PARP Inhibitors in Newly Diagnosed and Recurrent Ovarian Cancer.

Ovarian cancer is the most lethal gynecologic malignancy, characterized by a high death-to-incidence ratio. Platinum-based chemotherapy is the mainstay of treatment for newly diagnosed and platinum-sensitive recurrent ovarian cancer. Poly (ADP-ribose) polymerase inhibitors (PARP inhibitors) have been incorporated into the treatment strategy for ovarian cancer. PARP inhibitors showed particular benefit for patients harboring defects in DNA repair pathways. Accumulating evidence showed that PARP inhibitors provide a benefit in newly diagnosed advanced ovarian cancer, even in the absence of BRCA mutation, as reported in the PRIMA, PRIME, and ATHENA-mono trials. Interestingly, the PAOLA-1 study provides another important finding, supporting the adoption of olaparib plus bevacizumab in patients with homologous recombination deficiency. Although those results are exciting, several patients develop resistance to PARP inhibitors. Hence, new combinations are under investigation to identify new treatment strategies to overcome this resistance. Currently, researchers are focused on the possibility to adopt PARP inhibitors even in the setting of platinum-resistant disease. The present critical review aims to report the current landscape and further perspective for strengthening PARP inhibitors' effectiveness in newly diagnosed and recurrent ovarian cancer.

Outcomes of High-Grade Cervical Dysplasia with Positive Margins and HPV Persistence after Cervical Conization.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

Hysterectomy: Let's Step Up the Ladder of Evidence to Look Over the Horizon.

Hysterectomy is one of the most common non-obstetric gynecological surgical procedures carried out in Western countries [...].

Advances on Prevention and Screening of Gynecologic Tumors: Are We Stepping Forward?

According to 2020 comprehensive global cancer statistics published by the International Agency for Research on Cancer, gynecologic malignancies accounted overall for 16 [...].

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia.

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.

Modified intestinal isolation bag as promising tool in promoting bowel resumption after ovarian cancer cytoreductive surgery: a randomized clinical trial.

PURPOSE: Postoperative ileus (POI) impairs patient recovery, prolonging hospital stay after major surgery in ovarian cancer (OvCa) patients. Thus, intraoperative bowel isolation is expected to reduce manipulation-related impairment. The aim of this study was to investigate the impact of intraoperative intestinal isolation bag on POI in OvCa patients submitted to primary surgery. METHODS: A randomized trial including patients managed with or without isolation bag during OvCa primary surgery was conducted. Patients were selected by consecutive randomization. Primary endpoints were the time between surgery and resumption of bowel motility (as passage of first/continued flatus), assessing of postoperative nausea or vomiting and return to regular diet. Secondary endpoint was the impact of intestinal isolation bag on length of hospitalization in the two groups. RESULTS: Ninety-two patients respecting inclusion criteria were eligible to be enrolled in the study (48 patients as Group 1 and 44 patients as Group 2). Thirty-eight (79.2%) patients, in which intraoperative isolation bag was used, experienced first/continued flatus within 3 days from surgery and they were susceptible to be discharged within 5 days, compared, respectively, to 34.3% of Group 2 (n = 15). Advantages were more evident in patients whose surgery took over 220 min (OR 0.02, CI 95% 0.001-0.57; p < 0.001) despite the type of surgical effort made. CONCLUSION: Despite the small sample size, our study showed that the use of intestinal isolation bag can reduce incidence of POI and length of stay in OvCa patients submitted to primary cytoreductive surgery.

High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

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.

Pregnant women's knowledge and behaviour to prevent cytomegalovirus infection: an observational study.

OBJECTIVES: Congenital cytomegalovirus (cCMV) infection can negatively affect pregnancy outcomes, but may be prevented by simple precautions. Literature suggests that gynaecologists do not always adequately inform about preventive behaviour and most pregnant women have a low-level knowledge regarding cCMV infection. The aim of this study is to evaluate knowledge and risk behaviours related to cCMV infection in an unselected group of pregnant women. METHODS: An institutional based cross-sectional study was conducted in three Maternal and Fetal Divisions in Rome between November and February 2019 on 296 pregnant women, their knowledge on cCMV was measured using six cytomegalovirus (CMV) related questions. RESULTS: Out of the 296 respondents, 59.1% had heard, read or seen information about cCMV infection. Regarding the way of transmission, 96/296 (32.4%) correctly recognize children as a potential source of the infection but only 25/296 (8.44%) knew all prevention practices, 28/296 (9.5%) of women reported that they have never performed cCMV test during pregnancy. CONCLUSIONS: The results of this survey show that knowledge on cCMV infection among pregnant women is poor. This highlights the need to improve counselling on all preventive practices for cCMV infection during perinatal care consultation.

Assessing the Long-Term Role of Vaccination against HPV after Loop Electrosurgical Excision Procedure (LEEP): A Propensity-Score Matched Comparison.

Background: Primary prevention through vaccination is a prophylactic approach aiming to reduce the risk of developing human papillomavirus (HPV)-related lesions. No mature and long-term data supported the adoption of vaccination in women undergoing conization. Methods: This is a retrospective multi-institutional study. Charts of consecutive patients undergoing conization between 2010 and 2014 were collected. All patients included had at least 5 years of follow-up. We compared outcomes of patients undergoing conization plus vaccination and conization alone. A propensity-score matching algorithm was applied in order to reduce allocation biases. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. Results: Overall, charts of 1914 women were analyzed. The study group included 116 (6.1%) and 1798 (93.9%) women undergoing conization plus vaccination and conization alone, respectively. Five-year recurrence rate was 1.7% (n = 2) and 5.7% (n = 102) after conization plus vaccination and conization alone, respectively (p = 0.068). After the application of a propensity-score matching, we selected 100 patients undergoing conization plus vaccination and 200 patients undergoing conization alone. The crude number of recurrences was 2 (2%) and 11 (5.5%) for patients undergoing conization plus vaccination and conization alone, respectively (p = 0.231). Vaccination had no impact on persistent lesions (no negative examination between conization and new cervical dysplasia; p = 0.603), but reduced the risk of recurrent disease (patients who had at least one negative examination between conization and the diagnosis of recurrent cervical dysplasia; p = 0.031). Conclusions: Patients having vaccination experience a slightly lower risk of recurrence than women who had not, although not statistically significantly different. Further evidence is needed to assess the cost effectiveness of adopting vaccination in this setting.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

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.

Successful preterm pregnancy in a rare variation of Herlyn-Werner-Wunderlich syndrome: a case report.

BACKGROUND: Herlyn-Werner-Wunderlich syndrome (HWWS) is an uncommon congenital anomaly of the female urogenital tract, characterised by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. We reported the difficult pregnancy course complicated by an extremely rare and unique case of this syndrome associated with ectrodactyly, a clinical combination never described in literature. CASE PRESENTATION: A 28- year-old nulliparous woman previously diagnosed for HWWS associated with ectrodactyly of the right foot and with a history of abdominal left hemi-hysterectomy, ipsilateral salpingectomy, vaginal reconstruction when she was an adolescent. She suffered from threats of abortion in the first trimester, recurrent urinary tract infections during all pregnancy. At 33 weeks + 5 days of gestational age, she was hospitalized for premature rupture of the membranes and uterine contractions and a caesarean section was performed because of breech presentation. Postpartum period was complicated by a pelvic abscess resolved with parental antibiotic therapies. CONCLUSIONS: Our literature review shows an unusual aspect in our case: HWWS is not classically associated with skeletal anomalies. Moreover, the most frequent urogenital side affected is the right, not left side as in this woman. Preterm spontaneous rupture of membranes and fetal abnormal presentation represent frequent complications and probably post-caesarean infections are related to pregnancies in the context of this syndrome.

The Role of Hysteroscopy in Evaluating Postmenopausal Asymptomatic Women with Thickened Endometrium.

BACKGROUNDS AND AIMS: This study aims to compare hysteroscopic and histological findings in asymptomatic postmenopausal patients with thickened endometrium. MATERIALS AND METHODS: A retrospective study involving case records of 295 asymptomatic postmenopausal women with a thickened endometrium >5 mm diagnosed at transvaginal ultrasound (TVS). Patients (women) underwent hysteroscopy with biopsy between 2009 and 2015, and they were followed up at National Cancer Institute of Bari and at University Hospital of Pisa. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of hysteroscopy were evaluated. RESULTS: Inclusion criteria were TVS, hysteroscopy, and endometrial biopsy. When the hysteroscopic findings were normal, a sensitivity of 100%, specificity of 98.6%, PPV of 95.2%, and NPV of 100% were achieved. For polyps and myomas, we found 100%, 98.7%, 99.5%, and 100%, respectively. In case of endometrial hyperplasia, a sensitivity of 66.7%, a specificity of 100%, a PPV of 100%, and a NPV of 98.1% were achieved. For endometrial cancer hysteroscopy, sensitivity, specificity, PPV, and NPV were 100%, 99.6%, 75%, and 100%, respectively. CONCLUSIONS: Hysteroscopy allows an accurate diagnosis in benign endometrial pathology and suspect of malignant endometrial pathology in postmenopausal women with thickened endometrium.

Prescribing exercise for prevention and treatment of gestational diabetes: review of suggested recommendations.

Exercise has been proved to be safe during pregnancy and to offer benefits for both mother and fetus; moreover, physical activity may represent a useful tool for gestational diabetes prevention and treatment. Therefore, all women in uncomplicated pregnancy should be encouraged to engage in physical activity as part of a healthy lifestyle. However, exercise in pregnancy needs a careful medical evaluation to exclude medical or obstetric contraindications to exercise, and an appropriate prescription considering frequency, intensity, type and duration of exercise, to carefully balance between potential benefits and potential harmful effects. Moreover, some precautions related to anatomical and functional adaptations observed during pregnancy should be taken into consideration. This review summarized the suggested recommendations for physical activity among pregnant women with focus on gestational diabetes.

Robot-assisted surgery for the radical treatment of deep infiltrating endometriosis with colorectal involvement: short- and mid-term surgical and functional outcomes.

PURPOSE: Sexual and urinary dysfunctions are complications in radical treatment of deep infiltrating endometriosis (DIE) with colorectal involvement. The aim of this article is to report the preliminary results of our single-institution experience with robotic treatment of DIE, evaluating intraoperative and postoperative surgical outcomes and focusing on the impact of this surgical approach on autonomic functions such as urogenital preservation and sexual well-being. METHODS: From January 2011 through December 2013, a case series of 10 patients underwent robotic radical treatment of DIE with colorectal resection using the da Vinci System. Surgical data were evaluated, together with perioperative urinary and sexual function as assessed by means of self-administered validated questionnaires. RESULTS: None of the patients reported significant postoperative complications. Questionnaires concerning sexual well-being, urinary function, and impact of symptoms on quality of life demonstrated a slight worsening of all parameters 1 month after surgery, while data were comparable to the preoperative period 1 year after surgery. Dyspareunia was the only exception, as it was significantly improved 12 months after surgery. CONCLUSIONS: Robot-assisted surgery seems to be advantageous in highly complicated procedures where extensive dissection and proper anatomy re-establishment is required, as in DIE with colorectal involvement. Our preliminary results show that robot-assisted surgery could be associated with a low risk of complications and provide good preservation of urinary function and sexual well-being.

Management of endometrial cancer in Italy: a national survey endorsed by the Italian Society of Gynecologic Oncology.

INTRODUCTION: Endometrial carcinoma (EC) is a frequent cancer in developed countries, but with evidence for discrepant clinical management. Under the auspices of the Italian Society of Gynecologic Oncology (SIOG), we conducted a survey among Italian centers with ≥20 surgeries for gynecological cancer per year, trying to depict a reliable picture of EC management in our country. METHODS: The questionnaire focused on preoperative/surgical staging and adjuvant treatment. Of the 283 questionnaires delivered, 35% were sent back. RESULTS: Diagnostic hysteroscopy is performed in 78% of centers. In clinical stage I, 52% adopt a laparotomic access, 15% totally laparoscopic, 9% laparoscopic/vaginal, 2% vaginal, 22% tailored approach. Elective use of laparoscopy significantly differs between institutions (p < 0.001): 40% (≥20 EC/yr) vs. 12% (<20). Pelvic and aortic lymphadenectomy is selectively performed by 77% and 68% of centers, respectively, depending on pre/intraoperative factors. Non-endometrioid histology, poor-grade and deep myoinvasion are indicated as the highest-risk factors. Adjuvant therapy is given to pathologically node-negative patients by 60%, and to intermediate-risk patients by 47%. Elective adjuvant treatment is still radiotherapy, but chemotherapy is adopted, mostly combined with radiation, by 40%. There is a multidisciplinary team in 64% of centers, but in 59% adjuvant treatment is to be administered outside the institution. CONCLUSIONS: These data demonstrate a significant improvement in the clinical care achieved over the last decades in Italy. Centralization of EC treatment would not be feasible neither useful. High-risk cases could be selected by an appropriate clinical screening, and these only referred to reference centers.