Resected Hepatocellular Carcinoma Patients Research Articles

Fas -670 A/G Polymorphism Predicts Prognosis of Hepatocellular Carcinoma after Curative Resection in Chinese Han Population

Background: Apoptosis, also called programmed cell death, is a genetically controlled process against hyperproliferation and malignancy. The Fas-Fas ligand (FasL) system is considered to be a major pathway for apoptosis in cells and tissues. Thus, this study aimed to investigate whether single nucleotide polymorphisms (SNPs) in Fas and FasL gene may have effects on the recurrence and survival of patients with hepatocellular carcinoma (HCC) after curative hepatectomy. Methods: We studied the relationship between Fas rs1800682, rs2234767 and FasL rs763110 polymorphisms and recurrence-free survival (RFS) as well as overall survival (OS) in 117 Chinese Han patients with HCC that underwent hepatectomy. Findings: In Kaplan–Meier survival analysis, only Fas rs1800682 (-670 A/G) was identified to be associated with RFS and OS. Compared with AA genotype, the AG/GG genotypes was significantly associated with better RFS (p = 0.008) and OS (p = 0.020). Moreover, multivariate Cox regression analysis showed that Fas rs1800682 remained as a significant independent predictor in RFS for the resected HCC patients (AG/GG vs. AA; adjusted HR 0.464, 95% CI 0.275-0.782, p=0.004), but is not an independent predictor in OS (p=0.395). Interpretation: This study demonstrated that Fas -670 G allele may play a protective role in the recurrence and survival of HCC patients with hepatectomy. Furthermore, Fas rs1800682 polymorphism might be a promising biomarker for HCC patients after hepatectomy. Funding Statement: This work was supported by grants from the Sichuan Science and Technology Program (No 2019YFS0370) and national university student innovation and entrepreneurship training programs (No C2019104465). Declaration of Interests: No potential conflicts of interest were disclosed. Ethics Approval Statement: This study was coincident with Declaration of Helsinki, and approved by the Ethics Committee of Sichuan University.

3:09 PM Abstract No. 138 Comparative outcome study of surgically resectable hepatocellular carcinoma patients versus those requiring neoadjuvant radioembolization prior to surgical resection

Surgical Resection is considered curative for those with solitary hepatocellular carcinoma (HCC) and preserved liver function, but it is limited to those with adequate future liver remnant (FLR). Radioembolization (Y90) is used to improve margins and increase FLR, converting patients to surgical candidates. We aimed to study outcome differences between HCC patients who underwent resection vs. those requiring neoadjuvant Y90 prior to resection. With IRB approval, we studied patients with HCC resected between 2011-2014. Patients were categorized as resectable per multidiscipline tumor board vs. those deemed initially unresectable but converted to surgical resection with neoadjuvant Y90 (radiation lobectomy). Recurrence and survival outcomes were compared between these cohorts. Time to recurrence (TTR), recurrence free survival (RFS), and overall survival (OS) and were estimated using Kaplan-Meier method. 17 treatment naïve patients underwent surgical resection vs. 13 HCC patients that required neoadjuvant Y90. Mean age was 60 for resection cohort vs. 63 for neoadjuvant Y90 cohort (P = 0.5). Median tumor size was 4.1 cm in resection cohort vs. 5.6 cm for neoadjuvant Y90 cohort (P = 0.28). All patients had Child-Pugh A liver function. There was 1 (6%) 90-day mortality rate in resection cohort and 0% in neoadjuvant Y90 cohort. Resection cohort explants showed 100% viable tumors without necrosis. At explant, 5 (38%) had complete tumor necrosis and 8 (62%) had partial (>50%) necrosis in the neoadjuvant Y90 cohort. Time to recurrence analysis was similar between cohorts; median was not reached at 80 months follow-up. RFS was similar between cohorts, where 5-year RFS was 51% for resection cohort vs. 56% for neoadjuvant Y90 cohort (P = 0.67). Overall survival outcomes were also similar between cohorts, with 5-year OS of 74% for resection patients vs. 83% for neoadjuvant Y90 patients (P = 0.59). Neoadjuvant Y90 can convert patients with HCC initially declared unresectable and denied surgery into resection candidates. This approach imparts the same recurrence and survival advantages as those deemed optimal resection candidates at presentation.

The Pre- and Postoperative FIB-4 Indexes Are Good Predictors to the Outcomes of HBV-Related HCC Patients after Resection.

Background and Aim Liver fibrosis is associated with the prognosis of patients with hepatocellular carcinoma (HCC) after resection. The fibrosis-4 (FIB-4) index is an accurate and noninvasive marker to determine the degree of liver fibrosis. Here, we evaluated the effect of pre- and postoperative FIB-4 index in predicting the outcomes after resection of HCC in patients who have chronic hepatitis B (CHB) infection. Methods A total of 534 CHB patients with HCC who received curative hepatectomy between 2001 and 2016 at Kaohsiung Chang Gung Memorial Hospital, Taiwan, were enrolled in this study. The impact of the FIB-4 index (preoperative and the 1st year after operation) on overall survival (OS) and recurrence-free survival (RFS) was evaluated. Results There was a significant association between the preoperative FIB-4 index and Metavir fibrosis stage (p < 0.01). The multivariate analysis showed that preoperative FIB‐4 > 2 is an independent risk factor for RFS and OS after HCC curative resection [hazard ratio (HR), 1.902; 95% CI, 1.491–2.460; p < 0.001, and HR, 2.207; 95% CI, 1.420–3.429; p < 0.001, respectively]. Notably, preoperative FIB-4 is also an independent risk factor for RFS (HR, 1.219; p = 0.035) in noncirrhotic patients. Furthermore, patients had deteriorated FIB-4 1 year after operation [definition: the value (the 1st year FIB‐4 after operation minus preoperative FIB‐4) > 1] and had an adverse outcome in RFS and OS (p < 0.001, both). Conclusion The pre and postoperative FIB-4 indexes are useful clinical markers to predict the prognosis in HBV-HCC patients after curative hepatectomy.

ALPPS for hepatocarcinoma under cirrhosis: a feasible alternative to portal vein embolization.

Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors. Preoperative portal vein embolization (PVE) is currently the most accepted treatment before major hepatic resection for HCC in patients with liver fibrosis or cirrhosis and associated insufficient future liver remnant (FLR). In the last decade, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique has been described to obtain an increase of volume regarding PVE and a decrease of drop out. The initial excessive morbidity and mortality of this technique have decreased drastically due to a better selection of patients, the learning curve and the use of less aggressive variations of the original technique in the first stage. For both techniques a complete preoperative assessment of the FLR is the most important issue and only patients with and adequate FLR should be resected. ALPPS could be a feasible technique in very selected patients with HCC and cirrhosis. As long as it is performed in an experienced center could be used as a first choice technique versus PVE or could be used as a rescue technique in case of PVE failure.

Impact of Surveillance in Chronic Hepatitis B Patients on Long-Term Outcomes After Curative Liver Resection for Hepatocellular Carcinoma

BackgroundClinical guidelines recommend surveillance in high-risk population to early detect hepatocellular carcinoma (HCC), when curative treatment such as liver resection can be applied. However, it is largely unknown whether surveillance would provide long-term survival benefits to these high-risk patients who have received curative liver resection for HCC. MethodsA prospectively maintained database on patients with chronic hepatitis B infection who underwent curative liver resection for HCC from 2003 to 2014 was reviewed. Patients’ overall survival and recurrence were compared between the groups of patients whose HCCs were diagnosed by surveillance or non-surveillance, as well as between the groups of patients operated in the first (2003–2008) and second (2009–2014) 6-year periods. ResultsOf 1075 chronic hepatitis B patients with HCC, 452 (42.0%) patients were diagnosed by preoperative surveillance. Compared with the non-surveillance group, the OS and RFS rates were significantly better in the surveillance group (both P < 0.001). Surveillance was associated with a 55% decrease in the overall survival risk and a 48% decrease in the recurrence risk (HR 0.45, 95% CI 0.38–0.53, and HR 0.52, 95% CI 0.44–0.61). Compared with the first period, a significant reduction of 12% and 19% in the overall death and recurrence risks, respectively, was observed in the second period (HR 0.88, 95% CI 0.78–0.97, and HR 0.81, 95% CI 0.70–0.95). ConclusionSurveillance for HCC was associated with favorable long-term overall and recurrence-free survival rates after curative liver resection of HCC in patients with chronic hepatitis B.

Circulating levels of PD-L1 and Galectin-9 are associated with patient survival in surgically treated Hepatocellular Carcinoma independent of their intra-tumoral expression levels

Tumor expression of immune co-inhibitory ligands, such as PD-L1 and Galectin-9, have potential prognostic value in Hepatocellular Carcinoma (HCC). Circulating levels of these molecules, however, have hardly been studied. This study aims to assess the prognostic significance of circulating PD-L1 and circulating Galectin-9 in patients with resected HCC, and to compare their prognostic significance to the intra-tumoral expression of these same molecules. Archived tissues and stored peripheral blood samples from 81 patients who underwent HCC resection or liver transplantation, with curative intent, were used. Immunohistochemistry was performed to determine intra-tumoral expression of PD-L1 and Galectin-9, while ELISA was used to quantify their respective circulating levels. High circulating PD-L1 (HR 0.12, 95%CI 0.16–0.86, p = 0.011) and high circulating Galectin-9 (HR 0.11, 95%CI 0.15–0.85, p = 0.010) levels were both associated with improved HCC-specific survival. Surprisingly, there was no correlation between circulating levels of PD-L1 and Galectin-9 and their intra-tumoral expression levels. In fact, circulating levels of PD-L1 and Galectin-9 were predictive of HCC-specific survival independently of intra-tumoral levels and baseline clinicopathologic characteristics. Combined analysis of circulating levels and intra-tumoral expression of PD-L1 (HR 0.33, 95%CI 0.16–0.68, p = 0.002) and Galectin-9 (HR 0.27, 95%CI 0.13–0.57, p = 0.001) resulted in more confident prediction of survival. In conclusion, circulating PD-L1 and Galectin-9 levels prognostically differentiate resected HCC patients, independently of their intra-tumoral expression. Combining circulating and intra-tumoral expression levels of PD-L1 or Galectin-9 further improves the prognostic values of these immune biomarkers.

Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients

BackgroundDue to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is still a challenge to determine patients’ prognosis. We aim to identify new prognostic markers for resected HCC patients.Methods274 patients were retrospectively identified and samples collected from Zhongshan hospital, Fudan University. We analyzed the gene expression patterns of tumors and compared expression patterns with patient survival times. We identified a “9-gene signature” associated with survival by using the coefficient and regression formula of multivariate Cox model. This molecular signature was then validated in three patients cohorts from internal cohort (n = 69), TCGA (n = 369) and GEO dataset (n = 80).ResultsWe identified 9-gene signature consisting of ZC2HC1A, MARCKSL1, PTGS1, CDKN2B, CLEC10A, PRDX3, PRKCH, MPEG1 and LMO2. The 9-gene signature was used, combined with clinical parameters, to fit a multivariable Cox model to the training cohort (concordance index, ci = 0.85), which was successfully validated (ci = 0.86 for internal cohort; ci = 0.78 for in silico cohort). The signature showed improved performance compared with clinical parameters alone (ci = 0.70). Furthermore, the signature predicted patient prognosis than previous gene signatures more accurately. It was also used to stratify early-stage, HBV or HCV-infected patients into low and high-risk groups, leading to significant differences in survival in training and validation (P < 0.001).ConclusionsThe 9-gene signature, in which four were upregulated (ZC2HC1A, MARCKSL1, PTGS1, CDKN2B) and five (CLEC10A, PRDX3, PRKCH, MPEG1, LMO2) were downregulated in HCC with poor prognosis, stratified HCC patients into low and high risk group significantly in different clinical settings, including receiving adjuvant transarterial chemoembolization and especially in early stage disease. This new signature should be validated in prospective studies to stratify patients in clinical decisions.

Short-term and long-term outcomes of liver resection for HCC patients with portal vein tumor thrombus

BackgroundPortal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) is a sign of advanced stage disease, which is associated with poor prognosis. Liver resection (LR) may provide better prognosis in selected patients. In the present study, we aimed to assess information from HCC patients with PVTT who died within 3 months or 2 years after LR in order to identify preoperative factors correlated to short-term or long-term survival, by which inappropriate selection of patients for LR might be avoided in the future.MethodsA retrospective cohort study consisting of 487 consecutive cases of HCC patients with PVTT was performed from 2008 to 2010 at Eastern Hepatobiliary Surgery Hospital. Medical records, including laboratory values, imaging results and treatment information, were obtained from participants. Study endpoints were survival at 3 months and 2 years post-hepatectomy. Logistic regression analysis was utilized to determine the significant pre-operative factors influencing short-term or long-term survival.ResultsIn multivariable analysis, α-fetoprotein, total bilirubin and radiologic ascites were significantly associated with short-term survival, while α-fetoprotein level, clinical significant portal hypertension, extent of PVTT and tumor differentiation were factors significantly associated with long-term survival.ConclusionsThe independent risk factors of poor short-term survival were the liver function-associated, such as factors radiologic ascites and total bilirubin, while tumor differentiation indicating the tumor biology was associated with longer-term survival. In addition, α-fetoprotein was a risk factor associated with both short-term and longer-term survivals.

Conditional survival of patients with hepatocellular carcinoma undergoing curative intent resection: Analysis of the national cancer database

Background: Hepatocellular carcinoma (HCC) is a lethal malignancy rising in both incidence and mortality worldwide. Conditional survival (CS) estimates represent the probability that a patient will survive additional number of years, because the patient has already survived a given amount of time, and better define the survival potential over time. We analyzed the CS estimates of resected patients from the time of surgical resection. Methods: A retrospective analysis of patients who had curative intent surgical resection for HCC was performed using the National Cancer Data Base (NCDB) from 2004-2014. Crude survival curves were generated using the Kaplan-Meier method. For the purposes of the CS analysis, we assessed the probability of surviving an additional 5 years (CS5), given that the patient had already survived 2 years. As such, the 5-year CS for patients who had survived (S) “X” years was computed as CS5 S(x+5)/S(x). CS estimates were also stratified by clinicopathologic variables of interest. Results: The NCDB captured 11,357 patients who underwent resection for HCC. The characteristics of the patients and tumors include: male gender (74.1%), white race (78.7%), Charlson Deyo score of 0-1 (72.5%), intermediate tumor grade (53.1%), margin-negative resection (88.5%), 30-day mortality (3.2%) and 90-day mortality (5.4%). Table 1 shows that, for example, for the OS, the unconditional 5-year survival probability is 65.9%, but given that those have survived 2 years, the additional 5-year survival probability is 84.7% (in red). Also, the unconditional 4-year survival probability is 71.0%, given that the person survived 2 or 3 years, the 4-year survival probabilities are 85.1 and 78.6% respectively (in blue). Similarly, the 5-year CS for patients who have survived 2 years is as follows for: age < 65 (92.9%), intermediate grade (85.2%), margin-negative resection (84.8%), no radiation therapy (84.6%), and no systemic therapy (81.2%). The overall survival was highly statistically significant between different groups within each of these variables (p < 0.0004). Conclusion: CS estimates following resection in HCC patients reflect an improved survival for a given length of time survived compared to the respective unconditional survival. However, the CS declines for each successive year survived reflecting other variables that (perhaps not oncologic) that impact survival in HCC. CS estimates provides more accurate prognostic information for the individual resected HCC patients, and can be used by clinical clinicians to guide further therapy and follow up years after resection.

Meta-analysis of concurrent hepatectomy with extrahepatic bile duct resection in hepatocellular carcinoma patients with bile duct tumor thrombi

Meta-analysis of concurrent hepatectomy with extrahepatic bile duct resection in hepatocellular carcinoma patients with bile duct tumor thrombi

In-hospital Mortality after Surgical Resection in Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus.

Background: Survival benefit of surgical resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) has been approved recently. However, risk factors for in-hospital mortality in these patients remain unclear. We aimed to determine risk factors and reduce the mortality of these patients.Methods: We analyzed data for 521 of all 1531 HCC patients with PVTT underwent surgery. The primary outcome measure was in-hospital mortality after surgical resection. Univariate and Multivariate cox-regression were performed to identify independent predictors of in-hospital mortality. The methods of Kaplan-Meier, bootstrap and ten-fold-cross validation were applied to validate the risk factors.Results: 521 of 1531 patients in 2004-2012 occurred for the diagnosis of HCC associated with PVTT and underwent surgical resection as a training cohort. Other 325 patients in 2013-2016 were included as a validation cohort. Overall mortality of postoperative in-patients was 3.3% (17/521) and 2.8 % (9/325), respectively. Univariate analysis of mortality revealed that frequency of hospitalization, total albumin, different types of PVTT, bleeding volume, blood transfusion, resection volume, and tumor volume were related with mortality. Therefore, the bootstrap validation reflected that the risk factors of multivariate cox regression in model1(frequency of hospitalization, bleeding volume, and tumor volume) and model 2 (frequency of hospitalization, bleeding volume and total albumin) were stable with mortality in hospital. Ten-fold cross-validation of cox regression analysis showed that the mean C-statistic with 95%CI of model1 and model2 respectively were 0.887(0.779-0.976) and 0.867(0.789-0.966) for predicting in-hospital mortality. Consistency results of models were in the training cohort and validation cohort.Conclusion: Total albumin, tumor volume, intraoperative bleeding and frequency of hospitalization were independent predictive factors for in-hospital mortality in HCC patients with PVTT under surgery. Further study is warranted to utilize these factors to lower in-hospital mortality.

Meta-analysis of concurrent hepatectomy with extrahepatic bile duct resection in hepatocellular carcinoma patients with bile duct tumor thrombi

Meta-analysis of concurrent hepatectomy with extrahepatic bile duct resection in hepatocellular carcinoma patients with bile duct tumor thrombi

Perivascular Tumor-Infiltrating Leukocyte Scoring for Prognosis of Resected Hepatocellular Carcinoma Patients

Introduction: Liver resection is a curative treatment for hepatocellular carcinoma (HCC). Tumor-infiltrating leukocytes (TILs) are important players in predicting HCC recurrence. However, the invasive margin could not be confirmed as relevant for HCC. The migration of immune cells into HCC may originate from intratumoral vessels. No previous study has examined perivascular (PV) infiltration. Method: Tumors from 60 patients were examined. Immunohistochemistry was performed against CD3, CD8, CD20, and CD66b. TILs were counted in the PV regions using an algorithm for quantification of the tumor immune stroma (QTiS). The results were correlated with overall (OS) and disease-free survival (DFS), clinical parameters, and laboratory values. Result: PV infiltration of TILs was predominant in resected HCC. Higher PV infiltration of CD3+ (p = 0.016) and CD8+ (p = 0.028) independently predicted better OS and DFS, respectively. CD20+ showed a trend towards better DFS (p = 0.076). Scoring of CD3+, CD8+, and CD20+ independently predicted OS and DFS (p < 0.01). The amount of perivascular-infiltrating CD3+ cells is an independent predictor of better OS, and CD8+ cells independently predict prolonged DFS. Conclusion: Our novel perivascular infiltration scoring (PVIS) can independently predict both DFS and OS in resected HCC patients.

Portal hypertension predicts short-term and long-term outcomes after hepatectomy in hepatocellular carcinoma patients

Background and aims: The impact of portal hypertension (PH) on postoperative short-term outcomes and long-term survival in hepatocellular carcinoma (HCC) patients has lately been discussed controversially. This study aimed to explore the influence of PH on postoperative outcomes in HCC patients undergoing surgical resection.Methods: Patients undergoing hepatectomy for HCC from 2010 to 2014 were enrolled. The impact of PH on postoperative complications, posthepatectomy liver failure (PHLF) and overall survival (OS) was evaluated.Results: A total of 355 HCC patients were enrolled; 129 (36.3%) experienced postoperative complications and 21 (5.9%) developed PHLF. PH was identified as an independent predictor of PHLF. Patients with PH experienced a higher incidence of complications and PHLF than patients without PH. On the Cox proportional hazards regression model, PH was verified as a risk factor of OS for BCLC stage 0/A and B patients. Patients without PH had significantly better long-term survival compared to patients with PH both in the total cohort and in cirrhosis subgroup.Conclusion: Liver resection in HCC patients with PH showed a significantly increased postoperative complications and PHLF, and revealed a decreasing long-term survival than non-PH patients. Besides, tumor burden also played an important role in determining the OS. However, due to the improvement in surgical technique and perioperative management, surgery was feasible in carefully selected HCC patients with PH.

Perivascular Tumor-Infiltrating Leukocyte Scoring for Prognosis of Resected Hepatocellular Carcinoma Patients.

Liver resection is a curative treatment for hepatocellular carcinoma (HCC). Tumor-infiltrating leukocytes (TILs) are important players in predicting HCC recurrence. However, the invasive margin could not be confirmed as relevant for HCC. The migration of immune cells into HCC may originate from intratumoral vessels. No previous study has examined perivascular (PV) infiltration. Tumors from 60 patients were examined. Immunohistochemistry was performed against CD3, CD8, CD20, and CD66b. TILs were counted in the PV regions using an algorithm for quantification of the tumor immune stroma (QTiS). The results were correlated with overall (OS) and disease-free survival (DFS), clinical parameters, and laboratory values. PV infiltration of TILs was predominant in resected HCC. Higher PV infiltration of CD3+ (p = 0.016) and CD8+ (p = 0.028) independently predicted better OS and DFS, respectively. CD20+ showed a trend towards better DFS (p = 0.076). Scoring of CD3+, CD8+, and CD20+ independently predicted OS and DFS (p < 0.01). The amount of perivascular-infiltrating CD3+ cells is an independent predictor of better OS, and CD8+ cells independently predict prolonged DFS. Our novel perivascular infiltration scoring (PVIS) can independently predict both DFS and OS in resected HCC patients.

Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety

BackgroundThe optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma (HCC) patients with solitary tumor and microvascular invasion (MVI) is controversial. This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization (TACE) after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor ≥ 5 cm and MVI.MethodsIn this randomized, open-labeled, phase III trial, HCC patients with a solitary tumor ≥ 5 cm and MVI were randomly assigned (1:1) to receive either 1–2 cycles of adjuvant TACE after hepatectomy (Hepatectomy-TACE) or hepatectomy alone (Hepatectomy Alone). The primary endpoint was disease-free survival (DFS); the secondary endpoints included overall survival (OS) and adverse events.ResultsBetween June 1, 2009, and December 31, 2012, 250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group (n = 125) or the Hepatectomy Alone group (n = 125). Clinicopathological characteristics were balanced between the two groups. The median follow-up time from randomization was 37.5 months [interquartile range 18.3–48.2 months]. The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [17.45 months (95% confidence interval [CI] 11.99–29.14) vs. 9.27 months (95% CI 6.05–13.70), hazard ratio [HR] = 0.70 (95% CI 0.52–0.95), P = 0.020], respectively. The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group [44.29 months (95% CI 25.99–62.58) vs. 22.37 months (95% CI 10.84–33.91), HR = 0.68 (95% CI 0.48–0.97), P = 0.029]. Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group, although these were generally mild and manageable. The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction.ConclusionHepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor ≥ 5 cm and MVI, with acceptable toxicity.

Precision Oncology With Radiogenomics: Non-invasive Interrogation of Liver Cancer Genomics to Select Drug Therapy and Monitor Patient Response

Background: Significant intratumoral heterogeneity is present in hepatocellular carcinoma (HCC) and single biopsy samples severely underread the genomic profile of the tumor. This confounds drug development in HCC and makes it extremely challenging to stratify and prognosticate patients to select therapy on the basis of genomic biomarkers. Multiregion sampling of surgically resected HCC allows for these intratumoral heterogeneity to be unraveled and this is currently carried out in our prospective PLANET (Precision Medicine in Liver Cancer across an Asia-Pacific Network) program. However, multiregion sampling is not practical in unresectable HCC cases, which comprise 80% of the disease burden. Radiogenomics studies on liver, lung and head-and-neck cancers have established the capability of radiomics analysis in capturing intratumor heterogeneity with the identification of radiomics signatures that are representative of underlying gene expression patterns. Aim: On this basis, our PLANET program has adopted a radiogenomics approach to characterize the intratumoral heterogeneity in HCC. Methods: This approach will leverage on the correlation of distinctive imaging traits in CT scans against the gene expression profiles of surgically resected HCC patients. Our PLANET program and the data-science enterprise Holmusk have embarked on close collaborative efforts to develop an algorithm that characterizes intratumoral heterogeneity based on distinctive traits in the CT scans. Results and conclusion: The development of such an algorithm is potentially ground-breaking as it allows for the noninvasive interrogation of liver cancer genomics and prognostication of HCC patients. This allows the easy screening of patients for therapeutic targets in vivo and will significantly improve the selection of drug therapy and monitoring of therapeutic response in HCC.

Liver surface nodularity quantification from preoperative CT images for the assessment of the perioperative risk after liver resection for HCC

Introduction: While Liver surface nodularity (LSN) quantification on routine CT images allows to accurately detect severe fibrosis and clinically significant portal hypertension (CSPH), its value in the anticipation of post-operative morbidity after liver resection for hepatocellular carcinoma (HCC) remains to be assessed. Methods: All patients undergoing hepatectomy for HCC between 2012-2017 at a single center were retrospectively analyzed. LSN was measured on the left liver lobe on preoperative CT scans. The feasibility of LSN measurement was assessed and the association between LSN and major postoperative morbidity was analyzed. Results: Among 199 resected HCC patients, 173 (86.9%) had an underlying liver disease, including cirrhosis in 68 (35.1%) patients. CSPH was observed in 8 (13.1%) of the 61 patients undergoing preoperative hepatic vein pressure gradient. LSN measurement was feasible in 144 patients (72.4%) with a mean time of 88 (±29) seconds. Mean LSN was 2.46 (±0.37). LSN was significantly increased in patient with cirrhosis (2.68±0.40 vs. 2.33±0.29, p=0.001) and CSPH (2.82±0.29 vs. 2.40±0.29, p=0.001). Overall and major postoperative complications occurred in 118 (59.3%) and 40 (20.1%) patients, respectively. Mean CCI was 17.18 (±21.04). The AUROC of LSN for predicting major complications was 0.614 (p=0.044) with a cut-off value of 2.62. On multivariate analysis, LSN ≥ 2.62 (HR=3.08, 95% CI: 1.21-7.81, p=0.018) and per-operative transfusion (HR=5.89, 95%CI: 2.17-15.99, p=0.001) were independent risk factors for major complications. Conclusion: LSN measurement is feasible in the vast majority of patients and represents a valuable tool in the anticipation of major postoperative complications following hepatectomy for HCC.

Impact of body composition on survival and morbidity after liver resection in hepatocellular carcinoma patients

BackgroundHepatocellular carcinoma is the most common innate liver tumor. Due to improved surgical techniques, even extended resections are feasible, and more patients can be treated with curative intent. As the liver is the central metabolic organ, preoperative metabolic assessment is crucial for risk stratification. Sarcopenia, obesity and sarcopenic obesity characterize body composition and metabolic status. Here we present the impact of body composition on survival after liver resection in patients with hepatocellular carcinoma. MethodsA retrospective database analysis of 70 patients who were assigned for liver resection due to hepatocellular carcinoma was conducted. For assessment of sarcopenia and obesity, skeletal muscle surface area was measured at lumbar vertebra 3 level (L3) in preoperative four-phase contrast enhanced abdominal CT scans, and L3 muscle index and body fat percentage were calculated. ResultsUnivariate analysis comparing the survival curves using the score test demonstrated superior postoperative overall survival for sarcopenic (P = 0.035) and sarcopenic obese (P = 0.048) patients as well as a trend favoring obese (P = 0.130) subjects. Whereas multivariate analysis could not identify significant difference in postoperative survival regarding sarcopenia, obesity or sarcopenic obesity. Only large tumor size, multifocal disease and male gender were risk factors for long-term survival. ConclusionsSarcopenia, obesity and sarcopenic obesity are indeed no risk factors for poor postoperative survival in this study. Our data do not support the evaluation of sarcopenia, obesity and sarcopenic obesity before liver resection in hepatocellular carcinoma patients.

Development and Validation of a New Tumor-Based Gene Signature Predicting Prognosis of HBV/HCV-Included Resected Hepatocellular Carcinoma Patients

Development and Validation of a New Tumor-Based Gene Signature Predicting Prognosis of HBV/HCV-Included Resected Hepatocellular Carcinoma Patients