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Cryoablation is a process that uses extreme
cold Cold is the presence of low temperature, especially in the atmosphere. In common usage, cold is often a subjective perception. A lower bound to temperature is absolute zero, defined as 0.00K on the Kelvin scale, an absolute thermodynamic ...
to destroy tissue. Cryoablation is performed using hollow needles (cryoprobes) through which cooled, thermally conductive, fluids are circulated. Cryoprobes are positioned adjacent to the target in such a way that the freezing process will destroy the diseased tissue. Once the probes are in place, the attached cryogenic freezing unit removes heat from ("cools") the tip of the probe and by extension from the surrounding tissues. Ablation occurs in tissue that has been frozen by at least three mechanisms: # formation of ice crystals within cells thereby disrupting membranes, and interrupting cellular metabolism among other processes; # coagulation of blood thereby interrupting bloodflow to the tissue in turn causing ischemia and cell death; and # induction of
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
, the so-called programmed cell death cascade. The most common application of cryoablation is to ablate solid tumors found in the lung, liver, breast, kidney and prostate. The use in prostate and renal cryoablation are the most common. Although sometimes applied in
cryosurgery Cryosurgery is the use of extreme cold in surgery to destroy abnormal or diseased tissue; thus, it is the surgical application of cryoablation. The term comes from the Greek words cryo (κρύο) ("icy cold") and surgery (''cheirourgiki'' – χ� ...
through laparoscopic or open surgical approaches, most often cryoablation is performed percutaneously (through the skin and into the target tissue containing the tumor) by a medical specialist, such as an interventional radiologist. The term is from '' cryo-'' + ''
ablation Ablation ( la, ablatio – removal) is removal or destruction of something from an object by vaporization, chipping, erosive processes or by other means. Examples of ablative materials are described below, and include spacecraft material for ...
''.


Prostate

Prostate The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and phys ...
cryoablation is moderately effective but, as with any prostate removal process, also can result in impotence. Prostate cryoablation is used in three patient categories: # as primary therapy in patients for whom sexual function is less important or who are poor candidates for radical retropubic prostatectomy (RRP, surgical removal of the prostate); # as salvage therapy in patients who have failed brachytherapy (the use of implanted radioactive "seeds" placed within the prostate) or external beam radiation therapy (EBRT); and # focal therapy for smaller, discrete tumors in younger patients.


Bone cancer

Cryoablation has been explored as an alternative to
radiofrequency ablation Radiofrequency ablation (RFA), also called fulguration, is a medical procedure in which part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from medium frequency alternati ...
in the treatment of moderate to severe pain in people with metastatic bone disease. The area of tissue destruction created by this technique can be monitored more effectively by CT than RFA, a potential advantage when treating tumors adjacent to critical structures.


Renal

Cryoablation has similar outcomes to radiofrequency ablation when treating
renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, re ...
.


Breast cancer

Cryoablation for breast cancer is typically only possible for small tumors. Often surgery is used following cryoablation. As of 2014 more research is required before it can replace
lumpectomy Lumpectomy (sometimes known as a tylectomy, partial mastectomy, breast segmental resection or breast wide local excision) is a surgical removal of a discrete portion or "lump" of breast tissue, usually in the treatment of a malignant tumor or brea ...
.


Cardiac

Another type of cryoablation is used to restore normal electrical conduction by freezing tissue or heart pathways that interfere with the normal distribution of the heart’s electrical impulses. Cryoablation is used in two types of intervention for the treatment of
arrhythmias Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
: (1)
catheter In medicine, a catheter (/ˈkæθətər/) is a thin tubing (material), tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgi ...
-based procedures and (2) surgical operations. A catheter is a very thin tube that is inserted into a vein in the patient’s leg and threaded to the heart where it delivers energy to treat the patient’s arrhythmia. In surgical procedures, a flexible probe is used directly on an exposed heart to apply the energy that interrupts the arrhythmia. By cooling the tip of a cryoablation catheter (
cardiology Cardiology () is a branch of medicine that deals with disorders of the heart and the cardiovascular system. The field includes medical diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular h ...
) or probe ( heart surgery) to sub-zero temperatures, the cells in the heart responsible for conducting the arrhythmia are altered so that they no longer conduct electrical impulses.


Fibroadenoma

Cryoablation is also currently being used to treat fibroadenomas of the breast. Fibroadenomas are
benign Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
breast tumors that are found in approximately 10% of women (primarily ages 15–30). In this procedure which has been approved by the U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA), an ultrasound-guided probe is inserted into the fibroadenoma and extremely cold temperatures are then used to destroy the abnormal cells. Over time the cells are reabsorbed into the body. The procedure can be performed in a doctor's office setting with
local anesthesia Local anesthesia is any technique to induce the absence of sensation in a specific part of the body, generally for the aim of inducing local analgesia, that is, local insensitivity to pain, although other local senses may be affected as well. It ...
and leaves very little scarring compared to open surgical procedures.


Catheter-based procedures

Different catheter-based ablation techniques may be used and they generally fall into two categories: (1) cold-based procedures where tissue cooling is used to treat the arrhythmia, and (2) heat-based procedures where high temperature is used to alter the abnormal conductive tissue in the heart.


Cryoablation

Cold temperatures are used in cryoablation to chill or freeze cells that conduct abnormal heart rhythms. The catheter removes heat from the tissue to cool it to temperatures as low as -75 °C. This causes localized scarring, which cuts undesired conduction paths. This is a much newer treatment for supraventricular tachycardia (SVT) involving the atrioventricular (AV) node directly. SVT involving the AV node is often a contraindication for using radiofrequency ablation because of the risk of injuring the AV node, forcing patients to receive a permanent pacemaker. With cryoablation, areas of tissue can be mapped by limited, reversible, freezing (e.g., to -10 C). If the result is undesirable, the tissue can be rewarmed without permanent damage. Otherwise, the tissue can be permanently ablated by freezing it to a lower temperature (e.g., -73 C). This therapy has revolutionized
AV nodal reentrant tachycardia AV-nodal reentrant tachycardia (AVNRT) is a type of abnormal fast heart rhythm. It is a type of supraventricular tachycardia (SVT), meaning that it originates from a location within the heart above the bundle of His. AV nodal reentrant tachycar ...
(AVNRT) and other AV nodal tachyarrhythmias. It has allowed people who were otherwise not a candidate for radiofrequency ablation to have a chance at having their problem cured. This technology was developed at The Montreal Heart Institute in the late 1990s. The therapy was successfully adopted in Europe in 2001, and in the US in 2004 following the "Frosty Trial". In 2004, the technology was pioneered in the midwest United States at Miami Valley Hospital in Dayton, Ohio by Mark Krebs, MD, FACC, Matthew Hoskins, RN, BSN and Ken Peterman, RN, BSN. These electrophysiology experts were successful in curing the first 12 candidates in their facility. Cryoablation for AVNRT and other arrhythmias do have some drawbacks. A recent study concluded that procedure times are slightly higher on average for cryoablation than for traditional radio-frequency (heat-based) ablations. Also, higher rate of equipment failures were recorded using this technique. Finally, even though short term success rate is equivalent to RF treatments, cryoablation appears to have a significantly higher long term recurrence rate.


Site testing

Cryotherapy Cryotherapy, sometimes known as cold therapy, is the local or general use of low temperatures in medical therapy. Cryotherapy may be used to treat a variety of tissue lesions. The most prominent use of the term refers to the surgical treatment, s ...
is able to produce a temporary electrical block by cooling down the tissue believed to be conducting the arrhythmia. This allows the physician to make sure this is the right site before permanently disabling it. The ability to test a site in this way is referred to as site testing or cryomapping. When ablating tissue near the
AV node The atrioventricular node or AV node electrically connects the heart's atria and ventricles to coordinate beating in the top of the heart; it is part of the electrical conduction system of the heart. The AV node lies at the lower back section of t ...
(a special conduction center that carries electrical impulses from the atria to the ventricles), there is a risk of producing heart block – that is, normal conduction from the atria cannot be transmitted to the ventricles. Freezing tissue near the AV node is less likely to provoke irreversible heart block than ablating it with heat.


Surgical procedures

As in catheter-based procedures, techniques using heating or cooling temperatures may be used to treat arrhythmias during heart surgery. Techniques also exist where incisions are used in the open heart to interrupt abnormal electrical conduction ( Maze procedure).
Cryosurgery Cryosurgery is the use of extreme cold in surgery to destroy abnormal or diseased tissue; thus, it is the surgical application of cryoablation. The term comes from the Greek words cryo (κρύο) ("icy cold") and surgery (''cheirourgiki'' – χ� ...
involves the use of freezing techniques for the treatment of arrhythmias during surgery. A physician may recommend cryosurgery being used during the course of heart surgery as a secondary procedure to treat any arrhythmia that was present or that may appear during the primary openchest procedure. The most common heart operations in which cryosurgery may be used in this way are
mitral valve repair Mitral valve repair is a cardiac surgery procedure performed by cardiac surgeons to treat stenosis (narrowing) or regurgitation (leakage) of the mitral valve. The mitral valve is the "inflow valve" for the left side of the heart. Blood flows ...
s and
coronary artery bypass graft Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage") is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest pai ...
ing. During the procedure, a flexible cryoprobe is placed on or around the heart and delivers cold energy that disables tissue responsible for conducting the arrhythmia.


Vascular Malformations

Cryoablation has recently been used to treat low-flow
vascular malformation A vascular malformation is a blood vessel or lymph vessel abnormality. Vascular malformations are one of the classifications of vascular anomalies, the other grouping is vascular tumors. They may cause aesthetic problems as they have a growth cyc ...
s such as
venous malformation A vascular malformation is a blood vessel or lymph vessel abnormality. Vascular malformations are one of the classifications of vascular anomalies, the other grouping is vascular tumors. They may cause aesthetic problems as they have a growth cyc ...
s (VM) and fibroadipose vascular anomalies (FAVA). Cryoablation has proved effective for treating these disorders both as primary treatment and after
sclerotherapy Sclerotherapy (the word reflects the Greek ''skleros'', meaning ''hard'') is a procedure used to treat blood vessel malformations (vascular malformations) and also malformations of the lymphatic system. A medicine is injected into the vessels, wh ...
.


Cryoimmunotherapy

Cryoimmunotherapy is an oncological treatment for various cancers that combines cryoablation of tumor with
immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
treatment. In-vivo cryoablation of a tumor, alone, can induce an immunostimulatory, systemic anti-tumor response, resulting in a cancer vaccine – the
abscopal effect The abscopal effect is a hypothesis in the treatment of metastatic cancer whereby shrinkage of untreated tumors occurs concurrently with shrinkage of tumors within the scope of the localized treatment. R.H. Mole proposed the term “abscopal” (� ...
. However, cryoablation alone may produce an insufficient immune response, depending on various factors, such as high freeze rate. Combining cryotherapy with immunotherapy enhances the immunostimulating response and has synergistic effects for cancer treatment.


History

The use of cold for pain relief and as an anti-inflammatory has been known since the time of
Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history o ...
(460–377 BC). Since then there have been numerous accounts of ice used for pain relief including from the Ancient Egyptians and Avicenna of Persia (AD 982–1070). Since 1899, Dr. Campbell White used refrigerants for treating a variety of conditions, including: lupus erythematosus, herpes zoster, chancroid, naevi, warts, varicose leg ulcers, carbuncles, carcinomas and epitheliomas. De Quervain successfully used of carbonic snow to treat bladder papillomas and bladder cancers in 1917. Dr. Irving S. Cooper, in 1913, progressed the field of cryotherapy by designing a liquid nitrogen probe capable of achieving temperatures of -196 °C, and utilizing it to treat of Parkinson's disease and previously inoperable cancer. Cooper's cryoprobe advanced the practice of cryotherapy, which led to growing interest and practice of cryotherapy. In 1964, Dr. Cahan successfully used his liquid nitrogen probe invention to treat uterine fibroids and cervical cancer. Cryotherapy continued to advance with Dr. Amoils developing a liquid nitrogen probe capable of achieving cooling expansion, in 1967. With the technological cryoprobe advancements in the 1960s, came wider acceptance and practice of cryotherapy. Since the 1960s, liver, prostate, breast, bone, and other cancers were being treated with cryoablation in many parts of the world. Japanese physician Dr. Tanaka began treating metastatic
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...
cryoablation in 1968. For the next three decades, Dr. Tanaka successfully treated small and localized as well as advanced and unresectable breast cancer with minimally invasive cryoablation. All of Dr. Tanaka's breast cancer cases were considered incurable: advanced, unresectable, and resistant to radiotherapy, chemotherapy, and endocrine therapy. At the same time, physicians, including Dr. Ablin and Dr. Gage, started utilizing cryoablation for the treatment of prostate and
bone cancer A bone tumor is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as from lung, breast, thy ...
. Dr. Paul J. Wang MD and Dr. Peter L. Friedman MD, PhD invented cryoablation for the heart and cardiac arrhythmia in 1988. Their patents were for the cryoablation catheter and cryogenic mapping (US Patents 5147355A and 5423807A). The 1980s and 1990s saw dramatic advancement in apparatus and imaging techniques, with the introduction of CMS Cryoprobe, and Accuprobe. CT,
MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
,
ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...
guided cryoprobes became available and improved the capabilities of cryoprobes in treatment. Excited by the latest advancements in cryotherapy, China embraced cryotherapy in the 1990s, to treat many oncological conditions. With the benefits well-established, the FDA approved the treatment of prostate cancer with cryoablation in 1998.


See also

*
Interventional radiology Interventional radiology (IR) is a medical specialty that performs various minimally-invasive procedures using medical imaging guidance, such as x-ray fluoroscopy, computed tomography, magnetic resonance imaging, or ultrasound. IR performs b ...


References

{{Male genital procedures Surgical procedures and techniques Cooling technology Interventional radiology