PAX8 Positivity, Abnormal p53 Expression, and p16 Negativity in a Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of the Literature.

Primary endometrial squamous cell carcinoma (PESCC) is a rare entity. As the clinicopathologic features and the immunophenotype have not been completely defined yet, here we report our experience and review of the literature on this topic. A 73-yr-old nulliparous woman presented with pelvic pain and vaginal bleeding. Endometrial biopsy showed a carcinoma with squamous differentiation infiltrating the myometrium. Total hysterectomy with bilateral salpingo-oophorectomy and selective pelvic lymphadenectomy was performed. Definitive diagnosis was squamous carcinoma of the endometrium, with one lymph node metastasis (stage IIIC1). Immunohistochemistry evidenced immunoreactivity of the tumor cells for cytokeratin 5, p63, cytokeratin 7, PAX8, PTEN, and cyclin D1, aberrant p53 overexpression, and Ki-67 reactivity in ~70% of the tumor cells. Estrogen and progesterone receptor, PAX2, WT1, and p16 were negative. Our case was the first PAX8-positive PESCC in the literature, underlining the Mullerian system origin of this neoplasm. Abnormal p53 expression of this case confirmed its role in the pathogenesis of PESCC. Further studies on a large number of cases are needed to better understand the pathologic features and the immunophenotype of PESCC.

Feasibility of hand-assisted laparoscopic sentinel node biopsy in open endometrial cancer surgery.

Background: The aim of this preliminary retrospective study was to assess the feasibility and accuracy of Indocyanine Green (ICG) sentinel node (SLN) sampling using a laparoscopic camera during open endometrial cancer surgery.Material and methods: Retrospective study. Fourteen women with endometrial cancer, not fit for a complete laparoscopic staging, underwent SLN mapping using the IMAGE1 camera during open surgery.Results: The median age of patients was 67 (range 33-86) years. Median BMI was 31 (range 23-58). Mean operative time 157.5 minutes and hospital stay three days. The overall detection rate of SLN mapping was 93%. Bilateral detection was 86%. No post-operative short or long-term complications were observed.Conclusions: Real-time NIR technology supported by the IMAGE1 S is a reliable system and represents a promising method for SLN mapping in selected cases with EC and severe surgical risks, during 48 traditional open approaches. The use of laparoscopy ICG in open surgery seems to be a feasible and useful tool for the detection of SLN in endometrial cancer patients with intraoperative and/or postoperative high morbidity risk. It represents a valid alternative to robotic surgery, particularly in countries and centers where the robotic platform or SPY system for open surgery are not available.

Repeated two cycles of ulipristal acetate treatment improve the quality of life in premenopausal women with heavy menstrual bleeding dependent on uterine myomas, without impairment of bone health.

This observational study was conducted in premenopausal women who presented themselves at the Obstetrics and Gynecology Department of the University Hospital of Cagliari (Italy), for heavy menstrual bleeding (HMB) dependent on uterine myomas. After a screening visit, 19 women without contraindications to ulipristal acetate (UPA) treatment, were included in the study that envisaged 12 months of observation in which each subject was asked to assume UPA (tablet of 5 mg, ESMYA®, one tablet a day for 3 months: first cycle) two menstrual cycles of interruption and a second ESMYA® cycle, followed by 3 months of observation (third follow-up month, visit 4). The significant decrease of myoma volume, diagnosed after the first ESMYA® cycle, persisted until the visit 4. The HMB significantly decreased during the ESMYA® treatment and persisted until visit 4. The quality of life (QoL), evaluated with the questionnaire SF-36, significantly improved during the study. The values of estradiol (E2), biochemical parameters of bone metabolism, as well as those of lumbar and hip bone mineral density, did not change during the study in comparison with basal levels. The efficacy of two repeated ESMYA® cycles to treat uterine myomas and their related symptoms improves the QoL without interfering with bone health.

Long-acting reversible contraception (LARC) with the intrauterine system with levonorgestrel (6 mcg/d): observational study on the acceptability, quality of life, and sexuality in Italian women.

This observational study was conducted in healthy premenopausal women, who presented themselves for contraception with an intrauterine system (IUS) releasing LNG (6 mcg/d) (Jaydess®, Bayer, Germany) at the outpatient Family Planning Clinics of the Departments of Obstetrics and Gynaecology of the Universities of Cagliari and Sassari (CA/SS), University-Hospitals of CA/SS (Italy). After a screening visit, 31 women without contraindications to Jaydess® were included in the study. No difficulty in Jaydess® insertion (Ji) was found in 87% of subjects, with pelvic pain (PP) (visual analogic scale, VAS:5.33 ± 2.54) reported by 27/31 subjects at the Ji. Pelvic pain was reported by 17/31 subjects on the first day (VAS: 3.07 ± 3.1), 16/31 subjects on the second day (VAS:2.37 ± 2.71), and 11/31 subjects on the third day (VAS:1.18 ± 2.02) from Ji, with a significant (p < .001) decrease in the intensity. The primary purposes of the study were to evaluate whether a 12-month-treatment (12-M-T) with Jaydess® interferes on either the quality of life (QoL) or sexuality. Jaydess® did not modify either QoL or sexuality in the 25 subjects who completed the 12-M-T. Throughout the 12-M-T, PP, or pregnancies were not found; the menstrual blood loss was significantly (p < .0001) reduced, and the intensity VAS of dysmenorrhea (#14 subjects) significantly (p < .001) improved.

The stimulation of the vaginal immune system with short-term administration of a vaginal gel containing fraction of Propionibacterium acnes, hyaluronic acid and polycarbophil is efficacious in vaginal infections dependent on disorders in the vaginal ecosystem.

The vaginal immune system (VIS) is the first defense against antigens recognized as foreign. Substances capable of locally activating the VIS could be a valid strategy to treat vulvo-vaginal infections (VVI), caused by changes in the vaginal ecosystem, such as bacterial vaginosis (BV), vulvo-vaginal candidiasis (CA), and mixed vaginitis (MV). Bacterial lysates, obtained by crushing bacterial cultures, exert immuno-modulatory activities. The parietal fraction from Propionibacterium acnes is a patent of Depofarma (MoglianoVeneto, Italy). The preparation that associates such fraction to hyaluronic acid and polycarbophil is a registered trademark, commercially available in Italy as vaginal gel, Immunovag®. The study aimed to evaluate whether a 5-day-treatment with Immunovag® improves the symptoms and signs of VVI, in 60 women with Gardnerella vaginalis (GV), 154 with CA, 95 with MV, diagnosed with vulvar vaginal swab (VVS), and in 283 with BV, diagnosed with the Amsel criteria. At the end of the treatment (visit 2), the symptoms and signs of VVI disappeared in a significant number of subjects (χ2p < .02 vs pre-treatment) in all VVI groups, and their intensity was significantly (p < .0002) reduced in the subjects in which they were still present. Immunovag® represents a valid treatment of VVI induced by changes in the vaginal ecosystem.

Deep Infiltrating Endometriosis: Comparison Between 2-Dimensional Ultrasonography (US), 3-Dimensional US, and Magnetic Resonance Imaging.

OBJECTIVES: To evaluate the diagnostic accuracy of 2-dimensional (2D) and 3-dimensional (3D) transvaginal ultrasonography (US) in comparison with magnetic resonance imaging (MRI) for identification of deep infiltrating endometriosis. METHODS: In this prospective observational study, 159 premenopausal women who underwent surgery for a clinical suspicion of deep infiltrating endometriosis were prospectively enrolled. All women underwent 2DUS, 3DUS, and MRI. The following 3 locations of deep endometriosis were considered: (1) intestinal; (2) other posterior lesions (retrocervical septum, rectovaginal septum, uterosacral ligaments, and vaginal fornix); and (3) anterior. The sensitivity, specificity, positive predictive value, and negative predictive value of 2D and 3D transvaginal US in comparison with MRI were determined. RESULTS: Intestinal deep infiltrating endometriosis was identified by 2DUS in 56 of 66 patients, by 3DUS in 59 of 66, and by MRI in 61 of 66. A receiver operating characteristic curve analysis showed optimal results for 2DUS, 3DUS, and MRI (areas under the curve, 0.86, 0.915, and 0.935, respectively) with a statistically significant difference between 2DUS and MRI (P = .0103), even when the 95% confidence interval showed an overlap. Other posterior deep infiltrating endometriosis was identified by 2DUS in 55 of 75 patients, by 3DUS in 65 of 75, and by MRI in 66 of 75. A receiver operating characteristic curve analysis showed very good results for 2DUS, 3DUS, and MRI (areas under the curve, 0.801, 0.838, and 0.857) with no statistically significant differences. In the 12 women with deep infiltrating endometriosis in the anterior location, the nodules were correctly identified by 2DUS in 3 of 12 patients, by 3DUS in 5 of 12, and by MRI in 6 of 12. CONCLUSIONS: Our results seem to suggest that there is a statistically significant difference between 2DUS and MRI for the intestinal location of deep infiltrating endometriosis, whereas no differences were found among the techniques for the other locations.

Dienogest. A possible conservative approach in bladder endometriosis. Results of a pilot study.

Deep endometriosis involvement of the bladder is uncommon but it is symptomatic in most of the cases. Although laparoscopic excision is very effective, some patients with no pregnancy desire require a medical approach. We performed a pilot study on the effect of a new progestin dienogest on bladder endometriosis. Six patients were treated for 12 months with dienogest 2 mg/daily. Pain, urinary symptoms, quality of life, nodule volume and side effects were recorded. During treatment, symptoms improved very quickly and the nodules exhibit a remarkable reduction in size. Dienogest may be an alternative approach to bladder endometriosis.

Immunohistochemical Markers in Endometrial Cancer: Latest Updates.

Ten years ago, The Cancer Genome Atlas (TGCA) Research Network classified endometrial cancer into four molecular categories with prognostic significance, suggesting sensitivity to postsurgical treatments [...].

Effective Surgical Management of a Large Serous Ovarian Cyst in a Morbidly Obese Middle-Aged Woman: A Case Study and Literature Review.

BACKGROUND In contemporary gynecological practice, encountering giant ovarian tumors is a rarity. While most are benign and of the mucinous subtype, the borderline variant only accounts for approximately 10% of these cases. This paper addresses the paucity of information about this specific subtype, emphasizing critical elements of managing borderline tumors that can pose life-threatening complications. Additionally, a review of other documented cases of the borderline variant in the literature is also included to foster a deeper understanding of this uncommon condition. CASE REPORT We present the multidisciplinary management of a 52-year-old symptomatic woman with a giant serous borderline ovarian tumor. Preoperative assessment showed a multiloculated pelvic-abdominal cyst responsible for compression of the bowel and retroperitoneal organs, and dyspnea. All tumor markers were negative. Together with anesthesiologists and interventional cardiologists, we decided to perform a controlled drainage of the cyst of the tumor, to prevent hemodynamic instability. Subsequent total extrafascial hysterectomy, contralateral salpingo-oophorectomy, and abdominal wall reconstruction, followed by admission to the intensive care unit, were also conducted by the multidisciplinary team. During the postoperative period, the patient experienced a cardiopulmonary arrest and acute renal failure, which were managed by dialysis. After discharge, the patient underwent oncologic followup, and after 2 years, she was found to be completely recovered and disease free. CONCLUSIONS Intraoperative controlled drainage of Giant ovarian tumor fluid, planned by a multidisciplinary management team, constitutes a valid and safe alternative to the popular choice of "en bloc" tumor resection. This approach avoids rapid changes in body circulation, which are responsible for intraoperative and postoperative severe complications.

HE4 Tissue Expression as A Putative Prognostic Marker in Low-Risk/Low-Grade Endometrioid Endometrial Cancer: A Review.

Low-grade stage I endometrioid endometrial carcinomas should have an excellent prognosis, but a small subset of these cancers can relapse. The search for putative immunohistochemical prognostic markers for relapse in low-risk/low-grade endometrioid endometrial cancers remains open. Among the candidate molecules that may implicate the roles of immunohistochemical risk markers, we focused our attention on human epididymis protein 4 (HE4) after a review of the literature. Few authors have devoted themselves to this topic, and none have found a correlation between the tissue expression of HE4 and the molecular classification of endometrial cancer. Five different variants of HE4 mRNA and multiple protein isoforms of HE4 were identified many years ago, but current HE4 assays only measure the total HE4 expression and do not distinguish the different proteins encoded by different mRNA variants. It is important to have an approach to distinguish specific variants in the future.

New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study.

Human epididymal secretory protein 4 (HE4) elevation has been studied as a crucial biomarker for malignant gynecological cancer, such us ovarian cancer (OC). However, there are conflicting reports regarding the optimal HE4 cut-off. Thus, the goal of this study was to develop an analytical approach to harmonize HE4 values obtained with different laboratory resources. To this regard, six highly qualified Italian laboratories, using different analytical platforms (Abbott Alinity I, Fujirebio Lumipulse G1200 and G600, Roche Cobas 601 and Abbott Architett), have joined this project. In the first step of our study, a common reference calibration curve (designed through progressive HE4 dilutions) was tested by all members attending the workshop. This first evaluation underlined the presence of analytical bias in different devices. Next, following bias correction, we started to analyze biomarkers values collected in a common database (1509 patients). A two-sided p-value < 0.05 was considered statistically significant. In post-menopausal women stratified between those with malignant gynecological diseases vs. non-malignant gynecological diseases and healthy women, dichotomous HE4 showed a significantly better accuracy than dichotomous Ca125 (AUC 0.81 vs. 0.74, p = 0.001 for age ≤ 60; AUC 0.78 vs. 0.72, p = 0.024 for age > 60). Still, in post-menopausal status, similar results were confirmed in patients with malignant gynecological diseases vs. patients with benign gynecological diseases, both under and over 60 years (AUC 0.79 vs. 0.73, p = 0.006; AUC 0.76 vs. 0.71, p = 0.036, respectively). Interestingly, in pre-menopausal status women over 40 years, HE4 showed a higher accuracy than Ca125 (AUC 0.73 vs. 0.66, p = 0.027), thus opening new perspective for the clinical management of fertile patients with malignant neoplasms, such as ovarian cancer. In summary, this model hinted at a new approach for identifying the optimal cut-off to align data detected with different HE4 diagnostic tools.

Immunohistochemical Markers in Endometrial Cancer.

In 2018, 382,069 new cases of uterine cancer were registered worldwide and 89,929 deaths from this cancer were reported [...].

Intraoperative sentinel lymph node detection by vital dye through laparoscopy or laparotomy in early endometrial cancer.

BACKGROUND AND OBJECTIVES: Recent studies reported the feasibility of intraoperative lymphatic mapping in women with endometrial cancer but none of these studies compared the sentinel lymph nodes (SLNs) detection rates obtainable through laparoscopy or laparotomy. The purpose of this study was to address this issue. METHODS: Thirty-four patients with clinical stage I-II endometrial cancer were enrolled in this prospective comparative trial. Four milliliters of Patent Blue Violet were injected into the cervix after the induction of general anesthesia. The assessment of SLNs was done in 17 patients through laparoscopy and in 17 patients through laparotomy as first step of systematic pelvic lymphadenectomy. Both SLNs and non-SLNs were evaluated for micrometastases. RESULTS: The SLNs detection rate was significantly higher (82%) for laparoscopy than for laparotomy (41%; P = 0.008). Pelvic lymph node metastases were present in 6 out of 34 patients (18%) but only 3 (50%) of these patients were correctly identified. CONCLUSIONS: SLNs detection rate is significantly higher through laparoscopy than through laparotomy after vital dye pericervical injection but intraoperative vital dye pericervical injection is not reliable as part of standard care for predicting lymphatic spread in women with early stage endometrial cancer.

What women want: Fertility sparing surgery in Borderline ovarian tumours patients and pregnancy outcome.

OBJECTIVE: Borderline ovarian tumours (BOTs) are characterized by the presence of cellular proliferation and nuclear atypia without stromal invasion. Compared to malignant ovarian tumours, BOTs have better prognoses. The most important treatment of BOT is surgery. Considering the good prognosis of BOT, fertility-sparing surgery (FSS) can be considered for young women who desire to preserve fertility. Our study evaluated the pregnancy rate in patients with childbearing desire, the efficacy and risk of recurrence of women affected by BOTs who have undergone FSS. MATERIALS AND METHODS: Patients characteristics have been restrospectively retrieved for diagnosis made from June 2000 to December 2017 from San Raffaele Hospital and Policlinico Cagliari. Patients underwent FSS for BOT were interviewed about child wishing and pregnancy outcomes. RESULTS: 85 patients were recruited for the study. Median age at diagnosis was 33 years. Unilateral salpingo-oophorectomy was performed in 33 patients (38%), unilateral cystectomy in 40 (47%) and 12 underwent both procedures (14%). 40 women (50%) tried to conceive after surgery. The pregnancy rate was 73% and live birth rate was 67%. Childbearing desire and age at diagnosis were significantly associated with the pregnancy rate. CONCLUSIONS: Conservative surgical treatment seems to be a reasonable therapeutic option for women with BOTs who wish to preserve fertility. Our results suggest that the obstetric outcomes after FSS are promising. Maternal desire and the age of diagnosis are the most important factors affecting PR after surgery. Fertility counselling should be an integral part of the clinical management of women with BOT.

Urinary profiles associated with bacterial metabolites from asymptomatic pregnant women with at term or preterm premature rupture of membranes: a pilot study.

Objective: Premature rupture of membranes (PROM) and preterm premature rupture of membranes (pPROM) are frequent conditions with a not fully understood multifactorial etiology. It has been suggested that infection may be the leading cause of pPROM. Metabolomics is nowadays recognized as a successful and versatile approach for the investigation of several pathological conditions, including pregnancy-related ones. However, collecting samples such as fetal fluids or placenta poses a limit on the clinical application of this strategy. Therefore, the aim of this study was to detect urinary metabolites that could be associated with bacterial infection in PROM and pPROM and to understand its role in these different conditions, using readily available samples such as urines.Methods: Urine samples were collected from pregnant women who experienced rupture of membranes: (1) at term (≥37 weeks) not in labor (NLPROM); (2) at term in labor (LPROM); (3) preterm (<37 weeks) not in labor (pPROM). Samples were analyzed using a GC-MS platform. Student's t-test, Pearson correlation coefficient, principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) were applied to observe differences between groups.Results: Results showed that lactic acid, erythritol, and ethanolamine levels were significantly higher in pPROM than in PROM (NLPROM + LPROM considered as one single group). These three metabolites might be associated with bacterial infections since they derive from bacterial metabolic processes and environments.Conclusions: This study might be useful to understand the mechanisms underlying the etiology of pPROM and PROM, and urine samples might represent a useful and readily available sample to discriminate preterm high-risk women.

Materno-Fetal and Neonatal Complications of Diabetes in Pregnancy: A Retrospective Study.

The aim of this case-control study was to evaluate maternal-fetal and neonatal clinical outcomes in a group of patients with gestational diabetes mellitus (GDM) and pregestational diabetes such as diabetes mellitus type 1 (DM1) and diabetes mellitus type 2 (DM2) and compare them with those of patients without diabetes. A total of 414 pregnant women, nulliparous and multiparous, with single pregnancy were recruited. The selected patients were divided into two groups. Among 207 patients (group cases), 183 had GDM and 24 pregestational diabetes (of which n = 17 diagnosed with DM1 and n = 7 with diagnosis of DM2). Two-hundred-seven patients with a negative pathologic history of GDM, DM1 and DM2 represented the population of controls (group control). We reported an incidence of preterm delivery of 23.2% in the group of cases, of 18.3% in the group of patients with GDM and 66.7% in the group of patients DM1/2. Fetal growth disorders, such as intrauterine growth retardation (IUGR), small for gestational age (SGA), fetal macrosomia, were detected in four fetuses out of 207 (1.93%) in the control group and 20 fetuses out of 207 in the case group (9.67%, p-value 0.001); of these 16 of 183 fetuses of the GDM group (8.74%, p-value 0.002) and 4 of 24 fetuses of the DM1/2 group (16.67%, p-value 0.005). A very strong correlation between diabetes mellitus type 1 and preeclampsia (p-value < 0.0001) was observed. Close monitoring of pregnant women with diabetes is recommended to prevent maternal-fetal and neonatal complications.

Conservative treatment for well-differentiated endometrial cancer: when and why it should be considered in young women.

The aim of this review was to update current knowledge on the conservative treatment of endometrial cancer (EC) based on a literature review. A web-based search in the MEDLINE database was carried out on EC management and treatment. All relevant information has been collected and analysed. Case series were mainly found in the literature search. Conservative treatments were offered to young patients with stage I low-grade endometrioid carcinomas of the endometrium. Different options included high/low dose progestin treatments, hysteroscopic resection of the disease, a levonorgestrel intrauterine device or a combination of various strategies. The overall complete response rate was near 76.5% with a recurrence rate of up to 33.8%. Pregnancy outcomes reached rates of 64.8% for live births. The current clinical outcomes show that conservative treatment aimed at preserving fertility is feasible for stage I endometrial well-differentiated adenocarcinomas in motivated patients under close monitoring.

New Keystone flap application in vulvo-perineal reconstructive surgery: A case series.

OBJECTIVE: This study aimed to evaluate the application of the Keystone flap technique and the long-term results of vulvovaginal reconstruction after vulvar surgery. METHODS: This is the first case series describing the application of the Keystone perforator island flaps (KPIF) technique to close a wide defect after radical vulvectomy. We prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients. The benefits, cosmetic results and satisfaction of patients were analyzed in the follow up. RESULTS: Five patients were selected for the study: four underwent radical vulvectomy for squamous cell vulvar cancer, and one underwent vulvar wide excision for Paget disease followed by reconstruction with the Keystone flap technique. The defects were successfully covered by the Keystone flap technique in all patients. CONCLUSIONS: Keystone flaps seem to be easy to design and elevate, and it offers rapid fasciocutaneous closure in wide vulvo-perineal defects with excellent long-term results.

Systemic therapy for the treatment of endometrial cancer.

Introduction: Endometrial cancer (EC) is one of the most frequent gynecological cancers worldwide. The gold standard treatment of EC is most certainly surgery and may very well be the only therapy in the early stages of disease. To improve outcomes in non-early EC, adjuvant therapy is often employed but this is not standardized. Adjuvant options can include radiotherapy, chemotherapy or a combination of both. Adjuvant chemotherapy could be indicated in high-risk stage I and II or advanced stage EC. Several clinical trials are ongoing in an attempt to define the optimal adjuvant treatment. Furthermore, chemotherapy is the front-line therapy in advanced unresectable, metastatic or recurrent endometrial cancer. Areas covered: Herein, the authors review the first-line chemotherapy for the treatment of endometrial cancer and provide their expert perspectives on these therapies. Expert opinion: Chemotherapy is fundamental in advanced/recurrent EC. Further evidence is needed to characterize the role of adjuvant chemotherapy. Future studies should consider genomic and molecular heterogeneities to identify even more efficient tailored therapies.