The Influence of Visceral Adiposity on Overall Survival: Exploring "Obesity Paradox" Among Hepatocellular Carcinoma Patients Who Receiving Immunotherapy.

Purpose: The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions. Patients and Methods: Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models. Results: A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS (P = 0.001). The protections of VATI (P = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared (P = 0.146), but the effect of SMD on OS did not (P = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI. Conclusion: This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.

CRAFITY score benefits hepatocellular carcinoma patients treated with transarterial chemoembolization and lenvatinib.

BACKGROUND: The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib. METHODS: This retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression-free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort. RESULTS: We included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p < 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p < 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS. CONCLUSIONS: The CRAFITY score, utilizing C-reactive protein and alpha-fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions.

Predicting Survival Using Whole-Liver MRI Radiomics in Patients with Hepatocellular Carcinoma After TACE Refractoriness.

PURPOSE: To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance. MATERIALS AND METHODS: Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared. RESULTS: Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > - 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007). CONCLUSION: The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance.

Prognostic Effect of Sarcopenia in Hepatocellular Carcinoma Patients Targeted with Interventional Therapy Combined with Immunotherapy and Targeted Therapy.

Objective: To investigated the association between sarcopenia and the prognosis and adverse events of hepatocellular carcinoma (HCC) patients undergoing interventional therapy combined with immunotherapy and targeted therapy. Methods: Between January 2019 and December 2022, patients with unresectable HCC who received interventional therapy combined with immunotherapy and targeted therapy were included in this study. Total skeletal muscle area at the L3 level was normalized for height in m2 as the skeletal muscle index (SMI). All patients were divided into low and high SMI group according to the median SMI. Results: Ninety-six consecutive patients were included eventually, with 49 patients in the high-SMI group and 47 patients in the low-SMI group. In the low-SMI group, the median overall survival (OS) was 459.00 days (95% CI, 334.76-583.24 days), and the 3-, 6-, and 12-month OS rates were 100%, 89.4% and 68.1%, respectively. In the high-SMI group, the median OS was not reached, and the 3-, 6-, and 12-month OS rates were 100%, 98% and 79.5%, respectively (p<0.05). SMI and Barcelona Clinic Liver Cancer (BCLC) C stage were independent prognostic factors for OS (p<0.05). In the low-SMI group, 26 patients had treatment-related adverse events (TRAEs), resulting in dose adjustment or treatment suspension for 10 patients. In the high-SMI group, 33 patients had TRAEs, and 18 patients received dose adjustment or treatment suspension; the between-group difference was nonsignificant (p>0.05). Conclusion: SMI is associated with the prognosis of HCC patients receiving interventional therapy combined with immunotherapy and targeted therapy, and sarcopenia is an independent risk factor for OS. However, sarcopenia does not seem to predict the occurrence of adverse events.

The Role of GNMT and MMP12 Expression in Determining TACE Efficacy: Validation at Transcription and Protein Levels.

Purpose: Transarterial chemoembolization (TACE) represents a significant therapeutic modality for hepatocellular carcinoma (HCC). We aimed to develop a gene signature to accurately predict patient TACE response and explore the underlying mechanisms. Methods: Three independent datasets were utilized, including GSE104580, GSE14520 and external validation from the Cancer Hospital Chinese Academy of Medical Sciences. GSE104580 was randomly partitioned into a training set and a validation set, whereas GSE14520 was categorized into a resection group and a TACE group. Logistic regression was used to develop a TACE effectiveness model. Immunohistochemistry is utilized to confirm the protein expression trends of the signature genes. Immune infiltration and functional enrichment analyses were conducted to investigate the potential underlying mechanisms. Results: A 2-gene signature consisting of glycine N-methyltransferase (GNMT) and matrix metalloproteinase-12 (MMP12) was constructed, and based on this, all the patients were assigned TACE effectiveness scores and categorized into high effectiveness (HE) and low effectiveness (LE) groups. The HE group exhibited a better prognosis than the LE group in the various cohorts (p < 0.05). In the external validation set, immunohistochemistry confirmed the expression of the signature genes exhibiting an upregulated trend of GNMT in the HE group and MMP12 in the LE group, the LE group also exhibited a poorer prognosis [for overall survival (OS), HE group: 881 days vs LE group: 273 days (p < 0.05), and for progression-free survival (PFS), HE group: 458 days vs LE group: 136 days (p < 0.05)]. Multivariate analysis in all the datasets identified LE status as an independent risk factor for OS, disease-free survival (DFS) and PFS. The infiltration level of M0 macrophages and activated mast cells in the LE group was significantly higher than in the HE group. The hypoxia signaling pathway and glycolysis pathway were significantly enriched in the LE group. Conclusion: The loss of GNMT and the overexpression of MMP12 may be critical factors influencing TACE efficacy.

Reclassification of therapeutic response of unresectable hepatocellular carcinoma to anti-angiogenic therapy and immunotherapy using alpha RECIST.

OBJECTIVES: To assess the therapeutic response of HCC to antiangiogenic therapy plus immunotherapy by integrating RECIST 1.1 and alpha-fetoprotein (AFP) response at the 6th week to predict overall survival (OS). METHODS: This retrospective study included 150 and 214 patients with HCC who received combination therapy in training and validation cohorts. The medical images and AFP levels obtained at baseline and 6th week were collected. AFP response stratification: partial response (PR): AFP% ≥ 75% decline; stable disease (SD): AFP% < 75% decline and ≤ 10% elevation; progressive disease (PD): AFP% > 10% elevation. The alpha-RECIST was: PR: RECIST 1.1-PR or AFP-PR; PD: AFP-PD or RECIST 1.1-PD and does not satisfy AFP-PR; SD: neither PR nor PD. OS was compared using Kaplan-Meier curves. The predictive ability of various criteria was evaluated using the concordance index and time-dependent area under the receiver-operating characteristic curve. RESULTS: RECIST 1.1 achieved significant OS stratification (p = 0.020) for AFP < 20 ng/mL. For AFP ≥ 20 ng/mL, alpha-RECIST showed better performance than RECIST 1.1, mRECIST, and AFP response according to C-index (0.73 vs 0.66 vs 0.68 vs 0.69). The National Cancer Center (NCC) strategy utilized RECIST 1.1 for AFP < 20 ng/mL and alpha-RECIST for AFP ≥ 20 ng/mL and showed better performance than RECIST 1.1, mRECIST and AFP response according to C-index (0.73 vs 0.67 vs 0.69 vs 0.64). The performances of alpha-RECIST and NCC Strategy were confirmed in the validation cohort (C-index = 0.77 and 0.74). CONCLUSIONS: The alpha-RECIST and NCC Strategy achieved better survival stratification in patients with HCC under combination therapy in the AFP ≥ 20 ng/mL group and the whole cohort compared to the RECIST 1.1, mRECIST, and AFP response. CLINICAL TRANSLATIONAL RELEVANCE: The alpha-RECIST and National Cancer Center strategy are optimal methods for determining therapeutic response to a combination of anti-angiogenic therapy plus immunotherapy and facilitating accurate prognostic stratification for HCC in the AFP ≥ 20 ng/mL group and the whole cohort, which may help oncologists for early identification of responders and progression at 6 weeks and clinical decision-making. KEY POINTS: • RECIST 1.1 is indicated for patients with baseline alpha-fetoprotein (AFP) < 20 ng/mL. • For patients with baseline AFP ≥ 20 ng/mL, integrating RECIST 1.1 and AFP response (alpha-RECIST) may aid in the early identification of survival benefits and progression definition prior to the administration of additional efficacious drugs. • The National Cancer Center strategy is an optimal stratified strategy for determining therapeutic response to a combination of anti-angiogenic therapy and immunotherapy for HCC based on baseline AFP levels.

Cuproptosis-related immune checkpoint gene signature: Prediction of prognosis and immune response for hepatocellular carcinoma.

Immune checkpoint genes (ICGs), the foundation of immunotherapy, are involved in the incidence and progression of hepatocellular carcinoma (HCC). Cuproptosis is characterized by copper-induced cell death, and this novel cell death pathway has piqued the interest of researchers in recent years. It is worth noting that there is little information available in the literature to determine the relationship between cuproptosis and anti-tumor immunity. We identified 39 cuproptosis-related ICGs using ICGs co-expressed with cuproptosis-related genes. A prognostic risk signature was constructed using the Cox regression and the least absolute shrinkage and selection operator analysis methods. The signature was built using the Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma database. The TCGA and International Cancer Genome Consortium cohorts were classified into two groups; the low- and high-risk groups were determined using a prognostic signature comprised of five genes. The multivariate Cox regression analysis revealed that the signature could independently predict overall survival. Furthermore, the level of immune infiltration analysis revealed the robustness of the prognostic signature-immune cell infiltration relationship observed for Tregs, macrophages, helper T cells, and naive B cells. Both groups showed significant differences in immune checkpoint expression levels. The gene enrichment analysis was used for characterization, and the results revealed that enriching various pathways such as PI3K-AKT-mTOR signaling, glycolysis, Wnt/beta-catenin signaling, and unfolded protein response could potentially influence the prognosis of patients with HCC and the level of immune infiltration. The sensitivity of the two groups of patients to various drug-targeted therapy methods and immunotherapy was analyzed. In conclusion, the findings presented here lay the foundation for developing individualized treatment methods for HCC patients. The findings also revealed that studying the cuproptosis-based pathway can aid in the prognosis of HCC patients. It is also possible that cuproptosis contributes to developing anti-tumor immunity in patients.

Efficacy and safety of atezolizumab plus bevacizumab combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma.

Background: Atezolizumab plus bevacizumab has been proved to have promising antitumor activity and tolerable safety in patients with unresectable hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) also demonstrated high response rates and favorable survival for patients with advanced HCC. This study aimed to explore the preliminary clinical efficacy and safety of atezolizumab plus bevacizumab combined with HAIC for patients with treatment-naive advanced HCC. Methods: Between October 2020 and September 2021, patients with advanced HCC who initially received atezolizumab plus bevacizumab combined with HAIC of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) from three hospitals in China were reviewed for eligibility. The efficacy was evaluated by tumor response rate and survival, and the safety was evaluated by the frequency of key adverse events (AEs). Results: In total, 52 eligible patients with advanced HCC who received triple therapy were included in this study. The objective response rates (ORRs) based on mRECIST and RECIST1.1 criteria were 67.3% and 44.2%, respectively. The median progression-free survival (PFS) of patients was 10.6 months (95% CI, 8.37-13.8), and the overall survival (OS) was not reached. Extrahepatic metastasis was an independent risk factor associated with PFS. All AEs were controlled and no treatment-related deaths occurred. Conclusion: Atezolizumab plus bevacizumab combined with HAIC-FOLFOX had a significant therapeutic effect and manageable AEs in patients with advanced HCC, which may be a potential treatment option for advanced HCC.

A Machine Learning Model Based on Health Records for Predicting Recurrence After Microwave Ablation of Hepatocellular Carcinoma.

Background and Aim: Early recurrence (ER) presents a challenge for the survival prognosis of patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate machine learning (ML) models using clinical data for predicting ER after microwave ablation (MWA). Methods: Between August 2005 and December 2019, 1574 patients with early-stage HCC underwent MWA at four hospitals were reviewed. Then, 36 clinical data points per patient were collected, and the patients were assigned to the training, internal, and external validation set. Apart from traditional logistic regression (LR), three ML models-random forest, support vector machine, and eXtreme Gradient Boosting (XGBoost)-were built and validated for their predictive ability with the area under ROC curve (AUC). Algorithms such as SHapley Additive exPlanations (SHAP) and local interpretable model-agnostic explanations (LIME) were used to realize their interpretability. Results: The three ML models all outperformed LR (P < 0.001 for all) in predictive ability. When nine variables (tumor number, platelet, α-fetoprotein, comorbidity score, white blood cell, cholinesterase, prothrombin time, neutrophils, and etiology) were extracted simultaneously using recursive feature elimination with cross-validation, the XGBoost model achieved the best discrimination among all models, with an AUC value 0.75 (95% CI [confidence interval]: 0.72-0.78) in the training set, 0.74 (95% CI: 0.69-0.80) in the internal validation set, and 0.76 (95% CI: 0.70-0.82) in the external validation set, and it was interpreted depending on the visualization of risk factors by the SHAP and LIME algorithms. The predictive system of post-ablation recurrence risk stratification was provided on online (http://114.251.235.51:8001/) based on XGboost analysis. Conclusion: The XGBoost model based on clinical data can effectively predict ER risk after MWA, which can contribute to surveillance, prevention, and treatment strategies for HCC.

Effects of Early TACE Refractoriness on Survival in Patients with Hepatocellular Carcinoma: A Real-World Study.

Purpose: To investigate the effect of early transarterial chemoembolization (TACE) refractoriness on hepatocellular carcinoma (HCC) patient survival and to explore whether viable lesions > 50% after two consecutive TACE treatments negatively affect the prognosis of HCC patients. Patients and Methods: From January 2014 to August 2017, 323 HCC patients who received TACE as the initial treatment were analyzed. TACE refractoriness was diagnosed according to the Japan Society of Hepatology 2021 version. Propensity score matching (PSM) was used to create a 1:1 matched group (nonrefractoriness vs refractoriness). To determine survival outcomes and prognostic factors, the Kaplan-Meier method and Cox proportional hazards model were used. Results: In total, 51.1% of patients developed early TACE refractoriness (n = 165). After PSM, 120 patients from each group were matched and analyzed. The median overall survival (OS) time of the early TACE refractoriness group was significantly shorter than that of the nonrefractory group [21 months (95% CI: 15.7-26.3) vs 34 months (95% CI: 27.5-40.5), p = 0.002]. Thirty-eight patients with viable lesions >50% after two consecutive TACE procedures were identified and matched with patients of non-refractoriness. No significant difference in median OS was observed [35 months (95% CI: 21.6-48.5) vs 31 months (95% CI: 25.4-36.6), p = 0.611]. Multivariate analysis revealed that the BCLC stage, tumor size, tumor capsule, tumor distribution, α-fetoprotein level (AFP), and early TACE refractoriness were independent risk factors for prognosis in HCC patients. Conclusion: Early TACE refractoriness may shorten the OS of HCC patients. However, viable lesions >50% after two consecutive TACE treatments did not impair the survival of patients. It may be inappropriate to consider these patients as having developed TACE refractoriness.

[Comparison of Clinical Efficacy of Thermal Ablation vs. Surgical Resection of Metachronous Colorectal Liver Metastasis].

Objective: To compare the treatment efficacy of thermal ablation versus surgical resection of metachronous colorectal liver metastasis (CRLM) and to explore the potential candidates suited for thermal ablation. Methods: The data of 319 patients with CRLM who underwent radical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences between November 2007 and January 2021 were retrospectively collected. The patients were divided into two groups, the thermal ablation group and the surgical resection group, according to the actual treatments they received. Propensity score matching (PSM) was applied to balance the baseline characteristics between the two groups. Cox regression analysis was conducted to identify the risk factors for recurrence and survival. Survival analysis was performed for intergroup comparison. Results: Using PSM at 1∶1 ratio, 92 patients were included in the thermal ablation group and 92 patients were included in the surgical resection group.The median overall survival (OS) in the thermal ablation group was 49 (95% confidence interval, 37-76) months, which was shorter than that of the surgical resection group ( P<0.01). Multivariate Cox regression analysis indicated that the T staging of primary tumor, number of metastatic tumor, maximum diameter of metastatic tumor, preoperative serum carcinoembryonic antigen (CEA) level, and treatment method were independent risk factors affecting OS. Compared with the surgical resection group, the thermal ablation group demonstrated higher hepatic recurrence rate (59.8% vs. 23.9%, P<0.01), shorter disease-free survival (DFS) (10 months vs. 33 months, P<0.01), and shorter length of hospital stay (7 days vs. 14 days, P<0.01). Subgroup analysis, conducted with the data of the 319 patients before PSM, showed that early recurrence patients who underwent thermal ablation or surgical resection had comparable median OS (29 months vs. 42 months, P=0.35). For the non-early recurrence patients, the median OS of the thermal ablation group was shorter than that of the surgical resection group ( P<0.01). Conclusion: For the treatment of CRLM, the efficacy of surgical resection was better than that of thermal ablation. However, the efficacy was comparable between the two treatments for early recurrence patients of CRLM.

Gastrodin modified polyurethane conduit promotes nerve repair via optimizing Schwann cells function.

Peripheral nerve regeneration and functional recovery remain a major clinical challenge. Nerve guidance conduit (NGC) that can regulate biological behavior of Schwann cells (SCs) and facilitate axonal regeneration through microenvironmental remodeling is beneficial for nerve regeneration and functional recovery. Gastrodin, a main constituent of a Chinese traditional herbal medicine, has been known to display several biological and pharmacological properties, especially antioxidative, anti-inflammatory and nerve regeneration. Herein, polyurethane (PU) NGCs modified by different weight ratio of Gastrodin (0, 1 and 5 wt%) were designed for sequential and sustainable drug release, that created a favorable microenvironment for nerve regeneration. The scaffold showed suitable pore structure and biocompatibility in vitro, and evidently promoted morphological and functional recovery of regenerated sciatic nerves in vivo. Compared to the PU and 1%Gastrodin/PU scaffolds, the 5%Gastrodin/PU significantly enhanced the proliferation, migration and myelination of SCs and up-regulated expression of neurotrophic factors, as well as induction of the differentiation of PC12 cells. Interestingly, the obvious anti-inflammatory response was observed in 5%Gastrodin/PU by reduced expression of TNF-α and iNOS, which also evidenced by the few fibrous capsule formation in the subcutaneous implantation. Such a construct presented a similarity to autograft in vivo repairing a 10 mm sciatic nerve defects. It was able to not only boost the regenerated area of nerve and microvascular network, but also facilitate functional axons growth and remyelination, leading to highly improved functional restoration. These findings demonstrate that the 5%Gastrodin/PU NGC efficiently promotes nerve regeneration, indicating their potential for use in peripheral nerve regeneration applications.

Synergistic anti-inflammatory and osteogenic n-HA/resveratrol/chitosan composite microspheres for osteoporotic bone regeneration.

The development of functional materials for osteoporosis is ultimately required for bone remodeling. However, grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation. In this work, nano-hydroxyapatite (n-HA)/resveratrol (Res)/chitosan (CS) composite microspheres were designed to create a beneficial microenvironment and help improve the osteogenesis by local sustained release of Res. Study of in vitro release confirmed the feasibility of n-HA/Res/CS microspheres for controlled Res release. Notably, microspheres had anti-inflammatory activity evidenced by the decreased expression of pro-inflammatory cytokines TNF-α, IL-1ß and iNOS in RAW264.7 cells in a dose dependent manner. Further, enhanced adhesion and proliferation of BMSCs seeded onto microspheres demonstrated that composite microspheres were conducive to cell growth. The ability to enhance osteo-differentiation was supported by up-regulation of Runx2, ALP, Col-1 and OCN, and substantial mineralization in osteogenic medium. When implanted into bone defects in the osteoporotic rat femoral condyles, enhanced entochondrostosis and bone regeneration suggested that the n-HA/Res/CS composite microspheres were more favorable for impaired fracture healing. The results indicated that optimized n-HA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.

Assessment of the Outcomes of Intrahepatic Cholangiocarcinoma After Ultrasound-Guided Percutaneous Microwave Ablation Based on Albumin-Bilirubin Grade.

OBJECTIVE: To determine whether albumin-bilirubin (ALBI) grade could be used to predict the outcomes of patients with intrahepatic cholangiocarcinoma (ICC) who underwent ultrasound-guided percutaneous microwave ablation (MWA). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. We studied 52 treatment-naïve patients with 74 ICC lesions according to the Milan criteria who subsequently underwent MWA from April 2011 to March 2018. Overall survival (OS) and recurrence-free survival (RFS) were compared in groups classified by Child-Pugh score and ALBI grade, which were statistically analyzed with the log-rank test. Cox proportional hazard regression analyses were used to determine the prognostic factors for survival in patients with ICC. RESULTS: The median follow-up time was 21.2 months (3.2-78.7 months). Seventeen patients died during this period. After MWA, the cumulative 1-, 3-, and 5-year OS rates were 87.4%, 51.4%, and 35.2%, respectively, and the cumulative 1-, 3-, and 5-year RFS rates were 68.9%, 56.9%, and 56.9%, respectively. The major complication rate was 3.8% (2/52). Stratified according to ALBI grade, the cumulative 1-, 3-, and 5-year OS rates were 95.5%, 72.4%, and 72.4% for patients with ALBI grade 1 and 62.5%, 40.6%, and 36.3% for patients with ALBI grade 2, respectively, showing a significant difference (P = 0.006). Multivariate analysis results showed that older age (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.11-2.82; P = 0.002), tumor size ≥ 3 cm in diameter (HR: 11.33, CI: 2.24-34.52; P = 0.021) and ALBI grade (HR: 8.23, CI: 1.58-58.00; P = 0.004) may be predictors of poor OS. CONCLUSION: ALBI grade was validated as a significant biomarker for predicting survival in ICC patients within the Milan criteria who underwent MWA.

Syntheses and characterization of anti-thrombotic and anti-oxidative Gastrodin-modified polyurethane for vascular tissue engineering.

Vascular grafts must avoid negative inflammatory responses and thrombogenesis to prohibit fibrotic deposition immediately upon implantation and promote the regeneration of small diameter blood vessels (<6 mm inner diameter). Here, polyurethane (PU) elastomers incorporating anti-coagulative and anti-inflammatory Gastrodin were fabricated. The films had inter-connected pores with porosities equal to or greater than 86% and pore sizes ranging from 250 to 400 µm. Incorporation of Gastrodin into PU films resulted in desirable mechanical properties, hydrophilicity, swelling ratios and degradation rates without collapse. The released Gastrodin maintained bioactivity over 21 days as assessed by its anti-oxidative capability. The Gastrodin/PU had better anti-coagulation response (less observable BSA, fibrinogen and platelet adhesion/activation and suppressed clotting in whole blood). Red blood cell compatibility, measured by hemolysis, was greatly improved with 2Gastrodin/PU compared to other Gastrodin/PU groups. Notably, Gastrodin/PU upregulated anti-oxidant factors Nrf2 and HO-1 expression in H2O2 treated HUVECs, correlated with decreasing pro-inflammatory cytokines TNF-α and IL-1ß in RAW 264.7 cells. Upon implantation in a subcutaneous pocket, PU was encapsulated by an obvious fibrous capsule, concurrent with a large amount of inflammatory cell infiltration, while Gastrodin/PU induced a thinner fibrous capsule, especially 2Gastrodin/PU. Further, enhanced adhesion and proliferation of HUVECs seeded onto films in vitro demonstrated that 2Gastrodin/PU could help cell recruitment, as evidenced by rapid host cell infiltration and substantial blood vessel formation in vivo. These results indicate that 2Gastrodin/PU has the potential to facilitate blood vessel regeneration, thus providing new insight into the development of clinically effective vascular grafts.

Cholecystectomy is associated with higher risk of recurrence after microwave ablation of hepatocellular carcinoma: a propensity score matching analysis.

Objective: To explore the association between cholecystectomy and the prognostic outcomes of patients with hepatocellular carcinoma (HCC) who underwent microwave ablation (MWA). Methods: Patients with HCC (n = 921) who underwent MWA were included and divided into cholecystectomy (n = 114) and non-cholecystectomy groups (n = 807). After propensity score matching (PSM) at a 1:2 ratio, overall survival (OS) and disease-free survival (DFS) rates were analyzed to compare prognostic outcomes between the cholecystectomy (n = 114) and non-cholecystectomy groups (n = 228). Univariate and multivariate Cox analyses were performed to assess potential risk factors for OS and DFS. Major complications were also compared between the groups. Results: After matching, no significant differences between groups were observed in baseline characteristics. The 1-, 3-, and 5-year OS rates were 96.5%, 82.1%, and 67.1% in the cholecystectomy group, and 97.4%, 85.2%, and 74.4% in the non-cholecystectomy group (P = 0.396); the 1-, 3-, and 5-year DFS rates were 58.4%, 34.5%, and 26.6% in the cholecystectomy group, and 73.6%, 44.7%, and 32.2% in the non-cholecystectomy group (P = 0.026), respectively. The intrahepatic distant recurrence rate in the cholecystectomy group was significantly higher than that in the non-cholecystectomy group (P = 0.026), and the local tumor recurrence and extrahepatic recurrence rates did not significantly differ between the groups (P = 0.609 and P = 0.879). Multivariate analysis revealed that cholecystectomy (HR = 1.364, 95% CI 1.023-1.819, P = 0.035), number of tumors (2 vs. 1: HR = 2.744, 95% CI 1.925-3.912, P < 0.001; 3 vs. 1: HR = 3.411, 95% CI 2.021-5.759, P < 0.001), and γ-GT levels (HR = 1.003, 95% CI 1.000-1.006, P < 0.024) were independent risk factors for DFS. The best γ-GT level cut-off value for predicting median DFS was 39.6 U/L (area under the curve = 0.600, P < 0.05). A positive correlation was observed between cholecystectomy and γ-GT level (r = 0.108, 95% CI -0.001-0.214, P = 0.047). Subgroup analysis showed that the DFS rates were significantly higher in the non-cholecystectomy group than the cholecystectomy group when γ-GT ≥39.6 U/L (P = 0.044). The 5-, 10-, 15-, 20-, and 25-year recurrence rates from the time of cholecystectomy were 2.63%, 21.93%, 42.11%, 58.77%, and 65.79%, respectively. A significant positive correlation was observed between cholecystectomy and the time from cholecystectomy to recurrence (r = 0.205, 95% CI 0.016-0.379, P = 0.029). There were no significant differences in complications between groups (P = 0.685). Conclusions: Patients with HCC who underwent cholecystectomy were more likely to develop intrahepatic distant recurrence after MWA, an outcome probably associated with increased γ-GT levels. Moreover, the recurrence rates increased with time.