Relaxin as a potential diagnostic biomarker for ovarian cancer- A prospective study.

Ovarian cancer is a leading cause of female mortality worldwide. Although novel approaches on this disease have been developed, overall survival rates remain moderate due to the lack of scientific evidence promoting screening at early stages of the disease. A number of biomarkers have been suggested as predictive for this type of cancer. The role of relaxin in endometrial cancer is well documented but the scientific evidence is lacking with regards to ovarian cancer. We studied patients with ovarian cancer, benign ovarian cyst and healthy patients too. The levels of relaxin have been found to be an adequate diagnostic biomarker for ovarian cancer. We also presented the different range of Ca125, HE4 and ROMA in these three groups. Randomised control trials need to be conducted though, in order to elucidate the true role of relaxin in these cases.

Successful conservative medical management of an interstitial ectopic pregnancy at 10 weeks of gestation: A case report.

BACKGROUND: Interstitial pregnancy is a rare type of ectopic pregnancy, accounting for 2-6% of ectopic pregnancies, but it can be life threatening. There is no clear consensus on management, either surgical or medical, and it depends on hemodynamic stability and whether fertility-sparing treatment is requested. CASE PRESENTATION: We present the case of a 35-year-old woman (G2, P1) who was diagnosed with an interstitial pregnancy at 10 weeks of gestation following in vitro fertilization. She was hemodynamically stable and requested fertility-sparing treatment. She was managed successfully with methotrexate and folinic acid with a hospital stay of 17 days. CONCLUSION: Interstitial pregnancy can be managed medically. However, these patients require close monitoring.

Microbiome affecting reproductive outcome in ARTs.

Current scientific evidence reveals the importance of the human microbiome in health and disease. The presence of microbiota within the male and female reproductive tract has been well-documented and present theories imply that a possible disruption of their concentrations may have adverse effects on reproductive health and reproductive outcomes. Altered endometrial and vaginal microbiome could potential affect the reproductive outcome in infertile couples undergoing assisted reproductive techniques. Analysis of seminal fluids could also facilitate a prompt and appropriate approach in cases of abnormal male reproductive microflora. Essential knowledge on this subject could provide fertility experts better understanding with regards to unexplained fertility, increasing the success rates of ARTs. In this review, we summarise the current knowledge on the microbiota of the male and female reproductive tract and its impact on the success rates of ARTs in infertile couples.

Preeclampsia and long-term coronary artery disease: How to minimize the odds?

Preeclampsia (PE) is a hypertensive disorder of pregnancy that can cause detrimental obstetric outcomes if not managed properly. Current evidence demonstrates higher risk for long-term cardiovascular disease in preeclamptic women. Even in uncomplicated pregnancies, the heart work overload often reveals subtle cardiac defects or abnormalities, which otherwise remain undiagnosed in women without a history of pregnancy. Pathophysiologic patterns occurring in PE patients resemble biochemical responses observed in cases of cardiovascular disease. It has been estimated that women with an obstetric history of PE are more likely to develop coronary artery disease in the long run. Currently, additionally to whether any approach could actually contribute to minimizing mortality and morbidity among these affected populations, there is no consensus regarding management for these patients. In this review we summarized the current scientific evidence regarding the correlation between PE and long-term coronary artery disease. Based on this knowledge, we propose postpartum and lifetime management for these high-risk patients in order to minimize morbidity and mortality within this population.

Endometriosis in adolescence: Early manifestation of the traditional disease or a unique variant?

Little is known about Endometriosis in Adolescents and its prevalence is yet to be estimated. Traditional Endometriosis seems to be, by far, quite different with this unique variant when it comes to clinical presentation, management and course of the disease. Further research needs to be conducted in order to classify these two, phenomenically similar, diseases. Adolescents with a history of dysmenorrhea and chronic pelvic pain (CPP) imply findings suggestive of endometriosis. The severity of the disease is variable, from superficial endometriosis to deep endometriotic lesions or even ovarian endometriomas. The course of the disease also suggests the necessity of a more personalized approach since among adolescents, endometriosis could resolve or even aggravate with no particular pathophysiological pattern. Some studies suggest that appropriate treatment should be based on the understanding of the pathophysiologic mechanisms. Long term course of the disease, as well as, a high recurrence rate pose a difficulty to scientists, deciding conservative over operative surgery. Some believe that early operation on superficial forms of endometriosis could potentially prevent deep endometriotic lesions in the long-run. Others find medication such as, combined oral contraceptive pills (COCPs), progestins, levonorgestrel intrauterine device or gonadotrophin releasing hormone analogues (GnRHa), more appropriate for this age group. Last but not least, operation with post-operative hormonal treatment remains the most common treatment approach. Nevertheless, our limited understanding of the disease, as well as, particular factors needed to be taken into consideration, for instance, bone formation in this age group, underline the necessity of further studies, needed to be appointed, in order to determine the best diagnostic and therapeutic approach.

Female genital tract microbiota affecting the risk of preterm birth: What do we know so far? A review.

Spontaneous Preterm birth (SPTB) is a common obstetric complication affecting 12.9 million births worldwide and is the leading cause of neonatal morbidity and mortality. Disruption in the vaginal microbiota has an impact on the maternal immunological profile leading to SPTBs. Scientists have struggled to link maternal infectious agents with the dysregulation of the maternal immune response in cases of SPTBs. Throughout the last decade, important findings regarding the role of microbiota and its genome, the so-called microbiome, have linked alterations within the population of the microorganisms in our bodies with changes in nutrition, immunity, behaviour and diseases. In this review, evidence regarding the female genital tract microbiota and microbiome has been examined to help further our understanding of its role in disrupting the maternal immune system resulting in spontaneous preterm birth.

Changing the way we train surgeons in the 21th century: A narrative comparative review focused on box trainers and virtual reality simulators.

The traditional method of acquiring surgical skills by observing and assisting in surgical procedures involving human beings has been challenged during the past several years. Lessons obtained from aviation suggested that the use of simulators is related to reduced costs, increased efficiency in performing certain tasks and above all safety. A shift in paradigm is also required in modern surgical training. The development of endoscopic surgery allowed for the incorporation of medical simulators into training programmes. A review of the literature was conducted using specific inclusion and exclusion criteria, for articles published up to July 31th, 2018. Relevant studies were identified using computerized bibliographic searches of MEDLINE database. The keywords that were used in various combinations were: "Medical Simulators", "Surgical Training", "Laparoscopy", "Surgical Skills", "Box trainers", "Virtual reality simulators", "Surgical Education". Surgical training with box trainers and/or virtual reality simulators confers a significant benefit in terms of surgical skills development, increases patient safety and reduces costs. Nevertheless, the use of virtual reality simulators was significantly more expensive. Simulation training allows trainees to learn from their mistakes, to repeat surgical tasks multiple times so as to establish muscle memory, and enhance skill competency with the aid of informative feedback. Simulators are necessary for the development of the skills required to meet the specific needs of endoscopic surgery in the 21st century. Teaching hospitals should introduce simulation training programmes in order to increase efficiency, reduce costs and improve patient safety. As medical advancements continue to transform the way we perform surgery day by day, simulation training will play a pivotal role in every surgical specialty.

Sentinel lymph node detection by intranipple injection of patent blue dye in breast cancer: a preliminary report of a feasibility study.

Sentinel lymph node (SLN) biopsy is a well established option for assessing axillary lymph node status in breast cancer. Several techniques have been applied so far (superficial or deeper ones). Based on anatomical features of the lymphatic drainage in the breast, we assessed the feasibility of an intranipple approach for SLN mapping. Our data support the feasibility of SLN detection by our technique, with a high rate of SLN identification, which could be used in clinical practice as an alternative to the peri-areolar approach.

Women's knowledge and utilization of gynecological cancer prevention services in the Northwest of Greece.

PURPOSE OF INVESTIGATION: In Greece an organized cervical or breast cancer screening program does not exist and the population coverage is unknown. METHODS: Women of all ages completed a questionnaire, which assessed women's awareness of and participation in breast and cervical screening and human papillomavirus (HPV) vaccination. The women were randomly approached in public areas. RESULTS: 1,012 women completed the questionnaire. 52% of the women over 39 years old had undergone mammography in the last year and 76% of the women over 20 years old had a cervical smear test within the last three years in an opportunistic basis. In addition, the likelihood of having regular mammograms was positively associated with the likelihood of having regular cervical smears. Fifty percent of the responders did not identify HPV as the cause of cervical cancer and 38% were not aware of the HPV vaccine. From the women aged 16 to 28 years old, 11% had been vaccinated against HPV and an additional 23% intended to have the vaccine in the next six months. CONCLUSION: Knowledge and utilization of mammography and cervical screening was quite satisfactory, although HPV vaccination coverage was low. Preventive services could be improved through the development of a plan for the information of the public and the distribution of the HPV vaccine.

Reproductive outcome in patients treated by oral methotrexate or laparoscopic salpingotomy for the management of tubal ectopic pregnancy.

OBJECTIVE: To determine the reproductive outcome of women who have received methotrexate or been treated by laparoscopic salpingotomy (LS) for ectopic tubal pregnancy. STUDY DESIGN: The study consisted of 123 participants, all women with tubal pregnancies, who had been treated either by methotrexate per os or by laparoscopic salpingotomy. The reproductive outcome of these women was estimated after a follow-up time-period of ten years. RESULTS: In the methotrexate group, consisting of 34 women, the fertility rate was 82% with a mean interval time to conceive of 9.4 months after the treatment. In the group treated by LS, consisting of 89 women, the fertility rate was 82.6% and the mean interval time to conceive was 11.7 months. CONCLUSION: The reproductive outcome of the women who received either per os treatment of methotrexate or LS for tubal pregnancy, remains high. Both therapeutic methods constitute reliable solutions for managing ectopic pregnancy.

Fetal anal atresia presenting as transient bowel dilatation at 16 weeks of gestation.

Congenital anal atresia is a rare abnormality which in two thirds of the cases is associated with other congenital abnormalities or syndromes. Prenatal diagnosis is usually achieved in cases with coexisting abnormalities. The diagnosis of isolated anal atresia is extremely difficult and can be suspected in the presence of colon dilatation. We present the case of a fetus in which marked dilatation of the colon was diagnosed at 16 weeks of gestation. Four weeks later the sonographic appearance of the bowel was normal and remained normal for the rest of the pregnancy. Anal atresia was diagnosed immediately after birth and corrected surgically. No other abnormalities were present. This case report illustrates that in anal atresia, bowel dilatation may be only transient.

Selecting distending medium for out-patient hysteroscopy. Does it really matter?

BACKGROUND: The aim of this prospective randomized study was to evaluate the role of carbon dioxide (CO2) and normal saline for diagnostic accuracy in out-patient hysteroscopy. METHODS: Women admitted to our Department in order to undergo total abdominal hysterectomy also underwent diagnostic hysteroscopy, 12-24 h prior to surgery. The selection of distending medium was made after randomization. Two groups of patients were formed, group A (CO2; n=39) and group B (normal saline; n=35). More than half of the women in the study population were post-menopausal. Post-hysteroscopy, all women were asked to rank any symptom that they felt during the procedure on a 4-point scale (0=none; 1=mild; 2=severe; 3=inability to perform hysteroscopy). The hysteroscopic diagnosis was compared with the macroscopic findings and the histological examination of the surgical specimen after hysterectomy. RESULTS: The percentage who completed hysteroscopy was 89.74% within group A and 97.14% within group B. Most patients of both groups felt some pain of mild intensity. The diagnostic accuracy of hysteroscopy was similar for both media when major pathology [large polyps (group A 91.7%; group B 92.7%), myomas (group A 81.25%; group B 92.7%) and/or hyperplasia (group A 87.5%; group B 90.2%)] of the endometrial cavity was detected. In contrast, in cases of minor pathology (small polyps, mucosal elevations, crypts, hypervascularization), hysteroscopy with saline presented with significantly higher diagnostic accuracy (85.4%) compared with hysteroscopy with CO2 (64.6%). CONCLUSIONS: In out-patient hysteroscopy, CO2 and normal saline were comparable with regard to patient discomfort and for the detection of major pathology of the endometrial cavity. Normal saline seems to be the most appropriate medium for the detection of minor pathology of the endometrial cavity.

Apoptosis in human endometrium and endometriosis.

Apoptosis plays a critical role in maintaining tissue homeostasis and represents a normal function to eliminate excess or dysfunctional cells. Accumulated evidence suggests that apoptosis helps to maintain cellular homeostasis during the menstrual cycle by eliminating senescent cells from the functional layer of the uterine endometrium during the late secretory and menstrual phase of the cycle. The BCL-2 family and Fas/FasL system have been extensively studied in human endometrium and endometriotic tissues. Eutopic endometrium from women with endometriosis reportedly has some fundamental differences compared with normal endometrium of women without endometriosis. The differences could contribute to the survival of regurgitating endometrial cells into the peritoneal cavity and the development of endometriosis. One mechanism that recently gained a lot of interest is the finding that apoptosis appeared in eutopic and ectopic endometrium of patients with endometriosis. This study is a current review of the literature focused on the physiological role of apoptosis in normal endometrium and the alterations in regulation of apoptosis in eutopic and ectopic endometrium from women with endometriosis. Similarities in characteristics of endometriosis at a molecular level with gynaecological tumours are also discussed. Finally, the role of apoptosis in the treatment of endometriosis is reviewed to link the basic research findings into clinical applications.

Factors affecting outcome after incomplete excision of cervical intraepithelial neoplasia.

PURPOSE: Conservative treatment for cervical intraepithelial neoplasia (CIN) by ablative or excisional techniques is widely used. However, women with incomplete excision have a variable risk of CIN recurrence. The aim of this study was to identify possible risk factors for recurrence of CIN after large loop excision of the transformation zone (LLETZ) with involved margins of excision. METHODS: All cases of women treated with LLETZ for CIN between 1989-2000, in whom histological evaluation of the excised specimen revealed extension of CIN to the excision margins, were retrospectively studied. A woman was considered to have recurrence when she had histologically confirmed CIN following a second LLETZ or hysterectomy during the follow-up period. The characteristics that were examined as possible risk factors were age, parity, smoking habit, grade of initial lesion and extension to the endo- or ectocervical margin. RESULTS: Treatment failure was diagnosed in 18 out of 65 (27.7%) women with involved margins. The only characteristic that reached statistical significance was age. The mean age of women with recurrence was 35.8 years, whereas the mean age of women without recurrence was 32.8 years (p = 0.044). Also, a trend was evident in women with high-grade initial lesions (CIN II-III) (p = 0.168) and involvement of the endocervical margins (p = 0.149). No differences were observed between the two groups regarding parity and smoking habit. CONCLUSIONS: Increased age is a risk factor for recurrence in women with incomplete excision of CIN after LLETZ. Larger studies are required for definite conclusions.

An observational study of women with positive HPV-DNA tests and normal cytology and colposcopy.

PURPOSE: High risk human papillomaviruses (HPV) are implicated in the aetiology of malignant cervical disease. The usefulness of HPV DNA tests in identifying women at risk of cervical cancer as an adjunct to cervical cytology is under evaluation. PATIENTS AND METHODS: This is a retrospective analysis of 47 women positive for high risk HPV but with negative cytology and negative colposcopy at the start of the study. Women were observed for three years or more (in 96% cases) using six-monthly combined HPV DNA tests, cytological and colposcopic evaluation. RESULTS: At the end of follow-up, 29/47 (62%) women were still positive for high risk HPV, 45/47 (96%) women had normal cytology and 47/47 (100%) women continued to have normal colposcopy. CONCLUSIONS: Normal colposcopy has an excellent negative predictive value for HPV positive women with normal cytology. These women can be safely screened cytologically on a three-yearly basis.

Surgical management of early stage cervical cancer: ten years experience from one Greek health region.

PURPOSE OF INVESTIGATION: Cervical cancer is the second most common malignancy in women, in both incidence and mortality. In the present study, we report our results of treating 93 consecutive patients with early invasive cervical cancers (Stages I-IIA). METHODS: The patients of this study comprised all women recognized with stage I-IIA cervical cancer during 1991-2000. Patients with stage IA1 cervical cancer without lymphvascular space involvement underwent either conservative management by means of large loop conization or simple hysterectomy. The remaining patients underwent radical hysterectomy and lymphadenectomy or radiation therapy. Mean (+/- SD) duration of follow-up was 6 (+/- 1.7) years. RESULTS: The mean (+/- SD) age of patients with stage I-IIA cervical cancer was 41.3 (+/- 9.1) year. Thirty-five patients with stage [A1 disease were managed conservatively with loop excision and 19 patients subsequently became pregnant. Fifty-two patients with stage IA2, IB and IIA cervical carcinoma underwent radical hysterectomy and lymphadenectomy. CONCLUSION: Young women with stage IA1 cervical carcinoma wishing future fertility who undergo loop excision have a 100% cure rate. Women with stage IA2, IB, and IIA cervical cancer should undergo radical hysterectomy and lymphadenectomy or radiation therapy.

Large loop excision of the transformation zone for treating cervical intraepithelial neoplasia: a 12-year experience.

BACKGROUND: Although the existing evidence suggests that there is no obviously superior conservative method for treating cervical intraepithelial neoplasia (CIN), one of the most widely used is the large loop excision of the transformation zone (LLETZ). MATERIALS AND METHODS: A total of 897 women who were treated with LLETZ at our colposcopy clinic from 1989 to 2000 were retrospectively studied. RESULTS: Forty women did not have significant cervical pathology (4.5% over-treatment rate). Clear margins of excision were obtained in 748 (88.5%) of the 845 cases of CIN or microinvasive cancers. Treatment failure rates were 4.7% for clear margins and 26.8% for involved or uncertain. CONCLUSION: LLETZ is a fast and reliable method of treating CIN and microinvasive carcinoma. Generalized cauterization of the resulting crater should be avoided and satellite HPV lesions ablated. Involved margins have a higher treatmentfailure rate, therefore a larger excision is recommended as cervical craters regenerate. Treatment in pregnant women can be delayed until postpartum provided they have adequate surveillance during pregnancy.

Vaginoscopic hysteroscopy and transvaginal sonography in the evaluation of patients with abnormal uterine bleeding.

STUDY OBJECTIVE: To compare accuracy of vaginoscopic hysteroscopy, a new method of outpatient hysteroscopy, with that of transvaginal sonography in diagnosing intracavitary pathology in women with abnormal uterine bleeding. DESIGN: Retrospective comparative study (Canadian Task Force classification II-2). SETTING: Department of gynecology in a tertiary care university hospital. PATIENTS: Three hundred ninety-seven consecutive patients. INTERVENTIONS: Vaginoscopic hysteroscopy, transvaginal sonography, and histologic evaluation of endometrium. MEASUREMENTS AND MAIN RESULTS: Findings at hysteroscopy and sonography were compared with histopathologic results, considered the gold standard diagnosis. Sensitivity, specificity, and positive and negative likelihood ratios were 92%, 95%, 18.4, and 0.08 for vaginoscopic hysteroscopy and 67%, 87%, 5.15, and 0.38 for transvaginal sonography, respectively. CONCLUSION: Vaginoscopic hysteroscopy is quick and well tolerated, and more accurate in detecting intracavitary uterine pathology than transvaginal sonography. More research is required to determine its place in patients with abnormal uterine bleeding, especially premenopausal women.

The use of transvaginal sonography and vaginoscopic hysteroscopy in women on tamoxifen.

BACKGROUND AND OBJECTIVES: Long-term administration of tamoxifen causes endometrial changes. The aim of this study was to evaluate the role of transvaginal sonography and vaginoscopic hysteroscopy in the screening of patients on tamoxifen. METHODS: Seventy patients with breast cancer treated with tamoxifen 20 mg daily underwent transvaginal sonography and vaginoscopic hysteroscopy, a modified relatively painless approach, at the beginning of the treatment and at a follow-up visit approximately 9 months after its initiation. RESULTS: At the follow-up visit, the mean uterine dimensions and mean endometrial thickness as measured by ultrasound were significantly larger, and pulsatility and resistance indices of the uterine arteries as measured by Doppler were significantly lower. Sonography revealed abnormal endometrial thickness in 73% (51 of 70) of the patients, and 83% (58 of 70) had hysteroscopical changes. Sonography missed 1 case of endometrial adenocarcinoma. CONCLUSIONS: Vaginoscopic hysteroscopy, an approach that causes reduced pain, can add significantly to the sensitivity of transvaginal sonography for the detection of endometrial changes in patients with breast cancer receiving tamoxifen. It is recommended for every patient prior to the initiation of treatment and at the follow-up visits.