Accuracy of combinations of visual inspection using acetic acid or lugol iodine to detect cervical precancer: a meta-analysis.

BACKGROUND: Visual inspection of the cervix with acetic acid (VIA) or with Lugol's iodine (VILI) have been evaluated for cervical cancer screening in developing countries. OBJECTIVES: To assess the diagnostic accuracy and clinical utility of visual methods to detect cervical intraepithelial neoplasia grade 2+ (CIN2+) using: (1) VIA alone; (2) VILI alone; (3) co-testing; and (4) VILI as a triage test of a positive VIA result. SEARCH STRATEGY: PubMed, EMBASE, and the Cochrane Library were searched up to May 2016. SELECTION CRITERIA: All reports on the accuracy of VIA and VILI, or combinations of VIA/VILI, to detect CIN2+ were identified. Histology and colposcopy when no biopsy was taken were used as the reference standard. DATA COLLECTION AND ANALYSIS: Selected studies were scored on methodological quality, and sensitivity and specificity were computed. Clinical utility was assessed from the positive predictive value (PPV) and the complement of the negative predictive value (cNPV). MAIN RESULTS: We included 23 studies comprising 101 273 women. The pooled sensitivity and specificity of VILI was 88 and 86%, respectively. VILI was more sensitive, but not less specific, compared with VIA (relative sensitivity = 1.11; 95% confidence interval, 95% CI, 1.06-1.16; relative specificity = 0.98; 95% CI 0.95-1.01). Co-testing was hardly more sensitive, but significantly less specific, than VILI alone. VILI to triage VIA-POSITIVE women was not less sensitive, but more specific, compared with VIA alone (relative sensitivity = 0.98, 95% CI 0.96-1.01; relative specificity = 1.04, 95% CI 1.02-1.05). The average PPVs were low (range 11-16%), whereas the cNPV varied between 0.3% (VILI, co-testing) and 0.6% (triage). CONCLUSIONS: Although imperfect, VILI alone appeared to be the most useful visual screening strategy. TWEETABLE ABSTRACT: VILI alone seems to be the most useful visual screening test for cervical cancer screening.

Endometriosis after menopause: physiopathology and management of an uncommon condition.

Endometriosis is a hormone-dependent inflammatory disease that is usually characterized by infertility and pain symptoms. This disease mainly occurs during the reproductive years and is rarely diagnosed after menopause. We discuss the physiopathology of this condition after menopause as well as treatment options and the risk of malignant transformation. Occurrence or progression of postmenopausal endometriosis lesions could be related to extra-ovarian production of estrogen by endometriosis lesions and adipose tissue, which becomes the major estrogen-producing tissue after menopause. Postmenopausal women with symptomatic endometriosis should be managed surgically because of the risk of malignancy; medical treatments can be used in cases of pain recurrence after surgery. Aromatase inhibitors act by decreasing extra-ovarian estrogen production and by blocking the feed-forward stimulation loop between inflammation and aromatase within endometriosis lesions. The evidence is currently insufficient to support a conclusion about the optimal hormone replacement therapy for women with endometriosis. The question of malignant transformation of endometriosis in response to hormone replacement therapy in women with a history of endometriosis remains unanswered and needs a long-term follow-up study to evaluate the risk of an adverse outcome. Further studies should be performed to determine the optimal management of menopausal women with endometriosis.

Myoma migration: an unexpected "effect" with Ulipristal acetate treatment.

OBJECTIVE: Uterine myomas are one of the most common benign tumours, occurring in 20-40% of women of reproductive age. Ulipristal acetate (UPA) is a possible option for medical treatment of myomas. It induces amenorrhea and can reduce myoma volume before surgical treatment. Since its introduction in our department, we uncovered an unknown effect: migration of myoma. CLINICAL CASE REPORTS: We describe three clinical case of myoma migration following three months UPA pre-operative treatment. The first woman presented with a FIGO 2 myoma, which migrated in FIGO 3. A previously planned hysteroscopy converted into a laparoscopy. The second woman also presented with a FIGO 2 myoma, which migrated in FIGO 3. Initially, a hysteroscopy was planned, but ultimately surgery was no longer required. The third woman presented with a FIGO 2-5 myoma, which migrated in FIGO 1. The previously planned laparoscopy converted into a vaginal myomectomy. CONCLUSIONS: UPA induces a proapoptotic and anti proliferative effect of leiomyoma cells. It reduces expression of VEGF and reduces collagen deposition in the extracellular matrix. These mechanisms could induce migration of myoma. UPA as pre-operative treatment can induce migration of myoma and, therefore, can lead to perioperative conversion of surgery.

[Appropriateness of the prescriptions of conventional versus new oral anticoagulants at discharge from a department of internal medicine]. / Pertinence des prescriptions d'anticoagulants oraux à la sortie d'un service de médecine interne d'un hôpital régional suisse.

BACKGROUND: The recently introduced oral direct anticoagulants (ODAs), presumably safer, and with comparable efficacy to the vitamin K antagonists (VKAs), may reshape the world of anticoagulation medicine. This study aimed to assess the prescription appropriateness of ODAs and VKAs at discharge from hospital. METHODS: We performed a one year retrospective study between August 2012 and July 2013 in the department of internal medicine of a regional hospital (HVs Sion) using Electronic Medical Records. All patients receiving an ODA were included and matched to a patient treated with a VKA. The appropriateness of prescription at discharge was defined by an adequate indication and dosing, the absence of contraindication, a minimal risk of drug-drug interactions and no major bleeding or venous thromboembolism during the hospitalization. The bleeding risk was evaluated with the HAS-BLED score when the indication was atrial fibrillation (AF). RESULTS: Out of the 44patients included (22 with an ODA and 22 with a VKA), 38 received an appropriate prescription according to all criteria. Two patients had an inadequate dosing. A potential drug-drug interaction was detected in 3patients receiving a VKA and in 1patient receiving an ODA. No major contraindication was found, but a relative contraindication was discussed in 3cases. The majority of patients receiving an ODA for an AF had a minor bleeding risk. CONCLUSION: No significant difference was ascertained between the two groups regarding the appropriateness of prescription. Our results suggest that ODAs were cautiously used in our setting.

Stage IVB endometrial cancer: clinical course and survival of patients with single and multiple metastases.

OBJECTIVE: Metastatic endometrial cancer (EC) at initial presentation is a rare disease. The present aim was to evaluate prognostic factors and overall survival in patients diagnosed with metastatic EC. STUDY DESIGN: Using data from the Geneva Cancer Registry, the authors included all patients diagnosed with Stage IVB EC from 1980-2007. Estimates of survival were calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 38 patients were identified. The most frequent metastases were peritoneal or pleural carcinomatosis (66%, n=25) and hematogenous metastases (53%, n=20). Five-year survival rate was 5.7% (95% confidence interval: 0.0-13.3), and median survival was 7.6 months. Survival of patients with a single metastasis at the time of diagnosis was longer than for patients with multiple metastases (16 versus two months, respectively; p < 0.00 1). CONCLUSION: Metastatic EC is rare disease with very poor prognosis particularly for patients with multiple site metastases.

Effect of estetrol on Beta-Endorphin level in female rats.

INTRODUCTION: Estetrol (E4), a naturally occurring estrogen produced exclusively by human fetal liver, is currently being evaluated for potential use in contraception and menopausal care in humans. The present study was designed to profile E4 effects on the central nervous system, to assess the in vivo effects of E4 administration on Beta-Endorphin (ß-END) release in specific brain structures and to evaluate whether E4 has synergic or antagonistic effects on estradiol-mediated ß-END synthesis. EXPERIMENTAL: Intact female adult rats received different doses of E4 and ovariectomized (OVX) rats received different doses of E4 or E2V or combinations of both drugs. The concentrations of ß-END were assessed in the frontal and parietal cortex, hippocampus, hypothalamus, neurointermediate lobe, anterior pituitary and plasma. RESULTS: E4 at the dose of 1mg/kg/day did not alter ß-END content in most brain areas, as well as, plasma levels of intact animals E4 administered at a dose of 5mg/kg/day decreased ß-END content in the hippocampus, hypothalamus, and in the neurointermediate lobe, as well as, plasma levels, compared to intact animals receiving vehicle. E4 increased ß-END values in the frontal cortex, but not in the plasma, following the administration of 1mg/kg/day in OVX rats, whereas treatment with 5mg/kg/day in OVX rats induced a significant increase in ß-END levels in most brain areas and in the plasma. However, in the presence of estradiol, E4 showed an estrogen-antagonistic effect in selected brain structures at the dose of 5mg/kg/day and in plasma levels of ß-END at the dose of 1mg/kg/day and 5mg/kg/day. CONCLUSION: In OVX rats, E4 increases CNS and peripheral levels of ß-END, behaving as a weak estrogen-agonist. The antagonistic effect observed after combined estradiol and E4 administration further profiles E4 as a natural SERM.

Neurobiology of DHEA and effects on sexuality, mood and cognition.

Dehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, are the most abundant steroid hormones in the humans. However, their physiological significance, their mechanisms of action and their possible roles as treatment are not fully clarified. Biological actions of DHEA(S) in the brain involve neuroprotection, neurite growth, neurogenesis and neuronal survival, apoptosis, catecholamine synthesis and secretion, as well as anti-oxidant, anti-inflammatory and antiglucocorticoid effects. In addition, DHEA affects neurosteroidogenis and endorphin synthesis/release. We also demonstrated in a model of ovariectomized rats that DHEA therapy increases proceptive behaviors, already after 1 week of treatment, affecting central function of sexual drive. In women, the analyses of clinical outcomes are far from being conclusive and many issues should still be addressed. Although DHEA preparations have been available in the market since the 1990s, there are very few definitive reports on the biological functions of this steroid. We demonstrate that 1 year DHEA administration at the dose of 10mg provided a significant improvement in comparison with vitamin D in sexual function and in frequency of sexual intercourse in early postmenopausal women. Among symptomatic women, the spectrum of symptoms responding to DHEA requires further investigation, to define the type of sexual symptoms (e.g. decreased sexual function or hypoactive sexual desire disorder) and the degree of mood/cognitive symptoms that could be responsive to hormonal treatment. In this regard, our findings are promising, although they need further exploration with a larger and more representative sample size. This article is part of a Special Issue entitled: Essential role of DHEA.

Effect of estetrol administration on brain and serum allopregnanolone in intact and ovariectomized rats.

INTRODUCTION: Estetrol (E4), a naturally occurring estrogen only produced by the human fetal liver, is being evaluated in human studies for potential use in contraception and menopausal care. The present study was designed to profile E4 in the central nervous system, to assess the in vivo effects of E4 administration on allopregnanolone (AP) synthesis in specific brain structures and to evaluate whether E4 has synergic or antagonistic effects on estradiol-mediated AP synthesis. MATERIAL AND METHODS: Intact female adult rats received different doses of E4, and ovariectomized OVX rats received different doses of E4 or E2V or combinations of both drugs. The concentrations of AP were assessed in the frontal and parietal cortex, hippocampus, hypothalamus, anterior pituitary, and serum. RESULTS: E4 did not alter AP in intact animals in any region. E4 at a dosage of 5mg/kg/day increased AP levels in different brain areas and in the serum of OVX animals. However, in the presence of estradiol, E4 showed an estrogen-antagonistic effect on the brain and serum levels of AP. CONCLUSION: E4 increases the CNS and peripheral levels of AP, behaving as a weak estrogen-agonist in OVX rats. The antagonistic effect observed with E2V co-administration further profile E4 as a natural SERM.

Spontaneous ectopic tubal pregnancy after laparoscopic tubal sterilisation by segmental isthmic partial salpingectomy.

A 33-year-old woman with a history of tubal sterilisation, presented to our gynaecological emergency unit with acute abdominal pain and signs of peritonism. The first day of her last menstruation occurred 4 weeks and 4 days before. Urine pregnancy test was positive and transvaginal ultrasound revealed an empty uterus with a heterogeneous mass below the right ovary. We performed a laparoscopy, which confirmed a previous isthmic partial salpingectomy and the presence of an ectopic pregnancy in the right distal remnant tube. Total salpingectomy of the remnant parts of the tube was performed and the postoperative course was uneventful.

How many ovarian cancer patients are eligible for fertility-sparing surgery?

OBJECTIVE: To assess how many epithelial ovarian cancer (EOC) patients are eligible for fertility-sparing surgery (FSS) in a population-based study. STUDY DESIGN: Using data from the Geneva Cancer Registry, we conducted a retrospective review of all women diagnosed with epithelial ovarian cancer (EOC) between January 1979 and December 2008. Patients were classified into two age groups ("young group"≤45 years and "old group">45 years) and as "eligible for FSS" (FIGO IA, G1-G2 or unilateral ICG1) and "non-eligible for FSS" (FIGO IA, G3; IC G2-G3; IB or II-IV). Patients and tumor characteristics were tested with the chi-square test. Estimates of survival were calculated using the Kaplan-Meyer method and differences between groups were analyzed by the log-rank test. RESULTS: A total of 888 EOC patients were analyzed. The young group included 87 patients (9.8%): eleven (1.2%) were identified as eligible for FSS and 6 (0.6%) were nulliparous. The annual incidence of EOC women eligible for FSS in Geneva was 0.48/100,000 (0.5 women/year) and the expected annual incidence rate for Switzerland (8 million inhabitants) is 6.5 women/year. CONCLUSION: Only a very small proportion of EOC patients are eligible for FSS. These results highlight the need to centralize FSS data in dedicated European units, in order to maintain expertise and quality of care for these patients.

Advances in neurosteroids: role in clinical practice.

The steroidogenic endocrine glands and local synthesis both contribute to the pool of steroids present in the central nervous system and peripheral nervous system. Although the synthesis of neurosteroids in the nervous system is now well established, the spectrum of respective functions in regulating neuronal and glial functions remains to be fully elucidated. From the concept of neurosteroids derives another treatment strategy: the use of pharmaceutical agents that increase the synthesis of endogenous neurosteroids within the nervous system. This approach has so far been hampered by lack of knowledge concerning the regulation of the biosynthetic pathways of neurosteroids and their relationship with sex steroids produced by the peripheral gland or with exogenous steroids. The present review summarizes some of the available clinical and experimental findings supporting the critical role of neurosteroids during fertile life and reproductive aging and their relationship with endogenous and exogenous sex steroids. The brain metabolism of synthetic progestins and the implications of DHEA treatment in postmenopausal women will also be discussed.

Tubal endometrioma within a twisted fallopian tube: a clinically complex diagnosis.

BACKGROUND: Endometriotic lesions affect the fallopian tubes in 6% of patients with endometriosis and adhesions involve the salpinges in 26%. Different studies report that 45%-70% of adolescents with chronic pelvic pain have endometriosis diagnosed at the time of laparoscopy. CASE: We report a case of an 18-year-old girl with a tubal torsion due to a tubal endometrioma. The endometriotic nodule before laparoscopy appeared to be located in the rectovaginal septum. At laparoscopy, a right fallopian tube torsion was visible and several adhesions were connecting the lesion to the pouch of Douglas' walls. SUMMARY AND CONCLUSION: The tenacious adhesions, which welded the nodule to the walls of the pouch of Douglas, did not allow to distinguish at the MRI a tubal endometrioma from a rectovaginal endometriotic mass, justifying the false diagnosis.

[What's new in gynecology and obstetrics]. / Gynécotogie et obstétrique.

Because of the lack of screening methods, ovarian cancer remains one of the major causes of mortality in gynecological oncology. Prevention by salpingectomy, based on a concept about the origin of serous carcinoma, may be proven effective in the future. Regarding cervical cancer, screening methods are improving and the benefit of HPV-HR testing has been recently demonstrated. Metabolic requirements and exercise are modified during pregnancy. Present recommendations are for pregnant women to practice regular moderate exercise, as in a non-pregnant population. This guideline, despite being reasonable, is not based on strong evidence. A randomised trial is ongoing in our Department to evaluate the effects of exercise in women with gestational diabetes.

Overexpression of GRP78 in complete hydatidiform moles.

OBJECTIVE: Hydatidiform moles, subdivided into partial moles (PM) and complete moles (CM), are abnormal pregnancies with a disturbed invasive behavior. We had previously shown that MMP-2 and p53 proteins are overexpressed in CM versus PM, and that in primary cytotrophoblasts p53 protein is stabilized by complexing to the 78kDa glucose-regulated protein (GRP78) which is involved in cytotrophoblasts invasion process. The present study aims to compare the transcript expression profile of p53, MMP-2 and GRP78 in hydatidiform moles. METHODS: A retrospective study was performed by RT-qPCR and immunostaining on paraffin-embedded tissues of 19 PM, 16 CM and 16 control (CTRL) samples of gestational age 8-12 weeks. RESULTS: Expression of MMP-2 transcript was significantly overexpressed in CM compared to CTRL samples (p=0.031). In contrast, expression of p53 transcript was similar among the samples. This suggests a regulation of p53 in CM at the protein level. GRP78 cDNA was significantly overexpressed in CM compared to CTRL (p=0.021) and to PM (p=0.011). At the protein level, immunostaining of GRP78 was on average stronger in CM than PM samples. CONCLUSIONS: Collectively, present data suggest that in CM, p53 is normally expressed at the mRNA level but probably complexes at the protein level with the overexpressed GRP78, leading to accumulation of p53 protein. Moreover, since GRP78 and MMP-2 are increased in CM and known to play key roles in invasion, our results suggest that GRP78 and MMP-2 should be investigated as prognostic markers of hydatidiform moles.

[Trophoblastic diseases: a multidisciplinary approach, a first Swiss center]. / Maladies trophobtastiques: une prise en charge pluridisciplinaire, un premier centre suisse.

Trophoblastic diseases are rare and complex. The Center for trophoblastic diseases, the first in Switzerland, was founded in Geneva in January 2009 to formalize the collaboration between obstetricians-gynecologists, pathologists, geneticists, radiologists and oncologists. At the physician's request and with patient consent, an integrative diagnosis is proposed after centralized review of the histological slides, anti-p57KIP2 immunohistochemistry, and ploidy analysis by QF-PCR (Quantitative fluorescent polymerase chain reaction). The referring physician receives treatment and beta-hCG dosage recommendations. This pluridisciplinary diagnostic and therapeutic approach allows optimal surveillance and treatment of patients.

[LESS, NOTES and robotic surgery in gynecology: an update and upcoming perspectives]. / Chirurgie LESS, NOTES et robotique en gynécologie: mise au point et perspectives.

Laparoscopy revolutionized the gynecological surgical world during the 1980's and 1990's and has changed the approach to surgical procedures ever since. Minimal invasive surgery procedures are now the standard of care for many gynecological operations. At the beginning of the 21st century, robotic gynecological surgery, laparo-endoscopic single site surgery (LESS) and natural orifice transluminal endoscopic surgery (NOTES) may be on the threshold of another such revolutionary breakthrough. In this article, we review the present place of these new techniques in gynecological surgery and discuss their future perspective.

[Septic arthritis]. / Arthrite septique.

Septic or acute bacterial arthritis is a medical emergency. The primary physician must suspect this condition even when clinical symptoms are non specific or with simultaneous inflammatory arthropathy. Septic arthritis can have serious complications. Optimal care requires hospital admission in general. Synovial fluid aspiration and its correct interpretation, the appropriate choice and timely administration of empiric antibiotic therapy can limit destruction of the joint's cartilage. The adaptation of the antibiotic regimen after reception of microbiological results and the adequate treatment in full length require interdisciplinary collaboration between the hospital physician, including the specialist in infectious diseases, the microbiology laboratory and post-hospital care.

[Diagnostic of Pneumocystis jirovecii pneumonia in a non HIV patient]. / Diagnostic de la pneumonie à Pneumocystis jirovecii chez le patient non VIH.

Pneumocystis jirovecii pneumonia is an opportunistic infection affecting not only HIV patient but also patients with others causes of immunosuppression. The reference method for the diagnostic is the direct visualization of the pathogen in induced sputum or in bronchoalveolar lavage with a low sensibility. Direct immunofluorescence does not increase significantly this sensibility on IS. The PCR has been demonstrated to have 100% sensitivity. This gives rise to the problem of falsely positive results in patients, colonized by P. jiroveci (8,9-26,9%) but suffering from a pneumonia due to another pathogen. Use of quantitative PCR or serum beta-D-glucan, might be helpful to distinguish colonization from infection. This paper reviews the literature on the diagnostic of PCP in non HIV patients.

[Ovarian cancer screening: recommendations for clinical pratice]. / Dépistage du cancer de l'ovaire: recommandations pour la pratique clinique.

Ovarian cancer accounts for a minority of female cancers but remains the leading cause of death from gynaecologic cancers and the fifth leading cause of all cancer-related deaths among women. More than two thirds of cases of ovarian cancer are diagnosed once the disease becomes symptomatic, i.e. at an advanced stage. Though early detection constitutes a legitimate aim, no screening approach has yet been shown to reduce ovarian cancer mortality. In particular, ovarian imagery with endovaginal ultrasonography and serum tumor markers (CA-125) dosage performed in asymptomatic individuals have not proven their efficacy. Screening of asymptomatic women is not therefore recommended because of the limited prevalence of ovarian cancer in the general population.