In recent years, radiofrequency ablation (RFA) has been recognized by both doctors and patients for its minimally invasive, safe and reliable efficacy in the treatment of liver tumors, and has been widely performed at home and abroad. However, with the increase in the number of cases and the expansion of technology, the issue of complication prevention and control has gradually attracted attention. Therefore, we should have a comprehensive and correct understanding and management of the possible complications in the process of RFA for hepatocellular carcinoma. In this paper, we discuss the complications in RFA treatment of hepatocellular carcinoma and their prevention and treatment measures based on the complications we encountered in the treatment and combined with domestic and international literature.
I. General overview
As a typical means of minimally invasive treatment for hepatocellular carcinoma, RFA is gaining more and more attention due to its advantages of low complication rate, wide indications and reliable efficacy.
II. Serious complications and their prevention and treatment
1. Death.
The morbidity and mortality rate of hepatocellular carcinoma treated with RFA is relatively low, which is mainly caused by serious complications. They include liver failure, bleeding, sepsis, bile duct injury, colon perforation, pericardial tamponade and so on. The occurrence of patient death in the perioperative period is the most serious complication during RFA treatment. In order to reduce and avoid patient death, the grasp of indications, close observation and treatment during and after surgery and the accumulation of experience of the therapist should help to reduce the occurrence of such cases. Early detection and treatment of serious complications as early as possible is also a very important aspect.
2. Intra-abdominal bleeding.
Due to the thick RFA electrode, bleeding is extremely likely to occur when the larger intrahepatic vessels are pierced and the patient has coagulation dysfunction. Bleeding can occur in the subperitoneal, intratumoral, intrahepatic and needle tract.
Most bleeding can stop on its own, but if the puncture injures a large vessel, it may cause fatal hemorrhage. Preoperative examination and correction of abnormal coagulation is an indispensable part of the procedure, and RFA treatment can be delayed if necessary. During the treatment, the RF electrode placed under ultrasound guidance should avoid the large intrahepatic vessels and try to pass as much surrounding normal liver tissue as possible so that there is sufficient support around the needle tract. When cauterizing the needle tract at the end of the treatment, the electrode should be slowly withdrawn to achieve adequate hemostasis. All these methods can reduce the occurrence of bleeding, especially hemorrhage. The patient’s vital signs and blood count should be routinely monitored at the end of RF treatment, and if abdominal bleeding is detected, the needle tract can be examined by Doppler ultrasound to distinguish whether the bleeding is caused by venous or arterial rupture. The early treatment of intra-abdominal bleeding is mainly conservative treatment, including blood transfusion and fluid replacement, etc. Most of the bleeding can be stopped and absorbed by themselves, and transarterial embolization treatment or surgical treatment can be performed in severe cases.
3.Thoracic complications.
Chest complications are seen in RFA for hepatomegaly. Most clinical complications are seen in hemothorax, pneumothorax, pleural effusion, etc. Diaphragmatic hernia, pericardial effusion and pus accumulation have also been reported. These complications are usually seen after ablation of right hepatic tumors, especially those close to the diaphragm. The main reason may be that the intercostal or diaphragmatic vessels are damaged during puncture and the thicker RF electrode is used, coupled with the patient’s combined cirrhosis and poor postoperative coagulation mechanism causing thoracic hemorrhage; or when the lesion is near the diaphragm and RFA treatment is performed, the heat is easily conducted through the diaphragm to the pleural side, causing a stronger pleural reaction and the occurrence of hemothorax and simple pleural effusion. The hemorrhagic pleural fluid and simple pleural effusion occur.
For chest complications, our current practice is to routinely take chest X-ray 1-5 d after surgery for those with lesions near the diaphragm and those with postoperative pulmonary symptoms, and no special treatment is needed when a small amount of pneumothorax or effusion is found, which usually does not have serious consequences and does not affect the efficacy. If the lung compression is more than 1/3 or respiratory distress is obvious, puncture and exhaust or closed drainage of the chest cavity should be performed immediately. Most of the cases can be cured by conservative treatment; while pericardial effusion or pus accumulation can be achieved with good results by percutaneous puncture and drainage.
For the prevention of chest complications, the main purpose is to circumvent the puncture route and avoid penetration of the puncture needle into the chest cavity as much as possible; when it is completely unavoidable, the establishment of artificial pleural fluid can be considered to reduce the complications caused by puncture.
4. Abscesses.
Liver abscess mainly occurs in patients with hepatocellular carcinoma with biliary tract abnormalities such as bile-intestinal anastomosis or immune deficiency, which is mainly caused by the presence of bacteria in small intrahepatic bile ducts after bile-intestinal anastomosis or biliary obstruction caused by recurrence of lesions and easy co-infection of necrotic lesions after RFA treatment to form liver abscess. Liver abscess can cause sepsis, infectious shock and can further develop into multi-organ failure or even death. It usually appears one week after RFA treatment, but also 5 months after treatment. Prophylactic anti-infective therapy is recommended for all these high-risk patients prone to liver abscess at the time of RFA, and some scholars even recommend receiving anti-infective therapy for 3 months after RFA treatment for these high-risk groups. Abdominal infection is less common than liver abscess, and strict asepsis during treatment is the key to prevent abdominal infection.
It is not difficult to diagnose liver abscess in the presence of fever, elevated white blood cells, and gas found in the treated area after RFA treatment. However, when some patients have only a low fever without other symptoms or only mild discomfort after surgery, liver abscess is often not easily diagnosed early because it can be easily confused with fever caused by tumor necrosis after RFA treatment in such cases, or even in some patients who develop fever months after ablation therapy is performed. Therefore, for fever lasting more than 2 weeks, possible abscess formation should be considered. After early and clear diagnosis, most liver abscesses can be cured after appropriate antimicrobial treatment and percutaneous needle aspiration or percutaneous drainage.
5. Bile duct injury.
Bile duct injury includes bile duct stricture, bile duct hematoma or hemorrhage, biliary fistula, etc., the incidence of which is 0,1% to 1,0%. According to the cause of the injury, it can be divided into mechanical injury during puncture and thermal injury during treatment, and the small bile ducts around the lesion are damaged during RFA treatment. Therefore, when performing RFA treatment, if combined with obstructive xanthogranuloma, it should be regarded as a contraindication unless the biliary obstruction is effectively removed. When the tumor is close to the bold duct, it is very easy to damage the bold duct because the treatment area should be considered to contain the tumor and its surrounding 1,0 safety margin as completely as possible, which requires us to consider the relationship between efficacy and complications comprehensively and decide the treatment plan so as to achieve efficacy and bold duct safety, which is also closely related to the operator’s skills and experience. Hepatocellular carcinoma located in the first hilar region, the bile duct injury in the hilar region caused during the treatment can lead to severe obstructive jaundice. Some scholars have achieved some results by instilling cold isotonic saline to the bile duct to reduce bile duct injury or to prevent f raw placement of stents; however, the former lacks the support of large sample results, and the latter has the concern of causing infection after surgery. In such cases, we believe that surgical resection or mediated hepatic vascular embolization, or laparoscopic ultrasound-guided RFA should be chosen whenever possible.
The incidence of severe bile duct injury is not high in clinical practice. Most bile duct injuries are manifested as biliary fistulas at the ablation site, biliary strictures, dilatation of the bile duct ends or formation of bile tumors, which are usually treated conservatively or do not require treatment. For some patients with bile duct stenosis with obstructive jaundice, percutaneous hepatic bile duct drainage, bile duct internal duct drainage or stent placement can be performed.
6.Injury of adjacent organs.
When the tumor is located in the periphery of the liver or adjacent to important tissues, it is easy to cause damage to the surrounding organs. Especially when the pursuit of thermal coagulation reaches the safe distance of 0.5~1.0cm outside the boundary of tumor, it is more likely to cause thermal injury to the surrounding tissues. When RFA treatment is performed in these areas, the safety of the treatment should be carefully considered. The most common adjacent organ injuries are colon perforation, gastric perforation, duodenal perforation, and gallbladder and diaphragm injury. When there is a history of surgery in the upper abdomen and intra-abdominal adhesions are considered, percutaneous RFA treatment is risky. In such cases, laparoscopic ultrasound-guided RFA or open RFA is recommended whenever possible, and surgical resection or hepatic vascular embolization intervention is also an option.
In addition, there is a delayed sign of thermal injury to the adjacent organs, especially the cavernous organs. This is manifested by the onset of symptoms only a few days after RFA treatment, and we have early encountered a case of colonic perforation only 7 d after RVA treatment. The reason for this is that the intestinal wall is damaged and necrotic due to heat conduction, but unlike mechanical injury, the necrosis of the intestinal wall takes some time to fall off, so it appears as a delayed cavity organ perforation.
For the prevention of adjacent organ injury, one is to master the indications for RFA treatment, especially to choose the appropriate modality for cases adjacent to the liver surface, the top of the diaphragm and those with a history of upper abdominal surgery. Second, the puncture and treatment must be implemented with the help of imaging guidance. Third, postoperative observation of the patient should be strengthened for early detection and appropriate treatment. Some scholars have also tried to establish artificial ascites to isolate the liver from the surrounding organs.
7. Liver insufficiency.
As a local treatment for liver cancer, RFA has less damage to liver function compared with surgery, mainly manifested as a transient increase in aminotransferase, and some patients have increased jaundice index or even jaundice after surgery. The reason is that RFA causes necrosis of normal liver cells around the cancer foci, which results in transient impairment of liver function and causes elevated aminotransferase or jaundice. Loss of liver function after RF treatment is rare, with an incidence of <0.1%. Loss of hepatic function is often accompanied by sepsis, caused by causes related to peritonitis, liver abscess, portal vein thrombosis or excessive ablation volume after rfa treatment. There are also reports in the literature of rfa treatment in patients with cirrhotic decompensated hepatocellular carcinoma, all of whom completed treatment successfully.
For patients with large hepatocellular carcinoma (diameter >5,0cm) with liver function grade B, it is recommended that treatment should not pursue complete destruction of the lesion at one time, but can be completed in 2-3 times; otherwise, due to long treatment time, more necrotic tissues and more damage to peri-cancerous liver tissues, liver insufficiency or even failure may easily occur after surgery. For those with ChildC liver function, the use of liver-protective drugs, elimination of ascites, correction of hypoproteinemia and abnormal coagulation function before ablation can effectively improve the safety of treatment after their liver function basically reaches ChildB level.
8. Other serious complications.
Electrode plate skin burns, tumor needle tract implantation metastasis, etc. can be encountered in the clinic. The occurrence of skin burns can be reduced and prevented by paying attention to the application of skin electrode plates in thick muscles and using large area electrode plates as much as possible before RFA treatment. The incidence of tumor needle tract implantation metastasis is not high. Although there is an early report in the literature showing a relatively high incidence of implantation metastasis in RFA by biopsy, the incidence of tumor implantation metastasis is not high in other reports, and the incidence is 0.5% in a multicenter study. Note that cautery coagulation of the electrode needle tract is an effective measure to reduce needle tract implantation metastasis. Other complications include renal failure, cardiac complications, etc. Careful perioperative management is the key to prevent such complications.
III. Minor complications
Minor complications are similar to serious complications, but the difference lies in their severity. These complications do not require special treatment, but they need to be observed, and they also need to understand its risk factors and preventive measures. They include pain, fever, asymptomatic pleural effusion, biliary tumor, hepatic vein thrombosis, etc.
As RFA treatment for hepatocellular carcinoma becomes more popular, the occurrence of complications will increase, and familiarity with their causes and their management measures will help increase the safety of RFA treatment. We believe that the complication rate of RFA for liver tumors is low and most of them can be prevented. Patients with cirrhotic decompensated hepatocellular carcinoma treated with rfa have successfully completed treatment.