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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 7  |  Page : 1563-1566

Safety and efficacy of transarterial interventional therapy for treatment of hepatocellular carcinoma with peritoneal metastases


Department of Interventional Radiology, The General Hospital of Chinese People's Liberation Army, Beijing, China

Date of Web Publication19-Dec-2018

Correspondence Address:
Feng Duan
Department of Interventional Radiology, The General Hospital of Chinese People's Liberation Army, Beijing 100853
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_984_17

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 > Abstract 


Purpose: The aim of this study was to evaluate the safety and efficacy of transarterial interventional therapy for the treatment of hepatocellular carcinoma (HCC) patient with peritoneal metastases.
Materials and Methods: A total of 7 HCC patients with peritoneal metastases were treated by interventional therapy. Combined treatment with transarterial chemoembolization for intrahepatic lesions and transarterial embolization for peritoneal metastases was performed through hepatic artery, gastroduodenal artery, and superior mesenteric artery.
Results: Treatment resulted in an objective response of 85.7% Modified Response Evaluation Criteria in Solid Tumors. No severe adverse effects were observed.
Conclusions: Transarterial interventional therapy can be performed safely and may improve the prognosis of HCC patients with peritoneal metastases.

Keywords: Hepatocellular carcinoma, interventional radiology, metastases, peritoneal


How to cite this article:
Duan F, Bai Y, Cui L, Li X, Yan J. Safety and efficacy of transarterial interventional therapy for treatment of hepatocellular carcinoma with peritoneal metastases. J Can Res Ther 2018;14:1563-6

How to cite this URL:
Duan F, Bai Y, Cui L, Li X, Yan J. Safety and efficacy of transarterial interventional therapy for treatment of hepatocellular carcinoma with peritoneal metastases. J Can Res Ther [serial online] 2018 [cited 2019 Jun 25];14:1563-6. Available from: http://www.cancerjournal.net/text.asp?2018/14/7/1563/247738




 > Introduction Top


Hepatocellular carcinoma (HCC) is one of the most common cancers and ranked the third most common cause of cancer-related mortality around the world.[1],[2] Distant metastasis is one of the main reasons for treatment failure in HCC patients. According to previous reports, the incidence of peritoneal metastasis in HCC patients varies between 0.06% and 2.66%, while the true incidence is likely higher.[3] However, until now, there is no standard treatment for HCC with peritoneal metastases. In this article, a retrospective study of seven HCC patients with peritoneal metastases was carried out to evaluate the safety and efficacy of transarterial interventional therapy for treatment of HCC patients with peritoneal metastases.


 > Materials and Methods Top


Ethical approval was obtained from the Hospital Research Ethics Committee. Between January 2016 and January 2017, a total of 7 patients who were diagnosed with advanced HCC with peritoneal metastases were treated by transarterial interventional therapy. All seven patients were with no other organ metastasis and without portal vein thrombus. Three patients combined sorafenib and six patients underwent surgical treatment before the interventional therapy, of which the treatment effects were considered to be uncertain. Baseline characteristics of included patients are summarized in [Table 1]. The number of peritoneal metastases ranged from 1 to 8, with a size of peritoneal metastases ranging from 2.1 cm to 21.4 cm.
Table 1: Baseline characteristics of patients

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Management of the perioperative period is similar to the procedure previously described.[4],[5] Briefly, treatment evaluation consisted of a complete history and physical examination. Laboratory and medical tests were done within 3 days before treatment and included blood cell count, liver and renal panels, and serum tumor markers. Plain computed tomography (CT) scan of the chest, tri-phase CT scan, or dynamic magnetic resonance imaging (MRI) of abdomen were performed within 2 weeks before treatment [Figure 1]a and [Figure 2]a. The fluorodeoxyglucose positron emission tomography scan was optional.
Figure 1: A 35-year-old male patient was diagnosed as hepatocellular carcinoma recurrence with peritoneal metastases 6 months after hepatectomy. (a) Abdominal computed tomography scan shows peritoneal metastases in the right lower abdominal cavity. (b) Superselective angiography of superior mesenteric artery branch shows that this branch feeds the peritoneal metastases. (c) Superselectively catheterized with a 2.7 Fr microcatheter of the superior mesenteric artery branch, which feeds the metastases, is treated with 4 ml lipiodol. (d) Follow-up computed tomography image shows lipiodol deposition in the peritoneal metastases

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Figure 2: A 47-year-old male patient was diagnosis as hepatocellular carcinoma recurrence with multiple peritoneal metastases 2 years after hepatectomy. (a) Abdominal magnetic resonance imaging scan shows multiple peritoneal metastases lesions. (b) Superselective angiography of gastroduodenal artery shows that branches of the gastroduodenal artery feed the peritoneal metastases. (c) Superselectively catheterized with a 2.7 Fr microcatheter of the gastroduodenal artery branch which feeds the metastases is treated with 15 ml lipiodol. (d) Follow-up computed tomography image shows lipiodol deposition in the peritoneal metastases

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Eligibility criteria for transarterial chemoembolization (TACE) procedures included white blood cell ≥ 4.0 × 109, platelet ≥ 50 × 1012, red blood cell ≥ 3.5 × 109, Child-Pugh Class A, and normal renal function.

All transarterial interventional procedures were performed through Artis Zee digital subtraction angiography (DSA) (SIEMENS, Germany). After a routine preoperative preparation, transarterial interventional therapy was performed under sterile conditions, with the patient under local anesthesia. The right femoral artery was cannulated using a 4F vascular sheath (Radifocus Introducer II; Terumo Corp., Japan) by Seldinger technique. Selective angiography of celiac artery, gastroduodenal artery (GDA) [Figure 2]b, and superior mesenteric artery (SMA) [Figure 1]b was performed using a 4F hepatic artery catheter (HE, Terumo Corp., Japan) inserted through the vascular sheath.

According to the angiography, maximum catheter selectivity of the hepatic artery, GDA, and SMA was achieved using a microcatheter (Progreat, Terumo Corp., Japan), with administration from subsegmental and segmental branches afferent to the tumor lesions, often with the microcatheter wedged.

Concentrated chemotherapeutic and lipiodol (Guerbet Corp., France) was administrated in branches of the hepatic artery. Drug dosages per procedure varied, ranging from 5 to 20 mL for lipiodol, 30–50 mg of doxorubicin [6] (Pfizer Pharmaceuticals Ltd, USA), and 50–150 mg oxaliplatin (Sanofi Pharmaceuticals Co., Ltd, France), depending on the size of the tumor lesion and laboratory results. Lipiodol were mixed up with doxorubicin and oxaliplatin; lipiodol-chemotherapeutic agents were administered until stasis, minimizing reflux into nontarget vessels. Particle embolic materials such as gelatin sponge (500–700 um, AILIKANG Co., Ltd, China)[7] or polyvinyl alcohol particles (500–700 um, PVA, COOK Co., Ltd, USA, used in patients with a high blood flow) were injected as supplement when stasis was not achieved after delivery of 20 ml lipiodol.

Lipiodol alone was administrated in branches of GDA and SMA, as shown in [Figure 1]c and [Figure 2]c, with maximum catheter selectivity according to DSA imaging. Lipiodol volume administered depended on the tumor size of the metastases. In general, 2 ml lipiodol was administrated for 1 cm lesion, while total maximum volume was <20 ml lipiodol. Lipiodol was administered until near stasis. If stasis was not achieved after 20 ml lipiodol, gelatin sponge was injected as supplement in GDA branches. No particle embolic material was injected in SMA branches.

After the procedure, patients were administered polyenephosphatidylcholine (465 mg, intravenous [IV], qd, Chengdu Tiantaishan Pharmaceutical Co., China) and glutathione (1800 mg, IV, qd, Laboratorio Farmaceutico C.T.S.R.L, Italy) to normalize liver function, as well as painkillers (Oxycodone Hydrochloride prolonged-release Tablets, 20 mg, q. 12 h, Bard Pharmaceuticals Limited), and antiemetic (Cefmetazole, 2 g, IV, bid, Herbin Pharmaceutical Co., China) if necessary for 3 days. Bowel necrosis was monitored by abdominal physical examination twice per day. On the 3rd day after completion of TACE, patients were assessed for adverse effects by undergoing a thorough physical examination, blood cell count, and liver and renal panels. The patients were discharged from the hospital when laboratory results were within normal range.

Patients were followed up monthly [Figure 1]d and [Figure 2]d. Another session of interventional treatment was performed if residual disease or new tumor lesions (both intrahepatic and peritoneal) were present.

Evaluation

Treatment-related toxicity was graded according to NCI-CTCAE version 4.0.[6] Responses were defined using the Modified Response Evaluation Criteria in Solid Tumors criteria [8] based on an enhanced abdominal CT or MRI.


 > Results Top


A total of 14 transarterial interventional procedures were performed in seven patients. Treated arteries included branches of hepatic artery (7 cases), GDA (5 cases), and SMA (4 cases). Radiologically confirmed complete response (CR), partial response (PR), and progressive disease for intrahepatic disease were observed in 4, 2, and 1 patients, respectively. Radiologically confirmed CR and PR for peritoneal metastases were observed in 2 and 5 patients, respectively [Table 2].
Table 2: Response to treatment

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No metastasis to organs, other than peritoneum was observed in all patients during the treatment period. Two patients with bloody ascites were treated by intraperitoneal chemotherapy 2 weeks after the last transarterial interventional session. The chemotherapy protocol consisted of a peritoneal perfusion with 50 mg cisplatin and 500 mg 5-fluorouracil at day 1 and day 5. Radiologically confirmed PR of peritoneal metastases was achieved in these two patients. In 3 patients, treatment was combined with oral administration of sorafenib. One patient died of liver failure 6 months after the 1st transarterial interventional procedure.

Side-effects were observed in four patients who experienced abdominal pain, while six patients experienced nausea, which was considered as treatment-induced adverse effects resulting from transarterial interventional therapy. Severe (Grade 3 or Grade 4) adverse effects associated with transarterial interventional therapy were not observed and no bowel necrosis was noted.


 > Discussion Top


Extrahepatic metastases are seen in 64% of patients with HCC. The most frequent sites of extrahepatic metastases are lung, abdominal lymph nodes, adrenal glands, and bone, while metastases to the peritoneum are unusual.[9],[10],[11] Peritoneal metastases may occur spontaneously in HCC, but also as a result of percutaneous techniques such as biopsy and ablation, and through surgery. With the increasing use of aforementioned medical practices for HCC treatment, this problem is likely more widespread. Within the group of patients presented here, six had undergone medical treatments before. However, there is little experience with treatment of HHC-related peritoneal metastases to date. Takemura et al.[12] performed surgical resection on patients with peritoneal metastases. These patients had limited number of peritoneal lesions, including those found incidentally during surgery and or intrahepatic lesions or if present these were predicted to be locally controllable, and these patients had no ascites with sufficient hepatic functional reserve.[13] However, most patients with peritoneal metastases are beyond the range of these indications. In the study, interventional therapy was implemented for the treatment of peritoneal metastases, which resulted in an optimized outcome.

SMA embolization is accompanied by a high risk of bowel necrosis limiting safety of this approach. It was hypothesized that lipiodol alone without chemotherapeutic agents is more safe which we confirmed as there was no bowel necrosis noted. We believe that this may result from first, maximum superselective catheterization to avoid damage to normal bowel and second, the hypervascular nature of peritoneal metastases as compared to normal bowel, which favors accumulation of embolic materials in these lesions over healthy bowel tissue. Although no serious complications were observed, it is important to realize that the total amount of lipiodol delivered into SMA or GDA in our study was <20 ml and no particle embolic materials were delivered into the branches of SMA.

Because this is a short-term retrospective study, survival analysis was not conducted. However, the clinical symptoms in patients, such as abdominal distension and abdominal pain, were significantly less compared to previous treatment. Furthermore, hepatic artery chemoembolization was performed simultaneously, which likely improves survival of patients.

The study has several limitations which include the retrospective design and small number of patients. A study on a larger number of patients with long-term follow-up is underway.


 > Conclusions Top


Transarterial interventional therapy can be safely performed in HCC patients with peritoneal metastases for both intrahepatic lesions and peritoneal lesions. Treatment resulted in favorable and radiologically confirmed responses. Further investigations on long-term survival should be performed in the future.

Acknowledgment

First of all, I would like to extend my sincere gratitude to our departmental chair for all these support. I am deeply grateful of the help from our physicians, engineers, nurses as well as other staff of the department.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Ma KW, Cheung TT. Surgical resection of localized hepatocellular carcinoma: Patient selection and special consideration. J Hepatocell Carcinoma 2017;4:1-9.  Back to cited text no. 1
    
2.
Rossi L, Zoratto F, Papa A, Iodice F, Minozzi M, Frati L, et al. Current approach in the treatment of hepatocellular carcinoma. World J Gastrointest Oncol 2010;2:348-59.  Back to cited text no. 2
    
3.
Perkins JD. Seeding risk following percutaneous approach to hepatocellular carcinoma. Liver Transpl 2007;13:1603.  Back to cited text no. 3
    
4.
Duan F, Yu W, Wang Y, Liu FY, Song P, Wang ZJ. Trans-arterial chemoembolization and external beam radiation therapy for treatment of hepatocellular carcinoma with a tumor thrombus in the inferior vena cava and right atrium. Cancer Imaging 2015;15:7.  Back to cited text no. 4
    
5.
Duan F, Wang MQ, Liu FY, Wang ZJ, Song P, Wang Y. Sorafenib in combination with transarterial chemoembolization and bronchial arterial chemoinfusion in the treatment of hepatocellular carcinoma with pulmonary metastasis. Asia Pac J Clin Oncol 2012;8:156-63.  Back to cited text no. 5
    
6.
Bai Z, Qin Y, Zhu G, Zhao G, Deng G, Guo J, et al. Efficacy and safety of epirubicin applied in transcatheter arterial chemoembolization for hepatocellular carcinoma: A meta-analysis. J Cancer Res Ther 2018;14:133-8.  Back to cited text no. 6
    
7.
Zhou J, Liu Y, Ren Z, Zhang Y, Zhang M. Transarterial chemoembolization with gelatin sponge microparticles for Barcelona clinic liver cancer stage C and large hepatocellular carcinoma: Initial clinical experience. J Cancer Res Ther 2017;13:767-72.  Back to cited text no. 7
    
8.
U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) [EB/OL]. Available from: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_Revisions.txt. [Last accessed on 2018 Sep 28].  Back to cited text no. 8
    
9.
Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010;30:52-60.  Back to cited text no. 9
    
10.
Katyal S, Oliver JH 3rd, Peterson MS, Ferris JV, Carr BS, Baron RL, et al. Extrahepatic metastases of hepatocellular carcinoma. Radiology 2000;216:698-703.  Back to cited text no. 10
    
11.
Terada T, Maruo H. Unusual extrahepatic metastatic sites from hepatocellular carcinoma. Int J Clin Exp Pathol 2013;6:816-20.  Back to cited text no. 11
    
12.
Takemura N, Hasegawa K, Aoki T, Sakamoto Y, Sugawara Y, Makuuchi M, et al. Surgical resection of peritoneal or thoracoabdominal wall implants from hepatocellular carcinoma. Br J Surg 2014;101: 1017-22.  Back to cited text no. 12
    
13.
Nielsen JA, Putcha RV, Roberts CA. The increasing incidence of remote metastasis: A case report of metastatic hepatocellular carcinoma to the rectosigmoid. Tumori 2014;100:e31-4.  Back to cited text no. 13
    


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