Ablation therapy is a type of treatment that is guided by imaging technology to directly kill tumors locally, and currently radiofrequency and microwave ablation and anhydrous alcohol injection are the most common. Ablation can be performed through skin approach or during laparoscopic or open surgery. Ultrasound-guided percutaneous ablation has the significant advantages of being minimally invasive, safe, simple, easy to perform repeatedly, and relatively low cost, and has been widely used in China because of its high clinical compliance for primary liver cancer patients with cirrhotic background and high tendency of recurrence. Liu Xiaofeng, Department of Gastroenterology, General Hospital of Jinan Military Region
1. Indications and contraindications
(1) Indications: For patients with single tumor ≤5 cm in diameter or multiple nodules (within 3 cm) with maximum diameter ≤3 cm, without vascular or bile duct invasion or distant metastasis, and with liver function Child-Pugh grade A or B, radiofrequency or microwave ablation is the best alternative to surgery.
For small hepatocellular carcinoma with a single tumor diameter ≤3 cm, radical ablation can mostly be obtained, and alcohol ablation may also achieve the same goal.
Due to the limitations of local treatment, ablation is not recommended for lesions >5 cm according to the current technology. For multiple lesions or larger tumors, the combination of pre-treatment hepatic artery chemoembolization (TACE or TAE) + radiofrequency treatment is significantly better than radiofrequency treatment alone, depending on the patient’s liver function. For tumors located on the surface of the liver, adjacent to the cardiodiaphragm and gastrointestinal canal region, open or laparoscopic treatment can be chosen, or radiofrequency combined with anhydrous alcohol injection. In addition, TACE or other treatments after radiofrequency surgery may also improve the efficacy.
(2) Contraindications: (1) tumors located on the visceral surface of the liver, of which more than 1/3 are exposed; (2) liver function Child-Pugh grade C, TNM stage IV or tumor is infiltrative; (3) significant atrophy of the liver, tumor is too large and the scope of ablation needs to reach 1/3 of the liver volume; (4) recent bleeding from ruptured esophageal (gastric fundus) varices; (5) diffuse hepatocellular carcinoma, combined with portal trunk to secondary branch cancer emboli or hepatic vein (6) severe failure of major organs; (7) active infection, especially biliary inflammation; (8) uncorrectable coagulation dysfunction and hematologic disease with severe blood abnormalities; (9) persistent massive ascites; (10) impaired consciousness or cachexia.
2. Basic technical requirements
(1) It is emphasized that the operation should be guided by imaging technology to ensure the safety, accuracy and effectiveness of the treatment.
(2) The scope of ablation should aim to include 0.5 cm of paracancerous tissues in order to obtain a “safe margin” and completely kill the tumor. For infiltrating or metastatic carcinoma with unclear boundary and irregular shape, it is recommended to extend the safe peri-tumor area to 1 cm or more if the adjacent liver tissues and structural conditions permit.
(3) The standard method to assess local efficacy is to determine whether the tumor is completely ablated (Complete response, CR) by contrast-enhanced CT/magnetic resonance imaging (MRI) or ultrasonography about one month after ablation. A lesion that has achieved CR shows a complete absence of blood supply (i.e., it shows no enhancement). If ablation is incomplete, additional treatment can be given immediately. If CR cannot be obtained after 3 ablations, ablation therapy should be abandoned and other treatments should be used instead.
(4) After treatment, regular follow-up review should be performed to detect possible local recurrent lesions and new intrahepatic lesions in a timely manner, and to effectively control tumor progression by taking advantage of the minimally invasive safety of percutaneous ablation and its simplicity and ease of repeated performance.
3. Selection and application of common ablation methods
(1) Radiofrequency ablation (RFA)
Radiofrequency ablation is used to treat liver tumors by inserting a needle-like electrode into the tumor and generating heat energy to destroy the tumor cells after electrification.
There are three ways of RF therapy: ultrasound-guided percutaneous RF ablation, laparoscopic RF ablation, and open intraoperative RF ablation. The percutaneous RF ablation method is very traumatic, leaving only a needle eye on the skin, and most patients can be discharged 24 h after surgery.
② Case selection.
Tumor size: Large tumor size makes it difficult to ablate all of them and increases the chance of recurrence after treatment. It is generally believed that tumor diameter within 3 cm is suitable for radiofrequency ablation treatment, and between 3 and 5 cm can be combined with the specific situation, more than 5 cm is not suitable for radiofrequency ablation treatment.
Number of tumor: Within 3 lesions of primary liver cancer is the indication for radiofrequency ablation treatment; more than 3 lesions are not suitable for radiofrequency ablation treatment.
Location of tumor: ① Tumor located next to large blood vessels. If the energy of ablation damages the large blood vessels, it will bring serious consequences, so it should be considered carefully and measures should be taken according to different situations. For example, tumor located between hepatic vein and inferior vena cava, surgery often cannot be completely removed, while radiofrequency ablation treatment for tumor in such area, with controlled dose can use the flushing cooling effect of blood flow to avoid vascular damage, while tumor tissue can achieve complete coagulation necrosis due to lower tolerance to heat than normal tissue. And tumors located near hepatic artery and portal vein trunk are the minefield of radiofrequency treatment. ② Tumors located next to the bold duct. Bile flow is slow and basically does not have cooling flushing effect, and bile duct injury will cause liver failure, so tumors located next to the bold duct should not be treated by radiofrequency ablation.
③ Combined application of radiofrequency ablation therapy and transhepatic artery embolization therapy: Transhepatic artery embolization therapy is to block the hepatic artery through vascular route. However. However, the blood supply of primary hepatocellular carcinoma also comes from the portal vein, so the tumor can still obtain blood supply from it and continue to grow after the hepatic artery embolization treatment. In clinical situations, we often encounter cases where all the arteries around the tumor have been embolized but the tumor continues to grow uncontrollably, so transhepatic artery embolization is a kind of palliative treatment. Although radiofrequency therapy is a curative therapy, it is also often difficult to inactivate all tumors efficiently because of the rich blood supply of liver cancer and the blood flow tends to carry away the heat. If the hepatic artery is embolized first and then radiofrequency treatment is performed, the effect of blood flow taking away heat can be reduced and the effect of radiofrequency can be improved; while radiofrequency treatment is beneficial to inactivate the tumor tissues supplied by portal vein and make up for the shortage of embolization treatment.
(4) Problems: Radiofrequency ablation has the problems of causing needle tract metastasis, surrounding organ damage due to puncture and inducing liver cancer rupture, etc. Besides, it is not suitable for liver cancer located in the image blind area.
(2) Microwave ablation (MWA): MWA is also a commonly used thermal ablation method. Randomized and retrospective comparative studies have shown that there is no significant difference between MWA and RFA in terms of local efficacy, complication rate and long-term survival. The current MWA technique is also capable of inactivating tumors in a single session. Establishing a temperature monitoring system can regulate the effective thermal field range and ensure the coagulation effect. For tumors with rich blood supply, the main trophoblastic vessels of the tumor should be blocked by coagulation before inactivating the tumor, which can improve the efficacy.
(3) Anhydrous alcohol injection (PEI): PEI is suitable for the treatment of small hepatocellular carcinoma within 3 cm in diameter and recurrent small hepatocellular carcinoma. For hepatocellular carcinoma or recurrent foci above 3 cm that are not suitable for surgery, it can also play a role of palliative treatment. Clinically, 10%-25% of lesion sites are close to tissue organs such as hepatoportal, gallbladder and gastrointestinal tract, which may be damaged by thermal ablation treatment such as radiofrequency or microwave, therefore, alcohol injection or combined with thermal ablation can be used for tumors in these sites to prevent complications.
(4) High intensity focused ultrasound (HIFU): Compared with other ablation methods, HIFU is a new technology of non-invasive extracorporeal conformal treatment of tumors with exact efficacy. Transient thermal effect is the main principle of HIFU in treating liver cancer, and HIFU uses the good penetration, directionality and focusability of ultrasound and its propagation in human tissues to convert the vibration energy of sound waves into thermal movement of molecules to produce heat energy for therapeutic effect.
① Indications: single nodule with diameter ≤12cm; right hepatocellular carcinoma with satellite foci ≤4; postoperative recurrence and failure of TAE treatment; liver function Child grade A and B.
② Contraindications: hepatocellular carcinoma: diffuse type (≥5 nodes); advanced hepatocellular carcinoma with severe jaundice, hepatic encephalopathy, massive ascites and cachexia.
③ Combination therapy: For hepatocellular carcinoma, the mode of HIFU treatment after interventional embolization with iodine oil with chemotherapeutic agents is mostly used.
④Problems: HIFU has a small focusing area and often needs to be performed repeatedly; there is a blind area for tumor detection by ultrasound; the irradiation channel is obstructed by the rib during treatment, and even the rib needs to be removed, which is against the original purpose of minimally invasive; the liver is affected by respiratory motion, which makes accurate positioning difficult. At present, HIFU is not considered as a separate treatment modality for PLC, but can be considered as a complementary treatment after TACE, or as a palliative treatment.
(5) Ablation therapy and surgery for small hepatocellular carcinoma
At present, there is a controversy in academic circles as to whether surgical treatment or percutaneous ablation therapy is preferred for hepatocellular carcinoma under 5 cm.
In clinical practice, the appropriate initial treatment should be selected based on the patient’s liver function and physical condition, the size, number and location of the tumor, the technical strength of the unit and the patient’s wishes. It is generally believed that surgical resection should be preferred if the patient can tolerate anatomical hepatectomy, as it can remove microscopic metastases in the corresponding liver segment or lobe and effectively prevent postoperative recurrence. Most experts believe that surgical treatment is still the first choice for the treatment of small hepatocellular carcinoma. For hepatocellular carcinoma ≤5 cm that meets the indications of both local surgical treatment and ablation treatment, surgical treatment should be performed when available, and local ablation can be another treatment option in addition to surgical resection. For hepatocellular carcinoma deep or central to the liver ≤3 cm, local ablation can be preferred to achieve the efficacy of surgical resection and obtain radical cure under minimally invasive treatment; for hepatocellular carcinoma 3-5 cm, the treatment effect can be improved by selecting appropriate instruments and needles, mastering reasonable ablation techniques and accumulating certain treatment experience. In addition, liver transplantation also belongs to the category of surgical treatment, and there is a lack of data comparing ablation therapy with liver transplantation and anatomical hepatectomy. There is a lack of evidence-based medical evidence for whether multi-point or fractionated ablation or open or laparoscopic ablation can be performed for large hepatocellular carcinoma (>5 cm), and therefore it is not recommended.
Both radiofrequency ablation and microwave ablation cause necrosis of tumor cells through thermal effects. However, there is no significant difference between them in terms of local efficacy, complications, and survival rate. After the ablation treatment, the necrosis of the lesion should be observed regularly, and if there is any residual lesion, it should be treated actively to improve the efficacy of the ablation.