Histopathological and Immunohistochemical Prognostic Factors in High-Grade Non-Endometrioid Carcinomas of the Endometrium (HG-NECs): Is It Possible to Identify Subgroups at Increased Risk?

Endometrial cancer is an emerging disease with an increase in prevalence of aggressive histotypes in recent years. BACKGROUND: In the present study, potential histopathological and immunohistochemical prognostic markers were investigated. Consecutive cases of high-grade non-endometrioid carcinoma (HG-NEC) of the endometrium were considered. METHODS: Each surgical specimen was routinely processed; the most significant block was selected for immunohistochemistry and tested for ER, PR, ki67, p53, E-cadherin, ß-catenin, Bcl-2 and cyclin D1. For each immunomarker, the percentage of positive tumor cells was evaluated (%) and dichotomized as low and high according to the distribution in the study population. Follow-up was collected for disease-free survival (DFS) and overall survival (OS). Thirty-three cases were eligible: 19 resulted in FIGO I-II; 14 resulted in FIGO III-IV. Twelve patients suffered a recurrent disease (mean follow-up 24.6 months); 8 patients died of the disease (mean follow-up 26.6 months). RESULTS: Women with recurrent disease demonstrated a significantly higher Bcl2% (35.84 ± 30.96% vs. 8.09 ± 11.56%; p = 0.0032) while DOD patients had higher ki67% (75 ± 13.09% vs. 58.6 ± 19.97%; p = 0.033) and Bcl2% of border significance (34.37 ± 34.99% vs. 13 ± 17.97%; p = 0.078). As expected, FIGO III-IV had a worse DFS (HR = 3.34; 95% CI: 1.1-10.99; p = 0.034) and OS (HR = 5.19; 95% CI: 1.27-21.14; p = 0.0217). Bcl-2-high patients (Bcl2 > 10%) demonstrated a significantly worse DFS (HR = 9.11; 95% CI: 2.6-32.4; p = 0.0006) and OS (HR = 7.63; 95% CI: 1.7-34; p = 0.0084); moreover, PR low patients (PR ≤ 10%) had significantly worse DFS (HR = 3.74; 95% CI: 1.2-11.9; p = 0.02). CONCLUSIONS: HG-NEC represents a heterogeneous group of endometrial aggressive neoplasms with a worrisome prognosis, often at an advanced stage at presentation. Bcl-2 and PR may represent promising markers to identify a subgroup of patients having an even worse prognosis requiring a careful and close follow-up.

Perforator flaps for vulvar reconstruction: basic principles.

BACKGROUND AND AIM: In vulvar cancer, the standard treatment is radical local excision, with immediate reconstruction. Reconstruction aims to restore anatomy and function of the external female genitalia, facilitating preservation of normal body image, sexual function, and micturition and defecation functions. METHODS: The purpose of this paper is to describe the principles of perforator flaps for vulvar reconstruction. RESULTS: Basic concepts, indications and operative technique are discussed and detailed. CONCLUSIONS: In vulvar reconstruction, the use of perforator flaps is a superior surgical technique when compared to the use of conventional flaps.

Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer.

Introduction Patients with high-grade serous ovarian cancer (HGSOC) have a poor prognosis, and current chemotherapy regimens for treating advanced disease are far from satisfactory. Prexasertib (LY2606368) is a novel checkpoint kinase inhibitor (CHK) under investigation for the treatment of HGSOC. Data from a recent phase II trial showed promising efficacy and safety results for treating wild-type BRCA HGSOC. Areas covered This article reviews the available data on the pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of prexasertib in the treatment of HGSOC. Expert opinion Until now, prexasertib demonstrated clinical activity in phase I and II clinical trial for treating wild-type BRCA HGSOC, whereas its promising efficacy as monotherapy and combined with olaparib in BRCA-mutated HGSOC has been preliminary evidenced only in phase I studies. Compared to other drugs of the same class, prexasertib showed a better tolerability profile, causing moderate hematological toxicity. Further studies are needed to confirm efficacy and safety profiles of prexasertib in combined regimens. New early clinical trials may investigate prexasertib administered with programmed cell death ligand 1 (PD-L1) and PI3 K inhibitors due to the preclinical evidence of a synergic action.

Borderline ovarian tumours: management in the era of fertility-sparing surgery.

Borderline ovarian tumours (BOTs) are ovarian neoplasms characterised by epithelial proliferation, variable nuclear atypia and no evidence of destructive stromal invasion. BOTs account for approximately 15% of all epithelial ovarian cancers. Due to the fact that the majority of BOTs occur in women under 40 years of age, their surgical management often has to consider fertility-sparing approaches. The aim of this mini-review is to discuss the state of the art of fertility-sparing surgery for BOTs with a specific focus on the extent of surgery, post-operative management and fertility.

Obstetric outcome and incidence of congenital anomalies in 2351 IVF/ICSI babies.

PURPOSE: The aim of this study was to provide a comprehensive follow-up of fetal and perinatal outcome and the incidence of congenital anomalies in babies born after fresh embryo transfers compared to those conceived spontaneously in infertile couples. METHODS: Retrospective comparative analysis of all clinical pregnancies from fresh cleavage-stage embryo transfer cycles (IVF and ICSI) compared with infertile patients who conceived spontaneously in the same time period (control). Congenital anomalies were classified following the European Surveillance of Congenital Anomalies (EUROCAT) classification. RESULTS: A total of 2414 assisted reproductive technology (ART) pregnancies were compared to 582 spontaneous conceptions in the control infertile group representing 2306 deliveries. No significant differences were found in pregnancy outcome between the two groups (delivery rate, abortion rate, ectopic pregnancies, medical abortions for fetal anomalies, single and twins mean gestational age, and weight at delivery). A significant difference (p < 0.001) was found in the twin (21.3 vs 2.3 %) and triplet rates (2.3 vs 0 %). A total of 2351 babies were delivered in the ART group and 449 in the control group. A total of 90 babies (3.8 %) were diagnosed with a major congenital anomaly in the ART group and 15 (3.3 %) in the control group (p = ns). The overall rate of major congenital anomalies (105/2800) in ART and spontaneous pregnancies in infertile couples was significantly higher when compared to the EUROCAT 2.0 versus 3.75 % (p = 0.0002). DISCUSSION: Babies born after ART treatments and from spontaneous conception in infertile couples had rates of congenital anomalies higher than those recorded by the EUROCAT. However, the rates of anomalies were not different within the infertile population whether conceived by ART or spontaneously. These data suggest that the diagnosis of infertility in itself is the common denominator for the increase in the rates of anomalies seen in both ART and spontaneous conceptions.

Frozen section pathology at time of hysterectomy accurately predicts endometrial cancer in patients with preoperative diagnosis of atypical endometrial hyperplasia.

OBJECTIVES: A significant number of women diagnosed with atypical endometrial hyperplasia (AEH) on endometrial biopsy will be diagnosed with endometrial cancer (EC) on the hysterectomy specimen at permanent section. Surgical treatment for AEH and EC differ substantially. We have assessed the concordance in EC between frozen and permanent sections on patients undergoing hysterectomy for AEH. MATERIALS AND METHODS: A retrospective review of 66 frozen sections on patients undergoing hysterectomy for AEH was performed. Frozen and permanent section diagnoses were categorized as negative or positive for malignancy. Permanent section carcinomas were classified as low or high risk based on their histopathology, myometrial invasion and differentiation. Correlation between frozen and permanent section and sensitivity, specificity, PPV, NPV and accuracy of frozen section in predicting EC in permanent section were calculated. Likelihood of diagnosing EC on frozen section was compared based on risk stratification at permanent section. RESULTS: Frozen and permanent sections revealed malignancy in 43.9% and 56% of the patients respectively. 94.1% of high risk carcinomas were identified as EC at frozen section as compared to 55% of low risk EC. Concordance was good (κ=0.75). Sensitivity, specificity, NPV, PPV and accuracy in predicting EC at frozen section were 73%, 93.1%, 73% and 93.1% respectively. Carcinomas were detected at frozen section significantly more often if they were at high risk. CONCLUSIONS: The substantial agreement between frozen and permanent sections allows minimizing under- and overtreatment of women undergoing hysterectomy for AEH. High risk EC are efficiently identified in frozen section.

Spontaneous regression of transplacental metastases from maternal melanoma in a newborn: case report and review of the literature.

We describe a rare case of transplacental-transmitted maternal melanoma to the placenta and foetus during the second pregnancy of a 28-year-old woman. She was aware of a greyish-brown nodular lesion on the right gluteus during her first pregnancy. On histological examination, this lesion resulted to be an amelanocitic melanoma. Breast metastases occurred during her second pregnancy, 18 months after the surgical excision; an emergency Caesarean section performed for the recrudement of her clinical conditions confirmed widespread metastases to the liver, spleen and peritoneum. The patient died 2 weeks after delivery. The newborn, at 3 months of age, presented metastases secondary to maternal melanoma, which were resistant to chemotherapy. The disease regressed spontaneously and the child is now 24 months, alive in complete remission.

Pre- and post-operative work-up in patients affected by early cervical cancer and eligible for fertility-sparing treatment: role of MRI with saline hydrocolpos.

Nowadays young women affected by early invasive uterine cervical cancer (stage IA2-IB1) may be offered a fertility-sparing treatment: the radical trachelectomy with pelvic lymph node dissection. This procedure consists in surgical removal of cervix uteri, proximal parametrial tissue, and vaginal cuff. The morphology and the functions of corpus uteri are preserved. Women candidates for trachelectomy must be closely selected. Gynecologist oncologist needs an imaging modality that can accurately value the tumoral diameter and which can demonstrate proximal extension of tumor to ensure surgical clear resection margins (especially the cranial one). Magnetic resonance imaging (MRI) is a very useful examination in pre-operative study of women affected by early cervical cancer. The aim of this study is to evaluate the role of MRI with hydrocolpos about pre- and post-operative work-up in women eligible for fertility-sparing treatment.

Peripartum cardiomyopathy.

According to current definition, peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular dysfunction and symptoms of heart failure occur in the last month of pregnancy. It has been reported that the incidence of PPCM is 1 in 3,000-4,000 live births. The pathogenesis is poorly understood, however, infectious, immunologic, and nutritional causes have been hypothesized. Clinical presentation includes usual signs and symptoms of heart failure, and unusual presentations such as thromboembolism. Diagnosis is based upon the clinical presentation of congestive heart failure and the objective evidence of left ventricular systolic dysfunction. Early diagnosis and initiation of treatment are essential to optimize pregnancy outcome. Patients with systolic dysfunction during pregnancy are treated similar to patients who are not pregnant. The mainstays of medical therapy are digoxin, loop diuretics, sodium restriction and afterload reducing agents (hydralazine and nitrates). Due to a high risk for venous and arterial thrombosis, anticoagulation with subcutaneous heparin should be instituted. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be avoided during pregnancy because of severe adverse neonatal effects. Effective treatment reduces mortality rates and increases the number of women who fully recover left ventricular systolic function. The prognosis is poor in patients with persistent cardiomyopathy. Subsequent pregnancies are often associated with recurrence of left ventricular systolic dysfunction.

Evaluation of endometrial thickness in hormone receptor positive early stage breast cancer postmenopausal women switching from adjuvant tamoxifen treatment to anastrozole.

Evaluation of endometrial thickness by transvaginal ultrasonography (TVUS) in postmenopausal estrogen receptor positive breast cancer patients treated with anastrozole after tamoxifen therapy. This study included 70 postmenopausal estrogen receptor positive breast cancer patients who switched to anastrozole after tamoxifen; patients had endometrial thickness >4mm and no endometrial malignancy. Endometrial thickness was measured after anastrozole treatment. Endometrial thickness during anastrozole therapy was lower than after tamoxifen therapy (p<0.001); the mean reduction in endometrial thickness was 4.5mm (+/-3.0). Cystic endometrial appearance was more frequent in patients under tamoxifen than in those under anastrozole (p<0.001). Duration of tamoxifen therapy was not correlated to the endometrial thickness at the time of its suspension. Duration of tamoxifen therapy and endometrial thickness at the time of tamoxifen suspension was correlated to the relative reduction of endometrial thickness during anastrozole therapy. Anastrozole reverses tamoxifen-induced increased endometrial thickness and sonographic endometrial cystic appearance.