Eastern Hepatobiliary Surgery Hospital

BackgroundNo neoadjuvant treatment has been considered to be standard therapy for patients with resectable intrahepatic cholangiocarcinoma with high-risk factors for recurrence. The GOLP regimen (gemcitabine–oxaliplatin, lenvatinib, and an anti–programmed death 1 antibody) has shown promising efficacy with a manageable safety profile in advanced intrahepatic cholangiocarcinoma and biliary tract cancer.MethodsIn a phase 2–3 trial, we randomly assigned, in a 1:1 ratio, patients with resectable high-risk intrahepatic cholangiocarcinoma to the neoadjuvant group (intravenous gemcitabine–oxaliplatin plus toripalimab every 3 weeks for three cycles and oral lenvatinib once daily for 9 weeks, followed by curative resection) or the control group (curative resection and no neoadjuvant treatment). All patients received adjuvant capecitabine for eight cycles after surgery. The primary end point was event-free survival. Secondary end points included overall survival and safety.ResultsA total of 178 patients underwent randomization (88 patients to the neoadjuvant group and 90 to the control group). At the interim analysis at a median follow-up of 16.9 months, the median event-free survival was significantly longer in the neoadjuvant group (18.0 months; 95% confidence interval [CI], 13.8 to 27.6) than in the control group (8.7 months; 95% CI, 7.2 to 12.4) (P<0.001). Overall survival at 24 months was 79% (95% CI, 70 to 90) in the neoadjuvant group and 61% (95% CI, 50 to 75) in the control group (hazard ratio for death, 0.43; 95% CI, 0.23 to 0.79; P=0.005, which did not meet the significance criterion [two-sided alpha, 0.0019]). Across all treatment phases, adverse events occurred in 97% of the patients in the neoadjuvant group and in 70% of those in the control group. During the neoadjuvant phase, adverse events of grade 3 or higher occurred in 28% of the patients, and treatment-related adverse events of grade 3 or higher in 26%. No treatment-related adverse event led to death.ConclusionsNeoadjuvant GOLP led to significantly longer event-free survival than control therapy, with mainly low-grade adverse events, among patients with resectable high-risk intrahepatic cholangiocarcinoma. (Funded by the Clinical Research Plan of Shanghai Hospital Development Center and others; ZSAB-neoGOLP ClinicalTrials.gov number, NCT04669496.)

BackgroundApproximately 5%–10% of patients with differentiated thyroid cancer (DTC) develop resistance to radioactive iodine (RAI), leading to unsatisfactory survival rates. The optimal medication for advanced or metastatic RAI-resistant differentiated thyroid cancer (RAIR-DTC) remains unclear.MethodsWe conducted a Bayesian network meta-analysis based on a systematic search of six electronic databases. The primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), objective response rate (ORR), and grade ≥3 adverse events (AEs). Hazard ratios (HRs) with 95% credible intervals (CrIs) were used for time-to-event outcomes, while odds ratios (ORs) with 95% CrIs were used for binary outcomes. A separate Bayesian network meta-analysis was performed for each endpoint.ResultsOur study included 9 RCTs involving 1,760 patients with RAIR-DTC. Lenvatinib, anlotinib, apatinib, and cabozantinib all significantly improved PFS versus placebo (HRs: 3.85–5.36), with lenvatinib ranking first overall (SUCRA: 81.97%) and showing sustained benefit up to 24 months. Apatinib provided early PFS advantage but waning efficacy beyond 6–9 months. No treatment significantly improved OS, though apatinib consistently ranked highest for OS. Lenvatinib achieved the highest objective response rate (OR = 143.18; SUCRA: 82.09%). For grade ≥3 adverse events, no treatment differed significantly from placebo; however, apatinib ranked highest in safety (SUCRA = 93.16%).ConclusionLenvatinib demonstrates the greatest benefit in both PFS and ORR among the evaluated TKIs for RAIR-DTC, suggesting it as a potential preferred first-line option. The time-dependent efficacy patterns of other TKIs warrant further investigation.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251089713, identifier CRD420251089713.

Postoperative delirium (POD) following cardiac surgery is a severe complication, and early identification of delirium risk remains a challenge in clinical practice. While machine learning (ML) has garnered increasing attention in health care applications, effective early prediction tools remain limited in current clinical practice. Recent investigations have explored the effectiveness of ML-based methods for identifying the risk of POD in patients undergoing cardiac surgery. However, more evidence is required to validate the feasibility of these methods. This study aims to ascertain the performance of ML in identifying the risk of POD following cardiac surgery, providing evidence for the development or updating of future ML-based assessment tools. A comprehensive literature search was conducted across 4 databases-PubMed, the Cochrane Library, Embase, and Web of Science-through August 30, 2024, to identify studies investigating individual POD risk prediction using ML approaches and nomograms. The risk of bias of the models in the included studies was assessed leveraging the Prediction Model Bias Risk Assessment Tool. Subgroup analyses were performed based on datasets, validation methods, study types, risk of bias, and model types. The analysis incorporated 28 original studies comprising 80,143 patients undergoing cardiac surgery, of whom 6326 developed POD. Meta-analysis revealed that, in validation datasets, the c-index, sensitivity, and specificity for delirium prediction reached 0.805 (95% CI 0.759-0.852), 0.72 (95% CI 0.65-0.79), and 0.78 (95% CI 0.71-0.83), respectively. Logistic regression was the primary modeling method. In validation datasets, the c-index, sensitivity, and specificity reached 0.773 (95% CI 0.724-0.823), 0.73 (95% CI 0.64-0.80), and 0.70 (95% CI 0.65-0.74), respectively. ML-based prediction tools for POD following cardiac surgery demonstrate promising performance. However, the limited number of studies and validation approaches necessitate cautious interpretation of these findings. Future multicenter studies are warranted to develop more robust ML-based prediction tools, enabling precise risk stratification and targeted preventive interventions for POD.

BACKGROUNDThe health challenges of partial hepatectomy in patients with clinically significant portal hypertension (CSPH) have been a subject of study for decades. No meta-analysis has systematically evaluated the relationship between CSPH and posthepatectomy liver failure (PHLF), despite its potential role as a critical factor in surgical decision-making. This systematic review and meta-analysis investigated the incidence of PHLF in patients with and without CSPH.AIMTo include more recent studies and focus on short-term postoperative outcomes, particularly the association between CSPH and PHLF. Additionally, stratified analyses were also performed according to CSPH and PHLF assessment methods, study design, study period, surgical technique, and underlying liver diseases.METHODSA comprehensive literature search was conducted in EMBASE, PubMed, MEDLINE, ScienceDirect, Elsevier, and Cochrane databases using combinations of the following terms: (“portal hypertension” OR “hypertension, portal” OR “portal hypertensions”) AND (“hepatectomy” OR “hepatectomies” OR “liver resection”) AND (“liver failure” OR “hepatic failure” OR “liver decompensation”). Studies published from January 1996 to April 2025, 21 published studies were finally included in the systematic review and meta-analysis. The quality assessment was performed independently by using the Newcastle-Ottawa Scale. Odds ratios (OR) and 95% confidence intervals (CI) were calculated and compared using a random-effects model. Heterogeneity was assessed with the χ2 test, and the degree of inconsistency was measured using I2. A P value < 0.05 or I2 > 50% indicated substantial heterogeneity. Sensitivity analysis was conducted to test the robustness of the findings and to identify potential sources of bias.RESULTSA total of 6981 patients (1453 patients with CSPH and 5529 patients without CSPH) were finally included in this study. Compared with patients without CSPH, the incidences of PHLF increased in patients with CSPH (OR = 3.14; 95%CI: 2.45-4.02; P < 0.001). Subsequent subgroup analysis suggested that the diagnostic methods for CSPH is a potential interfering factor in PHLF, the OR was maximal in hepatic venous pressure gradient measurement groups (OR = 15.61; 95%CI: 2.11-115.35; P = 0.007).CONCLUSIONThe presence of CSPH should be considered as a significant risk factor, it still should be taken into account seriously prior to surgery and needs strict perioperative management. Meanwhile, different methods of diagnosing CSPH could influence PHLF.

Abstract Genome‐wide hypertranscription is a hallmark of malignant progression. However, the development of precise and controlled RNA degradation within biological systems continues to pose significant challenges. Current base‐pairing or RNase‐based therapeutics rely on sequence recognition and inherent instability within the tumor microenvironment significantly diminishes therapeutic efficacy. Here, we establish a vacancy defect‐induced electron homing strategy to achieve enzyme‐free RNA degradation. Introducing 5% sulfur vacancies into Bi 2 S 3 disrupts the Bi‐S coordination and induces lattice distortion, which drives electron accumulation at the bismuth center and enhances their adsorption with double‐bonded oxygen in phosphodiester bonds. This vacancy‐driven electron homing lowers the reaction barrier from 2.01 to 0.95 eV by enhancing Bi‐O coordination, which polarizes the nearby P‐O bond and facilitates nucleophilic attack at the phosphorus center. Valence electron redistribution efficiently breaks phosphodiester bonds to degrade RNA and induces tumor cell apoptosis. This mechanism significantly inhibits tumor proliferation by regulating ERI3 expression in vitro and in vivo. Our work demonstrates a physics‐based approach for direct bond activation and establishes vacancy engineering as a general principle for tuning electron states and modulating bond reactivity in biological systems.

Sintilimab plus bevacizumab (Sin + Bev) is recommended as a first-line treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT); however, its efficacy remains limited. This study aimed to assess the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with Sin + Bev for HCC with PVTT. This retrospective study included 69 HCC patients with PVTT treated at two centers in China from August 2021 to December 2022. Patients received either SBRT + Sin + Bev (n = 31) or Sin + Bev alone (n = 38). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and treatment-related adverse events (TRAEs). Baseline characteristics showed similar distributions between the two groups. SBRT + Sin + Bev group showed a significant increase in both median OS (18.9 vs 9.3 months, P < .001), median PFS (9.1 vs 4.7 months, P = .0015), and ORR (64.6% vs 26.3%, P = .031) compared to Sin + Bev group. TRAEs in SBRT + Sin + Bev group were mostly manageable and acceptable compared to Sin + Bev group. Multivariate analysis confirmed that SBRT + Sin + Bev was an independent prognostic factor for better OS (P < .001) and better PFS (P < .001). SBRT combined with sintilimab plus bevacizumab appears to improve treatment efficacy and demonstrates a favorable safety and feasibility profile for HCC with PVTT.

Background:Obesity impairs liver regeneration by promoting chronic inflammation and metabolic dysfunction, especially in conditions like non-alcoholic fatty liver disease. Portal vein embolization (PVE), used to stimulate liver growth pre-hepatectomy, is less effective in obese subjects. Nicotinamide riboside (NR), a NAD+ precursor, improves mitochondrial function and lipid metabolism, but its role in liver regeneration under obese conditions remains unclear. Our study tried to investigate the effects and underlying mechanisms of NR on liver regeneration after PVE in high-fat diet (HFD)-induced obese rats.Methods:HFD-fed rats underwent PVE and were treated with or without NR. Liver regeneration was assessed by histology, 5-ethynyl-2′-deoxyuridine (EdU) incorporation, immunohistochemistry, and liver function tests. NAD+ levels were quantified to confirm NR activity. Proteomics, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Ontology (GO) analysis, quantitative real-time PCR (qPCR), and western blotting were used to explore molecular mechanisms, focusing on the MCART1/ASB3 axis.Results:Obesity impaired liver regeneration post-PVE, as evidenced by lipid accumulation, inflammation, reduced hepatocyte proliferation, and elevated liver enzymes. NR supplementation restored NAD+ levels, improved liver function, increased proliferative activity, and reduced steatosis. Mechanistically, NR upregulated MCART1 and ASB3 expression, promoting energy and lipid metabolism essential for regeneration.Conclusions:NR promotes liver regeneration after PVE in obese rats by enhancing NAD+-dependent metabolic pathways through the MCART1/ASB3 axis, offering a potential therapeutic strategy for obesity-associated liver dysfunction.