IDEAL-IQ measurement can distinguish dysplastic nodule from early hepatocellular carcinoma: a case-control study.

Background: Previous studies have confirmed that malignant transformation of dysplastic nodule (DN) into hepatocellular carcinoma (HCC) is accompanied by reduction of iron content in nodules. This pathological abnormality can serve as the basis for magnetic resonance imaging (MRI). This study was designed to identify the feasibility of iterative decomposition of water and fat with echo asymmetry and least squares estimation-iron quantitative (IDEAL-IQ) measurement to distinguish early hepatocellular carcinoma (eHCC) from DN. Methods: We reviewed MRI studies of 35 eHCC and 23 DN lesions (46 participants with 58 lesions total, 37 males, 9 females, 31-80 years old). The exams include IDEAL-IQ sequence and 3.0T MR conventional scan [including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and Gadopentic acid (Gd-GDPA)-enhanced]. Then, 3 readers independently diagnosed eHCC, DN, or were unable to distinguish eHCC from DN using conventional MRI (CMRI), and then assessed R2* value of nodules [R2* value represents the nodule iron content (NIC)] and R2* value of liver background [R2* value represents the liver background iron content (LBIC)] with IDEAL-IQ. Statistical analysis was conducted using the t-test for comparison of means, the Mann-Whitney test for comparison of medians, the chi-square test for comparison of frequencies, and diagnostic efficacy was evaluated by using receiver operating characteristic (ROC) curve. Results: This study evaluated 35 eHCC participants (17 males, 6 females, 34-81 years old, nodule size: 10.5-27.6 mm, median 18.0 mm) and 23 DN participants (20 males, 3 females, 31-76 years old, nodule size: 16.30±4.095 mm). The NIC and ratio of NIC to LIBC (NIC/LBIC) of the eHCC group (35.926±12.806 sec-1, 0.327±0.107) was lower than that of the DN group (176.635±87.686 sec-1, 1.799±0.629) (P<0.001). Using NIC and NIC/LBIC to distinguish eHCC from DN, the true positive/false positive rates were 91.3%/94.3% and 87.0%/97.1%, respectively. The rates of CMRI, NIC and NIC/LBIC in diagnosis of eHCC were 77.1%, and 94.3%, 97.1%, respectively, and those of DN were 65.2%, 91.3%, and 87.0%, respectively. The diagnosis rate of eHCC and DN by CMRI was lower than that of NIC and NIC/LBIC (eHCC: P=0.03, 0.04, DN: P=0.02, 0.04). Conclusions: Using IDEAL-IQ measurement can distinguish DN from eHCC.

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

The relationship between the efficacy of thermal ablation and inflammatory response and immune status in early hepatocellular carcinoma and the progress of postoperative adjuvant therapy.

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease. Thermal ablation has the advantages of being equivalent to surgical resection, minimally invasive, low cost and significantly reducing hospital stay. Therefore, it is recommended as one of the first-line radical treatment for early HCC. However, with the deepening of research on early HCC, more and more studies have found that not all patients with early HCC can obtain similar efficacy after radical thermal ablation, which may be related to the heterogeneity of HCC. Previous studies have shown that inflammation and immunity play an extremely important role in the prognostic heterogeneity of patients with HCC. Therefore, the inflammatory response and immune status of patients may be closely related to the efficacy of early HCC after curative thermal ablation. This article elaborates the mechanism of high inflammatory response and poor immune status in the poor prognosis after radical thermal ablation of early HCC, and clarifies the population who may benefit from adjuvant therapy after radical thermal ablation in patients with early HCC, which provides a new idea for the precise adjuvant treatment after radical ablation of early HCC in the future.

Classification tree analysis to evaluate the most useful magnetic resonance image type in the differentiation between early and progressed hepatocellular carcinoma.

AIM: Using classification tree analysis, we evaluated the most useful magnetic resonance (MR) image type in the differentiation between early and progressed hepatocellular carcinoma (eHCC and pHCC). METHODS: We included pathologically proven 214 HCCs (28 eHCCs and 186 pHCCs) in 144 patients. The signal intensity of HCCs was assessed on in-phase (T1in) and opposed-phase T1-weighted images (T1op), ultrafast T2-weighted images (ufT2WI), fat-saturated T2-weighted images (fsT2WI), diffusion-weighted images (DWI), contrast enhanced T1-weighted images in the arterial phase (AP), portal venous phase (PVP), and the hepatobiliary phase. Fat content and washout were also evaluated. Fisher's exact test was performed to evaluate usefulness for the differentiation. Then, we chose MR images using binary logistic regression analysis and performed classification and regression tree analysis with them. Diagnostic performances of the classification tree were evaluated using a stratified 10-fold cross-validation method. RESULTS: T1in, ufT2WI, fsT2WI, DWI, AP, PVP, fat content, and washout were all useful for the differentiation (p < 0.05), and AP and T1in were finally chosen for creating classification trees (p < 0.05). AP appeared in the first node in the tree. The area under the curve, sensitivity and specificity for eHCC, and balanced accuracy of the classification tree were 0.83 (95% CI 0.74-0.91), 0.64 (18/28, 95% CI 0.46-0.82), 0.94 (174/186, 95% CI 0.90-0.97), and 0.79 (95% CI 0.70-0.87), respectively. CONCLUSIONS: AP is the most useful MR image type and T1in the second in the differentiation between eHCC and pHCC.

High rates of treatment stage migration for early hepatocellular carcinoma and association with adverse outcomes: An Australian multicenter study.

Background and Aim: The rate of contraindications to percutaneous ablation (PA) for inoperable early hepatocellular carcinoma (HCC) and subsequent outcomes is not well described. We investigated the prevalence and outcomes of inoperable early HCC patients with contraindications to PA, resulting in treatment stage migration (TSM). Methods: Barcelona Clinic Liver Cancer (BCLC) 0/A patients diagnosed between September 2013 and September 2019 across five hospitals were identified. Primary endpoint was proportion of BCLC 0/A HCCs with contraindications to PA. Secondary endpoints included overall survival (OS), local tumor control (LTC), and recurrence-free survival (RFS). The causal effects of PA versus TSM were assessed using a potential outcome means (POM) framework in which the average treatment effects (ATEs) of PA were estimated after accounting for potential selection bias and confounding. Results: Two hundred twenty patients with inoperable BCLC 0/A HCC were identified. One hundred twenty-two patients (55.5%) had contraindications to PA and received TSM therapy, 98 patients (44.5%) received PA. The main contraindication to PA was difficult tumor location (51%). Patients who received TSM therapy had lower median OS (2.4 vs 5.3 years), LTC (1.0 vs 4.8 years), and RFS (0.8 vs 2.9 years); P < 0.001, respectively, compared with PA. The ATE for PA versus TSM yielded an additional 1.11 years (P = 0.019), 2.45 years (P < 0.001), and 1.64 years (P < 0.001) for OS, LTC, and RFS, respectively. Three-year LTC after PA was suboptimal (65%). Conclusion: Our study highlights high rates of contraindication to PA in early HCCs, resulting in TSM and poorer outcomes. The LTC rate for PA appears suboptimal despite being considered as curative therapy. Both findings support the exploration of improved treatment options for early HCCs.

Evaluation of tumor mutational burden in small early hepatocellular carcinoma and progressed hepatocellular carcinoma.

While researchers know that tumor mutational burden (TMB) is low in hepatocellular carcinoma (HCC), prior studies have not investigated TMB in cirrhosis, small early HCC and progressed HCC. HCC (n = 18) and cirrhosis (n = 6) cases were identified. TMB was determined by a 1.7 megabase, 409-gene next-generation sequencing panel. TMB values were defined as the number of nonsynonymous variants per megabase of sequence. There was no significant difference between cirrhosis versus small early HCC or between cohorts when stratified by size, early versus progressed, differentiation or morphology. There was a significant difference between cirrhosis and small early HCC versus progressed HCC (p = 0.045), suggesting TMB may be related to HCC progression. TMB similarities in small early HCC and background cirrhosis suggest TMB is not a useful tool for diagnosing small early HCC. Additional study is needed to address TMB in histological and molecular subsets of HCC.

Diagnostic role of contrast-enhanced ultrasonography versus conventional B-mode ultrasonography in cirrhotic patients with early hepatocellular carcinoma: a retrospective study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) is very important for the prognosis of patients. However, there are very few studies that compared the diagnostic accuracy of contrast-enhanced ultrasonography (CEUS) and B-mode ultrasonography for early HCC in cirrhotic patients. METHODS: This retrospective study included cirrhotic patients, who were suspected of early HCC between January 2020 and June 2021. The diagnosis of patients was based on the pathology results of surgery or biopsy. Demographic and clinical characteristics of included patients were recorded. The diagnoses of suspected lesions using both types of ultrasonography were recorded, and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of early HCC in cirrhotic patients were calculated. RESULTS: Eventually, 137 patients with solitary lesions in the liver were included in this study, including 89 patients diagnosed with HCC and 48 patients diagnosed with non-HCC. The median diameter of suspected lesions was 26 mm, and the median level of alpha fetoprotein (AFP) was 37.2 ng/mL. When comparing the demographic and clinical characteristics of cirrhotic patients with HCC and non-HCC, it was found that patients with HCC had significantly higher levels of AFP than those with non-HCC (P=0.03). The sensitivity, specificity, PPV, NPV, and accuracy of CEUS in early HCC were 73%, 93.8%, 95.6%, 65.2% and 80.3%, respectively. In CEUS, all of these parameters were much higher than those in B-mode ultrasonography, i.e., 64%, 75%, 82.6%, 52.9%, and 67.9%. It was also found that the diagnostic accuracy of CEUS was much higher than that of B-mode ultrasonography especially regarding lesions <20 mm. To further improve the sensitivity of CEUS in early HCC, AFP was combined with CEUS for the diagnosis of early HCC. As a result, the sensitivity, specificity, PPV, NPV, and accuracy of CEUS combined with AFP level were 83.1%, 87.5%, 92.5%, 73.7%, and 84.7%, respectively. CONCLUSIONS: Our study confirmed that CEUS' diagnostic accuracy for early HCC in cirrhotic patients was significantly higher than that of B-mode ultrasonography. However, the sensitivity of CEUS needs to be improved further, and the combination of CEUS and AFP level may be a potential solution.

A nomogram to predict microvascular invasion in early hepatocellular carcinoma.

AIM: To construct an integrated nomogram combining protein induced by vitamin K antagonist-II (PIVKA-II), alpha fetoprotein (AFP) and other clinical factors to detect microvascular invasion (MVI) in early hepatocellular carcinoma (HCC) patients with single nodule. METHODS: One hundred and eleven early HCC patients were enrolled in the present study and 43 early HCC patients were diagnosed with MVI. Serum levels of PIVKA-II, AFP and other laboratory indicators were detected. Chi-squared test, t-test and logistic regression were employed in statistic analysis. A nomogram combining independent predictors was constructed and internal validated. RESULTS: In early HCC patients with MVI, PIVKA-II serum level was significantly higher than those without MVI (385.97 mAU/ml vs 67.08 mAU/ml; P < 0.01), as well as AFP serum level (81.6 ng/mL vs 9.15 ng/mL P = 0.001). PIVAK-II, AFP serum levels and tumor size were independent risk factors for MVI in early HCC, which was employed to develop a logistic regression model. The area under the ROC curve (AUROC) of the model was 0.74 (95%CI 0.65 - 0.84). A nomogram combining PIVKA-II, AFP and tumor size was constructed and calibration curves showed that the model was accurate in predicting the risk of MVI in early HCC patients. CONCLUSION: The present study indicates that a preoperative nomogram combining PIVKA-II, AFP and tumor size could estimate the preoperative probability of MVI in early HCC patients, which may help clinicians in choosing treatment options and prognosis evaluation.

Factors predicting long-term outcomes of early-stage hepatocellular carcinoma after primary curative treatment: the role of surgical or nonsurgical methods.

BACKGROUND: We quantified the elusive effects of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment. METHODS: Patients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) rates were compared. A polytomous logistic regression was used to estimate factors for early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression. RESULTS: One hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Neither match analysis based on propensity score nor multiple adjustment regression yielded a significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (> 20 ng/mL), and multinodularity significantly increased risk of early recurrence (< 1 year). In contrast, hepatitis B virus, hepatitis C virus and multinodularity were significantly associated with late recurrence (> 1 year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR = 1.55, 95% CI:1.01-2.36), clinically significant portal hypertension (CSPH) (HR = 1.97, 95% CI:1.26-3.08), early recurrence (HR = 6.62, 95% CI:3.79-11.6) and late recurrence (HR = 3.75, 95% CI:1.99-7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment. In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS compared to RFA with or without TACE. CONCLUSION: Host and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary.

Multiregional whole-genome sequencing of hepatocellular carcinoma with nodule-in-nodule appearance reveals stepwise cancer evolution.

Recent genetic analyses revealed genetic heterogeneity in hepatocellular carcinoma (HCC), although it remains unclear how genetic alterations contribute to the multistage progression of HCC, especially the early step from hypovascular liver nodules to hypervascular HCC. We conducted multiregional whole-genome sequencing on HCCs with a nodule-in-nodule appearance, consisting of inner hypervascular HCC surrounded by hypovascular HCC arising from a common origin, and identified point mutations, structural variations, and copy-number variations in each specimen. According to the genetic landscape of the inner and outer regions, together with the pathological and radiological findings, we examined the stepwise evolution of cancer cells from slow-growing HCC to rapid-growing HCC. We first demonstrated that most tumor cells consisting of hypovascular well-differentiated HCCs already harbored thousands of point mutations and even several structural variations, including chromosomal translocations and chromothripsis, as the trunk events. Telomerase reverse transcriptase (TERT)-associated aberrations, including promoter mutations, chromosomal translocation, and hepatitis B virus DNA integration, as well as abnormal methylation status, were commonly detected as the trunk aberrations, while various liver cancer-related genes, which differed in each case, had additionally accumulated in the inner dedifferentiated nodules. Further, differences in the trunk and branch mutational signatures suggested a multistep contribution to the mutagenesis in each case. In conclusion, genomic alterations associated with the TERT gene could be the key driver events to form the hypovascular HCC, and additional case-specific driver mutations accumulate during the progression phase, forming intra- and inter-tumoral heterogeneity, confirming the importance of genetic testing before targeting therapy. These data shed light on the process of multistep hepatocarcinogenesis and will be helpful toward investigating new therapeutic strategies for HCC. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Minimally invasive surgery versus radiofrequency ablation for single subcapsular hepatocellular carcinoma ≤ 2 cm with compensated liver cirrhosis.

BACKGROUND: There is currently no consensus regarding the relative applicability of minimally invasive treatment, including radiofrequency ablation (RFA) and minimally invasive surgery (MIS) in patients with a single small peripheral hepatocellular carcinoma (HCC) and compensated cirrhosis. This study investigated the clinical outcomes of MIS and RFA for single subcapsular HCC ≤ 2 cm in patients with compensated cirrhosis. METHODS: In this retrospective study, we enrolled 75 patients who had a single subcapsular HCC ≤ 2 cm along with Child-Pugh class A cirrhosis and a preoperative platelet count ≥ 100 k/µl. These patients underwent RFA (n = 39) or MIS (n = 36) between 2010 and 2016. Clinical outcomes including disease-free survival (DFS), survival without recurrence beyond the Milan criteria (RBM), and overall survival (OS) were compared. RESULTS: The 7-year DFS rates in the MIS and RFA groups were 86.1% and 35.9% (p < 0.001), respectively, the 7-year RBM rates were 88.9% and 66.7% (p = 0.014), respectively, and the 7-year OS rates were 97.2% and 82.1% (p = 0.008), respectively. RFA was associated with more ipsilateral lobe recurrence (20% vs. 83.4%, p = 0.004), and 40% were in direct contact with the ablation penumbra. A Cox proportional hazard analysis identified RFA as an independent predictor of mortality (adjusted hazard ratio, 9.625, p = 0.038). No major complications occurred in either group. RFA patients had a shorter hospital stay (median of 2 vs. 6 days, p < 0.001) and operation time (median of 23.5 vs. 216 min, p = 0.001). CONCLUSIONS: MIS was associated with a better 7-year OS, RBM, and DFS among patients with single subcapsular HCC ≤ 2 cm, Child-Pugh A liver function, and no clinically significant portal hypertension when compared to those who underwent percutaneous RFA.

Multi-marker diagnosis method for early Hepatocellular Carcinoma based on surface plasmon resonance.

Early diagnosis of Hepatocellular Carcinoma (HCC) is an important means to raise the survival rate of patients. Multi-marker combined detection is a powerful tool of early HCC diagnosis. Traditional detection methods are not effective and accurate because it is difficult to achieve combined detection of multiple markers. In this paper, we selected Alpha Fetoprotein (AFP) and miRNA-125b as the combined detection markers to improve the simultaneously diagnostic sensitivity and specificity. The anti-AFP monoclonal antibody and the DNA probes paired with the miRNA-125b were modified on the surface of surface plasmon resonance (SPR) sensor respectively to specifically recognize AFP and miRNA-125b in serum. In order to enhance the SPR response signal and detection sensitivity, Double Antibody Sandwich Method (DASM) and S9.6 antibody enhanced method were applied to achieve low detection limit of the two markers. Experimental results showed that AFP (25-400 ng/mL) was accurately detected by DASM and the detection limit of miRNA-125b by S9.6 antibody enhanced method reached 123.044 pM. These results verified the feasibility of the multi-marker detection method in early diagnosis of HCC.

A Simple-to-Use Nomogram for Predicting the Survival of Early Hepatocellular Carcinoma Patients.

Objective: This study aimed to develop and validate a simple-to-use nomogram for early hepatocellular carcinoma (HCC) patients undergoing a preoperative consultation and doctors conducting a postoperative evaluation. Methods: A total of 2,225 HCC patients confirmed with stage I or II were selected from the Surveillance, Epidemiology, and End Results database between January 2010 and December 2015. The patients were randomly divided into two groups: a training group (n = 1,557) and a validation group (n = 668). Univariate and multivariate hazards regression analyses were used to identify independent prognostic factors. The Akaike information criterion (AIC) was used to select variables for the nomogram. The performance of the nomogram was validated concerning its ability of discrimination and calibration and its clinical utility. Results: Age, alpha-fetoprotein (AFP), race, the degree of differentiation, and therapy method were significantly associated with the prognosis of early HCC patients. Based on the AIC results, five variables (age, race, AFP, degree of differentiation, and therapy method) were incorporated into the nomogram. The concordance indexes of the simple nomogram in the training and validation groups were 0.707 (95% CI: 0.683-0.731) and 0.733 (95% CI: 0.699-0.767), respectively. The areas under the receiver operating characteristic (ROC) curve of the nomogram in the training and validation groups were 0.744 and 0.764, respectively, for predicting 3-year survival, and 0.786 and 0.794, respectively, for predicting 5-year survival. Calibration plots showed good consistency between the predictions of the nomogram and the actual observations in both the training and validation groups. Decision curve analysis (DCA) showed that the simple nomogram was clinically useful, and the overall survival significantly differed between low- and high-risk groups divided by the median score of the nomogram in the training group (P < 0.001). Conclusion: A simple-to-use nomogram based on a large population-based study is developed and validated, which is a conventional tool for doctors to facilitate the individual consultation of preoperative patients and the postoperative personalized evaluation.

Stromal morphological changes and immunophenotypic features of precancerous lesions and hepatocellular carcinoma.

AIMS: To evaluate stromal histopathological features and immunostaining expression for differential diagnosis of low- and high-grade dysplastic nodules (HGDN) to early and progressed hepatocellular carcinomas (eHCC, pHCC). MATERIALS: We evaluated sinusoid capillarisation (SC), solitary artery (SA), ductular reaction (DR), stromal invasion and expression of six biomarkers (GPC3, HSP70, GS, CD34, CK19, EpCAM) in a series of 97 cases. RESULTS: Stromal morphological changes, including SC, DR and SA, exhibited significant differences in differential diagnosis. In one indicator, SC had the best sensitivity (90.00%) and accuracy (85.42%), and SA had the best specificity at 88.89 %. In combinations, SC +and SA +were favourable and optimal. The immunoreactivity of GPC3, HSP70 and GS increased significantly in line with the stepwise progression of hepatocarcinogenesis. CONCLUSIONS: Stromal histopathology features are useful for diagnosing HGDN, eHCC and small HCC. The immunostaining panel of GPC3, HSP70 and GS can also be supplementary.

The impact of transarterial chemoembolization induced complications on outcomes after liver transplantation: A propensity-matched study.

BACKGROUND: Loco-regional complications of transarterial chemoembolization (TACE) may adversely affect technical aspects of the liver transplantation (LT). This study reviewed the impact of those complications on postoperative outcomes encompassing implications on graft selection. METHODS: A retrospective, propensity score matching (1:1) analysis accounting for donor and recipient confounders was performed on a dataset of patients undergoing LT for hepatocellular carcinoma. Outcomes of patients who had TACE (TACE-group) were compared with those who did not (NoTACE-group). RESULTS: A total of 57 matched pairs were analyzed. TACE achieved effective tumor control (Pre-TACE vs Post-TACE; Median: 44 mm [interquartile range: 43-50] vs 17 mm [0-36]; P = .002) on imaging follow-up. TACE group had, at the hepatectomy, higher incidence of ischemia-related complications (adhesions of the necrotic tumor, cholecystitis, and/or bile duct necrosis) (40.4% vs 10.5%; P = .001). Overall major post-LT complications rate (Dindo-Clavien ≥3) were similar (P = .134). Those in the TACE group with donors after circulatory death (DCD) had 4.6% 90-day mortality and 54.3% major complication rate compared to 6.9% and 77.3% (P = .380 and P = .112, respectively). CONCLUSION: TACE was an effective bridging procedure that may complicate LT inducing ischemic-related complications; nevertheless, it has not shown repercussions on mortality or morbidity after the procedure, even using donors after circulatory death.

Microvascular invasion and positive HB e antigen are associated with poorer survival after hepatectomy of early hepatocellular carcinoma: A retrospective cohort study.

BACKGROUND: We aimed to identify the independent predictive factors of microvascular invasion (MVI) for curative resection of HCC and to investigate the impacts of MVI and HBeAg on long-term recurrence and survival after resection. METHODS: The clinicopathological parameters of 237 patients with HCC with MVI who underwent hepatic resection from April 2005 to November 2010 were investigated. Clinical features and factors associated with the clinical outcomes of 386 patients with HCC without MVI were used for comparison. RESULTS: Multivariate stepwise logistic regression analysis revealed that alpha-fetoprotein level>100µg/L, positive HBeAg, and tumour size were independent prognostic factors in patients with HCC with MVI. The overall survival (OS) of patients in the HCC with MVI group was significantly poorer compared with the HCC without MVI group (P<0.001). However, patients with HCC without MVI group exhibited a significantly better recurrence-free survival rate (RFS) (P<0.001). While the HCC with positive HBeAg group exhibited significantly lower OS compared with the HCC with negative HBeAg group (P=0.007). CONCLUSIONS: AFP level>100µg/L, positive HBeAg, and tumour size>2cm are independent indicators of poorer prognosis for HCC with MVI. The present study confirmed that microvascular invasion itself had a negative impact on patient survival; moreover, HBeAg was an independent risk factor influencing OS, while not RFS of patients with HCC underwent hepatectomy. It is important to predict the presence of MVI before hepatic resection to determine treatment strategies.

Novel Mahalanobis-based feature selection improves one-class classification of early hepatocellular carcinoma.

Detection of early hepatocellular carcinoma (HCC) is responsible for increasing survival rates in up to 40%. One-class classifiers can be used for modeling early HCC in multidetector computed tomography (MDCT), but demand the specific knowledge pertaining to the set of features that best describes the target class. Although the literature outlines several features for characterizing liver lesions, it is unclear which is most relevant for describing early HCC. In this paper, we introduce an unconstrained GA feature selection algorithm based on a multi-objective Mahalanobis fitness function to improve the classification performance for early HCC. We compared our approach to a constrained Mahalanobis function and two other unconstrained functions using Welch's t-test and Gaussian Data Descriptors. The performance of each fitness function was evaluated by cross-validating a one-class SVM. The results show that the proposed multi-objective Mahalanobis fitness function is capable of significantly reducing data dimensionality (96.4%) and improving one-class classification of early HCC (0.84 AUC). Furthermore, the results provide strong evidence that intensity features extracted at the arterial to portal and arterial to equilibrium phases are important for classifying early HCC.

Utility of percutaneous radiofrequency ablation alone or combined with transarterial chemoembolization for early hepatocellular carcinoma.

Percutaneous radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) is an effective, standard therapy against small hepatocellular carcinoma (HCC). However, there is debate regarding the effectiveness of RFA combined with TACE (RFA/TACE) compared with RFA alone. These two approaches were compared for the treatment of early HCC. The present study examined 83 HCC tumors in 83 patients treated with RFA between April 2007 and August 2014 at three medical institutions. All HCCs were single hypervascular tumors, with a median diameter of 16 mm (range, 6-30 mm). The overall survival (OS) rate of all patients (n=83) was 97.5% at 1 year, 82.8% at 3 years and 48.6% at 5 years, and the local recurrence rate of all patients was 14.3% at 1 year, 32.3% at 3 years and 36.5% at 5 years. The tumor-free survival (TFS) rate of all patients was 95.1% at 1 year, 56.3% at 3 years and 23.4% at 5 years. Compared with RFA alone, RFA/TACE significantly improved OS (P<0.001), intrahepatic distant recurrence (IDR; P=0.038) and TFS (P=0.010). A univariate analysis of prognostic indicators revealed that age <70 years (P=0.008), aspartate transaminase <40 IU/l (P=0.003), alanine aminotransferase <40 IU/l (P=0.006) and platelet count >10×104/µl (P=0.05) were associated with a high survival rate. Multivariate analysis identified RFA/TACE [hazard ratio (HR), 0.108; P=0.001] as an independent prognostic indicator. RFA/TACE was identified as the only independent indicator of IDR (HR: 0.467; P=0.042) and TFS (HR: 0.452; P=0.012). RFA/TACE improved OS rate, IDR and TFS compared with RFA alone. The data suggested that RFA/TACE should be considered for the treatment of single hypervascular HCC.

Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma.

AIM: To evaluate whether pathologically early hepatocellular carcinoma (HCC) exhibited local tumor progression after radiofrequency ablation (RFA) less often than typical HCC. METHODS: Fifty pathologically early HCCs [tumor diameter (mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter (mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion (namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method. RESULTS: During the follow-up period for the 50 pathologically early HCCs, 49 (98%) of the nodules did not exhibit local tumor progression. However, 1 nodule (2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46 (24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0% (7/187), 16.0% (30/187), 21.9% (41/187) and 24.6% (46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test (P = 0.002). CONCLUSION: The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs.

Personalized treatment of patients with very early hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), in its very early stage, is heterogeneous both in terms of liver function (i.e., presence or absence of portal hypertension, model for end-stage liver disease score, Child-Pugh score 5 or 6, bilirubin level) and tumor characteristics (i.e., location, alpha-fetoprotein values, pathological features such as microvascular invasion, tumor grade and satellitosis). Existing evidence in comparing different curative options for patients with very early HCC is poor due to small sample sizes and lack of solid subgroup analyses. Large observational studies are available, with the potential to identify effective interventions in different subgroup of patients and to discover which treatments work "in a real world setting". These studies suggest some important treatment selection strategies in very early HCC patients. According to extent of liver resection, and liver function, percutaneous ablation or liver resection are the recommended first line therapies in these patients. Laparoscopic surgery (resection or ablation) is the preferable strategy when the tumor is in the surface of the liver or close to extra-hepatic organs. Due to scarce donor resources and competition with patients at high transplant benefit (HCC patients unsuitable for non-transplant radical therapies and non-HCC patients with decompensated cirrhosis), transplantation is recommended only as second line therapy in patients with very early stage HCC in case of tumor recurrence or liver failure after ablation or liver resection.