L1CAM expression as a predictor of platinum response in high-risk endometrial carcinoma.

For high-risk endometrial cancer (EC) patients, adjuvant chemotherapy is recommended to improve outcome. Yet, predictive biomarkers for response to platinum-based chemotherapy (Pt-aCT) are currently lacking. We tested expression of L1 cell-adhesion molecule (L1CAM), a well-recognised marker of poor prognosis in EC, in tumour samples from high-risk EC patients, to explore its role as a predictive marker of Pt-aCT response. L1CAM expression was determined using RT-qPCR and immunohistochemistry in a cohort of high-risk EC patients treated with Pt-aCT and validated in a multicentric independent cohort. The association between L1CAM and clinicopathologic features and L1CAM additive value in predicting platinum response were determined. The effect of L1CAM gene silencing on response to carboplatin was functionally tested on primary L1CAM-expressing cells. Increased L1CAM expression at both genetic and protein level correlated with high-grade, non-endometrioid histology and poor response to platinum treatment. A predictive model adding L1CAM to prognostic clinical variables significantly improved platinum response prediction (C-index 78.1%, P = .012). In multivariate survival analysis, L1CAM expression was significantly associated with poor outcome (HR: 2.03, P = .019), potentially through an indirect effect, mediated by its influence on response to chemotherapy. In vitro, inhibition of L1CAM significantly increased cell sensitivity to carboplatin, supporting a mechanistic link between L1CAM expression and response to platinum in EC cells. In conclusion, we have demonstrated the role of L1CAM in the prediction of response to Pt-aCT in two independent cohorts of high-risk EC patients. L1CAM is a promising candidate biomarker to optimise decision making in high-risk patients who are eligible for Pt-aCT.

Color-dye injection of monochorionic placentas and correlation with pregnancy complications.

INTRODUCTION: Vascular anastomoses in monochorionic (MC) twin placenta can be easily identified with color-dye injection. The aim of this study is to analyze the relationship between different type of anastomoses and twin pregnancy complications. METHODS: From January 2011 to October 2014, MC placentas were analyzed with color-dye injection and five group of pregnancies were identified: those that were not complicated (NC), those complicated with selective intrauterine growth restriction (sIUGR), twin-twin transfusion syndrome (TTTS), or twin anemia-polycitemia sequence (TAPS) and those with amniotic fluid discordance (AFD) between twins. Cases of TTTS treated with endoscopic laser coagulation of placenta anastomoses or cases with in utero death of one twin were excluded. RESULTS: A total of 118 MC placentas were observed, 58 (49%) NC, 35 (30%) sIUGR, 10 (8%) TTTS, 13 (11%) AFD and 2 (2%) TAPS. The median number of anastomoses was 7 (range 1-15), 8 (2-18), 4 (2-11), 7 (2-13) and 1 (1-1), respectively. At least one artero-venous anastomoses was found in the placenta observed, while the prevalence of artero-arterial anastomoses was 95% for NC, 91% for sIUGR, 60% for TTTS, and 77% for AFD; no TAPS placenta had this type of anastomoses. The diameter of arteroarterial anastomoses was greater in the AFD group (3.3 mm), compared to the NC, sIUGR and TTTS groups (2.3, 2.5 and 1.4 respectively, p 0.04). DISCUSSION: In this large serie of MC placenta analyzed with color-dye injection, a specific distribution of anastomoses emerged for twins with amniotic fluid discordance, which points to a need for intensive surveillance.

High-risk borderline ovarian tumors: analysis of clinicopathological features and prognostic impact of different follow-up strategies.

OBJECTIVES: Borderline ovarian tumors (BOTs) represent 10-20% of all epithelial ovarian malignancies. Most of them are comparable to benign cysts but a high-risk group has been recognized. The aim of the study was to analyze different follow-up strategies in high-risk patients. METHOD: Patients with BOT treated at our institution from 1992 to 2011 were retrospectively reviewed. Clinicopathological features influencing prognosis were analyzed and two different follow-up strategies compared [6-month laparoscopic look (LPS-look): group A vs. ultrasound/CA-125 evaluation: group B]. RESULTS: 70 patients with high-risk BOTs were identified. After a median progression-free survival (PFS) of 43 months, 27% of patients experienced recurrences. Six months after diagnosis, 26 high-risk patients were submitted to LPS-look: at surgery, 6 out of 10 patients presenting evidence of disease were optimally debulked while in the remaining 4, only biopsies were performed. No difference in PFS was registered between group A and B patients, nevertheless a significant increase in PFS was registered among completely versus incompletely debulked patients with evidence of disease at laparoscopy. CONCLUSION: Clinical follow-up remains the gold standard for BOTs. These very preliminary data seem to suggest that LPS-look may have an impact on the secondary PFS in a subgroup of high-risk patients.

Two-dimensional HyCoSy with contrast tuned imaging technology and a second-generation contrast media for the assessment of tubal patency in an infertility program.

OBJECTIVE: To compare the efficiency of hysterosalpingo-contrast-sonography performed with air and saline (Hydro-HyCoSy) with HyCoSy performed with contrast media (SonoVue) and contrast-tuned imaging technology (CnTI-SonoVue-HyCoSy) considering hysterosalpingography (HSG) and laparoscopy (LPS) as reference tests and to evaluate the learning curve of this procedure. DESIGN: Retrospective study. SETTING: Reproductive unit of a university hospital. PATIENT(S): Forty-two infertile female patients. INTERVENTION(S): HyCoSy were performed with a 2.4-mm intrauterine catheter. Patients underwent HSG or LPS as controls. MAIN OUTCOME MEASURE(S): Mean age, sensitivity, specificity, positive and negative predictive value, kappa value, and diagnostic accuracy were evaluated for statistical analysis. RESULT(S): Sensitivity, specificity, and positive and negative predictive values of Hydro-HyCoSy were 91%, 71%, 55%, and 95%, respectively, while for CnTI-SonoVue-HyCoSy they were 87%, 84%, 69%, and 94%. The diagnostic accuracy of Hydro-HyCoSy and of CnTI-SonoVue-HyCoSy were 77% and 85%, with a Cohen's kappa of 0.52 and 0.66, respectively. CnTI-SonoVue-HyCoSy does not require a learning curve period. CONCLUSION(S): CnTI-SonoVue-HyCoSy is more accurate than Hydro-HyCoSy for the assessment of fallopian tubes. The very high normal predictive value of Hydro-HyCoSy suggests that this procedure could be performed as a screening examination, whereas CnTI-SonoVue-HyCoSy could be used as a second-step technique.

Reproductive assistance in HIV-1 discordant couples.

PURPOSE OF REVIEW: The total number of people living with HIV has reached 39.5 million. In developed countries, the major risk for HIV transmission is by heterosexual intercourse. The general condition and life expectancy of many patients with HIV infection is very good, and three-quarter of these individuals are in their reproductive years. For these reasons a large number of young couples are expected to make future plans to have children. Assisted reproduction in HIV-1 discordant couples has become important for clinicians in preventing HIV-1 transmission. RECENT FINDINGS: The main theme covered in this article is epidemiology of HIV-1 in the world, the biology of the virus present in the sperm, the recently published guidelines from the American Society for Reproductive Medicine and ethics recommendations concerning assisted reproduction in people infected by virus, and all clinical aspects and scientific data published that have been modified to allow assisted reproduction in HIV-serodiscordant couples. SUMMARY: To evaluate in clinical practice the safety of HIV-1 assisted reproduction with sperm washing and the outcome of assisted reproductive technologies offered to HIV-1 serodiscordant couples counselled for the prevention of HIV transmission.