Predictive factors of sentinel lymph node failed mapping in endometrial carcinoma patients: a systematic review and meta-analysis.

OBJECTIVE: In endometrial carcinoma patients, sentinel lymph node bilateral mapping fails in 20-25% of cases, with several factors affecting the likelihood of detection. However, pooled data about predictive factors of failure are lacking. The aim of this systematic review and meta-analysis was to assess the predictive factors of sentinel lymph node failed mapping in endometrial cancer patients undergoing sentinel lymph node biopsy. METHODS: A systematic review and a meta-analysis was performed searching all studies assessing predictive factors of sentinel lymph node failed mapping in apparent uterine-confined endometrial cancer patients undergoing sentinel lymph node biopsy through the cervical injection of indocyanine green. The associations between sentinel lymph node failed mapping and predictive factors of failure were assessed, calculating the odds ratio (OR) with 95% confidence intervals. RESULTS: Six studies with a total of 1345 patients were included. Compared with patients with sentinel lymph node bilateral successful mapping, patients with sentinel lymph node failed mapping showed: OR 1.39 (p=0.41) for body mass index >30 kg/m2; OR 1.72 (p=0.24) for menopausal status; OR 1.19 (p=0.74) for adenomyosis; OR 0.86 (p=0.55) for prior pelvic surgery; OR 2.38 (p=0.26) for prior cervical surgery; OR 0.96 (p=0.89) for prior Cesarean section; OR 1.39 (p=0.70) for lysis of adhesions during surgery before sentinel lymph node biopsy; OR 1.77 (p=0.02) for indocyanine green dose <3 mL; OR 1.28 (p=0.31) for deep myometrial invasion; OR 1.21 (p=0.42) for International Federation of Gynecology and Obstetrics (FIGO) grade 3; OR 1.89 (p=0.01) for FIGO stages III-IV; OR 1.62 (p=0.07) for non-endometrioid histotype; OR 1.29 (p=0.25) for lymph-vascular space invasion; OR 4.11 (p<0.0001) for enlarged lymph nodes; and OR 1.71 (p=0.022) for lymph node involvement. CONCLUSION: Indocyanine green dose <3 mL, FIGO stage III-IV, enlarged lymph nodes, and lymph node involvement are predictive factors of sentinel lymph node failed mapping in endometrial cancer patients.

Prevalence and Risk Factors of Central Sensitization in Women with Endometriosis.

STUDY OBJECTIVE: To assess prevalence of central sensitization (CS) and its association with demographic and clinical factors in patients with endometriosis. DESIGN: Single-center, observational, cross-sectional study. SETTING: Tertiary center. PATIENTS: Consecutive patients with endometriosis referred to the center from January 15, 2022, to April 30, 2022. INTERVENTIONS: For each enrolled patient, demographic and clinical data were collected, and the presence of CS was measured using the CS Inventory questionnaire (score ≥40). MEASUREMENTS AND MAIN RESULTS: Primary study outcome was CS prevalence, and secondary study outcomes were the associations between demographic and clinical factors and CS. The 95% confidence intervals for CS prevalence were obtained with Bayesian-derived Jeffreys method, and the associations between CS and demographic and clinical factors were evaluated with the chi-square test and Fisher's exact test, where appropriate. The variables significantly associated with CS were then included in a multivariable logistic regression model. The significance level was set at .05 for all analyses. During the study period, 285 eligible women were enrolled. CS prevalence was 41.4% (95% confidence interval, 35.8-47.2). At univariable analysis, infertility, moderate to severe pain symptoms (except for dyschezia), altered bowel movements, posterolateral parametrium involvement, hormonal therapy failure (HTF), and most of central sensitivity syndromes were significantly associated with CS occurrence. Multivariable analysis only confirmed the significant association of CS with moderate to severe chronic pelvic pain, posterolateral parametrium involvement, HTF, migraine or tension-type headache, irritable bowel syndrome, and anxiety or panic attacks. CONCLUSION: CS has a high prevalence in patients with endometriosis, especially in those with moderate to severe chronic pelvic pain, posterolateral parametrium involvement, HTF, and 3 central sensitivity syndromes (i.e. migraine or tension-type headache, irritable bowel syndrome, anxiety or panic attacks). Given the association with HTF, identifying CS through CS Inventory might be useful to counsel the patient and to choose multimodal treatment.

Diagnostic and prognostic value of Bcl-2 in uterine leiomyosarcoma.

BACKGROUND: Uterine leiomyosarcoma (uLMS) may show loss of expression of B-cell lymphoma-2 (Bcl-2) protein. It has been suggested that Bcl-2 loss may both be a diagnostic marker and an unfavorable prognostic marker in uLMS. OBJECTIVE: To define the diagnostic and prognostic value of Bcl-2 loss in uLMS through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to May 2020 for all studies assessing the diagnostic and prognostic value of Bcl-2 loss of immunohistochemical expression in uLMS. Data were extracted to calculate odds ratio (OR) for the association of Bcl-2 with uLMS vs leiomyoma variants and smooth-muscle tumors of uncertain malignant potential (STUMP), and hazard ratio (HR) for overall survival; a p value < 0.05 was considered significant. RESULTS: Eight studies with 388 patients were included. Loss of Bcl-2 expression in uLMS was not significantly associated with a diagnosis of uLMS vs leiomyoma variants and STUMP (OR = 2.981; p = 0.48). Bcl-2 loss was significantly associated with shorter overall survival in uLMS (HR = 3.722; p = 0.006). High statistical heterogeneity was observed in both analyses. CONCLUSION: Loss of Bcl-2 expression appears as a significant prognostic but not diagnostic marker in uLMS. The high heterogeneity observed highlights the need for further research and larger studies.

Third Trimester Myocardial Performance Index in Fetuses from Women with Hyperglycemia in Pregnancy: A Systematic Review and Meta-Analysis.

INTRODUCTION: The myocardial performance index (MPI) has been proposed to evaluate cardiac dysfunction in newborns from diabetic mothers. Although MPI is routinely assessed in newborns, its role in the evaluation of fetuses from women with hyperglycemia in pregnancy (HIP) is still under evaluation. We aimed to evaluate the differences in third trimester fetal MPI in pregnant women with hyperglycemia compared to healthy controls. MATERIALS AND METHODS: Seven electronic databases were searched for all studies assessing women with HIP who underwent evaluation of fetal left MPI during pregnancy compared to a control group. The summary measures were reported as mean differences (MD) in the mean fetal left MPI between women with HIP and healthy controls, with a 95 % confidence interval (CI). A post hoc subgroup analysis based on the type of HIP - pregestational diabetes, GDM, or gestational impaired glucose tolerance (GIGT) - was performed as an additional analysis. RESULTS: 14 studies assessing 1326 fetuses (580 from women with HIP and 746 from controls) were included. Women with HIP had a significantly higher mean left fetal MPI compared to controls (MD 0.08; 95 %CI: 0.05 to 0.11; p < 0.00 001). Subgroup analysis according to the type of HIP concurred with the overall analysis for women with DM (MD 0.07; 95 %CI: 0.01 to 0.13; p = 0.02) and for women with GDM (MD 0.012; 95 %CI: 0.07 to 0.17; p < 0.00 001) but not for women with GIGT (MD -0.01, 95 % CI -0.28 to 0.27; p = 0.96). CONCLUSION: Fetal left MPI is increased in pregnancies with HIP appearing as a potential marker of cardiac dysfunction.

Prevalence of sonographic signs in women with uterine sarcoma: a systematic review and meta-analysis.

OBJECTIVE: To assess the prevalence of sonographic signs in women with uterine sarcoma. MATERIALS AND METHODS: A systematic review and meta-analysis were performed. Five electronic databases were searched from inception to June 2022 for all studies allowing calculation of the prevalence of sonographic signs in women with uterine sarcoma. Pooled prevalence with 95% confidence intervals was calculated for each sonographic sign and was a priori defined as "very high" when it was ≥ 80%, "high" when it ranged from 80% to 70%, and less relevant when it was ≤ 70%. RESULTS: 6 studies with 317 sarcoma patients were included. The pooled prevalence was: · 25.0% (95%CI:15.4-37.9%) for absence of visibility of the myometrium. · 80.5% (95%CI:74.8-85.2%) for solid component. · 78.3% (95%CI:59.3-89.9%) for inhomogeneous echogenicity of solid component. · 47.9% (95%CI:41.1-54.8%) for cystic areas. · 80.7% (95%CI:68.3-89.0%) for irregular walls of cystic areas. · 72.3% (95%CI:16.7-97.2%) for anechoic cystic areas. · 54.8% (95%CI:34.0-74.1%) for absence of shadowing. · 73.5% (95%CI:43.3-90.9%) for absence of calcifications. · 48.7% (95%CI:18.6-79.8%) for color score 3 or 4. · 47.3% (95%CI:37.0-57.8%) for irregular tumor borders. · 45.4% (95%CI:27.6-64.3%) for endometrial cavity not visualizable. · 10.9% (95%CI:3.5-29.1%) for free pelvic fluid. · 6.4% (95%CI:1.1-30.2%) for ascites. · 21.2% (95%CI:2.1-76.8%) for intracavitary process. · 81.5% (95%CI:56.1-93.8%) for singular lesion.. CONCLUSION: Solid component, irregular walls of cystic areas, and singular lesions are signs with very high prevalence, while inhomogeneous echogenicity of solid component, anechoic cystic areas, and absence of calcifications are signs with high prevalence. The remaining signs were less relevant.

The impact of hysterectomy on oncological outcomes in patients with borderline ovarian tumors: A systematic review and meta-analysis.

BACKGROUND: Surgical management of Borderline ovarian tumors (BOT) can range from unilateral cystectomy to a more extensive surgical staging. However, the role of hysterectomy within the surgical staging is still debated. AIM: To assess the impact of hysterectomy on survival outcomes in BOT patients. MATERIALS AND METHODS: 5 electronic databases were searched from their inception to April 2021 for all peer-reviewed, retrospective or prospective studies, which compared treatment including hysterectomy versus treatment not including hysterectomy for BOT, in terms of recurrence and/or death. Pooled odds ratios (OR) with 95% confidence interval for recurrence, death due to BOT and death of any cause were calculated comparing hysterectomy group versus no hysterectomy group. Subgroup analyses for recurrence were based on BOT histotype (mucinous and serous) and FIGO stage (I and II-III). RESULTS: Twelve studies assessing 2223 patients were included. Compared to no hysterectomy group, hysterectomy group showed an OR of 0.23 (p = 0.00001) for recurrence, 1.26 (p = 0.77) for death due to BOT and 4.23 (p = 0.11) for death of any cause. At subgroup analyses, compared to no hysterectomy group, hysterectomy group showed an OR for recurrence of 0.21 (p = 0.003) in serous subgroup, of 0.46 (p = 0.18) in mucinous subgroup, of 0.23 (p = 0.0006) in FIGO stage I subgroup, and of 0.29 (p = 0.04) in FIGO stage II-III subgroup. CONCLUSIONS: Uterine-sparing surgery might be recommended in all BOT patients since it seems to increase the risk of recurrence, but not those of death due to disease or death of any cause.

Lymphovascular space invasion in endometrial carcinoma: A prognostic factor independent from molecular signature.

BACKGROUND: The 2020 ESGO/ESTRO/ESP guidelines stratify the prognosis of endometrial carcinoma (EC) patients combining The Cancer Genome ATLAS (TCGA) molecular signature and pathological factors, including lymphovascular space invasion (LVSI). However, little is known about the prognostic independence of LVSI from molecular signature. AIM: To assess whether the prognostic value of LVSI is independent from the TCGA signature. MATERIAL AND METHODS: A systematic review and meta-analysis was performed by searching 5 electronic databases from their inception to March 2021. All peer-reviewed studies reporting assessing LVSI as a prognostic factor independent from the TCGA groups in EC were included. Multivariate HRs with 95% confidence interval (CI) were pooled separately for overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS). The absence of LVSI was considered as a reference. In DFS analyses, locoregional and distant recurrence were separately considered for one study. RESULTS: Six studies with 3331 patients were included in the systematic review and three studies with 2276 patients in the meta-analysis. LVSI showed a pooled multivariate HR of 1.818 (CI 95%, 1.378-2.399) for OS, 1.849 (CI 95%, 1.194-2.863) for DSS, 1.377 (CI 95%, 1.008-1.880) for DFS excluding one study, 1.651 (CI 95%, 1.044-2.611) for DFS additionally considering locoregional recurrence from one study, and 1.684 (CI 95%, 1.05-2.701) for DFS additionally considering distant recurrence from the same study. CONCLUSION: LVSI has a prognostic value independent of TCGA signature, as well as age and adjuvant treatment, increasing the risk of death of any cause, death due to EC and recurrent or progressive disease by 1.5-2 times.

Clinicopathological Features Associated with Microsatellite Instability/Mismatch Repair Deficiency in Uterine Carcinosarcoma: A Quantitative Systematic Review.

INTRODUCTION: Recent studies suggested that microsatellite instability/mismatch repair deficiency (MSI/MMR-d) might define a clinicopathologically distinct subset of uterine carcinosarcomas (UCSs). OBJECTIVE: The aim of this study was to compare clinicopathological features between MSI/MMR-d and microsatellite-stable/mismatch repair-proficient (MSS/MMR-p) UCSs. METHODS: A quantitative systematic review was performed by searching electronic databases from January 2000 to January 2021. All studies assessing MSI/MMR status in UCS were included. Odds ratio (OR) with a significant two-tailed p value <0.05 was used to assess the association of MSI/MMR-d with clinicopathological features. RESULTS: Eleven studies with 783 patients were included. MSI/MMR-d was directly associated with endometrioid (pure: p < 0.001; pure + mixed: p < 0.001), undifferentiated/dedifferentiated (p < 0.001), and clear cell carcinoma component (p = 0.046), and inversely associated with age >60 (p = 0.034), serous carcinoma component (pure: p < 0.001; pure + mixed: p < 0.001), heterologous sarcoma component (p = 0.027), TP53-mutation/p53-abnormal expression (p < 0.001), and recurrence (p < 0.001). MSI/MMR-d showed no significant association with advanced FIGO stage (OR = 1.259; p = 0.517), low-grade carcinoma component (pure: p = 0.596; pure + mixed: p = 0.307), mixed carcinoma component (p = 1), and proportion of patients "dead of disease" (p = 0.352), "alive with disease" (p = 1) or with "no evidence of disease" (p = 0.458). CONCLUSION: MSI/MMR-d UCSs show younger age, more common endometrioid, undifferentiated or clear cell carcinoma component, and less common serous carcinoma component, heterologous sarcoma component, and TP53 mutation than MSS/MMR-p UCSs. Given the discrepancy between recurrence rate and oncologic outcomes at the last follow-up, further studies are necessary to define whether MSI/MMR-d UCSs have better prognosis.

Histological Prognostic Factors of Endometrial Cancer in Patients with Adenomyosis: A Systematic Review and Meta-Analysis.

BACKGROUND: A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been hypothesized based on a different prevalence of favorable EC histological prognostic factors. However, pooled risk of EC unfavorable histological prognostic factors in patients with adenomyosis has never been calculated. OBJECTIVES: We aimed to assess the risk of EC unfavorable histological prognostic factors in patients with adenomyosis. METHODS: All studies with data about histological prognostic factors of EC in patients with and without adenomyosis were included. Relative risk for each unfavorable histological prognostic factor of EC, such as nonendometrioid histotype, FIGO grade 3, FIGO stage II-IV, lymphovascular space invasion (LVSI), and deep myometrial invasion, was calculated in patients with adenomyosis compared to patients without adenomyosis. RESULTS: Seven studies with 4,439 patients were included in the quantitative analysis. EC patients with adenomyosis showed a pooled RR of 0.77 (p = 0.05) for nonendometrioid histotype, 0.55 (p < 0.00001) for FIGO grade 3, 0.60 (p = 0.005) for FIGO stage II-IV, 0.75 (p = 0.004) for LVSI, and 0.65 (p = 0.001) for deep myometrial invasion. CONCLUSION: EC patients with adenomyosis have a significantly decreased risk for unfavorable histological prognostic factors of EC compared to EC patients without adenomyosis. Such findings might explain the supposed better EC prognosis in patients with adenomyosis.

Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis.

BACKGROUND: In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP). OBJECTIVE: To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I-II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05. RESULTS: Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026). CONCLUSION: CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.

Obstetric A&E unit admission and hospitalization for obstetrical management during COVID-19 pandemic in a third-level hospital of southern Italy.

BACKGROUND: The COronaVIrus Disease 2019 (COVID-19) has spread in Italy since February 2020, inducing the government to call for lockdown of any activity, apart primary needs, during the months March-May 2020. During the lockdown, a reduction of admissions and hospitalizations for ischemic diseases was noticed. Purpose of this study was to observe if there has been the same reduction trend in Accident & Emergency (A&E) unit admissions also for obstetric-gynecological conditions. METHODS: Medical records and electronic clinical databases were searched for all patients who were admitted to the obstetric A&E department or hospitalized at the Gynecology and Obstetrics Unit of University hospital of Naples Federico II, during the quarter March-May in the years 2019 and 2020. The mean ± standard deviation (SD) of monthly admission to the obstetric A&E department and hospitalization of the year 2020 was compared with that of the year 2019, using the unpaired T test with α error set to 0.05 and 95% confidence intervals (95% CI). RESULTS: Admissions were 1483 in the year 2020 and 1786 in 2019. Of total, 1225 (37.5%) women were hospitalized: 583 in the year 2020, 642 in 2019. Mean ± SD of patients monthly admitted to our obstetric A&E department was 494 ± 33.7 in the year 2020, and 595.3 ± 30.9 in 2019, with a mean difference of - 101.3 (95% CI - 103.5 to - 99.1; p < 0.0001). Mean ± SD of patients monthly hospitalized to our department was 194 ± 19.1 in the year 2020, 213.7 ± 4.7 in 2019, with a mean difference of - 19.7 (95% CI - 23.8 to - 15.6; p < 0.0001). CONCLUSION: A significant decrease in the mean of monthly admissions and hospitalizations during the COVID-19 pandemic when compared to the previous year was found also for obstetric-gynecological conditions. Further studies are necessary to assess COVID-19 impact and to take the most appropriate countermeasures.

TCGA Molecular Prognostic Groups of Endometrial Carcinoma: Current Knowledge and Future Perspectives.

The four TCGA-based molecular prognostic groups of endometrial carcinoma (EC), i.e., POLE-mutant, mismatch repair (MMR)-deficient, p53-abnormal, and "no specific molecular profile" (NSMP), have recently been integrated into ESGO-ESTRO-ESP guidelines. The POLE-mutant and MMR-deficient groups are associated with high mutational load, morphological heterogeneity, and inflammatory infiltration. These groups are frequent in high-grade endometrioid, undifferentiated/dedifferentiated, and mixed histotypes. POLE-mutant ECs show good prognosis and do not require adjuvant treatment, although the management of cases at stage >II is still undefined. MMR-deficient ECs show intermediate prognosis and are currently substratified based on clinicopathological variables, some of which might not have prognostic value. These groups may benefit from immunotherapy. P53-mutant ECs are typically high-grade and often morphologically ambiguous, accounting for virtually all serous ECs, most carcinosarcomas and mixed ECs, and half of clear-cell ECs. They show poor prognosis and are treated with chemoradiotherapy; a subset may benefit from HER2 inhibitors or PARP inhibitors. The NSMP group is the most frequent TCGA group; its prognosis is highly variable and affected by clinicopathological/molecular factors, most of which are still under evaluation. In conclusion, the TCGA classification has improved diagnosis, risk stratification, and management of EC. Further studies are needed to resolve the points of uncertainty that still exist.

Ascertaining the Effects of Tissue Sealers on Minor Laparoscopic Procedures between Obstetrics and Gynecology Residents: A Prospective Cohort Study.

Background and Objectives: The type of instrumentation used during laparoscopic surgery might impact on the learning curve of resident surgeons. The aim of this study was to investigate differences in operator satisfaction and surgical outcomes between tissue sealers and classic bipolar instruments during gynecological laparoscopies performed by residents. Materials and Methods: A prospective cohort study conducted at two tertiary university hospitals between March 2019 and March 2021, on consecutive procedures: salpingo-oophorectomies (Group 1) and salpingectomies (Group 2), subdivided according to the utilized device: radiofrequency tissue sealers (Groups A1 and A2) or bipolar forceps (Groups B1 and B2). Results: 80 procedures were included. Concerning salpingo-oophorectomies, better visibility (8.4 ± 0.8 vs. 7.3 ± 0.9; p = 0.03), reduced difficulty (5.4 ± 1.2 vs. 7.0 ± 1.4; p = 0.02), improved overall satisfaction (9.2 ± 0.4 vs. 7.6 ± 1.0; p = 0.02) and reduced procedure time (7.8 ± 3.4 vs. 12.6 ± 3.1; p = 0.01) were reported by residents using tissue sealers. Intraoperative blood loss (12.2 ± 4.7 mL vs. 33.2 ± 9.7 mL; p = 0.01) and 24 h postoperative pain (4.5 ± 1.1 vs. 5.7 ± 1.8; p = 0.03) were lower in group A1 than B1. For salpingectomies, a significant reduction in duration was found in A2 compared to B2 (7.2 ± 3.4 min vs. 13.8 ± 2.2 min; p = 0.02). Tissue sealers enhanced visibility (8.1 ± 1.1 vs. 6.7 ± 1.4; p = 0.01), difficulty (6.5 ± 1.1 vs. 7.5 ± 0.9; p = 0.04) and improved satisfaction (9.3 ± 0.5 vs. 7.5 ± 0.6; p = 0.01). Moreover, hemoglobin loss and postoperative pain were reduced in A2 relative to B2 [(8.1 ± 4.2 % vs. 4.5 ± 1.1%; p = 0.02) and (5.1 ± 0.9 vs. 4.1 ± 0.8; p = 0.03), respectively] Conclusions: The use of sealing devices by residents was related to reduced difficulty as well improved visibility and overall satisfaction, with improved surgical outcomes.

The Use of near Infra-Red Radiation Imaging after Injection of Indocyanine Green (NIR-ICG) during Laparoscopic Treatment of Benign Gynecologic Conditions: Towards Minimalized Surgery. A Systematic Review of Literature.

Background and Objectives: To assess the use of near infrared radiation imaging after injection of indocyanine green (NIR-ICG) during laparoscopic treatment of benign gynecologic conditions. Materials and Methods: A systematic review of the literature was performed searching 7 electronic databases from their inception to March 2022 for all studies which assessed the use of NIR-ICG during laparoscopic treatment of benign gynecological conditions. Results: 16 studies (1 randomized within subject clinical trial and 15 observational studies) with 416 women were included. Thirteen studies assessed patients with endometriosis, and 3 studies assessed non-endometriosis patients. In endometriosis patients, NIR-ICG use appeared to be a safe tool for improving the visualization of endometriotic lesions and ureters, the surgical decision-making process with the assessment of ureteral perfusion after conservative surgery and the intraoperative assessment of bowel perfusion during recto-sigmoid endometriosis nodule surgery. In non-endometriosis patients, NIR-ICG use appeared to be a safe tool for evaluating vascular perfusion of the vaginal cuff during total laparoscopic hysterectomy (TLH) and robotic-assisted total laparoscopic hysterectomy (RATLH), and intraoperative assessment of ovarian perfusion in adnexal torsion. Conclusions: NIR-ICG appeared to be a useful tool for enhancing laparoscopic treatment of some benign gynecologic conditions and for moving from minimally invasive surgery to minimalized surgery. In particular, it might improve treatment of endometriosis (with particular regard to deep infiltrating endometriosis), benign diseases requiring TLH and RATLH and adnexal torsion. However, although preliminary findings appear promising, further investigation with well-designed larger studies is needed.

3D Patient-Specific Virtual Models for Presurgical Planning in Patients with Recto-Sigmoid Endometriosis Nodules: A Pilot Study.

Background and Objective: In recent years, 3D printing has been used to support surgical planning or to guide intraoperative procedures in various surgical specialties. An improvement in surgical planning for recto-sigmoid endometriosis (RSE) excision might reduce the high complication rate related to this challenging surgery. The aim of this study was to build novel presurgical 3D models of RSE nodules from magnetic resonance imaging (MRI) and compare them with intraoperative findings. Materials and Methods: A single-center, observational, prospective, cohort, pilot study was performed by enrolling consecutive symptomatic women scheduled for minimally invasive surgery for RSE between November 2019 and June 2020 at our institution. Preoperative MRI were used for building 3D models of RSE nodules and surrounding pelvic organs. 3D models were examined during multi-disciplinary preoperative planning, focusing especially on three domains: degree of bowel stenosis, nodule's circumferential extension, and bowel angulation induced by the RSE nodule. After surgery, the surgeon was asked to subjectively evaluate the correlation of the 3D model with the intra-operative findings and to express his evaluation as "no correlation", "low correlation", or "high correlation" referring to the three described domains. Results: seven women were enrolled and 3D anatomical virtual models of RSE nodules and surrounding pelvic organs were generated. In all cases, surgeons reported a subjective "high correlation" with the surgical findings. Conclusion: Presurgical 3D models could be a feasible and useful tool to support surgical planning in women with recto-sigmoidal endometriotic involvement, appearing closely related to intraoperative findings.

An emerging role for BAG3 in gynaecological malignancies.

BAG3, a member of the BAG family of co-chaperones, is a multidomain protein with a role in several cellular processes, including the control of apoptosis, autophagy and cytoskeletal dynamics. The expression of bag3 is negligible in most cells but can be induced by stress stimuli or malignant transformation. In some tumours, BAG3 has been reported to promote cell survival and resistance to therapy. The expression of BAG3 has been documented in ovarian, endometrial and cervical cancers, and studies have revealed biochemical and functional connections of BAG3 with proteins involved in the survival, invasion and resistance to therapy of these malignancies. BAG3 expression has also been shown to correlate with the grade of dysplasia in squamous intraepithelial lesions of the uterine cervix. Some aspects of BAG3 activity, such as its biochemical and functional interaction with the human papillomavirus proteins, could help in our understanding of the mechanisms of oncogenesis induced by the virus. This review aims to highlight the potential value of BAG3 studies in the field of gynaecological tumours.

Clinico-pathological features associated with mismatch repair deficiency in endometrial undifferentiated/dedifferentiated carcinoma: A systematic review and meta-analysis.

BACKGROUND: Endometrial undifferentiated/dedifferentiated carcinoma (UDC/DDC) is a recently described aggressive variant of endometrial carcinoma, which shows mismatch repair (MMR) deficiency in about half of cases. AIM: To assess whether MMR-deficient UDC/DDC have distinct clinico-pathological features. MATERIALS AND METHODS: A systematic review and meta-analysis was performed by searching 4 electronic databases from their inception to October 2020 for all studies reporting clinicopathological characteristics of UDC/DDC series. Student t-test (for continuous variables), Cox regression analysis (for overall survival) and odds ratio (OR, for dichotomous variables) were used with a significant p-value < 0.05; data were pooled by using a random effect model. RESULTS: Twelve studies were included. MMR-deficiency was significantly associated with older age (p = 0.024), p53-wild-type (p = 0.005), ARID1A loss (p = 0.001) and PD-L1 expression (p = 0.019), but not with overall survival (p = 0.307), extension beyond corpus (p = 0.787) or beyond uterus (p = 0.403), presence of a differentiated component (p = 0.461), loss of expression of cytokeratins (p = 0.698), EMA (p = 0.309), estrogen receptor (p = 0.605), PAX8 (p = 0.959), SMARCA4/BRG1 (p = 0.321), SMARCB1/INI1 (p = 0.225) or claudin-4 (p = 0.094), or POLE exonuclease domain mutation p = (0.773). CONCLUSIONS: In UDC/DDC, MMR-deficiency appears associated with older age, p53-wild type and ARID1A loss, suggesting the possibility of a distinct pathway underlying dedifferentiation; the association with PD-L1 expression is attributable to the high mutational load and may have therapeutic implications. On the other hand, MMR-deficiency appears not to be associated with prognosis, stage, loss of differentiation markers or POLE mutation.

Prognostic value of myometrial invasion and TCGA groups of endometrial carcinoma.

BACKGROUND: 2021 ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma (EC) encourage molecular classification and propose a new prognostic risk stratification based on both pathologic and molecular features. Although deep myometrial invasion (DMI) has been considered as a crucial risk factor in EC, it is unclear if its prognostic value is independent from The Cancer Genome ATLAS (TCGA) groups. AIM: To assess if the prognostic value of DMI is independent from the TCGA groups in EC patients. MATERIALS AND METHODS: A systematic review and meta-analysis was performed by searching through 5 electronic databases, from their inception to March 2021, for all studies that allowed to assess DMI as a prognostic factor independent of the TCGA groups in EC patients. Pooled hazard ratio (HR) of DMI for overall survival (OS) and disease-free survival (DFS) was calculated at multivariable analyses including TCGA groups as a variable. Superficial myometrial invasion (<50% of myometrial thickness) was considered as a reference. In DFS analyses, locoregional and distant recurrence were separately considered for one study. RESULTS: Five studies with 2469 patients were included in the systematic review and 3 studies with 1549 patients in the meta-analysis. Pooled HR of DMI was 1.082 (CI 95% 0.85-1.377; p = 0.524) for OS, 1.709 (CI 95% 1.173-2.491; p = 0.005) for DFS, 1.585 (CI 95% 1.154-2.178; p = 0.004) for DFS additionally considering locoregional recurrence for one study, and 1.701 (CI 95% 1.235-2.344, p = 0.001) for DFS additionally considering distant recurrence for the same study. CONCLUSIONS: DMI does not appear as an independent prognostic factor for OS in EC patients; instead, it seems to affect the risk of recurrence independently from the TCGA groups. Further studies are necessary to confirm these findings and to assess the prognostic impact of DMI separately in each TCGA group.

Clear cell endometrial carcinomas with mismatch repair deficiency have a favorable prognosis: A systematic review and meta-analysis.

INTRODUCTION: In the ESGO/ESTRO/ESP guidelines for endometrial carcinoma management, the risk category of clear cell carcinoma (CCC) is not well defined. In fact, while p53-abnormal (p53abn) CCC are known to be aggressive, the prognosis of mismatch repair-deficient (MMRd) and p53-wild-type (p53wt) CCCs is less clear. OBJECTIVE: To assess the prognostic value of the MMRd and p53wt groups in CCC through a systematic review and meta-analysis. METHODS: Electronic databases were searched from their inception to February 2021. All studies reporting p53 expression, MMR proteins expression and survival outcomes in endometrial CCC (either pure or mixed) were included. Kaplan-Meier and Cox regression survival analyses with hazard ratio (HR) for overall survival (OS) were performed by using the p53abn group as reference; a significant p-value<0.05 was adopted. RESULTS: Six studies with 136 CCC (114 pure and 22 mixed) were included. Five-year OS was 95.7 ± 4.3% in the MMRd group, 48.4 ± 8.4% months in the p53wt group and 40.6 ± 10.4% in the p53abn group. The hazard of death was significantly lower in the MMRd group than in the p53abn group (HR = 0.062; p = 0.007), while it did not significantly differ between the p53wt and the p53abn group (HR = 0.673; p = 0.222). The POLEmut group could not be analyzed due to the absence of deaths. Similar results were observed in the pure CCC and mixed CCC subgroups. CONCLUSION: MMRd CCCs seem to have a favorable prognosis and might be lumped together with MMRd endometrioid carcinoma for management purpose. On the other hand, p53wt CCCs appear prognostically more similar to p53abn CCCs.

Tumor-infiltrating lymphocytes and POLE mutation in endometrial carcinoma.

BACKGROUND: Polymerase-ε (POLE)-mutated endometrial carcinomas (ECs) have displayed an increased number of tumor-infiltrating lymphocytes (TIL) compared to POLE-wild-type ECs. However, it is unclear if TIL may aid in identifying POLE-mutated ECs when molecular data are unavailable. The identification of a POLE mutation surrogate may be crucial to translate TCGA/ProMisE risk assessment in the clinical practice. AIM: To assess TIL as histological surrogate of POLE mutation in EC. MATERIALS AND METHODS: Seven electronic databases were searched from their inception to September 2020 for studies that allowed data extraction about TIL and TCGA/ProMisE groups of EC. We calculated pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on SROC curves of TIL in distinguishing POLE-mutated from i) POLE-wild-type, ii) no specific molecular profile (NSMP), iii) POLE-wild-type/MMR-proficient, iii) MMR-deficient ECs. RESULTS: 10 studies assessing 1169 women were included in the qualitative analysis. TIL-high pattern showed: sensitivity = 0.65, specificity = 0.63, LR + =2.06, LR- = 0.48, DOR = 4.39, AUC = 0.7532 for POLE-mutant vs POLE-wild-type ECs; sensitivity = 0.85, specificity = 0.73, LR + =2.80, LR- = 0.22, DOR = 15.17 for POLE-mutant vs NSMP ECs; sensitivity = 0.85, specificity = 0.66, LR + =2.49, LR- = 0.25, DOR = 10.30 for POLE-mutant vs POLE-wild-type/MMR-proficient ECs; sensitivity = 0.68, specificity = 0.44, LR + =1.38, LR- = 0.64, DOR = 2.68, AUC = 0.6694 for POLE-mutant vs MMR-deficient ECs. CONCLUSION: TIL-high pattern shows a moderate accuracy in distinguishing POLE-mutated from POLE-wild-type ECs after the exclusion of MMR-deficient cases. TIL might be considered in an integrate algorithm to identify POLE-mutated ECs when sequencing is unavailable. Further studies are necessary in this regard.