Application of texture signatures based on multiparameter-magnetic resonance imaging for predicting microvascular invasion in hepatocellular carcinoma:Retrospective study

BACKGROUND Despite continuous changes in treatment methods,the survival rate for advanced hepatocellular carcinoma(HCC)patients remains low,highlighting the importance of diagnostic methods for HCC.AIM To explore the efficacy of texture analysis based on multi-parametric magnetic resonance(MR)imaging(MRI)in predicting microvascular invasion(MVI)in preoperative HCC.METHODS This study included 105 patients with pathologically confirmed HCC,categorized into MVI-positive and MVI-negative groups.We employed Original Data Analysis,Principal Component Analysis,Linear Discriminant Analysis(LDA),and Non-LDA(NDA)for texture analysis using multi-parametric MR images to predict preoperative MVI.The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software,with results expressed as the misjudgment rate(MCR).RESULTS Texture analysis using multi-parametric MRI,particularly the MI+PA+F dimensionality reduction method combined with NDA discrimination,demonstrated the most effective prediction of MVI in HCC.Prediction accuracy in the pulse and equilibrium phases was 83.81%.MCRs for the combination of T2-weighted imaging(T2WI),arterial phase,portal venous phase,and equilibrium phase were 22.86%,16.19%,20.95%,and 20.95%,respectively.The area under the curve for predicting MVI positivity was 0.844,with a sensitivity of 77.19%and specificity of 91.67%.CONCLUSION Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI,portal venous,and equilibrium phases.This study provides an objective,non-invasive method for preoperative prediction of MVI,offering a theoretical foundation for the selection of clinical therapy.

Postoperative adjuvant therapy for hepatocellular carcinoma with microvascular invasion

Hepatocellular carcinoma(HCC)is one of the most lethal tumors in the world.Liver resection(LR)and liver transplantation(LT)are widely considered as radical treatments for early HCC.However,the recurrence rates after curative treatment are still high and overall survival is unsatisfactory.Microvascular invasion(MVI)is considered to be one of the important prognostic factors affecting postoperative recurrence and long-term survival.Unfortunately,whether HCC patients with MVI should receive postoperative adjuvant therapy remains unknown.In this review,we summarize the therapeutic effects of transcatheter arterial chemoembolization,hepatic arterial infusion chemotherapy,tyrosine protein kinase inhibitor-based targeted therapy,and immune checkpoint inhibitors in patients with MVI after LR or LT,aiming to provide a reference for the best adjuvant treatment strategy for HCC patients with MVI after LT or LR.

Preoperative prediction of microvascular invasion in hepatocellular carcinoma using ultrasound features including elasticity

BACKGROUND Microvascular invasion(MVI)is an important predictor of poor prognosis in patients with hepatocellular carcinoma(HCC).Accurate preoperative prediction of MVI in HCC would provide useful information to guide the choice of therapeutic strategy.Shear wave elastography(SWE)plays an important role in hepatic imaging,but its value in the preoperative prediction of MVI in HCC has not yet been proven.AIM To explore the value of conventional ultrasound features and SWE in the preoperative prediction of MVI in HCC.METHODS Patients with a postoperative pathological diagnosis of HCC and a definite diagnosis of MVI were enrolled in this study.Conventional ultrasound features and SWE features such as maximal elasticity(Emax)of HCCs and Emax of the periphery of HCCs were acquired before surgery.These features were compared between MVI-positive HCCs and MVI-negative HCCs and between mild MVI HCCs and severe MVI HCCs.RESULTS This study included 86 MVI-negative HCCs and 102 MVI-positive HCCs,including 54 with mild MVI and 48 with severe MVI.Maximal tumor diameters,surrounding liver tissue,color Doppler flow,Emax of HCCs,and Emax of the periphery of HCCs were significantly different between MVI-positive HCCs and MVI-negative HCCs.In addition,Emax of the periphery of HCCs was significantly different between mild MVI HCCs and severe MVI HCCs.Higher Emax of the periphery of HCCs and larger maximal diameters were independent risk factors for MVI,with odds ratios of 2.820 and 1.021,respectively.CONCLUSION HCC size and stiffness of the periphery of HCC are useful ultrasound criteria for predicting positive MVI.Preoperative ultrasound and SWE can provide useful information for the prediction of MVI in HCCs.

Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion

AIM To investigate the efficacy and safety of postoperative adjuvant transcatheter arterial chemoembolization(PA-TACE) in preventing tumor recurrence and improving survival in Barcelona Clinic Liver Cancer(BCLC) early(A) and intermediate(B) stage hepatocellular carcinoma(HCC) patients with microvascular invasion(MVI).METHODS A total of 519 BCLC A or B HCC patients treated by liver resection alone or followed by PA-TACE between January 2012 and December 2015 were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors for recurrence-free survival(RFS) and overall survival(OS). Multiple logistic regression was used to identify the clinicopathological characteristics associated with MVI. The rates of RFS and OS were compared among patients with or without MVI treated with liver resection alone or followed by PA-TACE. RESULTS Univariate and multivariate analyses demonstrated that serum AFP level > 400 ng/m L, tumor size > 5 cm, tumor capsule invasion, MVI, and major hepatectomy were risk factors for poor OS. Tumor capsule invasion, MVI, tumor size > 5 cm, HBV-DNA copies > 1 x 104 IU/m L, and multinodularity were risk factors for poor RFS. Multiple logistic regression identified serum AFP level > 400 ng/m L, tumor size > 5 cm, and tumor capsule invasion as independent predictors of MVI. Both OS and DFS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent liver resection alone. Patients without MVI did not show a significant difference in OS and RFS between those treated by liver resection alone or followed by PA-TACE.CONCLUSION PA-TACE is a safe adjuvant intervention and can efficiently prevent tumor recurrence and improve the survival of BCLC early-and intermediate-stage HCC patients with MVI.

Radiomics for the detection of microvascular invasion in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common primary liver cancer,accounting for about 90%of liver cancer cases.It is currently the fifth most common cancer in the world and the third leading cause of cancer-related mortality.Moreover,recurrence of HCC is common.Microvascular invasion(MVI)is a major factor associated with recurrence in postoperative HCC.It is difficult to evaluate MVI using traditional imaging modalities.Currently,MVI is assessed primarily through pathological and immunohistochemical analyses of postoperative tissue samples.Needle biopsy is the primary method used to confirm MVI diagnosis before surgery.As the puncture specimens represent just a small part of the tumor,and given the heterogeneity of HCC,biopsy samples may yield false-negative results.Radiomics,an emerging,powerful,and non-invasive tool based on various imaging modalities,such as computed tomography,magnetic resonance imaging,ultrasound,and positron emission tomography,can predict the HCC-MVI status preoperatively by delineating the tumor and/or the regions at a certain distance from the surface of the tumor to extract the image features.Although positive results have been reported for radiomics,its drawbacks have limited its clinical translation.This article reviews the application of radiomics,based on various imaging modalities,in preoperative evaluation of HCC-MVI and explores future research directions that facilitate its clinical translation.

Anatomic resection improved the long-term outcome of hepatocellular carcinoma patients with microvascular invasion:A prospective cohort study

BACKGROUND The long-term effect of anatomic resection(AR)is better than that of nonanatomic resection(NAR).At present,there is no study on microvascular invasion(MVI)and liver resection types.AIM To explore whether AR improves long-term survival in patients with hepatocellular carcinoma(HCC)by removing the peritumoral MVI.METHODS A total of 217 patients diagnosed with HCC were enrolled in the study.The surgical margin was routinely measured.According to the stratification of different tumor diameters,patients were divided into the following groups:≤2 cm group,2-5 cm group,and>5 cm group.RESULTS In the 2-5 cm diameter group,the overall survival(OS)of MVI positive patients was significantly better than that of MVI negative patients(P=0.031).For the MVI positive patients,there was a statistically significant difference between AR and NAR(P=0.027).AR leads to a wider surgical margin than NAR(2.0±2.3 cm vs 0.7±0.5 cm,P<0.001).In the groups with tumor diameters<2 cm,both AR and NAR can obtain a wide surgical margin,and the surgical margins of AR are wider than that of NAR(3.5±5.8 cm vs 1.6±0.5 cm,P=0.048).In the groups with tumor diameters>5 cm,both AR and NAR fail to obtain wide surgical margin(0.6±1.0 cm vs 0.7±0.4 cm,P=0.491).CONCLUSION For patients with a tumor diameter of 2-5 cm,AR can achieve the removal of peritumoral MVI by obtaining a wide incision margin,reduce postoperative recurrence,and improve prognosis.

Prediction of microvascular invasion in solitary hepatocellular carcinoma≤5 cm based on computed tomography radiomics

BACKGROUND Liver cancer is one of the most common malignant tumors,and ranks as the fourth leading cause of cancer death worldwide.Microvascular invasion(MVI)is considered one of the most important factors for recurrence and poor prognosis of liver cancer.Thus,accurately identifying MVI before surgery is of great importance in making treatment strategies and predicting the prognosis of patients with hepatocellular carcinoma(HCC).Radiomics as an emerging field,aims to utilize artificial intelligence software to develop methods that may contribute to cancer diagnosis,treatment improvement and evaluation,and better prediction.AIM To investigate the predictive value of computed tomography radiomics for MVI in solitary HCC≤5 cm.METHODS A total of 185 HCC patients,including 122 MVI negative and 63 MVI positive patients,were retrospectively analyzed.All patients were randomly assigned to the training group(n=124)and validation group(n=61).A total of 1351 radiomic features were extracted based on three-dimensional images.The diagnostic performance of the radiomics model was verified in the validation group,and the Delong test was applied to compare the radiomics and MVIrelated imaging features(two-trait predictor of venous invasion and radiogenomic invasion).RESULTS A total of ten radiomics features were finally obtained after screening 1531 features.According to the weighting coefficient that corresponded to the features,the radiomics score(RS)calculation formula was obtained,and the RS score of each patient was calculated.The radiomics model exhibited a better correction and identification ability in the training and validation groups[area under the curve:0.72(95%confidence interval:0.58-0.86)and 0.74(95%confidence interval:0.66-0.83),respectively].Its prediction performance was significantly higher than that of the image features(P<0.05).CONCLUSION Computed tomography radiomics has certain predictive value for MVI in solitary HCC≤5 cm,and the predictive ability is higher than that of image features.

Radiomic analysis based on multi-phase magnetic resonance imaging to predict preoperatively microvascular invasion in hepatocellular carcinoma

BACKGROUND The prognosis of hepatocellular carcinoma(HCC)remains poor and relapse occurs in more than half of patients within 2 years after hepatectomy.In terms of recent studies,microvascular invasion(MVI)is one of the potential predictors of recurrence.Accurate preoperative prediction of MVI is potentially beneficial to the optimization of treatment planning.AIM To develop a radiomic analysis model based on pre-operative magnetic resonance imaging(MRI)data to predict MVI in HCC.METHODS A total of 113 patients recruited to this study have been diagnosed as having HCC with histological confirmation,among whom 73 were found to have MVI and 40 were not.All the patients received preoperative examination by Gd-enhanced MRI and then curative hepatectomy.We manually delineated the tumor lesion on the largest cross-sectional area of the tumor and the adjacent two images on MRI,namely,the regions of interest.Quantitative analyses included most discriminant factors(MDFs)developed using linear discriminant analysis algorithm and histogram analysis with MaZda software.Independent significant variables of clinical and radiological features and MDFs for the prediction of MVI were estimated and a discriminant model was established by univariate and multivariate logistic regression analysis.Prediction ability of the above-mentioned parameters or model was then evaluated by receiver operating characteristic(ROC)curve analysis.Five-fold cross-validation was also applied via R software.RESULTS The area under the ROC curve(AUC)of the MDF(0.77-0.85)outperformed that of histogram parameters(0.51-0.74).After multivariate analysis,MDF values of the arterial and portal venous phase,and peritumoral hypointensity in the hepatobiliary phase were identified to be independent predictors of MVI(P<0.05).The AUC value of the model was 0.939[95%confidence interval(CI):0.893-0.984,standard error:0.023].The result of internal five-fold cross-validation(AUC:0.912,95%CI:0.841-0.959,standard error:0.0298)also showed favorable predictive efficacy.CONCLUSION Noninvasive MRI radiomic model based on MDF values and imaging biomarkers may be useful to make preoperative prediction of MVI in patients with primary HCC.

Liver resection versus liver transplantation for hepatocellular carcinoma within the Milan criteria based on estimated microvascular invasion risks

Background:Preoperative prediction of microvascular invasion(MVI)in hepatocellular carcinoma(HCC)may optimize individualized treatment decision-making.This study aimed to investigate the prognostic differences between HCC patients undergoing liver resection(LR)and liver transplantation(LT)based on predicted MVI risks.Methods:We analysed 905 patients who underwent LR,including 524 who underwent anatomical resection(AR)and 117 who underwent LT for HCC within the Milan criteria using propensity score matching.A nomogram model was used to predict preoperative MVI risk.Results:The concordance indices of the nomogram for predicting MVI were 0.809 and 0.838 in patients undergoing LR and LT,respectively.Based on an optimal cut-off value of 200 points,the nomogram defined patients as high-or low-risk MVI groups.LT resulted in a lower 5-year recurrence rate and higher 5-year overall survival(OS)rate than LR among the high-risk patients(23.6%vs 73.2%,P<0.001;87.8%vs 48.1%,P<0.001)and low-risk patients(19.0%vs 45.7%,P<0.001;86.5%vs 70.0%,P=0.002).The hazard ratios(HRs)of LT vs LR for recurrence and OS were 0.18(95%confidence interval[CI],0.09–0.37)and 0.12(95%CI,0.04–0.37)among the high-risk patients and 0.37(95%CI,0.21–0.66)and 0.36(95%CI,0.17–0.78)among the low-risk patients.LT also provided a lower 5-year recurrence rate and higher 5-year OS rate than AR among the high-risk patients(24.8%vs 63.5%,P=0.001;86.7%vs 65.7%,P=0.004),with HRs of LT vs AR for recurrence and OS being 0.24(95%CI,0.11–0.53)and 0.17(95%CI,0.06–0.52),respectively.The 5-year recurrence and OS rates between patients undergoing LT and AR were not significantly different in the low-risk patients(19.4%vs 28.3%,P=0.129;85.7%vs 77.8%,P=0.161).Conclusions:LT was superior to LR for patients with HCC within the Milan criteria with a predicted high or low risk of MVI.No significant differences in prognosis were found between LT and AR in patients with a low risk of MVI.

Evaluation of Preoperative Microvascular Invasion in Hepatocellular Carcinoma Through Multidimensional Parameter Combination Modeling Based on Gd-EOB-DTPA MRI

Background and Aims:The study established and compared the efficacy of the clinicoradiological model,radiomics model and clinicoradiological-radiomics hybrid model in predicting the microvascular invasion(MVI)of hepatocellular carcinoma(HCC)using gadolinium ethoxybenzyl diethylene triaminepentaacetic acid(Gd-EOB-DTPA)enhanced MRI.Methods:This was a study that enrolled 602 HCC patients from two institutions.Least absolute shrinkage and selection operator(Lasso)method was used to screen for the most important clinicoradiological and radiomics features that predict MVI pre-operatively.Three machine learning algorithms were used to establish the clinicoradiological,radiomics,and clinicoradiological-radiomics hybrid models.Area under the curve(AUC)of receiver operating characteristic(ROC)curves and Delong’s test were used to compare and quantify the predictive performance of the models.Results:The AUCs of the clinicoradiological model in training and validation cohorts were 0.793 and 0.701,respectively.The radiomics signature of arterial phase(AP)images alone achieved satisfying predictive efficacy for MVI,with AUCs of 0.671 and 0.643 in training and validation cohort,respectively.The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images achieved AUCs of 0.824 and 0.801 in training and validation cohorts,0.812 and 0.805 in prospective validation and external validation cohorts,respectively.The hybrid model provided the best prediction results.The results of the Delong test revealed that there were statistically significant differences among the clinicoradiological-radiomics hybrid model,clinicoradiological model,and radiomics model(p<0.05).Conclusions:The combination of clinicoradiological factors and fusion radiomics signature of AP and VP images based on Gd-EOB-DTPA-enhanced MRI can effectively predict MVI.

Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review

Hepatocellular carcinoma(HCC)being a leading cause of cancer-related death,has high associated mortality and recurrence rates.It has been of great necessity and urgency to find effective HCC diagnosis and treatment measures.Studies have shown that microvascular invasion(MVI)is an independent risk factor for poor prognosis after hepatectomy.The abnormal expression of biomacromolecules such as circ-RNAs,lncRNAs,STIP1,and PD-L1 in HCC patients is strongly correlated with MVI.Deregulation of several markers mentioned in this review affects the proliferation,invasion,metastasis,EMT,and anti-apoptotic processes of HCC cells through multiple complex mechanisms.Therefore,these biomarkers may have an important clinical role and serve as promising interventional targets for HCC.In this review,we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.

Microvascular invasion of hepatocellular carcinoma predicts microvascular invasion of its recurrence: potential implications for salvage liver transplantation?

Background:Microvascular invasion(MVI)can only be assessed on a full surgical specimen.We aimed at evaluating,whether the histology of the primary tumor is predictive of MVI in a hepatocellular carcinoma(HCC)recurrence.Methods:Patients,who underwent liver resection or orthotopic liver transplantation(OLT)for recurrent HCC from January 2001 until June 2018 were eligible for this retrospective analysis.Resected specimens were evaluated for HCC subtype/morphology,vessels encapsulating tumor clusters(VETC)-pattern and MVI.Dichotomous parameters were analyzed using χ^(2)-test andϕ-values,with P values<0.05 being considered significant.Results:Of 230 HCC recurrences,37(16.1%)underwent repeated liver resection(n=22)or OLT(n=15).Of these,67.6%initially exceeded the Milan criteria.MVI correlated Milan criteria(P=0.005),tumor size(P=0.015)and VETC-pattern(P=0.034)in the primary specimen.The recurrences shared many features of the primary HCC such as tumor grade(P=0.002),VETC-pattern(P=0.035),and MVI(P=0.046).In recurrences,however,only the concordance with the Milan criteria correlated with MVI(P=0.018).No patient without MVI in the primary HCC revealed MVI on early recurrence(<2 years)(P=0.035).Conclusions:HCC recurrences share many biological features of the primary tumor.Moreover,early recurrences of MVI-negative HCC never revealed MVI.This finding offers novel concepts,e.g.,patient selection for salvage OLT.

Prediction of the lymphatic,microvascular,and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging

BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study reported the relationship between magnetic resonance imaging(MRI)parameters and LMPI.AIM To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs(NFPNETs).METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study.The patients were divided into group 1(n=34,LMPI negative)and group 2(n=27,LMPI positive).The clinical characteristics and qualitative MRI features were collected.In order to predict LMPI status in NF-PNETs,a multivariate logistic regression model was constructed.Diagnostic performance was evaluated by calculating the receiver operator characteristic(ROC)curve with area under ROC,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accuracy.RESULTS There were significant differences in the lymph node metastasis stage,tumor grade,neuron-specific enolase levels,tumor margin,main pancreatic ductal dilatation,common bile duct dilatation,enhancement pattern,vascular and adjacent tissue involvement,synchronous liver metastases,the long axis of the largest lymph node,the short axis of the largest lymph node,number of the lymph nodes with short axis>5 or 10 mm,and tumor volume between two groups(P<0.05).Multivariate analysis showed that tumor margin(odds ratio=11.523,P<0.001)was a predictive factor for LMPI of NF-PNETs.The area under the receiver value for the predictive performance of combined predictive factors was 0.855.The sensitivity,specificity,PPV,NPV and accuracy of the model were 48.1%(14/27),97.1%(33/34),97.1%(13/14),70.2%(33/47)and 0.754,respectively.CONCLUSION Using preoperative MRI,ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.

Concerns about how to simultaneously determine microvascular invasion and pathological response after transarterial chemoembolization before hepatocellular carcinoma surgery

Microvascular invasion(MVI)is classified as the strongest risk factor for recurrence and poor prognosis after surgical treatment of hepatocellular carcinoma(HCC).The same results after liver transplantation reflect how MVI reflects the poor prognosis of HCC(1,2).

Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety

Background:The optimal strategy for adjuvant therapy after curative resection for hepatocellular carcinoma(HCC)patients with solitary tumor and microvascular invasion(MVI)is controversial.This trial evaluated the efficacy and safety of adjuvant transcatheter arterial chemoembolization(TACE)after hepatectomy versus hepatectomy alone in HCC patients with a solitary tumor≥5 cm and MVI.Methods:In this randomized,open-labeled,phase III trial,HCC patients with a solitary tumor≥5 cm and MVI were randomly assigned(1:1)to receive either 1-2 cycles of adjuvant TACE after hepatectomy(Hepatectomy-TACE)or hepatectomy alone(Hepatectomy Alone).The primary endpoint was disease-free survival(DFS);the secondary end-points included overall survival(OS)and adverse events.Results:Between June 1,2009,and December 31,2012,250 patients were enrolled and randomly assigned to the Hepatectomy-TACE group(n=125)or the Hepatectomy Alone group(n=125).Clinicopathological characteristics were balanced between the two groups.The median follow-up time from randomization was 37.5 months[interquartile range 18.3-48.2 months].The median DFS was significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group[17.45 months(95%confidence interval[CI]11.99-29.14)vs.9.27 months(95%CI 6.05-13.70),hazard ratio[HR]=0.70(95%CI 0.52-0.95),P=0.020],respectively.The median OS was also significantly longer in the Hepatectomy-TACE group than in the Hepatectomy Alone group[44.29 months(95%CI 25.99-62.58)vs.22.37 months(95%CI 10.84-33.91),HR=0.68(95%CI 0.48-0.97),P=0.029].Treatment-related adverse events were more frequently observed in the Hepatectomy-TACE group,although these were generally mild and manageable.The most common grade 3 or 4 adverse events in both groups were neutropenia and liver dysfunction.Conclusion:Hepatectomy followed by adjuvant TACE is an appropriate option after radical resection in HCC patients with solitary tumor≥5 cm and MVI,with acceptable toxicity.

Impact of pathological response after preoperative transcatheter arterial chemoembolization(TACE)on incidences of microvascular invasion and early tumor recurrence in hepatocellular carcinoma:a multicenter propensity score matching analysis

Background:To study the influence of pathological responses(PR)after transcatheter arterial chemoembolization(TACE)on incidences of microvascular invasion(MVI)and early recurrence in hepatocellular carcinoma(HCC)patients.Methods:Between 2013 to 2015,consecutive HCC patients who underwent liver resection with“curative”intent at three hospitals were enrolled in this study.Patients with different areas of PR after preoperative TACE were compared with those without preoperative TACE on the incidences of MVI,early recurrence rates and patterns of recurrence before and after propensity score matching(PSM).Results:Of 1,970 patients,737 patients who received preoperative TACE were divided into three groups according to the areas of PR:≥90%(n=226),60-90%(n=447),and<60%(n=64).PR≥90%was an independent protective factor of incidences of MVI[odds ratio(OR),0.144;95%confidence interval(CI),0.082-0.245,P<0.001)and early recurrence(HR,0.742;95%CI,0.561-0.963,P=0.032);while PR<60%was an independent risk factor of incidences of MVI(OR,6.076;95%CI,3.004-11.728,P<0.001)and early recurrence(HR,1.428;95%CI,1.095-1.929;P=0.009).Furthermore,patients with PR<60%were significantly more likely to develop multiple intrahepatic recurrences involving multiple hepatic segments when compared with patients without preoperative TACE.Conclusions:This study indicated the area of PR after TACE was closely associated with the incidences of MVI and early tumor recurrence.Patients with PR<60%were at significantly higher risks of having more MVI,early and multiple tumor recurrences.

Diagnostic Accuracy of the Apparent Diffusion Coefficient for Microvascular Invasion in Hepatocellular Carcinoma: A Meta-analysis

Background and Aims:Microvascular invasion(MVI)is a major risk factor for the early recurrence of hepatocel-lular carcinoma(HCC)and it seriously worsens the prog-nosis.Accurate preoperative evaluation of the presence of MVI could greatly benefit the treatment management and prognosis prediction of HCC patients.The study aim was to evaluate the diagnostic performance of the apparent dif-fusion coefficient(ADC),a quantitative parameter for the preoperative diagnosis MVI in HCC patients.Methods:Original articles about diffusion-weighted imaging(DWI)and/or intravoxel incoherent motion(IVIM)conducted on a 3.0 or 1.5 Tesla magnetic resonance imaging(MRI)system indexed through January 17,2021were collected from MED-LINE/PubMed,Web of Science,EMBASE,and the Cochrane Library.Methodological quality was evaluated using Quality Assessment of Diagnostic Accuracy Studies 2(QUADAS-2).The pooled sensitivity,specificity,and summary area un-der the receiver operating characteristic curve(AUROC)were calculated,and meta-regression analysis was per-formed using a bivariate random effects model through a meta-analysis.Results:Nine original articles with a total of 988 HCCs were included.Most studies had low bias risk and minimal applicability concerns.The pooled sensitivity,specificity and AUROC of the ADC value were 73%,70%,and 0.78,respectively.The time interval between the index test and the reference standard was identified as a pos-sible source of heterogeneity by subgroup meta-regression analysis.Conclusions:Meta-analysis showed that the ADC value had moderate accuracy for predicting MVI in HCC.The time interval accounted for the heterogeneity.

Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection

BACKGROUND Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma(HCC)has great significance for patient prognosis.AIM To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced magnetic resonance imaging(MRI)combined with clinical features in predicting early recurrence of HCC after resection.METHODS A total of 161 patients with pathologically confirmed HCC were enrolled.The patients were divided into early recurrence and non-early recurrence group based on the follow-up results.The clinical,laboratory,pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed.RESULTS Of 161 patients,73 had early recurrence and 88 were had non-early recurrence.Univariate analysis showed that patient age,gender,serum alpha-fetoprotein level,the Barcelona Clinic Liver Cancer stage,China liver cancer(CNLC)stage,microvascular invasion(MVI),pathological satellite focus,tumor size,tumor number,tumor boundary,tumor capsule,intratumoral necrosis,portal vein tumor thrombus,large vessel invasion,nonperipheral washout,peritumoral enhancement,hepatobiliary phase(HBP)/tumor signal intensity(SI)/peritumoral SI,HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation.Multivariate logistic regression analysis showed that patient age,MVI,CNLC stage,tumor boundary and large vessel invasion were independent predictive factors.External data validation indicated that the area under the curve of the combined predictors was 0.861,suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC.CONCLUSION Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

Finding the seed of recurrence:Hepatocellular carcinoma circulating tumor cells and their potential to drive the surgical treatment

The treatment for hepatocellular carcinoma(HCC)relies on liver resection,which is,however,burdened by a high rate of recurrence after surgery,up to 60%at 5 years.No pre-operative tools are currently available to assess the recurrence risk tailored to every single patient.Recently liquid biopsy has shown interesting results in diagnosis,prognosis and treatment allocation strategies in other types of cancers,since its ability to identify circulating tumor cells(CTCs)derived from the primary tumor.Those cells were advocated to be responsible for the majority of cases of recurrence and cancer-related deaths for HCC.In fact,after being modified by the epithelial-mesenchymal transition,CTCs circulate as“seeds”in peripheral blood,then reach the target organ as dormant cells which could be subsequently“awakened”and activated,and then initiate metastasis.Their presence may justify the disagreement registered in terms of efficacy of anatomic vs non-anatomic resections,particularly in the case of microvascular invasion,which has been recently pointed as a histological sign of the spread of those cells.Thus,their presence,also in the early stages,may justify the recurrence event also in the contest of liver transplant.Understanding the mechanism behind the tumor progression may allow improving the treatment selection according to the biological patient-based characteristics.Moreover,it may drive the development of novel biological tailored tests which could address a specific patient to neoadjuvant or adjuvant strategies,and in perspective,it could also become a new method to allocate organs for transplantation,according to the risk of relapse after liver transplant.The present paper will describe the most recent evidence on the role of CTCs in determining the relapse of HCC,highlighting their potential clinical implication as novel tumor behavior biomarkers able to influence the surgical choice.

The role of intraoperative electron radiotherapy in centrally located hepatocellular carcinomas treated with narrow-margin (<1 cm) hepatectomy: a prospective, phase 2 study

Background: Postoperative radiotherapy (RT) is known to play an important role in the treatment of hepatocellular carcinomas (HCCs), but the specific role of intraoperative electron radiotherapy (IOERT) in HCCs remains unclear. The aim of this study was to investigate the safety and efficacy of IOERT in centrally located HCCs treated with narrow-margin (<1 cm) hepatectomy. Methods: This was a single-center, phase 2, prospective non-randomized controlled study, including 268 patients with centrally located HCCs who underwent narrow-margin hepatectomy. The patients were subsequently allocated to the IOERT group (n=59) or to the control group (n=65). The primary outcome of the study was to compare recurrence-free survival (RFS) between the IOERT group and the control group, and the secondary outcome was to compare overall survival (OS) rate between the two groups. Results: Of 268 patients enrolled, a total of 124 were included in the study: 59 in IOERT group, 65 in control group. The 1-, 2-, 3-year RFS rates were 79.3%, 62.1% and 45.8% for patients in the IOERT group, and 47.6%, 28.6%, and 22.9% for patients in the control group, respectively (P=0.025). The 1-, 2-, and 3-year OS rates were 100.0%, 94.9%, and 83.7% for patients in the IOERT group, and 92.3%, 87.5%, and 79.4% for patients in the control group, respectively (P=0.314). Subgroup analysis of MVI (+) patients revealed that RFS and OS are significantly prolonged in the IOERT subgroup as compared to the control, whereas there was no significant difference of RFS and OS between the two groups in MVI (−) patients. Conclusions: IOERT for centrally located HCCs with concurrent narrow-margin hepatectomy was feasible and safe. Statistically better RFS rate was observed in the IOERT group compared to the control group. Subgroup analysis revealed that IOERT was more beneficial for postoperative survival of HCC patients with MVI. Trial Registration: ChiCTR-TRC-12002802;www.who.int/ictrp.