CRYOTHERAPY

Dr Rama Charan Potturi

 • Definition
• History
• Principle & Mechanism
• Indications
• Contraindications
CONTENTS • Equipment
• Pre-op-> Procedure -> Post-op
• Complications
• Comparison with other modalities
• Advantages
• Disadvantages
• Conclusion
Definition

Cryotherapy refers to the use of substances at freezing temperatures for

controlled destruction of cells of abnormal or diseased tissue.

• KYROS - “icy cold” in Greek

• SYN: cryosurgery, cryocautery

A brief …
• 2500 BC Egyptians: cold to treat inflammation

• James Arnott, 1840s: salt solution with crushed ice to destroy tumours

• James Dewar, 1888: Vacuum flask to store & transport liquid Nitrogen

• A C White, 1899: cotton-tipped applicator dipped into liquefied air (-190 c)

successfully treated warts, precancerous & cancerous lesions.

• 1945, following World War II –Liq Nitrogen became commercially available

• Irving Cooper, 1961: developed first cryosurgical probe

CRYOGENS
Cryogen is a freezing substance used for withdrawal of heat to induce reduction in tissue temperature

Ice : 0c
Salt-ice : -20 c
Principle & Mechanism

“Heat flows spontaneously from warmer substance to colder substance”

Rapid heat transfer from tissue

Cellular injury, vascular stasis, occlusion and

Immunomodulation

Tissue destruction - CRYONECROSIS

On spraying cryogen-

• Rapid transfer of heat from tissue to cryogen with ice formation in

extracellular (EC) compartment. Extra &

• EC solutes become concentrated -> movement of IC fluid along osmotic

gradient extracellularly-> dehydration & shrinkage of cell. During thaw,
rapid osmosis into cell->cell membrane rupture

• EC Ice crystals also damage cell membrane mechanically (denting)

• Intracellular ice formation -> damages organelles

• Vasoconstriction & increased viscosity-> stasis + endothelial damage ->

platelet aggregation & microthrombi formation producing ischemic necrosis

• Thaw-> vasodilation with flow of emboli-> reperfusion injury

Picture from Goel et al(2009) Adjuvant Approaches to Enhance Cryosurgery. Journal of biomechanical engineering. 131. 074003.
10.1115/1.3156804.
• Cryotherapy postulated to induce apoptosis of tumor cells through
molecular response.

• Evidence present that immune recognition of remaining viral or tumor

cells beyond the margins of freezing site develops

• May promote generation of long term memory cells which have

protective role against further disease
• Differential sensitivity of different tissue to cryodamage:

-Melanocytes - very sensitive (-4 to -8c

- Keratinocytes ( -20 to -30c)
-Dermal collagen – cryo-resistant (-30 to -40 c)
Indications

1. Vascular: Hemangiomas, pyogenic granuloma, angiokeratomas, cherry angiomas

2. Benign tumours: skin tags, DPNs, syringomas, milia, Xanthelasma , SK
3. Acne: Nodular acne
4. Viral infections: Cutaneous warts, condyloma acuminata, MC
5. Inflammatory dermatoses: hypertrophic LP, Prurigo nodularis
6. Infectious dermatoses: cutaneous leishmaniasis, cutaneous larva migrans
7. Premalignant lesions: Bowen’s disease, Actinic keratosis, Leukoplakia, erythroplasia of queyrat
8. Malignant tumors: SCC, BCC and malignant melanoma
Contraindications

Absolute RELATIVE
• Blood dyscrasias of unknown disorders • Keloidal tendency.
• Platelet deficiency • Collagen vascular diseases.
• Cold intolerance • Dark-skinned individuals (risk of developing protracted
• Raynaud’s disease. hypopigmentation)
• Cold urticaria. • Lesions over eyelid margins, ala nasi and hair-bearing
areas (risk of developing cicatricial alopecia).
• Cryoglobulinemia.
• Patients with sensory loss at lesion sites
• Lesions in areas of compromised circulation.
• Pyoderma gangrenosum
• Sclerosing or recurrent BCC
• SCC in high risk areas like temple or nasolabial folds.
Equipment & setting
- Cryotherapy ideally undertaken in fully equipped minor OT with good lighting, appropriate
minimal sterilization and storage facilities

a) Cryogun/cryogen spray canister: Portable, lightweight, handheld device with trigger to

begin and end cooling.
b) Cryo-spray nozzle, spray tips, neoprene or polystyrene cones.
c) Cryoprobe: Available in various shapes and sizes. Cooled by spray of cryogen.
d) Cryogen storage device: Metal cylinders/ containers that store gaseous cryogens as compressed
gas and have inbuilt internal pressure equalization mechanism.

- Cryogen is transferred to cryogun before procedure by siphon or tilting

container to pour into gun via funnel.
- Insulated gloves worn while transferring cryogen
Picture taken from ACSI by Dr Venkataram Mysore; Chapter: Cryotherapy pg: 263
Pre-Procedure
• Written informed consent taken

• Detailed history of general medical condition, previous Rx with results and

whether primary or recurrent lesion, taken.

• H/o sensitivity to cold, cold urticaria, Raynaud’s phenomenon or vascular

insufficiency

• Physical examination:- size, margin, location, depth, biological behaviour

and approximation to superficial nerves
• Area to be treated exposed and cleaned with spirit/povidone-iodine.

• Intralesional/topical anaesthesia: usually not required. Maybe used for

malignant lesions since longer freeze time required to ablate deeper
malignant tissue - severe pain.

• Analgesic/antianxiety drug administered.

• Surrounding normal skin insulated (multi-layered) to prevent spray.

• Eyes, nares and ears protected with goggles, gauze or padding.

Procedure
1. Timed spot freeze technique
a) Open spray method - paint brush method
- spiral method
b) Confined spray method

2. Use of Cryoprobe
3. Dipstick method
4. Histo-freezer
5. Intralesional Cryotherapy
6. Forceps/Clamp technique
7. Thermo-coupled device
Timed spot freeze technique

• Direct spraying of cryogen from handheld gun device.

• Nozzle is held at a distance of 1 cm and lesion and perilesional area should be covered with ice-
field

• Even after icefield forms, spray continued for some more time

• Lesion allowed to thaw before administering second freeze (if indicated)

• Skin palpated to know if thawing has occurred completely

Freeze-Thaw Cycle (FT)
- Cryogen sprayed until an ice ball forms that
completely encompasses lesion (confirmed by
palpating) and desired margin is reached.
- For adequate treatment, the lateral spread of
freeze: 1-2mm in benign, 2-3mm in
premalignant, 5 mm in cancerous lesions
- Spray continued (holding time) after which
lesion is allowed to thaw completely to
complete one FT cycle.
- Complete thawing is suggested by
disappearance of frozen white surface.
A)Direct: If lesion <2cm, rounded & defined. Spray aimed at centre of
lesion.

B)Open-spray: for larger areas with superficial lesions

1)paintbrush: starting at one end; moving up and down

2)Spiral: Starting at circumference moving inside with circular motion

C)Confined-spray: Sprayed through cones to restrict field diameter.

Useful when vital organs present in vicinity
Other methods
Cryoprobe: Suitable size probe attached to cryogen and applied directly. More suitable for
deeper lesions ( ~2cm)
Dipstick: Cotton dipped bud dipped in cryogen and applied with pressure. Cheap but less
effective. Requires more freeze thaw cycles.
Intralesional Cryotherapy: Ideal for scars and keloids (depth >2cm). Wide bored needle is
inserted parallel to skin surface into keloid and cryogen is injected. The epithelial layer is
not damaged (avoiding hypopigmentation post-op)
Cryo-roller: Ideal for larger, superficial lesions. Metallic cylinder is dipped in cryogen and
rolled over lesion.
Histofreezer: Small unit containing a liquid-gas mixture of dimethyl ether & propane in an
aerosol spray can. Sprayed through narrow tube to cotton applicator, which is applied to
wart. The mixture evaporates and freezes the wart. A temperature of –50°C is reached at
cotton tip, that freezes the wart.
Gentler method (higher temp) less effective than liq N2 by spray method; N/A in India
Post-procedure
• Patient explained about immediate skin reactions post cryotherapy.
- Lesion site: peripheral erythema occurring 0-30 minutes after therapy, edema within few
minutes to hours.
-Blister formation 1–3 days later, followed by crusting lasting up to 2 weeks.
-Crust falls off -> pinkish discoloration or erythematous atrophic scar.
-Patient asked to apply topical steroid & antibiotic combination.
• Large blister->punctured with sterile needle, or aspirated with roof left
in position as natural protective film.
• NSAID administered.
• Treated area left open, washed gently with soap and water and patted
dry.
Results
Complications

Can occur due to

Inappropriate patient
selection

Aggressive freezing at
sensitive sites

More freeze-thaw cycles

than recommended

Complications can be immediate, delayed and protracted

 Complications in Cryotherapy
IMMEDIATE DELAYED PROTRACTED
Edema and blister Hemorrhegic necrotic Hypopigmentation at site
formation blister (destruction of
melanocytes)
Pain (during & immediately Wound infection Atrophy
after)
Headache (head & neck Delayed wound healing Cicatricial alopecia
lesions)
Vasovagal attack Scar hypertrophy (rare) Milia
Bleeding (rare) Temporary hypoesthesia
(lesions close to superficial
nerves)

Rare events- cartilage damage, traumatic neuroma

 Comparison with other modalities

1. BCC:
-Cryotherapy comparable to photodynamic therapy or surgery in efficacy
(PDT better cosmetic result)
-Inferior to radiotherapy; (recurrence rate 4% vs 39 %)

2. AKs:
- Cryotherapy superior to ablative CO2 laser for isolated AKs on scalp & face
(78 to 72% at 3 months) with significantly better remission( 78 to 22 % at 12
m)
- Cryotherapy inferior to 5-FU and Imiquimod (ICR- 70% vs 94% vs 85%)

1. Tchanque-Fossuo CN, Eisen DB. A systematic review on the use of cryotherapy versus other treatments for basal cell carcinoma. Dermatol Online J. 2018;24(11):13030/qt49k1c38t. Published 2018
Nov 15.

2. Zane C, Facchinetti E, Rossi MT, Specchia C, Ortel B, Calzavara-Pinton P. Cryotherapy is preferable to ablative CO2 laser for the treatment of isolated actinic keratoses of the face and scalp: a
randomized clinical trial. Br J Dermatol. 2014;170(5):
3. Keloid:

-liq Nitrogen cryotherapy with ILS better result (dec. pain, pruritus) with lesser recurrence to only liq N cyro

-average scar volume decreased (range:51%-63%), but complete scar eradication not achieved. Scar recurrence

(range: 0% to 24%). Hypopigmentation posttreatment seen mostly in Fitzpatrick 4–6 skin type patients.

-IL cryo more effective with lesser side effects

4. Warts:

-Equally effective as Salicylic acid topical (62% vs 65%)

3. van Leeuwen, Michiel C. E. MD*; Bulstra, Anne Eva J. BSc*; Ket, Johannes C. F.†; Ritt, Marco J. P. F. MD, PhD*; van Leeuwen, Paul A. M. MD, PhD‡; Niessen, Frank B. MD, PhD* Intralesional Cryotherapy for the Treatment of Keloid Scars, Plastic and
Reconstructive Surgery – Global Open: June 2015 - Volume 3 - Issue 6 - p e437
Barara, M., Mendiratta, V., & Chander, R. (2012). Cryotherapy in treatment of keloids: evaluation of factors affecting treatment outcome. Journal of cutaneous and aesthetic surgery, 5(3), 185–189.
  Old patients (esp with pacemakers in whom electrocautery is
Special cases contraindicated)
where  Patients on anticoagulants.

cryotherapy can  Subjects allergic to anaesthetic agents.

 Patients with transmissible conditions such as HIV and hepatitis.
be used :  Genital lesions during pregnancy
 Children (too young may feel anxious)
• OPD procedure- safe, fast, no anesthesia required
• Inexpensive and affordable option for variety of conditions
• Safety for physician as well- relatively “No touch” technique
• Can be done in all age groups; minimal side effects
• Multiple lesions at multiples sites; less time consuming
• Safe during pregnancy
• Good cosmetic results
• PAIN – MC complaint and cause for anxiety
• Multiple sessions required for recalcitrant lesions
• Post treatment oedema and blisters- significant concern
• Dark-skinned people-hypopigmentation following procedure
is cause for concern
• Longer healing time and possible alopecia (if hair bearing
site) with deep freezing
 What the future
holds…
• Role in future is intricately linked with the
improvement in imaging methodology
• Will benefit from newer non-invasive real-time
imaging techniques like confocal microscopy and
optical coherence tomography
• These will provide info reg depth, volume and
histology providing better margin control while
freezing can be visualised in situ
 Conclusion
 Cryotherapy - simple and effective procedure which can be
performed on OPD basis
 Cost-effective modality for various benign and malignant lesions
 Can be used safely in elderly patients and pregnant women.
 Clinician should be aware of possible complications and avoid over
aggressive therapy
 Pt to be counselled regarding the immediate and late complications
and the need for multiple sessions
 References

• Kang S et al(2019) Fitzpatrick’s Dermatology In General Medicine. 9th ed. New York: McGraw-Hill, pg.3791-95.

• Bolognia, J., Jorizzo, J. L., & Schaffer, J. V. (2018). Dermatology. Cryosurgery: Pasquoli P Philadelphia: Elsevier
Saunders. Pg. 2385-92

• Sacchidanand S et al (2015) IADVL Textbook of Dermatology 4th ed ; Cryotherapy: Amruta B, Satish A; Bhalani
Publishers. Pg-2424-31

• Savant S(2017) Textbook of Dermatosurgery & Cosmetology: Principles & Practice (3rd ed) Cryosurgery. Bhalani
2017; pg 284-204

• Tchanque-Fossuo CN, Eisen DB. A systematic review on the use of cryotherapy versus other treatments for
basal cell carcinoma. Dermatol Online J. 2018;24(11):13030/qt49k1c38t. Published 2018 Nov 15.
-Mysore V (2017) ACSI Textbook of Cutaneous & Aesthetic Surgery 2nd ed: Cryosurgery: Khandpur S; Jaypee Publishers. pg
264-71

- Tchanque-Fossuo CN, Eisen DB. A systematic review on the use of cryotherapy versus other treatments for basal cell
carcinoma. Dermatol Online J. 2018;24(11):13030/qt49k1c38t. Published 2018 Nov 15.

- Zane C, Facchinetti E, Rossi MT, Specchia C, Ortel B, Calzavara-Pinton P. Cryotherapy is preferable to ablative CO2 laser for
the treatment of isolated actinic keratoses of the face and scalp: a randomized clinical trial. Br J Dermatol. 2014

- van Leeuwen, Michiel C. E. MD*; Bulstra, Anne Eva J. BSc*; Ket, Johannes C. F.†; Ritt, Marco J. P. F. MD, PhD*; van Leeuwen,
Paul A. M. MD, PhD‡; Niessen, Frank B. MD, PhD* Intralesional Cryotherapy for the Treatment of Keloid Scars, Plastic and
Reconstructive Surgery – Global Open: June 2015 - Volume 3 - Issue 6 - p e437

-Barara, M., Mendiratta, V., & Chander, R. (2012). Cryotherapy in treatment of keloids: evaluation of factors affecting
treatment outcome. Journal of cutaneous and aesthetic surgery, 5(3), 185–189.
THANK
YOU!