Chemoprevention of hepatocellular carcinoma using N-acetylgalactosamine-conjugated siRNAs.

The ability to prevent hepatocellular carcinoma (HCC) in patients with chronic liver disease remains an unmet clinical need. We performed a head-to-head comparison of N-acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA)-mediated inhibition of five genes (CDK1, PD-L1, CTNNB1, SMYD3, ANLN) to prevent cancer in four distinct autochthonous HCC mouse models. siRNA targeting Cdk1 and Anln (siCdk1 and siAnln, respectively) increased overall survival in the CTNNB1/MYC hydrodynamic transfection (HDT) model, in which HCC formation is driven by oncogenes.

Somatic mutations in TBX3 promote hepatic clonal expansion by accelerating VLDL secretion.

Somatic mutations that increase clone fitness or resist disease are positively selected, but the impact of these mutations on organismal health remains unclear. We previously showed that Tbx3 deletion increases hepatocyte fitness within fatty livers. Here, we detected TBX3 somatic mutations in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

Somatic loss-of-function mutations in CIDEB reduce hepatic steatosis by increasing lipolysis and fatty acid oxidation.

Background & Aims: Somatic and germline CIDEB mutations are associated with protection from chronic liver diseases. The mechanistic basis and whether CIDEB suppression would be an effective therapy against fatty liver disease remain unclear.

Methods: 21 CIDEB somatic mutations were introduced into cells to assess functionality.

Impact of age on clinical outcomes among patients with hepatocellular carcinoma: A systematic review and meta-analysis.

Background & Aims: Older adults have lower treatment eligibility and worse survival across cancer types; however, the association between age and outcomes in patients with hepatocellular carcinoma (HCC) has not been well characterized.

Methods: We performed a search of the PubMed, Ovid MEDLINE, and EMBASE databases from January 2000 to July 2022 to identify studies reporting tumor stage, curative treatment, and overall survival among patients with HCC, stratified by age. Using the DerSimonian and Laird method for a random-effects model, we calculated pooled risk ratios (RRs) for curative treatment receipt and hazard ratios (HRs) for overall survival among younger and older patients (per age thresholds in each study).

Clinicopathologic Features of Untreated Colorectal Cancer with Acellular Mucin-Only Lymph Nodes.

Lymph nodes (LNs) containing only acellular mucin are considered negative for metastasis in treated colorectal cancers (CRCs). However, no data exist on how to stage these LNs in untreated CRCs. We collected 63 untreated CRC cases with LNs containing only acellular mucin from 27 US institutions and 23 additional cases from the Dutch Nationwide Pathology Databank.

The evolving role of liver biopsy: Current applications and future prospects.

Histopathologic evaluation of liver biopsy has played a longstanding role in the diagnosis and management of liver disease. However, the utility of liver biopsy has been questioned by some, given the improved imaging modalities, increased availability of noninvasive serologic tests, and development of artificial intelligence over the past several years. In this review, we discuss the current and future role of liver biopsy in both non-neoplastic and neoplastic liver diseases in the era of improved noninvasive laboratory, radiologic, and digital technologies.

Spatial omics-based machine learning algorithms for the early detection of hepatocellular carcinoma.

Background: Worldwide, hepatocellular carcinoma (HCC) is the second most lethal cancer, although early-stage HCC is amenable to curative treatment and can facilitate long-term survival. Early detection has proved difficult, as proteomics, transcriptomics, and genomics have been unable to discover suitable biomarkers.

Methods: To find new biomarkers of HCC, we utilized a spatial omics N-glycan imaging method to identify altered glycosylation in cancer tissue (n = 53) and in paired serum of individuals with HCC (n = 23).

Laboratory Features and Pathology of Cytokine Storm Syndromes.

The laboratory diagnosis of cytokine storm syndromes (CSSs), i.e., hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS), is often challenging.

Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial.

Background: Hepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient navigation to promote HCC screening process completion in patients with cirrhosis.

Methods: Between April 2018 and September 2021, we conducted a multicentre pragmatic randomised clinical trial comparing mailed outreach plus patient navigation for HCC screening (n=1436) versus usual care with visit-based screening (n=1436) among patients with cirrhosis at three US health systems.

Clinical Data Do Not Reliably Predict Duodenal Histology at Follow-up in Celiac Disease: A 13 Center Correlative Study.

Validated nonbiopsy methods to assure duodenal mucosal healing in celiac disease are lacking, yet ongoing mucosal injury is associated with anemia, osteoporosis, and lymphoma. Most providers utilize clinical data as surrogates of mucosal status to avoid additional esophagogastroduodenoscopy. The reliability of such surrogates to predict mucosal recovery has been incompletely evaluated.

Proportion of Time Covered by Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis.

Introduction: Hepatocellular carcinoma (HCC) surveillance is associated with improved early tumor detection, but effectiveness is limited by underuse. We characterized adherence to HCC surveillance using proportion of time covered (PTC) and estimated its association with clinical outcomes among patients with cirrhosis.

Methods: We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems.

Hepatocellular Carcinoma Surveillance Patterns and Outcomes in Patients With Cirrhosis.

Background & Aims: Hepatocellular carcinoma (HCC) surveillance is associated with improved early detection and reduced mortality, although practice patterns and effectiveness vary in clinical practice. We aimed to characterize HCC surveillance patterns in a large, diverse cohort of patients with HCC.

Methods: We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems.

Herpes Proctitis in Men Mimicking Rectal Adenocarcinoma: Two Cases of an Easily Overlooked Diagnosis in the Proximal Rectum.

We describe two cases of rectal herpes simplex virus (HSV) infection in men that clinically mimicked rectal adenocarcinoma. Herpes infection in this location more commonly presents as an anal mass with viral inclusions in squamous epithelial cells. We report these cases to increase awareness of the unusual presentation as a proximal rectal mass with viral inclusions in endothelial cell nuclei.

Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease.

Somatic mutations in nonmalignant tissues accumulate with age and injury, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate genes in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to nonalcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss of Mboat7, a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance.

Multi-Institutional Study of Pathologist Reading of the Programmed Cell Death Ligand-1 Combined Positive Score Immunohistochemistry Assay for Gastric or Gastroesophageal Junction Cancer.

The assessment of the expression of programmed cell death ligand-1 (PD-L1) using immunohistochemistry (IHC) has been controversial since its introduction. The methods of assessment and the range of assays and platforms contribute to confusion. Perhaps the most challenging aspect of PD-L1 IHC is the combined positive score (CPS) method of interpretation of IHC results.