Aspects of cancer related
lymphoedema
Vaughan Keeley
Derby UK
Dublin, Sept 2014
Aspects of cancer related
lymphoedema
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What causes it?
How can we detect it early?
Can it be prevented?
The problem of cellulitis
Lymphoedema in head and neck cancer
Surgery for lymphoedema
What causes lymphoedema after
cancer treatment?
• Most studies have involved breast cancer
related lymphoedema (BCRL)
• Ideas are changing
How common is BCRL?
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Overall 21.4%
18.9% by 2yr
5.6% after sentinel node biopsy (SNB)
19.9% after axillary node clearance (ANC)
(Disipio et al 2013)
• BUT... difficulty with definitions and length
of follow-up.
Defining lymphoedema
• Difficulty defining early lymphoedema
Diagnostic criteria for BCRL
– 10% difference between limbs,
– 200ml difference between limbs,
– 2cm difference circumferential measurements
– 10% change from baseline
– >3% change from baseline (sub-clinical)
– Patient reported symptoms (swelling,
heaviness)
Incidence at 30 months by
definition
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200ml diff
10% diff
2cm circ diff
Swelling / heaviness
• (Armer, 2009)
67 (58-76) %
45 (33-59) %
91 (84-96) %
41 (31-54) %
Risk factors for BCRL
• Strong evidence for:
• Extensive surgery (ANC; greater no. of LNs
removed; mastectomy)
• Overweight / obesity
(Disipio, 2013)
Other possible risk factors for BCRL
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Radiotherapy
Drain, wound or infection complications
Cording
Seroma formation
Taxane chemotherapy
Skin puncture.
Oestrogen receptor negative cancers?
What causes BCRL?
• “Conventional model”
• Destruction of lymphatics / lymph nodes by
treatment
• Obstructive lymphoedema
But....
6% women develop BCRL after SNB
alone.
80% of women don’t develop BCRL
after ANC
BCRL takes months/years to develop
Distribution is not uniform
Research observations:
 Local lymph flow  when oedema
present
  pumping pressure in lymphatics in
established BCRL
Study of breast cancer patients
followed at 7m and 30m
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at 7m there was no impairment
of lymph drainage if no swelling.
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those destined to develop
lymphoedema had highest lymph
flow in muscle + subcutis

lymph flow was also  in the
other (unoperated side) arm
Conclusions
• This suggests a constitutional
predisposition (both arms affected)
• A possible genetic effect
• The high lymph flow may lead to
damage to the lymph vessels over time
and therefore the flow will reduce and
swelling develop (delayed onset)
Early detection and prevention
• It is evident that early mild lymphoedema is
easier to treat than advanced lymphoedema
with fat / fibrosis
• How early can it be detected?
• Can it be prevented?
Early detection 1
• By limb volume measurement:
- comparison with pre-op measurements
- sensitive method eg Perometry
- “subclinical” swelling (3% change?)
- early intervention reduces swelling (and
possibly prevents progression?) (Stout,
2008)
Early detection 2
• By bioimpedance spectroscopy
- measures fluid changes in the tissues (the
first stage of swelling)
- evidence that this may detect lymphoedema
months before a volume change is measured
BEA
• Multi-frequency Bioimpedance in the Early
Detection of Lymphoedema after Axillary
Surgery
- a multicentre study in UK examining whether
BIS can detect BCRL before changes in limb
volume (by Perometer) after ANC
- aim – n=1100
- recruitment to date = 1016 (Derby = 280)
BEA – early results
• n=556
• Lymphoedema defined as 10% change in
relative arm volume (RAVC)
• Incidence at 12m = 13.7%; at 24m = 25.0%
• Predictive factors: ER neg; no. of positive
nodes; RAVC at 6m >= 5%-<10%
Limitations of these methods
• At present, both Perometry and BIS do not
measure hand swelling well
• Localised swelling may develop which is
“diluted” by whole limb measurements
• Differential swelling - may be detectable
with segmental BIS or Perometry; new
methods being developed
The benefit of pre-operative
measurements
• May facilitate early detection
• May help identify high risk groups /
consider introduction of preventative
measures
Prevention?
• Can the incidence of lymphoedema be
reduced / condition prevented?
- change in surgical / RT methods?
- exercise?
- MLD?
- compression?
- precautions incl weight management?
Change in Surgery / RT?
• SNB associated with lower incidence of
BCRL than ANC
• RT method changes - ? effect
(NB more breast oedema since WLE + RT)
Exercise
• Exercise programmes may help to reduce
incidence
(Box et al 2002; Torres Lacomba et al
2010)
Changing advice on exercise of “at risk” arm.
MLD (manual lymphatic
drainage)
• Mixed evidence:
- no effect (Devoogdt et al 2011)
- positive effect (Zimmermann et al 2012)
Compression
• Possible effect of preventing progression of
subclinical lymphoedema by wearing a
compression sleeve for 1 month (Stout,
2008)
• Current UK study in progress: PLACE
PLACE
Prevention of Lymphoedema after Axillary
Clearance by early External Compression.
• An RCT of the use of a compression garment for 1
year v standard care / precautions in women with a
4-8% increase in arm volume (Perometry) by 9
months post-ANC
• Outcome measure – lymphoedema in each group at
1 year and 18months after randomisation
• Early treatment or prevention?
Progress with PLACE
• Slow recruitment
• Fewer women than predicted reached
threshold changes in RAVC
• Currently expanding to those who have only
had SNB
• Local recruitment = 22 (total = approx 80)
Genetic predisposition
• A number of candidate genes
• Samples being collected as part of BEA
study.
Precautionary measures
• Avoid injuries including cuts and abrasions,
for example, wear gloves when gardening
• Use a thimble when sewing
• Use an oven glove when cooking
• Take care when ironing
• Avoid tight clothing including tight bra
straps
Precautionary measures 2
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Avoid irritating cosmetics/soaps
Avoid sunburn
Avoid insect bites/cat scratches
Use an electric razor for shaving
Avoid obesity
Precautionary measures 3
• Avoid injections or venipuncture in the “at
risk” arm
• Avoid blood pressure measurement in the
“at risk” arm
• Seek medical advice if “at risk” arm
becomes inflamed or swollen
Breast lymphoedema
• Increasingly recognised following WLE and
radiotherapy
• Difficult to measure
• Clinical diagnosis
• Treatment – MLD / compression / taping
etc
• More research required.
Cellulitis and lymphoedema
What is cellulitis?
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also called erysipelas, acute inflammatory
episodes etc.
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bacterial infection of skin + tissues under
skin
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more common in people with
lymphoedema / recurrent
Why are people with
lymphedema prone to cellulitis?
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Lymph nodes / lymph vessels
are part of the immune
system – fighting infection
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In lymphoedema the local
immune system is less
effective
Why are people with
lymphedema prone to cellulitis?
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Lymph nodes / lymph vessels
are part of the immune
system – fighting infection
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In lymphoedema the local
immune system is less
effective
Is it definitely cellulitis?
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features as above
no specific tests
some tests may be helpful:white blood cell count
CRP (C-reactive protein)
swabs for culture
What else can it be?
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raised venous pressure
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deep vein thrombosis
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eczema / dermatitis
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contact sensitivity
etc
Which bacteria cause it?
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Not entirely clear
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Beta haemolytic Streptococci
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Staphylococcus aureus
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? others (e.g. in genital cellulitis)
How is it treated?
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Antibiotics – oral / intravenous
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Remove compression – temporarily
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Pain relief -
Paracetamol
avoid non-steroidal
anti-inflammatories (e.g. ibuprofen)
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Rest
Which antibiotics?
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BLS / LSN Consensus guidelines
www.thebls.com
www.lymphoedema.org
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evidence of best treatment is
lacking
Antibiotics at home: (oral):
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Amoxicillin 500 mg three times a
day for at least 2 weeks
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Flucloxacillin is an alternative
Antibiotics in hospital: (intravenous):
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if v. unwell, low blood pressure
etc or getting worse on oral
antibiotics
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Flucloxacillin 1 g every 6 hrs until
temperature normal etc. then oral
What may cause an episode of cellulitis?
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Broken skin
Others
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cuts
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insect bites
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Athlete’s foot / fungal infection
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eczema / dermatitis
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ulcers
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ingrowing toenail
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? sore throat
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? stress
Recurrent cellulitis
UK survey
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396 patients with
lymphoedema and
cellulitis
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76% had previous
episodes of cellulitis
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average 1.8 episodes in
previous year
Why is this a problem?
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acute cellulitis – unpleasant, may
need hospital admission; loss of
time at work etc.
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cellulitis damages lymph vessels
making lymphoedema worse
How can I reduce the chance of
getting cellulitis?
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Skin care
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Control of swelling
Precautions
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insect repellent
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antiseptic creams
for cuts
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treat dermatitis,
ingrowing toenail,
Athlete’s foot etc
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avoid cuts e.g.
gloves when
gardening, avoid
bare feet in garden
Prophylactic antibiotics?
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if 2 or more episodes of
cellulitis in 1 yr.
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address risk factors
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control swelling
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Phenoxymethylpenicillin
(1 year to begin with)
Frequently asked questions
Q: How soon after infection should I
wear my compression garment
again?
A: As soon as is comfortable. If
broken skin, may need bandage /
dressings
Q: Should I keep a course of
antibiotics at home, in case I get
cellulitis?
A: This may be advisable if you
have repeated episodes and a
familiar pattern, especially if
foreign travel.
Thank you!