Favorable Survival with Non-curative Treatments for Patients with Early-Stage Hepatocellular Carcinoma After Liver Transplant Denial.

BACKGROUND: Many patients are not candidates for liver transplant for non-tumor-related reasons including medical comorbidities and non-adherence. The prognosis of patients with hepatocellular carcinoma (HCC) who are not liver transplant candidates in the era of locoregional therapy (LRT) including y90 is not well defined. AIMS: This study seeks to evaluate outcomes and the natural history of early-stage HCC in patients who were denied liver transplant listing due to non-tumor reasons and instead were treated with LRT. METHODS: A retrospective evaluation was performed for all patients who completed liver transplant evaluation with their tumor within Milan criteria but were denied due to non-tumor reasons and were treated with LRT at a single tertiary referral center. RESULTS: The 61 patients included had a favorable overall survival, with a median survival 60.3 months (86.9% at 1 year and 52.7% at 5 years). Patients with Child-Pugh A cirrhosis (n = 34) had significantly longer overall survival compared to those with Child-Pugh B/C cirrhosis (median survival of 70.3 months versus 26.1 months, p = 0.005). Survival in patients with Child-Pugh A at 1, 3, and 5 years was 97%, 80%, and 73%, respectively, compared to 74%, 41%, and 31% in patients with Child-Pugh B/C. CONCLUSIONS: In a small single-center cohort, patients with HCC who were denied liver transplant due to non-tumor reasons and underwent LRT and had Child-Pugh A cirrhosis had survival approaching the national average for patients who undergo liver transplantation. Patients with Child-Pugh B/C cirrhosis had significantly worse outcomes than those with Child-Pugh A.

Malignant Peritoneal Mesothelioma Presenting as Mucinous Ascites.

We present a rare case of a 46-year-old man presenting with mucinous ascites secondary to malignant peritoneal mesothelioma (MPM) that was diagnosed via colonoscopy with biopsies. Both our findings and the clinical presentation were unique. While it is widely known that asbestos exposure is commonly associated with pleural mesothelioma, 6-10% of malignant mesotheliomas arise from the peritoneum. To date, only 4 cases of MPM with the primary tumor site in the colon have been described in the literature.

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease.

The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance in tissues. In this review, we highlight the lipids and carbohydrates that provoke hepatocyte injury and the mechanisms involved in lipotoxicity and glucotoxicity, including endoplasmic reticulum stress, oxidative stress and mitochondrial impairment. Through upregulation of proteins involved in various pathways including PKR-like ER kinase (PERK), CCAAT/enhancer-binding homologous protein (CHOP), c-Jun NH2-terminal kinase-1 (JNK), Bcl-2 interacting mediator (BIM), p53 upregulated modulator of apoptosis (PUMA), and eventually caspases, hepatocytes in lipotoxic states ultimately undergo apoptosis. The protective role of certain lipids and possible targets for pharmacological therapy are explored. Finally, we discuss the role of high fructose and glucose diets in contributing to organelle impairment and poor glucose transport mechanisms, which perpetuate hyperglycemia and hyperlipidemia by shunting of excess carbohydrates into lipogenesis.