Software for doing computations in graded Lie algebras

We introduce the Macaulay2 package GradedLieAlgebras for doing computations in graded Lie algebras presented by generators and relations.Comment: 5 page

Transcriptomic and metabolomic analysis of peri-tumoral hepatic tissue in hepatocellular carcinoma: unveiling the molecular landscape of immune checkpoint therapy resistance

Background: Hepatocellular carcinoma (HCC) often resists traditional treatments, necessitating new therapeutic approaches. With immune checkpoint therapy emerging as a promising alternative, understanding its resistance mechanisms becomes crucial.Methods: Using 22 samples from 11 HCC patients, we conducted a comprehensive transcriptomic and metabolomic analysis of peri-tumoral hepatic tissues from those treated with Atezolizumab.Results: We identified significant metabolic alterations and a correlation between the COMMD3-BMI1 gene and Dephospho-CoA metabolite. Findings suggest these as potential markers for therapeutic resistance, as evidenced by upregulated COMMD3-BMI1 and downregulated Dephospho-CoA in non-responsive patients, with animal models further supporting these observations.Discussion: The study highlights COMMD3-BMI1 and Dephospho-CoA as critical actors in immune checkpoint therapy resistance in HCC, providing insights and potential pathways for more effective therapeutic strategies

A radiomics model based on preoperative gadoxetic acid–enhanced magnetic resonance imaging for predicting post-hepatectomy liver failure in patients with hepatocellular carcinoma

BackgroundPost-hepatectomy liver failure (PHLF) is a fatal complication after liver resection in patients with hepatocellular carcinoma (HCC). It is of clinical importance to estimate the risk of PHLF preoperatively.AimsThis study aimed to develop and validate a prediction model based on preoperative gadoxetic acid–enhanced magnetic resonance imaging to estimate the risk of PHLF in patients with HCC.MethodsA total of 276 patients were retrospectively included and randomly divided into training and test cohorts (194:82). Clinicopathological variables were assessed to identify significant indicators for PHLF prediction. Radiomics features were extracted from the normal liver parenchyma at the hepatobiliary phase and the reproducible, robust and non-redundant ones were filtered for modeling. Prediction models were developed using clinicopathological variables (Clin-model), radiomics features (Rad-model), and their combination.ResultsThe PHLF incidence rate was 24% in the whole cohort. The combined model, consisting of albumin–bilirubin (ALBI) score, indocyanine green retention test at 15 min (ICG-R15), and Rad-score (derived from 16 radiomics features) outperformed the Clin-model and the Rad-model. It yielded an area under the receiver operating characteristic curve (AUC) of 0.84 (95% confidence interval (CI): 0.77–0.90) in the training cohort and 0.82 (95% CI: 0.72–0.91) in the test cohort. The model demonstrated a good consistency by the Hosmer–Lemeshow test and the calibration curve. The combined model was visualized as a nomogram for estimating individual risk of PHLF.ConclusionA model combining clinicopathological risk factors and radiomics signature can be applied to identify patients with high risk of PHLF and serve as a decision aid when planning surgery treatment in patients with HCC

Failure to perform second-stage operation after first one of associating liver partition and portal vein ligation for staged hepatectomy: analysis of 62 cases

Objective To summarize the clinical reasons for failing to perform the second stage of operation after the first stage of operation of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), and to explore the risk factors affecting the second stage of operation. Methods A sectional-cross study was conducted on 62 patients (54 males and 8 females, age: 49.1±10.4) with liver tumors who were continuously treated with ALPPS from October 2013 to December 2021. The patients were divided into the second stage of operation group and the non-second-stage operation group according to whether they accepted the second stage of operation or not. The clinical reasons why patients were failing to have the second stage of operation were collected. The data of patients, including the tumor diameter, clinical stages, Child-Pugh score, liver separation mode, liver function (levels of transaminase, bilirubin and albumin) in the preoperative and postoperative of first stage operation period, and complications were analyzed. Results Among the 62 patients, 45 patients successfully underwent the second stage of operation, and 17 patients failed to accept the second stage of operation, accounting for 27.4%. Among the patients who failed to accept the second stage of operation, there were 2 cases in the open ALPPS group, 11 cases in the radiofrequency assisted ALPPS (RALPS) group, and 4 cases in the laparoscopic ALPPS group. The difference of maximum tumor diameter and the formation of portal vein tumor thrombus was statistically significant (P < 0.05). In terms of liver function, the differences in the level of albumin and total bilirubin tested before the first stage of operation and the level of aspartate aminotransferase and total bilirubin tested after the first stage of operation were statistically significant(P < 0.05). Pulmonary inflammation, pleural effusion and ascites were common complications of the first stage operation. There was significant difference between the 2 groups in complications of ascites of the first stage of operation(P < 0.05). There was significant difference in the incidence of complications(≥grade Ⅲ) between the 2 groups (P < 0.001). The clinical causes that patients failed to accepted the second stage of operation were no obvious liver hyperplasia, insufficient future liver remnant volume (FLRV), poor liver function and hepatic reserve function, complications and progression of tumor. Multivariate analysis showed that the risk factors affecting the second stage of operation were the maximum tumor diameter, the formation of tumor thrombus and the grade of complications of the first stage operation. Conclusion ALPPS should be selected carefully for patients with large tumor and portal vein thrombosis

Percutaneous ultrasound-guided ‘three-step’ radiofrequency ablation for giant hepatic hemangioma (5–15 cm): a safe and effective new technique

Purpose To evaluate the safety and efficacy of percutaneous ultrasound-guided ‘three-step’ radiofrequency ablation (RFA) for the treatment of giant hepatic hemangioma. Materials and methods Patients with giant hepatic hemangioma who underwent percutaneous ultrasound-guided ‘three-step’ RFA (n = 52) and conventional RFA (n = 54) at our center from June 2013 to December 2017 were retrospectively analyzed. The ‘three-step’ RFA proceeds as follows. Step 1: Ablate the feeding artery of the hemangioma. Step 2: Aspirate blood from the tumor. Step 3: Ablation the lesion. Intraoperative information, postoperative recovery, therapeutic effects, and complications were compared between the two groups. Results The duration of RFA was significantly shorter (19.2 ± 0.8 min versus 44.5 ± 2.8 min, p < 0.001), the number of punctures was significantly lower (3.2 ± 0.1 versus 4.7 ± 0.3, p = 0.002), and the duration of hospital stay was significantly shorter (9.0 ± 0.5 versus 11.5 ± 0.7, p = 0.013) in the TS-RFA group than in the C-RFA group. The complete ablation rate (86.5% versus 40.7%), the maximum postoperative pain score (2.5 ± 1.3 versus 4.1 ± 2.0) and symptom relief were also significantly better in the TS-RFA group than in the C-RFA group (p < 0.05). No postoperative death occurred in either group. There were no grade III or higher complications in the TS-RFA group, but one patient in the C-RFA group developed the grade III complication of postoperative abdominal bleeding. Conclusions ‘Three-step’ RFA is a safe and effective minimally invasive treatment for giant hepatic hemangioma. It is worthy of further promotion and application

The Short-Term Efficacy of Novel No-Touch Combined Directional Perfusion Radiofrequency Ablation in the Treatment of Small Hepatocellular Carcinoma with Cirrhosis

Background No-touch combined directed perfusion radiofrequency ablation (NTDP-RFA) is a new technique for the treatment of hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the short-term efficacy of this new technique for the treatment of small HCC with cirrhosis. Methods From January 2017 to March 2018, 56 consecutive patients treated with NTDP-RFA at our center were enrolled in this retrospective study. All NTDP-RFA procedures involved the use of internally cooled wet electrodes with a directional injection function, which can perform both intraelectrode cooling and extraelectrode saline perfusion. Survival curves were analyzed using Kaplan–Meier methods, and Cox proportional hazards regression analyses were used to assess predictors of tumor progression and overall survival. Operative characteristics and complications were also assessed. Results No technical failure occurred, and the complete ablation rate after single NTDP-RFA treatment was 98.2%. The median tumor diameter and ablation time were 26 (18.0 − 28.0) mm and 8 (6 – 8) min, respectively. Mild complications occurred in five patients (8.9%) postoperatively, and the median hospital stay was 4 (4 − 5) days. In the 18 patients (32.1%) with poor liver function reserve (indocyanine green retention rate at 15 min > 15%, their liver function returned to normal on the third day after the postoperation. The 1- and 2-year local and distant progression rates were 1.7%, 7.1%, 3.5% and 10.7%, respectively. Conclusions NTDP-RFA in the treatment of small HCC with cirrhosis has a low incidence of complications and provides a high survival rate without local tumor progression

Hepatitis B virus X protein suppresses caveolin-1 expression in hepatocellular carcinoma by regulating DNA methylation

<p>Abstract</p> <p>Background</p> <p>To understand the molecular mechanisms of caveolin-1 downregulation by hepatitis B virus X protein (HBx).</p> <p>Methods</p> <p>The DNA methylation status of the caveolin-1 promoter was examined by nested methylation-specific PCR of 33 hepatitis B virus (HBV)-infected hepatocellular carcinoma (HCC) samples. The SMMC-7721 hepatoma cell line was transfected with a recombinant HBx adenoviral vector, and the effects of HBx protein on caveolin-1 expression and promoter methylation were examined and confirmed by sequencing. A reporter gene containing the caveolin-1 promoter region was constructed, and the effects of HBx on the transcriptional activity of the promoter were also studied.</p> <p>Results</p> <p>Methylation of the caveolin-1 promoter was detected in 84.8% (28/33) of HBV-infected HCC samples. Expression of caveolin-1 was significantly downregulated (P = 0.022), and multiple CpG sites in the promoter region of caveolin-1 were methylated in SMMC-7721 cells after HBx transfection. Transfected HBx significantly suppressed caveolin-1 promoter activity (P = 0.001).</p> <p>Conclusions</p> <p>HBx protein induces methylation of the caveolin-1 promoter region and suppresses its expression.</p

Impact of body composition on the prognosis of hepatocellular carcinoma patients treated with transarterial chemoembolization: A systematic review and meta-analysis

Objectives: To summarize current evidence about the influence of body composition on the prognosis of patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) treatment. Methods: Public databases were systematically searched to identify relevant studies published from the inception of the database up to May 2023. Studies that evaluated the association between body composition and clinical outcomes in HCC patients who underwent TACE were included. A pre-designed table was applied to summarize relevant information. Meta-analysis was performed to estimate the association of body composition with overall survival. Results: Fourteen studies were included in this review, including 3631 patients (sample size range: 56–908, median 186). All body composition measurements (including skeletal muscle area, visceral and subcutaneous adipose area, and bone mineral density) were based on computer tomography. The commonly used parameter was skeletal muscle index at 3rd lumbar vertebra level (8/14). Three studies evaluated the correlations of body composition changes with the prognosis after TACE. Most studies (12/14) identified body composition parameters as an independent indicator for overall survival, progression-free survival, and treatment response rate. The hazard ratio of different body composition parameters ranged from 1.01 to 2.88, and hazard ratio of body composition changes ranged from 1.88 to 5.93. The pooled hazard ratio of sarcopenia for overall survival was 1.38 (95 %CI: 1.20–1.58). Conclusions: Body composition seems to be an important prognostic factor for a poorer clinical outcome after TACE treatment in patients with hepatocellular carcinoma. Future prospective studies with a larger sample size are required to confirm these findings. Registration study: This study has been prospectively registered at the PROSPERO platform (https://www.crd.york.ac.uk/prospero/) with the registration No. CRD42022345602

Radiomics Models for Predicting Microvascular Invasion in Hepatocellular Carcinoma: A Systematic Review and Radiomics Quality Score Assessment

Preoperative prediction of microvascular invasion (MVI) is of importance in hepatocellular carcinoma (HCC) patient treatment management. Plenty of radiomics models for MVI prediction have been proposed. This study aimed to elucidate the role of radiomics models in the prediction of MVI and to evaluate their methodological quality. The methodological quality was assessed by the Radiomics Quality Score (RQS), and the risk of bias was evaluated by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Twenty-two studies using CT, MRI, or PET/CT for MVI prediction were included. All were retrospective studies, and only two had an external validation cohort. The AUC values of the prediction models ranged from 0.69 to 0.94 in the test cohort. Substantial methodological heterogeneity existed, and the methodological quality was low, with an average RQS score of 10 (28% of the total). Most studies demonstrated a low or unclear risk of bias in the domains of QUADAS-2. In conclusion, a radiomics model could be an accurate and effective tool for MVI prediction in HCC patients, although the methodological quality has so far been insufficient. Future prospective studies with an external validation cohort in accordance with a standardized radiomics workflow are expected to supply a reliable model that translates into clinical utilization