Lower Limb Lymphedema Awareness among Gynecological Cancer Patients: An International Survey Supported by the European Network of Gynecological Cancer Advocacy Groups (ENGAGe) Group.

INTRODUCTION: Patient awareness of postoperative lymphedema in the field of gynecologic oncology has been poorly documented in the international literature. We wished to capture and document the awareness among gynecological cancer survivors about postoperative lymphedema, including aspects such as the adequacy of perioperative counseling, management, and quality of life. METHODS: A web-based survey comprising 25 multiple-choice questions was distributed to gynecological cancer advocacy groups within the European Network of Gynecological Cancer Advocacy Groups (ENGAGe) group. The survey was validated in a pilot group of gynecological patients prior to distribution. RESULTS: Overall, 386 women from 20 countries completed the questionnaire. Only half of the patients (n = 211) knew what lymphedema is, whereas 52% of the respondents stated that they were never informed at their pre-operative assessment about the potential risk of developing lymphedema. Fifty-three percent of those women who were informed about the risk and management of lymphedema received information through self-initiative, connecting mainly with patient groups or online. Approximately 84% of patients with lymphedema reported that they informed their doctor about their symptoms. Ninety-four patients (55.3%, which is not 55% of the 386) were treated for lymphedema. Forty-five women out of 136 reported that lymphedema significantly affected their everyday lives. DISCUSSION: We report a large lack of awareness and a significant gap of knowledge about the risks and treatment options related to postoperative lymphedema among gynecological cancer survivors. Institutional practice routines and awareness among professionals need to be urgently recalled and adapted to adequately inform and support gynecological cancer patients.

Awareness, knowledge and attitudes of human papillomavirus infection, screening and vaccination: a survey study in Greece.

PURPOSE: To evaluate the awareness and existing knowledge of a portion of the Greek population about prevention, screening, and HPV vaccination. METHODS: A questionnaire designed in Google forms has been distributed through social media between June 2021 and December 2021 in men and women aged > 16 years old. Statistical analysis was performed using the SPSS 20.0 program. Inferential analysis was performed to evaluate differences in responses among men and women. RESULTS: We enrolled 2685 participants. Of those, 2285 were women, 386 were men, while 14 respondents chose not to respond to this question. Various age groups were detected with those aged between 26 and 30 years old being the predominant one. Participants with a higher education constituted 36.5% of the population. Most respondents were married (59.8%). In socioeconomic terms 75.5% of participants were employed whereas, monthly income ranged between 1000 and 1500 euros in the predominant group (36.8%). Only 40% of females and 3.9% of males were vaccinated against HPV. Adolescent immunization, acceptability rates reached 92.7% among female and 82.1% among male responders. Although, only a small proportion of the participants were not aware of the existence of HPV, 24.1% of males and 23.4% of females had the impression that condom use may provide absolute immunity to HPV and only 51.6% of males and 60.4% of females were aware about the high prevalence of HPV in the general population. Logistic regression analysis indicated that male participants as well as those aged > 50 years and those choosing to reject vaccination had decreased knowledge of the basic pathophysiology of HPV infection, as well as knowledge related to the existence and use of HPV DNA as a screening tool and the existence and efficacy of HPV vaccination. CONCLUSION: Our results indicate that although awareness of the existence of HPV infection is high in Greek general population, the actual perception of the pathophysiology of transmission and importance of HPV testing and vaccination is low. Targeting specific population groups is essential to help increase HPV coverage and screening.

Chemotherapy response score as a predictor of survival in ovarian cancer patients.

OBJECTIVE: The chemotherapy response score (CRS) has been widely adopted as a predictive tool for ovarian cancer survival. In the present study, we seek to define differences in survival rates among patients grouped in the traditionally established three-tiered system and those who have not been offered debulking surgery. STUDY DESIGN: We designed a retrospective cohort study involving women treated with chemotherapy and offered interval or late debulking surgery for ovarian cancer. Twenty-eight women were not considered for a debulking procedure for various reasons. Of the 89 women who were finally offered interval debulking or late debulking surgery, 28 had a CRS 1 score, 34 had a CRS 2 score and 27 had a CRS 3 score. RESULTS: Significant differences were noted in the progression-free survival (PFS) and overall survival (OS) of patients based on the CRS stratification, although survival rates were considerably longer for all three groups compared to those of patients who were not offered surgery. Cox regression univariate analysis revealed that suboptimal debulking and CRS 1 or no surgery had a significant negative impact on PFS and OS rates. The binary stratification of CRS (CRS 1-2 vs CRS 3) revealed comparable differences in the PFS and OS to those in the groups that were stratified as platinum resistant and platinum sensitive. CONCLUSION: The chemotherapy response score is a significant determinant of ovarian cancer survival that helps evaluate the risk of early disease relapse and death and may soon be useful in guiding patient-tailored treatment.

Prognostic Nutritional Index as a Predictive Biomarker of Post-Operative Infectious Morbidity in Gynecological Cancer Patients: A Prospective Cohort Study.

Malnutrition significantly impacts the post-operative process of gynecological cancer patients. A prominent variable for determining perioperative morbidity is the Prognostic Nutritional Index (PNI). To investigate PNI's predictive value on the risk of post-operative infections, we conducted a prospective cohort study involving women who underwent surgery for gynecological malignancies. Out of the 208 patients enrolled, 28 (13.5%) were malnourished and post-operative infections occurred in 43 patients. Notably, there was a significant difference in PNI between patients who developed infections and those who did not (p = 0.027), as well as between malnourished patients and those with normal nutritional status (p = 0.043). Univariate analysis showed that preoperative PNI predicts the risk of post-operative infections better than post-operative white blood cell count (AUC of 0.562 vs 0.375). However, the most accurate diagnostic results in the multivariate analysis were obtained from random forest and classification tree models (AUC of 0.987 and 0.977, respectively). Essentially, PNI and post-operative white blood cell count provided the best information gain according to rank probabilities. In conclusion, PNI appears to be a critical parameter that merits further investigation during the preoperative evaluation of gynecological malignancies.

Lower Urinary Tract Symptoms in Greek Women After Menopause: The LADY Study.

INTRODUCTION AND HYPOTHESIS: The genitourinary syndrome of menopause (GSM), apart from symptoms related to vulvovaginal atrophy (VVA), also consists of lower urinary tract symptoms (LUTS). Based on the common embryological origin of the genital and lower urinary system, the presence of estrogen receptors, and the high prevalence of VVA and LUTS in the menopausal population, the two conditions can coexist. This study is aimed at investigating the prevalence and risk factors of LUTS in a sample of Greek peri- and postmenopausal women. METHODS: Four hundred and fifty (450) women, aged 40-70 years, attending three outpatient gynecology clinics for routine examination, completed a structured interview and responded to a validated questionnaire (International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms, ICIQ-FLUTS). RESULTS: Urinary urgency or frequency affected 51.6% and dysuria 43.6% of the participants. Mild urgency or frequency was described by 25.6%, moderate by 14.4%, and severe by 11.6% of the women. Mild dysuria was reported by 26.26%, moderate by 5.8%, and severe by 11.6%. Age, weight, BMI, and number of pregnancies and abortions correlated with a higher ICIQ-FLUTS score. Women with moderate/severe symptoms of VVA, such as irritation, a burning sensation, and pruritus of the vulva or vagina, had a higher ICIQ-FLUTS score than women without such symptoms (beta coefficient 2.42, CI 1.204, 3.635, p < 0.001). CONCLUSIONS: Lower urinary tract symptoms are very common among peri- and postmenopausal women and are linked to symptoms of VVA. Our data support the need for prompt evaluation of women transitioning to menopause, as these symptoms compromise the quality of life.

Detection of High-Grade Cervical Intraepithelial Neoplasia by Electrical Impedance Spectroscopy in Women Diagnosed with Low-Grade Cervical Intraepithelial Neoplasia in Cytology.

The authors attempt to address the importance of timely detection and management of cervical intraepithelial neoplasia (CIN) to prevent cervical cancer. The study focused on the potential of electrical impedance spectroscopy (EIS) as an adjunct to colposcopy, aiming to enhance the accuracy of identifying high-grade cervical lesions. Colposcopy, a widely used technique, exhibited variable sensitivity in detecting high-grade lesions, which relies on the expertise of the operator. The study's primary objective is to evaluate the effectiveness of combining colposcopy with EIS in detecting high-grade cervical lesions among patients initially diagnosed with low-grade CIN based on cytology. We employed a cross-sectional observational design, recruiting 101 women with abnormal cervical cytology results. The participants underwent colposcopy with acetic acid and subsequent EIS using the ZedScan device. The ZedScan results are categorized into color-coded probability levels, with red indicating the highest likelihood of high-grade squamous intraepithelial lesions (HSIL) occurrence. Results revealed that ZedScan exhibits a sensitivity rate of 89.5% and a specificity rate of 84% for detecting high-grade lesions. Colposcopy, on the other hand, recorded a sensitivity rate of 85.5% and a specificity rate of 92%. The agreement rate between ZedScan and biopsy is 79.2%, as indicated by a kappa coefficient of 0.71, while the agreement rate between colposcopy and biopsy is 74.3%, with a kappa coefficient of 0.71.

Thoracic epidural analgesia as part of an enhanced recovery program in gynecologic oncology: a prospective cohort study.

OBJECTIVE: To evaluate the safety and the effectiveness of thoracic epidural analgesia as part of the enhanced recovery after surgery (ERAS) multimodal analgesic protocol in patients with gynecologic oncology who have undergone laparotomy for suspected or confirmed malignancy. METHODS: We conducted a prospective cohort study, following an enhanced recovery after surgery pathway, among patients who had undergone laparotomy for confirmed or suspected gynecological malignancy between January 2020 and September 2021. All patients who underwent laparotomy at the gynecologic oncology department for the aforementioned reason during that time were considered eligible. Patients (n=217) were divided into two groups: epidural (n=118) and non-epidural (n=99) group. Both groups were treated with the standard ERAS departmental analgesic protocol. The primary outcomes were length of hospital stay, complications, and readmission rates. RESULTS: Data from 217 patients (epidural group, n=118 vs non-epidural group, n=99) with median age of 61 years (IQR 53-68) were analyzed. The most common type of cancer was of ovarian origin (85/217, 39.2%, p=0.055) and median (Aletti) surgical complexity score was 3 (p=0.42). No differences were observed in the patients' demographics, clinical, and surgical characteristics. Primarily, median length of stay was 4 days in both groups with statistically significant lower IQR in the epidural group (3-5 vs 4-5, p=0.021). Complication rates were more common in the non-epidural group (38/99, 38.3% vs 36/118, 30.5%, p<0.001) with similar rates of grade III (p=0.51) and IV (0%) complications and readmission rates (p=0.51) between the two groups. Secondarily, the epidural group showed lower pain scores (p<0.001) on the day of surgery and in the first post-operative day (p<0.001), higher mobilization rates on the day of surgery (94.1% vs 57.6%, p<0.001), faster removal of urinary catheter (p<0.001), shorter time to flatus (p<0.001), and less nausea on the day of surgery (p<0.001). CONCLUSION: In this study we showed that thoracic epidural analgesia, when used as part of an ERAS protocol, is safe and offers more favorable pain relief along with a number of additional benefits, improving the peri-operative experience of patients with gynecologic cancer.

Enhanced Recovery After Surgery Protocols in Obese Gynecological Oncology Patients: A Single-Center Experience.

Objective The aim of this study is to present our experience and evaluate the safety and outcomes of the implementation of Enhanced Recovery After Surgery (ERAS) protocols in obese patients who underwent surgery for suspected or confirmed gynecological malignancies. Method From January 2020 to September 2021, 217 patients underwent laparotomy for a confirmed or suspected gynecological malignancy following a 19-element ERAS pathway. The patients were divided into two groups: obese (BMI ≥ 30 kg/m2, n = 104) and non-obese (BMI < 30, n = 113). Both groups were treated with a 19-element ERAS protocol. Results After dividing the 217 patients into two groups, significantly more comorbidities were observed in the obese group (diabetes mellitus: 23% vs. 8%, p = 0.004; ASA score grade 3: 25.0% vs. 6.2%, p < 0.001), as well as higher rates of endometrial cancer (51.9% vs. 17.7%, p < 0.001) compared to the non-obese group. The overall ERAS compliance rates when matched element by element were similar. Postoperatively, complication rates of all grades were significantly higher in the obese group (46.1% vs. 27.4%, p < 0.001) without differences in the length of stay, readmission, and reoperation rates. Conclusion In this retrospective study, we showed that obese gynecological oncology patients can be safely managed with ERAS protocols perioperatively while potentially minimizing the adverse outcomes in these otherwise high-risk patients.

sFLT1, PlGF, the sFLT1/PlGF Ratio and Their Association with Pre-Eclampsia in Twin Pregnancies-A Review of the Literature.

Twin pregnancies demonstrate a 2-3-fold higher chance of developing PE compared to singletons, and recent evidence has demonstrated that the sFLT1/PIGF ratio is strongly associated with PE, adverse pregnancy outcomes, as well as imminent deliveries due to PE complications. The primary objective of this systematic review was to summarise the available data on the levels of sFLT1, PlGF and their ratios in twin pregnancies and to investigate their association with the development of PE, adverse pregnancy outcomes and the timing of the delivery. A systematic search of Ovid Embase, Web of Science, Science Direct, PubMed, Ovid Medline, Google Scholar and CINAHL was carried out. sFLT1 levels and the sFLT1/PIGF ratio appeared higher in twins compared to singleton pregnancies, especially in the third trimester, while PlGF levels appeared higher up until the third trimester, with their values showing no difference or being even lower than in singletons thereafter. The sFLT1/PIGF ratio has been reported to be an independent marker of adverse outcomes related to pre-eclampsia and is associated with the mean time until delivery in an inverse manner. Further research is required in order to establish the optimal sFLT1/PIGF cut-off values and to stratify the risk of adverse outcomes in twin pregnancies.

Optimal Time Interval between Neoadjuvant Platinum-Based Chemotherapy and Interval Debulking Surgery in High-Grade Serous Ovarian Cancer.

BACKGROUND: There is limited data on the optimal time interval between the last dose of neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) in high-grade serous ovarian carcinoma (HGSC). METHODS: We retrospectively identified patients with stage IIIC/IV HGSC who received NACT followed by IDS during a 15-year period (January 2003-December 2018) in our Institution. RESULTS: Overall, 115 patients with stage IIIC/IV HGSC were included. The median age of diagnosis was 62.7 years (IQR: 14.0). A total of 76.5% (88/115) of patients were diagnosed with IIIC HGSC and 23.5% (27/115) with IV HGSC. Median PFS was 15.7 months (95% CI: 13.0-18.5), and median OS was 44.7 months (95% CI: 38.8-50.5). Patients were categorized in groups according to the time interval from NACT to IDS: <4 weeks (group A); 4-5 weeks (group B); 5-6 weeks (group C); >6 weeks (group D). Patients with a time interval IDS to NACT ≥4 weeks had significantly shorter PFS (p = 0.004) and OS (p = 0.002). Median PFS was 26.6 months (95% CI: 24-29.2) for patients undergoing IDS <4 weeks after NACT vs. 14.4 months (95% CI: 12.6-16.2) for those undergoing IDS later (p = 0.004). Accordingly, median OS was 66.3 months (95% CI: 39.1-93.4) vs. 39.4 months (95% CI: 31.8-47.0) in the <4 week vs. >4 week time interval NACT to IDS groups (p = 0.002). On multivariate analysis, the short time interval (<4 weeks) from NACT to IDS was an independent factor of PFS (p = 0.004) and OS (p = 0.003). CONCLUSION: We have demonstrated that performing IDS within four weeks after NACT may be associated with better survival outcomes. Multidisciplinary coordination among ovarian cancer patients is required to avoid any unnecessary delays.

New boundaries for fertility sparing management in endometrial cancer.

PURPOSE OF REVIEW: The increasing rates of endometrial cancer in premenopausal women that accompanies modern lifestyle options that enhance the prevalence of obesity as well as the trend of delayed childbearing are expected to increase the need for fertility sparing techniques. Currently, the cornerstone of fertility sparing treatment is hormonal handling with progestin treatment and is reserved for women with well differentiated endometrioid lesions that are limited in the myometrial layer. RECENT FINDINGS: Innovative approaches in the surgical treatment of patients with the use of operative hysteroscopy seem to offer decreased intervals to remission of lesions and longer progression free survival. Recent small case series also dictate that patients with endometrioid lesions of medium differentiation as well as those with superficial myometrial invasion may be adequately treated with the use of operative hysteroscopy. Moreover, the novel classification system may help better understand patients that will likely respond better to hormonal treatment. SUMMARY: In the near future, further data from clinical trials will be available that will help optimize patient selection as well select surgical and medical options that will help establish a personalized approach of fertility preservation in endometrial cancer patients.

Tumor free distance from serosa and survival rates of endometrial cancer patients: A meta-analysis.

Myometrial invasion and its extent have been directly associated with the risk of relapse as well as the overall survival of endometrial cancer patients. Tumor free distance from the serosal surface of the uterine wall has been investigated the last years by several studies, however, to date, its importance remains unknown. The present meta-analysis is based on a systematic search of the Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases and has been designed according to the PRISMA guidelines. Nine studies were included in the present systematic review that recruited pathology slides from 1,598 endometrial cancer patients and their meta-analysis indicated that TFD was significantly associated with the progression free survival of patients with endometrial cancer (OR 0.36, 95% CI 0.20, 0.65). The disease specific survival was not affected by the TFD (OR 0.30, 95% CI 0.09, 1.01). Sensitivity analyses revealed, however, that both the progression free and overall survival rates were associated with TFD. Significant discrepancies were observed in terms of histological subtypes and stage of the disease among included patients, hence, the actual importance of TFD in specific subgroups remains unknown. Future studies must evaluate the importance of this pathology marker particularly in patients with endometrioid subtypes and early-stage disease, as it is believed that in this group its importance will be more predictive as it will not be skewed by the presence of more important factors such as more aggressive histology and advanced stage disease.

Pre-Operative Neutrophil-to-Lymphocyte Ratio as a Predictor of Post-Operative Infectious Morbidity in Gynecologic Oncology Patients.

Background: Neutrophil-to-lymphocyte ratio (NLR) has been described as a predictor of progression-free and overall survival, and in the field of peri-operative care it seems to be a factor that can help discriminate patients at risk of developing post-operative complications. In the present study we sought to determine whether NLR is useful as a biomarker in predictive models that aim to identify patients with gynecologic cancer undergoing surgery at risk of developing post-operative infectious morbidity. Patients and Methods: We designed a prospective cohort study that enrolled 208 patients with gynecologic cancer. Post-operative infectious morbidity was evaluated based on a 30-day follow-up interval from the procedure. Results: Forty-three patients (20.5%) developed post-operative infectious morbidity. Using an optimal cutoff value of 1.7 for the pre-operative NLR we observed that the sensitivity of the biomarker was 76.7% and the specificity 73.3% with a produced area under the curve of 0.760 (95% confidence interval [CI], 0.680-0.839). Univariable logistic regression indicated that NLR is a predictor of post-operative morbidity. Cox regression analysis revealed that NLR was the only factor that was associated with the timing of infectious morbidity (hazard ratio [HR], 1.339; 95% CI, 1.180-1.519; p < 0.001). Using random forest analysis and decision trees we achieved a diagnostic accuracy of the predictive model that exceeded 90%. Conclusions: Neutrophil-to-lymphocyte ratio may be a factor that could potentially help evaluate the risk of post-operative morbidity in patients with gynecologic cancer.

Chemotherapy Response Score in Ovarian Cancer Patients: An Overview of Its Clinical Utility.

The chemotherapy response score has been developed over the last few years as a predictive index of survival outcomes for patients with advanced-stage epithelial ovarian cancer undergoing interval debulking surgery. While its importance in predicting patients at risk of developing recurrences earlier seems to be important, its accuracy in determining patients with a shorter overall survival remains arbitrary. Moreover, standardization of the actual scoring system that was initially developed as a 6-tiered score and adopted as a 3-tiered score is still needed, as several studies suggest that a 2-tiered system is preferable. Given its actual importance in detecting patients with shorter progression-free survival, research should also focus on the actual predictive value of determining patients with platinum resistance, as a suboptimal patient response to standard neoadjuvant chemotherapy might help determine patients at risk of an earlier recurrence. In the present review, we summarize current knowledge retrieved from studies addressing outcomes related to the chemotherapy response score in epithelial ovarian cancer patients undergoing neoadjuvant chemotherapy and discuss differences in outcome reporting to help provide directions for further research.

Undifferentiated-dedifferentiated endometrial carcinoma; the reappearance of an old friend with insights into the new data.

Endometrial carcinoma is a common malignancy in women and shows increasing incidence. Except for its two main pathogenetic types I and II, the continuing evolution on molecular genetics have led to a new classification system (TCGA), that includes four main molecular subtypes: (i) POLE-mutant (ultramutated), (ii) hypermutated (MSI), (iii) copy-number low/MSS (p53wt) and (iv) copy-number high/serous-like (p53mut). The undifferentiated and dedifferentiated endometrial carcinomas are rare and clinically aggressive variants, comprising about 10% of the high-grade endometrial carcinomas and 2% of the endometrial carcinomas in general. Until recently, they were under-recognized and not fully described morphologically and immunohistochemically/molecularly. Their recognition diagnostically is crucial because of their poor prognosis; approximately 40% of patients with these subtypes will die within 0.5-20 months after diagnosis, so additional therapeutic strategies are important for an effective management. Because of their rarity, the responsiveness to other than conventional treatment, such as immunotherapy, has not been sufficiently investigated yet. The aim of this review is to provide an update on the knowledge about these two uncommon subtypes according to the current literature.

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma.

STUDY QUESTION: How should fertility-sparing treatment of patients with endometrial carcinoma be performed? SUMMARY ANSWER: Forty-eight recommendations were formulated on fertility-sparing treatment of patients with endometrial carcinoma. WHAT IS KNOWN ALREADY: The standard surgical treatment of endometrial carcinoma consisting of total hysterectomy with bilateral salpingo-oophorectomy drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) provide comprehensive guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment. STUDY DESIGN SIZE DURATION: A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. PARTICIPANTS/MATERIALS SETTING METHODS: ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practising clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgement was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives. MAIN RESULTS AND THE ROLE OF CHANCE: The multidisciplinary development group formulated 48 recommendations in four sections; patient selection, tumour clinicopathological characteristics, treatment and special issues. LIMITATIONS REASONS FOR CAUTION: Of the 48 recommendations, none could be based on level I evidence and only 16 could be based on level II evidence, implicating that 66% of the recommendations are supported only by observational data, professional experience and consensus of the development group. WIDER IMPLICATIONS OF THE FINDINGS: These recommendations provide guidance to professionals caring for women with endometrial carcinoma, including but not limited to professionals in the field of gynaecological oncology, onco-fertility, reproductive surgery, endoscopy, conservative surgery and histopathology, and will help towards a holistic and multidisciplinary approach for this challenging clinical scenario. STUDY FUNDING/COMPETING INTERESTS: All costs relating to the development process were covered from ESGO, ESHRE and ESGE funds. There was no external funding of the development process or manuscript production. G.S. has reported grants from MSD Italia S.r.l., advisory boards for Storz, Bayer, Astrazeneca, Metronic, TESARO Bio Italy S.r.l and Johnson & Johnson, and honoraria for lectures from Clovis Oncology Italy S.r.l. M.G. has reported advisory boards for Gedeon Richter and Merck. The other authors have reported no conflicts of interest. DISCLAIMER: This document represents the views of ESHRE, ESGO and ESGE which are the result of consensus between the relevant stakeholders and where relevant based on the scientific evidence available at the time of preparation. The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type.

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma.

The standard surgical treatment of endometrial carcinoma, consisting of total hysterectomy with bilateral salpingo-oophorectomy, drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) provide comprehensive information on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment.A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE), and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment (patient selection, tumor clinicopathological characteristics, treatment, special issues) in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts from across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified by a systematic search, was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives.

Identification of Risk Factors of Recurrence Among Patients With Vulvar Paget Disease Treated With Conservative Surgery.

OBJECTIVES: Vulvar Paget disease (VPD) is a benign disease with high recurrence rates. Standard treatment involves conservative surgery with wide local excision of the lesion. The purpose of the present study is to identify factors that increase the risk of relapse. MATERIALS AND METHODS: We conducted a retrospective study and included patients treated with conservative surgery for noninvasive VPD. Cox regression analysis was carried out to assess the independent effect of age, presence of positive margins, tumor size greater than 4 cm, bilateral lesions, and compositive morbidity and pathology on recurrence free survival. Post hoc power analysis was performed with the G-power tool using an α error of 0.05. RESULTS: Overall, 39 patients were included with a median age of 70 years (46-85 years). Of those, 19 patients relapsed within a median duration of 30.5 months (5-132 months). Twelve patients (63%) experienced at least a second relapse. The presence of composite comorbidity significantly affected the interval to recurrence (30.09 vs 71.80 months, p = .032). Univariate Cox regression analysis revealed that the presence of composite pathology features was indicative of a higher risk of recurrence (hazard ratio = -3.71, p = .024). The sample size did not allow for adequate power for this latter finding. Microscopically involved tumor margins and tumor size greater than 4 cm did not predict patients at risk of experiencing relapsing disease. CONCLUSIONS: Patients with noninvasive VPD experience high relapse rates. The presence of concurrent benign vulvar pathology may increase these rates, although larger sample sizes are needed to ascertain our findings.

Factors That Affect Survival Outcomes in Patients with Endometrial Clear Cell Carcinoma.

Background: Clear cell carcinoma (CCC) is a rare aggressive histologic subtype of endometrial cancer with a high relapse rate. In the present study, we sought to evaluate the prognostic factors of disease relapse and overall survival. Methods: We conducted retrospective cohort studies that included endometrial CCC patients treated at our institution. Predictive variables of survival outcomes were evaluated considering factors that determine the survival of patients with endometrioid carcinoma. Results: Fifty-five patients with a median age of 68 years and a median follow-up period of 31 months were included in the present study. Recurrence-free and overall survival rates did not differ among patients with early-stage and advanced-stage disease (RFS HR 1.51 (95% CI 0.63, 3.61), OS HR 1.36 (0.56, 3.31)). Patients with upper abdominal metastases had significantly shorter progression-free and overall survival intervals (log-rank < 0.001). The Gehan-Breslow-Wilcoxon analysis indicated worse survival rates for patients with advanced disease (p = 0.040); however, the log-rank test that gave equal weight to all time points did not reveal significant differences (log-rank = 0.576). Conclusion: Clear cell carcinoma is an aggressive histologic subtype of endometrial cancer that seems to be moderately affected by known predictors of survival rates in endometrioid carcinoma patients, except for the disease stage. Further research is needed to evaluate whether the molecular profiling of these patients may help predict survival outcomes.

Subarachnoid hemorrhage in a postpartum mother: A rare manifestation of an uncommon disease.

Subarachnoid hemorrhage, a potentially lethal medical emergency, represents an atypical clinical manifestation of gestational choriocarcinoma. We present the uncommon case of a 31-year-old primigravid female who presented with cerebral oncotic aneurysmal rupture, five weeks after vaginal delivery. Albeit the absence of neurological deficits after endovascular embolization, the patient was soon readmitted, complaining of fever, abdominal pain, and fetid lochia, all suggestive of puerperal endometritis. Upon a comprehensive diagnostic work-up, she was subsequently diagnosed with metastatic choriocarcinoma. Early initiation of multiagent chemotherapy, despite being in septic shock associated with Escherichia coli bacteremia, resulted in favorable prognosis.