Assessment of sentinel Lymph node mapping with different volumes of Indocyanine green in early-stage ENdometrial cancer: the ALIEN study.

OBJECTIVE: To evaluate the impact of different volumes of indocyanine green (ICG) on the detection rate and bilateral mapping of sentinel lymph nodes in patients with apparent uterine-confined endometrial cancer. METHODS: All patients who underwent surgical staging with sentinel node mapping in six reference centers were included. Two different protocols of ICG intracervical injection were used: (1) 2 mL group: total volume of 2 mL injected superficially; (2) 4 mL group: total volume of 4 mL, 2 mL deeply and 2 mL superficially. Logistic regression was used to analyze factors that could influence dye migration and detection rates. A sensitivity analysis was carried out to determine how independent variables could affect the sentinel node detection rate. RESULTS: Of 442 eligible patients, 352 were analyzed (172 in the 2 mL group and 180 in the 4 mL group). The bilateral detection rates of the 2 mL and 4 mL groups were 84.9% and 86.1%, respectively (p=0.76). The overall detection rate was higher with a volume of 4 mL than with 2 mL (97.8% vs 92.4%, respectively; p=0.024). In the univariate analysis the rate of bilateral mapping fell from 87.5% to 73.5% when the International Federation of Gynecology and Obstetrics (FIGO) 2009 tumor stage was >IB (p=0.018). In the multivariate analysis, for both overall and bilateral detection rates a statistically significant difference emerged for the volume of ICG injected and FIGO 2009 stage >IB. Increasing body mass index was associated with worse overall detection rates on univariate analysis (p=0.0006), and significantly decreased from 97% to 91% when the body mass index exceeded 30 kg/m2 (p=0.05). CONCLUSIONS: In patients with early-stage endometrial cancer, a volume of 2 mL ICG does not seem to compromise the bilateral detection of sentinel lymph nodes. In women with obesity and FIGO 2009 stage >IB, a 4 mL injection should be preferred.

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.

Feasibility of Intraoperative Proctosigmoidoscopy After Discoid Bowel Resection for Deep Infiltrating Endometriosis: A Pilot Multicenter Study.

STUDY OBJECTIVE: Although surgery is the gold standard treatment for pain refractory to medical management or partial occlusion owing to rectosigmoid endometriosis, surgical resection can be associated with major perioperative complications. From general surgery experience, intraoperative proctosigmoidoscopy has shown encouraging results as a feasible, safe, and effective technique in reducing the risk of complications related to intestinal anastomosis after segmental resection. Unfortunately, there are no studies evaluating its role after discoid resection for rectosigmoid endometriosis. DESIGN: A pilot, multicentric, observational, prospective, cohort study. SETTING: Two academic hospitals, from March 1 to December 31, 2022. PATIENTS: We enrolled all consecutive fertile-age patients affected by symptomatic endometriosis scheduled for laparoscopic discoid bowel resection. Inclusion criteria were (1) age between 18 and 50 years, (2) diagnosis of rectosigmoid endometriosis performed by transvaginal ultrasound and/or magnetic resonance imaging, and (3) women scheduled for laparoscopic discoid bowel resection of endometriosis at low risk of segmental resection. INTERVENTIONS: During data analysis, enrolled patients were divided into 2 study groups for comparisons based on whether or not the intraoperative proctosigmoidoscopy was performed upon surgeons' discretion after discoid resection for treating endometriosis, in addition to standard integrity tests. Primary outcome was the rate of intraoperative proctosigmoidoscopy success. Secondary study outcomes were the differences between the intraoperative proctosigmoidoscopy group and the nonintraoperative proctosigmoidoscopy group in (1) mean of total operative time and (2) rate of perioperative complications. MEASUREMENTS AND MAIN RESULTS: A total of 28 patients were enrolled and equally distributed in the 2 groups. The rate of intraoperative proctosigmoidoscopy success was 86%. No significant difference was reported between the 2 groups in terms of total operative time (p = .1) and intraoperative and postoperative complications (p = .5 and p = 1, respectively), with no surgical complication related to intraoperative proctosigmoidoscopy. CONCLUSION: Intraoperative proctosigmoidoscopy seems as a feasible and non-time-consuming intraoperative procedure in women undergone discoid resection for rectosigmoid endometriosis. Larger studies with longer follow-up period are necessary to confirm our findings and assess clinical benefits over standard procedure.

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.

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.

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.

Cimicifuga racemosa isopropanolic extract for menopausal symptoms: an observational prospective case-control study.

OBJECTIVE: We aimed to investigate the effectiveness of isopropanolic extract of Cimicifuga Racemosa (iCR) on reducing menopausal symptoms. MATERIALS AND METHODS: A single-center observational prospective case-control study was performed to assess the improvement of menopausal symptoms in menopausal women undergone iCR administration (cases) or no treatment (controls). Menopausal symptoms were assessed through a modified version of the Menopause Rating Scale questionnaire (mMRS) at T0 (baseline), T1 (1-month follow-up), and T2 (3 months follow-up). Univariate comparisons between cases and controls were performed by using the unpaired T test for two-tailed P value with α = 0.05 significance level. RESULTS: A total of 163 women (83 cases and 80 controls) were enrolled in the study. The difference in menopausal symptoms between cases and controls from T0 to T2, and from T0 to T1, was found significant for all analyses. In particular, the difference in all menopausal symptoms was 20.56 ± 0.90 points (95%CI: 18.77-22.33, p < .001) from T0 to T2, and 10.69 ± 0.6 (95%CI: 9.49-11.88, p < .001) from T0 to T1. CONCLUSION: iCR may be effective in reducing menopausal symptoms, both after 1 month and after 3 months of treatment. The improvement was higher in vasomotor symptoms, sleep problems, and irritability.

Cervical elastography using E-Cervix™ for prediction of preterm birth in twin pregnancies with threatened preterm labor.

OBJECTIVE: To evaluate the prediction performance of E-Cervix™ for preterm birth in twin pregnancies with threatened preterm labor. METHODS: This was a single-center retrospective cohort study of twin pregnancies presenting to obstetrics triage for threatened preterm labor (PTL) between 23 0/7 - 33 6/7 weeks who received screening for PTL with transvaginal ultrasound cervical length (TVU CL) and cervical elastography with E-Cervix™ at the time of triage. Cervical elastography parameters were examined and compared between women who delivered preterm and those who did not. The quantification of cervical strain was calculated by a data analysis system that directly analyzes raw data from the region of interest (ROI) and described as hardness ratio (HR), mean strain level within 1 cm from internal (IOS) and external (EOS) os. RESULTS: 63 twin gestations without prior preterm birth and with threatened PTL between 23 0/7 - 33 6/7 weeks of gestation were included in the study. 27 (42.9 %) had cervical length < 25 mm, and were admitted for true PLT. Out of the 36 women with cervical length ≥ 25 mm, 6 (16.7 %) were admitted. Women with threatened PTL had significantly higher HR compared to those with true PTL (p < 0.01), and significantly lower IOS and EOS. Women who delivered preterm had significantly higher HR compared to those who did not delivery preterm and significantly lower IOS and EOS, in overall cohort, and in the subset of women with true PTL. Incidences of HR < 50 % and < 35 % were statistically significantly higher in women who delivered preterm compared to those who did not (p < 0.01). CONCLUSION: Cervical elastography with E-Cervix™ may be useful for assessment of twin gestations presenting to obstetrics triage for threatened PTL.

Diagnostic accuracy of MRI in the differential diagnosis between uterine leiomyomas and sarcomas: A systematic review and meta-analysis.

BACKGROUND: Differential diagnosis between uterine leiomyomas and sarcomas is challenging. Magnetic resonance imaging (MRI) represents the second-line diagnostic method after ultrasound for the assessment of uterine masses. OBJECTIVES: To assess the accuracy of MRI in the differential diagnosis between uterine leiomyomas and sarcomas. SEARCH STRATEGY: A systematic review and meta-analysis was performed searching five electronic databases from their inception to June 2023. SELECTION CRITERIA: All peer-reviewed observational or randomized clinical trials that reported an unbiased postoperative histologic diagnosis of uterine leiomyoma or uterine sarcoma, which also comprehended a preoperative MRI evaluation of the uterine mass. DATA COLLECTION AND ANALYSIS: Sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve on summary receiver operating characteristic of MRI in differentiating uterine leiomyomas and sarcomas were calculated as individual and pooled estimates, with 95% confidence intervals (CI). RESULTS: Eight studies with 2495 women (2253 with uterine leiomyomas and 179 with uterine sarcomas), were included. MRI showed pooled sensitivity of 0.90 (95% CI 0.84-0.94), specificity of 0.96 (95% CI 0.96-0.97), positive likelihood ratio of 13.55 (95% CI 6.20-29.61), negative likelihood ratio of 0.08 (95% CI 0.02-0.32), diagnostic odds ratio of 175.13 (95% CI 46.53-659.09), and area under the curve of 0.9759. CONCLUSIONS: MRI has a high diagnostic accuracy in the differential diagnosis between uterine leiomyomas and sarcomas.

Unveiling therapeutic potentials and exploring maternal-fetal health benefits of metformin in pregnancy: A scoping review.

This scoping review synthesizes evidence on metformin's use during pregnancy, encompassing diverse conditions like gestational diabetes, type 1 and type 2 diabetes, polycystic ovary syndrome (PCOS), and obesity. Metformin demonstrates comparable efficacy to insulin in gestational diabetes, positive outcomes in type 2 diabetes pregnancies, and potential benefits in reducing complications. The review highlights nuances in its effects across conditions, indicating advantages such as reduced risk of macrosomia and cesarean section in gestational diabetes. However, its prophylactic role in preventing gestational diabetes and associated complications remains inconclusive. In obese pregnant women, mixed results are observed, with potential benefits in reducing pre-eclampsia risk. Metformin shows promise in preventing preterm birth and late miscarriage in PCOS pregnancies. Categorizing patient subgroups is crucial for identifying advantages, especially in gestational diabetes and type 2 diabetes. Challenges arise from study heterogeneity, necessitating standardized indications for dosage, timing, and postpartum follow ups. Efforts to identify patient characteristics influencing metformin efficacy are crucial for tailored therapy. Although metformin emerges as a viable option in complicated pregnancies, comprehensive research, standardized protocols, and subgroup identification efforts will enhance clinical utility, ensuring evidence-based therapies and optimal maternal and fetal outcomes. Bridging existing knowledge gaps remains imperative for advancing metformin's role in pregnancy management.

Extrauterine adenomyoma: A case report and systematic review of the literature.

OBJECTIVE: To describe a case of extrauterine adenomyoma (EA) and review all the cases of EA in the literature. METHODS: Pubmed/MEDLINE, Embase, and Google Scholar from 1807 to December 2022. All studies reporting the histologic diagnosis of an EA. We collected the following data: patient's age, size and location of adenomyoma, presence of endometriosis and adenomyosis, past gynecologic treatment, symptoms, diagnostic imaging, surgical intervention, alternative/adjuvant treatment, associated malignancy, and follow up. RESULTS: Sixty-seven studies with 85 patients were included. Pain was the most frequent symptom (69.5%). Among diagnostic examinations, ultrasonography was used in 60 out of 81 reported cases, with several radiologic features described. EA was located inside the pelvis in 77.6% of patients. Adnexa were the most frequent site of the disease (24, 28.2%). History of endometriosis or adenomyosis was described in 35 patients (35, 41.2%). Uterine tissue morcellation was reported in 6 of the 85 patients (7.1%). Associated malignancy was detected in 9 out of 85 patients with available data (10.6%). There were two recurrences of disease. CONCLUSION: Specific imaging features of EA are yet to be described in the literature. History of endometriosis and adenomyosis or uterine tissue morcellation may be suggestive of EA. Histologic examination can give a definitive diagnosis and exclude malignant transformation.

Conservative re-treatment of women with atypical endometrial hyperplasia and early endometrial carcinoma: We can hope, at least.

BACKGROUND: In women with recurrent disease who were conservatively treated for atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EEC), the reasons why conservative treatment was chosen persist and outcomes of performing a conservative re-treatment are unclear, as pooled estimates on oncologic outcomes of such a re-treatment are lacking. OBJECTIVES: To provide pooled estimates of oncologic outcomes of conservative re-treatment in women with recurrent AEH or EC. SEARCH STRATEGY: A systematic review and meta-analysis was performed by searching six electronic databases from their inception to March 2022. SELECTION CRITERIA: Studies that allowed extraction of data about oncologic outcomes of conservative re-treatment of women with recurrent AEH and EEC after a conservative treatment. DATA COLLECTION AND ANALYSIS: Pooled prevalence of complete response (CR), poor response (PR), and recurrence after conservative re-treatment was calculated. MAIN RESULTS: Fifteen studies (12 retrospective and 3 prospective) with 492 women (42.1% AEH and 57.9% EEC) were included in the systematic review, and 10 studies (8 retrospective and 2 prospective) were suitable for the meta-analysis. Pooled prevalence was 85.3% (95% confidence interval [CI] 77.0%-91.0%) for CR, 14.7% (95% CI 9.0%-23.0%) for PR, and 40.4% (95% CI 15.5%-71.4%) for recurrence. CONCLUSIONS: Conservative re-treatment in AEH or EC recurrent women has a high CR rate and acceptable recurrence rate that might allow it to be considered a safe and viable option, at least as a first round of conservative treatment. Women with an unsatisfied desire for motherhood or with high surgical risk might avoid hysterectomy and attempt childbearing or spare high-risk surgery.

Comparison of perioperative surgical outcomes between contained and free manual vaginal morcellation of large uteruses following total laparoscopic hysterectomy.

OBJECTIVE: To compare contained and free manual vaginal morcellation of large uteruses after total laparoscopic hysterectomy (TLH) in women at low risk of uterine malignancy in terms of feasibility and safety. METHODS: A single-center, observational, retrospective, cohort study was carried out including all patients undergoing TLH requiring manual vaginal morcellation for specimen extraction of large uteruses from January 2015 to August 2021 at the Division of Gynecology and Human Reproduction Physiopathology, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Bologna, Italy. Patients were divided into two groups according to the type of manual vaginal morcellation (contained or free), and compared in terms of demographic, clinical, and perioperative data. RESULTS: In all, 271 patients were included: 186 (68.6%) in the contained morcellation group and 85 (31.4%) in the free morcellation group. The mean operative time was significantly lower in the contained morcellation group compared with the free morcellation group (median [interquartile range] 130 [45] vs. 155 [60] min; P < 0.001). No significant difference was found in complications related to the morcellation step, overall, intraoperative and postoperative complications, estimated blood loss, length of hospital stays, uterine weight, and rate of occult malignancy between the two groups. CONCLUSION: Contained vaginal manual morcellation of the uterus after total laparoscopic hysterectomy using a specimen retrieval bag appears to be a safe procedure with significantly lower operative time than free vaginal manual morcellation.

Progression of adenomyosis: Rate and associated factors.

OBJECTIVE: To evaluate the rate of disease progression and the factors associated with such progression in patients with an ultrasound diagnosis of adenomyosis. METHODS: This was a single center, prospective, observational, cohort study performed at a tertiary referral center. Patients who obtained an ultrasound diagnosis of adenomyosis from May 2022 to August 2022 were recruited. Demographic, clinical and ultrasound data were recorded at the first visit (T0) and after 12 months (T1) for enrolled patients and compared between T0 and T1. The study population was divided in two groups according to progression (increase in uterine volume >20%) or stability/regression (decrease or increase in uterine volume ≤20%) of adenomyosis at T1. Primary study outcome was the rate of adenomyosis progression, while secondary study outcome was the association of adenomyosis progression with demographic and clinical factors. Post hoc subgroups analyses for primary and secondary study outcomes were performed based on hormonal therapy (untreated and treated). RESULTS: A total of 221 patients were enrolled in the study, with no significant difference in terms of baseline data among the two study groups and no patients were lost to follow-up. The overall rate of adenomyosis progression was 21.3% (47/221 patients). The rate was 30.77% in hormonally untreated women, and 18.34% in hormonally treated women. Progression was associated with the presence of focal adenomyosis of the outer myometrium (P = 0.037), moderate to severe dysmenorrhea (P = 0.001), chronic pelvic pain (P = 0.05), dyschezia (P = 0.05), and worsening of chronic pelvic pain (P = 0.04) at T1. CONCLUSION: Adenomyosis showed a rate of disease progression of 21.3% at the 12-month follow-up (30.77% in hormonally untreated women, and 18.34% in hormonally treated women). The presence and/or worsening of painful symptoms, such as severe dysmenorrhea, dyschezia and chronic pelvic pain, as well as the presence focal adenomyosis of the outer myometrium, might help identify patients at higher risk of disease progression and tailor their follow-up.

Port Site Metastasis in Women with Low- or Intermediate-Risk Endometrial Carcinoma: A Systematic Review of Literature.

Background: Port site metastasis (PSM) has been reported as a rare metastasis in women with endometrial carcinoma (EC). However, even more rarely, it has also been described in patients with low- or intermediate-risk EC. Unfortunately, knowledge appears limited on the topic. Objectives: Our objective was to systematically review the literature on PSM in low- or intermediate-risk EC. Search Strategy: A systematic review of the literature was performed by searching six electronic databases from their inception to January 2023. Selection Criteria: We included in our research all peer-reviewed studies which reported PSM in low- or intermediate-risk EC women. Data Collection and Analysis: Data on PSM were collected from the included studies and compared. Results: Seven studies with 13 patients (including our case) were included in the systematic review. PSM was reported in patients with low- or intermediate-risk EC independently from tumor histologic characteristics, endoscopic approach, lymph node staging type, number and site of the port, route of specimen removal, prevention strategies for PSM, and concomitant metastases. Among several proposed treatments, local resection and radiotherapy with or without chemotherapy might be the most appropriate ones. Nevertheless, the prognosis appears poor. Conclusions: In patients with low- or intermediate-risk EC, PSM can occur as a rare metastasis, regardless of tumor characteristics or surgical strategy. Unfortunately, no consensus has been reached regarding treatment, and the prognosis appears poor. Additional cases are needed in order to confirm and further explore this rare EC metastasis.

Detection and Classification of Hysteroscopic Images Using Deep Learning.

BACKGROUND: Although hysteroscopy with endometrial biopsy is the gold standard in the diagnosis of endometrial pathology, the gynecologist experience is crucial for a correct diagnosis. Deep learning (DL), as an artificial intelligence method, might help to overcome this limitation. Unfortunately, only preliminary findings are available, with the absence of studies evaluating the performance of DL models in identifying intrauterine lesions and the possible aid related to the inclusion of clinical factors in the model. AIM: To develop a DL model as an automated tool for detecting and classifying endometrial pathologies from hysteroscopic images. METHODS: A monocentric observational retrospective cohort study was performed by reviewing clinical records, electronic databases, and stored videos of hysteroscopies from consecutive patients with pathologically confirmed intrauterine lesions at our Center from January 2021 to May 2021. Retrieved hysteroscopic images were used to build a DL model for the classification and identification of intracavitary uterine lesions with or without the aid of clinical factors. Study outcomes were DL model diagnostic metrics in the classification and identification of intracavitary uterine lesions with and without the aid of clinical factors. RESULTS: We reviewed 1500 images from 266 patients: 186 patients had benign focal lesions, 25 benign diffuse lesions, and 55 preneoplastic/neoplastic lesions. For both the classification and identification tasks, the best performance was achieved with the aid of clinical factors, with an overall precision of 80.11%, recall of 80.11%, specificity of 90.06%, F1 score of 80.11%, and accuracy of 86.74 for the classification task, and overall detection of 85.82%, precision of 93.12%, recall of 91.63%, and an F1 score of 92.37% for the identification task. CONCLUSION: Our DL model achieved a low diagnostic performance in the detection and classification of intracavitary uterine lesions from hysteroscopic images. Although the best diagnostic performance was obtained with the aid of clinical data, such an improvement was slight.

Molecular Factors Predicting Ovarian Chemotoxicity in Fertile Women: A Systematic Review.

Background: Recent advances in cancer diagnosis and treatment have significantly improved survival rates among women of reproductive age facing cancer. However, the potential iatrogenic loss of fertility caused by chemotherapeutic agents underscores the need to understand and predict chemotherapy-induced ovarian damage. This study addresses this gap by systematically reviewing the literature to investigate genetic markers associated with chemotherapy-induced ovarian failure (CIOF). Objective: The primary objective is to identify genetic markers linked to CIOF, contributing to a comprehensive understanding of the factors influencing fertility preservation in female cancer survivors. Methods: A systematic review was conducted using PubMed, EMBASE, Web of Science, Scopus, and OVID electronic databases from inception through December 2023. Studies were included if they featured genomic assessments of genes or polymorphisms related to CIOF in women with histologically confirmed tumors. Exclusion criteria comprised in vitro and animal studies, reviews, and pilot studies. The resulting four human-based studies were scrutinized for insights into genetic influences on CIOF. Results: Of the 5179 articles initially identified, four studies met the inclusion criteria, focusing on alkylating agents, particularly cyclophosphamide, and anthracyclines. Su et al. explored CYP3A41B variants, revealing modified associations with CIOF based on age. Charo et al. investigated GSTA1 and CYP2C19 polymorphisms, emphasizing the need to consider age and tamoxifen therapy in assessing associations. Oktay et al. delved into the impact of BRCA mutations on anti-Müllerian hormone (AMH) levels post-chemotherapy, supported by in vitro assays. Van der Perk et al. focused on childhood cancer survivors and revealed significant associations of CYP3A43 and CYP2B6*2 SNPs with AMH levels. Conclusions: This systematic review analyzes evidence regarding genetic markers influencing CIOF, emphasizing the complex interplay of age, specific genetic variants, and chemotherapy regimens. The findings underscore the need for a personalized approach in assessing CIOF risk, integrating genetic markers with traditional ovarian reserve testing. The implications of this study extend to potential advancements in fertility preservation strategies, offering clinicians a comprehensive baseline assessment for tailored interventions based on each patient's unique genetic profile. Further research is essential to validate these findings and establish a robust framework for integrating genetic markers into clinical practice.

Sonographic Cortical Development and Anomalies in the Fetus: A Systematic Review and Meta-Analysis.

The aim of this systematic review is to report the normal cortical development of different fetal cerebral fissures on ultrasound, describe associated anomalies in fetuses with cortical malformations, and evaluate the quality of published charts of cortical fissures. The inclusion criteria were studies reporting development, anomalies, and reference charts of fetal cortical structures on ultrasound. The outcomes observed were the timing of the appearance of different cortical fissures according to different gestational age windows, associated central nervous system (CNS) and extra-CNS anomalies detected at ultrasound in fetuses with cortical malformation, and rate of fetuses with isolated anomaly. Furthermore, we performed a critical evaluation of the published reference charts for cortical development on ultrasound. Random-effect meta-analyses of proportions were used to combine the data. Twenty-seven studies (6875 fetuses) were included. Sylvian fissure was visualized on ultrasound in 97.69% (95% CI 92.0-100) of cases at 18-19, 98.17% (95% CI 94.8-99.8) at 20-21, 98.94% (95% CI 97.0-99.9) at 22-23, and in all cases from 24 weeks of gestation. Parieto-occipital fissure was visualized in 81.56% (95% CI 48.4-99.3) of cases at 18-19, 96.59% (95% CI 83.2-99.8) at 20-21, 96.85% (95% CI 88.8-100) at 22-23, and in all cases from 24 weeks of gestation, while the corresponding figures for calcarine fissure were 37.27% (95% CI 0.5-89.6), 80.42% (95% CI 50.2-98.2), 89.18% (95% CI 74.0-98.2), and 96.02% (95% CI 96.9-100). Malformations of cortical development were diagnosed as an isolated finding at ultrasound in 6.21% (95% CI 2.9-10.9) of cases, while they were associated with additional CNS anomalies in 93.79% (95% CI 89.1-97.2) of cases. These findings highlight the need for large studies specifically looking at the timing of the appearance of the different brain sulci. Standardized algorithms for prenatal assessment of fetuses at high risk of malformations of cortical development are also warranted.

Molecular Signature of Endometrial Cancer with Coexistent Adenomyosis: A Multicentric Exploratory Analysis.

Adenomyosis has been associated with better survival outcomes in women with endometrial cancer. However, although the endometrial cancer patients' risk stratification has been revolutionized by molecular findings, the impact of the molecular signature on the favorable prognosis of endometrial cancer patients with coexistent adenomyosis is unknown. The aim of our study was to compare the prevalence of molecular groups at poor and intermediate prognosis between endometrial cancer patients with and without coexistent adenomyosis. A multicentric, observational, retrospective, cohort study was performed to assess the differences in the prevalence of p53-abnormal expression (p53-abn) and mismatch repair protein-deficient expression (MMR-d) signatures between endometrial cancer patients with and without coexistent adenomyosis. A total of 147 endometrial cancer patients were included in the study: 38 in the adenomyosis group and 109 in the no adenomyosis group. A total of 37 patients showed the MMR-d signature (12 in the adenomyosis group and 25 in the no adenomyosis group), while 12 showed the p53-abn signature (3 in the adenomyosis group and 9 in the no adenomyosis group). No significant difference was found in the prevalence of p53-abn (p = 1.000) and MMR-d (p = 0.2880) signatures between endometrial cancer patients with and without coexistent adenomyosis. In conclusion, the molecular signature does not appear to explain the better prognosis associated with coexistent adenomyosis in endometrial cancer patients. Further investigation of these findings is necessary through future larger studies.