The emerging and challenging role of PD-L1 in patients with gynecological cancers: An updating review with clinico-pathological considerations.

Over recent years, there has been significant progress in the development of immunotherapeutic molecules designed to block the PD-1/PD-L1 axis. These molecules have demonstrated their ability to enhance the immune response by prompting T cells to identify and suppress neoplastic cells. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in gynecological malignancies is extremely variable based on tumor stage and molecular subtypes. As a result, a class of monoclonal antibodies targeting the PD-1 receptor and PD-L1, known as immune checkpoint inhibitors, has found successful application in clinical settings. In clinical practice, the standard method for identifying suitable candidates for immune checkpoint inhibitor therapy involves immunohistochemical assessment of PD-L1 expression in neoplastic tissues. The most commonly used PD-L1 assays in clinical trials are SP142, 28-8, 22C3, and SP263, each of which has been rigorously validated on specific platforms. Gynecologic cancers encompass a wide spectrum of malignancies originating from the ovaries, uterus, cervix, and vulva. These neoplasms have shown variable response to immunotherapy which appears to be influenced by genetic and protein expression profiles, including factors such as mismatch repair status, tumor mutational burden, and checkpoint ligand expression. In the present paper, an extensive review of PD-L1 expression in various gynecologic cancer types is discussed, providing a guide for their pathological assessment and reporting.

Integrated histological parameters define prognostically relevant groups in atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia.

OBJECTIVE: To assess the risk of endometrial carcinoma following a diagnosis of atypical hyperplasia/endometrioid intraepithelial neoplasia by endometrial biopsy, stratified based on integrated histological parameters. METHODS: All women with atypical hyperplasia/endometrioid intraepithelial neoplasia undergoing hysterectomy within 1 year of diagnosis without progestin treatment were included. Patients were subdivided into three study groups, based on two criteria: (a) grade of nuclear atypia and (b) foci (<2 mm) of confluent glands with no intervening stroma: low-grade, high-grade, and confluent glands. The rate of endometrial carcinoma on the subsequent hysterectomy was assessed in each study group, and differences between study groups were assessed using Fisher's exact test, with a significant p value <0.05. Reproducibility was assessed by using Cohen's κ. RESULTS: Ninety-six patients were included. Overall, 36 of 96 patients (37.5%) had endometrial carcinoma on the subsequent hysterectomy. The number of endometrial carcinomas was 4 of 42 (9.5%) in the low-grade group, 14 of 28 (50.0%) in the high-grade group, and 18 of 26 (69.2%) in the confluent glands group. The rate of endometrial carcinoma was significantly higher in the high-grade group than in the low-grade group (p<0.001), whereas it did not significantly differ between the high-grade group and the confluent glands group (p=0.176). The reproducibility among pathologists was moderate for low-grade versus high-grade (κ=0.58) and substantial for confluent glands versus low-grade (κ=0.63) and high-grade (κ=0.63). CONCLUSION: Atypical hyperplasia/endometrioid intraepithelial neoplasia can be stratified into prognostically relevant groups based on integrated histological parameters, with a possible major impact on patient management.

Diagnostic Accuracy of Ultrasound in the Diagnosis of Uterine Leiomyomas and Sarcomas.

BACKGROUND: Differential diagnosis between uterine leiomyomas and sarcomas is challenging. Ultrasound shows an uncertain role in the clinical practice given that pooled estimates about its diagnostic accuracy are lacking. OBJECTIVES: To assess the accuracy of ultrasound in the differential diagnosis between uterine leiomyomas and sarcomas. DATA SOURCES: A systematic review was performed searching 5 electronic databases (MEDLINE, Web of Sciences, Google Scholar, Scopus, and ClinicalTrial.gov) from their inception to June 2023. METHODS OF STUDY SELECTION: All peer-reviewed observational or randomized clinical trials that reported an unbiased postoperative histologic diagnosis of uterine leiomyoma or uterine sarcoma that also comprised a preoperative ultrasonographic evaluation of the uterine mass. TABULATION, INTEGRATION, AND RESULTS: Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve on summary receiver operating characteristic were calculated for each included study and as pooled estimate, with 95% confidence interval (CI); 972 women (694 with uterine leiomyomas and 278 with uterine sarcomas) were included. Ultrasound showed pooled sensitivity of 0.76 (95% CI, 0.70-0.81), specificity of 0.89 (95% CI, 0.87-0.92), positive and negative likelihood ratios of 6.65 (95% CI, 4.45-9.93) and 0.26 (95% CI, 0.07-1.0) respectively, diagnostic odds ratio of 23.06 (95% CI, 4.56-116.53), and area under the curve of 0.8925. CONCLUSIONS: Ultrasound seems to have only a moderate diagnostic accuracy in the differential diagnosis between uterine leiomyomas and sarcomas, with a lower sensitivity than specificity.

Atypical glandular cells and predictive features of malignancy in Pap smears: A retrospective monocentric study.

OBJECTIVE: The introduction of cytological screening with the Papanicolau smear significantly reduced cervical cancer mortality. However, Pap smear examination can be challenging, being based on the observer ability to decode different cytological and architectural features. This study aims to evaluate the malignancy rate of AGC (atypical glandular cells) category, investigating the relationships between cytological and histological diagnosis. METHODS: Eighty-nine patients, diagnosed as AGC at cytological evaluation and followed up with biopsy or surgical procedure at Policlinico Gemelli Hospital, Rome, Italy, were included in the study. The cytopathological architectural (feathering, rosette formation, overlapping, loss of polarity, papillary formation, three-dimensional formation) and nuclear (N/C ratio, nuclear enlargement and hyperchromasia, mitoses, nuclei irregularity, evident nucleoli) features of AGC were evaluated. Statistical analyses were performed to assess cyto-histological correlation and determine the relevance of architectural and nuclear features in the diagnosis of malignancy. RESULTS: Of the 89 AGC patients, 48 cases (53.93%) were diagnosed as AGC-NOS and 41 (46.07%) were diagnosed as AGC-FN, according to the Bethesda classification system. The follow-up biopsies or surgical resections revealed malignancy in 46 patients (51.69%). The rates of malignancy for AGC-NOS and AGC-FN were 35.41% and 70.73% respectively. Furthermore, analysing cytopathological features, we found that both architectural and nuclear criteria were statistically significant (p < 0.05). Only overlapping, nuclear irregularity and increased N/C ratio were not found to be statistically significant for detecting malignancy. CONCLUSIONS: Cytological diagnosis of glandular lesions remains a valid tool, when appropriate clinical correlation and expert evaluation are available.

Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Endometrial Cancer: A Review on Immunohistochemistry Staining Patterns and Clinical Implications.

Among the four endometrial cancer (EC) TCGA molecular groups, the MSI/hypermutated group represents an important percentage of tumors (30%), including different histotypes, and generally confers an intermediate prognosis for affected women, also providing new immunotherapeutic strategies. Immunohistochemistry for MMR proteins (MLH1, MSH2, MSH6 and PMS2) has become the optimal diagnostic MSI surrogate worldwide. This review aims to provide state-of-the-art knowledge on MMR deficiency/MSI in EC and to clarify the pathological assessment, interpretation pitfalls and reporting of MMR status.

Race and ethnicity reporting in endometrial cancer literature.

OBJECTIVES: There is evidence that there are differences in survival outcomes among patients with endometrial cancer of different ethnic groups. We aimed to assess the quantity and quality of race/ethnicity reporting in the literature on endometrial cancer published from January 2020 to December 2020. METHODS: In this systematic review, electronic searches of PubMed, MEDLINE, Web of Sciences, Scopus, and Cochrane Library databases were performed for all articles published in 2020. A total of 3330 articles were reviewed, of which 949 (35%) peer-reviewed human-based articles focusing on endometrial cancer were included. Non-research-focused articles, review articles, meta-analyses, case reports, and non-human studies were excluded. We analyzed the proportion of studies reporting race/ethnicity and assessed the quality of reporting with regard to the adherence to the International Committee of Medical Journal Editors (ICMJE) recommendations. We evaluated the influence of study characteristics on race/ethnicity reporting and compared articles published in journals which adhere to the ICMJE recommendations against those that did not explicitly state that they did. RESULTS: Of the 949 (28.5%) included articles, 166 (17.5%) reported race/ethnicity of patients, with low quality of reporting. The reporting rate of race/ethnicity was similar when comparing articles from ICMJE and non-ICMJE journals (62 (20.4%) vs 104 (16.1%); p=0.11), prospective versus retrospective studies (53 (22.7%) vs 113 (15.8%); p=0.02), and national versus international studies (147 (17.5%) vs 19 (17.4%); p=0.99). Studies performed in the WHO region of Americas were significantly more consistent in reporting race compared with other regions (119 (44.7%) vs 23 (6.8%) European, 2 (7.4%) Eastern Mediterranean, 21 (7.1%) Western Pacific, 0 (0%) South-East Asia; p<0.001). Female corresponding authors were significantly more consistent in reporting race than male authors (94 (22.5%) vs 72 (13.6%); p<0.001). CONCLUSIONS: Human-based articles focusing on endometrial cancer have a low frequency and quality of race/ethnicity reporting, even in journals claiming to follow ICMJE recommendations.

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.

Postchemotherapy Endometrioid to Gastrointestinal Histotype Shift in Recurrent Endometrial Carcinoma.

Herein, we report a case of low-grade endometrial endometrioid carcinoma recurred on the vaginal stump, which showed a complete histotype shift toward a gastrointestinal-type carcinoma after chemotherapy. The recurrent tumor increased in volume during chemotherapy. Postchemotherapy histologic examination showed a pure mucinous signet-ring cell pattern with positivity for cytokeratin 20 and CDX2, focal SATB2 expression and negativity for cytokeratin 7 and estrogen and progesterone receptors. Such features led to consider a diagnosis of metastasis from a primary carcinoma of the gastrointestinal tract. The accurate exclusion of any primary lesions of gastrointestinal and of other sites allowed identifying the tumor as the recurrent endometrial carcinoma. Our case highlights that chemotherapy may induce a histotype shift from endometrioid carcinoma to gastrointestinal-type carcinoma; such occurrence might be a mechanism of resistance and might provide new insights on the sensitiveness of different histotypes to systemic therapies. Considering the possibility of a shift from endometrioid to gastrointestinal-type carcinoma may be useful for a correct diagnosis and an appropriate patient management.

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.

C-reactive Protein for Predicting Early Postoperative Complications in Patients Undergoing Laparoscopic Shaving for Deep Infiltrating Endometriosis.

STUDY OBJECTIVE: To assess the accuracy of C-reactive protein (CRP) in predicting early postoperative complications in patients undergoing elective laparoscopic shaving for rectosigmoid deep infiltrating endometriosis (DIE). DESIGN: A single-center observational retrospective cohort study. SETTING: Third-level referral center for endometriosis. PATIENTS: A total of 294 patients were included in the study. All of them underwent elective laparoscopic shaving for rectosigmoid DIE. INTERVENTIONS: Postoperative CRP levels (assessed from day 3 onward, every 48 hours, until hospital discharge) and early postoperative complications were reviewed to assess CRP as a predictive marker of postoperative complications. MEASUREMENTS AND MAIN RESULTS: The study outcomes were the association between early postoperative complications and CRP levels, the optimal CRP cutoff, and its predictive accuracy. Twenty-five patients (8.5%) experienced early postoperative complications. Five patients with postoperative complications within 2 days of surgery were excluded from the analysis. On postoperative day 3 the difference in the means of CRP levels between patients with and without complications was 2.5 mg/dL (95% CI, 1.0-4.1), whereas on day 5 the difference was 5.3 mg/dL (95% CI, 3.3-7.5), with a significant increase of 2.8 mg/dL (95% CI, 0.2-5.5). On postoperative day 7 the difference was 11.4 mg/dL (95% CI, 8.2-14.6), with an increase of 6.1 mg/dL (95% CI, 2.2-9.9) from day 5. The mean CRP level in the group with complications showed an increase of 1.2 mg/dL (95% CI, -1.3 to 3.8) from day 3 to day 5 and of 6.2 mg/dL (95% CI, 2.6-9.8) from day 5 to day 7. The optimal cutoff for the CRP level in predicting early postoperative complications was 3.1 mg/dL on postoperative day 3 and 5.2 mg/dL on postoperative day 5, with a sensitivity of 87.5% (95% CI, 52.9-97.8) and 80% (95% CI, 37.6-96.4), a specificity of 62.5% (95% CI, 52.1-71.9) and 91.2% (95% CI, 81.1-96.2), a positive predictive value of 17.5% (95% CI, 8.7-31.9) and 44.4% (95% CI, 18.9-73.3), a negative predictive value of 98.2% (95% CI, 90.6-99.7) and 98.1% (95% CI, 90.1-99.7), and an area under the receiver operating characteristic curve of 75.0% (95% CI, 61.9-80.1) and 85.6% (95% CI, 74.1-96.5), respectively. CONCLUSION: CRP on postoperative day 5 seemed to be a moderately accurate predictive marker of early postoperative complications in the patients who had undergone elective laparoscopic shaving for rectosigmoid DIE.

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.

Prognostic predictors in recurrent adult granulosa cell tumors of the ovary: a systematic review and meta-analysis.

BACKGROUND: Ovarian adult granulosa cell tumours are low-grade malignant sex cord-stromal neoplasm with a low recurrence rate. Prognostic factors for recurrence include tumor stage, tumor rupture in Stage I neoplasms and the presence of residual tumors after surgery. However, in recurrent tumors, prognostic factors for overall survival (OS) are lacking. In the present paper, we conducted a systematic meta-analysis with the aim to assess prognostic factors for OS in patients with recurrent GCT. METHODS: Electronic databases were searched for all studies assessing prognostic factors in recurrent adult granulosa cell tumor of the ovary. Student T test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p value < 0.05 was considered significant. RESULTS: Eleven studies analyzing 102 recurrent tumors were included in the systematic review. Tumor stage and localization of recurrent tumors were significantly associated with OS on Kaplan-Meier analysis; Cox regression analysis showed a HR of 0.879 for the stage II, of 3.052 for the stage III, and of 2.734 for stage IV tumor was significantly associated with OS (p = 0.037); observed HRs for abdominal and thoracic locations were of 2.405 and of 4.024, respectively. CONCLUSIONS: In conclusion, the present article emphasizes the prognostic significance of tumor stage > II and extrapelvic anatomic sites of recurrences in patients with recurrent granuolase cell tumors of the ovary.

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.