Comparison of laparoscopic hepatectomy and radiofrequency ablation for small hepatocellular carcinoma patients: a SEER population-based propensity score matching study.

This study was designed to compare the efficacy of laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) in terms of their therapeutic effect on small hepatocellular carcinoma (SHCC). The SEER database was employed to integrate SHCC patients who had received treatment with either LH (n = 1132) or RFA (n = 797). The LH group (n = 623) and the RFA group (n = 623) were matched with 1:1 propensity score matching (PSM) in order to reduce the possibility of selection bias. The Kaplan-Meier method and Cox proportional hazards regression method were employed to ascertain the prognostic factors associated with overall survival (OS) and disease-specific survival (DSS). Both before and after PSM, the 1, 3 and 5-years OS and DSS were significantly higher in the LH groups compared to the RFA group. Besides, for SHCC with tumor size ≤ 2cm (n = 418), even P values not reaching statistical significance, the survival curves were compatible with a superiority of LH over RFA for OS and DSS in overall (P = 0.054 and P = 0.077), primary SHCC (P = 0.110 and P = 0.058) and recurrent SHCC (P = 0.068 and P = 1.000) cohorts. In contrast, for SHCC with tumor size between 2 and 3 cm (n = 828), LH group always had a better OS and DSS in the all cohorts (all P < 0.05). In addition, higher AFP level, poor differentiation grade, recurrent tumor and treatment type were independent prognostic factors for OS, while poor differentiation grade, larger tumor size and treatment type were the independent prognostic factors for DSS (all P < 0.05). LH was associated with better OS and DSS than RFA in SHCC patients. Even in tumor size ≤ 2 cm, LH still should be the first choice as its long-term survival benefits.

Nomograms established for predicting microvascular invasion and early recurrence in patients with small hepatocellular carcinoma.

BACKGROUND: In this study, we aimed to establish nomograms to predict the microvascular invasion (MVI) and early recurrence in patients with small hepatocellular carcinoma (SHCC), thereby guiding individualized treatment strategies for prognosis improvement. METHODS: This study retrospectively analyzed 326 SHCC patients who underwent radical resection at Wuhan Union Hospital between April 2017 and January 2022. They were randomly divided into a training set and a validation set at a 7:3 ratio. The preoperative nomogram for MVI was constructed based on univariate and multivariate logistic regression analysis, and the prognostic nomogram for early recurrence was constructed based on univariate and multivariate Cox regression analysis. We used the receiver operating characteristic (ROC) curves, area under the curves (AUCs), and calibration curves to estimate the predictive accuracy and discriminability of nomograms. Decision curve analysis (DCA) and Kaplan-Meier survival curves were employed to further confirm the clinical effectiveness of nomograms. RESULTS: The AUCs of the preoperative nomogram for MVI on the training set and validation set were 0.749 (95%CI: 0.684-0.813) and 0.856 (95%CI: 0.805-0.906), respectively. For the prognostic nomogram, the AUCs of 1-year and 2-year RFS respectively reached 0.839 (95%CI: 0.775-0.903) and 0.856 (95%CI: 0.806-0.905) in the training set, and 0.808 (95%CI: 0.719-0.896) and 0.874 (95%CI: 0.804-0.943) in the validation set. Subsequent calibration curves, DCA analysis and Kaplan-Meier survival curves demonstrated the high accuracy and efficacy of the nomograms for clinical application. CONCLUSIONS: The nomograms we constructed could effectively predict MVI and early recurrence in SHCC patients, providing a basis for clinical decision-making.

Nomogram prediction of vessels encapsulating tumor clusters in small hepatocellular carcinoma ≤ 3 cm based on enhanced magnetic resonance imaging.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma (HCC). However, it seems that no one have focused on predicting VETC status in small HCC (sHCC). This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC (≤ 3 cm) patients. AIM: To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients. METHODS: A total of 309 patients with sHCC, who underwent segmental resection and had their VETC status confirmed, were included in the study. These patients were recruited from three different hospitals: Hospital 1 contributed 177 patients for the training set, Hospital 2 provided 78 patients for the test set, and Hospital 3 provided 54 patients for the validation set. Independent predictors of VETC were identified through univariate and multivariate logistic analyses. These independent predictors were then used to construct a VETC prediction model for sHCC. The model's performance was evaluated using the area under the curve (AUC), calibration curve, and clinical decision curve. Additionally, Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence, just as it is with the actual VETC status and early recurrence. RESULTS: Alpha-fetoprotein_lg10, carbohydrate antigen 199, irregular shape, non-smooth margin, and arterial peritumoral enhancement were identified as independent predictors of VETC. The model incorporating these predictors demonstrated strong predictive performance. The AUC was 0.811 for the training set, 0.800 for the test set, and 0.791 for the validation set. The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets. Furthermore, the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC. Finally, early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group, regardless of whether considering the actual or predicted VETC status. CONCLUSION: Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC (≤ 3 cm) patients, and it holds potential for predicting early recurrence. This model equips clinicians with valuable information to make informed clinical treatment decisions.

Laparoscopic-assisted microwave ablation in treatment of small hepatocellular carcinoma: safety and efficacy in comparison with laparoscopic hepatectomy.

Laparoscopic-assisted microwave ablation (LAMWA), as one of the locoregional therapies, has been employed to treat hepatocellular carcinoma (HCC). This study aims to compare the efficacy and safety of LAMWA and laparoscopic hepatectomy in the treatment of small HCC.This study included 140 patients who met the inclusion criteria. Among them, 68 patients received LAMWA and 72 patients underwent laparoscopic hepatectomy. The perioperative condition, liver function recovery, the alpha fetoprotein (AFP) level, morbidities, hospitalization time, overall survival (OS), disease-free survival (DFS) and recurrence rate between the two groups were compared. The rate of complete elimination of tumor tissue was 100% and the AFP level was returned to normal within 3 months after surgery in both groups (P > 0.05). The mean alanine transaminase (ALT) and aspartate transaminase (AST) peak in the LAMWA group was lower than that in the laparoscopic hepatectomy group (259.51 ± 188.75 VS 388.9 ± 173.65, P = 0.000) and (267.34 ± 190.65 VS 393.1 ± 185.67, P = 0.000), respectively. The mean operation time in the LAMWA group was shorter than that in the laparoscopic hepatectomy group (89 ± 31 min VS 259 ± 48 min, P = 0.000). The blood loss in the LAMWA group was less than that in the laparoscopic hepatectomy group (58.4 ± 64.0 ml VS 213.0 ± 108.2 ml, P = 0.000). Compared with the laparoscopic hepatectomy group, patients in the LAMWA group had lower mean hospital stay (4.8 ± 1.2d VS 11.5 ± 2.9d, P = 0.000). The morbidities of the LAMWA group and the hepatectomy group were 14.7%(10/68) and 34.7%(25/72), respectively (P = 0.006). The one-, three-, and five-year OS rates were 88.2%, 69.9%, 45.6% for the LAMWA group and 86.1%, 72.9%, 51.4% for the laparoscopic hepatectomy group (P = 0.693). The corresponding DFS rates for the two groups were 76.3%, 48.1%, 27.9% and 73.2%, 56.7%, 32.0% (P = 0.958). Laparoscopic-assisted microwave ablation is a safe and effective therapeutic option for selected small HCC.

Laparoscopic liver resection is superior to radiofrequency ablation for small hepatocellular carcinoma: a systematic review and meta-analysis of propensity score-matched studies.

BACKGROUND: The approach in small hepatocellular carcinoma (HCC) is controversial, no prospective randomized trials to compare ablative or surgical approaches. We compared the surgical and oncological outcomes after laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) in small HCC patients based on matched cohort studies that performed propensity score matching (PSM). METHODS: We systemically searched the PubMed, Cochrane Library, Embase, Web of Science, and the Chinese BioMedical Literature (CBM) databases. All published propensity score-matched studies that compared LH and RFA for small HCC were included in this study. RESULTS: Eight studies with a total of 1273 small HCC cases were included. The results of the meta-analysis revealed that there was no significant difference in the 1- year overall survival (OS) rate between the two groups, whereas the LH group had significantly higher 3- year overall survival rate (RR = 1.14, 95% CI 1.08-1.20, p < 0.00001) as well as 1- and 3-year disease-free survival (DFS) rates (RR = 1.31, 95% CI 1.22-1.42, p < 0.00001; RR = 1.66, 95% CI 1.46-1.90, p < 0.00001) than the RFA group. Meanwhile, the local recurrence rate and intrahepatic distant recurrence rate were significantly lower in the LH group than in the RFA group (RR = 0.29, 95% CI 0.20-0.42, p < 0.00001; RR = 0.67, 95% CI 0.49-0.92, p = 0.01). In comparison with the LH group, the RFA group had a lower incidence of overall and major postoperative complications (RR = 1.81, 95% CI 1.47-2.24, p < 0.00001; RR = 2.76, 95% CI 1.48-5.12, p = 0.001), but there was no significant difference in postoperative mortality between the two groups. In addition, further comparison of single postoperative complications showed that the incidence of ascites was lower in the RFA group than in the LH group (RR = 3.62, 95% CI 1.64-7.96, p = 0.001), whereas there was no significant difference in the incidence of postoperative bleeding, abdominal infection and bile leakage between the two groups (RR = 3.50, 95% CI 0.74-16.61, p = 0.11; RR = 5.00, 95% CI 0.59-42.23, p = 0.14; RR = 4.00, 95% CI 0.45-35.23, p = 0.21). Besides, the hospital stay was shorter in the RFA group than in the LH group (MD = 4.29, 95% CI 2.06-6.53, p = 0.0002). CONCLUSIONS: Our meta-analysis demonstrated that in comparison with RFA in the treatment of small HCC, LH provided superior long-term OS and DFS together with lower rates of local and intrahepatic distant recurrence after surgery. However, RFA was associated with better short-term outcomes.

Differential diagnosis of small hepatocellular carcinoma and dysplastic nodule based on diffusion weighted imaging radiomics model / 实用放射学杂志

Objective To investigate the diagnostic value of diffusion weighted imaging(DWI)-based radiomics model to identify small hepatocellular carcinoma(＜2 cm)(SHCC)and dysplastic nodule(DN)in the background of hepatitis cirrhosis.Methods A total of 93 cases SHCC and 25 cases with DN with complete enhanced MRI images and surgically pathologically confirmed were collected retrospectively.Chi-square test was performed to analyze the signal characteristics of DWI and enhanced triphasic MRI images between the two groups.ITK-SNAP was used to draw the region of interest(ROI)on DWI,and FAE software was applied for extraction,selec-tion,and construction of support vector machine(SVM)models(dividing into training set and test set according to the ratio of 7∶3).The diagnostic performance of model was evaluated by receiver operating characteristic(ROC)curve.Results There were statisti-cally significant differences in enhanced triphasic MRI and DWI between SHCC and DN(P＜0.05).The area under the curve(AUC)of the DWI-SVM model training set was 0.936,and sensitivity,specificity and accuracy was 95.4％,88.2％and 93.9％,respec-tively,and the AUC of the test set was 0.911,and sensitivity,specificity and accuracy was 85.7％,87.5％and 86.1％,respectively,which were all significantly better than the diagnostic efficacy of DWI(AUC=0.720).Conclusion DWI-SVM model with signifi-cantly higher AUC and specificity can effectively differentiate SHCC from DN in the background of hepatitis cirrhosis.

Differentiation between small hepatocellular carcinoma (<3 cm) and benign hepatocellular lesions in patients with Budd-Chiari syndrome: the role of multiparametric MR imaging.

Objective: To investigate the value of multiparametric MR imaging to differentiate between small hepatocellular carcinoma (s-HCC) versus benign liver lesions in patients with Budd-Chiari syndrome. Methods: 12 patients with benign hepatocellular lesions and 32 patients with small (<3 cm) HCCs were assessed. MRI images were reviewed by two radiologists blinded to the patient background information; lesion T1 and T2 signal intensities and ADC values were compared with the background liver. Enhancement of lesion relative to hepatic parenchyma [(T1Enh-T1liver)/T1liver] in the arterial, venous, and delayed phases was also compared between the two groups. A multivariable logistic model was developed using these categorical measures; the predictive value of the model was tested using the Area Under the Receiver operating characteristic (AU-ROC) curve for logistic models. P-values <0.05 were considered statistically significant. Results: There were consistent differences in T1lesion/T1liver, and T2lesion/T2liver, and ADClesion/ADCliver between benign hepatocellular lesions versus the sHCC group (p<0.001, p<0.001, p = 0.045, respectively). Lesion-to-background liver enhancement in the portal venous and delayed phases was different between the benign lesions versus sHCC (p=0.001). ROC analysis for the logistic model that included the T1 ratio, T2 ratio, and portal venous enhancement ratio demonstrated excellent discriminatory power with the area under the curve of 0.94. Conclusion: Multiparametric MR imaging is a useful method to help differentiate benign liver lesions from sHCC in patients with Budd-Chiari syndrome.

Optimal treatment for small HCC (<3 cm): Resection, liver transplantation, or locoregional therapy?

Hepatocellular carcinoma (HCC) remains the most common form of liver cancer, accounting for 90% of all primary liver cancers. Up to 30% of HCC cases could be small (2-3 cm in diameter) at the time of diagnosis with advances in imaging techniques and surveillance programmes. Treating patients with early-stage HCC can be complex and often requires interdisciplinary care, owing to the wide and increasing variety of treatment options, which include liver resection, liver transplantation, and various locoregional therapies offered by interventional radiology and radiation oncology. Decisions regarding the optimal management strategy for a patient involve many considerations, including patient- and tumour-specific characteristics, as well as socioeconomic factors. In this review, we aim to comprehensively summarise the commonly used therapies for single, small HCC (<3 cm), with a focus on the impact of tumour size (<2 cm vs. 2-3 cm), as well as a brief discussion on the cost-effectiveness of the different treatment options.

Gadoxetic acid-enhanced MRI with a focus on LI-RADS v2018 imaging features predicts the prognosis after radiofrequency ablation in small hepatocellular carcinoma.

Introduction: Gadoxetic acid-enhanced magnetic resonance imaging (MRI) contributes to evaluating the prognosis of small hepatocellular carcinoma (sHCC) following treatment. We have investigated the potential role of gadoxetic acid-enhanced MRI based on LI-RADS (Liver Imaging Reporting and Data System) v2018 imaging features in the prognosis prediction of patients with sHCC treated with radiofrequency ablation (RFA) as the first-line treatment and formulated a predictive nomogram. Methods: A total of 204 patients with sHCC who all received RFA as the first-line therapy were enrolled. All patients had undergone gadoxetic acid-enhanced MRI examinations before RFA. Uni- and multivariable analyses for RFS were assessing using a Cox proportional hazards model. A novel nomogram was further constructed for predicting RFS. The clinical capacity of the model was validated according to calibration curves, the concordance index (C-index), and decision curve analyses. Results: Alpha fetoprotein (AFP) > 100 ng/ml (HR, 2.006; 95% CI, 1.111-3.621; P = 0.021), rim arterial phase hyperenhancement (APHE) (HR, 2.751; 95% CI, 1.511-5.011; P = 0.001), and targetoid restriction on diffusion-weighted imaging (DWI) (HR, 3.289; 95% CI, 1.832-5.906; P < 0.001) were considered as the independent risk features for recurrence in patients with sHCC treated with RFA. The calibration curves and C-indexes (C-index values of 0.758 and 0.807) showed the superior predictive performance of the integrated nomogram in both the training and validation groups. Discussion: The gadoxetic acid-enhanced MRI features based on LI-RADS v2018, including rim APHE, targetoid restriction on DWI, and the AFP level, are the independent risk factors of recurrence in patients with sHCC treated with RFA as the first-line therapy. The predictive clinical-radiological nomogram model was constructed for clinicians to develop individualized treatment and surveillance strategies.

Radiomics nomogram based on multi-parametric magnetic resonance imaging for predicting early recurrence in small hepatocellular carcinoma after radiofrequency ablation.

Background: There are few studies on the application of radiomics in the risk prediction of early recurrence (ER) after radiofrequency ablation (RFA). This study evaluated the value of a multi-parametric magnetic resonance imaging (MRI, mpMRI)-based radiomics nomogram in predicting ER of small hepatocellular carcinoma (HCC) after RFA. Materials and methods: A retrospective analysis was performed on 90 patients with small HCC who were treated with RFA. Patients were divided into two groups according to recurrence within 2 years: the ER group (n=38) and the non-ER group (n=52). Preoperative T1WI, T2WI, and contrast-enhanced MRI (CE-MRI) were used for radiomic analysis. Tumor segmentation was performed on the images and applied to extract 1316 radiomics features. The most predictive features were selected using analysis of variance + Mann-Whitney, Spearman's rank correlation test, random forest (importance), and least absolute shrinkage and selection operator analysis. Radiomics models based on each sequence or combined sequences were established using logistic regression analysis. A predictive nomogram was constructed based on the radiomics score (rad-score) and clinical predictors. The predictive efficiency of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC). Decision curve analysis (DCA) was used to evaluate the clinical efficacy of the nomogram. Results: The radiomics model mpMRI, which is based on T1WI, T2WI, and CE-MRI sequences, showed the best predictive performance, with an AUC of 0.812 for the validation cohort. Combined with the clinical risk factors of albumin level, number of tumors, and rad-score of mpMRI, the AUC of the preoperative predictive nomogram in the training and validation cohorts were 0.869 and 0.812, respectively. DCA demonstrated that the combined nomogram is clinically useful. Conclusions: The multi-parametric MRI-based radiomics nomogram has a high predictive value for ER of small HCC after RFA, which could be helpful for personalized risk stratification and further treatment decision-making for patients with small HCC.

Impact of WTAP in small HCC and paired adjacent non-neoplastic liver tissue on recurrence: A cohort study with external extension analysis.

Background: To evaluate prognostic value of WTAP levels in tumor and paired adjacent non-neoplastic liver tissues (PANLT) for cases of hepatitis B virus (HBV)-positive Asian small hepatocellular carcinoma (sHCC) patients who received curative partial hepatectomy. Method: The investigation with two external cohorts were included. Associations between hazard risk of recurrence and continuous WTAP levels were investigated with restricted cubic spline models. Cox and inverse probability weighting models were established for survival analysis. Based on interaction effects, further stratification analysis was performed. Landmark analysis was employed to analyze cases of late recurrence. Finally, sensitivity analysis was performed to assess unmeasured confounders. Findings: In an investigation cohort of 307 patients, restricted cubic spline models indicated that hazard risk of recurrence increases with elevated WTAP levels for sHCC and PANLT. However, using Cox and inverse probability weighting models, no significant differences were observed in recurrence-free survival (RFS) between groups with different WTAP levels in sHCC. Multivariate analysis showed that patients with high PANLT WTAP levels had significantly worse RFS (HR 1.567, 95% CI 1.065-2.307; p = 0.023). Based on the significant interaction effect between WTAP levels in sHCC and PANLT, stratification analysis revealed that recurrence risk is more pronounced in patients with high WTAP levels in both PANLT and sHCC. Landmark analysis showed that late recurrence was more likely to occur in patients with high PANLT WTAP levels (HR 2.058, 95% CI 1.113-3.805; p = 0.021). Moreover, the detrimental effects of elevated PANLT WTAP levels on RFS were validated with two external cohorts. Sensitivity analysis confirmed the robustness of results. Conclusion: Increased PANLT WTAP expression levels independently predict high recurrence risk in HBV-positive Asian sHCC patients. Both tumor tissues and PANLT need to be considered together in future clinical practice to obtain a more comprehensive and accurate evaluation for recurrence risk.

Establishment of Nomogram Model for Minimally Invasive Treatment of Small Hepatocellular Carcinoma Based on CD8+T Cell Counts.

Purpose: Minimally invasive treatment of small hepatocellular carcinoma (HCC) is the main way of treatment, which can cause the change of HCC immune microenvironment. T lymphocytes are an important part of the immune microenvironment and may be powerful predictors of prognosis. The purpose of this study was to explore the effect of T lymphocytes on the prognosis of HCC and establish a prognostic model. Patients and Methods: We conducted a retrospective study of 300 patients with small HCC and developed a clinical prediction model. The selection of modeling variables was performed by combining backward stepwise Cox regression using Akaike's Information Criteria (AIC) and the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Establish a dynamic nomogram model to predict 1-, 2-, and 3-year overall survival (OS). Receiver operating characteristic curve (ROC curve) was used to verify the model discriminative ability, calibration curve was used to examine the model calibration ability, and decision curve analysis (DCA) was used to evaluate the clinical value. Results: The nomogram to predict the OS of small HCC includes the following four variables: aspartate aminotransferase (AST), alpha fetoprotein (AFP), C-reactive protein (CRP) and CD8+T cell counts, represented liver function index, tumor-related index, Inflammatory index and immune-related index, respectively. The area under the receiver operating characteristic curves (AUC) of predicting 1-, 2-, and 3-year overall survival were 0.846, 0.824 and 0.812, and the model was excellent in discrimination, calibration and clinical applicability. Conclusion: Our study provides a nomogram based on CD8+T cell counts that can help predict the prognosis of small HCC after minimally invasive treatment, which suggests that T lymphocytes can be used as a prognostic factor for HCC. Larger trials are needed to verify our results.

Transcatheter arterial chemoembolization alone versus combined with microwave ablation for recurrent small hepatocellular carcinoma after resection: a retrospective comparative study.

PURPOSE: To compare the efficacy and safety of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) versus TACE alone for the treatment of recurrent small hepatocellular carcinoma (sHCC) after resection. MATERIALS AND METHODS: From June 2015 to January 2020, a total of 45 patients with recurrent sHCC (size ≤ 3 cm) treated by TACE-MWA or TACE were included in this study. The radiological response at 1-, 3-, 6-month after initial treatment [modified Response Evaluation Criteria in Solid Tumors (mRECIST)], progression-free survival (PFS), overall survival (OS), and complications were evaluated. RESULTS: The TACE-MWA group showed better 1-, 3-, 6-month tumor response rates than TACE group. The corresponding 1-, 3-, and 5-year PFS rates were 76.5%, 70.6%, and 70.6% for the TACE-MWA group, and 56.1%, 15.0%, and 15.0% for the TACE group (P = 0.003). The 1-, 3-, and 5-year OS rates were 100.0%, 82.1%, and 61.5% for the TACE-MWA group, and 89.0%, 58.1%, and 50.8% for the TACE group (P = 0.389), respectively. Moreover, no major complications related to treatment were observed in either of the groups. Compared with the TACE group, the TACE-MWA group had a significantly lower number of re-TACE sessions (P = 0.003). CONCLUSIONS: Although TACE alone provides equivalent effectiveness for recurrent sHCC in terms of OS rates, TACE-MWA had better 1-, 3-, 6-month tumor response rates and may prolong tumor PFS time.

Comparison of the safety and efficacy of hepatic resection and radiofrequency ablation in the treatment of single small hepatocellular carcinoma: systematic review and meta-analysis.

Background: The present study aimed to compare the safety and efficacy of minimally invasive hepatic resection (HR) and radiofrequency ablation (RFA) in the treatment of single small hepatocellular carcinoma via systematic review and meta-analysis. Methods: We conducted electronic literature searches of PubMed, Embase, and The Cochrane Library databases, A case-controlled trial comparing HR and RFA in the treatment of single small hepatocellular carcinoma published between 2010 and January 15, 2022 was searched and reported outcomes were overall survival, postoperative complications, intraoperative blood loss, duration of surgery, and recurrence. Literature met inclusion criteria were screened out, and the quality of the methodology used in the included literature was evaluated using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan 5.4 software. Results: Eleven articles were included, including 2,001 patients, including 1,071 in the RFA group and 930 in the HR group. Offset risk assessment results are published offset. Meta-analysis showed that the overall survival rate at 1, 3, and 5 years in RFA group was higher than that in HR group, the difference between the two groups was statistically significant at 1 year [odds ratio (OR) =1.57, 95% confidence interval (CI): 1.14, 2.17, P=0.006], 3 years (OR =1.81, 95% CI: 1.42, 2.30, P<0.00001], and 5 years (OR =1.87, 95% CI: 1.47, 2.37, P<0.00001). The incidence of postoperative complications was significantly lower in the RFA group than in the human resources group [risk ratio (RR) =1.75, 95% CI: 1.02, 3.00, P=0.04], and length of hospital stay [standard mean difference (SMD) =2.92, 95% CI: 0.54, 5.30, P=0.02], operation time (SMD =2.87, 95% CI: 2.57, 3.16, P<0.00001) were shorter than those in HR group. However, the recurrence rate of RFA group was higher than that of HR group (OR =0.49, 95% CI: 0.36, 0.66, P<0.00001). Conclusions: RFA has the advantage of having more advantages and fewer complications in the treatment of small hepatocellular carcinoma. Minimal complications can occur for patients when achieving satisfactory treatment results. A new treatment option is available for clinicians in the treatment of small liver cancer.

Targeted-detection and sequential-treatment of small hepatocellular carcinoma in the complex liver environment by GPC-3-targeted nanoparticles.

Despite advancements in diagnostic methods and therapeutic strategies, the mortality rate of hepatocellular carcinoma (HCC) remains as high as its incidence rate. Most liver cancers are detected in the advanced stages, when treatment options are limited. Small HCC is difficult to diagnose and is often overlooked by current imaging methods because of the complexity of the liver environment, especially in cirrhotic livers. In the present study, we developed a tumor "cruise missile", mesoporous Fe3O4-containing glucose oxidase-conjugated GPC3 peptide nanoparticles (FGP NPs). It was designed to enhance the accuracy of small HCC visualization to 85.7% using combined ultrasound/photoacoustic imaging in complex liver environment, which facilitated sequential catalytic targeted therapy for small HCC. In a carcinogen-induced mouse HCC model, FGP NPs could be used to accurately diagnose HCC in a liver cirrhosis background as well as distinguish HCC nodules from other abnormal liver nodules, such as cirrhosis nodules and necrotic nodules, by dynamic contrast-enhanced photoacoustic imaging. In a mouse xenograft HCC model, highly reactive oxygen species were formed by sequential catalytic reactions, which promoted HCC cell apoptosis, significantly increasing the survival of the model mice. The present study provides a basis for the precise detection and elimination of small HCCs in the complex liver environment.

Cost-benefit analysis of hepatic resection, radiofrequency ablation and liver transplantation in small hepatocellular carcinoma.

OBJECTIVE: The aim of the present study was to evaluate the cost-effectiveness ratio of surgical treatment options for small hepatocellular carcinoma (SHC) by using the decision tree model and providing a reference for the clinical therapeutic decisions for SHC. METHODS: The data of 719 cases with SHC in the BCLC 0-A who were treated in the past were collected. The survival duration and treatment cost of patients in each experimental group after hepatic resection (HR), radiofrequency ablation (RFA), and orthotopic liver transplantation (OLT) were statistically analyzed. RESULTS: For SHC with a diameter of less than 3.0 cm, HR, RFA, and OLT had similar cost-effectiveness ratios. OLT could achieve a longer life expectancy, but it was greatly affected by the dropout rate while waiting for the liver donor. RFA was preferred when the willingness to pay (WTP) < 2,5000 RMB/QALY, OLT was preferred when WTP > 75,000 RMB/QALY, and HR was preferred when WTP was between the two. EXPERT OPINION: HR in SHC with OLT had the longest life expectancy, but due to the limitations of organ sources, OLT was the preferred treatment option when the WTP was large enough.

Global DNA 5hmC and CK195hmC+ Contents: A Promising Biomarker for Predicting Prognosis in Small Hepatocellular Carcinoma.

BACKGROUND: 5-Hydroxymethylcytosine (5hmC) with dynamic existence possesses multiple regulatory functions. Whereas, 5hmC's impact on small hepatocellular carcinoma (SHCC) remains unclear. The present work focused on characterizing 5hmC content within SHCC and assessing the possibility of using global genomic 5hmC level as the predicative factor of clinical outcome. METHODS: This study applied ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in measuring 5mC, 5fC and 5hmC contents. In addition, immunohistochemistry (IHC) was adopted to measure CK19 and 5hmC contents. RESULTS: Research showed 5mC, 5hmC, and 5fC contents from global genomics of SHCC reduced extensively compared with healthy samples (p < 0.001). Moreover, SHCC was associated with lymph node metastasis (LNM). Greater 5mC and 5hmC levels were observed in non-metastasis group compared with the metastasis group (p < 0.001). Correlation analysis between the HBV DNA level and 5mC, 5fC and 5hmC levels exhibited that HBV DNA was associated with 5mC, 5hmC, and 5fC content reduction, which was verified in the cytological experiments. Moreover, 5hmC content had a negative correlation with the expression level of CK19 in SHCC. The decrease in 5hmC and CK19 containing 5hmC positive cell (called CK195hmC+) should be ascribed to the bad prognosis among SHCC patients. CONCLUSIONS: The contents of 5hmC and CK195hmC+ of genomic DNA might be adopted for predicting SHCC survival as an important biomarker.

Efficacy of radiofrequency ablation versus laparoscopic liver resection for hepatocellular carcinoma in China: a comprehensive meta-analysis.

INTRODUCTION: Hepatocellular carcinoma (HCC) has been the second leading cause of cancer-related death in China. Radiofrequency ablation is a relatively novel treatment that may improve the treatment of HCC. AIM: To evaluate and compare the efficacy and safety of radiofrequency ablation (RFA) versus laparoscopic liver resection (LLR) in the treatment of HCC. MATERIAL AND METHODS: We searched for relevant published studies in English (PubMed, Cochrane Library, EMBASE) and in Chinese (CBM, CNKI and Wanfang) from their inception until September 23, 2019. The quality of included studies was evaluated by the Newcastle-Ottawa Scale. RESULTS: A total of 19 retrospective studies including 2038 patients were eligible for the meta-analysis. The results of the meta-analysis demonstrated that LLR was superior to RFA in terms of 3-year overall survival rate (OR = 0.62), 1 to 3-year disease-free survival rates (OR = 0.57; OR = 0.41, respectively) and local recurrence rates (OR = 2.71). CONCLUSIONS: The meta-analysis demonstrates that laparoscopic liver resection should be preferred in tumors of size 3-5 cm, while for < 3 cm the long term results are equal.

Comparison of unenhanced magnetic resonance imaging and ultrasound in detecting very small hepatocellular carcinoma.

BACKGROUND: In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites. In the surveillance of very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona clinical stage 0), we demonstrated that the tumor markers alpha-fetoprotein and PIVKA-Ⅱ are not so useful. Therefore, we must survey with imaging modalities. The superiority of magnetic resonance imaging (MRI) over ultrasound (US) to detect HCC was confirmed in many studies. Although enhanced MRI is now performed to accurately diagnose HCC, in conventional clinical practice for HCC surveillance in liver diseases, unenhanced MRI is widely performed throughout the world. While, MRI has made marked improvements in recent years. AIM: To make a comparison of unenhanced MRI and US in detecting very small HCC that was examined in the last ten years in patients in whom MRI and US examinations were performed nearly simultaneously. METHODS: In 394 patients with very small HCC nodules, those who underwent MRI and US at nearly the same time (on the same day whenever possible or at least within 14 days of one another) at the first diagnosis of HCC were selected. The detection rate of HCC with unenhanced MRI was investigated and compared with that of unenhanced US. RESULTS: The sensitivity of unenhanced MRI for detecting very small HCC was 95.1% (97/102, 95% confidence interval: 90.9-99.3) and that of unenhanced US was 69.6% (71/102, 95% confidence interval: 60.7-78.5). The sensitivity of unenhanced MRI for detecting very small HCC was significantly higher than that of unenhanced US (P < 0.001). Regarding the location of HCC in the liver in patients in whom detection by US was unsuccessful, S7-8 was identified in 51.7%. CONCLUSION: Currently, unenhanced MRI is a very useful tool for the surveillance of very small HCC in conventional clinical follow-up practice.

Plasmonic-doped melanin-mimic for CXCR4-targeted NIR-II photoacoustic computed tomography-guided photothermal ablation of orthotopic hepatocellular carcinoma.

Effective and noninvasive diagnosis and prompt treatment of early-stage hepatocellular carcinoma (HCC) are urgently needed to reduce its mortality rate. Herein, the integration of high-resolution diagnostic second near-infrared (NIR-II) photoacoustic computed tomography (PACT) and imaging-guided targeted photothermal ablation of orthotopic small HCC (SHCC) is presented for the first time, which was enabled by a plasmonic platinum (Pt)-doped polydopamine melanin-mimic nanoagent. As designed, an antibody-modified nanoagent (designated Pt@PDA-c) with a plasmonic blackbody-like NIR absorption and superior photothermal conversion efficiency (71.3%) selectively targeted and killed CXCR4-overexpressing HCC (HepG2) cells, which was validated in in vitro experiments. The targeted accumulation properties of Pt@PDA-c in vivo were previously recognized by demonstrating effective NIR-II PA imaging and photothermal ablation in a subcutaneous HCC mouse model. Subsequently, with real-time quantitative guidance by PACT for the accurate diagnosis of intraabdominal SHCC (approximately 4 mm depth), the effective and noninvasive photothermal ablation of SHCCs was successfully demonstrated in an orthotopic tumor-bearing mouse model without damaging adjacent liver tissues. These results show a great potential of NIR-II PACT-guided noninvasive photothermal therapy as an innovative phototheranostic approach and expand the biomedical applications of melanin-mimic materials. STATEMENT OF SIGNIFICANCE: In this paper, we report the first diagnostic NIR-II photoacoustic computed tomography (PACT)-guided noninvasive photothermal ablation of small hepatocellular carcinoma (SHCC) located in deep tissues in orthotopic tumor-bearing mice; this process is empowered by a polydopamine-based melanin-mimic tumor-targeting nanoagent doped with plasmonic platinum that provides superior NIR-II (1064 nm) absorption and photothermal conversion efficiency of 71.3%. Following surface modification with anti-CXCR4 antibodies, the nanoagent (namely Pt@PDA-c) can selectively target CXCR4-overexpressed HepG2 carcinoma cells and tumor lesions, and serve as the theranostic agent for both NIR-II PACT-based diagnosis of orthotopic SHCC (diameter less than 5 mm) and efficient NIR-II PTT in vivo. This study may also extend the potential of melanin-derived blackbody materials for optical-biomedical and water distillation applications.