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 Table of Contents  
REVIEW
Year : 2018  |  Volume : 4  |  Issue : 4  |  Page : 102-108

Transarterial embolization for hepatocellular adenomas: Case report and literature review


1 Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University; Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, Guangxi, China
2 Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China
3 Department of Medicine, Section of Hematology and Oncology, University of Illinois at Chicago, Chicago, IL, USA
4 Basic Medical College of Guangxi Medical University, Nanning, Guangxi, China

Date of Submission15-Jul-2018
Date of Acceptance16-Aug-2018
Date of Web Publication31-Aug-2018

Correspondence Address:
Prof. Bang-De Xiang
Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi
China
Prof. Le-Qun Li
Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ctm.ctm_24_18

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  Abstract 


Hepatocellular adenoma (HCAs) is a rare benign tumor in the liver. Bleeding and malignant transformation are the two severe outcomes of HCAs. Transarterial embolization (TAE) is used to treat HCAs; however, its role in an elective setting is uncertain. Here, we report a case with HCA treated by TAE in an elective setting, followed by resection after 2 months, because of stable disease. Further, we performed a comprehensive review of PubMed database for studies published between January 2000 and June 2018 involving TAE to treat HCA. The review included 22 studies involving 1504 patients with HCA, of whom 89.4% were female. Only 171/1504 (11.4%) patients received TAE, among whom resection was avoided in 80 (46.8%) patients, of whom 31 (38.7%) were bleeding before TAE and 49 (61.3%) were not. Based on data of 115 tumors reviewed, the rate of complete and partial response were 9.6% and 74.8%, respectively, with an overall (complete + partial) response of 84.3%. No mortality or adverse side effects were noted. Therefore, both in elective setting and in the setting of bleeding, TAE can be considered safe in the management of HCAs and may be regarded as reasonable alternative management to hepatic resection.

Keywords: Avoiding hepatic resection, hepatocellular adenomas, transarterial embolization, tumor reduction


How to cite this article:
Zhong JH, Chen K, Ahir BK, Huang Q, Wu Y, Liao CC, Jia RR, Xiang BD, Li LQ. Transarterial embolization for hepatocellular adenomas: Case report and literature review. Cancer Transl Med 2018;4:102-8

How to cite this URL:
Zhong JH, Chen K, Ahir BK, Huang Q, Wu Y, Liao CC, Jia RR, Xiang BD, Li LQ. Transarterial embolization for hepatocellular adenomas: Case report and literature review. Cancer Transl Med [serial online] 2018 [cited 2018 Sep 19];4:102-8. Available from: http://www.cancertm.com/text.asp?2018/4/4/102/240295




  Introduction Top


Hepatocellular adenoma (HCA) is a rare benign tumor of the liver. Annual incidence of HCA is estimated to be 1 per 1 million in the general population.[1] It is found mostly in women and is associated with female hormones.[2] The long-term use of oral contraceptives is considered as the main risk factor. New HCA risk factors include obesity, metabolic syndrome, and anabolic steroid exposure.[3] In clinics, most patients already have large tumors (> 5 cm) at initial diagnosis because of being asymptomatic. Therefore, HCA is usually discovered accidentally based on abdominal imaging performed for other reasons.

Bleeding and malignant transformation are the two main severe outcomes of HCA. Symptomatic bleeding occurs in about 14% of patients, and the risk of such bleeding increases with tumor diameter.[2] The risk of malignant transformation into hepatocellular carcinoma (HCC) can be up to 6% in women and up to 47% in men.[2],[4] In addition, about 7% of the nodules are considered borderline between HCA and HCC.[2] Therefore, hepatectomy is a common initial treatment for large HCA (> 5 cm), especially in male patients owing to the higher incidence of malignant transformation. However, hepatectomy is also associated with a morbidity rate of 20% and a mortality rate of 3%.[5],[6] Therefore, transarterial embolization (TAE) is an alternate option for treating HCA, especially for those complicated by hemorrhage.[7] TAE is associated with less blood loss and lower risk of postoperative complications than resection.[8],[9] Moreover, TAE may be superior to hepatectomy if the HCA involves multiple tumors or if the tumor is difficult to reach during resection. More importantly, TAE may also reduce the risk of HCC transformation of HCA.[10]

Here, we report a single patient case study, with large HCA, successfully treated by elective TAE. Moreover, to clarify the suitability of elective TAE in patients with nonbleeding HCA or who are at low risk of intraoperative bleeding, we comprehensively reviewed the clinical studies of TAE, which treated both bleeding and nonbleeding HCA. We focused on post-TAE outcomes such as tumor size reduction and need for hepatectomy.

This study was approved by the Institutional Review Board of the Tumor Hospital of Guangxi Medical University. Written informed consent was obtained from the patient for his information to be stored in the hospital database and to be used for research purposes.


  Case Report Top


A 53-year-old male was admitted to the Department of Hepatobiliary Surgery of the Affiliated Tumor Hospital of Guangxi Medical University (Nanning, China) on 3 January 2012 with approximately 2-months' history of mild pain in the left upper quadrant of the abdomen. No nausea and vomiting were recorded. On physical examination, sensitive to percussion with a mass was found in the left upper quadrant. No other positive clinical manifestations or positive sign were observed on palpation.

Computed tomography (CT) scans [Figure 1] identified a mixed density tumor shadow in the left upper abdominal cavity (15.8 cm × 12.0 cm). The arterial phase of enhanced scanning showed uneven enhancement while the venous phase showed relatively equal density. The lesion and the left lobe of the liver were not clearly demarcated and were closely related to the gastric wall and spleen, and applied pressure on the spleen and the left kidney. The density of the left outer lobe of the liver was slightly lower, the arterial phase of the enhanced scanning was relatively low, and the venous phase was equal. No abnormal density was found in the remaining liver. No definite abnormality was found in the gallbladder, pancreas, kidney and adrenal gland. No definite enlarged lymph nodes were seen in the peritoneum. No ascites observed. Vascular reconstruction showed that the left upper abdominal mass had an abundant blood supply and was supplied by the left hepatic artery and its branches. The diagnosis of the tumor from CT was a mesenchymal tissue from liver, cholangiocellular carcinoma, or HCC. The tests for alpha-fetoprotein and hepatitis B and C virus were negative. Liver function was Child-Pugh Class A.

The patient was suggested to receive hepatic resection. However, the patient did not agree to receive resection, but TAE. Therefore, to avoid bleeding, he received TAE in an elective setting. Chemotherapy agent was not used. Obvious morbidity was not found after TAE. About 2 months later, the patient came back to hospital to get checked for the efficacy of TAE. CT found that the tumor in the left upper abdominal cavity was stable. Liver function was still Child-Pugh Class A. Therefore, the patient was suggested to receive hepatic resection again. At this time, he and his family agreed to receive resection.

Postoperative pathology found that the tumor in the left outer lobe of liver (size 15.5 cm × 13.3 cm × 9.0 cm) had a large number of lesions scattered in dark red soft spongy like lesions. The remaining liver tissue sections were gray-yellow in nature. The diagnosis was HCA with hemorrhage. No significant morbidity was observed in this patient after resection. During 46 months' follow-up, the patient was alive without any malignant transformation.

Methods of literature review

PubMed database was systematically searched for studies published between 1 January 2000 and 30 June 2018 involving TAE to treat HCA. Studies had to meet the following criteria to be included in the final analysis: (a) publication after 2000, when radiological interventional techniques became common; (b) HCA patient population treated by elective or emergency TAE (TAE alone, prior to surgery, or after surgery); and (c) a case series (involving at least four patients), case–control or cohort design reporting on post-TAE outcomes.
Figure 1: Computed tomography scans: a mixed density tumor shadow in the left upper abdominal cavity (15.8 cm × 12.0 cm). (a) Venous phase; (b) arterial phase; (c) delayed phase

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The following primary outcome data were collected: reason for TAE, number of resections avoided (bleeding/non-bleeding), malignant transformation, and TAE-related complications. Another primary outcome was tumor response rate based on RECIST guidelines.[11]

Elective TAE was defined as TAE conducted instead of resection, such as in the case of nonbleeding HCA or for reasons other than avoiding intraoperative blood loss. Emergency TAE was defined as TAE conducted to treat active bleeding orto avoid intraoperative bleeding. Avoidance of resection was defined as no post-TAE resection as a result of tumor size reduction or involution and/or the cessation of complaints during the follow-up period. Cases in which tumor size merely remained stable or in which tumors were judged to be unresectable before and after TAE were not counted as avoidance of hepatic resection.

Results of literature review

A total of 22 studies were included in the review [Table 1],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33] which included 1504 patients with HCA, 89.4% of whom were female. A total of 171 of 1504 (11.4%) patients received TAE. Of the 171 patients who received TAE, 116 (67.8%) had bleeding HCA, and 55 (32.2%) had nonbleeding HCA. Intended elective TAE was performed in 54 of 171 (31.6%) patients. Adenomatosis was observed in 9 of 171 (5.3%) patients. Embolization materials used in TAE were described in five of the included studies.[19],[22],[23],[25],[31] These materials included tris-acryl gelatin microspheres, platinum coils, polyvinyl alcohol particles, absorbable gelatin sponge particles, and lipiodol. Baseline histopathology was not described in the included studies, and no malignant transformation was observed in the 209 tumors, during a median follow-up time of 40 months.
Table 1: Characteristics of the included studies

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Among the 171 patients treated by TAE, the resection was avoided in 80 (46.8%), of whom 31 (38.7%) were bleeding before TAE and 49 (61.3%) were not. Of the 64 cases in which resection was avoided, 59 (92%) were because of tumor regression, while the reasons for the remaining 5 (7.8%) are unknown. Of the 75 patients with resection after TAE, resection was based on protocol in 68 (90.1%), persistent tumor in 3 (4%), and intra-abdominal hematoma in 2 (2.7%) [Table 2].

Nine included studies involving 79 of all 171 (46.2%) patients who underwent TAE, reported whether or not tumor size changed after the procedure.[15],[19],[20],[23],[24],[25],[26],[30],[31] Data from 115 tumors were used to examine disease response rates based on the revised RECIST criteria [Table 2]. Response rates were as follows: complete response, 9.6% (11/115); partial response, 74.8% (86/115); progressive disease, 4.3% (5/115); and stable disease, 11.3% (13/115). The rate of overall (complete + partial) response was 84.3%.

Most studies recorded no complications related to TAE. None of the studies reported procedural complications or mortality. Nevertheless, some patients experienced self-limited post-TAE syndrome including pain, fever, nausea/vomiting, and fatigue. In rare cases, this led to a hospital stay > 24 h. Two patients experienced moderate post-TAE syndrome, requiring a hospital stay > 24 h or a return to the emergency room.[15] One patient developed diabetic ketoacidosis after TAE,[15] while another patient experienced sepsis due to a cyst.[12]


  Discussion Top


Although HCA diameter will become significantly smaller with the occurrence of menopause and as time progresses,[34] bleeding and malignant transformation are the primary long-term problems associated with HCA. Bleeding risk is thought to be quite low for tumors < 5 cm. Its risk increases with tumor diameter.[35] In general, hepatic resection is recommended for HCA involving tumors ≥ 5 cm. However, resection is associated with higher risk of postoperative morbidity and longer recovery than other TAE. Therefore, some centers use TAE as an alternative procedure to treat HCA with or without (re) bleeding.
Table 2: Outcomes of the included studies

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In our report, the patient had large HCA and HCA-related hemorrhage. Among 46 months follow-up, rebleeding and malignant transformation were not observed. Our literature review of available evidence also suggests that TAE is a safe and effective alternative to resection for patients with bleeding or nonbleeding HCA and that it can help patients to avoid the need for hepatectomy. Overall tumor response rate was as high as 84.3% after TAE.

HCA is rare in Asia but prevalent in Europe. Almost all included studies were from Europe. Only one study with seven patients was from Asia.[25] Among the included 1504 patients with HCA, 89.4% were female. However, in China, the percentage of male HCA patients reportedly ranges from 38.5% to 62.3%.[36],[37],[38] Our unpublished data also showed that 53.8% patients with HCA were male (n = 65). These differences may reflect HCA subtypes based on distinct molecular alterations or mediating pathways between Europe and Asia.

In recent years, HCA subtypes based on distinct molecular alterations have been identified.[39] These types are H-HCA, β-HCA, I-HCA, and U-HCA.[40] This classification is important and may impact the choice of treatment even more than lesion size. For example, activating mutations of β-catenin may be associated with malignant transformation, while mutations in hepatocyte nuclear factor 1α may be associated with steatotic lesions. Unfortunately, neither our case report nor the literature review could compare post-TAE outcomes for different HCA subtypes, due to inadequate data reporting in the included studies. The expression of β-catenin was reported in five of the included studies.[14],[20],[21],[24],[27] The rate of β-catenin expression was 4.5% (14/308). In addition, a good relationship existed between MR data and genotype-phenotype classification.[36]

Our case report and literature review suggest that TAE is quite safe, rarely leading to major complications. The most common complication among patients was self-limited post-TAE syndrome, which includes pain, fever, nausea/vomiting, and fatigue. Among the included studies, one patient developed diabetic ketoacidosis, while the other experienced sepsis due to a cyst after TAE. No mortality was reported in any of the studies in this review.

Our case report, the patient demonstrated a tumor s[Table 2] months after TAE. Of the included studies for literature review, TAE was associated with tumor reduction in nearly half of the patients, based on revised RECIST criteria,[11] which allow relative objective assessment.[41] These results suggest good ability to reduce tumor size. On the other hand, the proportions of patients showing partial response or progressive disease varied widely across studies, suggesting the need to systematically optimize TAE treatment, such as patient criteria for elective TAE. The follow-up time of our patient and those in the reviewed studies could be too short to assess whether TAE can reduce the risk of malignant transformation. HCA is a slow-growing benign tumor; longer follow-up are needed. Apparent diffusion coefficient value may provide a potential indicator of malignant transformation.[36] However, the routine follow-up of HCA < 5 cm in postmenopausal women may be not needed.[34]

In conclusion, the available evidence suggests that TAE can be considered safe for treating HCA either as an elective procedure or when performed as an acute intervention because of bleeding. Elective TAE can be a reasonable alternative to hepatic resection for HCA since it can reduce the tumor size and alleviate disease symptoms, reducing the need for hepatic resection.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This study was supported in part by the Guangxi University of Science and Technology Research Projects (KY2015LX056), the Self-Raised Scientific Research Fund of the Ministry of Health of Guangxi Province (Z2016512, Z2015621, GZZC15-34, Z2014241), the Graduate Course Construction Project of Guangxi Medical University (YJSA2017014), and the Foundation Ability Enhancement Project for Young Teachers in Guangxi Universities (2018KY0122).

Conflicts of interest

There are no conflicts of interest.



 
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