Sequential Transcatheter Arterial Chemoembolization Research Articles

Sequential transcatheter arterial chemoembolization and portal vein embolization before hepatectomy for the management of patients with hepatocellular carcinoma: a systematic review and meta-analysis.

R0 resection is the gold standard for the treatment of hepatocellular carcinoma. However, residual liver deficiency remains a major obstacle to hepatectomy. This article aims to explore the short-term and long-term efficacy of preoperative sequential transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE) in the treatment of hepatocellular carcinoma. Multiple electronic literature databases up to February 2022 were searched. Furthermore, clinical studies comparing sequential TACE + PVE with portal vein embolization (PVE) were included. The outcomes included hepatectomy rate, overall survival, disease-free survival, overall morbidity, mortality, posthepatectomy liver failure, the percentage increase in FLR. Five studies included 242 patients who received sequential TACE + PVE and 169 patients received PVE. The sequential TACE + PVE group demonstrated more favorable results in terms of hepatectomy rate (OR = 2.37; 95% CI 1.09-5.11; P = 0.03), overall survival (HR 0.55; 95% CI 0.38 to - 0.79; P = 0.001), disease-free survival (HR 0.61; 95% CI 0.44-0.83; P = 0.002), and percentage increase in FLR (MD = 4.16%; 95% CI 1.13-7.19; P = 0.007). The pooled results did not demonstrate significant differences in overall morbidity, mortality, and posthepatectomy liver failure between the sequential TACE + PVE and PVE groups. Preoperative sequential TACE + PVE has been shown to be a safe and feasible treatment for hepatocellular carcinoma to improve resectability, and it has been shown to provide better long-term oncological outcomes than PVE.

Clinical evaluation of percutaneous endovascular radiofrequency ablation for portal vein tumor thrombus: experience in 120 patients.

Portal vein tumor thrombosis (PVTT) secondary to primary liver carcinoma (PLC) is commonly associated with poor prognosis and poses great challenge. This study was to evaluate the efficacy and safety of percutaneous endovascular radiofrequency ablation (RFA) in treatment of PVTT. Consecutive patients who were performed endovascular RFA because of PVTT in single-institution in recent 8years were retrospectively reviewed, compared with patients who underwent only sequential transcatheter arterial chemoembolization (TACE) during the contemporary period. Patency of portal vein, complications, and overall survival (OS) were investigated. One hundred and 20 patients who underwent endovascular RFA and 96 patients who underwent only sequential TACE were included. No severe complications happened in both groups. Except the higher rates of severe fever and moderate pain in the study group, no difference was found in the incidence of side effects and complications. The effective rate in the study group was (78.3%, 94/120) significantly higher than the comparison group (35.4%, 34/96). The median survival time and 1-3years cumulative survival rates in the study group were 15.7months and 42.5%, 21.7%, 2.5%, respectively, and 11.3months, 21.9%, 9.4%, 0 correspondingly in the comparison group, without significant difference. Type of PVTT and Child-Pugh classification of liver function were independent risk factors, and OS was significantly improved by endovascular RFA and subsequent therapy. Endovascular RFA is technically safe and feasible for unresectable PLC and PVTT to improve the prognosis and quality of life.

Clinical efficacy of computed tomography-guided microwave ablation sequential transcatheter arterial chemoembolization under edge calculation for primary liver cancer over 5 cm in diameter

Clinical efficacy of computed tomography-guided microwave ablation sequential transcatheter arterial chemoembolization under edge calculation for primary liver cancer over 5 cm in diameter

Therapeutic Efficacy Evaluation and Underlying Mechanisms Prediction of Jianpi Liqi Decoction for Hepatocellular Carcinoma

Objective: The aim of this study was to assess the therapeutic effects of Jianpi Liqi decoction (JPLQD) in hepatocellular carcinoma (HCC) and explore its underlying mechanisms. Methods: The characteristics and outcomes of HCC patients with intermediate stage B who underwent sequential conventional transcatheter arterial chemoembolization (cTACE) and radiofrequency ablation (RFA) only or in conjunction with JPLQD were analysed retrospectively. The plasma proteins were screened using label-free quantitative proteomics analysis. The effective mechanisms of JPLQD were predicted through network pharmacology approach and partially verified by ELISA. Results: Clinical research demonstrated that the Karnofsky Performance Status (KPS), traditional Chinese medicine (TCM) syndrome scores, neutropenia and bilirubin, median progression-free survival (PFS), and median overall survival (OS) in HCC patients treated with JPLQD were superior to those in patients not treated with JPLQD (all P<0.05). The analysis of network pharmacology, combined with proteomics, suggested that 52 compounds targeted 80 potential targets, which were involved in the regulation of multiple signaling pathways, especially affecting the apoptosis-related pathways including TNF, p53, PI3K-AKT, and MAPK. Plasma IGFBP3 and CA2 were significantly up-regulated in HCC patients with sequential cTACE and RFA therapy treated with JPLQD than those in patients not treated with JPLQD (P<0.001). The AUC of the IGFBP3 and CA2 panel, estimated using ROC analysis for JPLQD efficacy evaluation, was 0.867. Conclusion: These data suggested that JPLQD improves the quality of life, prolongs the overall survival, protects liver function in HCC patients, and exhibits an anticancer activity against HCC. IGFBP3 and CA2 panels may be potential therapeutic targets and indicators in the efficacy evaluation for JPLQD treatment, and the effective mechanihsms involved in the regulation of multiple signaling pathways, possibly affected the regulation of apoptosis.

Laparoscopic Right Hepatectomy for Hepatocellular Carcinoma Following Sequential TACE–PVE: A Multicentric Analysis of Textbook Outcome

Purpose: Major hepatectomy for hepatocellular carcinoma (HCC) is often preceded by sequential transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE). Laparoscopic approach offers better short-term outcome, especially through a higher rate of Textbook Outcome (TO) achievement. Thus, the ideal strategy would be to propose a laparoscopic approach after TACE/PVE for HCC. However, laparoscopic major hepatectomy in the context of underlying liver disease remains a challenging procedure. The aim of the present study was to assess short-term outcome and long-term outcome in a multicentric series of patients who underwent laparoscopic or open right hepatectomy following TACE/PVE for HCC. Method: All patients with HCC who underwent major hepatectomy after TACE/PVE were retrospectively included. Quality of surgical care was defined by TO combining 6 criteria. Short and long-term outcome were compared between the (LLR) group and the open liver resection (OLR) group before and after propensity score matching (PSM). Results: Between 2005 and 2019, 117 patients were included, 41 patients in LLR group and 76 patients in OLR group. OLR patients had larger tumors (median 65 mm vs 37 mm, p<0.001). Overall morbidity was comparable between LLR and OLR groups (52 vs 46%, p=0.79) as well as severe complications (11 vs 14%, p=1.00) ). Tumor-free margin was obtained in 96% of patients in LLR and 86% in OLR group (p=0.06). After PSM, patients’ and tumoral characteristics were comparable between LLR (n=27) and OLR (n=28) patients, as well as postoperative morbidity (overall morbidity 52% in matched LLR vs 46% in matched OLR, p=0.79). Five-year overall (OS) and disease-free survival (DFS) weren’t different between the 2 groups (55% in matched LLR vs 77% in matched OLR, p= 0.35; and 13% in matched LLR vs 17% in matched OLR, p=0.97, respectively). In LLR group, TO was completed in 66% of patients vs 37% in OLR group (p=0.02). Laparoscopic resection was the only predictive factor for TO achievement (HR 4.27, [1.77-10.28], p=0.001). Completion of TO was independently associated with a better 5-year OS (65.2% vs 42.5%, p=0.007) but not with 5-year DFS (26.9% vs 13.0%, p=0.17). Conclusion: Major LLR after TACE/PVE should be considered as an effective option with increasing chance of TO achievement and also, a better 5-year OS.

Sequential transcatheter arterial chemoembolization and portal vein embolization before right hemihepatectomy in patients with hepatocellular carcinoma

BackgroundRecent studies showed that sequential selective transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE) provided better future liver remnant (FLR) regeneration rate and disease-free survival following surgery compared with PVE alone. The present study aimed to clarify whether preoperative sequential TACE and PVE before right hemihepatectomy can reduce postoperative hepatocellular carcinoma (HCC) recurrence and improve long-term disease-free and overall survival. MethodsRecurrence and survival outcomes were retrospectively evaluated in 205 patients with HCC who underwent right hemihepatectomy by a single surgeon from November 1993 to November 2017. Patients were divided into four groups according to the procedure performed before the surgery: sequential TACE and PVE (TACE-PVE), PVE-only, TACE-only, or naïve control groups. The baseline patient and tumor characteristics, postoperative outcomes, recurrence-free survival and overall survival were analyzed. ResultsBaseline patient and tumor characteristics upon diagnosis were similar in all four groups, while sequential TACE and PVE were well tolerated. The TACE-PVE group had a higher mean increase in percentage FLR volume compared with that of the PVE-only group (17.46% ± 6.63% vs. 12.14% ± 5.93%; P = 0.001). The TACE-PVE group had significantly better overall and disease-free survival rates compared with the other groups (both P < 0.001). ConclusionsSequential TACE and PVE prior to surgery can be an effective therapeutic strategy for patients with HCC scheduled for major hepatic resection. The active application of preoperative sequential TACE and PVE for HCC would allow more patients with marginal FLR volume to become candidates for major hepatic resection by promoting compensatory FLR hypertrophy without the deterioration of basal hepatic functional reserve or tumor progression.

Sequential transcatheter arterial chemoembolization and portal vein embolization versus portal vein embolization alone before major hepatectomy for patients with large hepatocellular carcinoma: An intent-to-treat analysis

BackgroundLittle is known about the value of sequential transcatheter arterial chemoembolization and portal vein embolization compared with portal vein embolization alone before major hepatectomy for large hepatocellular carcinoma. We aimed to compare early and long-term outcomes of these two strategies. MethodsWe included all consecutive patients with large hepatocellular carcinoma (≥50 mm) scheduled for sequential transcatheter arterial chemoembolization and portal vein embolization or portal vein embolization alone before major hepatectomy from January 2005 to December 2015. Comparisons were made on an intent-to-treat basis. ResultsA total of 55 patients were included as follows: sequential transcatheter arterial chemoembolization and portal vein embolization (n = 27) and portal vein embolization alone (n = 28). Baseline patient and tumor characteristics were similar in the 2 groups. Downstaging after transcatheter arterial chemoembolization changed the initial strategy in 4 patients who finally underwent liver transplant (n = 1) and limited hepatectomy (n = 3). Overall survival and progression-free survival were better in the transcatheter arterial chemoembolization group compared with the portal vein embolization alone group (3-year overall survival of 60% vs 20%; P = .01 and 3-year progression-free survival of 35% vs 0%; P < .001). The proportion of patients who finally underwent hepatectomy after transcatheter arterial chemoembolization plus portal vein embolization was 91% vs 68% after portal vein embolization alone (P = .08). Hypertrophy of the future remnant liver after portal vein embolization was greater after transcatheter arterial chemoembolization (43% vs 31%, P = 0.03). After resection, the group that received transcatheter arterial chemoembolization and portal vein embolization experienced better progression-free survival compared with portal vein embolization alone (3-year progression-free survival of 28% vs 0%; P = .03). ConclusionOur results suggest that transcatheter arterial chemoembolization before portal vein embolization increases the degree of hypertrophy of the future remnant liver after portal vein embolization and yields improved oncologic outcomes in patients with large hepatocellular carcinomas planned for major hepatectomy.

Effect of microvascular invasion on prognosis of patients with hepatocellular carcinoma after hepatectomy

Objective To investigate the effect of microvascular invasion (MVI) on tumor recurrence of hepatocellular carcinoma (HCC) patients after hepatectomy, the efficacy of sequential transcatheter arterial chemoembolization (TACE) on positive MVI patients after hepatectomy, and the effect of comprehensive treatment on the prognosis of patients with tumor recurrence. Methods The retrospective cross-sectional study was conducted. The clinicopathological data of 136 HCC patients who underwent hepatectomy in the First Affiliated Hospital of Air Force Medical University from February 2015 to December 2016 were collected. Patients were treated with TACE, radiofrequency ablation (RFA) and molecular-targeted drugs after hepatectomy, and patients with tumor recurrence selected 1 or 2 above treatments. The patient received postoperatively outpatient reexaminations every 3 months to detect tumor recurrence and survival. Follow-up was from the day of the surgery to death or December 2017. Observation indicators: (1) treatment after hepatectomy; (2) effect of MVI on tumor recurrence of HCC patients after hepatectomy: clinicopathological features and tumor recurrence rate between positive and negative MVI patients; (3) efficacy of TACE on positive MVI patients: clinicopathological features and tumor recurrence rate in positive MVI patients with or without TACE; (4) effect of comprehensive treatment on the prognosis of patients with tumor recurrence. Measurement data with normal distribution were represented as ±s and analyzed using the independent-samples t test. Comparisons of count data were analyzed using chi-square test or Fisher exact probalility. The tumor recurrence rate and survival rate were calculated by the Kaplan-Meier method, and Log-rank test was used for survival analysis. Results (1) Treatment after hepatectomy: of 136 patients undergoing hepatectomy, 117 underwent single hepatectomy and 19 combined sequential TACE; 59 had HCC recurrence, including 22 receiving comprehensive treatment. (2) Effect of MVI on tumor recurrence of HCC patients after hepatectomy: ① Clinicopathological features: of 117 patients undergoing single hepatectomy, positive MVI was detected in 49 patients, including 44 males and 5 females, with an age of (52±10)years old; 49 patients were in Child-Pugh grade A, including 36 combined with liver cirrhosis and 13 without liver cirrhosis; positive and negative alpha-fetoproteins (AFPs) were respectively detected in 34 and 15 patients. Negative MVI was detected in 68 patients, including 54 males and 14 females, with an age of (55±11)years old; 65 and 3 patients were respectively in Child-Pugh grade A and B, including 52 combined with liver cirrhosis and 16 without liver cirrhosis; positive and negative AFPs were respectively detected in 39 and 29 patients. There was no statistically significant difference in gender, age, Child-Pugh score of liver function, liver cirrhosis and comparison of AFP between positive and negative MVI patients (χ2=2.258, t=-1.626, χ2=0.804, 0.138, 1.758, P>0.05). ② Tumor recurrence rate: The 6-month and 1-year tumor recurrence rates after hepatectomy were respectively 30.77%, 30.61% in 117 patients undergoing single hepatectomy and 42.86%, 51.02% in 49 of 117 patients with positive MVI and 22.06%, 27.94% in 68 of 117 patients with negative MVI, showing statistically significant differences in 6-month and 1-year tumor recurrence rates between positive and negative MVI patients (χ2=5.738, 6.465, P 0.05). ② Tumor recurrence: the 6-month and 1-year tumor recurrence rates after hepatectomy were respectively 0, 28.57% in 7 positive MVI patients with sequential TACE and 42.86%, 51.02% in 49 positive MVI patients without sequential TACE, showing a statistically significant difference in 6-month tumor recurrence rate (χ2=4.800, P 0.05). (4) Effect of comprehensive treatment on the prognosis of patients with tumor recurrence: of 59 patients with tumor recurrence, 37 didn′t receive comprehensive treatment, 34 of 37 died within 1-year postoperatively, including 30 deaths within 6-month postoperatively, and 1-year survival rate was 8.10%; 22 received comprehensive treatment, including 4 deaths within 1-year postoperatively, and 1-year survival rate was 81.80%, showing a statistically significant difference in 1-year survival rate (χ2=32.698, P<0.05). Conclusions MVI is one of the important risk factors affecting HCC recurrence and metastasis after hepatectomy. The combined TACE after hepatectomy can reduce the HCC recurrence rate of MVI positive patients, and active comprehensive treatment after HCC recurrence can significantly prolong the survival time of patients. Key words: Hepatic neoplasms; Surgical resection; Microvascular invasion; Transcatheter arterial chemoembolization; Comprehensive treatment; Recurrence rate; Survival time

Liver Injury and Tumor-Inhibiting Effect of Sequential Transcatheter Arterial Chemoembolization and Portal Venous Embolization on Rabbit VX2 Liver Carcinoma.

BackgroundThe concepts of sequential transcatheter arterial chemoembolization (TACE) and portal venous embolization (PVE) were proposed to prevent the detrimental tumor growth-inducing effect of PVE and to facilitate growth of further future liver remnant (FLR). This study aimed to investigate the effect of sequential TACE and PVE on liver damage and the therapeutic effect in a rabbit VX2 liver tumor model.Material/MethodsRabbits bearing VX2 liver tumors were randomly divided into TACE+PVE, TACE, PVE, and Sham groups. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and alkaline phosphatase (ALP) at 6 h, 24 h, 3 days, and 7 days were measured by ELISA assay. Tumor diameter on day 7 was measured and the tumor sections with cleaved caspase-3 was stained and observed.ResultsPlasma ALT, AST, and ALP levels were significantly increased at the first hours after the interventions. The TACE group had higher increases than the TACE+PVE and PVE alone groups. ALT, AST, and ALP levels decreased on day 7 and presented a trend to return to the baseline level. The TACE+PVE group showed stronger tumor-inhibiting effect than the TACE and PVE alone groups and also induced the highest level of tumor cell apoptosis.ConclusionsThe liver damage caused by TACE+PVE is mild and recoverable. TACE+PVE showed stronger tumor-inhibiting effect than in the TACE and PVE group and also induced the highest level of tumor cell apoptosis.

Treatment of Small Hepatocellular Carcinoma (≤2 cm) in the Caudate Lobe with Sequential Transcatheter Arterial Chemoembolization and Radiofrequency Ablation

To evaluate technical feasibility and treatment results of sequential transcatheter arterial chemoembolization (TACE) and cone-beam computed tomography-guided percutaneous radiofrequency ablation (CBCT-RFA) for small hepatocellular carcinoma (HCC) in the caudate lobe. Institutional review board approved this retrospective study. Radiologic database was searched for the patients referred to perform TACE and CBCT-RFA for small caudate HCCs (≤2cm) between February 2009 and February 2014. A total of 14 patients (12 men and 2 women, mean age; 61.3years) were included. Percutaneous ultrasonography-guided RFA (pUS-RFA) and surgery were infeasible due to poor conspicuity, inconspicuity or no safe electrode pathway, and poor hepatic reserve. Procedural success (completion of both TACE and CBCT-RFA), technique efficacy (absence of tumor enhancement at 1month after treatment), and complication were evaluated. Treatment results including local tumor progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS), and progression-free survival (PFS) were analyzed. Procedural success and technique efficacy rates were 78.6% (11/14) and 90.9% (10/11), respectively. Average follow-up period was 45.3months (range, 13.4-64.6months). The 1-, 3-, and 5-year LTP probabilities were 0, 12.5, and 12.5%, respectively. IDR occurred in seven patients (63.6%, 7/11). The 1-, 3-, and 5-year PFS probabilities were 81.8, 51.9, and 26%, respectively. The 1-, 3-, and 5-year OS probabilities were 100, 80.8, and 80.8%, respectively. Combination of TACE and CBCT-RFA seems feasible for small HCC in the caudate lobe not amenable to pUS-RFA and effective in local tumor control.

Absence of Benefit of Transcatheter Arterial Chemoembolization (TACE) in Patients with Resectable Solitary Hepatocellular Carcinoma

This study aimed to assess the prognostic impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term survival outcomes in patients undergoing resection of small solitary hepatocellular carcinoma (HCC). Enrolled patients had undergone macroscopic curative resection of solitary 2-5 cm HCC with (n = 105) or without (n = 830; control group) preoperative TACE. TACE group was divided into subgroups A (n = 68, 1-2 TACEs within 12 months), B (n = 23, ≥ 3 TACEs within 12 months), and C (n = 14, TACE prior to 12 months). The number of TACE sessions was 1.8 ± 1.6. In TACE A-C subgroups, pathological response of tumor necrosis >50 % at median post-TACE period after final TACE was observed in 41 (60.3 %) at 1.9 months, 10 (43.5 %) at 2.1 months, and 2 (14.3 %) at 18.9 months, respectively. The 5-year tumor recurrence and patient survival rates were 62.8 and 70.4 % in TACE group and 51.4 and 83.4 % in control group, respectively (p ≤ 0.003). Median periods of postoperative tumor recurrence in TACE A-C subgroups and control group were 35, 13, 14, and 55 months, respectively (p < 0.001); and postoperative survival periods at 75 % survival rate were 51, 38, 51, and 98 months, respectively (p = 0.003). TACE-induced extensive tumor necrosis did not improve postoperative prognosis in TACE A subgroup (p ≥ 0.053). Postoperative prognosis after preoperative sequential TACE and portal vein embolization was comparable to that of the control group (p ≥ 0.052). Preoperative TACE for small solitary HCCs may adversely affect post-resection prognosis, irrespective of pathological responses. Preoperative TACE should be avoided for patients with resectable small HCCs.

Prognostic effect of preoperative sequential transcatheter arterial chemoembolization and portal vein embolization for right hepatectomy in patients with solitary hepatocellular carcinoma.

Backgrounds/AimsBoth preoperative transcatheter arterial chemoembolization (TACE) alone and portal vein embolization (PVE) alone have a detrimental prognostic effect on the post-resection outcomes in patients with hepatocellular carcinoma (HCC). The main objective of this study was to assess the prognostic impact of preoperative TACE on the long-term survival outcomes in patients undergoing preoperative PVE and right liver resection for solitary HCC.MethodsPatients who underwent macroscopic curative right liver resection of solitary HCC that lied between 3.0 and 7.0 cm (n=113) with or without preoperative TACE and PVE were selected for the study, making these subjects were divided into three groups; the TACE-PVE group (n=27), the PVE-alone group (n=13), and the control group (n=73). The subjects in the three groups were followed up for ≥36 months or until death.ResultsThe 1-, 3-, 5-, and 10-year overall patient survival rates of all 113 patients were 96.5%, 88.2%, 81.3% and 65.0%, respectively. The 1-, 3-, 5-, and 10-year overall patient survival rates were 96.3%, 83.4%, 83.4% and 47.6% respectively in the TACE-PVE group; 84.6%, 76.9%, 57.7% and 19.2% respectively in the PVE-alone group; and 98.6%, 91.7%, 85.1% and 81.7% respectively in the control group (p=0.047). Patients were also sub-grouped according to tumor size, and those with a tumor of up to cutoff at 5 cm showed no prognostic difference (p=0.774), but tumor size >5 cm was associated with inferior patient survival only in the TACE-PVE group (p=0.018).ConclusionsPreoperative sequential TACE and PVE appear to be compliant to the conventional oncological concept in addition to induction of the future remnant liver regeneration. Therefore, we suggest that preoperative TACE should be come first whenever preoperative PVE for major hepatectomy is planned, especially in patients with hypervascular HCC tumors.

Safety and Efficacy of Sequential Transcatheter Arterial Chemoembolization and Portal Vein Embolization prior to Major Hepatectomy for Patients with HCC

To evaluate the safety and efficacy of sequential transcatheter arterial chemoembolization (TACE )and portal vein embolization (PVE) before major hepatectomy for patients with hepatocellur carcinoma (HCC). In this retrospective case-control study, data were collected from patients who underwent sequential TACE and PVE prior to major hemihepactectomy. Liver volumes were measured by computed tomography volumetry before TACE, and preoperation to assess degree of future remnant liver (FRL) hypertrophy and to check whether intro- or extrohepatic metastasis existed. Liver function was monitored by biochemistry after TACE, prior to and after major hepatectomy. Mean average FRL volume increased 32.3-71.4% (mean 55.4%) compared with preoperative FRL volume. After TACE, liver enzymes were elevated, but returned to normal in four weeks. During PVE and resection, no patient had intro- or extrohepatic metastasis. Sequential TACE and PVE is an effective method to improve resection opportunity, expand the scope of surgical resection, and greatly reduce postoperative intra- and extrahepatic metastasis.

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 con-formal 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 af-fecting 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 regi-men for unresectable HCC

Recurrent Hepatocellular Carcinoma Treated with Sequential Transcatheter Arterial Chemoembolization and RF Ablation versus RF Ablation Alone: A Prospective Randomized Trial

To compare prospectively the effects of radiofrequency (RF) ablation after transcatheter arterial chemoembolization (TACE) with those of RF ablation alone in the treatment of recurrent hepatocellular carcinoma (HCC). This study was approved by the institutional ethics committee, and all patients gave written informed consent. From January 2002 to December 2006, 139 patients with recurrent HCC measuring 5 cm in diameter or smaller were randomized to receive either sequential TACE and RF ablation (sequential treatment group, n=69) or RF ablation alone (RF ablation group, n=70). The survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. Bonferroni correction was applied when multiple comparisons were performed. P<.0083 (.05÷6) was considered indicative of a statistically significant difference. The 1-, 3-, and 5-year overall survival rates were 94%, 69%, and 46%, respectively, for the sequential treatment group and 82%, 47%, and 36% for the RF ablation group (P=.037). The corresponding recurrence-free survival rates were 80%, 45%, and 40% for the sequential treatment group and 64%, 18%, and 18% for the ablation group (P=.005). At subgroup analyses, the overall survival for the sequential treatment group was better than that for the RF ablation group for patients with tumor recurrence 1 year or less after initial treatment (P=.004) and those with tumors measuring 3.1-5.0 cm (P=.002) but not for those with tumor recurrence more than 1 year after initial treatment (P=.421) and those with tumors 3.0 cm or smaller (P=.478). The recurrence-free survival in the sequential treatment group was better than that in the RF ablation group for patients with tumors measuring 3.1-5.0 cm (P<.001) but not for those with tumors 3.0 cm or smaller (P=.204). For recurrence-free survival, there was no significant difference between the two groups for patients with tumor recurrence 1 year or less or more than 1 year after initial treatment (P=.020 and P=.111, respectively). Logistic regression analysis showed that treatment allocation and the interval between initial treatment and tumor recurrence were significant prognostic factors for overall survival, whereas the interval between initial treatment and tumor recurrence, treatment allocation, and tumor size were significant prognostic factors for recurrence-free survival. The efficacy of sequential TACE-RF ablation is better than that of RF ablation alone for recurrent HCC.

Sequential Transcatheter Arterial Chemoembolization and Portal Vein Embolization versus Portal Vein Embolization Only before Major Hepatectomy for Patients with Hepatocellular Carcinoma

To evaluate the safety and efficacy of sequential transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE) prior to surgery in hepatocellular carcinoma (HCC) patients and to compare the clinical outcome of the combined procedure with that of a matched group of patients undergoing PVE alone. From 1997 to 2008, 135 patients with HCC underwent sequential TACE and PVE (n = 71) or PVE alone (n = 64) before right hepatectomy. PVE was performed mean 1.2 months after TACE. In both groups, computed tomography (CT) and liver volumetry were performed before and 2 weeks after PVE to assess degree of left lobe hypertrophy. Baseline patient and tumor characteristics were similar in the two groups. After PVE, the chronological changes of liver enzymes were similar in the two groups. The mean increase in percentage future liver remnant (FLR) volume was higher in the TACE + PVE group (7.3%) than in the PVE-only group (5.8%) (P = 0.035). After surgery, incidence of hepatic failure was higher in the PVE-only group (12%) than in the TACE + PVE (4%) group (P = 0.185). Overall (P = 0.028) and recurrence-free (P = 0.001) survival rates were significantly higher in the TACE + PVE group than in the PVE-only group. Sequential TACE and PVE before surgery is a safe and effective method to increase the rate of hypertrophy of the FLR and leads to longer overall and recurrence-free survival in patients with HCC.

Induction of Tumor Growth After Preoperative Portal Vein Embolization: Is It a Real Problem?

Although preoperative portal vein embolization (PVE) is an effective means to increase future remnant liver (FRL) volume, little has been published on possible adverse effects. This review discusses the clinical and experimental evidence regarding the effect of PVE on tumor growth in both embolized and nonembolized liver lobes, as well as potential strategies to control tumor progression after PVE. A literature review was performed using MEDLINE with keywords related to experimental and clinical studies concerning PVE, portal vein ligation (PVL), and tumor growth. Cross-references and references from reviews were also checked. Clinical and experimental data suggest that tumor progression can occur after preoperative PVE in embolized and nonembolized liver segments. Clinical evidence indicating possible tumor progression in patients with colorectal metastases or with primary liver tumors is based on studies with small sample size. Although multiple studies demonstrated tumor progression, evidence concerning a direct increase in tumor growth rate as a result of PVE is circumstantial. Three possible mechanisms influencing tumor growth after PVE can be recognized, namely changes in cytokines or growth factors, alteration in hepatic blood supply and an enhanced cellular host response promoting local tumor growth after PVE. Post-PVE chemotherapy and sequential transcatheter arterial chemoembolization (TACE) before PVE have been proposed to reduce tumor mass after PVE. We conclude that tumor progression can occur after PVE in patients with colorectal metastases as well as in patients with primary liver tumors. However, further research is needed in order to rate this risk of tumor progression after PVE.

Sequential Transcatheter Arterial Chemoembolization and Portal Vein Embolization for Hepatocellular Carcinoma: The University of Tokyo Experience

When undertaking portal vein embolization (PVE) in patients with hepatocellular carcinoma (HCC), the following possibilities should be considered: (1) failure to induce hypertrophy of the nonembolized segments due to the underlying liver disease, (2) acceleration of tumor growth by occlusion of the portal venous flow because HCC is a hypervascular tumor fed exclusively by hepatic arterial flow, and (3) poor efficacy of PVE due to the presence of arterioportal shunts frequently observed in cases of liver cirrhosis and HCC. With these in mind, we performed sequential transcatheter arterial chemoembolization (TACE) and PVE in 45 patients with HCC undergoing major liver resection. This double preparation was well tolerated, enhanced the hypertrophy process in the nonembolized segments, and suppressed the tumor growth during the preparation period. Furthermore, PVE also functioned as a preoperative test to select patients for major liver resection. Sequential TACE and PVE is an effective preoperative intervention in patients with HCC scheduled for major liver resection.