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.     

Clinical evaluation of transcatheter arterial embolization and one-shot chemotherapy in hepatocellular carcinoma

The therapeutic effect and the prognosis of transcatheter arterial embolization (TAE) and one-shot chemotherapy were studied in 90 cases of unresectable hepatocellular carcinoma (HCC). A therapeutic effect, which was assessed by the serum concentration of alpha-fetoprotein, angiography, computed tomography and ultrasonography, was seen in 33 (83%) out of 40 cases treated with TAE, and in 16 (32%) out of 50 cases treated with one-shot chemotherapy. In the cases that received TAE, the cumulative percentage survival rates at 6 months, 12 months, and 24 months were 75%, 48% and 20%, respectively. In contrast, the survival rates in the cases that received one-shot chemotherapy were 30%, 10% and 2%, respectively. In addition, the prognosis on the basis of the degree of tumor invasion of the portal vein was studied. In cases with the same degree of tumor invasion, the survival rate of the cases treated with TAE was significantly higher than that of those treated with one-shot chemo-therapy, except for those cases with tumor invasion of the main portal vein. These results show that TAE should be performed as the therapy of first choice in unresectable cases of HCC.     

CT引导经导管动脉化疗栓塞治疗肝细胞癌

目的探讨CT引导经导管动脉化疗栓塞（transcatheter arerial chemoembolization,TACE）治疗肝细胞癌（hepatocellular carcinoma,HCC）的初步疗效,分析局部复发的危险因素。方法对32例患者的34个HCC病灶进行了CT引导TACE治疗。结果32例中26例实现局部控制,6例出现局部复发。采用Logistic回归分析发现,TACE治疗后中央型HCC病灶是局部复发的危险因素（P=0．0408）。结论CT引导TACE是治疗小HCC的好方法,其局部控制率高、复发率低。中央型HCC是TACE术后局部复发的危险因素。     

Segmental transcatheter arterial embolization for primary hepatocellular carcinoma

ＩＮＴＲＯＤＵＣＴＩＯＮＳｅｇｍｅｎｔａｌｔｒａｎｓｃａｔｈｅｔｅｒａｒｔｅｒｉａｌｅｍｂｏｌｉｚａｔｉｏｎ（ＳＬｐＴＡＥ）ｈａｓｂｅｃｏｍｅｏｎｅｏｆｅｘｃｅｌｅｎｔｉｎｔｅｒｖｅｎｔｉｏｎａｌｍｅｔｈｏｄｓｆｏｒｐｒｉｍａｒｙｈｅｐａｔｏｃｅｌ...     

Subsegmental transcatheter arterial embolization for small hepatocellular carcinoma

BACKGROUND/AIMS: The evaluation of long-term outcome of subsegmental transcatheter arterial embolization, which was designed to bring about sufficient anti-tumor effect, in the primary cases of small hepatocellular carcinoma. METHODOLOGY: We analyzed and compared the anti-tumor effect and the survival rate in the primary cases of solitary small hepatocellular carcinoma (< or = 3 cm) with cirrhosis treated by subsegmental transcatheter arterial embolization, chemolipiodolization or percutaneous ethanol injection therapy during the last eight years, retrospectively. RESULTS: The complete tumor necrosis by one session of subsegmental transcatheter arterial embolization, which means that treated tumor showed complete response and did not show local recurrence thereafter, was seen in approximately 50% of the cases. The rate of complete tumor necrosis was superior to that in the patients treated by chemolipiodolization although it was lower than that in the patients treated by percutaneous ethanol injection therapy. Both of the 5- and 7-year survival rates in the patients treated by subsegmental transcatheter arterial embolization were 41.2%. It was slightly higher than those in the other treatment groups without significant difference. CONCLUSIONS: Subsegmental transcatheter arterial embolization might be effectively performed as an initial treatment for the primary cases of the solitary small hepatocellular carcinoma when tumor was fully supplied by hepatic arterial blood regardless of small size.     

Pulmonary complications of transcatheter arterial chemoembolization for hepatocellular carcinoma

Transcatheter arterial chemoembolization (TACE) is an effective palliative intervention that is widely accepted for the management of hepatocellular carcinoma (HCC). Post-TACE pulmonary complications resulting in acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are rare events. Pulmonary complications after TACE are thought to be related to chemical injury subsequent to the migration of the infused ethiodized oil or chemotherapeutic agent to the lung vasculature, facilitated by arteriovenous (AV) shunts within the hyper-vascular HCC. We review herein the literature on pulmonary complications related to TACE for HCC. Post-TACE pulmonary complications have included pulmonary oil embolism, interstitial pneumonitis, chemical pneumonitis, ALI, ARDS, lipoid pneumonia, acute eosinophilic and neutrophilic pneumonia, bilious pleuritis, pulmonary abscess, pulmonary tumor embolism, and possibly pulmonary metastasis with HCC. The risk factors associated with post-TACE pulmonary complications identified in the literature include large hyper-vascular HCC with AV shunts, large-volume Lipiodol infusion, and embolization via the right inferior phrenic artery. However, the absence of known risk factors is not a guarantee against serious complications. An astute awareness of the potential post-TACE pulmonary complications should expedite appropriate therapeutic interventions and increase potential for early recovery.     

Biliary phenotype of hepatocellular carcinoma after preoperative transcatheter arterial chemoembolization

Background and Aim: Transcatheter arterial chemoembolization (TACE) is now the mainstay of treatment for non‐curative hepatocellular carcinoma (HCC), and hoped to have chemotherapeutic and ischemic effects; however, the histopathological changes of HCC caused by TACE have not been sufficiently discussed so far. We aimed to assess the morphological and immunohistochemical features of HCC treated with TACE by immunostaining cytokeratin (CK) 7, CK14, CK19 and vimentin, and to correlate these data with observed clinicopathological characteristics. Methods: Eighty cases of surgically resected HCC with preoperative TACE and 146 cases of HCC resected without TACE as a control were analyzed. Results: The incidences of intrahepatic metastasis, poorly differentiated histology, multinucleated giant cells, mitotic figures and cytoplasmic inclusion bodies in the TACE group were significantly higher than those in the non‐TACE group. The TACE group showed reactivity for CK7 in 56.3% (45/80) of patients, CK14 in 12.5% (10/80), CK19 in 23.8% (19/80) and vimentin in 6.3% (5/80) of patients. CK19 expression in the TACE group was significantly higher than in the non‐TACE group (P = 0.0423). There was no correlation between immunoreactivity and the number of times TACE was carried out, but the expression of CK19 and vimentin in the massive necrotic group was higher than that in the mild necrotic group (P = 0.0197, P = 0.0229, respectively). Only TACE was an independent determinant of CK19 expression in all cases by multivariate analysis. Conclusions: These results suggest that preoperative TACE may have an impact on the biliary phenotype of HCC. Some post‐therapeutic HCC patients might develop HCC with a biliary phenotype indicating more aggressive malignancies.     

肝癌动脉化疗栓塞效果的病理评价

目的研究肝细胞癌经动脉化疗栓塞治疗后癌肿的变化，探索提高疗效的方法。方法对动脉化疗栓塞治疗后行手术的３９例肝癌和１１例对照标本进行坏死程度与包膜、治疗次数、病理类型、分化、血管损伤及淋巴细胞浸润诸因素相关性的分析。结果完全坏死者６例，３０％＿９５％坏死者１４例，仅５％坏死及无坏死者１９例，１１例ＤＳＡ无坏死。癌肿坏死程度与肿癌分化、治疗次数、淋巴细胞浸润无关，而与病理类型、包膜、血管损伤有关。结论肝癌动脉化疗栓塞是中晚期肝癌目前唯一可取的治疗方法。对于有包膜的肝细胞癌，只要治疗能达到癌肿部位，即使一次治疗，也可收到明显的效果。对于如何使每例都达到彻底的癌肿坏死是值得进一步探讨的。     

肝癌动脉化疗栓塞效果的病理评价

目的研究肝细胞癌经动脉化疗栓塞治疗后癌肿的变化，探索提高疗效的方法．方法对动脉化疗栓塞治疗后行手术的３９例肝癌和１１例对照标本进行坏死程度与包膜、治疗次数、病理类型、分化、血管损伤及淋巴细胞浸润诸因素的相关性分析．结果完全坏死者６例，３０％～９５％坏死者１４例，仅５％坏死及无坏死者１９例，１１例ＤＳＡ无坏死．癌肿坏死程度与肿瘤分化、治疗次数、淋巴细胞浸润无关，而与病理类型、包膜、血管损伤有关．结论肝癌动脉化疗栓塞对于有包膜的中晚期肝细胞癌有明显效果．     

肝动脉灌注羟基喜树碱和栓塞治疗原发性肝癌

目的观察经肝动脉插管栓塞和灌注化疗药物羟基喜树碱、５ＦＵ、丝裂霉素（ＭＭＣ）、顺铂治疗（ＴＡＣＥ）进展期肝癌（ＨＣＣ）２１例的疗效和副作用．方法应用ＴＡＣＥ治疗２１例中晚期ＨＣＣ患者,其中Ⅱ期１５例,Ⅲ期６例．结果接受ＴＡＣＥ患者２１例,治疗总有效率为８０９％,平均生存期９１ｍｏ,半年和一年生存率分别为７１５％和４２４％．Ⅱ期患者获得的平均生存期、半年和一年生存率分别为１０５ｍｏ,８６７％,６０％;明显优于Ⅲ期患者的５３ｍｏ,３６７％,０％（Ｐ＜００１）．多次治疗的平均生存期为１１２ｍｏ,明显优于单次治疗的６８ｍｏ（Ｐ＜００１）．副作用有恶心、呕吐、发热、白细胞下降和肝功能异常．结论羟基喜树碱经肝动脉灌注联合栓塞是治疗进展期ＨＣＣ的有效手段．     

Alpha-fetoprotein in patients with hepatocellular carcinoma after transcatheter arterial embolization

To assess the usefulness of alpha-fetoprotein (AFP) in monitoring treatment effects of transcatheter arterial embolization (TAE) in hepatocellular carcinoma (HCC) patients, a total of 31 sets of AFP levels after TAE in 21 HCC patients were analysed by linear regression between logarithmic AFP levels and days. Eleven sets of AFP data with poor linear declination were accompanied with poor TAE results except in one patient who had chronic hepatitis with acute exacerbations. Twenty sets of data with good linear declination in the first month after TAE indicated good TAE results. Seven of them showed no evidence of tumour recurrence nor elevated AFP levels within a follow-up of 6 months. The mean, standard deviation and range of half-lives of AFP in the non-recurrent group were 5.0, 1.6 and 2.9-7.2 days, respectively. The others experienced late tumour recurrence that was detected by rebound of AFP levels except one who had another non-AFP-secreting HCC. Thus, the results might be used as a reference in monitoring the treatment effects of TAE and the timing selection of repeated TAE.     

Cerebral lipiodol embolism following transcatheter arterial chemoembolization for hepatocellular carcinoma

Cerebral lipiodol embolism (CLE) is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC). The authors present a case of CLE that occurred after the second hepatic arterial chemoembolization for HCC, and attempt to introduce several plausible mechanisms of CLE, after reporting the clinical and radiological findings and reviewing the medical literature.     

Histopathological findings after ultraselective transcatheter arterial chemoembolization for hepatocellular carcinoma

Aim:  To evaluate the histopathologic findings in the surgical specimen of hepatocelluar carcinoma after transcatheter arterial chemoembolization (TACE) at the most distal portion of the sub-subsegmental artery of the liver (ultraselective TACE).
Methods:  Histolopathologic findings from nine tumors with a mean diameter of 3.1 cm ± 1.7 from patients who underwent hepatectomy after ultraselective TACE were evaluated, especially with regard to the relationship between peritumoral liver parenchymal necrosis and portal vein visualization during TACE. Portal vein visualization was classified into three grades by a spot digital radiograph obtained just after TACE: 0, no obvious portal vein visualization; 1, visualization of the portal vein adjacent to the tumor; and 2, visualization in the whole embolized area or extending into the surrounding non-embolized areas. Unenhanced computed tomography (CT) was obtained 1 week later and surgical resection was performed 37 ± 6.3 days after ultraselective TACE.
Results:  Portal vein visualization during TACE was classed as grade 1 in 5 tumors and grade 2 in 4. Histopathologically, complete tumor necrosis was observed in 7 tumors (77.8%). In 2 tumors (1 of grade 1, the other grade 2), a small viable portion or viable daughter nodule was seen. Macroscopic parenchymal necrosis adjacent to the tumor was observed in all 4 grade 2 tumors including gas-containing areas on CT obtained 1 week after TACE.
Conclusions:  Ultraselective TACE induces not only complete tumor necrosis but also peritumoral parenchymal necrosis, similar to that after radiofrequency ablation, when the portal veins are markedly visualized during the TACE procedure.     

The radiological prognostic factors of transcatheter arterial chemoembolization to hepatocellular carcinoma

Transcatheter arterial chemoembolization (TACE) is the recommended treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the HCC radiological characteristics associated with prognosis of patients with intermediate stage HCC receiving TACE. Patients with HCC BCLC stage B from January 2005 to December 2009 were collected. According to mRECIST criteria, patients with complete response and partial response were assigned to the objective response (OR) group, while those with stable disease and progressive disease were assigned to the nonobjective response (non-OR) group. Among a total of 128 enrolled patients, there were 66 (51.6%) and 62 (48.4%) patients in the OR group and non-OR group, respectively. The clinical parameters in the two groups were similar, although HCC size was smaller in the OR group. Logistic analysis found combined radiological characteristics including complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush were significant correlated with achievement of OR (odds ratio 2.46, 95% CI 1.08–5.61, P = .032). However, no radiological characteristics had significant strength to predict overall survival. Patients with OR after TACE had significantly longer survival time than those with non-OR. Combined characteristics of complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush had a positive impact on OR in TACE. In patients receiving TACE, those who achieved OR had a better overall survival.     

Biliary migration of hepatocellular carcinoma fragment after transcatheter arterial chemoembolization therapy

Occasional side-effects of transcatheter arterial chemoembolization therapy in hepatocellular carcinoma are essentially related to tissue necrosis. We report the case of a patient with hepatocellular carcinoma who experienced an acute common bile duct obstruction a few weeks after such a procedure, in the absence of obvious biliary tract invasion. An endoscopic sphincterotomy relieved the obstruction. At histology, the intra-biliary material was identified as a fragment of hepatocellular carcinoma. We discuss the causes of obstructive jaundice in the setting of hepatocellular carcinoma as well as in the specific situation of transcatheter arterial chemoembolization therapy.     

Recurrences of hepatocellular carcinoma following initial remission by transcatheter arterial chemoembolization

BACKGROUND AND AIMS: The aim of this study was: (i) to define the characteristics of hepatocellular carcinoma (HCC) associated with recurrences following initial remission by transcatheter arterial chemoembolization (TACE); (ii) to evaluate the patterns of recurrences; and (iii) find a better surveillance method of detecting recurrent HCC. METHODS: Out of 230 consecutive HCC patients who underwent TACE, 77 with initial remission were followed prospectively for at least 12 months. We compared the recurrence rates according to the characteristics of the tumors and analyzed the locations of the recurrent HCC. The diagnostic efficacies of CT scans with serum AFP, angiography and Lipiodol CT scan in detecting recurrent HCC were also evaluated. RESULTS: Recurrent HCC was detected in 40 patients during a median period of 27 months. The recurrence rate of multinodular HCC was higher than the single nodular type. All six patients with portal vein thrombosis recurred. Even though 45% of recurrences were adjacent to original tumors, 63% were separated from them (8% at both). Hepatocellular carcinoma with heterogeneous Lipiodol uptake tended to recur at the site adjacent to the original tumors more frequently than HCC with homogeneous Lipiodol uptake. Only 18 of 40 recurrent HCC were initially detected by serum alpha-fetoprotein (AFP) and CT scans: 19 by angiography and three only by Lipiodol CT scan. CONCLUSION: Our data indicated that HCC of the multinodular type and with portal vein thrombosis recur more frequently following initial remission by TACE. It is also suggested that regular angiography in addition to serum AFP and CT scan may be valuable in detecting recurrent HCC. Other treatment modalities may need to be combined to ablate tumors completely and to therefore reduce recurrences, especially in HCC with heterogeneous Lipiodol uptake.     

Angioechographic evaluation of tumor thrombi and the effect of transcatheter arterial embolization in patients with hepatocellular carcinoma

Background: Background: Transcatheter arterial embolization (TAE) is considered to be relatively ineffective in the treatment of portal and/or hepatic vein tumor thrombi associated with hepatocellular carcinoma (HCC). However, we have seen patients with a positively enhanced tumor thrombus on angioechography where necrosis has occurred after TAE. In this study, we compared the angioechographic enhancement of tumor thrombi with the effect of TAE to assess the use of this method in predicting the efficacy of TAE, and in predicting survival. Methods: Angioechography, using a small amount of CO₂ gas injected into the hepatic artery, was performed before TAE in 41 HCC patients with tumor thrombi of the portal vein (PVTT; n= 35) or hepatic vein (HVTT; n= 6). The relationship between the enhancement of the thrombi and the efficacy of TAE was investigated by follow-up ultrasonography. Results: All 13 PVTT that decreased in size had shown positive enhancement (PE) before treatment (P < 0.001), while 6 of the 7 cases (86%) in which the lesions increased in size had shown negative enhancement (NE). The survival of patients with PE was significantly longer than that of patients with NE (P < 0.005). Multivariate analysis identified two clinical variables associated with survival, angioechographic findings of PVTT, and age. There were no correlations between enhancement and HVTT. Conclusions: Determination of enhancement of PVTT on angioechography was useful in predicting the efficacy of TAE treatment of HCC and the survival time. Angioechography may be valuable in treatment decisions for HCC patients with PVTT, especially as a guide to the effectiveness of TAE. Received: March 1, 2001 / Accepted: November 2, 2001