Primary Liver Cancer Patients Research Articles

Survival and Cardiovascular Disease Mortality among Primary Liver Cancer Patients: A Population-based Study

BackgroundThe prognosis of primary liver cancer (PLC) was influenced by death due to non-cancer causes, particularly death related to cardiovascular disease (CVD). This study aimed to analyze mortality of non-cancer causes and identify the independent risk factors associated with CVD-related deaths in PLC patients. MethodsIn total, 112140 patients were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019). Independent risk factors for death from CVD in patients with PLC were identified by Cox proportional hazards model. ResultsThe median follow-up time of all PLC patients was 76 months (interquartile range (IQR): 36-129). The median overall survival (OS) was 12 months (IQR: 3-40). Patients with intrahepatic cholangiocarcinoma (ICC) had shorter OS than patients with hepatocellular carcinoma (HCC) (8 vs. 14 months; P < 0.001). A total of 87299 deaths were observed, among which 61477 (70.42% of all deaths) were from PLC, and 12727 (14.58% of all deaths) were from other cancers. Of all non-cancer deaths (9276, 10.63%), 2860(30.86%) were results of CVD. PLC patients had higher risks on CVD-related deaths, compared with general population (standard mortality ratio, SMR, 2.20; 95% confidence interval, CI, 2.12-2.28). Typically, the highest SMRs appeared in the first year following cancer diagnosis. The multivariable analysis revealed the characteristics listed as followed to be independently risk factors of CVD: age, male (hazard ratio, HR: 1.248, 95%CI: 1.147-1.359), black race (HR: 1.334, 95%CI: 1.195-1.490), year 2016-2019 of diagnosis (HR 0.758, 95%CI: 0.671-0.856), ICC (HR: 1.202, 95%CI: 1.086-1.330), without surgery (HR: 2.479, 95%CI: 2.266-2.711) and without chemotherapy (HR: 2.211, 95%CI: 2.033-2.403). ConclusionIt is essential to take cardiovascular health into consideration at the time of diagnosis for PLC patients as the risk of CVD mortality is significantly higher than that of general population.

Application of radioactive iodine-125 microparticles in hepatocellular carcinoma with portal vein embolus.

Radioactive iodine-125 (125I) microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors, especially hepatocellular carcinoma. Patients with hepatocellular carcinoma frequently experience portal vein embolism, which exacerbates the difficulty and complexity of treatment. 125I particles, used in local radiotherapy, can directly act on tumor tissue and reduce damage to surrounding healthy tissue. Through retrospective analysis, this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment. To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function. The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed. Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein (combination group), while 44 patients received treatment with transcatheter arterial chemoembolization alone (control group). The therapeutic effects on tumor lesions, primary liver cancer, and portal vein tumor embolisms were compared between the two groups. Changes in relevant laboratory indexes before and after treatment were evaluated. The t test was used to compare the measurement data between the two groups, and the χ 2 test was used to compare the counting data between groups. The tumor lesion response rate in the combination group (59.62% vs 38.64%) and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus (80.77% vs 59.09%) were significantly greater than those in the control group (χ 2 = 4.196, 5.421; P = 0.041, 0.020). At 8 wk after surgery, the serum alpha-fetoprotein, portal vein main diameter, and platelet of the combined group were significantly lower than those of the control group, and the serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin were significantly greater than those of the control group (t = 3.891, 3.291, 2.330, 3.729, 3.582, 4.126; P < 0.05). The serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery (P < 0.05), and the peripheral blood platelet, alpha-fetoprotein, and main portal vein diameter were significantly less than those of the same group before surgery (P < 0.05). In patients with primary liver cancer and a thrombus in the portal vein, transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone. However, during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.

CAIM: coverage-based analysis for identification of microbiome.

Accurate taxonomic profiling of microbial taxa in a metagenomic sample is vital to gain insights into microbial ecology. Recent advancements in sequencing technologies have contributed tremendously toward understanding these microbes at species resolution through a whole shotgun metagenomic approach. In this study, we developed a new bioinformatics tool, coverage-based analysis for identification of microbiome (CAIM), for accurate taxonomic classification and quantification within both long- and short-read metagenomic samples using an alignment-based method. CAIM depends on two different containment techniques to identify species in metagenomic samples using their genome coverage information to filter out false positives rather than the traditional approach of relative abundance. In addition, we propose a nucleotide-count-based abundance estimation, which yield lesser root mean square error than the traditional read-count approach. We evaluated the performance of CAIM on 28 metagenomic mock communities and 2 synthetic datasets by comparing it with other top-performing tools. CAIM maintained a consistently good performance across datasets in identifying microbial taxa and in estimating relative abundances than other tools. CAIM was then applied to a real dataset sequenced on both Nanopore (with and without amplification) and Illumina sequencing platforms and found high similarity of taxonomic profiles between the sequencing platforms. Lastly, CAIM was applied to fecal shotgun metagenomic datasets of 232 colorectal cancer patients and 229 controls obtained from 4 different countries and 44 primary liver cancer patients and 76 controls. The predictive performance of models using the genome-coverage cutoff was better than those using the relative-abundance cutoffs in discriminating colorectal cancer and primary liver cancer patients from healthy controls with a highly confident species markers.

Age-related nomogram revealed optimal therapeutic option for older patients with primary liver cancer: less is more.

Age bias in therapeutic decisions for older patients with cancer exists. There is a clear need to individualize such decisions. Based on the Surveillance, Epidemiology and End Results (SEER) database, 5081 primary liver cancer (PLC) patients between 2010 and 2014 were identified and divided into <64, 64-74 and >74 years group. Each group was randomly divided into training and internal validation cohorts, and patients who were diagnosed between 2015 and 2016 were included as an external validation. The nomogram model predicting overall survival (OS) was generated and evaluated based on the Cox regression for the influencing factors in prognosis. The K-M analysis was used to compare the difference among different treatments. KM analysis showed a significant difference for OS in three age groups (P < 0.001). At the same time, we also found different prognostic factors and their importance in different age groups. Therefore, we created three nomograms based on the results of Cox regression results for each age group. The c-index was 0.802, 0.766, 0.781 respectively. The calibration curve and ROC curve show that our model has a good predictive efficacy and the reliability was also confirmed in the internal and external validation set. An available online page was established to simplify and visualize our model (http://124.222.247.135/). The results of treatment analysis revealed that the optimal therapeutic option for PLCs was surgery alone. The optimal therapeutic option for older PLCs was surgery alone. The generated dynamic nomogram in this study may be a useful tool for personalized clinical decisions.

Factors Associated with Primary Liver Cancer Survival in a Southern Italian Setting in a Changing Epidemiological Scenario.

A retrospective observational study utilising cancer incidence data from a population-based registry investigated determinants affecting primary liver cancer survival in a southern Italian region with high hepatitis viral infection rates and obesity prevalence. Among 2687 patients diagnosed between 2006 and 2019 (65.3% male), a flexible hazard-based regression model revealed factors influencing 5-year survival rates. High deprivation levels [HR = 1.41 (95%CI = 1.15-1.76); p < 0.001], poor access to care [HR = 1.99 (95%IC = 1.70-2.35); p < 0.0001], age between 65 and 75 [HR = 1.48 (95%IC = 1.09-2.01); p < 0.05] or >75 [HR = 2.21 (95%CI = 1.62-3.01); p < 0.0001] and residing in non-urban areas [HR = 1.35 (95%CI = 1.08-1.69); p < 0.01] were associated with poorer survival estimates. While deprivation appeared to be a risk factor for primary liver cancer patients residing within the urban area, the geographic distance from specialised treatment centres emerged as a potential determinant of lower survival estimates for residents in the non-urban areas. After balancing the groups of easy and poor access to care using a propensity score approach, poor access to care and a lower socioeconomic status resulted in potentially having a negative impact on primary liver cancer survival, particularly among urban residents. We emphasise the need to interoperate cancer registries with other data sources and to deploy innovative digital solutions to improve cancer prevention.

CAIM: Coverage-based Analysis for Identification of Microbiome.

Accurate taxonomic profiling of microbial taxa in a metagenomic sample is vital to gain insights into microbial ecology. Recent advancements in sequencing technologies have contributed tremendously toward understanding these microbes at species resolution through a whole shotgun metagenomic (WMS) approach. In this study, we developed a new bioinformatics tool, CAIM, for accurate taxonomic classification and quantification within both long- and short-read metagenomic samples using an alignment-based method. CAIM depends on two different containment techniques to identify species in metagenomic samples using their genome coverage information to filter out false positives rather than the traditional approach of relative abundance. In addition, we propose a nucleotide-count based abundance estimation, which yield lesser root mean square error than the traditional read-count approach. We evaluated the performance of CAIM on 28 metagenomic mock communities and 2 synthetic datasets by comparing it with other top-performing tools. CAIM maintained a consitently good performance across datasets in identifying microbial taxa and in estimating relative abundances than other tools. CAIM was then applied to a real dataset sequenced on both Nanopore (with and without amplification) and Illumina sequencing platforms and found high similality of taxonomic profiles between the sequencing platforms. Lastly, CAIM was applied to fecal shotgun metagenomic datasets of 232 colorectal cancer patients and 229 controls obtained from 4 different countries and primary 44 liver cancer patients and 76 controls. The predictive performance of models using the genome-coverage cutoff was better than those using the relative-abundance cutoffs in discriminating colorectal cancer and primary liver cancer patients from healthy controls with a highly confident species markers.

Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together?

Primary liver cancer, represented mainly by hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA), is one of the most common and deadliest tumors worldwide. While surgical resection or liver transplantation are the best option in early disease stages, these tumors often present in advanced stages and systemic treatment is required to improve survival time. The emergence of immune checkpoint inhibitor (ICI) therapy has had a positive impact especially on the treatment of advanced cancers, thereby establishing immunotherapy as part of first-line treatment in HCC and CCA. Nevertheless, low response rates reflect on the usually cold or immunosuppressed tumor microenvironment of primary liver cancer. In this review, we aim to summarize mechanisms of resistance leading to tumor immune escape with a special focus on the composition of tumor microenvironment in both HCC and CCA, also reflecting on recent important developments in ICI combination therapy. Furthermore, we discuss how combination of ICIs with established primary liver cancer treatments (e.g. multikinase inhibitors and chemotherapy) as well as more complex combinations with state-of-the-art therapeutic concepts may reshape the tumor microenvironment, leading to higher response rates and long-lasting antitumor immunity for primary liver cancer patients.

Clinical Characteristics of Non-B and Non-C Biopsy-Proven Primary Liver Cancers in an HBV- Endemic Area: A Retrospective Study.

To explore the distribution of probable causes and clinical characteristics of non-B and non-C (NBNC) primary liver cancer (PLC) patients in the HBV-endemic region. A total of 86 individuals with biopsy-proven NBNC-PLC were enrolled. NBNC-PLC patients were defined as negative for both anti-HCV antibodies and five serum hepatitis B markers. Patients' characteristics were collected from medical records. Among them, most of the NBNC-PLC patients had intrahepatic cholangiocarcinoma (ICC) (81.4%), and 12.8% had hepatocellular carcinoma (HCC). The NBNC ICC group had more platelet count, GGT, and CA199 levels; approximately two-thirds were female, and it was more often present in patients with biliary inflammatory diseases, especially intrahepatic biliary lithiasis. The NBNC HCC group was older and had a higher proportion of dyslipidemia, obesity, cirrhosis, and AFP levels. Our data revealed that most of the NBNC PLC patients were ICC. Female patients with biliary inflammatory diseases and higher CA199 levels had an increased risk of ICC, and patients with metabolic risk factors and elevated AFP levels were more likely to develop HCC. Additional research should be performed to verify this finding.

Abstract 985: An effective cfDNA methylation-based assay in discriminating primary liver cancer from cirrhosis or chronic hepatitis virus infection: marker discovery, phase I pilot, and phase II clinical validation

Abstract Background: Early detection of primary liver cancer (PLC) in individuals with liver cirrhosis (LC) or chronic hepatitis virus infection (CHVI) improves survival. Timely, effective, and affordable tools with high sensitivity are urgently needed in clinical practice. Methods: Tissue and/or plasma samples from 159 healthy individuals and 89 PLC, LC, or CHVI patients were sequenced by a targeted methylation panel (~70,000 CpGs) to screen candidate methylated DNA markers (MDMs). In phase I, the performance of each selected MDM was validated in 175 plasma samples (PLC, n=101; LC/CHVI, n=74) by a CO-methylation aMplification rEal-Time PCR (COMET) assay. Logistic models were then trained and validated in phase II with 310 plasma samples (hepatocellular carcinoma [HCC], n=212; combined hepatocellular-cholangiocarcinoma [cHCC-CC], n=12; LC/CHVI, n=106; training vs. validation, 2:1). Results: The methylation levels of eleven selected MDMs with top performance showed a significant increase in PLC compared with LC/CHVI in both tissue and plasma samples (P&amp;lt;0.05). In phase I, eight of the above eleven MDMs with an area under the curve (AUC) over 0.80 to differentiate PLC and LC/CHVI were chosen for further investigation. In phase II, the MDM-based logistic model achieved sensitivity of 87.2% (95% confidence interval [CI], 80.8%-92.4%) and 88.0% (78.4%-94.4%), at respective specificity of 97.1% (90.1%-99.7%) and 100% (90.3%-100%) in the training and validation sets. In the validation set, sensitivity in patients with BCLC stage 0, diameter&amp;lt;3 cm, AFP-negative, and PIVKA-II-negative was 90.0% (55.5%-99.7%), 88.9% (65.3%-98.6%), 80.6% (64.0%-91.8%), and 81.3% (54.4%-96.0%), respectively. The classifier achieved similar sensitivity in patients with or without HBV/HCV infection (88.2% vs 90.0%). Additionally, our model detected 19 of 24 (79.3%, 57.8%-92.9%) intrahepatic cholangiocarcinoma. Combining AFP and PIVKA-II, the model achieved higher sensitivity of 93.3% (85.1%-97.8%) and specificity of 100.0% (90.3%-100%). Conclusion: In conclusion, the present study demonstrated the feasibility of using an easy-to-implement cfDNA methylation assay (COMET) to discriminate early-stage liver cancer from other liver diseases, with superior accuracy over AFP and PIVKA-II. Notably, the combination of the COMET, AFP, and PIVKA-II increased the overall sensitivity, indicating the potential benefit of integrating these approaches in clinical practices. Moving forward, further investigation is needed to validate these findings in larger prospective clinical studies. Keywords: primary liver cancer, early detection, liver cirrhosis, chronic hepatitis virus infection, methylated plasma DNA marker. Citation Format: Yang Tian, Yanan Wang, Mingxin Pan, Lei Zhang, Qiancheng You, Bingsi Li, Shangli Cai, Feng Shen, Guoyue Lv. An effective cfDNA methylation-based assay in discriminating primary liver cancer from cirrhosis or chronic hepatitis virus infection: marker discovery, phase I pilot, and phase II clinical validation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 985.

Engaging stimulatory immune checkpoint interactions in the tumour immune microenvironment of primary liver cancers - how to push the gas after having released the brake.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the first and second most common primary liver cancer (PLC). For decades, systemic therapies consisting of tyrosine kinase inhibitors (TKIs) or chemotherapy have formed the cornerstone of treating advanced-stage HCC and CCA, respectively. More recently, immunotherapy using immune checkpoint inhibition (ICI) has shown anti-tumour reactivity in some patients. The combination regimen of anti-PD-L1 and anti-VEGF antibodies has been approved as new first-line treatment of advanced-stage HCC. Furthermore, gemcibatine plus cisplatin (GEMCIS) with an anti-PD-L1 antibody is awaiting global approval for the treatment of advanced-stage CCA. As effective anti-tumour reactivity using ICI is achieved in a minor subset of both HCC and CCA patients only, alternative immune strategies to sensitise the tumour microenvironment of PLC are waited for. Here we discuss immune checkpoint stimulation (ICS) as additional tool to enhance anti-tumour reactivity. Up-to-date information on the clinical application of ICS in onco-immunology is provided. This review provides a rationale of the application of next-generation ICS either alone or in combination regimen to potentially enhance anti-tumour reactivity in PLC patients.

An Evaluation Analysis for Computed Tomography Image Quality of Primary Liver Cancer Lesions Based on Deep Learning Image Reconstruction.

Abdominal multi-slice helical computed tomography (CT) and contrast-enhanced scanning have been widely recognized clinically. The impact of the deep learning image reconstruction (DLIR) on the quality of dynamic contrast-enhanced CT imaging of primary liver cancer lesions was evaluated through comparison with the filtered back projection (FBP) and the new generation of adaptive statistical iterative reconstruction-V (ASIR-V). We evaluated the image noise of the lesion, fine structures inside the lesion, and diagnostic confidence in 48 liver cancer subjects. The CT values of the solid part of the lesion and the adjacent normal liver tissue and the systolic and diastolic blood pressure (SD) values of the right paravertebral muscle were measured. The muscle SD value was considered as the background noise of the image, and the signal noise ratio (SNR) and contrast signal-to-noise ratio (CNR) of the lesion and normal liver parenchyma were calculated. High consistency in the evaluation of image noise (Kappa = 0.717). The Kappa values for margin/pseudocapsule, fine structure within the lesion, and diagnostic confidence were 0.463, 0.527, and 0.625, respectively. Besides, the differences in SD, SNR and CNR data of reconstructed lesion images among the six groups were statistically significant. The contrast-enhanced CT image noise of DLIR-H in the portal venous phase is much lower than that of ASIR-V and FBP in primary liver cancer patients. In terms of the lesion structure display, the new reconstruction algorithm DLIR is superior.

Development and validation of a machine learning-based early prediction model for massive intraoperative bleeding in patients with primary hepatic malignancies.

Surgical resection remains the primary treatment for hepatic malignancies, and intraoperative bleeding is associated with a significantly increased risk of death. Therefore, accurate prediction of intraoperative bleeding risk in patients with hepatic malignancies is essential to preventing bleeding in advance and providing safer and more effective treatment. To develop a predictive model for intraoperative bleeding in primary hepatic malignancy patients for improving surgical planning and outcomes. The retrospective analysis enrolled patients diagnosed with primary hepatic malignancies who underwent surgery at the Hepatobiliary Surgery Department of the Fourth Hospital of Hebei Medical University between 2010 and 2020. Logistic regression analysis was performed to identify potential risk factors for intraoperative bleeding. A prediction model was developed using Python programming language, and its accuracy was evaluated using receiver operating characteristic (ROC) curve analysis. Among 406 primary liver cancer patients, 16.0% (65/406) suffered massive intraoperative bleeding. Logistic regression analysis identified four variables as associated with intraoperative bleeding in these patients: ascites [odds ratio (OR): 22.839; P < 0.05], history of alcohol consumption (OR: 2.950; P < 0.015), TNM staging (OR: 2.441; P < 0.001), and albumin-bilirubin score (OR: 2.361; P < 0.001). These variables were used to construct the prediction model. The 406 patients were randomly assigned to a training set (70%) and a prediction set (30%). The area under the ROC curve values for the model's ability to predict intraoperative bleeding were 0.844 in the training set and 0.80 in the prediction set. The developed and validated model predicts significant intraoperative blood loss in primary hepatic malignancies using four preoperative clinical factors by considering four preoperative clinical factors: ascites, history of alcohol consumption, TNM staging, and albumin-bilirubin score. Consequently, this model holds promise for enhancing individualised surgical planning.

Symptom clusters and nutritional status in primary liver cancer patients receiving transcatheter arterial chemoembolization.

Introduction: symptom clusters (SCs) are highly prevalent among patients diagnosed with primary liver cancer. Malnutrition poses a heightened risk for a more pronounced total symptom cluster score. Objective: this study aimed to identify SCs and assess the nutritional status of patients undergoing transcatheter arterial chemoembolization (TACE). Furthermore, it aimed to investigate the association between nutritional status and symptom clusters. Methods: primary liver cancer patients who were scheduled to receive TACE were recruited. Symptoms data were collected using the MD Anderson Symptom Inventory (MDASI-C) and the Symptom Module specific to Primary Cancer (TSM-PLC). Nutritional assessment relied on the Nutritional Risk Screening-2002 (NRS-2002) and blood biochemistry. The SCs were extracted using exploratory factor analysis, while the relationship between SCs and nutritional status was evaluated using Spearman correlation analysis. Results: the study included 226 patients, four distinct symptom clusters emerged: emotional-psychological symptom cluster, upper gastrointestinal symptom cluster, post-embolization-related symptom cluster, and liver function impairment symptom cluster. 68.14 % of patients were found to be at high risk of malnutrition. Our study revealed significant differences in Scs scores between patients at risk of malnutrition and those without such risk (p < 0.050). Notably, we observed a positive correlation between NRS-2002 scores and the scores of all symptom clusters (r = 0.205 to 0.419, p < 0.001), while a negative correlation was observed between prealbumin levels and the scores of all symptom clusters (r = -0.183 to -0.454, p < 0.001). Conclusion: the study highlights the high risk of malnutrition among liver cancer patients receiving TACE and the positive correlation between high malnutrition risk and Scs scores.

Intraperitoneal PD-1 monoclonal antibody for the treatment of advanced primary liver cancer with malignant ascites: a single-arm, single-center, phase Ib trial

Advanced primary liver cancer patients with malignant ascites have a poor prognosis and lack effective treatment plans. This phase Ib study aims to explore the safety and clinical efficacy of intraperitoneal anti-programmed cell death protein 1 (PD-1) antibody in these patients. Patients received sintilimab 100 mg intraperitoneally plus best supportive care on days 1, 8, and 15 in three cycles of 4 weeks. The course was repeated every 28 days until intolerable toxicity had developed or disease progression. The primary endpoint was safety, while the secondary endpoints were objective response rate (ORR), ascites control rate (ACR), and overall survival (OS). From February 2021 through November 2022, a total of 21 patients (14 hepatocellular carcinoma and 7 cholangiocarcinoma) were enrolled to receive intraperitoneal sintilimab. Twelve patients had adverse events (AEs). The most common grade 3 AEs were fatigue, rash, and abdominal pain. No grade ≥4 AEs occurred in any patients. ORR was only evaluated in 13 patients, including partial response in 4, stable disease in 7, and progressive disease in 2. A reduction in the median maximum diameter of the tumor after treatment was observed; however, there was no statistical significance among patients. The objective remission rate of ascites was 43.75%, and the median OS for all 21 patients was 17.6 weeks. This exploratory study represents the first trial to demonstrate the safety and clinical efficacy of intraperitoneal anti-PD-1 antibody administration. No unexpected safety concerns were identified. A large, multicenter, prospective study is needed to confirm the promising clinical efficacy.

Clinical characteristics and outcomes of patients with primary liver cancer and immune checkpoint inhibitor-associated adrenal insufficiency: A retrospective cohort study

BackgroundAdrenal insufficiency (AI) is a rare, but potentially serious adverse event associated with immune checkpoint inhibitors (ICIs). This study aims to examine the incidence, clinical features and the clinical correlation between occurrence of AI and efficacy in primary liver cancer (PLC) patients treated with ICIs; and to evaluate the significance of the continuation of ICIs treatment in PLC patients who developed AI. MethodsBetween January 2020 and March 2022, 47 PLC patients with ICIs-associated AI (AI cohort) were screened from Zhongshan Hospital, Fudan university, a general hospital in China. Between December 2019 and August 2021, 419 PLC patients who were treated with ICIs were reviewed to identify those without immune- associated adverse events (irAEs) (control cohort). Clinical features and outcomes of the PLC patients from the two cohorts were compared. ResultsTotally, 47 PLC patients with AI (AI cohort) and 63 PLC patients without irAEs (control cohort) were included. The incidence of grades 3–4 of AI and all irAEs were 40.4 % and 48.9 %, respectively. The median three-year survival was significantly longer in the AI cohort than that in the control cohort (26.3 months (95 % CI: 18.9––33.5) vs.16.1 months (95 % CI:10.4––21.7); p = 0.021). Multivariable cox proportional hazards regression model showed that the development of AI remained significantly associated with improved overall survival (HR = 0.561; p = 0.033) in the adjusted regression analysis. ConclusionThe current study demonstrated that PLC patients undergoing ICIs therapy and developing AI after ICIs treatment had favorable survival outcomes compared to those without irAEs.

Impact of perioperative SARS-CoV-2 Omicron infection on postoperative complications in liver cancer hepatectomy: A single-center matched study

ObjectivesTo explore the effects of perioperative SARS-CoV-2 Omicron infection on postoperative complications in patients with liver cancer. MethodsA propensity-matched study was conducted, which included patients with primary liver cancer who underwent hepatectomy from September 01, 2022 to January 20, 2023. Patients who infected SARS-CoV-2 Omicron during the perioperative period (7 days before to 30 days after surgery) were matched 1:1 with noninfected patients. The primary outcomes, which were COVID-19-related major complications and liver resection-specific complications, were analyzed using multivariate logistic regression. ResultsA total of 243 patients were included, with 63 cases of perioperative infections, of which 62 were postoperative infections. The overall 30-day postoperative mortality rate was 1.6% (4/243). Compared to noninfected patients, those with perioperative infections showed no significant difference in the occurrence of adverse postoperative outcomes. However, they had a higher rate of 30-day readmission after surgery (11.1% vs 0%, P = 0.013). Perioperative SARS-CoV-2 infection was not associated with “major cardiorespiratory complications” or “liver resection-specific complications”, but age, pre-existing comorbidities, and tumor type were related to these outcomes. ConclusionPerioperative SARS-CoV-2 Omicron infection did not increase the incidence of postoperative complications in patients with liver cancer. However, those patients had a higher rate of 30-day readmission after surgery.

The Mediating Effect of Resilience on the Relationship Between Symptom Burden and Anxiety/Depression Among Chinese Patients with Primary Liver Cancer After Liver Resection.

Primary liver cancer (PLC) is a common cancer of the digestive system. Patients with PLC often experience a heavy symptom burden and along with a significant levels of anxiety and depression after liver resection. High levels of symptom burden can lead to increased anxiety and depression, whereas high levels of resilience can alleviate these conditions. Therefore, we aimed to explore the relationships among symptom burden, resilience, and anxiety/depression in Chinese patients with PLC after liver resection and to determine whether resilience mediates the relationship between symptom burden and anxiety/depression. A total of 223 postoperative PLC patients were recruited from two public hospitals in Anhui Province, China. All participants completed the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Connor-Davidson Resilience Scale (CD-RISC). The mediating effect of resilience was estimated using the bootstrap method via IBM SPSS AMOS 26.0. The mean HADS score was 12.37 ± 6.03 points in postoperative PLC patients. Among these patients, 78 (34.98%) had anxiety, and 64 (28.70%) had depression, as indicated by a subscale score ≥ 8. Pearson correlation analysis revealed that anxiety/depression was positively associated with symptom burden (p < 0.05) and negatively associated with resilience (p < 0.05). Furthermore, resilience partially mediated the relationship between symptom burden and anxiety/depression (β = 0.04; 95% confidence interval: 0.01-0.08). The levels of anxiety and depression in postoperative PLC patients should be decreased. Resilience partially mediated the relationship between symptom burden and anxiety/depression, but the indirect effect was much weaker than the direct effect of symptom burden on anxiety/depression. Consequently, rather than focusing primarily on resilience interventions, joint symptom-psychological interventions focusing on symptoms should be considered for patients with PLC after hepatectomy to reduce the levels of anxiety/depression.

Genome-wide profiling of transcription factor activity in primary liver cancer using single-cell ATAC sequencing

Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open chromatin profiles reflect the compositional diversity of liver cancer, identifying both malignant and microenvironment component cells. TF motif enrichment levels of 31 TFs strongly discriminate HCC from iCCA tumors. These TFs are members of the nuclear/retinoid receptor, POU, or ETS motif families. POU factors are associated with prognostic features in iCCA. Overall, nuclear receptors, ETS and POU TF motif families delineate transcription regulation between HCC and iCCA tumors, which may be relevant to development and selection of PLC subtype-specific therapeutics.

Prediction model of ocular metastasis from primary liver cancer: Machine learning-based development and interpretation study.

Ocular metastasis (OM) is a rare metastatic site of primary liver cancer (PLC). The purpose of this study was to establish a clinical predictive model of OM in PLC patients based on machine learning (ML). We retrospectively collected the clinical data of 1540 PLC patients and divided it into a training set and an internal test set in a 7:3 proportion. PLC patients were divided into OM and non-ocular metastasis (NOM) groups, and univariate logistic regression analysis was performed between the two groups. The variables with univariate logistic analysis p < 0.05 were selected for the ML model. We constructed six ML models, which were internally verified by 10-fold cross-validation. The prediction performance of each ML model was evaluated by receiver operating characteristic curves (ROCs). We also constructed a web calculator based on the optimal performance ML model to personalize the risk probability for OM. Six variables were selected for the ML model. The extreme gradient boost (XGB) ML model achieved the optimal differential diagnosis ability, with an area under the curve (AUC) = 0.993, accuracy = 0.992, sensitivity = 0.998, and specificity = 0.984. Based on these results, an online web calculator was constructed by using the XGB ML model to help clinicians diagnose and treat the risk probability of OM in PLC patients. Finally, the Shapley additive explanations (SHAP) library was used to obtain the six most important risk factors for OM in PLC patients: CA125, ALP, AFP, TG, CA199, and CEA. We used the XGB model to establish a risk prediction model of OM in PLC patients. The predictive model can help identify PLC patients with a high risk of OM, provide early and personalized diagnosis and treatment, reduce the poor prognosis of OM patients, and improve the quality of life of PLC patients.

Effect of bevacizumab administered prior to transarterial chemoembolization on the therapeutic effects of lenvatinib given post-TACE in primary liver cancer patients.

To determine the therapeutic effects of lenvatinib combined with bevacizumab following transarterial chemoembolization (TACE) in patients with primary liver cancer. 100 patients with primary liver cancer were recruited in the period from January 2020 to January 2021 and allocated with randomization into a control group (n=50) and a test (bevacizumab) group (n=50). The patients in the control group received lenvatinib for 4weeks following TACE, whereas those in the test group received bevacizumab for 6weeks prior to TACE and subsequent therapy with lenvatinib for 4weeks. The serum concentration of interferon-γ (INF-γ), interleukin-10 (IL-10), soluble interleukin-2 receptor (sIL-2R), interleukin-12 (IL-12), superoxide dismutase (SOD), total antioxidant capacity (TAOC), glutathione (GSH), malondialdehyde (MDA), total bilirubin (TBil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), carbohydrate antigen 242 (CA242), CA724, α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were determined in both groups at the commencement of treatment in January 2020 and 12 months later and compared with the observed therapeutic effects. The concentrations of CA242, CEA, CA724, and AFP in the bevacizumab group were lower than those in the control group (p<0.05). The concentration of IL-12 and INF-γ in the bevacizumab group were higher, but the levels of IL-10 and sIL-2R lower than in the control group (p<0.05). In the bevacizumab group, the level of MDA was lower, whereas the levels of TAOC, SOD, and GSH were higher than those in the control group (p<0.05). The bevacizumab group also had lower levels of ALT, TBil, and AST and a higher level of ALP than control group (p<0.05). The response rate based on tumor status (size, progression) in the bevacizumab group was higher than in the control group (p<0.05). The therapeutic effects of lenvatinib following TACE in primary liver cancer are significantly greater when combined with bevacizumab administered for 6weeks prior to TACE.