Predicting the Risk of nOdal disease with histological and Molecular features in Endometrial cancer: the prospective PROME trial.

OBJECTIVE: To assess the role of histopathological and molecular features in predicting the risk of nodal metastases in apparent early-stage endometrial cancer patients undergoing sentinel node mapping. METHODS: This is a prospective trial. Consecutive patients with apparent early-stage endometrial cancer, undergoing laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and sentinel node mapping, were enrolled. Histological and molecular features were used to predict the node positivity. RESULTS: Charts of 223 apparent early-stage endometrial cancer patients were included in this study. Four (1.8%) patients were excluded from this study due to the lack of data about molecular features. Additionally, nine (4%) patients did not meet the inclusion criteria (due to the presence of peritoneal carcinomatosis or bulky nodes (the presence of p53 abnormality correlated with the presence of advanced stage disease (p<0.001)). The study population included 178 (84.8%) and 32 (15.2%) patients with endometrioid and non-endometrioid endometrial cancer, respectively. According to pathological uterine risk factors, 93 (44.3%), 45 (21.4%), 40 (19.1%), and 32 (15.2%) were classified as low, intermediate, intermediate-high, and high-risk, respectively. Using the surrogate molecular classification, 10 (4.8%), 42 (20%), 57 (27.1%), and 101 (48.1%) were included in the POLE mutated, p53 abnormal, MMRd/MSI-H, and NSMP, respectively. Overall, 41 (19.5%) patients were detected with positive nodes. Molecular features were not associated with the risk of having nodal metastases (OR 1.03, 95% CI 0.21 to 5.05, p=0.969 for POLE mutated; OR 0.788, 95% CI 0.32 to 1.98, p=0.602 for p53 abnormal; OR 1.14, 95% CI 0.53 to 2.42, p=0.733 for MMRd/MSI-H). At multivariable analysis, only deep myometrial invasion (OR 3.318, 95% CI 1.357 to 8.150, p=0.009) and lymphovascular space invasion (OR 6.584, 95% CI 2.663 to 16.279, p<0.001) correlated with the increased risk of positive nodes. CONCLUSION: Our data suggest that molecular classification does not seem useful to tailor the need of nodal dissection in apparent early-stage endometrial cancer. p53 abnormality predicts the risk of having advanced disease at presentation. Further external validation is needed. CLINICAL TRIAL REGISTRATION: NCT05793333.

Surgical Outcomes and Complications of Myomectomy: A Prospective Cohort Study.

STUDY OBJECTIVE: To investigate postoperative surgical and non-surgical complications that occur within 30 days following myomectomy procedures, whether laparoscopic or via open surgery. DESIGN: Prospective cohort study SETTING: Del Ponte Women's and Children's Hospital, Varese, Italy. PATIENTS: Women undergoing myomectomy either with laparoscopic or open surgery from July 2020 to June 2023 INTERVENTIONS: Data of consecutive patients who underwent abdominal myomectomy procedures, either via laparoscopy or open abdominal surgery were collected. The study examined patient characteristics, size and location of fibroids, surgical data, and complications. Univariate and multivariable analyses were employed to identify factors contributing to postoperative Clavien-Dindo grade ≥ II complications. MEASUREMENTS AND MAIN RESULTS: Overall 383 patients were included in the study. The univariate analysis showed intramural fibroid type (p = .0009), large fibroid size (p = .03), and extended operative times (p = .05) were associated with postoperative complications. Open surgical approach (p <.001) and uterine cavity opening (p = .02) also contributed to complications. Postoperative anemia emerged as the most prevalent complication. In the multivariable analysis, the open surgical approach emerged as the only independent factor associated with an increased risk of grade ≥ II complications (odds ratio 7.37; p <.0001). CONCLUSION: In this study we found an increased likelihood of complications in case of open myomectomy. While the presence of potential selection bias may have impacted this finding, it could provide valuable insights for clinicians and surgical teams in the strategic planning of myomectomy procedures.

The effect of ulipristal acetate on tumor necrosis factor α, insulin-like growth factor 1, and plasminogen activator inhibitor-1 serum levels in patients with symptomatic uterine fibroids.

Introduction: Uterine fibroids (UFs) are benign tumors of the female reproductive system originating from the smooth muscle of the uterus. Currently, progesterone is known to play a key role in the differentiation of the myometrial tissue to form UFs and their abnormal growth. The mechanism of action of progesterone in UF tumorigenesis involves its effect on increasing the concentrations and dysregulation of selected growth factors. Material and methods: A retrospective cohort study was performed to evaluate and compare tumor necrosis factor α (TNF-α), insulin-like growth factor 1 (IGF-1), plasminogen activator inhibitor-1 (PAI-1) serum concentrations in patients with UFs without prior hormonal treatment, patients with UFs treated with a 3-month standard ulipristal acetate (UPA - a type of selective progesterone receptor modulator) scheme (5 mg/day) and in control patients without UFs. A total of 120 patients were divided into 3 groups (controls, UFs with UPA treatment, UFs without UPA treatment). Results: There were no significant differences in TNF-α serum concentrations between patients with UFs who underwent UPA treatment and patients who did not. Serum concentrations of IGF-1 and PAI-1 did not show significant intergroup differences. Conclusions: No significant differences were found between TNF-α concentrations in the serum of patients with UFs treated with UPA, and patients without UPA treatment. In addition, our data analysis did not show significant differences in the concentrations of IGF-1 and PAI-1 between patients with UFs and the control group. Further studies on the dependence of specific symptoms on selected growth factors are mandatory.

Robotic-assisted hysterectomy for benign gynecologic disease in the United States: in-hospital use of opioid and non-opioid analgesics.

To compare the in-hospital opioid and non-opioid analgesic use among women who underwent robotic-assisted hysterectomy (RH) vs. open (OH), vaginal (VH), or laparoscopic hysterectomy (LH). Records of women in the United States who underwent hysterectomy for benign gynecologic disease were extracted from the Premier Healthcare Database (2013-2019). Propensity score methods were used to create three 1:1 matched cohorts stratified in inpatients [RH vs. OH (N = 16,821 pairs), RH vs. VH (N = 6149), RH vs. LH (N = 11,250)] and outpatients [RH vs. OH (N = 3139), RH vs. VH (N = 29,954), RH vs. LH (N = 85,040)]. Opioid doses were converted to morphine milligram equivalents (MME). Within matched cohorts, opioid and non-opioid analgesic use was compared. On the day of surgery, the percentage of patients who received opioids differed only for outpatients who underwent RH vs. LH or VH (maximum difference = 1%; p < 0.001). RH was associated with lower total doses of opioids in all matched cohorts (each p < 0.001), with the largest difference observed between RH and OH: median (IQR) of 47.5 (25.0-90.0) vs. 82.5 (36.0-137.0) MME among inpatients and 39.3 (19.5-66.0) vs. 60.0 (35.0-113.3) among outpatients. After the day of surgery, fewer inpatients who underwent RH received opioids vs. OH (78.7 vs. 87.5%; p < 0.001) or LH (78.6 vs. 80.6%; p < 0.001). The median MME was lower for RH (15.0; 7.5-33.5) versus OH (22.5; 15.0-55.0; p < 0.001). Minor differences were observed for non-opioid analgesics. RH was associated with lower in-hospital opioid use than OH, whereas the same magnitude of difference was not observed for RH vs. LH or VH.

Pre-Pandemic Predictivity of Anxious-Depressive Symptoms in Post-Surgical Traumatic Distress in Hysterectomy for Benign Disease and COVID-19 Outbreak: A Case-Control Study.

Background: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic led to several needed containment measures that conditioned the onset of depressive, anxiety, and post-traumatic stress symptoms in the population. These symptoms, especially if not diagnosed and treated, can also occur in patients undergoing medical care or surgery, with a high impact on people's lives and causing low adherence to treatment. The study evaluates whether the spread of the coronavirus disease 2019 (COVID-19) worsened the onset of post-surgical distress and symptoms of anxiety and depression in a population undergoing hysterectomy for benign disease during the pandemic era, comparing it with a population with the same characteristics but recruited before COVID-19. Methods: The sample was evaluated before surgery (T1), post-operatively (T2), and 3 months after surgery (T3) through a sociodemographic questionnaire and through the HADS (Hospital Anxiety and Depression Scale) to evaluate anxious-depressive symptoms and the PCL-5 (Post-traumatic Stress Disorder Checklist for DSM-5) to assess the onset of post-surgical distress. Results: Patients treated after the COVID-19 pandemic showed a higher depressive symptoms rate compared with those treated before (p-value = 0.02); conversely, pre-COVID-19 patients were more prone to develop post-traumatic stress disorder (PTSD) (p-value = 0.04). A significant association between the occurrence of PTSD and anxiety-depressive symptoms registered at T2 (p-value = 0.007) and T3 (p-value < 0.0001) emerged. In the end, the COVID-19 pandemic has exerted a detrimental influence on the mental well-being of the patients under investigation, with a notable exacerbation of their mood disturbances. Conclusions: The findings advocate for the implementation of psychometric and psychodiagnostic assessments to promptly detect high-risk scenarios that could lead to PTSD, compromising treatment compliance and exacerbating the overall outcome, resulting in substantial direct and indirect burdens.

Macroplastique Is a Safe and Effective Long-term Surgical Treatment for Stress Urinary Incontinence: Prospective Study with 10-Year Follow-up.

BACKGROUND AND OBJECTIVE: Until a few years ago, a midurethral sling was considered the gold standard for the treatment of female stress urinary incontinence (SUI) after failure of conservative therapies. However, criticisms regarding the rate of mesh exposure and lack of long-term efficacy have led to reconsideration of other surgical procedures. Our aim was to investigate long-term subjective and objective outcomes after injection of Macroplastique, a urethral bulking agent. METHODS: We prospectively enrolled all consecutive women complaining of pure SUI symptoms with urodynamically proven SUI who received a Macroplastique injection. We investigated patient-reported subjective outcomes using International Consultation on Incontinence Questionnaire-Short Form, Urogenital Distress Inventory, Patient Global Impression of Improvement, and Visual Analog Scale (VAS) questionnaires, and the cough stress test to assess objective outcomes. Adverse events were recorded during follow-up. KEY FINDINGS AND LIMITATIONS: At 10 yr after Macroplastique injection, the objective cure rate was 56% and 71% of patients reported that they were satisfied. Long-term data revealed no significant decline in subjective or objective cure rates. No serious complications were reported. Study limitations include the small sample size and the lack of pad tests and bladder diaries for postoperative evaluations. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study shows that Macroplastique injection can be an effective and safe option for the treatment of female SUI in the long term, even when used in the first-line setting. PATIENT SUMMARY: We evaluated outcomes for women with stress urinary incontinence (SUI) who were treated with an injection of Macroplastique gel into the wall of the urethra to prevent leakage of urine. We found that this is a safe option for treatment of female SUI that is effective in the long term.

Long-term therapy with dienogest or other oral cyclic estrogen-progestogen can reduce the need for ovarian endometrioma surgery.

BACKGROUND: Almost 10% of women in reproductive age are diagnosed with ovarian endometriomas and can experience symptoms and infertility disorders. Ovarian endometriomas can be treated with medical or surgical therapy. OBJECTIVE: To assess whether long-term therapy with dienogest or oral cyclic estrogen-progestogens is effective in reducing the size of ovarian endometriomas, alleviating associated symptoms, and reducing the requirement for surgery. DESIGN: Prospective non-interventional cohort study. METHODS: We enrolled childbearing women diagnosed with ovarian endometriomas. We collected demographic, clinical, and surgical data, including the evaluation of ovarian endometrioma-associated symptoms and pain using the visual analog scale. We grouped the women according to treatment regimen into dienogest, estrogen-progestogens, and no-treatment. Patient's assessment was performed at baseline and after 12 months evaluating the largest ovarian endometrioma diameter (in millimeters) and the associated symptoms. Furthermore, we analyzed the impact of hormonal treatment in a sub-group of women fulfilling at baseline the criteria for a first-line surgical approach (ovarian endometrioma > 30 mm with visual analog scale > 8 or ovarian endometrioma > 40 mm before assisted reproductive treatments or any ovarian endometrioma(s) > 60 mm). RESULTS: We enrolled 142 patients: 62, 38, and 42 in dienogest, estrogen-progestogens, and no-treatment groups, respectively. No significant differences were found regarding baseline characteristics. After 12 months, the mean largest ovarian endometrioma diameter increased in the no-treatment group (31.1 versus 33.8; p < 0.01), while a significant reduction was registered in the dienogest (35.1 versus 25.8; p < 0.01) and estrogen-progestogens (28.4 versus 16.7; p < 0.01) groups; no significant difference in ovarian endometrioma diameter reduction between these two latter groups was noted (p = 0.18). Ovarian endometrioma-associated symptoms and pain improved in dienogest and estrogen-progestogens groups, with a significantly greater effect for dienogest than for estrogen-progestogens for dysmenorrhea (74% versus 59%; p < 0.01). In the sub-group of women eligible for first-line surgery at baseline, long-term treatment with dienogest and estrogen-progestogens reduced surgical eligibility by 30%. CONCLUSIONS: Decreased mean largest ovarian endometriomas'diameter after 12 months and reduction of the need for surgical treatment by 30% were observed in dienogest and estrogen-progestogens groups. Long-term treatment with dienogest had a greater effect in alleviating dysmenorrhea and pain.

Impact of surgery on reproductive outcomes in women with deep endometriosis and proven presurgical infertility: Facts and controversies.

In women with proven infertility and deep endometriosis (DE), optimal management is controversial. To date, there is no clear evidence on the association between infertility and different stages of rASRM, nor is there clear guidance from leading scientific societies for surgical treatment of DE patients. A comprehensive literature search was conducted on the main databases for English-language trials describing the effectiveness of surgery for DE in patients with proven infertility; 16 studies were deemed eligible for inclusion in this systematic review (CRD42024498888). Quantitative analysis was not possible because of the heterogeneity of the data. A descriptive summary of the results according to location of pathology, surgical technique used, and whether assisted reproductive technology (ART) was needed or not was provided. A total of 947 infertile women were identified, 486 of whom became pregnant, with an average pregnancy rate of 51.3%. Our review suggests that surgery can be of valuable help in improving reproductive outcomes by improving the results of ART. It has not been possible to reach robust conclusions on the outcomes of surgery based on the location of DE because of the heterogeneity of evidence available to date. Overall, although some data encourage first-line surgical management, further investigation is needed to determine its effective application before or after ART failure.

Sentinel node mapping, sentinel node mapping plus back-up lymphadenectomy, and lymphadenectomy in Early-sTage cERvical caNcer scheduled for fertilItY-sparing approach: The ETERNITY project.

OBJECTIVE: To investigate the safety of sentinel node mapping for patients with early-stage cervical cancer undergoing cervical conization plus nodal evaluation. METHODS: The ETERNITY project is a retrospective, multi-institutional study collecting data of patients with early-stage cervical cancer undergoing fertility-sparing treatment. Here, we compared outcomes related to three methods of nodal assessment: sentinel node mapping (SNM), SNM plus backup lymphadenectomy (SNM + LND); pelvic lymphadenectomy (LND). RESULTS: Charts of 123 patients (with stage IA1-IB1 cervical cancer) were evaluated. Median patients' age was 34 (range, 22-44) years. SNM, SNM + LND, and LND were performed in 32 (26 %), 31 (25.2 %), and 60 (48.8 %) patients, respectively. Overall, eight (6.5 %) patients were diagnosed with positive nodes. Two (3.3 %), three (9.7 %), and three (9.4 %) patients were detected in patients who had LND, SNM + LND, and SNM respectively. Considering the 63 patients undergoing SNM (31 SNM + LND and 32 SNM alone), macrometastases, micrometastases, and isolated tumor cells were detected in four (3.2 %), three (2.4 %), and one (0.8 %) patients, respectively. All patients with positive nodes discontinued the fertility sparing treatment. Other two patients (one (1.7 %) in the LND group and one (3.1 %) in the SNM group) required hysterectomy even after negative nodal evaluation. After a median follow-up of 53.6 (range, 1.3, 158.0) months, nine (7.3 %) and two (1.6 %) patients developed cervical and pelvic nodes recurrences, respectively. Disease-free (p = 0.332, log-rank test) and overall survival (p = 0.769, log-rank test) were similar among groups. CONCLUSIONS: In this retrospective experience, SNM upholds long-term oncologic effectiveness of LND, reducing morbidity.

Sentinel node mapping in high-intermediate and high-risk endometrial cancer: Analysis of 5-year oncologic outcomes.

OBJECTIVE: To assess 5-year oncologic outcomes of apparent early-stage high-intermediate and high-risk endometrial cancer undergoing sentinel node mapping versus systematic lymphadenectomy. METHODS: This is a multi-institutional retrospective, propensity-matched study evaluating data of high-intermediate and high-risk endometrial cancer (according to ESGO/ESTRO/ESP guidelines) undergoing sentinel node mapping versus systematic pelvic lymphadenectomy (with and without para-aortic lymphadenectomy). Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: Overall, the charts of 242 patients with high-intermediate and high-risk endometrial cancer were retrieved. Data on 73 (30.1%) patients undergoing hysterectomy plus sentinel node mapping were analyzed. Forty-two (57.5%) and 31 (42.5%) patients were classified in the high-intermediate and high-risk groups, respectively. Unilateral sentinel node mapping was achieved in all patients. Bilateral mapping was achieved in 67 (91.7%) patients. Three (4.1%) patients had site-specific lymphadenectomy (two pelvic areas only and one pelvic plus para-aortic area), while adjunctive nodal dissection was omitted in the hemipelvis of the other three (4.1%) patients. Sentinel nodes were detected in the para-aortic area in eight (10.9%) patients. Twenty-four (32.8%) patients were diagnosed with nodal disease. A propensity-score matching was used to compare the aforementioned group of patients undergoing sentinel node mapping with a group of patients undergoing lymphadenectomy. Seventy patient pairs were selected (70 having sentinel node mapping vs. 70 having lymphadenectomy). Patients undergoing sentinel node mapping experienced similar 5-year disease-free survival (HR: 1.233; 95%CI: 0.6217 to 2.444; p = 0.547, log-rank test) and 5-year overall survival (HR: 1.505; 95%CI: 0.6752 to 3.355; p = 0.256, log-rank test) than patients undergoing lymphadenectomy. CONCLUSIONS: Sentinel node mapping does not negatively impact 5-year outcomes of high-intermediate and high-risk endometrial cancer. Further prospective studies are warranted.