Comprehensive characterization of a Canadian cohort of von Hippel-Lindau disease patients.

Von Hippel-Lindau disease (VHL) is a heritable condition caused by pathogenic variants in VHL and is characterized by benign and malignant lesions in the central nervous system (CNS) and abdominal viscera. Due to its variable expressivity, existing efforts to collate VHL patient data do not adequately capture all VHL manifestations. We developed a comprehensive and standardized VHL database in the web-based application, REDCap, that thoroughly captures all VHL manifestation data. As an initial trial, information from 86 VHL patients from the University Health Network/Hospital for Sick Children was populated into the database. Analysis of this cohort showed missense variants occurring with the greatest frequency, with all variants localizing to the α- or ß-domains of VHL. The most prevalent manifestations were central nervous system (CNS), renal, and retinal neoplasms, which were associated with frameshift variants and large deletions. We observed greater age-related penetrance for CNS hemangioblastomas with truncating variants compared to missense, while the reverse was true for pheochromocytomas. We demonstrate the utility of a comprehensive VHL database, which supports the standardized collection of clinical and genetic data specific to this patient population. Importantly, we expect that its web-based design will facilitate broader international collaboration and lead to a better understanding of VHL.

Laparoscopic and robotic hysterectomy in endometrial cancer patients with obesity: a systematic review and meta-analysis of conversions and complications.

OBJECTIVE DATA: Robotic assistance may facilitate completion of minimally invasive hysterectomy, which is the standard of care for the treatment of early-stage endometrial cancer, in patients for whom conventional laparoscopy is challenging. The aim of this systematic review was to assess conversion to laparotomy and perioperative complications after laparoscopic and robotic hysterectomy in patients with endometrial cancer and obesity (body mass index, ≥30 kg/m2). STUDY: We systematically searched MEDLINE, EMBASE, and Evidence-Based Medicine Reviews (January 1, 2000, to July 18, 2018) for studies of patients with endometrial cancer and obesity (body mass index, ≥30 kg/m2) who underwent primary hysterectomy. STUDY APPRAISAL AND SYNTHESIS METHODS: We determined the pooled proportions of conversion, organ/vessel injury, venous thromboembolism, and blood transfusion. We assessed risk of bias with the Institute of Health Economics Quality Appraisal Checklist for single-arm studies, and Newcastle-Ottawa Quality Scale for double-arm studies. RESULTS: We identified 51 observational studies that reported on 10,800 patients with endometrial cancer and obesity (study-level body mass index, 31.0-56.3 kg/m2). The pooled proportions of conversion from laparoscopic and robotic hysterectomy were 6.5% (95% confidence interval, 4.3-9.9) and 5.5% (95% confidence interval, 3.3-9.1), respectively, among patients with a body mass index of ≥30 kg/m2, and 7.0% (95% confidence interval, 3.2-14.5) and 3.8% (95% confidence interval, 1.4-9.9) among patients with body mass index of ≥40 kg/m2. Inadequate exposure because of adhesions/visceral adiposity was the most common reason for conversion for both laparoscopic (32%) and robotic hysterectomy (61%); however, intolerance of the Trendelenburg position caused 31% of laparoscopic conversions and 6% of robotic hysterectomy conversions. The pooled proportions of organ/vessel injury (laparoscopic, 3.5% [95% confidence interval, 2.2-5.5]; robotic hysterectomy, 1.2% [95% confidence interval, 0.4-3.4]), venous thromboembolism (laparoscopic, 0.5% [95% confidence interval, 0.2-1.2]; robotic hysterectomy, 0.5% [95% confidence interval, 0.1-2.0]), and blood transfusion (laparoscopic, 2.8% [95% confidence interval, 1.5-5.1]; robotic hysterectomy, 2.1% [95% confidence interval, 1.6-3.8]) were low and not appreciably different between arms. CONCLUSION: Robotic and laparoscopic hysterectomy have similar rates perioperative complications in patients with endometrial cancer and obesity, but robotic hysterectomy may reduce conversions because of positional intolerance in patients with morbid obesity. Existing literature is limited by selection and confounding bias, and randomized trials are needed to inform practice standards in this population.

Comprehensive identification of pleiotropic loci for body fat distribution using the NHGRI-EBI Catalog of published genome-wide association studies.

We conducted a hypothesis-free cross-trait analysis for waist-to-hip ratio adjusted for body mass index (WHRadjBMI ) loci derived through genome-wide association studies (GWAS). Summary statistics from published GWAS were used to capture all WHRadjBMI single-nucleotide polymorphisms (SNPs), and their proxy SNPs were identified. These SNPs were used to extract cross-trait associations between WHRadjBMI SNPs and other traits through the NHGRI-EBI GWAS Catalog. Pathway analysis was conducted for pleiotropic WHRadjBMI SNPs. We found 160 WHRadjBMI SNPs and 3675 proxy SNPs. Cross-trait analysis identified 239 associations, of which 100 were for obesity traits. The remaining 139 associations were filtered down to 101 unique linkage disequilibrium block associations, which were grouped into 13 categories: lipids, red blood cell traits, white blood cell counts, inflammatory markers and autoimmune diseases, type 2 diabetes-related traits, adiponectin, cancers, blood pressure, height, neuropsychiatric disorders, electrocardiography changes, urea measurement, and others. The highest number of cross-trait associations were found for triglycerides (n = 10), high-density lipoprotein cholesterol (n = 9), and reticulocyte counts (n = 8). Pathway analysis for WHRadjBMI pleiotropic SNPs found immune function pathways as the top canonical pathways. Results from our original methodology indicate a novel genetic association between WHRadjBMI and reticulocyte counts and highlight the pleiotropy between abdominal obesity, immune pathways, and other traits.