Rational: The growing population of young cancer survivors and a trend toward postponing pregnancy until later years in life are leading to a deeper attention towards understanding treatment-induced sequelae, and, in particular, the effects of cancer and/or treatment on fertility. Nowadays, the infertility risks potentially associated with molecular targeted therapies are not established, and clinical reports are sparse. Moreover, the increasing use of molecular targeted drugs in the adjuvant setting and in diseases with better prognosis makes preservation of fertility a major topic in current research. Patient's concerns: Here, we report the case of an 18-year-old woman, with a 3-cm superficial lump of the right breast, who had no remarkable family or medical history. Menarche had occurred at the age of 14 years, with normal regular periods. Diagnosis: High-grade angiosarcoma, with metastatic progression and multiple relapse, was diagnosed. Interventions: After diagnosis, right radical mastectomy was carried out with no evidence of residual disease. No adjuvant treatment was delivered. Lymph node metastasis were found later and chemotherapy with doxorubicin 25 mg/m²/day and ifosfamide 1 g/m²/day (both on days 1–3) every 21 days was administered. During treatment, the patient reported menstrual irregularities but no amenorrhea. Due to further local relapse a few years later, the patient was treated for progressive metastatic disease with gemcitabine 1000 mg/m² on days 1 and 8 every 21 days for 6 cycles, and underwent surgery, followed by pegylated liposomal doxorubicin, 50 mg/m² on day 1 every 28 days. After further disease progression 5 years after first diagnosis, pazopanib was administered at a dose of 800 mg daily for 10 months. Outcomes: The patient experienced a transient ovarian insufficiency possibly due to pazopanib. Since amenorrhea developed within 2 months from the initiation of pazopanib treatment and menses returned regularly only after discontinuation of the treatment itself. Lessons: This is the first case report that strongly suggests a correlation between pazopanib exposure and development of ovarian insufficiency. Our case tantalizes to inspire additional preclinical and clinical research on the true incidence, possible dose dependence, and reversibility of pazopanib (and other TKIs) -induced ovarian failure.

Background: Liver cirrhosis (LC) is a leading global cause of morbidity and mortality, with inflammation playing a key role in disease progression and clinical complications of LC. The Neutrophil/Lymphocyte Ratio (NLR), a readily available marker of systemic inflammation, has been linked to short-term adverse outcomes in LC, but data on long-term follow-up are limited. This study aimed to investigate the relationship between NLR and long-term all-cause mortality in an unselected cohort of LC patients. Methods: Data were gathered from the Italian multicenter observational study “PRO-LIVER”. Patients with available data to calculate NLR at baseline were included. Baseline clinical determinants of NLR and the association of NRL with all-cause mortality at 2-year follow-up were evaluated. Results: From the overall cohort (n = 753), 506 patients with LC (31% female, mean age 64.8 ± 11.9 years) were included in the analysis. Median value of NLR was 2.42 (Interquartile Range [IQR]: 1.61–3.52). At baseline, patients with NLR ≥ 2.42 were more likely to have Child–Pugh B or C, hepatocellular carcinoma (HCC), or portal vein thrombosis (PVT). After a median follow-up of 21 months, 129 patients died: 44 (17%) with NLR < 2.42 and 85 (34%) with NLR ≥ 2.42 (p < 0.001). At multiple-adjusted Cox regression analysis, NLR ≥ 2.42 was independently associated with all-cause mortality (HR: 1.65; 95% CI: 1.12–2.44; p = 0.012), along with age, Child–Pugh C class, HCC and PVT. Conclusions: NLR is associated with long-term all-cause mortality in LC. NLR may serve as a potentially easily available tool to aid risk refinement in LC. Trial registration number: ClinicalTrials.gov Identifier: NCT01470547.

7065 Background: N2 nodal downstaging following neoadjuvant therapy for Stage IIIA(N2) NSCLC correlates with improved survival after lung resection. Pathologic assessment of nodes following neoadjuvant therapy may avoid unnecessary thoracotomy. Repeat mediastinoscopy has increased risk and limited efficacy. VATS may provide a safe alternative for restaging. Methods: The primary objective of this prospective multi-institutional study was to determine the feasibility of VATS restaging of ipsilateral nodes in mediastinoscopy proven stage IIIA(N2) NSCLC following 2 cycles neoadjuvant platinum-based chemotherapy (chemo) and/or ≥ 40 Gy radiotherapy (XRT) prior to thoracotomy. The goal of VATS re-staging was to biopsy 3 (-) lymph node stations, 1 (+) N2 node, or pleural carcinomatosis. Results: 70 evaluable patients (pts) were accrued from 10 institutions, 47% male, 97% white, and 71% aged between 50 and 69 years. 60% had performance status (PS) = 0, 40% PS = 1. 47 pts (67%) had XRT, 68 (97%) had chemo. Number of VATS incisions ranged from 1 to 4, median 3. Median time of VATS was 63 minutes, range from 27 to 313. VATS restaging met criteria in 40 pts (57%) and revealed: 4 pleural carcinomatosis, 17 persistent N2 disease, 19 had 3 (-) nodal stations. An additional 13 VATS (18.6%) found no evidence of persistent N2 disease, but had inadequate nodal sampling due to unanticipated obliteration of nodal tissue. Thus, 53 VATS (76%, 95% CI: 64 - 85%) were able to restage the mediastinum. VATS was unsuccessful in 17 (24%): 11 due to adhesions/fibrosis, 4 from tumor bulk preventing nodal access, 1 VATS was aborted due to airway injury, and 1 had inadequate lung deflation. Of the 53 completed VATS, 21 provided cancer tissue, and 31 had histologic tissue obtained during thoracotomy. N2 downstaging occurred in 32 pts (46%). Sensitivity of VATS was 75%, specificity was 100%, and negative predictive value was 75.8%. No deaths, but 1 airway injury was directly attributed to VATS. Conclusions: VATS restaging was feasible and provided pathologic assessment of ipsilateral nodes in treated IIIA(N2) NSCLC. New treatment paradigms can be built on pathologic restaging. No significant financial relationships to disclose.

Background: Adherence to healthy dietary patterns, such as the Mediterranean diet (Med-diet), is recommended for the maintenance of cardiovascular health. The determinants for adherence to Med-diet and its importance in secondary cardiovascular disease prevention are still unclear. The aim of the study was to evaluate the influence of sex- and psycho-socio-cultural (i.e., gender-related) factors on Med-diet adherence and its role in preventing major cardiovascular events (MACEs) in patients with ischemic heart disease (IHD). Methods: Med-diet adherence was evaluated among 503 consecutive adults with IHD. MACEs were collected during a long-term follow-up. Results: Male Bem Sex-Role Inventory score (i.e., male personality traits) and physical functional capacity were associated with higher adherence, while cohabitation with a smoker and physical inactivity with poorer adherence. During a median follow-up of 22 months, 48 participants experienced MACEs (17.5%, 8.1%, and 3.9% of patients with low, medium, and high adherence, respectively; p = 0.016). At multivariate Cox--regression analysis, a greater adherence remained inversely associated with MACEs (HR: 0.49; 95% CI: 0.29–0.82; p = 0.006) after adjusting for confounding factors. Conclusion: The study suggests that gender-related factors have a role in maintaining a healthy dietary pattern. Improving Med-diet adherence may lower the risk of recurring cardiovascular events.