CRYOSURGERY

INNOVATIONS IN
MUSCULOSKELETAL TUMOR MANAGEMENT

Abigail Tud, MD-MBA, FPOA

Philippine Orthopedic Center
Taipei Veterans General Hospital

Taipei Veterans
General Hospital
 OUTLINE

I. Introduction
II. Brief history of cryogens for oncologic applications
III. Relevance to the Philippine setting
IV. Advantages over other methods of limb sparing surgery
V. Case examples
VI. Conclusion
AT THE END OF THE LECTURE,
ATTENDEES ARE EXPECTED TO:

1. Be able to enumerate the two most common cryogens used in surgical/orthopedic

oncology today
2. Be able to discuss at least two advantages of liquid nitrogen over carbon dioxide as
cryogenic adjuvant
3. Be able to summarize this technique's overall relevance to low-resource settings such as
the Philippines
INTRODUCTION

• Cryogens are not so novel!

• First presented at the Great Exhibition in London, 1851

ApparatusJames
was BULKY
Arnott,and difficult to use
English surgeon
Tumors had(1797-1883)
to be visualized EXTERNALLY
to be treated with success (at a time
BEFORE asepsis and anesthesia)
à Salt solutions with crushed
ice at -18º to -24º C to
Success at achieving complete tumor
Arnott’s Liquid air/ CO2 / freeze breast and cervical
Liquid
destruction could not be ascertained
salt solution O2 dry ice nitrogen cancers

1850s 1870s 1900s 1950s

INTRODUCTION

• Progressive research
• Late 1800’s : experiments on liquid O2 and CO
• 1900’s : CO2 in the form of carbonic snow
• 1950’s : Liquid nitrogen first used for medical
applications
Arnott’s Liquid air/ CO2 / Liquid
salt solution O2 dry ice nitrogen

1850s 1870s 1900s 1950s

INTRODUCTION

• Progressive research
• Liquid nitrogen is now the most popular
cryogenic adjuvant in use

Temperature: -196C
Depth: 5 to 8mm
Arnott’s Liquid air/ CO2 / Liquid
salt solution O2 dry ice nitrogen

1850s 1870s 1900s 1950s Bickels J et al. The role and biology of cryosurgery in the treatment of bone
tumors . Acta Orthop Scand 1999; 70 (3):308-315
INTRODUCTION: CRYOSURGERY USING
LIQUID NITROGEN (LN)

• Introduced as a local adjuvant in the 1970’s Minimum temperature for MSK

tumor cell necrosis (Gage et al)
• Mechanism of Action:
Freezing rate
Protein
denaturation

Liquid nitrogen
Mechanical
Microvascular
membrane
disruption Failure Freezing rate

Bickels J et al. The role and biology of cryosurgery in the treatment of bone
tumors . Acta Orthop Scand 1999; 70 (3):308-315
A BRIEF HISTORY OF CRYOGENS IN
ORTHOPEDIC ONCOLOGY

• Cryosurgery using Liquid Nitrogen (LN)

• Late 1960s to 1970s
• Marcove and Miller LN
48M: lytic lesion,
poured Relief of
proximal humerus
directly pain!
secondary to MBD
into cavity

Bickels J et al. The role and biology of cryosurgery in the treatment of bone tumors
Acta Orthop Scand 1999; 70 (3):308-315
A BRIEF HISTORY OF CRYOGENS IN
ORTHOPEDIC ONCOLOGY

Recycled bone as an option for limb salvage in

orthopedic oncology: concept overview

Bone tumor excision with appropriate margins

|
V
Earlier modalities: irradiation, pasteurization
More recent: liquid nitrogen
|
V
Tumor cells destroyed, structure of bone preserved
|
V
“Recycled autograft” can be used for reconstruction
à minimizes extensive metallic implant use
A BRIEF HISTORY OF CRYOGENS IN
ORTHOPEDIC ONCOLOGY

• Caveats:
1. Thermal (cold) injury à FROSTBITE
2. Secondary fracture
3. Temporary neuropraxia

CONCERNS
Professor Po Kuei Wu, MD, PhD, MBA
Ultra-low temperature liquid: Chief, Division of Joints Reconstruction
Head, Therapeutical and Research Center for
ü Decreased visualization Musculoskeletal Tumors
ü Frost bite Taipei Veterans General Hospital
ü Soft tissue necrosis
OVERVIEW OF LN APPLICATIONS FOR
MUSCULOSKELETAL TUMORS

Adjuvant for Pedicle vs free freezing

extended curettage after resection with
appropriate margins

Tumor-bearing
bone

FNEC
GENERAL COMPARISON OF ADJUVANTS:
HOW DO THEY COMPARE?
ADJUVANT MECHANISM OF ACTION ADVANTAGES DISADVANTAGES
Ease of use
Argon beam Thermo-electric: protein coagulation Availability
Comparable recurrence

Bone necrosis
Low concentration (5%) better to
Soft tissue necrosis
Phenol Chemical: protein denaturation extend margins
Systemic toxicity
Comparable recurrence
Carcinogenic potential
Pathologic fracture
Thermal: fast freeze à fast thaw Comparable recurrence
LN Soft tissue injury
= cell injury and inflammation
Nerve palsy

Thermal: fast freeze à slow thaw

Avoids LN complications No long-term studies, not for
FNEC intracellular ice crystallization-recrystallization,
Comparable recurrence high grade malignancies
cytoplasmic dehydration
Chen CF et al. A safety comparative study between FNEC and LN for cryotherapy of musculoskeletal tumors. Cryobiology. 2018 Aug;83:34-39.
Mittag et al. 2013. cytotoxic effect and tissue penetration of phenol for adjuvant treatment of giant cell tumours. Oncol Lett: 5(5), 1595-1598.
Zenker, M. 2008. argon plasma coagulation. GMS Krankehhyg Interdiszip: 3(10) Doc 15.
Puri, A. and M. Agarwal. 2007. Treatment of giant cell tumor of bone: Current concepts. Indian J Orthop. 2007 Apr-Jun; 41920:101-108.

OVERVIEW OF LN APPLICATIONS FOR
MUSCULOSKELETAL TUMORS
Adjuvant for
extended curettage
Free (FF) vs Pedicle Freezing (PF)
FF: 9.8mos = longer
Time to union
PF: 4.8mos
FF: 15.4% = higher
Rate of non-union
PF: no osteotomy
Pedicle vs free freezing
FF: 6 / 13 patients
after resection with Post-op complications
PF: 2 / 7 patients
appropriate margins
 RELEVANCE TO THE PHILIPPINE SETTING

• LOCAL CHALLENGES TO LIMB SALVAGE

Sarcomas vs Carcinomas
• Metallic endoprosthesis replacement (EPR) is the current standard for YOUNGER, AND/ OR WITH LONGER
complex extremity reconstructions in foreign centers FOLLOW-UP
ü Modularity
ü Quick return to function MEAN TIME TO FAILURE:
47 MONTHS
ü Aesthetics Most common modes:
ü COVERED BY INSURANCE 1. Infection
2. Implant loosening
Lack of Lost to Hilot and
finances follow-up arbularyo
Henderson ER et al. 2011. Failure mode classification for tumor
endoprostheses: retrospective review of five institutions and a literature
review. J Bone Joint Surg Am 2011; 93:418-29. Population data from TVGH courtesy of Dr. PQ Wu
ADVANTAGES OVER EPR IN THE CONTEXT
OF THE FILIPINO PATIENT
CASE 1: AF, 20M SURGERY PERFORMED CASE 2: AN, 22M
<< Extended curettage with
FNEC, bone cement and plate
(pre-op denosumab x 4)

Proximal femoral resection +

Endoprosthetic Replacement
(pre-op denosumab x 3) >>

Pre-operative function (MSTS)*

10/30 15/30

Latest MSTS score

30/30 (2.5 years postop) 28/30

VAS/ Pain: both 0/10

Php 80,000** Php 650,000.00**

APPROXIMATE COST OF
fully-covered by PCSO (money sent by aunt in the US)
PATIENT- SELECTED
INTERVENTION

*Musculoskeletal Tumor Society score for function, focused on lower extremity

**Amount as indicated by implant provider
CASE EXAMPLES
22F : OSTEOGENIC SARCOMA,
R I G H T D I S TA L F E M U R S / P P E D I C L E
F R E E Z I N G , ROTAT I N G H I N G E K N E E
R E P L AC E M E N T

Liquid nitrogen
CASE EXAMPLES
22F : OSTEOGENIC SARCOMA,
R I G H T D I S TA L F E M U R S / P P E D I C L E
F R E E Z I N G , ROTAT I N G H I N G E K N E E
R E P L AC E M E N T

Day 3 4 months
Day 10: trip to
South Korea!
CASE EXAMPLES
61M : RECURRENT UPS, LEFT FEMUR
W I T H M U LT I P L E S K I P M E TA S TA S E S ,
S / P C U R E T TAG E , B O N E G R A F T A N D
D I S TA L F E M O R A L L O C K E D P L AT I N G

Radiographs from outside institution, taken

prior to first surgery (intralesional margins)
CASE EXAMPLES
61M : RECURRENT UPS, LEFT FEMUR
W I T H M U LT I P L E S K I P M E TA S TA S E S ,
S / P C U R E T TAG E , B O N E G R A F T A N D
D I S TA L F E M O R A L L O C K E D P L AT I N G
CASE EXAMPLES
61M : RECURRENT UPS, LEFT FEMUR
W I T H M U LT I P L E S K I P M E TA S TA S E S ,
S / P C U R E T TAG E , B O N E G R A F T A N D
D I S TA L F E M O R A L L O C K E D P L AT I N G

After total femur resection, Specimen is thawed for 20 Trial hip and knee Side plate applied
bone is immersed 20 mins mins implants placed
CASE EXAMPLES
61M : RECURRENT UPS, LEFT FEMUR
W I T H M U LT I P L E S K I P M E TA S TA S E S ,
S / P C U R E T TAG E , B O N E G R A F T A N D
D I S TA L F E M O R A L L O C K E D P L AT I N G

Day 5 post-surgery
CASE EXAMPLES
61M : RECURRENT UPS, LEFT FEMUR
W I T H M U LT I P L E S K I P M E TA S TA S E S ,
S / P C U R E T TAG E , B O N E G R A F T A N D
D I S TA L F E M O R A L L O C K E D P L AT I N G

Day 5 post-surgery 1 month post-surgery

CONCLUSION
• Cryosurgery has been around for decades! Liquid nitrogen is the most popular cryogen in use today with clear
advantages over CO2 / dry ice:
1. Lower temperature = better tumor necrosis
2. Deeper tissue penetration

• Biologic reconstruction after cryosurgery: an economical option with evidence-based results for limb salvage
surgery relevant to the PH setting when performed correctly, for the right indication
• Just because you think you can do it, should you do it? Consider your capabilities and the patient’s well-being

• Take home reminders for general as well as Oncology subspecs:

• Define surgeon and patient factors that increase efficiency of surgery, limit morbidity, improve recovery and function
• TEAMWORK MAKES THE DREAM WORK! Communicate, share the load, and when in doubt, REFER J
WE ARE NOW AT THE END OF THE
LECTURE! HOPEFULLY, EVERYONE WILL:

1. Be able to enumerate the two most common cryogens used in surgical/orthopedic

oncology today
2. Be able to discuss at least two advantages of liquid nitrogen over carbon dioxide as
cryogenic adjuvant
3. Be able to summarize this technique's overall relevance to low-resource settings such as
the Philippines
THANK YOU!