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Establishing a prognostic model for endometrial cancer (EC), that individualizes risk and management plan per patient and disease characteristics.this is multicentre retrospective study conducted in 9 European gynaecologic cancer centres. Women with confirmed EC between January 2008 to December 2015 were included. Demographics, disease characteristics, management, and follow-up information were collected. Cancer-specific survival (CSS) and disease-free survival (DFS) at 3 and 5 years comprise the primary outcomes of the study. Machine learning algorithms were applied to patient and disease characteristics. Model I: pre-treatment model. Calculated probability was added to management variables (model II: treatment model), and the second calculated probability was added to perioperative and postoperative variables (model III).Out of 1,150 women, 1,144 were eligible for 3-year survival analysis and 860 for 5-year survival analysis. Model I, II, and III accuracies of prediction of 5-year CSS were 84.88%/85.47% (in train and test sets), 85.47%/84.88% and 87.35%/86.05%, respectively. Model I predicted 3-year CSS at an accuracy of 91.34%/87.02%. Accuracy of model I, II and III in predicting 5-year DFS were 74.63%/76.72%, 77.03%/76.72%, and 80.61%/77.78%, respectively.Endometrial Cancer Individualised Scoring System (ECISS) is a novel machine learning tool assessing patient-specific survival probability with high accuracy.

The predictors of positive endocervical margin (EM) and a cone-depth cutoff value are not established in the fully visible transformation zone (TZ). The present study aimed to assess the independent variables associated with positive EM in women with high-grade cervical intraepithelial neoplasia (CIN) and fully visible TZ.The current investigation was a retrospective study including women with fully visible TZ and CIN 3 cone histology between 2014 and 2019. The sample was divided into women with positive versus those with negative EM. Univariate and multivariate analyses were performed. Finally, receiver operating characteristic curve analysis was also used.A total of 123 of 517 women (23.8%) showed positive EM at conization. Multivariate analysis found a positive association with type 2 TZ (odds ratio [OR], 2.17 [95% confidence interval (CI), 1.19-3.94]) and lesion extension ≥2 cervical quadrants (OR, 35.57 [95% CI, 17.96-70.45]). Cone depth was inversely related to positive EM (OR, 0.71 [95% CI, 0.63-0.80]). In women with type 2 TZ and lesion extension ≥2 cervical quadrants, the cutoff value was achieved at 8-mm cone depth (area under the curve, 0.79 [95% CI, 0.67-0.90]).In women with high-grade CIN and fully visible TZ undergoing conization, the lesion extension and the TZ subtype (1 or 2) should be considered. A no less than 9-mm cone depth provided a fair predictive value in achieving free EM.

It is unknown whether human papillomavirus (HPV) status impacts the prognosis of early stage cervical glandular lesions. This study assessed the recurrence and survival rates of in situ/microinvasive adenocarcinomas (AC) according to HPV status during a 5-year follow-up. The data were retrospectively analyzed in women with available HPV testing before treatment. One hundred and forty-eight consecutive women were analyzed. The number of HPV-negative cases was 24 (16.2%). The survival rate was 100% in all participants. The recurrence rate was 7.4% (11 cases, including four invasive lesions (2.7%)). Cox proportional hazards regression showed no difference in recurrence rate between HPV-positive and HPV-negative cases (p = 0.148). HPV genotyping, available for 76 women and including 9/11 recurrences, showed a higher relapse rate for HPV-18 than HPV-45 and HPV-16 (28.5%, 16.6%, and 9.52%, p = 0.046). In addition, 60% and 75% of in situ and invasive recurrences, respectively, were HPV-18 related. The present study showed that most ACs were positive for high-risk HPV, and the recurrence rate was unaffected by HPV status. More extensive studies could help evaluate whether HPV genotyping may be considered for recurrence risk stratification in HPV-positive cases.

Uterine fibroids are the most common cause of solid pelvic tumours, occurring in 20-30% of fertile women and presenting clinical complications that seriously affect women's health. They commonly cause severe symptoms, such as heavy, prolonged menstrual bleeding and anaemia. The study of microscopic and macroscopic vascular aspects of uterine fibroids is important for understanding the clinical manifestations of uterine fibroids, for predicting the effectiveness of alternative treatments to surgery, i.e. uterine artery embolization, for improving surgery outcomes and for carrying out a differential diagnosis with other benign conditions, e.g. adenomyosis, or malignancy, e.g. leiomyosarcoma, and to develop new therapeutic approaches. In this review, current knowledge of how the vascular network and angiogenesis are implied in the formation of uterine fibroids and in the pathogenesis of related symptoms is explored, and evidence on the role of ultrasound in evaluating fibroid vascularization is summarized. This review combines anatomical, morphological and biomolecular information related to angiogenic mechanisms with diagnostic and clinical information, highlighting the various interconnections. Uterine and fibroid vascularization need further investigation to gain a deeper understanding of the pathogenetic elements that lead to the formation of uterine fibroids and their clinical manifestations.

Human papillomavirus (HPV) is the most common sexually transmitted infection. The implementation of primary prevention aims to reduce the burden of HPV infection and HPV-related disease. However, HPV-related diseases are still a concern, even in high-income countries. Approximately 570 000 new cervical cancer cases are diagnosed in Italy every year. Prophylactic HPV vaccines have been developed to minimize the spread of HPV. Growing evidence supports the administration of HPV vaccines (even just one dose) in reducing the prevalence of HPV infection and HPV-related disease including cancers. HPV vaccines are characterized by a high level of efficacy (>95%) in women who are naïve to HPV; however, they do not increase clearance in patients with ongoing HPV infection. With more than 200 million doses administered to date, HPV vaccines are considered to be safe and effective at preventing HPV-related infections and cancers. In this review we aim to review the current evidence regarding HPV vaccination and to describe trends in HPV vaccination coverage in Italy. In Italy, vaccination against HPV has been included in the National Immunization Plan (NIP) since 2007–2008. Using data abstracted from the Italian Ministry of Health, we analyzed changes in HPV vaccination coverage. We observed that HPV vaccines are underutilized and coverage rates are decreasing. Looking at the target population (females and males aged 11–12 years) in Italy, a decrease in coverage rates was observed. A call for action, improved HPV awareness, and education are the key elements to enhance the widespread adoption of HPV vaccination.

Foetal ductus arteriosus (DA) constriction can be found in complex foetal heart malformations, but rarely as an isolated defect. Although many cases of DA constriction are usually related to Non-steroidal Anti-Inflammatory Drugs (NSAIDs) maternal intake, other causes remain without an established aetiology and are referred to as idiopathic. Recently, a wide range of risks factors or substances (polyphenol-rich foods intake, naphazoline, fluoxetine, caffeine and pesticides) showed a definitive effect upon the pathway of inflammation, causing DA constriction. We report a case of a premature DA constriction in a woman whose possible risk factor was identified in her maternal occupational exposure to solvents and a comprehensive literature review of 176 cases of NSAID-unrelated DA constriction. A 30-year-old Asian woman was referred to our institution at 33 gestational weeks and 0 days because of suspicion of premature DA constriction. The woman had no history of medication intake, including NSAIDs, alcohol, tobacco or polyphenol-rich-food consumption during pregnancy. A detailed foetal echocardiography revealed a normal cardiac anatomy with hypertrophic, hypokinetic and a dilated right ventricle due to right pressure overload, holosystolic tricuspid regurgitation, and, at the level of the DA, high systolic and diastolic velocities, indicating premature ductal restriction. The right outflow showed dilatation of the pulmonary artery with narrow DA. An urgent caesarean section was performed at 33 gestational weeks and 4 days due to worsening of DA PI and signs of right pressure overload, despite the interruption of exposure to solvents. We assume a relationship exists between premature DA constriction and a maternal occupational exposure to solvents. This hypothesis is reinforced by the presence of associated foetal malformations in in two of the patient’s children. Further research is needed to confirm the role of exposure to solvents and toxic chemicals in the pathogenesis of DA constriction, also with experimental animal models.KEY MESSAGESMany cases of DA constriction are usually related to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) maternal intake.A wide range of risks factors or substances (polyphenol-rich foods intake, naphazoline, fluoxetine, caffeine and pesticides) can cause foetal DA constriction.Further investigation are needed to confirm the role of maternal exposure to solvents in the pathogenesis of DA constriction.

Cervical cancer prevention guidelines include Human Papillomavirus (HPV) test, cytology, and HPV-16/18 typing for triage to determine the risk of cervical intraepithelial neoplasia (CIN) grade 3 as the best proxy of cervical cancer risk. In doing that, they do not consider how age can modify the type-specific risk of CIN3. The present study aimed to evaluate the age-related distribution of HPV genotypes affecting the risk-assessment in cervical cancer screening programs: non-screening-type-HPV and non-HPV-16/18 in unvaccinated women with CIN3.Retrospective multi-institutional study, including HPV genotyped women with CIN3 on cone histology treated between 2014 and 2019. The sample was divided into three categories of age:30, 30-44, ≥45. HPV genotypes were grouped in non-screening-type-HPV (not-including genotypes 16/18/31/33/35/39/45/51/52/56/58/59/66/68) and non-HPV-16/18. Associations and trends between different age-groups and HPV genotypes were measured.1332 women were analyzed. Non-screening-type-HPV CIN3 were 73 (5.5%). Non-HPV-16/18 were found in 417 participants (31.3%). Women over 45 associated with non-screening-type HPV [odds ratio (OR) = 1.87, 95% confidence interval (CI) 1.07-3.25; p = 0.027]. Non-screening-type-HPV prevalence increased significantly with age (3.9% vs 5.1% vs 9.0%, p = 0.016). Women under 30 showed a lower rate of non-HPV-16/18 (OR = 0.65, 95% CI 0.47-0.89; p = 0.007). There was a positive trend with age of non-HPV-16/18 CIN3 (23.6% vs 32.1% vs 38.0%, p = 0.0004).The proportion of CIN3 lesions unrelated to genotypes detected by primary screening tests increased with age. This implies that age probably modifies the risk of CIN3 and possibly of cancer associated with HPV types. The risk-based recommendation should take into consideration age to define the management of HPV positive women.

Background: This study aimed to systematically review the existing literature on uterine smooth muscle tumor of uncertain malignant potential (STUMP) to provide information about characteristics and outcomes of patients and the risk factors for recurrence over a period of 60 years (1960–2021). Methods: According to PRISMA guidelines, we searched for "uterine smooth muscle tumor of uncertain malignant potential" in PubMed (all fields) and Scopus (Title/Abstract/Keywords) databases (accessed on 1 January 2022). Relevant articles were obtained in full-text format and screened for additional references. The only filter used was the English language. Studies including full case description of patients with histopathological diagnosis of STUMP in accordance with Stanford criteria were included. Results: Thirty-four studies, including 189 cases, were included. The median age was 43 years, and in 21.5% of cases there was a recurrence of the disease. Bivariate analysis showed a significant association between use of morcellation without bag and risk of recurrence (p = 0.001). Unprotected morcellation during demolitive or conservative surgery was independently associated with a higher risk of disease recurrence with a relative risk of 2.94 (p < 0.001). A significant progressive decrease in the recurrence rate was observed over time (r = −0.671, p = 0.008). The percentage of patients who underwent surgery followed by in-bag protected morcellation significantly increased after the publication of the U.S. Food and Drug Administration alert about the risk linked to this procedure (p = 0.01). Conclusions: Unprotected morcellation of the lesion is associated with the relapse of the disease. However, this clinical condition showed a drastic decrease over time. This could likely be due to the increased awareness by surgeons of the importance of customizing surgical treatment.

To analyze the clinical management, the outcomes, and the trend in hysterectomy rates (HR) in patients who underwent this procedure for cervical intraepithelial neoplasia (CIN).Multicentric retrospective observational study conducted on 242 patients who underwent hysterectomy for CIN between 2010 and 2020 in nine Italian institutions. Hysterectomy for invasive or micro-invasive neoplasia, sub-total hysterectomy, or trachelectomy were excluded.A significant increase in the trend of HR for CIN was recorded (P = 0.002, r = 0.81; C.I. 95%: 0.415-0.949); HR increased from 0.46% in the year 2010 to 3.32% in 2020. The mortality rate was 0.4%, and 5% had operative complications. On definitive histopathology examination, a CIN of any grade was recorded in 71.5% of cases, and an occult invasive cancer in 1.24%. No pathology or CIN1 was found in 26.8% of cases, suggesting over treatment. During follow-up, a vaginal lesion was recorded in 5% of cases.A significant increase in the number of hysterectomies performed for CIN in the last 10 years was recorded. Hysterectomy for CIN can lead to complications, risk of the onset of vaginal lesions, and risk of overtreatment, and remains, in the first instance, an unacceptable treatment, to be proposed only after adequate counseling.

To evaluate the impact of healthcare reorganization during the severe acute respiratory syndrome coronavirus 2 pandemic on Italian colposcopy clinic activities, focusing on cervical excision procedures, follow-ups for conservative management of low-grade lesions, and follow-ups post cervical excision.Retrospective study conducted in 14 Italian colposcopy clinics. The number and clinical characteristics of cervical excisions, follow-ups for conservative management of low-grade lesions, and follow-ups after cervical excision were compared between the period March 1, 2019 to February 29, 2020 (pre-pandemic) and March 1, 2020 to February 28, 2021 (pandemic) with a Poisson regression analysis.In the pandemic period, the number of cervical excisions was reduced by 8.8% (95% confidence interval [CI]=-15.6% to -2%; p=0.011). Excisions were less frequently performed in the operating room (-35.1%; 95% CI=-47.6% to -22.6%; p0.001), the number of patients from spontaneous screening was reduced by -14.0% (95% CI=-23.4% to -4.6%; p=0.003), and the CO2-laser technique was used less frequently (-30%; 95% CI=-45.1% to -15.0%; p0.001). As compared to the pre-pandemic period, the number of follow-ups for conservative management of low-grade lesions was reduced by -26.7% (95% CI=-39.0% to -14.4%; p0.001), and the follow-up appointments after cervical excision were reduced by -51.0% (95% CI=-58.1% to -43.9%; p0.001).The most significant impact of the healthcare reorganization during the coronavirus disease 2019 pandemic was on follow-ups after cervical excision. The resumption of disrupted activities should follow a risk-based prioritization, starting from women in follow-up after cervical excision. It is advisable that the trend of performing cervical excision as an outpatient procedure is maintained in the post-pandemic period.

To evaluate the risk of endometriosis recurrence according to the mode of delivery (cesarean section vs. vaginal birth) in patients who had become pregnant with a live birth after surgery for endometriosis.A retrospective cohort study. A Cox proportional-hazards regression was performed to evaluate the risk factors for endometriosis recurrence at 36 months of follow-up after the last pregnancy.Academic hospital.Patients who have had ≥1 pregnancy with a live birth following conservative surgery for ovarian endometriosis performed from January 2009 to December 2016 at our institution.Patients who underwent ≥1 cesarean section after surgery for endometriosis.The recurrence rate of endometriosis after live-birth pregnancies obtained after the first surgery for endometriosis.Patients with a history of ≥1 cesarean section after surgery for endometriosis have a higher risk of endometriosis recurrence than the patients who have had a vaginal birth, with an adjusted hazard ratio of 2.25 (95% confidence interval, 1.27-3.96).A cesarean section after surgery for endometriosis is associated with a twofold high risk of endometriosis recurrence with respect to vaginal birth. A different follow-up approach may be needed in those patients, and avoiding inappropriate indications for cesarean sections in pregnant patients with a history of surgery for endometriosis is necessary.

Objectives The aim of this survey was to evaluate the different surgical approaches for women with high-grade vaginal intraepithelial neoplasia (HG-VaIN) used in 8 hospitals in central and northern Italy in the last 20 years. In particular, the baseline characteristics of the patients and factors potentially leading to excisional treatment rather than ablation were considered. Moreover, the clinical outcome of patients treated for HG-VaIN (disease persistence or recurrence and progression toward invasive vaginal cancer) was analyzed. Materials and methods The medical records of all women initially diagnosed with HG-VaIN and subsequently treated in 8 Italian hospitals from January 1996 to December 2016 were analyzed in a multicenter retrospective case series. Results Among the 226 women included, 116 (51.3%) underwent ablative procedures and 110 underwent excisional surgery (48.7%). An ablative procedure was preferred in cases where multiple lesions were found on colposcopic examinations. Physicians decided more frequently to perform excisional procedures in women with menopausal status, high-grade referral cervical cytology, previous hysterectomy for human papillomavirus-related disease, or VaIN 3 on colposcopic-guided biopsy. Conclusions The surgical treatment of HG-VaIN should be tailored according to the clinical characteristics of each woman and each lesion. However, in potentially high-risk cases (VaIN 3, previous hysterectomy for human papillomavirus-related disease, and menopausal women) or in those cases in which an occult invasive disease cannot be ruled out, an excisional approach should be preferred.In any case, long-term follow-up is advisable in women treated for HG-VaIN.

In the context of the COVID-19 pandemic, patients need to be evaluated within 2-4 weeks in the following cases: cytology result of "squamous cell carcinoma," "atypical glandular cells, favor neoplastic," "endocervical adenocarcinoma in situ," or "adenocarcinoma"; histopathological diagnosis of suspected invasion from cervical/vaginal biopsy, or invasive disease after a cervical excision procedure, vaginal excision, or vulvar biopsy/excision; sudden onset of strongly suggestive symptoms for malignancy. Digital imaging technologies represent an important opportunity during the COVID-19 pandemic to share colposcopic images with reference centers, with the aim of avoiding any concentration of patients. All patients must undergo screening for COVID-19 exposure and should wear a surgical mask. A high-efficiency filter smoke evacuation system is mandatory to remove surgical smoke. Electrosurgical instruments should be set at the lowest possible power and not be used for long continuous periods to reduce the amount of surgical smoke. The following personal protective equipment should be used: sterile fluid-repellant surgical gloves, an underlying pair of gloves, eye protection, FFP3 mask, surgical cap, and gown. The colposcope should be protected by a disposable transparent cover. A protective lens that must be disinfected after each use should be applied. The use of a video colposcope should be preferred.

Objective Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p, Synopsis The prevalence of patients with early-stage endometrial cancer (EC) has been lower during coronavirus disease 2019 (COVID-19) pandemic than before its onset. Further evidence is needed to assess the impact of COVID-19 pandemic on survival outcomes of EC patients.

A retrospective study was conducted on patients subjected to laparoscopic myomectomy at our institution from January 2017 to December 2018 to identify predictive factors of blood loss. Two multiple regression models were run to predict intraoperative blood loss and haemoglobin drop. Predictors of an increased intraoperative blood loss and haemoglobin drop were the presence of three-four fibroids at ultrasound (+47 ml

This study aimed to evaluate the emotional path, impact on everyday life, and adequacy of patient education throughout the diagnostic and therapeutic journey of women who received a positive human papillomavirus (HPV) test or Pap smear result. An online survey was designed to determine the demographic characteristics, dominant feelings throughout the diagnostic and therapeutic procedures, major lifestyle changes, impact on social life, and perceived adequacy of patient information in Italian women with a positive HPV test or abnormal cervical cytology result. In this study, the phases of the “patient's journey” included the initial test, waiting for colposcopy or biopsy, waiting for surgery, and follow-up. Anxiety, worry, and fear were the most frequently cited emotions during the initial tests and intervals between procedures. Anxiety and fear gradually decreased during the journey until surgery, and higher levels of optimism were observed postsurgery. The most frequently reported lifestyle changes were attempts to boost the immune system, increased precautions in sexual practices, and dietary changes. Social life is affected by changes in sexual and intimate relationships with partners. Women reported receiving insufficient patient education on the diagnosis and its implications, progression, management, personal care, and resolution. Significant attention should be given to the psychosocial aspects of the entire patient journey after receiving a positive HPV test or an abnormal Pap smear result. It is essential to establish a good rapport between patients and healthcare professionals, and to educate women regarding the condition by minimizing the gap between the perceived and desired adequacy of information.

A comprehensive literature review was performed to determine the relationship between HPV infection and infertility and the eventual role of the 9-valent vaccine for infertility prevention. The search was extended from January 1997 through July 2021. Data collected from selected articles focused on three main topics: statistical associations between HPV prevalence and assisted reproductive technology (ART) outcome, association between HPV and characteristics of semen, and associations between HPV and miscarriage. Articles that identified HPV genotypes were selected for this review to study the possible role of the 9-valent vaccine in infertility prevention. To date, there is no agreement on the implication HPV female infection has on the fertility and miscarriage rate. Although it can be stated that HPV prevalence among couples with infertility undergoing ART treatment is consistent, it does not seem to affect the performance of oocytes. Otherwise, HPV infection affects sperm parameters, in particular spermatozoa motility. When an association can be found, most cases of HR-HPV involved are those included in the 9-valent vaccine. The correlation between HPV male infection both with asthenozoospermia and increased risk of pregnancy loss could recommend the extension of anti-HPV vaccination to adolescent males along with cancer prevention. Despite the fact that the relation between 9-valent HPV genotypes involved in female infection and miscarriage/infertility is not clear, the impact of this virus on health reproduction is evident. Considering this, the importance of HPV vaccination in adolescent females is confirmed. A vaccine efficacy study could be useful to confirm the importance of primary prevention for couple reproductive health.

Simple Summary Endometriosis is a disease that affects 6–10% of women of reproductive age. Although it is a benign condition, endometriotic lesions have around a 1% risk of malignant transformation. Since endometriosis is an estrogen-dependent disease, it can be expected to resolve or disappear in menopause. However, the prevalence of menopausal endometriosis is 2–4%. In these cases, the risk of malignant transformation is a rare but possible event. Data on the risk of these occurrences are scarce and of low quality. The most studied risk factors related to malignant transformation were hormone replacement therapy and the use of tamoxifen. However, the results were inconclusive. Furthermore, the impact of previous endometriosis and related surgery is unclear. Thus, we felt the need for an updated review on this topic focusing on the distribution of recurrent clinical conditions over a period of 50 years. In this regard, a systematic literature review on the malignant transformation of endometriosis-related lesions in postmenopause was performed to provide useful clinical information about patient characteristics, HRT use, and outcomes. Abstract Objective: This study aimed to systematically review the existing literature on malignant transformation of postmenopausal endometriosis to provide information about patient characteristics, hormonal replacement therapy (HRT) use, and outcomes over a period of 52 years (1969–2021). Methods: According to PRISMA guidelines, we searched for (endometriosis OR endometriotic) AND (cancer OR malignancy OR malignant transformation) AND (menopause OR menopausal OR postmenopause OR postmenopausal) in Pubmed (all fields) (accessed on 12 February 2021) and Scopus (Title/Abstract/Keywords) (accessed on 12 February 2021) databases. The only filter used was the English language. Relevant articles were obtained in full-text format and screened for additional references. Eligibility/inclusion criteria: studies including full case description of malignant transformation of endometriosis-related lesions in postmenopause. Results: 75 studies, including 90 cases, were retrieved. The mean age was 55.8 ± 8.5 years. Overall, about 65% of women had a positive personal history of endometriosis/adenomyosis, and 64% of women underwent previous hysterectomy ± bilateral salpingo-oophorectomy. Forty-nine of 74 women used HRT (66.2%). Among the women who used HRT, estrogen-only treatment was taken by approximately 75%. Duration of HRT was longer than five years in 63.3% of cases. About 70% of subjects had histology of endometrioid adenocarcinoma or clear cell carcinoma. Follow-up outcome, available for 61 women, showed a survival rate of 78.7%, recurrence of 9.8%, death of 11.5%. The duration of follow-up had a median of 12 months (interquartile range, 6.75–25 months). Interestingly, over the years of case publication there was a significant inverse correlation with previous history of endometriosis (r = −0.28, p = 0.007), HRT use (r = −0.31, p = 0.006), and previous definitive surgery (r = −0.42, p < 0.001). Conclusions: In the malignant transformation of postmenopausal endometriosis, there are some recurrent clinical conditions: previous endometriosis, major definitive surgery before menopause, and estrogen-only HRT for a relatively long time. However, these clinical conditions have shown a drastic decrease over time. This could likely be the consequence of different attitudes and management of gynecologists linked to up-to-date scientific evidence about the use of major surgery in gynecological pathologies. Malignant transformation of postmenopausal endometriosis is a clinical challenge to be explored further.

Luca Giannella,1 Giovanni Delli Carpini,1 Jacopo Di Giuseppe,1 Giorgio Bogani,2 Barbara Gardella,3 Ermelinda Monti,4 Carlo Antonio Liverani,4 Alessandro Ghelardi,5 Salvatore Insinga,1 Michele Montanari,1 Francesco Raspagliesi,2 Arsenio Spinillo,3 Paolo Vercellini,4 Elena Roncella,4 Andrea Ciavattini1 1Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, Ancona, Italy; 2Gynecologic Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy; 3Department of Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, Università degli Studi di Pavia, Pavia, Italy; 4Gynaecology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy; 5Azienda Usl Toscana Nord-Ovest, UOC Ostetricia e Ginecologia, Ospedale Apuane, Massa, ItalyCorrespondence: Andrea CiavattiniWoman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, via Filippo Corridoni, 16, Ancona, 60123, ItalyTel +390715962172Fax +3907136576Email ciavattini.a@libero.itAim: In the post-vaccination era, the starting age and time intervals of cervical screening could change (older age and longer screening intervals). This scenario may be achieved by significantly reducing human papillomavirus (HPV) 16/18 prevalence (genotypes included in the current vaccines). In this regard, assessing the trend over time of these HPV infections in high-grade cervical lesions can provide information on the objective. The present study aimed to evaluate the trend of HPV 16/18 over the years 2007– 2018 in women with cervical intraepithelial neoplasia (CIN) grade 3.Methods: This is a retrospective multi-institutional study including HPV genotyped and unvaccinated women under 30 with CIN3. The sample was divided into the following periods: 2007– 2010, 2011– 2014, 2015– 2018. HPV genotypes were grouped in genotypes 16/18, genotypes 31/33/35/52/58/67 (genetically related to HPV16), genotypes 39/45/59/68/70 (genetically related to HPV18), genotypes 31/33/45/52/58 (high-risk types included in the nonavalent vaccine), possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85), low-risk HPV (genotypes 6/11/40/42/43/44/54/55/61). The trend between periods and HPV genotypes was measured using the Cochran–Armitage test for trend.Results: The final analysis included 474 participants. HPV 16/18 prevalence decreased significantly over the years (77.8% vs 68.9% vs 66.0%, respectively, Ptrend=0.027). Possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85) showed a significant negative prevalence trend over time (4.9% vs 1.1% vs 1.3%, respectively, Ptrend=0.046). Finally, there was a significant positive trend over the years for high-risk HPV genotypes 31/33/45/52/58 in women under 25 (9.9% vs 17.0% vs 24.0%, respectively, Ptrend=0.048).Conclusion: The prevalence of CIN3 lesions related to HPV 16/18 genotypes decreased over time from 2007 to 2018. These data highlight a herd effect of the HPV vaccine. However, fifteen years after HPV vaccine introduction, we are still a long way from herd immunity. The increase in high-risk types 31/33/45/52/58 will need to be reassessed when the nonavalent vaccine impact will be more reliable.Keywords: cervical cancer, cervical intraepithelial neoplasia, cervical cancer screening program, HPV vaccine, HPV-16/18

Objective To evaluate the risk factors for recurrence of high‐grade disease after cervical excision in women living with HIV (WLWH), with a specific interest in the role of high‐risk (HR‐) HPV positivity. Methods Multicentric retrospective study conducted on WLWH who underwent cervical excision between January 1987 and June 2017 in six Italian institutions. The rate of high‐grade recurrence was determined. Risk factors for recurrence and HR‐HPV positivity were determined with the Log‐rank test and Cox proportional hazards regression models. Results A total of 271 WLWH were included in the final analysis. A high‐grade recurrence was found in 58 (21.4%) patients. Age 41 years or more at inclusion and HR‐HPV positivity during follow up were independently associated with a higher risk of disease recurrence with relative risks of 4.15 (95% confidence interval [CI] 2.01–8.58, P, Synopsis High‐risk‐HPV positivity during long‐term follow up is a risk factor for high‐grade disease recurrence after cervical excisional treatment in women living with HIV.

Objective: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. Methods: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. Results: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). Conclusions: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Cervical cancer is relatively rare in high-income countries, where organized screening programs are in place, as well as opportunistic ones. As the human papillomavirus (HPV) vaccination rates increase, the prevalence of cervical precancers and cancers is going to decrease rapidly very soon, even if, in the most optimistic scenario, it is unlikely that optimal vaccination coverage will be achieved. Then, the optimal screening paradigm for cervical cancer prevention in the postvaccination era is still debated. Screening guidelines are being developed with the aim of reducing the number of tests a woman needs during her lifetime, in order to receive the maximum benefit from screening, while decreasing potential harms that may result with the use of a screening strategy (overdiagnosis, overtreatment, anxiety, and costs). With this purpose in mind, new management guidelines for cervical cancer screening abnormalities are recommendations based on risks, not on results. This review aims to summarize the process that led to the introduction of the HPV DNA test in screening programs and the different screening strategies. Moreover, it aims to introduce the new risk-based guidelines for the future, where full HPV genotyping can resize the risk on the basis of specific high-risk genotypes. In the same way, the data regarding HPV vaccination could be introduced as soon as women vaccinated with the nonavalent vaccine reach the screening age, with the recommendation of a prolonged screening interval.

The present study aimed to perform an initial validation of the Thymic-Thoracic Ratio as a sonographic marker of conotruncal defects in non-syndromic fetuses and to assess the possible correlation between the grade of thymic hypoplasia and the severity of conotruncal defects.The study was conducted between January and June 2018 on singleton pregnant women who underwent fetal echocardiography at our institution. Fetuses with a diagnosis of conotruncal defects without 22q11.2 deletion composed the study group, while healthy appropriate for gestational age fetuses composed the control group. The Thymic-Thoracic Ratio was measured in all included fetuses and compared between the study and control group. A ROC curve analysis to evaluate the diagnostic performance of Thymic-Thoracic Ratio toward the diagnosis of conotruncal defects was performed, with determination of sensitivity, specificity, PPV, NPV, positive likelihood ratio, and negative likelihood ratio. The severity of conotruncal defects was defined with the Aristotle score in each newborn who underwent a surgical operation. The correlation between Thymic-Thoracic Ratio and Aristotle score was assessed.During the study period, 23 fetuses with conotruncal defects without 22q11.2 deletion constituted the study group, and 67 healthy appropriate for gestational age fetuses were included in the control group. The T-T ratio of the study group was significantly lower than the control group (0.32 ± 0.08 vs. 0.41 ± 0.08,T-T ratio measurement could be useful to identify fetuses at higher risk of conotruncal heart diseases, even without chromosomic deletion, with a cutoff of 0.35. Since a lower T-T ratio seems to be related to a worse surgical neonatal prognosis, it could be possible to provide effective counseling and refer patients to high-specialized centers for fetal echocardiography and cardiac surgery.

Background: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors. One of the most frequent localizations of PEComas is the female genitourinary tract, and the uterus is the most involved site after the kidney. Correct preoperative diagnosis is rarely achieved due to the presence of nonspecific imaging features. We report a case of a uterine PEComa with particular reference to ultrasound’s role in characterizing this rare occurrence. Case presentation: a 45-year-old White woman came to our observation for cyclic abdominopelvic pain and chronic constipation. The pre-surgical ultrasound examination showed a heterogeneous tumor that was 4 cm in size, localized on the right anterolateral uterine wall. The mass had well-delimited borders and a central hypoechoic portion. The use of color Doppler showed a rich, irregular vasculature in the center with low impedance. The preoperative diagnostic hypothesis was of a smooth muscle tumor of uncertain malignant potential. After careful counseling, a surgical approach was decided upon, including a total laparoscopic hysterectomy with bilateral salpingectomy. The histological and phenotypical features were consistent with a uterine PEComa. At the last follow-up, two years after surgery, the patient is alive and well. Conclusions: Uterine PEComa is a rare occurrence that should be included in the differential diagnosis of uterine wall tumors. It can appear as a small uterine mass with heterogeneous echogenicity and a rich vascular pattern during an ultrasound evaluation. This diagnostic suspicion may assist in better surgical planning.

Background/aim Clear cell carcinoma of the abdominal wall is a sporadic event. To date, about thirty cases have been reported in the literature. This article provides a case report and literature review of an infrequent occurrence with poor prognosis. Case report A 45-year-old woman with pelvic pain and an abdominal mass came to our attention. Her medical history was notable for two previous cesarean sections. Physical examination revealed a smooth, multilocular mass measuring about 20 cm, arising from the previous surgical scar. Histology revealed clear-cell carcinoma resulting from the transformation of abdominal wall endometriosis. Given the disease extent, the patient underwent front-line chemotherapy. After several and multiple chemotherapy regimens, there was a disease progression that resulted in the death of the patient in 7 months. The literature review showed that a previous cesarean section was present in 91% of cases. Besides, approximately 26.5% of women died within 12 months of being diagnosed. The mean age of women was 45.88 years, while the average size of the lesion was 11 cm. Conclusion Clear cell carcinoma is a rare but occurring event. Middle-aged women showing an abdominal wall mass in close relation with a surgical scar from a previous cesarean section must be promptly investigated. Treatment options usually include surgery and chemotherapy with poor results.

The COVID-19 pandemic caused by SARS-CoV-2 has radically changed global healthcare. On May 13, 2020, all countries of the European Region reported their COVID-19 status, with 1 757 814 confirmed cases and 157 923 confirmed deaths.[1][1] Each country has initiated measures to reduce the impact

Objective To create a prediction model including clinical variables for the prediction of premalignant/malignant endometrial pathology in premenopausal women with abnormal uterine bleeding (AUB). Methods This is an observational retrospective study including 240 premenopausal women with AUB referred to diagnostic hysteroscopy. Based on the presence of endometrial hyperplasia (EH) or cancer (EC), the women were divided into cases (EH/EC) and controls (no EH/EC). Univariate, stepwise logistic regression and ROC curve analysis were performed. Results 12 women had EH/EC (5%). Stepwise logistic regression analysis showed that EH/EC associated significantly with BMI ≥ 30 (OR=7.70, 95% CI 1.90 to 31.17), diabetes (OR=9.71, 95% CI 1.63 to 57.81), and a thickened endometrium (OR=1.20, 95% CI 1.08 to 1.34, criterion > 11 mm). The AUC was 0.854 (95% confidence intervals 0.803 to 0.896, p 11 mm, the percentage of premalignant/malignant endometrial pathology increases by 25%. It is likely that the simultaneous presence of several risk factors is necessary to significantly increase the probability of endometrial pathology.

Objective: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). Methods: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. Results: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). Conclusions: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

OBJECTIVES The aim of the present study was to observe the trend of length of cone excisions in women treated with cervical excision procedure in five institutions of Central and Northern Italy. MATERIALS AND METHODS A multicenter retrospective cohort study was conducted on women who underwent a cervical excision procedure between January 2006 and December 2014. The pertinent clinical, histopathological, and sociodemographic characteristics of each woman were collected. In particular, the length of the cone specimen was evaluated and all of the factors that potentially influenced the length of excision were considered. RESULTS A total of 1482 women who underwent a cervical excision procedure from January 2006 to December 2014 were included. A mean (SD) cone length of 12.9 (5.0) mm was reported, and mostly, a significant decrease during the whole study period emerged. Age (r = 0.1, p = .007) and preoperative diagnosis of glandular lesions (r = 0.1, p < .001) were significantly related to the length of cone excision on multivariate analysis. Compared with the carbon dioxide laser excisional procedure, loop electrosurgical excision procedure showed a negative correlation with the length of excision (r = -0.2, p < .001). CONCLUSIONS During the study period, a significant decrease in the length of cone excision was observed, probably reflecting the gynecologists' acquired awareness of the increased risk of adverse obstetric outcomes for future pregnancies in the case of wide cone excisions.

Objective To assess the effect of age on pre- and post-conization HPV genotype distribution. Method The present retrospective observational study included consecutive women with high-grade cervical intraepithelial neoplasia who underwent conization at the Cervical Cancer Screening Centre of Reggio Emilia, Italy, and University Hospital of Modena, Italy, between February 1, 2012, and October 31, 2014. Pre-conization and 6-month post-conization HPV genotyping results were compared between four age groups (