Transcatheter arterial chemoembolization combined with PD-1 inhibitors and Lenvatinib for hepatocellular carcinoma with portal vein tumor thrombus

BACKGROUND Hepatocellular carcinoma(HCC)patients complicated with portal vein tumor thrombus(PVTT)exhibit poor prognoses and treatment responses.AIM To investigate efficacies and safety of the combination of PD-1 inhibitor,transcatheter arterial chemoembolization(TACE)and Lenvatinib in HCC subjects comorbid with PVTT.METHODS From January 2019 to December 2020,HCC patients with PVTT types Ⅰ-Ⅳ were retrospectively enrolled at Beijing Ditan Hospital.They were distributed to either the PTL or TACE/Lenvatinib(TL)group.The median progression-free survival(mPFS)was set as the primary endpoint,while parameters like median overall survival,objective response rate,disease control rate(DCR),and toxicity level served as secondary endpoints.RESULTS Forty-one eligible patients were finally recruited for this study and divided into the PTL(n=18)and TL(n=23)groups.For a median follow-up of 21.8 months,the DCRs were 88.9%and 60.9%in the PTL and TL groups(P=0.046),res-pectively.Moreover,mPFS indicated significant improvement(HR=0.25;P<0.001)in PTL-treated patients(5.4 months)compared to TL-treated(2.7 months)patients.There were no treatment-related deaths or differences in adverse events in either group.CONCLUSION A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types Ⅰ-Ⅳ.

Nomogram predicting the prognosis of primary liver cancer after radiofrequency ablation combined with transcatheter arterial chemoembolization

BACKGROUND The incidence and mortality rates of primary hepatocellular carcinoma(HCC)are high,and the conventional treatment is radiofrequency ablation(RFA)with transcatheter arterial chemoembolization(TACE);however,the 3-year survival rate is still low.Further,there are no visual methods to effectively predict their prognosis.AIM To explore the factors influencing the prognosis of HCC after RFA and TACE and develop a nomogram prediction model.METHODS Clinical and follow-up information of 150 patients with HCC treated using RFA and TACE in the Hangzhou Linping Hospital of Traditional Chinese Medicine from May 2020 to December 2022 was retrospectively collected and recorded.We examined their prognostic factors using multivariate logistic regression and created a nomogram prognosis prediction model using the R software(version 4.1.2).Internal verification was performed using the bootstrapping technique.The prognostic efficacy of the nomogram prediction model was evaluated using the concordance index(CI),calibration curve,and receiver operating characteristic RESULTS Of the 150 patients treated with RFA and TACE,92(61.33%)developed recurrence and metastasis.Logistic regression analysis identified six variables,and a predictive model was created.The internal validation results of the model showed a CI of 0.882.The correction curve trend of the prognosis prediction model was always near the diagonal,and the mean absolute error before and after internal validation was 0.021.The area under the curve of the prediction model after internal verification was 0.882[95%confidence interval(95%CI):0.820-0.945],with a specificity of 0.828 and sensitivity of 0.656.According to the Hosmer-Lemeshow test,χ^(2)=3.552 and P=0.895.The predictive model demonstrated a satisfactory calibration,and the decision curve analysis demonstrated its clinical applicability.CONCLUSION The prognosis of patients with HCC after RFA and TACE is affected by several factors.The developed prediction model based on the influencing parameters shows a good prognosis predictive efficacy.

Radiofrequency ablation combined with transcatheter arterial chemoembolization for recurrent liver cancer

BACKGROUND The recurrence rate of liver cancer after surgery is high.Radiofrequency ablation(RFA)combined with transcatheter arterial chemoembolization(TACE)is an effective treatment for liver cancer;however,its efficacy in recurrent liver cancer remains unclear.AIM To investigate the clinical effect of TACE combined with RFA in the treatment of recurrent liver cancer.METHODS Ninety patients with recurrent liver cancer were divided into 2 groups according to treatment plan:Control(RFA alone);and experimental[TACE combined with RFA(TACE+RFA)].The incidence of increased alanine aminotransferase levels,complications,and other indices were compared between the two groups before and after the procedures.RESULTS One month after the procedures,the short-term efficacy rate and Karnofsky Performance Status scores of the experimental group were significantly higher than those of the control group(P<0.05).Alpha-fetoprotein(AFP)and total bilirubin levels were lower than those in the control group(P<0.05);The overall response rate was 82.22%and 66.67%in the experimental and control groups,respectively;The disease control rate was 93.33%and 82.22%in the experimental and control groups,respectively,the differences are statistically significant(P<0.05).And there were no statistical differences in complications between the two groups(P>0.05).CONCLUSION TACE+RFA was effective for the treatment of recurrent liver cancer and significantly reduced AFP levels and improved various indices of liver function.

Liver abscess and tracheal fistula induced by transcatheter arterial chemoembolization for hepatocellular carcinoma:A case report

BACKGROUND Transarterial chemoembolization(TACE)is a standard treatment for intermediate-stage hepatocellular carcinoma(HCC).The complications of TACE include biliary tract infection,liver dysfunction,tumor lysis syndrome,biloma,partial intestinal obstruction,cerebral lipiodol embolism,etc.There are few reports about tracheal fistula induced by TACE.CASE SUMMARY A 42-year-old man came to our hospital with cough and expectoration for 1 month after TACE for HCC.Laboratory test results showed abnormalities of albumin,hemoglobin,prothrombin time,C-reactive protein,D-dimer,and prothrombin.Culture of both phlegm and liver pus revealed growth of Citrobacter flavescens.Computed tomography showed infection in the inferior lobe of the right lung and a low-density lesion with gas in the right liver.Liver ultrasound showed that there was a big hypoechoic liquid lesion without blood flow signal.Drainage for liver abscess by needle puncture under ultrasonic guidance was performed.After 1 month of drainage and anti-infection therapy,the abscess in the liver and the infection in the lung were reduced obviously,and the symptom of expectoration was relieved.CONCLUSION Clinicians should be alert to the possibility of complications of liver abscess and tracheal fistula after TACE for HCC.Drainage for liver abscess by needle puncture under ultrasonic guidance could relieve the liver abscess and tracheal fistula.

Omics-imaging signature-based nomogram to predict the progression-free survival of patients with hepatocellular carcinoma after transcatheter arterial chemoembolization

BACKGROUND Enhanced magnetic resonance imaging(MRI)is widely used in the diagnosis,treatment and prognosis of hepatocellular carcinoma(HCC),but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment.Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival(PFS).AIM To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images.METHODS Delineate the regions of interest(ROI)in arterial phase,portal venous phase and delayed phase of enhanced MRI.After extracting the combinatorial features of ROI,the features are fused to obtain deep learning radiomics(DLR)_Sig.DeLong's test was used to evaluate the diagnostic performance of different typological features.K-M analysis was applied to assess PFS in different risk groups,and the discriminative ability of the model was evaluated using the Cindex.RESULTS Tumor diameter and diolame were independent factors influencing the prognosis of PFS.Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases(P<0.05).In deep transfer learning(DTL)and DLR,significant differences were observed between the multi-phase and individual phases feature sets(P<0.05).K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months,respectively,and the predicted probabilities of 6 months,1 year and 2 years were 92%,60%,40%and 98%,90%,73%,respectively.The C-index was 0.764,indicating relatively good consistency between the predicted and observed results.DTL and DLR have higher predictive value for 2-year PFS in nomogram.CONCLUSION Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph,it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC.

Percutaneous microwave ablation and transcatheter arterial chemoembolization for serum tumor markers and prognostics of middle-late primary hepatic carcinoma

BACKGROUND Primary hepatic carcinoma(PHC)has an insidious onset and is usually diagnosed in the middle and late stages.Although transcatheter arterial chemoembolization(TACE)is the preferred option for treating middle-and advanced-stage PHC,it has limited efficacy in killing tumor cells and poor long-term efficacy.TACE plus percutaneous microwave coagulation therapy(PMCT)is more effective than interventional therapy alone and can improve survival time.However,there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC.AIM To investigate the effect of PMCT+TACE on serum tumor markers and the prognosis of middle-late PHC.METHODS This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People’s Hospital between March 2018 and February 2021.Patients were divided into a single group(treated with TACE,n=75)and a combined group(treated with TACE+PMCT,n=75).Before and after treatment,the clinical efficacy and serum tumor marker levels[carbohydrate antigen 19-9(CA19-9),alpha-fetoprotein(AFP),and carcinoembryonic antigen(CEA)]of both groups were observed.The 1-year survival rates and prognostic factors of the two groups were analyzed.RESULTS The combined group had 21 and 35 cases of complete remission(CR)and partial remission(PR),respectively.The single group had 13 and 25 cases of CR and PR,decreased,with the decrease in the combined group being more significant(P<0.05).The 1-year survival rate of the combined group(80.00%)was higher than that of the single group(60.00%)(P<0.05).The average survival time within 1 year in the combined group was 299.38±61.13 d,longer than that in the single group(214.41±72.97 d,P<0.05).COX analysis revealed that tumor diameter,tumor number,and the treatment method were prognostic factors for patients with middle-late PHC(P<0.05).CONCLUSION TACE+PMCT is effective in treating patients with mid-late PHC.It reduces the levels of tumor markers,prolongs survival,and improves prognosis.

Clinical Analysis of Transcatheter Arterial Chemoembolization Sequential Microwave Ablation Combined with Targeted Therapy and Immunotherapy in the Treatment of Large Hepatocellular Carcinoma

Objective: To investigate the safety and efficacy of Transcatheter Arterial Chemoembolization (TACE), sequential Microwave Ablation (MWA) combined with targeted therapy and immunotherapy versus TACE combined with targeted therapy and immunotherapy in the treatment of large hepatocellular carcinoma (defined as tumor diameter > 5 cm). Methods: The prospective cohort study was conducted, with 81 patients with large hepatocellular carcinoma who were admitted to Jingzhou Central Hospital from 2018 to 2022, they were divided into two groups, 41 patients received TACE sequential MWA combined with targeted therapy and immunotherapy (observation group), and 40 patients received single TACE combined with targeted therapy and immunotherapy (control group). The short-term efficacies after 3 months of treatment, the Disease Control Rate (DCR), the Overall Survival (OS), adverse drug reactions and complications were compared and analyzed between the two groups. Results: The Objective Response Rate (ORR) of the observation group was significantly higher than that of the control group (ORR: 85.4% vs 57.5%, P = 0.005), The median Progression-Free Survival (PFS) and median OS of the observation group were better than those of the control group (mPFS: 16 months vs 10 months, P = 0.004;mOS: 39 months. vs 24 months, P = 0.008). The 1-, 2- and 3-year progression-free survival rates of the observation group were 72.9%, 50.4%, and 25.6%, and those of the control group were 30.4%, 11.0%, and 3.7%. The 1-, 2- and 3-year overall survival rates of the observation group were 78.9%, 71.7%, and 65.2%, and those of the control group were 65.1%, versus 42.1% and 36.9%. There was no significant difference in the incidence of adverse drug reactions and complications between the two groups. In this study, the adverse drug reactions were mild in Grades 1 - 2. Conclusion: TACE sequential MWA combined with targeted therapy and immunotherapy has efficacy and safety.

Analysis of tumor recurrence factors in patients of primary hepatocellular carcinoma with postoperative transcatheter arterial chemoembolization (TACE)

Objective： The aim of the study was to analyze the tumor recurrence factors in patients of primary hepatocellular carcinoma （PHC） with postoperative transcatheter arterial chemoembolization （TACE）. Methods： A total of 121 cases of PHC by TACE after 1-2 months of surgery was retrospectively analyzed, followed up and analyzed the free survival time and the factors related to tumor-free survival. Results： In all 121 cases, 1-, 2-, and 3-year tumor-free survival rates were 72.73%, 46.21% and 26.93%, respectively. Gender, age, HBV infection, tumor size, capsule is complete, degree of differentiation and the presence of vascular thrombosis were put into the COX proportional hazards model of survival time to select the influential variables. In the clinical data of all variables entering COX proportional hazards model, tumor size, tumor differentiation and the presence of vascular thrombosis were statistically significant contributions to the model. In the tumor diameter less than or equal 10 cm [P = 0.040, Exp （B） = 2.210], vascular thrombosis [P = 0.039, Exp （B） = 2.922] and the lower degree of tumor differentiation [P = 0.035, Exp （B） = 3.038], the risk of tumor recent recurrence increased. Conclusion： Tumor size, differentiation, and the presence of vascular thrombosis are the independent risk factors affecting the prognosis of PHC after TACE.

Pain management in patients with hepatocellular carcinoma after transcatheter arterial chemoembolisation: A retrospective study

BACKGROUND Pain after transcatheter arterial chemoembolisation(TACE)can seriously affect the prognosis of patients and the insertion of additional medical resources.AIM To develop an early warning model for predicting pain after TACE to enable the implementation of preventive analgesic measures.METHODS We retrospectively collected the clinical data of 857 patients(from January 2016 to January 2020)and prospectively enrolled 368 patients(from February 2020 to October 2022;as verification cohort)with hepatocellular carcinoma(HCC)who received TACE in the Hepatic Surgery Center of Tongji Hospital.Five predictive models were established using machine learning algorithms,namely,random forest model(RFM),support vector machine model,artificial neural network model,naive Bayes model and decision tree model.The efficacy of these models in predicting postoperative pain was evaluated through receiver operating characteristic curve analysis,decision curve analysis and clinical impact curve analysis.RESULTS A total of 24 candidate variables were included in the predictive models using the iterative algorithms.Age,preoperative pain,number of embolised tumours,distance from the liver capsule,dosage of iodised oil and preoperative prothrombin activity were closely associated with postoperative pain.The accuracy of the predictive model was compared between the training[area under the curve(AUC)=0.798;95%confidence interval(CI):0.745-0.851]and verification(AUC=0.871;95%CI:0.818-0.924)cohorts,with RFM having the best predictive efficiency(training cohort:AUC=0.869,95%CI:0.816-0.922;internal verification cohort:AUC=0.871;95%CI:0.818-0.924).CONCLUSION The five predictive models based on advanced machine learning algorithms,especially RFM,can accurately predict the risk of pain after TACE in patients with HCC.RFM can be used to assess the risk of pain for facilitating preventive treatment and improving the prognosis.

Jinlong capsule decreases adverse reactions after transcatheter arterial chemoembolization(TACE) in patients with hepatocellular carcinoma

Objective The aim of this study was to analyze whether Jinlong capsule could decrease adverse reactions after transcatheter arterial chemoembolization(TACE) in patients with hepatocellular carcinoma. Methods Eighty-two patients with hepatocellular carcinoma were randomly divided into the control group and experimental group. On the first day after TACE, the experimental group started receiving four Jinlong capsules orally three times daily, whereas the control group did not receive the treatment.Results The incidences of erythropenia and thrombocytopenia in the experimental group was lower than those in the control group(P = 0.040 and 0.033, respectively). The differences in serum levels of aminotransferase, albumin, potassium, and sodium between the two groups were significant(P = 0.034, 0.034, 0.013, and 0.044, respectively). The mean durations of stomachache and abdominal distension in the experimental group was significantly shorter than those in the control group(P = 0.004 and 0.021, respectively). However, there were no significant differences in the incidences of nausea, fever, and vomiting between the two groups(P = 0.490, 0.495, and 0.585, respectively). Conclusion The reduction in the incidence rate and duration of partial adverse reactions after TACE was observed in hepatocellular carcinoma patients treated with Jinlong capsule compared to untreated patients, suggesting possible beneficial effects exerted by Jinlong capsule on the reduction of TACE-induced liver damage, thereby improving liver function and, consequently, the quality of life.

Radiofrequency ablation or microwave ablation combined with transcatheter arterial chemoembolization in treatment of hepatocellular carcinoma by comparing with radiofrequency ablation alone

Objective：To compare radiofrequency ablation （RFA） or microwave ablation （MWA） and transcatheter arterial chemoembolization （TACE） with RFA or MWA monotherapy in hepatocellular carcinoma （HCC）.Methods：A prospective,randomized,controlled trial was conducted on 94 patients with HCC ≤7 cm at a single tertiary referral center from June 2008 to June 2010 at the Department of Hepatobiliary Surgery,the Second Affiliated Hospital of Southeast University.The patients were randomly assigned into the TACERFA or TACE-MWA （combined treatment group） and the RFA-alone or MWA-alone groups （control group）.The primary end point was overall survival.The secondary end point was recurrence-free survival,and the tertiary end point was adverse effects.Results：Until the time of censor,17 patients in the TACE-RFA or TACE-MWA group had died.The median follow-up time of the patients who were still alive for the TACE-RFA or TACE-MWA group was 47.5±11.3 months （range,29 to 62 months）.The 1-,3-and 5-year overall survival for the TACE-RFA or TACE-MWA group was 93.6％,68.1％ and 61.7％,respectively.Twenty-five patients in the RFA or MWA group had died.The median follow-up time of the patients who were still alive for the RFA or MWA group was 47.0±12.9 months （range,28 to 62 months）.The 1-,3-and 5-year overall survival for the RFA or MWA group was 85.1％,59.6％ and 44.7％,respectively.The patients in the TACE-RFA or TACE-MWA group had better overall survival than the RFA or MWA group [hazard ratio （HR）,0.526; 95％ confidence interval （95％ CO,0.334-0.823; P=0.002],and showed better recurrence-free survival than the RFA or MWA group （HR,0.582; 95％ CI,0.368-0.895; P=0.008）.Conclusions：RFA or MWA combined with TACE in the treatment of HCC ≤7 cm was superior to RFA or MWA alone in improving survival by reducing arterial and portal blood flow due to TACE with iodized oil before RFA.

A comparative study between Embosphere~ and conventional transcatheter arterial chemoembolization for treatment of unresectable liver metastasis from GIST

Objective：Transcatheter arterial chemoembolization （TACE） is a standard treatment for hepatocellular carcinoma （HCC） and/or some unresectable liver metastasis tumors.Hypervascular liver metastatic lesions such as metastasis from gastrointestinal stromal tumor （GIST） are an indication for transcatheter arterial embolization （TAE）.The purpose of this study was to evaluate the efficacy and safety of Embosphere（㊣）-TAE （Embo-TAE） in comparison with conventional TACE （cTACE） for the treatment of liver metastasis from GIST.Methods：A total of 45 patients who underwent TACE between Aug 2008 and Feb 2013 were enrolled.Patients with GIST who underwent TAE with Embosphere（㊣） （n=19） were compared with controls who received cTACE （n=26）.The primary end points were treatment response and treatment-related adverse events.The secondary end points were progression-free survival （PFS） and overall survival （OS）.Results：The treatment response of Embo-TAE group was significandy higher than that of the cTACE group （P＜0.001）.The PFS was significandy better in the Embosphere（㊣）-group than in the cTACE group （56.6 and 42.1 weeks,respectively; P=0.003）.However,there was no statistically significant difference in liver toxicity between the two groups （P＞0.05）.The median OS in the Embo-TAE group was longer than that in the cTACE group （74.0 weeks,95％ CI：68.2-79.8 vs.61.7 weeks,95％ CI：56.2-67.2 weeks） （unadjusted P=0.045）.The use of Embo-TAE significantly reduced the risk of death in patients with GIST with liver metastases according to the Cox proportonal hazards regression model [hazard ratio （HR）：0.149; 95％ CI：0.064-0.475].Conclusions：TAE with Embosphcre（㊣） showed better treatment response and delayed tumor progression compared with cTACE.There was no significant difference in treatment-related hepatic toxicities.EmboTAE thus appears to be a feasible and promising approach in the treatment of liver metastasis from GIST.

Balloon-occluded transcatheter arterial chemoembolization for hepatocellular carcinoma

Transcatheter arterial chemoembolization(TACE) is widely accepted as a treatment for patients with hepatocellular carcinoma(HCC) in the intermediate stage according to the Barcelona Clinic Liver Cancer(BCLC) guidelines. Recently, balloon-occluded TACE(B-TACE) was developed in Japan. Despite the lack of a clear definition, B-TACE is generally defined as the infusion of emulsion of chemotherapeutic agents with lipiodol followed by gelatin particles under the occlusion of feeding arteries by a microballoon catheter, which leads to the dense lipiodol emulsion(LE) accumulation in HCC nodules. This phenomenon cannot be explained only by the prevention of proximal migration and leakage of embolization materials; it further involves causing local changes in the hemodynamics of the surrounding occlusion artery and targeted HCC nodules. Balloon-occluded arterial stump pressure plays an important role in the dense LE accumulation in targeted HCC nodules. Although randomized controlled trials comparing the therapeutic effect and the prognosis of B-TACE to those of the other TACE procedures, such as conventional-TACE and drug-eluting beads TACE, are still lacking, B-TACE is thought to be a promising treatment. The purpose of this review is to summarize the mechanism, therapeutic effect, indication, prognosis and complications of BTACE.

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.

Association between vascular endothelial growth factor and metastasis after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma

BACKGROUND: Hypoxia up-regulates vascular endothelialgrowth factor (VEGF) and stimulates the growth of hepa-tocellular carcinoma (HCC) cells. This study was designedto investigate the association between changes in plasmaVEGF levels after transcatheter arterial chemoembolization(TACE) and HCC progression, especially in relation tometastasis.METHODS: Plasma VEGF levels were measured by quati-tative sandwich enzyme-linked immunosorbent assay(ELISA R&D system). Plasma VEGF levels were measuredbefore, 3 days and 4 weeks after TACE in 30 patients withHCC. The development of metastasis was evaluated at theend of the third month after TACE.RESULTS: The plasma VEGF levels of the 30 patients withHCC were 154.47±90.17 pg/ml. The total plasma VEGFlevels after TACE increased compared with their basal levels(P<0.05), and the plasma VEGF levels had a tendency toincrease in patients with heterogenous uptake of iodizdoiland portal vein thrombosis. Follow-up for six monthsshowed metastatic foci in 20 patients (74%) with increasedplasma VEGF, but none of the patients with decreased plas-ma VEGF developed metastasis.CONCLUSION: Increased plasma VEGF expression is asso-ciated with the development of metastasis in HCC after TA-CE.

Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization for hepatocellular carcinoma before liver transplantation

AIM:To assess the possible effect of two different types of preoperative transcatheter arterial chemoembolization(TACE)on recurrence-free survival after liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and to analyze the effects of TACE on tumor histology.METHODS:We retrospectively analyzed the histological features of 130 HCC nodules in 63 native livers removed at transplantation.Patients who received any other type of treatment such as radiofrequency tumor ablation,percutaneous ethanol ablation or who were not treated at all were excluded.All patients in the present study were within the Milan Criteria at the last imaging findings before transplantation.Doxorubicineluting bead TACE(DEB-TACE)was performed in 22patients(38 nodules),and conventional TACE(c-TACE)in 16(25 nodules).Patients’and tumors’characteristics were retrospectively reviewed.We performed a pernodule analysis of the explanted livers to establish the mean percentage of necrosis of any nodule treated by TACE(conventional or DEB)and a per-patient analysis to establish the percentage of necrosis in the cumulative tumor area,including 21 nodules not reached by TACE.Inflammatory and fibrotic changes in the tissue surrounding the tumor nodule were analyzed and categorized as poor/absent,moderate and enhanced reaction.Uni-and multivariate analysis of risk factors for HCC-recurrence were performed.RESULTS:The number and diameter of the nodules,the time spent on the waiting list and the number of treatments were similar in the two groups.A trend towards higher appropriate response rates(necrosis≥90%)was observed in the DEB-TACE group(44.7%vs32.0%,P=0.2834).The mean percentage of necrosis in the cumulative tumor area was 58.8%±36.6%in the DEB-TACE group and 50.2%±38.1%in the c-TACE group(P=0.4856).Fibrotic and inflammatory reactions surrounding the tumor nodule were markedly more common in the DEB-TACE group(P<0.0001,for both the parameters).The three-year recurrence-free survival was higher in DEB-TACE-treated patients than in conventionally treated patients(87.4%vs 61.5%,P=0.0493).Other factors affecting recurrence-free survival included viable tumor beyond Milan Criteria on histopathological examination,the percentage of necrosis on CTA≤50%and a pre-transplant serum-fetoprotein level greater than 70 ng/mL.On multivariate analysis,the lack of treatment with DEB-TACE,high levels of-fetoprotein and viable tumor beyond Milan Criteria at histology examination were identified as independent predictors of tumor recurrence.CONCLUSION:DEB-TACE can effectively promote tumor necrosis and improves recurrence-free survival after LT in HCC.

Sequential transcatheter arterial chemoembolization,three-dimensional conformal radiotherapy,and high-intensity focused ultrasound treatment for unresectable hepatocellular carcinoma patients

The purpose of this study was to evaluate the outcome of patients with unresectable hepatocellular carcinoma（HCC） treated by sequential therapy of transcatheter arterial chemoembolization（TACE）,three-dimensional conformal radiotherapy（3-DCRT） and high-intensity focused ultrasound（HIFU）.From October,2005 to September,2010,120 patients with unresectable HCC received the sequential treatments of several courses of TACE followed in 2-4 weeks by 3-DCRT and then a single session of HIFU with a curative intent.The median tumor irradiation dose was 40 Gy.Tumor response,toxicity and overall survival rate were analyzed.Clinicopathologic factors affecting the primary technique effectiveness and overall survival rates were investigated by univariate analysis or multivariate analysis.All 120 HCC patients were followed up by the last follow-up time.Among these patients,hepatic toxicities due to treatment were notable in 9 cases.Gastrointestinal bleeding after the overall treatment occurred in 2 cases,leukopenia of grade III was detected in 1 case,radiation-induced liver disease（RILD） was observed in 2 patients,and first-and second-degree skin burn around the HIFU treatment zone were observed in 2 patients and 1 patient,respectively.Among 120 patients,23,83 and 14 cases achieved partial response,stable disease and progressive disease,respectively.The overall survival rates at 1 year,3 years and 5 years were 70%,35% and 15%,respectively,with a median survival time of 26 months.Both Child-Pugh liver function grading and radiation dose were determined to be independent predictors for overall survival revealed by the multivariate analysis.It is concluded that the sequential therapy of TACE,3-DCRT and HIFU is a promising therapeutic regimen for unresectable HCC.

Combined therapy with transcatheter arterial chemoembolization and percutaneous microwave coagulation for small hepatocellular carcinoma

AIM:To assess the efficacy of combined transcatheter arterial chemoembolization(TACE)and percutaneous microwave coagulation therapy(PMCT)for small hepatocellular carcinoma(HCC). METHODS:Thirty-five patients with a total of 41 HCC nodules(≤3 cm in diameter)were treated with TACE followed by computed tomograghy(CT)-guided percutaneous microwave coagulation therapy(PMCT) within 1-3 wk. RESULTS:By biopsies and enhanced CT scans, complete necrosis of the tumor and 3-5 mm of the surrounding non-cancerous area were observed in 34 foci.In seven foci,incomplete necrosis of the surrounding parenchyma was observed.Serum alpha- fetoprotein(AFP)levels returned to normal 10 d after treatment in 25 patients who originally had high serum AFP levels.The follow-up period was 6-31 mo,and all patients remained alive.One patient had a recurrence in the subsegments of the liver,and another patient had a recurrence near the original lesion. CONCLUSION:Combined therapy with TACE and PMCT is a safe and effective treatment without severe complications for small HCC.

Effect of preoperative transcatheter arterial chemoembolization on angiogenesis of hepatocellular carcinoma cells

AIM： To evaluate the effects of four types of preoperative transcatheter arterial chemoembolization （TACE） on angiogenesis of hepatocellular carcinoma （HCC） ceils. METHODS： A total of 136 patients with HCC underwent liver resection. One to five courses of TACE prior to liver resection were performed in 79 patients （TACE group）, in which one to four courses of chemotherapy alone were performed in 11 patients （group A）; one to five courses of chemotherapy combined with iodized oil were performed in 33 patients （group B）; one to three courses of chemotherapy combined with iodized oil and gelatin sponge were performed in 23 patients （group C）, one to three courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge were performed in 12 patients （group D）. The other 57 patients only received liver resection （non-TACE group）. The microvessels were marked by CD31. The expression of CD31 and vascular endothelial growth factor （VEGF） protein were detected by immunohistochemical methods. RESULTS： The mean microvessel density （MVD） in HCC cells was significantly higher in groups A, B, C and D than in the nonACE group （P 〈 0.05）. The expression of VEGF protein in HCC cells were significantly higher in groups A, B, C and D than in the non-TACE group （P 〈 0.05）. MVD and the expression of VEGF protein were positively correlated. Mean MVD and the expression of VEGF protein were closely related to the number of courses of TACE and the interval of TACE. CONCLUSION： Four different types of preoperative TACE regimens enhanced angiogenesis in HCC cells by up-regulating the expression of VEGF protein. It is necessary to repress angiogenesis of liver cancer after TACE.

Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma

BACKGROUND Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma.METHODS A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients’ wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or threedimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups;the related factors affecting overall survival time were analyzed. RESULTS The median survival time of the control group was 10.5 mo;the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo;P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.