In order to promote the standardization of local ablation therapy for liver cancer, CSLC, CSCO and the Liver Cancer Group of the Chinese Medical Association Hepatology Branch jointly initiated and organized the participation of experts from various disciplines, such as surgery, oncology, ultrasound and intervention, to draft and formulate the Expert Consensus on the Standardization of Local Ablation Therapy for Liver Cancer for reference and discussion.
Local ablation therapy is a treatment to target tumors with the guidance of imaging technology and kill tumor tissues by physical or chemical methods. The imaging guidance techniques include ultrasound, CT and magnetic resonance imaging (MRI), while the treatment routes include percutaneous, trans-laparoscopic surgery and trans-open surgery.
The characteristics of local ablation therapy include: direct action on the tumor, which has the advantage of high efficiency and rapidity; the treatment area is limited to the tumor and its surrounding tissues, which has little impact on the organism and can be applied repeatedly. Local ablation therapy has developed rapidly in the past 20 years or so, and has become the 3rd major treatment for liver cancer after surgical resection and interventional therapy. Moreover, due to its precise efficacy, especially in the treatment of small hepatocellular carcinoma, radiofrequency ablation is considered as one of the radical treatments for small hepatocellular carcinoma because its efficacy is similar to that of surgical resection.
Treatment principle and classification
Local ablation therapy can be classified into chemical ablation therapy and physical ablation therapy according to its principle. Chemical ablation refers to the use of chemical methods (i.e. injecting chemical substances such as anhydrous alcohol, acetic acid, etc. into the lesion) to dehydrate, necrotize and disintegrate local tissue cells, so as to inactivate the tumor lesion. Currently, the main chemical ablation methods used in liver cancer treatment are PercutaneousEthanol Injection (PEI) and Percutaneous Acetic AcidInjection (PAI).
Physical ablation is a treatment method to inactivate tumor lesions by heating or freezing local tissues, mainly radiofrequency ablation (RFA), microwave coagulation therapy (MCT), cryoablation, focused ultrasound ablation (High Intensive Focused Ultrasound (HIFA)), etc. Intensive Focused Ultrasound (HIFU), laser ablation therapy, etc.
Treatment principles
1.The patient’s condition and the biological behavior of the tumor should be fully evaluated before the radiofrequency treatment (to predict the feasibility and effect, to determine the measures and steps of ablation treatment and combined treatment).
2.Full imaging evaluation should be performed before treatment, and treatment plan and strategy should be formulated according to the scope and location of tumor infiltration to ensure sufficient safety scope and obtain one-time, conformal and complete ablation treatment as far as possible.
3.Select the suitable imaging-guided pathway and monitor the treatment process.
4.Develop appropriate comprehensive treatment plan and scientific and reasonable follow-up plan.
Indications and contraindications
Indications
1.Single tumor with maximum diameter ≤5 cm; or the number of tumors ≤3 and maximum diameter ≤3 cm.
2.No vascular cancer embolism, adjacent organ invasion.
3.Hepatic function classification of Child-Pugh A or B, or the standard is achieved by medical treatment.
4.Single tumor with diameter >5 cm or multiple tumors with maximum diameter >3 cm that cannot be surgically resected, local ablation can be used as part of palliative treatment or combined treatment.
Contraindications
1.Large tumor, or diffuse hepatocellular carcinoma.
2.Complemented with cholangiocarcinoma embolism or adjacent organ invasion.
3.Hepatic function classification of Child-Pugh C, which cannot be improved by liver protection treatment.
4.Ruptured esophageal (fundic) variceal bleeding within 1 month before treatment.
5, Uncorrectable coagulation dysfunction and severe blood abnormalities, with severe bleeding tendency.
6, Intractable massive ascites, malignant fluid.
7, Active infection, especially inflammation of the biliary system, etc.
8.Severe liver, kidney, heart, lung, brain and other major organ failure.
9.Patients with impaired consciousness or unable to cooperate with treatment.
In addition, tumor in the first hilar region is a relative contraindication; tumor close to the gallbladder, gastrointestinal, diaphragm or protruding from the hepatic peritoneum is a relative contraindication to the percutaneous puncture route; lesions with extrahepatic metastases should not be considered as contraindications, and local ablation therapy can still be used to control the situation of intrahepatic lesions.
Preoperative preparation
1.Perfect examination before treatment: blood routine, biochemical routine, coagulation function, tumor markers, electrocardiogram, chest X-ray, ultrasonography, and cardiopulmonary function test if necessary.
2.Use ultrasound (try to choose ultrasonography if possible), liver stage III CT/MRI and other examinations to evaluate the tumor situation, and choose reasonable guidance methods and ablation treatment instruments.
3. Clearly diagnose and perform puncture biopsy if necessary (the diagnostic criteria refer to the diagnostic criteria established by the Professional Committee of Liver Cancer of China Anti-Cancer Association in 2001).
4.Preparation of skin for the surgical area and puncture site.
5.Preparation of ablation instruments: Check whether the ablation instruments are in working condition, whether they can work normally, whether the electrodes or lines are ready, etc. before treatment.
6.Signing informed consent for surgery: Each patient signs an informed consent form before the surgical treatment, informing the procedure, risks and prognosis possible and fully informed consent.
Treatment procedure
Local ablation therapy for hepatocellular carcinoma can be performed percutaneously, trans-laparoscopically or in open surgery.
Percutaneous local ablation therapy for hepatocellular carcinoma (guided by ultrasound or CT)
1.Fast for 8 hours before surgery, perform detailed ultrasound examination (or read CT film) to clarify the liver lesion, and formulate reasonable needle path and needle deployment plan.
2.Anesthesia plan should be selected according to the situation, such as local anesthesia at the puncture point, intravenous analgesia, intravenous anesthesia, epidural anesthesia and tracheal anesthesia and other analgesic anesthesia methods.
3.The surgical area is routinely disinfected and toweled.
4.Conduct another comprehensive ultrasound or CT scan to determine the entry point, entry angle and needle placement as well as the needle placement scheme; try to choose to pass through part of the normal liver first and then enter the tumor.
5. Try to choose intercostal needle entry, and under ultrasound/CT guidance, try to choose to pass through part of the normal liver first and then enter the tumor; the puncture should be accurately positioned to avoid repeated multiple punctures, which may lead to tumor implantation, damage to adjacent tissues or tumor rupture and bleeding; if the needle is too deep, the electrode needle should not be returned directly, but should be ablated in situ and then repositioned by retiring the needle to avoid tumor implantation; in general. should ablate the tumor in deeper parts first, and then ablate the tumor in shallower parts.
6.Refer to the instructions of each ablation therapy instrument to carry out ablation therapy, point by point. In order to ensure the effect of ablation treatment, the ablation range should aim to reach the safe boundary of 0.5 cm. The overlapping ablation method of one needle and multiple points can ensure the ablation range and reduce the occurrence of leakage; after the ablation is completed, the needle tract ablation should be carried out when the needle is dialed to prevent postoperative bleeding and tumor implantation along the needle tract.
7. Before the end of treatment, another ultrasound/CT is performed to fully scan the liver to make sure that the ablation scope has completely covered the tumor, aiming to have a safe ablation boundary of 0.5~1.0 cm and to exclude the possibility of complications such as tumor rupture, bleeding, (hem)pneumothorax.
Trans-laparoscopic local ablation treatment (for tumor located under the peritoneum of liver, or adjacent to gallbladder, gastrointestinal, etc., or unclearly shown by ultrasound/CT or difficult to percutaneous puncture)
If necessary, apply laparoscopic ultrasound scan to determine the number and location of tumor; separate and isolate the surrounding normal tissues and organs; insert the radiofrequency needle into the abdomen via percutaneous puncture, and insert the electrode needle into the tumor under direct laparoscopic view or laparoscopic ultrasound guidance, and arrange the needle according to the predetermined plan to perform ablation treatment; during the ablation process, the needle can be intermittently inserted (using hemostatic forceps and other instruments). During the ablation process, the blood flow into the liver can be intermittently and repeatedly blocked to improve the ablation efficiency and increase the scope of ablation; after the ablation is completed, careful examination is performed to make sure there is no active bleeding and adjacent organ damage.
Open local ablation therapy (applicable to those who are difficult to implement the above two methods, or whose tumor cannot be removed by surgical exploration)
Open the abdomen routinely; free the perihepatic ligament to expose the tumor; protect the surrounding normal tissues and organs; insert the electrode needle into the tumor under ultrasound guidance during the operation, place the needle according to the predetermined plan and ablate the tumor; intermittently or repeatedly block the blood flow into the liver during the ablation process to improve the ablation efficiency and increase the ablation range; carefully examine after the ablation is completed to make sure there is no active bleeding and adjacent organ damage; close the abdomen.
Postoperative precautions
Routinely fast, monitor vital signs for 4 hours and stay in bed for more than 6 hours after the operation, pay attention to monitoring blood routine, liver and kidney functions, etc.; and give treatment of liver protection, infection prevention, analgesia, hemostasis, etc. to prevent complications; active treatment should be carried out after the occurrence of complications.
Prevention and treatment of complications
Classification of complications
The complications of local ablation can be divided into minor complications and major complications.
Minor complication
Grade A: no treatment required, no adverse consequences; Grade B: little treatment required, no adverse consequences, including overnight observation only.
Major complication
Grade C: treatment required, prolonged hospital stay <48 hours;
Grade D: requires extensive treatment, increased level of medical care, and
Extended hospitalization >48 hours;
Grade E: Long-lasting sequelae;
Grade F: death.
Radiofrequency ablation has been reported in the literature to have a high safety profile. Mortality rates of 0-1% and complication rates of 0-12% have been reported in the literature. Among them, the incidence of minor complications is about 4.7%, mainly including fever, pain, superficial II degree skin burns, small amount of pleural effusion, small amount of pneumothorax, etc.; while the incidence of serious complications is about 2.2%, mainly including infection, gastrointestinal bleeding, intra-abdominal bleeding, tumor implantation, liver failure, intestinal perforation, etc. Adequate preoperative preparation, strict operation specification, accurate positioning and reducing the number of ablation are important methods to reduce the incidence of complications.
Types of complications
Post-ablation syndrome mainly manifests as fever, pain, etc. Rarely, there are hematuria and chills, etc. The specific causes are unknown. The treatment is mainly postoperative intensive monitoring, fluid infusion, pain relief, symptomatic treatment and regular testing of liver and kidney function.
Infection Mainly liver abscess, puncture site infection, etc. Preventive measures include strict aseptic operation and postoperative application of antibiotics to prevent infection.
Gastrointestinal bleeding The main causes are bleeding from varices in the lower esophagus or bleeding from stress ulcers. Prevention and treatment include preoperative management of portal hypertension in patients with severe portal hypertension; routine postoperative use of acid suppressants to prevent stress ulcer bleeding. Post-hemorrhage treatment includes detection of vital signs, fasting, aggressive volume expansion, fluid administration, hemostasis, blood transfusion, acid control, and pressure elevation, etc. Endoscopic hemostasis is performed when necessary.
Intra-abdominal hemorrhage Clinical manifestations depend on the amount of bleeding. A small amount of bleeding has no obvious symptoms. When the bleeding volume is large, there are often abdominal distension and abdominal pain, and in severe cases, there are cold sweat, blood pressure drop and shock symptoms. The reason is mainly because the tumor is more superficial and the tumor ruptures after puncture; or the patient has poor coagulation function and the liver puncture site bleeds.
Preventive measures include strict control of the indications, for patients with poor coagulation function in liver cirrhosis, perform correction before treatment; for superficial lesions, it is better to use laparoscopic or open direct vision; when percutaneous radiofrequency treatment, minimize the number of punctures; after needle ablation, another ultrasound or CT scan should be performed to exclude any tumor rupture, bleeding and other manifestations. Treatment includes detection of vital signs, active volume expansion, fluid transfusion, hemostasis, blood transfusion and pressure elevation, etc. If necessary, surgery should be performed to stop bleeding.
Tumor implantation Tumor implantation is mainly caused by repeated punctures. Preventive measures include puncture should be accurately positioned and repeated multiple punctures should be avoided; if the needle is too deep, the electrode needle should not be returned directly, but should be ablated in situ and then returned for repositioning.
Liver failure The main reason for liver failure is the heavy degree of cirrhosis before treatment and poor liver function of the patient; or the occurrence of serious complications (such as infection, bleeding, etc.). Preventive and therapeutic measures include strict control of the indications, Child-Pugh grade C liver function, massive ascites and severe jaundice are contraindications; postoperative attention to prevent other complications, prevention of infection and active liver protection treatment.
If the tumor is adjacent to the gallbladder, gastrointestinal tract, bile duct, diaphragm or located in the first hilar region or subhepatic pericardium, the ablation treatment under the percutaneous puncture route may easily cause thermal damage to the adjacent organs or vasculature. For tumors in these areas, laparoscopic or open surgery under direct vision radiofrequency ablation should be used as much as possible to isolate and protect the adjacent organs.
Efficacy evaluation and follow up
The efficacy of ablation should be evaluated by reviewing CT/MRI or ultrasonography of the liver at three stages 1 month after treatment.
Complete ablation (Complete Response, CR)
Follow-up CT/MRI or ultrasonography of the liver at three stages shows hypointense tumor area (hyperechoic on ultrasound) with no enhancement in the arterial phase.
Incomplete ablation (ICR)
The follow-up of CT/MRI or ultrasonography of the liver at three stages shows localized enhancement in the arterial phase of the tumor lesion, suggesting residual tumor.
In addition, for those who have tumor residual after treatment, re-ablation treatment can be performed. If there is still tumor residual after two ablations, it is determined that ablation treatment has failed and other treatment should be used.
Follow-up
In the first 2 months after the operation, the liver stage III CT/MRI or ultrasonography, as well as liver function and tumor markers are reviewed monthly to observe the necrosis of lesions and changes of tumor markers. After that, tumor markers, ultrasonography or liver stage III CT/MRI were repeated every 2 to 3 months ( ultrasonography and CT/MRI were performed at intervals). After two years, tumor markers, ultrasonography or liver III CT/MRI were reviewed every 3 to 6 months (ultrasonography and CT/MRI were performed at intervals). Tumor recurrence and progression were determined according to the follow-up results as follows.
Local tumor progression
After complete ablation of the tumor, new lesions appear at the edge of the ablation site, and the new lesions are connected to the ablation site.
New lesion
New lesion in other parts of the liver.
Distant recurrence
A metastasis outside the liver.
Other
Radiofrequency ablation of tumors in high-risk areas are risky if they are adjacent to the gallbladder, gastrointestinal tract, bile duct, diaphragm, etc. or located in the first hilar region or subhepatic pericardium. To perform radiofrequency ablation on tumors in these areas, there are risks of thermal damage to adjacent organs or vasculature, tumor rupture and bleeding, so special care should be taken.
For tumors in high-risk areas, ablation therapy should be performed under direct vision by laparoscopy or open surgery as much as possible in order to isolate and protect the adjacent organs. Radiofrequency ablation treatment under artificial pleural fluid, artificial ascites, or special maneuvers (e.g., lifting method) has also been reported.
Nevertheless, no significant difference in the efficacy of radiofrequency ablation for tumors at risk compared with other sites has been reported in the literature.
Radiofrequency ablation of large hepatocellular carcinoma
The ablation range that can be achieved in one ablation by the currently applied radiofrequency ablation therapy instrument is generally 3.0-5.0 cm, so for tumors >5.0 cm, it is difficult to achieve complete ablation by single-point radiofrequency therapy. In the literature, it has been reported that repeated multiple ablations using a multi-needle geometry model with a multi-point needle deployment scheme for the treatment of large hepatocellular carcinoma can achieve an ablation range of 7.0 cm or more.
Radiofrequency combined with other treatment methods
According to the literature, RF ablation combined with hepatic artery embolization chemotherapy (TACE) and PEI can improve the efficacy; especially for tumors >3 cm or multiple tumors, combined treatment is the most reasonable choice. For those who fail in radiofrequency ablation, other treatment modalities should be chosen, such as surgical resection, TACE, molecular targeted drugs such as sorafenib, etc.; for those with distant metastases, the combined application of effective systemic drug therapy should be considered.