Uterine perivascular epithelioid cell tumors (PEComa) and the accuracy of proposed classification systems in predicting the malignant versus non-malignant behavior.

OBJECTIVE: To compare the accuracy of available classification systems (Folpe, modified Folpe, Bennet, and Schoolmester) in predicting the behavior of uterine Perivascular Epithelioid Cell tumors (PEComas). METHODS: We reviewed the pathology registry to identify all uterine PEComas treated at our center. We conducted a systematic literature review searching electronic databases from inception to November 2023. We included all references reporting at least one case of uterine PEComa; cases associated with tuberous sclerosis complex were excluded. Patient-level data were extracted by identified records. Survival analysis was used to assess the accuracy of all proposed classification systems to classify uterine PEComas as malignant versus non-malignant. RESULTS: Six uterine PEComas were treated at our center. The literature search identified 101 uterine PEComas from 32 studies. Eighty-five out of 107 PEComas (28 studies and our series) reported enough follow-up data and details to apply all four classifications. The modified Folpe classification demonstrated the highest hazard ratio (HR) for relapse (HR:8.63; 95% confidence interval [CI] 2.06-36.1) and death due to PEComa (HR:6.8, 95%CI:0.89-51.6) for malignant versus non-malignant PEComas. Changing the cut-off of PEComa size to ≥8 cm and mitotic figures per 50 high power fields to ≥5, the HR for recurrence lowered (HR:6.26; 95% CI 2.20-17.80), but HR for death increased (HR:10.3; 95% CI 1.35-77.80). CONCLUSIONS: The modified Folpe classification was the most accurate in predicting the PEComa behavior. Changing the cut-off of PEComa size and number of mitotic figures may improve the accuracy in predicting death due to disease.

Intrauterine manipulator during hysterectomy for endometrial cancer: a systematic review and meta-analysis of oncologic outcomes.

OBJECTIVE: This study aimed to assess the effects on oncologic outcomes of intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer. DATA SOURCES: A systematic literature search was performed by an expert librarian in multiple electronic databases from inception to January 31, 2023. STUDY ELIGIBILITY CRITERIA: We included all studies in the English language that compared oncologic outcomes (recurrence-free, cause-specific, or overall survival) between endometrial cancer patients who underwent total laparoscopic or robotic hysterectomy for endometrial cancer with vs without the use of an intrauterine manipulator. Studies comparing only peritoneal cytology status or lymphovascular space invasion were summarized for completeness. No selection criteria were applied to the study design. METHODS: Four reviewers independently reviewed studies for inclusion, assessed their risk of bias, and extracted data. Pooled hazard ratios with 95% confidence intervals were estimated for oncologic outcomes using the random effect model. Heterogeneity was quantified using the I2 tests. Publication bias was assessed by funnel plot and Egger test. RESULTS: Out of 350 identified references, we included 2 randomized controlled trials and 12 observational studies for a total of 14 studies and 5,019 patients. The use of an intrauterine manipulator during hysterectomy for endometrial cancer was associated with a pooled hazard ratio for recurrence of 1.52 (95% confidence interval, 0.99-2.33; P=.05; I2=31%; chi square P value=.22). Pooled hazard ratio for recurrence was 1.48 (95% confidence interval, 0.25-8.76; P=.62; I2=67%; chi square P value=.08) when only randomized controlled trials were considered. Pooled hazard ratio for overall survival was 1.07 (95% confidence interval, 0.65-1.76; P=0.79; I2=44%; chi square P value=.17). The rate of positive peritoneal cytology or lymphovascular space invasion did not differ using an intrauterine manipulator. CONCLUSION: Intrauterine manipulator use during hysterectomy for endometrial cancer was neither significantly associated with recurrence-free and overall survival nor with positive peritoneal cytology or lymphovascular space invasion, but further prospective studies are needed.

Major vessel resection for complete cytoreduction in primary advanced and recurrent ovarian malignancies: A case series and systematic review of the literature - pushing the boundaries in oncovascular surgery.

INTRODUCTION: Oncovascular surgery (the removal of major blood vessels infiltrated by cancer) is challenging but can be key to achieve complete cytoreduction in patient with advanced ovarian cancer. The aim of this study was to review the literature on oncovascular surgery in ovarian cancer and to report the details of all the cases performed at our institution. METHODS: We retrospectively reviewed the database of ovarian cancer patients who underwent debulking surgery at the Department of Obstetrics and Gynecology of Verona University between January 2021 and 2023. Patients with at least one major vessel resection during cytoreduction were identified. We then systematically review the literature searching Pubmed and Embase from inception to January 2023 to report all cases of surgery for ovarian cancer with concomitant major vessel resection. RESULTS: Five patients with advanced/recurrent ovarian cancer underwent major vascular resection at our institution. Vascular involvement was preoperatively identified in all cases and no case of vascular resection was performed after accidental injury. The major vessels removed were the inferior vena cava (n = 2), the common iliac veins (n = 2), the external iliac arteries (n = 2), the left common iliac artery (n = 1), and the left external iliac vein (n = 1). All patients underwent other non-gynecological cytoreductive procedures prior to vessel removal and had R0 obtained. Three (60%) patients experienced one or more postoperative complications. The literature search identified a total of seven cases of major vessels resection in ovarian cancer surgery. A single or multiple major vessels were removed in two (28.6%) and five (72.4%) cases, respectively. All the seven patients underwent vascular reconstruction. Four (57.1%) patients reported postoperative complications. Overall, 66.7% of the 12 total identified patients were free from disease at the last follow-up [median 15.5 months (range 5-25)]. CONCLUSIONS: Oncovascular surgery is feasible in selected patients with ovarian cancer, provided that a multidisciplinary approach with customized care is available.

Perturbations in kinetics of the thrombin generation assay identify women at risk of preeclampsia in the first trimester and provide the rationale for a preventive approach.

BACKGROUND: Activation of the coagulation system and increased thrombin generation have been implicated in the pathophysiology of preeclampsia, and this rationale supports the administration of low-molecular-weight heparin to prevent this syndrome in patients at risk. Yet, randomized trials of this prophylactic measure have yielded contradictory results. A possible explanation is that only a subset of patients with preeclampsia have excessive thrombin generation and would benefit from the administration of low-molecular-weight heparin. Therefore, the key questions are whether and when patients who subsequently develop preeclampsia present evidence of abnormal thrombin generation. OBJECTIVE: This study aimed to determine (1) the kinetics of thrombin generation throughout gestation in women with a normal pregnancy and in those with early and late preeclampsia, and (2) the diagnostic performance of in vivo thrombin generation parameters to predict the development of preeclampsia. STUDY DESIGN: This retrospective, nested case-control study was based on a prospective longitudinal cohort of singleton gestations. Cases comprised women who developed preeclampsia (n=49), and controls consisted of patients with a normal pregnancy (n=45). Preeclampsia was classified into early-onset (n=24) and late-onset (n=25). Longitudinal changes in the parameters of the thrombin generation assay (lag time, time to peak thrombin concentration, peak thrombin concentration, endogenous thrombin generation, and velocity index) throughout gestation were compared between the study groups, and normal pregnancy percentiles were derived from the control group. We tested whether a single parameter or a combination of parameters, derived from the kinetics of thrombin generation, could identify patients who subsequently developed preeclampsia. Time-related parameters <10th percentile were considered short, and concentration-related parameters >90th percentile were considered high. RESULTS: (1) Patients who developed preeclampsia (early- and late-onset) had abnormal thrombin generation kinetics as early as 8 to 16 weeks of pregnancy; (2) patients with a combination of a short lag time and high peak thrombin concentration at 8 to 16 weeks of pregnancy had an odds ratio of 43.87 for the subsequent development of preeclampsia (area under the curve, 0.79; sensitivity, 56.8%; specificity, 92.7%; positive likelihood ratio, 7.76); (3) at 16 to 22 weeks of gestation, patients with a combination of a short lag time and a high velocity index had an odds ratio of 16 for the subsequent development of preeclampsia (area under the curve, 0.78; sensitivity, 62.2%; specificity, 92.5%; positive likelihood ratio, 8.29). CONCLUSION: During early pregnancy, the thrombin generation assay can identify the subset of patients at a greater risk for the development of preeclampsia owing to accelerated and enhanced production of thrombin. This observation provides a rationale for testing the efficacy of low-molecular-weight heparin in this subset of patients. We propose that future research on the efficacy of low-molecular-weight heparin and other interventions targeting the coagulation system to prevent preeclampsia should be focused on patients with abnormal kinetics of thrombin generation.

Meconium-stained amniotic fluid.

Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard. The condition has been attributed to the passage of fetal colonic content (meconium), intraamniotic bleeding with the presence of heme catabolic products, or both. The frequency of green-stained amniotic fluid increases as a function of gestational age, reaching approximately 27% in post-term gestation. Green-stained amniotic fluid during labor has been associated with fetal acidemia (umbilical artery pH <7.00), neonatal respiratory distress, and seizures as well as cerebral palsy. Hypoxia is widely considered a mechanism responsible for fetal defecation and meconium-stained amniotic fluid; however, most fetuses with meconium-stained amniotic fluid do not have fetal acidemia. Intraamniotic infection/inflammation has emerged as an important factor in meconium-stained amniotic fluid in term and preterm gestations, as patients with these conditions have a higher rate of clinical chorioamnionitis and neonatal sepsis. The precise mechanisms linking intraamniotic inflammation to green-stained amniotic fluid have not been determined, but the effects of oxidative stress in heme catabolism have been implicated. Two randomized clinical trials suggest that antibiotic administration decreases the rate of clinical chorioamnionitis in patients with meconium-stained amniotic fluid. A serious complication of meconium-stained amniotic fluid is meconium aspiration syndrome. This condition develops in 5% of cases presenting with meconium-stained amniotic fluid and is a severe complication typical of term newborns. Meconium aspiration syndrome is attributed to the mechanical and chemical effects of aspirated meconium coupled with local and systemic fetal inflammation. Routine naso/oropharyngeal suctioning and tracheal intubation in cases of meconium-stained amniotic fluid have not been shown to be beneficial and are no longer recommended in obstetrical practice. A systematic review of randomized controlled trials suggested that amnioinfusion may decrease the rate of meconium aspiration syndrome. Histologic examination of the fetal membranes for meconium has been invoked in medical legal litigation to time the occurrence of fetal injury. However, inferences have been largely based on the results of in vitro experiments, and extrapolation of such findings to the clinical setting warrants caution. Fetal defecation throughout gestation appears to be a physiologic phenomenon based on ultrasound as well as in observations in animals.

Intra-amniotic inflammation in the mid-trimester of pregnancy is a risk factor for neuropsychological disorders in childhood.

OBJECTIVES: Intra-amniotic inflammation is a subclinical condition frequently caused by either microbial invasion of the amniotic cavity or sterile inflammatory stimuli, e.g., alarmins. An accumulating body of evidence supports a role for maternal immune activation in the genesis of fetal neuroinflammation and the occurrence of neurodevelopmental disorders such as cerebral palsy, schizophrenia, and autism. The objective of this study was to determine whether fetal exposure to mid-trimester intra-amniotic inflammation is associated with neurodevelopmental disorders in children eight to 12 years of age. METHODS: This is a retrospective case-control study comprising 20 children with evidence of prenatal exposure to intra-amniotic inflammation in the mid-trimester and 20 controls matched for gestational age at amniocentesis and at delivery. Amniotic fluid samples were tested for concentrations of interleukin-6 and C-X-C motif chemokine ligand 10, for bacteria by culture and molecular microbiologic methods as well as by polymerase chain reaction for eight viruses. Neuropsychological testing of children, performed by two experienced psychologists, assessed cognitive and behavioral domains. Neuropsychological dysfunction was defined as the presence of an abnormal score (<2 standard deviations) on at least two cognitive tasks. RESULTS: Neuropsychological dysfunction was present in 45% (9/20) of children exposed to intra-amniotic inflammation but in only 10% (2/20) of those in the control group (p=0.03). The relative risk (RR) of neuropsychological dysfunction conferred by amniotic fluid inflammation remained significant after adjusting for gestational age at delivery [aRR=4.5 (1.07-16.7)]. Of the 11 children diagnosed with neuropsychological dysfunction, nine were delivered at term and eight of them had mothers with intra-amniotic inflammation. Children exposed to intra-amniotic inflammation were found to have abnormalities in neuropsychological tasks evaluating complex skills, e.g., auditory attention, executive functions, and social skills, whereas the domains of reasoning, language, and memory were not affected in the cases and controls. CONCLUSIONS: Asymptomatic sterile intra-amniotic inflammation in the mid-trimester of pregnancy, followed by a term birth, can still confer to the offspring a substantial risk for neurodevelopmental disorders in childhood. Early recognition and treatment of maternal immune activation in pregnancy may be a strategy for the prevention of subsequent neurodevelopmental disorders in offspring.

Maternal plasma cytokines and the subsequent risk of uterine atony and postpartum hemorrhage.

OBJECTIVES: To determine whether the maternal plasma concentrations of cytokines are higher in pregnant women with postpartum hemorrhage (PPH) compared to pregnant women without PPH. METHODS: A retrospective case-control study included 36 women with PPH and 72 matched controls. Cases and controls were matched for gestational age at delivery, labor status, delivery route, parity, and year of sample collection. Maternal plasma samples were collected up to 3 days prior to delivery. Comparison of the plasma concentrations of 29 cytokines was performed by using linear mixed-effects models and included adjustment for covariates and multiple testing. A false discovery rate adjusted p-value <0.1 was used to infer significance. Random forest models with evaluation by leave-one-out and 9-fold cross-validation were used to assess the combined value of the proteins in predicting PPH. RESULTS: Concentrations of interleukin (IL)-16, IL-6, IL-12/IL-23p40, monocyte chemotactic protein 1 (MCP-1), and IL-1ß were significantly higher in PPH than in the control group. This difference remained significant after adjustment for maternal age, clinical chorioamnionitis, and preeclampsia. Multi-protein random forest proteomics models had moderate cross-validated accuracy for prediction of PPH [area under the ROC curve, 0.69 (0.58-0.81) by leave-one-out cross validation and 0.73 (0.65-0.81) by 9-fold cross-validation], and the inclusion of clinical and demographic information did not increase the prediction performance. CONCLUSIONS: Pregnant women with severe PPH had higher median maternal plasma concentrations of IL-16, IL-6, IL-12/IL-23p40, MCP-1, and IL-1ß than patients without PPH. These cytokines could serve as biomarkers or their pathways may be therapeutic targets.

Molecular subclasses of preeclampsia characterized by a longitudinal maternal proteomics study: distinct biomarkers, disease pathways and options for prevention.

OBJECTIVES: The heterogeneous nature of preeclampsia is a major obstacle to early screening and prevention, and a molecular taxonomy of disease is needed. We have previously identified four subclasses of preeclampsia based on first-trimester plasma proteomic profiles. Herein, we expanded this approach by using a more comprehensive panel of proteins profiled in longitudinal samples. METHODS: Proteomic data collected longitudinally from plasma samples of women who developed preeclampsia (n=109) and of controls (n=90) were available from our previous report on 1,125 proteins. Consensus clustering was performed to identify subgroups of patients with preeclampsia based on data from five gestational-age intervals by using select interval-specific features. Demographic, clinical, and proteomic differences among clusters were determined. Differentially abundant proteins were used to identify cluster-specific perturbed KEGG pathways. RESULTS: Four molecular clusters with different clinical phenotypes were discovered by longitudinal proteomic profiling. Cluster 1 involves metabolic and prothrombotic changes with high rates of early-onset preeclampsia and small-for-gestational-age neonates; Cluster 2 includes maternal anti-fetal rejection mechanisms and recurrent preeclampsia cases; Cluster 3 is associated with extracellular matrix regulation and comprises cases of mostly mild, late-onset preeclampsia; and Cluster 4 is characterized by angiogenic imbalance and a high prevalence of early-onset disease. CONCLUSIONS: This study is an independent validation and further refining of molecular subclasses of preeclampsia identified by a different proteomic platform and study population. The results lay the groundwork for novel diagnostic and personalized tools of prevention.

Neonatal Outcomes of Water Delivery versus Land Delivery: A Retrospective Propensity Score Weighted Study.

OBJECTIVE: Recent evidence has shown that water delivery is safe for the mother, but high-quality evidence is not available for the newborn. Therefore, obstetric guidelines do not support it. This retrospective study aimed to contribute to the available evidence on maternal and neonatal outcomes associated with water delivery. STUDY DESIGN: Retrospective cohort study from prospectively collected birth registry data from 2015 to 2019. A total of 144 consecutive water deliveries and 265 land deliveries eligible for waterbirth were identified. The inverse probability of treatment weighting (IPTW) method was applied to address for confounders. RESULTS: We identified 144 women who delivered in water (water group) and 265 women who delivered on land (land group). One (0.7%) neonatal death was observed in the water delivery group. After IPTW adjustment, water delivery was significantly associated with a higher risk of maternal fever in puerperium (odds ratio [OR]: 4.98; 95% confidence interval [CI]: 1.86-17.02; p = 0.004), of neonatal cord avulsion (OR: 20.73; 95% CI: 2.63-2,674; p = 0.001), and of positive neonatal C-reactive protein (CRP > 5 mg/L; OR: 2.59; 95% CI: 1.05-7.24; p = 0.039); delivering in water was associated with lower maternal blood loss (mean difference: 110.40 mL; 95% CI: 191.01-29.78; p = 0.007), a lower risk of major (≥1,000 mL) postpartum hemorrhage (OR: 0.96; 95% CI: 0.92-0.99; p = 0.016), lower risk of manual placenta delivery (OR: 0.18; 95% CI: 0.03-0.67; p = 0.008) and curettage (OR: 0.24; 95% CI: 0.08-0.60; p = 0.002), lower use of episiotomy (OR: 0.02; 95% CI: 0-0.12; p < 0.001), and lower risk of neonatal ward admission (OR: 0.35; 95% CI: 0.25-0.48; p < 0.001). CONCLUSION: The present study showed that differences are present between water and land delivery, and among them is the risk of cord avulsion, a severe and potentially fatal event. In women choosing to deliver in water, a trained staffmust be present and immediate recognition of cord avulsion is key for a prompt management to avoid possible serious complications. KEY POINTS: · High-quality evidence is not available for neonatal safety of waterbirth; therefore, retrospective studies still represent the main body of evidence.. · Differences are present between water and land delivery, and among them, the increased risk of cord avulsion is a potentially fatal event.. · A trained staff must assist women who chose to deliver in water and cord avulsion must be promptly recognized and managed to avoid severe neonatal complications..

Effects of neuraxial analgesia technique on labor and maternal-fetal outcomes: a retrospective study.

PURPOSE: To compare the effects of epidural analgesia (EA) and combined spinal epidural analgesia (SEA) on labor and maternal-fetal outcomes. METHODS: We retrospectively identified and included 1499 patients with a single cephalic fetus who delivered at the study center from January 2015 to December 2018 and received neuraxial analgesia at the beginning of the active phase of labor (presence of regular painful contractions and cervical dilatation between 4 and 6 cm). Data including analgesia, labor characteristics, and maternal-fetal outcomes were retrieved from the prospectively collected delivery room database and medical records. RESULTS: SEA was associated with a shorter first stage of labor than EA, with a median difference of 60 min. On multivariable ordinal logistic regression analysis, neuraxial analgesia, gestational age, fetal weight, labor induction, and parity were independently associated with the first stage length: patients in the EA group were 1.32 times more likely to have a longer first stage of labor (95% CI 1.06-1.64, p = 0.012) than those in the SEA group. Additionally, a significantly lower incidence of fundal pressure was performed among patients who underwent SEA (OR 0.55, 95% CI 0.34-0.9, p = 0.017). No associations were observed between the used neuraxial analgesia technique and other outcomes. CONCLUSIONS: SEA was associated with a shorter length of the first stage of labor and a lower rate of fundal pressure use than EA. Further studies confirming the effects of SEA on labor management and clarifying differences in maternal-fetal outcomes will allow concluding about the superiority of one technique upon the other.

Effects of transdermal versus oral hormone replacement therapy in postmenopause: a systematic review.

PURPOSE: To summarize available evidence comparing the transdermal and the oral administration routes of hormone replacement therapy (HRT) in postmenopausal women. METHODS: We performed a systematic review of the literature on multiple databases between January 1990 and December 2021. We included randomized controlled trials and observational studies comparing the transdermal and oral administration routes of estrogens for HRT in postmenopausal women regarding at least one of the outcomes of interest: cardiovascular risk, venous thromboembolism (VTE), lipid metabolism, carbohydrate metabolism, bone mineral density (BMD), and risk of pre-malignant and malignant endometrial lesions, or breast cancer. RESULTS: The systematic literature search identified a total of 1369 manuscripts, of which 51 were included. Most studies were observational and of good quality, whereas the majority of randomized controlled trials presented a high or medium risk of bias. Oral and transdermal administration routes are similar regarding BMD, glucose metabolism, and lipid profile improvements, as well as do not appear different regarding breast cancer, endometrial disease, and cardiovascular risk. Identified literature provides clear evidence only for the VTE risk, which is higher with the oral administration route. CONCLUSIONS: Available evidence comparing the transdermal and oral administration routes for HRT is limited and of low quality, recommending further investigations. VTE risk can be considered the clearest and strongest clinical difference between the two administration routes, supporting the transdermal HRT as safer than the oral administration route.

Preeclampsia and eclampsia: the conceptual evolution of a syndrome.

Preeclampsia, one of the most enigmatic complications of pregnancy, is considered a pregnancy-specific disorder caused by the placenta and cured only by delivery. This article traces the condition from its origins-once thought to be a disease of the central nervous system, recognized by the occurrence of seizures (ie, eclampsia)-to the present time when preeclampsia is conceptualized primarily as a vascular disorder. We review the epidemiologic data that led to the recommendation to use diastolic hypertension and proteinuria as diagnostic criteria, as their combined presence was associated with an increased risk of fetal death and the birth of small-for-gestational-age neonates. However, preeclampsia is a multisystemic disorder with protean manifestations, and the condition can be present even in the absence of hypertension and proteinuria. Toxins gaining access to the maternal circulation have been proposed to mediate the clinical manifestations-hence, the term "toxemia of pregnancy," which was used for several decades. The search for putative toxins has challenged investigators for more than a century, and a growing body of evidence suggests that products of an ischemic or a stressed placenta are responsible for the vascular changes that characterize this syndrome. The discovery that the placenta can produce antiangiogenic factors, which regulate endothelial cell function and induce intravascular inflammation, has been a major step forward in the understanding of preeclampsia. We view the release of antiangiogenic factors by the placenta as an adaptive response to improve uterine perfusion by modulating endothelial function and maternal cardiovascular performance. However, this homeostatic response can become maladaptive and lead to damage of target organs during pregnancy or the postpartum period. Early-onset preeclampsia has many features in common with atherosclerosis, whereas late-onset preeclampsia seems to result from a mismatch of fetal demands and maternal supply, that is, a metabolic crisis. Preeclampsia, as it is understood today, is essentially vascular dysfunction unmasked or caused by pregnancy. A subset of patients diagnosed with preeclampsia are at greater risk of the subsequent development of hypertension, ischemic heart disease, heart failure, vascular dementia, and end-stage renal disease. However, these adverse events may be the result of a preexisting vascular pathologic process; it is not known if the occurrence of preeclampsia increases the baseline risk. Therefore, the understanding, prediction, prevention, and treatment of preeclampsia are healthcare priorities.

Cervical versus Utero-Ovarian Ligament Injection of the Tracer for the Pelvic Sentinel Lymph Node Mapping in Gynecologic Oncology: A Prospective Observational Study.

OBJECTIVE: In gynecologic oncology, the consolidated injection site for the pelvic sentinel lymph node mapping is the cervix. However, in apparent early-stage ovarian cancer, current trials map the pelvic area injecting the tracers in the utero-ovarian ligament. A different injection site is proposed based on a possible different lymphatic ovarian drainage through the utero-ovarian ligament and uterus and consequently a different pelvic sentinel lymph node mapping than the cervix; however, this was never proven. On that basis, this study aimed to investigate whether injecting the tracer in the utero-ovarian ligament map the same or a different pelvic sentinel lymph node than the cervix. DESIGN: A prospective observational study was conducted. METHODS: All consecutive women undergoing primary surgery for gynecologic malignancy with planned pelvic sentinel lymph node mapping were enrolled. The cervical injection was performed at 3 and 9 o'clock injecting indocyanine green. Bilateral utero-ovarian ligament injection was performed by injecting methylene blue. The probability of detecting the same sentinel lymph node (concordance rate) and the probability of detecting a different sentinel lymph node (discordance rate) in each hemipelvis were compared using McNemar's exact test. RESULTS: Out of 36 hemipelvis (18 patients), the overall detection rate with cervical indocyanine green injection was 86.1% (31/36) versus 52.8% (19/36) with utero-ovarian ligament methylene blue injection (p = 0.0004). Indocyanine green and methylene blue identified the same sentinel lymph node in all hemipelvis when sentinel lymph node mapping was obtained by both dyes (19/19; concordance rate 100%). No different or additional sentinel lymph nodes were identified by one of the two dyes (0/19; discordance rate 0%). The probability of detecting the same pelvic sentinel lymph node by the two injection sites was significantly higher than the probability of detecting a different pelvic sentinel lymph node (p < 0.0001). LIMITATIONS: The use of two different dyes with known different sentinel lymph node mapping performance impedes to evaluate differences in detection rate attributable to the two injection sites, limiting the comparison only in hemipelvis in which both dyes identified a sentinel lymph node. CONCLUSIONS: The cervix and utero-ovarian ligament are two sites for the tracer injection that have a higher probability of detecting the same than a different pelvic sentinel lymph node. Given the higher technical challenge in performing the utero-ovarian ligament injection, these results suggest that the injection of the tracer into the cervix could be a more reliable alternative for the pelvic sentinel lymph node mapping in ovarian cancer.

Practice changes in Italian Gynaecologic Units during the COVID-19 pandemic: a survey study.

The impact of Coronavirus disease 2019 pandemic on Italian Gynaecological Units practice and the compliance and satisfaction with available guidelines/recommendations is unknown. Therefore, a survey was conducted among all Italian Gynaecological Units Directors in April 2020. The response rate was 90% (135/150). 77.8% of centres performed surgery only for oncologic or not deferrable pathologies, and 9.6% was closed. 68.7% of directors were at least moderately satisfied by published guidelines/recommendations, but 94.8% of respondents identified limitations, mainly (83%) the absent definition of benign non-deferrable pathology. Responders considered as non-deferrable severe endometriosis (69.6%), endometriosis with organ failure/dysfunction (74.1%), and unresponsive symptomatic fibroids (89.6%). Despite guidelines/recommendations, respondents treated ovarian (77%) and endometrial (71.6%) cancer as usual. Only a minority of respondents reduced the laparoscopic approach (11.2%) and adopted all recommended surgical precautions (9.6%). Compliance with available guidelines/recommendations appears incomplete. Reconsidering guidelines/recommendations regarding oncological cases and specify non-deferrable benign pathologies would improve guidelines/recommendations compliance.Impact statementWhat is already known on this subject? The SARS-CoV-2 pandemic has profoundly influenced medical routine practice worldwide. Surgery units have been forced to reduce or even completely restrict their activity to re-allocate human resources. Many major international gynaecological societies have released statements and guidelines, providing various recommendations to guide practice changes. However, the impact of the SARS-CoV-2 pandemic on Italian Gynaecological Units practice and the compliance and satisfaction with available guidelines/recommendations is unknown.What do the results of this study add? Study results provide evidence showing how the SARS-CoV-2 pandemic has changed surgical activity in the Italian Gynaecological Units. Most centres reduced surgical activity, limiting surgery only for oncologic or not deferrable pathologies. Moreover, our research shows the level of compliance and satisfaction with available guidelines/recommendations and where they need to be improved. Most directors were at least moderately satisfied but identified different limitations. Guidelines/recommendations do not provide enough details, such as the absent definition of benign non-deferrable pathologies.What are the implications of these findings for clinical practice and/or further research? The limited compliance with available guidelines/recommendations and identified limitations suggest reconsidering guidelines/recommendations focussing on identified gaps. Provide more details, such as specifying non-deferrable benign pathologies, would improve guidelines/recommendations compliance.

Conservative Management of Atypical Endometrial Hyperplasia and Early Endometrial Cancer in Childbearing Age Women.

Total hysterectomy and bilateral adnexectomy is the standard treatment for atypical endometrial hyperplasia and early-stage endometrial cancer. However, the recommended surgical treatment precludes future pregnancy when these conditions are diagnosed in women in their fertile age. In these patients, fertility-sparing treatment may be feasible if the desire for childbearing is consistent and specific conditions are present. This review summarizes the available evidence on fertility-sparing management for atypical endometrial hyperplasia and early-stage endometrial cancer. Historically, oral progestins have been the mainstay of conservative management for atypical endometrial hyperplasia and stage IA endometrioid endometrial cancer with no myometrial invasion, although there is no consensus on dosage and treatment length. Intrauterine progestin therapy has proved a valid alternative option when oral progestins are not tolerated. GnRH analogs, metformin, and hysteroscopic resection in combination with progestins appear to increase the overall efficacy of the treatment. After a complete response, conception is recommended; alternatively, maintenance therapy with strict follow-up has been proposed to decrease recurrence. The risk of disease progression is not negligible, and clinicians should not overlook the risk of hereditary forms of the disease in young patients, in particular, Lynch syndrome. Hysterectomy is performed once the desire for childbearing desire has been established. The conservative management of atypical endometrial hyperplasia and early-stage endometrial cancer is feasible, provided a strong desire for childbearing and permitting clinical-pathological conditions. However, patients must be aware of the need for a strict follow-up and the risk of progression with a possible consequent worsening of the prognosis. More homogenous and well-designed studies are necessary to standardize and identify the best treatment and follow-up protocols.

Uterine artery closure at the origin vs at the uterus level in total laparoscopic hysterectomy: A randomized controlled trial.

INTRODUCTION: The transfusion rate in hysterectomies for benign pathology is almost 3%. However, despite the strong interest in reducing intraoperative bleeding, limited evidence is available regarding the technical aspects concerning uterine vessel management during a total laparoscopic hysterectomy (TLH). Uterine artery (UA) closure in TLH can be performed at the origin from the internal iliac artery or at the uterus level (UL). However, low-quality evidence is available regarding the superiority of one method over the other. MATERIAL AND METHODS: We performed a single-blind randomized (1:1) controlled trial (NCT04156932) between December 2019 and August 2020. One hundred and eighty women undergoing TLH for benign gynecological diseases were randomized to TLH with UA closure at the origin from the internal iliac artery (n = 90), performed at the beginning of the procedure by putting two clips per side at the origin, vs closure at the UL (n = 90). Intraoperative blood loss estimated from suction devices was the primary outcome. Secondary end points were perioperative outcomes, the conversion rate from one technique to the other, and complication rates with 4 months of follow up. RESULTS: Uterine artery closure at the origin was completed in all 90 patients (0%), whereas closure at the UL was converted to closure at the origin in 11 cases (12.2%; p < 0.001); failures were mainly associated with the presence of endometriosis (81.8% [9/11] vs 10.1% [8/79]; p < 0.001). In the intention-to-treat analysis, the intraoperative blood loss was higher in the group assigned to the closure at the UL (108.5 mL) than in the group with closure at the origin (69.3 mL); the mean difference was 39.2 mL (95% CI 13.47-64.93 mL; p = 0.003). Other perioperative outcomes and complications rates did not differ. CONCLUSIONS: Uterine artery closure at the origin reduces intraoperative blood loss during a TLH and appears to be more reproducible than closure at the UL without higher complication rates. However, the absent translation in clinical benefits impedes the support of a clinical superiority in all women. Closure at the origin may provide clinical advantages in the presence of severe preoperative anemia or pelvic anatomic distortion.

Reasons for exclusion from intravenous thrombolysis in stroke patients admitted to the Stroke Unit.

Intravenous (IV) thrombolysis is the treatment in ischemic stroke, but only the minority of patients receive this medication. The primary objective of this study was to explore the reasons associated with the decision not to offer IV thrombolysis to stroke patients admitted to the Stroke Unit (SU). We conducted a retrospective analysis based on data collected from 876 consecutive stroke patients admitted to the SU <12 h of symptoms onset, treated or not with IV thrombolysis at the discretion of the treating neurologist. Of the 876 patients, 449 were thrombolysed and 427 non-thrombolysed. Stroke onset >4.5 h (p = 0.001) and unknown time of onset (or stroke present on awakening) (p = 0.004) were reasons listed in the current SPC of Actilyse reasons for exclusion even they occurred singly, whereas mild deficit (or rapidly improving symptoms) (p < 0.001), extra-cranial conditions with increased risk of bleeding (p = 0.004), and history of SNC diseases (p = 0.001) only when they occurred in combination. Severe pre-stroke disability (p = 0.003) was extra-SPC reason for exclusion even when it occurred singly, whereas early CT hypodensity (p < 0.001) only when it occurred in combination. After stratification for intra-SPC reasons for exclusion, early CT hypodensity was associated with decision not offer IV thrombolysis in patients with mild deficit (p < 0.001), age >80 years (p < 0.001), stroke onset >4.5 h (p = 0.005), and unknown time of onset (p = 0.037), while severe pre-stroke disability (p = 0.025) and admission under non-stroke specialist neurologist assessment (p = 0.018) in patients with age >80 years. There are often unjustified reasons for exclusion from IV thrombolysis in SU.

Clinician perspectives on hysterectomy versus uterine preservation in pelvic organ prolapse surgery: A systematic review and meta-analysis.

BACKGROUND: Previous reviews on hysterectomy versus uterine-sparing surgery in pelvic organ prolapse (POP) repair did not consider that the open abdominal approach or transvaginal mesh use have been largely abandoned. OBJECTIVES: To provide up-to-date evidence by examining only studies investigating techniques currently in use for POP repair. SEARCH STRATEGY: MEDLINE and Embase databases were searched from inception to January 2023. SELECTION CRITERIA: We included randomized and non-randomized studies comparing surgical procedures for POP with or without concomitant hysterectomy. Studies describing open abdominal approaches or transvaginal mesh implantation were excluded. DATA COLLECTION AND ANALYSIS: A random effect meta-analysis was conducted on extracted data reporting pooled mean differences and odds ratios (OR) between groups with 95% confidence intervals (CI). MAIN RESULTS: Thirty-eight studies were included. Hysterectomy and uterine-sparing procedures did not differ in reoperation rate (OR 0.93; 95% CI 0.74-1.17), intraoperative major (OR 1.34; 95% CI 0.79-2.26) and minor (OR 1.38; 95% CI 0.79-2.4) complications, postoperative major (OR 1.42; 95% CI 0.85-2.37) and minor (OR 1.18; 95% CI 0.9-1.53) complications, and objective (OR 1.38; 95% CI 0.92-2.07) or subjective (OR 1.23; 95% CI 0.8-1.88) success. Uterine preservation was associated with a shorter operative time (-22.7 min; 95% CI -16.92 to -28.51 min), shorter hospital stay (-0.35 days, 95% CI -0.04 to -0.65 days), and less blood loss (-61.7 mL; 95% CI -31.3 to -92.1 mL). When only studies using a laparoscopic approach for both arms were considered, no differences were observed in investigated outcomes between the two groups. CONCLUSIONS: No major differences were observed in POP outcomes between procedures with and without concomitant hysterectomy. The decision to preserve or remove the uterus should be tailored on individual factors.