Cryosurgery

By Dr. Jyothish.k, GDC CALICUT

1. GOOD MORNING CRYOSURGERY Dr.JYOTHISH.K

2. It is the process of rapidly freezing tissue by exposing it to intensly low tempratures . Cryosurgery works by taking advantage of the destructive force of freezing temperatures on cells. At low temperatures, ice crystals form inside the cells, which can tear them apart. More damage occurs when blood vessels supplying the diseased tissue freeze 2 INTRODUCTION ( CRYOTHERAPY OR CRYOABLATION )

3. TECHNIQUES OF APPLICATION OF CRYOTHERAPY Ice towels Ice packs Immersion Ice cube massage Ice spray Cold gel 3

4. USES OF ICE THERAPY Reduces pain . Reduces muscle spasm. Reduces swelling. Promote repair of the damaged tissues. Provide excitatory stimulus to inhibited muscles . 4

5. HISTORY G reek word“ kryos ” means frost Local application of low temperature was first used by egyptians for pain relief, then during franco-american war for amputated limbs James Arnott , in 19 th century, stated that a very low temperature will arrest every inflammation which is near enough to the surface . The first cryogens were liquid air  and compressed carbon dioxide snow . Liquid nitrogen became available in the 1940s and currently is the most widely used cryogen. In 1961, Cooper and Lee developed the first cryotherapy probe system, involving the circulation of liquid nitrogen through a closed metal tube placed in direct contact with the target tissue.

6. Cryogens - Liquid nitrogen (most commonly used) : -196°C Nitrous oxide : - 89°C Solidified CO  2  (dry ice, CO  2  snow) : -78°C Chlorodifluoromethane : -41°C Dimethyl ether and propane : - 24°C (42°f) Argon

7. Liquid nitrogen Common method, The super-cooled liquid may be sprayed using cryogun on the diseased tissue, cryoprobe , or simply dabbed on with a cotton or foam swab . Carbon dioxide Less frequently, doctors use “carbon dioxide snow " formed into a cylinder or mixed with acetone to form a slush that is applied directly to the tissue.

8. Argon Recent advances in technology have allowed for the use of argon gas to drive ice formation using a principle known as the Joule-Thomson effect. This gives physicians excellent control of the ice, and minimizing complications using ultra-thin 17 gauge cryoneedles . Dimethyl ether – propane A mixture of dimethyl ether and propane is used in some preparations such as Dr. Scholl's Freeze Away . The mixture is stored in an aerosol spray type container at room temperature and drops to −41 °C when dispensed. The mixture is often dispensed into a straw with a cotton-tipped swab.

9. The apparatus consists of a container in which the pressurised refrigerant media (gases) are stored as liquid gases. It generates liquid nitrogen at temporature of -196*c Other refrigerants are carbon dioxide, nitrous oxide, & freon which may reach temprature of -20* to –90* A probe is connected to the content to the tube This probe is applied on the region of the abnornal tissue Time depends on temprature , size of lesion & type of tissue Freezing & thawning are done alternatively as many times as necessary for the lesion This process destroyes the tissue 9 APPARATUS

10. L iquid nitrogen or argon gas is circulated through a hollow instrument. The doctor uses ultrasound or MRI to guide the cryoprobe . A ball of ice crystals forms around the probe, freezing nearby cells. 2/6/2017 6:42:44 AM RT/15/CRYOSURGERY/45 10 MECHANISM OF ACTION

11. There are two systems and both require a cryogen . 1 . Open system: It involves direct application by cotton pellets or as spray , the heat is released by vaporization due to drop in temperature. Used when no control over depth is required 2. Closed system: This is based on three principle thermoelectric, evaporative and Joule Thomson effect. Used when depth orientation is required. METHODS OF CRYOTHEARPY

12. SPRAY PROBE FORCEPS 12 TECHNIQUE

13. Application techniques Probe freezing: It is done by direct application of a probe tip to the lesion. The cryogen circulates through the probe tip and super cools it, when allowed to contact the target tissue . In contact freezing , firm contact is made between the cryoprobe and the target tissue . While in penetration freezing probe penetrates the target tissue, providing a large area of direct contact. Spray freezing: It is done by direct application of the liquid nitrogen to the tissue and is the most destructive method. Liquid nitrogen is delivered to the target tissue at such a volume and velocity that it evaporates at the edge of the lesion.

14. How it Works The application of liquefied N₂0 sprayed directly on the skin will bring temperature fully under control (nitrous oxide always evaporates at (-)127⁰ Sophisticated micro-applicator technology enables an unprecedented level of accuracy of treatment from 1mm. The prevention of trauma to surrounding tissue will assure patient’s comfort The pressure of the spray at 721 psi will give maximum control over depth of freezing and will guarantee the results of the treatment .

15. Why Pressure ??? The penetration of the ice crystal into the lesion as a result of cryosurgery with the CryoProbe will go faster and deeper with minimal surface trauma. The freezing rate of CryoProbe is 1mm per 5 seconds Depth of treatment: the CryoProbe freezes up to a maximum 5 mm cell structure

16. Very cold gases are then passed through the needles, creating ice balls that destroy the gland(tumor).

17. 18 CRYOABLATION

18. 2/6/2017 6:43:03 AM RT/15/CRYOSURGERY/45 19 VIDEO

19. Mechanism of cryosurgery The destructive effect of freezing tissue has been categorized into two major mechanisms Immediate cell destruction Delayed cell destruction Direct effects Indirect effects

20. 1. Ice crystal formation: Rapid cooling causes formation of ice crystals from intracellular and extracellular fluid resulting in physical disruption of cell 2. Thermal shock: Damage of cell membrane due to freezing occurs and this alters cell permeability leading to cell death. 21 DIRECT EFFECTS

21. 3 . Cellular dehydration and electrolyte disruption: Initially during freezing the extracellular fluid alone forms ice which is limited by intracellular fluid and there is increase concentration of electrolyte in the extracellular fluid this causes movement of intracellular fluid to extracellular spaces where they again form ice crystals. This results in dehydration of cell , cell shrinkage, intracellular increase in electrolyte which is toxic to the cell and all together causes’ cell death . 22 DIRECT EFFECTS

22. 4 . Enzyme inhibition: Each enzyme requires particular temperature for their functioning which when altered prevents their function . 5. Effect on proteins: During the phase after cooling when the cells return to normal temperature imbibes more water as it has high concentration of electrolyte which result in swelling and rupture 23 DIRECT EFFECTS

23. 1. Vascular effect: Ischemic necrosis results due to vascular thrombus and micro-thrombus formation. 2. Immunological effect: Massive release of pathological cell antigen occurs making them susceptible for host surveillance mechanism . 25 INDIRECT EFFECTS

24. 2/6/2017 6:43:03 AM RT/15/CRYOSURGERY/45 26 VIDEO

25. Controlling parameters during cryosurgery Temperature cooling rate Thawing rate Freeze duration Repetitive freeze- thaw cycle

26. Cooling rate In cryosurgery, rapid cooling rate i.e. more than 50 C/min produces intracellular ice- crystals which is more destructive Such higher rates of cooling can only be achieved close to the cryoprobe Temperature Mazur stated that the lethal temperature range is between -5 C to -50 C. The treatment of tumor requires a tissue temperature at which all the abnormal cells are certainly dead.

27. Thawing rate Thawing rate should be slow and continued for longer time period; rapid thaw rates allow cell survival. Repetitive freeze- thaw cycle Rapid freezing and slow thawing do not guarantee effective cell destruction. Use of repeated freeze-thaw cycle is also beneficial in treatment of cancerous tumor

28. Bio-heat Equation Several heat transfer mechanisms occur during cryosurgery, including conduction, convection, metabolism and phase change. Heat transfer by conduction has been assumed to be the primary heat transfer process during cryosurgery since the cryoprobe operates at an extremely low temperature. Bio-heat transfer is the study of heat transfer in biological system. The fundamental heat transfer equation in biological tissue was firstly suggested by Pennes .

29. Pennes suggested that the rate of heat transfer between blood and tissue is proportional to the product of the volumetric perfusion rate and the difference between the arterial blood temperature and the local tissue temperature. He expressed that relationship as follows Where, h b is the rate of heat transfer per unit volume of tissue, V is the perfusion rate per unit volume of tissue, ρ b is the density of blood, c b is the specific heat of blood, K is a factor that accounts for incomplete thermal equilibrium between blood and tissue (0<K<1, for some cases K = 0) Ta is the temperature of arterial blood, and T is the local tissue temperature

30. Cryotherapy Benefits Benefits of Cyrosurgery in Veterinary Medicin Minimal/Painless No open wounds – No Bleeding No suturing No general anthesia – safe for older Rapid treatment time – only seconds Pinpoint Accuracy Less discomfort ,no hospitalization/minimal post op care. Predictable , low tissue damage. Minimal or no scarring. Can be an adjunctive therapy with surgery or radiation therapy in malignancy. Safe , easy to perform, inexpensive.

31. 1.Healing is slow 2. In lesions of the tongue the procedure can limit its function. 3. Volume of lesion can be beyond capacity 4. Extensive lesions are difficult to treat. 34 Disadvantages

32. Disadvantages of Cryosurgery As with the advantages of cryosurgery, the disadvantages can also be categorized into those for the clinician and those for the patient. Disadvantages for the clinician include the following: Liquid nitrogen needs to be delivered and stored. A liquid nitrogen generator may be purchased. If that is not done, nitrous oxide tanks or other supplies will need to be replenished as needed. The clinician must be certain of the diagnosis because no tissue will be sent for pathology. Cryosurgery is not as accurate as a scalpel or laser in cosmetic work. Disadvantages for the patient include: Erythema and swelling are the norm. Blistering is common. May require multiple visits. Hypopigmentation. Damage to adjacent structures such as joints and bones may lead to lameness and fracture. Risk of uncontrolled freezing - resulting in destruction of normal tissue.

33. CryoProbe Accurate Pinpoint Precision, Freezing Power and Pressure with the touch of your Fingertip! Manufacturers have devised various metal attachments to serve as heat-conducting probes for cryotherapy . Copper, because of its high conductivity, is typically used

34. Accuracy to the millimeter CryoProbe’s different micro applicators tips allow pinpoint accuracy to treat skin lesions from 1mm to 8mm in size! Blue dot applicator Applications 1-3 mm White dot applicator Applications 2-4 mm Green dot applicator Applications 3-6 mm Yellow dot applicator Applications 4-10 mm

35. Simple pencil type grip for easy use . Very accurate application .  Freezes to -89ºC and to a depth of 3mm . Interchangeable ‘contact’ heads for special applications including GUM, Podiatry & Dermatology . Avoids all of the storage and transport problems associated with traditional cryotherapy Once a cylinder has been attached CryoAlfa can be kept in a drawer without degradation of the N20 contents for approximately 3 months . Can be easily transported for use in home visits . The level of cold generated can be adjusted by the rate at which the button is depressed . 38 NEW ADVANTAGES

36. Lesions With the CryoProbe you will be able to treat (but not limited) to the following lesions successfully: Adenomas Epuli Pappilomas Granulomas Warts Small Sarcoids Eye Lid Tumors You will be able to quickly and easily treat skin lesions that you could not treat before without undesired side effects!

37. 2/6/2017 6:43:03 AM RT/15/CRYOSURGERY/45 40 LENTIGENOUS MACULES ACTINIC CHELITIS EROSIVE LICHEN PLANUS SKIN TAGS

38. 2/6/2017 6:43:03 AM RT/15/CRYOSURGERY/45 41 Xanthelasmes VIRAL WARTS SOLAR KERATOSES SEBORRHOEIC KERATOSIS

39. 42 BASAL CELL CARCINOMA

40. 2/6/2017 6:43:02 AM RT/15/CRYOSURGERY/45 43 CARCINOMA OF SKIN TOUNGE CARCINOMA

41. 2/6/2017 6:43:02 AM RT/15/CRYOSURGERY/45 44 AGGRESSIVE JAW LESIONS

42. VASCULAR MALFORMATIONS LEUKOPLAKIA HYPERPLASTIC LESIONS MUCOUS CYST FACIAL PAIN TMJ PAIN ORAL CANCER 45 OTHER ORAL USES

43. 46

44. 1. Cold urticarial patient develop redness and swelling in the skin 2. Cryoglobulinemia , abnormal blood protein results in gel formation resulting in ischemia or gangrene 3. Raynaud’s phenomena 4. Paroxysmal cold hemoglobinuria,hemoglobin is released from lysed red cells and is excreted in urine 5. Peripheral vascular disease 6. Patients undergoing immunosuppressive therapy 47 Contraindications

45. CONTRA-INDICATIONS TO ICE TREATMENT Cardiac Conditions Psychological: Peripheral Nerve Injuries Vasospastic Disease Peripheral Vascular Disease Cold Sensitivity 2/6/2017 6:42:48 AM RT/15/CRYOSURGERY/45 48

46. Cryotherapy is an effective treatment method for a variety of lesions of the head and neck region. It is advantageous over surgery and is well accepted by patients. Many a times it is used when the conventional therapy either fails or is contraindicated. But unless the physician is confirmed of the diagnosis and volume of lesion it is not advisable to use it. 49 CONCLUSION

47. 1. Cryosurgery – a practical manual – paola pasquali 2. Web 3. Cryotherapy - a novel treatment modality in oral lesions- international journal of pharmacy and pharmaceutical sciences. Issn - 0975-1491 vol 5, suppl 4, 2013 4. Reade pc. Cryosurgery in clinical dental practise.Int dent j 1979;29:1-11. 5. Leopard pj . Cryosurgery and its applications in oral surgery. Br j of oral surg 1975;13:128-52. 6. Orpwood rd. Cryosurgical apparatus. In: bradley pf , ed , cryosurgery of maxillofacial region. Vol.1.Boca raton , florida : crc press, 1986. 50 REFERENCES