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Generally, invasive treatment is contraindication for patients with severe thrombocytopenia, because it may increase risk of bleeding. However, many early hepatocellular carcinoma (HCC) patients with cirrhosis have platelet counts (PC) less than 50 × 10 9 /L due to hypersplenism. These patients are often accompanied by hepatic insufficiency, which makes hepatectomy impossible, and local thermal ablation (LTA) has become a major treatment. The aim of our study is to investigate the correlation between severe thrombocytopenia and bleeding after LTA in HCC patients with cirrhosis, and evaluate risk factors of bleeding. 473 patients with cirrhosis who underwent LTA for HCC from 2016 to 2020 were enrolled, and 709 ablations were performed in total. Based on preoperative PC, cases were divided into three groups, namely, group A (PC > 50 × 10 9 /L), group B (30 × 10 9 /L < PC ≤ 50 × 10 9 /L) and group C (PC ≤ 30 × 10 9 /L). The incidence of bleeding after LTA was compared among the three groups. Logistic regression was used to explore the risk factors for bleeding after ablation. The overall incidence of bleeding complications was 4.4%, and no significant difference was observed between group A, B, and C (3.9% vs. 6.4% vs. 3.3%, P = 0.410). In multivariate analysis, tumor diameter (OR = 2.657 per 1 cm, P < 0.001), and multiple lesions (≥ 3) (OR = 3.723, P = 0.006) were found to be independent predictors of bleeding after LTA. In small HCC patients with cirrhosis and hypersplenism, the PC range 30-50 × 10 9 /L will not increase the risk of bleeding after LTA. Tumor diameter and number of lesions are independent predictors for bleeding after LTA in HCC patients., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval and consent to participate The study was a retrospective study approved by Ethics Committee of Chinese PLA General Hospital (K-Y-2023–1-1–1), and informed consent was waived., (© 2024. The Author(s).)

Purpose: Narrow resection margin hepatocellular carcinoma (NRM-HCC) has a high incidence of early recurrence. Our study was designed to identify prognostic factors in patients with NRM-HCC, establish and validate a nomogram model to predict early recurrence of NRM-HCC patients., Methods: We retrospectively analyzed data from 2957 NRM-HCC patients who underwent radical hepatectomy at three medical centers between December 2009 and January 2015. Patients were randomly assigned to a training cohort (n = 2069) and a validation cohort (n = 888). Using univariate and multivariate COX regression to determine early relapse factors in NRM-HCC patients, and used these factors to construct a nomogram. The accuracy of the prediction was evaluated using the C-index, receiver operating characteristic (ROC) and calibration curve. Decision curve analysis (DCA) assessed the predictive value of the models. Finally, the recurrence-free survival of different risks was analyzed using Kaplan-Meier (K-M) method., Results: The nomogram of NRM model contains alpha-fetoprotein (AFP), alkaline phosphatase (ALP), tumor size, tumor number, microvascular invasion (MVI), tumor capsular, and satellite nodules. The model shows good discrimination with C-indexes of 0.71 (95% CI: 0.69-0.72) and 0.72 (95% CI: 0.70-0.75) in the train cohort and test cohort respectively. Decision curve analysis demonstrated that the model is clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different early recurrence. The web-based tools are convenient for clinical practice., Conclusions: NRM model demonstrated favorable performance in predicting early recurrence in NRM-HCC patients. This novel model will be helpful to guide postoperative follow-up and adjuvant therapy., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: To investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk-benefit profiles in clinical practice., Design: Retrospective multicentrer cohort study., Setting: Four Italian regions (Lombardy, Veneto, Lazio, Sardinia)., Methods: Data were integrated from the national transplant information system and administrative claims data from four Italian regions. All adults who underwent incident liver transplantation between 2009 and 2019 were identified and categorised into two groups: cirrhosis or hepatocellular carcinoma (HCC). The trend of immunosuppressive treatment over years was analysed, and their effectiveness/safety profiles were compared using multivariate Cox models (HR; 95% CI)., Main Outcome Measures: Mortality, transplant reject/graft failure, incidence of severe infections, cancer, diabetes, major adverse cardiovascular events and lipid-modifying agents use., Results: The study comprised 750 subjects in the cirrhosis cohort and 1159 in the HCC cohort. Over the study years, there was a decline in the use of cyclosporine-CsA, while combination therapy involving tacrolimus with other drugs increased compared with monotherapy. Overall, tacrolimus monotherapy use was slightly over 40% in both groups, followed by tacrolimus+mycophenolate (39.5%-cirrhosis; 30.6%-HCC) and tacrolimus+molecular target of rapamycin inhibitors (mTORi) (8.5%-cirrhosis; 13.3%-HCC). No significant differences emerged in risk-benefit profile of different tacrolimus-based therapies, except for a higher risk of mortality in cirrhosis subjects under tacrolimus monotherapy compared with tacrolimus+mycophenolate (HR: 2.07; 1.17 to 3.65)., Conclusions: The study highlights a shift over time in postliver transplant therapeutic patterns, favouring the use of tacrolimus in combination with mycophenolate or mTORi, rather than monotherapy. Moreover, a potential association between tacrolimus monotherapy and increased mortality in the cirrhosis cohort was identified. Further research is warranted to investigate these findings more deeply and to optimise treatment strategies for liver transplant recipients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Scottish Inflammatory Prognostic Score (SIPS), an innovative scoring system, has emerged as a promising biomarker for predicting patient outcomes following cancer therapy. This study aimed to evaluate the value of SIPS as a prognostic indicator following hepatectomy in patients with hepatocellular carcinoma (HCC)., Methods: This retrospective study included 693 HCC patients who underwent hepatectomy. Survival outcomes were compared between propensity score-matched groups. Independent prognostic factors were identified through Cox regression analysis. Additionally, both traditional Cox proportional hazards models and machine learning models based on the SIPS were developed and validated., Results: A total of 693 HCC patients who underwent hepatectomy were included, with 102 in the high SIPS group and 591 in the low SIPS group. Following propensity score matching (1:3 ratio), both groups achieved balance, with 82 patients in the high SIPS group and 240 patients in the low SIPS group. The low SIPS group demonstrated significantly superior recurrence-free survival (RFS) (25 months vs. 21 months; P < 0.001) and overall survival (OS) (69 months vs. 58 months; P < 0.001) compared to the high SIPS group. Multivariable analysis identified SIPS as an independent adverse factor affecting both RFS and OS. The calibration curve for overall patient survival diagnosis displayed excellent predictive accuracy. Traditional COX prognostic models and machine learning models incorporating SIPS demonstrated excellent performance both the training and validation set., Conclusion: This study confirms the prognostic significance of SIPS in post-hepatectomy HCC patients, providing a practical tool for risk stratification and clinical decision-making. Further research and validation are needed to consolidate its role in prognostic assessment., Competing Interests: Declarations Ethics approval The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The research adhered to the guidelines of the Declaration of Helsinki (as revised in 2013) and received approval from the Ethics Committee of Guangxi Medical University Cancer Hospital (No. KY2024458). Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background and Objectives: Hepatocellular carcinoma (HCC) is a major global health concern, and emerging evidence suggests that TIGIT and NKG2A are potential immune checkpoints with implications for HCC progression. This study aimed to evaluate the prognostic significance of TIGIT and NKG2A expression in HCC patients who underwent radical liver resection., Methods: We conducted a retrospective analysis of 144 HCC patients who underwent radical liver resection. TIGIT and NKG2A expression levels were assessed using the immunoreactive score. Cox proportional hazards models were utilized to analyze the association between TIGIT/NKG2A expression and clinical characteristics, relapse-free survival (RFS), and overall survival (OS). Prognostic models for OS and RFS was developed and validated using concordance index and calibration curves. Additionally, the random forest algorithm was employed to identify independent risk factors for OS and RFS and their correlation with predicted survival., Results: TIGIT and NKG2A expression were identified as independent risk factors for RFS, while TIGIT expression alone significantly impacted OS. The prognostic models showed good discriminative ability, with concordance indices exceeding 0.7 for predicting 1-, 3-, and 5-year OS or RFS. Calibration curves confirmed the reliability of the nomograms for OS and RFS prediction. The areas under the ROC curve consistently exceeded 0.7 for predicting OS and RFS. Elevated levels of TIGIT and NKG2A expression were associated with diminished RFS, highlighting their importance as prognostic factors., Conclusions: Our study establishes the prognostic significance of TIGIT and NKG2A expression in predicting OS and RFS following radical liver resection for HCC patients. The developed prognostic models incorporating TIGIT and NKG2A expression hold promise for improving risk stratification and clinical management of HCC patients., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Racial and ethnic disparities in diagnosis and overall outcomes for HCC are well known. We present updated real-world data on racial or ethnic differences in LT and post-LT survival among patients with HCC in a large population-based database., Methods: We used the TriNetX database to retrospectively identify patients who had HCC (ICD-10 C22.0, C22.8) and underwent LT (CPT codes 47,135, 47,140, 47,140, 47,141, 47,142) from 2012 to 2022 and compared outcomes across racial and ethnic subgroups., Results: Majority of the patients were Caucasians (2403/2901, 84.8%), followed by African Americans (267/2901, 9.2%) Hispanic/Asian (231/2901, 7.9%). At follow up of 5 years, we noted no significant difference in mortality between AA and Caucasian patients [HR = 1.087 (95% CI 0.76, 1.56, p = 0.59)] as well as Hispanic/Asian and Caucasian patients [HR = 1.14 (95% CI 0.73, 1.78, p = 0.10)]., Conclusions: These results indicate that stringent implementation of policies aimed at ensuring equitable access to LT may contribute to bridging disparities in overall outcomes in HCC., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background The clinicopathologic-radiologic and prognostic characteristics of intratumoral fat in hepatocellular carcinoma (HCC) are critical for personalized treatment but remain understudied. Purpose To investigate the clinicopathologic-radiologic associations and prognostic implications of MRI-assessed intratumoral fat in HCCs. Materials and Methods This retrospective cohort study included consecutive adult patients who underwent resection for solitary HCCs and preoperative contrast-enhanced MRI from two tertiary-care hospitals in East Asia (March 2011 to December 2021) and Western Europe (September 2012 to December 2019). MRI scans were independently evaluated by three radiologists at each hospital. Based on Liver Imaging Reporting and Data System (LI-RADS) version 2018, intratumoral fat was defined as "fat in mass more than adjacent liver," and the homogeneous subtype was defined as intratumoral fat "in absence of mosaic and nodule-in-nodule architecture." Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analyses were conducted to identify factors associated with RFS and OS. Results A total of 933 patients were included in the Asian ( n = 736; median age, 53 years [IQR, 45-62 years]; 626 male) and European ( n = 207; median age, 64 years [IQR, 55-70 years]; 161 male) cohorts. MRI-assessed intratumoral fat was detected in 30% (215 of 726) and 31% (64 of 207) of patients in the Asian and European cohorts, respectively ( P = .72). In both cohorts, the steatohepatitic subtype, nonperipheral washout, enhancing capsule, and mosaic architecture were more frequent in tumors with intratumoral fat ( P value range, <.001 to .04). Intratumoral fat in general was not associated with RFS or OS in either cohort ( P value range, .48-.97). However, in the Asian cohort, homogeneous intratumoral fat was associated with longer RFS (hazard ratio [HR], 0.60; P = .009) and OS (HR, 0.33; P = .008) in multivariable Cox regression analyses. Conclusion MRI-assessed intratumoral fat was more frequent in steatohepatitic HCCs and associated with nonperipheral washout, enhancing capsule, and mosaic architecture. Although intratumoral fat was generally nonprognostic, homogeneous intratumoral fat was associated with longer RFS and OS in the Asian cohort. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Harmath in this issue.

Background/aim: Sarcopenia is diagnosed based on grip strength and skeletal muscle mass. Although decreased skeletal muscle mass has been reported to be associated with poor outcomes after hepatectomy, a few studies have included data on grip strength in hepatectomy candidates. This multicenter study investigated the clinical factors and postoperative complications associated with sarcopenia by assessing the grip strength and skeletal muscle mass in patients undergoing hepatectomy for hepatocellular carcinoma (HCC)., Patients and Methods: Data from patients who underwent hepatectomy for HCC between January 2020 and March 2022 were retrospectively collected from multi-institutional databases. Sarcopenia was defined as reduced grip strength and skeletal muscle mass. The patients were categorized into the sarcopenia and non-sarcopenia groups, and baseline characteristics and short term outcomes were compared between the two groups., Results: Overall, 253 patients were included, among which 36 (14.2%) had sarcopenia. The sarcopenia group was significantly associated with older age, low body mass index, comorbid heart or chronic pulmonary disease, cerebrovascular accident history, and overall and major postoperative complications compared to the non-sarcopenia group. Among major postoperative complications [Clavien-Dindo classification (CDC) ≥III], the incidence of bile leakage and intra-abdominal abscess were higher in the sarcopenia group than in the non-sarcopenia group. Multivariate analysis revealed that sarcopenia was an independent risk factor for overall and major postoperative complications (CDC ≥III)., Conclusion: Sarcopenia, defined by grip strength and skeletal muscle mass, is a predictor of overall and major complications after hepatectomy for HCC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Up to half of hepatocellular carcinoma(HCC) cases are diagnosed at an advanced stage,for which effective treatment options are lacking,resulting in a poor prognosis. In recent years,the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has demonstrated high efficacy in treating advanced HCC,significantly extending patients' survival,and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy,patients can obtain long-term survival benefits. In order to improve the long-term survival rate of the overall population with liver cancer and achieve the goal of a 15% increase in the overall 5-year survival rate outlined in the "Healthy China 2030" blueprint,the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association,Chinese Society of Liver Cancer,and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts in the field. These discussions focus on the latest progress since the release of Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma(2021 Edition) and have reached new consensus on the modifications and supplements to related key points. This consensus aims to further guide clinical practice,standardize medical behavior,and promote the development of the discipline.

Background: This study aimed to investigate the feasibility and efficacy of near-infrared fluorescence-guided laparoscopic anatomical hepatectomy (LAH) using a novel indocyanine green (ICG)-human serum albumin complex (HSA) in patients with hepatocellular carcinoma., Methods: Clinical data of hepatocellular carcinoma patients who underwent ICG-HSA fluorescence-guided LAH at our center from January 2024 to April 2024 were prospectively collected and analyzed. Ultraviolet absorption spectroscopy was used to test the absorption and stability of ICG-HSA complex solutions under different conditions. After determining the optimal ratio, the complex was administered intravenously during surgery to perform negative staining via Glissonean pedicle isolation. LAH was performed along the fluorescence-demarcated boundaries., Results: Thirty-one patients were included (24 men; mean age, 54.61 ± 13.54 years). The median maximum tumor diameter was 2.80 (interquartile range [IQR], 2.00-4.00) cm. S8 segmentectomy (22.6%) and right posterior segmentectomy (19.4%) were the most common resections performed. Successful fluorescence negative staining was achieved in all patients using ICG and HSA at a 1:6 molar ratio at room temperature. Mean operation time was 297.58 ± 85.53 min, Median intraoperative blood loss was 100.0 mL (IQR, 50.0-200.0). The median surgical margin distance was 0.90 cm (IQR, 0.40-1.50). The postoperative complication rate was 45.2% (35.5% Clavien-Dindo grade I and 9.7% grade II). The median length of hospital stay was 5.0 days (IQR, 4.0-5.0)., Conclusion: ICG-HSA-assisted LAH is safe and feasible. Compared with free ICG, the novel ICG-HSA complex exhibits better optical properties and in vivo stability, which can improve the accuracy of intraoperative liver segment localization and optimize the anatomical dissection plane. It has the potential to become an ideal fluorescent imaging agent for anatomical hepatectomy., (© 2024. The Author(s).)

Background: Liver resection and percutaneous thermal ablation (PTA) are considered curative option for hepatocellular carcinoma (HCC). This study aims to compare short- and long-term outcomes between open liver resection (OLR), laparoscopic liver resection (LLR), and PTA in elderly patients with single HCC and to define a liver map for therapeutic strategy according to HCC location and size., Methods: A multicenter retrospective study was conducted in 10 European Hospital Center, including 239 consecutive liver resection (OLR and LLR) and PTA in elderly patients ≥ 70 years old with single HCC ≤ 30 mm. Perioperative data and long-term oncological outcomes were collected and compared between groups before and after propensity score matching., Results: A total of 239 patients were enrolled, distributed as follows: 61 in the ORL group, 88 in the LLR group, and 90 in the PTA group. The hospital stay was longer in OLR and LLR groups compared to the PTA group (6, 5 and 3 days, respectively, p < 0.05). Morbidity was lower in the PTA group compared to the OLR group (11 vs. 26%, respectively, p < 0.05). Overall survival (OS) at 5 years was significantly higher in the OLR and LLR groups compared to the PTA group (82, 81, and 34%, respectively, p < 0.001). Disease-free survival (DFS) at 5 years was also significantly higher in the ORL and LLR groups compared to the PTA group (66, 50 and 20%, respectively, p < 0.001). These results were also confirmed after a propensity score matching analysis between surgery group (OLR and LLR) and the PTA group. PTA was the most used treatment for subcapsular and deep HCC not in contact with vascular structures compared to OLR and LLR., Conclusion: PTA in elderly patients ensures a shorter hospital stay and lower morbidity but worst survival compared to liver resection., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The widely accepted view that portal hypertension (PHT) is a contraindication to hepatectomy for patients with hepatocellular carcinoma (HCC) is being increasingly challenged. The long-term survival outcomes and safety of partial hepatectomy versus interventional treatment using ablation with or without pre-ablation transarterial chemoembolization (TACE) in patients with HBV-related HCC within the Milan criteria and with clinically significant PHT were compared in this study., Methods: This open-label randomized clinical trial was conducted on consecutive patients with clinically PHT and hepatitis B virus (HBV)-related HCC with tumors which were within the Milan criteria. These patients were randomized 1:1 to receive either partial hepatectomy or interventional treatment between December 2012 and June 2018. The primary endpoint was overall survival (OS); secondary endpoints included recurrence-free survival (RFS) and therapeutic safety., Results: Each of the 2 groups had 80 patients. The 1-, 3- and 5-year OS rates in the partial hepatectomy group and the interventional treatment group were 95.0%, 86.2%, 69.5% versus 93.8%, 77.5%, 64.9%, respectively (P = 0.325). The corresponding RFS rates were 78.8%, 55.0%, 46.2% versus 71.3%, 52.5%, 45.0%, respectively (P = 0.783). The partial hepatectomy group had a higher complication rate compared to the interventional group (67.5% vs. 20%, P < 0.001). However, the differences were mainly in Clavien-Dindo Grade I complications (P < 0.001), while not significant in Grade II/III/IV/V (All P > 0.05)., Conclusions: This study shows that partial hepatectomy treatment did not meet prespecified significance for improved OS and RFS compared to interventional treatment for patients with HBV-related HCC within the Milan criteria and with clinically significant PHT. However, partial hepatectomy is still a safe procedure and should be considered as a treatment option rather than a contraindication., (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat‐sen University Cancer Center.)

Background: Currently, there remains ongoing controversy about the selection of postoperative antiviral drugs for hepatocellular carcinoma (HCC) patients with concurrent metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatitis B virus (HBV) infection (HPMH) who underwent hepatectomy., Method: A multivariate Cox proportional hazards model and a propensity score matching (PSM) analysis were implemented to ensure equal baseline characteristics. The Kaplan‒Meier survival curves were employed for prognosis comparison between the two groups., Results: This study included 225 HPMH who all received post-hepatectomy antiviral therapy; with 107 in the tenofovir disoproxil fumarate (TDF) group and 118 in the entecavir (ETV) group. In the entire cohort, according to the multivariate analysis, patients in the TDF group showed better recurrence-free survival (RFS) (HR = 0.78; 95% CI, 0.55-0.95; p = 0.030) and overall survival (OS) (HR = 0.52; 95% CI, 0.30-0.97; p = 0.021) than those in the ETV group. After executing a PSM analysis, Kaplan‒Meier survival curve analysis disclosed significant differences for both RFS and OS between the two groups (p = 0.03 and p = 0.01, respectively)., Conclusions: In summary, our study suggests a more significant association of TDF in improving RFS and OS than ETV in HPMH who underwent hepatectomy through multivariate and PSM analysis. These findings indicate that the choice of antiviral drugs in HPHM holds crucial significance in guiding patient long-term prognosis., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of the study was to describe laparoscopic ultrasound (LUS) to guide microwave ablation (MWA) of hepatocellular carcinoma (HCC) in a dog., Animals: A 13-year-old female spayed Husky., Study Design: Case report., Methods: The dog was referred for laparoscopic MWA of a caudate lobe HCC measuring 2.7 cm × 1.9 cm× 2.3 cm. Laparoscopic ultrasound was used to guide percutaneous placement of a MWA probe within the caudate lobe mass. LUS was used to determine the tumor margins for placement of the probe within the medial and lateral aspects as well as the center of the mass. Additionally, LUS allowed visualization of vessels within the tumor so they could be avoided during probe placement., Results: Safe ablation was accomplished, and the dog recovered uneventfully with no complications. Follow-up computed tomography (CT) 3- and 12-months postoperatively revealed complete ablation of the caudate lobe mass. However, progressive increase in size of the right medial lobe mass occurred. Right medial liver lobectomy was performed 13 months after MWA, with a histopathologic diagnosis of HCC. The dog was euthanized 777 days post MWA and 1445 days post initial left lateral lobectomy for HCC., Conclusion: Laparoscopic ultrasound was useful in guiding complete and safe MWA of an HCC in this dog. Laparoscopic ultrasound should be considered when performing laparoscopic MWA of liver lesions in dogs., (© 2024 American College of Veterinary Surgeons.)

Background: The impact of metabolic dysfunction-associated fatty liver disease (MAFLD) on laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to compare the outcomes of LLR for MAFLD-HCC and Non-MAFLD-HCC., Methods: Patients with HCC who received LLR between October 2017 and July 2021 were enrolled. Inverse probability of treatment weighting (IPTW) was used to generate adjusted comparisons. Both short- and long-term outcomes were evaluated accordingly., Results: A total of 887 patients were enrolled, with 140 in MAFLD group and 747 in Non-MAFLD group. After IPTW adjustment, baseline factors were well matched. The MAFLD group was associated with more blood loss (210 vs 150 ml, p = 0.022), but with similar postoperative hospital stays and complication rates. The 1- and 3-year overall survival rates were 97.4% and 92.5% in MAFLD group, and 97.5% and 88.3% in Non-MAFLD group, respectively (p = 0.14). The 1- and 3-year disease-free survival rates were 84.8% and 62.9% in MAFLD group, and 80.2% and 58.8% in Non-MAFLD group, respectively (p = 0.31)., Conclusions: LLR for MAFLD-HCC was associated with more blood loss but with comparable postoperative recovery and long-term survival compared with Non-MAFLD-HCC patients. LLR is feasible and safe for HCC patients with MAFLD background., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Women on the liver transplant waiting list are less likely to undergo a transplant than men. Recent approaches to resolving this disparity have involved adjustments to Model for End-Stage Liver Disease (MELD) scoring, but this will not affect candidates who rely on exception scores rather than calculated MELD score, the majority of whom have hepatocellular carcinoma (HCC)., Objective: To evaluate the association between female sex, candidate size, and access to liver transplant among wait-listed patients with HCC., Design, Setting, and Participants: This retrospective cohort study used US transplant registry data of all adult (aged ≥18 years) wait-listed liver transplant candidates receiving an HCC exception score between January 1, 2010, and March 2, 2023., Exposure: Wait-listed liver transplant candidate sex., Main Outcomes and Measures: The association of female sex with (1) deceased-donor liver transplant (DDLT) and (2) death or waiting list removal for health deterioration were estimated using multivariable competing-risks regression. Results with and without adjustment for candidate height and weight (mediators of the sex disparity) were compared., Results: The cohort included 31 725 candidates with HCC (mean [SD] age at receipt of exception, 61.2 [7.1] years; 76.3% men). Compared with men, women had a lower 1-year cumulative incidence of DDLT (50.8% vs 54.0%; P < .001) and a higher 1-year cumulative incidence of death or delisting for health deterioration (16.2% vs 15.0%; P = .002). After adjustment, without accounting for size, women had a lower incidence of DDLT (subdistribution hazard ratio [SHR], 0.92; 95% CI, 0.89-0.95) and higher incidence of death or delisting (SHR, 1.06; 95% CI, 1.00-1.13) compared with men. When adjusting for candidate height and weight, there was no association of female sex with incidence of DDLT or death or delisting. However, at a height cutoff of 166 cm, short women compared with short men were still less likely to undergo a transplant (SHR, 0.93; 95% CI, 0.88-0.99)., Conclusions and Relevance: In this study, women with HCC were less likely to receive a DDLT and more likely to die while wait-listed than men with HCC; these differences were largely (but not entirely) explained by sex-based differences in candidate size. For candidates listed with exception scores, additional changes to allocation policy are needed to resolve the sex disparity, including solutions to improve access to size-matched donor livers for smaller candidates.

Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is poorly understood, while the predictive value of the staging in which it is included is controversial., Methods: Patients with cHCC-CCA underwent radical hepatectomy in two medical centers in China were enrolled and staged based on optimal cut-off values of tumor burden score (TBS), determined using the X-Tile. The association between TBS and prognosis was evaluated by Cox proportional hazard models and Kaplan-Meier curves with Log-rank test. TBS model and primary liver cancer (PLC) stages were compared by discrimination, consistency, and clinical utility, which were further validated by a 5-folds cross-validation., Results: A total of 192 patients were stratified into low, medium, and high TBS, comprising 92, 51 and 49 patients, respectively. Prognoses worsened with elevated TBS in both the training and validation cohorts. TBS was not only an independent prognostic indicator in univariate and multivariate cox regression, but also a stable risk factor in subgroup analysis according to baseline variables. TBS exhibited best discrimination within these predictive models, as evidenced by the highest c-index and area under curve values of time-dependent receiver operating curves within 5 years post-surgery. TBS calibration plots revealed favorable consistency between prediction and observation. Decision curve analysis suggested higher net benefits for TBS. A 5-folds cross-validation revealed consistent results., Conclusions: TBS could be applied to stratify cHCC-CCA patients after surgery into groups with statistically different prognoses. Moreover, TBS exhibited optimal prognostic value over all available PLC stages and may inform clinical decisions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: It has been described that recompensation can improve prognosis in patients with cirrhosis. However, recompensation after transjugular intrahepatic portosystemic shunt (TIPS) has not been studied. We evaluated the impact of recompensation after TIPS on the risk of hepatocellular carcinoma (HCC) and death, and we compared it with compensated cirrhosis patients., Methods: An observational study of consecutive patients with cirrhosis undergoing TIPS between 2008 and 2022 was performed. Baveno VII definition of recompensation was used including patients with or without diuretics/Hepatic encephalopathy prophylaxis. A prospective cohort of consecutive compensated cirrhosis patients was used for comparison., Results: Overall, 208 patients with cirrhosis were included, 92 compensated and 116 decompensated who underwent TIPS. After 1 year, 24% achieved recompensation. Liver function (MELD 12 ± 5 vs. 15 ± 6; p = .049), LDL-cholesterol (97 mg/dL vs. 76 mg/dL, p = .018), white cell count (7.96 × 10 9 /dL vs. 6.24 × 10 9 /dL, p = .039) and platelets (129 × 10 9 /dL vs. 101 × 10 9 /dL, p = .039) were associated with recompensation. Recompensation was associated with a reduction in the risk of HCC (p = .020). Multivariable analysis showed that this risk was significantly higher in non-recompensated patients (p = .003) but no differences were observed in recompensated compared with compensated patients (p = .816). Similarly, decompensated patients presented lower survival rates (p = .011), while no differences were observed between recompensated and compensated patients (p = .677)., Conclusions: Recompensation after TIPS has a clear impact on the incidence of HCC and death, with a similar prognosis than patients with compensated cirrhosis. Liver function is associated with recompensation, suggesting the importance of considering early TIPS in patients with indication., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Purpose: To assess the performance of FLIS in predicting adverse outcomes, namely post-hepatectomy liver failure (PHLF) and death, in patients who underwent liver surgery for malignancies., Methods: All consecutive patients who underwent liver resection and 1.5 T gadoxetic acid MR were enrolled. PHLF and overall survival (OS) were collected. Two radiologists with 18 and 8 years of experience in abdominal imaging, blinded to clinical data, evaluated all images. Radiologists evaluated liver parenchymal enhancement (EnQS), biliary contrast excretion (ExQS), and signal intensity of the portal vein relative to the liver parenchyma (PVsQs). Reliability analysis was computed with Cohen's Kappa. Cox regression analysis was calculated to determine which factors are associated with PHLF and OS. Area Under the Receiver Operating Characteristic curve (AUROC) was computed., Results: 150 patients were enrolled, 58 (38.7 %) in the HCC group and 92 (61.3 %) in the non-HCC group. The reliability analysis between the two readers was almost perfect (κ = 0.998). The multivariate Cox analysis showed that only post-surgical blood transfusions and major resection were associated with adverse events [HR=8.96 (7.98-9.88), p = 0.034, and HR=0.99 (0.781-1.121), p = 0.032, respectively] in the whole population. In the HCC group, the multivariable Cox analysis showed that blood transfusions, major resection and FLIS were associated with adverse outcomes [HR=13.133 (2.988-55.142), p = 0.009, HR=0.987 (0.244-1.987), p = 0.021, and HR=1.891 (1.772-3.471), p = 0.039]. The FLIS AUROC to predict adverse outcomes was 0.660 (95 %CIs = 0.484-0.836), with 87 % sensitivity and 33.3 % specificity (81.1-94.4 and 22.1-42.1)., Conclusions: FLIS can be considered a promising tool to preoperative depict patients at risk of PHLF and death., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To investigate the efficacy and safety of ultrasound (US)-guided microwave ablation (MWA) without artificial ascites (AA) inpatients with sub-cardiac (SC) liver cancers., Methods: This retrospective study included patients with the left lobe and caudate lobe of the liver cancer who underwent US-guided MWA in our institute from January 2020 to December 2022. According to whether the target lesion was located ≤5 mm from the pericardium, patients were divided into the SC group and the non-sub-cardiac (NSC) group. In the SC group, AA was not employed during the ablation procedure. The results of technical success, technical efficiency, local tumour progression (LTP), and major complications were recorded., Results: A total of 79 patients with 87 lesions were enrolled. There were 38 patients with 38 lesions in the SC group and 41 patients with 49 lesions in the NSC group. The median follow-up of all patients was 15 (range, 3-44) months. There was no significant difference in technical success rates (100% vs 100%), technique efficiency rates (100% vs 95.7%), LTP rates (2.63% vs 0%,), and major complication rates (2.63% vs 7.32%) between the SC group and the NSC group (P > .05). No cardiac-related complications occurred., Conclusions: US-guided MWA without AA for SC liver cancers was safe and effective., Advances in Knowledge: The clinical prognosis of thermal ablation without AA in the treatment of SC liver cancers is still unclear. The finding of this study provided evidence supporting the efficacy and safety of US-guided MWA without AA for treating this tricky location., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Hepatocellular carcinoma (HCC) presents a significant global health burden, with varying survival rates across regions. The presence of pulmonary metastases (PM) in HCC predicts a poorer prognosis, yet the global understanding of the progression and management is limited., Methods: This study aims to systematically review the burden of PM in HCC, document current treatment approaches, and evaluate treatment effectiveness through meta-analysis. A comprehensive literature search was conducted across multiple databases. Articles were screened, and data extraction was performed independently by two reviewers. Statistical analyses were conducted to synthesise data and assess treatment outcomes., Results: A total of 82 articles were included, comprising a population of 3241 participants with documented PM. Our analysis revealed a linear relationship between the HCC population size and the occurrence of PM (p < 0.005). Surgical intervention demonstrated the lowest hazard ratio (0.128) and significantly improved survival rates compared to other treatment modalities. However, data quality limitations underscore the need for further research to delineate patient subsets benefitting from surgical intervention for PM., Conclusion: Our findings advocate for continued investigation into PM management strategies, notably the role of surgical resection alongside systemic therapies, to improve outcomes in HCC patients with PM., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the safety of propofol sedation administered by interventional radiologists during radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC)., Materials and Methods: Propofol sedation was administered by interventional radiologists in 72 patients (85 procedures, 93 tumors) during RFA for HCC between August 2018 and December 2020. Interventional radiologists equipped with adequate knowledge and skills in sedation and respiratory management were responsible for sedation. Sedation was carefully assessed based on vital signs, including end-tidal carbon dioxide, consciousness status, and bispectral index. The primary endpoint was the incidence of sedation-related complications, which were evaluated separately as respiratory and cardiovascular complications. Secondary endpoints were technical success rate, ablation-related complications, and local tumor control rate. Technical success was defined as completion of ablation in the planned area. Complications were evaluated using the Clavien-Dindo classification. Sedation-related complications, technical success rate, and ablation-related complications were evaluated on a procedure basis, and local tumor control was evaluated on a tumor basis., Results: Respiratory and cardiovascular complications were observed in eight (8/85, 9.4%) and two (2/85, 2.4%) patients, respectively. Four patients required the jaw thrust maneuver due to glossoptosis, whereas a decrease in oxygen saturation to < 90% was recorded in the other four patients. However, these were temporary, and none required manual ventilation or endotracheal intubation. Bradycardia (< 50 bpm) was detected in two patients; one recovered immediately without treatment, whereas the other rapidly improved after atropine sulfate administration. No severe hypotension (< 80 mmHg) was observed. The technical success rate was 100% (85/85). Grade 3 ablation-related complications were identified in three patients (3/85, 3.5%). The local tumor control rate was 95.7% (89/93)., Conclusion: Propofol sedation can be safely administered by interventional radiologists during RFA for HCC. Although it requires special safety considerations, it may be a sedation option during hepatic RFA., (© 2024. The Author(s).)

Objective: This study aims to assess the efficacy and safety of CT-guided percutaneous cryoablation in treating hepatocellular carcinoma (HCC) located explicitly in high-risk sites., Materials and Methods: Data were collected retrospectively from 685 HCC patients undergoing percutaneous cryoablation at Tianjin Medical University Cancer Hospital between January 2018 and December 2021. Of these, 106 patients had lesions in high-risk sites, defined as a minimum distance of less than 10 mm from the heart/great vessels, diaphragm, gastrointestinal tract, and gallbladder, as determined by preoperative CT or MRI imaging. Technical success rate, complete ablation rate, and complications at 1, 12, and 24 months post-surgery were evaluated. A statistical analysis of the ablation effect difference between the high-risk site and non-high-risk site groups was conducted, utilizing propensity score matching (PSM) to mitigate patient selection bias. Univariate and multivariate logistic regression analyzes were performed to identify risk factors for the incidence of coronary heart disease., Results: The study comprised 106 cases in the high-risk group and 218 cases in the non-high-risk group. After PSM analysis until December 2021, 95 matched pairs were included. Both groups demonstrated a 100% intraoperative technical success rate, and no major complications related to cryoablation were observed. Follow-up ranged from 24 to 38 months. The complete ablation rate was 82.1% and 71.7% in the high-risk group and 83.9% and 73.9% in the non-high-risk group at 12 and 24 months, respectively. There was no significant difference in complete ablation rates between the two groups before and after PSM (P > 0.05). Multivariate analysis identified the distance between the tumor edge and high-risk site ≤ 5 mm and preoperative transarterial chemoembolization (TACE) treatment as independent risk factors for cryoablation effect., Conclusion: CT-guided percutaneous cryoablation proves to be a safe and effective approach for HCC patients with high-risk sites, serving as an alternative to surgical treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Patients with liver tumors that are in contact with the major hepatic veins may require hepatic vein resection to achieve an adequate surgical margin; however, the potential for venous congestion and impaired remnant liver function must be considered. We introduce the anatomy of the hepatic vein related to Laennec's capsule as well as the surgical techniques to overcome these limitations in the laparoscopic approach. 1,2 PATIENTS AND METHODS: A patient with hepatocellular carcinoma underwent resection of the paracaval portion of the caudate lobe. A 4.5-cm tumor was located on the hepatic hilum, compressing the middle and right hepatic veins (MHV and RHV). The Laennec's capsule around the hepatic veins consists of cardiac and hepatic layers. In the inter-Laennec approach, the hepatic veins and inferior vena cava were continuously exposed from the root side, during entry into the space between the hepatic and cardiac Laennec's capsules. 3,4 Hence, the cardiac Laennec's capsule was preserved on the venous side, and the strength of the hepatic vein walls was maintained without exposing the tumor. Parenchymal transection was performed while preserving the MHV and RHV., Results: The operative time was 331 min, with minimal estimated blood loss. The patient was discharged on postoperative day 6 without complications. A pathological examination revealed the presence of focal capsular invasion; however, the surgical margin was maintained by leaving the hepatic Laennec's capsule on the tumor side., Conclusions: Understanding the structure of the Laennec's capsule can contribute to the establishment of safe and feasible liver resection techniques., (© 2024. Society of Surgical Oncology.)

Background: Repeat open hepatectomy (ROH) for recurrent liver tumors is the preferred approach especially after initial open hepatectomy (OH). The aim of this study is to assess feasibility and safety of repeat laparoscopic hepatectomy (RLH) after initial OH in 2 high volume hepato-biliary hospitals., Methods: Patients were retrieved from prospective data bases from 2012 to 2020. The patients were divided into two groups according to the approach used for repeat hepatectomy, ROH and RLH groups., Results: Sixty-seven patients matched the criteria, 20 in RLH and 47 in ROH. Diagnoses were hepatocellular carcinoma in 52.3%, intrahepatic cholangiocarcinoma in 7.7% and colorectal liver metastases in 40%. Median operative time and blood loss were lower in RLH (199 vs 260 min, and 100 vs 400 ml respectively), as well as overall postoperative complications (20% vs 49%). There were 2 conversions (10%) due to adhesions and one died of postoperative pancreatitis in RLH. Median hospital stay was lower in RLH (5 vs 9 days)., Conclusion: RLH is a feasible, safe technique and a realistic option to be considered in selected patients after previous OH. Early conversion should be considered when adhesions are more severe than expected., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Robotic surgery has emerged as a promising approach for managing complex hepatic malignancies. This report presents a case of a single-port robotic liver resection for a patient with recurrent hepatocellular carcinoma (HCC) and metastases, focusing on the surgical technique and outcomes., Method: An 18-year-old female with a history of left hepatectomy for fibrolamellar HCC underwent robotic liver resection using the Da Vinci SP Surgical System. The procedure entailed excising a 30 mm tumor in liver segment 4 (Sg4) along with peritoneal metastases in the superior pole of the spleen and cardiophrenic lymph node metastasis. Surgical techniques comprised adhesiolysis, resection of the peritoneal nodule, Sg4 partial liver resection, and excision of the cardiophrenic lymph node., Results: The operative time was 310 min, with a blood loss of 37 mL. The patient experienced an uneventful postoperative course and was discharged home after 8 days. Partial liver resection of Sg4 revealed a moderately differentiated HCC with negative resection margins. Additionally, excision of peritoneal metastases in the superior pole of the spleen and cardiophrenic lymph nodes, consistent with metastasis, was performed. Notably, the Da Vinci SP system's relocation function proved useful in this case, particularly in slender patients with multiple distant metastases., Conclusion: This case underscores the importance of technological advancements in robotic surgery. The Da Vinci SP system, with its advantageous features, shows promise in challenging clinical scenarios. Its ability to facilitate precise navigation and manipulation within the patient's restricted abdominal cavity contributed to the observed successful outcome., (© 2024. Society of Surgical Oncology.)

Rationale and Objectives: Microvascular invasion (MVI) is a key prognostic factor for hepatocellular carcinoma (HCC). The predictive models for solitary HCC could potentially integrate more comprehensive tumor information. Owing to the diverse findings across studies, we aimed to compare radiomic and non-radiomic methods for preoperative MVI detection in solitary HCC., Materials and Methods: Articles were reviewed from databases including PubMed, Embase, Web of Science, and the Cochrane Library until April 7, 2023. The pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated using a random-effects model within a 95% confidence interval (CI). Diagnostic accuracy was assessed using summary receiver-operating characteristic curves and the area under the curve (AUC). Meta-regression and Z-tests identified heterogeneity and compared the predictive accuracy. Subgroup analyses were performed to compare the AUC of two methods according to study type, study design, tumor size, modeling methods, and imaging modality., Results: The analysis incorporated 26 studies involving 3539 patients with solitary HCC. The radiomics models showed a pooled sensitivity and specificity of 0.79 (95%CI: 0.72-0.85) and 0.78 (95%CI: 0.73-0.82), with an AUC at 0.85 (95%CI: 0.82-0.88). Conversely, the non-radiomics models had sensitivity and specificity of 0.74 (95%CI: 0.65-0.81) and 0.88 (95%CI: 0.82-0.92) and an AUC of 0.88 (95%CI: 0.85-0.91). Subgroups with preoperative MRI, larger tumors, and functional imaging had higher accuracy than those using preoperative CT, smaller tumors, and conventional imaging., Conclusion: Non-radiomic methods outperformed radiomic methods, but high heterogeneity calls across studies for cautious interpretation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: The right upper transversal hepatectomy (RUTH) is considered a complex technique of parenchymal-sparing hepatectomies. The intraoperative management of the right hepatic vein (RHV) is still controversial because it may cause obstruction of outflow in the remnant hepatic segment. The aim of this study is to present our experience of laparoscopic RUTH and the strategy of RHV resection and reconstruction in different settings., Methods: Five patients who underwent laparoscopic RUTH for liver tumor were enrolled retrospectively. Clinical and pathological features of the patients, peri-operative treatment, as well as short- and long-term outcomes were collected for analysis., Results: Laparoscopic RUTH was successfully performed in all five patients. Two individuals underwent RUTH while preserving RHV. Among the remaining patients who underwent RUTH with RHV resection, one patient underwent RHV reconstruction but the others did not. Immediate or long-term venous related complications did not occurred in a median follow-up period of nine months., Conclusions: Laparoscopic RUTH surgery for tumors in the right upper region of the liver is safe and feasible. The strategic workflow we proposed for the resection and reconstruction of the RHV offers a reliable method for preserving liver parenchyma and reducing the risk of postoperative liver failure., (Copyright © 2024. Published by Elsevier Ltd.)

Background: There is still poor evidence about the safety and feasibility of laparoscopic liver resection (LLR) for huge (> 10 cm) hepatocellular carcinomas (HCC). The aim of this study was to assess the short- and long-term outcomes of LLR versus open liver resection (OLR) for patients with huge HCC from real-life data from consecutive patients., Methods: Data regarding all consecutive patients undergoing liver resection for huge HCC were retrospectively collected from a Korean referral HPB center. Primary outcomes were the postoperative results, while secondary outcomes were the oncologic survivals., Results: Sixty-three patients were included in the study: 46 undergoing OLR and 17 LLR. Regarding postoperative outcomes, there were no statistically significant differences in estimated blood loss, operation time, transfusions, postoperative bile leak, ascites, severe complications, and R1 resection rates. After a median follow-up of 48.4 (95% CI 8.9-86.8) months, there were no statistically significant differences in 3 years OS (59.3 ± 8.7 months vs. 85.2 ± 9.8 months) and 5 years OS (31.1 ± 9 months vs. 73.1 ± 14.1 months), after OLR and LLR, respectively (p = 0.10). Similarly, there was not a statistically significant difference in both 3 years DFS (23.5% ± 8.1 months vs. 51.6 ± months) and 5 years DFS (15.7 ± 7.1 months vs. 38.7 ± 15.3 months), respectively (p = 0.13), despite a potential clinically significant difference., Conclusion: LLR for huge HCC may be safe and effective in selected cases. Further studies with larger sample size and more appropriate design are needed to confirm these results., (© 2024. The Author(s).)

Background: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients., Methods: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs., Results: Of 497 elderly patients, 157 (31.6 ​%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 ​%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 ​% vs. 72.1 ​%, P ​< ​0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 ​% confidence interval 1.879-6.198, P ​< ​0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy., Conclusion: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology., Competing Interests: Declaration of competing interest We confirm that this work is original and has not previously been published. None of the authors have any financial disclosures or conflict of interest. Approval for this study was obtained from the Ethics Committee of the participating hospitals. All the authors have been involved in the design, performance, and interpretation of data of this study, and in drafting the article and its critical revision. Should the article be accepted, all authors agree to transfer copyright to your journal., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Artificial intelligence-based models might improve patient selection for liver transplantation in hepatocellular carcinoma. The objective of the current study was to develop artificial intelligence-based deep learning models and determine the risk of recurrence after living donor liver transplantation for hepatocellular carcinoma., Methods: The study was a single-center retrospective cohort study. Patients who underwent living donor liver transplantation for hepatocellular carcinoma were divided into training and validation cohorts (n = 192). The deep learning models were used to stratify patients in the training cohort into low- and high-risk groups, and 5-year recurrence-free survival was assessed in the validation cohort., Results: The median follow-up period was 59.1 (33.9-72.4) months. The artificial intelligence model (pretransplant factors) had an area under the curve of 0.86 in the training cohort and 0.71 in the validation cohort. The largest tumor diameter and alpha-fetoprotein level had the greatest Shapley Additive exPlanations values for recurrence (>0.4). The 5-year recurrence-free survival rates in the low- and high-risk groups were 92.6% and 45% (P < .001). In the second artificial intelligence model (pretransplant factors + grade), the area under the curve for the validation cohort was 0.77, with 5-year recurrence-free survival rates of 96% and 30% in the low- and high-risk groups (P < .001). None of the low-risk patients outside the Milan and University of California San Francisco Criteria had recurrence during follow-up., Conclusions: The artificial intelligence-based hepatocellular carcinoma transplant recurrence models might improve patient selection for liver transplantation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess the prognostic impact of preoperative MRI features on outcomes for single large hepatocellular carcinoma (HCC) (≥ 8 cm) after surgical resection., Material and Methods: This retrospective study included 151 patients (mean age: 59.2 years; 126 men) with a single large HCC who underwent gadoxetic acid-enhanced MRI and surgical resection between 2008 and 2020. Clinical variables, including tumor markers and MRI features (tumor size, tumor margin, and the proportion of hypovascular component on hepatic arterial phase (AP) (≥ 50% vs. < 50% tumor volume) were evaluated. Cox proportional hazards model analyzed overall survival (OS), recurrence-free survival (RFS), and associated factors., Results: Among 151 HCCs, 37.8% and 62.2% HCCs were classified as ≥ 50% and < 50% AP hypovascular groups, respectively. The 5- and 10-year OS and RFS rates in all patients were 62.0%, 52.6% and 41.4%, 38.5%, respectively. Multivariable analysis revealed that ≥ 50% AP hypovascular group (hazard ratio [HR] 1.7, p = 0.048), tumor size (HR 1.1, p = 0.006), and alpha-fetoprotein ≥ 400 ng/mL (HR 2.6, p = 0.001) correlated with poorer OS. ≥ 50% AP hypovascular group (HR 1.9, p = 0.003), tumor size (HR 1.1, p = 0.023), and non-smooth tumor margin (HR 2.1, p = 0.009) were linked to poorer RFS. One-year RFS rates were lower in the ≥ 50% AP hypovascular group than in the < 50% AP hypovascular group (47.4% vs 66.9%, p = 0.019)., Conclusion: MRI with ≥ 50% AP hypovascular component and larger tumor size were significant factors associated with poorer OS and RFS after resection of single large HCC (≥ 8 cm). These patients require careful multidisciplinary management to determine optimal treatment strategies., Clinical Relevance Statement: Preoperative MRI showing a ≥ 50% arterial phase hypovascular component and larger tumor size can predict worse outcomes after resection of single large hepatocellular carcinomas (≥ 8 cm), underscoring the need for tailored, multidisciplinary treatment strategies., Key Points: MRI features offer insights into the postoperative prognosis for large hepatocellular carcinoma. Hypovascular component on arterial phase ≥ 50% and tumor size predicted poorer overall survival and recurrence-free survival. These findings can assist in prioritizing aggressive and multidisciplinary approaches for patients at risk for poor outcomes., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: We sought to assess the impact of various perioperative factors on the risk of severe complications and post-surgical mortality using a novel maching learning technique., Methods: Data on patients undergoing resection for HCC were obtained from an international, multi-institutional database between 2000 and 2020. Gradient boosted trees were utilized to construct predictive models., Results: Among 962 patients who underwent HCC resection, the incidence of severe postoperative complications was 12.7% (n = 122); in-hospital mortality was 2.9% (n = 28). Models that exclusively used preoperative data achieved AUC values of 0.89 (95%CI 0.85 to 0.92) and 0.90 (95%CI 0.84 to 0.96) to predict severe complications and mortality, respectively. Models that combined preoperative and postoperative data achieved AUC values of 0.93 (95%CI 0.91 to 0.96) and 0.92 (95%CI 0.86 to 0.97) for severe morbidity and mortality, respectively. The SHAP algorithm demonstrated that the factor most strongly predictive of severe morbidity and mortality was postoperative day 1 and 3 albumin-bilirubin (ALBI) scores., Conclusion: Incorporation of perioperative data including ALBI scores using ML techniques can help risk-stratify patients undergoing resection of HCC., Competing Interests: Conflicts of interest None declared., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: We aimed to develop a preoperative model to predict overall survival (OS) in patients with hepatoma undergoing liver resection (LR)., Methods: Patients who underwent LR for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, or B hepatoma were enrolled. Tumor burden score (TBS) scores were determined using the following equation: TBS (Pinna et al., 2018) 2 = (largest tumor size [in cm])(Pinna et al., 2018) 2 ​+ ​(tumor number) (Pinna et al., 2018) 22. The cutoff values for radiographic TBS were based on our recently published paper: low, <2.6; medium, 2.6-7.9; high, >7.9., Results: Multivariate analysis showed that radiographic TBS (low: referent; medium: HR ​= ​2.89; 95 ​% CI: 1.60-5.21; p ​< ​0.001; high, HR ​= ​7.60; 95 ​% CI: 3.80-15.2; p ​< ​0.001), AFP (<400 ​ng/mL: referent; ≧400 ​ng/mL: HR ​= ​1.67, 95 ​% CI: 1.11-2.52, p ​= ​0.014), and cirrhosis (absence: referent; presence: HR ​= ​1.88, 95 ​% CI: 1.30-2.72, p ​< ​0.001) were associated with OS. A simplified risk score was superior to BCLC system in concordance index (0.688 vs. 0.623)., Conclusions: We have developed a preoperative model that performs better in predicting OS than the BCLC system., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose for all authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction and Objectives: The absence of melanoma 2 (AIM2) protein triggers the activation of the inflammasome cascade. It is unclear whether AIM2 plays a role in hepatocellular carcinoma (HCC) and radiofrequency ablation (RFA), which uses radiofrequency waves to treat tumors. In this study, we investigated if RFA could induce pyroptosis, also called cell inflammatory necrosis, in HCC through AIM2-inflammasome signaling in vivo and in vitro., Materials and Methods: BALB/c nude mice were used to generate HepG2 or SMMC-7721 cell-derived tumor xenografts. HCC cells with knockdown or overexpression of AIM2 were created using short hairpin RNA (shRNA) and expression vector transfection, respectively, for functional and mechanistic studies. Downstream effects were examined using flow cytometry, qRT-PCR, ELISAs, and other molecular assays., Results: RFA significantly suppressed tumor growth in HCC cell xenografts. Flow cytometry analysis revealed that RFA could induce pyroptosis. Furthermore, AIM2, NLRP3, caspase-1, γ-H2AX, and DNA-PKc had significantly greater expression levels in liver tissues from mice treated with RFA compared with those of the controls. Additionally, interleukin (IL)-1β and IL-18 expression levels were significantly higher in the HCC cell-derived xenograft mice treated with RFA compared with those without RFA. Notably, a significantly greater effect was achieved in the RFA complete ablation group versus the partial ablation group. Knockdown or overexpression of AIM2 in HCC cells demonstrated that AIM2 exerted a role in RFA-induced pyroptosis., Conclusions: RFA can suppress HCC tumor growth by inducing pyroptosis via AIM2. Therefore, therapeutically intervening with AIM2-mediated inflammasome signaling may help improve RFA treatment outcomes for HCC patients., Competing Interests: Conflicts of interest None., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Rationale and Objectives: The proliferative nature of hepatocellular carcinoma (HCC) is closely related to early recurrence following radical resection. This study develops and validates a deep learning (DL) prediction model to distinguish between proliferative and non-proliferative HCCs using dynamic contrast-enhanced MRI (DCE-MRI), aiming to refine preoperative assessments and optimize treatment strategies by assessing early recurrence risk., Materials and Methods: In this retrospective study, 355 HCC patients from two Chinese medical centers (April 2018-February 2023) who underwent radical resection were included. Patient data were collected from medical records, imaging databases, and pathology reports. The cohort was divided into a training set (n = 251), an internal test set (n = 62), and external test sets (n = 42). A DL model was developed using DCE-MRI images of primary tumors. Clinical and radiological models were generated from their respective features, and fusion strategies were employed for combined model development. The discriminative abilities of the clinical, radiological, DL, and combined models were extensively analyzed. The performances of these models were evaluated against pathological diagnoses, with independent and fusion DL-based models validated for clinical utility in predicting early recurrence., Results: The DL model, using DCE-MRI, outperformed clinical and radiological feature-based models in predicting proliferative HCC. The area under the curve (AUC) for the DL model was 0.98, 0.89, and 0.83 in the training, internal validation, and external validation sets, respectively. The AUCs for the combined DL and clinical feature models were 0.99, 0.86, and 0.83 in these sets, while the AUCs for the combined DL, clinical, and radiological model were 0.99, 0.87, and 0.8, respectively. Among models predicting early recurrence, the DL plus clinical features model showed superior performance., Conclusion: The DL-based DCE-MRI model demonstrated robust performance in predicting proliferative HCC and stratifying patient risk for early postoperative recurrence. As a non-invasive tool, it shows promise in enhancing decision-making for individualized HCC management strategies., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: In hepatocellular carcinoma (HCC), postoperative recurrence remains high. This study aimed to evaluate the recurrence patterns and prognosis of HCC after curative hepatectomy., Methods: Among 352 patients with primary HCC who underwent initial hepatectomy between January 2002 and December 2022, 151 with recurrence were assessed for the relationship between recurrence pattern and prognosis., Results: The early recurrence group (within 6 months postoperatively; n = 38) had significantly higher serum alpha-fetoprotein (p = 0.002), des-γ-carboxyprothrombin (DCP; p = 0.004) levels and Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.001), larger tumor size (p < 0.001), higher incidence of multiple tumors (p = 0.002) and lower overall survival (OS) (p < 0.001) than the late recurrence group (> 6 months postoperatively; n = 113). The tumor size (p = 0.013) and BCLC stage (p = 0.001) were independent risk factors for early recurrence within 6 months in multivariate analysis. The multiple recurrence group (intrahepatic multinodular recurrence or distant metastasis; n = 89) had significantly lower prognostic nutritional index (p = 0.026), larger tumor size (p = 0.017), lower incidence of liver cirrhosis (p = 0.03) than the single recurrence group (single nodule recurrence; n = 62). The multiple recurrence group, especially patients with ≥ three intrahepatic nodules and distant metastases, had lower postoperative OS (p < 0.001) and shorter time to recurrence (p < 0.001) than the single recurrence group. When the patients were classified into three groups: late recurrence with one or two tumors (Group A; n = 74), early recurrence or three or more tumors or distant metastasis (Group B; n = 54), and early recurrence with three or more tumors or distant metastasis (Group C; n = 23), OS was significantly lower in Groups B and C than Group A (p < 0.001)., Conclusions: Patients with early recurrence within 6 months after surgery and three or more recurrence nodule or distant metastasis exhibited poor prognosis after initial recurrence, and they should be carefully followed up., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between KRAS rs712 polymorphism and HCC. However, the relationship between KRAS rs712 polymorphism and HCC recurrence after LT remained unclear. A total of 93 HCC patients who underwent LT from March 2008 to Dec 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as KRAS rs712. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The KRAS rs712 genotype frequencies were determined using the Χ 2 test and the minor allele frequencies (MAFs) of KRAS rs712 genotypes were calculated by Hardy-Weinberg equilibrium. We found that the recipient KRAS rs712 polymorphism was significantly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and recipient KRAS rs712 genotype were proved to be independent risk factors for HCC recurrence after LT. Patients with donor TG/TT genotypes had a significantly higher RFS and OS than TT genotype. The TNM stage, microvascular invasion, Milan criteria, treatment and recipient KRAS rs712 genotype were independent factors for the RFS of LT patients. Recipient KRAS rs712 polymorphism is associated with HCC recurrence after liver transplantation and plays as a promising bio-predictor of overall survival rate of HCC risks after hepatic transplantation., (© 2024. The Author(s).)

Background: The study purpose was to develop a machine learning (ML)-based predictive model for event-free survival (EFS) in patients with hepatocellular carcinoma (HCC) undergoing stereotactic ablative radiotherapy (SABR)., Methods: Patients receiving SABR for HCC at a single institution, between 2017 and 2020, were included in the study. They were split into training and test (85%:15%) cohorts. Events of interest were HCC recurrence or death. Three ML models were trained, the features were selected, and the hyperparameters were tuned. The performance was measured using Harrell's C index with the best-performing model being tested on the unseen cohort., Results: Overall, 41 patients were included (training = 34, test = 7) and 64 lesions were analysed (training = 50, test = 14), resulting in 30 events (60% rate) in the training set (death = 6, recurrence = 24) and 8 events (57% rate) in the test set (death = 5, recurrence = 3). A Cox regression model, using age at treatment, albumin, and intra-lesional fat identified through MRI as variables, had the best performance with a mean training score of 0.78 (standard deviation (SD) 0.02), a mean validation of 0.78 (SD 0.18), and a test score of 0.94., Conclusions: Predicting the outcomes in patients with HCC, following SABR, using a novel model is feasible and warrants further evaluation.

To explore the application value of postoperative contrast-enhanced ultrasound (CEUS) parameters for lymph node metastasis (LNM), tumor, node, metastasis staging, and treatment response evaluation of resected hepatocellular carcinoma (HCC). We retrospectively analyzed 100 patients with liver cancer who underwent liver CEUS at our hospital between October 2020 and October 2022. The patient's LNM, pathological staging, and therapeutic effects were recorded based on the histopathological results. CEUS parameters were analyzed and compared CEUS parameters between different lymph node metastases, pathological stages, and therapeutic effects. Twenty-three patients experienced LNM, 77 patients did not experience LNM; and the rise time (RT), peak intensity (PI), and area under the curve (AUC) of the metastatic group were significantly smaller than those of the nonmetastatic group (P < .05). 44 cases were classified into groups I to II by pathological staging, and 56 cases were classified into groups III to IV. The RT, PI, and AUC of groups III to IV were significantly lower than those of groups I-II (P < .05). Seventy-nine cases were complete necrosis, 21 cases were residual or recurrent; The RT, PI, and AUC of the residual or recurrent group were significantly lower than those of the complete necrosis group (P < .05). The receiver operating characteristic curve shows that RT, PI, and AUC have a certain value in evaluating LNM, pathological staging, and treatment response of HCC, and the combined evaluation/evaluation value of these 3 factors is relatively high. The postoperative CEUS parameters RT, PI, and AUC can be used for LNM, pathological staging evaluation, and treatment response evaluation of HCC. Moreover, the combination of the 3 parameters is feasible and valuable in evaluating LNM, tumor, node, metastasis staging, and treatment response of HCC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: The purpose of this study was to interpret real-world clinical data to analyze the surgical safety and survival outcomes of patients with initial unresectable hepatocellular carcinoma (uHCC) after conversion therapy., Methods: A retrospective analysis was performed on 2984 hepatocellular carcinoma (HCC) patients hospitalized in Shandong Cancer Hospital Affiliated to Shandong First Medical University from June 1st, 2019 to June 1st, 2023. Clinicopathological features, response to systemic and/or loco-regional treatments, surgical resection rate after conversion therapy, surgical safety, and postoperative recurrence were analyzed., Results: A total of 38 patients were successfully converted to obtain surgical resection. 35 patients underwent radical resection. A high objective response rate (ORR) (52.6% under RECIST v1.1 and 78.9% under mRECIST criteria) was observed in patients under conversion therapy, and the disease control rate (DCR) was 100%. Pathologic complete response (pCR) was 42.9%. Treatment-related adverse events (TRAEs) of any grade were observed in 37 patients (97.4%). Safety of conversion or direct surgery continues to improve. The median follow-up time was 19.3 months. The 1-year Disease-free survival (DFS) rate of patients with direct surgery and patients with conversion surgery were 91.4% and 86.8%, respectively., Conclusions: With conversion therapy, a small percentage (1.81%) of uHCC patients are likely to be converted to radical resection. Local combined systemic therapy is a relatively safe and effective conversion therapy, and the safety of surgery is gradually improved after successful conversion. Preliminary follow-up data showed satisfactory survival benefits for patients undergoing conversion surgery., Trial Registration: This was a retrospective study and it did not interfere with treatment decisions., (© 2024. The Author(s).)

Radiofrequency ablation (RFA) is an effective treatment for hepatocellular carcinoma (HCC), but the recurrence rate remains high due to angiogenesis in residual cancer cells. We used thermal stimulation to simulate the post-RFA microenvironment. The expression profile of circRNAs between normal control HCC cell-derived exosomes and exosomes after heat stimulation were analyzed by RNA sequencing. Quantitative real-time PCR was applied to evaluate the expression of circPTPRK in exosomes and human umbilical vein endothelial cells (HUVECs). Then, the functions of heat-stimulated HCC cell-derived exosomes and exosomal circPTPRK on HUVECs were unveiled. Transcriptome sequencing was utilized to determine targeted genes of circPTPRK. Heat-stimulated HCC cell-derived exosomes augmented cell proliferation, migration, and angiogenesis of HUVECs. In total, 229 differentially expressed circRNAs were obtained, including 211 upregulated circRNAs and 18 downregulated circRNAs in heat-stimulated HCC cell-derived exosomes. The expression of circPTPRK was remarkably increased in heat-stimulated HCC cell-derived exosomes and the HUVECs incubated with them. Heat-stimulated HCC cell-derived exosomes with circPTPRK knockdown significantly inhibited cell proliferation, migration, and angiogenesis of HUVECs. Mechanistic studies indicated that PLA2G4E is a downstream target of circPTPRK, and PLA2G4E overexpression reversed the inhibitory effect of circPTPRK knockdown on HUVEC angiogenesis. Our results indicated that exosomal circPTPRK activated HUVEC angiogenesis by upregulating PLA2G4E expression., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Zhu, He and Qi.)

As important components in the tumor microenvironment, interleukin-8 (IL-8) and integrin β3 play a key role in the progression and metastasis of hepatocellular carcinoma (HCC). This study aimed to determine the expression of IL-8 and integrin β3 and their prognostic value in patients with HCC after hepatectomy. We investigated the expression of IL-8 and integrin β3, their clinical significance, as well as their correlation in the cancer tissue of 130 patients with HCC using immunohistochemistry. The prognostic value of IL-8 and integrin β3 was investigated through the follow-up of patients with HCC after hepatectomy. In HCC, IL-8 expression had a positive correlation with integrin β3 expression. Increased expressions of IL-8 and integrin β3 were indicators of tumor progression and poor prognosis in patients with HCC after hepatectomy. IL-8 positive specimens exhibited a higher proportion of macrovascular invasion, larger tumor size, poor differentiation, and advanced tumor-node-metastasis (TNM) stage (P < .05, respectively). Integrin β3 positive group exhibited a higher proportion of TNM III-staged tumors (P < .05). The results indicated that macrovascular invasion, advanced TNM stage, and integrin β3 expression were independent unfavorable prognostic factors in HCC after hepatectomy. Integrin β3 expression was proved to be an independent unfavorable prognostic factor in HCC after hepatectomy. Targeting integrin β3 might be a potential therapeutic approach in preventing tumor progression in HCC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background & Aims: The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B., Methods: Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD)., Results: Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378-0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379-0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results., Conclusion: Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation., (© 2024. The Author(s).)

Purpose: The aim of this study was to determine whether preoperative body mass index (BMI) was associated with postoperative morbidity after laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC)., Methods: A total of three groups of patients were categorized based on preoperative BMI: low-BMI (≤ 18.4 kg/m 2 ), normal-BMI (18.5-24.9 kg/m 2 ) and high-BMI (≥ 25.0 kg/m 2 ). Baseline clinicopathological characteristics, operative variables, and postoperative 30-day mortality and morbidity were recorded and compared among the three groups. The independent risk factors for postoperative morbidity, including surgical site infection (SSI), were identified using univariate and multivariate analyses., Results: Among 226 included patients, 20 (8.8%), 122 (54%), and 84 (37.2%) patients had low, normal, and high BMI, respectively. There were no significant differences in postoperative 30-day mortality rates in patients with low BMI and high BMI compared with those with normal BMI (5% and 1.2% vs. 0%, P = 0.141 and P = 0.408, respectively). However, postoperative morbidity rates were significantly higher in patients with low BMI and high BMI compared to those with normal BMI (40% and 32.1% vs. 17.2%, P = 0.032 and P = 0.020, respectively). According to multivariate analysis, both low and high BMI were independent risk factors of increased postoperative morbidity (OR: 5.03, 95% CI: 1.02-25.6, P = 0.047, and OR: 4.53, 95% CI: 1.75-12.8, P = 0.003, respectively). Low and high BMI were also identified as independent risk factors of increased postoperative SSI rates (OR: 6.25, 95% CI: 1.60-23.8, P = 0.007, and OR: 2.89, 95% CI: 1.04-8.77, P = 0.047, respectively)., Conclusion: A higher incidence of postoperative morbidity including SSI after LLR for HCC was found in low-BMI and high-BMI patients compared to normal-BMI patients., Clinical Trials Registration: Not applicable because this is a retrospective observational study., (© 2024. The Author(s).)

Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially aiding liver regeneration. However, their role in PHLF is still unknown., Methods: Our study included nine patients with hepatocellular carcinoma (HCC) undergoing PHx: three patients with PHLF, three patients undergoing the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure, and three matched controls without complications after PHx. Patient plasma was collected before PHx as well as 1 and 5 days after. EVs were isolated by ultracentrifugation, and extracted proteins were subjected to quantitative mass spectrometry using a super-SILAC mix prepared from primary and cancer cell lines., Results: We identified 2625 and quantified 2570 proteins in the EVs of PHx patients. Among these, 53 proteins were significantly upregulated and 32 were downregulated in patients with PHLF compared to those without PHLF. Furthermore, 110 proteins were upregulated and 78 were downregulated in PHLF patients compared to those undergoing ALPPS. The EV proteomic signature in PHLF indicates significant disruptions in protein translation, proteostasis, and intracellular vesicle biogenesis, as well as alterations in proteins involved in extracellular matrix (ECM) remodelling and the metabolic and cell cycle pathways, already present before PHx., Conclusions: Longitudinal proteomic analysis of the EVs circulating in the plasma of human patients undergoing PHx uncovers proteomic signatures associated with PHLF, which reflect dying hepatocytes and endothelial cells and were already present before PHx.

Purpose: Hepatocellular carcinoma (HCC) is one of the malignant tumors responsible for high mortality and recurrence rates. Although liver transplantation (LT) is an effective treatment option for HCC, ischemia-reperfusion injury (IRI) is a contributor to HCC recurrence after LT. Moreover, prolonged cold ischemia time (CIT) is a risk factor for IRI during LT, and there is insufficient clinical evidence regarding the impact of CIT on HCC recurrence after LT., Patients and Methods: This retrospective study analyzed 420 patients who underwent LT for HCC between February 2015 and November 2020 at The First Affiliated Hospital, Sun Yat-sen University. The duration of CIT was defined as the time from clamping of the donor aorta until portal reperfusion., Results: A total of 133 patients (31.7%) experienced tumor recurrence after LT, and CIT > 568 min was the independent risk factor for HCC recurrence (OR, 2.406; 95% CI [1.371-4.220]; p = 0.002). Multivariate Cox's regression analysis revealed that the recipients' gender, exceeding Milan criteria, poor differentiation, and alpha-fetoprotein (AFP) ≥400 ng/ml in CIT > 568 min group were independent risk factors for disease-free survival. The peak 7-day postoperative alanine aminotransferase (ALT) level ( p  < 0.001), the peak 7-day postoperative aspartate aminotransferase (AST) level ( p  < 0.001), the peak 7-day postoperative peak total bilirubin (TBIL) level ( p  = 0.012), and the incidence of early allograft dysfunction (EAD) ( p  = 0.006) were significantly higher in the CIT > 568 min group compared to the CIT ≤ 568 min group. Moreover, the amount of fresh frozen plasma (FFP) infusion during the operation increased ( p  = 0.02), and the time of mechanical ventilation postoperative was longer ( p  = 0.045)., Conclusion: An effective strategy to improve the prognosis is to reduce CIT; this strategy lowers the recurrence of HCC in patients undergoing LT, especially those within the Milan criteria., Competing Interests: The authors declare there are no competing interests., (©2024 Yu et al.)

Background: This study aimed to compare the survival outcomes of transarterial chemoembolization (TACE) between patients with early recurrent hepatocellular carcinoma (rHCC) after hepatic resection, stratified by cytokeratin (CK) 19 expression., Methods: A retrospective analysis was conducted on 63 patients with early rHCC after hepatic resection who underwent TACE between January 2017 and December 2021. Patients were divided into two groups based on CK19 expression: CK19-negative (n=31) and CK19-positive (n=32). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to identify independent risk factors for OS and PFS., Results: The CK19-negative group demonstrated a significantly longer median OS compared to the CK19-positive group (635 days vs. 432 days, p=0.013). Similarly, the CK19-negative group had a longer median PFS than the CK19-positive group (291 days vs. 117 days, p=0.014). Multivariate Cox analysis identified Child-Pugh A grade, CK19-negative expression, and increased TACE sessions as protective factors for OS. No severe TACE-related adverse events were observed., Conclusion: In patients with early rHCC after hepatic resection, those with CK19-positive expression had poorer survival outcomes following TACE compared to CK19-negative patients. These findings suggest the need for additional therapies to improve survival in CK19-positive individuals., (© 2024. The Author(s).)