Modern applications of cryosurgery in oncology

Cancer a diseases that cause cells in the body to change and loos the control. Most of the types of cancer cells form a mass called a tumor. Breast Cancer is a type of cancer that begins in the breast . Most breast cancers begin in the breast tissue made up of glands called lobules and the ducts that connect the lobules to the nipple. The remainder of the breast is made up of fatty, connective, and lymphatic tissues [1]. Breast cancer is the most common cancer in US women and is the second leading cause of cancer death among women. In 2019, an estimated 268,600 new cases of invasive breast cancer will be diagnosed among women. More than 3.8 million US women with a history of breast cancer were alive as per the survey report on January 1, 2019. More than 150,000 breast cancer survivors are living with metastatic disease, three-fourths of whom were originally diagnosed with stage I-III [2]. Even though there are various treatment options like Systemic therapy, Surgery, Radiation therapy, Chemotherapy: Hormonal therapy, Targeted therapy and Immunotherapy. The modern cryosurgery technology give complete cure.


Introduction
Cancer a diseases that cause cells in the body to change and loos the control. Most of the types of cancer cells form a mass called a tumor. Breast Cancer is a type of cancer that begins in the breast . Most breast cancers begin in the breast tissue made up of glands called lobules and the ducts that connect the lobules to the nipple. The remainder of the breast is made up of fatty, connective, and lymphatic tissues [1]. Breast cancer is the most common cancer in US women and is the second leading cause of cancer death among women. In 2019, an estimated 268,600 new cases of invasive breast cancer will be diagnosed among women. More than 3.8 million US women with a history of breast cancer were alive as per the survey report on January 1, 2019. More than 150,000 breast cancer survivors are living with metastatic disease, three-fourths of whom were originally diagnosed with stage I-III [2]. Even though there are various treatment options like Systemic therapy, Surgery, Radiation therapy, Chemotherapy: Hormonal therapy, Targeted therapy and Immunotherapy. The modern cryosurgery technology give complete cure.

Cryosurgery technology
Cryosurgery technology has made great strides in the last few years. Cryosurgery is a potential alternative for the various disease treatment due to the resulting changes that occur to tissues during and after the freeze-thaw process and initial clinical results. Cryosurgery being established as a primary in situ therapy for breast cancer and also to various other diseases. Modern Technological advancements of cryosurgery technology, advances in ultrasound technologies that allow accurate real time visualization of the cryosurgical process [3].

Brief history of cryosurgery
In 11 th century, 980-1037 Cold is used for anesthetic property [4]. Hippocrate stated that the use of cold water in an acute gout attack was used with success on himself [5], in 1650. In 16th century , 1661 effect of cold as an anaesthetic [6]. In Russian campaign cold and snow applied to reduce pain and haemorrhage. During the Russian campaign the temperature below -50° C , the effect of cold has a sedative effect on the brain and nervous system.in 1777 cold showed the destructive effect when used in the treatment of tumours. [7][8][9][10] In 1851 so many studies has been conducted on cold or ice and it applications as anesthetic and in cancer at -12 o C to -55 o C. In 1882 Paris , use extreme cold as produced by methyl chloride to treat tumours [11]. In 1833 ice cold water is used to treat chronic cervicitis. In 19th century , certain tumours are treated

Mechanisms of freezing injury
In 1960 the cryosurgery procedure adopted fast freezing ,slow thawing and repetition of the same cycle were followed.
In 1964 Cooper identifi ed the holding the tissue at 200C for one minute could induce necrosis process [13]. In cryosurgery the tissue has been freeze with a help of cryosurgical probe brought in contact with the abnormal tissue. The probe is cooled due to the circulation of cooling fl uid. The probe will deliver the cooling fl uid. Within few minutes the cooling begins.
The cooling fl uid extract the heat from the tissues, though the probe. At that time the frozen tissue has a temperature distribution that ranges from a low cryogenic temperature at the tissue surface in contact with the probe to the phase transformation temperature on the outer edge of the frozen lesion. In the cryosurgical protocols ,after freezing ,the frozen tissue is heating and thawing. The frozen tissue is warmed with the help of probe surface by a warming fl uid circulating through the cryosurgical probe. Cryosurgery procedure may last to several minutes to an hour. The cell near to the probe surface will be cooled at higher cooling rate and to lower temperature than away from probe.The cell at different locations will be at different temperatures for various period of time. The cell damage during the cooling and freezing can be: Nano scale ,micron scale and macro scale. The damage during cryosurgery can be of two types acute and long term [13][14][15]. the plasma proteins will be weakens and make them fragility to mechanical damage. The denaturation of proteins due to change in the intracellular ion and temperature. Most of the cell can withstand the cool temperature above the freezing but it depends on the time scale in the cryosurgery process. The major exceptions are the cell that are highly sensitive to the ions are platelets ,during cooling the platelets allows the infl ux of calcium and it appears to trigger activation of platelets. This cascade of process will end in the platelet aggregation and this leads to obstruction of blood vessels in the cooled region. Meiotic spindles are sensitive to hypothermia, resulting in depolymerization. oocytes cooled to 0°C for 2 min to 3 min, the meiotic spindle cooled at 0°C for 3min are shortened and disappeared [18][19].  intracellular organelle and cell membrane disruption has been implicated. The freezing may stimulate immunological injury.

The effect of freezing
The immune system become sensitized to the destroyed frozen tissue, it leads to the attack. The freezing involves the vascular and connective tissue damage.The freezing results in stasis of blood fl ow ,which lead to ischemia and to cell necrosis [24][25][26].

Effects of thawing and warming
Thawing and warming induce cellular damage. During thawing, ice melts, the extracellular solution is hypotonic, causing rupture to the membrane. When thawing is rapid some cells may remain hypertonic at body temperature, which could induce metabolic disruption and additional damage [27]. The effects of thawing depends on the freezing temperature and cooling rate. The slow thawing allows solute to maximum ice growth and recrystallization to take place. The thawing before an another cycle is important in to the success of cryosurgery [28]. The rapid cooling followed by rapid thawing is benefi cial.
During rapid cooling, the ice crystals tend to be small, with high surface energies. The longer the thawing, the easier the ice to recrystallize, especially crystals with high surface energies.
The larger ice crystals can be more destructive than the smaller ones, the size of the crystals and the force generated during recrystallization [29]. During warming , in a frozen state , ice tends to recrytalize at high subzero temparature.
Recrytalization will cause further disruption of extracellular and macroscopic structure of the tissue [30,31]. with percutaneous cryotherapy.Using ultrasonic or CT scan guidance, this minimally interference was carried out [34].

Cryosurgery in breast cancer
The mean main lesion diameter was 16 ± 12 mm (size range 5-45 mm). During the follow-up period, we obtained full regression of the primary breast lesion without recurrence in 15 patients. After the operation, all were instantly relaxed and lastingly through all follow-up. These fi ndings indicate that primary breast lesion cryosurgery appears to be well suited for metastatic patients' palliative care, especially due to its good tolerance, low complication rate and ability to provide local or analgesic control [34].
Under CT guidance a single board certifi ed interventional radiologist performed all cryoablation sessions. Percutaneous cryoablation was performed using a cryoablation unit based on the argons. To determine the correct positioning of the tumor ablation probes, both preoperative CT and MRI images were compared. All the procedures were conducted under conscious sedation, using 50 μg fentanyl citrate intravenous bolus, and local anesthesia. Vital signs were continuously tracked throughout the entire process. To determine the degree of tumor necrosis, all patients, except three, were tested preoperatively and post-operatively with breast MRI. The mean size for the tumor was 3.02 ± 1.4 cm. Six patients developed multicenter disease. Complete tumor necrosis at 2-month and 6-month follow-up was 85.7 percent, and 100 percent , respectively, as 5 patients with tumors > 3 cm required redo cryoablation. No patient had signifi cant complications. During an average 46-month follow-up (range 3-84), 7 patients (20%) suffered local recurrences treated with redo cryoablation, and 7 (20%) died as a result of disease progression. The fi ndings indicate cryoablation of the primary tumor in the treatment of patients with stage IV breast cancer is safe and reliable [35].
Cryoablation is a safe breast-conserving treatment for Breast Cancer. Achieved excellent rates of local tumor control(90%), on an average sub optimal local tumor control was noted compared with RF ablation. An advantage of cryoablation over RF ablations the possibility to perform the procedure under local anesthesia and potentially on an outpatient basis. The best clinical results are achieved when small(o-15mm)ductal tumors are treated with an ice ball larger than the tumor [36].

Nipple adenoma
A 29-year-old woman with a three-year history of serosanguineous intermittent-painless discharge from her left nipple with regular mammography and ultrasound. The patient was diagnosed with nipple adenoma and was confi rmed. Cryosurgery is a technique of minimally invasive surgery that stands as a tissue-sparing alternative for this benign condition. The dermoscopic pattern identifi ed by us is unspecifi ed but polymorphic vessels will trigger a biopsy to get a defi nitive diagnosis. This is the fi rst dermoscopic diagnosis of such condition to our knowledge and the second recorded case of a positive cryosurgical operation [37].

Application of cryosurgery techniques in various clinical aspects
Dermatology: The application of cryosurgery/cryotherapy in dermatology. The skin cryosurgery requires rapid freezing and slow thawing, minimum tissue temperature of -25 to -60 o C. Frozen tissue reacts immediately after thawing, followed