Lymphedema Research
HN Mayrovitz, PhD, Professor of Physiology
College of Medical Sciences, Nova Southeastern
University, Ft. Lauderdale, Florida 33328
• Lymphedema Physiology
• Research into Early Detection
• Research into a New Therapy
• ‘Evolving’ Research Projects
The Lymphatic System
and Lymphedema
Arterial
system
Venous
System
Blood
Capillaries
Lymphatic
Capillaries
Lymphatic
Vessels
Lymph
Nodes
Lym
ph
ati
c S
ys
tem
The Third
Circulatory
System
Heart
Arteries
FiltrationResorption
~30 liters/day
Normal Fluid Balance
Blood Capillary
~27 liters/day
TISSUE AND CELLS
Lymphatic Capillary
Normal Fluid Balance
protein~3 liters/day
(10% of filtered) Back to
Venous
System
Start of the
Lymphatic
System
FiltrationResorption
~30 liters/day
Blood Capillary
~27 liters/day
Overload = Edema
+ [Protein]
= Lymphedema
If Net Filtration Exceeds
Lymphatic Transport Capacity
Excess --> Lymphatics
Fluid +
Protein
capillary
Excess
Fluid +
Protein Lymphatics
blood
capillary
NORMAL
Excess
Accumulates
Fluid +
Protein Lymphatics
ABNORMAL
Overload = Edema
+ Protein = Lymphedema
Overload = Edema
+ [Protein]
= Lymphedema
If net filtration exceeds
lymphatic transport capacity
Complications
System
Works
OK Here
System
Not OK
Here
Fluid +
Protein
PROTEINS
Proteins Accumulate if Lymphatic Dysfunction
More
Filtration
capillary
Complications
Lymphatic vessel/node
•Trauma
•Removal
•Radiation
•Blockage
•Overload
•Genetic - Primary
Fluid +
Protein
PROTEINS
Proteins Accumulate if Lymphatic Dysfunction
Macrophages
Fibrosis
More
Filtration
capillary
Complications
Fluid +
Protein
PROTEINS
Proteins Accumulate if Lymphatic Dysfunction
Macrophages
Stimulus for Chronic Inflammation
Vasodilation
• Increased filtration
• Tissue warmingBacterial
Growth
Bacterial/Fungal Infections
Fibrosis
More
Filtration
capillary
Complications
Research into Early Detection
“Recognizing lymphedema early and
treating it promptly is the best way
to manage the condition”
Judith R. Casley-Smith & J.R. Casley-Smith
Surgery
Radiation
Lym
ph
ed
em
a S
eve
rity
70 - 80 % of patients at risk = 0 lymphedema
Time
Ultimate Goal - Catch it EarlyMore Treatable – Less Complications
Surgery
Radiation
Symptoms
Seek TherapyLym
ph
ed
em
a S
eve
rity
70 - 80 % of patients at risk = 0 lymphedema
Fibrosis
Time
Ultimate Goal - Catch it EarlyMore Treatable – Less Complications
•Feeling of heaviness
•Tingling
•A ring or watch gets tight
•Skin feels “tight”
•Diminished flexibility
•Limb more easily fatigued
•Visual swelling
Surgery
Radiation
Symptoms
Seek Therapy
Reduce & Arrest
Lym
ph
ed
em
a S
eve
rity
70 - 80 % of patients at risk = 0 lymphedema
Fibrosis
Time
Ultimate Goal - Catch it EarlyMore Treatable – Less Complications
CDP
Surgery
Radiation
Symptoms
Seek Therapy
Reduce & Arrest
Lym
ph
ed
em
a S
eve
rity
70 - 80 % of patients at risk = 0 lymphedema
Early Detection
“Sub-Clinical”
Fibrosis
Time
Ultimate Goal - Catch it EarlyMore Treatable – Less Complications
Tissue Water via Dielectric Constant
MoistureMeter-D
• Low power 300 MHz
incident wave
• Reflected wave depends
on the tissue’s
dielectric constant
• Dielectric constant
depends on total tissue
water (free + bound)
• Pure water has a
dielectric constant of
about 78
• Calibrated for each
probe from 1 - 80
Penetration Depth (0.5 – 5 mm)
0.5 1.5 2.5 5.0 mm
Modified from Mellor et al. 2004
Gel
Entry
Echo
Dermis
Subcutis0.80 - 1.2 mm
ventral
1.8 - 2.8 mm
Low water
content
High water
content
Normal Arm Lymphedematous Arm
20 MHz Ultrasound Imaging
Subjects and Protocol
12 women with unilateral arm lymphedema (74 ± 16 yrs)
12 premenopausal women (25.5 ± 3.7 yrs)
12 postmenopausal women (61.0 ± 6.7 yrs)
Affected
Arm
Control
Arm
Segment
Volume4 cm VA VC
Measurements on lymphedema patients prior to treatment
Measurements on premenopausal 4 days after menses
0
40
80
120
160
200
240
280
320
360
Right or Control Arm
Left or Affected Arm
Segmental Volumes
Premenopausal Postmenopausal Lymphedema
Vo
lum
e (
ml)
P<0.001
%Edema
39 ± 16%
0
10
20
30
40
50
60
Right or Control Arm
Left or Affected Arm
Tissue Water (2.5 mm)D
iele
ctr
ic C
on
sta
nt
Premenopausal Postmenopausal Lymphedema
P<0.001
0.6
1
1.4
1.8
2.2 No overlap
Normal vs. Patients
Premenopausal Postmenopausal1.021 ± 0.068 1.014 ± 0.063
Dominant/Non-Dominant
PatientsAffected/Control
1.600 ± 0.315
Die
lectr
ic C
on
sta
nt
(Rati
o)
Diagnostic Utility
Study Outcome
Criteria as of now for the limited data set:
• For at-risk unilateral arms: Arm TDC ratio > 1.2
• For bilateral arms or using absolute values:
Threshold depends on depth (3 sd)
Depth 0.5 mm 1.5 mm 2.5 mm 5.0 mm
TDC >42 >37 >37 >32
Currently an ongoing study with assessments
prior to and for up to two years after surgery
Tissue water measured at multiple ‘at-risk’ sites
Early Detection Research Study
Research into a ‘New’ Therapy
‘Standard’ Pump
New Approach
• Initial ‘preparation phase’
• ‘Light-touch’ drainage
0
10
20
30
40
50
60
70
0 10 20 30 40 50
G1
G2
G3
G4
G5
Pressure Timing and Pattern
Lympha Press® System
Pre
ss
ure
(m
mH
g)
Seconds
0
10
20
30
40
50
60
70
0 10 20 30 40 50
G1
G2
G3
G4
G5
Pressure Timing and Pattern
Flexitouch® System
Pre
ss
ure
(m
mH
g)
Seconds
‘Standard’ ‘New Approach’
Pump pressures and patterns widely different!
Current Research Study
How important is it to use a preparatory phase?
In women with unilateral arm lymphedema
will using the full garment set result in
greater tissue fluid reductions?
Research into Tissue Properties
• Pitting Edema
• Fibrosis
Goal: Simple but accurate ways to
assess therapeutic effectiveness
Evolving ResearchQuantifying ‘pitting’ edema
Evolving Research
Fibrosis and tissue property changes
‘New’ Therapies: All needing validation
‘Electromagnetic Therapies’
Radio waves
Microwaves
Infrared Waves
Light Waves
Pulsed Radio Frequency Waves
Coil
Current
B-Field
• Seven post-mastectomy
patients in pilot study
• Unilateral Lymphedema
All had prior CDT Tx
• Each Pt. treated 4-6
times over 2-weeks
• During this interval
no other Tx provided
Subjects and Protocol
• Skin blood perfusion
(SBF) by laser-Doppler
on affected arm
• Transcutaneous O2
(PO2) on affected and
contralateral arm
SBF
PO2
PO2
Physiological Measurements
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0.64 0.50 0.42 0.41 0.35
0 1 2 3 4
Treatments* p< 0.01 vs. initial edema volume
** *
*
N=7
Ed
em
a V
olu
me
(L
)
Further
Reduction
Through
4th Tx
Edema Volume
Decreased
After one Tx
Example SBF Response
Skin
Blood
Flow
BASE ACTIVE OFF
10” 60” 20”
0.5
4.5
SBF Increased
Mean
Pulsatile
• PRFT shows potential benefit
• Lymphedema reduced with one treatment
• Initial PILOT findings are encouraging, BUT
need placebo controlled studies
Pilot Study Outcomes
SPECULATION Mechanisms similar to those
that increased SBF also
increase lymph drainage
Expanding collateral channels
Increasing lymphoangiomotoricity
Top Related