Implementing Enhanced Recovery After Surgery for hysterectomy in a hospital network with audit and feedback: A stepped-wedge cluster randomised trial.

OBJECTIVE: To evaluate the effectiveness of implementing the Enhanced Recovery After Surgery (ERAS) protocol in patients undergoing elective hysterectomy in a network of regional hospitals, supported by an intensive audit-and-feedback (A&F) approach. DESIGN: A multi-centre, stepped-wedge cluster randomised trial (ClinicalTrials.gov NCT04063072). SETTING: Gynaecological units in the Piemonte region, Italy. POPULATION: Patients undergoing elective hysterectomy, either for cancer or for benign conditions. METHODS: Twenty-three units (clusters), stratified by surgical volume, were randomised into four sequences. At baseline (first 3 months), standard care was continued in all units. Subsequently, the four sequences implemented the ERAS protocol successively every 3 months, after specific training. By the end of the study, each unit had a period in which standard care was maintained (control) and a period in which the protocol, supported by feedback, was applied (experimental). MAIN OUTCOME MEASURES: Length of hospital stay (LOS), without outliers (>98th percentile). RESULTS: Between September 2019 and May 2021, 2086 patients were included in the main analysis with an intention-to-treat approach: 1104 (53%) in the control period and 982 (47%) in the ERAS period. Compliance with the ERAS protocol increased from 60% in the control period to 76% in the experimental period, with an adjusted absolute difference of +13.3% (95% CI 11.6% to 15.0%). LOS, moving from 3.5 to 3.2 days, did not show a significant reduction (-0.12 days; 95% CI -0.30 to 0.07 days). No difference was observed in the occurrence of complications. CONCLUSIONS: Implementation of the ERAS protocol for hysterectomy at the regional level, supported by an A&F approach, resulted in a substantial improvement in compliance, but without meaningful effects on LOS and complications. This study confirms the effectiveness of A&F in promoting important innovations in an entire hospital network and suggests the need of a higher compliance with the ERAS protocol to obtain valuable improvements in clinical outcomes.

A randomized controlled trial on the oncologic outcomes of use of the intrauterine manipulator in the treatment of apparent uterine-confined endometrial carcinoma: the MANEC Trial.

BACKGROUND: The intrauterine manipulator used during a hysterectomy for endometrial cancer has been suggested as a reason for worsening oncologic outcomes. However, only a few non-randomized retrospective studies have investigated this association. PRIMARY OBJECTIVES: To compare 4-year recurrence-free survival in the group of patients who undergo hysterectomy using an intrauterine manipulator with that of those who undergo hysterectomy without it. STUDY HYPOTHESIS: Patients with endometrial cancer who undergo laparoscopic hysterectomy performed with an intrauterine manipulator would have a lower recurrence-free survival than patients who undergo laparoscopic hysterectomy without a manipulator. TRIAL DESIGN: Multicenter, parallel arm, open-label, randomized controlled trial. MAJOR INCLUSION/EXCLUSION CRITERIA: Adult women diagnosed with apparently uterine-confined endometrial cancer of any histology are eligible. We exclude women who had synchronous or previous (<5 years) invasive cancer, had a WHO performance score >2, and had inadequate baseline organ function. PRIMARY ENDPOINTS: 4-Year recurrence-free survival defined as any relapse or death related to endometrial cancer or treatment calculated from randomization to the date of the first recurrence-free survival event. SAMPLE SIZE: With an accrual time of 4 years, a minimum follow-up length of 4 years, and a two-sided type I error of 0.05, we need to enroll 515 women per arm to have a statistical power of 80% to reject the null hypothesis (HR for recurrence=1), assuming that patients who undergo hysterectomy with the use of the intrauterine manipulator have a 3-year recurrence rate of 12.5% and without the use of the intrauterine manipulator of 8.5% (HR for recurrence=1.50), and that 5% of patients are lost at follow-up in each arm, with a median time of 24 months. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual completion is expected in 2028, and result presentation in 2032. TRIAL REGISTRATION: ClinicalTrial.gov ID NCT05687084.

SUrgical Access and Pattern of Recurrence of Endometrial Cancer: The SUPeR Study, a Multicenter Retrospective Observational Study.

STUDY OBJECTIVE: To evaluate recurrence rate and pattern in apparently early-stage endometrial cancer (EC) treated with minimally invasive surgery (MIS) and compare it to the "historical" populations treated by laparotomy. Secondary outcomes were to establish if, among MIS recurrent patients, intermediate-high/high-risk patients presented the same recurrence pattern compared to those at low/intermediate-risk and to evaluate time to first recurrence (TTR) of the study population. DESIGN: Multicenter retrospective observational study. SETTING: Five Italian Gynecologic Oncology referral centers. PATIENTS: All patients with proven recurrence of apparently early-stage EC treated with MIS from January 2017 to June 2022 . The laparotomic historical cohort was obtained from Laparoscopy Compared With Laparotomy for Comprehensive Surgical Staging of Uterine Cancer: Gynecologic Oncology Group Study (LAP2) and Laparoscopic Approach to Cancer of the Endometrium trials. INTERVENTIONS: Evaluation of recurrence rate and pattern. MEASUREMENTS AND MAIN RESULTS: Seventy-seven recurrences occurred on the total of 1028 patients treated with MIS for apparently early-stage EC during a median follow-up time of 36 months. The rate of recurrence in our cohort did not differ significantly from the rate of the historical cohort (7.4% vs 7.9%, odds ratio 0.9395, 95% CI 0.6901-1.2792). No significant differences were noticed for local, abdominal, nodal, and multiple site recurrence patterns; distant site recurrence appeared more likely in patients from the historical cohort. Postoperative low/intermediate risk patients had a higher likelihood of local recurrence compared to intermediate-high/high risk patients. Mean TTR was 19 months. No significant difference of TTR was observed for each pattern of recurrence compared to others. CONCLUSION: MIS appears to be safe for the treatment of early-stage EC. We did not identify any recurrence pattern specifically associated with MIS in early-stage EC.

Anatomical distribution of sentinel lymph nodes in patients with endometrial cancer: a multicenter study.

OBJECTIVE: Sentinel lymph node (SLN) mapping represents the standard approach in uterine confined endometrial cancer patients. The aim of this study was to evaluate the anatomical distribution of SLNs and the most frequent locations of nodal metastasis. METHODS: This was an observational retrospective multicenter study involving eight high volume gynecologic cancer centers in Italy. We reviewed 1576 patients with a histologically confirmed diagnosis of endometrial cancer from September 2015 to June 2020. All patients underwent total hysterectomy with salpingo-ophorectomy and SLN mapping. RESULTS: A total of 3105 SLNs were mapped and removed, 2809 (90.5%) of these were bilateral and 296 (9.5%) unilateral. The overall detection rate was 93.4% (77.9% bilateral and 15.5% unilateral). The majority of SLNs (80%) and positive SLNs (77.8%) were found at the external iliac and obturator level in both endometrioid and non-endometrioid endometrial cancer. Negative SLNs were more frequent in patients with endometrioid compared with non-endometrioid cancer (91.9% vs 86.1%, p<0.0001). Older patients, a higher body mass index, and non-endometrioid histology were more likely to have 'no mapping' (p<0.0001). Univariate and multivariate analysis showed that higher body mass index and age at surgery were independent predictive factors of empty node packet and fat tissue (p=0.029 and p<0.01, respectively). CONCLUSION: The most frequent sites of SLNs and metastases were located in the pelvic area below the iliac vessel bifurcation. Our findings showed that older age, a higher body mass index, and non-endometrioid histology had a negative impact on mapping.

Successful laparoscopic surgical removal of a caesarean scar pregnancy (CSP) using temporary uterine artery ligation.

STUDY OBJECTIVE: To demonstrate a laparoscopic technique to remove a scar pregnancy. DESIGN: Stepwise demonstration of the surgical technique. SETTING: Santa Croce and Carle Hospital, Cuneo. INTERVENTION: Patient B.B. is a woman referred to our center for a suspected cesarean scar pregnancy (CSP) at 9 weeks gestation. CSP occurs approximately in 6% of all ectopic pregnancies. The estimated incidence is reported to be 1:1800 to 1:2500 in cesarean deliveries. Depending on its location, CSP can be categorized as either type 1, if the growth is in the uterine cavity, or type 2, if it expands toward the bladder and the abdominal cavity. If inadequately managed, it can lead to severe complications; most of them are hemorrhagic and can threaten the woman's life. There are several therapeutic approaches: local excision seems to be the most effective choice in type 2 CSP. In expert hands, the laparoscopic approach is perhaps the best surgical choice as tissue dissection, electrosurgical hemostasis, and vascular control can be effectively managed with minimal invasive access. Because severe intraoperative bleeding can occur, retroperitoneal vascular control is mandatory in this surgery. In type 1 CSP curettage, aspiration or hysteroscopic approach can be considered if the CSP is of small dimensions. A hysteroscopic approach can also be helpful in type 2 CSP during the laparoscopic removal, as intrauterine guidance. A potassium chloride local injection can be considered in a preoperative stage in the presence of a fetal heart rate. The systemic administration of methotrexate is usually ineffective as single agent, but it can be useful if administered as adjuvant therapy. Uterine artery embolization can be useful in an emergency setting to manage severe bleeding, but it can lead to complications in subsequent pregnancies and, more rarely, to premature ovarian failure. Considering poor bleeding at presentation, feasible dimensions, and the woman's desire for future pregnancy, ultrasound-guided aspiration and curettage was attempted. Because endouterine removal was incomplete, methotrexate injection was proposed as adjuvant therapy, but the administration was postponed as the patient tested positive for coronavirus disease 2019. A month later, beta-human chorionic gonadotropin level dropped from over 16 000 to 271 mU/mL, so an ultrasound and biochemical follow-up was performed. A month later, despite a low beta-human chorionic gonadotropin value, an increase in dimensions was observed at ultrasound, so surgical laparoscopic removal was offered. In this video article, laparoscopic removal of scar pregnancy is discussed in the following surgical steps: (1) Temporary closure of uterine arteries at the origin, using removable clips. (2) Retroperitoneal dissection to safely manage the scar pregnancy. (3) Dissection of the myometrial-pregnancy interface. (4) Double layer suture on the anterior uterine wall. CONCLUSION: Laparoscopic surgical management is a very effective surgical approach to remove CSP. Knowledge of retroperitoneal dissection and vascular control is necessary to carry out this surgical intervention safely and effectively.

Intraoperative Ultrasound for Bowel Deep Infiltrating Endometriosis: A Preliminary Report.

The decision to perform either conservative surgery or segmental bowel resection for bowel deep infiltrating endometriosis (DIE) is made intraoperatively, after a preoperative assessment, based on the nodule's features. We introduce a technique to evaluate DIE bowel nodules using laparoscopic intraoperative ultrasound (US) during laparoscopic radical treatment of 9 cases of DIE invading the bowel. Once the bowel lesion was isolated, an intraoperative 12-4-MHz US transducer was placed on the surface of the nodules to study their US features and to gain measurements. Deep infiltrating endometriosis nodules appear at intraoperative US as hypoechoic elliptical lesions with a clear definition of margins and the depth of infiltration of the rectal wall.

Traditional McCall culdoplasty compared to a modified McCall technique with double ligament suspension: anatomical and clinical outcomes.

INTRODUCTION AND HYPOTHESIS: This study compared anatomical and clinical outcomes of traditional McCall culdoplasty versus a modified McCall technique with double ligament suspension (DLS). METHODS: This retrospective study presents outcomes of 68 patients who underwent vaginal hysterectomy and vaginal suspension for apical prolapse ≥ stage II according to the POP-Q score system, at, between January 2016 and February 2018. In 34 women vaginal cuff suspension was obtained with traditional McCall culdoplasty (McCall group), while in 34 women we performed a modified McCall, which consists of a double ligament suspension (DLS group), suspending the vaginal cuff to uterosacral ligaments and also to adnexal peduncles. Primary outcome was prolapse recurrence ≥ stage II according to the POP-Q system. Fisher's, Mann-Whitney U and Student's t tests were used for statistical analysis. RESULTS: There were no statistical differences among patients' preoperative characteristics, operative time, blood loss or postoperative complications. Follow-up mean duration was 23.2 ± 6.7 and 22.4 ± 8.7 months in the McCall and DLS group, respectively. Prolapse recurrence occurred in 11 (32.3%) women in the McCall group versus 2 (5.9%) women in the DLS group (p < 0.05): among them, 2 patients (5.9%) in the McCall group and 1 (2.9%) in the DLS group required further treatment. Total vaginal length was 6.1 ± 0.9 cm in the McCall group versus 6.9 ± 0.7 cm in the DLS group (p < 0.001). No statistical difference in quality of life assessment was observed. CONCLUSIONS: DLS group patients had better anatomical outcomes and lower recurrence rates than McCall group patients, without increasing operative time or complications. A prospective study with more cases is needed to confirm our data.

Sentinel Lymph Node Biopsy in the Treatment of Endometrial Cancer: Why We Fail? Results of a Prospective Multicenter Study on the Factors Associated with Failure of Node Mapping with Indocyanine Green.

BACKGROUND: The sentinel lymph node (SLN) mapping for endometrial cancer staging is gaining wide diffusion, but there is no definitive evidence on the factors associated with the failure of mapping. OBJECTIVES: To analyze the factors associated with the possible failure of bilateral SLN mapping with indocyanine green (ICG). METHODS: A prospective observational study without control on 110 patients with endometrial cancer apparently confined to the uterus, underwent laparoscopic surgical staging with SLN mapping with ICG. RESULTS: Possible risk factors associated with bilateral mapping failure were analyzed, and a multivariate analysis was performed. The bilateral detection rate for SLNs mapping was 72.7%, whereas at least one SLN was detected in 79.1% of patients. No SLNs were identified in 6.3%. None of the patients or features related to tumor were associated with a risk of failure of the method. The only factor analyzed that was significantly associated with the success of bilateral mapping was the surgeon (p = 0.003). CONCLUSIONS: Neither obesity nor the presence of lymph node metastases was associated with mapping failure. However, there remains a need for further studies to understand all the mechanisms linked to the unsuccessful method results and to reduce the use of systematic lymphadenectomy in the case of mapping failure.

Lymph node evaluation in high-risk early stage endometrial cancer: A multi-institutional retrospective analysis comparing the sentinel lymph node (SLN) algorithm and SLN with selective lymphadenectomy.

OBJECTIVE: The aim of this study was to determine the impact of the sentinel lymph node mapping algorithm (SLN-A) on the staging in high-risk endometrial cancer (EC) compared to SLN plus selective lymphadenectomy (S-LND). METHODS: We retrospectively analyzed the database from a multicenter collaboration that included women with high risk features who underwent primary surgical staging. RESULTS: One-hundred and seventy-one women were identified (171), 66 in the SLN-A and 105 in the S-LND group, respectively. Pelvic LD was performed on 115 patients (67.2%) and aortic dissection was performed in 54/105 of the women in the S-LND group (51%). The 5-year comparison did not show a significant difference in the strategy adopted for nodal staging, regarding disease-free survival (DFS) [HR: 0.82; 95% CI 0.53-1.28; p = 0.390]. CONCLUSIONS: In this study focusing on women with EC in the HR groups, we did not find a difference in the 5-year DFS when comparing the SLN-A strategy with S-LND. The SLN strategy did not seem to compromise the prognosis of patients with a higher risk of recurrence.

Tailoring radicality in diaphragmatic surgery for deep endometriosis: A matter of choice.

Diaphragmatic endometriosis (DpE) is a rare disease localization which represents an important clinical challenge. The main criticisms toward the proper DpE management consist of poor consensus on both surgical indications and the choice between different surgical techniques available to treat the disease. Furthermore, only weak recommendations are provided by current guidelines and surgical management is mostly based on surgeon's experience. As consequence, the lack of standardization about the surgical treatment led to the risk of under- or over-treatments in patients suffering from this form of endometriosis. The latest evidence-based data suggest to adopt a lesion-oriented surgical approach serving as a guide in daily surgical activities, in order to ensure a tailored radicality and reduce the rate of surgery-related complications. Diaphragmatic endometriosis surgery should be performed only by expert surgeons with an extensive oncogynecologic expertise since it represents a technically demanding procedure. A multidisciplinary approach is also mandatory in order to adequately select and treat these patients by minimizing the risk of additional morbidity.

Laparoscopic Treatment of Bulky Nodes in Primary and Recurrent Ovarian Cancer: Surgical Technique and Outcomes from Two Specialized Italian Centers.

(1) Background: Minimally invasive surgery (MIS) represents a feasible approach in early-stage ovarian cancer, while this question is still unsolved for advanced and recurrent disease. (2) Methods: In this retrospective, multicenter study, we present a series of 21 patients who underwent MIS for primitive or recurrent epithelial ovarian cancer (EOC) with bulky nodal metastasis and discuss surgical technique and outcomes in relation to the current literature. (3) Results: Complete cytoreduction at primary debulking surgery was obtained in 86% of cases. No complication occurred in our patients intraoperatively and only 11.1% of our patients experienced grade 2 and 3 postoperative complications. Notably, all the patients with isolated lymph nodal recurrence (ILNR) were successfully treated with a minimally invasive approach with no intra- or postoperative complications. (4) Conclusions: The results of our study are consistent with those reported in the literature, demonstrating that MIS may represent a safe approach in advanced and recurrent EOC with nodal metastasis if performed on selected patients by expert surgeons with an adequate setting and appropriate technique.

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

Activated leukocyte cell adhesion molecule soluble form: a potential biomarker of epithelial ovarian cancer is increased in type II tumors.

Activated leukocyte cell adhesion molecule (ALCAM) is involved in cell-cell interactions in cancer. Shedding of its ectodomain by the metalloprotease ADAM17/TACE generates a soluble form (sALCAM). Here, we show that serum sALCAM levels were significantly higher in epithelial ovarian cancer (EOC) (p < 0.005) than in controls. The performance of sALCAM as classifier, tested by receiver operating characteristic curve, resulted in an area under the curve (AUC) of 0.8067. Serum sALCAM levels showed direct correlation with Carbohydrate Antigen-125 (CA125/MUC16). Moreover, significantly higher levels were found in type II tumors, even in stage I/II, suggesting that elevated sALCAM is an early feature of aggressive EOC. In addition, sALCAM levels were higher in ascites than in sera, suggesting local processing of ALCAM in the peritoneal cavity. In immunodeficient mice, intraperitoneally implanted with a human EOC cell line, human sALCAM progressively increased in serum and was even higher in the ascites. The biochemical characterization of the sALCAM in EOC sera and ascites, showed two predominant forms of approximately 95 and 65 kDa but no EOC-specific isoform. In addition, full-length transmembrane ALCAM but no soluble form was detected in tumor-derived exosomes found in ascites. Finally, in vitro invasion assays showed that inhibition of ADAM17/TACE activity decreased EOC invasive properties, while opposite effects were mediated by a sALCAM-Fc chimera and by an antibody interfering with ALCAM/ALCAM interactions. Altogether these data suggest that sALCAM is a marker of EOC, which correlates with more aggressive type II tumors, and that ADAM17/TACE activity and sALCAM itself mediate enhanced invasiveness.

Ki67 as a Predictor of Response to PARP Inhibitors in Platinum Sensitive BRCA Wild Type Ovarian Cancer: The MITO 37 Retrospective Study.

BACKGROUND: There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC). METHODS: MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010-2021 in 15 centers. Ki67 expression was assessed locally by certified pathologists on formalin-fixed paraffin embedded (FFPE) tissues. Median Ki67 was used as a cut-off. RESULTS: A total of 136 patients were eligible and included in the analysis. Median Ki67 was 45.7% (range 1.0-99.9). The best response to platinum according to median Ki67 was 26.5% vs. 39.7% complete response (CR), 69.1% vs. 58.8% partial response (PR), 4.4% vs. 1.5% stable disease (SD). The best response to PARPi according to median Ki67 was 19.1% vs. 36.8% CR, 26.5% vs. 26.5% PR, 26.5 vs. 25% SD, 27.9% vs. 16.2% progressive disease (PD). No statistically significant differences in progression free survival (PFS) and overall survival (OS) were identified between low and high Ki67. PFS and OS are in line with registration trials. CONCLUSIONS: Ki67 at diagnosis did not discriminate responders to PARPi.

The Risk of Recurrence in Endometrial Cancer Patients with Low-Volume Metastasis in the Sentinel Lymph Nodes: A Retrospective Multi-Institutional Study.

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

Retrospective Analysis of the Correlation of MSI-h/dMMR Status and Response to Therapy for Endometrial Cancer: RAME Study, a Multicenter Experience.

BACKGROUND: There is poor evidence regarding sensitivity to chemotherapy in endometrial cancer (EC) based on microsatellite instability (MSI)/mismatch repair (MMR) status. METHODOLOGY: The RAME study is a retrospective analysis aiming to assess response to chemotherapy in MSI-high (h)/deficient (d) MMR and MSI-low (l)/proficient (p) MMR EC patients. Primary endpoints were recurrence-free survival (RFS) for patients with localized disease and progression-free survival (PFS) and overall survival (OS) in patients with advanced/recurrent disease. RESULTS: A total of 312 patients treated between 2010 and 2022 in four high-volume Multicenter Italian Trial in Ovarian cancer and gynecological malignancies (MITO) centers were selected. In total, 239 patients had endometrioid EC (76.6%), 151 had FIGO stage I at diagnosis (48.9%) and 71 were MSI-h/dMMR (22.8%). Median age was 65 (range 31-91) years. Among patients with localized disease, median RFS was 100.0 months (95% CI 59.4-140.7) for MSI-l/pMMR and 120.9 months (60.0-181.8) for MSI-h/dMMR (p = 0.39). Seventy-seven patients received first-line chemotherapy for advanced/recurrent disease. Patients with MSI-h/dMMR ECs had a significantly worse OS (p = 0.039). In patients receiving platinum-based chemotherapy, no statistically significant differences in PFS (p = 0.21) or OS (p = 0.057) were detected, although PFS and OS were numerically longer in the MSI-l/pMMR population. CONCLUSIONS: Patients with metastatic MSI-h/dMMR EC receiving first-line chemotherapy had a significantly worse OS.

Predicting Response to Anthracyclines in Ovarian Cancer.

(1) Background: Anthracyclines are intriguing drugs, representing one of the cornerstones of both first and subsequent-lines of chemotherapy in ovarian cancer (OC). Their efficacy and mechanisms of action are related to the hot topics of OC clinical research, such as BRCA status and immunotherapy. Prediction of response to anthracyclines is challenging and no markers can predict certain therapeutic success. The current narrative review provides a summary of the clinical and biological mechanisms involved in the response to anthracyclines. (2) Methods: A MEDLINE search of the literature was performed, focusing on papers published in the last two decades. (3) Results and Conclusions: BRCA mutated tumors seem to show a higher response to anthracyclines compared to sporadic tumors and the severity of hand-foot syndrome and mucositis may be a predictive marker of PLD efficacy. CA125 can be a misleading marker of clinical response during treatment with anthracyclines, the response of which also appears to depend on OC histology. Immunochemistry, in particular HER-2 expression, could be of some help in predicting the response to such drugs, and high levels of mutated p53 appear after exposure to anthracyclines and impair their antitumor effect. Finally, organoids from OC are promising for drug testing and prediction of response to chemotherapy.

Vacuum delivery in all-fours position: is it a valuable, brand-new option?

Since all-fours birth position is considered to decrease the rate of failure of vaginal birth and the risk of negative maternal and fetal outcomes, we wondered if all-fours would be favorable in case of operative vaginal delivery with obstetrical vacuum. We performed a simulation of vacuum application on a mannequin settled in all-fours position and we filmed this new application for diffusion among clinicians. We suggest that the all-fours position be considered and investigated in further studies as a possible way of delivery in case of operative vaginal delivery.

Implementation of the ERAS (Enhanced Recovery After Surgery) protocol for hysterectomy in the Piedmont Region with an audit&feedback approach: Study protocol for a stepped wedge cluster randomized controlled trial. A study of the EASY-NET project.

INTRODUCTION: ERAS (Enhanced Recovery After Surgery) is a perioperative program combining multiple evidence-based interventions designed to reduce the surgical stress response. Despite the publication of dedicated guidelines, ERAS application to gynecologic surgery outside clinical studies has been slow and fragmented. To promote the systematic adoption of the ERAS program in the entire regional hospital network in Piedmont an Audit-and-Feedback approach (A&F) has been adopted within a cluster randomized controlled trial, aiming to estimate the true impact of the protocol on a large, unselected population. METHODS: The study protocol provides for a multicenter stepped wedge cluster randomized trial, focused on women undergoing an hysterectomy, for comparison between standard perioperative management and perioperative management according to the ERAS protocol. The primary outcome is the length of hospital stay (LOS). Secondary outcomes are: post-operative complications, quality-of-recovery at 24-hours after surgery, 30-day readmissions, patients' satisfaction, healthcare costs. The compliance to all the ERAS items is monitored with an A&F approach. All the gynecologic units of Piedmont hospitals are involved and all the patients hospitalized for elective hysterectomy in the period of the study are included. Centers, stratified by surgical volume and randomly assigned to four groups, are randomly ordered to activate the ERAS protocol in four periods, every three months. The planned calendar and the total duration of the study have been extended for six months due to the COVID-19 pandemic. The expected sample size of about 2400 patients has a high statistical power (99%) to detect a reduction of LOS of 1 day (effect size 0.5) and to estimate clinically meaningful changes in the other study endpoints. The study protocol has been approved by the Ethical Committee of all participating centers. Study results will be timely circulated within the hospital network and published in peer-reviewed journals. CONCLUSION: Results are expected to demonstrate positive clinical outcomes of the ERAS protocol even when its implementation is directed towards an entire regional network of gynecologic units, and not only towards selected and highly motivated centers. TRIAL REGISTRATION: NCT04063072.