The pattern of tumor progression on first-line immune checkpoint inhibitor-based systemic therapy for Chinese advanced hepatocellular carcinoma -CLEAP 004 study.

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.

The Barthel Index predicts surgical textbook outcomes following hepatectomy for elderly patients with hepatocellular carcinoma: A multicenter cohort study.

BACKGROUND: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients. METHODS: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs. RESULTS: Of 497 elderly patients, 157 (31.6 â€‹%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 â€‹%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 â€‹% vs. 72.1 â€‹%, P â€‹< â€‹0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 â€‹% confidence interval 1.879-6.198, P â€‹< â€‹0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy. CONCLUSION: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology.

[Diffuse Hepatoid Adenocarcinoma in the Peritoneal Cavity:Report of One Case].

Hepatoid adenocarcinoma is a rare and unique type of adenocarcinoma,resembling hepatocellular carcinoma in histopathology.Most cases occur in the stomach,lacking specific clinical and imaging manifestations,which leads to high rates of missed diagnosis and misdiagnosis.Hepatoid adenocarcinoma in the peritoneal cavity is even rarer.This article reports a case of hepatoid adenocarcinoma with the manifestation of diffuse peritoneal thickening,aiming to provide reference for clinical diagnosis and treatment.

Efficacy of ginseng-based Renshenguben oral solution for cancer-related fatigue among patients with advanced-stage hepatocellular carcinoma: A prospective multicenter cohort study.

BACKGROUND: Cancer-related fatigue (CRF) is a common and debilitating symptom experienced by patients with advanced-stage cancer, especially those undergoing antitumor therapy. This study aimed to evaluate the efficacy and safety of Renshenguben (RSGB) oral solution, a ginseng-based traditional Chinese medicine, in alleviating CRF in patients with advanced hepatocellular carcinoma (HCC) receiving antitumor treatment. METHODS: In this prospective, open-label, controlled, multicenter study, patients with advanced HCC at BCLC stage C and a brief fatigue inventory (BFI) score of ≥ 4 were enrolled. Participants were assigned to the RSGB group (RSGB, 10 mL twice daily) or the control group (with supportive care). Primary and secondary endpoints were the change in multidimensional fatigue inventory (MFI) score, and BFI and functional assessment of cancer therapy-hepatobiliary (FACT-Hep) scores at weeks 4 and 8 after enrollment. Adverse events (AEs) and toxicities were assessed. RESULTS: A total of 409 participants were enrolled, with 206 assigned to the RSGB group. At week 4, there was a trend towards improvement, but the differences were not statistically significant. At week 8, the RSGB group exhibited a significantly lower MFI score (P < 0.05) compared to the control group, indicating improved fatigue levels. Additionally, the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8 (P < 0.05). Subgroup analyses among patients receiving various antitumor treatments showed similar results. Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI, BFI, and FACT-Hep scores at week 8. No serious drug-related AEs or toxicities were observed. CONCLUSIONS: RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period, with no discernible toxicities. These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.

Comparison analysis of PD-1/PD-L1 inhibitors plus lenvatinib or gemcitabine/cisplatin as first-line treatment for patients with advanced intrahepatic cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive primary liver cancer, with increasing incidence worldwide. Effective first-line treatments for advanced ICC patients are currently limited. Therefore, our study aimed to assess the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in combination with gemcitabine/cisplatin (GC) and lenvatinib as first-line treatment in advanced ICC patients. Methods: This retrospective cohort study included 51 advanced ICC patients, among whom 25 patients were administered with PD-1/PD-L1 plus lenvatinib and 26 patients were administered with PD-1/PD-L1 plus GC. Baseline characteristics including demographic information, medical history, clinical characteristics, laboratory data, and imaging examination were collected. The primary endpoints were progression-free survival (PFS) and sixth- and ninth-month overall survival (OS) rate. Survival curve was plotted by the Kaplan-Meier method. A Cox proportion risk model was performed to investigate independent risk factors of PFS and OS. The secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events. Results: The median age of advanced ICC patients in our study was 58.0 (95% confidence interval [95% CI] = 48.0-72.4) years, with 33 male and 18 female patients. Patients in the PD-1/PD-L1 inhibitors plus lenvatinib group were more likely to be in ECOG grade above 1, develop ascites, and have an elevated level of ALT. The ORR was 16.0% in the PD-1/PD-L1 inhibitors plus lenvatinib group and 23.1% in the GC group (p = 0.777). The DCR was 52.0% in the lenvatinib group and 46.2% in the GC group (p = 0.676). The combination treatment of PD-1/PD-L1 inhibitors plus lenvatinib was associated with longer PFS than the GC group; however, it was not statistically significant (lenvatinib: 9.5 months, GC: 5.1 months, p = 0.454). The sixth-month and ninth-month OS rates were 82.0% and 76.9% in the lenvatinib group and 87.4% and 71.5% in the GC group. After adjusting for confounders, multivariate Cox regression analysis showed that ECOG grade above 1 was an independent risk factor for PFS (hazard ratio [HR] = 3.388, 95% CI = 1.312-8.746, p = 0.012) and OS (HR = 4.220, 95% CI = 1.131-15.742, p = 0.032). Conclusion: PD-1/PD-L1 inhibitors in combination with lenvatinib or GC all demonstrated significant efficacy and safety as first-line treatment in patients with advanced ICC. As for patients who refuse or are intolerant to chemotherapy, PD-1/PD-L1 plus lenvatinib would be recommended.

Anti-cancer treatment within two weeks serves as a risk factor for clinical outcomes among cancer patients with COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic has resulted in infections among patients with cancer. Our study aimed to investigate the potential adverse impact of anti-cancer treatments within 2 weeks of COVID-19 infection on clinical outcomes in patients with cancer. Methods: This retrospective cohort study analyzed 70 cancer patients with COVID-19 infection from the First Hospital of Jilin University in Changchun City, Jilin Province, between March and June 2022. Data on demographic characteristics, vaccination status, COVID-19 clinical classification, symptoms, complications, tumor-related characteristics, laboratory examinations and medical interventions were extracted from electronic medical record. The primary outcome of our study was Intensive Care Unit (ICU) admission. Logistic regression model was performed to investigate the association between anti-cancer treatments within 2 weeks after COVID-19 infection and the risk of ICU admission. Results: Of the 70 patients enrolled in this study, 37 received anti-cancer treatments within 2 weeks after COVID-19 infection. Patients receiving anti-cancer treatment were more likely to experience non-mild COVID-19, require oxygen therapy, develop acute respiratory distress syndrome (ARDS) and exhibit elevated inflammatory levels. The risk of ICU admission (P<0.001) and 30-day mortality after reverse transcriptase polymerase chain reaction (RT-PCR) negative conversion (P=0.007) was significantly higher in patients receiving anti-cancer treatments. In multivariate Logistic regression analysis, non-mild classification of COVID-19, anti-cancer treatments within 2 weeks and ECOG > 1were all independently associated with ICU admission after adjusting for confounder factors. The risk of ICU admission rose to 43.63 times (95% confidence interval=1.31-1452.94, P=0.035) in patients receiving anti-cancer treatments within 2 weeks. Conclusion: Anti-cancer treatments within 2 weeks of COVID-19 infection increase the risk of ICU admission and 30-day mortality after RT-PCR negative conversion in patients with cancer. It may be recommended to postpone cancer-related treatments for more than 2 weeks in cancer patients with COVID-19 infection.

The Characteristics and Treatment Outcomes of 71 Duodenal Brunner's Gland Adenomas with Endoscopic Submucosal Dissection.

INTRODUCTION: The aim of this study was to investigate outcomes of patients with duodenal Brunner's gland adenomas (BGAs) that were treated endoscopically. METHODS: We identified 71 consecutive patients treated at our center with endoscopic submucosal dissection (ESD) for their duodenal tumors diagnosed pathologically as BGAs over the period between January 1, 2011 and December 31, 2021. We retrospectively analyzed our experience and short- and long-term outcomes of ESD therapy on patients with BGAs. RESULTS: Among 71 BGA patients with an average age of 57 ± 11.7 years (range: 30-82), 48 (67.6%) were male and 23 (32.4%) were female. The accuracy of preoperative diagnosis with endoscopic ultrasonography was 44.0% (22/50). The H. pylori infection was found in 29 patients (29/71, 40.8%). The median size of BGAs was 1.5 cm (interquartile range [IQR] 0.8-2.7 cm). The most common location was the duodenum bulb (50/71, 64.8%). For the ESD procedure, the median operation time was 15.0 min (IQR 9.5-25.5 min). The en bloc and the complete resection rates were 97.2% and 92.3%, respectively. ESD-related mild acute obstructive pancreatitis was present in 2 patients (2/4, 50%) with BGAs located in the ampulla region. During the follow-up period, 1 patient with a positive peripheral margin experienced tumor recurrence 2 years after the initial ESD. There was no disease-related death for the cohort. CONCLUSION: ESD was an effective and safe therapeutic option for BGA patients with excellent outcomes. Long-term follow-up is needed.

Comparison between models for detecting hepatocellular carcinoma in patients with chronic liver diseases of various etiologies: ASAP score versus GALAD score.

BACKGROUND: Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma (HCC). Based on age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II) with/without AFP-L3, ASAP and GALAD models are potential diagnostic panels. The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases (CLDs). METHODS: A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chinese hospitals. The etiologies of CLDs included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Using area under the receiver operating characteristic curve (AUC) values, the diagnostic performances of ASAP and GALAD models were compared to detect HCC among patients with various etiologies of CLDs. RESULTS: Among 248 HCC patients and 722 CLD controls, the ASAP model demonstrated the highest AUC (0.886) to detect HCC at any stage, outperforming the GALAD model (0.853, P = 0.001), as well as any individual biomarker (0.687-0.799, all P < 0.001). In the subgroup analysis of various CLDs etiologies, the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology. In addition, the ASAP model performed better in detecting early-stage (BCLC stage 0/A) HCC versus the GALAD model. CONCLUSIONS: Despite using one less laboratory variable (AFP-L3), the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various etiologies of CLDs-related HCC.

Early Alpha-Fetoprotein Response Is Associated With Survival in Patients With HBV-Related Hepatocellular Carcinoma Receiving Lenvatinib.

BACKGROUND/PURPOSE: Lenvatinib is a first-line treatment for unresectable hepatocellular carcinoma (uHCC). We assessed the value of early alpha-fetoprotein (AFP) response for predicting clinical outcomes with lenvatinib treatment in patients with HBV-related uHCC and elevated AFP levels. METHODS: This retrospective analysis included patients with HBV-related uHCC and baseline AFP levels ≥20 ng/ml who received lenvatinib for >1 month between November 2018 and May 2021. Early AFP response was defined as a >20% decrease in AFP serum level from baseline after 4 weeks of lenvatinib treatment. Radiological response (Response Evaluation Criteria in Solid Tumors v1.1), progression-free survival, and overall survival were assessed in AFP responders and non-responders. RESULTS: Of the 46 patients analyzed, 30 (65.2%) were early AFP responders and 16 (34.8%) were non-responders. Compared to the non-responders, early AFP responders had a significantly higher objective response rate (34.5% vs 6.3%, p=0.0349), disease control rate (82.8% vs 50.0%; p=0.0203) and longer median progression-free survival (13.0 vs 7.0 months; HR, 0.464; 95% CI, 0.222-0.967; p=0.028). A subsequent multivariate analysis confirmed that early AFP response (HR, 0.387; 95% CI, 0.183-0.992; p=0.0154), Eastern Cooperative Oncology Group Performance Status of 0 (HR, 0.890; 95% CI, 0.811-0.976; p=0.0132) and Albumin-Bilirubin grade 1 (HR, 0.457; 95% CI, 0.269-0.963; p=0.0327) were independent prognostic factors for longer progression-free survival. CONCLUSION: AFP is an important prognostic factor and a predictive biomarker for survival benefit with lenvatinib treatment in patients with HBV-related uHCC.

Prognostic significance of sarcopenia in patients with hepatocellular carcinoma treated with lenvatinib: A retrospective analysis.

ABSTRACT: Our study investigated the correlation between sarcopenia and clinical outcomes in patients with hepatocellular carcinoma (HCC) treated with lenvatinib. We retrospectively evaluated 40 consecutive patients with unresectable HCC receiving lenvatinib between November 2018 and May 2020 at the First Hospital of Jilin University. Skeletal muscle mass was measured before treatment initiation. Prognostic significance was assessed with univariate and multivariate Cox proportional hazards models. Overall survival (OS) and progression-free survival (PFS) were evaluated for patients with and without sarcopenia. Sarcopenia was present in 23/40 patients (57.5%). After a median follow-up of 9.2 months, patients with sarcopenia had significantly worse OS and PFS compared with those without sarcopenia (OS: 8.4 months [m] vs 14.7 m, P = .02; PFS: 4.2 m vs 9.0 m, P = .04). Multivariate Cox proportional hazards models identified presence of sarcopenia as an independent risk factor for shorter OS (hazard ratio [HR], 0.257; 95% confidence interval [CI], 0.083-0.794; P = .02). In subgroup analysis, sarcopenia was associated with worse survival than non-sarcopenic patients, irrespective of age, Barcelona clinic liver cancer stage, or albumin-bilirubin grade. Our results show sarcopenia may be a predictor of poor prognosis in patients with HCC receiving lenvatinib. Management of sarcopenia is a vital factor for improving survival outcomes in patients with HCC.

Diverse and precision therapies open new horizons for patients with advanced pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a common cause of cancer-related death, and most patients are with advanced disease when diagnosed. At present, despite a variety of treatments have been developed for PDAC, few effective treatment options are available; on the other hand, PDAC shows significant resistance to chemoradiotherapy, targeted therapy, and immunotherapy due to its heterogeneous genetic profile, molecular signaling pathways, and complex tumor immune microenvironment. Nevertheless, over the past decades, there have been many new advances in the key theory and understanding of the intrinsic mechanisms and complexity of molecular biology and molecular immunology in pancreatic cancer, based on which more and more diverse new means and reasonable combination strategies for PDAC treatment have been developed and preliminary breakthroughs have been made. With the continuous exploration, from surgical local treatment to comprehensive medical management, the research-diagnosis-management system of pancreatic cancer is improving. This review focused on the variety of treatments for advanced PDAC, including traditional chemotherapy, targeted therapy, immunotherapy, microenvironment matrix regulation as well as the treatment targeting epigenetics, metabolism and cancer stem cells. We pointed out the current research bottlenecks and future exploration directions.

Association between early response of alpha-fetoprotein and treatment efficacy of systemic therapy for advanced hepatocellular carcinoma: A multicenter cohort study from China.

Background: Alpha-fetoprotein (AFP) is a well-identified biomarker in hepatocellular carcinoma (HCC). However, only limited AFP-related studies have evaluated its early response to systemic therapy. This study was performed with the aim of assessing the value of early AFP response in predicting overall survival (OS) and progression-free survival (PFS) in advanced HCC patients receiving systemic therapy. Methods: This cohort study included HCC patients with baseline AFP ≥ 200 ng/ml and no prior treatment history. A > 20% decline in the serum AFP level from baseline to the first follow-up (i.e., 4~6 weeks after treatment) was defined as an early AFP response. Patient demographic information, clinical characteristics, radiological response, and survival rates were compared between patients with early AFP response and patients without early AFP response. We further utilized multivariate Cox regression to seek characteristics related to OS and PFS. Results: Among 154 patients, 69 patients (44.8%) showed an early AFP response. The disease control rate (76.8 vs. 54.1%; P = 0.003) and objective response rate (38.4 vs. 11.8%; P = 0.001) were significantly higher in patients with an early AFP response. By performing multivariate analysis, early AFP response remained a prognostic factor for longer PFS (HR 0.546; 95% CI 0.371-0.804; P = 0.002) and longer OS (HR 0.529; 95% CI 0.335-0.834; P = 0.006). Conclusion: An early AFP response is correlated with longer overall survival and progression-free survival for advanced HCC patients receiving systemic therapy. Moreover, an early AFP response is an independent prognostic factor for longer OS and PFS.

Fatty acid transport protein-5 (FATP5) deficiency enhances hepatocellular carcinoma progression and metastasis by reprogramming cellular energy metabolism and regulating the AMPK-mTOR signaling pathway.

Aberrant lipid metabolism is an essential feature of hepatocellular carcinoma (HCC). Fatty acid transport protein-5 (FATP5) is highly expressed in the liver and is involved in the fatty acid transport pathway. However, the potential role of FATP5 in the pathogenesis of HCC remains largely unknown. Herein, we showed that FATP5 was downregulated in HCC tissues and even much lower in vascular tumor thrombi. Low expression of FATP5 was correlated with multiple aggressive and invasive clinicopathological characteristics and contributed to tumor metastasis and a poor prognosis in HCC patients. FATP5 inhibited the epithelial-mesenchymal transition (EMT) process and suppressed HCC cell migration and invasion, while silencing FATP5 had the opposite effects. Mechanistically, knockdown of FATP5 promoted cellular glycolytic flux and ATP production, thus suppressing AMP-activated protein kinase (AMPK) and activating its downstream signaling mammalian target of rapamycin (mTOR) to support HCC progression and metastasis. Activation of AMPK using metformin reversed the EMT program and impaired the metastatic capacity of FATP5-depleted HCC cells. Collectively, FATP5 served as a novel suppressor of HCC progression and metastasis partly by regulating the AMPK/mTOR pathway in HCC, and targeting the FATP5-AMPK axis may be a promising therapeutic strategy for personalized HCC treatment.

Development and validation of a novel online calculator for estimating survival benefit of adjuvant transcatheter arterial chemoembolization in patients undergoing surgery for hepatocellular carcinoma.

BACKGROUND AND AIMS: Although adjuvant transcatheter arterial chemoembolization (TACE) for resected hepatocellular carcinoma (HCC) may improve survival for some patients, identifying which patients can benefit remains challenging. The present study aimed to construct a survival prediction calculator for individualized estimating the net survival benefit of adjuvant TACE for patients with resected HCC. METHODS: From a multicenter database, consecutive patients undergoing curative resection for HCC were enrolled and divided into the developing and validation cohorts. Using the independent survival predictors in the developing cohort, two nomogram models were constructed for patients with and without adjuvant TACE, respectively, which predictive performance was validated internally and externally by measuring concordance index (C-index) and calibration. The difference between two estimates of the prediction models was the expected survival benefit of adjuvant TACE. RESULTS: A total of 2514 patients met the inclusion criteria for the study. The nomogram prediction models for patients with and without adjuvant TACE were, respectively, built by incorporating the same eight independent survival predictors, including portal hypertension, Child-Pugh score, alpha-fetoprotein level, tumor size and number, macrovascular and microvascular invasion, and resection margin. These two prediction models demonstrated good calibration and discrimination, with all the C-indexes of greater than 0.75 in the developing and validation cohorts. A browser-based calculator was generated for individualized estimating the net survival benefit of adjuvant TACE. CONCLUSIONS: Based on large-scale real-world data, an easy-to-use online calculator can be adopted as a decision aid to predict which patients with resected HCC can benefit from adjuvant TACE.

A novel online calculator based on noninvasive markers (ALBI and APRI) for predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma.

BACKGROUND AND AIM: Post-hepatectomy liver failure (PHLF) remains the primary cause of in-hospital mortality after hepatectomy. Identifying predictors of PHLF is important to improve surgical safety. We sought to identify the predictive accuracy of two noninvasive markers, albumin-bilirubin (ALBI) and aspartate aminotransferase to platelet count ratio index (APRI), to predict PHLF among patients with hepatocellular carcinoma (HCC), and to build up an online prediction calculator. METHODS: Patients who underwent resection for HCC between 2013 and 2016 at 6 Chinese hospitals were retrospectively analyzed. The independent predictors of PHLF were identified using univariate and multivariate analyses; derivative data were used to construct preoperative and postoperative nomogram models. Receiver operating characteristic (ROC) curves for the two predictive models, and ALBI, APRI, Child-Pugh, model for end-stage liver disease (MELD) scores were compared relative to predictive accuracy for PHLF. RESULTS: Among the 767 patients in the analytic cohort, 102 (13.3%) experienced PHLF. Multivariable logistic regression analysis identified high ALBI grade (>-2.6) and high APRI grade (>1.5) as independent risk factors associated with PHLF in both the preoperative and postoperative models. Two nomogram predictive models and corresponding web-based calculators were subsequently constructed. The areas under the ROC curves for the postoperative and preoperative models, APRI, ALBI, MELD and Child-Pugh scores in predicting PHLF were 0.844, 0.789, 0.626, 0.609, 0.569, and 0.560, respectively. CONCLUSIONS: ALBI and APRI demonstrated more accurate ability to predict PHLF than Child-Pugh and MELD. Two online calculators that combined ALBI and APRI were proposed as useful preoperative and postoperative tools for individually predicting the occurrence of PHLF among patients with HCC.

Lentivirus­mediated MDA7/IL24 expression inhibits the proliferation of hepatocellular carcinoma cells.

MDA7/IL24 is a member of the IL­10 gene family that functions as a cytokine. Notably, supra­physiological endogenous MDA7 levels have been indicated to suppress tumor growth and induce apoptosis in different cancer types. In the present study, MDA7 roles were investigated during the proliferation of hepatocellular carcinoma (HCC) cells and the molecular mechanisms underlying this process. A lentiviral vector expressing MDA7/IL24 (LV­MDA7/IL24) was constructed and used to infect HCC SMMC­7721 cells. The expression levels of MDA7/IL24 in these cells were determined using RT­qPCR and western blot analysis. The effects of LV­MDA7/IL24 on cell proliferation were analyzed using MTT and colony formation assays. Furthermore, the influence of LV­MDA7/IL24 on cell apoptosis and cell cycle distribution were detected using flow cytometry. The underlying molecular mechanisms were investigated using microarray and western blot analysis. The expression of MDA7/IL24 was confirmed to be significantly increased in the cells infected with LV­MDA7/IL24 compared with that the negative­control infected group. Lentivirus­mediated MDA7/IL24 expression was found to inhibit HCC cell proliferation and colony formation, and it also induced cell arrest and apoptosis. Microarray analysis and western blotting results indicated that multiple cancer­associated pathways and oncogenes are regulated by MDA7/IL24, including cell cycle regulatory and apoptosis activation pathway. In conclusion, it was determined that MDA7/IL24 inhibits the proliferation and reduces the tumorigenicity of HCC cells by regulating cell cycle progression and inducing apoptosis, indicating that it may be used as a potential prognostic and therapeutic target in HCC.

Prognostic value of serum AFP, AFP-L3, and GP73 in monitoring short-term treatment response and recurrence of hepatocellular carcinoma after radiofrequency ablation.

PURPOSE: Alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and Golgi protein 73 (GP73) levels have been widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether these tumor markers could be used to monitor short-term treatment response and recurrence of HCC in patients undergoing radiofrequency ablation (RFA). METHODS: Between July 2012 and July 2013, 53 consecutive patients with newly diagnosed HCC were prospectively enrolled in this study. Among these, 32 patients underwent RFA, after which they were followed up prospectively at the First Hospital of Jilin University in China. RESULTS: AFP, AFP-L3, and GP-73 values pre-RFA were not associated with tumor size, whereas AFP and GP-73 levels tended to be associated with tumor number, the presence of vascular invasion, deterioration of liver function, advanced-stage disease, and a poor performance status. GP-73 levels were dramatically elevated in the patients with hepatitis C-associated HCC. Neither pre-RFA nor 1-month post-RFA tumor marker values were associated with short-term outcome. The short-term recurrence rate of AFP-positive patients measured 1 month post-RFA was obviously higher than that of AFP-negative patients. CONCLUSIONS: AFP and GP-73 values were associated with clinical variables representing tumor growth and invasiveness, and the AFP value measured 1 month post-RFA was a strong predictor of short-term recurrence in patients with HCC.