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MASTER CLASS

Belgrade, Serbia
Wednesday May 21st, 8.30 15.00
NON-MELANOMA SKIN CANCER: A HOLISTIC
APPROACH & STATE OF THE ART

Treatment of NMSC
Cryosurgery: when and how

Pasquali, Paola
Pius Hospital de Valls (TA)
Spain

MASTER CLASS
Belgrade, Serbia
Wednesday May 21st, 8.30 15.00
NON-MELANOMA SKIN CANCER: A HOLISTIC
APPROACH & STATE OF THE ART

Treatment of NMSC
Cryosurgery: when and how

I do not have any relevant relationships with


industry
Pasquali, Paola
Pius Hospital de Valls (TA)
Spain

Treatment of NMSC . Cryosurgery: when and how

Basic Concepts of cryobiology


Cryoimmunology
Pre operative care
Equipment
Techniques
Indications
Cryobiopsy
Anatomical areas
HFUS and cryosurgery
Single vs Multiple lesion treatment
Palliative cryosurgery
Post operative care
Future considerations

Basic Concepts

Destruction of tissues using sub zero temperatures


Most common cryogen: Liquid Nitrogen (-196C)
Cancer cells are destroyed at around -50C
Temperature spreads in isotherms

C
R
Y
O
G
E
N

AIR

WATER

ICE

METAL

CRYOLESION
MECHANISM

DIRECT INJURY

VASCULAR INJURY

APOPTOSIS

IMMUNOLOGICAL

TIME of CYCLE

LOCATION

Extra- and
Intracellular ice
crystal formation
+ coagulation
necrosis

Freezing phase

Center of the
cryoinjury

Microcirculatory
failure+
Ischemic necrosis

Thawing phase

Periphery of the
cryoinjury

Cell death by
apoptosis

Up to 8 hours
after rewarming

Periphery of the
cryoinjury

T-cell response
mediated by
dendritic cells

Late event

Whole body

Pasquali P. Cryosurgery. In: Rigel D et al. (Eds.) Cancer of the Skin. 2nd Ed. 2011

Cryoimmunology
Tumor remains in situ upon cryosurgery procedure
After cryosurgical injury, there is release of tumoral
antigens
Tumoral antigens induce anti-tumoral response
First response is related to inflammation and it is a
short-lived, non-specific innate immune response
Balance between necrosis (inflammatory: neutrophils,
macrophages, and lymphocyte) and apoptosis (non
inflammatory)

Acquired immune response: Antigen presenting


cells (APCs) (macrophages and dendritic cells (DCs)).
Engulf the antigens and present them to T-cells via
major histocompatibility complex (MHC) Class I and
II.

Dendritic cells loaded with antigens now migrate to


lymph nodes where they undergo maturation,
becoming efficient APCs able to prime nave antigen
specific T-cells.

Moioli E, Krunic A. Immunological Aspects of Cryosurgery.


In: Baldi A, Pasquali P, Spugnini E. (Eds) Skin Cancer a Practical Approach. Springer ,2014.pp397-407

Adaptive Immune
Response

1
.

Abs

5
. Cytotoxic

Tumor

CD8+ T-cell
IFN
TNF
IL-1
IL-6

2
.

Th1

Antige
ns

4
to lymph.

APC
s

(+ IL-12)
MHC

node

PMN
3
s
. Macrophag
es

Bcell

mature
APC
Blood
Vessel

Th2
TCR

TCell

Minimal

Consent forms
Non invasive imaging
Confirm diagnosis
Pre operative conditions
of relevance
Post operative cures

Pre operative

Equipment
General

Sterile gloves
Antiseptic agents
Local anesthesia and syringes
Minor surgery equipment with suture kit/set; curettes
Cauterizing agent
Biopsy jars

Specific
LN Storage and Withdrawal /Gloves/ Base
Units
Tips/Probes/Chambers
Others
Photographic camera
HFUS
Software

Hand-held unit

Techniques
OPEN
Flat lesions or elevated
Irregular surface
Large or small
Ideal for superficial BCC

CLOSE
Ideal for nodular tumors

Needs to be adjusted to tumor


size

CHAMBER OR SEMI CLOSED

For fast and deep freezing


Ideal in metastasis
Needs to be adjusted to
tumor size

INTRALESIONAL

Invasive
Needs US

For large
tumors/Metastasis

Indications
Cryobiopsy
Basal cell carcinoma: except
morpheiform/sclerodermiform/
not well defined margins
Squamous cells carcinoma:
Kerathoacantomas/Well to
moderately differentiated SCC

Palliative treatment

Cryobiopsy

Anatomical location
Ear
Nose
Eyelid

Earlobe

Eyelid

Courtesy: Dr. Olle Larko


Gun Lindgren
Sahlgrenska Academy
University of Gothenburg
Sweden
Gothenburg University

Nose

HFUS AND CRYOSURGERY

HFUS: 22 MHz
100
R 16 m
P 0.8-1.5 mm
Resolution 48 m
Resolution 210 m
Resolution 72 m
Penetration: 4-6 mm
Penetration: 8-10 mm
Resolution 31m Penetration: 50-70 mm
Penetration: 3-5 mm
Resolution 158 m
Penetration: 35 mm

Resolution 210 m
Penetration: 50-70 mm

Trans Cryosurgery

Single vs Multiple NMSC

773x6133

797x 9767
1180 x 4767

IV

859x5400

523x8133

HHI Treatment

9 cm

Palliative treatment

Initial lesion

Dividing lesion into


segments

Segmental cryosurgery

Allow individual freezing


Fronts advance until
overlap

Initial lesion

Final lesion

Freezing
spot

Freezing stars at the center;


arrows indicate the direction of
advancement of freezing front

Smaller final lesion


after complete healing
That leaves a central scar

Fractional cryosurgery
After Goncalves JC. Fractional cryosurgery. A new technique for basal cell carcinomas of the eyelids and periorbital
area. Dermatol Surg 1997;23:475-481.

Cryoimmunology
C
R
Y
O

5 week imiquimod

Gaitanis G, Bassukas ID. Immunocryosurgery for non-superficial basal cell carcinoma: a prospective, openlabel phase III study for tumours 2 cm in diameter. Acta Derm Venereol. 2014 Jan;94(1):38-44.

Post operative care

Time and patience


Daily cleaning
Necretomies

Future considerations

Reflectance
Confocal
Microscopy
RCM is a noninvasive in vivo imaging technique
It relays on the natural variation of refractive indices in
tissue structures at different depths of the skin to
reconstruct the images.
In cryosurgery, it can be used a non-invasive
determination of lesion margins as well as a non-invasive
therapy monitoring

Optical Coherence
Tomography
OCT is a noninvasive in vivo imaging technique
OCT provides real-time, cross-sectional skin images to a depth
of up to 2 mm. It is based on an interferometric technique that
detects reflected or backscattered light from tissue
In cryosurgery, it can be used a non-invasive determination of
lesion margins as well as a non-invasive therapy monitoring

MASTER CLASS
Belgrade, Serbia
Wednesday May 21st, 8.30 15.00
NON-MELANOMA SKIN CANCER: A HOLISTIC
APPROACH & STATE OF THE ART

Treatment of NMSC
Cryosurgery: when and how

Thank you for your attention

Pasquali Paola, MD
Pius Hospital de Valls (TA)
Spain
pasqualipaola@gmail.com