Ketorolac Dosing and Outcomes in Neonates Following Congenital Heart Surgery: A Retrospective Analysis.

Background: Pain management is essential for postoperative surgery. Given the association of opioids with adverse outcomes, interest in the use of nonopioid analgesics, such as ketorolac, has increased. Published data on use in neonates are limited.

Comprehensive integrative profiling of upper tract urothelial carcinomas.

Background: Crosstalk between genetic, epigenetic, and immune alterations in upper tract urothelial carcinomas and their role in shaping muscle invasiveness and patient outcome are poorly understood.

Results: We perform an integrative genome- and methylome-wide profiling of diverse non-muscle-invasive and muscle-invasive upper tract urothelial carcinomas. In addition to mutations of FGFR3 and KDM6A, we identify ZFP36L1 as a novel, significantly mutated tumor suppressor gene.

Molecular characterization of sarcomatoid clear cell renal cell carcinoma unveils new candidate oncogenic drivers.

Sarcomatoid clear-cell renal cell carcinomas (sRCC) are associated with dismal prognosis. Genomic alterations associated with sarcomatoid dedifferentiation are poorly characterized. We sought to define the genomic landscape of sRCC and uncover potentially actionable therapeutic targets.

The changing landscape of clinical trials for mitochondrial diseases: 2011 to present.

We reviewed the status of interventional clinical trials for primary mitochondrial diseases. Using national and international search engines, we found 48 randomized controlled trials (RCTs) registered as of May 15, 2019. Consilience between lay and professional mitochondrial disease communities to engage in RCTs has increased, as has progress in developing new disease and treatment biomarkers and potential therapies.

Phase II randomised discontinuation trial of brivanib in patients with advanced solid tumours.

Background: Brivanib is a selective inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signalling. We performed a phase II randomised discontinuation trial of brivanib in 7 tumour types (soft-tissue sarcomas [STS], ovarian cancer, breast cancer, pancreatic cancer, non-small-cell lung cancer [NSCLC], gastric/esophageal cancer and transitional cell carcinoma [TCC]).

Patients And Methods: During a 12-week open-label lead-in period, patients received brivanib 800 mg daily and were evaluated for FGF2 status by immunohistochemistry.

6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial.

Background: In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events.

Methods: PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy.

Integrated Multi-omic Analysis of Esthesioneuroblastomas Identifies Two Subgroups Linked to Cell Ontogeny.

Esthesioneuroblastoma (ENB) is a rare cancer of the olfactory mucosa, with no established molecular stratification to date. We report similarities of ENB with tumors arising in the neural crest and perform integrative analysis of these tumors. We propose a molecular-based subtype classification of ENB as basal or neural, both of which have distinct pathological, transcriptomic, proteomic, and immune features.

Long-Term Survival in Gastroesophageal Junction Adenocarcinoma: Ramucirumab.

We report a case of long-term survival with complete response of liver metastases within RAINBOW, a randomized, controlled trial of ramucirumab 8 mg/kg intravenously (days 1, 15) versus placebo, both plus paclitaxel 80 mg/m intravenously (days 1, 8, 15), every 4 weeks in patients with previously treated advanced gastroesophageal junction adenocarcinoma. A 64-year-old man with gastroesophageal junction adenocarcinoma and liver metastases received first-line folinic acid, 5-fluorouracil plus oxaliplatin (FOLFOX) following jejunostomy. On liver progression, he enrolled in RAINBOW (April 2012), receiving ramucirumab.

Expression of long non-coding RNA MFI2-AS1 is a strong predictor of recurrence in sporadic localized clear-cell renal cell carcinoma.

Prediction of recurrence is a challenge for the development of adjuvant treatments in clear-cell renal cell carcinoma (ccRCC). In these tumors, expression of long non-coding RNAs (lncRNAs) are deregulated and closely associated with prognosis. Thus, we aimed to predict ccRCC recurrence risk using lncRNA expression.

Early onset breast cancer: differences in risk factors, tumor phenotype, and genotype between North African and South European women.

Purpose: This report compares the risk factors, the tumor phenotypes, and the BRCA1/BRCA2 genotype of early onset breast cancer (EOBC) patients between Southern Europe and North Africa.

Methods: Four hundred and fifty six women with invasive EOBC (≤40 years) were prospectively included from four centers in France (n = 270) and four centers in North Africa (Algeria, Egypt, Morocco, Tunisia; n = 186). Life style, tumor phenotype, familial history, BRCA1/BRCA2 genotype were compared between the two populations.

Inactivation and Mutation Drive a Convergence toward Loss of Function of H3K36 Writers in Clear Cell Renal Cell Carcinomas.

Extensive dysregulation of chromatin-modifying genes in clear cell renal cell carcinoma (ccRCC) has been uncovered through next-generation sequencing. However, a scientific understanding of the cross-talk between epigenetic and genomic aberrations remains limited. Here we identify three ccRCC epigenetic clusters, including a clear cell CpG island methylator phenotype (C-CIMP) subgroup associated with promoter methylation of VEGF genes (, and ).

[Prospective: How will renal, prostatic and urothelial tumours be treated in 10 years?].

Forward thinking does not seek to predict the future, to unveil it as if it were already in existence, rather, its aim is to help us to construct it. Although today's epidemiological and therapeutic situations for urogenital tumours can evolve over the next 10 years, diagnostic and therapeutic methods, as well as the treatment and implementation of innovations, are already rapidly changing. Rather than reducing our prospective thinking to the therapeutic treatment of cancer only, we will aim at proposing a global sanitary vision that includes diagnosis, therapies, prevention, routine utilisation of technomedicine, genomics and even nanomedicine.

Incidence, clinicopathological features and fusion transcript landscape of translocation renal cell carcinomas.

Aims: Translocation renal cell carcinoma (tRCC) is a rare subtype of kidney tumour characterized by translocations involving the transcription factor TFE3 or TFEB. tRCC was introduced into the World Health Organization classification in 2004, but much is still unknown about the natural history, clinicopathological features and outcomes of the disease. The aim of this study was to describe the landscape of fusion transcript in a large single-institution series of fluorescence in-situ hybridization (FISH)-confirmed tRCCs and then to compare it to morphological and clinical data.

Unique Transcriptomic Profile of Collecting Duct Carcinomas Relative to Upper Tract Urothelial Carcinomas and other Kidney Carcinomas.

Collecting duct carcinoma (CDC) is a kidney cancer subtype that is thought to arise from principal cells in distal parts of the collecting ducts. Some studies suggested an overlap of CDC with upper tract urothelial carcinoma (UTUC), making the pathological diagnosis challenging. Herein, we performed for the first time transcriptome sequencing of CDC and compared them to UTUC and renal cell carcinoma subtypes.

Cancer subtypes classification using long non-coding RNA.

Inter-tumor heterogeneity might explain divergent clinical evolution of cancers bearing similar pathological features. In the last decade, genomic has highly improved tumor subtypes classification through the identification of oncogenic or tumor suppressor drivers. In addition, epigenetics and long non-coding RNAs (lncRNAs) are emerging as new fields for investigation, which might also account for tumor heterogeneity.

DNA Methylation Signature Reveals Cell Ontogeny of Renal Cell Carcinomas.

Purpose: DNA methylation is a heritable covalent modification that is developmentally regulated and is critical in tissue-type definition. Although genotype-phenotype correlations have been described for different subtypes of renal cell carcinoma (RCC), it is unknown if DNA methylation profiles correlate with morphological or ontology based phenotypes. Here, we test the hypothesis that DNA methylation signatures can discriminate between putative precursor cells in the nephron.

Therapeutic Strategies for Patients With Metastatic Renal Cell Carcinoma in Whom First-Line Vascular Endothelial Growth Factor Receptor-Directed Therapies Fail.

Metastases are present in one third of renal cell carcinomas at diagnosis. The overall survival duration in metastatic renal cell carcinoma is approximately 22 months, which underlines the need for more effective systemic treatments. Therapies on the basis of antiangiogenic agents and inhibitors of the mammalian target of rapamycin have been approved for treatment of metastatic renal cell carcinoma, but only benefits for progression-free survival were demonstrated in the second-line setting.

Oncogenic viruses: Lessons learned using next-generation sequencing technologies.

Fifteen percent of cancers are driven by oncogenic human viruses. Four of those viruses, hepatitis B virus, human papillomavirus, Merkel cell polyomavirus, and human T-cell lymphotropic virus, integrate the host genome. Viral oncogenesis is the result of epigenetic and genetic alterations that happen during viral integration.

Genomic Characterization of Renal Cell Carcinoma with Sarcomatoid Dedifferentiation Pinpoints Recurrent Genomic Alterations.

Background: The genomic features underpinning renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) are not well understood, and at present, there are no specific or effective therapies for sRCC.

Objective: To identify genomic alterations in patients with sRCC.

Design, Setting, And Participants: We conducted genomic profiling on paired epithelial and sarcomatoid areas of three sRCC cases.

Pain thresholds following maximal endurance exercise.

Purpose: Physical exercise causes alterations in pain sensitivity. Many studies verified so-called exercise-induced analgesia caused by submaximal aerobic intensity. This study aimed to determine the effect of an endurance exercise to exhaustion on pain sensitivity of healthy young men.

Anticancer treatment and fertility: Effect of therapeutic modalities on reproductive system and functions.

The significant improvement of cancer treatments entailed a longer life in cancer survivors and raised expectations for higher quality of life with minimized long-term toxicity. Infertility and gonadal dysfunction are adverse effects of anticancer therapy or may be related to specific tumors. In female cancer survivors, premature ovarian failure is common after antineoplastic treatments resulting in infertility and other morbidities related to oestrogen deficiency such as osteoporosis.

Long non-coding RNA profiling links subgroup classification of endometrioid endometrial carcinomas with trithorax and polycomb complex aberrations.

Background: Integrative analysis of endometrioid endometrial carcinoma (EEC) using multiple platforms has distinguished four molecular subgroups. However, the landscape of expressed long non-coding RNAs (lncRNA) and their role in charting EEC subgroups and determining clinical aggressiveness remain largely unknown.

Results: Using stringent criteria, we identified 1,931 expressed lncRNAs and predicted potential drivers through integrative analysis.

Methylome sequencing for fibrolamellar hepatocellular carcinoma depicts distinctive features.

With the goal of studying epigenetic alterations in fibrolamellar hepatocellular carcinoma (FLC) and establish an associated DNA methylation signature, we analyzed LINE-1 methylation in a cohort of FLC and performed next-generation sequencing of DNA methylation in a training set of pure-FLCs and non-cirrhotic hepatocellular carcinomas (nc-HCC). DNA methylation was correlated with gene expression. Furthermore, we established and validated an epigenetic signature differentiating pure-FLC from other HCCs.

Atypical Presentation of Hepatocellular Carcinoma Mimicking a Gastric Hepatoid Adenocarcinoma: A Case Report.

The diagnosis of hepatocellular carcinoma (HCC) relies on imaging tools and biopsy. It usually does not present to be a challenge.Here we report the case of a 69-year-old patient with HCC, initially mistaken for a gastric hepatoid adenocarcinoma (HAC), with a favorable outcome after neoadjuvant chemotherapy.