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。     

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.     

Phase I/II study of a fine‐powder formulation of cisplatin for transcatheter arterial chemoembolization in hepatocellular carcinoma

Aim: The clinical feasibility of transcatheter arterial chemoembolization (TACE) with fine‐powder cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC) has not been investigated. A phase I/II study was conducted to investigate the safety and tolerability of fine‐powder CDDP when it was used with lipiodol and gelatin sponge particles for TACE. Methods: Fine‐powder CDDP emulsified in lipiodol was injected into tumor arteries. Embolization was subsequently performed with gelatin sponge particles. The CDDP dose was started at 45 mg/m² (level 1) and increased to 65 mg/m² in 10 mg/m² increments. Results: Thirteen patients were enrolled in phase I study since no dose limiting toxicity was observed in any patients, even in seven patients at level 3 (65 mg/m²), the recommended dose was 65 mg/m². The major adverse event was grade 3 thrombocytopenia, which occurred in 8% of patients. The incidence of hematological toxicities was 15% for leukocytopenia, 84% for thrombocytopenia, and 84% for anemia. Increased serum total bilirubin was observed in 54% and increased aspartate aminotransferase or alanine aminotransferase in all patients. All digestive tract symptoms (nausea 77%, anorexia 84%, vomiting 31%) were grade 2 or lower. Total adverse events were grade 3 or higher in 44%. The response rate in 19 patients who received the recommended dose was 21%. Conclusions: TACE with a fine‐powder formulation of CDDP at a dose of 65 mg/m² is well tolerated in patients with unresectable HCC.     

Comparative study of cisplatin and epirubicin in transcatheter arterial chemoembolization for hepatocellular carcinoma

Aim: Transcatheter arterial chemoembolization (TACE) is an established treatment for unresectable hepatocellular carcinoma (HCC). However, it is unclear which chemotherapeutic agent should be selected for TACE. The aim of this study was to compare the efficacy of cisplatin (CDDP) with that of epirubicin (EPI) in TACE for patients with unresectable or relapsed HCC. Methods: We performed a historical cohort study involving 131 patients treated with a first TACE, defined as either an initial treatment for previously untreated HCC or a first treatment for relapsed HCC after curative resections or ablations. Efficacy was estimated as the response rate (RR) and it was adjusted for the confounding factors that were defined in this study. Results: The RR were 62.5% (20/32) for the first TACE with CDDP and 51.5% (51/99) for that with EPI. In the adjusted analysis for a history of hepatectomy, percutaneous treatment combined with TACE and tumor factors, the odds ratio was 1.72 (95% confidence interval [CI] = 0.70–4.48). However, a test for interaction between the number of tumors and the chemotherapeutic agent was statistically significant (P = 0.016). In multiple HCC, the RR were 66.7% (10/17) for CDDP and 39.6% (30/46) for EPI. The odds ratio was 4.11 (95% CI = 1.14–17.2). Conclusion: CDDP may be more effective than EPI in TACE for multiple HCC. A randomized controlled study is needed to clarify the efficacy of CDDP in TACE in patients with multiple HCC.     

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.     

Multidetector-row computed tomography in the management of hepatocellular carcinoma with transcatheter arterial chemoembolization

With the introduction of spiral computed tomography and the development of novel imaging technology in recent years, multidetector-row computed tomography (MDCT) has increasingly been used for the diagnosis of various lesions, especially hepatocellular carcinoma (HCC), due to its volume acquisitions, short scanning time, and especially its double-phase scanning nature, which takes advantage of the dual blood supply of liver. Multidetector-row computed tomography is used to classify HCC into several types based on the blood supply and the histological characteristics of HCC. The evaluation of HCC by MDCT provides crucial clues for the doctors to adopt correct clinical management strategies such as the selection of the appropriate dose of lipiodol before transcatheter arterial chemoembolization (TACE) and the prediction of the prognosis of HCC after TACE. The MDCT scanning allows doctors to choose the region of interest and to evaluate the blood supply according to the lipiodol uptake in order to decide whether there is recrudescence and whether a repeated therapy should be taken. This review describes MDCT, its biphasic scanning, its evaluation of blood supply in HCC and the subsequent classification of HCC, its therapeutic significance before TACE and the prognostic value after TACE.     

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.     

Hemobilia immediately after transcatheter arterial chemoembolization using drug‐eluting beads for hepatocellular carcinoma with intrahepatic bile duct invasion

Transcatheter arterial chemoembolization (TACE) is used as a palliative treatment for unresectable hepatocellular carcinoma (HCC) worldwide. Recently, a novel drug delivery–embolic agent, the drug‐eluting bead (DEB), was introduced for TACE. There are a few reports of tumor hemorrhage after TACE using DEB (DEB‐TACE) for HCC. However, there have not been any reports of hemobilia immediately after DEB‐TACE for HCC with intrahepatic bile duct invasion. Here, the first such case is reported. A 71‐year‐old woman was admitted to our hospital to undergo DEB‐TACE for multiple HCCs with worsening left intrahepatic bile duct dilatation. She was diagnosed with HCC that extensively invaded the left hepatic duct. After DEB‐TACE through the left hepatic artery, a hepatic arteriogram showed extra flow of the contrast agent to the left hepatic and common bile ducts. Therefore, transcatheter arterial embolization (TAE) of the responsible vessel was carried out using coils, and no extra flow of the contrast agent was identified. The patient was discharged 14 days after TAE without deterioration of liver function. Although hemobilia immediately after DEB‐TACE is rare, there may be increased potential for hemobilia when DEB‐TACE is carried out for HCC with extensive bile duct invasion. We suggest that DEB‐TACE may be contraindicated for such cases.     

Fever after transcatheter arterial chemoembolization for hepatocellular carcinoma: incidence and risk factor analysis

Objective. Post-treatment fever frequently occurs in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE), but its incidence and clinical significance are unclear. The aim of this study was to identify the incidence and risk factors for fever after TACE in HCC patients. Material and methods. Forty-one consecutive HCC patients undergoing 73 sessions of TACE were included in the study. The incidence and possible risk factors associated with post-TACE fever were analyzed. Results. Forty-nine (67%) episodes of fever developed in 30 (73%) HCC patients after TACE, but none of the patients developed bacterial infection after TACE. Patients who developed fever were of younger age, had larger tumors, a higher dose of chemoembolization agents and a higher embolized volume compared with those without fever. Multivariate logistic regression disclosed that a dosage of doxorubicin plus iodized oil >23 during chemoembolization and tumor size >3 cm were significant predictors associated with the development of post-TACE fever (odds ratio: 3.749, 95% CI: 1.188–11.830, p=0.024 and odds ratio: 3.599, 95% CI: 1.107–11.706, p=0.033, respectively). Conclusions. Fever after TACE is common, but infectious complications are rare. Chemoembolization dosage and tumor size are predictive of fever after transcatheter arterial chemoembolization and may be of help in the prevention and care of this distressing complication.     

Efficacy of platinum analogue for advanced hepatocellular carcinoma unresponsive to transcatheter arterial chemoembolization with epirubicin

Aim:  Hepatocellular carcinoma (HCC) often shows resistance to transcatheter arterial chemoembolization (TACE). Such patients often have a poor prognosis and are unresponsive to other forms of therapy. The aim of this retrospective study was to determine the response to TACE using platinum analogues in patients deemed resistant to TACE using epirubicin.
Methods:  We studied 152 consecutive patients with advanced HCC resistant to TACE using epirubicin. All cases were treated with platinum analogue using transcatheter arterial chemotherapy with or without embolization.
Results:  Computed tomography at 3 months after therapy showed complete response (CR) in 6 patients (4.0%), partial response (PR) in 28 (18%), stable disease (SD) in 35 (23%), and progressive disease (PD) in 83 (55%). The cumulative survival rates for PR/CR patients who received platinum analogue-transcatheter arterial chemotherapy with or without embolization (81.8% at first year, 53.9% at second year, and 33.1% at third year) were significantly higher than those of SD/PD patients (36.6%, 17.5% and 7.4%, respectively) ( P  < 0.001). The 50% survival period was extended almost 1.4 year in PR/CR patients who received platinum analogue-transcatheter arterial chemotherapy with or without embolization.
Conclusion:  Our retrospective study is the first to report the efficacy of platinum analogues for advanced HCC unresponsive to TACE using epirubicin.     

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.     

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.