Neoadjuvant therapy is recommended for hepatocellular carcinoma at advanced stages. It is unknown whether robotic liver resection (RLR) is superior to open liver resection (OLR) after neoadjuvant therapy. We analyzed consecutive RLR and OLR patients from December 2020 to December 2023. Patient variables, short- and long-term outcomes were compared. A respective 1:3 propensity score-matched (PSM) analysis was performed between RLR and OLR groups. The analysis included 32 RLR and 386 OLR cases. After PSM, 29 RLR cases matched to 78 OLR cases. RLR had similar operative time, fewer blood loss (123 mL vs. 230 mL, P = 0.032), and shorter postoperative hospital stay (7.2 days vs. 10.4 days, P = 0.014) compared to OLR. RLR had similar incidence and grades of complications compared to OLR. No significant difference was found in recurrence-free and overall survival. RLR after neoadjuvant therapy was as safe and feasible as OLR, and could improve postoperative recovery and produce equivalent long-term survival outcomes.

Standardized clinical management of pancreatic adenocarcinoma (PDAC) remains challenging and high-volume centers provide essential insights for establishing effective multimodal treatment approaches. This retrospective observational study evaluated the impact of standardized, multimodal clinical management on survival outcomes in patients with PDAC across all stages, based on NCCN guidelines resectability criteria, at a high-volume center. From 2019, 4143 patients were diagnosed with PDAC, with 3268 patients receiving further treatment, including surgical resection and/or systemic therapy. The median overall survival (OS) was 18.5 (95 %CI 17.5-19.4) months for the treated cohort and the 5-year survival rate reached 23.3 %. Patients who underwent surgical resection had significantly improved median OS compared to those who received non-surgical treatments (28.4 months vs. 13.0 months, P < 0.001), with corresponding 5-year survival rates of 31.6 % vs. 15.0 %. Moreover, the patients who received NAT followed by surgical resection had improved survival outcomes compared to those who underwent upfront surgical resection in both resectable (median OS: 37.5 months vs. 28.9 months, P < 0.01) and borderline resectable group (median OS: 31.8 months vs. 18.4 months, P < 0.001). This study demonstrated a 5-year survival rate exceeding 20 % for PDAC across all stages at our center. The application of evidence-based treatment strategies through the multidisciplinary team, accompanying with standardized and comprehensive therapeutic managements, high patient adherence, have been considered as critical determinants in enhancing therapeutic efficacy and improving long-term prognosis for patients with PDAC.

Three-dimensional (3D) reconstruction technology, as a vital component of digital medicine, has emerged as a powerful tool in the field of hepatic surgery, particularly in the context of precision liver resection. This review examines the current applications and future prospects of 3D reconstruction technology in hepatic surgery, with a focus on its clinical progress in preoperative assessment, vascular protection, surgical planning, and intraoperative navigation. By accurately calculating liver volume, evaluating liver function reserves, and optimizing surgical strategies, 3D reconstruction significantly enhances the safety and efficacy of liver resection. In terms of vascular protection, 3D reconstruction enables precise localization of tumors relative to vascular structures and identification of vascular variations, thereby reducing intraoperative bleeding risks. For surgical planning, the integration of 3D reconstruction with virtual reality (VR) and augmented reality (AR) technologies allows for the creation of virtual surgical scenarios, optimization of surgical pathways, and reduction of operative time. In intraoperative navigation, 3D reconstruction combined with laparoscopic ultrasound, indocyanine green (ICG) fluorescence imaging, 3D printing, and mixed reality (MR) technologies has enabled real-time navigation, thereby improving surgical precision. Despite these advancements, 3D reconstruction technology still faces challenges, including high costs, time-consuming processes, data quality limitations, and suboptimal reconstruction of intrahepatic bile ducts. Looking ahead, the incorporation of artificial intelligence and big data into 3D reconstruction is expected to further refine preoperative planning and intraoperative navigation, driving the field of hepatic surgery toward greater intelligence and precision.

This single-center, randomized phase 3 trial (NCT03750669) evaluated sequential neoadjuvant nab-paclitaxel plus gemcitabine followed by modified FOLFIRINOX versus upfront surgery in 324 patients with resectable pancreatic cancer. Patients in the neoadjuvant group received nab-paclitaxel plus gemcitabine followed by modified FOLFIRINOX before surgery and then four cycles of adjuvant therapy (preferably gemcitabine plus capecitabine), while those in the upfront surgery group underwent immediate resection followed by six cycles of adjuvant therapy. The primary endpoint was event-free survival. Notably, 50% of patients had tumors in the pancreatic body or tail. Median event-free survival was 15.3 months (95% confidence interval [CI], 12.6-19.3) versus 10.9 months (95% CI, 9.1-13.5; hazard ratio [HR], 0.71; 95% CI, 0.54-0.93; p = 0.0136). Median overall survival was 35.4 months versus 27.2 months (HR, 0.73; 95% CI, 0.53-1.00; nominal p = 0.0477). Grade ≥3 adverse events occurred in 47.6% versus 30.7% of patients. This neoadjuvant regimen improves event-free survival with manageable safety.

571 Background: There is no universally accepted standard treatment option or strategy for post-surgery adjuvant therapy in hepatocellular carcinoma (HCC). Among BCLC A/B patients (pts) with MVI, adjuvant transarterial chemoembolization has been reported to provide a 1-year recurrence-free survival (RFS) rate of around 60-70%. We conducted a pilot study to explore the utility of donafenib combined with a PD-1 inhibitor as adjuvant therapy for pts at high risk of recurrence. Herein, we present the updated results with a median follow-up of 11.6 months. Methods: It was planned to enroll 30 HCC pts who had undergone radical surgery and presented with at least one of the following risk factors: a) Presence of microvascular invasion (MVI); b) Presence of satellite nodule(s); c) More than three tumor nodules; d) Portal vein tumor thrombus. Pts with invasion of the main portal venous system were excluded. Donafenib combined with a PD-1 inhibitor (i.e., toripalimab) was initiated at 4 to 8 weeks post-resection and was to be continued for up to six months, unless recurrence occurred or there was an intolerable adverse reaction. No other adjuvant therapies were permitted before enrollment and during the study, except for anti-virus treatment. The primary endpoint was the cumulative 1-year RFS rate. The secondary endpoints included overall survival, quality of life (QoL) measured with the FACT- Hepatobiliary questionnaire, and safety. Results: From June 2020 to November 2023, a total of 30 pts were recruited. 27 pts were included in the efficacy analysis. The median time from surgery to enrollment was 1.4 months. MVI was the most common risk factor (n=25, 92.6%). The majority of the pts had only one risk factor (n=23, 85.2%). As of the data cutoff on August 13, 2024, relapse had occurred in four pts and the median RFS was not reached. The 1-year RFS rate was 81.6% (90% CI, 67.8%-95.4%) in all evaluable pts. QoL showed a mild increase from baseline while on adjuvant therapy. No deaths were observed. In the 30 pts who had received at least one dose, the incidence of any grade and grade 3 treatment-related adverse events (TRAEs) were 90.0% (27/30) and 40.0% (12/30), respectively. No grade 4 or 5 TRAEs were reported. The grade 3 TRAEs occurring in at least two pts were palmar-plantar erythrodysesthesia syndrome (13.3%), rash (13.3%), increased alanine aminotransferase (10.0%), and increased aspartate aminotransferase (6.7%). Conclusions: The study's duration exceeded expectations due to slow recruitment. Nonetheless, it showed a promising outcome with a regimen of 6 months of adjuvant therapy with donafenib plus toripalimab in BCLC A/B pts at high risk of recurrence. An improvement in QoL was observed among patients during the adjuvant therapy. No new safety issues were identified. Clinical trial information: NCT04418401 .

BACKGROUND Portal vein stenosis (PVS) is a prevalent complication following pediatric liver transplantation (pLT) and significantly impacts long-term graft outcomes. This study assessed the efficacy and safety of balloon angioplasty and stent placement, calculated rates of restenosis or reintervention, and determined optimal interventional strategies for managing PVS following pLT. MATERIAL AND METHODS We retrospectively analyzed 884 pLT recipients at our institution. PVS occurred in 67 patients; 64 successfully underwent interventional procedures. We comparatively analyzed patients who achieved satisfactory results following initial balloon angioplasty with those who required subsequent interventions. Factors, including history of portal vein bridging and donor-recipient portal vein discrepancy rate, were analyzed. Significant factors were used to develop a logistic regression-based risk prediction model. Kaplan-Meier curves estimated patient and graft survival rates. RESULTS Fifty-two patients (81.25%) demonstrated satisfactory recovery following initial balloon angioplasty among the 64 pLT recipients with PVS. Twelve patients had restenosis; 10 underwent subsequent interventions with successful outcomes. A comparative analysis between the initial balloon angioplasty success group and the reintervention group showed significant differences between the groups with respect to portal vein bridging history and portal vein discrepancy rate (P<0.05). A logistic regression-based prediction model for restenosis was established. Kaplan-Meier survival analysis indicated an overall patient survival rate of 98.5% and a graft survival rate of 92.5% during the study period. CONCLUSIONS Patients with portal vein bridging history or poor donor-recipient PV matching are more prone to restenosis after initial balloon angioplasty. For such cases, we recommend direct stent placement as the initial treatment strategy.

ABSTRACT Introduction Standard treatments provide limited benefits for patients with intermediate‐ or advanced‐stage hepatocellular carcinoma (HCC). This retrospective observational study aimed to assess the potential improvements in outcomes associated with systemic therapies in patients receiving transarterial chemoembolization (TACE) for initially unresectable HCC. Methods Between February 2019 and March 2023, we reviewed patients diagnosed with intermediate‐to‐advanced HCC who were treated with either TACE or TACE combined with antiangiogenic agents and immune checkpoint inhibitors (combination therapy) as their initial treatment. To address potential confounding biases, patients were further stratified into surgical and non‐surgical cohorts, and separate analyses were conducted. The primary endpoints were progression‐free survival (PFS) and overall survival (OS), with safety profiles also evaluated. Results Among 279 patients with initially unresectable intermediate or advanced HCC, 156 successfully underwent curative‐intent liver resection after preoperative treatments (TACE group, n = 69; combination group, n = 87), while 123 patients continued with non‐surgical treatments (TACE group, n = 31; combination group, n = 92). After propensity score matching, 26 matched patient pairs were generated within the non‐surgical cohort. The combination group exhibited significantly improved PFS in non‐surgical patients compared with the TACE group (9.4 vs. 7.2 months, p = 0.043). Cox proportional hazards analysis further confirmed that combination therapy was associated with improved PFS (hazard ratio = 0.476, 95% confidence interval: 0.257–0.883, p = 0.019). For surgical patients exceeding the up‐to‐seven criteria, the combination group demonstrated superior median PFS (18.0 vs. 14.6 months, p = 0.03) and OS (not reached vs. 50.1 months, p = 0.049) compared with the TACE group. Adverse events were manageable, with no treatment‐related fatalities reported. Conclusion Combination therapy with TACE demonstrated enhanced survival benefits for patients with intermediate to advanced HCC, particularly in surgical patients with higher tumor burdens.

ObjectiveTo analyze the current status and influencing factors of sarcopenia in patients with bone tumors and to provide a reference for developing effective intervention programs.MethodsUsing a convenience sampling method，198 patients with bone tumors admitted to the orthopedics department of a tertiary grade A hospital in Yunnan province between August 2023 and January 2024 were recruited.Clinical data were collected， and muscle strength（grip strength），physical activity capacity（walking speed），and muscle mass（appendicular skeletal muscle index） were measured. Patients were assessed using the Patient⁃Generated Subjective Global Assessment，Kinesiophobia Scale⁃Short Form，Fried Physical Phenotype Frailty Scale， and Athens Insomnia Scale.Multivariate Logistic regression analysis was conducted to identify the influencing factors of sarcopenia in patients with bone tumors.ResultsThe incidence of sarcopenia among patients with bone tumors was 27.27%. Logistic regression analysis revealed that body mass index（BMI），regular exercise，osteoporosis，kinesiophobia，and frailty were significant influencing factors of sarcopenia in patients with bone tumors（P<0.05）.ConclusionThe prevalence of sarcopenia is high in patients with bone tumors. Healthcare professionals should promptly identify high⁃risk groups for sarcopenia and implement nutritional，exercise，and psychological interventions to improve patient outcomes.

BACKGROUND:Transcatheter arterial chemoembolization (TACE) combined with lenvatinib is an important modality for the treatment of unresectable hepatocellular carcinoma (HCC). To date, no prognostic analysis exists for clinical predictive models of TACE combined with lenvatinib in treating advanced unresectable HCC. A model was constructed through meta-analysis, and its validation was further enhanced by the collection of external clinical data, thereby providing guidance for clinical practice. AIM:To identify risk factors for unresectable HCC following TACE plus lenvatinib therapy and to construct a clinical prediction model. METHODS:We searched PubMed, Web of Science, EMBASE, and Cochrane Library databases for studies on TACE plus lenvatinib for unresectable HCC. Risk factors from the meta-analysis and sensitivity analyses were used to construct a prediction model. The validation set included clinical data from 106 eligible patients at the Affiliated Hospital of North Sichuan Medical College collected by June 1, 2023. RESULTS:This study included 43 group studies involving 5070 patients. Tumor number, microvascular invasion, Eastern Cooperative Oncology Group performance status, Child-Pugh stage, Barcelona Clinic Liver Cancer stage, extrahepatic metastases, alpha-fetoprotein level, and hepatitis B virus status were risk factors for overall survival and progression-free survival, while triple therapy was a protective factor for both. In the validation set, the overall survival prediction model had area under the curve values of 0.616, 0.643, and 0.706 at 1 year, 2 years, and 3 years, respectively, and the progression-free survival model had area under the curve values of 0.702, 0.696, and 0.670 at the corresponding time points, demonstrating good model performance. Calibration curves, Kaplan-Meier survival analysis, and decision curves further validated the efficacy of the model. CONCLUSION:Models based on nine variables from 43 group studies predicted the efficacy of TACE plus lenvatinib in unresectable HCC, supporting evidence-based clinical decisions and treatment strategies.

Background and Purpose:The survival of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) was poor. This study aimed to investigate the efficacy and safety of hepatic arterial interventional therapies (HAIT) combined with lenvatinib and programmed cell death-1 (PD-1) inhibitors for HCC patients with PVTT. Methods:In this retrospective study, HCC patients with PVTT treated with HAIT combined with lenvatinib and PD-1 inhibitors (H-L-P group) or lenvatinib plus PD-1 inhibitors (L-P group) between June 2020 and December 2023 were analyzed. Overall survival (OS), progression-free survival (PFS), and tumor response were evaluated to assess the efficacy, while treatment-related adverse events (TRAEs) were evaluated to assess the safety. Propensity score matching (PSM) was applied to balance the baseline differences. Results:In this study, 208 HCC patients with PVTT were enrolled, including 120 patients in H-L-P group and 88 patients in L-P group. After PSM, there were 74 patients per group, the H-L-P group showed significantly better median OS (19 months vs 14 months, p < 0.001) and median PFS (10 months vs 4 months, p < 0.001) than L-P group; higher objective response rate (ORR) (37.8% vs 16.2%, p < 0.001) and disease control rate (DCR) (78.4% vs 47.3%, p < 0.001) were observed in the H-L-P group. All TRAEs were controlled, and the three most prevalent TRAEs in the H-L-P group were elevated aspartate aminotransferase (AST), elevated alanine aminotransferase (ALT), and vomiting. Conclusion:Combining HAIT with lenvatinib and PD-1 inhibitors is a safe and promising treatment pattern for HCC patients with PVTT.

The incidence of post-transplant poral vein stenosis (PVS) is higher in pediatric liver transplantation, probably resulting from various portal vein (PV) reconstruction methods or other factors. 332 patients less than 12 years old when receiving liver transplantation (LT) were enrolled in this research. Portal vein reconstruction methods include anastomosis to the left side of the recipient PV trunk (type 1, n = 170), to the recipient left and right PV branch patch (type 2, n = 79), using vein graft interposition (type 3, n = 32), or end-to-end PV anastomosis (type 4, n = 50). The incidence of PVS was analyzed in terms to different PV reconstruction methods and other possible risk factors. PVS occurred in 35 (10.5

e16228 Background: There is no universally accepted standard treatment option or strategy for post-surgery adjuvant therapy for HCC. Among BCLC A/B patients with MVI, adjuvant TACE provided a 1-year recurrence-free survival rate (RFSR) of around 60-70%. We conducted a pilot study to explore the utility of donafenib combined with anti-PD-1 antibody as adjuvant therapy for pts with high risks of recurrence. Methods: It was planned to enroll 30 HCC pts who had undergone radical surgery and with at least one of the following risk factors: a) Presence of microvascular invasion (MVI); b) Presence of satellite nodule(s); c) > 3 tumor nodules; d) Portal vein tumor thrombus. Pts with invasion of main portal venous were excluded. Donafenib plus anti-PD-1 antibody was initiated at 4 to 8 weeks after resection and continued for up to six months. No other adjuvant therapies were allowed before enrollment and during the study, except for anti-virus treatment. The primary endpoint was the cumulative 1-year RFSR. The secondary endpoints included recurrence-free survival (RFS), overall survival, and safety. Results: From June 2020 to November 2023, a total of 30 pts were recruited. 27 pts were included in efficacy analysis. The mean and median follow-up time was 347.9 days and 179.5 days. The mean and median time from surgery to enrollment was 42.5 days and 42.0 days. MVI was the most common risk factor (Table). Majority of the pts had only one risk factor. Relapse occurred in two pts (7.4%) and RFS was very immature. The RFSR at one year was 89.7% (90% CI, 70.6%-96.7%) in all the evaluable pts, and slightly higher in pts with M1 or only one risk factor (92.9% [90% CI, 68.1%-98.6%] and 93.3% [90% CI, 69.9%-98.7%], respectively). No deaths were observed. In 30 pts who had received at least one dose, the incidence of grade 3 treatment-related adverse events (TRAEs) was 40.0% (12/30). No grade 4 or 5 TRAEs were reported. The grade 3 TRAEs occurred in ≥2 pts were palmar-plantar erythrodysesthesia syndrome (13.3%), rash (13.3%), alanine aminotransferase increased (10.0%), and aspartate aminotransferase increased (6.7%). Conclusions: These results showed that a regimen of 6 months of adjuvant therapy with donafenib plus anti-PD-1 antibody may be efficient to reduce recurrence for BCLC A/B pts at high risk of recurrence, particularly those with ≤2 risk factors. No new safety issues were noticed. Clinical trial information: NCT04418401 . [Table: see text]

Background: Pancreatic fistula after distal pancreatectomy is a common and potentially lethal complication. The optimal closure method for the pancreatic remnant during minimally invasive distal pancreatectomy (MDP) remains unclear. Methods: Data of consecutive patients who underwent MDP in our institution between July 2018 and June 2021 were collected. The outcomes of MDP with stapler and hand-sewn closure were compared. The primary outcome was clinically relevant postoperative pancreatic fistula (CR-POPF) per the International Study Group of Pancreatic Surgery definition. Results: Of the 384 patients (stapler closure, 339; hand-sewn closure, 45) enrolled, 249 developed CR-POPF (grades B and C: 242 and 7 patients, respectively). The rates of grade B and grade C POPF in the stapler group were similar to the corresponding rates in the hand-sewn group (64.6% and 1.5% vs 51.1% and 4.4%, P = .078 and P = .223, respectively). No differences between the stapler and hand-sewn groups were observed regarding the median operation time (207 vs 222 minutes, P = .139), incidence of major complications (16.5% vs 20.0%, P = .559), and mortality (0.2% vs 0%, P = 1.000). The independent risk factors of CR-POPF were abdominal abscess, prolonged operation time, and transection site (P = .004, .006, and .001, respectively). Conclusion: The incidence and severity of CR-POPF by stapler closure of the pancreatic stump were comparable to those associated with hand-sewn closure in MDP in this retrospective cohort. Randomized controlled trials are needed to verify this finding.

Background: Transarterial chemoembolization (TACE) based neoadjuvant therapy was proven effective in hepatocellular carcinoma (HCC). Recently, tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) also showed promise in HCC treatment. However, the prognostic benefits associated with these treatments remain uncertain. This study aimed to explore the relationship between pathologic response and prognostic features in HCC patients who received neoadjuvant therapy. Methods: HCC patients who received TACE either with or without TKIs/ICIs as neoadjuvant therapy before liver resection were retrospectively collected from the First Affiliated Hospital, Zhejiang University School of Medicine in China. Pathologic response was determined by calculating the proportion of non-viable area within the tumor. Major pathologic response (MPR) was defined as the presence of non-viable tumor cells reaching a minimum of 90%. Complete pathologic response (CPR) was characterized by the absence of viable cells observed in the tumor. Results: A total of 481 patients meeting the inclusion criteria were enrolled, with 76 patients (15.8%) achieving CPR and 179 (37.2%) reaching MPR. The median recurrence-free survival (mRFS) in the CPR + MPR group was significantly higher than the non-MPR group (31.3 vs. 25.1 months). The difference in 3-year overall survival (OS) rate was not significant. Multivariate Cox regression analysis identified failure to achieve MPR (hazard ratio = 1.548, 95% confidence interval: 1.122-2.134; P = 0.008), HBsAg positivity (HR = 1.818, 95% CI: 1.062-3.115, P = 0.030), multiple lesions (HR = 2.278, 95% CI: 1.621-3.195, P < 0.001), and baseline tumor size > 5 cm (HR = 1.712, 95% CI: 1.031-2.849, P = 0.038) were independent risk factors for RFS. Subgroup analysis showed that 67 of 93 (72.0%) patients who received the combination of TACE, TKIs, and ICIs achieved MPR + CPR. Conclusions: In individuals who received TACE-based neoadjuvant therapy for HCC, failure to achieve MPR emerges as an independent risk factor for RFS. Notably, the combination of TACE, TKIs, and ICIs demonstrated the highest rate of MPR.

4108 Background: TACE-based conversion therapies are warranted for over 70% of patients with intermediate-advanced unresectable hepatocellular carcinoma (uHCC). This study aimed to investigate the efficacy and safety of envafolimab plus lenvatinib and TACE as conversion therapy in uHCC. Methods: This is an open-label, prospective, single-arm, phase II study. Eligible patients with uHCC (Barcelona Clinic Liver Cancer Stage B or C) were consecutively enrolled. Patients will receive envafolimab subcutaneously (300 mg, Q3W) and Lenvatinib orally daily (12 mg/day (body weight ≥ 60 kg) or 8 mg/day (<60 kg)) during TACE sessions. TACE will be conducted every 6 weeks on demand according to investigators’ evaluation, mainly based on the proportion of viable tumors. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version1.1 (RECIST 1.1). Secondary endpoints were disease control rate (DCR) and duration of response (DoR) per RECIST 1.1 and mRECIST, progression-free survival (PFS), overall survival (OS), and safety. Results: Between February 2022 and July 2022, 38 patients were enrolled and included for primary efficacy and safety analysis. As of December 13, 2023, the median follow-up of 16.9 months (95CI, 6.7 to 24.2). The ORR and DCR were 47.4% (95%CI, 31.0% to 64.2%) and 78.9% (95%CI, 62.7% to 90.5%) per RECIST 1.1, respectively (with ORR and DCR of both 78.9% per mRECIST). The median PFS (mPFS) was 8.78 months (95CI, 5.23 to not avaliable (NA)), and the median OS (mOS) was immature with 1-year OS of 88.9%. The median DoR assessed per RECIST 1.1 was 6.7 months (7.7 months per mRECIST). Of 38 patients, 17 patients were assessed as successful conversion with a conversion success rate of 44.7%. Sixteen patients underwent surgery with the R0 resection rate of 100%, the pathological complete response (pCR) rate of 31.3%, and major pathological response (MPR) rate of 56.3%. Of 38 patients, overall incidences of AEs of any grade was 97.4%. Grade ≥3 treatment-related adverse events (TRAEs) were observed in 20 (52.6%) patients, which mainly included increased AST (34.2%), increased ALT (18.4%), and decreased platelet count (15.8%). No treatment-related death occurred. Conclusions: Envafolimab combined with lenvatinib and TACE yielded promising survival outcomes and conversion rate with a manageable safety profile in uHCC, representing a potential and feasible conversion therapy regimen for this population. Clinical trial information: NCT05213221 .

Pancreatic ductal adenocarcinoma (PDAC)/pancreatic cancer, is a highly aggressive malignancy with poor prognosis. Gemcitabine-based chemotherapy remains the cornerstone of PDAC treatment. Nonetheless, the development of resistance to gemcitabine among patients is a major factor contributing to unfavorable prognostic outcomes. The resistance exhibited by tumors is modulated by a constellation of factors such as genetic mutations, tumor microenvironment transforms, environmental contaminants exposure. Currently, comprehension of the relationship between environmental pollutants and tumor drug resistance remains inadequate. Our study found that PFOS/6:2 Cl-PFESA exposure increases resistance to gemcitabine in PDAC. Subsequent in vivo trials confirmed that exposure to PFOS/6:2 Cl-PFESA reduces gemcitabine’s efficacy in suppressing PDAC, with the inhibition rate decreasing from 79.5% to 56.7%/38.7%, respectively. Integrative multi-omics sequencing and molecular biology analyses have identified the upregulation of ribonucleotide reductase catalytic subunit M1 (RRM1) as a critical factor in gemcitabine resistance. Subsequent research has demonstrated that exposure to PFOS and 6:2 Cl-PFESA results in the upregulation of the RRM1 pathway, consequently enhancing chemotherapy resistance. Remarkably, the influence exerted by 6:2 Cl-PFESA exceeds that of PFOS. Despite 6:2 Cl-PFESA being regarded as a safer substitute for PFOS, its pronounced effect on chemotherapeutic resistance in PDAC necessitates a thorough evaluation of its potential risks related to gastrointestinal toxicity.

AbstractEvidences regarding the feasibility of transcatheter arterial chemoembolization (TACE)-based therapy for unresectable hepatocellular carcinoma (uHCC) remains limited. This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC. Eligible patients with uHCC received envafolimab and lenvatinib after TACE until disease progression, conversion to surgery, intolerable toxicities, or death. The primary endpoint was the objective response rate (ORR) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Between March 2022 and July 2022, 38 patients were included for safety analysis, and 36 patients were included for efficacy analysis. As of the data cutoff (13 December 2023), the median follow-up was 16.9 months. The ORR was 50%, and disease control rate (DCR) was 83.3% per RECIST 1.1 (ORR and DCR of both 83.3% per modified RECIST (mRECIST)). The median progression-free survival (PFS) was 7.58 months. Of 36 patients, 17 patients were converted to resectable HCC with a surgical conversion rate of 47.2%, and 16 patients underwent surgery with R0 resection rate of 100%, pathologic complete response (pCR) rate of 31.3%. Overall incidences of treatment-related adverse events (TRAEs) of any grade was 97.4%. Grade ≥ 3 TRAEs were observed in 52.6% patients. No treatment-related deaths occurred. Image mass cytometry (IMC) analysis revealed that combined treatment improved the immune status of the tumor microenvironment, and resident macrophages had the potential to predict efficacy of this treatment. Envafolimab plus lenvatinib and TACE yielded promising survival outcomes and conversion efficiency with a tolerable safety profile. Trial registration Clinical trials: NCT05213221.

e16202 Background: Adjuvant therapy may have an important role in decreasing recurrence rates and improve survival in selected pts with HCC following surgical resection. However, there is no standard treatment options or strategies. This study aimed to investigate the safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for HCC pts with high risks of recurrence. Methods: This prospective, open-label, single-arm study planned to enroll 30 pts who had undergone radical surgery and were diagnosed as HCC confirmed by histology or cytology with any of the following risk factors: a) Microvascular invasion (MVI); b) Satellite nodules in specimens; c) >3 tumor nodules; d) Portal vein tumor thrombosis (excluded main portal vein invasion). Donafenib combined with anti-PD-1 antibody was initiated at 4 to 8 weeks after surgical resection and continued for up to six months. The primary endpoint was the cumulative 1-year recurrence-free survival rate (RFSR). The secondary endpoints were recurrence-free survival (RFS), overall survival, and safety. Results: As of December 31st, 2022, a total of 23 pts received donafenib plus anti-PD-1 antibody (toripalimab) with a mean follow-up of 7.6 months (safety set). The most common risk factor was MVI (91%). 20 pts were included in efficacy set (three pts were excluded due to ineligibility), of whom 16 pts had one risk factor and four had two. Intrahepatic recurrence occurred in 3 pts (15%) and no extrahepatic metastasis or death was reported. The RFSR at one year was 83.0% (90%CI, 61.6%-93.1%) in all the pts from efficacy set, 81.9% (90%CI, 59.6%-92.6%) and 92.3% (90%CI, 66.0%-98.5%) in pts with MVI and MVI-low risk, and 85.1% (90%CI, 59.6%-95.1%) in pts with only one risk factor. The median RFS was not reached. The incidence of grade 3 adverse events related to donafenib and/or toripalimab was 52.2% (12/23). No pts had grade 4/5 adverse events. Adverse events leading to withdrawal of any and both treatments occurred in six (26.1%) and one (4.3%) pts, respectively. The most common grade 3 treatment-related adverse events (occurred in more than one patient) were palmar-plantar erythrodysesthesia syndrome (17.4%), rash (17.4%), alanine aminotransferase increased (13.0%), and aspartate aminotransferase increased (8.7%). Conclusions: These results were consistent with earlier reports. The combination of donafenib and toripalimab may be a promising adjuvant therapy for pts with MVI, satellite nodules or multiple tumor after hepatectomy. No safety issues were noted. Clinical trial information: NCT04418401 . [Table: see text]