Effects of p53 on apoptosis and proliferation of hepatocellular carcinoma cells treated with transcatheter arterial chemoembolization

AIM: To evaluate the effects of p53 on apoptosis and proliferation of hepatocellular carcinoma (HCC) cells treated with transcatheter arterial chemoembolization (TACE). METHODS: A total of 136 patients with HCC received TACE and other management before surgery were divided into TACE group and non-TACE group. TACE group included 79 patients who had 1-5 courses of TACE before surgery, of them, 11 patients had 1-4 courses of chemotherapy (group A), 33 patients had 1-5 courses of chemotherapy combined with iodized oil (group B), 23 patients had 1-3 courses of chemotherapy, iodized oil and gelatin sponge (group C), 12 patients had 1-3 courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge (group D). Non-TACE group included the remaining 57 patients who had surgery only. The extent of apoptosis was analyzed by transferase mediated dUTP nick end labeling (TUNEL) staining. The expressions of p53, Bcl-2, Bax, Ki-67 and PCNA protein were detected by immunohistochemical method. RESULTS: P53 protein expressions in trabecular and clear cells in HCC specimens were significantly lower than that in pseudoglandular, solid, poorly differentiated or undifferentiated and sclerosis HCC (P<0.05). Expression of p53 protein in HCC cells increased with the increase of pathological grades (P<0.05), and correlated positively with expressions of Ki-67 and PCNA protein, and negatively with Bcl-2 to Bax protein expression rate and AI (P<0.05). Expression of p53 protein was significantly higher in group A than in groups B, C, D and the non-TACE group, and was higher in group B than in groups C and D, and lower in group D than in the non-TACE group (P<0.05). CONCLUSION: Expression of p53 protein can enhance proliferation of HCC cells and suppress apoptosis of HCC cells after TACE.     

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.     

Radiation-induced hepatic toxicity after radiotherapy combined with chemotherapy for hepatocellular carcinoma

Aim: The purpose of the present study was to analyze hepatic toxicity following radiotherapy combined with regional chemotherapy for hepatocellular carcinoma (HCC). Methods: From 2001 to 2003, a total of 132 patients with HCC received 3-D conformal radiation therapy (3D-CRT) combined with chemotherapy. Patients were divided into two groups based on drug localization: the transcatheter arterial chemoembolization (TACE) group, where the chemotherapeutic drug (adriamycin) was localized within the tumor, and the non-TACE group, where the drugs (adriamycin, cisplatin, 5-fluorouracil) were diffusely spread over the entire liver. Results: Patients were evaluated by biochemical parameters for any hepatic toxicity prior to, during, and until 12 months after 3D-CRT. Hepatic toxicity was defined as radiation-induced liver disease (RILD) or combined modality-induced liver disease (CMILD), which is defined as RILD with abnormal elevation of total bilirubin levels. In the TACE group, three patients developed RILD (5.6%) and none developed CMILD. In the non-TACE group, three patients (3.7%) and seven patients (8.8%) developed RILD and CMILD, respectively. Conclusion: Hepatic toxicity following radiotherapy combined with regional chemotherapy for HCC might be influenced by the distribution of the chemotherapeutic drugs. A more precise understanding of hepatic toxicity from chemoradiotherapy will help design optimal treatments for HCC.     

Milan criteria are useful predictors for favorable outcomes in hepatocellular carcinoma patients undergoing liver transplantation after transarterial chemoembolization

INTRODUCTION Hepatocellular carcinoma (HCC) is a major global health problem involving more than 500 000 new cases a year. Several treatment modalities, such as liver transplantation (LT), surgical resection, radiofrequency ablation (RFA), and percutaneou…     

Indications for hepatectomy for hepatocellular carcinoma — What stage of the disease is the best indication for surgery?

To determine the clinical and tumor stage of hepatocellular carcinoma (HCC) that is the best indication for surgery, the postoperative long-term outcomes of patients who underwent hepatic resection were examined retrospectively. Of 975 patients with HCC who underwent regional therapy, 384 patients (39%) received hepatic resection (HR), 534 (55%) had transcatheter arterial chemoembolization (TACE), and the remaining 57 (6%) received percutaneous ethanol injection (PEI) into the tumor. The criteria defined by liver Cancer Study Group of Japan was used for staging and liver functional reserve (i.e., clinical staging).¹ In the 133 patients with stage I HCC, there were no significant differences among the survivals of the HR, TACE, and PEI groups. In the 314 patients with stage II HCC, the 5- and 7-year survival rates were 51% and 46% in the HR group, 23% and 10% in the TACE group, and 0% and 0% in the PEI group. The survival of the HR group was significantly better than the survivals of the TACE and PEI groups (P < 0.001). The 5- and 10-year survivals of the stage II HCC patients who had HR were 64% and 47% in the clinical stage I (i.e., good liver function) group, significantly better than the 5; and 10-year survivals (32% and 23%) in the clinical stage II (i.e., bad liver function) group (P < 0.0001). Patients with good liver function in stage II are expected to have better survival and are considered to be the most suitable for HR.     

Preoperative systemic 5-fluorouracil does not increase the risk of liver resection

BACKGROUND/AIMS: The majority of patients who underwent surgery for colorectal liver metastases have been previously treated with 5-FU either as adjuvant chemotherapy or as a primary treatment. We have performed a retrospective study to assess whether this chemotherapy increases the risk of liver resection. METHODOLOGY: Mortality, morbidity and histology of the resected liver of two groups of patients having colorectal liver metastases who underwent major resection were studied. The first group included 17 patients who had received at least 2 courses of 5-FU chemotherapy within 3 months prior to liver resection. The second group included 18 patients who had received no chemotherapy and who were used as controls. RESULTS: Perioperative mortality was nil. Intraoperative blood loss during liver resection (1 +/- 2.5 vs. 1.2 +/- 2 units) was similar in the two groups. Changes of liver function tests on days 2 and 5 were similar in the two groups. Morbidity rate was similar in the two groups (29 vs. 22%) with a mean duration of postoperative hospital stay of 19 +/- 9 days in the 5-FU group and 16 +/- 6 days in the control group. Although 7 (41%) patients in the 5-FU group had an abnormal parenchyma consistency as compared to only 3 (17%) in the control group, the pathological findings within the resected specimen were not different. CONCLUSIONS: 5-FU based systemic chemotherapy does not increase the risk of liver resections.     

吉西他滨联合奥沙利铂经肝动脉化疗栓塞防治肝癌术后复发

目的:探讨吉西他滨联合奥沙利铂经肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)在防治肝癌高危患者术后复发中的价值.方法:回顾性分析肝癌术后复发高危患者120例,88例术后3-6wk接受TACE治疗为TACE组,其中43例采用吉西他滨联合奥沙利铂组成的GEMOX方案(GEMOX组),45例使用传统化疗药物方案(对照组);32例因其他原因未接受TACE治疗作为为单纯手术组.通过6mo、12mo的随访,比较各组6mo、12mo术后复发率.结果:TACE组术后6mo、12mo肝内复发率(20.5%、43.8%)明显低于单纯手术组(37.5%、59.4%),两者均有统计学意义(χ2=6.512、4.573,P<0.05).在TACE组中,GEMOX组6mo术后复发率(11.6%)较对照组(28.9%)低,差异有统计学意义(χ2=4.026,P<0.05),两组12mo术后复发率无明显差异(χ2=0.876,P>0.05);在TACE不良反应中,GEMOX组白细胞减少及恶心、呕吐发生率较对照组低,差异有统计学意义(Z=-2.156、-2.295,P<0.05).结论:对肝癌术后复发高危患者进行预防性TACE有助于减少或延缓术后近期复发率,吉西他滨联合奥沙利铂方案疗效更佳.     

High—dose lodized Oil Transcatheter Arteri Chemoembolization For Patients with Large Hepatocellular Carcinoma

AIM: To conduct a randomized trial to evaluate the role ofusing high-dose iodized oil transcatheter arterialchemoembolization (TACE) in the treatment of largehepatocellular carcinoma(HCC).METHODS: From January 1993 to June 1998, 473 patientswith unresectable hepatocellular carcinoma were divided intotwo groups: 216 patients in group A received more than20mL iodized oil during the first TACE treatment; 257patients in group B received 5-15mL iodized oil in the sameway. The Child's classification and ICG-R15 for evaluatingthe liver function of the patients were done before thetreatment. During the TACE procedure the catheters wasinserted into the target artery selectively and the tumorvsssels were demonstrated with contrast medium in thehepatic angiography. The anticancer drugs mixed withiodized oil (Lipiodol) were Epirubicin and Mitomycin. Ingroup A, 112 cases received 20-29mL Lipiodol in the firstprocedure, 85 cases 30-39mL, 19 cases more than 40mL.The largest dose was 53 mL and the average dose was28.3mL. In group B, 119 cases received 5-10mL Lipiodol,138 cases received 11-15mL, and the average dose was11 .8mL.RESULTS: High-dose Lipiodol chemoembolization causedtolerable side effects and a little hurt to the liver function inthe patients with Child grade A or ICG-R15 ＜ 20. But thepatients with child grade B or ICG-R15 ＞ 20 had higher risk ofliver failure after high-dose TACE. More type Ⅰ and type Ⅱlipiodol accumulations in CT scan after 4 weeks of TACEwere seen in the group A patients than those in the group Bpatients( P＜ 0.01). The resection rate and complete tumornecrosis rate in group A were higher than those of group B(P ＜ 0.05). The 1-, 2-, 3-year survival rates of group Apatients with Child grade A were 79.2%, 51.8% and 34.9%,respectively, better than those of group B (P＜0.001).CONCLUSION: High-dose Lipiodol can result in morecomplete tumor necrosis by blocking both arteries and smallportal veins of the tumor. High-dose TACE for treatment oflarge and hypervascular hepatocellular carcinoma ispractically acceptable with the better effect than the routinedose. For the patients with large and hypervascular tumor ofChild grade A liver function or ICG-R15 less than 20%, oilychemoembolization with 20-40mL Lipiodol is recommended.     

Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the monoethylglycinexylidide test

OBJECTIVES: Transcatheter arterial chemoembolization (TACE) is the major treatment modality for patients with unresectable hepatocellular carcinoma (HCC). Hepatic failure after TACE is relatively common in patients with preexisting liver dysfunction. The purpose of this study was to evaluate whether the monoethylglycinexylidide test and other parameters might predict hepatic failure after TACE in HCC patients. METHODS: One hundred forty-two HCC patients undergoing TACE were enrolled into this study. Before TACE, their venous blood was collected 15 min after a bolus injection of lidocaine (1 mg/kg body weight). A fluorescence polarization immunoassay was used to measure monoethylglycinexylidide oncentrations in their sera. Univariate and multivariate analyses were performed on the monoethylglycinexylidide test and other parameters between patients with and without hepatic failure after TACE. RESULTS: Nineteen patients (13.4%) suffered hepatic failure after TACE. Univariate analysis revealed that the monoethylglycinexylidide concentration (17.7+/-5.8 vs 43.9+/-13.2 ng/ml), Child-Pugh score (6.9+/-0.6 vs 6.0+/-0.7), indocyanine green retention ratio at 15 min (32.4+/-6.5% vs 15.7+/-5.8%), prolonged PT, and serum total bilirubin and albumin showed significant differences between patients with and without hepatic failure after TACE. After a multiple logistic regression, only the monoethylglycinexylidide test was an independent predictor of hepatic failure (OR = 1.68, 95% CI = 1.07-2.65, p = 0.026). Among the 19 hepatic failure patients, three (15.8%) died of hepatic failure associated with TACE within 1 month after this procedure. CONCLUSIONS: As a predictor of hepatic failure after TACE, the monoethylglycinexylidide test is better than conventional liver function tests and clinical parameters. The monoethylglycinexylidide test may be used to select patients with relatively good liver reserves for safe TACE treatment.     

Combined endovascular brachytherapy,sorafenib, and transarterial chemobolization therapy for hepatocellular carcinoma patients with portal vein tumor thrombus

AIM To evaluate the safety and efficacy of combined endovascular brachytherapy(EVBT),transarterial chemoembolization(TACE),and sorafenib to treat hepatocellular carcinoma(HCC) patients with main portal vein tumor thrombus(MPVTT).METHODS This single-center retrospective study involved 68 patients with unresectable HCC or those who were unfit for liver transplantation and percutaneous frequency ablation according to the BCLC classification. All patients had Child-Pugh classification grade A or B,Eastern Cooperative Oncology Group(ECOG)performance status of 0-2,and MPVTT. The patients received either EVBT with stent placement,TACE,and sorafenib(group A,n = 37),or TACE with sorafenib(group B,n = 31). The time to progression(TTP) and overall survival(OS) were evaluated by propensity score analysis.RESULTS In the entire cohort,the 6-,12-,and 24-mo survival rates were 88.9%,54.3%,and 14.1% in group A,and 45.8%,0%,and 0% in group B,respectively(P 0.001). The median TTP and OS were significantly longer in group A than group B(TTP: 9.0 mo vs 3.4 mo,P 0.001; OS: 12.3 mo vs 5.2 mo,P 0.001). In the propensity score-matched cohort,the median OS was longer in group A than in group B(10.3 mo vs 6.0 mo,P 0.001). Similarly,the median TTP was longer in group A than in group B(9.0 mo vs 3.4 mo,P 0.001). Multivariate Cox analysis revealed that the EVBT combined with stent placement,TACE,and sorafenib strategy was an independent predictor of favorable OS(HR = 0.18,P 0.001). CONCLUSION EVBT combined with stent placement,TACE,and sorafenib might be a safe and effective palliative treatment option for MPVTT.     

Interventional oncology: new options for interstitial treatments and intravascular approaches

Superselective TACE is defined as TACE from the distal portion of the feeding subsegmental hepatic artery to evoke strong ischemic effects on a small area of the liver, thus avoiding damage to liver function. Lipiodol (iodized oil) is semi-fluid, and it can flow into the surrounding portal venules and hepatic sinusoids through peribiliary plexus (PBP) and the drainage route from the hypervascular HCC. Therefore, the reversed flow from the hepatic sinusoids and portal venules to the peripheral portion of the tumor and daughter nodules can be blocked by Lipiodol injected before a particulate embolus (such as gelatin sponge particles). Common complications of superselective TACE are mild local pain and fever and temporary minimal changes of liver function. Reported CR ratio of definitely hypervascular HCC are around 30–60% by superselective TACE with Lipiodol for hypervascular HCC less than 5 cm. According to a nationwide survey by the Liver Cancer Study Group of Japan (LCSGJ), overall 5-year survival rate was 26% in patients with HCCs not indicated for surgery or RFA (PEI), mainly treated by segmental or subsegmental TACE using Lipiodol. Therefore, this TACE technique should be widely introduced as the first line technique for TACE therapy of HCC.     

Preoperative systemic chemotherapy does not modify strategy of liver resection

BACKGROUND/AIMS: Most patients who undergo surgical resection of colorectal liver metastases have been previously treated with chemotherapy as adjuvant therapy or as a primary treatment. The aim of this retrospective study was to compare morbidity, mortality, liver function and histology of the liver specimens in patients undergoing colorectal liver metastases (CRLM) resection with and without a history of previous chemotherapy. METHODOLOGY: Records of 210 patients who underwent CRLM resection in our institution between January 1996 and March 2003 were retrospectively reviewed. We selected for further analysis medical charts of 40 patients who didn't receive a combined treatment concurrently to liver resection. Group I included 25 patients who did not receive adjuvant chemotherapy. Group II included 15 patients who received chemotherapy in the 3 months before liver resection. RESULTS: Postoperative mortality was 0% and 0.7% in group I and II respectively. Specific liver complications and pulmonary complications were similar in the two groups: 20% and 32% us. 33% respectively. The mean length of stay in the hospital was similar in the two groups (19 +/- 14 vs. 14 +/- 8). Changes of liver function test were similar in the two groups. Pathologic examination of liver specimens was not different in the two groups. CONCLUSIONS: Preoperative systemic chemotherapy didn't increase the risk of liver resection.     

Hepatic expression of the proliferative marker Ki-67 and p53 protein in HBV or HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma

To evaluate hepatic expression of the nuclear proliferative marker Ki-67 and the p53 oncoprotein in hepatitis B virus (HBV)/HCV cirrhosis in relation to dysplastic liver cell changes and hepatocellular carcinoma (HCC). We studied needle liver biopsies from 107 patients with cirrhosis and no HCC (52 HBV, 55 HCV) who had been assessed for protocol studies, and 57 cirrhotic patients with HCC (40 HBV, 17 HCV). We evaluated small and large cell dysplastic changes along with the expression of Ki-67 and p53 by immunohistochemistry. The labelling index (LI) was defined as the proportion (%) of positive-stained nuclei of the 500 measured. Large and small cell dysplastic changes were observed in 12 and 9% of specimens respectively. Only small cell changes were associated with Ki-67 expression. Ki-67 LI was 5.50 +/- 5.7 in cirrhosis (13.90 +/- 3.84 in those with small cell dysplastic changes vs 4.64 +/- 4.98 in those without, P < 0.01), 10.2 +/- 5.95 in cirrhosis with HCC (P < 0.05) and 18.56 +/- 10 in HCC (P < 0.01). Neither the presence of small cell dysplastic changes nor the expression of Ki-67 was related to severity or aetiology of cirrhosis. Expression of p53 was observed in 30% of the non-tumorous and in 53% of the neoplastic tissue obtained from patients with HCC, with no differences between HCV and HBV. Ki-67 and p53 expression was associated with the tumour grade (P < 0.001). Our observations clearly demonstrate the association between the proliferation activity and the morphological changes in the cirrhotic liver from the non-dysplastic to dysplastic lesion to HCC. They also support the hypothesis that p53 alterations are a rather late event in carcinogenesis and related to HCC grade. And finally, they suggest that the final steps of hepatocarcinogenesis are common and independent of the aetiology of the chronic viral infection.     

High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity

The prevalence, risk factors, and clinical significance of high liver cell proliferative activity were investigated in 208 well-compensated cirrhotic patients (150 men; 50 years; 135 with chronic hepatitis C) who had been under prospective surveillance for hepatocellular carcinoma (HCC) with annual abdominal ultrasound (US) and serum alpha-fetoprotein (AFP) determination. Immunostaining for proliferating cell nuclear antigen (PCNA) was employed to assess liver cell proliferative activity in formalin-fixed, paraffin-embedded liver specimens. The percentage of reactive nuclei was calculated by a computer-assisted image analysis system. The overall PCNA labeling index (LI) ranged from 0.1% to 12.5% (mean, 2.1%), being significantly higher in the 50 patients who developed HCC during 88 +/- 42 months of follow-up than in the 158 patients who remained cancer-free (3.6% +/- 2.4% vs. 1.6% +/- 1.5%; P <.0001). By receiver operating curve (ROC), a 2.0% cut-off value of PCNA-LI discriminated between patients at high and low risk for developing cancer. By multivariate analysis, high histologic grading scores and gender were associated to PCNA LI >2.0%. The yearly incidence of HCC was 5.2% for the 80 patients with PCNA-LI >2.0% compared with 1.1% for the 128 with low PCNA-LI (relative risk, 4.90; 95% CI, 2.63-9.55). By multivariate analysis, PCNA-LI >2.0% was the strongest independent predictor of cancer (hazard ratio, 5.49; 95% CI, 2.90-10.37). Overall, survival was significantly lower in patients with high liver cell proliferative activity rates than in those with low proliferative rates (10% vs. 75%; P <.0001). In conclusion, development of HCC in patients with compensated cirrhosis seems to be reliably predicted by liver cell proliferation status.     

Transarterial chemoembolization for inoperable,early stage hepatocellular carcinoma in patients with Child-Pugh grade A and B: results of a comparative study in 96 Chinese patients

OBJECTIVE: The efficacy of transarterial chemoembolization (TACE) in prolongation of survival is controversial. We conducted a comparative study to determine whether TACE treatment had any survival benefit for patients with unresectable hepatocellular carcinoma (HCC) and with relatively preserved liver function. METHODS: In all, 96 patients with unresectable HCC of Okuda stage I or II and Child-Pugh grade A or B were recruited. A total of 80 patients (group 1) who received TACE were compared to 16 patients (group 2) who were treated conservatively. RESULTS: The median survival time of group 1 patients was significantly longer than that of group 2 patients (31.2 vs 14.1 months respectively, p = 0.0126). The cumulative survival rates at 6 months, 1 yr, 2 yr, 3 yr, and 4 yr of group 1 compared to group 2 were as follows: 93.8% versus 62.5% (p = 0.002); 86.3% versus 62.5% (p = 0.023); 78.8% versus 50% (p = 0.017); 57.5% versus 50% (p = ns); and 51.3% versus 43.8% (p = ns), respectively. Tumor response was observed in 28% of patients receiving TACE. Patients with higher pretreatment albumin levels, lower pretreatment alpha-fetoprotein levels, and Okuda stage I disease were associated with a favorable response to TACE. CONCLUSION: TACE treatment improved survival in patients with unresectable HCC in the early stages and with relatively preserved liver function.     

Novel biomarkers GEP/ABCB5 regulate response to adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma

Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor(GEP) and ATP-dependent binding cassette(ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. Methods: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low(GEP-/ABCB5-), intermediate(either GEP +/ABCB5-or GEP-/ABCB5 +) and high(GEP +/ABCB5 +). Early recurrence(recurrence within 2 years after resection) and disease-free survival were analyzed. Results: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone( P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. Conclusions: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group(either GEP +/ABCB5-or GEP-/ABCB5 +). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.     

Combined hepatectomy and radiofrequency ablation versus TACE in improving survival of patients with unresectable BCLC stage B HCC

BACKGROUND: Combined hepatectomy and radiofrequency ablation(RFA) provides an additional treatment for patients with Barcelona Clinic Liver Cancer(BCLC) stage B hepatocellular carcinoma(HCC) who are conventionally deemed unresectable. This study aimed to analyze the outcome of this combination therapy by comparing it with transarterial chemoembolization(TACE). METHODS: We retrospectively reviewed 51 patients with unresectable BCLC stage B HCC who had received the combination therapy. We compared the survival of these patients with that of 102 patients in the TACE group(control). Prognostic factors associated with worse survival in the combination group were analyzed.RESULTS: No differences in tumor status and liver function were observed between the TACE group and combination group. The median survival time for the combination group and TACE group was 38(6-54) and 17(3-48) months, respectively(P0.001). The combination group required longer hospitalization than the TACE group [8(5-14) days vs 4(2-9) days,P0.001]. More than two ablations decreased the survival rate in the combination group. CONCLUSIONS: Combined hepatectomy and RFA yielded a better long-term outcome than TACE in patients with unresectable BCLC stage B HCC. Patients with a limited ablated size(≤2 cm), a limited number of ablations(≤2), and adequate surgical margin should be considered candidates for combination therapy.     

Adjuvant transarterial chemoembolization for patients with hepatocellular carcinoma after radical hepatectomy: a real world study

Abstract

Objective: To investigate the clinical value of the adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) after radical resection, and identify the potential beneficiaries.

Methods: Patients were identified through the primary liver cancer big data (PLCBD) between 2012 and 2015. Overall survival (OS) between adjuvant TACE group and non-TACE was evaluated by Kaplan-Meier before and after propensity scoring match (PSM). Subgroup analysis was conducted stratified by risk factors.

Results: A total of 2066 HCC patients receiving radical resection were identified. Patients with multiple tumors, tumor diameter >5?cm, satellite, and advanced stage were more likely to accept adjuvant TACE. Before PSM, the 1-, 3-, and 5-year OS rates in the TACE group and non-TACE group were 89%, 58%, 17%, and 88%, 53%, 13% (p?=?.43), respectively. While, the corresponding rates were 89%, 58%, 17%, and 86%, 49%, 11%, (p?=?.038), respectively after 1:1 PSM. In addition, patients were found to significantly benefit from adjuvant TACE if they had age ≥50?years, no cirrhosis, AFP ≤ 200?ng/ml, surgical margin <1?cm, tumor diameter >5?cm, no capsule, no satellite, or CN stage Ib/IIa (all p?<?.05), but patients with age < 50?years, tumor size ≤5?cm, or CN stage Ia were found to significantly benefit from radical resection in DFS (all p?<?.05).

Conclusion: Currently, we concluded that not all of patients with HCC would benefit from adjuvant TACE. Patients with age ≥50?years, tumor size >5?cm, or CN stage Ib/IIa were strongly recommended to receive adjuvant TACE.     

Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with liver metastases

AIM: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) for gastrointestinal stromal tumor (GIST) with liver metastases after the failure of tyrosine kinase inhibitors (TKIs).METHODS: Patients with histologically confirmed CD117-positive GIST with liver metastases who were resistant and/or intolerant to prior imatinib and/or sunitinib and who received TACE for at least one treatment cycle or only best supportive care and TKI reintroduction were eligible for the study. The patients were divided into two groups: those in TACE group received TACE treatment containing 5-20 mL iodized oil and 40-80 mg doxorubicin hydrochloride and TKI reintroduction or best supportive care, those in control group only received TKI reintroduction or best supportive care. The primary end-point was overall survival and the secondary end-points were, progression-free survival (PFS), response rates, and safety.RESULTS: Sixty patients admitted between June 2008 and October 2011 were eligible for this study, including 22 in TACE group and 38 in control group. In the TACE group, 12 (54.5%) achieved liver partial response, 5 (22.7%) had stable disease, and 5 (22.7%) had liver progressive disease. Disease control rate of liver metastases was 77.3% in the TACE group and 39.5% in the control group. The median liver PFS in TACE group was 47.1 wk (95% CI: 23.9-70.3). The median PFS in TACE group was longer than in control group (30.0 wk, 95% CI: 20.1-39.9 vs 12.9 wk, 95% CI: 11.9-13.9) (P = 0.0001). The median overall survival in TACE group was also longer than in control group (68.5 wk, 95% CI: 57.4-79.6 vs 25.7 wk, 95% CI: 23.2-28.2) (P = 0.0001). TACE treatment significantly reduced the risk of death (hazard ratio: 0.109). Patients without extrahepatic metastases treated with TACE had significantly better prognosis. Most of the adverse events were of grade 1 or 2 and tolerable.CONCLUSION: TACE is effective and well tolerated in GIST patients with liver metastases after TKI failure, and it may be an optional treatment for this disease.     

肿瘤切除前TACE对巴塞罗那临床肝癌分期B期患者预后的影响

目的探讨肿瘤切除术前行经皮股动脉穿刺肝动脉化疗栓塞术（TACE）对巴塞罗那临床肝癌（BCLC）分期B期患者预后的影响。方法对309例首次行肝癌切除术的BCLC分期B期患者的临床资料进行回顾性分析,根据术前是否行TACE分为联合组和手术组,用两独立样本t检验和PearsonX2检验比较两组一般临床资料,用Log—rank检验和Cox比例风险回归模型比较两组生存率。结果两组一般临床资料无统计学差异（P〉0．05）;联合组和手术组中位生存期分别为36、26个月,组间比较P〈0．05（X2=9．226）;治疗方式、肿瘤直径、手术切缘和血清AFP水平是影响患者生存率的危险因素（P〈0．05）,且治疗方式是影响患者预后的独立危险因素（RR为1．576,95％CI为1．157—2．146,P=0．004）。结论对于BCLC分期B期患者,在切除术前给予辅助性TACE治疗有望延长术后生存时间。