Expert Consensus on Clinical Practice of Multi-Model Ablation for Treatment of Liver Malignant Tumors

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 Yinghua 2*, GUO Jianhai1, WANG Jian2, GUAN Haitao2, YANG Wuwei3, ZHU Baorang3, YU Haipeng4, XING Wenge4

(1. Department of Interventional Therapy, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research [Ministry of Education], Beijing 100142, China; 2. Department of Interventional Vascular Surgery, Peking University First Hospital, Beijing 100034, China; 3. Department of Tumor Minimally Invasive Treatment, the Fifth Medical Center, Chinese PLA General Hospital, Beijing 100071, China; 4. Department of Intervention, Tianjin Medical University Cancer Hospital, Tianjin 300060, China)

[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 multimodal 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 multimodal ablation for liver cancer.

[Keywords] liver neoplasms; multi-modal ablation; clinical practice; expert consensus

DOI: 10.13929/j.issn.1672-8475.2021.01.006

Liver malignant tumors mainly include primary liver cancers and hepatic metastases. The proportion of patients who suffer from primary liver cancers and can receive radical surgery is relatively low, and even if the primary lesion is surgically removed, the postoperative recurrence rate is high [1-2]. In addition, liver is one of the most common sites of malignant tumor metastasis, and liver metastasis often indicates a poor prognosis. In recent years, ablation technologies have been widely used in the treatment of liver malignant tumors. According to the 2019 National Comprehensive Cancer Network (NCCN) Liver Cancer Clinical Practice Guidelines, local ablation can achieve curative effect when the lesion diameter is not greater than 3 cm. For lesions with the diameter greater than 3 cm but not greater than 5 cm with specific indications, transcatheter arterial chemoembolization (TACE) and ablation therapy can be combined with other treatments [3-4]. In addition to the characteristics of radiofrequency ablation, microwave ablation and other ablation technologies, cryoablation has the advantages of good patient tolerance, multi-needle combination, good conformity, large ablation volume, clear ablation treatment area, promotion of tumor antigen release, activation of immune system, etc. Therefore, it has broad prospects for the treatment of liver malignant tumors [5-6].

The co-ablation system adopts liquid nitrogen as the refrigerant, which can be easily obtained. The lowest freezing temperature can reach -196°C, and the ablation range of a single needle is larger. Using anhydrous ethanol as the heat medium, the ablation needle can be heated to 80°C after freezing, and ice balls can be dissolved more quickly. At the same time, the puncture needle passage can be ablated, bleeding can be reduced, tumor implantation and metastasis can be prevented, thus ensuring higher safety. The core performance of the system has certain advantages compared with international similar products such as argon-helium knife [7-8]. Moreover, the low-voltage system has low operating cost and ensures convenient operation, which is suitable for clinical application in county-level and other grass-roots institutions nationwide. In order to promote the standardization of this technology for local ablation of liver malignant tumors, the expert consensus of this operating specification is formulated for reference with the participation of experts from multiple disciplines and the clinical application that has been carried out.

1. Equipment principle and treatment principle

The co-ablation system was researched and developed by Tsinghua University and the Technical Institute of Physics and Chemistry, CAS as an original and new generation of tumor ablation equipment with complete independent intellectual property rights. It mainly destroys and kills tumor cells by directly damaging cells, destroying tumor capillary blood vessel, and inducing body immune response, poptosis and other mechanisms [9-13].

As a local tumor ablation technology, the co-ablation system follows the specific principles as shown in the literature [13].

2. Indications and contraindications

2.1 The indications [13-23] should meet the criteria of Article 2.1.1 and 2.1.2 or 2.1.3.

2.1.1 Liver function and physical strength ① Liver function is graded as Child-Pugh A or B, or reaches this standard after medical treatment; ② The score of the US Eastern Cooperative Oncology Group (ECOG) is 0~2 points.

2.1.2 Curative ablation ① Primary liver cancer: The maximum diameter of single tumor is less than or equal to 5 cm, without vascular, bile duct invasion and extrahepatic metastasis; the number of multiple tumor lesions is less than 3, the maximum diameter is less than or equal to 3 cm, and there is no vascular, bile duct invasion and extrahepatic metastasis. ② Metastatic liver tumor: the primary lesion has been effectively controlled, there is no metastasis to other extrahepatic sites or extrahepatic metastasis is stable, and the maximum diameter of single tumor is less than or equal to 5 cm, there is no vascular or bile duct invasion; the number of multiple tumor lesions is less than 3, the maximum diameter is less than or equal to 3 cm and there is no vascular or bile duct invasion.

2.1.3 Palliative ablation therapy: It aims to reduce tumor load, relieve clinical symptoms, improve the quality of life and work with other treatments; for the patients who suffer from primary liver cancer and metastatic liver tumor lesions and cannot meet the curative ablation criteria, and the survival period is longer than 3 months.

2.2 Contraindications [13-23] ① Diffuse liver cancer; ② Liver function is graded as Child-Pugh C, and liver protection treatment fails to significantly improve liver function; ③ Esophageal (gastric fundus) variceal bleeding occurs within 1 month, and it is evaluated that there is still a high risk of gastrointestinal bleeding; ④ Uncorrectable coagulation dysfunction; ⑤ Complicated with intractable massive peritoneal effusion; ⑥ Complicated with active infection or sepsis; ⑦ Severe failures or cachexia of liver, kidney, heart, lung and brain and other important organs; ⑧ Disturbance of consciousness or unable to cooperate with treatment; ⑨ Estimated survival period <3 months.

3. Preoperative preparation

See the literature [13] for the conventional preoperative disinfections and anesthesia methods. According to the location of lesion and its adjacency with the surrounding tissues and organs, sterile liquid, sterile air and sterile albumin foam can be used for tissue isolation, including the preparation of artificial peritoneal effusion, artificial pleural effusion, artificial pneumothorax and inter-tissue injection. When the lesions are adjacent to skin, it should be heated and protected, and warm saline gauze should be used to protect the surrounding tissues.

Preoperative preparations include: ① performing clear diagnosis according to the standards and procedures of the National Health Commission’s “Diagnosis and Treatment Standard for Primary Liver Cancers (Edition 2019)” [23]; ② performing abdominal enhanced CT, MRI or contrast-enhanced ultrasound to evaluate tumor lesions, and selecting reasonable and feasible imaging guidance methods as appropriate; ③ improving preoperative routine examination, and ensuring patients and their families sign informed consent for operations.

4. Operating steps

4.1 Perform imaging-guided percutaneous liver tumor local ablation CT or ultrasound to guide the co-ablation treatment and monitor the whole procedure; CT guidance is recommended; monitor vital signs in real time; establish intravenous infusion route and maintain smoothness; select the treatment position, fix and operate for positioning and determine ablation probe arrangement scheme, test ablation probe and equipment, and perform anesthesia, puncture and positioning and other specific steps. See the literature [13] for details.

In most cases, the freezing process of the ablation needle lasts for 10 to 20 min, and the temperature of the needle tip can be monitored by the equipment. Re-warming after each time freezing, natural re-warming or heating re-warming can be used. In most cases, it lasts for 5 to 10 min, and the temperature of heating re-warming can be up to 80°C. One freezing-thawing cycle consists of one time of freezing and one time of re-warming, and the number of freezing-thawing cycles is determined according to the condition of the lesion, which is repeated 2 to 3 times in most cases. Purpose of the treatment: After the ablation is completed, the ablation range should be 5-10 mm beyond the edge of the lesion in principle. During the ablation process, the changes such as the boundary of cryoablation, the coverage of tumor by ice balls in multidimensional space, and the adjacency with the surrounding normal tissues and organs should be monitored at intervals of 5 to10 min, and the treatment parameters should be adjusted timely if necessary. See the literature [13] for the handling after ablation.

4.2 Local liver tumor ablation through laparoscopic or open surgery

4.2.1 Laparoscopic local ablation of liver tumors is suitable for tumors located under the liver capsule, or adjacent to the gallbladder, intestines and stomach, etc., or when ultrasound/CT shows unclear images or it is difficult to perform percutaneous puncture. See the Expert Consensus on Local Ablation of Primary Liver Cancers [24] for specific operations.

4.2.2 The local ablation of liver tumors through open surgery is suitable for curative treatment and has a high safety for the lesions adjacent to blood vessels, gallbladder, intestines and stomach. See the Expert Consensus on Local Ablation of Primary Liver Cancers [24] for specific operations.

5 Postoperative precautions

5.1 General treatment: Select body positions for the recovery period of patients according to specific puncture sites; ensure continuous oxygen uptake, perform bedside ECG, blood pressure and blood oxygen monitoring, and pay close attention to vital signs and complications. When the freezing range is large, attention should be paid to keep warm. In addition, enough intake and output volume should be ensured. If necessary, hydration, diuresis and alkalization of urine should be carried out to prevent renal function injury. Closely observe whether blood leaks from the wound. When the ablation is close to the skin, local hot compress can be performed for more than 60 min. Patients are fasted for 6 h after ablation through open surgery, followed by semi-liquid diet; for those patients at risk of gastrointestinal injury during treatment, postoperative fasting is recommended until flatus. In most cases, patients can get out of bed for some appropriate activities 12 h after the surgery.

5.2 Hemostatic agents: Patients can be given appropriate hemostatic drugs once they suffer from intraoperative and postoperative bleeding.

5.3 Antibiotics: Antibiotics should be used in accordance with the Guidelines for the Clinical Use of Antimicrobial Drugs (Edition 2015) [25].

5.4 Hormone: Large-area ablation may produce a strong stress response, and adrenocortical hormone can be used as appropriate for preventive treatment for 1 to 3 days.

5.5 Treatment of liver protection: The absorption of necrotic tissues after surgery will increase the liver burden. Under such circumstance, the treatment of liver protection and other supportive treatment can be performed as appropriate. In most cases, liver function can be restored to the preoperative level after short-term treatment.

6. Prevention and treatment of complications

6.1 The main syndromes after the ablation include fever and general malaise, most of which are transient and self-limiting. For tumors with a diameter greater than 5 cm, it is recommended to perform ablation separately. Once symptoms occur, corresponding treatments such as defervescence and fluid infusion can be performed against specific symptoms.

6.2 Infections are manifested as puncture infection, liver abscess, etc. Preventive measures include performing strict aseptic operation, avoiding one-time large-area ablation of bile duct area, giving antibiotic anti-infection treatment after operation, drainage of liver abscess if necessary, and injection of antibiotics into abscess cavity for anti-infection treatment.

6.3 Bleeding is manifested as abdominal bleeding, esophageal and gastric variceal bleeding, and peptic ulcer and needle tract bleeding. Preventive measures are as follows. In detail, the puncture path should be designed to avoid passing through large blood vessels, and adjusting puncture needles repeatedly, treat portal hypertension to reduce the risk of bleeding, and inhibit acid to prevent stress ulcer. The heating function can be turned on before removing the ablation needle, and the temperature of the co-ablation needle can reach up to 80°C, which can bring the hemostatic effect of the needle passage into full play. It is recommended to perform routine monitoring of vital signs after surgery and pay dynamic attention to changes of blood routine. Once bleeding occurs, refer to Expert Consensus on Emergency Nursing for Fatal Haemorrhage (2019) [26], and perform intervention timely depending on the urgency and severity of diseases.

6.4 Tumor deposit: Repeated punctures may lead to tumor deposit and metastasis. Preventive measures include locating the lesion as accurately as possible before puncture and minimizing the influence of breathing on punctures. If it is necessary to adjust the position of ablation needle, the needle should be repositioned after the ablation is completed in situ.

6.5 Liver failure may be caused by poor preoperative liver functions or large intraoperative ablation areas. Surgical indications should be strictly controlled. Child-Pugh C liver function, large amount of ascites and severe jaundice are classified as contraindications. For large tumors (diameter > 5 cm), ablation can be performed in several times, and supportive treatments, such as liver protection and anti-infection, are recommended after surgery.

6.6 Injury of adjacent organs: When percutaneous puncture ablation is performed on tumors in high-risk sites such as adjacent gallbladder, gastrointestinal tract, bile duct, diaphragm, etc. or located in the first hepatic portal region, subcapsular, etc., take care not to damage adjacent organs. Otherwise, perforations of gastrointestinal tract and gallbladder, biloma formation, diaphragmatic hernia and other complications may occur. If necessary, ask a surgeon for emergency intervention.

7. Local efficacy evaluation and follow-up

Laboratory examination, imaging examination, general condition of patients and clinical physical examination should be carried out one month after treatment to comprehensively evaluate the curative effect of ablation treatment. Refer to the literature [27] for the specific evaluation criteria. See the literature [13] for the follow-up schedule. Follow-up contents: ① Perform liver or abdominal enhanced MRI or enhanced CT, liver contrast-enhanced ultrasound and other examinations to judge liver tumor through blood supply of tumor in arterial phase; ② Reexamine liver and kidney function and coagulation function, and perform hepatitis virological detection on patients with primary liver cancer [13] to observe the whole body tumor, general condition and organ function of patients.

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List of Editorial Board Members

Written by:

Gao Song (Peking University Cancer Hospital), Wang Jian (Peking University First Hospital), Yang Wuwei (Fifth Medical Center of Chinese PLA General Hospital), Yu Haipeng (Tianjin Medical University Cancer Institute & Hospital) and Xing Wenge (Tianjin Medical University Cancer Institute & Hospital).

Responsible editorial board members

Wang Zhongmin (Ruijin Hospital Shanghai Jiao Tong University School of Medicine), Yan Zhiping (Zhongshan Hospital Fudan University), Zhu Xu (Peking University Cancer Hospital), Cheng Yingsheng (Shanghai Tenth People’s Hospital), Zhang Fujun (Sun Yat-sen University Cancer Center), Xing Wenge (Tianjin Medical University Cancer Institute & Hospital), Xiao Yueyong (First Medical Center of Chinese PLA General Hospital), Zheng Jiasheng (Beijing Youan Hospital Capital Medical University), Yang Renjie (Peking University Cancer Hospital), Xu Ke (First Affiliated Hospital of China Medical University), Zou Yinghua (Peking University First Hospital) and Teng Gaojun (Zhongda Hospital Southeast University).

Editorial board members (sorted by Pinyin of surnames)

Chen Hui (Peking University Cancer Hospital), Cheng Yingsheng (Shanghai Tenth People’s Hospital), Duan Feng (First Medical Center of Chinese PLA General Hospital), Duan Liuxin (PLA Rocket Force Characteristic Medical Center), Fan Weijun (Sun Yat-sen University Cancer Center), Fan Huasong (Sixth Medical Center of PLA General Hospital), Feng Weijian (Fu Xing Hospital, Capital Medical University), Gao Song (Peking University Cancer Hospital), Gu Yuming (Affiliated Hospital of Xuzhou Medical University), Guan Haitao (Peking University First Hospital), Guo Jianhai (Peking University Cancer Hospital), Han Lei (Beijing Daxing District Hospital), Han Jianjun (Shandong Cancer Hospital), Hou Chuanwei (Jilin Guowen Hospital), Hu Kaiwen (Dongfang Hospital Beijing University of Chinese Medicine), Huang Ming (Yunnan Cancer Hospital), Huang Jinhua ((Sun Yat-sen University Cancer Center), Jin Long (Beijing Friendship Hospital, Capital Medical University), Li Huai (Xiamen Humanity Hospital), Li Hui (People’s Hospital of Henan Province), Li Xiao (Cancer Hospital Chinese Academy of Medical Sciences), Li Hailiang (Henan Cancer Hospital), Li Jiaping (First Affiliated Hospital Sun Yat-sen University), Li Quanwang (Dongfang Hospital 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 University Cancer Hospital), Liu Yu’e (People’s Hospital of Shanxi Province), Lu Ligong (Zhuhai People’s Hospital), Ma Yilong (Cancer Hospital Affiliated to Guangxi Medical University), Mao Aiwu (Tongren Hospital Shanghai Jiao Tong University), Meng Zhiqiang (Fudan University Shanghai Cancer Center), Mou Wei (the Southwest Hospital of AMU), Ni Caifang (First Affiliated Hospital of Soochow University), Niu Lizhi (Guangzhou Fuda Cancer Hospital), Ren Weixin (First Affiliated Hospital of Xinjiang Medical University), Shao Guoliang (Fujian Cancer Hospital), Shao Haibo (First Hospital of China Medical University), Si Tongguo (Tianjin Medical University Cancer Institute & Hospital), Song Li (Peking University First Hospital), Su Hongying (First Hospital of China Medical University), Sun Junhui (First Affiliated Hospital, Zhejiang University), Tang Jun (Shandong Medical Imaging Research Institute), Teng Gaojun (Zhongda Hospital Southeast University), Wang Jian (Peking University First Hospital), Wang Maoqiang (First Medical Center of Chinese PLA General Hospital), Wang Weidong (Medical Innovation Research Department, the PLA General Hospital), Wang Xiaodong (Peking University Cancer Hospital), Wang Zhongmin (Ruijin Hospital Shanghai Jiao Tong University School of Medicine), Wu Gang (First Affiliated Hospital of Zhengzhou University), Xiao Yueyong (First Medical Center of Chinese PLA General Hospital), Xing Wenge (Tianjin Medical University Cancer Institute & Hospital), Xiong Bin (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology), Xu Ke (First Hospital of China Medical University), Xu Linfeng (Sun Yat-sen Memorial Hospital of 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 Medical University), Yang Renjie (Peking University Cancer Hospital), Yang Weizhu (Fujian Medical University Union Hospital), Yang Zhuwei (Fifth Medical Center of Chinese PLA General Hospital), Yang Yefa (Shanghai Oriental Hepatobiliary Surgery Hospital), Yang Zhengqiang (Cancer Hospital Chinese Academy of Medical Sciences), Ye Xin (First Affiliated Hospital Of Shandong First Medical University), Yin Guowen (Jiangsu Cancer Hospital), Yu Changlu (Tianjin Third Central Hospital), Yu Haipeng (Tianjin Medical University Cancer Institute & Hospital), Yu Youtao (Fourth Medical Center of Chinese PLA General Hospital), Zhai Bo (Renji Hospital Shanghai Jiao Tong University School of Medicine), Zhang Lin (Beijing Tsinghua Changgung Hospital), Zhang Jing (Guangzhou Women and Children Medical Center), Zhang Fujun (Sun Yat-sen University Cancer Center), Zhang Yuewei (Beijing Tsinghua Changgung 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 (Affiliated Hospital of Guizhou Medical University), Zhou Chengzhi (First Affiliated Hospital of Guangzhou Medical University), Zhu Xu (Peking University Cancer Hospital), Zhu Baorang (Fifth Medical Center of Chinese PLA General Hospital) and Zou Yinghua (Peking University First Hospital).