lymphedema research - limbvolumesprofessional
TRANSCRIPT
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