Sentinel lymph node biopsy in uterine cervical cancer patients: ready for clinical use? A review of the literature.

Sentinel lymph node biopsy has been widely studied in a number of cancer types. As far as cervical cancer is concerned, this technique has already been used, revealing both positive results and several issues to be solved. The debate on the role of sentinel lymph node biopsy in cervical cancer is still open although most of the studies have already revealed its superiority over complete lymphadenectomy and the best handling possible of the emerging practical problems. Further research should be made in order to standardize this method and include it in the clinical routine.

Estimations of water balance after validating and administering the water balance questionnaire in pregnant women.

Dehydration during pregnancy may be harmful for the mother and fetus; thus our objective was to understand whether pregnant women balance water intake and loss. The Water Balance Questionnaire (WBQ) was modified to reflect pregnancy (WBQ-P). Validation was performed using 3-day diaries (n = 60) and hydration indices in urine (osmolality, specific gravity, pH and color, n = 40). The WBQ-P was found valid according to Kedhal τ-b coefficient agreement. The WBQ-P was administered to 95, 100 and 97 women per trimester, in Greece. Median (IQR) water balance, intake and loss were, respectively, 203 (-577, 971), 2917 (2187, 3544) and 2658 (2078, 3391) ml/day; these did not differ among the trimesters or between pregnant and non-pregnant women. However, more pregnant women were falling in the higher quartiles of water balance distribution. No differences in sources of water intake were identified except that women in the third trimester had lower water intake from beverages.

Impact of postpartum influenza vaccination of mothers and household contacts in preventing febrile episodes, influenza-like illness, healthcare seeking, and administration of antibiotics in young infants during the 2012-2013 influenza season.

BACKGROUND: Influenza is associated with an increased risk for serious illness, hospitalization, and mortality in infants aged <6 months. However, influenza vaccines are not licensed for administration in this age group. The study evaluated the effectiveness of postpartum influenza vaccination of mothers and household members in infants. METHODS: The influenza vaccine was offered to mothers and household members of neonates born or hospitalized in 3 hospitals prior to the 2012-2013 season. Mothers were contacted every 2 weeks during the influenza season, and data regarding the onset of fever and/or respiratory symptoms in infants, healthcare seeking, hospitalization, and administration of antibiotics were collected. RESULTS: The study group consisted of 553 mothers who delivered 573 neonates. The influenza vaccine was administered to 841 of 1844 (45.6%) household contacts. Vaccination coverage rates ranged between 41.9% for neonates siblings and 49% for mothers. Five hundred thirty infants were analyzed for vaccine effectiveness. For outcomes in the infant, postpartum maternal vaccination had 37.7% effectiveness against acute respiratory illness (ARI), 50.3% against a febrile episode, 53.5% against influenza-like illness (ILI), 41.8% against related healthcare seeking, and 45.4% against administration of antibiotics. Multiple logistic regression analyses showed that maternal influenza vaccination was significantly associated with a decreased probability for febrile episodes, ARIs, and/or ILIs in infants, related healthcare seeking, and/or administration of antibiotics during the influenza season. Vaccination of other household contacts had no impact. CONCLUSIONS: Maternal postpartum vaccination against influenza was associated with a significant reduction of influenza-related morbidity, healthcare seeking, and antibiotic prescription in infants during the influenza season.

Laparoscopically assisted vaginal radical hysterectomy: systematic review of the literature.

Laparoscopically assisted vaginal radical vaginal hysterectomy (LAVRH), a minimally invasive technique that seems to be an attractive alternative to traditional surgery, remains unexplored in the treatment of cervical cancer. We searched Medline (1966-2013) and Scopus (2004-2013) search engines, as well as reference lists from all included studies. Ten studies were retrieved; including 6 retrospective cohort studies, 2 prospective cohort studies, 1 retrospective randomized trial, and a phase II randomized control trial. LAVRH provided equal recurrence-free rates when performed in patients with tumors not exceeding 2 cm in greatest diameter. Its main advantages seem to be less intraoperative blood loss and more radical pelvic lymphadenectomy. The primary disadvantages of the technique are a higher rate of disease-positive surgical margins, resulting in the need for adjuvant therapy, and the slow learning curve required for a surgeon to gain expertise. With use in minimally invasive surgery of newer techniques such as total laparoscopic radical hysterectomy and robotic-assisted radical hysterectomy, and possible future adoption of more conservative techniques such as cervical conization with pelvic lymphadenectomy, the question remains as to whether LAVRH will be adopted by the surgical community or lost to oblivion.

Circadian clock gene expression is impaired in gestational diabetes mellitus.

Dysfunction of the circadian clock genes is involved in the development of obesity and type 2 diabetes (T2D). Since gestational diabetes mellitus (GDM) and T2D share common genetic and phenotypic features, in the present study, we investigated the status of the circadian clock in a cohort of 40 Greek pregnant women with GDM, four with T2D and 20 normal controls. Peripheral blood mRNA transcript levels of 10 clock genes (CLOCK1, BMAL1, PER1, PER2, PER3, PPARΑ, PPARD, PPARG, CRY1 and CRY2) were determined by real-time quantitative PCR. GDM patients expressed significantly lower transcript levels of BMAL1, PER3, PPARD and CRY2 compared to control women (p < 0.05). No significant difference was documented between GDM women maintained either under insulin treatment or diet. A positive correlation was found between the expression of BMAL1 versus CRY2 (r = 0.45, p = 0.003) and BMAL1 versus PPARD (r = 0.43, p = 0.004). Further investigation on the functional relevance of these clock genes, disclosed that expression of PER3 correlated negatively with HbA1C levels (r = -0.36, p = 0.022). These data document for the first time that the expression of BMAL1, PER3, PPARD and CRY2 genes is altered in GDM compared to normal pregnant women and support the notion that deranged expression of clock genes may play a pathogenic role in GDM.

The major circadian pacemaker ARNT-like protein-1 (BMAL1) is associated with susceptibility to gestational diabetes mellitus.

AIMS: Recently a relationship between circadian clock function and the risk for type 2 diabetes (T2D) has been shown. BMAL1 is a key component of the mammalian molecular clock. Two SNPs in the BMAL1 gene have been identified to confer T2D susceptibility. In the present study we investigated for the first time the association between the BMAL1 gene and the risk for GDM, in a Greek population. METHODS: We studied 185 women with GDM and 161 non-diabetic controls for BMAL1 polymorphisms. For BMAL1 mRNA expression, peripheral leukocytes were harvested from 20 GDM and 20 control women, harboring different genotypes for the tested polymorphisms, using real-time quantitative PCR. RESULTS: The minor allele (A) of the BMAL1 rs7950226 (G>A) polymorphism was found to be significantly associated with an increased risk of GDM (P=0.025). Analysis of the second BMAL1 rs11022775 (T>C) polymorphism, showed that the C-allele frequency was strongly increased in women with GDM (P=4.455e-06). The CC genotype was also significantly overrepresented in GDM vs. controls (P=0.00001). Additionally, the rs7950226G/rs11022775C and rs7950226A/rs11022775C haplotypes were also found to be associated with increased susceptibility to GDM. Furthermore, the expression levels of BMAL1 mRNA were significantly lower in GDM patients than in controls. CONCLUSION: These data suggest that the impairment of the BMAL1 clock gene expression is closely associated with GDM susceptibility.

Nodal, Nanog, DAZL and SMAD gene expression in human amniotic fluid stem cells.

The aim of this study was to investigate the expression of Nodal (NODAL Homolog (mouse), Nanog (Nanog Homeobox), DAZL (Deleted in Azoospermia Like) and SMAD (SMAD Family member) genes and their potential role in the regulation of self-renewal in human amniotic fluid-derived stem cells. In this experimental study human amniotic fluid-derived stem cells were analyzed for messenger RNA expression of Nodal. Immunocytochemistry also was performed to determine Nanog and DAZL. SMAD genes expression analysis was performed using cDNA Microarray analysis. Nodal mRNA was positively expressed in all samples of amniotic fluid derived stem cells. Amniotic fluid-derived stem cells showed strong immunoreactivity for molecular markers of undifferentiated human embryonic stem cells including Nanog and DAZL. Among the 8 SMAD genes expressions analyzed SMAD1, SMAD2, SMAD3, SMAD4 and SMAD7 showed positive expression. In conclusion amniotic fluid-derived stem cells seem to express Nodal, Nanog and DAZL and it speculated that the regulation of self-renewal in AFSc could be similar as in human embryonic stem cells.

Acceptance of a post-partum influenza vaccination (cocooning) strategy for neonates in Greece.

Young infants are at increased risk for influenza-associated serious illness, onset of complications, utilization of health-care services, and hospitalization. We investigated the feasibility and acceptance of an influenza vaccination (cocooning) strategy by household contacts implemented in a maternity hospital and the neonatal unit of a pediatric hospital in Athens. A total of 224 mothers (mean age: 30.2 years) who gave birth to 242 neonates were studied. Of them, 165 (73.7%) mothers were vaccinated. Multiple logistic regression revealed that statistically significant factors associated with increased vaccination rates among mothers were: being of Roma origin (p-value=0.002), being an immigrant (p-value=0.025), giving birth to a neonate with birth weight <2500g (p-value=0.012), and residing in a family with ≥4 family members (p-value=0.017). Of the 224 fathers, 125 (55.8%) received the influenza vaccine. Fathers of neonates whose mothers were vaccinated had 6-fold higher vaccination rates compared to fathers of neonates whose mothers refused vaccination (p-value<0.001). Overall, influenza vaccine was administered to 348 (46.9%) of a total of 742 household contacts of the 242 neonates. Upon entering the 2011-2012 influenza season, 51 (22.7%) of 224 families had all household contacts vaccinated against influenza (complete cocoon). Among parents, the statement "I do not want to receive the vaccine" was the prevalent reason for declining influenza vaccination, followed by the misconception "I am not at risk for contacting influenza" (41.1% and 38.2%, respectively).

Gestational diabetes mellitus shares polymorphisms of genes associated with insulin resistance and type 2 diabetes in the Greek population.

Gestational diabetes mellitus (GDM) and type 2 diabetes (T2D) share common pathophysiological features, including ß-cell dysfunction and insulin resistance. In this study, we investigated the association between GDM and five recently identified T2D susceptibility loci, in a Greek population. We studied 148 women with GDM and 107 non-diabetic unrelated pregnant Greek women, for polymorphisms in the TCF7L2 gene (rs7903146 C/T), the PPARG gene (Pro12Ala), the KCNJ11 gene (E23K), the IRS1 gene (G972R) and in the FOXC2 gene (-512C>T). The T-allele of the TCF7L2 rs7903146 (C/T) polymorphism was found to be significantly associated with an increased risk of GDM [p = 0.0003; odds ratio (OR) 2.04 (95%CI 1.38-3.00)]. Additionally, CT and TT genotypes were significantly overrepresented in women with GDM compared to controls (p = 0.0003 and p = 0.0148, respectively). Analysis of the IRS1 G972R polymorphism showed that the R-allele frequency was increased in women with GDM [(p = 0.009; OR 1.67 (95%CI 1.14-2.47)]. The genotypes and allele frequencies of the other polymorphisms studied did not statistically differ between the GDM and the control women. Thus, our data suggest that the common T2D susceptibility polymorphism of TCF7L2 (rs7903146 C/T) gene, and the G972R polymorphism of the IRS1 gene, seem to predispose to GDM in Greek women.

Metformin administration was associated with a modification of LH, prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome.

UNLABELLED: AIM. To elucidate the dynamics of FSH, LH, prolactin (PRL), TSH and insulin secretion in women with polycystic ovarian syndrome (PCOS) treated with metformin (MET). PATIENTS AND METHODS: In a prospective, controlled and randomised trial, 32 women with PCOS and 32 with normal cycle were recruited to receive MET (850 mg b.i.d.) or placebo (n: 16 for each subgroup) for an average of 40 days. Pituitary function and insulin secretion were assessed before and after intervention by GnRH-TRH tests and oral glucose tolerance test induced insulin response. RESULTS: Basal and area under the response curve (AURC) LH values were higher in PCOS than in normal controls before MET and declined following treatment in the former group (P < 0.05). Ovulatory PCOS responders had lower basal LH, AURC(LH) and AURC(PRL) values during MET than anovulatory cases (P < 0.05 for all) and AURCins was lower in ovulatory than anovulatory PCOS before and on MET (P < 0.02-P < 0.05), with a rise of QUICKY index in the former group during MET treatment (P < 0.05). FSH and TSH were similar. CONCLUSIONS: MET administration lowered LH activity in all PCOS women and in ovulatory responders and also compromised PRL stimulated secretion in the latter cases. These findings were indicative of an effect of MET on pituitary activity.

Simple structural chromosomal abnormalities in advanced stage of ovarian cancer.

BACKGROUND: Ovarian cancer represents the leading cause of death among patients with gynaecological cancer. The identification of chromosomal abnormalities is a useful strategy toward understanding tumourigenesis and specific chromosomal associations. Since single chromosomal changes might be primary events implicated in the initiation of the neoplastic process, the aim of the present study was to investigate the presence of simple structural chromosomal changes in ovarian cancer. MATERIALS AND METHODS: Reviewing on ascetic effusions samples cytogenetically studied by direct culture of tumour cells and a G-banding technique, two ovarian cancer cases were found which presented simple structural chromosomal abnormalities. RESULTS: The first case presented an abnormal clone of cells with an acquired pericentric inversion of chromosome 9, inv(9)(p11q13), as a sole anomaly. The second case presented simple chromosomal changes with involvement of the Xq23 chromosomal region, while a translocation t(X;11)(q23;q23) was also defined. CONCLUSIONS: The significance of the acquired pericentric inversion 9 in the development of the neoplastic process remains unknown. The chromosomal regions Xq23 and 11q23 need to be further investigated in association with clinicopathological parameters in ovarian cancer. The documentation of more ovarian cancer cases with simple chromosomal abnormalities is considered of major importance facilitating the identification of candidate genes involved in the neoplastic process. Improving the molecular understanding of ovarian cancer development and progression could facilitate the detection of specific tumour subtypes.

Use of annexin V for the identification of fetal cells in maternal circulation.

MACS with Annexin V-conjugated microbeads was used to isolate cells in apoptosis from the peripheral blood of 112 women at different weeks of gestation and from 15 women (60 samples) sequentially tested postpartum. FISH using X/Y probes was applied to quantitate fetal apoptotic cells. The mean apoptosis rate in the 16th-18th week was 6.5% and fetal cells constituted 5.1% of the apoptotic cell population. In the 26th-28th week it was 10.1%/7.5% and in the 37th-38th week 12.5%/9.9%, respectively. In samples obtained 30 min, 12h and 24h postpartum, the mean apoptosis was 25.1%, 12.5 and 6.1%, respectively and fetal cells constituted 14.8%, 2.1% and 0.16% of the apoptotic cells. Forty-eight h after delivery, apoptosis was 2.3% and no fetal cells were detected. Accurate estimation of the proportion of fetal cells undergoing apoptosis may facilitate the optimization of protocols for non-invasive prenatal diagnosis of chromosomal abnormalities.

Rapid clearance of fetal cells from maternal circulation after delivery.

We previously reported increased apoptosis in the maternal circulation during pregnancy, partly accounting for the presence of cell-free fetal DNA in maternal plasma. In the current study, apoptosis was quantitated in 60 peripheral blood samples obtained from 15 women sequentially tested postpartum using the binding of annexin V. FISH with X/Y probes was performed on annexin V-positive cells isolated by MACS in patients with male fetuses to estimate the proportion of fetal cells among the apoptotic cell population. Twenty-four women at the thirty-seventh to thirty-eighth week of gestation and 35 nonpregnant females were used as controls. Apoptosis rate in the thirty-seventh to thirty-eighth week was 12.5% (9.2-14.7%). At 30 minutes, 12 hours, 24 hours, and 48 hours postpartum, it was 25.1% (16.8-28.5%), 12.5% (10.9-14.1%), 6.1% (4.8-7.1%), and 2.3% (1.3-3.0%), respectively. Male apoptotic cells were identified in all cases with male fetuses at 37 to 38 weeks of gestation, and the mean proportion was 9.9% (5.9-13.2%). The proportion of fetal cells 30 minutes after delivery was 14.8% (12.5-25.5%) and 12 hours postpartum 2.1% (0.8-4.1%). Male fetal apoptotic cells were detected in three of eight samples collected 24 hours after delivery from women who delivered males, at frequencies of 0.10%, 0.15%, and 0.25% (mean 0.16%). There were no fetal apoptotic cells 48 hours after delivery. Apoptosis partly accounts for the clearance of fetal cells from the maternal circulation. Because it is a rapid reaction, completed within 2-3 hours, persistence of fetal cells is possibly due to apoptosis-resistant progenitors or to defective regulation of apoptosis, leading to fetal cell microchimerism associated with autoimmune diseases.