Placenta Accreta Spectrum: A Comprehensive Review of Guidelines.

Importance: Placenta accreta spectrum (PAS) represents a range of disorders characterized by abnormal placental invasion and is associated with severe maternal morbidity and mortality. Objective: The aim of this study was to review and compare the most recently published major guidelines on the diagnosis and management of this potentially life-threatening obstetric complication. Evidence Acquisition: A descriptive review of guidelines from the American College of Obstetricians and Gynecologists, the Royal Australian and New Zealand College of Obstetricians and Gynecologists, the International Society for Abnormally Invasive Placenta, the Royal College of Obstetricians and Gynecologists, the International Federation of Gynecology and Obstetrics, and the Society of Obstetricians and Gynecologists of Canada on PAS disorders was carried out. Results: There is a consensus among the reviewed guidelines regarding the definition and the diagnosis of PAS using specific sonographic signs. In addition, they all agree that the use of magnetic resonance imaging should be limited to the evaluation of the extension to pelvic organs in case of placenta percreta. Moreover, American College of Obstetricians and Gynecologists, Royal College of Obstetricians and Gynecologists, International Federation of Gynecology and Obstetrics, and the Society of Obstetricians and Gynecologists of Canada agree that screening for PAS disorders should be based on clinical risk factors along with sonographic findings. Regarding management, they all highlight the importance of a multidisciplinary team approach and recommend delivery by elective cesarean section at a tertiary center with experienced staff and appropriate resources. Routine preoperative ureteric stenting and occlusion of pelvic arteries are universally not recommended. Moreover, hysterectomy following the delivery of the fetus, expectant management with placenta left in situ, and conservative management in case of focal disease and desired fertility are all considered as acceptable treatment options. The reviewed guidelines also suggest some measures for intraoperative and postoperative hemorrhage control and recommend prophylactic administration of antibiotics. Methotrexate after expectant management is unanimously discouraged. On the other hand, there is no common pathway with regard to the optimal timing of delivery, the recommended mode of anesthesia, the preferred skin incision, and the effectiveness of the delayed hysterectomy approach. Conclusions: PAS disorders are mainly iatrogenic conditions with a constantly rising incidence and potentially devastating consequences for both the mother and the neonate. Thus, the development of uniform international practice protocols for effective screening, diagnosis, and management seems of paramount importance and will hopefully drive favorable pregnancy outcomes.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy in recurrent ovarian cancer: 18 years of experience.

AIM: To identify the clinical and pathological factors associated with relapse in women who had undergone secondary cytoreductive surgery due to locally advanced recurrent ovarian cancer. METHODS: Women with locally advanced recurrent ovarian cancer who had undergone cytoreduction between 2000 and 2018 were included in this study. Demographic, clinical and biochemical intraoperative findings were recorded for each woman. All factors were assessed in order to identify which correlated with the outcomes of interest (i.e. disease relapse, mortality and morbidity). RESULTS: In total, 181 women who had undergone secondary cytoreduction were analysed. The hospital mortality rate was 1.7 % (n = 3) and the morbidity rate was 32.1 % (n = 58). Recurrence was recorded in 101 (55.8 %) women. Infiltration of large bowel lymph nodes was a negative prognostic indicator of morbidity (p = 0.029). A prior surgical score of 1 (PSS-1) [odds ratio (OR) 0.465] and complete cytoreduction (OR 0.518) were found to be significant independent predictors for disease relapse. Median overall survival was greater for patients with PSS-1 (151.3 vs 59.4 vs 44.1 months; p = 0.049) and patients with complete cytoreduction (137.6 vs 36.2 vs 10.0 vs 27.4 months; p < 0.001). CONCLUSION: Complete cytoreduction and PSS-1 are associated with reduced disease relapse and increased overall survival. Infiltration of large bowel lymph nodes is associated with increased morbidity.

CYLD expression in endometrial carcinoma and correlation with clinicohistopathological parameters.

OBJECTIVE: Endometrial cancer is a threat to women health worldwide. Cylindromatosis (CYLD) enzyme is a tumour suppressor, considered an effective prognostic marker in various malignancies, but its role in endometrial carcinoma is not fully elucidated. Here, we sought to estimate the prognostic value of CYLD expression in endometrial carcinoma. MATERIALS AND METHODS: CYLD levels were immunohistochemically evaluated in 65 patients with endometrial carcinoma and inferential statistics were applied. RESULTS: Low or negative CYLD expression significantly correlates with older ages, non-endometrioid and invasive carcinomas, tumours with moderate or poor differentiation and advanced stages. Moreover, non-endometrioid and invasive carcinomas are independent risk factors for weaker CYLD expression. Kaplan-Meier analysis illustrated that negative or low CYLD expression is statistically significantly associated with increased death risk, compared to moderate or high expression. CONCLUSION: This study demonstrates for the first time a clear correlation between CYLD expression and clinicohistopathological parameters of endometrial carcinoma patients, suggesting its use as a potential prognostic/predictive marker for Endometrial Carcinoma.

STORK: Collaborative Online Monitoring of Pregnancies Complicated with Gestational Diabetes Mellitus.

Background: A novel digital platform, named STORK, was developed in the COVID-19 pandemic when clinic visits were restricted. A study of its clinical use during the pandemic was conducted. The study aims to advance the state of the art in monitoring and care of pregnancies complicated with gestational diabetes mellitus (GDM) via online collaboration between patients and care providers. Methods: This study involved 31 pregnant women diagnosed with GDM and 5 physicians. Statistical comparisons were made in clinic-visit frequency and adverse outcomes between the STORK group and a historical control group of 32 women, compatible in size, demographics, anthropometrics and medical history. Results: The average number of submitted patient measurements per day was 3.6±0.4. The average number of clinic visits was 2.9±0.7 for the STORK group vs. 4.1±1.1 for the control group (p<0.05). The number of neonatal macrosomia cases was 2 for the STORK group vs. 3 for the control group (p>0.05); no other adverse incidents. Conclusions: The patient compliance with the pilot use of STORK was high and the average number of prenatal visits was reduced. The results suggest the general feasibility to reduce the average number of clinic visits and cost, with enhanced monitoring, case-specific adaptation, assessment and care management via timely online collaboration.

Axillary lymph node dissection vs. sentinel node biopsy for early-stage clinically node-negative breast cancer: a systematic review and meta-analysis.

ΟBJECTIVE: This study aimed at comparing survival outcomes between systematic axillary lymph node dissection (ALND) vs sentinel lymph node and axillary lymph node dissection only if sentinel positive (SLN ± ALND) in early-stage, clinically node-negative breast cancer patients. ΜETHODS: A systematic review and meta-analysis adhered to PRISMA guidelines was performed. Included studies were prospective randomized controlled trials (RCTs) comparing survival outcomes of ALND vs. SLN ± ALND in early-stage, node-negative breast cancer patients. Patients enrolled were only those with tumor size lower than 4 cm, clinically negative nodes and treated with breast-conservative surgery. Primary endpoints were locoregional recurrence, overall death and cancer-related death. RESULTS: There were four studies included in the analysis, enrolling overall 2982 patients, of which 1494 in ALND arm and 1488 in the SLN ± ALND arm. No statistically significant difference was observed in locoregional recurrence, breast cancer-related death and overall death. Locoregional recurrence was observed in 2.8% (ALND) vs. 4.1% (SLND ± ALND), (RR 0.69, 95% CI 0.20-2.30). Overall death rate was 7.0% vs. 6.8% respectively, (RR 1.00, 95% CI 0.73-1.39, I2 = 28.7%). Breast cancer-related death was 3.6% vs. 3.5%, respectively (SLN ± ALND), (RR 1.11, 95% CI 0.70-1.78, I2 = 0%). No statistically significant difference was observed in any of secondary study outcomes. CONCLUSIONS: Systematic axillary axillary lymph node dissection provides no survival benefit compared with sentinel lymph node dissection for early-stage clinically node-negative breast cancer patients.

Differential apoptotic activity in trophoblast of spontaneous abortions and normal pregnancies.

INTRODUCTION: Apoptosis is a key process during normal trophoblastic development and, consequently, the whole gestation. However, in trophoblastic differentiation in spontaneous abortions apoptosis has been hardly investigated. Therefore, the aim of the study was to investigate the correlation between apoptotic frequency in trophoblast and spontaneous abortion incidences. MATERIAL AND METHODS: A total of 72 trophoblastic tissue samples were immunohistochemically examined. 42 of 72 derived from first-trimester spontaneous abortions and the remaining 30 from elective terminations during the same trimester of pregnancy. TUNEL assay and M30 marker were used for apoptosis evaluation by immunohistochemistry. RESULTS: Comparative study of tissues from spontaneous abortions and elective pregnancy terminations demonstrated increased expression of both apoptotic markers in tissues derived from spontaneous abortions compared to normal pregnancies. In addition, statistical analysis correlated maternal age and gravidity with increased spontaneous abortion incidences. Moreover, both M30 and TUNEL staining were significantly correlated with maternal age and primigravidity in spontaneous abortion cases. CONCLUSIONS: Our data proved that elevated apoptotic activity during the first pregnancy trimester is clearly involved in spontaneous abortions. Moreover, two well-established apoptotic markers revealed high statistical significance in the evaluation of post-abortive tissues.

Dilatation and curettage in endometrial cancer. What is the correlation with hysterectomy histology? A 14 years retrospective cohort study.

PURPOSE: The aim of the present study is to evaluate the concordance between preoperative endometrial sampling histopathology performed by conventional dilatation and curettage (D&C) and final histopathological diagnosis after total hysterectomy concerning tumor grade and subtype in patients with endometrial cancer (EC). METHODS: In this comparative retrospective study, 203 women with endometrial cancer were included who underwent at first dilatation and curettage and then total hysterectomy. The preoperative histopathological report obtained by dilatation and curettage was compared with the final histopathology after total hysterectomy to assess the accuracy of endometrial sampling. RESULTS: Comparison of preoperative with postoperative histopathological results showed an overall 5.9% and 10.9% discordance regarding endometrial cancer histological subtype and grade, respectively. Six (4.9%) of the patients with preoperative grade 1 were grade 2 and 1 (0.8%) was found to be grade 3. Three (8.3%) of the patients with preoperative grade 2 were found to be grade 3 after hysterectomy. Discordance is higher for endometrioid endometrial cancer grade 2 (25%) compared with grade 1 (5.7%) and 3 (18.8%). CONCLUSION: Patients should be informed and consent for the potential discrepancy between the pre and postoperative histopathological features of malignancy. This discrepancy may result in either under or overtreatment. Thus, it should be accounted for when counseling for a major operation.

Isolated torsion of the fallopian tube associated with hydrosalpinx in a 17-year-old sexually inactive girl: A case report.

Isolated tubal torsion is an unusual cause of acute abdominal pain in young sexually inactive patients. However, it should be still taken into account regarding the differential diagnosis of such conditions.

Human papillomavirus in breast cancer of patients with cervical intraepithelial neoplasia or cervical cancer history. A systematic review and meta-analysis.

PURPOSE: Many cohort studies and meta-analyses support the oncogenic role of the human papilloma virus (HPV) on breast tissue. However, only a few studies examine the association between HPV-positive breast cancer and the prior history of high grade cervical intraepithelial neoplasia (CIN) or cervical cancer. The present systematic review and meta-analysis aimed to determine whether women with a history of high grade CIN or cervical cancer are at a higher risk of developing HPV-positive breast cancer. METHODS: MEDLINE, CENTRAL and Scopus databases as well as "gray literature" sources were searched for case-control studies, detecting and genotyping HPV genome in breast cancer patients with and without a history of CIN or cervical cancer, from inception to October 23, 2020. RESULTS: The meta-analysis included three case-control studies with 265 breast cancer patients in total. HPV related breast cancer was associated with a history of high grade CIN or cervical cancer [pooled odds ratio (OR) =7.98, 95% confidence interval (CI), 1.84 to 34.67]. This association remained regarding HPV-16 related breast cancer (pooled OR =7.60, 95% CI, 1.75 to 33.00). CONCLUSIONS: HPV was detected more frequently in breast cancer patients with CIN or cervical cancer history. Therefore, further research is necessary to understand better the HPV transmission route to the breast.

Breast Disorders in Adolescence: A Review of the Literature.

BACKGROUND: Adolescence is accompanied by a variety of changes in young breast development, which greatly affects the adolescent's psychology and socialization. SUMMARY: PubMed, EMBASE, and the Cochrane Library were searched for studies relative to epidemiology, clinical characteristics, diagnosis, and management of all breast disorders in adolescence and their consequences. Development disorders are breast asymmetry, breast atrophy, breast hypoplasia, hypomastia, juvenile breast hypertrophy, and tuberous breast. Breast congenital abnormalities include athelia, amastia, accessory breast tissue, polymastia, polythelia, and congenital disorders of nipples. Breast infections are commonly caused from Gram-positive coccus rather than Gram-negative bacteria. Breast abscess occurs when breast infections are not promptly treated. Nipple discharge is caused by a variety of conditions and should be managed carefully. Fibrocystic changes, cysts, and fibroadenomas are the most common benign masses in adolescence. Primary, secondary, or metastatic breast cancer is extremely rare in adolescence. However, clinicians should include breast cancer in the differential diagnosis of a breast mass in adolescence. KEY MESSAGES: Clinicians should be aware of all breast disorders that may occur in adolescence. Early diagnosis and treatment will result in the reassurance of adolescents and their families without any detrimental effect on their psychology, sexual behavior, and socialization. Adolescents with breast disorders may require a multidisciplinary approach by a pediatrician, a gynecologist specializing in pediatric-adolescent gynecology, a plastic surgeon, and a psychologist for the best management of breast disorders.

Lipid Disorders in Pregnancy.

Dyslipidemia represents a major risk factor for cardiovascular disease. In addition, severe hypertriglyceridemia is an important cause of acute pancreatitis. Accordingly, the increase in serum lipid levels that is observed during pregnancy has potentially important implications. The management of dyslipidemia in pregnancy is further complicated by the lack of safety data during this period for most of the lipid-lowering agents. In the present review, we discuss the most important lipid disorders in pregnant women and their management. Pregnancy is characterized by increases in both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, which might result in severe complications both for the mother and the fetus. Accordingly, LDL-C and triglyceride levels should be monitored during pregnancy, particularly in women with a history of dyslipidemia. Diet is the mainstay of management of dyslipidemia in pregnant women and apheresis can also be considered in patients with homozygous familial hypercholesterolemia or severe hypertriglyceridemia. However, there is a pressing need for studies that evaluate the safety of lipid-lowering agents during pregnancy.

Early delivery or expectant management for late preterm preeclampsia: A meta-analysis of randomized controlled trials.

INTRODUCTION: Currently, there is no consensus regarding the timing of delivery in women with non-severe preeclampsia at the late preterm period. The aim of the present meta-analysis is to compare expectant management with immediate delivery in pregnant women with preeclampsia between 34+0 and 36+6 gestational weeks, in terms of maternal and neonatal outcomes. MATERIAL AND METHODS: A search was conducted until October 1, 2020 and eligible studies were identified in MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (Central), the US Registry of clinical trials (www.clinicaltrials.gov), and sources of gray literature without limitations concerning the publication dates and languages. Randomized controlled trials, comparing planned delivery vs expectant management in women with preeclampsia at 34-37 weeks were included. The primary outcomes were neonatal intensive care unit (NICU) admission and progression to eclampsia. Secondary outcomes were HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, severe preeclampsia, composite adverse maternal outcome (defined by the presence of any of the potential preeclampsia-related complications, ranging from severe hypertension to maternal death), neonatal respiratory disease, and respiratory distress syndrome. Relative risks (RRs) and mean differences with 95% CI were used for the estimation of the effect sizes; the quality of the evidence was assessed per GRADE guidelines. RESULTS: The electronic search yielded 10 721 potential studies, of which six were fully reviewed and three (1773 participants) were included in the meta-analysis. Immediate delivery increased the risk for NICU admission, (RR 1.23, 95% CI 1.05-1.45) and decreased the risk for the composite adverse maternal outcome (RR 0.86, 95% CI 0.78-0.93). There were no differences for eclampsia (RR 0.55, 95% CI 0.16-1.85), HELLP syndrome (RR 0.58, 95% CI 0.25-1.33), severe preeclampsia (RR 0.27, 95% CI 0.02-3.52), respiratory disease of neonate (RR 1.04, 95% CI 0.75-1.44), and respiratory distress syndrome (RR 2.3, 95% CI 0.73-7.25). CONCLUSIONS: Immediate delivery of women with non-severe preeclampsia at the period of late prematurity decreases the risk of a composite adverse maternal outcome by 14%, at the cost of an increase in NICU admissions by 23%. The overall quality of the evidence for these outcomes is high, indicating a high degree of certainty for the results.

Human papilloma virus infection and miscarriage: is there an association?

Human papilloma virus (HPV) infection is the most common viral infection of the reproductive tract. HPV infection is more prevalent in pregnant than in age-matched non-pregnant women and its prevalence increases as pregnancy progresses. A number of reports evaluated the role of HPV infection in miscarriages. In the present review, we summarize the existing evidence regarding the association between HPV infection and miscarriage. It is still unclear whether HPV infection is associated with increased risk for miscarriage. Studies in the field yielded conflicting findings and their conclusions are limited by a small sample size and/or methodological limitations. On the other hand, preclinical data support a role of HPV infection in placental dysfunction. Given the high prevalence of HPV infection and the possibility that vaccination against HPV might protect against miscarriage, more studies are needed to elucidate whether this common infection is associated with increased risk for miscarriage.

Cervical, anal and oral HPV detection and HPV type concordance among women referred for colposcopy.

BACKGROUND: Infection with human papillomaviruses (HPVs) can cause benign and malignant tumours in the anogenital tract and the oropharynx both in men and women. The aim of the presented study was to investigate cervical, anal, and oral HPV-detection rates among women referred to colposcopy for abnormal Cervical Cancer (CaCx) screening results and assess the concordance of HPV-types among these anatomical sites. METHODS: Women referred to colposcopy at a single centre due to abnormal cytology, conducted for CaCx screening, were subjected to cervical Liquid-based Cytology (LBC) smear testing, anal and oral sampling. Routine colposcopy consisted in multiple biopsies and/or Endocervical Curettage (ECC). HPV-detection was performed by PCR genotyping in all three anatomical sites. In high-risk (hr) HPV-DNA positive samples either from anal canal or oral cavity, anal LBC cytology and anoscopy were performed, or oral cavity examination respectively. Descriptive statistics was used for the analysis of HPV-detection rates and phi-coefficient for the determination of HPV-positivity concordance between the anatomical sites. RESULTS: Out of 118 referred women, hr. HPV-DNA was detected in 65 (55.1%), 64 (54.2%) and 3 (2.5%) at cervix, anal canal and oral cavity respectively while low-risk HPV-DNA was detected in 14 (11.9%) and 11 (9.3%) at cervix and anal canal respectively. The phi-coefficient for cervix/anal canal was 0.392 for HPV16, 0.658 for HPV31, 0.758 for HPV33, - 0.12 for HPV45, 0.415 for HPV52 and 0.473 for HPV58. All values were statistically significant (p < 0.001). CONCLUSIONS: The results suggest that most HPV-types, high-risk and low-risk, detected in the cervix of women with prevalent cervical dysplasia, correlate with the ones detected in their anal canal. This particularly applies for the HPV-types included in the nonavalent HPV-vaccine (HPVs 6/11/16/18/31/33/45/52/58).

The Role of ARID1A in Endometrial Cancer and the Molecular Pathways Associated With Pathogenesis and Cancer Progression.

AT-rich interaction domain 1A gene (ARID1A) encodes for a subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, a chromatin remodeling complex, and it has been implicated in the pathogenesis of various cancer types. In this review, we discuss how ARID1A is linked to endometrial cancer and what molecular pathways are affected by mutation or inhibition of ARID1A. We also discuss the potential use of ARID1A not only as a prognostic biomarker, but also as a target for therapeutic interventions.

Greek gynecology healthcare professionals towards quality management systems.

PURPOSE: Today, quality management systems (QMS) are a promising candidate for the improvement of healthcare services. The purpose of this paper is to investigate the opinions/attitudes of gynecology healthcare professionals toward quality and quality management in healthcare facilities (HFs) in Greece. DESIGN/METHODOLOGY/APPROACH: An anonymous self-administered questionnaire was distributed to healthcare professionals, asking for opinions on quality objectives associated with the everyday workflow in HFs (e.g. management of patients, resources, etc.) and on QMS. The study was conducted in Hippokration Hospital of Thessaloniki, including 187 participants. Statistical assessment and analysis of the questionnaires were carried out. FINDINGS: Although 87.5 percent recognized the importance of potential QMS implementation and accreditation, over 50 percent believed that it would lead rather to increased workload and bureaucracy than to any considerable quality improvement. More than 60 percent were completely unaware of the implementation of quality objectives such as quality handbook, quality policy, audit meetings and accreditation status in their HFs. This unawareness was also reported in terms of patient, data, human and general resources management. Finally, awareness over medical malpractice and positive attitude toward official reporting were detected. ORIGINALITY/VALUE: Most respondents acknowledged the significance of quality, QMS implementation and accreditation in Greek hospitals. However, there was a critical gap in knowledge about quality management objectives/processes that could be possibly resolved by expert teams and well-organized educational programs aiming to educate personnel regarding the various quality objectives in Greek HFs.

Paraaortic lymphadenectomy in intermediate to high risk uterine endometrioid cancer : a retrospective evaluation.

PURPOSE: To investigate the impact on survival of paraaortic lymph node dissection (PALND) added to pelvic lymph node dissection (PLND) in patients with intermediate to high-risk endometrioid endometrial cancer (EC ). Surgical parameters and perioperative morbidity have been explored as well. METHODS: We retrospectively identified all eligible patients that received LND as part of their primary treatment at a single institution from January 2000 to December 2010. Survival curves for overall (OS), disease-specific (DSS) and disease-free (DFS) survival were plotted by the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazards regression was used for multivariable analysis for OS and DSS. RESULTS: 93 patients underwent PLND plus PALND in their initial operation (PALND group) and 177 patients underwent PLND only (no-PALND group). Patients in the non-PALND group were older, more obese and had higher rates of comorbidities. The median number of PLN and PALN retrieved were 26 and 13 respectively. Isolated PALN metastasis was seen in 2 (2.1%) patients. PALND was associated with longer operative time, higher transfusion rate and longer hospital stay. PALND group had a benefit in OS (p=0.033), which did not persist in DSS or DFS. Furthermore, the type of LND did not significantly improve either OS or DSS according to the multivariate analysis results. CONCLUSION: PALND had no therapeutic value per se in women with intermediate to high risk endometrioid tumors and the improvement seen in OS should rather be attributed to the better medical status of women who received PALND.