A giant paraesophageal hiatal hernia causing vocal fold paralysis

We report the case of a patient who presented with severe dysphonia as a consequence of a giant hiatal hernia that was paralysing the patient’s vocal folds

Spindle cell carcinoma: Two instances mistaken for vocal polyps

Spindle cell carcinoma is a variant of squamous carcinoma, with behavior that is apparently more aggressive than that of squamous carcinoma and that can produce distant lymphatic metastasis. It was first described by Virchow in 1864 [1], but the origin of the tumor is still not clear. The tumor is biphasic, with an epidermal component and a sarcomatous component involving spindle cells; transition zones between these components can be found [2–5]. In part due to this peculiar and complex nature, the tumor has accumulated various names since it was first described: sarcomatoid tumor, carci- nosarcoma, pleomorphic carcinoma, collision tumor, etc. [2,5,6]

A giant paraesophageal hiatal hernia causing vocal fold paralysis

We report the case of a patient who presented with severe dysphonia as a consequence of a giant hiatal hernia that was paralysing the patient’s vocal folds

Spindle cell carcinoma: Two instances mistaken for vocal polyps

Spindle cell carcinoma is a variant of squamous carcinoma, with behavior that is apparently more aggressive than that of squamous carcinoma and that can produce distant lymphatic metastasis. It was first described by Virchow in 1864 [1], but the origin of the tumor is still not clear. The tumor is biphasic, with an epidermal component and a sarcomatous component involving spindle cells; transition zones between these components can be found [2–5]. In part due to this peculiar and complex nature, the tumor has accumulated various names since it was first described: sarcomatoid tumor, carci- nosarcoma, pleomorphic carcinoma, collision tumor, etc. [2,5,6]

Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium

Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis

A map of human genome variation from population-scale sequencing

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10−8 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic researc