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To overcome obstacles within the Slovenian organised cervical cancer screening programme, a randomised pilot study of human papillomavirus (HPV) self-sampling among non-attenders was performed, aiming to assess three different screening approaches.

The aim of the study was to compare the frequency of positive peritoneal washings in endometrial cancer patients after either hysteroscopy (HSC) or dilatation and curettage (D&C).

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 INTEREST(S) 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. [ABSTRACT FROM AUTHOR]

The article focuses on patients with endometrial cancer and mentions hysteroscopy (HSC) and dilatation and curettage (D&C). Topics discussed include positive peritoneal cytology, diagnosis of endometrial cancer and endometrial biopsy. Other topics which includes peritoneal washings are also discussed.

Objective: The mutant genotype GG of the CYP17A1 gene polymorphism has been linked to higher levels of serum estradiol and thus might be associated with steroid-hormone dependent tumors. We decided to assess an association of CYP17A1 polymorphism with uterine leiomyomas (ULM) and multiple ULM by conducting a meta-analysis and subgroup analysis. Methods: We searched the HuGE Navigator and PubMed databases using the terms "leiomyoma" and "CYP17A1" for articles published by October 1, 2010. Our article in press was added. The selection criteria were (i) cases having ULM, (ii) controls showing no ULM from the same ethnic group, (iii) cases and controls not overlapping. The subgroup analysis included cases having multiple ULM, predisposing black women mostly present with multiple ULM. Pooled risk ratio was calculated using χ ^{2} statistic. Results: Five papers fulfilled the selection criteria for meta-analysis and two papers for the subgroup analysis. The meta-analysis revealed no association of CYP17A1 polymorphism with all ULM. A high pooled risk ratio for multiple ULM was associated with the presence of mutant genotype GG (RR 3.25). Conclusion: CYP17A1 polymorphism may be associated with multiple ULM but not with all ULM. The future research might enable us to predict the course of the disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether polymorphism in CYP17A1 gene is associated with uterine leiomyomas (ULM) and to evaluate differences in epidemiologic and genetic factors among solitary and multiple leiomyomas.Design: Prospective case control study.Setting: Tertiary gynecology department.Patient(s): One hundred eighty-one women with clinically and surgically diagnosed ULM, 41 healthy control subjects, and 92 population control subjects.Intervention(s): Completing the questionnaires, peripheral venous puncture.Main Outcome Measure(s): Polymerase chain reaction and restriction-fragment-length polymorphism analyses were performed to genotype women regarding the CYP17A1 -34 A/G (rs743572) gene polymorphisms. Epidemiologic data was collected by questionnaire and compared between women with ULM and healthy control subjects.Result(s): Women with multiple ULM had higher prevalence of positive family history, lower age at menarche, lower parity, higher percentage of smoking, younger age at first sexual intercourse, lower prevalence of CYP17A1 AA genotype and lower CYP17A1 A allele frequency than healthy control subjects. These trends were not apparent among women with solitary ULM.Conclusion(s): Carriage of CYP17A1 AA is protective for developing ULM in our population. Women with solitary ULM mostly resembled healthy control subjects, whereas women with multiple ULM differed in CYP17A1 AA genotype and external stimuli. [ABSTRACT FROM AUTHOR]

Lower limb lymphoedema (LLL) is the most disabling adverse effect of surgical staging of pelvic lymph nodes. However, the lack of standardisation of volumetric LLL assessment hinders direct comparison between the studies and makes LLL reporting unreliable. The aim of our study is to report outcomes from a prospective trial that have implications for LLL assessment standardisation. In the prospective international multicentre trial SENTIX, a group of 150 patients with stage IA1–IB2 cervical cancer treated by uterine surgery with bilateral sentinel lymph node biopsy was prospectively evaluated by objective LLL assessment, based on limb volume change (LVC) using circumferrential limb measurements and subjective patient-reported swelling. The assessments were conducted in six-month periods over 24 months post-surgery. Patient LVC substantially fluctuated in both positive and negative directions, which were comparable in frequency up to ±14% change. Thirty-eight patients experienced persistent LVC increase >10% classified as LLL, with nine months median time to onset. Some 34.2% of cases experienced onset later than one year after the surgery. Thirty-three patients (22%) experienced transient oedema characterised as LVC >10%, which resolved without intervention between two consequent follow-up visits. No significant correlation between LVC >10% and a patient-reported swelling was observed. Given that we observed comparable fluctuations of the the lower-limb volumes after surgical treatment of cervical cancer in both positive and negative direction up to ±14%, the diagnostic threshold for LLL diagnosis based on LVC should be increased to >15% LVC. The distinction of transient oedema from persistent LLL requires repeated measurements. Also, as one-third of LLL cases are diagnosed >1-year post-surgery, a sufficient follow-up duration needs to be ensured. Patient-reported swelling correlated poorly with LVC and should only be used as an adjunct to objective LLL assessment. Trial registration: ClinicalTrials.gov : NCT02494063 • A volumetric threshold for lower limb lymphoedema diagnosis should be increased to ≥15%. • LLL diagnosis requires repeated measurements and a prolonged follow-up period >1 year. • Patient-reported swelling should only be used as an adjunct to objective measurement. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: None declared.

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 ., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology., Methods: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative., Trial Registration: ClinicalTrials.gov (NCT02494063)., Results: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases., Interpretation: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Objective: The mutant genotype GG of the CYP17A1 gene polymorphism has been linked to higher levels of serum estradiol and thus might be associated with steroid-hormone dependent tumors. We decided to assess an association of CYP17A1 polymorphism with uterine leiomyomas (ULM) and multiple ULM by conducting a meta-analysis and subgroup analysis., Methods: We searched the HuGE Navigator and PubMed databases using the terms "leiomyoma" and "CYP17A1" for articles published by October 1, 2010. Our article in press was added. The selection criteria were (i) cases having ULM, (ii) controls showing no ULM from the same ethnic group, (iii) cases and controls not overlapping. The subgroup analysis included cases having multiple ULM, predisposing black women mostly present with multiple ULM. Pooled risk ratio was calculated using χ ^{2} statistic., Results: Five papers fulfilled the selection criteria for meta-analysis and two papers for the subgroup analysis. The meta-analysis revealed no association of CYP17A1 polymorphism with all ULM. A high pooled risk ratio for multiple ULM was associated with the presence of mutant genotype GG (RR 3.25)., Conclusion: CYP17A1 polymorphism may be associated with multiple ULM but not with all ULM. The future research might enable us to predict the course of the disease.

Background: Ultrasound morphology of massive central pulmonary artery thromboemboli (TE) is an independent predictor of 30-day mortality. The aim of this study was to asses ex vivo lysibility of morphologically different TE., Methods: Forty-five central pulmonary artery TE, collected at autopsies, were divided into hypoechoic (group A) and hyperechoic (group B) categories. TE were lysed with alteplase in a perfusing system simulating pulmonary circulation for 1 hour., Results: The grey scale mean of thrombi in group B was higher compared with group A (64 +/- 7 vs. 38 +/- 7, respectively, P < .01). Spontaneous lysis in group A did not differ compared with group B (2.2% +/- 0.5% vs. 2.1% +/- 0.4%, P = .4). After incubation with alteplase, the weight of TE was reduced more in group A than in group B (16% +/- 2% vs. 11% +/- 2%, P < .001). The grey scale mean negatively correlated with the percentage of TE weight reduction (0.768) (P < .001)., Conclusion: Ultrasound morphology of TE from central pulmonary arteries correlates significantly with ex vivo lysibility. Hypoechoic TE are more susceptible to thrombolysis than hyperechoic TE.