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Background: In endometrial carcinoma (EC) patients, sentinel lymph node (SLN) biopsy has shown the potential to reduce post-operative morbidity and long-term complications, and to improve the detection of low-volume metastasis through ultrastaging. However, while it has shown high sensitivity and feasibility in low-risk EC patient groups, its role in high-risk groups is still unclear. Aim: To assess the role of SLN biopsy through the cervical injection of indocyanine green (ICG) in high-risk groups of early-stage EC patients. Materials and methods: Seven electronic databases were searched from their inception to February 2021 for studies that allowed data extraction about detection rate and accuracy of SLN biopsy through the cervical injection of ICG in high-risk groups of early-stage EC patients. We calculated pooled sensitivity, false negative (FN) rate, detection rate of SLN per hemipelvis (DRh), detection rate of SLN per patients (DRp), and bilateral detection rate of SLN (DRb), with 95% confidence interval (CI). Results: Five observational cohort studies (three prospective and two retrospective) assessing 578 high risk EC patients were included. SLN biopsy sensitivity in detecting EC metastasis was 0.90 (95% CI: 0.03–0.95). FN rate was 2.8% (95% CI: 0.6–11.6%). DRh was 88.4% (95% CI: 86–90.5%), DRp was 96.6% (95% CI: 94.7–97.8%), and DRb was 80% (95% CI: 75.4–83.9). Conclusion: SLN biopsy through ICG cervical injection may be routinely adopted instead of systematic pelvic and para-aortic lymphadenectomy in surgical staging for high-risk groups of early-stage EC patients, as well as in low-risk groups.

Introduction Robot‐assisted laparoscopic surgery (RALS) has gained widespread application in several surgical specialties. Previous studies on the feasibility and safety of RALS vs standard laparoscopy (S‐LPS) for rectosigmoid endometriosis are limited and reported conflicting data. This study aims to compare S‐LPS and RALS in patients with rectosigmoid endometriosis in terms of perioperative surgical and clinical data. Material and methods This is a multicentric, observational, prospective cohort study including 44 patients affected by rectosigmoid endometriosis referred to two tertiary referral centers for endometriosis from September 2018 to September 2019. Patients were divided into two groups: 22 patients underwent S‐LPS, and 22 underwent RALS. Our primary outcome was to compare operative time (from skin incision to suture) between the two groups. Secondary outcomes included: operative room time (patient entry into operative room and patient out), estimated blood loss, laparotomic conversion rate, length of hospital stay, perioperative complications, and evaluation of endometriosis‐related symptoms at 12‐month follow up. Results The two groups were comparable regarding preoperative and surgical data, except for higher rates of hysterectomies and bilateral uterosacral ligament removal procedures in the RALS group. Also after adjusting for these discrepancies, operative time was similar between S‐LPS and RALS. Operative room time was statistically longer in the RALS group compared with that of S‐LPS. No statistically significant difference was found concerning other study outcomes. Pain and bowel symptoms improved in both groups at 12‐month follow up. Conclusions If performed by expert teams, RALS provides similar perioperative outcomes compared with S‐LPS in rectosigmoid endometriosis surgical treatment, except for longer operative room time.

Study Objective To evaluate feasibility of near-infrared (NIR)–indocyanine green (ICG) imaging for bowel vascularization assessment after full-thickness bowel resection for rectosigmoid endometriosis (RSE). Design This is a prospective, single-center, preliminary study on consecutive patients who were symptomatic submitted to discoid or segmental resection for RSE and NIR-ICG evaluation for vascular assessment of the anastomotic line from May 2018 to January 2020. Setting Tertiary university hospital. Patients Thirty-two women with RSE meeting eligibility criteria were included for study analysis. Interventions NIR-ICG evaluation of anastomotic line vascularization after RSE removal. Measurements and Main Results Fluorescence degree of the anastomotic line was assessed with a 0 to 2 Likert scale, as follows: 0 or “absent” (no fluorescence observed), 1 or “irregular” (not uniform distribution or weak fluorescence), and 2 or “regular” (uniform distribution of fluorescence and similar to the proximal colon). In all the patients included in the study (100%), NIR-ICG imaging allowed the evaluation of fluorescence degree of the anastomotic line. No adverse reaction related to ICG use was recorded. The protocol did not greatly lengthen operating time (median, 4 [range, 3–5] minutes). Excellent interoperator agreement was observed. Most of the patients (31 of 32, 96.9%) showed regular fluorescence on the anastomotic line; in 1 patient with irregular fluorescence at NIR-ICG after discoid excision, the anastomotic suture was reinforced through interrupted stitches. We had 1 case of anastomotic leakage after segmental resection with intraoperative good fluorescence at NIR-ICG evaluation. Conclusion NIR-ICG imaging for anastomotic perfusion assessment after discoid or segmental resection for RSE seems to be a feasible, safe, and reproducible method.

To assess prevalence of central sensitization (CS) and its association with demographic and clinical factors in patients with endometriosis.Single-center, observational, cross-sectional study.Tertiary center.Consecutive patients with endometriosis referred to the center from January 15, 2022, to April 30, 2022.For each enrolled patient, demographic and clinical data were collected, and the presence of CS was measured using the CS Inventory questionnaire (score ≥40).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.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.

Introduction Several studies have assessed the histological co-existence of endometrial carcinoma (EC) and adenomyosis. However, the significance of this association is still unclear. Objective To assess the prevalence of adenomyosis in women with EC for a better understanding of the association between the two diseases. Materials and methods A systematic review and meta-analysis was performed by searching electronics databases from their inception to March 2020, for all studies that allowed extraction of data about prevalence of adenomyosis in EC patients. Adenomyosis prevalence was calculated for each included study and as pooled estimate, with 95% confidence interval (CI). Results Eight retrospective cohort studies assessing 5573 EC patients were included in our analysis. Of total, 1322 were patients with adenomyosis, and 4251 were patients without adenomyosis. Pooled prevalence of adenomyosis in EC patients was 22.6% (95% CI 12.7–37.1%). Conclusion Adenomyosis prevalence in EC patients was not different from that reported for other gynecological conditions. The supposed association between the two diseases appears unsupported.

To assess uterine artery arteriosclerosis prevalence in women undergoing total hysterectomy for benign diseases, and any associations between clinical, laboratory, and ultrasound factors and uterine artery arteriosclerosis occurrence.A single center, observational, prospective, cohort study was performed enrolling all symptomatic patients scheduled for total hysterectomy from May to December 2021. Our outcomes were: uterine artery arteriosclerosis prevalence and the difference in clinical, laboratory, and ultrasonographic factors between patients with and without uterine artery arteriosclerosis.Forty women were included. Uterine artery arteriosclerosis prevalence was 70%. Body mass index (BMI) (P = 0.04) and triglycerides (P = 0.04) were significantly higher in patients with uterine artery arteriosclerosis than in patients without; while high-density lipoprotein (HDL) (P = 0.02) was significantly lower. Uterine arteries with arteriosclerosis showed higher peak systolic velocity (PSV) values compared with vessels without arteriosclerosis (P = 0.05).Uterine artery arteriosclerosis shows a high prevalence in women undergoing total hysterectomy for benign diseases. Higher BMI, serum triglycerides, and PSV, and lower serum HDL appear as risk factors for uterine artery arteriosclerosis.

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.

BACKGROUND It is unclear whether uterine carcinosarcoma (UCS) is more aggressive than endometrial serous carcinoma (SC) and clear cell carcinoma (CCC). OBJECTIVES To compare the prognosis of UCS to that of endometrial SC and CCC, through a systematic review and meta-analysis. SEARCH STRATEGY Four electronic databases were searched from January 2000 to October 2020. SELECTION CRITERIA All studies assessing hazard ratio (HR) for death in UCS vs SC and/or CCC. DATA COLLECTION AND ANALYSIS HRs for death with 95% confidence interval were extracted and pooled by using a random-effect model. A significant p-value

Objective: To study the economic impact of ovarian tissue cryopreservation and transplantation (OTC) in post-pubertal patients who underwent high-risk gonadotoxic chemotherapy. Methods: A decision tree model was used to determine the live birth rate and cost-effectiveness of OTC versus non-OTC. The incremental cost-effectiveness ratio (ICER) was calculated. A sensitivity analysis was performed under the assumption that the costs of ovarian cortex retrieval, cryopreservation, and storage for patients with cancer might be covered by the national health system or health insurance. Results: Patients had the greatest probability of achieving live birth after high-risk chemotherapy when they underwent OTC versus non-OTC. Although cryopreservation of ovarian tissue results in higher live birth rates, it is always more expensive. Cost-effectiveness increases when the majority of patients completes the path of tissue cryopreservation plus transplantation after 5years. Conclusion: Although OCT has been demonstrated as a procedure for effective fertility preservation in fertility-age women with cancer, no cost-effectiveness analysis has been performed until now. This model could help healthcare systems to allocate coverage for OCT.

Objective To assess the association between sonographic findings at transperineal ultrasound (TPU) and chronic constipation (CC) in women with endometriosis. Methods An observational prospective cohort study was performed by enrolling all women with endometriosis scheduled for surgery between September 2019 and October 2020. Women underwent TPU at rest and during Valsalva maneuver evaluating levator-hiatal-area (LHA), antero-posterior diameter (APD), and levator ani muscle (LAM) coactivation. Ultrasound findings were compared between women with and without CC in the whole study population, and subsequently in two subgroups (only ovarian endometriosis and deep infiltrating endometriosis [DIE]). Results In all, 87 women were enrolled: 29 (33%) with CC and 58 (67%) without CC. Women with endometriosis and CC showed a smaller LHA during Valsalva, less LHA and APD enlargement from rest to maximum Valsalva, and a higher prevalence of LAM coactivation compared with women without CC. In the ovarian subgroup, women with CC had smaller LHA at Valsalva, less enlargement of LHA and APD from rest to maximum Valsalva, and higher prevalence of LAM coactivation compared with non-CC patients. In the DIE subgroup, TPU did not significantly differ between CC and non-CC patients. Conclusion TPU signs of pelvic floor muscle hypertonia are more frequent in endometriosis patients with CC compared with those without constipation, particularly in women affected by isolated ovarian endometriosis.

Objective To evaluate the functional outcomes of nerve-sparing surgery for deep infiltrating endometriosis (DIE) with or without posterolateral parametrectomy. Methods A multicenter, observational, retrospective, cohort study was performed including all symptomatic women who underwent nerve-sparing laparoscopic excision of DIE and preoperative and postoperative assessment of functional outcomes through validated questionnaires between April 2019 and March 2020. Women with posterolateral parametrial DIE (P-group) and women with no parametrial involvement (NP-group) were compared in terms of preoperative and postoperative functional outcomes related to pelvic organs assessed through validated questionnaires (KESS and GIQLI for bowel function, BFLUTS for urinary function, and FSFI for sexual function); pain symptoms at 3-month follow up assessed through an 11-point visual analogue scale (VAS) for dyschezia, dysmenorrhea, dyspareunia and chronic pelvic pain; surgical outcomes; and rate of urinary voiding dysfunction at 3-month follow up. Results One-hundred patients were included: 69 in the P-group and 31 in the NP-group. Preoperative and postoperative values of questionnaires, pain symptoms, and postoperative complication rates were comparable between the two groups, except for postoperative dyspareunia and sexual dysfunction, which were statistically higher in the P-group. Only patients in the P-group experienced urinary voiding dysfunction, but no statistical significance was reached (P = 0.173). Conclusion Posterolateral parametrectomy for DIE appears to be associated with a higher risk of postoperative dyspareunia and sexual dysfunction.

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.

Simple Summary Endometrial cancer (EC) reportedly have a better prognosis in patients with coexistent adenomyosis. It is possible to hypothesize that this difference may be attributable to different clinical profiles. On this account, we aimed to define the clinical profile of endometrial cancer (EC) patients with and without adenomyosis through a systematic review and meta-analysis. We included 8 studies with 5681 patients and found that EC women with adenomyosis were less likely to be nulliparous than EC women without adenomyosis, while no significant differences were found with regard to age, BMI, and premenopausal status. Abstract A better endometrial cancer (EC) prognosis in patients with coexistent adenomyosis has been reported. Unfortunately, it is still unclear if this better prognosis is related to a more favorable clinical profile of adenomyosis patients. We aimed to evaluate differences in the clinical profiles of EC patients with and without adenomyosis. A systematic review and meta-analysis was performed by searching seven electronics databases for all studies that allowed extraction of data about clinical characteristics in EC patients with and without adenomyosis. Clinical characteristics assessed were: age, Body Mass Index (BMI), premenopausal status, and nulliparity. Mean difference in mean ± standard deviation (SD) or odds ratio (OR) for clinical characteristics between EC patients with and without adenomyosis were calculated for each included study and as a pooled estimate, and graphically reported on forest plots with a 95% confidence interval (CI). The Z test was used for assessing the overall effect by considering a p value < 0.05 as significant. Overall, eight studies with 5681 patients were included in the qualitative analysis, and seven studies with 4366 patients in the quantitative analysis. Pooled mean difference in mean ± SD between EC women with and without adenomyosis was −1.19 (95% CI: −3.18 to 0.80; p = 0.24) for age, and 0.23 (95% CI: −0.62 to 1.07; p = 0.60) for BMI. When compared to EC women without adenomyosis, EC women with adenomyosis showed a pooled OR of 1.53 (95% CI: 0.92 to 2.54; p = 0.10) for premenopausal status, and of 0.60 (95% CI: 0.41 to 0.87; p = 0.007) for nulliparity. In conclusion, there are not significant differences in clinical characteristics between EC patients with and without adenomyosis, with the exception for nulliparity. Clinical features seem to not underlie the better EC prognosis of patients with adenomyosis compared to patients without adenomyosis.

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.

Background Polymerase-e (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.

Objective: To evaluate effectiveness and reproducibility of qualitative and quantitative near-infrared indocyanine green (NIR-ICG) analyses as a tool for anastomotic perfusion assessment after full-thickness bowel resection for rectosigmoid endometriosis (RSE). Methods: Symptomatic women with RSE undergoing minimally invasive full-thickness surgical excision of RSE and NIR-ICG evaluation from November 2019 to July 2020 were included. Study outcomes were the accuracy of qualitative and quantitative NIR-ICG analyses in predicting bowel fistula and their reproducibility. NIR-ICG predictive accuracy was assessed by calculating sensitivity, specificity, and area under the curve on receiver operating characteristic curves with 95% confidence intervals (CI). NIR-ICG reproducibility was assessed through Cohen's k coefficient to determine interoperator agreement between two observers. Results: Of 33 patients, 2 (6%) developed bowel fistula. In predicting bowel fistula, qualitative and quantitative NIR-ICG evaluations showed sensitivity of 100% and 100%, specificity of 71% and 93%, and area under the curve of 0.86 (95% CI 0.67–1.00) and 0.96 (95% CI 0–1.00), respectively. Regarding interoperator agreement rate, it was reported as excellent for the qualitative analysis and very good for the quantitative analysis. Conclusion: Qualitative and quantitative NIR-ICG evaluations might be effective and reproducible tools for anastomotic perfusion assessment after discoid or segmental resection for RSE. Quantitative evaluation might be even more effective than qualitative evaluation in predicting bowel fistula.