Abstract Objective(s) This prospective observational cohort study aimed to evaluate whether women with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection during the first trimester of pregnancy are at higher risk of adverse obstetric and neonatal outcomes compared to negative patients. Study Design Seromolecular testing for SARS‐CoV‐2 was performed at 12, 16, 21 weeks, and at delivery; the cohort was then subdivided into a first‐trimester SARS‐CoV‐2‐positive (case) group and a SARS‐CoV‐2‐negative (control) group. The primary outcome was a composite adverse obstetric outcome, defined as the presence of either abortion, preterm delivery, preterm prelabor rupture of membranes, preeclampsia, intrauterine growth restriction, stillbirth; and a composite measure of adverse neonatal events, including either 1‐ and 5‐min Apgar score ≤ 7, neonatal intensive care unit admission and congenital birth defects. Maternal symptoms and antibody titer were secondarily assessed. Results A total of 17 of 164 women tested positive for SARS‐CoV‐2 (10.3%) in the first trimester. One SARS‐CoV‐2‐positive patient who gave birth at another hospital was excluded. Composite adverse obstetric outcome was observed in 6.2% (1/16) SARS‐CoV‐2‐positive and 10.5% (11/105) SARS‐CoV‐2‐negative women; composite adverse neonatal outcome in 12.5% (2/16) and 7.6% (8/105), respectively. In the newborns of women who had developed IgG antibodies, the same antibodies were detected in arterial cord blood and the nasopharyngeal swab tested negative for SARS‐CoV‐2. No maternal pneumonia or hospital admission due to coronavirus disease‐19 were recorded. Conclusion Asymptomatic or mildly symptomatic women during the first trimester of pregnancy did not experience significantly more adverse events than SARS‐CoV‐2‐negative women.
Abstract Patients with advanced ovarian cancers have experienced little improvement in overall survival with standard treatments even after the incorporation of anti-angiogenic therapies. Besides anti-PARP inhibitors, matching individual critical genomic alterations with the best available drugs has not advanced as in other cancers, likely because a handful of cancer-related genes are mutated at high frequency, while many more are found mutated at much lower frequencies. This so called “mutation tail” is not only long but also mostly unexplored. We used Patient Derived Xenografts (PDXs) to identify actionable cancer genes and PDX Derived Tumor Cells (PDTCs) to accelerate the discovery of treatment options. We envisioned that the alleged weakness of PDX models, i.e. lack of human stromal and immune cells, might be instrumental to identify mutations in cancer and to test approved or experimental targeted drugs as monotherapy or in different combinations to link biomarkers to treatments. Forty-nine PDX lines from metastatic epithelial ovarian carcinomas have been propagated and fully characterized as far as histology, immunohistochemistry of epithelial and high-grade serous-specific markers and presence of TP53 and BRCA1/2 mutations. Copy number variations (CNV) analysis and Whole Exome Sequencing (WES) were carried out PDX lines derived from naïve metastatic high-grade epithelial ovarian carcinomas, which came out to be refractory/resistant to platinum drugs. We studied non-synonymous mutations with allele frequencies ≥0.1. Only mutations in cancer genes listed in databases were further analyzed. SNPdb allowed ruling out polymorphisms. SIFT and PROVEAN softwares predicted deleterious or damaging effects onto the protein sequences. DGIdb helped selecting actionable genes. We identified in one PDX line, a possibly loss-of-function mutation of the PIK3R1 gene (encoding the p85alpha regulatory subunit of PI3K) had an allele frequency=0.9 in early and late passages. Moreover, in two micro-dissected FFPE samples of the source tumor this mutation had an allele frequency nearly identical to that of the mutated TP53. Hence, PIK3R1W624R could be a trunk mutation in the PDX line and possibly in the human counterpart. Treatment options were assayed ex-vivo, on short-term cultures of PDTCs of the PIK3R1W624R PDX line. Buparlisib, a pan-class I PI3K inhibitor, showed the ability to block proliferation of PDTCs and the growth in vivo of PDXs in regression preclinical trial. These data proofed-the-concept that a PDX-based pipeline is able to unveil actionable pathways for the treatment of advanced/metastatic ovarian cancer. Citation Format: Martina Olivero, Jessica Erriquez, Maddalena Arigoni, Sonia Capellero, Concetta D'Ambrosio, Gloria Mittica, Fulvio Borella, Dionyssios Katsaros, Silvana Privitera, Enrico Berrino, Tiziana Venesio, Giorgio Valabrega, Raffaele Calogero and Maria Flavia Di Renzo. PATIENT DERIVED XENOGRAFTS (PDXS) AND PDX DERIVED TUMOR CELLS (PDTC) ALLOW THE IDENTIFICATION OF ACTIONABLE CANCER GENES AND TREATMENT OPTIONS FOR PLATINUM REFRACTORY/RESISTANT OVARIAN CARCINOMAS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-023.
Background: The management of early breast cancer (BC) needs supervision and skill maintenance, and should be performed by specialists working as a team in multidisciplinary breast units. This approach aims to improve the long-term survival and quality of life of patients with BC. Methods: This was a prospective observational study including patients newly diagnosed with operable BC. The study encompassed the pre-surgical phase, throughout the diagnostic and surgical workout, and included post-therapeutic master multidisciplinary team meetings (MTMs) sessions, between 2019 and 2022. Results: We enrolled 280 patients with BC from eight breast units. The Senonetwork indicators regarding diagnosis, waiting time, loco-regional treatment, and adjuvant therapy were collected for each patient discussed. Conclusions: Overall, the majority of quality indicators were respected among breast units. The most critical issue referred to timing indicators: more than 30 days from MTM to surgery, more than 42 days from diagnosis to surgery, and more than 60 days from the first screening mammogram to surgery for many patients. Some aspects of the histopathological diagnosis of intraductal BC also need to be improved. Furthermore, other critical issues in our study regarded some aesthetical indicators, demonstrating low interest in these essential quality indicators.
Despite Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) -induced Oxidative Stress (OxS) being well documented in different organs, the molecular pathways underlying placental OxS in late-pregnancy women with SARS-CoV-2 infection are poorly understood. Herein, we performed an observational study to determine whether placentae of women testing positive for SARS-CoV-2 during the third trimester of pregnancy showed redox-related alterations involving Catalase (CAT) and Superoxide Dismutase (SOD) antioxidant enzymes as well as placenta morphological anomalies relative to a cohort of healthy pregnant women. Next, we evaluated if placental redox-related alterations and mitochondria pathological changes were correlated with the presence of maternal symptoms. We observed ultrastructural alterations of placental mitochondria accompanied by increased levels of oxidative stress markers Thiobarbituric Acid Reactive Substances (TBARS) and Hypoxia Inducible Factor-1 α (HIF-1α) in SARS-CoV-2 women during the third trimester of pregnancy. Importantly, we found an increase in placental CAT and SOD antioxidant enzymes accompanied by physiological neonatal outcomes. Our findings strongly suggest a placenta-mediated OxS inhibition in response to SARS-CoV-2 infection, thus contrasting the cytotoxic profile caused by Coronavirus Disease 2019 (COVID-19).
Abstract Background and Objectives Italy was severely affected by the severe acute respiratory syndrome coronavirus 2 pandemic. Our Institution, Piedmont's largest tertiary referral center, was designated as a non‐COVID‐19 hospital and activities were reorganized to prioritize critical services like oncological care. The aim of this study was to investigate the efficacy in preserving the oncological surgical practice at our Institution during the most critical months of the COVID‐19 epidemic by analyzing the surgical pathology activity. Methods The number of oncological surgical resections submitted to histopathological examination from 9th March 2020 to 8th May 2020 were collected as well staging/grading data and compared with the previous three pre‐COVID‐19 years (2017–2019). Results Overall, no decrease was observed for most tumor sites (5/9) while breast resections showed the largest drop (109 vs. 160; −31.9%), although a full recovery was already noticed during the second half of the period. Conversely, the selected control benchmarks showed a sharp decrease (−80.4%). Distribution of pathological TNM stages (or tumor grades for central nervous system tumors) showed no significant differences during the lockdown compared with previous years ( p > .05). Conclusions The present data suggest the possibility of preserving this cornerstone oncological activity during an evolving public health emergency thanks to a prompt workflow reorganization.
Background: Tubular carcinoma (TC) is a low proliferative grade 1 (G1) breast cancer (BC). Despite its favorable outcome and allegedly lower aggressiveness, patients are treated like other luminal G1 BC, with radiotherapy (RT) and hormonal therapy (HT). We performed: (1) a retrospective study comparing a TC cohort and a control series of luminal G1 BC and (2) a systematic review and meta-analysis focused on TC outcome. Materials and Methods: We selected a series of 572 G1 luminal BC patients [111 TC, 350 not otherwise specified (NOS), and 111 special-type (ST) BC] with follow-up and clinico-pathological data, who underwent local excision followed by RT at Città della Salute e della Scienza Hospital, Turin. Moreover, 22 and 13 studies were included in qualitative and quantitative meta-analysis, respectively. Results: TCs were generally smaller (≤10 mm) ( P < 0.001), with lower lymph node involvement ( P < 0.001). TCs showed no local and/or distant recurrences, while 16 NOS and 2 ST relapsed ( P = 0.036). Kaplan–Meier curves confirmed more favorable TC outcome (DFI: log-rank test P = 0.03). Meta-analysis data, including the results of our study, showed that the pooled DFI rate was 96.4 and 91.8% at 5 and 10 years, respectively. Meta-regression analyses did not show a significant influence of RT nor HT on the DFI at 10 years. Conclusions: Compared to the other G1 BCs, TCs have an excellent outcome. The meta-analysis shows that TC recurrences are infrequent, and HT and RT have limited influence on prognosis. Hence, accurate diagnosis of TC subtype is critical to ensuring a tailored treatment approach.
