Pan-immune inflammation value as a prognostic biomarker for cancer patients treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) represent a paradigm shift in the development of cancer therapy. However, the improved efficacy of ICIs remains to be further investigated. We conducted a systematic review and meta-analysis to evaluate the pan-immunoinflammatory value (PIV) and PILE score used to predict response to ICI therapy. Methods: We searched selected databases for studies on pan-immune inflammation values and their association with outcomes of treatment with immune checkpoint inhibitors. We used hazard ratios (HRS) and 95% confidence intervals (CI) to summarize survival outcomes. All data analyses were performed using STATA 15.0. Results: 7 studies comprising 982 patients were included in the meta-analysis. The pooled results showed that higher PIV was significantly associated with shorter overall survival OS (HR = 1.895, 95%CI: 1.548-2.318) and progression-free survival (PFS) (HR = 1.582, 95%CI: 1.324-1.890). Subgroup analyses also confirmed the reliability of the results. Conclusions: High PIV and PILE metrics are associated with lower survival in cancer patients receiving ICIs.

Leveraging an immune cell signature to improve the survival and immunotherapy response of lung adenocarcinoma.

Background: Immune cells play a critical role in the prognosis of cancer. However, the function of different immune cell types in lung adenocarcinoma (LUAD) and the development of a prognostic signature based on immune cell types have not been comprehensively investigated. Methods: We collected and included a total of 2499 LUAD patients and performed calculations to determine the penetration level of 24 immune cells. This examination was conducted using the macro-gene-based approach provided by ImmuCellAI. We performed a meta-analysis using Lasso-Cox analysis to establish the immune cell pair score (ICPS). We conducted a survival analysis to measure differences in survival across ICPS-risk groups. Wilcox test was used to measure the difference in expression level. Spearman correlation analysis was used for the relevance assessment. Results: We collected a total of 24 immune cell types to construct cell pairs. Utilizing 17 immune cell pairs, we constructed and validated the ICPS, which plays a critical role in stratifying survival and dynamically monitoring the effectiveness of immunotherapy. Additionally, we identified several candidate drugs that target ICPS. Conclusions: The ICPS shows promise as a valuable tool for identifying suitable candidates for immunotherapy among patients. Our comprehensive assessment of immune cell interactions in LUAD contributes to a deeper understanding of infiltration patterns and functions, thereby guiding the development of more efficacious immunotherapy strategies.

Characteristics of lactate metabolism phenotype in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer, and more effective prognostic markers are needed. Lactic acid has been proved to be an important metabolite involved in cancer development, metastasis, and the tumor microenvironment, affecting the prognosis of patients. The role of lactic acid metabolism regulators (LAMRs) in HCC is still unclear. In this study, we analyzed the status of LAMRs, a gene list containing lactate from Molecular Signatures database, in HCC and consensus clustering was performed based on these LAMRs. Cluster B showed higher infiltrations of immune cells, higher TME scores, and a poorer prognosis. We further constructed a risk score based on DEGs using LASSO and COX regression analysis between two clusters, which could effectively predict the prognosis of TCGA-LIHC patients. The GSE14520 cohort confirmed the result. We also examined the correlation of risk scores with clinical characteristics, genetic mutations, drug sensitivity, immune checkpoint inhibitors(ICIs), and immunotherapy. In conclusion, our findings will facilitate a further understanding of the role of partial lactate metabolism related genes in HCC and suggest a new risk score to predict prognosis.

Construction of a Nomogram to Predict Overall Survival in Patients with Early-Onset Hepatocellular Carcinoma: A Retrospective Cohort Study.

Hepatocellular carcinoma (HCC) is a widespread and impactful cancer which has pertinent implications worldwide. Although most cases of HCC are typically diagnosed in individuals aged ≥60 years, there has been a notable rise in the occurrence of HCC among younger patients. However, there is a scarcity of precise prognostic models available for predicting outcomes in these younger patients. A retrospective analysis was conducted to investigate early-onset hepatocellular carcinoma (EO-LIHC) using data from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2018. The analysis included 1392 patients from the SEER database and our hospital. Among them, 1287 patients from the SEER database were assigned to the training cohort (n = 899) and validation cohort 1 (n = 388), while 105 patients from our hospital were assigned to validation cohort 2. A Cox regression analysis showed that age, sex, AFP, grade, stage, tumor size, surgery, and chemotherapy were independent risk factors. The nomogram developed in this study demonstrated its discriminatory ability to predict the 1-, 3-, and 5-year overall survival (OS) rates in EO-LIHC patients based on individual characteristics. Additionally, a web-based OS prediction model specifically tailored for EO-LIHC patients was created and validated. Overall, these advancements contribute to improved decision-making and personalized care for individuals with EO-LIHC.

Uridine Inhibits Hepatocellular Carcinoma Cell Development by Inducing Ferroptosis.

Uridine is a key metabolite used as a substrate for the production of DNA, RNA, and glucose, and it is mainly synthesized in the liver. Currently, it is not known whether uridine levels are altered in the tumor microenvironment of patients with hepatocellular carcinoma (HCC) and whether uridine can be a target for tumor therapy. In this study, the detection of genes associated with de novo uridine synthesis, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) (n = 115), and dihydroorotate dehydrogenase (DHODH) (n = 115) in HCC tissues through tissue microarrays revealed that the expression of CAD and DHODH was higher in tumor compared with paraneoplastic tissues. Next, we collected tumor tissues from surgically resected HCC patients and the corresponding adjacent non-tumor tissues (n = 46) for LC-MS/MS assays. The results showed that the median and interquartile ranges of uridine content in non-tumor and tumor tissues were 640.36 (504.45-807.43) and 484.22 (311.91-626.73) nmol/g, respectively. These results suggest that uridine metabolism is disturbed in HCC patients. To further investigate whether uridine can be used as a tumor-therapeutic target, a series of high concentrations of uridine were incubated with HCC cells in vitro and in vivo. It was observed that uridine dose-dependently inhibited the proliferation, invasion, and migration of HCC cells by activating the ferroptosis pathway. Overall, these results reveal for the first time the range of uridine content in human HCC tissues and suggest that uridine may be a new target for HCC therapy.

Blood biomarkers predict outcomes in patients with hepatocellular carcinoma treated with immune checkpoint Inhibitors: A pooled analysis of 44 retrospective sudies.

OBJECTIVE: We conducted the first meta-analysis to identify the predictive significance of baseline blood biomarkers (such as neutrophil to lymphocyte ratio (NLR), early alpha-fetoprotein (AFP) response, albumin-bilirubin (ALBI), AFP, platelet to lymphocyte ratio (PLR), C-reactive protein (CRP), protein induced by vitamin K absence II (PIVKA-II), and lymphocyte to monocyte ratio (LMR)) in hepatocellular carcinoma (HCC) patients treated with immune checkpoint inhibitors (ICIs). METHODS: Eligible articles were retrieved using PubMed, the Cochrane Library, EMBASE, and Google Scholar by November 24, 2022. Clinical outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and hyperprogressive disease (HPD). RESULTS: A total of 44 articles with 5322 patients were included in this meta-analysis. The pooled results demonstrated that patients with high NLR levels had significantly poorer OS (HR: 1.951, P < 0.001) and PFS (HR: 1.632, P < 0.001), lower ORR (OR: 0.484, P < 0.001) and DCR (OR: 0.494, P = 0.027), and higher HPD (OR: 8.190, P < 0.001). The patients with high AFP levels had shorter OS (HR: 1.689, P < 0.001) and PFS (HR: 1.380, P < 0.001), and lower DCR (OR: 0.440, P < 0.001) than those with low AFP levels, however, there was no difference in ORR (OR: 0.963, P = 0.933). We also found that early AFP response was correlated with better OS (HR: 0.422, P < 0.001) and PFS (HR: 0.385, P < 0.001), higher ORR (OR: 7.297, P < 0.001) and DCR (OR: 13.360, P < 0.001) compared to non-responders. Besides, a high ALBI grade was significantly related to shorter OS (HR: 2.440, P = 0.009) and PFS (HR: 1.373, P = 0.022), lower ORR (OR: 0.618, P = 0.032) and DCR (OR: 0.672, P = 0.049) than those with an ALBI grade 1. CONCLUSION: The NLR, early AFP response, and ALBI were useful predictors of outcomes in HCC patients treated with ICIs.

GNB1 promotes hepatocellular carcinoma progression by targeting BAG2 to activate P38/MAPK signaling.

G-proteins are intracellular partners of G-protein-coupled receptors. As a member of the G-protein family, GNB1 has been shown to play a pro-cancer role in lung cancer and breast cancer. However, the biological function and detailed mechanisms of GNB1 in hepatocellular carcinoma progression are unclear. In this study, we investigated the effects of GNB1 and its possible mechanism of action in hepatocellular carcinoma (HCC). The clinical significance of GNB1 was evaluated in a large cohort of HCC patients, showing that GNB1 was overexpressed in HCC compared to adjacent normal liver tissues, and increased GNB1 expression was associated with poor prognosis. We also demonstrated that GNB1 enhances cell proliferation, colony formation, and cell migration and invasion in vitro and promotes the epithelial-to-mesenchymal transition process in HCC cells. Tumor xenograft model assay confirmed the oncogenic role of GNB1 in tumorigenicity in nude mice. Activation of P38 signaling was found in the GNB1 overexpressed HCC cells. Further intervention of P38 confirmed it as an important signaling pathway for the oncogenic role of GNB1 in HCC. Moreover, co-immunoprecipitation followed by liquid chromatograph-mass spectrometry identified that GNB1 exerted oncogenic functions via the interaction of BAG2 and activated P38 signaling pathway. Together, our results reveal that GNB1 plays a pivotal oncogenic role in HCC by promoting the P38 pathway via cooperating with BAG2. GNB1 may serve as a prognostic biomarker for patients with HCC.

USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt/mTOR signaling.

Thioredoxin reductase 1 (TXNRD1) is one of the major redox regulators in mammalian cells, which has been reported to be involved in tumorigenesis. However, its roles and regulatory mechanism underlying the progression of HCC remains poorly understood. In this study, we demonstrated that TXNRD1 was significantly upregulated in HCC tumor tissues and correlated with poor survival in HCC patients. Functional studies indicated TXNRD1 knockdown substantially suppressed HCC cell proliferation and metastasis both in vitro and in vivo, and its overexpression showed opposite effects. Mechanistically, TXNRD1 attenuated the interaction between Trx1 and PTEN which resulting in acceleration of PTEN degradation, thereby activated Akt/mTOR signaling and its target genes which conferred to elevated HCC cell mobility and metastasis. Moreover, USF2 was identified as a transcriptional suppressor of TXNRD1, which directly interacted with two E-box sites in TXNRD1 promoter. USF2 functioned as tumor suppressor through the downstream repression of TXNRD1. Further clinical data revealed negative co-expression correlations between USF2 and TXNRD1. In conclusion, our findings reveal that USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt/mTOR signaling.

Effects of PPIs use on clinical outcomes of urothelial cancer patients receiving immune checkpoint inhibitor therapy.

Objective: Immune checkpoint inhibitors (ICIs) have recently demonstrated promising performance in improving the prognosis of urological cancer patients. The goal of this meta-analysis was to determine the impact of PPI use on the clinical outcomes of urological cancer patients receiving ICI therapy. Methods: Before 6 May 2022, the eligible literature was searched using PubMed, EMBASE, Cochrane Library, and Google Scholar. The clinical outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: A total of six articles met the inclusion criteria, and of the 1980 patients with advanced or metastatic urothelial cancers (UC) included. The meta-analysis displayed that PPI use could increase the risk of progression by 50.7% (HR: 1.507, 95% CI: 1.327-1.711, p < 0.001) and death by 58.7% (HR: 1.587, 95% CI: 1.367-1.842, p < 0.001), and reduce the ORR (OR: 0.503, 95% CI: 0.360-0.703, p < 0.001) in UC patients receiving ICIs. No significant heterogeneity and publication bias existed. Sensitivity analysis proved that the results were stable and reliable. Conclusion: The meta-analysis indicated that concomitant PPI use was significantly associated with low clinical benefit in UC patients.

Mycobiota and C-Type Lectin Receptors in Cancers: Know thy Neighbors.

Numerous studies have demonstrated the importance of gut bacteria in the development of malignancy, while relatively little research has been done on gut mycobiota. As a part of the gut microbiome, the percentage of gut mycobiota is negligible compared to gut bacteria. However, the effect of gut fungi on human health and disease is significant. This review systematically summarizes the research progress on mycobiota, especially gut fungi, in patients with head and neck cancer (HNC), esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), pancreatic cancer, melanoma, breast cancer, and lung carcinoma-induced cachexia. Moreover, we also describe, for the first time in detail, the role of the fungal recognition receptors, C-type lectin receptors (CLRs) (Dectin-1, Dectin-2, Dectin-3, and Mincle) and their downstream effector caspase recruitment domain-containing protein 9 (CARD9), in tumors to provide a reference for further research on intestinal fungi in the diagnosis and treatment of malignant tumors.

DDR1 promotes hepatocellular carcinoma metastasis through recruiting PSD4 to ARF6.

Discoidin domain receptor 1 (DDR1) is a member of the receptor tyrosine kinase family, and its ligand is collagen. Previous studies demonstrated that DDR1 is highly expressed in many tumors. However, its role in hepatocellular carcinoma (HCC) remains obscure. In this study, we found that DDR1 was upregulated in HCC tissues, and the expression of DDR1 in TNM stage II-IV was higher than that in TNM stage I in HCC tissues, and high DDR1 expression was associated with poor prognosis. Gene expression analysis showed that DDR1 target genes were functionally involved in HCC metastasis. DDR1 positively regulated the migration and invasion of HCC cells and promoted lung metastasis. Human Phospho-Kinase Array showed that DDR1 activated ERK/MAPK signaling pathway. Mechanically, DDR1 interacted with ARF6 and activated ARF6 through recruiting PSD4. The kinase activity of DDR1 was required for ARF6 activation and its role in metastasis. High expression of PSD4 was associated with poor prognosis in HCC. In summary, our findings indicate that DDR1 promotes HCC metastasis through collagen induced DDR1 signaling mediated PSD4/ARF6 signaling, suggesting that DDR1 and ARF6 may serve as novel prognostic biomarkers and therapeutic targets for metastatic HCC.

SHC4 promotes tumor proliferation and metastasis by activating STAT3 signaling in hepatocellular carcinoma.

BACKGROUND: The Src homology and collagen 4 (SHC4) is an important intracellular adaptor protein that has been shown to play a pro-cancer role in melanoma and glioma. However, the biological function and detailed mechanisms of SHC4 in hepatocellular carcinoma progression are unclear. This study aimed to evaluate the potential prognostic and treatment value of SHC4 in patients with HCC. METHODS: The expression status of SHC4 in HCC tissues were investigated by immunohistochemistry and western blotting. Clinical significance of SHC4 was evaluated in a large cohort of HCC patients. The effects of SHC4 repression or overexpression on migration, invasion, and tumor growth were detected by colony formation assay, wound healing, transwell assays, and xenograft assay. Cell cycle and EMT-related proteins were detected by western blotting and immunofluorescence. In addition, the molecular regulation between SHC4 and STAT3 signaling in HCC were discovered by western blotting, immunofluorescence and xenograft assay. RESULTS: SHC4 was overexpressed in HCC compared to adjacent normal liver tissues and increased SHC4 expression was associated with high AFP level, incomplete tumor encapsulation, poor tumor differentiation and poor prognosis. SHC4 was shown to enhance cell proliferation, colony formation, cells migration and invasion in vitro, and promotes cell cycle progression and EMT process in HCC cells. Tumor xenograft model assay confirmed the oncogenic role of SHC4 in tumorigenicity in nude mice. Moreover, activation of STAT3 signaling was found in the SHC4 overexpressed HCC cells and HCC tissues. Further intervention of STAT3 confirmed STAT3 as an important signaling pathway for the oncogenic role of SHC4 in HCC. CONCLUSIONS: Together, our results reveal that SHC4 activates STAT3 signaling to promote HCC progression, which may provide new clinical ideas for the treatment of HCC.

[Corrigendum] High PLK4 expression promotes tumor progression and induces epithelial­mesenchymal transition by regulating the Wnt/ß­catenin signaling pathway in colorectal cancer.

Subsequently to the publication of the above article, and a Corrigendum that has already been published with the intention of showing the corrected version of Fig. 5 (DOI: 10.3892/ijo.2021.5213; published online on May 5, 2021), the authors have realized that only the data for Fig. 5C needed to be corrected with respect to the original figure published in the article, and there was no need to have presented replacement data for Fig. 5E in the previous Corrigendum. The further revised version of Fig. 5, featuring the corrected data for Fig. 5C, is shown on the next page. All the authors agree to this Corrigendum. Note that the revisions made to this figure do not adversely affect the results reported in the paper, or the conclusions stated therein. The authors regret that Fig. 5 was not presented in its finally revised form in the previous Corrigendum, and offer their apologies to the Editor and to the readers of the Journal. [the original article was published in International Journal of Oncology 54: 479­490, 2019; DOI: 10.3892/ijo.2018.4659].

[Corrigendum] High PLK4 expression promotes tumor progression and induces epithelial­mesenchymal transition by regulating the Wnt/ß­catenin signaling pathway in colorectal cancer.

Subsequently to the publication of the above article, the author realized that Fig. 5 on p. 486 contained some errors on account of the figure having been compiled incorrectly; essentially, the published version of the figure contained incorrect images for the panels presented in Fig. 5C and E. The authors were able to re­examine their original data, and identify the data that was intended to have been shown for these figure parts. The corrected version of Fig. 5 is shown on the next page, featuring the correct data for Fig. 5C and E, including new bar charts showing the quantification of these data. The authors confirm that these data continue to support the main conclusions presented in their paper, and are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum. They also apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 54: 479­490, 2019; DOI: 10.3892/ijo.2018.4659].

EXO1 Plays a Carcinogenic Role in Hepatocellular Carcinoma and is related to the regulation of FOXP3.

Exonuclease 1 (EXO1), a member of the RAD2 nuclease family, was first described as possessing 5' to 3' nuclease activity and 5' structure-specific endonuclease activity. Here, we show that EXO1 is significantly upregulated in HCC tumor tissues and that high EXO1 expression is significantly correlated with liver cirrhosis. We further demonstrate that EXO1 knockdown decreases proliferation and colony forming abilities of HCC cells in vitro and tumorigenicity in vivo, as well as decreases migration and invasive capabilities of HCC cells. Alternatively, EXO1 overexpression significantly increases the proliferation, colony forming ability, and migration and invasive capabilities of HCC cells in vitro. Additionally, we truncated a region upstream of the transcription start site (TSS) of EXO1 and used the region with the strongest transcriptional activity to predict that the transcription factor FOXP3 can bind to the EXO1 promoter. Bioinformatics analysis found that FOXP3 was positively correlated with EXO1 and luciferase reporter assays and RT-PCR confirmed that FOXP3 could enhance the transcriptional activity of EXO1. CCK-8 assays showed that depletion of FOXP3 further reduces cell proliferation ability after knocking down of EXO1 in vitro. Taken together, our findings indicate that EXO1 acts as an oncogene in HCC and its expression level is related to FOXP3 activity.

PTPRε Acts as a Metastatic Promoter in Hepatocellular Carcinoma by Facilitating Recruitment of SMAD3 to TGF-ß Receptor 1.

BACKGROUND AND AIMS: Transforming growth factor beta (TGF-ß) suppresses early stages of tumorigenesis, but contributes to the migration and metastasis of cancer cells. However, the role of TGF-ß signaling in invasive prometastatic hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated the roles of canonical TGF-ß/mothers against decapentaplegic homolog 3 (SMAD3) signaling and identified downstream effectors on HCC migration and metastasis. APPROACH AND RESULTS: By using in vitro trans-well migration and invasion assays and in vivo metastasis models, we demonstrated that SMAD3 and protein tyrosine phosphatase receptor epsilon (PTPRε) promote migration, invasion, and metastasis of HCC cells in vitro and in vivo. Further mechanistic studies revealed that, following TGF-ß stimulation, SMAD3 binds directly to PTPRε promoters to activate its expression. PTPRε interacts with TGFBR1/SMAD3 and facilitates recruitment of SMAD3 to TGFBR1, resulting in a sustained SMAD3 activation status. The tyrosine phosphatase activity of PTPRε is important for binding with TGFBR1, recruitment and activation of SMAD3, and its prometastatic role in vitro. A positive correlation between pSMAD3/SMAD3 and PTPRε expression was determined in HCC samples, and high expression of SMAD3 or PTPRε was associated with poor prognosis of patients with HCC. CONCLUSIONS: PTPRε positive feedback regulates TGF-ß/SMAD3 signaling to promote HCC metastasis.

miR-144-5p and miR-451a Inhibit the Growth of Cholangiocarcinoma Cells Through Decreasing the Expression of ST8SIA4.

Accumulating evidences indicate that non-coding RNAs play crucial roles in the progression of an extensive range of carcinomas. This study aimed to investigate the action mechanism of miR-144-5p and miR-451a in cholangiocarcinoma. We found that miR-144-5p and miR-451a were significantly decreased in cholangiocarcinoma patient samples compared to the adjacent normal bile duct samples. The downregulation of these two miRNAs was correlated with a more advanced disease state of cholangiocarcinoma patients. Overexpression of miR-144-5p and miR-451a suppressed the proliferation, invasion and migration of cholangiocarcinoma cells in vitro and inhibited xenograft tumor growth. Knockdown of these two miRNAs had the opposite effects. miR-144-5p and miR-451a regulated the expression of ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4 (ST8SIA4), and presented a correlation with ST8SIA4 in patient samples. Overexpression of ST8SIA4 promoted the proliferation, invasion and migration of cholangiocarcinoma cells, and the changes were reversed by upregulating the expression of miR-144-5p and miR-451a. Our findings indicated that miR-144-5p and miR-451a displayed a tumor suppressor role through decreasing the expression of ST8SIA4 in cholangiocarcinoma.

TGF-ß1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p.

Increasing evidence has suggested that liver cancer arises partially from transformed hepatic progenitor cells (HPCs). However, the detailed mechanisms underlying HPC transformation are poorly understood. In this study, we provide evidence linking the coexistence of hepatitis B virus X protein (HBx) and transforming growth factor beta 1 (TGF-ß1) with miR-199a-3p in the malignant transformation of HPCs. The examination of liver cancer specimens demonstrated that HBx and TGF-ß1 expression was positively correlated with epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 90 (CD90). Importantly, EpCAM and CD90 expression was much higher in the specimens expressing both high HBx and high TGF-ß1 than in those with high HBx or high TGF-ß1 and the double-low-expression group. HBx and TGF-ß1 double-high expression was significantly associated with poor prognosis in primary liver cancer. We also found that HBx and TGF-ß1 induced the transformation of HPCs into hepatic cancer stem cells and promoted epithelial-mesenchymal transformation, which was further enhanced by concomitant HBx and TGF-ß1 exposure. Moreover, activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway was involved in the malignant transformation of HPCs. miR-199a-3p was identified as a significantly upregulated microRNA in HPCs upon HBx and TGF-ß1 exposure, which were shown to promote miR-199a-3p expression via c-Jun-mediated activation. Finally, we found that miR-199a-3p was responsible for the malignant transformation of HPCs. In conclusion, our results provide evidence that TGF-ß1 cooperates with HBx to promote the malignant transformation of HPCs through a JNK/c-Jun/miR-199a-3p-dependent pathway. This may open new avenues for therapeutic interventions targeting the malignant transformation of HPCs in treating liver cancer.

Resection might be a meaningful choice for hepatocellular carcinoma with portal vein thrombosis: A systematic review and meta-analysis.

BACKGROUND: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the presence of portal vein tumor thrombosis (PVTT) is considered to indicate an advanced stage of hepatocellular carcinoma (HCC) with nearly no cure. Hepatic resection and transarterial chemoembolization (TACE) have recently been recommended for treatment of HCC with PVTT. METHODS: We conducted a systematic review to compare the overall survival between patients with HCC and PVTT undergoing hepatectomy, TACE or conservative treatment including sorafenib chemotherapy. The PubMed, Web of Science, and Cochrane Library databases were searched. All relevant studies were considered. Hazard ratios with 95% confidence intervals were calculated for comparison of the cumulative overall survival. Ten retrospective studies met the inclusion criteria and were included in the review. RESULTS: Overall survival was not higher in the hepatectomy group than TACE group. But survival rate was higher in hepatectomy group than conservative group. The subgroup analysis demonstrated that hepatectomy was superior in patients without PVTT in the main trunk than in patients with main portal vein invasion. In patients without main PVTT, hepatectomy has showed more benefit than TACE. However, there has been no significant difference between the hepatectomy and TACE groups among patients with main PVTT. CONCLUSION: For patients with resectable HCC and PVTT, hepatectomy might be more effective in patients without PVTT in the main trunk than TACE or conservative treatment.

Histologic severity of liver cirrhosis: A key factor affecting surgical outcomes of hepatocellular carcinoma in patients with portal hypertension.

BACKGROUND: Portal hypertension (PH), which is closely associated with the severity of liver cirrhosis, has been suggested as a contraindication of liver resection for hepatocellular carcinoma (HCC). We aimed to explore the role of a potential player, histologic severity of liver cirrhosis, in affecting surgical outcomes of the patients with both HCC and PH. METHODS: A total of 374 HCC patients with PH underwent resection for HCC were retrospectively reviewed. By using the Laennec staging system, the patients were divided into two groups: the mild-moderate cirrhosis (MMC) group and the severe cirrhosis (SC) group. Propensity score matching (PSM) was conducted at a 1:1 ratio between the two groups, and 89 patients were matched for each group. Short-term and long-term outcomes were compared between two groups before and after PSM. RESULTS: The overall morbidity and 30-days mortality were significantly higher in the SC group than the MCC group (52.9% vs. 30.1%, P < 0.001 and 6.9% vs. 0.7%, P = 0.002). Severe cirrhosis was identified as an independent predictor of postoperative liver-related complications. Patients with MMC exhibited better 5-year overall survival (39.9% vs. 16.9%, P < 0.001) and disease-free survival (10.5% vs. 4.4%, P < 0.001) than those with SC. Multivariate analysis indicated that severe cirrhosis was significantly associated with lower disease-free survival and overall survival. These results were further confirmed in the PSM cohort. CONCLUSIONS: Histologic severity of liver cirrhosis determines the surgical outcomes of patients with both HCC and PH, and PH is not an absolute contraindication of liver resection.