Interventional embolisation for patients with cirrhosis and recurrent or persistent hepatic encephalopathy related to spontaneous portosystemic shunts: protocol for a prospective, non-randomised controlled study.

INTRODUCTION: The presence of spontaneous portosystemic shunts (SPSS) has been identified to be associated with hepatic encephalopathy (HE) in patients with cirrhosis. Nevertheless, the role of interventional embolisation in managing such patients remains poorly defined. Consequently, this prospective controlled study aims to assess the efficacy and safety of interventional embolisation as a therapeutic approach for patients with cirrhosis and recurrent or persistent HE related to SPSS. METHODS AND ANALYSIS: Cirrhotic patients diagnosed with recurrent or persistent HE associated with SPSS will be recruited for this study, and assigned to either the interventional embolisation group or the standard medical treatment group. The efficacy endpoints encompass the evaluation of postoperative alleviation of HE symptoms and the incidence of overt HE recurrence during the follow-up period, as well as the duration and frequency of hospitalisations for HE, alterations in liver function and volume, and overall survival. The safety endpoints encompass both immediate and long-term postoperative complications. ETHICS AND DISSEMINATION: This study will be conducted in strict adherence to the principles of good clinical practice and the guidelines outlined in the Declaration of Helsinki. Ethical approval for the trial has been obtained from the Ethics Committee of Mengchao Hepatobiliary Hospital of Fujian Medical University (2023_013_02). Written informed consent will be obtained from all the participants by the treating physician for each patient prior to their enrolment. The documented informed consent forms will be retained as part of the clinical trial records for future reference. The study findings will be disseminated through publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300072189.

Directed Network Comparison Using Motifs.

Analyzing and characterizing the differences between networks is a fundamental and challenging problem in network science. Most previous network comparison methods that rely on topological properties have been restricted to measuring differences between two undirected networks. However, many networks, such as biological networks, social networks, and transportation networks, exhibit inherent directionality and higher-order attributes that should not be ignored when comparing networks. Therefore, we propose a motif-based directed network comparison method that captures local, global, and higher-order differences between two directed networks. Specifically, we first construct a motif distribution vector for each node, which captures the information of a node's involvement in different directed motifs. Then, the dissimilarity between two directed networks is defined on the basis of a matrix, which is composed of the motif distribution vector of every node and the Jensen-Shannon divergence. The performance of our method is evaluated via the comparison of six real directed networks with their null models, as well as their perturbed networks based on edge perturbation. Our method is superior to the state-of-the-art baselines and is robust with different parameter settings.

Anatomic versus non-anatomic resection for early-stage intrahepatic cholangiocarcinoma: a propensity score matching and stabilized inverse probability of treatment weighting analysis.

BACKGROUND: Radical resection is still the most cost-effectiveness curative strategy for intrahepatic cholangiocarcinoma (ICC), but it remains controversial on the survival benefit of anatomic resection (AR). In this study, we sought to compare the oncologic outcomes between AR versus non-AR (NAR) as the primary treatment for early-stage ICC patients. METHODS: Data of ICC patients who underwent hepatectomy and staged at AJCC I were retrospectively collected from 12 hepatobiliary centers in China between Dec 2012 and Dec 2015. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) analysis were performed to minimize the effect of potential confounders, and the perioperative and long-term outcomes between AR and NAR groups were compared. RESULTS: Two hundred seventy-eight ICC patients staged at AJCC I were eligible for this study, including 126 patients receiving AR and 152 patients receiving NAR. Compared to the NAR group, the AR group experienced more intraoperative blood loss before and after PSM or stabilized IPTW (all P > 0.05); AR group also experienced more intraoperative transfusion after stabilized IPTW (P > 0.05). In terms of disease-free survival (DFS) and overall survival (OS), no significant differences were observed between the two groups before and after PSM or stabilized IPTW (all P > 0.05). Multivariable Cox regression analyses found that AR was not an independent prognostic factor for either DFS or OS (all P > 0.05). Further analysis also showed that the survival benefit of AR was not found in any subgroup stratified by Child-Pugh grade (A or B), cirrhosis (presence or absence), tumor diameter (≤ 5 cm or > 5 cm) and pathological type (mass-forming or non-mass-forming) with all P > 0.05. CONCLUSION: Surgical approach does not influence the prognosis of patients with stage I primary ICC, and NAR might be acceptable and oncological safety.

miR-122-3p Alleviates LPS-Induced Pyroptosis of Macrophages via Targeting NLRP1.

OBJECTIVE: Sepsis, a life-threatening organ dysfunction, is among the leading causes of mortality in intensive care units. Sepsis occurrence is associated with macrophage pyroptosis, and microRNAs (miRNAs) have emerged as key factors in this process. However, the specific role of miR-122-3p in pyroptosis during sepsis progression and its underlying mechanisms remain to be fully elucidated. METHODS: We established an in vitro sepsis model using lipopolysaccharide (LPS)-activated macrophages, followed by transfection of a miR-122-3p mimic into RAW264.7 macrophages. We subsequently determined the effects of miR-122-3p on cell viability and pyroptosis using cell viability, western blot, and qPCR assays. The binding affinity between miR-122-3p and NLR pyrin domain containing 1 (NLRP1) mRNA was then confirmed using a dual-luciferase reporter assay. Finally, the secretion of pro-inflammatory cytokines (interleukin (IL)-2, IL-6, and tumor necrosis factor-α (TNF-α) was determined using ELISA. RESULTS: The results revealed that LPS treatment lead to a significant increase in the production of pro-inflammatory cytokines including IL-2, IL-6, and TNF-α in RAW264.7 cells. We observed that overexpression of miR-122-3p effectively restored cell viability and attenuated the expression of key inflammatory markers promoted by LPS, such as caspase-1, pro-caspase-1, IL-18, IL-1ß, NLRP3, apoptosis-associated speck-like protein containing CARD, and cleaved- gasdermin-D. Our data indicate that miR-122-3p is capable of directly bounding to NLRP1 and inhibiting its expression. CONCLUSIONS: These results confirmed that miR-122-3p plays a crucial role in the inhibition of sepsis by suppressing macrophage pyroptosis in an NLRP1-dependent manner. Therefore, miR-122-3p presents as a promising therapeutic target for sepsis.

Resection Margin Width Does Not Influence the Prognosis of Solitary Hepatocellular Carcinoma After Anatomic Resection: A Real-World Study from China.

Purpose: The influence of resection margin (RM) width on the prognosis of solitary hepatocellular carcinoma (HCC) following anatomical resection (AR) has yet to be determined. Therefore, we conducted a real-world study to identify the optimal RM width and assess its impact on the outcomes of solitary HCC patients undergoing AR. Methods: The data pertaining to patients diagnosed with solitary HCC who underwent AR between December 2012 and December 2015 were retrospectively collected. The optimal cutoff value for the width of the RM was determined using X-tile software. The Kaplan-Meier method was utilized to compare the overall survival (OS) and disease-free survival (DFS) between the narrow and wide RM groups. Additionally, propensity score matching (PSM) was performed to minimize potential bias in the data. Results: Of the 1033 patients who met the inclusion criteria, 293 (28.4%) were categorized into the narrow RM group (≤4 mm) and 740 (71.6%) into the wide RM group (> 4mm). Before and after PSM, there were no significant differences in OS and DFS between the two groups (before PSM: OS, HR=0.78, P=0.071; DFS, HR=0.95, P=0.620; after PSM: OS, HR=0.77, P=0.150; DFS, HR=0.90, P=0.470). Multivariate analysis demonstrated that RM width was not an independent risk factor for DFS and OS both before and after PSM (all P>0.05). However, subgroup analyses revealed that patients with ALBI grade 1, absence of cirrhosis, and AJCC stage II significantly benefited from wide RM in OS (all P< 0.05). Similarly, patients without HBV infection and absence of cirrhosis also exhibited significant benefits from wide RM in DFS (both P< 0.05). Conclusion: In patients with solitary HCC undergoing AR, the width of the RM does not appear to have a significant impact on their prognosis. However, in certain selected patients, a wider RM may confer benefits.

Prevalence, clinical characteristics, and outcomes of spontaneous portosystemic shunt in patients with hepatitis B-related cirrhosis: A multicenter study from China.

BACKGROUND: The impact of spontaneous portosystemic shunt (SPSS) on decompensated events and mortality for patients with hepatitis B-related cirrhosis remains poorly investigated. AIMS: To evaluate the prevalence, clinical characteristics, and outcomes of SPSS among patients with hepatitis B-related cirrhosis. METHODS: Patients who were diagnosed with hepatitis B-related cirrhosis were retrospectively recruited. All eligible patients were classified into SPSS and non-SPSS groups and their clinical characteristics and outcomes were compared and analyzed. RESULTS: Of the 1282 patients included in this study, SPSS was identified in 488 patients (38.1%). SPSS group had more severe liver function impairment, higher prevalence and severity of esophageal and gastric varices (EGV), and a higher prevalence of EGV bleeding (EGVB), portal vein thrombosis (PVT), hepatic encephalopathy (HE), ascites, and hepatocellular carcinoma (HCC, all P<0.05). During the follow-up period, SPSS group experienced a significantly higher incidence of EGVB, PVT, and HE (all P<0.05); however, there was no significant difference in the incidence of ascites, HCC, and mortality between the two groups (all P>0.05). CONCLUSION: With hepatitis B-related cirrhosis, SPSS was common and characterized by severe liver damage and a high prevalence of decompensated events. Moreover, patients with SPSS had higher risks of EGVB, PVT, and HE.

Spontaneous portosystemic shunts outside the esophago-gastric region: Prevalence, clinical characteristics, and impact on mortality in cirrhotic patients: A systematic review and meta-analysis.

BACKGROUND: Spontaneous portosystemic shunt (SPSS) other than esophago-gastric varices is one of the consequences of cirrhosis-induced portal hypertension (PHT), but its role is not fully understood. Therefore, we conducted a systematic review and meta-analysis to determine the prevalence and clinical characteristics of SPSS (excluding esophago-gastric varices) and its impact on mortality in patients with cirrhosis. METHODS: Eligible studies were identified from MedLine, PubMed, Embase, Web of Science, and Cochrane Library between Jan 1, 1980 and Sep 30, 2022. Outcome indicators were SPSS prevalence, liver function, decompensated events, and overall survival (OS). RESULTS: Totally, 2015 studies were reviewed, of which 19 studies recruiting 6884 patients were included. On pooled analysis, the prevalence of SPSS was 34.2% (26.6%∼42.1%). SPSS patients had significantly higher Child-Pugh scores and grades and Model for End-stage Liver Disease scores (all P<0.05). Moreover, SPSS patients experienced a higher incidence of decompensated events, including hepatic encephalopathy, portal vein thrombosis, and hepatorenal syndrome (all P<0.05). Additionally, SPSS patients had significantly shorter OS than the non-SPSS group (P<0.05). CONCLUSIONS: In patients with cirrhosis, SPSS outside the esophago-gastric region is common, characterized by severe impairment of liver function, high rates of decompensated events, including HE, PVT, and hepatorenal syndrome, as well as a high mortality rate.

Factor structure of the patient health questionnaire-9 and measurement invariance across gender and age among Chinese university students.

The Patient Health Questionnaire-9 (PHQ-9) has been widely used to screen depression symptoms. The present research aimed to assess the reliability and validity of PHQ-9, besides measurement invariance of the PHQ-9 across gender and age among Chinese university students. A total of 12,957 Chinese college students from 2 universities in Henan and Hainan provinces (China) completed the questionnaires via WeChat. This research reported the psychometric properties of PHQ-9 and measurement invariance of the PHQ-9 across gender and age among Chinese university students. Compared with 1-factor model, the 2-factor (affective factor and somatic factor) model of PHQ-9 showed a better fit index in Chinese university students. Without the last 2 items, the 2-factor model of the PHQ-9 showed satisfactory reliability, validity, and good fit index (e.g., Root mean square error of approximation = 0.060, Goodness-of-fit index = 0.982, Comparative fit index = 0.986, and Tucker-Lewis index = 0.974). The Cronbach's alpha of PHQ-9 was 0.874. Multi-group analysis across gender and age demonstrated that measurement equivalency for the 2-factor model of the PHQ-9 was established (e.g., Root mean square error of approximation < 0.08, Comparative fit index > 0.90 and Tucker-Lewis index > 0.90). The 2-factor model of the PHQ-9 without the items of "movement" and "desire to die" showed a better fit index in Chinese university students. The measurement equivalence across gender and age for the 2-factor model of the PHQ-9 can be established among Chinese university students.

Systematic review of adjuvant external beam radiotherapy for hepatocellular carcinoma following radical hepatectomy.

BACKGROUND AND AIM: Recurrence remains the main bottleneck hindering outcomes of hepatectomy for hepatocellular carcinoma (HCC). Owing to technological advances, external beam radiotherapy (EBRT) is being increasingly used in the management of HCC; however, there is no consensus on the role of adjuvant EBRT following hepatectomy. METHODS: A systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. PubMed, MedLine, Embase, the Cochrane Library, Web of Knowledge were used to screen eligible studies (published as of May 1st, 2022) that evaluated the clinical safety and efficacy of EBRT for HCC receiving hepatectomy. The endpoints were disease-free survival (DFS), overall survival (OS), and adverse events (AEs). RESULTS: A total of ten studies were eligible (three randomized controlled trials, one phase II trial, and six retrospective comparative studies). The pooled hazard ratio (HR) for median DFS and OS were both in favor of adjuvant EBRT compared with surgery alone (all P < 0.05), and the advantage of adjuvant EBRT was also confirmed in subgroups stratified by different populations (narrow margin, P < 0.05; microvascular invasion, P < 0.05; portal vein tumor thrombus, P < 0.05) and study designs (prospective studies, P < 0.05; retrospective studies, P < 0.05). Adjuvant EBRT was also found to be superior to adjuvant TACE (P < 0.05). Pooled rates of overall AEs and severe AEs were 65.3% and 12.2%, but no fatal AEs were reported. CONCLUSION: Adjuvant EBRT can be considered for HCC patients, especially those with a high risk of recurrence. Further studies are required for validation of these findings.

Corrigendum: The Significance of Transarterial Chemo(embolization) Combined With Tyrosine Kinase Inhibitors and Immune Check Point Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review.

[This corrects the article DOI: 10.3389/fimmu.2022.913464.].

The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review.

Background and Aims: Regardless of great progress in early detection of hepatocellular carcinoma (HCC), unresectable HCC (uHCC) still accounts for the majority of newly diagnosed HCC with poor prognosis. With the promising results of a double combination of transarterial chemo(embolization) and tyrosine kinase inhibitors (TKIs), and TKIs and immune checkpoint inhibitors (ICIs), a more aggressive strategy, a triple combination of transarterial chemo(embolization), TKIs, and ICIs has been tried in the recent years. Hence, we aimed to conduct a systematic review to verify the safety and efficacy of the triple therapy for uHCC. Methods: PubMed, MedLine, Embase, the Cochrane Library, and Web of Knowledge were used to screen the eligible studies evaluating the clinical efficacy and safety of triple therapy for patients with uHCC up to April 25th 2022, as well as Chinese databases. The endpoints were the complete response (CR), objective response rate (ORR), disease control rate (DCR), conversion rate, progression-free survival (PFS) rate, overall survival (OS) rate, and the incidence of adverse events (AEs). Results: A total of 15 studies were eligible with 741 patients receiving transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with TKIs and ICIs. The pooled rate and 95% confidence interval (CI) for CR, ORR, and DCR were 0.124 (0.069-0.190), 0.606 (0.528-0.682), and 0.885 (0.835-0.927). The pooled rates for PFS at 0.5 years and 1 year were 0.781 (0.688-0.862) and 0.387 (0.293-0.486), respectively. The pooled rates for OS at 1, 2, and 3 years were 0.690 (0.585-0.786), 0.212 (0.117-0.324), and 0.056 (0.028-0.091), respectively. In addition, the pooled rate and 95%CI for the conversion surgery was 0.359 (0.153-0.595). The subgroup analysis of control studies showed that triple therapy was superior to TACE+TKIs, TKIs+ICIs, and TKIs in CR, ORR, and DCR, conversion rate; PFS; and OS. No fatal AEs were reported, and the top three most common AEs were elevated ALT, elevated AST, and hypertension, as well as severe AEs (grading ≥3). Conclusion: With the current data, we concluded that the triple therapy of TACE/HAIC, TKIs, and ICIs would provide a clinical benefit for uHCC both in short- and long-term outcomes without increasing severe AEs, but the conclusion needs further validation. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO/, Review registry: CRD42022321970.

Splenic vein embolization as a feasible treatment for patients with hepatic encephalopathy related to large spontaneous splenorenal shunts.

INTRODUCTION AND OBJECTIVES: Although splenic vein embolization (SVE) has been performed for the management of patients with hepatic encephalopathy (HE) related to large spontaneous splenorenal shunts (SSRS) in recent years, its role remains poorly defined. In this study, we aimed to explore the safety and efficacy of SVE for HE patients with large SSRS. MATERIALS AND METHODS: Data from cirrhotic patients who were confirmed to have recurrent or persistent HE related to large SSRS and underwent SVE from January 2017 to April 2021 were retrospectively collected and analyzed at our center. The primary endpoints were the change of HE severity at 1 week after embolization and the recurrence of HE during the follow-up period. The secondary endpoints were procedure-related complications and changes in laboratory indicators and hepatic function (Child-Pugh score/grade and model for end-stage liver disease score). RESULTS: Of the eight cirrhotic patients included in the study, six were diagnosed with recurrent HE, and the others were diagnosed with persistent HE. Embolization success was achieved for all patients (100%), and no immediate procedure-related complications, de novo occurrence, or aggravation of symptoms related to portal hypertension were observed during the long-term follow-up. HE status was assessed at 1 week after embolization. The results demonstrated that the symptoms were mitigated in three patients and resolved completely in five patients. During the follow-up period, all patients were free of HE within 1 month after embolization, but one patient experienced the recurrence of HE within 6 months and another one experienced the recurrence of HE within 1 year. Compared with the preoperative parameters, the Child-Pugh score and grade were significantly improved at 1 week and 1 month after embolization (all P<0.05), and the serum ammonia level was significantly lower at 1 month after embolization (P<0.05). CONCLUSIONS: SVE could be considered as a feasible treatment for patients with HE related to large SSRS, but further validation is required.

Exploring the clinical value of preoperative serum gamma-glutamyl transferase levels in the management of patients with hepatocellular carcinoma receiving postoperative adjuvant transarterial chemoembolization.

BACKGROUND: Preoperative serum gamma-glutamyl transferase (γ-GT) levels is significantly related to the prognosis of hepatocellular carcinoma (HCC), but its clinical value in the management of postoperative adjuvant transarterial chemoembolization (PA-TACE) has rarely been explored. This study aimed to investigate whether γ-GT levels could be taken as a biomarker to guide the management of PA-TACE in resectable HCC. METHODS: HCC patients receiving radical resection were identified through the primary liver cancer big data (PLCBD) from December 2012 to December 2015. Prognostic factors of overall survival (OS) and disease-free survival (DFS) were identified by univariate and multivariate cox analyses, and subgroup analysis was conducted between PA-TACE group and non-TACE stratified by γ-GT levels before and after 1:1 propensity score matching (PSM). RESULTS: γ-GT level was found to be an independent risk factor of OS and DFS in 1847 HCC patients receiving radical resection (both P < 0.05), and patients with elevated γ-GT(> 54.0 U/L) have a shortened median OS and DFS, compared with those with normal γ-GT (both P < 0.001). In the subgroup of patients with normal γ-GT, there were no significant differences between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P > 0.05), and PA-TACE was not a significant prognostic factor of both OS and DFS before and after PSM (all P > 0.05). In the subgroup of patients with elevated γ-GT, significant differences were found between groups of PA-TACE and non-TACE in terms of median OS and DFS before and after PSM (all P < 0.05), and PA-TACE was an independent prognostic factor of both OS and DFS (all P < 0.05). CONCLUSION: Currently, we concluded that patients with more advanced HCC also have more elevated γ-GT, and these patients with elevated γ-GT would be benefited more from PA-TACE after radical resection.

Prognostic Value of Lymph Node Dissection for Intrahepatic Cholangiocarcinoma Patients With Clinically Negative Lymph Node Metastasis: A Multi-Center Study From China.

BACKGROUND: The clinical value of lymph-node dissection (LND) for intrahepatic carcinoma (ICC) patients with clinically negative lymph node metastasis (LNM) remains unclear; hence we conducted a multi-center study to explore it. METHODS: Patients who were diagnosed ICC with clinically negative LNM and underwent hepatectomy with or without LND from December 2012 to December 2015 were retrospectively collected from 12 hepatobiliary centers in China. Overall survival (OS) was analyzed using the Kaplan-Meier method, and then subgroup analysis was conducted stratified by variables related to the prognosis. RESULTS: A total of 380 patients were eligible including 106 (27.9%) in the LND group and 274 (72.1%) in the non-LND group. Median OS in the LND group was slightly longer than that in the non-LND group (24.0 vs. 18.0 months, P = 0.30), but a significant difference was observed between the two groups (24.0 vs. 14.0 months, P = 0.02) after a well-designed 1:1 propensity score matching without increased severe complications. And, LND was identified to be one of the independent risk factors of OS (HR = 0.66, 95%CI = 0.46-0.95, P = 0.025). Subgroup analysis in the matched cohort showed that patients could benefit more from LND if they were male, age <60 years, had no HBV infection, with ECOG score <2, CEA ≤5 ug/L, blood loss ≤400 ml, transfusion, major hepatectomy, resection margin ≥1 cm, tumor size >5 cm, single tumor, mass-forming, no satellite, no MVI, and no perineural invasion (all P < 0.05). Furthermore, only patients with pathologically confirmed positive LNM were found to benefit from postoperative adjuvant therapy (P < 0.001). CONCLUSION: With the current data, we concluded that LND would benefit the selected ICC patients with clinically negative LNM and might guide the postoperative management.

Meta-Analysis of Postoperative Adjuvant Hepatic Artery Infusion Chemotherapy Versus Surgical Resection Alone for Hepatocellular Carcinoma.

BACKGROUND: To systematically identify the long-term efficacy of postoperative adjuvant hepatic artery infusion chemotherapy (HAIC) for patients with hepatocellular carcinoma (HCC). METHODS: PubMed, MedLine, Embase, the Cochrane Library, and Web of Science were searched to collect the eligible studies up to March 31, 2021, that compared the surgical resection (SR) versus SR+HAIC for HCC patients. The endpoints were overall survival (OS) rates and disease-free survival (DFS) rates, and the effect size was determined by hazard ratio (HR) with 95% CI. RESULTS: A total of 12 studies (two randomized controlled trials (RCTs) and 10 non-RCTs) including 1,333 patients were eligible for this meta-analysis. The pooled results showed that OS and DFS rates in the SR+HAIC group were both better than those in the SR alone group (HR = 0.56, 95% CI = 0.41-0.77, p < 0.001; HR = 0.66, 95% CI = 0.55-0.78, p < 0.001, respectively). Furthermore, the subgroup analysis showed that patients would benefit from SR+HAIC regardless of chemotherapy regimens and courses (all p < 0.05), and patients with microvascular or macrovascular invasion would also benefit more from SR+HAIC in terms of OS and DFS (all p < 0.05). CONCLUSION: Postoperative adjuvant HAIC could improve the long-term prognosis of HCC patients, especially for those with microvascular or macrovascular invasion, regardless of chemotherapy regimens and courses, but it deserves further validation.

Stereotactic body radiotherapy versus radiofrequency ablation for hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: To compare the efficacy and safety of stereotactic body radiotherapy (SBRT) with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: PubMed, MedLine, EMBASE, the Cochrane Library and Web of Science were searched to identify potentially eligible studies comparing the efficacy and safety of SBRT with RFA for HCC from January 1990 to May 2020. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were used to determine the effect size for overall survival (OS), local control (LC) and complications. RESULTS: Seven studies including 7928 patients were enrolled in this meta-analysis. The results showed that SBRT was not inferior to RFA based on the pooled HR for OS (HR = 1.09, 95%CI = 0.78-1.52, p = .62); however, the pooled HR for the LC rate showed the superiority of SBRT (HR = 0.54, 95%CI = 0.35-0.84, p = .006). Subgroup analysis showed that the pooled HR for the LC rate favored SBRT in patients with tumors sized >2 cm (HR = 0.41, 95%CI = 0.23-0.74, p = .003), but no significant difference was observed in patients with tumors sized ≤2 cm (HR = 0.56, 95%CI = 0.25-1.28, p = .17). In addition, no significant differences in the incidence of late severe complications were observed between the SBRT and RFA groups (OR = 1.01, 95%CI = 0.59-1.73, p = .97). CONCLUSIONS: Based on the current data, we concluded that SBRT was well tolerated with an OS equivalent to that with RFA; SBRT was superior to RFA in terms of LC of HCC, especially in those with tumors sized >2 cm.

Clinical Significance of C-Reactive Protein to Albumin Ratio in Patients with Hepatocellular Carcinoma: A Meta-Analysis.

AIM: To evaluate the prognostic significance of C-reactive protein to albumin ratio (CAR) for clinical outcomes in hepatocellular carcinoma (HCC) patients. Material and Methods. Eligible studies were searched by PubMed, MedLine, the Cochrane Library, from January 1, 2000, to June 30, 2019, investigating the prognostic value of CAR in patients with HCC. Primary endpoint was OS. Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size. RESULTS: 7 records including 2208 patients published since 2014 were enrolled into our meta-analysis. Clinicopathological characteristics were also correlated with the level of CAR. The pooled HR for the OS rate between low and high CAR groups was 2.13 (95% CI 1.70~2.68, P < 0.00001) using a random model, but sensitivity analysis showed that the pooled HR for the OS rates did not change substantially after removal of any included study. As for patients receiving surgery, the pooled HR for the OS rate between low and high CAR groups was 2.04 (95% CI 1.59~2.61, P < 0.00001). Subgroup analysis showed that CAR could be a prognostic biomarker for HCC patients regardless of regions (China, HR = 1.75, 95% CI 1.51~2.02; Japan, HR = 3.36, 95% CI 2.07~5.45; Korea, HR = 2.26, 95% CI 1.47~4.47; respectively), the cut-off value (<0.1, HR = 2.84, 95% CI 1.90~4.24; >0.1, HR = 1.99, 95% CI 1.52~2.61; respectively), and sample size (<200, HR = 2.85, 95% CI 2.01~4.03; >200, HR = 1.75, 95% CI 1.52~2.02; respectively). CONCLUSION: With the current data, we clearly concluded that CAR was closely correlated with prognosis of patients with HCC. Multicenter, prospective randomized trials are warranted to confirm the conclusion.

Does intermittent pringle maneuver loss its clinical value in reducing bleeding during hepatectomy? A systematic review and meta-analysis.

BACKGROUND: The intermittent Pringle's maneuver (IPM) is conducted mainly during the procedure of hepatectomy to control intraoperative blood loss (IBL), but it has been questioned since improvement of surgical technology and intraoperative management. Hence, we conducted a systematic review and meta-analysis to validate the clinical value of IPM. MATERIALS AND METHODS: Eligible studies that were designed to evaluate the IPM in the procedure of hepatectomy were searched for on PubMed, Medline, and other databases from establishment of the database to October 2019. The primary endpoints were IBL and intraoperative blood transfusion (IBT). The risk ratio (RR) with 95% confidence interval (CI) was used to determine the effect size. RESULTS: A total of 16 studies with six randomized controlled trials (RCTs) were enrolled in this meta-analysis, including 1,770 cases in the IPM group and 1,611 cases in the non-IPM group. Overall, there were no significant differences between the IPM and non-IPM groups in the amount of IBL and the incidence of IBT (RR = 0.96, 95% CI 0.67-1.37, P = 0.82), which was also confirmed in the subgroups of RCTs (P > 0.05). However, subgroup analyses showed that for patients with colorectal liver metastasis (CRLM), the amount of IBL was generally higher in the IPM group than in the non-IPM group, and the incidence of IBT was significantly higher in the IPM group (RR = 7.17, 95% CI 1.91-26.94, P = 0.004). In addition, no significant differences were observed in terms of postoperative complications between the two groups (all P > 0.05). CONCLUSION: With the current data, we concluded that IPM had lost its value in patients with CRLM, although it remained controversial in patients with hepatocellular carcinoma.

Not All Hepatocellular Carcinoma Patients with Microvascular Invasion After R0 Resection Could Be Benefited from Prophylactic Transarterial Chemoembolization: A Propensity Score Matching Study.

BACKGROUND: Prophylactic transarterial chemoembolization (p-TACE) is strongly recommended for hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI), but the potential beneficiaries remain controversial. METHODS: Data of HCC patients with MVI who underwent R0 resection between December 2013 and December 2015 were identified through the primary liver cancer big data. Disease-free survival (DFS) and overall survival (OS) were compared between patients who received p-TACE or not using Kaplan-Meier survival curves before and after propensity scoring match (PSM). RESULTS: A total of 695 patients were eligible for this study, including 199 patients (28.6%) receiving p-TACE and 496 patients (71.4%) receiving resection alone. In the crude cohort, median DFS and OS were longer in the p-TACE group than those in the non-TACE group without significant differences (25.0 months vs 24.2 months, P=0.100; 48.0 months vs 46.5 months, P=0.150; respectively), but significant differences were observed both in DFS and OS (both P<0.05) after 1:1 PSM. p-TACE was identified as one of the independent risk factors of both DFS and OS using multivariate analysis in the matched cohort (HR=0.69, 95% CI=0.54-0.88; HR=0.66, 95% CI=0.50-0.88; respectively). Subgroup analysis showed that p-TACE could beneficiate patients if they were male, aged ≥50 years old, had HBV infection, preoperative AFP level ≥400 ng/mL, Child-Pugh grading A, no transfusion, single tumor, tumor diameter ≥5cm, Edmondson-Steiner grading I/II, capsule, or BCLC stage A, CNLC stage Ib, AJCC stage II both in DFS and OS (all P<0.05). CONCLUSION: With the current data, we concluded that not all HCC patients with MVI would be benefited from p-TACE, and p-TACE could benefit patients with "middle risk" according to the current staging systems.