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.

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.

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.

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.

Completion surgery after concomitant chemoradiation in locally advanced cervical cancer: a comprehensive analysis of pattern of postoperative complications.

BACKGROUND: We provided a comprehensive analysis of rate, pattern, and severity of early and late postoperative complications in a very large, single-institution series of locally advanced cervical cancer (LACC) patients administered CT/RT plus radical surgery (RS). METHODS: A total of 362 consecutive LACC (FIGO stage IB2-IVA) patients were submitted to RS after CT/RT at the Gynecologic Oncology Unit of the Catholic University (Rome/Campobasso). At 4 weeks after CT/RT, patients were evaluated for objective response and triaged to radical hysterectomy and pelvic ± aortic lymphadenectomy. Surgical morbidity was classified according to the Chassagne's grading system. RESULTS: Most cases underwent type III-IV radical hysterectomy (N = 313, 86.5 %); pelvic lymphadenectomy was performed in all patients, while 116 patients (32.1 %) were also submitted to aortic lymphadenectomy. A total of 93 patients (25.7 %) experienced any grade postoperative complications, and 60 (16.6 %) had ≥grade 2 complications; grade 3-4 complications occurred in 21 patients (5.8 %). Of all early postoperative complications (N = 100), 31 (31.0 %) were urinary, 9 (9.0 %) were gastrointestinal, and 45 (45.0 %) were vascular. Of all late complications (N = 31), 20 (64.5 %) were urinary, 7 (22.6 %) gastrointestinal, and 2 (6.4 %) were vascular. Multivariate analysis showed that not complete clinical response to treatment retained an independent, unfavorable association with risk of development of postoperative morbidity, while advanced stage, and aortic lymphadenectomy showed only a borderline value. CONCLUSIONS: Failure to achieve clinical complete response to treatment and, to a lesser extent, more advanced stage, and aortic lymphadenectomy, were associated with a higher risk of developing any grade as well as ≥grade 2 complications.

Secondary analyses from a randomized clinical trial: age as the key prognostic factor in endometrial carcinoma.

OBJECTIVE: The purpose of this study was to explore in greater depth the outcomes of the Italian randomized trial investigating the role of pelvic lymphadenectomy in clinical early stage endometrial cancer. In the attempt to identify the patients with poorer prognosis, the impact of age and body mass index were also thoroughly investigated by cancer-specific survival (CSS) analyses. STUDY DESIGN: Survival outcomes of trial patients were analyzed in relation to age (≤65 years and >65 years) in the 2 arms (lymphadenectomy and no lymphadenectomy) and in the whole population of the trial. RESULTS: Univariate and multivariable analyses of CSS and overall survival (OS) of patients showed that age >65 years is a strong independent poor prognostic factor (5-y OS 92.1% and 78.4% in ≤65 years and >65 years patients, respectively, P < .0001; 5-y CSS 93.8% and 83.5% in ≤65 years and >65 years patients, respectively, P = .003). Among women ≤65 years, node negative patients had 94.4% 5-y OS and 96.3% 5-y CSS vs 74.3% 5-y OS and 74.3% 5-y CSS for node positive patients (P = .009 and P = .002, respectively), while among women >65 y, node negative patients had 75.7% 5-y OS and 83.6% 5-y CSS vs 74.1% 5-y OS and 83.3% 5-y CSS for node positive patients (P = .55 and P = .58, respectively). Univariate and multivariable survival analyses in the whole trial population showed that older age, and higher tumor grade and stage were significantly associated to a worse prognosis. CONCLUSION: Older women faced an intrinsic poorer survival whether or not they underwent lymphadenectomy, and, unexpectedly, irrespective of the presence of nodal metastasis. Only in older patients was obesity (body mass index >30) significantly associated with scarce prognosis.

Laparoscopic approach for peripartum hysterectomy.

Abnormal placentation is the most common indication for peripartum hysterectomy. To date, the approach described in the literature is laparotomy, which is associated with high morbidity and mortality. A 30-year-old gravida 4 para 3 had a postpartum diagnosis of placenta percreta. She was first treated conservatively. On day 3 after delivery, because of persistent vaginal bleeding, she underwent a laparoscopic hysterectomy. No postoperative complications occurred, and the patient was discharged on postoperative day 3. Laparoscopic peripartum hysterectomy could become the approach of choice in selected patients with abnormal placentation to avoid complications associated with laparotomy.

Robotic management of major vessel injury during pelvic lymphadenectomy.

Laparoscopic management of major vessel lesion is a challenging task during pelvic lymphadenectomy, and conversion is frequently necessary. Robotic surgery overcomes the limits of laparoscopy in vascular suturing. We describe a case of a 79-year-old woman with stage IB G3 endometrial adenocarcinoma, where an external iliac vein injury occurred during pelvic lymphadenectomy. This is the first case report that describes robotic management of a major vascular injury during pelvic lymphadenectomy by use of endoscopic bulldog clamps and robotic intracorporeal vascular sutures.

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.

Perioperative outcomes of total laparoendoscopic single-site hysterectomy versus total robotic hysterectomy in endometrial cancer patients: a multicentre study.

OBJECTIVE: To compare the peri-operative outcomes between total laparo-endoscopic single-site (LESS) and robotic approaches for the staging and treatment of early stage endometrial cancer patients. METHODS: A multicentre retrospective study involving three Italian gynaecological groups and one American centre. The peri-operative outcomes of LESS and robotic approach were compared in similar groups of patients, with regard to surgical outcomes and intra- and post-operative parameters and complications. RESULTS: During the study period, 75 patients submitted to a total LESS hysterectomy and 75 patients received a total robotic hysterectomy. The median operative time - 122 versus 175 min (p=0.0001) - and the estimated blood loss - 50 versus 80 mL (p=0.03) - were slightly more favourable in the LESS group. The intra-operative complications were equally distributed (p=0.99); in the robotic group there were 4 (5.3%) post-operative grade IIIb complications versus 1 (1.3%) in the LESS group (p=0.172). CONCLUSIONS: The LESS and robotic approaches both appear reasonable and each may have benefits and limitations depending upon the patient population. Further studies are needed to validate these preliminary conclusions.

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 [...].

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 [...].

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+.

Laparoscopic adnexectomy of suspect ovarian masses: surgical technique used to avert spillage.

Herein is described and evaluated a safe laparoscopic adnexectomy technique for retroperitoneal dissection of suspect ovarian masses including the underlying peritoneum fixed to the ovary. Adopting this technique in cases of suspect adnexal masses enables the reduction of spilling and ensures an intact specimen. Twenty-two consecutive patients with suspect adnexal masses 10 cm or smaller underwent laparoscopic adnexectomy. Patients with bilateral suspect ovarian masses that required bilateral adnexectomy were enrolled only if they were no longer of childbearing age. Laparoscopy was feasible in all patients. No tumor spillage occurred. In 5 patients (23.6%), minilaparotomy was required to extract the specimen. Mean (SD) operating time was 80 (35-160) minutes, and estimated blood loss was 50 (10-100) mL. No major intraoperative complications occurred. Median (range) postoperative stay was 1 (1-3) day. Definitive pathologic analysis revealed benign pathologic conditions in 18 patients (81.8%), an ovarian tumor with low malignant potential in 3 patients (13.7%), and ovarian cancer in 1 patient (4.5%) in whom findings at frozen-section analysis were inconclusive. Median (range) follow-up of malignant ovarian tumors and of tumors with low malignant potential was 27 (21-29) months. No recurrence or port-site metastasis developed during follow-up. The data are encouraging for adoption of this technique to avert spillage during laparoscopic management of suspect adnexal masses, especially those firmly adherent to the peritoneum. However, the procedure must be validated in a larger series of patients to standardize the technique.