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Cryoablation (cryo)

Principle
Cryoablation was patented in the US for use in aviation. Cryoablation devices include trocar-type probes of various thicknesses, which are guided into tumor tissue using imaging devices. Cryoprobes deliver liquefied argon to reduce the temperatures to -160 to -180℃, which results in the formation of ice crystals within the tumor tissue. The cryoprobe then delivers helium to warm the tissue to 25℃. This rapid change in temperature disrupts tumor tissue. The speed at which the temperature drops determines how ice crystals form within the tumor tissue. A rate of 100℃ per minute appears to be ideal, subsequently leading to the death of the tumor cells when the temperature increases to -10℃. During argon-helium cryoablation, tissue in the center of the tumor is disrupted by the freezing of water. The surrounding tissue is not frozen; however, the difference in osmotic pressure caused by the rupturing of central cells is often sufficient to cause the death of surrounding cells. Cryoablation can also freeze blood vessels, which can have an effect equivalent to that of blood clots, wherein ischemia causes further tumor necrosis. The freezing of tumor cells also appears to make them more sensitive to chemotherapy or radiotherapy; however, there is currently insufficient evidence to support this supposition.
 

Benefits of cryo
Normal tissue and organs proximal to the tumor are not damaged by cryoablation. Cryoablation is a minimally invasive surgery, and when percutaneously applied, this method produces little bleeding and a small wound. This technique is suitable for patients of any age and condition. Frozen tumor cells activate the immune system to clear the dead cancer cells. Among the ablation methods, argon-helium cryoablation is particularly well-suited to the treatment of larger tumors and tumors with blood vessels. Large vessels are less susceptible to freezing, such that cryoablation can be used to treat tumors proximal to large vessels. The type and number of probes depends on the size of ice crystals and therapeutic range desired by the surgeon. Rapid freezing is able to block nerve conduction and stop pain, which makes it a natural anaesthetic.

As many as eight argon-helium cryoablation probes can be implemented simultaneously, and multiple tumors can be treated at once. As with thermal ablation, cryoablation can be combined with other treatment methods, such as surgery and chemotherapy.
 

Limits of cryo
Cryoablation is inappropriate for patients with multiple metastases and those in advanced stages of cancer. As with thermal ablation, cryoablation is a local treatment best suited to patients with a small number of tumors or tumors within a single organ. In cases where the tumor is more than half the size of the liver, argon-helium cryoablation can cause liver failure. Treating a tumor that is too large or treating too many tumors at once can result in the excessive release of tumor necrotic substances, resulting in shock. Thus, large tumors are generally divided into several regions to be frozen separately. Cryoablation has been used to treat tumors exceeding eight centimeters in size; however, five centimeters remains the limit in treating liver tumors.

The cryoprobe is thick enough to ablate a large region, but it also creates a larger insertion that increases the risk of bleeding. Thus, tumors are generally accessed using laparoscopic or surgical methods. Cryoablation is limited with regard to control of the shape of the frozen zone, monitoring the formation of ice crystals, and minimizing damage in surrounding healthy tissue. A single treatment cycle takes approximately ten minutes. In a clinical setting, one treatment cycle is generally sufficient to reach ninety-five percent of the target tissue; however, ensuring complete eradication of the tumor requires repeated treatment cycles. Despite the fact that therapeutic efficiency is lower than that of thermal ablation; a cryoablation system can cost as much as several hundred thousand dollars. Thus, except in special circumstances, thermal ablation is generally preferred.
 

When to use

  1. According to the literature, cryoablation has been used for cancers of the prostate, liver, gallbladder, kidney, pancreas, breast, bone, skin and other soft tissue. In Taiwan, this method is commonly used for liver, kidney, lung and prostate cancer. Health insurance in Taiwan partially covers the cost of treatment for kidney and prostate cancer. The American Urological Association officially listed cryoablation as a formal treatment option for the treatment of local prostate cancer (first to third stages, without metastasis).
  2. Cryoablation can be performed surgically or percutaneously using tomography or ultrasound for guidance. The visibility of ice in the CT makes it possible to confirm that the entire tumor has been effectively treated, without damage to normal tissue. In the case of prostate cancer, four to eight probes are usually inserted from the perineum using ultrasound for guidance.
     

Preoperative considerations of cryo

  1. Regular testing of blood, liver and kidney function, and coagulation.
  2. Patients who receive the CT-guided procedure may need to undergo transcatheter arterial embolization to facilitate positioning. It is not required for patients who receive the ultrasound-guided procedure.
  3. Consent forms.
  4. Patients receiving local anesthesia do not have to fast, but they must not eat excessively. Patients undergoing systemic anesthesia must observe fasting for no less than six hours.
     

Intraoperative considerations of cryo

  1. Use of local anesthesia, intravenous anesthesia, or general anesthesia as required.
  2. Use of ultrasound-guided or CT-guided procedures as needed for treatment.
  3. Selection of percutaneous treatment, endoscopic therapy, or conventional surgical treatment.
  4. Intraoperative conscious patients in any discomfort should contact healthcare providers.
  5. Successful treatment usually requires at least two cycles of freezing and thawing, such that treatment affects the entire tumor and 5-10 mm of healthy tissue. Multiple cryoprobes are commonly required for large tumors.
     

Postoperative considerations of cryo

  1. Patients that undergo percutaneous treatment should lie down or lie on one side for at least six hours to facilitate hemostasis. This is not necessary for patients that undergo endoscopic or conventional surgery.
  2. Patients that undergo percutaneous treatment may begin drinking or eating six hours after treatment. They must continue fasting if vomiting ensues and/or they feel discomfort. Patients that undergo endoscopic or conventional surgery should follow the advice of their physician with regard to the intake of food and liquids.
  3. It is normal for a portion of the wound to be painful and/or exhibit signs of bleeding. If the pain becomes too severe, a physician or nurse should be contacted for advice.
  4. Routine tests of blood and inflammation should be reviewed the following day to check for complications.
  5. The gauze covering the percutaneous wound may be removed after 24 hours.
  6. Ultrasound is unable to distinguish changes in the tumor after treatment. Thus, computerized tomography or magnetic resonance imaging must be used to track tumor progress. This is generally conducted at the first examination one month after treatment to ensure that any viable tumors are dealt with in a timely manner. Further regular examinations are then conducted every three to four months.
     

Risks and Complications
Common complications include bleeding, abnormal clotting, platelet destruction, pain, damage to treated organs (e.g., bile duct injury when treating the liver and hematuria when treating the kidney), lung complications, and infection. These issues are observed in 15% of patients. Following treatment of the prostate, the incidence of urinary incontinence is less than 10% and the incidence of rectal fistula is 0-3%. In 3-4% of patients, cryoablation can lead to cryoshock through the formation of free radicals, resulting in multi-organ failure.​