Chemical ablation therapy for hepatocellular carcinoma
(I) Overview (history and development)
Chemical ablation is the injection of anhydrous alcohol or 50%-75% acetic acid into the tumor to kill cancerous tissues, and the former is far more widely used than the latter. 1983, Sugiura et al. in Japan reported the injection of anhydrous ethanol in percutaneous liver cancer puncture under ultrasound guidance, which pioneered the image-guided liver cancer ablation therapy. It has been popularized worldwide. After 20 years of development, surgical treatment (hepatic resection and liver transplantation), regional treatment (transhepatic artery treatment) and local treatment (ablation treatment) have become the three major means of hepatocellular carcinoma treatment. There are three ablation routes: percutaneous, trans-laparoscopic surgery and open surgery, with percutaneous ablation being the most commonly used. The advantages of percutaneous ablation are that it can be performed under local anesthesia or additional intravenous analgesia without hospitalization, and it is minimally invasive and easy for repeated treatment. Imaging guidance is an essential condition and one of the key techniques in the ablation process. Most of the punctures of percutaneous ablation are done under ultrasound guidance, which has the advantages of real-time imaging, good accuracy, lightness and flexibility.
(II) Clinical characteristics
Hepatitis virus, aflatoxin and drinking water contamination are the three major factors associated with the occurrence of hepatocellular carcinoma. The general pathological typing of hepatocellular carcinoma can be divided into three types: giant, nodular and diffuse. Its clinical manifestations mainly include pain and fullness in the right upper abdomen, epigastric mass, loss of appetite, weakness and emaciation.
Liver resection is still the first choice for hepatocellular carcinoma treatment. Most patients with hepatocellular carcinoma are in progressive stage or combined with cirrhosis at the time of consultation, and only 10% to 37% can undergo hepatic resection. Within 2 years after surgery, 30% to 50% of tumors recur, and the recurrence rate can be as high as 80% at 5 years. Although liver transplantation can simultaneously treat coexisting end-stage liver disease, it is difficult and expensive to source donors. As the application of surgical treatment is limited, the majority of patients in fact need to receive regional or local treatment, of which various ablative therapies as local treatment can be another powerful weapon in addition to the scalpel in clinical work.
(iii) Indications and contraindications for interventional therapy.
Indications.
1. small hepatocellular carcinoma: small hepatocellular carcinoma with diameter ≤ 3 cm and number not more than 3 is the best target for ablation therapy.
This year, the application of MP-PEIT can ablate tumors up to 5 cm in diameter.
2. Treatment of recurrent hepatocellular carcinoma: after patients have been treated by surgical resection and other means, the liver function has been damaged to a certain extent, and ablation therapy is beneficial to preserve the liver reserve for tolerating retreatment in case of recurrence, which facilitates repeated treatment.
3. Indications for enlarging resection with surgical treatment: If the main tumor is located in one liver lobe and there are only a few subfoci on the opposite side, in this case, surgical resection of the main tumor and intraoperative ablation of subfoci can be used.
4. Combined with TACE to improve local and long-term efficacy: the local efficiency of TACE for progressive liver cancer is about 35% on average, and if ablation therapy is added, it can further kill the residual cancer and strongly curb the development of the disease.
5. As a bridge to liver transplantation: Due to insufficient donor source, the recipient needs to wait for surgery, timely ablation treatment of tumor can make the waiting time more than 1~2 years.
Contraindications: The lesion is close to important tissues and organs such as the porta hepatis, gallbladder, heart, diaphragm or gastrointestinal tissues, or the patient has obvious coagulation disorder or poor liver function that has reached Child C level.
(D) Postoperative management and efficacy judgment
Observe the patient for at least 0.5h after the operation, and those without abnormalities can go home to rest. If the number of puncture needles in one treatment is large, it is better to stay in hospital for overnight observation.
There are several methods to determine whether the tumor is completely inactivated 1 week to 1 month after ablation: (1) Ultrasound examination. Two-dimensional gray-scale ultrasound and color Doppler ultrasound are not very reliable in determining the efficacy. Nowadays, the developed real-time ultrasonography has greatly improved the accuracy of ultrasound judgment. The absence of enhancement of the lesion under ultrasonography is definite evidence that the tumor has been inactivated. (2) No enhancement of the lesion on dynamic CT scan. (3) If the serum AFP is elevated before surgery, the AFP value should return to normal after treatment for a period of time. (4) If necessary, tumor biopsy should be performed to confirm the presence or absence of surviving cancer cells, and attention should be paid to the tumor margin to ensure the authenticity of the results.
The two main factors affecting the local efficacy are the size of the tumor and the location of the tumor. If the tumor is located at the top of the diaphragm or near the organs such as gastrointestinal and gallbladder, it is difficult to achieve the most satisfactory display of the lesion due to the interference of gas in the lung or gas in the digestive tract.
(V) Principles and prevention of complications of interventional treatment
The incidence of alcohol ablation complications is about 1.7%~3.2%, and the main complications are as follows.
Fever: It is the most common side effect, with a frequency of about 44%-65%. The reason may be related to the body’s reaction to trauma and the absorption of tumor tissue necrosis. It usually appears on the day of treatment or the 1st day after treatment and lasts for 2 weeks. Generally, no special treatment is needed. Those who exceed 38℃ can take oral antipyretic and analgesic drugs, which can mostly relieve. If persistent hyperthermia occurs, bacterial inflammation should be noted, and blood tests and liver ultrasonography should be performed promptly to determine the presence of liver abscesses and other foci of infection.
Intra-abdominal organ tissue injury: When puncturing under imaging guidance, the path of ablation needle should avoid important tissue structures in the abdominal cavity, and the location of the needle tip must be confirmed before starting ablation.
Bleeding: Most patients with primary liver cancer combined with cirrhosis may have coagulation dysfunction, which should be carefully evaluated and appropriate corrective measures should be taken before ablation treatment.
Liver damage: Excessive or repeated use of alcohol can aggravate pre-existing liver damage. The use of drugs to eliminate ascites and correct hypoproteinemia before ablation can effectively improve the safety of treatment for those with Child C liver function.
Pleural effusion: Most of the cases have no conscious symptoms and need to be treated in about 2% of cases, and the measures are thoracentesis aspiration or closed drainage.
Infection: Ultrasound-guided abscess puncture and aspiration and anti-infection treatment. Strict asepsis helps to reduce the complications of infection.
Needle tract implantation: Special attention should be paid to the completeness of tumor ablation.
Pain: Alcohol is more irritating and causes pain during treatment, and some still need analgesic treatment after surgery. The pain is particularly significant in tumors near the hepatic peritoneum, and the addition of a small amount of local anesthetic to the preparation may alleviate the symptoms.
Other rare complications include pneumothorax or hemothorax, cardiac arrhythmia, renal failure and myoglobinuria.
Mastering the appropriate treatment indications, following strict aseptic principles, accurate imaging guidance and standardized ablation operations are important for preventing complications. The treatment room should be routinely equipped with emergency drugs and items such as oxygen, suction and defibrillator. Good anesthesia and analgesia during treatment are helpful to reduce cardiovascular complications.
(VI) Typical case report
The patient was a 53-year-old male with a history of hepatitis B and cirrhosis for more than 20 years, and was found to have a 2.1 cm diameter hepatic S4 occupying lesion on ultrasound during physical examination. Enhanced CT examination also suggested hepatocellular carcinoma. The case was diagnosed clinically, and multi-polar anhydrous alcohol injection ablation was performed under ultrasound guidance, and a total of 25 ml of anhydrous alcohol was injected; the ultrasonography was repeated one month after the operation, which showed no enhancement in all three stages of the lesion, and the ablation was judged to be complete (Figure 7-1-5 and Figure 7-1-6).
The patient was a 50-year-old male with a history of hepatitis B and cirrhosis for 15 years. Two years after ablation treatment for hepatocellular carcinoma, ultrasound revealed an occupying hepatic S5 lesion with a diameter of 3.3 cm. Ultrasonography showed that the lesion was uniformly hyperenhanced in the arterial phase and hypoenhanced in the portal and delayed phases of fading, which was consistent with hepatocellular carcinoma. The ablation was performed under ultrasound guidance, and a total of 38 ml of anhydrous alcohol was injected; the ultrasonography was repeated one month after the procedure, showing no enhancement in all three phases of the lesion, which was judged as complete ablation (Figure 7-1-9).
(VII) Conclusion/summary
Alcohol relies on the toxicity of the agent itself to kill cancer, and the effect is more definite. The complete ablation rate (complete tumor inactivation rate) for ≤3 cm nodules is 70% to 80%. The local recurrence rate is 15%-20%. The long-term survival rates of 1, 3, 5 and 10 years are 92%-97%, 65%-74%, 38%-48% and 23% respectively, which are not significant compared with other regional or local treatments or even surgical resection.
Previously, chemical ablation was generally only applicable to lesions up to 3 cm in diameter, which was a major limitation. The main drawback is that it is difficult to monitor the degree of infiltration of the injection into the tumor, and some factors will affect the complete dispersion of the fluid and reduce the effect of tumor elimination, such as more interstitial components of the tumor tissue, i.e., harder texture, higher hydraulic pressure of the tissue gap within the tumor, the presence of fibrous septum, and leakage of the fluid outside the tumor with blood vessels. In recent years, with the progress of thermal ablation technology, alcohol ablation has been replaced in foreign countries, and the indications are limited to those who are not suitable for thermal ablation or for the treatment of vascular cancer thrombus. In recent years, due to the application of MP-PEIT, the shortcomings of traditional PEIT can be overcome to a certain extent, and tumors of 5 cm in size can be ablated. And because chemical ablation is the least traumatic, the easiest to operate and the least expensive among ablation methods, and thus has the best clinical compliance, it still has great practical value and development prospects.