Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 17  |  Issue : 3  |  Page : 777-783

Factors influencing postembolization syndrome in patients with hepatocellular carcinoma undergoing first transcatheter arterial chemoembolization


Sun Yat-Sen University Cancer Center, Guangdong, China

Date of Submission21-Jan-2021
Date of Acceptance29-Mar-2021
Date of Web Publication9-Jul-2021

Correspondence Address:
Hong-Yan Shao
No. 651 Dongfeng East Road, Yuexiu District, Guangzhou, Guangdong
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.jcrt_132_21

Rights and Permissions
 > Abstract 


Context: Postembolization syndrome (PES) is the most common complication in patients with hepatocellular carcinoma (HCC) who had undergone transcatheter arterial chemoembolization (TACE). PES was defined as fever, nausea and/or vomiting, and abdominal pain and these symptoms develop within 1–3 days after TACE. However, few studies have explored the factors influencing PES in patients with TACE for the first time.
Aims: We explored the factors influencing PES in patients with HCC undergoing TACE for the first time.
Settings and Design: The present study was a hospital-based study conducted in the tertiary care hospital of Guangzhou with a retrospective study design.
Subjects and Methods: In this single-center retrospective study, a total of 242 patients with HCC were included in the first TACE program between November 1, 2018 and November 31, 2019.
Statistical Analysis Used: T-test and Chi-square test revealed the factors affecting the occurrence of PES. Correlation analysis (Spearman) explored the relationship between these factors and PES. Binary logistics analyzed the predictive factors of PES.
Results: The probability of PES in patients with HCC undergoing TACE for the first time was 55.45%. Types of embolic agents (r = 0.296), types of microspheres (r = 0.510), number of microspheres (r = 0.130), maximum diameter of microspheres used (r = 0.429), type of drug (r = 0.406), and drug loading (r = 0.433) were positively correlated with PES (P < 0.05). Serum albumin was negatively correlated with PES (P = 0.008, r = −0.170). Binary logistic regression analysis revealed that drug loading microspheres (odds ratio [OR] = 0.075, 95% confidence interval [CI] = 0.031–0.180) and serum albumin (OR = 0.182, 95% CI = 0.068–0.487) were the protective factors influencing PES, while drug loading was the risk factor of PES (OR = 1.407, 95% CI = 1.144–1.173).
Conclusions: Drug loading microspheres, serum albumin, and drug loading were the predictors of PES after the first TACE.

Keywords: Hepatocellular carcinoma, postembolization syndrome, transcatheter arterial chemoembolization


How to cite this article:
He JJ, Yin XX, Wang T, Chen MY, Li XL, Yang XJ, Shao HY. Factors influencing postembolization syndrome in patients with hepatocellular carcinoma undergoing first transcatheter arterial chemoembolization. J Can Res Ther 2021;17:777-83

How to cite this URL:
He JJ, Yin XX, Wang T, Chen MY, Li XL, Yang XJ, Shao HY. Factors influencing postembolization syndrome in patients with hepatocellular carcinoma undergoing first transcatheter arterial chemoembolization. J Can Res Ther [serial online] 2021 [cited 2021 Jul 26];17:777-83. Available from: https://www.cancerjournal.net/text.asp?2021/17/3/777/321009

Jing-jing He and Xi-xi Yin contributed equally to this work and co-first authors





 > Introduction Top


The incidence and mortality of liver cancer in China is ranked third among all cancers. Hepatocellular carcinoma (HCC) is the most common among liver cancers and it causes a great burden.[1],[2],[3] In recent years, transcatheter arterial chemoembolization (TACE) is often used as the preferred method of nonsurgical treatment, since its efficacy has been affirmed.[3],[4],[5] However, there are many complications accompanying TACE. The most common complication is postembolization syndrome (PES), which is defined as a syndrome that occurs 1–3 days after TACE and is characterized by fever, nausea and/or vomiting, and abdominal pain, etc.[6],[7] Although the duration of PES is self-limiting, extensive research has shown that 80%–90% of patients experience PES after TACE and have a prolonged hospital stay. In addition, PES also brings a bad treatment experience to patients undergoing TACE for the first time.[6],[8],[9]

At present, a few studies have explored the risk factors influencing the development of PES in patients with HCC after TACE.[10],[11],[12] In these studies, the risk factors include tumor size and number and without a super-selective fashion, it also includes dose of doxorubicin and female gender, among others. However, the predictive factors for PES are not consistent after TACE. Therefore, we explored the factors that would affect the occurrence of PES, the relationship between them, and determined which factors are the risks or protective factors for PES in the first TACE inpatients.


 > Subjects and Methods Top


This study is a single-center retrospective study that obtained the consent of the department and the hospital and included patients who signed an informed consent before admission. The study was approved by an ethics committee and all the procedures were followed as per the Declaration of Helsinki. Written informed consent was waived by the institutional review board and no funding support was received for this study.

Study participants

Between November 1, 2018 and November 31, 2019, a total of 242 patients with HCC with first TACE who were admitted to the intervention department of our hospital were selected. Inclusion criteria: (1) Patients >18 years who were diagnosed with HCC by abdominal B-ultrasound, alpha-fetoprotein examination, liver computed tomography, or magnetic resonance imaging; (2) Patients who have lost the opportunity for surgery or recurred after resection during treatment; and (3) Patients with a range of liver cancer lesions that is relatively limited and suitable for postinterventional radiotherapy. Exclusion criteria: (1) Preoperative patients with other tumors or serious complications; (2) Patients with diffuse intrahepatic disease; and (3) Patients with fever caused by infection.

In this study, PES was defined as a syndrome that occurred 1–3 days after TACE and it is characterized by fever, nausea and/or vomiting, and abdominal pain, etc., We used Verbal Rating Scales, which is a common and feasible pain assessment method for patients with cancer,[13] to assess the pain level of patients after TACE. The pain was recorded in 4 levels: Level 3, which is characterized by continuous pain, severe effect on sleep, need to be given opioid control, or more than 2 times of moderate pain; Level 2, which affects sleep and requires nonopioid pain control; Level 1, which is a mild intermittent pain, does not affect sleep, requires nonsteroid pain control; and Level 0, which indicates no pain.

Preprocedural and procedural details

The TACE procedure ascended through the femoral artery to the blood supply artery associated with the liver tumor. The operation was performed by interventional radiologists with rich working experience (more than 5 years). Operator preference, drug availability, and patient's economic conditions were the determining factors for the use of conventional TACE versus drug loading embolic TACE. The uniform used for iodized oil was produced by GUERBET and the specification was 10 ml/piece (with iodine 480 mg/ml). The uniform use of polyvinyl alcohol drug-loaded microspheres and blank microspheres were produced by Suzhou Hengrui Jiali Biomedical Technology Co., Ltd., and the specification was blue, drug loading ratio was 1 g embolization microspheres versus 7 ml physiological sodium chloride solution with diameters of 40–120, 100–300, 300–500, and 500–700 μm.

After the procedure, patients returned to the ward and the ward nurse observed whether the patients had symptoms of discomfort. We deal with different symptoms in PES and record them in the electronic medical record. Finally, all the PES information was recorded in the electronic medical record.

Statistical analysis

IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA) was used for the data analysis. P < 0.05 was considered statistically significant. We compared the distribution of PES and non-PES groups. T-test was used in the measurement data, which was expressed as ± s; Chi-square test was used in the count data, which was expressed as percentages. The influencing factors were the compared (P < 0.05), correlation analysis (Spearman) between the influence factors and PES were done, and binary logistics regression was to the influencing factors, considering the current situation of PES as the dependent variable and the influence factors (P < 0.05) as the independent variable.


 > Results Top


Participant characteristics

A total of 242 patients with HCC, who received TACE for the first time, were selected from the medical record dataset for this study. As shown in [Table 1], the average age of the participants was 54.64 ± 12.77 (range = 23–88) years. Of these patients, 86.78% were male, mean body mass index was 22.20 ± 3.15 (range = 14.42–30.82) kg/m2, 32.64% were conventional TACE, 54.55% were had PES. The most common symptom of PES was abdominal pain (47.93%), with 27.69% of the patients having an abdominal pain of level 2.
Table 1: Characteristics of study patients (n=242)

Click here to view


In [Table 2], we compared the general data and disease treatment data of patients with and without PES after embolization. The influencing factors included the type of embolization agent, type of microspheres, number of microspheres, maximum diameter of microspheres used, type of drug, drug loading, Eastern Cooperative Oncology Group Performance Status (ECOG PS), and serum albumin (P < 0.05).
Table 2: Comparisons of postembolization with and without postembolization syndrome (n=242)

Click here to view


Relationship between the influence factors and postembolization syndrome

As shown in [Table 3], there were six influencing factors (including the type of embolization agent, type of microspheres, number of microspheres, maximum diameter of the microspheres used, type of drug, and drug loading) that were positively correlated (P < 0.05) with the occurrence of PES. The correlation coefficients between these aforementioned factors and PES were 0.296, 0.510, 0.130, 0.429, 0.406, and 0.433, respectively. Serum albumin was negatively correlated with the occurrence of PES (r = −0.170, P = 0.008). Among them, the type of microspheres had the greatest correlation with the occurrence of PES (r = 0.510, P < 0.001).
Table 3: Correlation analysis between the influence factors and postembolization syndrome

Click here to view


Influence factors of postembolization syndrome in the first transcatheter arterial chemoembolization inpatients

[Table 4] shows the value of these influencing factors before their inclusion in the regression model. Results from the binary logistics performed on the development data of the PES are summarized in [Table 5]. The predictors included types of embolic agents (drug loading microsphere), drug loading, and serum albumin. The results indicated that drug loading (odds ratio [OR] = 0.075, 95% confidence interval [CI] = 0.031–0.180) and serum albumin (OR = 0.182, 95% CI = 0.068–0.487) were the protective factors and that drug loading (OR = 1.407, 95% CI = 1.144–1.730) was the risk factor for the development of PES. None of the other variables were associated with PES (all P > 0.05).
Table 4: Included factors assignment in binary logistics

Click here to view
Table 5: Binary logistic regression analysis of predictors of postembolization syndrome in patients with transcatheter arterial chemoembolization for the first time

Click here to view



 > Discussion Top


In recent years, the technology of TACE has become more mature. Our study used the method of super-selective catheter embolization in TACE. Many studies[5],[12],[13],[14],[15] had confirmed that this method can improve patient's response and reduce toxicity. Our study found that the incidence of PES was 55.45%. In other studies,[10],[16],[17] the incidence of PES ranged from 60% to 80%. In comparison, our results are slightly lower and the reason may be that we administered 40 mg of parecoxib sodium to the patients 1 h before and after TACE. Parecoxib sodium, a parenteral COX-2 selective inhibitor, is used for the treatment of pain for a duration of about 12 h.[18] It was recently demonstrated that administration of parecoxib resulted in significantly reduced local inflammatory factors interleukin-2 and prostaglandin E2.[19] In this study, we compared the general information and disease treatment plans of the PES group and non-PES group and found that the factors that were different included type of embolization agent, type of microspheres, number of microspheres, maximum diameter of microspheres used, type of drug, and drug loading (P < 0.05). The results showed that these factors may have a certain impact on the occurrence of PES. The correlation analysis and binary logistics regression results showed that most of these factors were correlated with the occurrence of PES (except ECOG PS). Interestingly, we found that only types of embolic agents (drug loading microspheres), drug loading, and serum albumin were the predictors of PES. The results of this study were not exactly the same with some previous studies. Arslan et al.[11] investigated a total of 316 patients with TACE and found that tumor size and number of tumors treated and adopting a super-selective fashion in the procedure were related to the development of PES. However, Mariana et al.[10] found that dose of doxorubicin, size of the largest nodule treated, and female gender were risk factors for PES (n = 563). Furthermore, Padia et al.[20] compared the safety of 100–300 and 300–500 μm embolic agents and found that the former has a lower probability of PES (n = 61). The reason for the difference may be that other studies are investigated patients with multiple TACEs and that the methods of choosing TACE were also inconsistent. This study is investigated patients with TACE for the first time. In the study by Khalaf et al.,[12] it was found that multiple TACEs would also affect the predictive model for PES occurrence.

We also found that types of embolic agents (drug loading microspheres) and serum albumin are protective factors for PES and that drug loading is a risk factor for PES. This result indicates that patients with drug-eluting bead (DEB)-TACE embolization and high serum albumin are less likely to develop PES than patients with traditional TACE and low serum albumin. DEB-TACE patients with a large drug load may have a higher probability of PES than DEB-TACE patients with a small drug load. This is an interesting discovery, as previous studies have shown that[21],[22],[23] DEB-TACE and C-TACE have similar effects and that the safety of DEB-TACE is higher. Our research has indirectly validated this finding, and serum albumin, as one of the Child–Pugh rating indicators, can be used as one of the indicators to predict the outcome of patients with HCC after TACE.[24] In our findings, serum albumin can also be used as one of the indicators to predict the occurrence of PES. In addition, the greater the drug loading of the drug-eluting microspheres, the stronger the toxicity and side effects of the drug,[25] which makes it easier to understand that drug loading is a risk factor for PES.

Overall, this study explores the influencing factors of PES in patients undergoing TACE for the first time. This is different from other studies.[10],[11],[12] Often, the experience after the first TACE will affect the patient's treatment experience and poor experience will affect the patient's confidence in the treatment in terms of quality of life. Once severe PES occurs, the patient's hospital stay will be prolonged and the patient's economic burden will consequently increase.[26] In addition, Mason et al.[27] found that the occurrence of PES may increase the mortality of patients. Therefore, medical staffs can use the results of this analysis regarding influencing factors of PES to intervene in advance in order to know which factors are more likely to cause the occurrence of PES. Taking measures in advance aids the achievement of the goal of improving the quality of life of patients and improving the treatment experience.

Limitation

Several limitations should be acknowledged in our study. Our study is a retrospective study, which collected the symptoms that occurred during the patient's hospitalization, but failed to collect the symptoms that occurred after the patient was discharged. In addition, we did not establish a predictive model, which is a relatively regrettable thing, due to sample size problem. In future studies, attention should be paid to the symptoms of patients within 2 weeks after surgery (as Yinglu et al.[28] found that the appearance of PES lasts for 1–2 weeks) and the amount of collected samples should be increased to establish a predictive model for PES after the first TACE.


 > Conclusions Top


The probability of PES in patients with HCC undergoing TACE for the first time is 55.45%, even though analgesia has been done before and after TACE. Drug loading microspheres, serum albumin, and drug loading were the predictors of PES after the first TACE. Drug loading microspheres and serum albumin were the protective factors of PES, while drug loading was the risk factor of PES.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
WHO. Globocan 2018 World Fact Sheet: China [EB/OL]. Available from: https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf. [Last accessed on 2020 Nov 20].  Back to cited text no. 1
    
2.
El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012;142:1264-73.e1.  Back to cited text no. 2
    
3.
Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: A 2017 update. Hepatol Int 2017;11:317-70.  Back to cited text no. 3
    
4.
Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: A randomised controlled trial. Lancet 2002;359:1734-9.  Back to cited text no. 4
    
5.
Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: An update. Hepatology (Baltimore, Md) 2011;53:1020-2.  Back to cited text no. 5
    
6.
Blackburn H, West S. Management of postembolization syndrome following hepatic transarterial chemoembolization for primary or metastatic liver cancer. Cancer Nurs 2016;39:E1-8.  Back to cited text no. 6
    
7.
Vogl TJ, Naguib NN, Nour-Eldin NE, Rao P, Emami AH, Zangos S, et al. Review on transarterial chemoembolization in hepatocellular carcinoma: Palliative, combined, neoadjuvant, bridging, and symptomatic indications. Eur J Radiol 2009;72:505-16.  Back to cited text no. 7
    
8.
Fiorentini G, Aliberti C, Tilli M, Mulazzani L, Graziano F, Giordani P, et al. Intra-arterial infusion of irinotecan-loaded drug-eluting beads (DEBIRI) versus intravenous therapy (FOLFIRI) for hepatic metastases from colorectal cancer: Final results of a phase III study. Anticancer Res 2012;32:1387-95.  Back to cited text no. 8
    
9.
Leung DA, Goin JE, Sickles C, Raskay BJ, Soulen MC. Determinants of postembolization syndrome after hepatic chemoembolization. J Vasc Interv Radiol 2001;12:321-6.  Back to cited text no. 9
    
10.
Lima M, Dutra S, Gomes FV, Bilhim T, Coimbra É. Risk factors for the development of postembolization syndrome after transarterial chemoembolization for hepatocellular carcinoma treatment. Acta Med Port 2018;31:22-9.  Back to cited text no. 10
    
11.
Arslan M, Degirmencioglu S. Risk factors for postembolization syndrome after transcatheter arterial chemoembolization. Curr Med Imaging Rev 2019;15:380-5.  Back to cited text no. 11
    
12.
Khalaf MH, Sundaram V, AbdelRazek Mohammed MA, Shah R, Khosla A, Jackson K, et al. A predictive model for postembolization syndrome after transarterial hepatic chemoembolization of hepatocellular carcinoma. Radiology 2019;290:254-61.  Back to cited text no. 12
    
13.
Hjermstad MJ, Fayers PM, Haugen DF, Caraceni A, Hanks GW, Loge JH, et al. Studies comparing numerical rating scales, verbal rating scales, and visual analogue scales for assessment of pain intensity in adults: A systematic literature review. J Pain Symptom Manage 2011;41:1073-93.  Back to cited text no. 13
    
14.
Miyayama S, Matsui O. Superselective conventional transarterial chemoembolization for hepatocellular carcinoma: Rationale, technique, and outcome. J Vasc Interv Radiol 2016;27:1269-78.  Back to cited text no. 14
    
15.
Duan F, Wang EQ, Lam MG, Abdelmaksoud MH, Louie JD, Hwang GL, et al. Superselective chemoembolization of HCC: Comparison of short-term safety and efficacy between drug-eluting LC beads, quadraspheres, and conventional ethiodized oil emulsion. Radiology 2016;278:612-21.  Back to cited text no. 15
    
16.
Jun CH, Ki HS, Lee HK, Park KJ, Park SY, Cho SB, et al. Clinical significance and risk factors of postembolization syndrome fever in patients with hepatocellular carcinoma. World J Gastroenterol 2013;19:284-9.  Back to cited text no. 16
    
17.
Kogut M, Chewning RH, Harris WP, Hippe DS, Padia SA. Postembolization syndrome after hepatic transarterial chemoembolization: Effect of prophylatic steroids on postprocedure medication rRequirements. J Vasc Interv Radiol 2013;24:326-31.  Back to cited text no. 17
    
18.
Lv N, Kong Y, Mu L, Pan T, Xie Q, Zhao M. Effect of perioperative parecoxib sodium on postoperative pain control for transcatheter arterial chemoembolization for inoperable hepatocellular carcinoma: A prospective randomized trial. Eur Radiol 2016;26:3492-9.  Back to cited text no. 18
    
19.
Zhu Y, Wang S, Wu H, Wu Y. Effect of perioperative parecoxib on postoperative pain and local inflammation factors PGE2 and IL-6 for total knee arthroplasty: A randomized, double-blind, placebo-controlled study. Eur J Orthop Surg Traumatol 2014;24:395-401.  Back to cited text no. 19
    
20.
Padia SA, Shivaram G, Bastawrous S, Bhargava P, Vo NJ, Vaidya S, et al. Safety and efficacy of drug-eluting bead chemoembolization for hepatocellular carcinoma: Comparison of small-versus medium-size particles. J Vasc Interv Radiol 2013;24:301-6.  Back to cited text no. 20
    
21.
Khalaf M, Abdelrazek M, Wang D, Shah R, Kothary N. 4:12 PM Abstract No. 330 Analgesic and antiemetic requirement for post-embolization syndrome after cTACE versus DEB-TACE. J Vasc Interv Radiol 2018;29 Suppl 4:S142.  Back to cited text no. 21
    
22.
Li H, Wu F, Duan M, Zhang G. Drug-eluting bead transarterial chemoembolization (TACE) vs conventional TACE in treating hepatocellular carcinoma patients with multiple conventional TACE treatments history: A comparison of efficacy and safety. Medicine (Baltimore) 2019;98:e15314.  Back to cited text no. 22
    
23.
Hong K, Khwaja A, Liapi E, Torbenson MS, Georgiades CS, Geschwind JF. New intra-arterial drug delivery system for the treatment of liver cancer: Preclinical assessment in a rabbit model of liver cancer. Clin Cancer Res 2006;12:2563-7.  Back to cited text no. 23
    
24.
Park Y, Kim BK, Park JY, Kim DY, Ahn SH, Han KH, et al. Feasibility of dynamic risk assessment for patients with repeated trans-arterial chemoembolization for hepatocellular carcinoma. BMC Cancer 2019;19:363.  Back to cited text no. 24
    
25.
Pomoni M, Malagari K, Moschouris H, Spyridopoulos TN, Dourakis S, Kornezos J, et al. Post embolization syndrome in doxorubicin eluting chemoembolization with DC bead. Hepatogastroenterology 2012;59:820-5.  Back to cited text no. 25
    
26.
Zang S, Xu Y, Liang SN. Multiple linear regression analysis of factors related to the hospitalization days in HCC patients after transcatheter hepatic arterial chemoembolization. J Interv Radiol (China) 2015;24:80-3.  Back to cited text no. 26
    
27.
Mason MC, Massarweh NN, Salami A, Sultenfuss MA, Anaya DA. Post-embolization syndrome as an early predictor of overall survival after transarterial chemoembolization for hepatocellular carcinoma. HPB (Oxford) 2015;17:1137-44.  Back to cited text no. 27
    
28.
Yinglu F, Changquan L, Xiaofeng Z, Bai L, Dezeng Z, Zhe C. A new way: Alleviating postembolization syndrome following transcatheter arterial chemoembolization. J Altern Complement Med 2009;15:175-81.  Back to cited text no. 28
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Subjects and Methods>Results>Discussion>Conclusions>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed64    
    Printed0    
    Emailed0    
    PDF Downloaded7    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]