Resection For Hepatocellular Carcinoma Research Articles

Prognostic effect of DNA methylation of BTG2 gene in Chinese hepatocellular carcinoma

BackgroundThis study aims to develop a prognostic model for overall survival based on potential methylation sites within B-cell translocation gene 2 (BTG2) in Chinese patients with hepatocellular carcinoma (HCC). MethodsThis is a retrospective study. The beta values of nine CpG sites and RSEM normalized count values of BTG2 gene were extracted from the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) (TCGA-LIHC) dataset, with the beta value representing the methylation level by indicating the ratio of the intensity of the methylated bead type to the combined locus intensity. Pyrosequencing was performed to determine the range of methylation values surrounding cg01798157 site in BTG2 gene. A weighted linear model was developed to predict the overall survival (OS). ResultsThe beta value of cg01798157 was significantly negatively associated with the mRNA expression of BTG2 in the TCGA-LIHC dataset (Spearman's rho = −0.5306, P = 2.27 × 10−27). The methylation level of cg01798157 was significantly associated with OS in the cohort of 51 Chinese HCC patients (Hazard ratio = 0.597, 95% CI: 0.434–0.820, P = 0.001). Multivariate Cox regression analysis identified methylation level of cg01798157, cirrhosis, and microvascular invasion as independent prognostic factors. The prognostic efficiency of death risk score was superior to that of cirrhosis or microvascular invasion alone. ConclusionsThe methylation level of cg01798157 in BTG2 may be an epigenetic biomarker in Chinese patients with resectable HCC.

Noninvasive Visualization of Tumor Blood Vessels within Hepatocellular Carcinoma by Application of Superb Microvascular Imaging to Contrast-Enhanced Ultrasonography.

The combination or sequential use of systemic therapies, such as lenvatinib and locoregional therapies, can improve the curability rate of hepatocellular carcinoma. This is based on the notion that lenvatinib remodels abnormal tumor vessels into normal vessels, potentially enhancing the efficacy of locoregional therapies. In this case report, we achieved noninvasive visualization of tumor blood vessels by applying superb microvascular imaging (SMI) to contrast-enhanced ultrasonography (CEUS). A man in his 80s with a borderline resectable hepatocellular carcinoma received preoperative therapy using lenvatinib. The patient achieved a complete response after lenvatinib therapy, underwent hepatectomy, and maintained a cancer-free status. CEUS and SMI revealed a decrease in tumor blood vessels at 1 week after lenvatinib administration and a decrease in tumor perfusion at 2 weeks. Although CEUS alone is adequate for noninvasive real-time evaluation of tumor perfusion, it is not sufficient to achieve accurate assessments of tumor blood vessels. We performed a noninvasive time-course evaluation of vascular normalization after lenvatinib administration by applying SMI. The evaluation of vascular normalization with lenvatinib therapy using CEUS and SMI can support the decision to proceed to conversion therapies.

Abstract 7364: Comprehensive multi-omics analysis for resectable hepatocellular carcinoma uncovers biomarkers to predict microvascular invasion

Abstract Introduction: Microvascular invasion (MVI) is a well-known prognostic factor in predicting cancer relapse after curative resection of resectable hepatocellular carcinoma (HCC).Therefore, there is a clear unmet need for a precision strategy based on cancer-specific multi-omics features to predict the MVI feature at the initial diagnosis of HCC. Methods: Using gene expression profiling for resected human HCC (Discovery cohort, n=240), we identified the transcriptomic signature predicting the MVI feature. Comprehensive analyses were performed using the dataset from the cancer dependency map (DepMap) project, including cancer-specific molecular characterization with multi-omics data, and drug sensitivity with compound screening, and integrative in-silico prediction methods to uncover MVI. The transcriptomic signature predicting the MVI feature were validated in independent translational cohorts (TCGA-LIHC; n=373, KOREA; n=188, TOKYO; n=183, MODENA; n=78, ZHONGSHAN; n=159). Results: The MVI signature with 1028 genes was identified from robust statistical testing from the discovery cohort, and robust validation for the prediction performance of the MVI signature showed significant accuracy in the validation cohort (AUC=0.865, p<0.01). Multi-omics analysis revealed aggressive tumor biology associated with the MVI signature and specified biomarkers. Conclusions: Integrative multi-omics profiling for resectable HCC uncovers biomarkers to predict MVI. A novel combination of biomarkers performs in sorting out the tumor with aggressive tumor biology. A precision strategy to discover resectable tumors beneficial from surgical resection can be established from consecutive clinical trials based on this translational study. Citation Format: Incheon Kang, Woo Young Kwon, Sung Hwan Lee. Comprehensive multi-omics analysis for resectable hepatocellular carcinoma uncovers biomarkers to predict microvascular invasion [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 7364.

Feasibility and safety of robotic liver resection for huge (≥10cm) hepatocellular carcinoma in a single centre: A propensity score-matched single-surgeon study.

The applicability of robot-assisted resection for huge hepatocellular carcinoma (HCC) of ≥10cm remains contentious with limited available data. This retrospective analysis involved 337 patients who underwent robotic liver resection for HCC by a single surgeon. Propensity score matching (PSM) was employed to compare perioperative indicators between patients with regular and huge HCC. The regular HCC group exhibited a shorter median operative duration than the huge HCC group. The IWATE criteria revealed higher scores in the huge HCC group than in the regular HCC group. No significant differences were observed between the two groups in Pringle time, drainage tube removal, duration of hospital stays, blood loss volume, blood product transfusion, margin status, conversion rate to open surgery, bile leakage, in-hospital mortality, and reoperation rate. Robotic liver resection is feasible for huge HCC, with effective perioperative risk management potentially improving outcomes for subsequent minimally invasive surgeries.

Effect of Sarcopenia on the Prognosis of Clinical Outcomes in Patients With Hepatocellular Carcinoma After Hepatic Resection.

We aimed to study the prognostic impact of sarcopenia on overall survival (OS), disease-free survival (DFS), and postoperative outcomes among patients with Hepatocellular carcinoma (HCC) who underwent curative hepatic resection. Data were collected retrospectively from patients with HCC underwent curative hepatic resection and preoperative abdominal computed tomography (CT) at our institution between January 2010 and December 2020. Sarcopenia was evaluated by the skeletal muscle mass at the inferior direction of the third-lumbar-vertebra (L3) cross-sectional area based on preoperative CT imaging using software analysis. Cutoff values for skeletal muscle index (SMI) were 43.75 and 41.10cm2/m2 for males and females. The patients were classified into sarcopenia and nonsarcopenia groups. The association between preoperative sarcopenia and clinicopathological factors, impact of sarcopenia on survival, and postoperative outcomes were analyzed. Sarcopenia was present in 39 of 83 (47.0%) patients who underwent curative hepatic resection for HCC and was significantly correlated with lower SMI, lower serum albumin levels, higher intraoperative blood loss, higher postoperative complications, and longer hospital stay. The 5-year OS was significantly lower in sarcopenic patients than in nonsarcopenic patients (58.2% vs 83.6%; P = .006), but the 5-year DFS was not significantly different between the 2 groups. Multivariate analysis revealed that sarcopenia was a significant risk factor for poor OS (HR 4.728; 95% CI, 1.458-15.329; P = .010). Sarcopenia was identified as a prognostic factor for poor OS after hepatic resection, and major postoperative complications were more frequent in sarcopenia. Early sarcopenia detection and management may improve OS and clinical outcomes in postoperative HCC.

Abstract 6982: The roles of NDRG1 in HCC progression and its clinical significance

Abstract Background: Hepatocellular carcinoma (HCC) is prevalent globally and the third leading cause of cancer-related mortality. N-myc downstream regulated 1 (NDRG1) was found to be tumor promoting in some cancers while suppressive in others. The expression of NDRG1 is induced by stress signals such as DNA damage and hypoxia. In HCC, it has been found to promote proliferation and metastasis. Contradictory results, however, were also suggested on the functions of NDRG1. Methods: Our own HCC cohort and multiple publicly available databases were examined for NDRG1 expression and clinicopathologic correlation. NDRG1 expression under hypoxic conditions was investigated. Various functional assays were performed for NDRG1-knockdown HCC cell lines Huh-7 and PLC/PRF/5. Results: With RT-qPCR analysis on our 102 pairs of patients’ HCC tumor and corresponding non-tumorous liver samples, we found NDRG1 to be upregulated in HCC tumors. Similarly, RNA-sequencing analysis comparing 41 pairs of samples confirmed NDRG1 enrichment in HCC tumors. The upregulation was significantly and positively correlated with the absence of tumor encapsulation and cellular differentiation. These were further supported by TCGA and ICGC databases, in which upregulation of NDRG1 was significantly correlated with poor HCC patient overall survival. Interestingly, in the TCGA database, only 17% of the HCC cases were inferred to have copy number amplification of NDRG1 gene while NDRG1 mutations were rarely found. As hypoxia is a major tumor microenvironmental factor in HCC, we investigated NDRG1’s expression level in HCC cells under hypoxic or normoxic conditions and found significant increase in NDRG1 expression under hypoxic environment. We further found that NDRG1 knockdown inhibited cell proliferation, self-renewal ability, and migration. RT-qPCR analysis found lower LGR5 and SOX2 expression upon NDRG1 knockdown. This is in line with the positive correlation between NDRG1 and various cancer stemness-related gene expression, including LGR5, CD24, MYC, SOX2, and NOTCH1, in TCGA database. Lastly, in the resected HCC tumors on which spatial transcriptomics using Visium 10X and single-cell RNA-sequencing using Chromium 10X were performed, we found NDRG1 enrichment in both tumors cells and cancer associated fibroblasts (CAFs). Conclusion: NDRG1 was found to be significantly upregulated in HCC cells in our in-house cohort and publicly available databases. NDRG1 consistently promotes various oncogenic features of HCC cells, including proliferation, self-renewal ability, and migration. In addition, NDRG1 was found to be enriched in both the HCC cells and CAFs. Citation Format: Jingyi Lu, Lu Tian, Yu-Man Tsui, Xia Wong, Qingyang Zhang, Daniel Wai-Hung Ho, Irene Oi-Lin Ng. The roles of NDRG1 in HCC progression and its clinical significance [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 6982.

Abstract 2586: Heterogeneous enhancement pattern of Gd-EOB-DTPA-enhanced MRI predicts vessels encapsulating tumor clusters (VETC)-positive hepatocellular carcinoma

Abstract Background: Vessels encapsulating tumor clusters (VETC) pattern is known as a distinct hepatocellular carcinoma (HCC) vascularization that correlates with angiogenic status, lower lymphocytic infiltration, and higher recurrence rates. Despite the molecular and clinical significance of VETC+ HCC, its characteristics on radiological imaging have not been clearly elucidated. We aimed to characterize VETC+ HCC on gadolinium-ethoxybenzyl-diethylene-triamine-pentaacetic acid-enhanced MR imaging (EOB-MRI) and provide pathological evidence. Method: We studied 204 surgically resected HCCs with preoperative EOB-MRI. VETC+ HCC was defined as ≥1% VETC occupied area evaluated by CD34 immunostaining. The visual pattern classification of the arterial and hepatobiliary phase images is shown in Table 1. To investigate the relationships between imaging patterns and VETC+ HCC, we evaluated immunohistochemical expression of h-caldesmon+ arterial vessel density (AVD) and OATP1B3. Result: In the arterial phase, VETC+ HCCs showed heterogeneous hypervascular pattern and homogeneous hypovascular pattern. Accordingly, VETC+ HCCs had lower AVD than VETC− HCCs, as well, VETC regions had lower AVD than other regions within the same tumor. In the hepatobiliary phase, VETC+ HCCs were observed more frequently in heterogeneous hyperintense pattern (36%) compared to homogeneous hyperintense pattern (5%). Hyperintensity in the hepatobiliary phase was correlated with high expression of OATP1B3. Among tumors with high OATP1B3 expression, VETC regions showed decreased expression of OATP1B3. Conclusion: VETC+ HCC showed reduced vascularity and heterogeneous hyperintensity in the hepatobiliary phase of EOB-MRI. These findings were explained by locally reduced AVD and downregulated OATP1B3 expression in the VETC regions. The potency to predict VETC+ HCCs by radiological findings could improve HCC treatment strategy. Relationship between enhancement patterns and VETC+ HCC in arterial and hepatobiliary phase Arterial phase Hypervascular/Homogeneous Hypervascular/Heterogeneous Hypovascular/Homogeneous Hypovascular/Heterogeneous Rim-like Number of tumors 68 103 8 15 11 VETC+ HCC (%) 6 (9%) 32 (31%) 3 (37%) 3 (20%) 1 (9%) Hepatobiliary phase Hyperintense/Homogeneous Hyperintense/Heterogeneous Hypointense/Homogeneous Hypointense/Heterogeneous Number of tumors 21 39 115 31 VETC+ HCC (%) 1 (5%) 14 (36%) 23 (20%) 8 (26%) Citation Format: Kosuke Matsuda, Akihisa Ueno, Junya Tsuzaki, Yutaka Kurebayashi, Ken Yamazaki, Masashi Tamura, Masahiro Jinzaki, Yuta Abe, Yasushi Hasegawa, Minoru Kitago, Michiie Sakamoto. Heterogeneous enhancement pattern of Gd-EOB-DTPA-enhanced MRI predicts vessels encapsulating tumor clusters (VETC)-positive hepatocellular carcinoma [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 2586.

Predicting One-year Recurrence of HCC based on Gadoxetic Acid-enhanced MRI by Machine Learning Models.

Accurate prediction of recurrence risk after resction in patients with Hepatocellular Carcinoma (HCC) may help to individualize therapy strategies. This study aimed to develop machine learning models based on preoperative clinical factors and multiparameter Magnetic Resonance Imaging (MRI) characteristics to predict the 1-year recurrence after HCC resection. Eighty-two patients with single HCC who underwent surgery were retrospectively analyzed. All patients underwent preoperative gadoxetic acidenhanced MRI examination. Preoperative clinical factors and MRI characteristics were collected for feature selection. Least Absolute Shrinkage and Selection Operator (LASSO) was applied to select the optimal features for predicting postoperative 1-year recurrence of HCC. Four machine learning algorithms, Multilayer Perception (MLP), random forest, support vector machine, and k-nearest neighbor, were used to construct the predictive models based on the selected features. A Receiver Operating Characteristic (ROC) curve was used to assess the performance of each model. Among the enrolled patients, 32 patients experienced recurrences within one year, while 50 did not. Tumor size, peritumoral hypointensity, decreasing ratio of liver parenchyma T1 value (ΔT1), and α-fetoprotein (AFP) levels were selected by using LASSO to develop the machine learning models. The area under the curve (AUC) of each model exceeded 0.72. Among the models, the MLP model showed the best performance with an AUC, accuracy, sensitivity, and specificity of 0.813, 0.742, 0.570, and 0.853, respectively. Machine learning models can accurately predict postoperative 1-year recurrence in patients with HCC, which may help to provide individualized treatment.

Imaging and prognostic characterization of fat-containing hepatocellular carcinoma subtypes.

Steatohepatitic hepatocellular carcinoma (SH-HCC) is characterized by intratumoral fat with > 50% inflammatory changes. However, intratumoral fat (with or without inflammation) can also be found in not-otherwise specified HCC (NOS-HCC). We compared the imaging features and outcome of resected HCC containing fat on pathology including SH-HCC (> 50% steatohepatitic component), NOS-HCC with < 50% steatohepatitic component (SH-NOS-HCC), and fatty NOS-HCC (no steatohepatitic component). From September 2012 to June 2021, 94 patients underwent hepatic resection for fat-containing HCC on pathology. Imaging features and categories were assessed using LIRADS v2018. Fat quantification was performed on chemical-shift MRI. Recurrence-free and overall survival were estimated. Twenty-one patients (26%) had nonalcoholic steatohepatitis (NASH). The median intra-tumoral fat fraction was 8%, with differences between SH-HCC and SH-NOS-HCC (9.5% vs. 5% p = 0.03). There was no difference in major LI-RADS features between all groups; most tumors were classified as LR-4/5. A mosaic architecture on MRI was rare (7%) in SH-HCC, a fat in mass on CT was more frequently depicted (48%) in SH-HCC. A combination of NASH with no mosaic architecture on MRI or NASH with fat in mass on CT yielded excellent specificity for diagnosing SH-HCC (97.6% and 97.7%, respectively). The median recurrence-free and overall survival were 58 and 87months, with no difference between groups (p = 0.18 and p = 0.69). In patients with NASH, an SH-HCC may be suspected in L4/LR-5 observations with no mosaic architecture at MRI or with fat in mass on CT. Oncological outcomes appear similar between fat-containing HCC subtypes.

Reflections and perspectives on adjuvant treatment in the setting of resected hepatocellular carcinoma

Hepatectomy is a curative procedure in selected patients affected by hepatocellular carcinoma (HCC). However, recurrence rates are as high as 70% five years after resection, and having a valid postoperative systemic regimen would represent a significant improvement in the care of HCC patients. While burgeoning evidence is emerging around the use of immunotherapy in the setting of resected HCC, little is yet known to allow the widespread use of immunotherapy after surgery. Here, we pointed out some reflections and perspectives on adjuvant strategies for patients with resected HCC and discussed potential benefits and drawbacks.

Prognostic benefit of preoperative transarterial chemoembolization in upfront resectable large hepatocellular carcinoma: a multicentric propensity score based analysis of European high-volume centers

BackgroundHepatocellular carcinoma (HCC) have a dismal prognosis and any effective neoadjuvant treatment has been validated to date. We aimed to investigate the role of neoadjuvant transarterial chemoembolization (TACE) in upfront resectable HCC larger than 5 cm. MethodsThis is a multicentric retrospective study comparing outcomes of large HCC undergoing TACE followed by surgery or liver resection alone before and after propensity-score matching (PSM). ResultsA total of 384 patients were included of whom 60 (15.6%) received TACE. This group did not differ from upfront resected cases neither in terms of disease-free survival (p = 0.246) nor in overall survival (p = 0.276). After PSM, TACE still did not influence long-term outcomes (p = 0.935 and p = 0.172, for DFS and OS respectively). In subgroup analysis, TACE improved OS only in HCC ≥10 cm (p = 0.045), with a borderline significance after portal vein embolization/ligation (p = 0.087) and in single HCC (p = 0.052). ConclusionsTACE should not be systematically performed in all resectable large HCC. Selected cases could however potentially benefit from this procedure, as patients with huge and single tumors or those necessitating of a PVE.

Magnetic resonance elastography as a preoperative assessment for predicting intrahepatic recurrence in patients with hepatocellular carcinoma

PurposeMagnetic resonance elastography (MRE) is a noninvasive tool for diagnosing hepatic fibrosis with high accuracy. We investigated the preoperative clinical and imaging predictors of intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC), and evaluated MRE as a predictor of intrahepatic recurrence. MethodsWe retrospectively evaluated 80 patients who underwent preoperative contrast-enhanced magnetic resonance imaging (MRI) with two-dimensional MRE and curative resection for treatment-naïve HCC between May 2019 and December 2021. Liver stiffness (LS) was measured on the elastograms, and the optimal cutoff of LS for predicting intrahepatic recurrence was obtained using receiver operating characteristic (ROC) analysis. An LS above this cutoff was defined as MRE-recurrence. Preoperative imaging features of the tumor were assessed on MRI, including features in the Liver Imaging Reporting and Data System and microvascular invasion (MVI). Recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method, and differences were compared using the log-rank test. Using a Cox proportional hazards model, we conducted a multivariable analysis to investigate the factors affecting recurrence-free survival. ResultsDuring a median follow-up period of 32 months (range, 4–52 months), thirteen patients (16.3%) developed intrahepatic recurrence. ROC analysis determined an LS cutoff of ≥4.35 kPa to define MRE-recurrence. The 4-year RFS rate was significantly higher in patients without MRE-recurrence than in those with MRE-recurrence (93.4% vs. 48.9%; p = 0.001). In multivariable analysis, MRE-recurrence (Hazard ratio [HR], 5.9; 95% confidence interval [CI], 1.5–23.1) and MVI (HR, 3.4; 95% CI, 1.0–11.3) were independent predictors of intrahepatic recurrence. ConclusionsPatients without MRE-recurrence had significantly higher RFS rates than those with MRE-recurrence. MRE-recurrence and MVI were independent predictors of intrahepatic recurrence in patients after curative resection for HCC.

Impact and outcomes of liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension

Impact and outcomes of liver resection for hepatocellular carcinoma in patients with clinically significant portal hypertension

The relationship between tumor-infiltrating neutrophils and clinical outcomes in patients with resectable hepatocellular carcinoma

BackgroundThe impact of tumor-infiltrating neutrophils (TINs) on clinical outcomes has been reported in various cancer types, but their role in hepatocellular carcinoma (HCC) has not been fully evaluated. The aim of this study was to investigate the prognostic values for TINs in HCC patients undergoing curative resection.MethodsWe assessed immune markers (CD3, CD4, CD8, CD66b) using immunohistochemistry in 115 patients who underwent curative resection for HCC. We analyzed the prognostic values for tumor-infiltrating immune cells, including neutrophils, and other clinicopathological factors.ResultsIn the Multivariate Cox analysis of overall survival (OS), alpha-fetoprotein (AFP) ≥ 100 ng/mL (hazard ratio (HR), 2.74, 95% confidence interval (CI), 1.17–6.44; P = 0.021) and Barcelona Clinic Liver Cancer (BCLC) B/C stage (HR, 3.98, 95% CI, 1.68–9.43; P = 0.020) were found to be independent poor prognostic factors in HCC patients undergoing resection. The presence of CD66b+TINs was observed in 66 (57.4%) patients. However, CD66b+TINs were not associated with recurrence-free survival and OS.ConclusionsOur study identified low CD66b+TINs in resectable HCC, and CD66b+ TINs did not have a significant role for the clinical outcomes of patients undergoing curative resection. The results suggest that TINs may play a role in more advanced stages of HCC.

Comparative analysis of perioperative and long-term outcomes of patients with hepatocellular carcinoma: Nonalcoholic fatty liver disease versus viral hepatitis.

Despite the accumulating evidence regarding the oncological differences between nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) and viral infection-related HCC, the short- and long-term outcomes of surgical resection of NAFLD-related HCC remain unclear. While some reports indicate improved postoperative survival in NAFLD-related HCC, other studies suggest higher postoperative complications in these patients. Patients with NAFLD and those with hepatitis viral infection who underwent hepatectomy for HCC at our department were retrospectively analyzed. The clinical, surgical, pathological, and survival outcomes were compared between the two groups. Among the 1047 consecutive patients who underwent hepatectomy for HCC, 57 had NAFLD-related HCC (NAFLD group), and 727 had virus-related HCC (VH group). The body mass index and serum glycated hemoglobin levels were significantly higher in the NAFLD group than in the VH group. There were no significant differences in operative time and bleeding amount. Moreover, the morbidity and the length of postoperative hospital stays were similar across both groups. The pathological results showed that the tumor size was significantly larger in the NAFLD group than in the VH group. No significant differences between the groups in overall or recurrence-free survival were found. In a subgroup analysis with matched tumor diameters, patients in the NAFLD group had a better prognosis after hepatectomy than those in the VH group. Surgical outcomes after hepatectomy were comparable between the groups. Subgroup analysis reveals early detection and surgical intervention in NAFLD-HCC may improve prognosis.

The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis.

The role of hepatic venous pressure gradient (HVPG) measurement in risk stratification before liver resection is an ongoing area of debate. This study examines the impact of preoperative HVPG levels on overall survival (OS)/time to recurrence (TTR) and postoperative complications after hepatic resection of hepatocellular carcinoma (HCC). Thirty-eight HCC patients undergoing HVPG measurement before liver resection at Cambridge University Hospitals NHS Foundation Trust between January 2014 and April 2022 were retrospectively analysed. Statistical analysis comprised univariable/multivariable Cox/logistic regression to identify risk factors of reduced OS/TTR or 90-day post-resection complications and Kaplan-Meier estimator, log-rank, chi-squared, Fisher's exact, and Mann-Whitney U test, or Student's t-test for survival/subgroup analysis. The median HPVG was 6 (range: 0-14) mmHg. The HVPG was an independent risk factor for poorer TTR in the overall cohort (cut-off: ≥7.5 mmHg (17.18/43.81 months; P = 0.009)). In the subgroup analysis of cirrhotic patients (N = 29 (76%)), HVPG was additionally an independent risk factor for lower OS (cut-off: ≥8.5 mmHg [44.39/76.84 months; P = 0.012]). The HVPG had no impact on OS/TTR in non-cirrhotic patients (N = 9 (24%)), nor was it associated with postoperative complications in any cohort. In conclusion, preoperative HVPG levels are useful predictors for TTR and OS in cirrhotic HCC patients undergoing hepatic resection.

A commentary on 'Comparison of survival benefit and safety between surgery following conversion therapy versus surgery alone in patients with surgically resectable hepatocellular carcinoma at CNLC IIb/IIIa stage: a propensity score matching study'.

A commentary on 'Comparison of survival benefit and safety between surgery following conversion therapy versus surgery alone in patients with surgically resectable hepatocellular carcinoma at CNLC IIb/IIIa stage: a propensity score matching study'.

Deep learning-based accurate diagnosis and quantitative evaluation of microvascular invasion in hepatocellular carcinoma on whole-slide histopathology images.

Microvascular invasion (MVI) is an independent prognostic factor that is associated with early recurrence and poor survival after resection of hepatocellular carcinoma (HCC). However, the traditional pathology approach is relatively subjective, time-consuming, and heterogeneous in the diagnosis of MVI. The aim of this study was to develop a deep-learning model that could significantly improve the efficiency and accuracy of MVI diagnosis. We collected H&E-stained slides from 753 patients with HCC at the First Affiliated Hospital of Zhejiang University. An external validation set with 358 patients was selected from The Cancer Genome Atlas database. The deep-learning model was trained by simulating the method used by pathologists to diagnose MVI. Model performance was evaluated with accuracy, precision, recall, F1 score, and the area under the receiver operating characteristic curve. We successfully developed a MVI artificial intelligence diagnostic model (MVI-AIDM) which achieved an accuracy of 94.25% in the independent external validation set. The MVI positive detection rate of MVI-AIDM was significantly higher than the results of pathologists. Visualization results demonstrated the recognition of micro MVIs that were difficult to differentiate by the traditional pathology. Additionally, the model provided automatic quantification of the number of cancer cells and spatial information regarding MVI. We developed a deep learning diagnostic model, which performed well and improved the efficiency and accuracy of MVI diagnosis. The model provided spatial information of MVI that was essential to accurately predict HCC recurrence after surgery.

Surgical resection for hepatocellular carcinoma: a single-centre's one decade of experience.

Liver cancer is the third leading cause of global cancer deaths, and hepatocellular carcinoma is its most common type. Liver resection is one of the treatment options for hepatocellular carcinoma (HCC). This study aims to explore our hospital's more than a decade of experience in liver resection for HCC patients. This is a retrospective cohort study on HCC patients undergoing resection from 2010 to 2021 in a tertiary-level hospital in Jakarta, Indonesia. Mortality rates were explored as the primary outcome of this study. Statistical analysis was done on possible predictive factors using Pearson's χ2. Survival analysis was done using the Log-Rank test and Cox Regression. Ninety-one patients were included in this study. The authors found that the postoperative mortality rates were 8.8% (in hospital), 11.5% (30 days), and 24.1% (90 days). Excluding postoperative mortalities, the long-term mortality rates were 44.4% (first year), 58.7% (3 years), and 69.7% (5 years). Cumulatively, the mortality rates were 46.4% (1 year), 68.9% (3 years), 77.8% (5 years), and 67.0% (all time). Significant predictive factors for cumulative 1-year mortality include large tumour diameter [odds ratio (OR) 14.06; 95% CI: 2.59-76.35; comparing <3cm and >10cm tumours; P<0.01], positive resection margin (OR 2.86; 1.17-77.0; P=0.02), and tumour differentiation (P=0.01). Multivariate analysis found hazard ratios of 6.35 (2.13-18.93; P<0.01) and 1.81 (1.04-3.14; P=0.04) for tumour diameter and resection margin, respectively. The mortality rate of HCC patients undergoing resection is still very high. Significant predictive factors for mortality found in this study benefit from earlier diagnosis and treatment; thus, highlighting the importance of HCC surveillance programs.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion.

For resectable hepatocellular carcinoma (HCC), radical hepatectomy is commonly used as a curative treatment. However, postoperative recurrence significantly diminishes the overall survival (OS) of HCC patients, especially with microvascular invasion (MVI) as an independent high-risk factor for recurrence. While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients, the specific role of adjuvant therapies in those with MVI remains unclear. To conduct a network meta-analysis (NMA) to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen. A systematic literature search was conducted on PubMed, EMBASE, and Web of Science until April 6, 2023. Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included. Hazard ratios (HRs) with 95% confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA. Fourteen eligible trials (2268 patients) reporting five different therapies were included. In terms of reducing the risk of recurrence, radiotherapy (RT) [HR = 0.34 (0.23, 0.5); surface under the cumulative ranking curve (SUCRA) = 97.7%] was found to be the most effective adjuvant therapy, followed by hepatic artery infusion chemotherapy [HR = 0.52 (0.35, 0.76); SUCRA = 65.1%]. Regarding OS improvement, RT [HR: 0.35 (0.2, 0.61); SUCRA = 93.1%] demonstrated the highest effectiveness, followed by sorafenib [HR = 0.48 (0.32, 0.69); SUCRA = 70.9%]. Adjuvant therapy following hepatectomy may reduce the risk of recurrence and provide a survival benefit for HCC patients with MVI. RT appears to be the most effective adjuvant regimen.