cervical length, and parity. CONCLUSIONS: TS measurement during pregnancy demonstrated high feasibility and reliability. Furthermore, TS significantly correlated with gestational age, cervical length, and parity.

Reliability of cervix elastography in the late first and second trimester of pregnancy.

PURPOSE: To evaluate the reliability of cervical elastography as a new ultrasound tool for cervical stiffness assessment in pregnancy. MATERIALS AND METHODS: Pilot prospective cohort study including 10 consecutive unselected pregnancies in the late first and second trimester. Ultrasound was performed by two blinded experienced operators using a 9-MHz vaginal probe. One raw dataset per patient was acquired by each operator after two cycles of gentle compression and relaxation of the cervix. Strain values were independently assessed by each operator using commercial offline analysis software (TDI-Q: Tissue Doppler Imaging - Quantification, Toshiba Medical Systems). The interobserver reliability of strain measurements was evaluated using the intraclass correlation coefficient (ICC). RESULTS: The mean ± SD gestational week of the study population was 19 ±â€Š4.1.  Raw data acquirement and strain evaluation were feasible in all ten patients. In total, 40 strain measurements were performed: 20 for each operator (10 for self-acquired raw data and 10 for raw data acquired by the other operator). The mean strain value was 0.33 ±â€Š0.05, the mean of the differences among the measurements was 10.77 % ±â€Š4.41 %. The obtained interobserver ICC agreement values comparing the different subsets of strain measurement ranged between 0.91 and 0.96. CONCLUSION: Late first and second trimester cervical elastography was shown to be feasible and to have a high interobserver reliability. Its clinical value needs to be assessed in further studies on selected obstetric populations.

Risk factors for chronic pelvic pain in a cohort of primipara and secondipara at one year after delivery: association of chronic pelvic pain with autoimmune pathologies.

AIM: Over genetic and obsteteric factors, also autoimmunity may be involved in female chronic pelvic pain (CPP) pathogenesis. Our study aims to determinate the prevalence of CPP after one year from delivery, and to investigate the possible influence on CPP of concomitant autoimmune conditions. Methods. We selected a cohort of caucasian primipara and secondipara who delivered in our clinic in 2006. We collected personal, clinical and obstetric data, and asked them about pelviperineal painful symptoms. Results. Mean maternal age is 35.52 years (±4.70), 27.65% of women delivered by cesarean section, 61.04% spontaneously and 11.32% by operative assistance, with partoanalgesia in 10.39% of cases, episiotomy in 41.19%, vaginoperineal tears in respectively 14.10% I degree, 11.13% II degree and 0.93% III-IV degree; 43.60% of women have ever undergone abdominopelvic surgery, 32.84% by laparotomy-laparoscopy, 7.05% by hysteroscopy, 5.01% limited to perineum. Chronic autoimmune diseases affect 78.48% of women, allergies 7.79%, rheumatic pathologies 1.3%, autoimmune endocrinopathies 71.8%; 26.53% of women report pelviperineal painful symptoms, being already present in 2.23% of cases, 12.43% generalised pelvic pain, 4.27% bladder pain, 2.60% vulvodynia, 17. 07% dyspareunia. By monovariate analysis CPP results influenced by III-IV degree vaginoperineal tears, operative assistance, preexisting CPP, previous and actual urinary incontinence, previous abdominopelvic surgical interventions and chronic rheumatic pathologies. Furthermore, rheumatic disease, operative assistance and previous CPP are predictive factors for CPP in the postpartum (AUC=58.10%). Conclusion. Delivery may highlight CPP symptoms in predisposed women affected by chronic autoimmune pathologies.

Ultrasonographic assessment of cervix size and its correlation with female characteristics, pregnancy, BMI, and other anthropometric features.

PURPOSE: Cervical length during the first trimester of pregnancy has not been completely investigated yet. The objective of our study is to compare cervical size in the first ten gestational weeks with that of non-pregnant women, and to determine its correlation with maternal factors, including age, anthropometric features, and reproductive history. METHODS: We collected retrospective data about women who applied to the Obstetrics and Gynecology Outpatients Facility of Udine between February and June 2009, selecting both pregnant and non-pregnant women possessing a transvaginal ultrasonographic measurement of their cervix, and focusing on their age, parity, BMI, cervical, and uterine size. Data were analyzed by R (version.2.8.0), considering significant P < 0.05. RESULTS: 135 women were recruited. By multivariate linear regression, both cervical length and width result independently influenced by pregnancy status, and among non-pregnant nullipara, cervical length results to be significantly lower in women younger than 20 (P < 0.05). CONCLUSIONS: During the first ten gestational weeks, cervix results to be longer and wider than in non-pregnant women, suggesting the possible existence of early gestational, morphological, uterine, and cervical modifications. Women under the age of 20 have a significantly shorter cervix, suggesting an incomplete cervix maturity in this group of women, which may justify the higher prevalence of pre-term births in teenage pregnancies.

[Retrospective analysis of one year of cesarean sections: indications and risk factors associated with intrapartum cesarean section]. / Analisi retrospettiva su un anno di tagli cesarei: indicazioni e fattori di rischio per taglio cesareo in travaglio di parto.

AIM: Cesarean section (CS) is currently the most commonly performed surgical intervention worldwide. Indications include previous CS, podalic presentation and fetal macrosomia in antepartum CS, fetal distress, and prolonged first or second phase of labor in intrapartum CS. Despite the marked reduction in fetal mortality and morbidity in selected circumstances, maternal complication rates associated with CS are far higher than with vaginal delivery. The aim of this study was to evaluate the indications and maternal and fetal outcomes in a population undergoing antepartum or intrapartum CS and to analyze the risk factors of intrapartum CS. METHODS: An analysis was conducted on data from 1748 deliveries performed at the Gynecology-Obstetrics Clinic of the University of Udine during 2006. A total of 603 medical records of the mothers who had delivered by CS and their infants were analyzed. The Indications and maternal and fetal outcomes were evaluated in mothers who had undergone elective CS, emergency antepartum or intrapartum CS; multivariate analysis was then performed to define the risk factors associated with intrapartum CS. RESULTS: Cesarean sections accounted for 34.5% of all deliveries performed during 2006, of which 42.1% were elective CS, 21.1% emergency antepartum CS, and 36.8% intrapartum CS. The principal reason for CS delivery was previous CS in elective CS, gestational hypertension in emergency antepartum CS, and cardiotocographic alterations in emergency intrapartum CS. Multivariate logistic regression analysis showed that the independent risk factors for intrapartum CS were excessive weight gain during pregnancy and medically induced labor. CONCLUSION: A more accurate evaluation of the mother's and neonate's needs could help to improve the current rates of CS. This could be achieved by selection of cases in which there is a real need for CS and by acting on modifiable risk factors of intrapartum CS such as excessive weight gain during pregnancy.

Four primary malignancies successively occurred in a BRCA2 mutation carrier: a case report.

Carriers of BRCA2 germline mutation have a significantly increased lifetime risk of breast and ovarian cancer compared to non carriers. Several other carcinomas seem to be associated with BRCA2 mutations: pancreas, prostate, larynx, gallbladder, bile duct cancer, and malignant melanoma. We described a case of a 67-year-old BRCA2 mutation carrier of Caucasian, non-Jewish, ethnic origin who successively developed 4 primary malignancies in 30 months: breast ductal carcinoma, chronic lymphatic leukemia, ovarian serous papillary carcinoma, and endocervical adenocarcinoma. This is the first case of 4 primary malignancies in a BRCA mutation carrier, also occurred in such a short observation period. Chronic lymphatic leukemia and endocervical adenocarcinoma have not been yet associated to BRCA2 germline mutation.

[Management of gynecological tumors associated with BRCA1 and BRCA2 germline mutations. Case report and literature review]. / Management dei tumori ginecologici associati a mutazioni germinali BRCA1 e BRCA2. Caso clinico e review della letteratura.

Genetic investigation of BRCA1 and BRCA2 germline mutations is, nowadays, a diagnostic procedure with practical clinical applications. The role of this genes in DNA repair and stability and in cancer development is now well recognised. Most involved are breast and ovarian cancers, but, less frequently, other gynecological cancers like cervical, corpus uteri and Fallopian tubes cancers and also other non gynecological malignancies. We report the case of a 67-year-old patient with strong familiarity for breast cancer, with a BRCA2 germline mutation, who developed in 30 months 4 primary malignancies: in chronological order, breast cancer, chronic lymphatic leukemia, and synchronous ovarian and endocervical adenocarcinoma. A better knowledge of the biological and clinical behaviour of BRCA related cancers is of strategical importance in the management of patients with strong familiar neoplastic history or with genetic test positivity. An adequate counselling can help in the management of these cancers in the prevention and early diagnosis taking also into consideration the possibility of a prophylactic surgery.

[Premature ovarian failure in patients affected by oncohematological disease]. / L'insufficienza ovarica prematura dopo chemioterapia in pazienti con neoplasie ematologiche.

AIM: Premature ovarian failure (POF) can be considered a consequence of chemotherapy performed in patients affected by oncohematological disease. The aim of this study was to evaluate the administration of GnRh analogs (aGnRh) to prevent gonadal toxicity associated with cancer treatment. METHODS: From April 1996 to May 2002 a total of 49 fertile women affected by oncohematological diseases (Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute leukemia) and treated with chemotherapy were evaluated. Ovarian function was studied through a 40.7 month observation period, after chemotherapy, in 3 different groups: women treated with aGnRh, oral contraceptives treatment and no preventive-treatment. The differences in these groups as to menstrual cycle, blood ovarian hormones, age at diagnosis, type and dosage of chemotherapy administered were evaluated. Statistical analysis was performed by chi2 test with Yates correction and Fisher test. RESULTS: All patients treated with aGnRh and chemotherapy achieved a good ovarian function. A normal ovarian function was also obtained in 75% of patients treated with oral contraceptives and only in 59.3% of women with no preventive treatment. Significant difference was found comparing aGnRh group with no preventive-treatment group (P<0.05). No significant differences were found between other groups. CONCLUSIONS: Use of GnRh analogs administered before beginning chemotherapy prevents from gonadal damage in all cases observed. Higher chemotherapy toxicity and older age at diagnosis time decrease ovarian function.

Increased frequency of the immunoglobulin enhancer HS1,2 allele 2 in coeliac disease.

BACKGROUND: Coeliac disease (CD) is characterized by increased immunological responsiveness to ingested gliadin in genetically predisposed individuals. This genetic predisposition is not completely defined. A dysregulation of immunoglobulins (Ig) is present in CD: since antiendomysium antibodies (anti-EMA) are of the IgA class. One polymorphic enhancer within the locus control region (LCR) of the immunoglobulin heavy chain cluster at the 3' of the C alpha-1 gene was investigated. The correlation of the penetrance of the four different alleles of the HS1,2-A enhancer of the LCR-1 3' to C alpha-1 in CD patients compared to a control population was analysed. METHODS: A total of 115 consecutive CD outpatients, on a gluten-free diet, and 248 healthy donors, age- and sex-matched, from the same geographical area were enrolled in the study. HS1,2-A allele frequencies were investigated by nested polymerase chain reaction (PCR). RESULTS: The frequency of allele 2 of the enhancer HS1,2-A gene was increased by 30.8% as compared to the control frequency. The frequency of homozygosity for allele 2 was significantly increased in CD patients. Crude odds ratio (OR) showed that those with 2/2 and 2/4 (OR 2.63, P < 0.001 and OR 2.01, P = 0.03) have a significantly higher risk of developing the disease. In contrast, allele 1/2 may represent a protective genetic factor against CD (OR 0.52, P = 0.01). CONCLUSIONS: These data provide further evidence of a genetic predisposition in CD. Because of the Ig dysregulation in CD, the enhancer HS1,2-A may be involved in the pathogenesis.

DNA sequence heterogeneity within the Epstein-Barr virus family of repeats in the latent origin of replication.

To detect the presence of variability in the tandemly repeated sequences of the Epstein-Barr virus latent origin of replication, we analyzed the length of the family of repeats in 14 lymphoblastoid and Burkitt's lymphoma cell lines by PCR amplification. The gel electrophoresis analysis of the PCR products revealed a broad banding pattern, characteristic of each line, consisting of several fragments, sometimes smeared, of variable length. This finding was interpreted as a result of the hairpin-like structures generated by the palindrome within the family of repeats, able to originate artefacts. Since the banding pattern was different only in strictly non-correlated cell lines, we supposed that the sequence of the repeat units was polymorphic. We therefore sequenced the family of repeats in three healthy bone marrow derived lymphoblastoid cell lines carrying an endogenous EBV as well as in a B95-8 infected cell line as control. The sequence analysis revealed that each line is different both in the number and in the sequence of repeats. At the 3' end of the family of repeats the B95-8 virus was found to have a 252 bp region missing in the GenBank standard sequence. This one is probably a partial sequence since it was shorter than the control specimens obtained from different sources of B95-8 DNA analyzed by Southern blot hybridization. The length analysis of the family of repeats can be used to characterize EBV strains by PCR.

The region 3' to Calpha1 gene of human IG heavy chain displays a polymorphic duplicated sequence and encodes an RNA associated with polysomes.

A highly spread polymorphism flanking the 3. Calpha1 human IG heavy chain gene was identified. This polymorphism allowed the detection of an internal duplication within the 3' flanking region of both Calpha1 and Calpha2. This region has a regulatory function with four enhancer structures also present at the 3' end of the human Calpha2 as well as in that of mouse and rat single Calpha genes. The 5682-bp sequence of clone lambdapl8 described here starts 3' of Calpha1 and presents three open reading frames; one of them contains part of the tandem repeats with the 20-bp consensus described previously that is expressed in a poly(A)+ RNA and found in three dbEST clones of the human tonsillar cDNA library. Here, we demonstrate that in the CLF1 B lymphoblastoid cell line, this transcript is associated with polysomes. We also discuss the possibility of the presence of a new regulatory gene that does not encode an immunoglobulin and maps in the human IG heavy chain gene cluster.

Primary effusion lymphoma containing human herpesvirus 8 DNA in two AIDS patients with Kaposi's sarcoma.

BACKGROUND AND OBJECTIVE: Primary effusion lymphomas (PELs) containing Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8/HHV-8) DNA sequences represent a distinct but heterogeneous group of rare non-Hodgkin's lymphomas of null-cell phenotype/B-cell origin. We aimed to describe the clinicopathologic features of two human immunodeficiency virus (HIV)-related PELs occurring in homosexual men with Kaposi's sarcoma (KS). DESIGN AND METHODS: Thoracentesis was followed by morphologic plus immunophenotypic studies and molecular analysis of tumor cell DNA by means of combination of polymerase chain reaction and Southern blot analysis. RESULTS: Patients developed recurrent lymphomatous effusions lacking tissue involvement, in the context of severe immunodepression (CD4 count < 60/microL) and anti-retroviral therapy. The effusions disclosed an immunoblast-like population CD45/CD30+, but B-cell- and T-cell-associated antigen negative, showing clonal immunoglobulin heavy chain gene rearrangements and harbouring HHV-8 DNA sequences. One case contained Epstein-Barr virus genome with no evidence of c-myc, bcl-2 and bcl-6 gene alterations. Both patients had aggressive disease. INTERPRETATIONS AND CONCLUSIONS: These cases represent additional examples of PEL associated with HHV-8 and confirm that the group of HIV-positive homosexual men may be at highest risk for PEL.