Iordanis Navrozoglou

Association of estrogen receptor gene polymorphisms with endometriosis

OBJECTIVE To explore the association of the estrogen receptor two-allele (point) polymorphism and multiallele (microsatellite) polymorphism with endometriosis. DESIGN Case-control study. SETTING Genetics and Endoscopy Unit, Department of Obstetrics and Gynecology, Ioannina University HOSPITAL, Ioannina, Greece. PATIENT(S) Fifty-seven women with surgically and histologically diagnosed endometriosis of stages I-IV. INTERVENTION(S) Diagnostic laparoscopy. MAIN OUTCOME MEASURE(S) Frequency and distribution of the estrogen receptor gene polymorphisms. RESULT(S) There was a statistically significant difference between the patients and the controls in the frequency of the two-allele Pvu II polymorphism (0.72 vs. 0.49) and in the median repeats of the (TA)n multiallele polymorphism (15 vs. 20 repeats). In both groups, linkage was found between the fewer (TA)n repeats (range, 12-19) and the positive Pvu II polymorphism. CONCLUSION(S) The variability of the estrogen receptor gene likely contributes to the pathogenesis of endometriosis.

Management and evolution of cervical intraepithelial neoplasia during pregnancy and postpartum.

OBJECTIVE To investigate the evolution of cervical intraepithelial neoplasia (CIN), and to evaluate the safety of cytological and colposcopical surveillance of women with CIN during pregnancy. STUDY DESIGN Ninety-eight women with antenatal cytological and/or colposcopical impression of CIN were followed up during pregnancy with cytology and colposcopy every 2 months. A cytological and colposcopical reevaluation 2 months postpartum was done, and large loop excision of the transformation zone (LLETZ) was performed if appropriate. Punch or loop biopsies were only taken if there was suspicion of microinvasion. RESULTS In 14 of 39 (35.9%) and in 25 of 52 (48.1%) women with antenatal impression of CIN I and CIN II-III, respectively, there was postnatal impression of regression. Seven women with findings suspicious of microinvasion underwent small loop biopsies during pregnancy, but early stromal invasion (< 1 mm) was seen in just one case. There was one more case of microinvasion (1.5 mm) diagnosed postnatally in which the antenatal impression was of CIN III. 84.6% of the women with regression compared to 67.3% of the women with stable disease or progression had a vaginal delivery (P = 0.057). CONCLUSION There is a considerable regression rate of CIN after pregnancy possibly attributable to the loss of the dysplastic cervical epithelium during cervical ripening and vaginal delivery. Frequent cytological and colposcopical evaluation seems to be safe. Small loop biopsies are recommended in cases of possible microinvasion.

Routine obstetrical ultrasound at 18–22 weeks: Our experience on 7,236 fetuses

OBJECTIVE This study aimed at examining the detection rate of congenital abnormalities by using routine ultrasonography at 18-22 weeks of gestation. METHODS The sample included 7,236 fetuses. A detailed sonographic examination was performed in each fetus and a neonatal evaluation or pathology examination was made to confirm the prenatal findings. RESULTS The total prevalence of fetal abnormalities in our sample was 2.24% (162/7,236). There were 29/162 (17.9%) fetuses with CNS abnormalities, 27/162 (16.7%) fetuses with gastrointestinal abnormalities, and 28/162 (17.3%) fetuses with urinary tract abnormalities. There were also 31/162 (19.1%) fetuses with cardiovascular abnormalities, 26/162 (16.0%) with malformation of the limbs and musculoskeletal system, and 21/162 (13%) fetuses with other various abnormalities. The overall sensitivity in detecting fetuses with congenital abnormalities was 80.25% (130/162). The sensitivity per system was 93.1% (27/29) for CNS, 45.2% (14/31) for cardiovascular system, 85.2% (23/27) for gastrointestinal system, 85.7% (24/28) for urinary system, 84.6% (22/26) for musculoskeletal system, and 95.2% (20/21) for the rest of the abnormalities detected. We performed 40 pregnancy terminations in the group of malformed fetuses. Among the fetuses considered as normal, 1.7% had chromosomal abnormalities. CONCLUSIONS The results indicate that routine sonographic examination at 18-22 weeks of gestation can detect the majority of congenital abnormalities. More experience is needed for the examination of the cardiovascular system, where the sensitivity was particularly low (14/31 or 45.2%).

A systematic review and meta-analysis of randomized studies comparing misoprostol versus placebo for cervical ripening prior to hysteroscopy

OBJECTIVE(S) Hysteroscopy is an effective method for examining the uterine cavity but has some limitations, including the occasional need for cervical dilatation. Misoprostol is routinely used for cervical dilatation in various procedures but has not gained wide acceptance for use before hysteroscopy. STUDY DESIGN This review includes randomized controlled trials which compare the use of misoprostol versus placebo by different routes and doses before diagnostic or operative hysteroscopy. The MEDLINE database and the Cochrane Central Register of Controlled Trials were searched for articles published from January 1970 to April 2010. The outcome measures studied were related either to the facilitation of the hysteroscopic procedure (need for cervical dilatation, cervical width at the beginning of hysteroscopy, duration of the procedure and complications such as cervical tear and uterine perforation) or to the medication side-effects. With regard to side-effects, we studied the incidence of nausea, diarrhea, abdominal pain, bleeding, and fever. RESULTS Vaginal misoprostol reduced the need for cervical dilatation in the total population of pre- and post-menopausal women to a statistically significant degree. In the subgroup of operative hysteroscopy the need for dilatation and the duration of the procedure were also significantly reduced. Most other outcomes relating to the facilitation of the procedure did not reach statistical significance. The side effects in the misoprostol group were significantly more frequent than in the placebo group. CONCLUSION(S) There is insufficient evidence to recommend the routine use of misoprostol before every hysteroscopy. As the lack of serious benefit from misoprostol is unlikely to be due to type II error, its use should be reserved for selected cases.

Effects of ball cauterization following loop excision and follow-up colposcopy

Objective To investigate whether central diathermy ball cauterization after loop excision affects satisfactory colposcopy at follow-up. Methods One hundred one consecutive women with the squamocolumnar junction visible at the ectocervix scheduled for loop excision were assigned alternately into two groups. In group A, diathermy ball cauterization was applied to the entire crater following excision. In group B, cauterization was avoided in a 2–3-mm zone around the new os. The women were re-examined 4 months postoperatively by colposcopy and microcolpohysteroscopy with specific intention to identify the location of the squamocolumnar junction. The examiners performing colposcopy and microcolpohysteroscopy were not aware of each others interpretation, or of the method of cauterization used. Results Follow-up colposcopy was satisfactory in 12 women in group A (24%) and 47 women in group B (92.2%) (P < .001). Forty-three women (86%) in group A and ten in group B (19.6%) had the squamocolumnar junction partly or fully located within the cervical canal (P < .001). Microcolpohysteroscopy located the squamocolumnar junction at a mean depth of 4.5 ± 2.4 mm (± standard deviation [SD]) in the women in group A and 1 ± 0.9 mm in group B (P < .001). Microcolpohysteroscopy could not be performed in 13 women in group A (26%) and one woman in group B (2%) (P < .001). Conclusion Diathermy ball cauterization at the new cervical os after loop excision results in a shift of the squamocolumnar junction toward the endocervical canal, and predisposes to cervical stenosis, thereby decreasing satisfactory colposcopy rates.

Immunohistochemical Study of the Angiogenetic Network of VEGF, HIF1α, VEGFR-2 and Endothelial Nitric Oxide Synthase (eNOS) in Human Breast Cancer

BackgroundThe role of Nitric Oxide (NO) in angiogenesis has not been fully clarified yet. A dual role for NO, either inductive or inhibitory, has been proposed on the basis of different effects that high or low concentrations of NO may exert on the angiogenic process. Additionally, it has been referred that NO may induce VEGF production, while VEGF may induce NO production via up-regulation of the endothelial nitric oxide synthase (eNOS), the two pathways being reverse. The aim of the current study was to investigate the expression of key molecules involved in these opposite pathways in primary breast cancer.MethodsRepresentative tumor samples from 242 patients with early-stage breast cancer (invasive ductal breast carcinomas) were investigated for the expression of VEGF, VEGFR-2, HIF1α, iNOS, and eNOS using immunohistochemistry.ResultsEndothelial NOS was found in 159 cases, VEGF in 131 cases, HIF-1α in 139 cases, VEGFR2 in 185 cases and inducible NOS (iNOS) in 22 cases. There was a significant correlation between the expression of VEGF and VEGFR-2, eNOS and VEGF, eNOS and VEGFR-2, eNOS and HIF1α. No statistically significant correlation was found between iNOS and the rest of the studied molecules.ConclusionsIn breast cancer cases, the major molecules regulating NO and VEGF production can be co-expressed in the individual carcinomas implying a possibility for the relevant pathways to be active; however appropriate functional experiments remain to be conducted to prove such a hypothesis

Primary atypical carcinoid of the breast: A case report and brief overview of evidence

Primary atypical carcinoid of the breast is rare. Herein we present a case of atypical carcinoid of the breast treated with surgery. The management plan is commented. Moreover an overview of the current evidence is presented. All the evidence is classified as level IV (opinion-based evidence) since there is no satisfactory case series to support a certain therapeutic decision. The treatment for an atypical carcinoid of the breast is the same one offered in patients diagnosed with primary infiltrating breast cancer. A multi-centric approach is needed in order to gather enough data to confidently support a certain management plan for these patients.

Reproduction after breast cancer

Breast cancer is the most frequently occurring cancer in women of developed countries, and as a result of new developments in breast cancer treatment, more women are cured after being diagnosed with this disease. It is important that fertility preservation strategies are addressed before chemotherapy, because chemotherapy may induce premature ovarian failure (depending on the womans age, the drugs used, the dosage and duration of treatment). Among possible solutions are embryos or oocytes cryopreservation, ovarian tissue cryopreservation-freezing with a subsequent orthotopic and heterotopic autotransplantation, whole ovary cryopreservation, ovarian suppression with gonadotropin-releasing hormone (GnRH) analogues, which inhibit ovarian follicular depletion induced by chemotherapeutic agents and in vitro fertilisation (IVF) after ovulation induction with aromatase inhibitors or tamoxifen.

CRH receptors in human reproduction.

BACKGROUND Corticotropin releasing hormone (CRH), the main peptide-mediator of stress, has been found in the female reproductive system. OBJECTIVE Herein, the role of CRH receptors in the female reproductive system is presented. RESULTS It is clear that CRH receptors are involved in the regulation of the hypothalamic-pituitaryovarian axis, while locally are associated with decidualization, embryonic implantation, early fetal development and triggering of parturition. CONCLUSION Abnormal CRH signaling may contribute to obstetrical pathophysiology, such as preeclampsia, abnormal placenta invasion, endometrial growth retardation and preterm delivery.

Alpha tocopherol transfer protein (αTTP) is expressed in endometrial carcinoma and is correlated with FIGO stage and 5-year survival.

BackgroundIncreased oxidative stress plays an important role in cancer development. Vitamin E is considered a potent anti-oxidant and its transfer protein αTTP facilitates its cellular delivery. We hypothesize that αTTP could be present in and have an impact on endometrial cancer.Materials and methodsIshikawa endometrial cancer cells were treated with BSO and AAPH to mimick oxidative stress conditions. αTTP was detected by immunocytochemistry and western blot. αΤΤP expression was then assessed in 191 endometrioid endometrial carcinomas. Immunopositivity was correlated with grade, FIGO stage, and 5-year survival. Immuno-reactivity was assessed with a semi-quantitative score.ResultsAAPH- and BSO-induced αTTP expression in Ishikawa cells. Immunohistochemical assessment of the 191 endometrial cancer cases showed that αTTP expression correlated with FIGO stage (p = 0.014) but not with grade. Five-year survival was significantly better in cases of lower αTTP expression compared to cases with higher expression (p = 0.041).ConclusionsThe current results show that αTTP plays a role in endometrial carcinoma. Possibly endometrial cancer cells attempt to protect themselves from increasing oxidative stress by up-regulating αTTP. Selective molecular interventions targeting oxidative stress escape strategies, e.g., by overexpression of αTTP, could, therefore, allow oxidative stress to damage cancer cell membranes and thus restrict cancer progression.