Prognostic significance of pan-immune-inflammation value in hepatocellular carcinoma treated by curative radiofrequency ablation: potential role for individualized adjuvant systemic treatment.

BACKGROUND: This study aimed to explore the prognostic role of pan-immune-inflammation value (PIV) and develop a new risk model to guide individualized adjuvant systemic treatment following radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with early-stage HCC treated by RFA were randomly divided into training cohort A (n = 65) and testing cohort B (n = 68). Another 265 counterparts were enrolled into external validating cohort C. Various immune-inflammatory biomarkers (IIBs) were screened in cohort A. Prognostic role of PIV was evaluated and validated in cohort B and C, respectively. A nomogram risk model was built in cohort C and validated in pooled cohort D. Clinical benefits of adjuvant anti-angiogenesis therapy plus immune checkpoint inhibitor (AA-ICI) following RFA was assessed in low- and high-risk groups. RESULTS: The cutoff point of PIV was 120. High PIV was an independent predictor of unfavorable recurrence-free survival (RFS) and overall survival (OS). RFS and OS rates of patients with high PIV were significantly lower than those with low PIV both in cohort B (PRFS=0.016, POS=0.011) and C (PRFS<0.001, POS<0.001). The nomogram model based on PIV, tumor number and BCLC staging performed well in risk stratification in external validating cohort C. Adjuvant AA-ICI treatment showed an added benefit in OS (p = 0.011) for high-risk patients. CONCLUSIONS: PIV is a feasible independent prognostic factor for RFS and OS in early-stage HCC patients who received curative RFA. The proposed PIV-based nomogram risk model could help clinicians identify high-risk patients and tailor adjuvant systemic treatment and disease follow-up scheme.

Key findingsHigh pan-immune-inflammation value (PIV) is an independent indicator of unfavorable recurrence-free survival (RFS) and overall survival (OS) for early-stage hepatocellular carcinoma (HCC) patients who received curative radiofrequency ablation (RFA).Adjuvant anti-angiogenesis target therapy plus immune checkpoint inhibitor (AA-ICI) treatment showed added benefit in OS for the high-risk patients defined by a nomogram risk model based on PIV, tumor number and BCLC staging.What is known and what is new?Inflammation and impaired host immunity are associated with carcinogenesis and progression of HCC. Increasing evidences showed that immune-inflammatory biomarkers (IIBs) had prognostic roles in early-stage HCC patients who received RFA. However, prognostic potential of PIV has not been determined in this setting.Herein, high PIV was first reported to be an independent risk factor of poor RFS and OS in early-stage HCC patients treated by curative RFA and helped to discriminate patients between low- and high-risk groups. Adjuvant AA-ICI treatment following RFA was beneficial to OS of patients in the high-risk group.What is the implication, and what should change now?For early-stage HCC with high-risk factors (high PIV, multiple tumor foci and more advanced BCLC stage), intensive follow-up and adjuvant systemic therapy following curative RFA were warranted.

Ultrasound-Guided Percutaneous Transhepatic Cholangioscopic Lithotripsy for the Treatment of Common Bile Duct Stones and Analysis of Risk Factors for Recurrence.

BACKGROUND: As a minimally invasive treatment for common bile duct (CBD) stones, ultrasound-guided percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) is gaining attention and recognition from the medical community. METHODS: A retrospective analysis was conducted on patients with CBD stones treated in our hospital from January 2016 to April 2022. Patients were divided into three groups: 77 treated with PTCSL, 93 with endoscopic retrograde cholangiopancreatography (ERCP), and 103 with laparoscopic common bile duct exploration (LCBDE). Their clinical data, perioperative indicators, and complications were analyzed comparatively. Then, risk factors for the post-PTCSL recurrence of CBD stones were analyzed by logistic regressions. Finally, the receiver operating characteristic curve was drawn. RESULTS: All perioperative indicators of the PTCSL group were better than the LCBDE group (P < 0.001). The incidences of cholangitis, hemobilia, and incisional infection after surgery were lower in the PTCSL group than in the LCBDE group (P < 0.05). Pancreatitis, reflux esophagitis, and papillary stenosis occurred less frequently in the PTCSL group than in the ERCP group (P < 0.05). Logistic regression analysis indicated that gallstones and family history were independent risk factors. The AUC for recurrent CBD stones predicted by multi-indicators was 0.895 (95% CI 0.792-0.999, P < 0.001) with a sensitivity of 96.7% and specificity of 68.8%. CONCLUSIONS: Ultrasound-guided PTCSL is a safe and effective treatment for CBD stones. Patients recovered quickly with fewer postoperative complications. It can be a first-line treatment for CBD stones. Gallstones and family history are independent risk factors for recurrent CBD stones, which provide a reference for clinicians in identifying the high-risk population needing close follow-up.

Using elastography-based multilayer perceptron model to evaluate renal fibrosis in chronic kidney disease.

BACKGROUND: Given its progressive deterioration in the clinical course, noninvasive assessment and risk stratification for the severity of renal fibrosis in chronic kidney disease (CKD) are required. We aimed to develop and validate an end-to-end multilayer perceptron (MLP) model for assessing renal fibrosis in CKD patients based on real-time two-dimensional shear wave elastography (2D-SWE) and clinical variables. METHODS: From April 2019 to December 2021, a total of 162 patients with CKD who underwent a kidney biopsy and 2D-SWE examination were included in this single-center, cross-sectional, and prospective clinical study. 2D-SWE was performed to measure the right renal cortex stiffness, and the corresponding elastic values were recorded. Patients were categorized into two groups according to their histopathological results: mild and moderate-severe renal fibrosis. The patients were randomly divided into a training cohort (n = 114) or a test cohort (n = 48). The MLP classifier using a machine learning algorithm was used to construct a diagnostic model incorporating elastic values with clinical features. Discrimination, calibration, and clinical utility were used to appraise the performance of the established MLP model in the training and test sets, respectively. RESULTS: The developed MLP model demonstrated good calibration and discrimination in both the training [area under the receiver operating characteristic curve (AUC) = 0.93; 95% confidence interval (CI) = 0.88 to 0.98] and test cohorts [AUC = 0.86; 95% CI = 0.75 to 0.97]. A decision curve analysis and a clinical impact curve also showed that the MLP model had a positive clinical impact and relatively few negative effects. CONCLUSIONS: The proposed MLP model exhibited the satisfactory performance in identifying the individualized risk of moderate-severe renal fibrosis in patients with CKD, which is potentially helpful for clinical management and treatment decision-making.

Circ-DENND4C up-regulates TCF4 expression to modulate hepatocellular carcinoma cell proliferation and apoptosis via activating Wnt/ß-catenin signal pathway.

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor in China. Advanced treatment like transcatheter hepatic arterial chemoembolization (TACE) has prolonged the lives of many HCC patients. However, the prognosis of most HCC patients remains unsatisfactory. Recently, circular RNAs (circRNAs) have been gradually unveiled to exert considerable functions in cancer. Promising circRNAs in HCC remains to be further elucidated. Methods: Gene expression was assessed by qRT-PCR and western blot. The function of circ-DENND4C in HCC was estimated by both in vitro and in vivo experiments. The location of circ-DENND4C in HCC cells was determined by subcellular fractionation and FISH assays. The association among molecules were analyzed through RNA pull down, RIP and luciferase reporter assays. Results: circ-DENND4C (DENN domain containing 4C), an oncogene identified in breast cancer, was overexpressed in HCC cells. Also, circ-DENND4C exerted pro-tumor functions in HCC through activating Wnt/ß-catenin pathway. Importantly, circ-DENND4C could augment transcription factor 4 (TCF4) expression to activate Wnt/ß-catenin signaling via sequestering miR-195-5p. Moreover, following rescue assays disclosed that circ-DENND4C mediated malignant phenotypes in HCC cells via up-regulating TCF4 through sponging miR-195-5p. Conclusion: circ-DENND4C boosted TCF4 expression to modulate malignant behaviors of HCC cells via activating Wnt/ß-catenin pathway, which might offer a promising target for HCC treatment.

Long noncoding RNA HCG22 suppresses proliferation and metastasis of bladder cancer cells by regulation of PTBP1.

Multifarious biological functions of long noncoding RNAs (lncRNAs) have been reported in various cancers including bladder cancer (BCa). This study aims to determine the biological role of a certain lncRNA in BCa. Consistent with the data of The Cancer Genome Atlas database, it was validated that lncRNA HLA complex group 22 (HCG22) was weakly expressed in BCa samples and lowly expressed HCG22 was closely correlated with low overall survival of the BCa patient. To verify the role of HCG22 in BCa progression, functional experiments were carried out in two representative BCa cells (J82 and T24) and the negative effects of HCG22 expression on the cell proliferation, migration, and epithelial-mesenchymal transition were identified. Mechanistically, polypyrimidine tract-binding protein 1 (PTBP1), which was highly expressed in BCa tissues and cell lines, was negatively regulated by HCG22 and the PTBP1-mediated Warburg effect was also obstructed by HCG22. Furthermore, HCG22 modulated the expression of PTBP1 through destabilizing human antigen R (HuR). And functional rescue assays confirmed that HCG22 functioned in bladder cancer through downregulating PTBP1. In conclusion, the present study revealed that HCG22 inhibited BCa progression via the HuR/PTBP1 axis, opening new prospects for potent therapeutic regimens for BCa patients.

Protection of skin with subcutaneous administration of 5% dextrose in water during superficial radiofrequency ablation in a rabbit model.

PURPOSE: This study was to evaluate the efficacy of subcutaneous administration of 5% dextrose in water (D5W), to prevent skin injury during radiofrequency (RF) ablation. MATERIALS AND METHODS: Twenty-four rabbits were divided into three groups: a pre-injection group, a perfusion group, and a control group. Ablative zones were created in the superficial part of the thigh muscle for 6 min. A needle was placed subcutaneously for injection of D5W, and a thermal sensor was positioned nearby for real-time temperature monitoring. The sizes of the ablative zones were measured by contrast-enhanced ultrasonography, and severity of the observed skin injury were scored semi-quantitatively and compared. RESULTS: The highest temperature, the duration of the temperature above 50 °C, and the rise time of the post-procedure temperature were all highest in the control group (p < 0.001), while these values were lower in the perfusion group than those in the pre-injection group (p < 0.001). Post-procedure skin injury was most severe in the control group (p < 0.001). On post-procedure day 1, no significant difference was found between the skin injury of the pre-injection group and the perfusion group (p = 0.091), while the skin injury of the perfusion group was less severe than that of the pre-injection group on post-procedure day 14 (p = 0.004). No significant difference was found in the sizes of the ablative zones among the groups (p = 0.720). CONCLUSION: Subcutaneous perfusion with D5W is effective in protecting the skin against burns during RF ablation without compromising the effect of ablation.