原发性肝癌的肝段动脉栓塞治疗

 本文报道50例肝癌肝段动脉栓塞治疗的1年、2年、3年、4年累积生存率分别83.8％, 65.4％, 42.9％, 24.5％, 总结分析了瘤周门脉碘油逆流的表现及临床价值, 本组病例门脉逆流出现率为64％, 作者认为肿瘤周围出现门脉碘油逆流是肿瘤碘油栓塞完全的标志之一, 可对肿瘤门脉供血起部分栓塞作用。     

Effectiveness of Lipiodol in transcatheter arterial embolization of hepatocellular carcinoma

The effectiveness of Lipiodol (iodized oil) in transcatheter arterial embolization (TAE) of hepatocellular carcinoma (HCC) was retrospectively evaluated using statistical analysis. A total of 343 HCC patients who underwent TAE at 5 institutions between 1984 and 1989 were divided into 2 groups: the GS-TAE group underwent TAE with Gelfoam sponge alone, whereas the LP-TAE group was given Lipiodol (LP) immediately before GS-TAE. The statisticalT value calculated for the LP-TAE group showed that the administration of LP, the tumor size, intrahepatic metastasis, portal vein infiltration, and serum total bilirubin and alpha-fetoprotein levels significantly (P<0.01) affected=" the=" patients'=" survival.=" both=" the=" cumulative=" survival=" determined=" using=" the=" kaplan-meier=" model=" and=" the=" cumulative=" hazard=" calculated=" using=" cox's=" proportional=" hazard=" model=" differed=" significantly=">P<0.01) between=" the=" gs-tae=" group=" and=" the=" lp-tae=" group=" (log-rank=" test).=" these=" results=" confirmed=" the=" effectiveness=" of=" lp=" used=" in=" combination=" with=" gelfoam=" sponge=" for=" tae=" of=">Presented at the Second International Symposium on Treatment of Liver Cancer. Taipei, 3–4 February 1991     

Anticoagulant-induced pseudothrombocytopenia occurring after transcatheter arterial embolization for hepatocellular carcinoma

Pseudothrombocytopenia (PTCP) is the in vitro phenomenon of anticoagulant-activated platelet agglutination that results in spuriously low platelet counts. We report the case of a 65-year-old man with EDTA- and sodium citrate-dependent PTCP occurring after transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) due to hepatitis C cirrhosis. Invasion of the portal and hepatic veins by HCC formed severe trans-tumoral arterio-venous shunts that were effectively treated by TAE. Two days after the therapy, PTCP was seen on blood count and continued for 4 months. The patient received unnecessary treatment for disseminated intravascular coagulation (DIC) until the diagnosis of PTCP was established. PTCP is a rare complication but should be considered after TAE for HCC; lack of recognition may lead the physician to misdiagnosis and patient mismanagement.     

肝癌肝动脉栓塞化疗术并发碘油肺栓塞的临床观察

探讨肝癌肝动脉栓塞化疗术并发碘油肺栓塞的发病机制、临床表现、治疗方法及预防措施。分析肝癌行TACE术后发生碘油肺栓塞7例患者的术前肝脏CT、术中DSA检查、术中所用的碘油量及化疗药物剂量、术中术后的临床表现、辅助检查及临床治疗情况。患者出现不同程度的咳嗽、咯血、呼吸困难和低氧血症,胸片可见片状密度增高影。给予吸氧、扩张支气管、必要时呼吸机辅助呼吸及其他支持治疗后好转。随访观察20d～2个月,复查胸片正常。7例病例病灶直径约>10cm,存在肝动脉-肝静脉瘘的5例,碘油用量>20mL的5例。初步研究结果提示,碘油肺栓塞常发生在巨块型肝癌,且多存在肝动脉-肝静脉瘘,碘油用量多>20mL,术中正确处理可减少此类并发症的发生。     

Histologic assessment of resected hepatocellular carcinoma after transcatheter hepatic arterial embolization

Ten cases of large hepatocellular carcinoma (HCC) (largest diameter, 6.5-15 cm) were surgically resected from 3 to 19 days after transcatheter hepatic arterial embolization (TAE) for histologic assessment of the effectiveness. Another two patients, including one with a small HCC (3.5 X 3 X 3 cm) who died of complications, were also studied. The patients' ages ranged from 20 to 64 years, 11 were men and 1 was a woman, and all positive for serum hepatitis B surface antigen. All 11 cases with large HCC were symptomatic before the HCC was clinically diagnosed. Alpha-fetoprotein levels were elevated in ten cases but immediately dropped to normal levels after TAE and resection in eight cases. An effective massive tumor coagulative necrosis of 99% already occurred 3 days after TAE. A necrosis involving more than 95% of the whole tumor mass was demonstrated in eight cases: one was a large HCC taken from an autopsy specimen, and TAE was done three times. This strongly indicates the effectiveness of TAE on the destruction of HCC. However, the presence of viable residual tumors in 11 cases also strongly argues for the necessity for surgical resection whenever it is possible. The failure of a complete necrosis was related to the extracapsular extension, liver invasion, satellite nodules, and portal vein involvement, and probably related to collateral and portal vein blood supply.     

Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas

Transcatheter arterial embolization (TAE) is a well-established technique for unresectable hepatic malignancies. However, TAE can temporally halt the growth of hepatic tumors by blocking their arterial supply, but often tumors rapidly develop collateral blood vessels via angiogenesis. We have previously demonstrated that intraportal delivery of adeno-associated viral particles expressing angiostatin leads to long-term expression of angiostatin capable of inhibiting angiogenesis and suppressing the outgrowth of tumors in the liver. Thus, we hypothesize that adeno-associated virus (AAV)-mediated antiangiogenic therapy could enhance the efficacy of TAE to combat liver cancers. To achieve this objective, we engineered a recombinant AAV vector encoding rat angiostatin. Intraportal delivery of this vector led to long term and stable transgenic expression of angiostatin locally in rat hepatocytes and suppressed the growth of CBRH7919 hepatocellular carcinomas established in rat livers by inhibiting formation of neovessels. Although TAE therapy led to necrosis of liver tumors and suppressed their growth, the neovessels of tumors were rapidly reformed 3 weeks after TAE. However, intraportal injection of AAV-angiostatin inhibited the angiogenesis stimulated by TAE, synergized with TAE in suppressing growth of tumors established in livers and prolonged the survival of rats. In conclusion, these encouraging results warrant future investigation of the use of antiangiogenic therapy for enhancing the therapeutic efficacy of TAE to treat unresectable liver cancers.     

Prognostic factors in patients with hepatocellular carcinoma treated by transcatheter arterial embolization

BACKGROUND: Transcatheter arterial embolization induces marked antitumor response in patients with hepatocellular carcinoma, but the survival benefit of transcatheter arterial embolization remains to be determined. This study investigated prognostic factors in patients with advanced hepatocellular carcinoma treated by transcatheter arterial embolization. METHODS: A total of 128 consecutive patients with non-resectable hepatocellular carcinoma, who had undergone transcatheter arterial embolization between May 1990 and August 1998, were analyzed to investigate prognostic factors. RESULTS: Median survival time and survival proportions at 1, 3 and 5 years were 3.3 years, 92.0, 54.6 and 23.4%, respectively. By multivariate analysis using the accelerated failure time model, age <60 years, hepatitis C virus antibody positivity, serum albumin >3.5 g/dl, absence of portal vein invasion and serum alpha-fetoprotein level <400 ng/ml were significantly associated with favorable survival. For clinical application, we also propose a prognostic equation with combination of specific prognostic factors, by which survival curves of each patient could be predicted directly. CONCLUSION: The findings of the current study may be helpful in predicting the life expectancy of hepatocellular carcinoma patients treated by transcatheter arterial embolization and in designing future clinical trials of transcatheter arterial embolization for hepatocellular carcinoma.     

Arterial chemotherapy and transcatheter arterial embolization therapy for non-resectable hepatocellular carcinoma

An assessment was made on the therapeutic effects of arterial chemotherapy and transcatheter arterial embolization (TAE) therapy on 378 cases with non-resectable hepatocellular carcinoma (HCC). For the 191 cases who had undergone arterial chemotherapy, 22% had a 1-year survival rate, 8.9% survived for 2 years, and 4.0% for 3 years. Of these, for the 128 cases who were compatible with our criteria for patient selection, the three survival rates were 31.4%, 12.2% and 5.9% respectively. However, for the other 63 cases, who were incompatible with our criteria, the 1-year survival rate was 1.6% and it was worse for the cases who had received supportive care alone. For the cases who had undergone arterial chemotherapy, the highest survival rates were obtained by the alternate administration of different anticancer agents, and the three survival rates were 39.0%, 13.1% and 4.9% respectively. For the 187 cases who had undergone TAE therapy, the 1-year survival rate was 66.2%, the 2-year survival rate 36.5%, and the 3-year survival rate 21.9%. For the 124 cases with a tumor progression rate of less than 20% in the liver (E1), the survival rates were 77.8%, 50.1% and 30.8% respectively. The peripheral venous drug concentrations of mitomycin C and adriamycin were lower, but were maintained for a longer period in TAE therapy than in arterial chemotherapy. These results suggest that consideration of the criteria for patient selection and the alternate administration of anticancer agents are necessary in arterial chemotherapy, and that the best therapeutic effects can be obtained by TAE therapy combined with chemotherapy for cases of non-resectable HCC because of the chemotherapeutic and ischemic effects on the tumors.     

Evaluation of the therapeutic effect of transcatheter arterial embolization for hepatocellular carcinoma

Transcatheter arterial embolization (TAE) has been widely performed for patients with hepatocellular carcinoma (HCC). However, the method of evaluating the therapeutic effect of TAE has not been established. We examined the rate of necrotic area to whole tumor (TN) by CT, the tumor regression rate (TR) and the reduction rate in serum alpha-fetoprotein (AFP) levels in patients with HCC who received hepatic resection within 3 months after TAE. In the evaluation of TN, the lipiodol accumulation in tumor was regarded as being necrotic. Rates of necrotic area, which were also examined pathologically (PN) in resected tumors, were compared with TN, TR and AFP reduction rates, respectively. Eighty-eight patients were enrolled in this study, and there was a significant positive correlation between TN and PN (r = 0.80, p < 0.001). Although TR significantly correlated to PN (p = 0.001), the correlation coefficient between them was low (r = 0.34). The correlation coefficients between AFP reduction rate and PN was 0.76 (p < 0.001) in 26 patients (30%) with an AFP level >/=200 ng/ml before TAE. The evaluation method using lipiodol accumulation in CT is the most useful for assessing the therapeutic effect of TAE, particularly when a sufficiently long interval exists between TAE and the evaluation, because of the highest correlation coefficient between TN and PN, and the availability of TN for all patients. The reduction rate in serum AFP levels was also useful in patients with AFP levels >200 ng/ml before treatment.     

Effect of transcatheter arterial embolization on the boundary architecture of hepatocellular carcinoma

Daughter nodules and intrahepatic metastases are resistant to conventional transcatheter arterial embolization therapy. To clarify the mechanism of this resistance, the boundaries of hepatocellular carcinomas and their relationship to the blood supply were studied. The boundaries of the hepatocellular carcinomas studied were classified as one of five types: encapsulated, granulation, stromal, replacing, or sinusoidal. The granulation and stromal types had a capsule-like structure, but lacked the hyalinization which is the hallmark of a true tumor capsule. The granulation and stromal types could also be differentiated from the encapsulated type because of their different blood supplies and the differing effects of transcatheter arterial embolization. When barium sulfate was infused into the portal vein, it did not enter into encapsulated tumors, but it entered granulation and stromal type tumors. Small nodules such as daughter nodules and intrahepatic metastases do not have capsules, and so have a blood supply that makes them resistant to conventional transcatheter arterial embolization therapy.     

132例原发性肝癌灌注化疗及栓塞治疗疗效观察

目的 探讨影响肝动脉灌注化疗＋栓塞治疗疗效的因素。方法 １９９３年１月￣１９９７年１０月,对１３２例不能切除的原发性肝癌行选择性插管灌注化疗及栓塞治疗５９７次,肝动脉灌注化疗＋栓塞者１２２例,单纯灌注化疗１０例。结果 １,２,３年生存率分别为８１．８％、３６．４％和１８．２％,疗效较治疗初期有显著提高。肿瘤分期、栓塞剂及其用量、侧支循环的形成以及肝动脉超选择性插管是影响疗效的主要因素。结论 合理施     

Retrospective study of short survival cases in hepatocellular carcinoma after transcatheter arterial embolization therapy

Twenty-two patients with hepatocellular carcinoma were treated with transcatheter arterial embolization therapy. In the six who died within about a month, serum albumin and Ch-E were lower, and total bilirubin and ICG R15 were higher than in the other cases. In four of them, more than 50% of the liver was occupied by tumor, and tumor thrombosis were found in the portal trunk or bilateral first portal branch. Five patients died of hepatic failure followed by upper gastrointestinal bleeding. One died of cachexia. The causes of short survival were 1) severe liver cirrhosis, 2) portal obstruction, 3) large tumor, 4) widespread TAE, 5) retrograde flow of gelfoam.     

Evaluation of nontumorous tissue damage by transcatheter arterial embolization for hepatocellular carcinoma.

The serial changes in serum hepatic enzyme activities by transcatheter arterial embolization (TAE) were analyzed in 17 patients with hepatocellular carcinoma to estimate the contribution to the value by the damage of tumor or nontumorous hepatic cells. The serum levels of relatively tumor-specific fructose 1,6-diphosphate (FDP) aldolase were elevated after TAE in the cases of both superselective and nonsuperselective TAE that were performed from the segmental and the nonsegmental hepatic artery, respectively, but we found the marked elevation of FDP aldolase in the cases of the superselective TAE. In contrast, the non-tumor-specific fructose 1-phosphate (F1P) aldolase was markedly elevated only in the cases of nonsuperselective TAE. The total amount of FDP aldolase released by TAE correlated significantly with the integrated tumor tissue volume (P less than 0.005), whereas the total amount of F1P aldolase output correlated significantly with the integrated nontumorous tissue volume (P less than 0.005) as defined by lipiodol accumulation on computerized tomography scan. The consequent changes in the total nontumorous liver volumes after TAE were also analyzed by the follow-up computerized tomography scan. The nonsuperselective TAE caused the significant total nontumorous liver atrophy when compared with the superselective TAE. The progression of the total nontumorous liver atrophy correlated significantly with F1P aldolase output by TAE (P less than 0.001) but not with FDP aldolase output. These results suggest that the outputs of FDP and F1P aldolase are useful to estimate the degree of the tumorous and nontumorous tissue damage by TAE, respectively, and F1P aldolase output can be used to predict the progression of liver atrophy caused by TAE.     

A pilot study of transcatheter arterial interferon embolization for patients with hepatocellular carcinoma

BACKGROUND: Systemic, high-dose interferon-alpha treatment given three times per week subcutaneously induces tumor regression in approximately 30% of patients with inoperable hepatocellular carcinoma (HCC). The objective of the current study was to determine the efficacy and safety of transcatheter arterial interferon embolization for the treatment of patients with inoperable HCC. METHODS: Eighteen patients with inoperable HCC were recruited to receive 3 different doses of interferon-alpha-2b (10 megaunits [MU]/m(2), 30 MU/m(2), or 50 MU/m(2)) at intervals of 8-12 weeks. Their tumor response, adverse events, and survival were monitored. RESULTS: In 14 patients with nondiffuse HCC, complete responses and partial responses (> 50% tumor reduction) were observed in 28.6% and 35.7% of patients, respectively. One of four patients with diffuse HCC had a partial response. Thirty-eight percent of patients had normalization of their alpha-fetoprotein level. The median ferritin level at the last follow-up was reduced significantly (765 pmol/L; range, 457-2720 pmol/L) compared with the baseline level (1980 pmol/L; range, 1100-3300 pmol/L; P = 0.011). The median survival was 15.9 months. Transient fever and rigor were the most common side effects observed. Five patients (27.8%) developed hypothyroidism. No significant liver decompensation was observed. CONCLUSIONS: This pilot study showed that transcatheter arterial interferon embolization was an effective method for the treatment of patients with inoperable HCC without significant hepatic toxicity.     

One-shot therapy and transcatheter arterial embolization (TAE) therapy of unresectable hepatocellular carcinoma

407 cases of unresectable hepatocellular carcinoma (HCC) occurring from 1970 to March 1985, including 107 cases receiving conservative therapy, 176 cases receiving one-shot therapy and 124 cases receiving transcatheter arterial embolization (TAE) therapy, were studied and the efficacy of chemotherapy was compared with that of TAE therapy. The results were as follows; One-year survival rate was 2.8% with a median survival time of 1.3 months in conservative therapy. In the 176 cases of one-shot therapy, one-year survival rate was 21.0%, two-year 6.8% and three-year 2.3% and the median survival time was 4.8% months. In 120 cases of one-shot therapy which were compatible with criteria for one-shot injection of anticancer drugs via the hepatic artery for HCC, one-year survival rate was 30%. However the rate was 1.8% in 56 cases which were not compatible with the criteria. In 37 cases in which Mitomycin C (MMC) and Adriamycin (ADR) were administered alternately, one-year survival rate was 41.7%, two-year 16.1% and three-year 4.3%. The highest survival rate was obtained by TAE therapy. One-year survival rate was 66.9%, two-year 33.8% and three-year 28.9%. Decrease of AFP after therapy was noted in 42.4% of cases given one-shot therapy and in 95.2% of cases given TEA therapy. The results suggest that alternate administration of anticancer agents produces good chemotherapeutic effects and that the best life-prolongation is obtained by TAE therapy.     

原发性肝癌行肝动脉化疗栓塞术后的并发症及其分析

目的 探讨原发性肝癌行经导管肝动脉化疗栓塞术(TACE)后的严重并发症,分析其原因和防治方法.方法 对573例原发性肝癌患者行TACE 1252次,针对术后发生的并发症进行影像学及化验检查,总结发生严重并发症的原因及其治疗、预防措施.结果 共发生上消化道出血3例,肝衰竭4例(其中死亡1例),肺栓塞1例,栓塞性胆囊炎4例,肝性脑病2例,胃穿孔后死亡1例,胆汁瘤2例.结论 原发性肝癌经TACE治疗后出现的严重并发症与患者术前肝功能较差、门静脉高压、术中化疗栓塞药物量大、药物返流及异位栓塞等有关.重视术前病例的选择,术中规范操作,尽可能超选择插管给药,术后加强护肝治疗和保护胃黏膜治疗,密切注意病情变化,可减少或防止TACE后严重并发症的发生.     

Clinical studies of intermittent hepatic arterial occlusion with infusion chemotherapy for unresectable hepatocellular carcinoma associated with arterioportal or arteriovenous shunts

Intermittent hepatic artery occlusion combined with infusion chemotherapy is a newly devised methodology. A double lumen balloon catheter was surgically inserted into the hepatic artery. Through the catheter, fluorouracil (5-Fu) was continuously infused and mitomycin (MMC) or adriamycin (ADM) was injected in one-shot at the time of blood flow occlusion. This new methodology was performed in 19 patients who had unresectable hepatocellular carcinoma. Although five of 19 cases had arterioportal (A-P) or arteriovenous (A-V) shunts, four of them also responded well and objective anti-tumor effects resulted. In addition, complications associated with A-P or A-V shunts such as bleeding from the digestive tract due to portal hypertension were well managed by this new methodology.     

Serum vascular endothelial growth factor in the course of transcatheter arterial embolization of hepatocellular carcinoma.

We previously reported that in vitro hypoxic condition enhanced VEGF level and its receptor expression in hepatic cancer cell line, HepG2. Transcatheter hepatic arterial embolization (TAE) therapy is one of the vasculo-occlusive and hypoxic challenges to hepatocellular carcinoma (HCC). Therefore, we examined the level of VEGF in sera of patients with HCC who underwent TAE during the course of the treatment. Thirty-eight patients with HCC and hepatitis C virus-positive cirrhosis were studied. Peripheral blood samples were taken before and 1, 3 and 7 days after TAE with informed consent. The serum levels of VEGF as well as hepatocyte growth factor (HGF), another hepatic remodeling factor, were measured. The molar ratio (BTR) of serum branched chain amino acid (BCAA) to tyrosine (Tyr), the serum levels of AST, ALT and LDH were also examined. Although the level of AST, ALT and LDH reached the peak value within 1 day after TAE, VEGF level increased significantly 7 days later. On the other hand, there were no significant alterations in the levels of HGF and BTR during the course of TAE. Although the level of HGF was significantly correlated with the level of VEGF before TAE, this correlation was no more observed after TAE. These data collectively suggest that VEGF may be secreted in response to clinical hypoxic intervention, TAE, independent of HGF or altered amino acid metabolism. VEGF may play a role as a sensitive marker for tumor ischemia.     

Prognostic factors in the treatment of hepatocellular carcinoma with transcatheter arterial embolization and arterial infusion.

From January 1986 to December 1988, a prospective trial of transcatheter arterial treatment was carried out for hepatocellular carcinoma (HCC). Two hundred seventy-five patients were included. Okuda's staging system was employed. Patients with Stage I and II HCC were treated by transcatheter arterial embolization (TAE) with a gelatin sponge containing an anti-cancer agent (protocol 1a); a gelatin sponge and iodized oil mixed with an anti-cancer agent (protocol 1b); or iodized oil mixed with an anti-cancer agent (protocol 2). Patients with Stage III HCC were treated with iodized oil with anti-cancer agent (protocol 2). As an exception, patients with an unsuccessful superselective catheterization into the proper hepatic artery by Seldinger technique or obstruction of the main trunk of the portal vein were treated with percutaneous transcatheter arterial infusion into the common hepatic artery regardless of stage (protocol 3). Tumor type and extension, area of tumor involvement, portal vein involvement, method of treatment, and presence of ascites and icterus were found to be the significant factors for an initial response to therapy. Treatment method was the most important factor. Respective survival rates at 1 and 2 years were 70.9% and 55.3% for protocol 1a; 62.3% and 43.8% for protocol 1b; 37.8% and 18.3% for protocol 2; and 16.5% and 0% for protocol 3. Many factors proved to significantly influenced prognosis; however, tumor type had the most important prognostic significance followed by AFP value, ascites, treatment protocol, and area of tumor involvement.