A new option for patients with mid- to late-stage liver cancer—Minimally invasive treatment with argon helium knife cryoablation

    With the continuous progress of science and technology, Endocare in the late 1990s applied high-pressure argon (cold medium) and high-pressure helium (hot medium) in cryotherapy. The speed, time and temperature of cooling and warming, the size and shape of the ice ball are fully controllable and precisely set, resulting in the present argon-helium superconducting surgical treatment system-argon helium knife, which was rapidly popularized in the United States and was first introduced to China by Professor Zhang Jiren of Zhujiang Hospital of Southern Medical University in 1999. Zhao Wenhua, Department of Minimally Invasive Oncology, Shandong Qianfo Mountain Hospital
 1.Mechanism of argon helium knife for liver cancer  
    When the gas passes through the evaporator at the tip of the metal rod, the air pressure of the high-pressure argon gas suddenly decreases and will absorb a lot of surrounding heat, while the temperature at the tip of the metal rod drops to 140℃-160℃. Regarding the basic mechanism of cryotherapy, most scholars believe that: 1, intracellular ice crystal formation and mechanical damage of ice crystals; 2, cell dehydration and crumpling, especially the reduction of bound water, will change the physicochemical properties of proteins and produce aggregation; 3, cellular electrolyte toxicity concentration and PH value change; 4, cell membrane lipoprotein component denaturation; 5, blood flow stasis and microthrombus formation. In the area close to the superconducting knife, the temperature drops rapidly to about 140℃-160℃, which causes ice crystals to form rapidly inside and outside the cells. Because the cell wall prevents the formation of ice crystals inside the cells, the solution will be filtered out from the formed ice crystals, making the intercellular fluid tension too strong, and the surrounding cells of the unfrozen liver parenchyma will be dehydrated to balance, and the resulting gradient of compounds will cause the expansion of blood vessels and the rupture of microvessels during the thawing period, so that the short-term hypoxia caused to the cells will cause the death of the surviving cells in the target area. Therefore, the cell death in the treatment target area is the combined effect of ice crystal formation inside and outside the cell, cell dehydration and electrolyte toxicity concentration, and microvascular rupture causing hypoxia.
2.Indications and advantages of argon helium knife for liver cancer treatment  
    In the treatment of primary or secondary hepatocellular carcinoma with argon helium knife, various methods can be adopted, such as common percutaneous targeted treatment of hepatocellular carcinoma under ultrasound or CT guidance; cryotherapy with laparoscopy; intraoperative ultrasound guidance or direct surgical view of hepatocellular carcinoma. It can be used for radical treatment or palliative treatment according to the general condition of the patient and the condition of the mass; it can be used for single treatment or split treatment. The main indications are: 1.tumor diameter less than 3cm, which can be treated radically; 2.combined with severe hepatitis and cirrhosis, liver function is poor and cannot tolerate surgical resection; 3.after resection of the main tumor, there is residual liver or cut edge; 4.recurrent hepatocellular carcinoma, because the residual liver is small, liver function may be lost after resection; 5.metastatic multiple small hepatocellular carcinoma; 6.large mass, which cannot be resected, which can be treated in stages 7. those whose tumors are close to large blood vessels and cannot be radically resected or those whose large hepatocellular carcinoma is found intraoperatively in the left or right half of the liver with unclear borders and imaging shows that the liver tissue on the tumor-free side is obviously compensated and enlarged to more than 50% of the whole liver and cannot be radically resected or the resection effect is judged to be poor or those with metastatic hepatocellular carcinoma whose primary foci can be resected and the number of intrahepatic carcinoma foci is less than 3. If the primary foci can be resected and the number of intrahepatic cancer foci is less than 3, intraoperative argon helium knife cryotherapy can be performed after dissection.
    Ar-He knife has unique advantages in the treatment of liver tumor: 1) less or no bleeding, freezing can make small blood vessels shrink or even coagulate, which has a better hemostatic effect; 2) less painful or even painless; 3) prevent or reduce the spread of cancer cells during surgery; 4) freezing immune effect, freezing may enhance the body’s immune response, thus inhibiting residual cancer cells; 5) can be combined with other treatments, such as interventional treatment plus Ar-He knife. treatment.
3.Effect of argon helium knife in treating liver tumor  
    In 30 cases of unresectable liver tumors treated with percutaneous puncture argon helium-targeted ultrasound using the Endocare surgical system at the First Military Medical University Cancer Center, the tumors were 2-10 cm in diameter and were followed up regularly, and CT showed that there was no enhancement in postoperative enhancement scans for tumors less than 3 cm in diameter, and 90% of the masses larger than 3 cm in diameter were destroyed, and AFP and CEA decreased and half of them returned to normal. Helling reported 9 cases of primary liver cancer and 19 cases of secondary liver cancer after cryoablation: 3 patients with primary liver cancer survived from 29 to 47 months, 2 patients with secondary liver cancer survived 12 and 16 months, respectively, and 9 patients survived with disease from 13 to 58 months, and the remaining survival time was less than 1 year with few complications, and the average hospital stay at the time of treatment was 6.7± 2.8 days at the time of treatment. Lee et al. summarized several studies of cryotherapy for primary and metastatic liver tumors and reported that the overall survival rate was 46%-89% in all patients with follow-up time of more than 20 months.
4. Complications of argon helium knife for liver tumors
    Complications of argon helium knife for liver tumor include: 1. Bleeding: including postoperative bleeding and postoperative hemorrhage. Postoperative bleeding mostly occurs within 48h after surgery, mainly two kinds of bleeding through frozen puncture tract and frozen rupture bleeding of liver peritoneum, and serious cases may appear hemorrhagic shock. The less severe cases can be controlled by conservative treatment, and Professor Qian Guojun of the Eastern Hepatobiliary Hospital of the Second Military Medical University applies dilating tubes with outer sheaths, and postoperative filling of gelatin sponge and hemostatic biogel by dilating tubes can significantly reduce the occurrence of bleeding. 2, postoperative upper gastrointestinal bleeding: postoperative upper gastrointestinal bleeding, mostly occurs 2 weeks after argon helium knife cryosurgery, clinically manifested as blood in the stool and other symptoms of gastrointestinal bleeding. The incidence is low and the specific cause is unknown, probably related to poor liver function and the wide range of freezing. 3, acute myoglobinuria: acute myoglobinuria after cryosurgery has been reported in almost all cases, and in most cases myoglobinuria is limited to 1 to 3 days postoperatively. In severe cases, myoglobinuria can lead to acute tubular necrosis and renal failure, so preoperative renal function should be checked, postoperative hydration and diuretics should be applied, and attention should be paid to alkalinizing the urine. 4. The clinical temperature during cryopreservation is too low, chills, and even cold shock occur. A device that circulates warmed air around the patient’s body can be used to control the temperature, and at the same time, intravenous or intramuscular injection of dexamethasone and other evidence-based treatment. 5, biliary fistula, pneumothorax, intestinal fistula and other complications that occur after injury to the perihepatic tissues. Therefore, adequate preoperative preparation and precise positioning are required, and intraoperative argon helium knife treatment should be performed intraoperatively if it is too close to the surrounding important tissues.6. Other complications include fever, pleural effusion, acute lung injury and liver failure.
    In 2008, the International Cryotherapy Society authorized Shandong Qianfushan Hospital as the International Tumor Cryotherapy Center of Ar-He knife and the International Research Center of Ar-He Cryotherapy. “At present, it is the earliest hospital in Shandong Province to carry out argon helium knife and the largest number of operations, and has carried out nearly 100 cases of argon helium knife cryotherapy for liver cancer, which has achieved good treatment results, greatly improved the patients’ life treatment and prolonged their lives.