4014 Background: Checkpoint inhibitors combined with anti-angiogenic therapy represents one of the standard first-line therapies for advanced hepatocellular carcinoma (aHCC). Nilvanstomig (ZG005) is a recombinant humanized anti-PD-1/TIGIT bispecific antibody. By blocking both pathways, it can synergistically activate T cells and enhance the anti-tumor activity of NK cells. This study evaluated ZG005 plus bevacizumab vs. sintilimab plus IBI305 (a bevacizumab biosimilar) as first-line therapy for aHCC. Methods: In this randomized, open-label, multicenter, phase 2 trial conducted in China, patients with aHCC who had not previously received systemic treatment were randomly assigned (1:1:1) to receive ZG005 10 mg/kg plus bevacizumab 15 mg/kg (Arm A); ZG005 20 mg/kg plus bevacizumab 15 mg/kg (Arm B); or sintilimab 200 mg plus IBI305 15 mg/kg (Arm C). All treatments were administered intravenously every 3 weeks until disease progression or unacceptable toxicity. Randomization was stratified by baseline AFP level ( < 400 vs. ≥400 ng/mL), macrovascular invasion or extrahepatic metastasis (presence vs. absence). The primary endpoint was IRC-assessed PFS per RECIST v1.1, with key secondary endpoints including PFS per mRECIST, ORR and DCR by both criteria, and OS. Results: As of the data cutoff (Nov 25, 2025), 95 patients were enrolled and received at least one dose of treatment (Arm A, n = 31; Arm B, n = 32; Arm C, n = 32). Baseline characteristics were well-balanced across the treatment arms. For all patients enrolled, the median age was 61 years (range, 37-75), with 85.3% of patients being male. Disease characteristics included BCLC stage B (28.4%) or C (71.6%), Child-Pugh score A5 (83.2%) or A6 (16.8%), baseline AFP ≥400 ng/mL in 45.3% of patients, and HBV positivity in 73.7%. Macrovascular invasion and/or extrahepatic metastasis were present in 71.6% (68/95) of patients. With a median follow-up of about 5 months, the IRC-assessed ORR was 32.3% in Arm A, 37.5% in Arm B, and 25.0% in Arm C per RECIST v1.1; the corresponding ORRs per mRECIST were 54.8%, 50.0%, and 34.4%. The IRC-assessed median PFS per RECIST v1.1 was not reached in Arm A or B, compared with 5.8 months in Arm C (Arm A vs. C: HR 0.40, 95% CI 0.15-1.05; Arm B vs. C: HR 0.28, 95% CI 0.10-0.79). The safety profiles were comparable across the three arms. No grade ≥3 hemorrhagic adverse events were reported in either Arm A or B. Conclusions: The combination of ZG005 and bevacizumab as first-line treatment in patients with aHCC demonstrated an early encouraging efficacy with an acceptable safety profile. Higher response rates and prolonged PFS were observed with the ZG005-based regimens. Longer follow up of the current study and future phase 3 trials are warranted to validate the efficacy and safety of ZG005 in combination with bevacizumab in aHCC. Clinical trial information: NCT06558227 .

Introduction:This retrospective observational study aimed to evaluate the safety and efficacy of Enhanced Recovery After Surgery (ERAS) protocols in older adult patients (≥65 years) with hepatocellular carcinoma (HCC) undergoing radical hepatectomy. Methods:In this retrospective observational study, 498 patients who underwent radical resection for HCC between January 2018 and December 2023 were included and divided into four groups: Older adult ERAS (OE Group, n=60), Younger adult ERAS (YE Group, n=148), Older adult non-ERAS (ONE Group, n=88), and Younger adult non-ERAS (YNE Group, n=202). Propensity score matching (PSM) was performed to balance baseline covariates, generating three pairwise matched cohorts: PSM-OE Group 1 vs PSM-YE Group (both n=37), PSM-OE Group 2 vs PSM-ONE Group (both n=53), and PSM-OE Group 3 vs PSM-YNE Group (both n=35). Short-term postoperative outcomes were compared across groups. Results:Results showed that postoperative pain control was significantly superior in PSM-OE Group 1 compared to PSM-YE Group (91.9% vs 70.3% pain-free, p=0.018) and in PSM-OE Group 2 compared to PSM-ONE Group (90.6% vs 69.8% pain-free, 7.328, p=0.013), with no significant difference between PSM-OE Group 3 and PSM-YNE Group (85.7% vs 74.3%, p=0.319). PSM-OE Group 2 had significantly shorter length of hospital stays (LOS: 13.17±4.71 vs 16.68±6.42 days, p=0.002) and length of postoperative stays (LPS: 6.94±3.26 vs 9.64±5.02 days, p=0.001) than PSM-ONE Group, while PSM-OE Group 3 also showed shorter LOS (13.31±4.74 vs 17.34±9.75 days, p=0.031) and LPS (7.26±3.53 vs 10.49±6.58 days, p=0.013) compared to PSM-YNE Group. The complication rate was notably lower in PSM-OE Group 2 than PSM-ONE Group (χ2=13.747, p=0.001), with no significant differences in complication rates between other matched pairs. Blood transfusion rates, average hospitalization costs, liver reserve function (assessed by PALBI score), and 30-day readmission rates (p=0.700) showed no significant differences across all matched cohorts. Multivariate regression analysis confirmed ERAS as an independent factor associated with reduced LOS (OR=1.733, p=0.038), LPS (OR=1.901, p=0.015), postoperative pain (OR=5.014, p=0.035), and complications (OR=5.235, p=0.021). Conclusion:ERAS protocols are safe and effective in enhancing postoperative recovery for older adult patients with HCC undergoing hepatectomy, supporting their adoption as standard perioperative care for this population.

Postoperative complications remain major determinants of outcomes after hepatectomy for hepatocellular carcinoma (HCC), but whether complications that prolong hospitalization are also those that contribute most to mortality remains unclear. This multicentre cohort study included 1,883 patients undergoing curative-intent hepatectomy for HCC across seven tertiary centers. Postoperative complications were categorized by organ system, and adjusted population-attributable fractions (PAFs) were calculated to estimate their contributions to 90-day mortality and prolonged hospital stay. Multivariable Cox models were used to assess associations with overall survival and recurrence-free survival. A divergence between hospitalization burden and mortality burden was observed. Liver surgery-specific complications accounted for the largest population-level burden of prolonged hospitalization (PAF 11.0%) and 90-day mortality (PAF 10.0%). Cardiovascular complications were the leading non-liver contributor to 90-day mortality (PAF 9.4%), despite a smaller contribution to prolonged hospitalization (PAF 4.1%). Pulmonary complications, cardiovascular complications, renal complications, and glucose dysregulation were independently associated with worse overall survival, whereas no complication domain was independently associated with recurrence-free survival. These findings show that postoperative recovery burden and mortality burden are not interchangeable after hepatectomy. Liver surgery-specific complications dominated hospitalization burden, whereas cardiovascular complications represented an underrecognized non-liver contributor to early mortality and worse long-term survival. An integrated perioperative framework incorporating systematic cardiovascular risk assessment may improve risk prioritization after hepatectomy for HCC.

Conversion therapy remains an uncommon strategy for managing unresectable hepatocellular carcinoma (uHCC) due to limited evidence supporting its efficacy. To address this gap, we initiated a prospective phase 2 multicenter trial (NCT04997850) comparing the LEN-TAP regimen, combining lenvatinib, transarterial chemoembolization (TACE), and PD-1 inhibitors, against TACE alone in uHCC patients. The study’s primary outcome was salvage liver resection (SLR) rate; secondary measures included objective response rate (ORR), overall survival (OS), event-free survival (EFS), recurrence-free survival (RFS), and safety profile. From October 2020 to November 2021, 142 eligible participants were assigned to LEN-TAP (n = 71) or TACE monotherapy (n = 71). At a median follow-up of 24.2 months, the LEN-TAP cohort exhibited a significantly higher SLR rate (59.2% vs. 18.3%, P < 0.001) and ORR (78.9% vs. 16.9%, P < 0.001). Median OS, EFS, and RFS were also substantially prolonged in the LEN-TAP cohort (not reached vs. 23.0 months, P < 0.001; 20.03 vs. 6.52 months, P < 0.001; 36.6 vs. 19.0 months, P = 0.048). Although grade 3 treatment-related AEs occurred more frequently with LEN-TAP (60.6% vs. 21.1%, P < 0.001), no grade 4 or higher toxicities were observed. Exploratory biomarker assessments via single-cell sequencing and flow cytometry linked elevated levels of circulating HLA-DR+CD38+CD8+ T cells with improved treatment response. These T cells appear to mediate antitumor activity potentially through the CXCR6–PI3K–AKT signaling axis. In summary, the LEN-TAP protocol demonstrates promising efficacy and acceptable tolerability as a conversion therapy in uHCC, with peripheral HLA-DR+CD38+CD8+ T cell abundance serving as a potential predictor of therapeutic benefit.

Current guidelines for chronic hepatitis B (CHB) have progressively expanded antiviral treatment indications, with age > 30 years increasingly being incorporated as an important criterion. However, real-world evidence regarding treatment outcomes in this expanded population remains limited. This study evaluated the 48-week treatment response and its independent predictors in treatment-naïve CHB patients aged > 30 years with a high baseline viral load. This retrospective study included 808 treatment-naïve CHB patients aged > 30 years with baseline HBV DNA ≥ 2000 IU/mL who received first-line nucleos(t)ide analogue (NA) monotherapy. Patients were classified into moderately high (MH; ≥ 2 × 103 to < 1 × 107 IU/mL) and extremely high (EH; ≥ 1 × 107 IU/mL) viral load groups. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to adjust for baseline imbalance. At week 48, the overall virological response (VR) rate was 90.0% (727/808). Among HBeAg-positive patients at baseline, the HBeAg seroclearance and seroconversion rates were 14.0% (59/422) and 11.8% (50/422), respectively. Compared with the MH group, the EH group had significantly lower rates of VR (81.8% vs. 95.5%, p < 0.001), HBeAg seroclearance (9.4% vs. 22.6%, p < 0.001) and HBeAg seroconversion (7.2% vs. 20.5%, p < 0.001). Multivariable Cox regression analysis showed that ALT ≥ 5 × ULN was independently associated with a higher likelihood of VR, whereas HBeAg positivity and HBV DNA ≥ 1 × 107 IU/mL were independently associated with a lower likelihood of VR. These associations remained robust after PSM and IPTW adjustment. First-line NA therapy achieved a favourable 48-week VR in CHB patients aged > 30 years with a high viral load. However, HBeAg positivity and extremely high viral load were associated with suboptimal response, supporting intensified monitoring and individualised management.

Accurate delineation of tumor boundaries is critical for the complete resection of early-stage liver cancer but remains a challenge for single-modality imaging. Here, we present SQ 905-Gd, a small-molecule squaraine-based dual-modality probe designed for NIR-II and MRI imaging to address this need. This probe uniquely leverages an aggregation-caused quenching (ACQ) effect and intrinsic liver-targeting properties to enable a double-reversal imaging strategy. Preoperatively, SQ 905-Gd enhances T1-weighted MRI, brightening liver tumors. Intraoperatively, the same aggregates quench NIR-II fluorescence, darkening tumors against normal tissue and allowing clear visualization of sub‑2 mm lesions. Additionally, fluorescence can be restored ex vivo by solvent extraction, enabling real-time confirmation of complete resection. To our knowledge, this is the first small-molecule dual-modal probe that utilizes in vivo ACQ to achieve bright/dark reversible contrast across both MRI and NIR-II imaging, offering a powerful tool for precise liver cancer surgery.

This study aimed to compare the diagnostic performance of 2 fat suppression techniques in diffusion-weighted imaging (DWI) for detecting and assessing focal liver lesions (FLLs): water excitation spectral heterogeneity adaptive radiofrequency pulses (WE-SHARP) and conventional spectral adiabatic inversion recovery (SPAIR). This prospective study enrolled eligible participants between October 2023 and August 2024. Various DWI techniques at 3T, SPAIR-DWI, WE-SHARP-DWI, and WE-SHARP-DWI with correction algorithms (WE-SHARP-DWI*), acquired at b values of 50, 400, 800, and 1200 s/mm², were used to evaluate FLLs. Two radiologists independently assessed several subjective image quality parameters: liver edge sharpness, vessel delineation, lesion conspicuity, fat suppression effectiveness, artifacts, and overall image quality. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values were also measured. The diagnostic performance of all 3 sequences was evaluated using receiver operating characteristic (ROC) curve analysis. The study included 158 patients (67 with malignant and 91 with benign lesions) and 25 volunteers. Compared with SPAIR-DWI, the subjective image quality parameters were superior for both WE-SHARP sequences (P < .001). SNR increased 2.15-fold with WE-SHARP-DWI and 2.93-fold with WE-SHARP-DWI*. CNR also improved substantially with the WE-SHARP sequences (30.75 ± 36.83 and 42.43 ± 53.23 vs. 13.49 ± 14.39). Further, WE-SHARP sequences demonstrated lower ADC measurement variability with lower standard deviations (32.80 ± 19.13 × 10⁻³ mm²/s and 34.39 ± 18.22 × 10⁻³ mm²/s vs. 51.48 ± 17.89 × 10⁻³ mm²/s) in normal liver and more pronounced ADC differences between benign and malignant lesions (1179 × 10⁻3 mm²/s and 1197 × 10⁻3 mm²/s vs. 1009 × 10⁻3 mm²/s.). The WE-SHARP-DWI techniques demonstrated improved diagnostic performance with higher sensitivity (0.95 vs. 0.88) and greater area under the ROC curve (0.98 vs. 0.95) compared with SPAIR-DWI. Both WE-SHARP-DWI techniques demonstrated superior image quality and diagnostic value for assessing FLLs than the conventional SPAIR technique. These techniques retained clinically acceptable image quality even at high b values.

We aimed to clarify whether laparoscopic liver resection (LLR) is better than open liver resection (OLR) concerning textbook outcome (TO) achievement for patients with hepatocellular carcinoma (HCC). Data from HCC patients who underwent liver resection from a multicenter database were retrospectively reviewed (n = 2617). Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups. Logistic regression analysis was performed to identify the risk factors that are independently associated with TO. Before PSM, more aggressive biological characteristics were observed in patients who underwent OLR. After PSM, 771 patients in each group were matched. The overall rate of TO achievement in patients with LLR (78.2

The Textbook Outcome (TO) is a composite outcome measure that integrates commonly utilized independent outcome measures to comprehensively reflect the optimal post-surgical treatment result. It is used to assess the quality of surgeries and has been widely employed in hepatobiliary and pancreatic surgeries. However, its utility in splenic surgery remains unknown. Patients with cirrhosis and portal hypertension are often managed with splenectomy. The objective of this study was to investigate the perioperative textbook outcomes of splenectomy and identify the risk factors associated with achieving textbook outcomes after undergoing splenectomy. The clinical data of 263 patients with portal hypertension and hypersplenism who underwent splenectomy at our hospital were retrospectively analyzed. Perioperative clinical data were statistically analyzed using t-test, Wilcoxon test, χ2 test, or Fisher exact test. The 10-year survival and the incidence of postoperative hepatocellular carcinoma (HCC) were assessed using the Kaplan-Meier method and compared using the Log-Rank test. Among the 263 enrolled patients, 139 (52.85%) achieved textbook outcomes. Multivariate analysis revealed that preoperative prothrombin time and splenic vein diameter were independent risk factors for attaining textbook outcomes in patients undergoing splenectomy. The success rate of minimally invasive surgery was comparable to that of open surgery. Patients with high prognostic nutritional index and low Child-Pugh scores exhibited higher success rates. At 10-years of follow-up, there was no significant differences observed in terms of overall survival or hepatocellular carcinoma (HCC) incidence. However, patients who achieved TO demonstrated a higher long-term survival rate and a lower HCC incidence. Textbook outcomes serve as a comprehensive tool for assessing the quality of splenectomy. This study offers valuable insights guiding surgical treatment decisions for splenic diseases.

BackgroundTo evaluate the effects of different types of nucleos(t)ide analogs on the survival rate of patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) after radical resection through a network meta-analysis.MethodsPubMed, Embase, the Cochrane Library, and CNKI databases were searched up to 6 March 2024. The NOS was used to assess the risk of bias in cohort studies, while the ROB tool in Review Manager was employed for randomized controlled trials. Data on overall survival (OS) and recurrence-free survival (RFS) were extracted from the literature to pool hazard ratios (HRs) and corresponding 95% CrIs. Meta-analysis was performed via R.Results24 studies involving 9,787 HBV-HCC patients were included. Compared with the control group, antiviral therapies using telbivudine (HR [95% CrI] = 0.23 [0.12,0.44]), tenofovir disoproxil fumarate (HR [95% CrI] = 0.40 [0.30,0.52]), lamivudine (HR [95% CrI] = 0.50 [0.34, 0.75]), adefovir (HR [95% CrI] = 0.55 [0.38,0.79]), and entecavir (HR [95% CrI] = 0.55 [0.43,0.71]) significantly improved OS. Among these, telbivudine (98.22%) and tenofovir disoproxil fumarate (76.12%) demonstrated superior effects in improving OS. Compared with the control group, antiviral therapies using telbivudine (HR [95% CrI] = 0.45 [0.28,0.70]), tenofovir disoproxil fumarate (HR [95% CrI] = 0.52 [0.44,0.62]), entecavir (HR [95% CrI] = 0.65 [0.55,0.77]),adefovir (HR [95% CrI] = 0.79 [0.65,0.94]),and lamivudine (HR [95% CrI] = 0.82 [0.71, 0.94]) significantly improved RFS. Telbivudine (SUCRA, 93.22%) and tenofovir disoproxil fumarate (SUCRA, 85.37%) exhibited superior effects in improving RFS.ConclusionWhen compared to other nucleos(t)ide analogs, telbivudine and tenofovir disoproxil fumarate exhibited the most notable effects.Systematic ReviewIdentifier CRD42024612794.

Background: A significant portion of primary liver cancer patients in China are diagnosed at intermediate-to-advanced stages, often making them ineligible for curative surgery. Furthermore, high postoperative recurrence rates, reaching up to 70%, pose a major challenge for long-term survival. The emergence of novel systemic treatments, such as immune checkpoint inhibitor combinations, and advancements in locoregional therapies have created new opportunities for conversion and perioperative strategies. This updated consensus aims to standardize the clinical application of these therapies based on the latest evidence, with the objective of improving patient prognosis. Methods: A multidisciplinary committee of 97 experts was convened to revise previous guidelines. The process involved a comprehensive search of medical databases and conference proceedings, with evidence graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Consensus statements were finalized through a formal electronic voting process, requiring at least 80% agreement for approval, resulting in 18 updated statements. Results: The consensus provides refined definitions for conversion and perioperative therapy. It recommends various strategies for oncological conversion, including systemic therapy with anti-angiogenic drugs plus immunotherapy, and locoregional approaches like precision transarterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC). The document strongly affirms surgical resection as a crucial step for achieving long-term survival after successful conversion and offers guidance on surgical timing and adjuvant therapy. For resectable patients with high-risk features, neoadjuvant and adjuvant treatments are outlined to mitigate recurrence. The consensus also advocates for using dynamic enhanced magnetic resonance imaging ( MRI) and the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria for efficacy assessment and underscores the essential role of a multidisciplinary team in management. Conclusions: This updated consensus offers standardized, evidence-based guidance for clinicians on implementing conversion and perioperative strategies to optimize patient-centered care and highlights the need for continued research to further refine these promising approaches.

OBJECTIVE:To systematically evaluate the efficacy and safety of different antithrombotic regimens for preventing portal vein system thrombosis (PVST) formation in patients with cirrhosis and portal hypertension undergoing splenectomy using a network meta-analysis method based on published literature. METHODS:A comprehensive search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, and three Chinese databases (CBM, CNKI, and Wanfang Data) from inception to June 2025. Studies involving different prophylactic antithrombotic regimens for patients with cirrhosis and portal hypertension who underwent splenectomy were included. Literature screening and assessment of the methodological quality of the included studies were performed using the Cochrane systematic review method, and characteristic information was extracted for network meta-analysis. The clinical outcomes included the incidence of PVST at postoperative month 1 (POM 1), postoperative month 3 (POM 3), and postoperative month 6 (POM 6), the incidence rate of bleeding and the course of antithrombotic prophylaxis. RESULTS:A total of 19 studies involving 1968 patients were included. Nine different prophylactic antithrombotic regimens were analyzed, including antiplatelet therapy (APT) alone; anticoagulation alone, including low-molecular-weight heparin (LMWH) + warfarin, LMWH + rivaroxaban, and rivaroxaban alone; anticoagulation combined with APT, including LMWH + APT, LMWH + warfarin + APT, LMWH + apixaban + APT, and rivaroxaban + APT; and placebo. The results of the network meta-analysis and direct meta-analysis revealed that rivaroxaban + APT had the best efficacy in reducing PVST-POM 1, PVST-POM 3, and PVST-POM 6, followed by LMWH + warfarin + APT. The efficacy of APT alone and placebo was relatively poor. The incidence rate of bleeding was similar among the different prophylactic antithrombotic regimens. Three months of postoperative prophylactic antithrombotic therapy could significantly reduce the incidence of PVST, whereas extending the course to 6 months provided no further reduction of the incidence of PVST. CONCLUSION:For patients with cirrhosis and portal hypertension undergoing splenectomy and with Child‒Pugh class A-B liver function, prophylactic antithrombotic regimens combining anticoagulation and APT, especially rivaroxaban + APT, show the best efficacy, significantly reducing the incidence of PVST without increasing the risk of bleeding. A 3-month postoperative prophylactic antithrombotic therapy may be the optimal preventive course.

OBJECTIVE:To evaluate the safety and efficacy of self-expanding metal stents (SEMS) for managing hepatic venous outflow obstruction (HVOO) following ex vivo liver resection and autotransplantation (ELRA). METHODS:We retrospectively analyzed patients who received SEMS placement for HVOO after ELRA between January 2018 and December 2024. The study analyzed details of vascular invasion, liver resection, vascular reconstruction during ELRA, and the condition before and after stent placement. Complications and short-term and long-term prognoses were also observed. RESULTS:The study included 10 patients who underwent SEMS placement for HVOO after ELRA. Three patients had preoperative stent placement for Budd-Chiari syndrome. During ELRA, 3 patients underwent left trisegmentectomy, and 7 underwent right trisegmentectomy. Six patients required artificial vascular grafts for inferior vena cava (IVC) reconstruction, and 4 patients underwent partial IVC resection with bovine pericardial patch reconstruction. All patients underwent HV-IVC end-to-side anastomosis after HV widening. Two cases used allogeneic vein reconstruction for hepatic venous outflow. The median time to HVOO after ELRA was 3.0 [IQR 2.0-7.3] months. Three patients experienced left hepatic vein (LHV) obstruction, and 7 experienced right hepatic vein (RHV) obstruction, with a median hepatic venous pressure gradient (HVPG) of 11.8 [IQR 8.8-14.1] mmHg. After stent placement, the HVPG decreased to a median of 2.8 [IQR 2.1-3.1] mmHg. The median follow-up period was 29.5 [IQR 11.3-55.8] months. During follow-up, one patient developed restenosis; other than this, no complications of grade III or higher occurred. CONCLUSION:In this single-center cohort, SEMS demonstrated favorable safety and efficacy for HVOO after ELRA, However, larger multicenter studies are required to validate these findings and assess long-term outcomes.

Previous studies have typically focused on the effect of high preoperative serum creatinine (SCr) levels on the prognosis of hepatocellular carcinoma (HCC) patients but have often ignored the role of low SCr levels. This study aimed to assess the impact of low SCr levels on HCC patient prognosis. 3857 patients who underwent primary liver resection from seven centers were divided into low, normal and high SCr groups according to their baseline SCr levels. Factors independently associated with textbook outcome (TO) and overall survival (OS) were analyzed. Propensity score matching (PSM) was used to balance the baseline characteristics between the low- and normal-SCr groups, as well as between the high- and normal-SCr groups. TO was observed in 2403 (62.3

Background: Hypothermic liver perfusion improves parenchymal tolerance to complex resections in patients requiring prolonged hepatic vascular exclusion (HVE). We aim to evaluate the benefit of liver resection using in-situ hypothermic portal perfusion (IHP) without venovenous bypass (VVB) for complex liver resection. Methods: We retrospectively reviewed all patients who underwent liver resection requiring HVE and IHP between 2019 and 2023 and compared them with patients who underwent ex vivo liver resection and auto-transplantation (ELRA) during the same period. Detailed intraoperative and postoperative data were recorded and analyzed, including operation time, vascular reconstruction time, blood loss, transfusion volume, and postoperative complications. Results: A total of 70 patients were included in both groups (33 in the IHP group and 37 in the ELRA group). The median operation time (11.5 vs. 12.5 hours, P<0.05) and anhepatic time (75 vs. 92 minutes, P<0.05) in the IHP group were significantly shorter than in the ELRA group. Intraoperative blood loss (900 vs. 1,200 mL) and the volume of red blood cells (3.5 vs. 4.5 units) and plasma transfused (800 vs. 1,840 mL) were also lower in the IHP group (P<0.05). The incidence of postoperative complications of grade III or higher was 15.2% in the IHP group, lower than 43.2% in the ELRA group (P<0.05). There were no significant differences in the mortality rate (3.0% vs. 8.1%) or in most complications, such as bile duct stricture and hepatic abscess (P>0.05). Conclusions: The modified techniques of complex liver resection using IHP without VVB were relatively safe and may provide a possibility of radical resection in some patients. Compared to the more traditional ELRA, the procedure simplified the surgical operation, shortened the operation time, and reduced the incidence of severe complications. However, further multi-center, prospective studies are needed to investigate the feasibility and resolve the aforementioned issues.

Pancreatic cancer is a highly aggressive malignancy associated with poor prognosis and early metastasis. However, the molecular mechanisms underlying its invasive behavior remain incompletely understood. Here, we identified WD repeat domain 3 (WDR3) as a key driver of pancreatic cancer cell invasion. WDR3 expression is significantly elevated in liver metastatic lesions and is correlated with disease progression. Functional assays revealed that WDR3 promotes cell migration and invasion by upregulating transforming growth factor-α (TGF-α). Mechanistically, WDR3 interacts with the m6A reader YTH domain-containing protein 1 (YTHDC1) and facilitates its K63-linked ubiquitination, resulting in increased cytoplasmic localization of YTHDC1. This modification enhances the stability of TGF-α mRNA, thereby promoting its expression. Knockdown of either WDR3 or YTHDC1 impairs TGF-α expression and suppresses cancer cell invasiveness, whereas YTHDC1 overexpression restores the metastatic phenotype in WDR3-deficient cells. Our findings reveal a novel WDR3-YTHDC1-TGF-α axis that drives pancreatic cancer progression and suggest that targeting WDR3 may be a promising therapeutic strategy.

Hypersplenism is a common complication of cirrhosis that is associated with significant impairment to patients' life quality. Splenectomy is often employed in clinical settings as a treatment for hypersplenism. While splenectomy is carried out for the purposes of alleviating hypersplenism-related adverse outcomes like thrombocytopenia or anaemia, studies have suggested alterations in the immune status, hemodynamics, and intestinal microbiota of patients following splenectomy, which may potentially influence the onset and progression of hepatocellular carcinoma (HCC). Additionally, patients have been found to face new health risks post-splenectomy, including infections and thrombosis, which could adversely impact their overall health and potentially increase the risk of HCC. Despite these findings, there is currently no consensus on whether splenectomy affects the risk of postoperative HCC in cirrhotic patients. This review synthesizes the pertinent literature on the incidence of HCC following splenectomy, with an emphasis on current evidence related to its physiology, pathophysiology, and epidemiology. Concepts such as immune status, hemodynamics changes, and intestinal microbiota in post-splenectomy patients are explored, in hopes that it can inform more individualized treatment approaches for patients.

Background: Adjuvant therapy for solitary large hepatocellular carcinoma (SLHCC) remained unclear. Methods: 1292 SLHCC patients treated with hepatectomy between January 2010 and December 2020 were included in this retrospective cohort study investigating adjuvant transarterial chemoembolization (TACE), recurrence free survival (RFS) and overall survival (OS). Results: Among the study cohort, 571 SLHCC patients (44.2%) with microvascular invasion and/or satellite lesion (mVI/S) burden were classified as aggressive SLHCC, while 721 patients without mVI/S were classified as non-aggressive SLHCC, showing significantly better 10-year OS rates (51.7% versus 21.2%, p <0.001). Adjuvant TACE could significantly improve RFS in non-aggressive SLHCC patients, with 5- and 10-year RFS rates of 56.8% and 25.3% (vs. 43.7% and 24.8% in untreated patients, p =0.043), a finding confirmed by inverse probability of treatment weighting (IPTW) analysis ( p =0.018). However, adjuvant TACE did not significantly impact OS in this group( p =0.52; IPTW: p =0.249). For aggressive SLHCC patients, adjuvant TACE showed benefits in both RFS (5-year: 35.6% vs 24.5%; 10-year: 18.1% vs 11.4%, p <0.001; IPTW: p <0.001)) and OS (5-year: 52.4% vs 40.9%; 10-year: 25.5% vs 19.2%, p =0.033; IPTW: p =0.029). The mVI/S burden was independent predictors of RFS (HR：1.53, 95%CI:1.32-1.76, p <0.001) and OS (HR：1.79, 95%CI:1.52-2.11, p <0.001) for SLHCC. Adjuvant TACE was associated with RFS (HR：0.74 95%CI:0.58-0.93, p =0.011) but not OS (HR：0.91, 95%CI:0.68-1.22, p =0.523) for non-aggressive SLHCC, while demonstrating significant benefit for RFS (HR：0.68, 95%CI:0.53-0.87, p <0.001) and OS (HR：0.72, 95%CI:0.57-0.91, p =0.007) for aggressive SLHCC. Conclusions: The mVI/S burden identified aggressive SLHCC subtypes. Adjuvant TACE improved both RFS and OS in aggressive SLHCC, but only RFS (not OS) in non-aggressive cases.

Hepatocellular carcinoma (HCC) patients with high-risk pathological features, which including microvascular invasion, poor tumor differentiation, and satellite nodules have poor overall survival (OS) and recurrence-free survival (RFS) after hepatectomy. However, for patients with high-risk pathological features, whether the prognoses after laparoscopic (LH) and open hepatectomy (OH) are similar remains unclear. Data from a multicenter database of patients with Barcelona Clinic Liver Cancer stage 0/A HCC and high-risk pathological features who underwent hepatectomy from 2014 to 2023 were reviewed (n = 985). The OS, RFS, and incidence of textbook outcome (TO) achievement of patients after LH versus OH were compared. After propensity score matching (PSM), the TO rate in the LH group (75.8