Citations

ABSTRACT Background The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH. Aims In the US multicentre SHUNT‐V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy. Methods Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices. DSI was calculated from clearances of labelled cholates after oral and intravenous administration. DSI ≤ 18.3 was evaluated as a cut‐off for ruling out LEV with acceptance criteria of negative likelihood ratio < 0.52 and sensitivity > 85%. Results SHUNT‐V enrolled 306 subjects; 275 had both DSI and endoscopy, and 238 had Child–Pugh A cirrhosis (52.1% MASLD/MASH, 25.2% chronic hepatitis C and 15.6% alcoholic liver disease; 87% were overweight, 64% were obese and 54% had diabetes). AUROCs for DSI ranged from 0.81 to 0.82 for LEV and 0.79 to 0.80 for all significant PH lesions. DSI 18.3 had sensitivity 96.3%–100% for LEV and 97.3%–100% for all significant PH lesions. If DSI ≤ 18.3 were used as the sole determinant to defer EGD, 27%–35% of EGDs could have been avoided with 0%–3.7% of LEV and 0%–2.7% of all significant PH lesions missed. Conclusions HepQuant DSI predicts the likelihood of LEV and significant PH lesions across a spectrum of patient characteristics and disease aetiologies. DSI, based on liver function and portal‐systemic shunting, can aid in the decision to defer endoscopy for varices in patients with Child–Pugh A cirrhosis. Trial Registration: The SHUNT‐V study was registered at ClinicalTrials.gov (NCT03583996)

Abstract Prostate cancer is a significant health concern and the most commonly diagnosed cancer in men worldwide. Understanding the complex process of prostate tumor evolution and progression is crucial for improved diagnosis, treatments, and patient outcomes. Previous studies have focused on unraveling the dynamics of prostate cancer evolution using phylogenetic or lineage analysis approaches. However, those approaches have limitations in capturing the complete disease process or incorporating genomic and transcriptomic variations comprehensively. In this study, we applied a novel computational approach to derive a prostate cancer progression model using multidimensional data from 497 prostate tumor samples and 52 tumor-adjacent normal samples obtained from The Cancer Genome Atlas study. The model was validated using data from an independent cohort of 545 primary tumor samples. By integrating transcriptomic and genomic data, our model provides a comprehensive view of prostate tumor progression, identifies crucial signaling pathways and genetic events, and uncovers distinct transcription signatures associated with disease progression. Our findings have significant implications for cancer research and hold promise for guiding personalized treatment strategies in prostate cancer. Significance: We developed and validated a progression model of prostate cancer using &gt;1,000 tumor and normal tissue samples. The model provided a comprehensive view of prostate tumor evolution and progression.

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.