Analysis of technical failure after 1,613 surgical microwave ablations: A propensity score-matched analysis.

BACKGROUND: Microwave ablation is becoming increasingly common for the treatment of liver tumors. Despite numerous studies aimed at identifying risk factors for local recurrence after microwave ablation, a consensus on modifiable risk factors for failure remains elusive, partly because of the limited statistical power of these studies. This study investigated the incidence of technical failure after microwave ablation, encompassing both incomplete ablation and local recurrence, and aimed to identify modifiable factors that reduce technical failure. METHODS: This retrospective review included patients who underwent surgical microwave ablation at a high-volume institution between October 2006 and March 2023. Univariate analysis, multivariate analysis, and propensity score matching were performed to identify risk factors for technical failure. RESULTS: A total of 1,613 surgical microwave ablations were performed on 3,035 tumors, with 226 instances (14% per procedure, 7.4% per tumor) of technical failure. Incomplete ablation occurred at a rate of 1.7% per tumor, whereas local recurrence was identified in 6.5% of ablations in per-tumor analysis. Body mass index >25 was significant for failure (odds ratio, 1.50; 95% confidence interval, 1.07-2.11; P < .05), suggesting that more difficult targeting may lead to increased technical failure rates. African American race (odds ratio, 1.62; 95% confidence interval, 1.16-2.27; P < .05), pre-microwave ablation transarterial chemoembolization (odds ratio, 1.54; 95% confidence interval, 1.08-2.21; P < .05), and previous ablation (odds ratio, 1.58; 95% confidence interval, 1.09-2.29; P < .05) were found to be statistically significant. CONCLUSION: On the basis of the largest microwave ablation database available to date, this study identified novel modifiable and nonmodifiable risk factors of microwave ablation failure. These results can lead to decreasing technical failure rates after microwave ablation.

The common p.Ile291Val variant of ERLIN1 enhances TM6SF2 function and is associated with protection against MASLD.

BACKGROUND: The ERLIN1 p.Ile291Val single-nucleotide polymorphism (rs2862954) is associated with protection from steatotic liver disease (SLD), but effects of this variant on metabolic phenotypes remain uncertain. METHODS: Metabolic phenotypes and outcomes associated with ERLIN1 p.Ile291Val were analyzed by using a genome-first approach in the UK Biobank (UKB), Penn Medicine BioBank (PMBB), and All of Us cohort. FINDINGS: ERLIN1 p.Ile291Val carriers exhibited significantly lower serum levels of alanine aminotransferase and aspartate aminotransferase as well as higher levels of triglycerides, low-density lipoprotein cholesterol, Apolipoprotein B, high-density lipoprotein cholesterol, and Apolipoprotein A1 in UKB, and these values were affected by ERLIN1 p.Ile291Val in an allele-dose-dependent manner. Homozygous ERLIN1 p.Ile291Val carriers had a significantly reduced risk of developing metabolic dysfunction-associated SLD (MASLD, adjusted odds ratio [aOR] = 0.92, 95% confidence interval [CI], 0.88-0.96). The protective effect of this variant was enhanced in patients with alcoholic liver disease. Our results were replicated in PMBB and the All of Us cohort. Strikingly, the protective effects of ERLIN1 p.Ile291Val were not apparent in individuals carrying the TM6SF2 p.Glu167Lys variant associated with increased risk of SLD. We analyzed the effects of predicted loss-of-function ERLIN1 variants and found that they had opposite effects, namely reduced plasma lipids, suggesting that ERLIN1 p.Ile291Val may be a gain-of-function variant. CONCLUSION: Our study contributes to a better understanding of ERLIN1 by investigating a coding variant that has emerged as a potential gain-of-function mutation with protective effects against MASLD development.

Outcomes after Surgical Microwave Ablation for the Treatment of Colorectal Liver Metastasis.

BACKGROUND: Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Of these, approximately 25% will have liver metastasis. We performed 394 microwave ablations (MWAs) and analyzed outcomes for survival and ablation failure. STUDY DESIGN: We conducted a retrospective review of patients who underwent a surgical MWA at a single-center high-volume institution from October 2006 to September 2022 using a prospectively maintained database. The primary outcome was overall survival. RESULTS: A total of 394 operations were performed on 328 patients with 842 tumors undergoing MWA. Median tumor size was 1.5 cm (range 0.4 to 7.0 cm), with the median number of tumors ablated per operation being 1 (range 1 to 11). A laparoscopic approach was used 77.9% of the time. Concomitant procedures were performed 63% of the time, most commonly hepatectomy (22.3%), cholecystectomy (17.5%), and colectomy (6.6%). Clavien-Dindo grade III or IV complication occurred in 12 patients (3.6%), and all of these patients had undergone concomitant procedures. Mortality within 30 days occurred in 4 patients (1.2%). The rate of incomplete ablation was 1.5% per tumor. Local recurrence occurred at a rate of 6.3% per tumor. Black patients were found to have a higher incidence of incomplete ablation and local recurrence. One-year survival probability was 91% (95% CI 87.9 to 94.3), with a mean overall survival of 57.6 months (95% CI 49.9 to 65.4 months). CONCLUSIONS: Surgical MWA offers a low-morbidity approach to treatment of colorectal liver metastasis, with low rate of failure. This large series reviews the outcomes of MWA as definitive treatment for colorectal liver metastasis.

A missense variant in human perilipin 2 (PLIN2 Ser251Pro) reduces hepatic steatosis in mice.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is characterised by the accumulation of lipid droplets (LDs) within hepatocytes. Perilipin 2 (PLIN2) is the most abundant protein in hepatic LDs and its expression correlates with intracellular lipid accumulation. A recently discovered PLIN2 coding variant, Ser251Pro (rs35568725), was found to promote the accumulation of small LDs in embryonic kidney cells. In this study, we investigate the role of PLIN2-Ser251Pro (PLIN2-Pro251) on hepatic LD metabolism in vivo and research the metabolic phenotypes associated with this variant in humans. Methods: For our animal model, we used Plin2 knockout mice in which we expressed either human PLIN2-Pro251 (Pro251 mice) or wild-type human PLIN2-Ser251 (Ser251 mice) in a hepatocyte-specific manner. We fed both cohorts a lipogenic high-fat, high-cholesterol, high-fructose diet for 12 weeks. Results: Pro251 mice were associated with reduced liver triglycerides (TGs) and had lower mRNA expression of fatty acid synthase and diacylglycerol O-acyltransferase-2 compared with Ser251 mice. Moreover, Pro251 mice had a reduction of polyunsaturated fatty acids-TGs and reduced expression of epoxygenase genes. For our human study, we analysed the Penn Medicine BioBank, the Million Veteran Program, and UK Biobank. Across these databases, the minor allele frequency of PLIN2-Pro251 was approximately 5%. There was no association with the clinical diagnosis of NAFLD, however, there was a trend toward reduced liver fat in PLIN2-Pro251 carriers by MRI-spectroscopy in UK Biobank subjects. Conclusions: In mice lacking endogenous Plin2, expression of human PLIN2-Pro251 attenuated high-fat, high-fructose, high-cholesterol, diet-induced hepatic steatosis compared with human wild-type PLIN2-Ser251. Moreover, Pro251 mice had lower polyunsaturated fatty acids-TGs and epoxygenase genes expression, suggesting less liver oxidative stress. In humans, PLIN2-Pro251 is not associated with NAFLD. Impact and Implications: Lipid droplet accumulation in hepatocytes is the distinctive characteristic of non-alcoholic fatty liver disease. Perilipin 2 (PLIN2) is the most abundant protein in hepatic lipid droplets; however, little is known on the role of a specific polymorphism PLIN2-Pro251 on hepatic lipid droplet metabolism. PLIN2-Pro251 attenuates liver triglycerides accumulation after a high-fat-high-glucose-diet. PLIN2-Pro251 may be a novel lipid droplet protein target for the treatment of liver steatosis.