Cryosurgery Therapy (CSA)

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Cryosurgery is a novel technique for treatment of cancer which has been approved by the United States Food & Drug Administration (FDA) in 1998 and China’s SFDA in 1999. Cryosurgery is an important ablation technique for tumors. It destroys tumors by cycles of freezing and thawing. Cryosurgery's destructive effects on tumors are due to two major mechanisms, one immediate, the other delayed. The immediate mechanism is the damaging effect of freezing and thawing the cells. The delayed mechanism is the progressive failure of microcirculation; ultimately, vascular stasis becomes operative as an important cause of tumor tissue destruction.

Cryosurgery mechanism-Click to zoom

Once the temperature falls below -40°C, ice crystals may form within the cells. Once it occurs, cell death is almost certain. During cryosurgery, progressive failure of microcirculation occurs due to a cascade of events: endothelial layer destruction causing vessel walls to become porous, interstitial edema, platelet aggregation, microthrombi, and ultimately vascular congestion and obliteration. It was theorized that during cryosurgery, the immune system of the host became sensitized to the tumor being destroyed by the cryosurgery. Any primary tumor tissue undamaged by the cryosurgery and the metastases were destroyed by the immune system after cryosurgery. This response was termed the "Cryo-Immunological response".

Procedure of cryosurgery

Cryosurgery is performed through intraoperative, endoscopic or percutaneous routes depending upon the location and size of tumor. It is performed by using argon-helium system. Two to three cycles of the freezing/thawing are performed. The freezing continues until the "ice-ball" formed at the tip if the cryoprobe is large enough to cover the tumor. A 5-10 mm margin of normal tissue is included in the freezing process. For larger tumors, multiple cryoprobes were used. In some cases, it may become necessary to perform at least 2-3 sessions of the cryoablation procedure. This is possible because the procedure is minimally invasive, and often does not require cutting. The probes are simply inserted through the skin and guided by real-time ultrasound or CT.

In cryosurgery tissue is frozen with a cryosurgical probes that is brought in good thermal contact with the undesirable tissue. Within several minutes after cooling begins, the temperature of the tissue in contact with the probe reaches the phase transition temperature and the tissue begins to freeze. As more heat is extracted the temperature of the probe continues to drop and the freezing interface begins to propagate outward from the probe into the tissue. A variable temperature distribution in both the frozen and unfrozen regions of the tissue ensues.

In typical cryosurgical protocols, after freezing was completed the cooling system keeps the tissue frozen for a desired period of time, followed by heating and thawing. The cells near the cryosurgical probe surface will be cooled with a higher cooling rate and to lower temperatures than those farther away from the probe. The cells at different locations in the frozen lesion will be at different temperature for various periods of times, as a function of their distance from the probe surface, the cooling material employed, the shape of the cryosurgical probes, the number of the cryosurgical probes used, the type of tissue frozen.

Cell damage during cooling and freezing occurs at several length scales: nanoscale (Armstrong) - molecular, mesoscale (micron) - cellular and macroscale (millimeter) - whole tissue. The damage during cryosurgery is of two types, acute - immediately during cryosurgery and long term.

Advantages

  • Cryosurgery is a localized medical procedure. It can be used as the sole means of cancer treatment or it can be combined with other conventional treatment techniques such as surgical operation, local, systematic, and natural treatments.
  • Combining cryosurgery with excision can be advantageous since freezing the tumor before excision minimizes the risk of spreading the cancerous cells during excision.
  • In addition to sparing healthy tissue, cryosurgery is advantageous because it is not dose-limited can be repeated as necessary in order to destroy all cancerous tissue.
  • In situations where the tumor is not removed after freezing, especially percutaneous cryosurgery, operative blood loss is small and post-surgical discomfort is minimized.
  • Cryoprobes are relatively small (generally in the range of 24 mm in diameter) and therefore they may be used in minimally invasive surgical procedures.
  • There are no major side effects which are commonly found in chemotherapy or radiotherapy.
  • Cryosurgery is adaptable for treatment of tumor close to large vessel which cannot be removed by operation.
  • Cryosurgery can treat small as well as large tumors, and solitary as well as multiple tumors.
  • Cryosurgery aims at a local effect, destruction in situ of neoplasms resistant to conventional treatments, but it also elicits an immunologic reaction (cryo-immunologic reaction) against cancer for eradication of residual or metastatic tumors.
  • There is evidence that the recurrence rate of cancer after cryosurgery is lower than that of operation.
 

Indication

 
Nearly all parenchymal cancers are prime candidates for cryoablation. These malignancies include:
  • Liver cancer
  • Lung cancer (non-small cell lung cancer).
  • Kidney cancer
  • Ovarian cancer
  • Pharyngeal cancer
  • Testicular cancer
  • Uterine tumors
  • Vaginal cancer
  • Pancreatic cancer
  • Breast cancer
  • Sarcoma and other benign or malignant lesions of bone
  • Prostate cancer
  • Skin cancer and melanoma
  • Head and neck cancer
  • Tumor of soft tissues
 
In addition, cryosurgery can be an effective treatment for the following:
  • Retinoblastoma (a childhood cancer that affects the retina of the eye).
  • Early-stage skin cancers (both basal cell and squamous cell carcinomas).
  • Precancerous skin growths known as actinic keratosis.
  • Pre-cancerous conditions of the cervix known as cervical intraepithelial neoplasia (abnormal cell changes in the cervix that can develop into cervical cancer).
 

Specificity

  • Cryoablation employs extremely, low temperature to destroy cancerous tissue. It has been shown to be as effective as surgical, resection for treatment of cancer some parenchymal organs (such as liver, lungs and kidney).
  • Because cryoablation is a focal treatment, it has the advantage over surgical resection of being able to destroy only the necessary amount of targeting tissue while sparing more noninvolved tissue of organ. This is of particular importance to patients with hepatocellular carcinoma, because the majority of these patients have cirrhosis and compromised liver functions. By sparing more "normal" liver, the patients will have greater liver reserve.
  • Because of the warming effect of flowing blood, large blood vessels, such as the aorta, superior or inferior vena cava and portal vein, are impervious to the effect of freezing, the Hence tumors close to these venous systems can be treated with cryo-ablation, whereas resection of tumors close to major vascular structures is not possible.
  • In contrast with ethanol injection or radiofrequency ablation, which are eligible only for small tumors, cryo-ablation is possible for treatment of larger or small tumors. Using various caliber of probes or simultaneous placement of more probes, cryo-ablation can treat the tumor as large as more than 10 cm in size.
  • The treatment can be safely repeated and may be used along with other treatments such as surgery, local, systematic, and natural treatments.

Several studies found that after presumed curative resection, many patients will re-recur, and approximately 25% of these patients will re-recur with the liver alone. This phenomenon suggests that metastatic disease is present, although undetected, within the liver of many patients at the time of resection. Study showed that partial hepatectomy has been associated with the stimulation of growth of this residual tumor. Possible mechanisms for this phenomenon have been proposed including the detrimental effects of surgical manipulation, the generalized immunosuppression provoked by resection, and partial hepatectomy. Growth factors such as FGF-basic which are produced by the liver 48h after partial resection may be the primary stimulus for residual tumor growth stimulation. It has been proved that an increase in survival after cryoablation of hepatic tumors in animals compared to controls that had undergone resection. Unlike partial hepatectomy, cryoablation of experimental liver cancer does not accelerate residual tumor growth in the liver or result in production of the growth factor FGF-basic. The lack of residual tumor growth stimulation may provide therapeutic benefit.

Adverse Effects

  • Cryosurgery does have side effects, although they may be less severe than those associated with surgery or radiation therapy. The effects depend on the location of the tumor.
  • Cryosurgery in the liver may cause damage to the bile ducts and/or major blood vessels, which can lead to hemorrhage (heavy bleeding) or infection.
  • Cryosurgery in lung cancer may induce pneumothorax and pleural effusion.
  • Cryosurgery for prostate cancer may affect the urinary system. Although it also may cause incontinence (lack of control over urine flow) and impotence (loss of sexual function), these side effects are often temporary.
  • When used to treat skin cancer (including Kaposi sarcoma), cryosurgery may cause scarring and swelling; if nerves are damaged, loss of sensation may occur, and, rarely, it may cause a loss of pigmentation and loss of hair in the treated area.
  • When used to treat tumors of the bone, cryosurgery may lead to the destruction of nearby bone tissue and result in fractures, but these effects may not be seen for some time after the initial treatment.

 
Summary

Cryosurgery is an important minimally invasive surgical technique. It can be potentially applied to any procedure in which scalpels are used to remove undesirable tissues. Currently, cryosurgery is being used in many medical fields, such as oncology, dermatology, gynecology, urology, neurology, pulmonary medicine, cardiology oncology and many others. Cryosurgery is also used in veterinary medicine. Imaging monitored cryosurgery has revived the field and numerous new applications are continuously emerging. With new applications came the need for better cryosurgical probes. It is anticipated that cryosurgery will become a standard technique in the minimally invasive surgeon armamentarium. To improve cryosurgery further, there is the need to develop a better fundamental understanding of the mechanisms of tissue damage during cryosurgery, to develop improved imaging techniques for cryosurgery, new and improved cryosurgical device technology and mathematical cryosurgery optimization techniques.


Cases:

1) Lung Cancer

2) Liver Cancer

3) Hysteromyoma

4) Lung cancer

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