1. Aspects of cancer related lymphoedema
Vaughan Keeley
Derby UK
Dublin, Sept 2014

2. Aspects of cancer related lymphoedema
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

3. What causes lymphoedema after cancer treatment?
Most studies have involved breast cancer related lymphoedema (BCRL)
Ideas are changing

4. How common is BCRL? 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.

6. Defining lymphoedema
Difficulty defining early lymphoedema

7. 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)

8. Incidence at 30 months by definition
200ml diff (58-76) %
10% diff (33-59) %
2cm circ diff (84-96) %
Swelling / heaviness (31-54) %
(Armer, 2009)

9. Risk factors for BCRL Strong evidence for:
Extensive surgery (ANC; greater no. of LNs removed; mastectomy)
Overweight / obesity
(Disipio, 2013)

10. Other possible risk factors for BCRL
Radiotherapy
Drain, wound or infection complications
Cording
Seroma formation
Taxane chemotherapy
Skin puncture.
Oestrogen receptor negative cancers?

11. What causes BCRL? “Conventional model”
Destruction of lymphatics / lymph nodes by treatment
Obstructive lymphoedema

14. 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

15. Research observations:
Local lymph flow  when oedema present
  pumping pressure in lymphatics in established BCRL

16. Study of breast cancer patients followed at 7m and 30m
at 7m there was no impairment of lymph drainage if no swelling.
those destined to develop lymphoedema had highest lymph flow in muscle + subcutis
lymph flow was also  in the other (unoperated side) arm

17. 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)

18. 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?

19. 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)

20. 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

21. 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)

22. 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%

23. 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

24. The benefit of pre-operative measurements
May facilitate early detection
May help identify high risk groups / consider introduction of preventative measures

25. Prevention?
Can the incidence of lymphoedema be reduced / condition prevented?
- change in surgical / RT methods?
- exercise?
- MLD?
- compression?
- precautions incl weight management?

26. Change in Surgery / RT?
SNB associated with lower incidence of BCRL than ANC
RT method changes - ? effect
(NB more breast oedema since WLE + RT)

27. 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.

28. MLD (manual lymphatic drainage)
Mixed evidence:
- no effect (Devoogdt et al 2011)
- positive effect (Zimmermann et al 2012)

29. 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

30. 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?

31. 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)

32. Genetic predisposition
A number of candidate genes
Samples being collected as part of BEA study.

33. 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

34. Precautionary measures 2
Avoid irritating cosmetics/soaps
Avoid sunburn
Avoid insect bites/cat scratches
Use an electric razor for shaving
Avoid obesity

35. 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

36. Breast lymphoedema
Increasingly recognised following WLE and radiotherapy
Difficult to measure
Clinical diagnosis
Treatment – MLD / compression / taping etc
More research required.

37. Cellulitis and lymphoedema

38. What is cellulitis?
also called erysipelas, acute inflammatory episodes etc.
bacterial infection of skin + tissues under skin
more common in people with lymphoedema / recurrent

39. Why are people with lymphedema prone to cellulitis?
Lymph nodes / lymph vessels are part of the immune system – fighting infection
In lymphoedema the local immune system is less effective

40. Why are people with lymphedema prone to cellulitis?
Lymph nodes / lymph vessels are part of the immune system – fighting infection
In lymphoedema the local immune system is less effective

41. Is it definitely cellulitis?
features as above
no specific tests
some tests may be helpful:-
white blood cell count
CRP (C-reactive protein)
swabs for culture

42. What else can it be? raised venous pressure deep vein thrombosis
eczema / dermatitis
contact sensitivity
etc

43. Which bacteria cause it?
Not entirely clear
Beta haemolytic Streptococci
Staphylococcus aureus
? others (e.g. in genital cellulitis)

44. How is it treated? Antibiotics – oral / intravenous
Remove compression – temporarily
Pain relief - Paracetamol
- avoid non-steroidal
anti-inflammatories (e.g. ibuprofen)
Rest

45. Which antibiotics? BLS / LSN Consensus guidelines www.thebls.com
evidence of best treatment is lacking

46. Antibiotics at home: (oral):
Amoxicillin 500 mg three times a day for at least 2 weeks
Flucloxacillin is an alternative

47. Antibiotics in hospital: (intravenous):
if v. unwell, low blood pressure etc or getting worse on oral antibiotics
Flucloxacillin 1 g every 6 hrs until temperature normal etc. then oral

48. What may cause an episode of cellulitis?
Broken skin - cuts
- insect bites
- Athlete’s foot / fungal infection
- eczema / dermatitis
- ulcers
- ingrowing toenail
Others - ? sore throat
- ? stress

49. Recurrent cellulitis
UK survey patients with lymphoedema and cellulitis
- 76% had previous episodes of cellulitis
- average 1.8 episodes in previous year

50. Why is this a problem?
acute cellulitis – unpleasant, may need hospital admission; loss of time at work etc.
cellulitis damages lymph vessels making lymphoedema worse

51. How can I reduce the chance of getting cellulitis?
Skin care
Control of swelling

52. Precautions - insect repellent - antiseptic creams for cuts
- treat dermatitis, ingrowing toenail, Athlete’s foot etc
- avoid cuts e.g gloves when gardening, avoid bare feet in garden

53. Prophylactic antibiotics?
- if 2 or more episodes of cellulitis in 1 yr.
- address risk factors
- control swelling
- Phenoxymethylpenicillin (1 year to begin with)

54. 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

55. 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.

56. Thank you!