BACKGROUND AND AIM:The benefit of combining linaclotide with polyethylene glycol (PEG) for improving bowel preparation quality and adenoma detection in patients at risk for inadequate bowel preparation remains uncertain. This study aimed to evaluate its efficacy and safety. METHODS:From August 2022 to July 2023, a multicenter, randomized trial assigned participants to a 2-day linaclotide or placebo plus PEG regimen. The primary endpoints included adequate bowel preparation rate and mean number of adenomas detected per colonoscopy. RESULTS:The modified intention-to-treat (mITT) (n=672) and per-protocol (n=574) analyses showed no significant differences in adequate bowel preparation rates (mITT: OR 1.26, 95% CI 0.73-2.16, P=0.406; per-protocol: OR 1.46, 95% CI 0.80-2.66, P=0.222) or the mean number of adenomas (mITT: mean difference -0.02, 95% CI -0.19-0.15, P=0.832; per-protocol: mean difference -0.06, 95% CI -0.25-0.13, P=0.530) between groups. However, linaclotide and PEG increased the mean number of polyps in the right colon (0.54 ± 1.9 vs. 0.27 ± 0.8; mean difference -0.27, 95% CI -0.49- -0.05, P=0.016), particularly in patients aged ≥70 years (mean difference -1.30, 95% CI -2.48- -0.13, P=0.033). CONCLUSIONS:A 2-day linaclotide regimen failed to improve the primary endpoints of bowel preparation adequacy or adenoma detection in high-risk patients.

e16309 Background: Neuroendocrine Tumor Liver Metastases (NETLM) represent the most critical prognostic factor in patients with disseminated neuroendocrine tumors, frequently leading to significant morbidity and mortality. For patients with unresectable NETLM, locoregional therapies targeting the liver are essential for disease management and symptom palliation. Transarterial embolization (TAE) and transarterial chemoembolization (TACE) are established locoregional therapies for unresectable neuroendocrine tumor liver metastases (NETLM). The potential survival benefit of adding hepatic arterial infusion chemotherapy (HAIC) to these therapies remains unclear. This study aimed to compare the efficacy and safety of TAE/TACE alone versus TAE/TACE combined with HAIC (TAE/TACE+HAIC) in patients with unresectable NETLM. Methods: A retrospective analysis was conducted on 101 patients with unresectable NETLM treated at Peking University Cancer Hospital between February 2012 and November 2024. Of these, 67 patients received TAE/TACE alone and 34 patients received TAE/TACE+HAIC. Propensity score matching (PSM) was employed to minimize selection bias. The primary endpoint was progression-free survival (PFS) and secondary endpoints included hepatic progression-free survival (hPFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: PSM resulted in 21 patient pairs with comparable baseline characteristics between TAE/TACE and TAE/TACE+HAIC cohorts. Among these patients, 5 were classified as G1, 33 as G2, and 4 as G3. TAE/TACE matched cohort exhibited a higher median OS compared with the TAE/TACE+HAIC cohort(71.3 months vs. 34.2 months; P = 0.01), while hPFS (15.8 months vs. 14.9 months; P = 0.7) and PFS (11.7 months vs. 11.2 months; P = 0.9) were similar. ORR and DCR did not differ significantly (ORR: 42.9% vs. 57.1%, P = 0.54; DCR: 100% vs. 95.2%, P = 1.0). The patients underwent a total of 233 treatments. No treatment-related deaths occurred and serious adverse events were comparable, except for higher rates of elevated transaminases (14.5% vs. 4.5%; P = 0.02) and hyperbilirubinemia (5.3% vs. 0%; P = 0.01) in the combined group. Conclusions: TAE/TACE alone was associated with superior survival outcomes and a more favorable safety profile in patients with unresectable NETLM. These findings suggest that TAE/TACE alone may be a more effective and safer treatment approach for this patient population. The combination therapy should be approached with caution due to unimproved survival outcomes and increased liver-related toxicities.

e16308 Background: Neuroendocrine carcinoma (NEC) is an aggressive malignancy characterized by rapid progression and high metastatic potential, leading to a dismal median overall survival (OS) of only 11–12 months in patients with metastatic disease. Platinum-based chemotherapy with etoposide plus cisplatin or carboplatin remains the standard first-line treatment; however, its clinical benefit is modest, with an objective response rate (ORR) of approximately 31% and a median progression-free survival (PFS) of merely 4 months, and no established second-line therapy is currently available, underscoring a substantial unmet clinical need. Although intra-arterial liver-directed therapies (IALT) are routinely used to treat liver metastases from well-differentiated neuroendocrine tumors, their efficacy and safety in poorly differentiated and highly proliferative neuroendocrine carcinoma liver metastases (NECLM) remain largely undefined. This study aimed to evaluate the clinical outcomes and safety of IALT in patients with NECLM. Methods: 30 patients with pathologically confirmed NECLM who underwent IALT at Peking University Cancer Hospital from February 2012 to November 2024 were retrospectively analyzed. Treatment modalities included transarterial chemoembolization (TACE) alone (n = 5), transarterial embolization (TAE) alone (n = 2), hepatic arterial infusion chemotherapy (HAIC) alone (n = 1), TACE combined with HAIC (n = 20) and TAE combined with HAIC (n = 2). The primary endpoint was PFS while secondary endpoints included hepatic PFS (hPFS), OS, ORR, disease control rate (DCR) and safety. Results: The study cohort exhibited a substantial disease burden, with 83.3% of patients presenting with synchronous liver metastases and 76.7% with extrahepatic disease; moreover, 86.7% had received prior systemic therapy. The intervention achieved an ORR of 36.7% and a DCR of 70.0%. Median OS was 8.35 months, while median hPFS and PFS were 5.1 months and 4.5 months, respectively. No treatment-related deaths occurred. Grade ≥3 adverse events were generally manageable and most commonly consisted of transaminase elevation (18.9%), abdominal pain (17.0%) and hyperbilirubinemia (7.5%). Conclusions: IALT demonstrated acceptable safety and modest efficacy in the high-risk NECLM patients with aggressive disease and limited therapeutic options. These results indicate that IALT may serve as a feasible locoregional treatment strategy for NECLM, warranting further investigation to refine patient selection and optimize treatment approaches.

Plasma adsorption (PA) is used to improve outcomes in liver fail-ure (LF). Data on adsorption capacity and its relationship to patient outcomes are limited. This single-center retrospective study included patients with LF who received PA at the First Affiliated Hospital of Zhejiang University School of Medicine in Hangzhou City, China, between October 2020 and October 2022, and examined the impact of adsorption volume (5 L vs. 6 L) on prognosis. The study included 230 PA treatments, of which nine were excluded due to missing data. The 5L column was used in 60 patients (118 treatments, 47 male), and the 6L column was used in 50 patients (103 treatments, 31 male). Treatment effectiveness was evaluated using length of hospital stay, liver transplantation, death, and improvement in disease-related symptoms. In both groups, PA in-creased white blood cells (WBC), international normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) but decreased hemoglobin, total bile acids, total bilirubin, and fibrinogen (all p<0.05). Plate-let levels decreased after 6L PA (p=0.033) but not after 5L PA (p=0.116). After PA, the 6L group had lower WBC than the 5L group (p=0.003), but there were no significant differences in the other parameters. The 5L and 6L columns did not differ significantly in hospital stay duration, liver transplantation, mortal-ity, or symptom improvement. However, the 5L column significantly reduced platelet destruction, shortened treatment time, and reduced the occurrence of complications, particularly thrombocytopenia-related risks. Hence, the results indicate that the 5L volume would be preferable clinically.

BACKGROUND:While partial splenic artery embolization (PSE) has been effectively employed in treating portal hypertension, cirrhosis, and idiopathic thrombocytopenia, its combination with hepatic artery infusion chemotherapy (HAIC) for the management of chemotherapy-induced hypersplenism (CIH) has not been previously explored. This retrospective study aims to provide clinical insights into this potential therapeutic approach. MATERIALS AND METHODS:We conducted a retrospective analysis involving patients with colorectal cancer liver metastases (CRLM) who received PSE in conjunction with HAIC (utilizing the FOLFOX regimen) to manage thrombocytopenia due to hypersplenism. Tumor response assessment followed the response evaluation criteria in solid tumors, while adverse reactions were categorized using the Common Terminology Criteria for Adverse Events (version 5.0). The primary objective was to attain a platelet (PLT) count of 100 × 10 9 /L, with secondary objectives encompassing evaluation of adverse events related to the combined therapy and its efficacy against liver metastases. RESULTS:From January 2018 to May 2023, 20 patients with CRLM and CIH were consecutively enrolled in this investigation, each undergoing PSE and HAIC. In total, PSE was performed 25 times. Median pre- and post-PSE PLT counts were 51 × 10 9 /L and 116 × 10 9 /L, respectively, with 80% of participants reaching the primary endpoint of a PLT count of ≥100 × 10 9 /L. Abdominal pain emerged as the most frequent postoperative complication, affecting 11 patients (44%). The objective response rate stood at 25%, while the disease-control rate was reported at 80%. The median progression-free survival was measured at 3.9 months, with a median overall survival of 13.8 months. CONCLUSION:The combination of PSE and HAIC (FOLFOX regimen) represents a safe and effective strategy for managing CIH and CRLM, demonstrating favorable outcomes in PLT count restoration and disease control.

4533 Background: The multicenter randomized phase 2/3 FRUSICA-2 trial (NCT05522231) demonstrated that fruquintinib plus sintilimab (F+S) significantly improved progression-free survival (PFS) (22.2 months vs 6.9 months) and objective response rate (ORR) (60.5% vs 24.3%) by blinded independent central review (BIRC) assessment compared to axitinib or everolimus (A/E) in Chinese patients (pts) with advanced renal cell carcinoma (aRCC) who had failed prior tyrosine kinase inhibitor therapy (Ye D, et al; 2025 ESMO). Considering that baseline tumor burden may correlate with efficacy outcome, we present the results of a relevant post-hoc subgroup analysis. Methods: Overall, 234 eligible pts were 1:1 randomized to receive either F+S or A/E. The primary efficacy endpoint was PFS assessed by BIRC per RECIST 1.1; secondary endpoints included investigator-assessed PFS, ORR, disease control rate, duration of response, time to response, and overall survival. This subgroup analysis evaluated BIRC-assessed PFS and ORR across subgroups defined by the number of target lesions (TLs) and metastatic sites (METs) at baseline. Results: At baseline, 79, 79, 32 and 44 pts had 1, 2, 3 and ≥4 TL(s), respectively. Metastatic disease was present in 117 (98.3%) pts in F+S arm and 110 (95.7%) pts in A/E arm, with a higher proportion of pts in F+S arm (88, 73.9%) having ≥3 METs than in A/E arm (67, 58.3%). By the data cut-off date of Feb 17, 2025, median follow-up for PFS was 16.6 months. As summarized in the table, F+S demonstrated superior PFS versus A/E across all subgroups, with unstratified hazard ratios (HRs) ranged from 0.28 to 0.50, as well as consistently longer median PFS. Similarly, improvements in ORR were observed across subgroups with odds ratios (ORs) ranged 2.46~7.22. Notably, in F+ S arm, fewer baseline TLs and METs appeared to correlate with longer median PFS, though such trend was not observed for ORR. Conclusions: Consistent with the primary analysis, F+S showed superior efficacy compared to A/E in terms of PFS and ORR in the second-line treatment of aRCC, regardless of the amount of baseline TLs or METs. Clinical trial information: NCT05522231 . Subgroup(F+S v A/E) 1 TL(38 v 41) 2 TLs(38 v 41) 3 TLs(16 v 16) ≥4 TLs(27 v 17) 1 MET(29 v 43) 2 METs(39 v 28) ≥3 METs(49 v 39) PFS, HR (95% CI) a 0.39 (0.20, 0.76) 0.33 (0.17, 0.66) 0.43 (0.17, 1.10) 0.28 (0.12, 0.62) 0.28 (0.13, 0.60) 0.50 (0.24, 1.04) 0.31 (0.18, 0.545) Median PFS, months b 24.9 vs 8.3 22.2 vs 6.9 15.3 vs 4.2 13.8 vs 6.9 24.9 vs 8.3 22.2 vs 8.3 NE vs 4.2 ORR, OR (95% CI) c 3.95 (1.35, 11.91) 4.65 (1.63, 13.43) 7.22 (1.17, 52.78) 5.53 (1.21, 28.76) 7.18 (2.22, 23.84) 2.46 (0.81, 7.76) 6.12 (2.13, 18.44) ORR, % 52.6 vs 22.0 65.8 vs 29.3 62.5 vs 18.8 63.0 vs 23.5 65.5 vs 20.9 53.8 vs 32.1 61.2 vs 20.5 NE, not estimable. a Based on an unstratified Cox proportional risk model. b Estimated using Kaplan-Meier method. c Exact 95% CI for OR was calculated using Cochran-Mantel-Haenszel method.

53 Background: Liver metastases are the main cause of death in colorectal cancer (CRC), yet only ~20% of patients qualify for surgery. For unresectable colorectal liver metastases (CRCLM), hepatic arterial infusion chemotherapy (HAIC) and drug-eluting bead transarterial chemoembolization (DEB-TACE) are common treatments. This study assesses the efficacy and safety of combining DEB-TACE with HAIC using FOLFOX or FOLFIRI. Methods: This retrospective study included 221 CRCLM patients treated at Peking University Cancer Hospital from 2018 to 2023. Of these, 182 received DEB-TACE with HAIC-FOLFOX and 39 with HAIC-FOLFIRI. Propensity score matching (PSM) minimized selection bias. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), hepatic PFS (hPFS), objective response rate (ORR), disease control rate (DCR), and treatment-related safety. Results: Propensity matching resulted in 38 pairs, achieving comparable baseline between DEB-TACE-HAIC-FOLFOX and DEB-TACE-HAIC-FOLFIRI cohorts. Of these pairs, 45 were male and 31 were female. Around 65.8% patients were younger than 65 years. The original locations of CRC in 67.1% of patients were on the left side. The middle to high grades of tumor were dominant (88.2%). Notably, 56.6% of patients harbored mutations in KRAS, NRAS or BRAF and extrahepatic metastasis occurred in 78.9% patients. Additionally, 75% patients were refractory to second line systemic therapy. Median hepatic progression-free survival (hPFS), progression-free survival (PFS), and overall survival (OS) were all slightly better in the matched DEB-TACE-HAIC-FOLFOX cohort, but not statistically significant (median hPFS: 8.6 vs. 5.8 months, P=0.206; median PFS: 6.4 vs. 4 months, P=0.062; median OS: 11.8 vs. 10.8 months, P=0.249). The objective response rate (ORR) was 36.8% in the DEB-TACE-HAIC-FOLFOX group and 39.5% in the DEB-TACE-HAIC-FOLFIRI group, with disease control rates (DCR) of 71.1% and 76.3%, respectively. These patients received 224 DEB-TACE plus HAIC treatments. There were no treatment-related deaths. Serious adverse events were comparable between the two groups, except for elevated transaminase. However, transaminase elevation was actually due to drug-eluting beads difference during DEB-TACE. With the further analysis of drug-eluting beads’ effect on adverse events, transaminase elevation, nausea, vomiting and pain occurred much frequently with DCB drug-eluting bead than HepaSphere drug-eluting bead; these differences were statistically significant. Conclusions: The combination of DEB-TACE with FOLFOX or FOLFIRI HAIC shows promising efficacy and tolerable safety for unresectable CRCLM. The FOLFIRI-based regimen is a viable alternative, especially for oxaliplatin-intolerant patients.

Liver fibrosis is a pivotal stage in the progression of chronic liver disease to cirrhosis or hepatocellular carcinoma, driven by persistent activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix (ECM). Emerging evidence indicates that dietary flavonoids, natural bioactive compounds with broad availability and multi-target regulatory potential, exert protective effects against liver fibrosis through pleiotropic mechanisms. This review systematically describes the pharmacological mechanisms by which flavonoids mitigate liver injury, including regulation of lipid metabolism, suppression of inflammatory responses, and inhibition of fibrogenesis. Furthermore, we focus on elaborating the specific pathways by which flavonoid monomers induce cell death and regulate cell states, and further explore how these compounds regulate macrophage polarization, protect hepatic sinusoidal endothelial cells, and inhibit pathological angiogenesis. Finally, we examine recent advances in nano-delivery systems and co-administration strategies designed to address clinical challenges such as poor bioavailability and rapid metabolism. In conclusion, natural flavonoids hold promise for anti-liver fibrosis therapy. This review provides a theoretical foundation for developing effective, targeted natural therapies for hepatic fibrosis and highlights that future research requires mechanism-driven research, formulation innovation, and clinical validation to enable personalized treatment.

Background: Gastric cancer (GC) is the fifth most common cancer and the fourth leading cause of cancer-related mortality worldwide. The liver is the primary metastatic site, and the prognosis of gastric cancer with liver metastasis (GCLM) remains poor. While transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are used for liver cancer, their roles in GCLM remain underexplored. Objectives: This study aimed to evaluate the efficacy and safety of drug-eluting bead TACE (DEB-TACE) combined with HAIC in patients with unresectable GCLM. Design: This was a retrospective, single-center cohort study. Methods: We retrospectively analyzed 62 patients with GCLM treated at Peking University Cancer Hospital between July 2018 and June 2023. Patients underwent 135 sessions using either HepaSphere beads plus HAIC-FOLFOX (HEPA-HAIC, n = 33) or DC bead plus HAIC-FOLFOX (DCB-HAIC, n = 29). The primary endpoint was median overall survival (mOS); secondary endpoints included median hepatic progression-free survival (mhPFS), median progression-free survival (mPFS), tumor response, and safety. Results: Among the patients (53 male, 9 female), 75.8% had intestinal-type cancer. Over 95% underwent prior treatments. The mOS was 10.7 months in both groups. The HEPA-HAIC cohort achieved longer mhPFS (8.6 vs 7.6 months) and mPFS (5.7 vs 4.4 months), though not statistically significant. Objective response rate and disease control rate were similar (30.3%/75.8% vs 31.0%/75.9%). Propensity score matching confirmed these findings. Univariate Cox regression suggested primary tumor location and carcinoembryonic antigen were prognostic for hPFS and OS, respectively. No treatment-related deaths occurred. Common adverse events (AEs) were transaminase elevation and pain. Nausea, vomiting, and severe pain were significantly less frequent with HEPA-HAIC (5.6% vs 31.7%, p = 0.001; 4.2% vs 31.7%, p < 0.001; 8.3% vs 22.2%, p = 0.01). Conclusion: DEB-TACE plus HAIC was feasible and demonstrated intrahepatic disease control with acceptable tolerability in unresectable GCLM; HEPA-HAIC showed a favorable safety profile.

Background:Chemotherapy combined with immune checkpoint inhibitor have prolonged survival of patients with advanced biliary tract cancers (BTCs), and the previous studies showed the synergistic anti-tumor effect of chemotherapy, anti-angiogenesis therapy, and immunotherapy. Hepatic arterial infusion chemotherapy (HAIC) achieved a higher tumor response and survival benefit in previous phase II studies for advanced BTCs. Thus, we conducted this phase II trial to evaluate the efficacy and safety of HAIC combined with bevacizumab and toripalimab for advanced BTCs. Methods:Treatment-naïve participants with advanced BTCs were recruited for this phase II trial. Combination therapy, comprising HAIC with bevacizumab (300 mg, day 1), oxaliplatin (40 mg/m2, 2 h, days 1-3), and 5-fluorouracil (800 mg/m2, 22 h, days 1-3) plus intravenous toripalimab (240 mg, day 1 before HAIC), was repeated every 4 weeks for a maximum of six consecutive cycles. Intravenous toripalimab (240 mg) and bevacizumab (300 mg) were administered every 4 weeks as maintenance treatment. The primary endpoint was objective response rate (ORR) according to Immune-Modified Response Evaluation Criteria in Solid Tumors criteria, and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Olink proximity extension assay with a Target 96 Immuno-Oncology panel was exploratory investigated. Results:Between July 2020 and January 2022, 32 participants were enrolled. The ORR was 84.38%, and the disease control rate was 96.88%. Median PFS and OS were 13.20 months [95% confidence interval (CI): 8.93-17.47] and 19.0 months (95% CI: 12.22-25.78), respectively. Grade 3 or higher adverse events (AEs) were observed in 10 participants (31.25%), and the most frequent grade 3 or higher AEs were elevated ALT/AST (4/32, 12.50%), elevated total bilirubin (3/32, 9.38%), and neutropenia (3/32, 9.38%). In exploratory analysis, Child-Pugh B [hazard ratio (HR): 22.65, 95% CI: 3.66-140.08, P=0.001] and high level of macrophage metalloproteinase-12 (HR: 5.99, 95% CI: 1.60-22.37, P=0.008) were indicated as the risk factors related to worse PFS. Conclusions:HAIC combined with bevacizumab and toripalimab may serve as an improved first-line treatment for advanced BTCs, which require a randomized control trial for verification. Trial Registration:This trial is registered at ClinicalTrail.gov (NCT04217954).

Background:Pulmonary artery intimal sarcoma (PAIS) is a rare aggressive malignant tumour that is easily confused with pulmonary embolism and poses considerable diagnostic challenges. Case summary:This case report details a 68-year-old male with progressive dyspnoea and chest tightness, initially misdiagnosed as pneumonia and pulmonary thromboembolism. Multimodal imaging, including echocardiography and contrast-enhanced computed tomography, identified an irregular mass within the pulmonary artery causing luminal stenosis, necessitating urgent surgical intervention. Histopathological examination confirmed PAIS. Postoperative recovery without adjuvant chemotherapy resulted in no recurrence or metastasis at a 2-year follow-up. Discussion:This case underscores the pivotal role of imaging in differentiating PAIS from thromboembolic conditions and highlights surgical resection as the cornerstone of treatment. Although the prognosis of PAIS remains poor, complete surgical excision may extend survival, emphasizing the importance of early multidisciplinary collaboration and long-term monitoring. This report advocates for increased clinical suspicion of PAIS in cases of refractory dyspnoea to reduce diagnostic delays.

BACKGROUND AIMS:Currently, there is limited evidence regarding the survival benefit of transjugular intrahepatic portal shunt (TIPS) placement in patients with advanced cirrhosis and recurrent ascites. This study aimed to assess whether TIPS improves the survival in such population compared with large volume paracenteses plus albumin (LVP + A). METHODS:This retrospective study included 462 patients with advanced cirrhosis and recurrent ascites who were treated with TIPS (N = 151) or LVP + A (N = 311) at 11 tertiary hospitals in China between September 2014 and September 2020. The Fine and Gray competing risk regression model was used to compare the outcomes between the two groups after adjusting for liver disease severity and other potential confounders. RESULTS:1-year overall survival was significantly higher in the TIPS group than in the LVP + A group (77.9% vs 47.3%; P < 0.001), with the relative risk of mortality reduced by 57% (adjusted HR = 0.43, 95% CI: 0.29 to 0.64; P < 0.001). Furthermore, TIPS group had a lower rate of further paracentesis (17.9% vs 100%; P < 0.001) and portal hypertension-related bleeding (5.8% vs 28.1%; P < 0.001) but a higher rate of overt hepatic encephalopathy (26.5% vs 6.4%; P < 0.001) compared with LVP + A group. CONCLUSIONS:In patients with advanced cirrhosis and recurrent ascites, TIPS improved the 1-year survival rates compared with LVP + A. Although TIPS increases the risk of overt hepatic encephalopathy, it can significantly decrease ascites recurrence and portal hypertension-related bleeding.

INTRODUCTION:This meta-analysis aimed to evaluate the determinants that influence mortality of individuals with liver failure who are undergoing the treatment of plasma exchange (PE). METHODS:The search for relevant literature was conducted from the beginning of the database records up to January 5, 2024, encompassing a range of databases such as PubMed, Embase, the Cochrane Library, Web of Science, as well as Chinese databases including China National Knowledge Infrastructure (CNKI), WanFang, and VIP. For the analysis of continuous variables, the weighted mean difference was utilized, while for categorical variables, the odds ratio was employed. Both statistical measures were presented alongside their respective 95% confidence intervals. Subgroup analyses were conducted based on liver failure type, volume of plasma exchanged, and HBV etiology. RESULTS:In total, 33 studies involving 5,842 patients were included. Older age, a higher Model for End-Stage Liver Disease score, the presence of hepatic encephalopathy, cirrhosis, hepatorenal syndrome, and peritonitis, elevated aspartate transaminase levels, low albumin level, low prothrombin activity, prolonged prothrombin time, low platelet, and white blood cell counts were associated with mortality in Chinese patients with liver failure who underwent PE (all p < 0.05). However, these influencing factors could vary depending on the type of liver failure and the exchange volume during PE. CONCLUSION:Several demographic indicators, liver function indicators, coagulation indicators, and routine blood are associated with mortality in patients with liver failure undergoing PE. This study may provide important clinical guidance for the care of patients with liver failure, helping to improve patient survival.

3561 Background: Hepatic arterial infusion chemotherapy (HAIC), a highly efficient local therapy for patients with colorectal liver metastases (CRLM), is supposed to have a synergetic effect when it is in combination with a systemic therapy. The aim of this study was to determine the recommended phase 2 dose (PR2D) of fruquintinib combine with HAIC and evaluate efficacy and safety in expansion cohort of patients with CRLM. Methods: This open-label, single-arm, phase Ib/II study (NCT05406206) enrolled patients with CRLM who had received at least two prior lines of treatment. In the dose-finding phase, based on a standard 3+3 design, patients were treated with HAIC involving oxaliplatin (85 mg/m2) and 5-FU (2000 mg/m2) on day 1 and 2 every 4 weeks, alongside fruquintinib (3mg, 4mg, 5mg, d3-23, q4w, respectively) until unacceptable toxicities, progressive disease, or death occurred. In the dose-expansion phase, patients received HAIC and RP2D of fruquintinib determined in the dose-escalation phase. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included RP2D, objective response rate (ORR; RECIST 1.1), disease control rate (DCR), overall survival (OS) and safety. Results: As of data cutoff date on January 30, 2024, a total of 30 patients were enrolled. 9 (30.0%) patients were female, and the mean age was 56 years, 22 (73.3%) patients were RAS/BRAF mutant. During the dose-escalation phase, 15 patients were enrolled, with 3, 6, and 6 patients receiving doses of 3 mg, 4 mg, and 5 mg, respectively. Only one dose-limiting toxicity occurred in a patient of 4 mg level (G3 hypertension failed to control with antihypertensive treatment within 7 days). RP2D of fruquintinib was established as 5 mg. Fifteen patients were evaluable for efficacy, with best response of pathological complete response in 1 patient, partial response in 5 patients and stable disease in 6 patients, yielding an ORR of 40.0% and DCR of 80.0%. Median hepatic-PFS and median PFS was 6.8 months (95% CI, 5.890-7.710) and 5.9 months (95% CI, 3.576-8.224), respectively. The median OS reached 15.0 months (95% CI, 8.671-21.329). 7 (23.3%) patients experienced G3/4 treatment-related adverse events (TRAEs). The most common TRAEs of all grades were voice alteration, hypertension, abdominal pain and hand-foot syndrome. Conclusions: The combination of HAIC and fruquintinib showed a manageable safety profile and survival benefit of heavily treated CRLM patient. Clinical trial information: NCT05406206 .

Aim: To analyze the risk factors for oxaliplatin (OXA)-induced severe hypersensitivity reactions and identify the recurrence rate of the reactions after an OXA rechallenge in patients treated with hepatic arterial infusion chemotherapy (HAIC). Methods: Among the 2251 patients treated with HAIC (OXA), 84 patients with gastrointestinal cancer who displayed hypersensitivity reactions between May 2013 and May 2022 were included in this study. Among the 84 patients, 23 (27.4%) developed severe anaphylactic reactions (grade III/IV), and 61 (72.6%) developed grade I/II reactions. We explored the risk factors for severe OXA-induced hypersensitivity reactions. Twenty-seven patients with grade I/II reactions underwent retreatment (HAIC with OXA), and the recurrence rate of the hypersensitivity reactions was determined. A multivariate logistic regression model was used to analyze the risk factors for OXA-induced hypersensitivity reaction. Results: In the study, multivariate analysis indicated that the dose of OXA (odds ratio [OR] 3.077, 95 % confidence interval [CI] 1.106-8.558, p = 0.031) was an independent risk factor for OXA-induced severe hypersensitivity reactions. Twenty-seven patients with non-severe hypersensitivity reactions underwent retreatment HAIC with OXA and 14 (51.9 %) experienced HSR recurrence, including 2 (7.4 %) who experienced hypersensitivity shock. Conclusions: The administration of OXA doses is a risk factor for OXA-induced severe hypersensitivity reactions in patients treated with HAIC (OXA). Rechallenging HAIC with OXA appears to be associated with a higher recurrence rate of the HSR.

e16164 Background: Drug-eluting bead transarterial chemoembolization (DEB-TACE) is established as a safe and effective treatment for advanced hepatocellular carcinoma (HCC). Recent advancements in molecular targeted agents and immunotherapy have led to exploration of combining DEB-TACE with tyrosine kinase inhibitors (TKIs) or immunotherapy. However, real-world evaluations of DEB-TACE in combination with TKIs or immunotherapy are limited. This study aimed to assess the efficacy and safety of DEB-TACE alone, DEB-TACE with TKIs, and DEB-TACE with TKIs and immunotherapy. Methods: This study retrospectively enrolled 124 patients with unresectable HCC treated at Peking University Cancer Hospital from April 2018 to April 2023. Patients were divided into three groups: DEB-TACE alone (DTACE, 45 patients), DEB-TACE plus TKI (DTACE+TKI, 51 patients), and DEB-TACE plus TKI and immunotherapy (DTACE+TKI+IM, 28 patients). Propensity score matching (PSM) was used to compare efficacy and safety between DTACE and DTACE+TKI. Primary endpoints were progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), disease control rate (DCR), assessed by RECIST Version 1.1. Adverse events were graded according to CTCAE version 5.0. Results: Among the patients, 99 were male and 25 were female, with 88.7% in BCLC-B or C stage. Before enrollment, 50.8% had received other treatments. In the DTACE+TKI+IM group, mPFS and mOS were higher compared to DTACE or DTACE+TKI alone (mPFS: 15.2 vs 9.2 for DTACE, 8.7 for DTACE+TKI; mOS: 32.3 vs 25.0 for DTACE, 20.9 for DTACE+TKI), though not statistically significant. ORR and DCR were 31.3% and 86.7% in DTACE, 35.3% and 84.3% in DTACE+TKI, and 39.3% and 96.4% in DTACE+TKI+IM, respectively. PSM analysis for DTACE and DTACE+TKI showed slightly better mPFS and mOS in DTACE+TKI (mPFS: 9.5 vs 9.2 months; mOS: 26.2 vs 19.4 months). No treatment-related deaths occurred, and serious adverse events (AEs) were comparable among the groups, with pain being the most common. AE. Notably, the frequency and severity of pain were closely related to the type of drug-eluting beads used, with the incidence of severe pain significantly lower in the HepaSphere DEB-TACE group compared to the CalliSphere or DCB group (0% versus 12.4% versus 19.7%, respectively; p < 0.001). Conclusions: DEB-TACE has been demonstrated as a safe, feasible, and efficacious treatment option for patients with unresectable HCC. There is a notable trend towards prolonged progression-free survival (PFS) and overall survival (OS) when DEB-TACE is combined with TKIs and immunotherapy. Moreover, HepaSphere DEB-TACE shows a lower incidence of severe pain compared to other types of drug-eluting beads, further highlighting its potential advantages in managing HCC.

Pharmacotherapy is crucial for advanced hepatocellular carcinoma (HCC). The multi-kinase inhibitor donafenib offers superior survival benefits over sorafenib. Donafenib has first-line status, but there is limited research for combination therapies with this anticancer agent. This study aimed to delineate donafenib's antitumor effects, including transcriptomics and proteomics to characterize gene expression changes in donafenib-treated HCC cell lines. In vitro and in vivo tumorigenicity studies were conducted to evaluate the combined antitumor effects of donafenib. Proteomic and transcriptomic analyses identified that donafenib downregulated fatty acid desaturase 2 (FADS2) at the protein and mRNA levels. In vitro and in vivo assays revealed an inhibitory effect of FADS2 blockade on HCC cell malignancy. The combination of donafenib and the FADS2 inhibitor sc-26,196 produced synergistic antitumor action, enhancing therapeutic efficacy in HCC cell lines and xenografted tumors in nude mice. These findings highlight the potential of FADS2 as a biomarker for HCC and show a promising combinatorial therapy for its treatment. Thus, we provide a theoretical basis for translating laboratory research into clinical applications.