Enhanced stiffness in peri-cancerous tissue: a marker of poor prognosis in papillary thyroid carcinoma with lymph node metastasis.

BACKGROUND: The prognostic significance of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains controversial. Notably, there is evidence suggesting an association between tissue stiffness and the aggressiveness of the disease. We therefore aimed to explore the effect of tissue stiffness on LNM-related invasiveness in PTC patients. METHOD: A total of 2492 PTC patients from 3 hospitals were divided into an LNM group and a non-LNM group based on their pathological results. The effects of interior lesion stiffness (E) and peri-cancerous tissue stiffness (Eshell) on the LNM-related recurrence rate and mortality in each patient with PTC subgroup were analyzed. The activation of cancer-associated fibroblasts (CAFs) and extracellular matrix component type 1 collagen (COL-I) in the lesion were compared and analyzed across different subgroups. The underlying biological basis of differences in each subgroup was identified using RNA sequencing (RNA-seq) data. RESULTS: The Eshell value and Eshell/E in the LNM group were significantly higher than those in the non-LNM group of patients with PTC (Eshell: 72.72 ±â€…5.63 vs 66.05 ±â€…4.46; Eshell/E: 1.20 ±â€…1.72 vs 1.09 ±â€…1.10, P < .001). When Eshell/E > 1.412 and LNM were both present, the recurrence rate and mortality were significantly increased compared to those of group of patients with LNM (91.67% and 7.29%, respectively). The CAF activation and COL-I content in the Eshell/E+ group were significantly higher than those in the Eshell/E- group (all P < .001), and the RNA-seq results revealed significant extracellular matrix (ECM) remodeling in the LNM-Eshell/E+ group. CONCLUSIONS: Stiff peri-cancerous tissue induced CAF activation, COL-I deposition, and ECM remodeling, resulting in a poor prognosis for PTC patients with LNM.

Evaluation of models to predict prognosis in patients with advanced hepatocellular carcinoma treated with TACE combined with apatinib.

BACKGROUND: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. METHODS: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. RESULTS: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. CONCLUSION: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.

Heterogeneous-Structure-Based AuNBs@TiO2 Nano-Photosensitizers for Computed Tomography Imaging Guided NIR-II Photodynamic Therapy and Cancer Metastatic Prevention.

Photodynamic therapy (PDT) is a minimally invasive cancer treatment that, despite its significant attention, faces limitations in penetration depth, which restrict its effectiveness. Herein, it is found that gold nanobipyramid (AuNBs) coated with TiO2 can form a core-shell heterogeneous structure (AuNBs@TiO2) with strong absorption at second near infrared (NIR-II) region. A substantial quantity of reactive oxygen species (ROS), including singlet oxygen (1O2), superoxide anion radicals, and hydroxyl radicals, can be rapidly generated when subjecting the AuNBs@TiO2 aqueous suspension to 1064 nm laser irradiation. The quantum yield for sensitization of 1O2 by AuNBs@TiO2 is 0.36 at 1064 nm light excitation. In addition, the Au element as high-Z atoms in the nanosystem can improve the ability of computed tomographic (CT) imaging. As compared to commercial iohexol, the AuNBs@TiO2 nanoparticle exhibits significantly better CT imaging effect, which can be used to guide PDT. In addition, the nano-photosensitizer shows a remarkable therapeutic effect against established solid tumors and prevents tumor metastasis and potentiates immune checkpoint blockade therapy. More importantly, here the great potentials of AuNBs@TiO2 are highlighted as a theranostic platform for CT-guided cancer photodynamic immunotherapy.

Sustained release hypoxia-activated prodrug-loaded BSA nanoparticles enhance transarterial chemoembolization against hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but facing the problem of low therapeutic effect. Conventional TACE formulations contain Lipiodol (LP) and chemotherapeutic agents characterized by burst release due to the unstable emulsion. Herein, we developed a novel TACE system by inducing bovine serum albumin (BSA) loaded hypoxia-activated prodrug (tirapazamine, TPZ) nanoparticle (BSATPZ) for sustained drug release. In the rabbit VX2 liver cancer model, TACE treatment induced a long-term hypoxic tumor microenvironment as demonstrated by increased expression of HIF-1α in the tumor. BSATPZ nanoparticles combined with LP greatly enhanced the anti-tumor effects of the TACE treatment. Compared to conventional TACE treatment, BSATPZ nanoparticle-based TACE therapy more significantly delayed tumor progression and inhibited the metastases in the lungs. The effects could be partially mediated by the rebuilt immune responses, as BSATPZ nanoparticle can served as an immunogenic cell death (ICD) inducer. Collectively, our results suggest that BSATPZ nanoparticle-based TACE therapy could be a promising strategy to improve clinical outcomes for patients with HCC and provide a preclinical rationale for evaluating TPZ therapy in clinical studies.

Efficacy and safety of precision-guided transjugular extrahepatic portosystemic shunt (TEPS) in the management of cavernous transformation of the portal vein with portal hypertension: a case series.

BACKGROUND AND AIMS: Performing a Transjugular intrahepatic portal system shunt (TIPS) in patients with portal vein cavernous transformation (CTPV) poses significant challenges. As an alternative, transjugular extrahepatic portal vein shunt (TEPS) may offer a potential solution for these patients. Nonetheless, the effectiveness and safety of TEPS remain uncertain. This case series study aimed to evaluate the efficacy and safety of TEPS in treating patients with CTPV portal hypertension complications. METHODS: The study encompassed a cohort of 22 patients diagnosed with CTPV who underwent TEPS procedures. Of these, 13 patients manifested recurrent hemorrhagic episodes subsequent to conventional therapies, 8 patients grappled with recurrent or refractory ascites, and 1 patient experienced acute bleeding but refused endoscopic treatment. Comprehensive postoperative monitoring was conducted for all patients to rigorously evaluate both the technical and clinical efficacy of the intervention, as well as long-term outcomes. RESULTS: The overall procedural success rate among the 22 patients was 95.5% (21/22).During the TEPS procedure, nine patients were guided by percutaneous splenic access, three patients were guided by percutaneous hepatic access, five patients were guided by transmesenteric vein access from the abdomen, and two patients were guided by catheter marking from the hepatic artery. Additionally, guidance for three patients was facilitated by pre-existing TIPS stents. The postoperative portal pressure gradient following TEPS demonstrated a statistically significant decrease compared to preoperative values (24.95 ± 3.19 mmHg vs. 11.48 ± 1.74 mmHg, p < 0.01).Although three patients encountered perioperative complications, their conditions ameliorated following symptomatic treatment, and no procedure-related fatalities occurred. During a median follow-up period of 14 months, spanning a range of 5 to 39 months, we observed four fatalities. Specifically, one death was attributed to hepatocellular carcinoma, while the remaining three were ascribed to chronic liver failure. During the follow-up period, no instances of shunt dysfunction were observed. CONCLUSIONS: Precision-guided TEPS appears to be a safe and efficacious intervention for the management of CTPV.

Hepatic-associated vascular morphological assessment to predict overt hepatic encephalopathy before TIPS: a multicenter study.

BACKGROUND: To provide patients the chance of accepting curative transjugular intrahepatic portosystemic shunt (TIPS) rather than palliative treatments for portal hypertension-related variceal bleeding and ascites, we aimed to assess hepatic-associated vascular morphological change to improve the predictive accuracy of overt hepatic encephalopathy (HE) risks. METHODS: In this multicenter study, 621 patients undergoing TIPS were subdivided into training (413 cases from 3 hospitals) and external validation datasets (208 cases from another 3 hospitals). In addition to traditional clinical factors, we assessed hepatic-associated vascular morphological changes using maximum diameter (including absolute and ratio values). Three predictive models (clinical, hepatic-associated vascular, and combined) were constructed using logistic regression. Their discrimination and calibration were compared to test the necessity of hepatic-associated vascular assessment and identify the optimal model. Furthermore, to verify the improved performance of ModelC-V, we compared it with four previous models, both in discrimination and calibration. RESULTS: The combined model outperformed the clinical and hepatic-associated vascular models (training: 0.814, 0.754, 0.727; validation: 0.781, 0.679, 0.776; p < 0.050) and had the best calibration. Compared to previous models, ModelC-V showed superior performance in discrimination. The high-, middle-, and low-risk populations displayed significantly different overt HE incidence (p < 0.001). Despite the limited ability of pre-TIPS ammonia to predict overt HE risks, the combined model displayed a satisfactory ability to predict overt HE risks, both in the low- and high-ammonia subgroups. CONCLUSION: Hepatic-associated vascular assessment improved the predictive accuracy of overt HE, ensuring curative chances by TIPS for suitable patients and providing insights for cirrhosis-related studies.

Prognostic Evaluation for Hepatocellular Carcinoma with Portal Vein Tumor Thrombus Patients Treated with Transarterial Chemoembolization Plus Molecular Targeted Therapies-Development and Validation of the ABPS Score.

RATIONALE AND OBJECTIVES: Transarterial chemoembolization (TACE) plus molecular targeted therapies has emerged as the main approach for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). A robust model for outcome prediction and risk stratification of recommended TACE plus molecular targeted therapies candidates is lacking. We aimed to develop an easy-to-use tool specifically for these patients. METHODS: A retrospective analysis was conducted on 384 patients with HCC and PVTT who underwent TACE plus molecular targeted therapies at 16 different institutions. We developed and validated a new prognostic score which called ABPS score. Additionally, an external validation was performed on data from 200 patients enrolled in a prospective cohort study. RESULTS: The ABPS score (ranging from 0 to 3 scores), which involves only Albumin-bilirubin (ALBI, grade 1: 0 score; grade 2: 1 score), PVTT(I-II type: 0 score; III-IV type: 1 score), and systemic-immune inflammation index (SII,<550 × 1012: 0 score; ≥550 × 1012: 1 score). Patients were categorized into three risk groups based on their ABPS score: ABPS-A, B, and C (scored 0, 1-2, and 3, respectively). The concordance index (C-index) of the ABPS scoring system was calculated to be 0.802, significantly outperforming the HAP score (0.758), 6-12 (0.712), Up to 7 (0.683), and ALBI (0.595) scoring systems (all P < 0.05). These research findings were further validated in the external validation cohorts. CONCLUSION: The ABPS score demonstrated a strong association with survival outcomes and radiological response in patients undergoing TACE plus molecular targeted therapy for HCC with PVTT. The ABPS scoring system could serve as a valuable tool to guide treatment selection for these patients.