Committee of Minimally Invasive Therapy in Oncology, Chinese Anti-Cancer Association; Chinese College of Interventionalists; Expert Committee on Interventional Therapy, Chinese Society of Clinical Oncology (CSCO); Chinese Society of Radiology, Interventional Group; Gao Song1, Zhu Xu1*, Zou Yinghua2*, Guo Jianhai1, Wang Jian2, Guan Haitao2, Yang Wuwei3, Zhu Baorang3, Yu Haipeng4, Xng Wenge4
(1. Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and translational Research [Ministry of Education], Beijing 100142; 2. Department of Interventional Vascular Surgery, Peking University First Hospital, Beijing 100034;
3. Department of Tumor Minimally Invasive Treatment, the Fifth Medical center, Chinese PLA General Hospital, Beijing 100071; 4. Department of Intervention, Tianjin Medical University Cancer Hospital, Tianjin 300060)
[Abstract] Tumor ablation is an important kind of methods for treating solid tumors. Cryoablation has been widely accepted because of its exact curative effect, less complications, minimal invasive and quick recovery. The new-generation cold and hot multi-modal ablation system is independently developed in China, which integrates deep cryogenic ablation and high intensity thermal ablation, and its efficacy and safety have been affirmed by clinical experts. After full and in-depth discussion by experts of many disciplines engaged in tumor ablation, this consensus was reached on the treatment standard of cold and hot multi-modal ablation for liver cancer.
[Keywords] Liver neoplasms; Multi-modal ablation; Clinical practice; Expert consensus
[CLC] | R735.7; R815 | [Document code] | A | [Article number] | 1672-8475(2021)01-0023-05 |
[Fund project] National key R&D plan project (2017YFC0114004), key R&D plan project of Beijing Municipal Science & Technology Commission (Z181100010118001).
[Author] Gao Song (1976-), male, from Dezhou, Shandong, PhD, chief physician. Research direction: imaging and nuclear medicine (interventional therapy). E-mail:drgaosong@163.com
[Corresponding author] Zhu Xu, Department of Interventional Therapy, Peking University Cancer Hospital, 100142. E-mail:drzhuxu@163.com
Zou Yinghua, Department of Interventional Vascular Surgery, Peking University First Hospital, 100034. E-mail:13801105222@139.com
[Received date] 2020-11-21 [Revised date] 2020-12-15
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Liver malignant tumors mainly include primary liver cancer and liver metastases. The proportion of patients with primary liver cancer who are eligible for curative surgery is relatively low, and even if the primary lesion is surgically resected, the postoperative recurrence rate is also high[1-2]. Moreover, the liver is one of the most common sites for malignant tumor metastasis, and liver metastases often indicate poor prognosis. In recent years, ablation techniques have been widely used in the treatment of liver malignant tumors. In 2019, the National Comprehensive Cancer Network (NCCN) clinical practice guidelines for liver cancer stated that local ablation can achieve curative effects when the lesion diameter is ≤3cm; for lesions with a diameter of 3cm< diameter ≤5cm that meet the indications, a combination of transcatheter arterial chemoembolization (TACE) and ablation therapy can be used[3-4]. In addition to the characteristics of other ablation techniques such as radiofrequency and microwave, cryoablation also has advantages such as good patient tolerance, the ability to use multiple needles in combination, good conformability, large ablation volume, clear ablation treatment area, promotion of tumor antigen release, and activation of the immune system. Cryoablation has a promising outlook for the treatment of liver malignant tumors[5-6].
The cold and hot multi-modal ablation system (co-ablation system) uses liquid nitrogen as the coolant, which is easily accessible, and can achieve a minimum freezing temperature of -196°C. It allows for a larger range of ablation with a single needle. It also utilizes anhydrous ethanol as the heat medium, which can heat the ablation needle to 80°C after the freezing process, facilitating faster dissolution of the ice ball. This system can simultaneously ablate the needle tract, reduce bleeding, prevent tumor needle tract implantation, and provide higher safety. Compared to international similar products like argon-nitrogen knives, this system has certain advantages in its core performance[7-8]. Additionally, the low-pressure system has low operating costs and is easy to operate, making it suitable for clinical promotion and application in grassroots units such as county-level healthcare facilities. In order to promote the standardization and normalization of this technique for local ablation treatment of liver malignant tumors, an expert consensus on this clinical practice has been developed for reference with the collaboration of multiple disciplinary experts and based on the clinical application experience.
The cold and hot multi-modal ablation system was developed by Tsinghua University and Technical Institute of Physics and Chemistry, CAS. It is an original and new generation tumor ablation device that possesses complete independent intellectual property rights. It mainly destroys and kills tumor cells through various mechanisms, such as direct cellular damage, disruption of tumor microvessel, induction of immune response in the body, and cell apoptosis[9-13].
As a local tumor ablation technique, the specific principles followed by the cold and hot multi-modal ablation system are described in reference [13].
2.1 Indications[13-23] need to meet the conditions of 2.1.1 and either 2.1.2 or 2.1.3.
2.1.1 Liver function and physical condition: ① liver function is classified as Child-Pugh A or B, or meets this standard through medical treatment; ② Eastern Cooperative Oncology Group (ECOG) score is between 0 and 2.
2.1.2 Curative ablation: ① primary liver cancer: a single tumor with a maximum diameter ≤5cm, no vascular or bile duct invasion, and no extrahepatic metastasis; multiple tumor lesions with a quantity of <3 and a maximum diameter ≤3cm, no vascular or bile duct invasion, and no extrahepatic metastasis; ② metastatic liver tumor: the primary lesion has been effectively controlled, no other extrahepatic metastasis or stable extrahepatic metastatic lesions, a single tumor with a maximum diameter ≤5cm, no vascular or bile duct invasion; multiple tumor lesions with a quantity of <3 and a maximum diameter ≤3cm, no vascular or bile duct invasion.
2.1.3 Palliative ablation: the purpose of treatment is to reduce tumor burden, alleviate clinical symptoms, improve quality of life, and complement other treatments; it is used for primary liver cancer and metastatic liver tumor lesions that do not meet the conditions for curative ablation and when the expected patient survival is >3 months.
2.2 Contraindications[13-23]: ① diffuse liver cancer; ② Child-Pugh C liver function grade, with no significant improvement in liver function despite liver protection treatment; ③ variceal rupture and bleeding in the esophagus (gastric fundus) within the past month, with a high risk of gastrointestinal bleeding after evaluation; ④ irreversible coagulation dysfunction that cannot be corrected; ⑤ concurrent refractory massive ascites; ⑥ concurrent active infection or sepsis; ⑦ severe organ failure or cachexia involving the liver, kidneys, heart, lungs, brain, or other important organs; ⑧ impaired consciousness or inability to cooperate with treatment; ⑨ expected survival time < 3 months.
The routine preoperative disinfection and anesthesia methods are described in references[13]. Based on the lesion location and its adjacent relationship with surrounding organs, sterile liquid, sterile air, and sterile albumin foam can be used for tissue isolation, including the production of artificial peritoneal effusion, artificial pleural effusion, artificial pneumothorax, and interstitial tissue injection. When the lesion is near the skin, it shall be protected with warming measures, and sterile gauze soaked in warm saline shall be used to protect the surrounding tissues.
Preoperative preparations include: ① clearly diagnosing it according to the standards and procedures specified in the Diagnosis and Treatment Specification for Primary Liver Cancer (2019 Edition)[23]by the National Health Commission of PRC; ②evaluating tumor lesions using enhanced abdominal CT, MRI, or ultrasound contrast imaging, and selecting appropriate imaging-guided methods as deemed necessary; ③ completing routine preoperative examinations and obtaining informed consent for surgery from the patient and their family members.
4.1 Imaging-guided percutaneous local ablation of liver tumors: CT or ultrasound can both guide cold and hot multi-modal ablation treatment with concurrent monitoring. It is recommended to use CT guidance; real-time monitoring of vital signs shall be conducted; establish and maintain a venous infusion pathway; choose the treatment position, fix and position the operation, and arrange the layout of the ablation probe. For specific steps such as testing the ablation probe and device, anesthesia, puncture, and positioning, please see reference[13].
The freezing process of the ablation needle generally lasts for 10 to 20 minutes, and the device can monitor the temperature at the tip of the needle. After each freezing cycle, a rewarming process is carried out, which can be achieved through natural rewarming or heating rewarming. This process generally lasts for 5 to 10 minutes. In the case of heating thawing, the temperature can reach up to 80℃. One freezing and one rewarming make up one cryoablation cycle. The number of cryoablation cycles is determined based on the lesion condition, generally repeated 2 to 3 times. When the treatment goal is complete ablation, the ablation range shall ideally extend beyond the lesion edge by 5 to 10mm; during the ablation process, it is necessary to monitor the changes in the frozen ablation boundary, the coverage of the tumor by the multidimensional ice ball, and the adjacent relationship with surrounding normal tissue organs every 5 to 10 minutes. Treatment parameters shall be adjusted promptly if necessary. Post-ablation handling shall refer to reference [13].
4.2 Local ablation of liver tumors under laparoscopy or laparotomy
4.2.1 Laparoscopic local ablation of liver tumors: it is applicable when the tumor is located beneath the liver capsule, or in proximity to the gallbladder, gastrointestinal tract, etc., or when ultrasound/CT imaging is unclear or percutaneous puncture is difficult. For specific operations, please refer to Expert Consensus on Local Ablation Treatment of Primary Liver Cancer[24].
4.2.2 Local ablation of liver tumors under laparotomy conditions: it is suitable for curative treatment and ensures high safety for lesions adjacent to blood vessels, gallbladder, and gastrointestinal tract. For specific operations, please refer to Expert Consensus on Local Ablation Treatment of Primary Liver Cancer[24].
5.1 General treatment: after the operation, the patient's recovery position shall be chosen based on the puncture site, with a preference for supine position; oxygen supplementation shall be provided, and bedside electrocardiography, blood pressure, and blood oxygen monitoring shall be performed to closely monitor vital signs and any complications. When the freezing range is large, attention shall be paid to keeping warm. Sufficient fluid intake and output shall be ensured, and hydration, diuresis, and urine alkalization may be necessary to prevent renal dysfunction. Pay attention to observe whether there is any bleeding from the incision. When the ablation range is close to the skin, local hot compress for more than 60 minutes can be applied. After open surgical ablation, patients shall refrain from eating for 6 hours. Afterward, they can consume a semi-liquid diet. For those at risk of gastrointestinal injury during the treatment process, it is recommended to refrain from eating until gas is passed. Generally, patients can get out of bed and move moderately after 12h postoperatively.
5.2 Hemostatic agents: in case of intraoperative or postoperative bleeding, hemostatic medications may be administered as needed.
5.3 Antibiotics: the use of antibiotics shall follow the Clinical Application Guidelines for Antimicrobial Drugs (2015 Edition)[25].
5.4 Hormones: extensive ablation may lead to significant stress responses. In such cases, adrenocortical hormone may be used for preventive treatment for 1-3 days as deemed appropriate.
5.5 Liver protection treatment: postoperative necrotic tissue absorption can increase the burden on the liver. Therefore, supportive treatments such as liver protection may be administered as deemed appropriate. Generally, after short-term treatment, liver function can recover to preoperative levels.
6.1 Post-ablation syndrome is mainly characterized by fever and general discomfort, often transient and self-limiting. For tumors with a diameter greater than 5cm, it is recommended to perform ablation in multiple times. Once symptoms occur, appropriate treatment such as abatement of fever and fluid infusion can be given accordingly.
6.2 Infection can manifest as infection at the puncture site, liver abscess, etc. Preventive measures include strict aseptic operation, avoiding large-area ablation of the bile duct area as much as possible, and postoperative antibiotic treatment to prevent infection. If necessary, liver abscess drainage and injection of antibiotics into the abscess cavity can also be performed for anti-infective treatment.
6.3 Bleeding can manifest as intra-abdominal hemorrhage, variceal bleeding from esophageal or gastric varices, gastrointestinal ulceration, and needle tract bleeding. Preventive measures include avoiding major blood vessels when designing the puncture path, avoiding repeated puncture adjustments, treating portal hypertension to reduce the risk of bleeding, and prophylactic acid suppression therapy to prevent stress ulcers. Before removing the ablation needle, the heating function can be activated. The temperature of the cold and hot multi-mode ablation needle can reach up to 80℃, which can effectively promote hemostasis at the needle tract. After the procedure, routine monitoring of vital signs shall be conducted, and dynamic attention shall be given to changes in blood routine. In the event of bleeding, timely intervention shall be provided according to the severity and urgency of the condition, with reference to the Expert Consensus on Emergency Nursing for Fatal Massive Hemorrhage (2019)[26].
6.4 Tumor implantation: repetitive and multiple punctures may lead to the implantation and metastasis of tumor cells. Preventive measures include accurately locating the lesion before puncture, and minimizing the impact of breathing on the puncture. If adjustment of the ablation needle position is necessary, it shall be repositioned after retreating the needle in its original location.
6.5 Liver failure: possible causes include poor preoperative liver function or excessive ablation in the operative area. It is necessary to strictly adhere to the indications for surgery. Contraindications include Child-Pugh C liver function, significant abdominal ascites, severe jaundice, etc. For larger tumors (diameter > 5cm), sequential ablation may be considered, and postoperative care shall focus on liver protection, infection prevention, and other supportive treatments.
6.6 Injury to adjacent organs: when performing percutaneous puncture-based ablation treatment for tumors located in high-risk areas such as the vicinity of the gallbladder, gastrointestinal tract, bile duct, diaphragm, or within the first hepatic hilum or subcapsular liver, caution must be exercised to avoid injury to adjacent organs. Complications such as gastrointestinal or gallbladder perforation, bile leak formation, diaphragmatic hernia, etc., may occur. If necessary, immediate intervention from a surgeon shall be sought.
Laboratory tests, imaging examinations, general condition of the patient, and clinical physical examinations shall be conducted one month after treatment to comprehensively evaluate the effectiveness of ablation therapy. See reference [27] for specific evaluation criteria and see reference [13] for follow-up schedule. Follow-up contents: ① performing liver or abdominal contrast-enhanced MRI, contrast-enhanced CT, liver ultrasound, or other imaging examinations to assess the status of liver tumors based on tumor blood supply during the arterial phase; ② re-evaluating liver and kidney function, as well as coagulation function. For patients with primary liver cancer, viral hepatitis testing shall be conducted[13], in order to observe the overall tumor condition, general patient status, and organ function.
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List of editorial board members
Author:
Gao Song (Beijing Cancer Hospital), Wang Jian (Peking University First Hospital), Yang Wuwei (Fifth Medical Center, General Hospital of the Chinese People's Liberation Army), Yu Haipeng (Tianjin Medical University Cancer Hospital), Xing Wenge (Tianjin Medical University Cancer Hospital).
Responsible editorial board members
Wang Zhongmin (Ruijin Hospital, Shanghai Jiaotong University School of Medicine), Yan Zhiping (Zhongshan Hospital, Fudan University), Zhu Xu (Beijing Cancer Hospital), Cheng Yingsheng (Shanghai Tenth People’s Hospital), Zhang Fujun (Sun Yat-Sen Univerisity Cancer Center), Xing Wenge (Tianjin Medical University Cancer Hospital), Xiao Yueyong (The First Medical Center of the General Hospital of the Chinese People's Liberation Army), Zheng Jiasheng (Beijing Youan Hospital, Capital Medical University), Yang Renjie (Beijing Cancer Hospital), Xu Ke (The First Hospital of China Medical University), Zou Yinghua (Peking University First Hospital), Teng Gaojun (Zhongda Hospital Southeast University).
Editorial board members (in alphabetical order of surnames)
Chen Hui (Beijing Cancer Hospital), Cheng Yingsheng (Shanghai Tenth People’s Hospital), Duan Feng (The First Medical Center of the General Hospital of the Chinese People's Liberation Army), Duan Liuxin (Rocket Force Characteristic Medical Center), Fan Weijun (Sun Yat-sen University Cancer Center), Feng Huasong (The Sixth Medical Center of PLA General Hospital), Feng Weijian (Fuxing Hospital, Capital Medical University), Gao Song (Peking University Cancer Hospital ), Gu Yuming (The Affiliated Hospital of Xuzhou Medical University), Guan Haitao (Peking University First Hospital), Guo Jianhai (Peking University Cancer Hospital), Han Lei (Beijing Daxing Hospital), Han Jianjun (Shandong Cancer Hospital), Hou Chuanwei (Jilin Guowen Hospital), Hu Kaiwen (Oriental Hospital of Beijing University of Chinese Medicine), Huang Ming (Yunnan Cancer Hospital), Huang Jinhua (Sun Yat-sen University Cancer Hospital), Jin Long (Beijing Friendship Hospital,Capital Medical University), Li Huai (Cancer Hospital Chinese Academy of Medical Sciences), Li Hui (Henan Provincial People's Hospital), Li Xiao (Cancer Hospital Chinese Academy of Medical Sciences), Li Hailiang (Henan Cancer Hospital), Li Jiaping (The First Affiliated Hospital,Sun Yat-sen University), Li Quanwang (Oriental Hospital of Beijing University of Chinese Medicine), Li Wentao (Fudan University Shanghai Cancer Center), Li Xiaoguang (Beijing Hospital), Lin Hailan (Fujian Cancer Hospital), Liu Chen (Peking University Cancer Hospital), Liu Jing (Technical Institute of Physics and Chemistry, CAS), Liu Rong (Zhongshan Hospital, Fudan University), Liu Ruibao (Harbin Medical Univerisity Cancer Hospital), Liu Yu’e (Shanxi Provincial People’s Hospital), Lu Ligong (Zhuhai People's Hospital), Ma Yilong (Guangxi Medical University Cancer Hospital), Mao Aiwu (Tongren Hospital Shanghai Jiaotong University), Meng Zhiqiang (Fudan University Shanghai Cancer Center), Mou Wei (First Affiliated Hospital of Army Medical University), Ni Caifang (The First Affiliated Hospital of Soochow University), Niu Lizhi (Fuda Cancer Hospital), Ren Weixin (The First Affiliated Hospital of Xinjiang Medical University), Shao Guoliang (Zhejiang Cancer Hospital), Shao Haibo (The First Hospital of China Medical University), Si Tongguo (Tianjin Medical University Cancer Hospital), Song Li (Peking University First Hospital), Su Hongying (The First Hospital of China Medical University), Sun Junhui (The First Affiliated Hospital Zhejiang University), Tang Jun (Shandong Institute of Medical Imaging), Teng Gaojun (Zhongda Hospital Southeast University), Wang Jian (Peking University First Hospital), Wang Maoqiang (The First Medical Center of the General Hospital of the Chinese People's Liberation Army), Wang Weidong (The First Medical Center of the General Hospital of the Chinese People's Liberation Army), Wang Xiaodong (Beijing Cancer Hospital), Wang Zhongmin (Ruijin Hospital, Shanghai Jiaotong University School of Medicine), Wu Gang (The First Affiliated Hospital of Zhengzhou University), Xiao Yueyong (The First Medical Center of the General Hospital of the Chinese People's Liberation Army), Xing Wenge (Tianjin Medical University Cancer Hospital), Xiong Bin (Union Hospitlal Tongji Medical College Huazhong University of Science and Technology), Xu Ke (The First Hospital of China Medical University), Xu Linfeng (Sun Yat-sen Memorial Hospital, Sun Yat-sen University), Yan Dong (Beijing Luhe Hospital, Capital Medical University), Yan Zhiping (Zhongshan Hospital, Fudan University), Yang Ning (Peking Union Medical College Hospital), Yang Jijin (Changhai Hospital, Naval Military Medical University), Yang Renjie (Peking University Cancer Hospital), Yang Weizhu (Fujian Medical University Union Hospital), Yang Wuwei (Fifth Medical Center, General Hospital of the Chinese People's Liberation Army), Yang Yefa (Shanghai Oriental Hepatobiliary Hospital), Yang Zhengqiang (Cancer Hospital Chinese Academy of Medical Sciences), Ye Xin (The First Affiliated Hospital of Shandong First Medical University), Yin Guowen (Jiangsu Cancer Hospital), Yu Changlu (Tianjin Third Hospital), Yu Haipeng (Tianjin Medical University Cancer Hospital), Yu Youtao (The Fourth Medical Center of the General Hospital of the Chinese People's Liberation Army), Zhai Bo (Renji Hospital, Shanghai Jiaotong University School of Medicine), Zhang Lin (Beijing Tsinghua Changgeng Hospital), Zhang Jin (Guangzhou Wemen and Children's Medical Center), Zhang Fujun (Sun Yat-sen Univerisity Cancer Center), Zhang Yuewei (Beijing Tsinghua Changgeng Hospital), Zhao Jianbo (Nanfang Hospital, Southern Medical University), Zheng Chuansheng (Union Hospital Tongji Medical College Huazhong University of Science and Technology), Zheng Jiasheng (Beijing Youan Hospital, Capital Medical University), Zhou Shi (The Affiliated Hospital of Guizhou Medical University), Zhou Chengzhi (The First Clinical College of Guangzhou Medical University), Zhu Xu (Peking University Cancer Hospital), Zhu Baorang (Fifth Medical Center, General Hospital of the Chinese People's Liberation Army), Zou Yinghua (Peking University First Hospital).