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Naoko Hashimoto,1 Jin Iwazawa,1 Shoichi Ohue,2 Takashi Mitani11Department of Radiology, Nissay Hospital, Nishiku, Osaka, Japan; 2Department of Radiology, Komatsu Hospital, Neyagawa, JapanObjective: We aimed to evaluate local tumor control after transarterial chemoembolization (TACE) for hepatocellular carcinoma using miriplatin and low-dose epirubicin combination therapy.Methods: We retrospectively analyzed the records of patients who underwent TACE using miriplatin plus low-dose epirubicin (30 patients, 61 nodules, August 2011–March 2012) and control patients who underwent TACE using miriplatin alone (36 patients, 70 nodules, June 2010–July 2011). The local control rate was compared between the two groups using the Kaplan–Meier estimator and the log-rank test. Factors affecting local tumor recurrence were analyzed using multivariate logistic regression analysis. Treatment-related toxicity was evaluated using the Common Terminology Criteria for Adverse Events.Results: The local control rates at 6 months and 1 year were 87% and 65% for the miriplatin plus low-dose epirubicin group, and 61% and 43% for the miriplatin group, respectively. Local tumor control rates were significantly better in the miriplatin plus low-dose epirubicin group than in the miriplatin group (P = 0.038). Multivariate analysis showed that the addition of epirubicin was an independent factor associated with better local tumor control (hazard ratio 0.2, P = 0.001). Overall incidence rates for adverse events were not significantly different between the two groups.Conclusion: Additional usage of low-dose epirubicin for TACE using miriplatin improved local tumor control of hepatocellular carcinoma with adverse effects comparable to those observed with TACE using miriplatin alone.Keywords: combination therapy, local recurrence, liver, embolization, comparative study

Jin Iwazawa1, Shoichi Ohue2, Naoko Hashimoto1, Takashi Mitani11Department of Radiology, Nissay Hospital, Nishiku, Osaka, 2Department of Radiology, Komatsu Hospital, Neyagawa, JapanPurpose: We aimed to compare the local control rates between miriplatin and epirubicin in lipiodol-based transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Patients and methods: Patients who underwent targeted TACE using miriplatin (47 patients, 66 lesions) or epirubicin (64 patients, 79 lesions) as the sole therapy were enrolled. The local control rates were compared using the Kaplan–Meier estimator with the log-rank test. The patient and tumor parameters were subjected to univariate and multivariate analyses using the Cox proportional hazards model.Results: The overall local recurrence rates were 39.3% and 31.6% for the miriplatin and epirubicin groups, respectively. The local control rate was significantly higher in the epirubicin group than in the miriplatin group (P < 0.001). The local control rates at 6 months and 1 year were 70.7% and 44.8% for the miriplatin group and 83.4% and 69.2% for the epirubicin group, respectively. Multivariate analysis showed that the serum a-fetoprotein level ≥20 ng/mL (hazard ratio 2.96; P < 0.001), miriplatin usage (hazard ratio 2.53; P = 0.002), and Child-Pugh class B (hazard ratio 1.89; P = 0.042) affected local progression.Conclusion: Lipiodol-based targeted TACE using miriplatin had inferior local control rates as compared to epirubicin in patients with HCC.Keywords: chemoembolization, miriplatin, epirubicin, liver, neoplasms

We developed segmental Lp-TAE, which is transcatheter hepatic sub-subsegmental, subsegmental, or segmental chemoembolization using Lipiodol introduced into the tumor-bearing hepatic sub-subsegment, subsegment, or segment as the target area. A total of 98 patients with nonresectable hepatocellular carcinoma (HCC) undergoing segmental Lp-TAE (Seg-Lp-TAE) were studied, and the relationship between the CT pattern observed after Seg-Lp-TAE (Seg-Lp-CT) and the therapeutic results obtained in those patients was evaluated. Seg-Lp-CT was classified into four types (type I, homogeneous; type II, defective; type III, inhomogeneous; and type IV, only slight accumulation, if any) according to the Lipiodol accumulation pattern observed after Seg-Lp-TAE. The cumulative nonrecurrence rates of type I were higher than those of types II–IV. The cumulative survival rates of type Ia, in which Lp accumulation is also seen around the main tumor, were the highest (93.8% at 1 year, 85.9% at 2 years, 85.9% at 3 years, and 57.3% at 4 years). The cumulative survival rates achieved with Seg-Lp-TAE were 89.2% at 1 year, 69.4% at 2 years, 58.9% at 3 years, 44.0% at 4 years, and 30.2% at 5 years, which were higher than those achieved with conventional Lp-TAE. Seg-Lp-TAE is very useful in the treatment of HCC limited to one sub-subsegment, subsegment, or segment, and it is important to choose subsubsegmental, subsegmental, subsegmental, or segmental Lp-TAE on the basis of the size and site of the tumor as well as the type and the number of feeding arteries.

Transcatheter hepatic segmental arterial chemoembolization using Lipiodol mixed with an anticancer drug followed by the injection of Gelfoam particles, introduced into the tumor-bearing hepatic segment as the target area (segemental Lipiodol-TAE), was carried out in 54 patients with hepatocellular carcinoma (HCC), 7 of whom were later resected. In 5 of the resected 7 cases, complete necrosis was histologically verified. No death due to HCC was encountered in 47 nonoperated cases, and better therapeutic results were obtained with segmental Lipiodol-TAE. It was concluded that this technique does not adversely affect normal tissues, and it does reinforece the effect of TAE.

Transcatheter arterial embolization (TAE) was performed in 97 patients with hepatocellular carcinoma. Ethiodol (iodized oil) containing an anticancer drug was infused via the hepatic artery followed by Gelfoam particles. The Ethiodol emulsion was selectively retained in the tumor vessels and also remained in the small daughter nodules that could not be detected by angiography or computed tomography (CT) prior to TAE. Ethiodol remained in the tumor for more than 1 year. Following TAE, main tumors and small daughter nodules appeared as areas of markedly high density on CT. In most patients there was a reduction in the tumor size following TAE, and serum alpha-fetoprotein levels were reduced in all patients whose initial levels had exceeded 400 ng/ml. This method is considered to be effective not only for treatment of hepatic tumor but also useful for evaluation of post-TAE changes in the tumor and diagnosis of small daughter nodules, due to the long-term accumulation of Ethiodol in tumor vessels.

Changes in tumor area and the attenuation value determined from computed tomography (CT) slice section of the tumor at its maximum size were investigated in 18 patients with hepatocellular carcinoma who were studied by CT after arterial embolization therapy. The tumor area was reduced in all cases after embolization therapy. Greater than 50% reduction of the tumor area occurred during the follow-up period in 13 cases (87%). In cases evaluated by follow-up CT, the relative attenuation value of tumor to nontumor regions decreased during the initial stage after embolization therapy, but showed a tendency towards greater elevation than in the initial stage, despite tumor reduction. This change in the attenuation value was considered to reflect necrosis and shrinkage of the tumor after embolization therapy. The absence of such changes in nontumor regions supports the use of arterial embolization therapy as an effective, conservative treatment for hepatocellular carcinoma. Follow-up examination by CT of hepatocellular carcinoma after embolization therapy contributes to the post-therapeutic evaluation of tumors and to the determination of the appropriate time for reembolization therapy.

肝細胞癌に対する肝動脈塞栓術(TAE)後の血清AFP値の推移を,TAE前のAFP値が400ng/ml以上の群(高値群)と未満の群(低値群)に分け,それぞれの群につきTAE後の期間(8週以内の初期変動と6カ月以上の長期変動),塞栓回数(1回施行群と2回以上施行群),塞栓物質の差異(GS:ゼラチンスポンジ使用群とLp:リピオドール併用群)について比較検討し,各種画像との関連についても検討した.高値群と低値群では,高値群のAFP下降がすみやかである以外は,両群にほとんど差はなかった.TAE 2回以上施行群の方が1回施行群よりもAFPが低値を維持する例が多く,くり返すTAEが延命に結びつく結果が得られた.塞栓物質としてGSにLpを併用した群は,GS単独群よりもTAE後のAFP下降がすみやかであり,さらにAFPの再上昇する割合も低く,Lp併用が効果的であることが判明した.US, CTならびに血管造影とAFP値の推移との間には相関性が認められる例が多かった.

腫瘍径が5cm以下の肝癌11切除例の臨床的検討結果を報告するとともに, これら症例の腫瘍の浸潤の状態, 腫瘍の組織型, 非腫瘍部の病変を教室でこれまでに経験した腫瘍径5cm以上の肝癌と腫瘍径別に病理組織学的に対比検討した. 腫瘍径別の組織像は径3～5cm, 3cm以下では全例に被膜形成があるも門脈内腫瘍塞栓は腫瘍径と関係なく75～93%に認めた. 被膜への浸潤の程度も腫瘍径と関係なく50%以上の症例に認めた. 腫瘍部の組織型は3cm以下では高分化型のものが多く, 肝硬変の合併は5cm以上の60%に比べて, 5cm以下では88～100%と高率にみられた. 腫瘍径が3cm以下の肝癌でも早期癌といえる所見ではなく, さらに小型の肝癌を発見し検討する必要がある.

Computed tomography (CT) is a good modality for diagnosing diseases of the retroperitoneal space and capable of showing the abnormality of inferior vena cava (IVC) without using invasive technique. To determine the incidence of the anomaly of IVC, the computed tomograms were investigated retrospectively. The incidence were 0.69% in left side IVC, 1.03% in double IVC and 0.08% in azygos continuation.

抗癌剤混入Lipiodolを併用した肝動脈塞栓術(Lp-TAE)後に肝切除を施行した12例の肝細胞癌を対象にして,手術前のLp-TAE後のCT (Lp-CT)像,切除肝連続切片の軟線X線像ならびに組織像を各々対比し,Lipiodolの主腫瘍と娘結節への集積状態とTAE効果を検討した.Lp-CT像は主腫瘍ならびに娘結節へのLipiodolの集積状態を反映し,小肝細胞癌と娘結節の診断に有効であった.主腫瘍の完全壊死を示した4例と95%以上壊死の認められた5例には,腫瘍内にLipiodolが密に集積し,これらのTAE成績は従来のgelatin sponge単独TAE群のそれを上回っていた.また,娘結節へのLipiodolの集積とTAE効果が組織学的に確認でき,Lp-TAEが娘結節の診断と治療に有効であることが実証できた.Lp-TAEならびに引き続き施行するLp-CTは,肝細胞癌に対する必須の術前検査法として評価されるべきである.

The detectability of small daughter nodules of hepatocellular carcinoma by computed tomography after hepatic arterial infusion of Lipiodol (iodized oil) and by infusion hepatic angiography was studied in 102 cases. The Lipiodol was selectively accumulated by the tumor. Tumors and small daughter nodules appeared as high-density areas on computed tomography. In 24 cases daughter nodules were identified only by computed tomography. In 50 cases computed tomography demonstrated superior ability to detect the daughter nodules when compared with infusion hepatic angiography. In 21 cases the daughter nodules were detected for the first time in areas other than the main site of the primary tumor. Lipiodol-computed tomography is very effective in the diagnosis of daughter nodules of hepatocellular carcinoma.

The therapeutic results of Lp-TAE (transcatheter arterial embolization with Gelfoam particles preceded by the infusion of a mixture of lipiodol and an anticancer drug via the proper hepatic artery) were evaluated in hepatocellular carcinomas (523 non-resected and 24 resected cases). Excellent therapeutic effects were confirmed not only for the main tumor but also for the the daughter nodules by a histological examination of the liver tissues resected after Lp-TAE. The cumulative 1-year, 2-year and 3-year survival rates in the 523 non-resected cases were 60.4%, 42.9% and 28.0% respectively. These survival rates were all higher than those achieved by Gelfoam TAE. The above results suggest the usefulness of Lp-TAE in the treatment of hepatocellular carcinoma.

Twelve cases of hepatocellular carcinoma treated by arterial embolization were followed with ultrasonography. Shrinkage of the tumor after the therapy was confirmed in all cases. Echo level reduction in the tumor occurred in 10 cases. High-level reverberation echoes with acoustic shadows emerged in seven cases; however, these echoes were not detected in any cases 3 weeks after the procedure. Echoes were considered either as the consequence of gas produced in the tumor or air trapped in the embolic substance. Ultrasonography, therefore, is an effective technique for the posttherapeutic evaluation of arterial embolization therapy for hepatocellular carcinoma.