|Year : 2017 | Volume
| Issue : 4 | Page : 631-635
Transarterial embolization with N-butyl 2-cyanoacrylate for the treatment of arterioportal shunts in patients with hepatocellular carcinoma
Feng Duan, Yanhua Bai, Li Cui, Xiaohui Li, Jieyu Yan, Haiyan Zhu
Department of Interventional Radiology, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China
|Date of Web Publication||13-Sep-2017|
Department of Emergency Medicine, The General Hospital of Chinese People's Liberation Army, Beijing 100853
Source of Support: None, Conflict of Interest: None
Aims: The aim of this study is to evaluate efficacy and safety of transarterial chemoembolization (TACE) with N-butyl 2-cyanoacrylate (NBCA) for the treatment of hepatocellular carcinoma (HCC) with arterioportal shunts (APS).
Subjects and Methods: From January 2008 to June 2014, 36 cases of HCC with APS were treated by TACE with NBCA. NBCA-lipiodol mixture was superselective delivered before routine TACE in HCC patients with APS. Recanalization of shunt, objective response, clinical adverse events, and survival rates was retrospectively studied.
Results: All interventional procedures were successful without any procedure relevant complications. The immediate APS improvement rate was 83.3% (30/36), and the APS improvement rate at first-time follow-up was 66.6% (20/30). Radiologically confirmed complete response (CR), partial response, stable disease, and progressive disease at 1 month after first chemoembolization were observed in 1 (2.7%), 19 (52.8%), 6 (16.7%), and 10 (27.8%) patients, respectively. Survival rates were 91.7% at 6 months, 47.2% at 1 year, and 13.9% at 2 years. The median survival time was 11 months. No severe adverse effects were noted.
Conclusions: The preliminary experience indicates TACE with NBCA can be safely performed and may improve prognosis of HCC with arterioportal shunt.
Keywords: Arterioportal shunt, chemoembolization, hepatocellular carcinoma, interventional radiology, N-butyl2-cyanoacrylate
|How to cite this article:|
Duan F, Bai Y, Cui L, Li X, Yan J, Zhu H. Transarterial embolization with N-butyl 2-cyanoacrylate for the treatment of arterioportal shunts in patients with hepatocellular carcinoma. J Can Res Ther 2017;13:631-5
|How to cite this URL:|
Duan F, Bai Y, Cui L, Li X, Yan J, Zhu H. Transarterial embolization with N-butyl 2-cyanoacrylate for the treatment of arterioportal shunts in patients with hepatocellular carcinoma. J Can Res Ther [serial online] 2017 [cited 2018 Aug 16];13:631-5. Available from: http://www.cancerjournal.net/text.asp?2017/13/4/631/214468
| > Introduction|| |
Hepatocellular carcinoma (HCC) is one of the world's most common malignant tumors. Its patient mortality rate of nearly one million per year ranks the third among all cancer patients., Although there have been a few promising developments of HCC treatment, for example, in the field of liver transplantation, surgical resection, ablation, and transarterial chemoembolization (TACE), the overall 2-year survival is still <50%. Especially for HCC patients with arterioportal shunts (APS), prognosis is extremely dissatisfying. We have achieved promising progress in the treatment of HCC with APS, using TACE with N-butyl 2-cyanoacrylate (NBCA). Here, the technique and obtained results in a cohort of 36 patients are presented.
| > Subjects and Methods|| |
Ethical approval was obtained from the Hospital Research Ethics Committee. Informed consent was obtained from all patients included in the study.
Patients and treatment protocol
From January 2008 to June 2014, 36 cases of HCC with APS were treated by TACE with NBCA (BRAUN, Spain), with a total number of 53 TACE with NBCA sessions and a total of 149 TACE sessions. Patients with APS were identified by abdominal contrast medium-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) and further confirmed by digital subtraction angiography (DSA). The baseline patient information and tumor characteristics are summarized in [Table 1].
The procedures during perioperative period are as previously described., Briefly, preoperation evaluation includes a complete history and physical examination, laboratory test within 3 days before treatment including blood cell count, liver and renal panels, serum tumor markers, plain CT scan of the chest and head, or positron emission tomography–CT (depending on the financial capacity of patients), triple-phase CT scan, or dynamic MRI of abdominal within 2 weeks before treatment.
All TACE procedures were performed through DSA (Artis Zee, SIEMENS, Germany; Innova 4100, GE, USA). After standard cannulation of the right femoral artery using a 4F vascular sheath, selective angiography of the celiac artery and superior mesenteric artery was performed using a 4F hepatic artery catheter (HE, Terumo Corp., Japan) through the vascular sheath.
According to the angiography, a microcatheter (Progreat, Terumo Corp., Japan) was superselectively cannulated as far as possible until the opening of the hepatic artery and portal vein fistulas. After rinsing the microcatheter with 50% glucose water, NBCA-lipiodol (Guerbet Corp., France) mixture was administered through the microcatheter. NBCA was mixed with lipiodol (Guerbet Corp., France) at a ratio ranging from 1:1 to 1:4 to control its polymerization time and to render it radiopaque. The exact ratio depends on size of the fistulas and distance from the head of the microcatheter to the opening of the fistulas. Generally speaking, the bigger the fistulas opening, the higher the NBCA versus lipiodol ratio; the greater the distance from the head of the microcatheter to the fistulas opening, the lower the NBCA versus lipiodol ratio. Dosage of NBCA mixture ranges between 0.5 and 5 ml with an average of 1.5 ml. NBCA mixture was administered until stasis with complete contrast medium retention in the portal vein. Then, the microcatheter was immediately removed and rinsed again with 50% glucose water, to prevent blockage in the microcatheter caused by the NBCA mixture [Figure 1], [Figure 2], [Figure 3], [Figure 4].
|Figure 1: Hepatic artery angiography of a 46-year-old male patient bearing hepatocellular carcinoma with hepatic artery and left branch of portal vein fistula, showing early portal vein contrast during arterial phase, as indicated by white arrow|
Click here to view
|Figure 2: Hepatic artery angiography in the same patient as in Figure 2, with superselective catheterization in the left branch of hepatic artery, after embolization of arterioportal shunts by N-butyl 2-cyanoacrylate-lipiodol mixture, demonstrating that the previous hepatic artery left branch of portal vein fistula disappeared|
Click here to view
|Figure 3: Hepatic artery angiography of a 55-year-old male patient, showing giant arterioportal shunts without a visible distal hepatic artery|
Click here to view
|Figure 4: Hepatic artery angiography of the same patient as in Figure 4, after N-butyl 2-cyanoacrylate embolization of the left and middle branch of hepatic artery, showing the distal hepatic artery without arterioportal shunts|
Click here to view
After embolization of APS with NBCA mixture, conventional TACE was applied. Complete angiography examination includes angiography of superselective hepatic artery branches, inferior phrenic artery, internal thoracic artery, and others if needed. Concentrated chemotherapeutic and lipiodol (Guerbet Corp., France) was administrated in afferent branch to the tumor lesion. Drug dosages used had been described previously.,
Postprocedure, patients were supported with treatments to normalize liver function, relieve pain, and inhibit acid secretion, according to their condition. Three days postprocedure, patients were reevaluated for blood cell count and liver and renal function. Patients with laboratory values within normal range were then discharged from the hospital. One month postprocedure, patients were reassessed with liver plain CT scan plus contrast-enhanced CT/MRI, lung plain CT scan, blood cell count, comprehensive metabolic panels, and tumor markers. According to the viability of the tumor, APS condition, and metastatic status, further treatments were determined.
Toxicities from treatments were graded according to NCI-CTCAE version 4.0. Responses were defined using the modified RECIST criteria based on an enhanced abdominal CT or MRI.
| > Results|| |
All interventional procedures were successful with no procedure relevant complications.
The immediate APS improvement rate was 83.3% (30/36), and the APS improvement rate at first-time follow-up was 66.6% (20/30). Radiologically confirmed complete response, partial response, stable disease, and progressive disease at 1 month after first chemoembolization were observed in 1 (2.7%), 19 (52.8%), 6 (16.7%), and 10 (27.8%) patients, respectively.
Survival rates were 91.7% at 6 months, 47.2% at 1 year, and 13.9% at 2 years. The median survival time was 11 months [Figure 5].
|Figure 5: Kaplan–Meier survival curve of the patient group with median survival of 11 months|
Click here to view
During follow-up, 12 patients developed lung metastasis, 2 developed adrenal metastasis, 2 developed bone metastasis, and 16 patients were also treated with oral administration of sorafenib. In addition, 19 patients died of liver failure, 4 patients died of gastrointestinal bleeding, and 10 patients died of unknown causes.
One patient suffered from severe coughing and suffocation symptoms at three minutes after administration of NBCA mixture. Improvements were seen after oxygen inhalation, sedation, and antivasospasm to support breathing. After the initial interventional procedure, 32 patients had, to a certain extent, abdominal pain and 28 patients experienced nausea. Symptoms generally were relieved after symptomatic treatment. Symptoms, which were considered as treatment-induced adverse effects from TACE and severe (grade 3 or 4) adverse effects associated with TACE, were not observed.
| > Discussion|| |
During disease progression, HCC tends to infiltrate the hepatic portal vein, resulting in direct communication between hepatic artery and portal vein, forming APS. Once APS has formed, secondary portal hypertension can cause intractable ascites and esophageal varices, which dramatically affect quality of life and overall survival. Meanwhile, large APS also impedes identification of the tumor-feeding artery during angiography, hindering TACE treatment. Therefore, it is important to close APS before TACE treatment. Such an embolization not only benefits subsequent tumor treatment (for instance, superselective catheterization of a tumor-feeding artery for chemoembolization) but also reduces portal hypertension to improve prognosis.
Currently, besides NBCA, widely used embolization materials include gel foam, PVA particles, ethanol, and coils for the treatment of APS., Selection of optimal embolization material is mainly dependent on the cause of the APS (e.g., trauma, tumor) and the size of a shunt. In case of embolization of large APS, gelatin sponge granule and PVA particles cannot achieve the expected effect because these two types of materials, with their relatively small diameter, can easily pass through the fistulas. Coils are sufficient for traumatic APS but not suitable for tumorous APS. This is because coils embolize mainly the hepatic artery branches, and this can facilitate the formation of collateral tumor-feeding arteries. Thus, coils cannot be used for APS embolization in cancer treatments. As ethanol is not visible under X-ray monitoring, which raises safety concerns, it is not considered as standard embolization material.
NBCA, also known as NBCA, is a liquid embolization material featuring low adhesion and no irritation, commonly mixed with super-liquefied lipiodol or lophendylate at different ratios for clinical application. In contact to hydroxyl ion in the blood, NBCA can instantaneously polymerize. As a material for permanent embolization, NBCA was frequently used in sclerotherapy under endoscopy and the treatment of interventional neurovascular embolization. Because of its liquid form, it can penetrate better than solid embolization materials. At the same time, because it can instantaneously polymerize in the blood, it is increasingly used in the treatment for embolization of emergent peripheral vessel bleeding, portal vein embolization before lobectomy of liver, and embolization of APS in primary liver cancer.,,
During treatment of high flow rate HAPS, the greatest concern is that the embolization material does not remain at fistulas but causes ectopic embolisms. Fortunately, the instantaneous polymerization feature of NBCA in blood can effectively prevent this problem. Besides, various in vivo polymerization times can be achieved by mixing NBCA with lipiodol at different ratios. Some studies showed substantial effect by applying 75% NBCA in lipiodol in cases with circulation time shorter than 0.5 s, 66% NBCA in lipiodol for circulation time of 0.5–1 s, and 33%–50% NBCA in lipiodol for circulation time of 1–2 s. However, we are aware of the subjectivity and deviations during the circulation time measurements, the optimal NBCA versus lipiodol ratio remains to be determined based empirically, and the key point is to make sure the NBCA-lipiodol mixture just embolize the fistula without branch of hepatic artery and portal vein.
During the embolization procedure, one patient from our group experienced transient coughing and suffocation. A possible reason for this is that, under portal hypertension, small communicational branches are formed between portal system and pulmonary circulation, through which NBCA passes and reaches the pulmonary circulation., This case alerts us that the NBCA entering portal vein should be avoided, and higher concentration of NBCA in lipiodol is favored for high flow rate APS to shorter its polymerization time in blood.
Regarding conventional TACE after NBCA embolization in APS, in some cases NBCA completely blocked the tumor-feeding artery, hence, it was not an option to proceed with superselective chemoembolization. For subsequent TACE (including 2nd, 3rd, etc.), a complete angiography, for instance superselective angiography of other hepatic arteries, inferior phrenic artery, and internal thoracic artery, is required to further identify arteries that are involved in the tumor blood supply network, to effectively eliminate the tumor.
The limitations of this study include the following: this is a retrospective study without a control group. In addition, patients received treatments other than TACE, which may have interfered with clinical outcome. The results obtained here on efficacy of NBCA embolization in liver cancer treatments are still not persuasive, and therefore, a prospective study including a control group shall be further pursued.
| > Conclusion|| |
The preliminary experience indicates TACE with NBCA can be safely performed and may improve prognosis of HCC with arterioportal shunt.
First of all, I/we would like to extend my sincere gratitude to our departmental chair for all these support. I/we am/are deeply grateful of the technical help from our physicians, engineers, and nurses. High tribute shall be paid to patients those who signed the consent form.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Ma KW, Cheung TT. Surgical resection of localized hepatocellular carcinoma: Patient selection and special consideration. J Hepatocell Carcinoma 2016;4:1-9.
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.
Golabi P, Fazel S, Otgonsuren M, Sayiner M, Locklear CT, Younossi ZM. Mortality assessment of patients with hepatocellular carcinoma according to underlying disease and treatment modalities. Medicine (Baltimore) 2017;96:e5904.
Duan F, Yu W, Wang Y, Liu FY, Song P, Wang ZJ, et al.
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.
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.
US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. NIH Publication #09-5410: Common Terminology Criteria for Adverse Events (CTCAE) v4.03: June 14, 2010.
Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010;30:52-60.
Ngan H, Peh WC. Arteriovenous shunting in hepatocellular carcinoma: Its prevalence and clinical significance. Clin Radiol 1997;52:36-40.
Huang MS, Lin Q, Jiang ZB, Zhu KS, Guan SH, Li ZR, et al.
Comparison of long-term effects between intra-arterially delivered ethanol and Gelfoam for the treatment of severe arterioportal shunt in patients with hepatocellular carcinoma. World J Gastroenterol 2004;10:825-9.
Chen Q, Tack C, Morcos M, Ruggiero M, Schlossberg P, Fogel J, et al.
Embolotherapy of an arterioportal fistula. Cardiovasc Intervent Radiol 2007;30:1047-51.
Takao H, Shibata E, Ohtomo K. Double-balloon-assisted n-butyl-2-cyanoacrylate embolization of intrahepatic arterioportal shunt prior to chemoembolization of hepatocellular carcinoma. Cardiovasc Intervent Radiol 2016;39:1479-83.
Miyayama S, Matsui O, Taki K, Minami T, Ito C, Shinmura R, et al.
Combined use of an occlusion balloon catheter and a microcatheter for embolization of the unselectable right inferior phrenic artery supplying hepatocellular carcinoma. Cardiovasc Intervent Radiol 2004;27:677-81.
Zhou WZ, Shi HB, Liu S, Yang ZQ, Zhou CG, Xia JG, et al.
Arterioportal shunts in patients with hepatocellular carcinoma treated using ethanol-soaked gelatin sponge: Therapeutic effects and prognostic factors. J Vasc Interv Radiol 2015;26:223-30.
Tokuda T, Tanigawa N, Shomura Y, Kariya S, Kojima H, Komemushi A, et al.
Transcatheter embolization for peripheral pseudoaneurysms with n-butyl cyanoacrylate. Minim Invasive Ther Allied Technol 2009;18:361-5.
Yonemitsu T, Kawai N, Sato M, Tanihata H, Takasaka I, Nakai M, et al.
Evaluation of transcatheter arterial embolization with gelatin sponge particles, microcoils, and n-butyl cyanoacrylate for acute arterial bleeding in a coagulopathic condition. J Vasc Interv Radiol 2009;20:1176-87.
Murata S, Tajima H, Nakazawa K, Onozawa S, Kumita S, Nomura K. Initial experience of transcatheter arterial chemoembolization during portal vein occlusion for unresectable hepatocellular carcinoma with marked arterioportal shunts. Eur Radiol 2009;19:2016-23.
Pollak JS, White RI Jr. The use of cyanoacrylate adhesives in peripheral embolization. J Vasc Interv Radiol 2001;12:907-13.
Frodsham A, Berkmen T, Ananian C, Fung A. Initial experience using N-butyl cyanoacrylate for embolization of lower gastrointestinal hemorrhage. J Vasc Interv Radiol 2009;20:1312-9.
Kallini JR, Gabr A, Hickey R, Kulik L, Desai K, Yang Y, et al.
Indicators of lung shunt fraction determined by technetium-99 m macroaggregated albumin in patients with hepatocellular carcinoma. Cardiovasc Intervent Radiol 2017 9.
Li Q, Ao GK, Duan F, Wang ZJ, Yan JY, Wang MQ. Incidence and therapeutic frequency of extrahepatic collateral arteries in transcatheter arterial chemoembolization of hepatocellular carcinoma: Experience from 182 patients with survival time more than 3 years. Eur J Radiol 2015;84:2555-63.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]