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BACKGROUND Undifferentiated embryonal sarcoma of the liver (UESL) is a neoplasm that rarely develops in adults. The main treatments for UESL are upfront gross total surgical resection and adjuvant multiagent chemotherapy. Here, we report a case of recurrent UESL in an adult treated with pembrolizumab and discuss a method to identify proper candidates for antibody of programmed cell death protein 1 (anti-PD-1) treatment. CASE SUMMARY A 69-year-old woman was admitted for abdominal pain that developed for 1 wk. Computed tomography showed a 16 cm mass in the right lobe of the liver. Right hemihepatectomy and lymphadenectomy were performed, and histological diagnosis was UESL. Six months later, the patient suffered from painless obstructive jaundice, and positron emission tomography-computed tomography revealed multiple metastases. Then, percutaneous transhepatic cholangial drainage was applied to reduce jaundice, and radiofrequency ablation was used to control the lesion near the hepatic hilum. However, the patient suffered from a serious fever caused by the tumor. The patient received treatment with pembrolizumab, and the prescribed dosage was 2 mg/kg every 3 wk. After the seventh dose, positron emission tomography-computed tomography revealed that the multiple metastases had nearly disappeared. Radiologic exam was used to evaluate the disease state, and no new lesions were found. Next-generation sequencing and immunohistology were applied to determine the reason why the patient had such a favorable response to pembrolizumab. Tumor mutation burden, microsatellite instability, and programmed death ligand 1 expression can be combined to predict the effect of PD-1 antibodies. When every one of these biomarkers are detected in a tumor patient, the patient may be a proper candidate for PD-1 antibodies. CONCLUSION Anti-PD-1 treatment for tumors needs further research to identify indications and proper biomarkers.

BACKGROUND: Angiography and subsequent endovascular therapy is an effective technique for delayed postoperative arterial hemorrhage (PAH) after hepatobiliary pancreatic surgery. In this research, we aimed to evaluate endovascular therapy choices for different sites of delayed PAH after hepatobiliary pancreatic surgery. METHODS: A total of 85 patients with delayed PAH who underwent endovascular therapy at the Department of Radioactive Intervention of Eastern Hepatobiliary Surgery Hospital were retrospectively enrolled. According to the hemorrhage site, participants were divided into 3 groups, all of whom then received embolization, covered stent placement, or a combination of both. Ongoing or recurrent hemorrhages, intervention times, complications associated with intervention, and mortality rate were documented. The chi-squared (χ(2)) test was used for statistical analysis. RESULTS: A total of 22 participants with arterial branch hemorrhage underwent superselective embolization. Overall, 81.8% (18/22) of patients underwent embolization once. The successful hemostasis rate was 77.3% (17/22), and the mortality rate was 13.6% (3/22). A total of 53 participants with arterial trunk hemorrhage underwent embolization or covered stent placement. The rate of multi-time intervention, failure to achieve hemostasis, complications associated with intervention, and mortality was lower in the stent group than in the embolization group, and there was a significant difference in complications between the 2 groups (χ(2)=4.93, P=0.026). Among a total of 10 patients with multisite hemorrhage who underwent embolization, covered stent placement, or a combination, the successful hemostasis rate was 20%; and the mortality rate was 70%. CONCLUSIONS: Superselective embolization is a safe treatment method for arterial branch hemorrhage, and covered stent placement may be a better choice for arterial trunk hemorrhage. Verification of these findings is required via additional large population studies.

Background and aims: Biliary thermal injury caused by microwave ablation (MWA) for a hepatocellular carcinoma (HCC) close to the central bile ducts always results in severe complications and leads to mortality. Some studies have demonstrated that intraductal cooling of the biliary tract with chilled saline during thermal ablation can successfully prevent these complications. In this study, we present a novel bile duct cooling technique through a percutaneous transhepatic cholangial drainage (PTCD) tube for preventing biliary thermal injury caused by MWA, and compare the feasibility and safety of the intraductal cooling technique when performed with a PTCD tube and with an endoscopic nasobiliary drainage (ENBD) tube. Methods: Participants were randomly assigned to undergo MWA of HCC with intraductal chilled saline perfusion through a PTCD tube or an ENBD tube. The main study outcomes were bile duct complications related to MWA and local tumor recurrence. p value

Background: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. Key Messages: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People’s Republic of China in December 2019.

CD147 is highly expressed in hepatocellular carcinoma (HCC) and associated with the invasion and metastasis of HCC. The efficacy of I131 -metuximab (I131 -mab), a newly developed agent that targets CD147, as a radio-immunotherapy for local HCC, has been validated in clinical practice. However, the synergistic anticancer activity and molecular mechanism of different conjugated components within I131 -mab remain unclear. In this study, the cytological experiments proved that I131 -mab inhibited the proliferation and invasion of HCC cells. Mechanically, this inhibition effect was mainly mediated by the antibody component part of I131 -mab, which could reverse the epithelial-mesenchymal transition of HCC cells partially by suppressing the phosphorylation of VEGFR-2. The inhibitory effect of I131 on HCC cell proliferation and invasion is limited, whereas, when combined with metuximab, I131 significantly enhanced the sensitivity of HCC cells to CD147-mab and consequently reinforced the anticancer effects of CD147-mab, suggesting that the two components of I131 -mab exerted synergistic anti-HCC capability. Furthermore, the experiments using SMMC-7721 human HCC xenografts in athymic nude mice showed that I131 -mab and CD147-mab significantly inhibited the growth of xenograft tumors and that I131 -mab was more effective than CD147-mab. In conclusion, our results elucidated the mechanism underlying the anti-HCC effects of I131 -mab and provided a theoretical foundation for the clinical application of I131 -mab.

Effective adjuvant treatment after hepatectomy for hepatocellular carcinoma (HCC) is an important area of research. Radioactive iodine (This randomised, controlled, multicentre, open-label, phase 2 trial was done at five medical centres in China. Patients aged 18-75 years who underwent curative-intent resection of histologically confirmed HCC expressing CD147 were randomly assigned (1:1) by a computer-generated random sequence, stratified by centre, to receive either adjuvant transarterial injection of one dose of 27·75 MBq/kgBetween April 1, 2009, and Nov 30, 2012, 485 patients were screened for eligibility. 329 (68%) of these patients were excluded and 156 (32%) were randomly assigned to receive eitherAdjuvantState Key Project on Infectious Diseases of China.

Compelling epidemiological evidences indicate a significant association between leukocyte mitochondrial DNA (mtDNA) content and incidence risk of several malignancies, including hepatocellular carcinoma (HCC). However, whether leukocyte mtDNA content affect prognosis of HCC patients and underlying mechanism has never been explored. In our study, leukocyte mtDNA content was measured in 618 HCC patients and its prognostic value was analyzed. Moreover, we detected the immunophenotypes of peripheral blood mononuclear cells (PBMCs) and plasma concentrations of several cytokines in 40 HCC patients and assessed the modulating effects of mtDNA content on immunosuppression in cell models. Our results showed that HCC patients with high leukocyte mtDNA content exhibited a significantly worse recurrence-free survival (RFS) and overall survival (OS) than those with low leukocyte mtDNA content. Leukocyte mtDNA content and TNM stage exhibited a notable joint effect in prognosis prediction. Furthermore, we found that patients with high leukocyte mtDNA content exhibited a higher frequency of CD4+CD25+FOXP3+ regulatory T (Treg) cells and lower frequency of NK cells in PBMCs and had higher TGF-β1 and lower TNF-α and IFN-γ plasma concentration when compared with those with low leukocyte mtDNA content, which suggests an immunosuppressive status. High leukocyte mtDNA content significantly enhanced the ROS-mediated secretion of TGF-β1, which accounted for higher Treg and lower NK frequency in PBMCs. In a conclusion, our study for the first time demonstrates that leukocyte mtDNA content is an independent prognostic marker complementing TNM stage and associated with an ROS-mediated immunosuppressive phenotype in HCC patients.

Hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus (PVTT) is associated with poor prognosis, early recurrence of HCC, and limited treatment options. Current guidelines do not have standardized diagnostic and treatment modalities, thus creating a need for a multidisciplinary treatment model for standardization of the treatment. Eastern Hepatobiliary Surgical Hospital (China) convened two working parties of experts from all the departments, to consolidate the current evidence, prevailing vision for the future, and experience of the practicing clinicians engaged in HCC management, so as to develop a consensus for PVTT diagnosis and treatment according to the GRADE system. Based on the quality of the existing evidence and the strength of recommendations, the consensus statements were categorized into 3 evidence levels (A/B/C) and 5 classes (I/II/IIa/IIb/III). The panel discussed and provided clarity on the management and research options in the field of HCC with PVTT. In addition, the panel also assessed the quality of the cited studies and assigned grades to the recommendation statements. Among the group of experts, there was excellent agreement with regard to effective diagnosis and treatment of HCC with PVTT. The recommendations of this consensus will provide guidance to physicians and clinical researchers on the effective management of HCC with PVTT.

Sorafenib is a multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma (HCC). However, therapeutic response to sorafenib was not equal among HCC patients. Here we present a novel system to provide quantitative information concerning sorafenib-related targets by simultaneous detection of phosphorylated ERK (pERK) and pAkt expressions in circulating tumor cells (CTCs) isolated from HCC patients. Our results showed that 90.0% of patients had a molecular classification of tissues concordant with that of CTCs. CTC counts showed a shaper decline in patients with pERK+/pAkt− CTCs after two weeks of sorafenib treatment (P < 0.01). Disease control rates were significantly different between patients with pERK+/pAkt− CTCs (11/15; 73.3%) and those without (13/44; 29.5%) (P < 0.05). Univariate and multivariate analysis indicated pERK+/pAkt− CTCs as an independent predictive factor of progression-free survival (PFS) (hazard ratio = 9.389; P < 0.01). PFS correlated with the proportion of pERK+/pAkt− CTCs (r = 0.968, P < 0.01), and was higher in patients with ≥ 40% pERK+/pAkt− CTCs compared to those with < 40% (8.4 vs. 1.3 mo; P < 0.05). In a validation set of twenty HCC patients, CTCs from patients with ≥ 40% pERK+/pAkt− CTCs had significantly higher inhibition rates of spheroid formation compared to those with < 40% (61.2 vs. 19.8%; P < 0.01). Our findings demonstrated that CTCs can be used in place of tumor tissue for characterization of pERK/pAkt expression. pERK+/pAkt− CTCs are most sensitive to sorafenib and an independent predictive factor of PFS in HCC patients treated with sorafenib.

FOXF2 is a member of the forkhead box (FOX) family of transcription factors. FOXF2 plays an important role in several tumors but its expression and role in hepatocellular carcinoma (HCC) remains unknown. Using immunohistochemistry, western blot, and real-time polymerase chain reaction, we analyzed FOXF2 expression in 295 clinicopathologically characterized HCC cases. Using RNA interference (RNAi), we investigated the effects of FOXF2 depletion on tumor cell behavior in vitro. Statistical analyses were used to determine associations between FOXF2 levels, tumor features, and patient outcomes. FOXF2 downregulation was observed in HCC tissues (p

Aberrant expression of genes in de novo lipogenesis (DNL) pathway were associated with various cancers, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of DNL genes have been reported to be associated with prognosis of some malignancies. However, the effects of SNPs in DNL genes on overall survival of HCC patients receiving transarterial chemoembolization (TACE) treatment are still unknown. In present study, nine SNPs in three genes (ACLY, ACACA and FASN) in DNL pathway were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 419 HCC patients treated with TACE, and their associations with HCC overall survival were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant and recessive). Although we did not find any significant results in total analysis (all p>0.05), our stratified data showed that SNP rs9912300 in ACLY gene was significantly associated with overall survival of HCC patients with lower AFP level and SNP rs11871275 in ACACA gene was significantly associated with overall survival of HCC patients with higher AFP level. We further identified the significant interactions between AFP level and SNP rs9912300 or rs11871275 in the joint analysis. Conclusively, our data suggest that genetic variations in genes of DNL pathway may be a potential biomarker for predicting clinical outcome of HCC patients treated with TACE.

CD147 is highly expressed in hepatocellular carcinoma (HCC) and associated with the invasion and metastasis of HCC. The efficacy of I

The functional abnormality of circadian regulation genes is involved in the development and progression of hepatocellular carcinoma (HCC). However, the association between functional single nucleotide polymorphisms (SNPs) in circadian gene NPAS2 and the overall survival of HCC patients treated with transcatheter arterial chemoembolization (TACE) has never been investigated. Six functional SNPs in the NPAS2 gene were genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese patients with HCC treated with TACE. Multivariate Cox proportional hazards model and Kaplan–Meier curves were used for the prognosis analysis. We found that two SNPs, rs1053096 and rs2305160, in the NPAS2 gene showed significant associations with overall death risk in HCC patients in the recessive model (hazard ratio [HR] = 1.48; 95% confidence interval [CI], 1.13–1.94; P = 0.004) and in the dominant model (HR = 1.63; 95% CI, 1.29–2.07; P < 0.001), respectively. Moreover, we observed a cumulative effect of these two SNPs on HCC overall survival, indicating a significant trend of increasing death risk with increasing number of unfavorable genotypes (P for trend < 0.001). Compared with the patients without any unfavorable genotypes, the HRs for patients with one and two unfavorable genotypes were 1.41 (95% CI, 1.10–1.82; P = 0.007) and 2.09 (95% CI, 1.46–2.97, P < 0.001), respectively. The haplotype and diplotype analyses further characterized the association between NPAS2 genotype and survival of HCC patients. Our results for the first time suggest that NPAS2 gene polymorphisms may serve as an independent prognostic marker for HCC patients treated with TACE.

Fast-track surgery (FTS), combining several techniques with evidence-based adjustments, has shown its effectiveness to accelerate recovery, reduce morbidity and shorten hospital stay in many operations. This randomized controlled study was carried out aiming to compare the short-term outcomes of partial hepatectomy for liver cancer managed with FTS or with conventional surgery (CS).To compare the short-term effects between FTS and CS, a randomized controlled trial was carried out for liver cancer patients undergoing partial hepatectomy from September 2010 to June 2012.Patients with liver cancers before receiving partial hepatectomy were randomized into the FTS group (n = 80) and the CS group (n = 80). Compared with the CS group, the FTS group had significantly less complications (P 0.05), shorter durations of nausea/vomiting, paralytic ileus and hospital stay, higher general comfort questionnaire measures (GCQ) by Kolcaba Line (all P 0.05), and lower serum levels of C-reactive protein on postoperative days 1, 3, and 5.FTS was safe and efficacious. It lessened postoperative stress reactions and accelerated recovery for patients undergoing partial hepatectomy for liver cancer.

Hepatocellular carcinoma (HCC) is the fifth and seventh most common cause of cancer in men and women, respectively. Transcatheter arterial chemoembolization (TACE) is the standardized therapy for the intermediate stage of HCC. However, the 3-year overall survival remains low (

Previous studies have reported that telomere length in peripheral blood leukocytes can predict the clinical outcome of several cancers. However, whether leukocyte telomere length is associated with the prognosis of hepatocellular carcinoma (HCC) remains to be determined. In this study, relative telomere length (RTL) in peripheral blood leukocytes was measured using a real-time PCR-based method for 269 HCC patients treated with transarterial chemoembolization (TACE) from two independent hospitals. The association between RTL and the overall survival (OS) of HCC was analyzed. The immunological function of the HCC patients with different leukocyte RTLs was evaluated. Multivariate analyses indicated that long leukocyte RTL was significantly associated with poor OS of HCC patients, with a hazard ratio of 2.04 (95% confidence interval, 1.46-2.86; P < 0.001). Kaplan-Meier analyses showed a significant difference of median survival time between patients with long and short RTL (log rank P < 0.001). Fluorescence-activated cell sorting analyses showed that the long RTL group had a significantly increased percentage of CD4(+)CD25(+)FOXP3(+) Treg in CD4(+) T cells compared with short RTL group (P = 0.002). In conclusion, our results suggest that leukocyte RTL may serve as an independent prognostic marker for HCC patients treated with TACE.

Purpose: To establish a sensitive and specific isolation and enumeration system for circulating tumor cells (CTC) in patients with hepatocellular carcinoma (HCC). Experimental Design: HCC cells were bound by biotinylated asialofetuin, a ligand of asialoglycoprotein receptor, and subsequently magnetically labeled by antibiotin antibody–coated magnetic beads, followed by magnetic separation. Isolated HCC cells were identified by immunofluorescence staining using Hep Par 1 antibody. The system was used to detect CTCs in 5 mL blood. Blood samples spiked with Hep3B cells (ranging from 10 to 810 cells) were used to determine recovery and sensitivity. Prevalence of CTCs was examined in samples from HCC patients, healthy volunteers, and patients with benign liver diseases or non-HCC cancers. CTC samples were also analyzed by FISH. Results: The average recovery was 61% or more at each spiking level. No healthy, benign liver disease or non-HCC cancer subjects had CTCs detected. CTCs were identified in 69 of 85 (81%) HCC patients, with an average of 19 ± 24 CTCs per 5 mL. Both the positivity rate and the number of CTCs were significantly correlated with tumor size, portal vein tumor thrombus, differentiation status, and the disease extent as classified by the TNM (tumor-node-metastasis) classification and the Milan criteria. HER-2 gene amplification and TP53 gene deletion were detected in CTCs. Conclusion: Our system provides a new tool allowing for highly sensitive and specific detection and genetic analysis of CTCs in HCC patients. It is likely clinically useful in diagnosis and monitoring of HCC and may have a role in clinical decision making. Clin Cancer Res; 17(11); 3783–93. ©2011 AACR.

BACKGROUND: Convincing evidence has indicated that an alteration in telomere length is involved in tumorigenesis. In epidemiologic studies, a strong correlation also has been observed consistently between relative telomere length (RTL) in peripheral blood leukocytes (PBLs) and susceptibility of many cancers. However, whether leukocyte RTL can be used as a predictor of risk for hepatocellular carcinoma (HCC) remains to be determined. METHODS: The RTL in PBLs was determined by measuring the telomere repeat copy number to single-copy gene number ratio in each sample compared with a reference DNA sample using a polymerase chain reaction-based method in this case-control study. The study participants included 240 patients with HCC (cases), a group of 240 healthy individuals (controls), and 120 noncancer controls with chronic liver disease (CLD). RESULTS: HCC cases exhibited a significantly longer RTL (median, 0.57; range, 0.21-3.3) than CLD controls (median, 0.46; range, 0.15-1.99; P < .001) and healthy controls (median, 0.39; range, 0.13-2.69; P < .001). Compared with individuals who had short RTL, individuals who had long RTL had a significantly increased risk of HCC when either healthy controls (adjusted odds ratio [OR], 7.28; 95% confidence interval, 4.46-11.88) or CLD controls (adjusted OR, 2.86; 95% confidence interval, 1.74-4.70) were used as the reference group. A significant dose-response relation was observed between HCC risk and long RTL (Ptrend < .001 for both control groups). In addition, there was a significantly positive RTL correlation between PBLs and normal liver tissues (r = 0.78; P < .001) or cirrhotic liver tissues (r = 0.67; P = .001). Furthermore, a significant joint effect on the risk of HCC was noted between RTL and smoking status or alcohol use. CONCLUSIONS: The current study produced the first epidemiologic evidence linking long RTL in PBLs to an increased risk of HCC. The authors concluded that these findings warrant further investigation in other populations. Cancer 2011;. © 2011 American Cancer Society.

Few options are available to treat patients with hepatocellular carcinoma (HCC). It was tested whether the combination of iodine-131(¹³¹I)-metuximab with chemoembolization could improve outcomes in patients with intermediate HCC. Between April 2008 and April 2009, 110 patients with unresectable HCC were treated with 113 intra-arterial ¹³¹I-metuximab injections combined with chemoembolization (mean, 1.03 per patient; median, 1; range, 1-2), followed by 264 sessions of transcatheter arterial chemoembolization (mean, 2.4 per patient; median, 3; range, 1-6). The survival rates at 6, 12, and 18 months were 88.2%, 79.1%, and 57.4%, respectively, by the Kaplan-Meier method. Of these patients, 12% exhibited grade 3/4 bilirubin toxicity, 5% exhibited grade 3/4 white blood count toxicity, and 7% exhibited grade 3/4 platelet toxicity. Response rates based on World Health Organization and European Association for the Study of the Liver criteria were 42.73% and 61.82%, respectively. The combination of ¹³¹I-metuximab and chemoembolization appeared to extend survival in patients with unresectable HCC compared with historical controls, as well as being well tolerated by patients with Child-Pugh A and B. This combination may represent a promising treatment modality for patients with intermediate HCC.

4018Background: TACE is often used to treat unresectable HCC (uHCC). However, there is no globally accepted consensus on the indication and definition of TACE failure. It is critical to reassess th...

Background Adequate control of bleeding is crucial during liver resection. This study analysed the safety and efficacy of hepatectomy under total hepatic vascular exclusion (THVE) in patients with tumours encroaching or infiltrating the hepatic veins and/or the inferior vena cava (IVC). Methods All patients undergoing liver resection with THVE between January 2000 and July 2006 were identified from a prospectively collected database containing 2400 patients. Data on patient demographics, surgical procedure and outcome were collected. Results A total of 87 patients scheduled for liver resection under THVE were identified, 77 with malignant tumours and ten with benign disease. THVE could not be used in two patients (2 per cent) owing to haemodynamic intolerance during trial clamping. Seventeen patients received simultaneous clamping of the portal triad and vena cava, and 68 had portal triad clamping followed by concomitant portal and vena cava clamping. The mean(s.d.) duration of THVE was 28·3(7·5) and 18·7(5·2) min respectively. Overall postoperative complication and operative mortality rates were 53 and 2 per cent respectively. Mean(s.d.) hospital stay was 16·8(4·7) days. Conclusion Major hepatic resection for tumours encroaching on the hepatic veins or IVC can be carried out under THVE with reasonable morbidity and mortality.

Background Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Transarterial chemoembolisation (TACE) is the standardized therapy for intermediate stage HCC. However, the prognosis for HCC patients treated by TACE greatly varies. Thus, there is a critical need for finding biomarkers to predict the prognosis of HCC patients. The amino acid transporter-2 (ASCT2) is involved in tumorigenesis and progression of many malignancies. This study aimed to evaluate the predictive role of two single nuclear polymorphisms (SNPs, rs3826793 and rs2070246) in the ASCT2 gene in HCC patients treated by TACE. Materials and methods Two functional SNPs (rs3826793 and rs2070246) in the ASCT2 gene were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese HCC patients treated by TACE. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier curves were used for the prognosis analyses. Results There was no significant association between two SNPs (rs3826793 and rs2070246) in the ASCT2 gene and overall survival of TACE treated HCC patients. However, we demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype (P=0.023). Conclusions We demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype.

Over-expression of de novo lipogenesis (DNL) pathway genes is associated with the prognosis of various types of cancers. However, effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and death of hepatocellular carcinoma (HCC) patients after surgery are still unknown. A total of 492 primary HCC patients treated with surgery were included in this study. Nine SNPs in 3 genes (ACACA, FASN and ACLY) of DNL pathway were genotyped. Multivariate Cox proportional hazard regression model and Kaplan-Meier curve were used to analyze the association of SNPs with clinical outcomes. Two SNPs in ACACA gene were significantly associated with overall survival of HCC patients. Patients carrying homozygous variant genotype (VV) in rs7211875 had significantly increased risk of death, while patients carrying VV genotype in rs11871275 had significant decreased risk of death, when compared with those carrying homozygous wild-type or heterozygous genotypes. Moreover, patients carrying VV genotype in rs11871275 had decreased recurrence risk, while patients carrying variant genotype in rs4485435 of FASN gene had increased recurrence risk. Further cumulative effect analysis showed significant dose-dependent effects of unfavorable SNPs on both death and recurrence. SNPs in DNL genes may serve as independent prognostic markers for HCC patients after surgery.

Metabolic reprogramming is an important hallmark of cancer cells, including the alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes. Previous studies have reported the associations between tumor formation and three core enzymes involved in the TCA cycle. However, the association between functional single nucleotide polymorphisms (SNPs) in one of TCA cycle key gene isocitrate dehydrogenase (IDH) and the overall survival of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE) has never been investigated. Five functional SNPs in IDH1 and IDH2 genes were genotyped using the Sequenom iPLEX genotyping system in a cohort of 419 unresectable Chinese HCC patients treated with TACE. Multivariate Cox proportional hazards model and Kaplan–Meier curve were used for the prognosis analysis. We found that SNPs rs12478635 in IDH1 and rs11632348 in IDH2 gene exhibited significant associations with death risk in HCC patients in the dominant model (HR 1.33; 95 % CI 1.02–1.73; P = 0.037) and in recessive model (HR 1.87; 95 % CI 1.27–2.75; P = 0.001), respectively. Moreover, we observed a cumulative effect of these two SNPs on HCC overall survival, indicating a significant trend of death risk increase with increasing number of unfavorable genotypes (P for trend = 0.001). Additionally, our data suggest that unfavorable genotypes of two SNPs may be used as an independent prognostic marker in those with advanced stage and patients with serum AFP

Background and aim Selective hepatic vascular exclusion (SHVE) has not been widely used because of difficulty in extrahepatic isolation of hepatic veins. This study aims to compare the results of SHVE using tourniquets or Satinsky clamps on major hepatic veins in partial hepatectomy for liver tumors involving the roots of hepatic veins. Methods Between June 2008 and March 2012, a randomized controlled trial was performed on patients undergoing liver resection to compare selective hepatic vascular exclusion using tourniquets or Satinsky clamps in partial hepatectomy. In the tourniquet group, the hepatic veins were completely isolated and occluded with tourniquets. In the Satinsky clamp group, the hepatic veins were dissected on the anterior and side walls only and they were clamped directly by Satinsky clamps. Results The time for dissecting hepatic veins was significantly shorter in the Satinsky clamp group (7.5 ± 6.6 min vs 21.3 ± 7.4 min) than the tourniquet group. In the tourniquet group, 5 hepatic veins could not be completely isolated and encircled. In 4 additional patients the hepatic vein was slightly torn during dissection. These 9 patients received successful occlusion using Satinsky clamps. In the Satinsky group, all occlusion of the hepatic vein was successful. There was a significant difference in the success rate in hepatic vein occlusion using the Satinsky and the tourniquet groups 60/60 vs 51/60, P = 0.0018. Conclusions Both techniques of hepatic vein occlusion were safe and efficacious. As the use of Satinsky clamps is safer, easier and took less time, it is recommended.

Background Control of bleeding is crucial during liver resection, and several techniques have been developed to achieve this. This study compared the safety and efficacy of selective hepatic vascular exclusion (SHVE) and Pringle manoeuvre in partial hepatectomy for liver tumours compressing or involving major hepatic veins. Methods All patients undergoing liver resection between January 2003 and December 2010 for liver tumours compressing or involving one or more major hepatic veins were identified retrospectively from a prospective institutional database. Either SHVE or Pringle manoeuvre was used to minimize blood loss during hepatectomy. Data on demographics and the intraoperative and postoperative course were analysed. Results From the database of 3900 patients, 1420 were identified who underwent liver resection for tumours encroaching on major hepatic veins using either SHVE (550) or the Pringle manoeuvre (870). Intraoperative blood loss (mean(s.d.) 480(210) versus 830(340) ml; P = 0·007) and transfusion requirements (mean(s.d.) 1·3(0·6) versus 2·9(1·4) units; P = 0·008) were significantly less in the SHVE group. In the Pringle group, hepatic vein injury resulted in major intraoperative bleeding of over 1000 ml in 65 patients (7·5 per cent) and air embolism in 14 (1·6 per cent), and three patients (0·3 per cent) died during surgery, whereas there was no major bleeding, air embolism or intraoperative death in the SHVE group. Postoperative liver failure, multiple organ failure and in-hospital death were significantly more common in the Pringle group (P = 0·019, P = 0·032 and P = 0·004 respectively). Conclusion SHVE was more efficacious than the Pringle manoeuvre in minimizing intraoperative bleeding and air embolism during partial hepatectomy for tumours encroaching on major hepatic veins, and decreased the postoperative liver failure rate.

Background Previous studies have revealed that circadian genes play important roles in cell proliferation, apoptosis, cell cycle control, DNA damage response and treatment response of chemotherapy agents in cancers. Aims We hypothesized that the polymorphisms in circadian genes may be associated with prognosis of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE). Methods Twelve functional single nucleotide polymorphisms (SNPs) in circadian negative feedback regulation genes (including CRY1, CRY2, PER1, PER2 and PER3) were genotyped using Sequenom iPLEX genotyping method in 337 HCC patients treated with TACE and analysed for associations with overall survival. Results Our data showed that one SNP rs2640908 in PER3 gene was significantly associated with overall survival of HCC patients (P = 0.027). Patients carrying at least one variant allele of rs2640908 (WV + VV) had a significantly decreased risk of death (hazard ratio, 0.71; 95% confidence interval, 0.53–0.90), when compared with those carrying homozygous wild-type alleles (WW). Kaplan–Meier analyses showed a significantly longer median survival time in patients with WV + VV genotypes of SNP rs2640908 than those with WW genotype (11.6 months vs. 8.1 months; log rank P = 0.030). In addition, we also observed a significant difference on the genotype distribution of SNP rs2640908 in patients with and without portal vein thrombus (P = 0.041). Conclusions Our study provides the first evidence that a single functional polymorphism of PER3 gene is significantly associated with overall survival in HCC patients treated with TACE.

Objective Most liver resections require champing of the hepatic pedicle (Pringle maneuver) to avoid excessive blood loss. But Pringle maneuver cannot control backflow bleeding of the hepatic vein. Resection of liver tumors involving hepatic veins may cause massive hemorrhage or air embolism from injuries of the hepatic vein. Although total hepatic vascular exclusion (THVE) can prevent bleeding of the hepatic vein effectively, it also may result in systemic hemodynamic disturbance because of the clamped inferior vena cava (IVC). SHVE, a new technique, can control the inflow and outflow of the liver without clamping the vena cava. We compared the effects of selective hepatic vascular exclusion (SHVE) and Pringle maneuver in resection of liver tumors involving the junction of the hepatic vein. Methods From January 2000 to October 2005, 2100 patients with liver tumors had undergone liver resections in our department. Among them, tumors of 235 cases adhered to or were close to the junction of one or more hepatic veins. Both SHVE and Pringle maneuver were used to control blood loss during hepatectomy. These 235 cases were divided into two groups: Pringle maneuver group (110) from January 2000 to December 2002 and SHVE group (125) from January 2003 to October 2005. Data were analyzed regarding the intraoperative and postoperative courses of the patients. In the SHVE group, total SHVE (clamping the porta hepatis and all major hepatic veins) was used in 69 cases and partial SHVE (clamping the porta hepatic and one or two hepatic veins) in 56 cases. There were three methods in hepatic veins occlusion: ligating with suture, encircling and occluding with tourniquets and clamping with Satinsky clamps. Results There was no difference between the two groups regarding the age, gender, tumor size, cirrhosis and HBsAg rate, ischemia time and operating time. Intraoperative blood loss and transfusion requirements were significantly decreased in the SHVE group. Hepatic veins rupture with massive blood loss occurred in 14 and air embolism in three during the tumor resection, but there was no massive blood loss and air embolism in the SHVE group due to hepatic vein occlusion. Postoperative bleeding, reoperation, liver failure and mortality rate were higher, and ICU stay and hospital stay were longer in the Pringle group than those in the SHVE group. Conclusion SHVE is much more effective than Pringle maneuver in controlling intraoperative bleeding. It can prevent massive blood loss and air embolism from hepatic veins rupture and can reduce the postoperative complication rate and mortality rate. Clamping the hepatic veins with Satinsky clamps is much safer and easier than ligating with suture and occluding with tourniquets.

To evaluate the efficacy of transarterial embolization (TAE) for intraperitoneal hemorrhage due to spontaneous rupture in hepatocellular carcinoma (HCC).Fourty-two patients with ruptured HCC were divided into 4 groups according to the type of their previous treatment: Group A-TAE followed by elective hepatectomy 15, Group B- TAE alone 11, Group C-emergency operation 6 and group D-medical conservative management 10.Celiac arteriography done before the present treatment showed extravasation of contrast material in 7 (26.9%) of the 26 patients in group A and B, and hypervascular tumor was observed in the rest. The hemostasis success rate of group A, B and C were 100%, which were much higher than that of group D (40%) (P0.05). The in-hospital mortality rates of group A, B and C were 0, 3.8% and 16.7% (P0.05), which were much lower than that of group D (80%) (P0.01). The 1-year survival rate of group A (76.3%) was higher than those in groups B (47.5%) and C (43.7%) (P0.05). There was no 1-year survivor in group D.Transarterial embolization is safe and effective for hemorrhage due to spontaneous rupture in hepatocellular carcinoma. For resectable lesions, TAE is a preferential treatment to be given first, then followed by elective hepatectomy.

Background Asialoglycoprotein receptor (ASGPR)-ligand-based separation combined with identification with Hep Par 1 or pan-cytokeratin (P-CK) antibody have been demonstrated to detect circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC). The aim of this study was to develop an improved enrichment and identification system that allows the detection of all types of HCC CTCs. Methods The specificity of the prepared anti-ASGPR monoclonal antibody was characterized. HCC cells were bound by ASGPR antibody and subsequently magnetically isolated by second antibody-coated magnetic beads. Isolated HCC cells were identified by immunofluorescence staining using a combination of anti-P-CK and anti-carbamoyl phosphate synthetase 1 (CPS1) antibodies. Blood samples spiked with HepG2 cells were used to determine recovery and sensitivity. CTCs were detected in blood samples from HCC patients and other patients. Results ASGPR was exclusively expressed in human hepatoma cell line, normal hepatocytes and HCC cells in tissue specimens detected by the ASGPR antibody staining. More HCC cells could be identified by the antibody cocktail for CPS1 and P-CK compared with a single antibody. The current approach obtained a higher recovery rate of HepG2 cells and more CTC detection from HCC patients than the previous method. Using the current method CTCs were detected in 89% of HCC patients and no CTCs were found in the other test subjects. Conclusions Our anti-ASGPR antibody could be used for specific and efficient HCC CTC enrichment, and anti-P-CK combined with anti-CPS1 antibodies is superior to identification with one antibody alone in the sensitivity for HCC CTC detection.

Background Telomerase expression is one of the characteristics of gastric cancer (GC) cells and telomerase activity is frequently up-regulated by a variety of mechanisms during GC development. Therefore, we hypothesized that elevated levels of activated telomerase might enhance GC risk due to increased propagation of cells with DNA damage, such as induced by γ-radiation. Methods To explore this hypothesis, 246 GC cases and 246 matched controls were recruited in our case-control study. TRAP-ELISA was used to assess the levels of telomerase activity at baseline and after γ-radiation and the γ-radiation-induced telomerase activity (defined as after γ-irradiation/baseline) in cultured peripheral blood lymphocytes (PBLs). Results Our data showed that there was no significant difference for the baseline telomerase activity between GC cases and controls (10.17 ± 7.21 vs. 11.02 ± 8.03, p = 0.168). However, after γ-radiation treatment, γ-radiation-induced telomerase activity was significantly higher in the cases than in the controls (1.51 ± 0.93 vs. 1.22 ± 0.66, p < 0.001). Using the median value of γ-radiation-induced telomerase activity in the controls as a cutoff point, we observed that high γ-radiation-induced telomerase activity was associated with a significantly increased GC risk (adjusted odds ratio, 2.45; 95% confidence interval, 1.83-3.18). Moreover, a dose response association was noted between γ-radiation-induced telomerase activity and GC risk. Age, but not sex, smoking and drinking status seem to have a modulating effect on the γ-radiation-induced telomerase activities in both cases and controls. Conclusion Overall, our findings for the first time suggest that the increased γ-radiation-induced telomerase activity in PBLs might be associated with elevated GC risk. Further confirmation of this association using a prospective study design is warranted.