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CORRESPONDENCE
Year : 2018  |  Volume : 14  |  Issue : 12  |  Page : 1233-1236

Treatment strategy for huge hepatocellular carcinoma with intrahepatic metastasis and macrovascular invasion: a case report and literature review


Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

Date of Web Publication11-Dec-2018

Correspondence Address:
Jie Wang
Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, No. 33 Yingfeng Road, Guangzhou 510289
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.204845

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 > Abstract 


Macrovascular invasion, such as tumor thrombus in the major portal vein (mPVTT) or major hepatic vein (mHVTT), is regarded as indicative of an advanced stage of hepatocellular carcinoma (HCC). To date, no effective treatment has been established for this kind of HCC. We herein present a case of huge HCC with intrahepatic metastasis, mPVTT, and mHVTT. The patient was successfully treated with surgical resection-based multidisciplinary treatment. The clinical presentation, treatment strategy, and outcome of this case were presented.

Keywords: Hepatectomy, hepatocellular carcinoma, major hepatic vein tumor thrombus, major portal vein tumor thrombus, multidisciplinary treatment, sorafenib


How to cite this article:
He C, Zhou Z, Xiao Z, Wang J. Treatment strategy for huge hepatocellular carcinoma with intrahepatic metastasis and macrovascular invasion: a case report and literature review. J Can Res Ther 2018;14, Suppl S5:1233-6

How to cite this URL:
He C, Zhou Z, Xiao Z, Wang J. Treatment strategy for huge hepatocellular carcinoma with intrahepatic metastasis and macrovascular invasion: a case report and literature review. J Can Res Ther [serial online] 2018 [cited 2019 Sep 17];14:1233-6. Available from: http://www.cancerjournal.net/text.asp?2018/14/12/1233/204845




 > Introduction Top


A large number of hepatocellular carcinoma (HCC) patients have intrahepatic metastasis together with major portal vein tumor thrombus (mPVTT) or major hepatic vein tumor thrombus (mHVTT) at diagnosis.[1],[2] However, the optimal treatment for HCC patients with intrahepatic metastasis and mPVTT/mHVTT remains controversial.[3],[4],[5],[6]

Evidence from studies suggests that surgical resection-based multidisciplinary treatment (MDT) including transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), or sorafenib in patients with HCC may provide better outcomes than each approach alone.[7],[8],[9] We herein report a case of huge HCC with intrahepatic metastasis, mPVTT, and mHVTT who was successfully treated with surgical resection-based MDT.


 > Case Report Top


A 56-year-old Chinese man was found to have advanced HCC. The patient is a hepatitis B virus (HBV) carrier but does not have liver cirrhosis. His initial symptom was significant weight loss. The patient did not claim any abdominal discomfort. The patient underwent TACE 1 month before admission to our hospital. Contrast-enhanced computed tomography (CT) revealed a huge carcinoma in the right lobe with areas of lipiodol deposition. Another lesion in the segment 2 was also detected. Tumor thrombi were found in the left and right portal vein, the main portal vein trunk, and the right hepatic vein [Figure 1]. Magnetic resonance images and positron emission tomography/CT showed similar findings to CT. Preoperative biochemical examinations showed alpha-fetoprotein (AFP) was 6427 ng/mL, HBV-DNA was <5.0 × 102 copies/mL. The patient's Child-Pugh score was five points (Class A), the model for end-stage liver disease score was eight, and the Eastern Cooperative Oncology Group (ECOG) Performance Status was zero. The patient was classified by the barcelona clinic liver cancer system as Stage C and tumor, node, metastasis staging system as IIIb.
Figure 1: Contrast-enhanced computed tomography findings before surgical resection. (a) A huge carcinoma in the right lobe with areas of lipiodol deposition, and another lesion in the segment 2. Tumor thrombus in the right portal vein was also detected (red arrow). (b and c) Tumor thrombus in the left portal vein (yellow arrow) and the main portal vein trunk (blue arrow). (d and e) Tumor thrombus in the right hepatic vein (green arrow)

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The patient subsequently underwent nonanatomic resection of the right liver and segment 2. Macroscopically, the liver was almost normal. The main tumor was about 12 cm × 12 cm. In the segment 2, a 3 cm × 3 cm metastatic lesion could be found. For PVTT, the right and left portal veins were exposed and incised, and thrombectomy was performed, respectively. For HVTT, the right hepatic vein was ligated at root site and the HVTT was resected en bloc with the tumor [Figure 2].
Figure 2: Contrast-enhanced computed tomography findings after surgical resection. (a) Arterial phase. (b-d) Venous phase

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The postoperative course was uneventful. The AFP level was decreased to 458 ng/mL on the 13th postoperative day [Figure 3]. The patient was discharged on the 19th postoperative day. Two months after surgery, metastatic lesions in the liver segment 5, left portal vein, and lung were detected. The patient then underwent three times TACE and twice RFA for liver and portal vein lesions successively, and once RFA for lung lesions. During this period, the patient has taken sorafenib (800 mg/day) in combination with S-1. Antiviral drug was also taken. Serum AFP assays were performed every 1–2 months and showed a gradual decrease but increased again in the latest 9 month [Figure 3]. Contrast-enhanced CT scan was also performed every 2–3 months for evaluation of treatment efficiency. Until April 2016, the patient had been alive for 20 months with an ECOG performance status of zero. This article was approved by the Ethics Committee at our institute. Informed consent was obtained from the patient.
Figure 3: Clinical course of the serum alpha-fetoprotein levels after surgical resection. AFP = Alpha-fetoprotein, TACE = Transcatheter arterial chemoembolization, RFA = Radiofrequency ablation

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 > Discussion Top


In the present report, the patient, who was found to have a huge HCC with intrahepatic metastasis, mPVTT, and mHVTT, underwent aggressive MDT combining surgery with the subsequent administration of sorafenib, repeated TACE and RFA. The patient achieved an acceptable survival of more than 20 months. So far, two studies of sorafenib as an adjuvant therapy for HCC resection have been reported.[9],[10] Although these two studies have an opposite conclusion, both of them did not include patients with macrovascular invasion, which is one of the indicators of advanced HCC. Conversely, other five cases reported in Japan utilized sorafenib as adjuvant management of surgery for HCC with macrovascular invasion.[11],[12] In those cases, surgical resection-based combination treatment provided long-time survival. However, because both of these reports come from Japan, we cannot get the English full text of them. To the best of our knowledge, this is the first case report of huge HCC with intrahepatic metastasis as well as macrovascular invasion in both portal vein and hepatic vein undergoing surgical resection and adjuvant MDT including sorafenib, TACE, and RFA.

Sorafenib is an oral multikinase inhibitor that has been proven to improve survival in patients with advanced HCC and extrahepatic spread or macrovascular invasion.[13],[14] Unfortunately, survival among these patients was modest, with the median overall survival of about 6 months in East Asian population.[3],[13],[15] In contrast to sorafenib alone, either the combination of locoregional therapies or the combination of locoregional therapy with sorafenib has been reported with promising survival benefit for advanced HCC.[16],[17] Zhu et al. studied the efficacy of TACE combined with sorafenib in patients with HCC and PVTT.[16] They found that combination therapy with TACE and sorafenib showed significant survival benefits compared with TACE alone.[16] Liu et al. reported that the combination of RFA with TACE is better than TACE alone in treating advanced HCC.[17] These studies suggest that combination therapies utilizing multimodal approaches may provide acceptable outcomes in advanced HCC patients. However, the optimal treatment for patients with HCC and intrahepatic metastasis as well as macrovascular invasion remains controversial.

Surgical resection with complete extirpation of tumor gives the best chance of a cure for patients with HCC. Owing to the improvement in surgical techniques and perioperative care, hepatectomy has become a reasonably safe treatment option with an acceptable mortality rate.[18] Aggressive surgical resection for HCC with macrovascular invasion has been proposed from some centers with acceptable outcomes.[19],[20],[21] In 2010, Shi et al. reported the median survival time of 78 HCC patients with mPVTT in their center was 10 months.[19] What's more, Roayaie et al. reported a median survival time of 13 months in 165 HCC patients with mPVTT who were treated with surgical resection.[20] On the other hand, Kokudo et al. retrospectively analyzed HCC patients with mHVTT or inferior vena cava tumor thrombus (IVCTT) in their center, and found that surgical resection, especially R0 resection, is associated with a good prognosis.[21] Their data showed a median survival time of 3.95 years in mHVTT group and 1.39 years in IVCTT group.[21] All these data suggest that surgical resection plus thrombectomy may offer a chance of long-time survival in HCC patients with macrovascular invasion.

In the present case, the patient was initially treated with TACE. However, after TACE, not only the tumor was not controlled, but also intrahepatic metastasis and mPVTT/mHVTT emerged. Under this condition, we performed surgical resection plus thrombectomy combined with administration of sorafenib, repeated TACE and RFA. The patient had been alive for 20 months after the treatment. Our case was consistent with the survival of patients treated with surgery mentioned above. Huge HCC with intrahepatic metastasis and mPVTT/mHVTT has been demonstrated to have higher incidence in tumor recurrence and mortality.[22] The patient in our case has experienced tumor recurrence since the 2nd month after surgical resection. However, through treatment with sorafenib and locoregional therapies, the patient kept long-time survival with an ECOG performance status of zero. Besides, compared with the published literature [Table 1], our treatment strategy had a better outcome.[23],[24],[25],[26] Thus, our case showed that the combination of surgery with the following sorafenib oral taking, TACE and RFA may result in an acceptable survival.
Table 1: Reported cases of huge hepatocellular carcinoma with major portal vein tumor thrombus and major hepatic vein tumor thrombus

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 > Conclusion Top


We reported here a huge HCC case with intrahepatic metastasis, mPVTT, and mHVTT, who was treated with surgical resection-based MDT, achieved a relatively long-term survival. Further studies are needed to evaluate the benefits of this treatment strategy for HCC patients with intrahepatic metastasis, mPVTT, and mHVTT.

Financial support and sponsorship

This study was supported by grants from the National Natural Science Foundation of China (Grant no. 81301768).

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Qin S, Cheng Y, Liang J, Shen L, Bai Y, Li J, et al. Efficacy and safety of the FOLFOX4 regimen versus doxorubicin in Chinese patients with advanced hepatocellular carcinoma: a subgroup analysis of the EACH study. Oncologist 2014;19:1169-78.  Back to cited text no. 1
    
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Zhang Y, Fan W, Wang Y, Lu L, Fu S, Yang J, et al. Sorafenib with and without transarterial chemoembolization for advanced hepatocellular carcinoma with main portal vein tumor thrombosis: A retrospective analysis. Oncologist 2015;20:1417-24.  Back to cited text no. 3
    
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Peng ZW, Guo RP, Zhang YJ, Lin XJ, Chen MS, Lau WY. Hepatic resection versus transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma with portal vein tumor thrombus. Cancer 2012;118:4725-36.  Back to cited text no. 4
    
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Fujino H, Kimura T, Aikata H, Miyaki D, Kawaoka T, Kan H, et al. Role of 3-D conformal radiotherapy for major portal vein tumor thrombosis combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma. Hepatol Res 2015;45:607-17.  Back to cited text no. 5
    
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Hirooka M, Koizumi Y, Kisaka Y, Abe M, Murakami H, Matsuura B, et al. Mass reduction by radiofrequency ablation before hepatic arterial infusion chemotherapy improved prognosis for patients with huge hepatocellular carcinoma and portal vein thrombus. AJR Am J Roentgenol 2010;194:W221-6.  Back to cited text no. 6
    
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Peng BG, He Q, Li JP, Zhou F. Adjuvant transcatheter arterial chemoembolization improves efficacy of hepatectomy for patients with hepatocellular carcinoma and portal vein tumor thrombus. Am J Surg 2009;198:313-8.  Back to cited text no. 7
    
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Song KD, Lim HK, Rhim H, Lee MW, Kim YS, Lee WJ, et al. Repeated hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma after hepatic resection: A propensity score matching study. Radiology 2015;275:599-608.  Back to cited text no. 8
    
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Wang SN, Chuang SC, Lee KT. Efficacy of sorafenib as adjuvant therapy to prevent early recurrence of hepatocellular carcinoma after curative surgery: A pilot study. Hepatol Res 2014;44:523-31.  Back to cited text no. 9
    
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Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol 2015;16:1344-54.  Back to cited text no. 10
    
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Kashiwazaki M, Hama N, Takiuchi D, Noguchi K, Hata T, Asukai K, et al. Resection and postoperative multidisciplinary treatment for hepatocellular carcinoma with massive portal venous tumor thrombus-A single-center experience. Gan To Kagaku Ryoho 2013;40:1675-7.  Back to cited text no. 11
    
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Hyuga S, Tomokuni A, Tomimaru Y, Wada H, Hama N, Kawamoto K, et al. Long-term survival in a case of advanced hepatocellular carcinoma with tumor thrombus in the portal vein and the right atrium (vp4, vv3) treated successfully with multidisciplinary therapies. Gan To Kagaku Ryoho 2014;41:2130-2.  Back to cited text no. 12
    
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Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10:25-34.  Back to cited text no. 13
    
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Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90.  Back to cited text no. 14
    
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Song DS, Song MJ, Bae SH, Chung WJ, Jang JY, Kim YS, et al. Acomparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. J Gastroenterol 2015;50:445-54.  Back to cited text no. 15
    
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Zhu K, Chen J, Lai L, Meng X, Zhou B, Huang W, et al. Hepatocellular carcinoma with portal vein tumor thrombus: treatment with transarterial chemoembolization combined with sorafenib – A retrospective controlled study. Radiology 2014;272:284-93.  Back to cited text no. 16
    
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Liu HC, Shan EB, Zhou L, Jin H, Cui PY, Tan Y, et al. Combination of percutaneous radiofrequency ablation with transarterial chemoembolization for hepatocellular carcinoma: observation of clinical effects. Chin J Cancer Res 2014;26:471-7.  Back to cited text no. 17
    
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Imamura H, Seyama Y, Kokudo N, Maema A, Sugawara Y, Sano K, et al. One thousand fifty-six hepatectomies without mortality in 8 years. Arch Surg 2003;138:1198-206.  Back to cited text no. 18
    
19.
Shi J, Lai EC, Li N, Guo WX, Xue J, Lau WY, et al. Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus. Ann Surg Oncol 2010;17:2073-80.  Back to cited text no. 19
    
20.
Roayaie S, Jibara G, Taouli B, Schwartz M. Resection of hepatocellular carcinoma with macroscopic vascular invasion. Ann Surg Oncol 2013;20:3754-60.  Back to cited text no. 20
    
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Kokudo T, Hasegawa K, Yamamoto S, Shindoh J, Takemura N, Aoki T, et al. Surgical treatment of hepatocellular carcinoma associated with hepatic vein tumor thrombosis. J Hepatol 2014;61:583-8.  Back to cited text no. 21
    
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Li Y, Xia Y, Li J, Wu D, Wan X, Wang K, et al. Prognostic nomograms for pre- and postoperative predictions of long-term survival for patients who underwent liver resection for huge hepatocellular carcinoma. J Am Coll Surg 2015;221:962-74.e4.  Back to cited text no. 22
    
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Luo X, Zhang B, Dong S, Zhang B, Chen X. Hepatocellular carcinoma with tumor thrombus occupying the right atrium and portal vein: A case report and literature review. Medicine (Baltimore) 2015;94:e1049.  Back to cited text no. 23
    
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Kitajima T, Hatano E, Mitsunori Y, Taura K, Fujimoto Y, Mizumoto M, et al. Complete pathological response induced by sorafenib for advanced hepatocellular carcinoma with multiple lung metastases and venous tumor thrombosis allowing for curative resection. Clin J Gastroenterol 2015;8:300-5.  Back to cited text no. 24
    
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Kawakami M, Koda M, Mandai M, Hosho K, Murawaki Y, Oda W, et al. Isolated metastases of hepatocellular carcinoma in the right atrium: Case report and review of the literature. Oncol Lett 2013;5:1505-8.  Back to cited text no. 25
    
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Florman S, Weaver M, Primeaux P, Killackey M, Sierra R, Gomez S, et al. Aggressive resection of hepatocellular carcinoma with right atrial involvement. Am Surg 2009;75:1104-8.  Back to cited text no. 26
    


    Figures

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