Predictors of Recurrence of Hepatocellular Carcinoma after Transarterial Chemoembolization: Role of Hepatocyte Growth Factor

Background: Hepatocellular carcinoma is the third leading cause of tumor related mortality and develops mostly in patients with chronic liver disease and liver cirrhosis. Human hepatocyte growth factor (HGF) is produced in various organs of the body and is characterized as a multifunctional factor with various biologic activities. Aim: Our aim was to investigate the predictive factors of recurrence specially the role of HGF in patients with HCC treated with TACE. Patients and Methods: one hundred HCC patients treated by TACE who achieved complete response were included and divided into two groups according to disease free survival (DFS) status at 1 year: the non-early recurrence (NER) group (1) and the early recurrence (ER) group (2). Univariate binary logistic regression analysis for the possible risk factors of recurrence showed that AFP, multinodularity and HGF level were significant. Conclusion: high AFP, multinodularity and high HGF were inter-related possible risk factors for 1-year recurrence of HCC in patients with initial remission following TACE.

Ship motion extreme short time prediction of ship pitch based on diagonal recurrent neural network

A DRNN (diagonal recurrent neural network) and its RPE (recurrent prediction error) learning algorithm are proposed in this paper .Using of the simple structure of DRNN can reduce the capacity of calculation. The principle of RPE learning algorithm is to adjust weights along the direction of Gauss-Newton. Meanwhile, it is unnecessary to calculate the second local derivative and the inverse matrixes, whose unbiasedness is proved. With application to the extremely short time prediction of large ship pitch, satisfactory results are obtained. Prediction effect of this algorithm is compared with that of auto-regression and periodical diagram method, and comparison results show that the proposed algorithm is feasible.

Predictive value of tumor markers in patients with recurrent hepatocellular carcinoma in different vascular invasion pattern

BACKGROUND： Four tumor markers for hepatocellular carcinoma（HCC）, alpha-fetoprotein（AFP）, glypican-3（GPC3）, vascular endothelial growth factor（VEGF） and des-gammacarboxy prothrombin（DCP）, are closely associated with tumor invasion and patient＇s survival. This study estimated the predictability of preoperative tumor marker levels along with pathological parameters on HCC recurrence after hepatectomy.METHODS： A total of 140 patients with HCC who underwent hepatectomy between January 2012 and August 2012 were enrolled. The demographics, clinical and follow-up data were collected and analyzed. The patients were divided into two groups： patients with macroscopic vascular invasion（Ma VI ＋） and those without Ma VI（Ma VI-）. The predictive value of tumor markers and clinical parameters were evaluated by univariate and multivariate analysis.RESULTS： In all patients, tumor size（〉8 cm） and Ma VI were closely related to HCC recurrence after hepatectomy. For Ma VI＋ patients, VEGF（〉900 pg/m L） was a significant predictor for recurrence（RR=2.421; 95% CI： 1.272-4.606; P=0.007）. The 1- and 2-year tumor-free survival rates for Ma VI＋ patients with VEGF ≤900 pg/m L versus for those with VEGF 〉900 pg/m L were 51.5% and 17.6% versus 19.0% and 4.8%（P〈0.001）. For Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were two independent risk factors for tumor recurrence（RR=2.307, 95% CI： 1.132-4.703, P=0.021; RR=3.150, 95% CI： 1.392-7.127, P=0.006; respectively）. The 1- and 2-year tumor-free survival rates for the patients with DCP ≤445 m Au/m L and those with DCP 〉445 m Au/m L were 90.4% and 70.7% versus 73.2% and 50.5% respectively（P=0.048）. The 1-and 2-year tumor-free survival rates for the patients with tumor size ≤8 cm and 〉8 cm were 83.2% and 62.1% versus 50.0% and 30.0%, respectively（P=0.003）.CONCLUSIONS： The Ma VI＋ patients with VEGF ≤900 pg/m L had a relatively high tumor-free survival than those with VEGF 〉900 pg/m L. In the Ma VI- patients, DCP 〉445 m Au/m L and tumor size 〉8 cm were predictive factors for postoperative recurrence.

QTc Interval Predicts Outcome of Catheter Ablation in Paroxysmal Atrial Fibrillation Patients with Type 2 Diabetes Mellitus

Catheter ablation has been recommended as a treatment option for paroxysmal atrial fibrillation（PAF） patients complicated with type 2 diabetes mellitus（T2DM）. PAF patients with T2 DM have a higher recurrence rate after catheter ablation. Prolongation of corrected QT（QTc） interval has been linked to poor outcomes in T2 DM patients. Whether the abnormal QTc interval is associated with the ablation outcome in the PAF patients with T2 DM remains unknown. In this study, 134 PAF patients with T2 DM undergoing primary catheter ablation were retrospectively enrolled. Pre-procedural QTc interval was corrected by using the Bazett＇s formula. Cox proportional hazards models were constructed to assess the relationship between QTc interval and the recurrence of AF. After a 29.1-month follow-up period, 61 patients experienced atrial tachyarrhythmia recurrence. Recurrent patients had a longer QTc interval than non-recurrent patients（425.2±21.5 ms vs. 414.1±13.4 ms, P=0.002）. Multivariate Cox regression analysis revealed that QTc interval [hazard ratio（HR）=1.026, 95% confidence interval（CI） 1.012–1.040, P=0.005] and left atrial diameter（LAD）（HR=1.125, 95% CI 1.062–1.192, P=0.003） were independent predictors of recurrent atrial tachyarrhythmia. Receiver operating characteristic analysis demonstrated that the cut-off value of QTc（418 ms） predicted arrhythmia recurrence with a sensitivity of 55.7% and a specificity of 69.9%. A combination of LAD and QTc was more effective than LAD alone（P〈0.001） in predicting arrhythmia recurrence after the procedure. QTc interval could be used as an independent predictor of arrhythmia recurrence in T2 DM patients undergoing AF ablation, thus providing a simple method to identify those patients who likely have a better outcome following the procedure.

A Blood Hepatocellular Carcinoma Signature Recognizes Very Small Tumor Nodules with Metastatic Traits

Background and Aims:Hepatocellular carcinoma(HCC)cases with small nodules are commonly treated with radi-ofrequency ablation(RFA),but the recurrence rate remains high.This study aimed to establish a blood signature for identifying HCC with metastatic traits pre-RFA.Methods:Data from HCC patients treated between 2010 and 2017 were retrospectively collected.A blood signature for meta-static HCC was established based on blood levels of alpha-fetoprotein and des-γ-carboxy-prothrombin,cell-free DNA(cfDNA)mutations,and methylation changes in target genes in frozen-stored plasma samples that were collected before RFA performance.The HCC blood signature was validated in patients prospectively enrolled in2021.Results:Of 251 HCC patients in the retrospective study,33.9% experienced recurrence within 1 year post-RFA.The HCC blood signature identified from these patients included des-γ-carboxy-prothrombin≥40mAU/mL with cfDNA mutation score,where cfDNA mutations occurred in the genes of TP53,CTNNB1,and TERT promoter.This signature effectively predicted 1-year post-RFArecurrence of HCC with 92% specificity and 91% sensitivity in the retrospective dataset,and with 87% specificity and 76% sensitivity in the prospective dataset(n=32 patients).Among 14 cases in the prospective study with biopsy tissues available,positivity for the HCC blood signature was associated with a higher HCC tissue score and shorter distance between HCC cells and microvasculature.Conclusions:This study established an HCC blood signature in pre-RFA blood that potentially reflects HCC with metastatic traits and may be valuable for predicting the disease’s early recurrence post-RFA.

Multicenter study of the clinicopathological features and recurrence risk prediction model of early-stage breast cancer with low-positive human epidermal growth factor receptor 2 expression in China (Chinese Society of Breast Surgery 021)

Background:Breast cancer with low-positive human epidermal growth factor receptor 2(HER2)expression has triggered further refinement of evaluation criteria for HER2 expression.We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors.Methods:Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association,from January 2015 to December 2016 were collected.The prognostic factors of these patients were analyzed.Results:Twenty-nine hospitals provided valid cases.From 2015 to 2016,a total of 25,096 cases of early-stage breast cancer were treated,7642(30.5%)of which had low-positive HER2 expression and were included in the study.After ineligible cases were excluded,6486 patients were included in the study.The median follow-up time was 57 months(4-76 months).The disease-free survival rate was 92.1%at 5 years,and the overall survival rate was 97.4%at 5 years.At the follow-up,506(7.8%)cases of metastasis and 167(2.6%)deaths were noted.Multivariate Cox regression analysis showed that tumor stage,lymphvascular invasion,and the Ki67 index were related to recurrence and metastasis(P<0.05).The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815(95%confidence interval:0.750-0.880).Conclusions:Early-stage breast cancer patients with low-positive HER2 expression account for 30.5%of all patients.Tumor stage,lymphvascular invasion,and the Ki67 index are factors affecting prognosis.The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years.Trial registration:ChiCTR.org.cn,ChiCTR2100046766.