Abstract Background The aim of this study was to investigate whether postoperative adjuvant transcatheter arterial chemoembolization (TACE) treatment in wide- and narrow-margin groups could improve the long-term prognosis of patients with hepatocellular carcinoma (HCC). Materials and Methods A total of 670 patients with HCC who underwent radical hepatectomy from January 2016 to December 2017 were enrolled, including 397 patients and 273 patients in the wide- and narrow-margin groups. Recurrence-free survival (RFS) and overall survival (OS) outcomes were compared in the wide-margin and narrow-margin groups with and without adjuvant TACE postoperatively, respectively. Propensity score matching (PSM) analysis was used to match patients between TACE and no TACE groups in a 1:1 ratio. Results The wide-margin resection was associated with better RFS and OS rates than narrow-margin resection for patients with HCC. Patients with postoperative adjuvant TACE had a better RFS and OS than patients without postoperative adjuvant TACE in the narrow-margin group and reduced the intrahepatic recurrence rate (39.1% vs. 52.6%, P = .036) and the local recurrence rate in the liver (11.2% vs. 21.4%, P = .032). But postoperative adjuvant TACE did not alter recurrence and survival outcomes in the wide-margin group. Similar results were noted after propensity score matching (PSM). Conclusion The wide-margin resection had better RFS and OS than the narrow-margin resection for patients with HCC. Postoperative adjuvant TACE was associated with reduced recurrence and improved OS after narrow-margin resection, but was not effective in the wide-margin resection.
The occurrence of hepatocellular carcinoma (HCC) is not entirely clear at present. This study comprehensively described the landscape of genetic aberrations in Chinese HCC patients using next-generation sequencing (NGS) and investigated the association of genetic aberrations with clinicopathological characteristics and prognosis.The clinicopathological data of 78 HCC patients undergoing surgery were retrospectively analyzed. The genomic DNA extracted from tumor samples was detected using a NGS-based gene panel.Mutations in TP53 (55%), TERT (37%), MUC16 (29%) and CTNNB1 (27%) were most common in HCC. The co-occurrences between frequently mutated genes occurring ≥10% were relatively common in HCC. Forty-eight (61.5%) cases harbored DNA damage repair gene mutations, mainly including PRKDC (11.5%), SLX4 (9.0%), ATM (7.7%), MSH6 (7.7%), and PTEN (6.4%), and 39 (50.0%) patients had at least one actionable mutation. FH amplification (odds ratio: 3.752, 95% confidence interval: 1.170-12.028, p=0.026) and RB1 mutations (odds ratio: 13.185, 95% confidence interval: 1.214-143.198, p=0.034) were identified as the independent risk factors for early postoperative recurrence in HCC.Our study provides a novel insight into the genomic profiling of Chinese HCC patients. FH amplification and RB1 mutations may be associated with an increased risk of early postoperative recurrence in HCC.
Hepatocellular carcinoma (HCC) is one of the most malignant cancers worldwide, with high mortality. However, the molecular regulatory mechanisms of liver cancer, especially transcriptional and post-transcriptional mechanisms, should be further studied. Here we used chromatin and cross-linking immunoprecipitation with high throughput sequencing methods (ChIP-seq and CLIP-seq) to capture the global binding profiles on RNAs and DNAs of Enhancer of zeste homolog 2 (EZH2) and its partner Jumonji And AT-Rich Interaction Domain Containing 2 (JARID2) in liver carcinoma cell lines (HepG2) and normal liver cell line (THLE-2), respectively. We also integrated HCC transcriptome data from the TCGA to analyze the expression pattern of bound genes. We found that EZH2 and JARID2 both showed distinct binding profiles between HepG2 and THLE-2 cells. By binding to the primary RNAs, bound transcripts of EZH2 and JARID2 in HepG2 showed significantly increased transcriptional levels in HCC patients. By performing gene set enrichment analysis (GSEA), the bound transcripts were also highly related to HCC development. We also found EZH2 and JARID2 could specifically bind to several long noncoding RNAs (lncRNAs), including H19. By exploring the DNA binding profile, we detected a dramatically repressed DNA binding ability of EZH2 in HepG2 cells. We also found that the EZH2-bound genes showed slightly increased transcriptional levels in HepG2 cells. Integrating analysis of the RNA and DNA binding profiles suggests EZH2 and JARID2 shift their binding ability from DNA to RNA in HepG2 cells to promote cancer development in HCC. Our study provided a comprehensive and distinct binding profile on RNAs and DNAs of EZH2 and JARID2 in liver cancer cell lines, suggesting their potential novel functional manners to promote HCC development.
Abstract Aims Few studies have investigated differences in sequential transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and simultaneous RFA‐TACE for the treatment of hepatocellular carcinoma (HCC) using the Milan criteria. This study explored the differences in safety and prognosis between sequential TACE‐RFA and simultaneous RFA‐TACE. Methods This retrospective real‐world study included 109 patients with HCC within the Milan criteria who underwent sequential TACE‐RFA ( n = 75) or simultaneous RFA‐TACE ( n = 34) at the Eastern Hepatobiliary Surgery Hospital between January 2017 and 2021. Postoperative complications, length of hospital stay, and long‐term prognosis were compared. The median follow‐up duration of these patients was 39.1 months. Overall survival (OS) and time to tumor recurrence (TTR) curves were plotted using the Kaplan−Meier method and were compared using the logarithmic rank test. Independent risk factors for OS and tumor recurrence (TR) were analyzed using the Cox risk regression model. Results Multivariate analysis showed that tumor diameter >3 cm (hazard ratio [HR]: 2.201, 95% confidence interval [CI]: 1.106–4.378, p = 0.025; HR: 2.236, 95% CI: 1.271–3.934, p = 0.005, respectively) and alpha‐fetoprotein (AFP) > 400 μg/L (HR: 2.362, 95% CI: 1.195–4.668, p = 0.013; HR: 1.798, 95% CI: 1.048–3.086, p = 0.033, respectively) were independent risk factors for OS and TTR, whereas the presence of multiple tumors (HR: 2.352, 95% CI: 1.127–4.907, p = 0.023) was an independent risk factor for TTR. Simultaneous RFA‐TACE did not have an effect on OS or TTR. After propensity score‐matched, comparable results were obtained and RFA‐TACE still had no effect on OS or TTR. No significant differences were observed in grade III/IV complications (2/75 [2.7%] vs. 1/34 [2.9%], p = 1.000) between the two groups. However, the RFA‐TACE group had fewer complications than the TACE‐RFA group (24/34 [70.6%] vs. 66/75 [88.0%], p = 0.026). The RFA‐TACE group had a shorter hospital stay and less total cost during hospitalization compared with the TACE‐RFA group (6.0 vs. 10.0 days, p < 0.001; 30,000 vs. 35,000 CNY, p < 0.001). Conclusions For HCC within the Milan criteria, there was no significant difference in OS and TTR between RFA‐TACE and TACE‐RFA. However, RFA‐TACE could reduce all‐grade complications and shorten the length of hospital stay compared with TACE‐RFA. Therefore, simultaneous RFA‐TACE may be considered for patients with HCC and good liver function falling within the Milan criteria.
Abstract Serum hepatitis B core‐related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aimed to explore the prognostic value of HBcrAg on patients with hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) after curative hepatectomy undergoing antiviral therapy (AVT). Data of 949 consecutive patients with HBV‐related HCC undergoing curative resection between 2010 and 2013 were reviewed. Serum HBcrAg levels were measured at surgery (baseline) for all patients and at the time of 2 years postoperatively (on‐treatment) for those without recurrence. Primary endpoint was tumor recurrence. High HBcrAg levels are associated with malignant phenotypes. HBcrAg independently affected both recurrence and overall survival (OS) in patients with negative hepatitis B e antigen (HBeAg−, p = .007 and p = .042, respectively) but not in their positive HBeAg (HBeAg+) counterparts ( p = .100 and p = .075, respectively). Patients with high baseline HBcrAg had higher late, but not early recurrence rates than those with low baseline HBcrAg levels, regardless of HBeAg status (HBeAg+: p = .307 for early, p = .001 for late; HBeAg−: p = .937 for early, p < .001 for late). On‐treatment HBcrAg independently affected late recurrence in patients stratified by both cirrhosis and HBeAg ( p < .001 for all). The predictive power of HBcrAg kinetics for late recurrence was better than that of the baseline and on‐treatment HBcrAg. High HBcrAg levels during long‐term AVT are associated with late recurrence of HCC after hepatectomy. Combining baseline and on‐treatment HBcrAg might be valuable in identifying patients at a high risk of relapse and stratifying surveillance strategies postoperatively.
The objective of this study was to investigate the impact of surgical margin and hepatic resection on prognosis and compare their importance on prognosis in patients with hepatocellular carcinoma (HCC).The clinical data of 906 patients with HCC who underwent hepatic resection in our hospital from January 2013 to January 2015 were collected retrospectively. All patients were divided into anatomical resection (AR) (n = 234) and nonanatomical resection (NAR) group (n = 672) according to type of hepatic resection. The effects of AR and NAR and wide and narrow margins on overall survival (OS) and time to recurrence (TTR) were analyzed.In all patients, narrow margin (1.560, 1.278-1.904; 1.387, 1.174-1.639) is an independent risk factor for OS and TTR, and NAR is not. Subgroup analysis showed that narrow margins (2.307, 1.699-3.132; 1.884, 1.439-2.468), and NAR (1.481, 1.047-2.095; 1.372, 1.012-1.860) are independent risk factors for OS and TTR in patients with microvascular invasion (MVI)-positive. Further analysis showed that for patients with MVI-positive HCC, NAR with wide margins was a protective factor for OS and TTR compared to AR with narrow margins (0.618, 0.396-0.965; 0.662, 0.448-0.978). The 1, 3, and 5 years OS and TTR rate of the two group were 81%, 49%, 29% versus 89%, 64%, 49% (P = .008) and 42%, 79%, 89% versus 32%, 58%, 74% (P = .024), respectively.For patients with MVI-positive HCC, AR and wide margins were protective factors for prognosis. However, wide margins are more important than AR on prognosis. In the clinical setting, if the wide margins and AR cannot be ensured at the same time, the wide margins should be ensured first.
Abstract Background Data on the impact of antiviral therapy(AVT) on the long-term outcomes of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) patients with cirrhosis after hepatectomy are limited. We aimed to determine the effect of AVT on HBV-related cirrhotic HCC. Methods A total of 1396 patients with HBV-related cirrhotic HCC who underwent curative resection and received entecavir for postoperative AVT were categorized into AVT and no-AVT groups. Recurrence and overall survival(OS) rates were compared, especially according to the initiation time of AVT, virological response, and low HBV levels. Results The 1-, 3-, 5- and 10-year recurrence rates in AVT group(n = 432) were lower than those in no-AVT group(n = 964, 26%, 49%, 65% and 76% vs. 29%, 69%, 87% and 92%,P < 0.001) and OS rates were higher(95%, 69%, 54% and 34% vs. 94%, 53%, 35% and 11%,P < 0.001). AVT was an independent factor for late, but not early, recurrence(P < 0.001). The 3-, 5-, and 10-year recurrence rates were similar between patients with only postoperative AVT and those with both pre-and postoperative AVT(P = 0.772). In the AVT group, the 3-, 5-, and 10-year recurrence rates in patients with persistent virological response(PVR) were lower than those in patients with low detectable viral levels(LDV, P = 0.003). Logistic analysis showed that the time to virological response(P < 0.001) and HBeAg positivity(P < 0.001) were independently associated with LDV. Patients with spontaneous or treatment-induced undetectable HBV showed the lowest and similar late recurrence rates(P = 0.796). Conclusions Long-term AVT, regardless of preoperative or postoperative initiation, reduced post-resection late recurrence in patients with HCC and cirrhosis, especially in those with PVR.
Abstract Background Hepatectomy is an effective treatment for synchronous colorectal liver metastases (SCLM) patients. However, whether to choose simultaneous hepatectomy (SIH) or staged hepatectomy (STH) is still controversial, especially during major hepatectomy (≥3 liver segments). Aims Compare the difference between the SCLM patients underwent SIH and STH, especially during major hepatectomy (≥3 liver segments). Methods and Results A meta‐analysis was conducted by analyzing the published data on the outcomes of SCLM patients underwent SIH or STH from January 2010 to December 2020 from the electronic databases. A random‐effects model was used to derive pooled estimates of odds ratio (OR) with 95% confidence interval (CI) for the explored outcomes. Eventually, 18 studies, including 5101 patients, were included this study. The result of meta‐analysis showed that SIH did not increase postoperative complications (pooled OR: 1.037; 95% CI: 0.897–1.200), perioperative mortality (pooled OR: 0.942; 95% CI: 0.552–1.607), 3‐year mortality (pooled OR: 1.090; 95% CI: 0.903–1.316) or 5‐year mortality (pooled OR: 1.077; 95% CI: 0.926–1.253), as compared with STH. Subgroup analysis showed that, simultaneous major hepatectomy (SIMH) also did not increase postoperative complications (pooled OR: 0.863; 95% CI: 0.627–1.188) or perioperative mortality (pooled OR: 0.689; 95% CI: 0.290–1.637) as compared with staged major hepatectomy (STMH). Conclusion Postoperative complications, perioperative mortality and long‐term prognosis had no significant difference between SIH and STH for SCLM patients. Besides, postoperative complications and perioperative mortality also had no significant difference between SIMH and STMH.
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