Population-based study on practice variation regarding preoperative systemic chemotherapy in patients with colorectal liver metastases and impact on short-term outcomes

IntroductionDefinitions regarding resectability and hence indications for preoperative chemotherapy vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study aimed to assess the variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands.Materials and methodsAll patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national database. Case-mix factors contributing to the use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30-day morbidity and 30-day mortality.ResultsIn total, 4469 patients were included of whom 1314 patients received preoperative chemotherapy and 3155 patients did not. Patients receiving chemotherapy were significantly younger (mean age (+SD) 66.3 (10.4) versus 63.2 (10.2) p < 0.001) and had less comorbidity (Charlson scores 2+ (24% versus 29%, p = 0.010). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 2% and 55%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.24, 0.98–1.55, p = 0.065), 30-day morbidity (OR 1.05, 0.81–1.39, p = 0.703) or with 30-day mortality (OR 1.22, 0.75–2.09, p = 0.467) was found.ConclusionSignificant hospital variation in the use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and use of preoperative chemotherapy was found.     

NLRP12 negatively regulates EtOH-induced liver macrophage activation via NF-κB pathway and mediates hepatocyte apoptosis in alcoholic liver injury

Alcohol-induced liver injury is characterized by abnormal liver dysfunction and excessive inflammation response. Recent years a wealth of data have been yielded indicating that EtOH (ethyl alcohol)-induced macrophage activation along with liver inflammation plays a dominating role in the progression of alcohol-induced liver injury. Here we found high expression of NLRP12 (Nucleotide-binding oligomerization domain protein 12, which is generally considered to be a negative regulator of inflammatory response) in EtOH-fed mouse liver tissue, primary Kupffer cells and EtOH-induced RAW264.7 cells. Additionally, overexpression of NLRP12 following Ad (adenovirus)-NLRP12-EGFP contributed to the attenuation of steatosis and inflammation in EtOH-fed mice model and EtOH-primed RAW264.7 cells. In parallel, Knockdown of NLRP12 aggravated the inflammatory response in RAW264.7 cells triggered by EtOH. Meanwhile, after administration of overexpression or inhibition of NLRP12 expression in vitro, the expression of phosphorylated protein of NF-kB signaling pathway was significantly affected. After increasing or decreasing the expression of NLRP12 in RAW264.7 cells, AML-12 cells were cultured with the supernatant of RAW264.7 cells stimulated by EtOH, and the percent of apoptosis ratio of AML-12 cells was remarkably altered. The study suggested that reduced inflammatory response induced by NLRP12-mediated inhibition of NF-kB pathway participated in the decrease of hepatocyte apoptosis in alcohol-induced liver injury. Collectively, these findings suggested the significance of NLRP12-mediated macrophage activation in alcohol-induced liver injury.     

The good,the bad,and the ugly facets of insulin resistance

Insulin is a potent anabolic hormone, and binding to its receptor activates downstream intracellular signaling pathways that regulate the nutrient metabolism, fluid homeostasis, growth, ionic transport, maintenance of vascular tone, and other functions. Insulin resistance (IR) is a condition characterized by subnormal cellular response to physiological levels of insulin. The IR is divided into three types (prereceptor, receptor, and postreceptor) based on the site of pathology. Beta cells attempt to overcome the IR by increasing the release of insulin, leading to hyperinsulinemia. IR is the predisposing factor for many metabolic and cardiovascular disorders. From the evolutionary perspective, the presence of IR offers a survival advantage in the face of starvation or stress. In this brief review, we discuss the different facets of insulin resistance and appraise the readers about the hitherto neglected beneficial advantages.     

肝细胞癌肝移植供肝选择策略

供肝数量不足是制约肝移植发展的主要因素,更是制约肝细胞癌肝移植治疗的突出因素。既往对肝细胞癌肝移植的研究多集中在受者选择标准、降期治疗、免疫抑制方案等方面,近年来研究发现供肝的选择对肝细胞癌肝移植术后肿瘤复发也有显著影响。笔者从临床供肝的主要类型、肝细胞癌肝移植适应证的把握、适应证内肝细胞癌肝移植和超适应证肝细胞癌肝移植的供肝选择以及供肝选择对肝细胞癌肝移植预后的影响进行深入探讨。     

Metabolic dysfunction-associated fatty liver disease — How relevant is this to primary care physicians and diabetologists?

Metabolic-dysfunction associated fatty liver disease (MAFLD) is a newly introduced entity hoping to more precisely define fatty liver disease. Despite the controversies surrounding MAFLD, the definition is getting more widely accepted by the global liver-health community. MAFLD represents a cohort of patients enriched with more advanced liver disease, cardio-renal and metabolic complications with increased mortality. This review aims to provide all primary care physicians and diabetologists with a clinical management update from a non-hepatologist’s perspective, and a summary of important findings from recent studies to raise disease awareness and highlight the relevance of MAFLD to their daily clinical practice.     

International trends in hepatocellular carcinoma incidence, 1978–2012

Primary liver cancer, the major histology of which is hepatocellular carcinoma (HCC), is the second leading cause of cancer death worldwide. We comprehensively examined recent international trends of primary liver cancer and HCC incidence using population-based cancer registry data. Incidence for all primary liver cancer and for HCC by calendar time and birth cohort was examined for selected countries between 1978 and 2012. For each successive 5-year period, age-standardized incidence rates were calculated from Volumes V to XI of the Cancer Incidence in Five Continents (CI5) series using the online electronic databases, CI5plus. Large variations persist in liver cancer incidence globally. Rates of liver cancer remain highest in Asian countries, specifically in the East and South-East, and Italy. However, rates in these high-risk countries have been decreasing in recent years. Rates in India and in most countries of Europe, the Americas and Oceania are rising. As the population seroprevalence of hepatitis B virus (HBV) continues to decline, we anticipate rates of HCC in many high-risk countries will continue to decrease. Treatment of hepatitis C virus (HCV) is likely to bring down rates further in some high-rate, as well as low-rate, countries with access to effective therapies. However, such gains in the control of liver cancer are at risk of being reversed by the growing obesity and diabetes epidemics, suggesting diabetes treatment and primary prevention of obesity will be key in reducing liver cancer in the longer-term.     

王晞星辨治大肠癌肝转移经验

介绍王晞星教授辨治大肠癌肝转移的临床经验。认为大肠癌肝转移的根本病机为肝脾两虚、痰瘀毒结;临证以调和肝脾为重,减毒消癥为辅,标本兼顾,攻补兼施;研创特色方药补中调肝汤,和法抗癌,疗效显著。并附验案1则。