Peripheral Th and NK cells are associated with response to lenvatinib plus PD-1 inhibitor in unresectable hepatocellular carcinoma.

The value of peripheral blood lymphocyte subpopulations in predicting responses to lenvatinib combination with programmed death-1 (PD-1) inhibitors in unresectable hepatocellular carcinoma (HCC) was investigated. Fifteen patients received objective responses (OR) and sixteen patients had non-objective responses (NOR) were analyzed. The counts of peripheral blood lymphocyte subpopulations from patients were measured before treatment, second (at week 3), and third doses (at week 6) of the PD-1 inhibitor administration, and correlated with responses. Helper T (Th) cells and natural killers (NK) cells were more abundant in the OR group and found to be important predictors of OR in a stepwise multivariate logistic regression analysis. These cutoff values of Th and NK cells could help to distinguish OR from NOR cases accurately and provide clinical benefits.

Conversion surgery for advanced hepatocellular carcinoma after combination treatment of lenvatinib and camrelizumab: a case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive malignancy with high morbidity and mortality. Conversion therapy can improve surgical resection rate and prolong survival time for patients with advanced HCC. We show that combination therapy with lenvatinib and camrelizumab is a novel approach to downstage unresectable HCC. CASE PRESENTATION: A 49-year-old man was diagnosed with massive HCC with hilar lymph node and lung metastases. Since radical resection was not feasible, lenvatinib and camrelizumab were administered as first-line therapy. After 10 cycles of camrelizumab and continuous oral administration of lenvatinib, the tumor exhibited striking shrinkage in volume indicating a partial radiological response, accompanied by a reduction in the alpha-fetoprotein levels, followed by salvage resection. Intriguingly, an improvement in predictive biomarkers, like lactate dehydrogenase (LDH) and neutrophil-to-lymphocyte ratio (NLR), was observed. Notably, the pathological examination found high levels of necrosis in the resected tumor, and flow cytometry analysis indicated a significant increase in the ratio of CD5+ and CD5- B lymphocytes in the peripheral blood. After the treatment, the overall survival period was over 24 months, and no recurrence was observed 17-month post-surgery. CONCLUSIONS: A combination of lenvatinib and camrelizumab may be a new conversion therapy for initially unresectable HCC to resectable HCC, thus contributing to improve the disease prognosis. In addition, the combination regimen could cause an activated immune response, and LDH, NLR, and CD5+ B-cell levels might be predictors for immunotherapy efficacy.

A novel prognostic signature based on four glycolysis-related genes predicts survival and clinical risk of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common cancer with limited cure and poor survival. In our study, a bioinformatic analysis was conducted to investigate the role of glycolysis in the pathogenesis and progression of HCC. METHODS: Single-sample gene set enrichment analysis (ssGESA) was used to calculate enrichment scores for each sample in TCGA-LIHC and GEO14520 according to the glycolysis gene set. Weighted gene co-expression network analysis identified a gene module closely related to glycolysis, and their function was investigated. Prognostic biomarkers were screened from these genes. Cox proportional hazard model and least absolute shrinkage and selection operator regression were used to construct the prognostic signature. Kaplan-Meier (KM) and receiver operating characteristic (ROC) curve analyses evaluated the prediction performance of the prognostic signature in TCGA-LIHC and ICGC-LIRI-JP. Combination analysis data of clinical features and prognostic signature constructed a nomogram. Area under ROC curves and decision curve analysis were used to compare the nomogram and its components. RESULTS: The glycolysis pathway was upregulated in HCC and was unfavorable for survival. The determined gene module was mainly enriched in cell proliferation. A prognostic signature (CDCA8, RAB5IF, SAP30, and UCK2) was developed and validated. KM and ROC curves showed a considerable predictive effect. The risk score derived from the signature was an independent prognostic factor. The nomogram increased prediction efficiency by combining risk signature and TNM stage and performed better than component factors in net benefit. CONCLUSION: The gene signature may contribute to individual risk estimation, survival prognosis, and clinical management.

CDK1, CCNB1, and CCNB2 are Prognostic Biomarkers and Correlated with Immune Infiltration in Hepatocellular Carcinoma.

BACKGROUND Orderly G2/M transition in the cell cycle is controlled by the cyclin-dependent kinase 1/cyclin B (CDK1/CCNB) complex. We aimed to comprehensively investigate the roles of CDK1, CCNB1, and CCNB2 via multi-omics analysis and their relationships with immune infiltration in hepatocellular carcinoma (HCC). MATERIAL AND METHODS The transcriptional data and the epigenetic and genetic alterations of CDK1, CCNB1, and CCNB2, as well as their impacts on prognosis in HCC patients, were identified using multiple databases. The correlations between expression of these genes and immune infiltration in HCC were then explored using the TIMER database. RESULTS Overall, mRNA expression of CDK1, CCNB1, and CCNB2 was up-regulated in various tumor tissues including HCC. Higher expression of these genes was associated with poorer prognosis in HCC patients. Lower promoter methylation of these genes might cause higher expression levels in tumor tissues of HCC. Genetic alterations and several methylated-CpG sites in these genes were significantly associated with survival. Notably, expression levels of CDK1, CCNB1, and CCNB2 were positively correlated with infiltrating levels of CD4⁺ T cells, CD8⁺ T cells, neutrophils, macrophages, and dendritic cells in HCC. In addition, significant correlations between the expression of these genes and various immune markers in HCC, such as PD-1, PDL-1, and CTLA-4, were also observed. CONCLUSIONS CDK1, CCNB1, and CCNB2 are potential prognostic biomarkers and associated with immune cell infiltration in HCC. The genes may be utilized to predict the reaction of immunotherapy. Combining inhibitors of these genes with immunotherapy may improve the survival time of HCC patients.

Real-Time Navigation Guidance Using Fusion Indocyanine Green Fluorescence Imaging in Laparoscopic Non-Anatomical Hepatectomy of Hepatocellular Carcinomas at Segments 6, 7, or 8 (with Videos).

BACKGROUND The right area and posterior area of the liver are considered relatively unfavorable portions for laparoscopic hepatectomy (LH) due to the limited gross inspection and poor tactile feedback. Fusion indocyanine green fluorescence fusion imaging (ICGFI) may be a reliable real-time navigation tool for LH. The aim of the present study was to evaluate the usefulness of ICGFI for laparoscopic non-anatomical hepatectomy in patients with hepatocellular carcinoma at the right area and posterior area. MATERIAL AND METHODS We conducted a retrospective comparison of surgical and perioperative outcomes for 21 hepatocellular carcinoma patients who had undergone LH with fusion ICGFI guidance and 21 matched patients who underwent the procedure without the guidance of ICGFI between November 2017 to August 2018. RESULTS Preoperative characteristics were comparable between the groups. Tumor fluorescence images were clearly displayed in all 21 ICGFI patients, providing precise information about tumor location. Laparoscopic parenchymal transection could be performed safely and quickly through tracing the fusion ICGFI on the cutting surface. Operation time was significantly reduced in the ICGFI group. Postoperative complications were comparable between the groups. There was no positive margin in either group. CONCLUSIONS These preliminary data suggest that fusion ICGFI may be a useful tool that provides real-time navigation for non-anatomical LH. It may assist in the safe and accurate completion of LH for tumors located at the right posterior areas. Further studies are needed to fully clarify the advantages and disadvantages of ICGFI in LH, including short-term perioperative outcomes and long-term prognosis.

Safety and Feasibility of a Laparoscopy-Assisted Non-Anatomic Resection Technique for Hepatocellular Carcinoma Located at Right Posterior Segments in Cirrhotic Patients: A Case-Controlled Study with Propensity Score Matching.

PURPOSE: The aim of this study was to compare the short- and long-term outcomes of laparoscopy-assisted resection for right posterior segment (LAR-RPS) with open resection (OR-RPS) performed by experienced hepatobiliary surgeons. METHODS: This was a prospective comparative nonrandomized study. RESULTS: The groups were comparable in terms of baseline demographics and clinicopathological data. Reduced operative time (254.88 ± 78.56 vs. 347.95 ± 82.56 min; p = 0.04) and estimated blood loss (477 ± 756 vs. 712 ± 836 mL; p = 0.03) were observed in LAR-RPS. Also, significant less duration of hospital stay (7.53 ± 2.68 vs. 12.57 ± 3.21 days; p < 0.001) was associated with LAR-RPS compared to OR-RPS. Long-term oncologic outcomes were comparable in 2 groups, in terms of both the overall and disease-free survival rates (p = 0.450 and 0.463, respectively). CONCLUSIONS: This study confirms that laparoscopic-assisted resection is a safe and effective operative procedure in those cirrhotic patients with a lesion in the right posterior section of the liver. When compared to the open approach, the laparoscopic-assisted approach reduces operative time and blood loss, as well as the length of hospital stay.

Is the era of intravenous proton pump inhibitors coming to an end in patients with bleeding peptic ulcers? Meta-analysis of the published literature.

AIMS: Oral and intravenous proton pump inhibitors (PPIs) are equipotent in raising gastric pH. However, it is not known whether oral PPIs can replace intravenous PPIs in patients with bleeding peptic ulcers. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials to compare oral and intravenous PPIs among patients with peptic ulcer bleeding. A search of all major databases and relevant journals from inception to April 2015, without a restriction on languages, was performed. RESULTS: A total of 859 patients from seven randomized controlled trials were included in the meta-analysis. Similar pooled outcome measures were demonstrated between the two groups in terms of oral PPIs vs. intravenous PPIs in the rate of recurrent bleeding within the 30-day follow-up period [risk ratio = 0.90; 95% confidence interval (CI): 0.58, 1.39; P = 0.62; I(2)  = 0%). In terms of the rate of mortality, both oral and intravenous PPIs showed similar outcomes, and the pooled risk ratio was 0.88 (95% CI: 0.29, 2.71; P = 0.82; I(2)  = 0%). Likewise, no significant difference was detected in the need for blood transfusion and length of hospital stay; the pooled mean differences were -0.14 (95% CI: -0.39, 0.12; P = 0.29; I(2)  = 32%) and -0.60 (95% CI: -1.42, 0.23; P = 0.16; I(2)  = 79%), respectively. CONCLUSIONS: Our results suggest that oral PPIs are a feasible, safe alternative to intravenous PPIs in patients with bleeding peptic ulcers, and may be able to replace intravenous PPIs as the treatment of choice in these patients.

Postoperative complications affect long-term survival outcomes following hepatic resection for colorectal liver metastasis.

BACKGROUND: The impact of postoperative complications (POCs) on long-term survival outcomes following hepatic resection for colorectal liver metastasis (CRLM) is in controversy. The aim of the present meta-analysis was to systematically evaluate the POC effect on overall survival (OS) and disease-free survival (DFS) in patients undergoing hepatic resection for CRLM. METHODS: We conducted a systematic review and meta-analysis of all observational studies to evaluate the POC effect on OS and DFS in patients undergoing hepatic resection for CRLM. A search for all major databases and relevant journals from inception to January 2014 without restriction on languages or regions was performed. POCs were extracted and graded according to a validated system of classification. Outcome measures were postoperative 1-, 2-, 3-, and 10-year OSs and DFSs. Both random-effects and fixed-effect models were used to pool the hazard ratios (HRs) of the survival outcomes. Test of heterogeneity was performed with the Q statistic. RESULTS: A total of 2370 patients were included in the meta-analysis. Both 5- and 10-year postoperative OSs showed significant decreases in patients with POCs (HR = 1.52; 95 % CI 1.27-1.83; P < 0.001 and HR = 1.36; 95 % CI 1.18-1.58; P < 0.001, respectively). Similar outcomes were also observed in terms of DFSs, with the 5- and 10-year HRs found to be 1.37 (95 % CI 1.23-1.53; P < 0.001) and 1.34 (95 % CI 1.17-1.53; P < 0.001), respectively, compared to no POC group. CONCLUSIONS: POCs are strongly related to long-term oncologic outcomes following hepatic resection for CRLM. Further efforts to refine surgical technique and postoperative management to avoid complications may improve the long-term oncological outcomes of the selected patients.

Murine double minute 2 rs2279744 polymorphism and hepatocellular carcinoma risk in East Asians: a meta-analysis.

Murine double minute 2 (MDM2) is a crucial negative regulator of p53 function through several mechanisms. There are many studies performed to assess the association between MDM2 rs2279744 polymorphism and hepatocellular carcinoma risk, but the impact of MDM2 rs2279744 polymorphism on hepatocellular carcinoma in East Asians is unclear owing to the inconsistent findings from previous studies. We conducted a comprehensive meta-analysis of epidemiological studies to shed some light on these contradicting results. We used pooled odds ratio (OR) with its 95 % confidence intervals (95 % CI) to assess the association. Overall, seven studies with a total of 4,993 subjects were finally included. The meta-analysis suggested that MDM2 rs2279744 polymorphism was significantly associated with increased risk of hepatocellular carcinoma in East Asians (G versus T: OR = 1.27, 95 % CI 1.06-1.52, P = 0.01; GG versus TT: OR = 1.59, 95 % CI 1.11-2.27, P = 0.01; GG/GT versus TT: OR = 1.41, 95 % CI 1.07-1.87, P = 0.02; GG versus TT/GT: OR = 1.32, 95 % CI 1.08-1.62, P = 0.008). Sensitivity analysis by excluding low-quality study still suggested that the association above was still significant. Thus, the findings from the meta-analysis support that MDM2 rs2279744 polymorphism is significantly associated with increased risk of hepatocellular carcinoma in East Asians.

Prognostic model for unresectable hepatocellular carcinoma treated with dual PD-1 and angiogenesis blockade therapy.

BACKGROUND AND AIMS: Dual programmed death 1 (PD-1) and angiogenesis blockade therapy is a frontline treatment for hepatocellular carcinoma (HCC). An accepted model for survival prediction and risk stratification in individual patients receiving this treatment is lacking. Aimed to develop a simple prognostic model specific to these patients. APPROACH AND RESULTS: Patients with unresectable HCC undergoing dual PD-1 and angiogenesis blockade therapy were included in training cohort (n=168) and validation cohort (n=72). We investigated the prognostic value of clinical variables on overall survival using a Cox model in the training set. A prognostic score model was then developed and validated. Predictive performance and discrimination were also evaluated. Largest tumor size and Alpha-fetoprotein concentration at baseline and Neutrophil count and Spleen volume change after 6 weeks of treatment were identified as independent predictors of overall survival in multivariable analysis and used to develop LANS score. Time-dependent receiver operating characteristic analysis, calibration curves, and C-index showed LANS score had favorable performance in survival prediction. Patients were divided into three risk categories based on LANS score. Median survival for patients with low, intermediate, and high LANS scores was 31.7, 23.5, and 11.5 months, respectively (p<0.0001). The disease control rates were 96.4%, 64.3%, and 32.1%, respectively (p<0.0001). The predictive performance and risk stratification ability of the LANS score were confirmed in validation and entire cohorts. CONCLUSION: The LANS score model can provide individualized survival prediction and risk stratification in patients with unresectable HCC undergoing dual PD-1 and angiogenesis blockade therapy.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma: A network meta-analysis.

BACKGROUND: With the rapid progress of systematic therapy for hepatocellular carcinoma (HCC), therapeutic strategies combining hepatic arterial infusion chemotherapy (HAIC) with systematic therapy arised increasing concentrations. However, there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC. AIM: To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC. METHODS: A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study. The outcomes of interest comprised overall survival (OS), progression-free survival (PFS), tumor response and adverse events. Hazard ratios (HR) and odds ratios (OR) with a 95% confidence interval (CI) were calculated and agents were ranked based on their ranking probability. RESULTS: HAIC outperformed Sorafenib (HR = 0.55, 95%CI: 0.42-0.72; HR = 0.51, 95%CI: 0.33-0.78; OR = 2.86, 95%CI: 1.37-5.98; OR = 5.45, 95%CI: 3.57-8.30; OR = 7.15, 95%CI: 4.06-12.58; OR = 2.89, 95%CI: 1.99-4.19; OR = 0.48, 95%CI: 0.25-0.92, respectively) and transarterial chemoembolization (TACE) (HR = 0.50, 95%CI: 0.33-0.75; HR = 0.62, 95%CI: 0.39-0.98; OR = 3.08, 95%CI: 1.36-6.98; OR = 2.07, 95%CI: 1.54-2.80; OR = 3.16, 95%CI: 1.71-5.85; OR = 2.67, 95%CI: 1.59-4.50; OR = 0.16, 95%CI: 0.05-0.54, respectively) in terms of efficacy and safety. HAIC + lenvatinib + ablation, HAIC + ablation, HAIC + anti- programmed cell death 1 (PD-1), and HAIC + radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone. HAIC + TACE + S-1, HAIC + lenvatinib, HAIC + PD-1, HAIC + TACE, and HAIC + sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC. HAIC + PD-1, HAIC + TACE + S-1 and HAIC + TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone. CONCLUSION: HAIC proved more effective and safer than sorafenib and TACE. Furthermore, combined with other interventions, HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Targeting pathogenic CD8+ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis.

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

The characteristics of Laennec's capsule around the hepatic veins: A histological study based on 71 liver surgical specimens.

Background: Laennec's capsule is a fibrous membrane attached to the surface of the liver, which is independent of the hepatic veins. However, the presence of Laennec's capsule surrounding the peripheral hepatic veins is controversial. This study aims to describe the characteristic of Laennec's capsule around the hepatic veins at all levels. Methods: Seventy-one hepatic surgical specimens were collected along the cross and longitudinal sections of the hepatic vein. Tissue sections of 3-4 mm were cut and stained with hematoxylin and eosin (H&E), resorcinol-fuchsin (R&F), and Victoria blue (V&B). Elastic fibers were observed around the hepatic veins. They were measured using K-Viewer software. Results: Morphologically, we observed a thin, dense fibrous layer (so-called Laennec's capsule) around the hepatic veins at all levels, which was different from the thick elastic fibers of the hepatic vein wall. Therefore, there was a potential gap between Laennec's capsule and the hepatic veins. Laennec's capsule was visualized significantly better with R&F and V&B staining compared to H&E staining. The thickness of Laennec's capsule around the main, first, and secondary branches of the hepatic vein were 79.86 ± 24.20 µm, 48.41 ± 18.25 µm, and 23.56 ± 10.03 µm in the R&F staining, and 80.15 ± 21.85 µm, 49.46 ± 17.52 µm, and 25.05 ± 11.03 µm in the V&B staining, respectively. They were significantly different from each other (P < .001). Conclusion: The hepatic veins were surrounded by Laennec's capsule at all levels, including the peripheral hepatic veins. However, it is thinner along the vein branches. The gap between the Laennec's capsule and hepatic veins shows potential supplemental value for liver surgery.

A novel clinical model for risk prediction and stratification of new-onset diabetes mellitus after distal pancreatectomy.

Background: The incidence of new-onset diabetes mellitus (NODM) after distal pancreatectomy (DP) remains high. Few studies have focused on NODM in patients with pancreatic benign or low-grade malignant lesions (PBLML). This study aimed to develop and validate an effective clinical model for risk prediction and stratification of NODM after DP in patients with PBLML. Methods: A follow-up survey was conducted to investigate NODM in patients without preoperative DM who underwent DP. Four hundred and forty-eight patients from Peking Union Medical College Hospital (PUMCH) and 178 from Guangdong Provincial People's Hospital (GDPH) met the inclusion criteria. They constituted the training cohort and the validation cohort, respectively. Univariate and multivariate Cox regression, as well as least absolute shrinkage and selection operator (LASSO) analyses, were used to identify the independent risk factors. The nomogram was constructed and verified. Concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA) were applied to assess its predictive performance and clinical utility. Accordingly, the optimal cut-off point was determined by maximally selected rank statistics method, and the cumulative risk curves for the high- and low-risk populations were plotted to evaluate the discrimination ability of the nomogram. Results: The median follow-up duration was 42.8 months in the PUMCH cohort and 42.9 months in the GDPH cohort. The postoperative cumulative 5-year incidences of DM were 29.1% and 22.1%, respectively. Age, body mass index (BMI), length of pancreatic resection, intraoperative blood loss, and concomitant splenectomy were significant risk factors. The nomogram demonstrated significant predictive utility for post-pancreatectomy DM. The C-indexes of the nomogram were 0.739 and 0.719 in the training and validation cohorts, respectively. ROC curves demonstrated the predictive accuracy of the nomogram, and the calibration curves revealed that prediction results were in general agreement with the actual results. The considerable clinical applicability of the nomogram was certified by DCA. The optimal cut-off point for risk prediction value was 2.88, and the cumulative risk curves of each cohort showed significant differences between the high- and low-risk groups. Conclusions: The nomogram could predict and identify the NODM risk population, and provide guidance to physicians in monitoring and controlling blood glucose levels in PBLML patients after DP.

Laboratory scoring system to predict hepatic indocyanine green clearance ability during fluorescence imaging-guided laparoscopic hepatectomy.

BACKGROUND: Indocyanine green (ICG) fluorescence played an important role in tumor localization and margin delineation in hepatobiliary surgery. However, the preoperative regimen of ICG administration was still controversial. Factors associated with tumor fluorescence staining effect were unclear. AIM: To investigate the preoperative laboratory indexes corelated with ICG fluorescence staining effect and establish a novel laboratory scoring system to screen specifical patients who need ICG dose adjustment. METHODS: To investigate the predictive indicators of ICG fluorescence characteristics in patients undergoing laparoscopic hepatectomy from January 2018 to January 2021 were included. Blood laboratory tests were completed within 1 wk before surgery. All patients received 5 mg ICG injection 24 h before surgery for preliminary tumor imaging. ImageJ software was used to measure the fluorescence intensity values of regions of interest. Correlation analysis was used to identify risk factors. A laboratory risk model was established to identify individuals at high risk for high liver background fluorescence. RESULTS: There were 110 patients who were enrolled in this study from January 2019 to January 2021. The mean values of fluorescence intensity of liver background (FI-LB), fluorescence intensity of gallbladder, and fluorescence intensity of target area were 18.87 ± 17.06, 54.84 ± 33.29, and 68.56 ± 36.11, respectively. The receiver operating characteristic (ROC) curve showed that FI-LB was a good indicator for liver clearance ability [area under the ROC curve (AUC) = 0.984]. Correlation analysis found pre-operative aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, adenosine deaminase, and lactate dehydrogenase were positively associated with FI-LB and red blood cell, cholinesterase, and were negatively associated with FI-LB. Total laboratory risk score (TLRS) was calculated according to ROC curve (AUC = 0.848, sensitivity = 0.773, specificity = 0.885). When TLRS was greater than 6.5, the liver clearance ability of ICG was considered as poor. CONCLUSION: Preoperative laboratory blood indicators can predict hepatic ICG clearance ability. Surgeons can adjust the dose and timing of ICG preoperatively to achieve better liver fluorescent staining.

A Pyroptosis-Based Prognostic Model for Immune Microenvironment Estimation of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), an aggressive malignant tumor, has a high incidence and unfavorable prognosis. Recently, the synergistic effect of pyroptosis in antitumor therapy and regulation of tumor immune microenvironment has made it possible to become a novel therapeutic method, but its potential mechanism still needs further exploration. METHODS: Differentially expressed genes with prognostic value in Liver Hepatocellular Carcinoma Project of The Cancer Genome Atlas (TCGA-LIHC) cohort were screened and incorporated into the risk signature by Cox proportional hazards regression model and least absolute shrinkage and selection operator. Kaplan-Meier (KM) curves and receiver operating characteristic (ROC) curves were applied to conduct survival comparisons and estimate prediction ability. The dataset of Liver Cancer-RIKEN, Japan Project from International Cancer Genome Consortium (ICGC-LIRI-JP) cohort was used to verify the reliability of the signature. Correlation analysis between clinicopathological characteristics, immune infiltration, drug sensitivities, and risk scores was conducted. Functional annotation analyses were performed for the genes differentially expressed between high-risk and low-risk groups. RESULTS: A risk signature consisting of 6 pyroptosis-related genes in HCC was developed and validated. KM curves and ROC curves revealed its considerable predictive accuracy. Higher risk scores meant more advanced grade, higher alpha-fetoprotein level, and stronger invasive ability. Overexpressed genes in high-risk population were more enriched in the immune-associated pathways, and these patients might be more sensitive to immune checkpoint inhibitors instead of Sorafenib. Intriguingly, 6 identified genes were promising to be prognostic biomarkers and therapeutic targets of HCC. CONCLUSIONS: The signature may have crucial clinical significance in predicting survival prognosis, immune infiltration, and drug efficacy based on pyroptosis-related genes.

Nomogram Based on Inflammatory Biomarkers to Predict the Recurrence of Hepatocellular Carcinoma-A Multicentre Experience.

Purpose: Our study aimed to identify inflammatory biomarkers and develop a prediction model to stratify high-risk patients for hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) recurrence after curative resection. Patients and Methods: A total of 583 eligible HBV-HCC patients with curative hepatectomy from Guangdong Provincial People's Hospital (GDPH) and Sun Ya-sen University Cancer Centre (SYSUCC) were enrolled in our study. Cox proportional hazards regression was utilized to evaluate potential risk factors for disease-free survival (RFS). The area under the receiver operating characteristic (ROC) curve (AUC) was utilized to assess the discrimination performance. Calibration plots and decision curve analyses (DCA) were used to evaluate the calibration of the nomogram and the net benefit, respectively. Results: Based on the systemic inflammation response index (SIRI), aspartate aminotransferase to neutrophil ratio index (ANRI), China Liver Cancer (CNLC) stage and microvascular invasion, a satisfactory nomogram was developed. The AUC of our nomogram for predicting 1-, 2-, and 3-year RFS was 0.767, 0.726, and 0.708 in the training cohort and 0.761, 0.716, and 0.715 in the validation cohort, respectively. Furthermore, our model demonstrated excellent stratification as well as clinical applicability. Conclusion: The novel nomogram showed a higher prognostic power for the RFS of HCC patients with curative hepatectomy than the CNLC, AJCC 8th edition and BCLC staging systems and may help oncologists identify high-risk HCC patients.

A Novel Blood Index-Based Model to Predict Hepatitis B Virus-Associated Hepatocellular Carcinoma Recurrence After Curative Hepatectomy: Guidance on Adjuvant Transcatheter Arterial Chemoembolization Choice.

BACKGROUND: Postoperative recurrence is a significant obstacle in hepatocellular carcinoma (HCC) treatment. This study aimed to construct a blood index-based model to predict hepatitis B virus-associated HCC (HBV-HCC) recurrence after curative hepatectomy. METHODS: A total of 370 patients who received initially curative hepatectomy for HBV-HCC were included in this study. A novel blood index signature (BIS) was identified and systematically analyzed for its recurrence predictive value. Following this, multivariate Cox regression analysis was performed to build a blood index-based nomogram. RESULTS: A BIS based on the aminotransferase-to-platelet ratio index and a systemic inflammatory response index was used to construct a nomogram. The model showed good clinical applicability and reliability. Notably, the patients in the high recurrence risk group tended to benefit from adjuvant transcatheter arterial chemoembolization (TACE). CONCLUSION: A reliable model was constructed to predict the HBV-HCC recurrence after curative hepatectomy. This model can guide the surgeons in selecting patients with high recurrence risk patients who may benefit from adjuvant TACE.