Small Hepatocellular Carcinoma Patients Research Articles

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

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). 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. 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). 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.

Ablative and non-surgical therapies for early and very early hepatocellular carcinoma: a systematic review and network meta-analysis.

A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function. To review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm). Systematic review and network meta-analysis. Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews. Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research. Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified (n ≥ 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included (n = 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials. Many studies were small and of poor quality. No comparative studies were found for some therapies. The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection. PROSPERO CRD42020221357. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in Health Technology Assessment; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.

Repeat hepatectomy versus microwave ablation for solitary and small (≤3 cm) recurrent hepatocellular carcinoma with early or late recurrence: A propensity score matched study

BackgroundRepeat hepatectomy (RH) and microwave ablation (MWA) are frequently used procedures for the treatment of recurrent hepatocellular carcinoma (HCC) after curative resection. This study aimed to compare the long-term outcomes of RH and MWA for solitary and small HCC with early or late recurrence. MethodThis retrospective study enrolled patients who underwent RH or MWA for solitary and small (≤3 cm) recurrent HCC at Tongji hospital between April 2006 and December 2020. Propensity score matching (PSM) was further employed to analyze the prognosis of different treatment methods. ResultsA total of 256 patients were analyzed, of whom 94 and 162 underwent RH and MWA, respectively. The overall treatment-related complication rate was higher in the RH group. Both recurrence-free survival (RFS) and overall survival (OS) rates of RH were significantly better than those of MWA. Multivariate analysis showed that MWA, early recurrence (within 24 months after initial resection), cirrhosis, and AFP >400 ng/ml were independent risk factors for poor prognoses of recurrent HCC. The stratified analysis demonstrated that MWA and RH had similar long-term outcomes in patients with early recurrence. Nevertheless, MWA had worse RFS and OS than RH in patients with late recurrence. The same results were obtained in the PSM analysis. ConclusionThe long-term outcomes of HCC patients with late recurrence were significantly better than those with early recurrence. RH should be the first choice for solitary small recurrent HCC patients with late recurrence, while MWA should be selected for those with early recurrence.

Portal hypertension may influence the registration of hypointensity of small hepatocellular carcinoma in the hepatobiliary phase in gadoxetic acid MR.

BackgroundThe aim of the study was to analyze the association between the liver uptake of Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) in the hepatobiliary phase (HBP) in cirrhotic patients and the presence of clinically significant portal hypertension (CSPH), and how these features impact on hepatocellular carcinoma (HCC) detection in the HBP.Patients and methodsPost-hoc analysis of a prospective cohort of 62 cirrhotic patients with newly US-detected nodule between 1–2 cm (study group). Twenty healthy subjects were used as control group. Qualitative and quantitative analysis of the liver contrast uptake in the HBP assessed by Relative Liver-Enhancement (RLE), Liver-Spleen (LSCR), Liver-Muscle (LMCR), and Liver-Kidney Contrast-Ratio (LKCR), Contrast Enhancement Index (CEI), and Hepatic Uptake (HUI), and biliary excretion, were registered. CSPH was confirmed invasively (HVPG > 10 mmHg) or by indirect parameters. The appearance of HCC at the HBP was analyzed.ResultsNineteen patients (30.6%) did not have CSPH. In 41 patients (66.1%) the final diagnosis was HCC. All indices were significantly higher in the control group, indicating a more intense HBP liver signal intensity compared to patients with cirrhosis, even if the comparison was restricted to patients with no CSPH. CSPH was associated to a lower rate of HCC hypointensity in the HBP (51.9% vs. 85.7% without CSPH, p = 0.004).ConclusionsLiver uptake of Gd-EOB-DTPA at the HBP is decreased in cirrhosis even if the liver function is minimally impaired and it falls down significantly in patients with CSPH compromising the recognition of hypointense lesions. This fact may represent a limitation for the detection of small HCC in patients with cirrhosis and CSPH.

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.

Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications.

Background and AimTo assess the profile of global histone modifications in small hepatocellular carcinoma (small HCC) and identify its prognostic value in predicting recurrence.MethodsThe expression profiles of global histone modifications, including H2AK5AC, H2BK20AC, H3K4me2, H3K9AC, H3K18AC, H4K12AC, and H4R3me2, were evaluated with immunohistochemistry in 335 HBV related small HCC patients. Two histone signature classifiers were then developed using least absolute shrinkage and selection operator Cox regression. A nomogram was built using the classifier and independent risk factors. The performances of the classifier and nomogram were assessed by receiver operating characteristic curves.ResultsHistone modifications were more pronounced in tumor tissues than in adjacent liver tissues. In tumor tissues, the risk score built based on the seven-histone signature exhibited satisfactory prediction efficiency, with an AUC = 0.71 (0.63–0.79) for 2-year survival in the training cohort. Patients with a high risk score had shorter recurrence-free survival than those with a low risk score (HR: 1.96, 95% CI: 1.24–3.08, p = 0.004; HR: 1.95, 95% CI: 1.12–3.42, p = 0.019; and HR: 1.97, 95% CI: 1.39–2.80, p < 0.001 for the training, validation and total cohorts, respectively). Furthermore, the statistical nomogram built using the histone classifier for early recurrence had a C-index = 0.68. In non-neoplastic liver tissues, the hepatic signature based on H3K4me2 and H4R3me2 was related to late recurrence (HR: 2.00, 95% CI: 1.15–3.48, p = 0.01).ConclusionGlobal histone modifications in tumor and adjacent liver tissues are novel predictors of early and late recurrence, respectively, in HBV-related small HCC patients.

The impact of thrombocytopenia on prognosis of HBV-related small hepatocellular carcinoma: a propensity score matching analysis

BackgroundThrombocytopenia was reported both detrimental and advantageous to hepatocellular carcinoma (HCC). However, there is little evidence showing clearly the clinical value of preoperative thrombocytopenia on the surgical outcome of patients with small HCC. This retrospective study aimed at elucidating the correlation between preoperative thrombocytopenia and surgical outcome of small HCC patients within Milan criteria treated with liver resection.MethodsData of hepatitis B virus (HBV)-related small HCC patients were retrospectively analyzed, and we performed the propensity score matching (PSM) analysis to overcome the imbalance of clinicopathological features. Patients enrolled were subsequently categorized into two groups according to preoperative platelet counts: thrombocytopenia group and non-thrombocytopenia group. Survival outcomes of the patients in both groups were described with the Kaplan-Meier method, and the difference was compared with a log-rank test. Cox regression analysis was applied to identify the risk factors of surgical outcome.ResultsAfter PSM, the estimated 1-, 3-, and 5-year overall survival (OS) rates for small HCC patients in the thrombocytopenia group were 94.5%, 77.0%, and 57.6%, and 95.0%, 79.6%, and 68.0%, respectively, for small HCC patients in the non-thrombocytopenia group (P = 0.042). And the 1-, 3-, and 5-year estimated recurrence-free survival (RFS) rates for small HCC patients in the thrombocytopenia group were 70.4%, 51.0%, and 42.1%, and 83.8%, 63.7%, and 46.7%, respectively, for small HCC patients in the non-thrombocytopenia group (P = 0.035). Multivariate analysis indicated preoperative thrombocytopenia was a significant prognosticator of poor RFS (hazard ratio (HR) = 1.388, 95% confidence interval (CI) 1.028~1.874, P = 0.033).ConclusionPreoperative thrombocytopenia had an undesirable impact on the recurrence of small HCC patients treated with liver resection.

The role of microwave ablation in treatment of small and medium sized hepatocellular carcinoma

Back ground and aim of work: Microwave ablation (MWA) is effective and safe technique used in treatment of hepatocellular carcinoma (HCC). The aim of this study is to investigate the role of microwave ablation in treatment of small and medium sized hepatocellular Carcinoma. Methods: This prospective study included 50 patients who underwent microwave ablation for small and medium size hepatocellular carcinoma with abdominal ultrasound guidance. All patients' demographic, laboratory investigations and complications were recorded. To evaluate efficacy of microwave ablation, Contrast-enhanced computed tomography was done one month and repeated three months after the ablation. Results: Complete ablation of the tumor was done in 92% of small HCC patients (less than or equal 3 cm) whereas in 64% among medium size HCC patients (more than 3 and up to 4 cm). Tumor recurrence was recorded in one patient (4%) with medium size HCC. There was significant decline in serum alpha fetoprotein levels one month after ablation compared to before the procedure. No major complications of the procedure or mortality were reported. Conclusion: Microwave ablation is safe and effective in small to medium size HCC tumors treatment with no recorded major complications or mortality in addition to acceptable local tumor control.

The Long-Term Efficacy of Radiofrequency Ablation Versus Laparoscopic Hepatectomy for Small Hepatocellular Carcinoma in East Asia: A Systematic Review and Meta-Analysis

Context: Hepatocellular carcinoma (HCC) is a common malignant cancer and the second leading cause of cancer-related deaths around the world. Radiofrequency ablation (RFA) and laparoscopic hepatectomy (LH) have been adopted for the treatment of HCC. The aim of the meta-analysis was to explore the long-term efficacy of RFA compared with LH for small HCC (sHCC) patients in the East Asian population. Evidence Acquisition: We performed a systematic review and meta-analysis by the literature search on PubMed, Cochrane Library, EMBASE, Chinese Biological Medical Literature (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang from their inception until October 10, 2019, for comparing the long-term efficacy outcomes of RFA with LH. Results: Fourteen retrospective studies with 1,390 subjects were included in the meta-analysis. Compared with the LH-treated group, RFA could raise the local recurrence rate under median follow-up duration and reduce disease-free survival (DFS) rates at 1 - 3 years. However, it failed to affect 5-year overall survival (OS) and DFS rates. In the subgroup analyses, different RFA approaches had significantly higher local recurrence rates than the LH group. A similar effect on OS and DFS rates within five years for single early (≤ 3 cm) HCCs and on the 1- and 5-year DFS rates for nodules ≤ 5 cm were observed between the two groups, but RFA approaches could reduce the 3-y OS and DFS rates for single nodules ≤ 5 cm. The percutaneous radiofrequency ablation (PRFA) group had significantly lower 3- and 5-year OS and the 1- and 3-year DFS rates than the LH group, while no significant difference in OS and DFS rates in the laparoscopic radiofrequency ablation (LRFA) approach. The RFA approach improved the 3-year OS compared with the LH group in Japan, but reduced the 3-year OS and DFS rates within 3 years in China. Conclusions: Our results support that LH treating sHCC had a better long-term efficacy and a lower local recurrence rate than RFA in the East Asian population. Further high-quality prospective studies are required to confirm the long-term efficacy.

Differentiation of regenerative nodule, dysplastic nodule, and small hepatocellular carcinoma in cirrhotic patients: a contrast-enhanced ultrasound-based multivariable model analysis.

To develop a contrast-enhanced ultrasound (CEUS)-based model for differentiating cirrhotic liver lesions and for active surveillance of hepatocellular carcinoma (HCC). Patients with focal liver lesions (FLLs) with biopsy/resection-proven pathology and pre-procedure CEUS were enrolled from our institution between January 2011 and November 2014. Univariable and multivariable regression models were constructed using qualitative CEUS features and/or contrast arrival time ratio (CATR). The optimism-adjusted Harrell's generalized concordance index (CH) was used to quantify the discriminatory ability of each CEUS feature and model. A total of 149 patients (113 men and 36 women) with 162 FLLs were enrolled with mean age 53.4 ± 12.7years. A 0.1-unit reduction in CATR was associated with a 68% increase in the odds of having a higher nodule ranking (RN < DN < small HCC) (OR, 0.32; 95% CI, 0.20-0.50, p < .001). Arterial phase hypoenhancement and isoenhancement were inversely associated with a higher nodule ranking compared to hyperenhancement. Late-phase isoenhancement was associated with lower odds of a higher nodule ranking. The CEUS + CATR model (CH 0.92, 0.89-0.95) provided greater discriminatory ability when compared to the CATR model (ΔCH 0.09, 0.04-0.13, p < .001) and the CEUS model (ΔCH 0.03, 0.01-0.05, p = .02). Our results provide preliminary evidence that multivariable regression model constructed using both qualitative CEUS features and CATR provides the greatest discriminatory ability to differentiate RN, DN, and small HCC in patients with cirrhosis, and might allow for active surveillance of the progression of cirrhotic liver lesions. • Proportional odds logistic regression models based on qualitative CEUS features and/or CATR can be used for differentiating cirrhotic liver lesions and for active surveillance of HCC. • The reduction of CATR (RN < DN < small HCC) was strongly associated with high-risk cirrhotic liver nodules. • Inclusion of CATR in the CEUS prediction model significantly improved its performance for cirrhotic liver lesions risk-stratification.

Clinical and contrast-enhanced image features in the prediction model for the detection of small hepatocellular carcinomas.

Purpose: To identify novel radiological features and clinical characteristics to improve diagnostic criteria for early detection of small hepatocellular carcinoma (HCC).Patients and Methods: We retrospectively recruited asymptomatic patients with no history of HCC but a high risk of HCC in whom a new, solitary, well-defined, solid nodule between 10 and 20 mm was detected through a screening ultrasound. We retrospectively collected all clinical data, and patients were examined using dynamic contrast-enhanced computed tomography or magnetic resonance imaging; subsequently, fine-needle biopsy was performed. A multivariate analysis of the predictors of small HCCs was performed by fitting a multiple logistic regression model with the stepwise variable selection method.Results: In total, 392 and 347 patients with a small liver nodule received a final pathologic confirmation of HCC and non-HCC, respectively. The estimated odds ratios and 95% confidence intervals of tumor size > 12.45 mm, age > 56.61 years, liver cirrhosis, hepatitis C virus (HCV) carrier status, ln alpha-fetoprotein (AFP) > 1.954, arterial phase enhancement, and portal or venous phase washout appearance without arterial phase enhancement were 2.0735 (1.4746-2.9155), 1.8878 (1.2949-2.7521), 1.6927 (1.1294-2.5369), 1.6186 (1.0347-2.5321), 2.0297 (1.3342-3.0876), 3.7451 (2.3845-5.8821), and 2.0327 (1.3500-3.0608), respectively. The area under the receiver operating characteristic curves for the diagnosis of small HCCs was 0.79 for arterial phase enhancement and 0.75 for portal or venous phase washout appearance without arterial phase enhancement.Conclusion: Clinical and contrast-enhanced image features are valuable in the prediction model for the detection and early diagnosis of small HCCs in patients with a high risk of HCC. In addition to negative portal or venous washout and negative arterial enhancement in images, age > 56.61 years, tumor size > 12.45 mm, HCV carrier status, and ln(AFP) > 1.954, are useful indicators for the early detection of small HCCs.

Development and Assessment of Novel Predictive Nomograms Based on APRI for Hepatitis B Virus-associated Small Solitary Hepatocellular Carcinoma with Stereotactic Body Radiotherapy.

Background: The correlation between serum inflammatory marker before treatment and the survival of patients with hepatitis B virus (HBV)-associated small solitary hepatocellular carcinoma (HCC) after stereotactic body radiotherapy (SBRT) remains unclear. The objective of our study is to estimate survival in such patients using multivariable prediction models and investigate the prognostic value of aspartate aminotransferase-to-platelet index (APRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) for HBV-associated small solitary HCC patients treated with SBRT.Patients and methods: Patients with HBV-associated small solitary HCC who were newly treated with SBRT were retrospectively analysed in our hospital from 2009 to 2016. We counted the APRI, NLR, PLR, and LMR before treatment and calculated their cut-off values for predicting overall survival (OS) and progression-free survival (PFS) by receiver operating characteristic (ROC) analysis. The random forest model combined with least absolute shrinkage and selection operator (LASSO) regression model for OS and PFS were used to screen potentially prognostic factors from serum inflammatory markers, demographic data, and clinical characteristics. Predictive models for OS and PFS were developed by multivariable COX regression and nomograms were constructed. Discrimination was assessed using the C-index. Internal validation was assessed using the Bootstrap method. Survival analysis was carried out to assess the prognostic value of serum inflammatory markers, and OS and PFS curves were compared by Kaplan-Meier analysis and Log-Rank test, respectively.Results: A total of 72 patients with HBV-associated small solitary HCC were recruited for the study. The median follow-up time was 2015 days (range, 232-3823 days). Age, tumor size, NLR, PLR, and APRI were used to construct nomogram for OS, while gender, age, TNM stage, portal hypertension, AFP, APRI were for PFS. The two models displayed good discriminations with C-indexes of 0.738 (95% CI: 0.632-0.844) and 0.657 (95% CI: 0.538-0.777), and their C-indexes in the internal validation cohort reached 0.790 (95% CI: 0.684-0.896) and 0.739 (95% CI: 0.619-0.859). The multivariable cox analysis indicated that APRI<0.47 was favourable independent prognostic factors for OS and PFS. Compared to APRI≥0.47, APRI<0.47 predicts better OS (p=0.003) and PFS (p=0.003).Conclusions: Nomograms based on APRI are superior in predicting OS and PFS in HBV-associated small solitary HCC patients who have received SBRT. APRI before treatment is a feasible and convenient prognostic indicator for OS and PFS, which helpfully determines the beneficial population of SBRT for HBV-associated small solitary HCC.

Biologically effective dose (BED) of stereotactic body radiation therapy (SBRT) was an important factor of therapeutic efficacy in patients with hepatocellular carcinoma (\u22645\u2009cm)

BackgroundTo explore the association between biologically effective dose (BED) and survival rates in Child-Pugh A classification (CP-A) small hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT).MethodsThis retrospective study included 108 small HCC patients who were treated with SBRT between 2011 and 2014. The prescribed dose delivered to the tumor were 48Gy/8f, 49Gy/7f, 50Gy/5f and 54Gy/6f. The median biologically effective dose (BED10) of the total prescribed dose was 100Gy (76.8–102.6Gy). Factors associated with the survival rate were examined using the Cox proportion hazards model, and the factors associated with radiation-induced liver injury (RILD) were examined by logistic regression analysis.ResultsFor these patients, the median follow-up time was 42 months (6–77 months), and the 1-, 2- and 3-year overall survival (OS) rates were 96.3, 89.8 and 80.6%, respectively. The 1-, 2- and 3-year progression-free survival (PFS) rates were 85.2, 70.1 and 60.6%, respectively. The 1-, 2- and 3-year local control (LC) rates were 98.1, 96.2 and 95.1%, respectively. The 1-, 2- and 3-year distant metastasis- free survival (DMFS) rates were 86.1, 72.8 and 61.2%. The OS, PFS and DMFS were significantly higher in the BED10 ≥ 100Gy group than in the BED10 < 100Gy group (OS: p = 0.020; PFS: p = 0.017; DMFS: p = 0.012). The PLT count was a predictive factor of RILD.ConclusionsSBRT is a safe and effective option for CP-A HCC patients. A BED10 value greater than 100Gy and lower CP score are associated with improved OS and PFS. Additionally, the peripheral PLT count are predictive factors of RILD.

Prognostic Value of Gamma-Glutamyl Transpeptidase to Lymphocyte Count Ratio in Patients With Single Tumor Size ≤ 5 cm Hepatocellular Carcinoma After Radical Resection.

Prediction of prognosis of hepatocellular carcinoma (HCC) has shown an important role in improving treatment outcomes and preventing disease progression, however, the prognostic indicator of HCC is still lacking. The purpose of this study is to investigate the predictive value of GLR (gamma-glutamyl transpeptidase to lymphocyte count ratio) in single HCC with a tumor size (TS) ≤ 5 cm. A retrospective analysis was performed on 272 patients with TS ≤ 5 cm who underwent radical resection. The Pearson χ2 test was applied to discuss the relationship between HCC and GLR, alpha-fetoprotein (AFP). Then univariate and multivariate analysis was utilized to predict the risk factors for survival prognosis in patients. In this study, GLR showed a positive relation with tumor size, tumor-node-metastasis (TNM) stage, microvascular invasion, early recurrence, and serum aspartate aminotransferase (AST) level, while the AFP value only correlated with drinking. Elevated GLR value had poor overall survival (OS) and progression-free survival (PFS) of TS ≤ 5 cm HCC patients, GLR level and tumor size were closely related to the prognosis of small HCC patients compared with AFP. GLR may serve as a prognostic marker for dynamic monitoring of HCC patients with single TS ≤ 5 cm after radical resection.

Efficacy and safety of radiofrequency ablation versus minimally invasive liver surgery for small hepatocellular carcinoma: a systematic review and meta-analysis.

The aim of this study was to compare radiofrequency ablation (RFA) with minimally invasive liver surgery (MIS) in the treatment of small hepatocellular carcinoma (SHCC) and to assess short-term and long-term clinical outcomes. PubMed, Embase, Cochrane Library, Web of science, and CBM were systematically searched for articles from inception to July 2018, comparing RFA and MIS in SHCC treatment. We evaluated overall survival (OS), disease-free survival (DFS), local recurrence, and complication rates, as well as hospitalization duration and operation times. Six retrospective studies were analyzed, including a total of 597 patients, 313 treated with RFA and 284 treated with MIS. OS rates were significantly higher in patients treated with MIS at 3years, when compared to RFA (OR 0.55; 95% CI 0.36 to 0.84). The 3-year DFS MIS rates were also superior to RFA (OR 0.63; 95% CI 0.41 to 0.98). In contrast, when compared to MIS, RFA demonstrated a significantly higher rate of local intrahepatic recurrences, (OR 2.24; 95% CI 1.47 to 3.42), and a lower incidence of postoperative complications (OR 0.34; 95% CI 0.22 to 0.53), as well as shorter operation times (OR - 145.31, 95% CI - 200.24 to - 90.38) and hospitalization duration (OR - 4.02,95% CI - 4.94 to - 3.10). We found that MIS led to higher OS, DFS, and lower local recurrences in SHCC patients. Meanwhile, RFA treatments led to significantly lower complication rates, shorter operation times, and hospitalization duration. Considering long-term outcomes, MIS was found to be superior to RFA. However, RFA may be an alternative treatment for patients presenting a single SHCC nodule (≤ 3cm), given its minimally invasive nature and its comparable long-term efficacy with MIS. Nevertheless, our findings should be explained with caution due to the low level of evidence obtained.

Nomogram to Assist in Surgical Plan for Hepatocellular Carcinoma: a Prediction Model for Microvascular Invasion

BackgroundMicrovascular invasion (MVI) relates to poor survival in hepatocellular carcinoma (HCC) patients. In this study, we aim at developing a nomogram for MVI prediction and potential assistance in surgical planning. MethodsA total of 357 patients were assigned to training (n = 257) and validation (n = 100) cohort. Univariate and multivariate analyses were used to reveal preoperative predictors for MVI. A nomogram incorporating independent predictors was constructed and validated. Disease-free survival was compared between patients, and the potential of the predicted MVI in making surgical procedure was also explored. ResultsPathological examination confirmed MVI in 140 (39.2%) patients. Imaging features including larger tumor, intra-tumoral artery, tumor type, and higher serum AFP independently correlated with MVI. The nomogram showed desirable performance with an AUROC of 0.803 (95% CI, 0.746–0.860) and 0.814 (95% CI, 0.720–0.908) in the training and validation cohorts, respectively. Good calibration were also revealed by calibration curve in both cohorts. The decision curve analysis indicated that the prediction nomogram was of promising usefulness in clinical work. In addition, survival analysis revealed that patients with positive-predicted MVI suffered a higher risk of early recurrence (P < 0.01). There was no difference in disease-free survival between anatomic or non-anatomic resection in large HCC or small HCC without nomogram-predicted MVI. However, anatomic resection improved disease-free survival in small HCC with nomogram-predicted MVI. ConclusionsThe nomogram obtained desirable results in predicting MVI. Patients with predicted MVI were associated with early recurrence and anatomic resection was recommended for small HCC patients with predicted MVI.

Microwave ablation provided better overall survival than liver resection for small hepatocellular carcinoma in patients with borderline liver function

Background: Microwave ablation (MWA) is showed to be at least as effective as, if not superior than, radiofrequency ablation in treating HCC. Studies comparing MWA and liver resection are lacking. The aim of this study is to evaluate the survival of patients who were treated with liver resection and MWA and to evaluate if the newly developed Albumin-Bilirubin (ALBI) grade can help in patient selections for liver resection or ablation. Methods: This is a retrospective analysis on patients who received curative liver resection and MWA for primary HCC from March 2009 to December 2015. Baseline clinical and laboratory parameters were retrieved and reviewed from the hospital database. Propensity score matching was used at 1:1 ratio. The ALBI grade was evaluated for their abilities of patient selection. Results: A total of 442 patients underwent MWA and liver resection for primary HCC during the study period. Propensity scoring matching was used and resulted in 63 matched pairs for further analysis. While liver resection still offered better overall and disease-free survivals in patients with ALBI grade 1, MWA provided a significantly better overall survival in patients with ALBI grade 2 or 3. (p=0.025) Conclusion: Microwave ablation, as a treatment for HCC, offered superior overall survival to liver resection in patients ALBI grade 2 or 3.

Tumor Location Influences Oncologic Outcomes of Hepatocellular Carcinoma Patients Undergoing Radiofrequency Ablation

Radiofrequency ablation (RFA) is recommended as a first-line therapy for small hepatocellular carcinoma (HCC). Tumor location is a potential factor influencing the procedure of RFA. To compare oncologic outcomes of RFA for different tumor locations, this retrospective study enrolled 194 patients with small HCC who had undertaken RFA. The HCC nodules were classified as peri-hepatic-vein (pHV) or non-pHV, peri-portal-vein (pPV) or non-pPV, and subcapsular or non-subcapsular HCC. The regional recurrence-free survival (rRFS), overall survival (OS), recurrence-free survival (recurrence in any location, RFS) and distant recurrence-free survival (dRFS) were compared. Operation failures were recorded in five pPV HCC patients, which was more frequent than in non-pPV HCC patients (p = 0.041). The 1-, 3-, and 5-year rRFS was 68.7%, 53.7%, and 53.7% for pHV patients and 85.1%, 76.1%, and 71.9% for non-pHV patients, respectively (p = 0.012). After propensity score matching, the 1-, 3-, and 5-year rRFS was still worse than that of non-pHV patients (p = 0.013). The OS, RFS, and dRFS were not significantly different between groups. Conclusions: A pHV location was a risk factor for the regional recurrence after RFA in small HCC patients. The tumor location may not influence OS, RFS, and dRFS. Additionally, a pPV location was a potential high-risk factor for incomplete ablation.

Liver resection versus radiofrequency ablation for hepatitis B virus-related small hepatocellular carcinoma.

BackgroundTo compare the outcomes of liver resection (LR) with radiofrequency ablation (RFA) for patients with hepatitis B virus (HBV)-related small hepatocellular carcinoma (HCC).MethodsA total of 122 HBV-related small HCC patients who underwent LR (n=64) or RFA (n=58) were involved in this retrospective study. Their basic clinical data, postoperative complications, survival outcomes, and prognostic factors were compared and analyzed.ResultsPatients in the LR group had more serious complications (11 versus 0) and longer postoperative hospital stays (11.3 versus 6.0 days) than those in the RFA group (all P<0.05). LR was associated with better recurrence-free survival (RFS) rates at 1, 3, and 5 years compared with RFA (90.4%, 65.9%, and 49.5% versus 79.3%, 50.3%, and 35.6%, P=0.037), but there was no significant difference in overall survival (OS) (95.2%, 78.1%, 58.6% versus 93.1%, 71.3%, 52.9%, P=0.309). Multivariate Cox analysis showed that the hepatic cirrhosis (hazard ratio [HR]: 2.13), tumor number (HR: 3.73), tumor diameter (HR: 1.92), and postoperative anti-HBV therapy (HR: 0.53) had predictive values for RFS, and the latter three (HR: 4.34, 2.30, and 0.44) were independent predictors of OS (all P<0.05).ConclusionLR might be considered the preferred method for patients with HBV-related small HCC, while RFA could apply to selective cases. Anti-HBV therapy after treatment was recommended.

Postoperative aspartate aminotransferase to lymphocyte ratio index change is an independent predictor of survival in patients with small hepatocellular carcinoma.

Elevated preoperative aspartate aminotransferase (AST) to lymphocyte ratio index (ALRI) is reported to be a prognostic factor for patients with hepatocellular carcinoma (HCC) after treatment. However, [DELTA] ALRI which represents the change from postoperative ALRI to preoperative ALRI change has received little attention. The present study was designed to evaluate the prognostic value of [DELTA] ALRI in small HCC patients after liver resection.A retrospective cohort study was performed to analyze 241 patients with small HCC who underwent liver resection. Patients were divided into Group A ([DELTA] ALRI < 0, n = 142) and group B ([DELTA] ALRI ≥ 0, n = 99) according to postoperative ALRI change. Clinical data, overall survival (OS), and recurrence-free survival (RFS) were compared between the 2 groups, and a multivariate analysis was used to identify prognostic factors.The 1, 3, and 5-year OS rates were 96.5%, 84.9%, and 70.8%, respectively, for group A, and 94.9%, 75.8%, and 59.7%, respectively for group B (P = .014). The corresponding 1, 3, and 5-year RFS rates were 78.2%, 54.6%, and 52.3%, respectively, for group A, and 62.6%, 40.1%, 24.5%, respectively, for group B (P < .001). The results of univariate and multivariate analysis indicated that [DELTA] ALRI was an independent prognostic factor for both RFS (P < .001, hazard ratio [HR] 2.192, 95% confidence interval 1.527–3.147) and OS (P < .001, HR 2.381, 95% confidence interval 1.503–3.771).A positive [DELTA] ALRI after liver resection predicts decreased OS and RFS in patients with small HCC.