Arterial and biliary complications after transarterial chemoembolization for hepatocellular carcinoma

Table 1 Literature review on arterial and biliary complications following transarterial chemoembolization for hepatocellular carcinoma

Ref.	Research type	Results	Conclusion
Arterial complications
Borrego Rivas et al[37], 2024	Case reports	A 73-year-old male patient presented with right hypochondriac pain and reticular erythematous lesions following the second TACE. Abdominal CT revealed changes caused by embolization and subcutaneous tissue swelling, without other relevant complications. The final diagnosis was livedo purpura, which resulted from microsphere migration of doxorubicin or unrecognized collateral vessels leading to microcirculatory occlusion and necrosis of the skin and subcutaneous tissue	This study reports in detail a case of livedo purpura, a significant arterial complication. It proposes that to reduce the incidence of such complications, the optimal strategy is to ensure the tip of the embolization catheter is positioned as close as possible to the tumor-feeding vessels. Additionally, preventive and therapeutic measures are discussed, such as local ice application prior to TACE to induce vasoconstriction, or local steroid injection after the appearance of skin rashes. However, it is also noted that local use of corticosteroids may lead to the exacerbation of lesions
Hieu et al[48], 2023	Case reports	A 76-year-old male patient with hepatocellular carcinoma developed sudden onset of motor weakness in both lower limbs and sensory impairment below the T10 dermatome following the second TACE. Spinal magnetic resonance imaging revealed intramedullary signal enhancement in the T1-T12 segments. The patient received supportive care, continuous rehabilitation, and high-dose steroid pulse therapy. Nearly complete recovery of sensory function was achieved, while motor function remained unchanged	This study reports in detail a case of spinal cord ischemia, a critical arterial complication. The proposed pathogenesis is that the embolic agent accidentally entered the spinal artery through the connection between the right inferior phrenic artery collaterals and the intercostal arteries, leading to spinal cord infarction. It is emphasized that to prevent these severe consequences, formulating individualized treatment strategies is crucial, including careful consideration of shunts and selection of vessels for lipiodol injection prior to TACE
Giampreti et al[40], 2022	Case reports	A 56-year-old male patient developed right-sided pain and a rapidly progressive livedo reticularis-like cutaneous reaction following epirubicin chemoembolization. CT imaging showed significant extrahepatic dissemination of epirubicin, which led to signs of systemic organ involvement in the patient. After receiving dexrazoxane therapy, both the cutaneous lesions and organ involvement in this critically ill patient were significantly improved, and laboratory parameters returned to normal	This study reports in detail a case of systemic dissemination of chemotherapeutic agents, a critical arterial complication. Systemic dissemination of chemotherapeutic agents during TACE may lead to severe consequences. For extensive cutaneous toxic reactions and severe systemic effects caused by the dissemination of anthracyclines during TACE, dexrazoxane infusion may serve as an effective therapeutic approach
Golfieri et al[15], 2021	Retrospective study	Propensity score matching was used to analyze 182 patients, aiming to compare the tumor response rates between B-TACE and TACE in patients with HCC	The study reported that the incidence of hepatic abscess in the B-TACE group was 2.2% (2/91), while the incidence of hepatic arterial pseudoaneurysm was 1.1% (1/91) in both the B-TACE group and the non-B-TACE group
Ruan et al[2], 2020	Retrospective study	A total of 2200 TACE procedures were performed in 816 patients with HCC, among whom 6 patients developed ARDS after TACE. The diameter of the lesions in these patients ranged from 5.0 cm to 10.2 cm, and 4 of them had lesions predominantly located in the left lateral segment of the liver. All patients underwent chemoembolization with a suspension of nedaplatin, epirubicin, and lipiodol. Symptoms of ARDS occurred in all patients within 24-48 hours postoperatively. Chest radiographs showed diffuse exudative changes in both lungs	The incidence of ARDS was provided in this study. It is proposed that the development of ARDS may be associated with the decomposition of lipiodol particles into toxic free fatty acids after their entry into lung tissue. Early administration of corticosteroids may be beneficial for improving prognosis and reducing mortality
Kim et al[41], 2020	Case reports	A 42-year-old male patient with HCC developed iohexol-induced pneumonia following TACE treatment. On the second post-TACE day, the patient presented with acute respiratory symptoms, including dyspnea and cough, accompanied by decreased oxygen saturation. Chest radiography and CT scans revealed multiple patchy infiltrates. The patient showed gradual improvement with supportive care and oxygen therapy, but failed to achieve complete recovery	This study reports in detail a case of iohexol-induced pneumonia, a critical arterial complication. It provides the imaging features, therapeutic approaches, and treatment efficacy of this complication. It is proposed that the presence of arteriovenous shunts within HCC may lead to the accidental entry of iohexol into the pulmonary vasculature
Fang et al[75], 2019	Retrospective study	Fourteen cases of TACE-related ALI were included. The patients had a mean age of 60.9 years, with a mean onset time of 2.4 days after TACE. Among them, 8 patients (57.1%) progressed to ARDS. Seven patients (50%) had underlying chronic respiratory diseases, and 6 patients (42.6%) were detected with hepatic arteriovenous fistulas; both indicators were significantly higher than those in the control group (P < 0.05). The most common symptom was dyspnea (92.9%). Common imaging abnormalities included pleural effusion (64.3%), diffuse pulmonary infiltration (42.9%), and lipiodol deposition in the lungs (42.9%). Eleven patients (78.6%) achieved remission after treatment, with a 30-day mortality rate of 21.4%	This study provides important information regarding patients with ALI, including clinical manifestations and their frequencies, imaging findings and their frequencies, as well as mortality rate. It is proposed that chronic respiratory diseases and hepatic arteriovenous fistulas may be important risk factors, and pulmonary lipiodol embolism may be the main cause of TACE-related ALI. For high-risk patients with HCC, close evaluation and monitoring should be performed during TACE to avoid this potentially fatal complication
Yamaguchi et al[39], 2018	Case reports	A patient with HCC developed fatal acute necrotizing pancreatitis and upper gastrointestinal ulcer as complications following TACE	This study reports in detail a case of acute necrotizing pancreatitis, a critical arterial complication. It is proposed that this complication is directly associated with embolic agent reflux and non-targeted embolization
Elsayed et al[42], 2018	Case reports	A 73-year-old patient with HCC underwent DEB-TACE using doxorubicin-loaded microspheres. Three days after the procedure, subcutaneous, erythematous, and tender nodules appeared in the abdomen. Positron emission tomography/CT scans showed mild avidity of these nodules, and biopsy confirmed fat necrosis. The nodules began to improve spontaneously two weeks after onset and stabilized at eight weeks	This study reports in detail a case of subcutaneous fat necrosis, a critical arterial complication. DEB-TACE may lead to the development of subcutaneous erythematous and tender nodules, which are manifestations of subcutaneous fat necrosis
Zhou et al[78], 2017	Retrospective study	Medical records of 1461 patients with HCC were reviewed. The main perioperative complications included hepatic decompensation (n = 66), puncture site bleeding (n = 45), infection (n = 33), severe thrombocytopenia (n = 8), upper gastrointestinal bleeding (n = 6), tumor bleeding (n = 4), and agranulocytosis (n = 3). A χ2 test showed that postoperative infection was not associated with preoperative white blood cell count, and puncture site bleeding was also not associated with thrombocytopenia caused by hypersplenism	It details the incidence rates of artery-related complications, such as puncture site bleeding (2.22%) and upper gastrointestinal bleeding (0.3%). The article indicates that puncture site bleeding is not associated with preoperative platelet count, but is mainly related to improper local compression
Nagpal et al[38], 2016	Case reports	A 54-year-old male patient developed periumbilical maculopapules after an uneventful TACE procedure. Retrospective imaging review revealed that this condition was consistent with non-targeted embolization of the hepatic falciform artery. The patient showed improvement after 3 weeks of treatment with oral nonsteroidal anti-inflammatory drugs	This study reports in detail a case of non-targeted embolization of the hepatic falciform artery, a critical arterial complication
Nakajima et al[36], 2016	Case reports	A 69-year-old male was admitted to the hospital due to abdominal pain. One month prior to admission, he had undergone the 8th transcatheter arterial intervention. Abdominal radiography and contrast-enhanced CT revealed a large amount of pneumatosis intestinalis in the small intestine, as well as venous thrombosis extending from the portal vein to the superior mesenteric vein. The thrombosis was reduced after anticoagulant therapy	This study reports in detail a case of paralytic ileus, a critical arterial complication. Abdominal imaging examinations confirmed that this complication was caused by thrombosis of the portal vein and superior mesenteric vein. For patients with HCC complicated with arteriovenous shunts, repeated transarterial injection therapy may be a risk factor for ileus. During transarterial injection, the accidental flow of lipiodol into the portal vein may induce thrombosis. Anticoagulant therapy administered to this patient achieved a favorable outcome
Biliary complications
Lu et al[59], 2024	Retrospective study	The incidence of biliary tract injury after TACE was 6.5% (55/847). Compared with patients without biliary tract injury, those in the biliary tract injury group showed statistically significant differences in preoperative ALP levels, history of hepatobiliary surgery, intraoperative lipiodol dosage, use of gelatin sponge particles, hypovascular tumors, and embolization sites. Additionally, the postoperative levels of total bilirubin, gamma-glutamyl transferase, and ALP in the biliary tract injury group were significantly higher than those in the group without biliary tract injury	It provides a clear incidence rate of biliary tract injury (6.5%). It is proposed that the risk factors for biliary tract injury after TACE include lipiodol dosage, gelatin sponge supplementation, embolization sites, and hypovascular tumors
Fang et al[67], 2023	Case reports	A 68-year-old male patient developed a bronchobiliary fistula following TACE for HCC. Two months after the initial TACE, the patient presented with a hepatic abscess and underwent drainage. Six months later, he developed cough with yellow sputum production, and magnetic resonance imaging confirmed hepatopulmonary abscesses complicated by a bronchobiliary fistula. Despite treatment with endoscopic retrograde cholangiopancreatography, drainage, and antibiotics, the patient’s condition deteriorated, and he eventually died of sepsis and multiple organ failure	This study reports in detail a case of bronchobiliary fistula, a critical biliary complication. It also indicates that bronchobiliary fistula should be immediately considered when a patient presents with biliary sputum expectoration. Bile accumulation in the liver and lungs may lead to tissue necrosis and chronic infection, necessitating early diagnosis and aggressive treatment
Xu et al[62], 2021	Retrospective study	A total of 693 TACE procedures were performed in 483 patients, from which 21 patients (4.3%) with biliary tract injury were identified. The results showed that patients who had undergone prior hepatectomy or received proximal arterial chemoembolization had a higher risk of postoperative biliary tract injury. The article also indicated that on non-contrast CT one week after the procedure, 14.3% (3/21) of the patients showed hyperdense shadows around the bile duct wall, while 76.2% (16/21) had an ALP level > 200 U/L. On CT, biliary tract injury manifested as intrahepatic bile duct dilatation (57.1%), biloma (25.7%), and hilar bile duct stenosis (17.1%), among other findings	It provides a clear incidence rate of biliary tract injury (4.3%) and explicitly mentions several types of biliary tract injury. It is proposed that biliary tract injury is not caused by a single factor, but rather the result of the combined effect of multiple factors, which is closely associated with the damage to biliary microvessels and subsequent chronic biliary infection, as well as the occurrence probability observed in imaging examinations. The main risk factors for biliary tract injury are identified, including a history of prior hepatectomy and proximal arterial embolization. Lipiodol deposition in the bile duct wall on postoperative CT and a significant increase in ALP levels are indicators for predicting biliary tract injury
Zhang et al[64], 2017	Retrospective study	This study retrospectively analyzed 1923 patients with HCC who underwent a total of 4695 TACE procedures. The results showed that the incidence of intrahepatic biloma was 1.04%. The 20 patients who developed biloma underwent an average of 2.75 TACE procedures. Among these patients, 11 cases were cystic or multiple cystic bilomas, 6 cases were branching bilomas, and 3 cases presented with both cystic and branching features	It clearly identifies the incidence of intrahepatic biloma as 1.04% and explicitly mentions several types of bilomas. It describes in detail the imaging features of bilomas on CT and magnetic resonance imaging. It is proposed that although intrahepatic biloma is rare, it still requires cautious management. Once signs of infection appear, timely administration of antibiotics, drainage, or even partial hepatectomy should be implemented
Dhamija et al[10], 2015	Retrospective study	A total of 305 TACE procedures were performed in 168 patients with HCC, among whom 6 patients (3.6%) developed biliary complications of varying severity, resulting in an overall complication incidence of 1.9%. The specific complications included 3 cases of mild intrahepatic bile duct dilatation, 1 case of bile duct stenosis, and 2 cases of intrahepatic biloma. Supportive treatment was administered to patients with intrahepatic bile duct dilatation, while percutaneous aspiration and nasobiliary drainage were performed for patients with infected biloma	It provides specific incidences of biliary complications based on the number of patients and procedures, which are 3.6% and 1.9% respectively. Several types of biliary complications are listed, such as intrahepatic bile duct dilatation, bile duct stenosis, and intrahepatic biloma

TACE: Transarterial chemoembolization; CT: Computed tomography; B-TACE: Balloon-occluded transarterial chemoembolization; HCC: Hepatocellular carcinoma; ARDS: Acute respiratory distress syndrome; ALI: Acute lung injury; DEB-TACE: Drug-eluting bead transarterial chemoembolization; ALP: Alkaline phosphatase.