Summary of the evidence of best practices for the prevention and treatment of embolism syndrome after TACE in primary liver cancer

Objective This study aims to retrieve, evaluate, and summarize domestic and foreign evidence on the prevention and treatment of embolism syndrome following transcatheter arterial chemoembolization (TACE) for primary liver cancer and to provide an evidence-based foundation for clinical practice. Methods Utilizing the “6S” model, we conducted a systematic search of UpToDate, BMJ Best Practice, domestic and foreign guidelines, and related databases on the prevention and treatment of embolism syndrome following TACE for primary liver cancer. This search included clinical decision-making, guidelines, systematic reviews, evidence summaries, randomized controlled trials, and expert consensus. The search time frame extended from January 1, 2013 to May 1, 2023. Evidence was synthesized after an independent review of the included studies by two investigators. Results A total of 11 articles were included in the analysis, comprising one clinical decision-making article, three clinical guidelines, six expert consensus articles, and one randomized controlled trial. We summarized 31 pieces of evidence across three categories: preoperative preparation, intraoperative interventions, and postoperative symptom management. Conclusion This study presents a comprehensive summary of the best available evidence on the prevention and treatment of embolism syndrome following TACE for primary liver cancer. These findings can serve as a valuable reference for clinical practitioners, enabling nurses to deliver individualized care based on the symptoms and specific needs of liver cancer patients. Systematic review registration http://ebn.nursing.fudan.edu.cn, identifier ES20232398.


Introduction
Primary liver cancer (PLC) is a malignant condition that predominantly includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and combined hepatocellular-cholangiocarcinoma (cHCC-CCA) (1).These cancers are characterized by their insidious onset, rapid progression, and poor prognosis (2).According to the 2020 global cancer statistics report, there were approximately 906,000 new cases of liver cancer, resulting in 830,000 deaths.This malignancy has become the fourth most prevalent malignant tumor worldwide and the second leading cause of cancerrelated deaths in China (3,4).It seriously affects the health of Chinese residents, and the burden of prevention and treatment of liver cancer diseases is increasing.
Primary liver cancer often presents without typical or earlystage symptoms, resulting in missed opportunities for surgical intervention.Surgical resection is feasible for only 10% to 30% of cases, and postoperative recurrence rates are notably high.Despite significant advancements in liver surgery, the majority of newly diagnosed HCC cases are not amenable to surgical resection (5,6).
With the advancement of interventional medicine, transcatheter arterial chemoembolization (TACE) has emerged as the primary non-surgical palliative treatment for liver cancer patients.TACE involves the injection of embolization agents into tumor blood vessels through the hepatic artery, leading to the blockage of the tumor's blood supply and inducing ischemic necrosis.This approach serves as a preventive and consolidative measure against recurrence in patients with PLC and has been shown to significantly improve overall patient survival rates (7)(8)(9).
While TACE is generally considered a safe procedure, it can lead to various postoperative complications that require caution and consideration.The most common complication is postembolization syndrome (PES), characterized by symptoms such as fever, liver pain, nausea, and vomiting (10).The reported incidence of PES varies widely, ranging from 15% to 90%, which can be attributed to bias arising from differing definitions of embolic syndrome and inadequate follow-up (11).Although PES is typically self-limiting, it significantly affects patient comfort, prolongs hospital stays, and may impact compliance to subsequent treatments (12).
Numerous studies focus on preventing and treating embolism syndrome following TACE, predominantly relying on original research, literature reviews, and meta-analyses.Nonetheless, their conclusions often lack the requisite evidence-based foundation for clinical translation.To address this gap, our study systematically searched both domestic and foreign evidence pertaining to the prevention and treatment of embolism syndrome after TACE and subsequently extracted and summarized this evidence.This study has been registered with the Evidence-Based Nursing Center of Fudan University (ES20232398).

Determining the problem and inclusion criteria
Herein the Population, Intervention, Professional, Outcome, Setting, Type of evidence (PIPOST) model was used to determine the basic research questions (13).The inclusion criteria for evidence were as follows: (1) P (population): The evidence's target population is patients with primary liver cancer after TACE, (2) I (intervention): The measures are aimed at preventing post-TACE syndrome, (3) P (professional): The evidence is applicable to medical staff, patients undergoing TACE, and their family members, ( 4) O (outcome): The outcome is the incidence of embolism syndrome after TACE, (5) S (setting): The evidence is applicable in medical institutions at all levels, and ( 6) T (type of evidence): The type of evidence resource include clinical decision-making, best practice, clinical guidelines, systematic reviews, evidence summaries, expert consensus, and relevant original research.
The English search strategy using PubMed as an example was as follows: 1

Literature quality evaluation
For guideline evaluation, we employed the British "Clinical Guidelines Research and Evaluation System" (AGREE II) (15) for quality evaluation, including 23 items in six areas: scope and purpose, participants, rigor of formulation, clarity, applicability, and editorial independence.Each item was rated on a scale of 1 to 7, with 7 indicating full compliance and 1 indicating non-compliance.For expert consensus evaluation, we followed the JBI Evidence-Based Health Care Center Expert Consensus (2017) evaluation standard (16) for quality assessment.Randomized controlled trials (RCTs) were evaluated using the JBI Evidence-Based Health Care Center's RCT paper quality evaluation tool (17).

Summary, classification, and recommendation level of evidence
The quality of evidence and the level of recommendation were assessed independently by two researchers.In cases of conflicting assessments, a third researcher participated in discussions to reach a consensus.When discrepancies arose among evidence from different sources, we applied principles prioritizing evidencebased, high-quality, and recently published evidence.
The clinical practice guidelines and clinical decisions included were graded using their original grading system, while evidence lacking a grading system was graded using the JBI Evidence Pregrading System (2014 version) to grade the original study on a scale of 1-5, with level 1 being the highest and level 5 being the lowest.
The recommendation level of evidence adopts the JBI Evidence Pre-grading and Evidence Recommendation Level System (2014 version) and refers to the grading system provided by the evidence itself.

Literature search results
We initially retrieved a total of 1,057 documents through a systematic search.After removing duplicates using NoteExpress and applying our inclusion criteria, we obtained the full-text copies of potentially relevant documents.Each full-text copy was carefully reviewed to confirm whether it met the inclusion criteria.Eventually, we included a total of 11 documents, comprising one clinical decision (18), three guidelines (7,19,20), six expert consensus (21-26), and one randomized controlled trial (27).The details of the included literature are summarized in Table 1.

Quality evaluation results of the guideline
In this study, we included three guidelines (7,19,20), and the quality evaluation results are detailed in Table 2.

Quality evaluation results of the expert consensus
Six expert consensus articles were included in this study (21)(22)(23)(24)(25)(26), and the quality evaluation results are shown in Table 3.

Quality evaluation results of clinical decision-making
O n e c l i n i c a l d e c i s i o n ( 1 8) f r o m U p T o D a t e w a s directly included.

Quality evaluation results of randomized controlled trials
A randomized controlled trial (27) from the Cochrane Library was included, and its quality was evaluated using evaluation tools.The evaluation result of item 6, "Whether the results evaluator was blinded," was "unclear", and the evaluation result of the other item was "Yes".The overall quality was high.

Evidence description and summary
According to the principle of evidence synthesis, the researchers summarized the evidence.A total of 31 pieces of evidence were summarized, divided into 3 evidence topics, as shown in Table 4 (preoperative preparation, intraoperative interventions, and postoperative symptom management).A flow chart of evidence transformation for the prevention and treatment of embolism syndrome after TACE is shown in Figure 1.

Clinical significance of the prevention and treatment of embolism syndrome after TACE based on evidence summary
TACE is an established treatment option for patients with unresectable liver disease, prolonging survival and improving the quality of life (28).Embolism syndrome, or at least some characteristic symptoms, is almost unavoidable following TACE (11).The predictive model constructed by Meredith C. Mason indicated that the bilobal and single-lobe distribution of tumors and the use of DEB-TACE were independent predictors of PES (11).The study of Mohamed H. Khalaf also pointed out that PES history, tumor burden, and DEB-TACE were important predictors of prolonged recovery (29).According to the study of Natascha Roehlen, preoperative tumor size, degree of cirrhosis, and DEB-TACE are predictors of PES (30).Embolism syndrome not only greatly impacts patient comfort post-treatment but also frequently leads to protracted hospital stays and treatment progression.Moreover, it emerges as a complicating factor in the diagnostic and therapeutic processes for healthcare practitioners, potentially giving rise to diagnostic complexities in cases characterized by fever and pain, thereby necessitating supplementary diagnostic tests (31).
Effective management of embolic syndrome is important from a clinical practice point of view, but there are currently no established guidelines.Although UpToDate and several countries have published guidelines for the diagnosis and treatment of liver cancer or clinical decision-making information, the evidence is long and the evidence for the prevention and treatment of embolic syndrome after TACE is relatively scattered.Therefore, following a rigorous process of quality assessment and evidence grading, this study aims to consolidate the most robust evidence pertaining to the prevention and treatment of embolism syndrome in patients undergoing TACE.This summary of evidence fully focuses on the evidence related to the prevention and treatment of embolic syndrome after TACE surgery, which will help nursing practitioners to acquire and understand the evidence efficiently, establish standardized prevention and management procedures for embolic syndrome after TACE, improve nursing practitioners' sensitivity to PES, reduce the incidence of PES, and reduce patient hospitalization time and cost.

Forming a multidisciplinary team and an Internet platform to strengthen the health education and follow-up system
Embolism syndrome after TACE is an unavoidable clinical problem marked by its multifaceted symptoms.Formulating and implementing effective and precise prevention and treatment strategies necessitate the collaborative efforts of a multidisciplinary team.This team typically comprises oncologists, nurses specializing in oncology care, gastroenterologists, pain management specialists and nurses, psychological counselors, nutritionists, and other healthcare professionals.Within this framework, physicians shoulder the responsibilities of symptom assessment and the development of tailored management plans, while nurses oversee patients, ensuring regular monitoring and recording of patient data.Nutritionists and psychological counselors, on the other hand, are entrusted with personalized management strategies tailored to the unique needs of individual patients.Patients with liver cancer have recurrent symptoms, and continuous management outside the hospital is an important part of systemic treatment.Establishing an Internet-based management platform for follow-up care is invaluable for healthcare managers.This platform streamlines the identification of symptoms and the monitoring of critical health indicators, enabling timely treatment recommendations.Beyond its utility in  facilitating multidisciplinary team collaboration, the Internet management platform also extends practical guidance to liver cancer patients as they navigate the complexities of systemic treatment outside the hospital setting to maximize the benefits of treatment for these patients (22).

the evaluation of each node is an important measure to prevent and treat embolism syndrome
Effective symptom management in surgical care relies on timely and methodical symptom assessment.to surgery, there is a need to promote robust public education by introducing patients to the surgery's purpose, process, and benefits.This builds patient confidence provides essential psychological support (32).During surgery, treatment plans address adverse reactions are implemented, improving patient tolerance and Continuously monitoring patient complaints, maintaining open communication, and promptly identifying and addressing issues also enhance surgical safety.The patients are monitored post-surgery for adverse reactions and discomfort, offering empathetic responses to their concerns.To boost patient tolerance and treatment compliance before discharge, thorough assessments are conducted, psychological support is provided, and follow-up plans are developed.

Limitations of this study
This study has certain limitations.Notably, some systematic reviews and meta-analyses were excluded during our systematic search as they focused on survival time or tumor response as

Summary
This study summarized 31 pieces of evidence for preventing and treating embolism syndrome in patients after TACE, serving as a valuable resource for clinical medical practitioners.The results presented here are derived from existing research conclusions.Nevertheless, individual patient cases may vary, necessitating tailored treatment plans based on specific patient conditions.When incorporating this evidence into clinical practice, healthcare professionals should exercise their expertise and consider the unique clinical circumstances, using the best available evidence as a foundation for informed decision-making in clinical nursing practice.Flow chart of evidence transformation for prevention and treatment of embolic syndrome after transcatheter arterial chemoembolization.
outcome measures.Additionally, several studies comparing various TACE techniques (cTACE or DEB-TACE), combinations of TACE with other treatments, and different drug predictions were omitted due to incomplete study designs or low-quality assessments.At the same time, the literatures included this study were mainly from Asia.The included people had different concepts and attitudes toward PES, and there were regional and cultural differences by different medical service systems and medical environments.Therefore, future research should aim to incorporate high-quality original studies to gain deeper insights into the effects of various TACE techniques and drug dosages on embolism syndrome.

TABLE 1
Basic characteristics of the included literature (n = 11).
ASCO, American Society of Clinical Oncology.

TABLE 2
Quality evaluation results of the guidelines (n = 3).
A, reliable evidence of effectiveness with clear clinical benefits, strongly recommended.B, may produce reliable or moderate evidence of effectiveness with limited clinical benefit, General recommendation.

TABLE 3
Quality evaluation results of expert consensus (n = 6).①Are the sources of the ideas clearly marked?(YES/NO) ②Does the opinion come from an influential expert in the field?(YES/NO) ③Whether the point of view presented is centered on the relevant population interests of the study?(YES/NO) ④Are the stated conclusions based on the analysis?Are ideas expressed logically?(YES/NO)⑤Was there any reference to other literature?(YES/NO) ⑥Are there any inconsistencies between the ideas presented and the previous literature?(YES/NO).Letter Y, indicates whether criteria ①-⑥ are met and decides whether to include evidence.

TABLE 4
(22,25) of the best evidence for the prevention and treatment of embolism post-TACE syndrome for primary liver cancer.Administer preventive antiemetic medication before each antitumor treatment (intravenous injections 30 min before the first dose, oral preparations 60 min before the first dose, and granisetron transdermal patches applied 24-48 h before the first dose) to cover the entire risk period(20,25)Predict or assess the possibility of nausea and vomiting based on the patient's previous experiences.Adjust the antiemetic regimen for the next cycle of antineoplastic treatment based on the efficacy observed in previous cycles(22,25)

TABLE 4 Continued
(24)9,23,24,26)ogical counseling to patients and use various methods like empathy, music, relaxation, and distraction to help manage pain.Consider threestep analgesic therapy for cancer pain if the pain persists(7,19,23,24,26)If vomiting occurs, place the patient on his or her side, turn the head to one side to facilitate vomit removal, and avoid aspiration.Provide oral hygiene care(22)Follow dietary principles such as small and frequent meals, choosing easily digestible foods, avoiding spicy or irritating foods, and not consuming excessively hot or cold foods.Consider using acidic fruits to relieve nausea(22)If vomiting is frequent, fast for 4 to 8 h, then gradually introduce a liquid diet.Transition to a refined protein, high-vitamin, high-carbohydrate, and low-fat diet as appropriate after 2 days.Enhance the appeal of food through color, aroma, and taste and encourage small, frequent meals.Consider adding ginger to the diet for nausea relief.Enteral or parenteral nutritional support may be needed for patients with severe dietary disturbances(24), reliable evidence of effectiveness with clear clinical benefits, strongly recommended.B, may produce reliable or moderate evidence of effectiveness with limited clinical benefit, General recommendation. A