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Gynecological neuroendocrine neoplasms are rare entities and can be divided into two groups: carcinoids and neuroendocrine carcinomas. Due to their rarity their management is not standardized. The aim of this work is to summarize and discuss the current literature evidence on this pathology. A scoping literature review was performed in multiple databases. Thirty-one studies were included: 30 case reports and one case series. Patients’ age ranged between 28 and 92 years. Surgery was the most used treatment and the surgical approach included local excision (N = 16/31; 51.6%) with (N = 5/16; 31.25%) or without (N = 11/16; 68.75%) inguinal lymphadenectomy. Adjuvant radiotherapy was delivered in 12 (38.7%) cases; instead, platinum-based therapies were frequently used when chemotherapy was chosen for adjuvant treatment. The overall survival ranged between 20 days to 4 years. However, further research is needed; currently, multimodal approach including surgery, chemotherapy and radiotherapy appeared safe and feasible for the treatment of these rare and aggressive diseases.

Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.5 years before diagnosis) from 113 presymptomatic women who were subsequently diagnosed with HGSOC (pre-HGSOC) and from 77 healthy women. Genome instability was detected through low-pass whole-genome sequencing of DNA derived from Pap test samples in terms of copy number profile abnormality (CPA). CPA values of DNA extracted from Pap test samples from pre-HGSOC women were substantially higher than those in samples from healthy women. Consistently with the longitudinal analysis of clonal pathogenic TP53 mutations, this assay could detect HGSOC presence up to 9 years before diagnosis. This finding confirms the continual shedding of tumor cells from fimbriae toward the endocervical canal, suggesting a new path for the early diagnosis of HGSOC. We integrated the CPA score into the EVA (early ovarian cancer) test, the sensitivity of which was 75% (95% CI, 64.97 to 85.79), the specificity 96% (95% CI, 88.35 to 100.00), and the accuracy 81%. This proof-of-principle study indicates that the early diagnosis of HGSOC is feasible through the analysis of genomic alterations in DNA from endocervical smears.

Bartholin gland carcinoma is an extremely rare disease. Information regarding treatment is scarce and there is no strict consensus on best practice. All studies reporting cases of Bartholin’s gland cancer were screened and evaluated for inclusion. Baseline characteristics of studies were extracted. A total number of 290 manuscripts collected were available for the review process. Studies included in a previous systematic review were not duplicated. In total, details of 367 patients were collected, as follows: histological features, clinical presentation, treatment, recurrent rate, treatment of recurrence and outcome. About 35% of Bartholin gland carcinoma were squamous cell carcinoma. Almost 50% of patients presented with advanced stage. The therapeutic approach was mainly surgery, and in 61% of those women lymph node assessment was performed. Recurrence occurred in 21% of cases. Bartholin gland cancer remains a challenge for gynecologic oncologists. Guidelines, centralization to referral centers and standardized therapy are needed.

Introduction: Standard treatment of newly diagnosed, advanced ovarian carcinoma (OC) consists of cytoreductive surgery followed by platinum-based chemotherapy with or without bevacizumab. Maintenance therapy with PARP inhibitors and olaparib-bevacizumab has recently shown to significantly improve progression-free survival in the first-line setting. Some practical aspects of maintenance therapy, however, are still poorly defined. Aim of the study: To provide guidance to clinicians in the selection of maintenance therapy for newly diagnosed, advanced ovarian carcinoma. Methods: A board of six gynecologic oncologists with expertise in the treatment of OC in Italy convened to address issues related to the new options for maintenance treatment. Based on scientific evidences, the board produced practice-oriented statements. Consensus was reached via a modified Delphi study that involved a panel of 22 experts from across Italy. Results: Twenty-seven evidence- and consensus-based statements are presented, covering the following areas of interest: use of biomarkers (BRCA mutations and presence of homologous recombination deficiency); timing and outcomes of surgery; selection of patients eligible for bevacizumab; definition of response to treatment; toxicity and contraindications; evidence of synergy of bevacizumab plus PARP inhibitor. Two treatment algorithms are also included, for selecting maintenance therapy based on timing and outcomes of surgery, response to platinum-based chemotherapy and biomarker status. A score for the assessment of response to chemotherapy is proposed, but its validation is ongoing. Conclusions: We provide here consensus statements and treatment algorithms to guide clinicians in the selection of appropriate and personalized maintenance therapy in the first-line setting of advanced OC management.

Introduction: Ovarian cancer is the most lethal gynecologic malignancy. Over 5200 new cases of this tumor are diagnosed yearly in Italy, resulting in more than 3600 deaths. In terms of molecular biology, five different ovarian cancer subtypes should be distinguished. Method: This article summarizes the evidence-based guidelines that the Italian Medical Oncology Association (AIOM) has developed with a multidisciplinary panel of experts, including pathologists, gynecologic oncologists, medical oncologists, and radiotherapists, with the support of methodologists, to help clinicians involved in the management of patients with ovarian cancer in their daily clinical practice. Results: The most relevant randomized clinical trials regarding surgery, chemotherapy, and molecularly targeted agents (bevacizumab and PARP inhibitors) in early, advanced, and recurrent disease have been critically analyzed. The levels of evidence and strength of recommendation have been reported for any issue. Conclusion: Women with a clinical suspicion of ovarian cancer should be centralized in referral centers. The BRCA test should be requested for all women with nonmucinous and nonborderline tumors, regardless of age and family history. BRCA testing could be preferentially performed on neoplastic tissue. In the presence of a positive tumor test, a genetic test should always be performed on a blood sample to differentiate between germline mutations, which require counseling and genetic testing of family members, and somatic mutations.

Purpose: To explore the potential of superb microvascular imaging (SMI) in visualizing brain microvessels in preterm neonates of different gestational ages (GA). Methods: In this retrospective, observational pilot study, 15 preterm newborns were equally divided into GA groups: extremely (GA < 28 weeks), very (28–31 weeks), and moderate to late (32–37 weeks) preterm. All patients underwent conventional transcranial ultrasounds during the first day of life following the American Institute of Ultrasound in Medicine practice guidelines. SMI was then performed; based on their SMI morphology and location, brain microvessels were classified as extrastriatal (cortical and medullary), striatal, or thalamic. Two examiners independently classified vessels as visible or invisible. To assess the association between vessel visibility and GA, binomial logistic regression analysis (separate for each microvessel group) was performed, taking visibility as a dependent variable and both examiners and GA as predictor variables. Results: A statistically significant difference among GA groups was found in sex (P = 0.030), birth weight (P = 0.007), and Apgar score within 1 min after birth (P = 0.024). Microvascular visibility increased with GA for superficial vessels (P < 0.05 for both cortical and medullary), while striatal and thalamic vessels were visible in all neonates irrespective of their GA. Conclusions: SMI technology shows promise to assess brain microvasculature in preterm neonates, even potentially providing data on early brain development.

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1–2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients’ conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.

Objective: To report mode of delivery and immediate neonatal outcome in COVID-19 infected women. Design: This is a retrospective study. Setting: Twelve hospitals in northern Italy. Participants: Pregnant women with COVID-19 confirmed infection who delivered. Exposure: COVID 19 infection in pregnancy. Methods: SARS-CoV-2 infected women who were admitted and delivered during the period 1-20 march 2020 were eligible. Data were collected from the clinical records using a standardized questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. Main Outcome and Measure: Data on mode of delivery and neonatal outcome. Results: 42 women with COVID-19 delivered at the participating centres: 24(57,1%, 95% CI= 41,0-72,3) delivered vaginally. An elective cesarean section was performed in 18/42 (42,9%, 95%CI 27,7-59,0) cases: in 8 cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42(45,2%, 95%CI 29,8-61,3) cases: of these 7/19(36,8%,95CI 16,3-61,6) required oxygen support and 4/19(21,1%,95%CI=6,1-45,6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the post-partum period: their new-borns tested positive for SARS-Cov-2 infection. In one case a new-born had a positive test after a vaginal operative delivery. Conclusions: Although post-partum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the new-born.

Purpose: This research aimed to investigate the socio-demographic, clinical, and psychological variables predictive of a greater functioning and quality of life in patients with gynecological cancer after their first cycle of carboplatin and taxol-based chemotherapy. Methods: The sample of the present research consisted of 104 patients. The European Organization on Research and Treatment of Cancer QLQ-C30, the State-Trait Anxiety Inventory-Form Y, and the Multidimensional Scale of Perceived Social Support were administered to each participant. Results: The analyses showed that higher state anxiety levels predicted a lower role, emotional, and social functioning and a lower general quality of life. Higher trait anxiety levels and social support perceived from one's friends predicted a greater role functioning. Similarly, having a relationship predicted a greater physical, cognitive, and social functioning. On the contrary, the presence of relapsed cancer was negatively associated with these patients' quality of life. Conclusions: The present study highlighted the importance of identifying patients at higher risk of experiencing lower levels of functioning and worse general quality of life to implement tailored interventions from the beginning of treatment, thus improving the quality of life of these patients throughout the chemotherapy treatment.

Objective: This open-label phase II clinical trial evaluated the antitumor activity and safety of trabectedin in patients with advanced ovarian (OC) or uterine carcinosarcomas (UC). Methods: Eligible patients were adults (≥18 years) with histologically proven recurrent OC/UC not amenable to surgery or radiotherapy who received up to two prior chemotherapy lines. Trabectedin 1.3 mg/m2 was administered as a 3-h infusion every three weeks. The primary endpoint was objective response rate (ORR) as per RECIST v.1.1. If at least 8 of 43 patients (18.6%) achieve an objective response, trabectedin would be declared worthy for further investigations. Results: Forty-five patients with either OC (n = 32) or UC (n = 13) from seven MITO centers across Italy were enrolled. The ORR was 11.9% (90% CI: 6–23) and included two patients with a complete response and three with a partial response. Eight patients (19.0%) had disease stabilization for a disease control rate of 31.0% (90% CI: 20–44). Median progression-free survival was 2.01 months (95% CI: 1.78–2.30) and median overall survival was 4.64 months (95% CI: 3.19–8.29). Neutrophil count decreases (n = 8, 18.2%) and transaminase increases (n = 6, 13.6%) were the most common grade 3–5 adverse events related with trabectedin. Two patients died due to trabectedin-related grade 5 hematological toxicity. Conclusion: Although trabectedin did not meet the prespecified activity criteria, it confers modest but clinically meaningful benefit to patients with advanced OC/UC as being as effective as any other available treatment for this indication. The toxicity profile appears in line with that previously reported for the drug.

Omphalopagus twins are joined ventrally in the umbilical region. In omphalopagus twins, liver's fusion is very frequent, being present in about 80% of cases. Two conjoined twins born in our Hospital were evaluated using plain x-rays, ultrasound (US), gastrointestinal xrays, Tc-99 hepatobiliary scintigraphy (SC) and contrast enhanced computed tomography (CT). There was no bony connection on conventional xrays, neither bowel communication on GI x-rays study. US demonstrated the fusion of left hepatic lobes and a not-quantifiable vascular shunt. Normal biliary function was demonstrated by Tc-99 SC. The first CT scan (twin A) showed irregular lobules in the site of hepatic fusion, a portoportal shunt and a venous vessel to the inferior vena cava of twin B. Only the second CT scan (twin B) showed an arterio-arterial partiallyextrahepatic shunts. The double CT scan allows to increase the probability of a correct individuation and description of vascular shunts for an effective preoperatory assessment. The omphalopagus twins in our case underwent planned surgical separation at 5 months of age. The surgery lasted 5 h and was not affected by any intraoperative complications.

Objective: Fertility loss due to cancer treatment can be a devastating experience for women and the couple. Undergoing fertility preservation can be a complex decision from both a medical and emotional point of view. The aim of the present study was to evaluate which socio-demographic and psychological factors predict a high motivation to undergo fertility preservation. Methods: Fifty-eight female cancer patients who accessed an Oncofertility Unit completed: a questionnaire to collect socio-demographic characteristics and the level of motivation, the Beck-Depression Inventory-II, the State-Trait Anxiety Inventory-Y, and the Fertility Problem Inventory. Results: Almost half of the sample (44.8%) declared a high motivation. At multiple logistic regression analysis only the “Need for parenthood” subscale of the FPI predicted a high motivation. We alternatively evaluated as possible predictor the construct “Representations about the importance of parenthood” (i.e., the sum of the “Need for Parenthood” and “Rejection of childfree lifestyle” subscales) in place of the two separate subscales. At multiple logistic regression analysis, only this variable predicted a high motivation to undergo fertility preservation. Conclusion: The most important predictor of a high motivation to undergo fertility preservation is the individual desire for parenthood. This implies that, regardless of socio-demographic characteristics, any woman of childbearing age should receive an appropriate counseling about fertility preservation.

Gestational trophoblastic disease (GTD) represents a spectrum of rare pregnancy-related disorders, including both premalignant and malignant entities. Although GTD's medical outcomes have been widely explored, limited data are available regarding the related psychological, sexual, and fertility issues. The present chapter aims to enhance comprehension of the psychosocial impact of GTD by discussing the main quantitative and qualitative evidence available in this field. Although patients globally report a good quality of life, clinically significant levels of anxiety and depression have been consistently found across studies. Similarly, despite the quality of couple relationships being generally satisfactory, they often complain of a lack of sexual desire. Moreover, pregnancy loss may raise significant and long-term fertility-related concerns. Specific socio-demographic and clinical factors have been identified as predictors of psychosocial outcomes. At the clinical level, research suggests that there is a need to provide multidisciplinary care to patients.

Objective: Referring to Leventhal's common-sense model, this observational cross-sectional study aimed at investigating the relationship between illness mental representations, coping mechanisms and psychological distress in a sample of women with gestational trophoblastic disease (GTD). Methods: Thirty-eight women diagnosed with GTD (18 with hydatidiform mole; 20 with gestational trophoblastic neoplasia) were asked to complete the Illness Perception Questionnaire—Revised, the Coping Orientation to the Problems Experienced, the State-Trait Anxiety Inventory—Form Y and the Beck Depression Inventory—Short Form. Demographic and clinical information was collected through a self-report questionnaire. Results: The sample did not report significant symptomatic distress in relation to GTD. Correlation analysis showed that the Emotional representations subscale of the Illness Perception Questionnaire—Revised was significantly associated with both state anxiety and depression; avoidant coping significantly and positively correlated with anxiety and depression, as well as with illness emotional representations. Mediation analysis revealed significant indirect effects of avoidant coping on both anxiety and depression through the mediation of emotional representations. Conclusion: Avoidant coping could lead women to develop emotional representations of illness characterised by negative affects, which in turn enhance distress levels. Results underline the importance to promote adaptive coping strategies, along with accurate illness perceptions, to foster better psychological adjustment to GTD.

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1–2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients’ conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.