What is cryotherapy

Cryotherapy literally means cold therapy. When you press a bag of frozen peas on a swollen ankle or knee, you are treating your pain with a modern (although basic) version of cryotherapy. Cryotherapy is also called cryosurgery, cryoablation, percutaneous cryotherapy or targeted cryoablation therapy, is a minimally invasive treatment that uses extreme cold to freeze and destroy diseased tissue, including cancer cells. Although cryotherapy and cryoablation can be used interchangeably, the term “cryosurgery” is best reserved for cryotherapy performed using an open, surgical approach.

Cryotherapy is a commonly used in-office procedure for the treatment of a variety of benign and malignant lesions. In one report, cryotherapy was the second most common in-office procedure after skin excision. The mechanism of destruction in cryotherapy is necrosis, which results from the freezing and thawing of cells. Treated areas reepithelialize. Adverse effects of cryotherapy are usually minor and short-lived.

Dermatologists have used cryotherapy since the turn of the century. After the development of the vacuum flask to store subzero liquid elements, such as nitrogen, oxygen, and hydrogen, the use of cryotherapy dramatically increased. By the 1940s, liquid nitrogen became more readily available, and the most common method of application was by means of a cotton applicator. In 1961, Cooper and Lee ¹⁾ introduced a closed-system apparatus to spray liquid nitrogen. In the late 1960s, metal probes became available. By 1990, 87% of dermatologists used cryotherapy in their practice ²⁾. The general advantages of cryotherapy are its ease of use, its low cost, and its good cosmetic results. Most skin cancers are treated with excision or other destructive procedures, such as electrodesiccation and curettage. Superficial basal cell skin cancers ³⁾ and Bowen disease can be treated with cryotherapy.

Recurrence rates for primary basal cell carcinoma vary with treatment modality. The 5-year recurrence rate for cryotherapy may be as low as 7.5% if lesions are chosen judiciously ⁴⁾. This percentage compares favorably with published recurrence rates following other procedures. Published rates include surgical excision, 10.1%; curettage and electrodesiccation, 7.7%; radiation therapy, 8.7%; and all non-Mohs modalities, 8.7%. Because these percentages are derived from various studies, rather than one randomized controlled study comparing the different modalities, they should be viewed as rough approximations. Well-circumscribed tumors are most suitable for cryotherapy. The indolent local growth of these well-circumscribed tumors accounts for the high cure rates quoted in the literature. In most instances, reimbursement for cryotherapy treatment of skin cancers is at the same rate as for destruction of benign lesions.

During cryotherapy, liquid nitrogen or high pressure argon gas flows into a needle-like applicator (a cryoprobe) creating intense cold that is placed in contact with diseased tissue. Physicians use image-guidance techniques such as ultrasound, computed tomography (CT) or magnetic resonance (MR) to help guide the cryoprobes to treatment sites located inside the body.

Cryotherapy commonly refers to a treatment in which surface skin lesions are frozen.

Cryogens used to freeze skin lesions include:

• Liquid nitrogen (the most common method used by doctors)
• Carbon dioxide snow (more commonly used 20 years ago)
• Dimethyl ether and propane or DMEP (available over the counter as Wartner®)

Cell injury occurs during the thaw, after the cell is frozen. Because of the hyperosmotic intracellular conditions, ice crystals do not form until -5°C to -10°C ( 23 °F to 14 °F). The transformation of water to ice concentrates the extracellular solutes and results in an osmotic gradient across the cell membrane, causing further damage. Rapid freezing and slow thaw maximize tissue damage to epithelial cells and is most suitable for the treatment of malignancies. Fibroblasts produce less collagen after a rapid thaw ⁵⁾. Therefore, a rapid thaw may be more suitable for the treatment of keloids or benign lesions in areas prone to scarring ⁶⁾.

Freeze damage can be seen when a steak is defrosted from the freezer. The steak juices that are seen when fully thawed represent the intracellular liquid that has escaped because of the damage to the cell wall. Low temperature also ensures maximum damage by further concentrating electrolytes intracellularly.

Keratinocytes need to be frozen to -50°C (-58 °F) for optimum destruction. Melanocytes are more delicate and only require a temperature of -5°C (23 °F) for destruction. This fact is the reason for the resulting hypopigmentation following cryotherapy on darker-skinned individuals. Malignant skin cancers usually need a temperature of -50°C (-58 °F), while benign lesions only require a temperature of -20°C to -25°C (-4 °F to -13 °F).

The last response to cryotherapy is inflammation, which is usually observed as erythema and edema. Inflammation is the response to cell death and helps in local cell destruction.

A thorough cryotherapy treatment causes basement membrane separation, which may result in blister formation.

What are some common uses of cryotherapy?

Cryotherapy can be applied topically (on the skin surface), percutaneously, or surgically. Topical cryotherapy is used typically in the case of skin and eye lesions. When the lesion is situated below the skin surface, a needle-like therapy probe or applicator needs to be placed through the skin. Occasionally, a surgical incision is required.

Cryotherapy is used to treat:

• skin tumors.
• pre-cancerous skin moles.
• nodules.
• skin tags.
• unsightly freckles.
• retinoblastomas, a childhood cancer of the retina.
• prostate, liver, and cervical cancers, especially if surgical resection is not possible.

Cryotherapy is also being used to treat tumors in other parts of the body, such as the kidneys, bones (including the spine), lungs, and breasts (including benign breast lumps called fibroadenomas). Although further research is needed to determine its long term effectiveness, cryotherapy has been shown to be effective in selected patients.

How does cryotherapy work?

Cryotherapy uses nitrogen or argon gas to create extremely cold temperatures to destroy diseased tissue. To destroy diseased tissue located outside the body, liquid nitrogen is applied directly with a cotton swab or spray device. For tumors located below the skin surface and deep in the body, the physician will use image-guidance to insert one or more applicators, or cryoprobes, through the skin to the site of the diseased tissue and then deliver the liquid nitrogen or argon gas.

Living tissue, healthy or diseased, cannot withstand extremely cold conditions and will die from:

• ice formation in the fluid outside cells, which results in cellular dehydration.
• ice formation within the cell. At approximately -40°C (-40°F) or less, intracellular lethal-ice crystals begin to form and will destroy almost any cell.
• bursting from both swelling caused by ice expansion inside the cell or shrinking caused by water exiting the cell.
• loss of blood supply. Cells die when their blood supply is choked off by ice forming within small tumor blood vessels, causing clotting. Since the average blood-clotting time is approximately 10 minutes, the extreme cold is maintained for at least 10-15 minutes, if not longer, to assure that lethal-ice temperatures have been reached. Direct observation of the ablation temperature is possible with some apparatuses.

Because cryotherapy consists of a series of steps that lead to cell death, tumors are repeatedly frozen and thawed; typically, two or more freeze-thaw cycles are used.

Once the cells are destroyed, the white blood cells of the immune system work to clear out the dead tissue.

Cryotherapy side effects

Immediate side effects:

• Pain- cryotherapy is usually well-tolerated but can sometimes be painful if a deep freeze has been necessary (i.e. to treat a basal cell carcinoma). This discomfort can occur both at the time of treatment and for a variable time thereafter. Painkillers (such as paracetamol) taken for the first 24 hours may relieve the discomfort; also taking a painkiller an hour or so prior to the anticipated treatment may reduce the discomfort.
• Swelling and redness- this is a normal immediate response to freezing the skin and usually settles after two to three days. For a short while the treated area may ooze a little watery fluid. Cryotherapy close to the eyes may induce prominent puffiness of the lower eyelids which settles within days.
• Blistering- this is also a common consequence of cryotherapy and blisters settle after a few days as the scab forms. Some people blister more easily than others and the development of blisters does not necessarily mean that the skin has been frozen too much. Occasionally the blisters may become filled with blood; this is harmless and should only be punctured if a blister is painful and very uncomfortable, using a sterile needle. We would suggest you gain advice from your doctor who performed the treatment before doing this.
• Infection- uncommonly, infection can occur, resulting in increased pain and the formation of pus: this may require topical antiseptic or antibiotic therapy from the doctor who performed the treatment or your doctor.

Subsequent side effects:

• Scarring- rarely, a scar will form, especially if a deep freeze has been necessary (i.e. to treat a basal cell carcinoma).
• Hypertropic/Keloid scarring– very rarely a raised scar can form following treatment with cryotherapy which appears as a rounded, hard growth on the skin. These are harmless lesions, more common in dark skinned individuals compared to Caucasians.
• Pigmentation changes- the skin at and around the treatment site may lighten or darken in colour, especially in dark-skinned people. This usually improves with time but may be permanent.
• Numbness- if a superficial nerve is frozen, it may result in numbness of the area of skin supplied by that nerve. Normal feeling usually returns within a matter of months.
• Treatment may not be effective, or the condition may recur.

Skin lesions treated with cryotherapy

Lesions that may treated by cryotherapy include:

• Actinic keratoses
• Viral warts in older children and adults
• Seborrhoeic keratoses (senile warts)
• Molluscum contagiosum in adults
• Skin tags*

*Diathermy may be more effective for acrochordons / fibroepithelial polyps.

The following skin cancers may be suitable for cryotherapy if performed by a medical practitioner with appropriate training and where the lesion has been identified by biopsy:

• Small, thin, typical, superficial basal cell carcinoma on trunk and limbs
• Small, typical intraepithelial squamous cell carcinoma on trunk and limbs

Specialist dermatologists sometimes freeze small skin cancers such as superficial basal cell and in situ squamous cell carcinomas (intraepidermal carcinoma, Bowen disease), but this is not always successful so careful follow-up is necessary.

Freezing may be the most suitable way of getting rid of many different kinds of surface skin lesion. It is relatively inexpensive, safe, and reliable. However, it is important that the skin lesion has been properly diagnosed. It should not be used to treat melanoma or any undiagnosed pigmented lesion that could be melanoma.

Liquid nitrogen

Cryotherapy using liquid nitrogen (temperature –196°C or –320.8°F) involves the use of a cryospray, cryoprobe or a cotton-tipped applicator. The nitrogen is applied to the skin lesion for a few seconds, depending on the desired diameter and depth of freeze. The treatment is repeated in some cases, once thawing has completed. This is known as a ‘double freeze-thaw’.

Carbon dioxide snow

Carbon dioxide cryotherapy involves making a cylinder of frozen carbon dioxide snow (–78.5°C or –109.3°F) or a slush combined with acetone. It is applied directly to the skin lesion.

Dimethyl ether and propane (DMEP)

DMEP works at a temperature of –57°C (–70.6 °F). It comes in an aerosol can available over the counter. It is used to treat warts using a foam applicator pushed onto the skin lesion for between 10 and 40 seconds, depending on its size and site.

Cryotherapy stings and may be painful, at the time and for a variable period afterwards. There may be immediate swelling and redness. This may be reduced by applying a topical steroid on a single occasion straight after freezing. Aspirin orally may also reduce the inflammation and discomfort.

Contraindications to cryotherapy

• Undiagnosed skin lesions
• Lesion for which tissue pathology is required
• Lesion within a circulation compromised area
• Melanoma
• Previous sensitivity or adverse reaction to cryosurgery
• Patient unable to accept side effects
• Patients with poor circulation
• Unconscious patients
• Young children
• Dark skinned patients

Precautions when using cryotherapy

• Areas not recommended for liquid nitrogen application: corners of eyes, fold of skin between nose and lip, skin surrounding nostrils and skin overlying nerves, e.g. sides of digits, below the knee in certain groups (eg diabetics, elderly)
• Re-appearance of a lesion previously treated with cryotherapy should be referred for review by medical practitioner
• Recurrent skin cancers after cryotherapy may be more difficult to treat
• Exercise care in patients with history of slow healing or skin infection
• Prolonged freezing may result in scarring – better to freeze lightly and for the patient to return for re-freeze if response is inadequate
• Cryotherapy leaves permanent white marks which may be very unsightly, especially in dark skinned patients
• Cryotherapy may sometimes cause nerve damage and on-going pain in some danger areas where the nerves lie superficially (eg sides of the fingers)

Complications of cryotherapy

The main concern is secondary wound infection, but this is uncommon. Infection may cause increased pain, swelling, thick yellow blister fluid, a purulent discharge and/or redness around the treated area. Consult your doctor if you are concerned: topical antiseptics and/or oral antibiotics may be necessary.

Other undesirable effects may include:

• Delayed healing and ulceration
• Local nerve damage (usually temporary)
• Permanent hypopigmentation or scar
• Persistent or recurrent skin lesions, necessitating further cryotherapy, surgery or other treatment.

Results of cryotherapy

After a standard freeze of a actinic keratosis, seborrhoeic keratosis or viral wart, the skin may appear entirely normal without any sign of the original skin lesion.

Looking after the treatment area

The treated area is likely to blister within a few hours. Sometimes the blister is clear and sometimes it is red or purple because of bleeding (this is harmless). Treatment near the eye may result in a puffy eyelid, especially the following morning, but the swelling settles within a few days. Within a few days a scab forms and the blister gradually dries up.

Usually no special attention is needed during the healing phase. The treated area may be gently washed once or twice daily, and should be kept clean. A dressing is optional, but is advisable if the affected area is subject to trauma or clothes rub on it.

When the blister dries to a scab, apply petroleum jelly (Vaseline) and avoid picking at it. The scab peels off after 5–10 days on the face and 3 weeks on the hand. A sore or scab may persist as long as 3 months on the lower leg because healing in this site is often slow.

Cryotherapy for warts

Warts are small growths on the skin that normally don’t cause pain. Some warts itch and may hurt, especially if they’re on your feet. There are five kinds of warts:

• Common warts usually appear on the hands
• Flat warts usually appear on the face and forehead
• Genital warts (condyloma) appear on the genitals, in the pubic area and between the thighs
• Plantar warts are found on the bottoms of the feet
• Subungual and periungual warts are found under or around the fingernails and toenails

What causes warts?

Warts are a type of infection caused by viruses in the human papillomavirus (HPV) family. There are more than 100 types of HPV. Warts can grow on all parts of your body. They can grow on your skin, on the inside of your mouth, on your genitals and on your rectal area. Common types of HPV tend to cause warts on the skin (such as the hands and fingers), while other HPV types tend to cause warts on the genitals and rectal area. Some people are more naturally resistant to the HPV viruses and don’t seem to get warts as easily as other people.

Can warts be passed from one person to another person?

Yes, warts on the skin may be passed to another person when that person touches the warts. It is also possible to get warts from using towels or other objects that were used by a person who has warts.

Warts on the genitals are very contagious and can be passed to another person during oral, vaginal or anal sex. It is important not to have unprotected sex if you or your partner has warts on the genital area. In women, warts can grow on the cervix (inside the vagina), and a woman may not even know she has them. She may pass the infection to her sexual partner without knowing it.

Will warts go away on their own?

Often warts disappear on their own, although it may take many months or even years for the warts to go away. But some warts won’t go away on their own. Doctors are not sure why some warts disappear and others do not.

Do warts on the skin need to be treated?

Generally, yes. Common warts are often bothersome. They can bleed and cause pain when they’re bumped. They can also be embarrassing, for example, if they grow on your face. Treatment may decrease the chance that the warts will be spread to other areas of your body or to other people.

How are warts on the skin removed?

First of all, it’s important to know that warts on the skin (such as on the fingers, feet and knees) and warts on the genitals are removed in different ways. Don’t try any home remedies or over-the-counter drugs to remove warts on the genital area. You could hurt your genital area by putting certain chemicals on it. You also shouldn’t treat warts on your face without talking to your doctor first. The following are some ways to remove common warts from the skin:

Talk to your doctor about which treatment is right for you.

• Applying salicylic acid. You can treat warts on places such as the hands, feet or knees by putting salicylic acid (one brand name: Compound W) on the warts. To get good results, you must apply the acid every day for many weeks. After you take a bath or shower, pat your skin dry lightly with a towel. Then put salicylic acid on your warts. The acid sinks in deeper and works better when it is applied to damp skin. Before you take a shower or a bath the next day, use an emery board or pumice stone to file away the dead surface of the warts.
• Applying cantharidin. Your doctor may use cantharidin on your warts. With this treatment, the doctor “paints” the chemical onto the wart. Most people don’t feel any pain when the chemical is applied to the wart. You’ll experience some pain and blistering of the wart in about 3 to 8 hours. After treatment with cantharidin, a bandage is put over the wart. The bandage can be removed after 24 hours. When mixtures of cantharidin and other chemicals are used, the bandage is removed after 2 hours. When you see your doctor again, he or she will remove the dead skin of the wart. If the wart isn’t gone after one treatment, your doctor may suggest another treatment.
• Applying liquid nitrogen. Your doctor may use liquid nitrogen to freeze the wart. This treatment is called cryotherapy or cryosurgery. Applying liquid nitrogen to the wart causes a little discomfort. To completely remove a wart, liquid nitrogen treatments may be needed every 1 to 3 weeks for a total of 2 to 4 times. If no improvement is noted, your doctor may recommend another type of treatment.
• Other treatments for warts on the skin. Your doctor can also remove warts on the skin by burning the wart, cutting out the wart or removing the wart with a laser. These treatments are effective, but they may leave a scar. They are normally reserved for warts that have not cleared up with other treatments.

How does cryotherapy work for wart?

Cryotherapy is a 2-step process that removes the wart without hurting the skin around it.

The first step is getting your wart ready to be removed. You can help with this step. The second step is freezing the wart, which will be done by your doctor in his or her office. You may need to have several freezing treatments before the wart is completely removed.
What do I need to do to prepare the wart for cryosurgery?

You must do some things on your own at home to get the wart ready for removal. Doing these things before you come to your doctor’s office can reduce the number of freezing treatments you need. You should do the following:

1. Every night for 2 weeks, clean the wart with soap and water and put 17% salicylic acid gel on it.
2. After putting on the gel, cover the wart with a piece of 40% salicylic acid pad (one brand name: Mediplast). Cut the pad so that it is a little bit bigger than the wart. The pad has a sticky backing that will help it stay on the wart.
3. Leave the pad on the wart for 24 hours. If the area becomes very sore or red, stop using the gel and pad and call your doctor’s office.
4. After you take the pad off, clean the area with soap and water, put more gel on the wart and put on another pad. If you are very active during the day and the pad moves off the wart, you can leave the area uncovered during the day and only wear the pad at night.

After 2 weeks of this treatment, your wart will have turned white and will look fluffy. Your doctor will then be able to remove the white skin layer covering the wart and use cryosurgery to freeze the base (root) of the wart. If your skin reacts strongly to cold, tell your doctor before cryosurgery.

Cryosurgery can be uncomfortable, but it usually isn’t too painful. The freezing is somewhat numbing. When your doctor places the instrument on your skin to freeze the wart, it will feel like an ice cube is stuck to your skin. Afterward, you may feel a burning sensation as your skin thaws out.

Healing after cryosurgery usually doesn’t take long. You will probably be able to enjoy all your usual activities while you heal, including bathing or showering. Cryosurgery leaves little or no scar. After the area has healed, the treated skin may be a bit lighter in color than the skin around it.

Do common warts ever come back?

Most of the time, treatment of warts on the skin is successful and the warts are gone for good. Your body’s immune system can usually get rid of any tiny bits of wart that may be left after a wart has been treated. Genital warts are more likely to come back because there’s no cure for the virus that causes them and because warts are more difficult to control in a moist environment. If warts come back, see your doctor to talk about other ways to treat them.

What are genital warts?

Genital warts may be small, flat, flesh-colored bumps or tiny, cauliflower-like bumps.

Genital warts are caused by the human papillomavirus (HPV). There are many kinds of HPV. Not all of them cause genital warts. HPV is associated with cancer of the vulva, anus and penis. However, it’s important to note that HPV infection doesn’t always lead to cancer.

Where do genital warts grow?

In men, genital warts can grow on the penis, near the anus, or between the penis and the scrotum. In women, genital warts may grow on the vulva and perineal area, in the vagina and on the cervix (the opening to the uterus or womb). Genital warts vary in size and may even be so small that you can’t see them.

How do you get HPV?

HPV is a sexually transmitted infection (STI). The most common way to get HPV is by having oral, vaginal or anal sex with someone who is infected with HPV. The only sure way to prevent genital warts is to not have sex. If you are sexually active, having sex only with a partner who isn’t infected with HPV and who only has sex with you will lower your risk of getting genital warts.

Just because you can’t see warts on your partner doesn’t mean he or she doesn’t have HPV. The infection can have a long incubation period. This means that months can pass between the time a person is infected with the virus and the time a person notices genital warts. Sometimes, the warts can take years to develop. In women, the warts may be where you can’t see them–inside the body, on the surface of the cervix.

Using condoms may prevent you from catching HPV from someone who has it. However, condoms can’t always cover all of the affected skin.

How do I prevent genital warts?

Genital warts are a sexually transmitted infection (STI) caused by the human papilloma virus (HPV). The only sure way to prevent genital warts is not to have sex. Using a condom may help prevent you from getting HPV, but condoms are not 100% effective. They do not cover all the affected skin, and you may still get HPV, even if you use a condom.

What about the HPV vaccine?

There are two types of HPV vaccine. Both types help protect against the HPV strains that are most likely to cause cervical cancer. One type also helps protect against the HPV strains that are most likely to cause genital warts.

Routine HPV vaccination is recommended for the following groups of people:

• Boys and girls ages 11 to 21
• Women ages 22 to 26
• Men ages 22 to 26 years of age who have a compromised immune system
• Gay and bisexual men

The vaccines are given as shots (injections in the upper arm) and require 3 doses. The vaccine is most effective if children receive it before they start having sex.

How are genital warts diagnosed?

If you notice warts in your genital area, see your doctor. Your doctor may be able to diagnose the warts just by examining you. For women, a Pap test can help detect changes on the cervix that are caused by genital warts can cause.

How are warts in the genital area treated?

Genital warts must be treated by your doctor. Do not try to treat the warts yourself.

Warts in the genital area can be removed, but there’s no cure for the viral infection that causes the warts. The virus goes on living inside your skin. This means that genital warts may come back even after they have been removed. You may need to have them removed more than once.

One way to remove the warts is to freeze them. This is called cryotherapy. The warts can also be taken off with a laser.

A treatment called the loop electrosurgical excision procedure (LEEP) can be used to remove the warts. With this method of removal, a sharp instrument shaped like a loop is passed underneath the wart and the wart is cut out of the skin.

Special chemicals can be used to remove the warts. These chemicals dissolve warts in the genital area. They may have to be applied to the area a number of times over a period of several weeks before the treatment is complete.

Chemicals you can buy at the store to remove warts from your hands should not be used for genital warts. They can make your genital skin very sore.

What if I don’t get genital warts treated?

Genital warts can grow if you do not get them treated. If you are sexually active, you also risk infecting your partner.

Certain kinds of HPV can cause abnormal cells to grow on the cervix. Sometimes, these cells can become cancerous if left untreated. Other kinds of HPV can cause cancer of the vulva, vagina, anus, or penis.

Cryotherapy for cervix (cervical intraepithelial neoplasia)

Cervical pre-cancer (cervical intraepithelial neoplasia) can be treated in different ways depending on the extent and nature of the disease. Less invasive treatments that do not require a hospital stay may be used. A general anaesthetic is occasionally needed, especially if the disease has spread locally, early invasion is suspected or previous out-patient treatment has failed. Surgery can be done with a knife, cryotherapy (freezing the abnormal cells), laser or cutting with a loop (an electrically charged wire). In cryotherapy, a circular metal probe is placed against the transformation zone. Hypothermia is produced by the evaporation of compressed refrigerant gas passing through the base of the probe. The cryonecrosis is achieved by crystallization of intracellular water. The effect tends to be patchy as sublethal tissue damage tends to occur at the periphery of the probe.

In non-controlled studies the success of treatment of CIN3 (cervical intraepithelial neoplasia 3) varied, between 77% and 93%, 87% ⁷⁾, 77% ⁸⁾, 82% ⁹⁾, 84% ¹⁰⁾, and 93% ¹¹⁾.

Utilising a double freeze-thaw-freeze technique improved the reliability in the observational study by Creasman 1984 ¹²⁾. Rapid ice-ball formation indicates that the depth of necrosis will extend to the periphery of the probe. The procedure can be associated with unpleasant vasomotor symptoms. In the trial of Schantz 1984 ¹³⁾, the single freeze technique was associated with a statistically non-significant increase in the risk of residual disease within 12 months compared with the double freeze technique. This 2013 Cochrane review ¹⁴⁾ found there was not enough evidence to confidently select the most effective technique and that more research is needed.

Cryotherapy for weight loss

The growing prevalence of obesity and overweight is of increasing concern because deposition of subvisceral fat in obesity is associated with increased risk of life-threatening conditions including cardiovascular disease, diabetes, metabolic syndrome, and some forms of cancer ¹⁵⁾.

Dietary interventions in obesity generally bring only short-term benefits, and attention has focused on alternative strategies for adipose tissue (fatty tissue) ablation including surgical removal and radiofrequency, ultrasound, and laser treatment [¹⁶⁾. An alternative approach, body cooling, involves either environmental cold exposure ¹⁷⁾ or devices to reduce the skin temperature ¹⁸⁾, leading to systemic or local exposure of fatty tissues to active cooling ¹⁹⁾.

Local adipose tissue cooling is used to manage obesity and overweight, but the mechanism is unclear ²⁰⁾. The current view is that acute local cooling of adipose tissue induces adipocyte cell disruption and inflammation (“cryolipolysis”) that lead to adipocyte cell death, with loss of subcutaneous fat being recorded over a prolonged period of weeks/months. A contrasting view is that adipose tissue loss via targeted cryotherapy might be mediated by thermogenic fat metabolism without cell disruption ²¹⁾.

With respect to tissue cooling, it has been hypothesized that adipocytes are more sensitive to cooling than other tissue types and that cooling leads to crystallization of cytoplasmic lipids, disruption of cellular integrity, cell death via apoptosis/necrosis, and inflammation, leading to selective loss of adipose tissue over a period of weeks to months by a process dubbed “selective cryolysis” or “cryolipolysis” ²²⁾, ²³⁾. Selective sensitivity of fatty tissue to cold has a long history, and for over a century there have been observations of local adipose tissue lesions in regions exposed to local cooling ²⁴⁾. However, a competing hypothesis is that cold exposure might act by boosting energy expenditure via fat metabolism and thermogenesis ²⁵⁾, ²⁶⁾, leading to reduction of fat mass without cell disruption. This possibility was long overlooked because it was thought that thermogenic adipose tissue, widely described in rodents, was not present in humans.

Two principal types of adipose tissue have been described in mammals: white adipose tissue (Wadipose tissue) and brown adipose tissue (Badipose tissue). The most abundant adipose cell types are the white adipocytes that contain a single intracellular lipid droplet and localize to specific depots within the body. White adipocytes store excess energy as lipid and function to regulate systemic energy balance through the release of adipokines that target peripheral tissues ²⁷⁾ and also target the brain to modulate appetite in response to excess energy supply ²⁸⁾. White adipose tissue (Wadipose tissue) expands by increasing the adipocyte size and/or number, and white adipose tissue (Wadipose tissue) expansion serves to protect tissues including the muscle and liver from lipotoxicity ²⁹⁾. Depots of Wadipose tissue are generally classified as visceral or subcutaneous, with the latter being considered to be protective, whereas the former are linked to metabolic disease ³⁰⁾.

The second major type of the adipose cell, the brown adipocyte, was overlooked in humans for many years until imaging with [18F]-fluorodeoxyglucose revealed that, like mice, humans also have extensive depots of brown adipose tissue (Badipose tissue) ³¹⁾. In contrast to white adipose tissue, brown adipose tissue adipocytes express uncoupling protein (UCP1) that permits mitochondria to metabolize fat via β-oxidation to generate heat ³²⁾. Brown adipocytes are widely distributed in the supraclavicular and neck regions, with additional paravertebral, mediastinal, para-aortic, and suprarenal localizations ³³⁾, and oxidative metabolism in Badipose tissue has been demonstrated to contribute directly to increased energy expenditure in response to acute cold exposure in humans ³⁴⁾. Importantly, numbers of brown adipocytes are thought to decline with age ³⁵⁾, and this may contribute to increasing incidence of overweight with age.

Brown adipose tissue depots can expand in both metabolic rate and cell number to maintain the body temperature in response to cooling. By triggering brown adipose tissue lipolysis and thermogenesis, cold exposure can reduce the body pool of fatty acids ³⁶⁾, and prolonged cold exposure can induce the proliferation and differentiation of precursors, leading to an increase in brown adipocyte numbers ³⁷⁾. There is also evidence that white adipose tissue can partly convert to brown adipose tissue-like adipocytes in response to different stimuli ³⁸⁾, suggesting that redirection of white adipose tissue precursors towards brown adipose tissue (“browning”) in response to cold exposure could contribute to obesity control.

Systemic/environmental cold exposure has inconveniences as a modality for managing obesity/overweight, and attention has focused on the application of cold temperatures directly to fat deposits with a view to stimulating dissipation of lipid depots. FDA approval was given in 2010 for the use of a tissue cryotherapy device aimed at reducing abdominal fat; the safety and efficacy of the procedure have now been widely demonstrated ³⁹⁾, ⁴⁰⁾.

Cooling of fatty tissue has been suggested to lead to adipocyte disruption/cell death and local inflammation (“selective cryolysis” or “cryolipolysis”) that precede adipose tissue loss ⁴¹⁾. The mechanistic basis is of direct clinical relevance because if tissue cryotherapy operates by inducing adipocyte cell death, then repeat procedures must be widely spaced (e.g., 8 weeks apart) to allow removal of cell debris and resolution of inflammation ⁴²⁾. Indeed, it has been reported that beneficial results are only observed after weeks or months, the recommended area for application is limited to local prominences of fatty tissue (“saddlebags”), and it is necessary to wait for a long period (1–3 months) before proceeding to a new zone ⁴³⁾. By contrast, others have suggested the possibility that the beneficial effects of body cooling might take place by increasing nonshivering thermogenesis ⁴⁴⁾; if confirmed, this would allow simultaneous application to different body regions, and moreover, repeated cryoexposure might be effective in driving the loss of adipose tissue ⁴⁵⁾.

Heat generation in response to cooling has generally been attributed to fatty acid β-oxidation. Exposure of mammalian cells to low temperatures (“cold shock”) causes widespread changes in gene expression ⁴⁶⁾. There is strong evidence that fat cells can directly sense low temperature and activate thermogenesis ⁴⁷⁾; cold-induced upregulation of the transcription factor Zfp516 induces the expression of UCP1 ⁴⁸⁾, and brown adipose tissue metabolic activity increases very rapidly following cold exposure ⁴⁹⁾. Indeed, cold exposure induces rapid triglyceride uptake from the blood ⁵⁰⁾, and adipose triglyceride lipase activity is instrumental in brown adipose tissue fat mobilization ⁵¹⁾. Nevertheless, the exclusive emphasis on fatty acid oxidation by brown adipose tissue may not be correct. It has been reported that, in human cold exposure, lipid oxidation only increased by 63%, whereas carbohydrate oxidation increased by 588% ⁵²⁾. brown adipose tissue contains significant endogenous glycogen stores, and cold exposure in rats and mice increases brown adipose tissue glucose uptake by an order of magnitude ⁵³⁾. Glycolysis could therefore make a major contribution to increased energy expenditure during cold exposure, although short-term energy expenditure via glycolysis may well subsequently equilibrate via longer-term cellular fat metabolism. Nevertheless, although increased brown adipose tissue uptake of both glucose and free fatty acids was reported in response to body cooling, it has been argued that triglyceride metabolism represents the primary energy source for cold-induced thermogenesis ⁵⁴⁾.

Despite the focus on brown adipose tissue, there is evidence that white adipose tissue may also contribute to cold-induced thermogenesis. Yoneshiro et al. ⁵⁵⁾ reported that only around 50% of subjects displayed cold-activated brown adipose tissue. Despite this, energy expenditure following cold exposure in their study also increased in subjects classified as brown adipose tissue negative, indicating that non-brown adipose tissue tissues may contribute. Because cold exposure does not appear to increase muscle energy metabolism ⁵⁶⁾, cold-induced thermogenesis in white adipose tissue could potentially explain the induced energy expenditure in brown adipose tissue-negative subjects. Furthermore, both white adipose tissue and brown adipose tissue are capable of metabolizing energy by pathways independent of UCP1 ⁵⁷⁾; it is therefore possible that both white adipose tissue and brown adipose tissue contribute to thermogenesis in response to tissue cooling. There may be two components to cold-induced adipose tissue loss, involving (i) rapid energy expenditure by white adipose tissue and/or brown adipose tissue, followed by (ii) slow adipose tissue loss as a result of continued metabolic activity, possibly including replenishment of glycogen stores via fat metabolism and, in the longer term, potentially facilitated by adaptive conversion of white adipose tissue to brown adipose tissue (“browning”). In support, although falling short of statistical significance, in a study, there was a trend towards continued adipose tissue loss over the days following single procedures ⁵⁸⁾. In a small number of subjects who were followed up for up to 3 months following multiple serial procedures, significant adipose tissue loss continued to take place for an extended period ⁵⁹⁾. Nevertheless, it was not possible to supervise these subjects for potential changes in activity/exercise and/or caloric intake during the follow-up period, and continuing changes therefore may not be unambiguously ascribed to metabolic changes induced by the cryotherapy procedure.

Does local tissue cooling cause adipose tissue reduction principally in the cooled tissue (as predicted by the cryolipolysis theory), or is there a systemic reduction? Following a single procedure, no changes were observed at a site not exposed to local cooling, but whole-body scanning indicated significant adipose tissue losses at nonexposed sites after three and six sequential procedures ⁶⁰⁾, indicating that systemic changes can take place after a longer time period. In addition to systemic depletion of fatty acid levels by brown adipose tissue metabolism, there are direct neuronal pathways between adipose tissue and the hypothalamus, leading to activation of the sympathetic nervous system and the release of noradrenaline that promotes brown adipose tissue activity ⁶¹⁾. A further contender is that systemic adipose tissue loss may be mediated by cytokines released from the cooled tissue, such as fibroblast growth factor type 21 and interleukin-6 ⁶²⁾, that might act both centrally (e.g., via the hypothalamus) and peripherally to modulate systemic fat metabolism ⁶³⁾. In support, brown adipose tissue transplantation in mice can induce systemic changes in the recipient ⁶⁴⁾. Behavioral changes (e.g., activity and food consumption) potentially mediated by endocrine targeting of the hypothalamus and/or hippocampus ⁶⁵⁾ may also take place, and further studies on the complex neuroendocrine interplay between body temperature, brown adipose tissue and white adipose tissue fat metabolism, and adaptive behavior are warranted.

Regarding the safety of the tissue cryotherapy procedure, no consistent changes in biochemical parameters were observed following tissue cooling, including markers of inflammation. No adverse effects were reported by the participants, confirming previous reports regarding the safety and efficacy of the procedure ⁶⁶⁾. However, there has been discussion about the possibility that, in mice, prolonged exposure to subthermoneutral temperatures might predispose to immune system deficiency ⁶⁷⁾ and could potentially increase the risk of infection or cancer. However, mice exposed to subthermoneutral temperatures are chronically maintained under these conditions for months to years. In humans, the induction of profound core hypothermia is an accepted medical procedure in both children and adults for the treatment of traumatic brain injury ⁶⁸⁾. Tissue cryotherapy, by contrast, is an acute local procedure, and no change in the body temperature (oral; mean change after the procedure, +0.3°C). Some scientists surmise that the benefits of combating obesity, a major health risk, are likely to substantially exceed the potential risks, if any, of short-term local tissue exposure to reduced temperatures. Moreover, the benefits of cryotherapy may not be restricted to combating obesity: in addition to reducing measures of obesity through cold-induced fat metabolism, cold exposure can have further beneficial effects such as promoting HDL “good” cholesterol turnover and reverse cholesterol transport, with likely protective effects against atherosclerosis and heart disease ⁶⁹⁾.

In summary, local cooling of abdominal fatty tissue significantly reduced the measures of obesity, including waist circumference, body weight, BMI, and fat content. Central observations are that (i) repeat procedures at short timescales produce progressive losses of adipose tissue, a finding inconsistent with “cryolipolysis” that is inferred to require weeks or longer between sequential treatments; (ii) blood profiling after the tissue cooling procedure gave no evidence of markers of inflammation or cell disruption; and (iii) calculated weight loss through thermogenesis alone was substantially consistent with estimates of heat extracted versus compensatory heat generation through enhanced tissue metabolism and thermogenesis. The findings of this study ⁷⁰⁾ indicate that cold-induced thermogenesis (cryothermogenesis) rather than adipose tissue disruption is likely to underlie the observed reductions in measures of obesity following local tissue cooling.

Cryotherapy in Cancer Treatment

Cryotherapy (also called cryosurgery) is the use of extreme cold produced by liquid nitrogen (or argon gas) to destroy abnormal tissue. Cryotherapy is used to treat external tumors, such as those on the skin. For external tumors, liquid nitrogen is applied directly to the cancer cells with a cotton swab or spraying device.

Cryotherapy is also used to treat tumors inside the body (internal tumors and tumors in the bone). For internal tumors, liquid nitrogen or argon gas is circulated through a hollow instrument called a cryoprobe, which is placed in contact with the tumor. The doctor uses ultrasound or MRI to guide the cryoprobe and monitor the freezing of the cells, thus limiting damage to nearby healthy tissue. (In ultrasound, sound waves are bounced off organs and other tissues to create a picture called a sonogram.) A ball of ice crystals forms around the probe, freezing nearby cells. Sometimes more than one probe is used to deliver the liquid nitrogen to various parts of the tumor. The probes may be put into the tumor during surgery or through the skin (percutaneously). After cryotherapy, the frozen tissue thaws and is either naturally absorbed by the body (for internal tumors), or it dissolves and forms a scab (for external tumors).

What types of cancer can be treated with cryotherapy?

Cryotherapy is used to treat several types of cancer, and some precancerous or noncancerous conditions. In addition to prostate and liver tumors, cryotherapy can be an effective treatment for the following:

• Retinoblastoma (a childhood cancer that affects the retina of the eye). Doctors have found that cryotherapy is most effective when the tumor is small and only in certain parts of the retina.
• Early-stage skin cancers (both basal cell and squamous cell carcinomas).
• Precancerous skin growths known as actinic keratosis.
• Precancerous conditions of the cervix known as cervical intraepithelial neoplasia (abnormal cell changes in the cervix that can develop into cervical cancer).
• Bone cancer
• Kidney cancer
• Liver cancer
• Lung cancer
• Prostate cancer

Cryotherapy is also used to treat some types of low-grade cancerous and noncancerous tumors of the bone. It may reduce the risk of joint damage when compared with more extensive surgery, and help lessen the need for amputation. The treatment is also used to treat AIDS-related Kaposi sarcoma when the skin lesions are small and localized.

Cryotherapy is also used to relieve the pain and other symptoms caused by cancer that spreads to the bone (bone metastasis) or other organs.

Researchers are evaluating cryotherapy as a treatment for a number of cancers, including breast, colon and kidney cancer. They are also exploring cryotherapy in combination with other cancer treatments, such as hormone therapy, chemotherapy, radiation therapy, or surgery.

In what situations can cryotherapy be used to treat prostate cancer? What are the side effects?

Cryotherapy can be used to treat men who have early-stage prostate cancer that is confined to the prostate gland. It is less well established than standard prostatectomy and various types of radiation therapy. Long-term outcomes are not known. Because it is effective only in small areas, cryotherapy is not used to treat prostate cancer that has spread outside the gland, or to distant parts of the body.

Some advantages of cryotherapy are that the procedure can be repeated, and it can be used to treat men who cannot have surgery or radiation therapy because of their age or other medical problems.

Cryotherapy for the prostate gland can cause side effects. These side effects may occur more often in men who have had radiation to the prostate.

• Cryotherapy may obstruct urine flow or cause incontinence (lack of control over urine flow); often, these side effects are temporary.
• Many men become impotent (loss of sexual function).
• In some cases, the surgery has caused injury to the rectum.

In what situations can cryotherapy be used to treat primary liver cancer or liver metastases (cancer that has spread to the liver from another part of the body)? What are the side effects?

Cryotherapy may be used to treat primary liver cancer that has not spread. It is used especially if surgery is not possible due to factors such as other medical conditions. The treatment also may be used for cancer that has spread to the liver from another site (such as the colon or rectum). In some cases, chemotherapy and/or radiation therapy may be given before or after cryotherapy. Cryotherapy in the liver may cause damage to the bile ducts and/or major blood vessels, which can lead to hemorrhage (heavy bleeding) or infection.

Does cryotherapy for cancer have any complications or side effects?

Cryotherapy 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. Cryotherapy for cervical intraepithelial neoplasia (CIN) has not been shown to affect a woman’s fertility, but it can cause cramping, pain, or bleeding. When used to treat skin cancer (including Kaposi sarcoma), cryotherapy 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, cryotherapy 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 and can often be delayed with other treatments. In rare cases, cryotherapy may interact badly with certain types of chemotherapy. Although the side effects of cryotherapy may be less severe than those associated with conventional surgery or radiation, more studies are needed to determine the long-term effects.

What are the advantages of cryotherapy for cancer treatment?

Cryotherapy offers advantages over other methods of cancer treatment. It is less invasive than surgery, involving only a small incision or insertion of the cryoprobe through the skin. Consequently, pain, bleeding, and other complications of surgery are minimized. Cryotherapy is less expensive than other treatments and requires shorter recovery time and a shorter hospital stay, or no hospital stay at all. Sometimes cryotherapy can be done using only local anesthesia.

Because physicians can focus cryosurgical treatment on a limited area, they can avoid the destruction of nearby healthy tissue. The treatment can be safely repeated and may be used along with standard treatments such as surgery, chemotherapy, hormone therapy, and radiation. Cryotherapy may offer an option for treating cancers that are considered inoperable or that do not respond to standard treatments. Furthermore, it can be used for patients who are not good candidates for conventional surgery because of their age or other medical conditions.

What are the disadvantages of cryotherapy for cancer treatment?

The major disadvantage of cryotherapy is the uncertainty surrounding its long-term effectiveness. While cryotherapy may be effective in treating tumors the physician can see by using imaging tests (tests that produce pictures of areas inside the body), it can miss microscopic cancer spread. Furthermore, because the effectiveness of the technique is still being assessed, insurance coverage issues may arise.

What does the future hold for cryotherapy for cancer treatment?

Additional studies are needed to determine the effectiveness of cryotherapy in controlling cancer and improving survival. Data from these studies will allow physicians to compare cryotherapy with standard treatment options such as surgery, chemotherapy, and radiation. Moreover, physicians continue to examine the possibility of using cryotherapy in combination with other treatments.

Where is cryotherapy for cancer currently available?

Cryotherapy is widely available in gynecologists’ offices for the treatment of cervical neoplasias. A limited number of hospitals and cancer centers throughout the country currently have skilled doctors and the necessary technology to perform cryotherapy for other noncancerous, precancerous, and cancerous conditions. Individuals can consult with their doctors or contact hospitals and cancer centers in their area to find out where cryotherapy is being used.

Cryotherapy for prostate cancer

The prostate gland is found only in males. It sits below the bladder and wraps around the urethra, the tube that carries urine out of the body. The prostate helps make semen.

Cryotherapy for prostate cancer involves freezing the cancer cells and cutting off their blood supply, causing cancer cells to die. As a minimally invasive procedure, cryotherapy for prostate cancer is sometimes used as an alternative to surgical removal of the prostate gland.

Cryotherapy when used to treat prostate cancer, a warming catheter is put into the urethra to keep it from freezing. Tiny needles are guided into the prostate tumors using ultrasound imagery to guide them. Argon gases are passed through the needles and exchanged with helium gases. This causes a freezing and warming cycle. The frozen, dead tissue then thaws and is naturally absorbed by the body.

In the past, cryotherapy for prostate cancer was associated with significantly higher levels of long-term side effects than were other prostate cancer treatments. Advances in technology have reduced these side effects. Many men, however, still experience long-term sexual dysfunction following cryotherapy for prostate cancer.

Cryotherapy might be used to treat men who have early-stage prostate cancer. Cryotherapy for prostate cancer can also be an option for men whose cancer has returned after other treatments.

Why is cryotherapy for prostate cancer done

Cryotherapy freezes tissue within the prostate gland. After being frozen, the prostate cancer cells die.

Your doctor may recommend cryotherapy for prostate cancer as an option at different times during your cancer treatment and for different reasons. Cryotherapy might be recommended:

• As the primary treatment for cancer, usually for early-stage cancer that is confined to your prostate
• After other cancer treatment, such as radiation therapy, to stop the growth of prostate cancer that has returned

Cryotherapy for prostate cancer generally isn’t recommended for men:

• Who have normal sexual function
• Who previously had surgery for rectal or anal cancer
• Whose prostates can’t be monitored with an ultrasound probe during the procedure
• Who have large tumors that can’t be treated with cryotherapy without damaging surrounding tissue and organs, such as the rectum or bladder

Why might I need cryotherapy for prostate cancer?

Cryotherapy may be a good treatment option for prostate cancer treatment in the following situations:

• Men with cancer in the prostate gland that hasn’t spread to other parts of the body
• Men who aren’t well enough to get radiation or procedure
• When the goal isn’t to cure, it may be useful for men who have cancer that has spread beyond the prostate gland and need treatment for symptoms
• Sometimes it’s used for men who have had unsuccessful results with radiation therapy

Some experts believe cryotherapy can be helpful when the prostate cancer cells aren’t as sensitive to radiation.

Cryotherapy may not be recommended for men who have a very large prostate gland.

Cryotherapy is less invasive than standard procedure. It involves needles that are put in through the skin under the scrotum, called the perineum. There is less blood loss, a shorter hospital stay, faster recovery, and less pain. It can be repeated, if needed.

There may be other reasons for your healthcare provider to recommend cryotherapy.

What are the risks of cryotherapy for prostate cancer?

As with any procedure, complications can occur. The risk of permanent erectile dysfunction is very high with cryotherapy. This makes it a better choice for men who aren’t as concerned about erectile dysfunction after treatment. Some other possible complications may include:

• Bleeding and/or blood in the urine
• Soreness or swelling in the region where the needles are put into the body (between the scrotum and the anus)
• Infection
• Swelling around the penis or scrotum
• Freezing may affect the bladder and intestines, which can lead to pain and burning sensations
• Urge to empty the bladder and bowels more often (usually goes away in several weeks)
• Urinary incontinence is rare, but this may be more common if the man has had radiation therapy in the past
• An abnormal connection (fistula) between the rectum and bladder or urethra is a rare complication

Rarely, side effects can include:

• Injury to the rectum
• Blockage of the tube (urethra) that carries urine out of the body
• Infection or inflammation of the pubic bone

There may be other risks depending on your condition. Be sure to discuss any concerns with your healthcare provider before the procedure.

How do I get ready for cryotherapy for prostate cancer?

Here are some things you can expect before cryotherapy for prostate cancer:

• Your healthcare provider will explain the procedure and you can ask questions.
• You will be asked to sign a consent form that gives your permission to do the procedure. Read the form carefully and ask questions if anything isn’t clear.
• Your doctor will review your medical history and do a physical exam to be sure you are in good health before you have the procedure. You may also need blood tests and other tests to make sure the cancer is confined to the prostate.
• You will be asked to fast (not eat or drink anything) for 8 hours before the procedure, generally after midnight.
• Tell your healthcare provider if you are sensitive to or allergic to any medicines, latex, iodine, tape, and anesthesia.
• Make sure your healthcare provider has a list of all medicines and all herbs, vitamins, and supplements that you’re taking. This includes prescribed and over-the-counter medicines.
• Tell your healthcare provider if you have a history of bleeding problems or if you are taking any anticoagulant (blood-thinning) medicines, aspirin, or any other medicines that affect blood clotting. You may need to stop these medicines before the procedure.
• If you smoke, stop as soon as possible. This improves your recovery and your overall health status.
• You will be asked to take a laxative and/or enema to empty your colon the night before procedure. Make sure you understand these directions and have the supplies you need.
• You may be given a sedative before the procedure to help you relax.

Based on your condition, your healthcare provider may request other specific preparation.

What happens during cryotherapy for prostate cancer?

Cryotherapy may require a one-day stay in the hospital. It may also be done as an outpatient procedure. Procedures may vary depending on your condition and your healthcare provider’s practices.

Generally, cryotherapy follows this process:

• You will be asked to remove any jewelry or other objects that might get in the way during procedure.
• You will be asked to remove your clothing and will be given a gown to wear.
• You will be asked to empty your bladder.
• An IV (intravenous) line will be put in your arm or hand.
• The doctor may choose regional anesthesia or general anesthesia. You will also get medicine to help you relax and pain medicines.
• If you get general anesthesia, a breathing tube may be put through your throat into your lungs and you will be connected to a ventilator. This will breathe for you during the procedure.
• The anesthesiologist will watch your heart rate, blood pressure, breathing, and blood oxygen level during the procedure.
• You will be placed on your back on the operating table with your legs up in stirrups.
• The healthcare provider will put a soft, flexible catheter through your penis and into your bladder to drain urine. The catheter will be filled with warm salt (saline) solution. It will help keep urine draining even if the prostate gland swells after the treatment. The catheter will also be used to keep the warm saline moving through the urethra to protect it from the cold temperatures used during the procedure.
• A transrectal ultrasound (TRUS) probe will be put into your rectum so that the prostate and nearby tissues can be seen on a computer screen.
• The healthcare provider will insert the cryoprobes (needles) into the preselected areas between the scrotum and anus. Gas will be put into the needles to freeze the nearby prostate tissue. The frozen area will stay frozen for only a few minutes then will be thawed by putting helium through the needles. This cycle may be repeated.
• The surgeon will use the ultrasound images to watch the freezing process to be sure only the cancer is being treated.
• The needles and TRUS probe will be removed and the urinary catheter will be left in your bladder.
• If used, the breathing tube will be taken out and you will breathe on your own.
• A sterile bandage/dressing will be applied.

What happens after cryotherapy for prostate cancer?

You’ll likely be able to go home the day of your procedure, or you may spend the night in the hospital. The catheter may need to remain in place for about two weeks to allow for healing. You might also be given an antibiotic to prevent infection.

Cryotherapy for prostate cancer usually results in very little blood loss. You may experience:

• Soreness and bruising for several days where the rods were inserted
• Blood in your urine for several days
• Problems emptying your bladder and bowels, which usually resolve over time

Sexual dysfunction, including impotence, is common after cryotherapy for prostate cancer.

In the hospital

After the procedure, you may be taken to a recovery room before being taken to a hospital room. You will be connected to monitors that will display your heart rate, blood pressure, breathing rate, and your oxygen level.

Once you are stable and awake, you will be taken to your hospital room. You may also start to drink liquids.

You may get pain medicine as needed, either by a nurse, or by giving it yourself through a device connected to your IV line.

You can gradually return to solid foods as you are able to handle them.

You may start to take antibiotics after the procedure is done and continue them for a few days after it. This is to help prevent infection.

Your recovery will continue to progress. You will probably have some bruising and swelling in the area where the probes were inserted. You will be encouraged to get out of bed and walk the same day. You may be able to go home the same or the next day.

You may notice some blood in your urine for a day or two after the procedure. Swelling in the penis or scrotum is common. You may also have pain in your belly (abdomen) and burning sensations which may make you feel the urge to go to the bathroom more often.

The catheter will stay in for 1 to 3 weeks to help urine drain while your prostate gland heals. You will be given instructions on how to care for the catheter at home.

Arrangements will be made for a follow-up visit with your healthcare provider.

Your healthcare provider may give you other instructions after the procedure, depending on your situation.

At home

Once you are home, it will be important to keep the surgical area clean and dry. Your healthcare provider will give you specific bathing instructions.

The needle insertion sites may be tender or sore for several days after cryotherapy. Take a pain reliever for soreness as recommended by your healthcare provider.

You shouldn’t drive until your healthcare provider tells you to. Other activity restrictions may also apply.

Be sure to keep any follow-up appointments so your healthcare provider can make sure you’re recovering well. The catheter will be taken out at one of these follow-up appointments.

Call your healthcare provider if you have any of the following:

• Changes in your urine output, color, or odor
• Inability to urinate once catheter is removed
• Increase in pain around the needle insertion sites
• Fever and/or chills
• Redness, swelling, bleeding, or other drainage from the needle insertion sites

Your healthcare provider may give you other instructions after the procedure, depending on your situation.

Cryotherapy for prostate cancer results

After cryotherapy for prostate cancer, you’ll have regular follow-up exams as well as periodic imaging scans and laboratory testing to check your cancer’s response to treatment.

The current method of cryotherapy for prostate cancer — which employs ultrasound guidance, newer-technology cryotherapy probes and strict temperature monitoring — has been in use for only several years. The long-term outcomes for this procedure are currently unknown.

Cryotherapy for preventing and treating muscle soreness after exercise in adults

Delayed onset muscle soreness describes the muscular pain, tenderness and stiffness experienced after high-intensity or unaccustomed exercise. Various therapies are in use to prevent or reduce muscle soreness after exercise and to enhance recovery. One more recent therapy that is growing in use is whole-body cryotherapy. Whole-body cryotherapy involves single or repeated exposure(s) to extremely cold dry air (below -100 °C or -148 °F) in a specialized chamber or cabin for two to four minutes per exposure, is currently being advocated as an effective intervention to reduce muscle soreness after exercise.

Elite-level athletic participation necessitates recovery from many physiological stressors, including fatigue to the musculoskeletal, nervous and metabolic systems ⁷¹⁾. Athletic participation may also result in exercise-induced muscle damage, which may lead to delayed-onset muscle soreness (DOMS) and decrements in subsequent performance ⁷²⁾. Various therapeutic modalities of recovery are currently used by athletes in an attempt to offset the negative effects of strenuous exercise ⁷³⁾.

Delayed-onset muscle soreness (DOMS) is a broad term used to describe the muscular pain, tenderness and stiffness experienced after high-intensity, eccentric (when the muscle is forcibly stretched when active) or unaccustomed exercise ⁷⁴⁾. Clinically associated with exercise-induced muscle damage, delayed-onset muscle soreness (DOMS) is proposed to result from mechanical disturbances of the muscle membrane that evoke secondary inflammation, swelling and free radical proliferation ⁷⁵⁾. These events typically peak 24 to 96 hours post exercise ⁷⁶⁾ and may reduce physical capacity via alterations in muscle length, maximal force and range of motion (Prasartwuth 2006; Saxton 1995). Although damage to the exercised musculature is linked to the biochemical expression of intracellular enzymes, compensatory neuromuscular recruitment patterns may contribute both central and peripheral factors to delayed-onset muscle soreness (DOMS) ⁷⁷⁾.

Symptoms associated with Delayed-onset muscle soreness (DOMS) typically dissipate within five to seven days post exercise with adequate rest ⁷⁸⁾. Nevertheless, various interventions have been advocated to prevent or treat, or both prevent and treat, exercise-induced muscle damage and associated delayed-onset muscle soreness (DOMS) . Interventions include cool-down, stretching, nutritional supplements, massage, hydrotherapy, compression, electrotherapy and non-steroidal anti-inflammatory medications ⁷⁹⁾. Despite their widespread popularity, empirical support for the use of these interventions for delayed-onset muscle soreness (DOMS) remains tenuous ⁸⁰⁾.

Whole-body cryotherapy  is increasingly used in sports medicine as treatment for muscle soreness after exercise. This treatment involves exposing individuals to extremely cold dry air (below -100 °C or -148 °F) for two to four minutes. To achieve the subzero temperatures required for whole-body cryotherapy, two methods are typically used: liquid nitrogen and refrigerated cold air. During these exposures, individuals wear minimal clothing, which usually consists of shorts for males and shorts and a crop top for females. Gloves, a woollen headband covering the ears, and a nose and mouth mask, in addition to dry shoes and socks, are commonly worn to reduce the risk of cold-related injury.

The first whole-body cryotherapy chamber was built in Japan in the late 1970s, but whole-body cryotherapy was not introduced to Europe until the 1980s, and has only been used in the USA and Australia in the past decade ⁸¹⁾. The treatment was initially intended for use in a clinical setting to treat patients with conditions such as multiple sclerosis ⁸²⁾ and rheumatoid arthritis ⁸³⁾; however, elite athletes have recently reported using the treatment to alleviate DOMS after exercise ⁸⁴⁾. Whole-body cryotherapy is commonly employed shortly (within 0 to 24 hours) after exercise, and the treatment is often repeated on the same day ⁸⁵⁾ or over several days ⁸⁶⁾.

In the field of athletic training, a new method of exposing people to these extreme temperatures, called partial-body cryotherapy, using a portable cryo-cabin, has recently been developed. This system has an open tank and exposes the body, except the head and neck, to temperatures below below -100 °C or -148 °F. Recently, recreational athletes have started to emulate elite athletes in using these treatments after exercise.

However, the currently available evidence from a well conducted systematic study ⁸⁷⁾ showed there is insufficient to support the use of whole-body cryotherapy for preventing and treating muscle soreness after exercise in adults. Furthermore, the best prescription of whole-body cryotherapy and its safety are not known.

Cryotherapy for Pain Management

Cryotherapy can be applied in various ways, including icepacks, coolant sprays, ice massage, and whirlpools, or ice baths. When used to treat injuries at home, cryotherapy refers to cold therapy with ice or gel packs that are usually kept in the freezer until needed. These remain one of the simplest, time-tested remedies for managing pain and swelling.

Cryotherapy is the “I” component of R.I.C.E. (rest, ice, compression, and elevation). This is a treatment recommended for the home care of many injuries, particularly ones caused by sports.

Cryotherapy for pain relief may be used for:

• Runner’s knee
• Tendonitis
• Sprains
• Arthritis pain
• Pain and swelling after a hip or knee replacement
• To treat pain or swelling under a cast or a splint
• Lower back pain

The benefits of applying ice include:

• It lowers your skin temperature.
• It reduces the nerve activity.
• It reduces pain and swelling.

Experts believe that cryotherapy can reduce swelling, which is tied to pain. It may also reduce sensitivity to pain. Cryotherapy may be particularly effective when you are managing pain with swelling, especially around a joint or tendon.

How to apply cold therapy

Putting ice or frozen items directly on your skin can ease pain, but it also can damage your skin. It’s best to wrap the cold object in a thin towel to protect your skin from the direct cold, especially if you are using gel packs from the freezer.

Apply the ice or gel pack for brief periods – about 10 to 20 minutes – several times a day. Check your skin often for sensation while using cryotherapy. This will help make sure you aren’t damaging the tissues.

You might need to combine cryotherapy with other approaches to pain management:

• Rest. Take a break from activities that can make your pain worse.
• Compression. Applying pressure to the area can help control swelling and pain. This also stabilizes the area so that you do not further injure yourself.
• Elevation. Put your feet up, or elevate whatever body part is in pain.
• Pain medicine. Over-the-counter products can help ease discomfort.
• Rehabilitation exercises. Depending on where your injury is, you might want to try stretching and strengthening exercises that can support the area as recommended by your healthcare provider.

Stop applying ice if you lose feeling on the skin where you are applying it. If cryotherapy does not help your pain go away, contact your healthcare provider. Also, you may want to avoid cryotherapy if you have certain medical conditions, like diabetes, that affect how well you can sense tissue damage.