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. 2012 Jan 4;12:6. doi: 10.1186/1471-2407-12-6

Table 1.

Basic study data

Study (Quality) Sample Size (Treatment + Control) 1) Cause of SE
2) Definition of SE
1) Time of SE Onset
2) Time of Tx initiation
3) Criteria to Start/stop Tx
Other Inclusion/Exclusion Criteria
RCT

Andersen
2000 [21]
Denmark
Fair (4)
20 + 22 1) BCa Tx
2)≥ 200 ml volume or ≥ 2 cm circumference difference between arms
1) After surgery
2)≥ 4 month post-BCa Tx
3) SE Dx/NR
Exclusion:
- bilateral BCa
- SE Tx < 3 months
- BCa recurrence
- severe SE (volume difference > 30%)

Bertelli
1991 [22]
Italy
Fair (4)
37 + 37 1) BCa Tx
2)> 10 cm and < 20 cm circumference difference between arms (mild SE)
1) Limb circumference ≥ 25% compared to baseline
2) NS
Inclusion:
- no metastases or relapse
- no Tx ≤ 6 months
- no lymphangitis
Exclusion:
- wearing cardiac stimulator
- currently receiving CT or RT

Bialoszewski
2009 [23]
Poland
Poor (3)
12 + 12 1) Lower extremity SE post-leg lengthening surgery
2) Physical examination and radiographic images to Dx SE
1) Following leg lengthening surgery
2) Post-surgery
3) Lower extremity SE/NR
Inclusion:
-age 15-40 years

Carati
2003 [11]
Australia
Good (8)
37 + 27 1) BCa Tx
2)> 200 ml volume or ≥ 2 cm circumference difference between arms
1) NR
2) NR
3) SE Dx/NR
Inclusion:
- female
Exclusion:
- co-morbidities present
- significant change ≤ 3 months
- unable to manipulate arm
- primary SE

Damstra
2009 [24]
Netherlands
Good (6)
18 + 18 1) BCa Tx
2) Moderate to severe SE (ISL definition)
1) 3-50 month post-surgery
2)≥ 12 month post-surgery
3) SE Dx/NR
Inclusion:
-female
-> 18 years
-12 months post BCa Tx without reoccurrence
Exclusion:
-allergy to materials
-systemic diseases
-arterial/venous disease

Didem
2005 [25]
Turkey
Fair (5)
27 + 26 1) BCa Tx
2) Arm circumference difference 2-5 cm
1)> 1 year after surgery
2) 3 year post-surgery
3) SE Dx/NR
Inclusion:
- SE ≥ 1 year
Exclusion:
- psychiatric
illness
- pain in axillary region
- cardiac disease
- uncontrolled hypertension
- malignancy

Dini
1998 [26]
Italy
Fair (5)
40 + 40 1) BCa Tx
2) Arm circumference difference of 2-5 cm
1)< 1 year
2)> 1 year after SE
3) SE Dx/difference in circumference > 10 cm in affected vs. unaffected limb/occurrence of harms
Inclusion:
- SE ≥ 1 year
- no lymphangitis, no evidence of local or distant relapse, no other serious or psychiatric illness
Exclusion:
- prior SE therapy
- bilateral breast surgery
- bilateral axillary node dissection

Hayes
2009 [27]
Australia
Good (6)
16 + 16 1) BCa Tx
2) Health professional diagnosis
1) NR
2)≥ 6 month after BCa Tx
3) SE Dx/occurrence of harms
Inclusion:
-< 76 years
- Unilateral BCa Tx ≥ 6 months ago
- able to travel to clinic

Hou
2008 [28]
China
Poor (3)
15 + 35 1) BCa Tx
2) NR
1) NR
2)> 5 year post-surgery
3) SE Dx/NR
Exclusion:
- radiotherapy

Irdesel
2007 [29]
Turkey
Fair (5)
10 + 11
1) BCa Tx
2) NR
1) 3-60 month
2)> 4 month post-BCa surgery
3) SE Dx/NR
Exclusion:
-BCa operation < 4 months ago
-recurrence or bilateral BCa
-stage 4 BCa
-elephantiasis
-congestive heart failure
-deep vein thrombosis
-acute infection

Jahr
2008 [30]
Germany
Fair (5)
11 + 10 1) BCa Tx
2) NR
1) NR
2) ~4 year post-surgery
3) SE Dx/NR
Inclusion:
- age 18-80 years
- living near study center
-≥ 6 weeks since RT
Exclusion:
- Tx ≤ 3 months ago
- acute inflammation
- acute thrombosis
- heart disease
- electronic implant
- pregnant
- sensitivity to electric fields

Johansson
1998 [31]
Sweden
Fair (4)
14 + 14 1) BCa Tx
2)> 10% difference in affected vs. unaffected arm
1) Median 9-10.5 month
2) Median 9-10.5 month
3) SE Dx/NR
Exclusion:
- previous contralateral breast disease
- comorbidity affecting swollen arm
- treatment ≤ 6 months (except compression sleeve)
- SE resolved during initial compression sleeve use

Kaviani
2006 [32]
Iran
Fair (5)
4 + 4 1) BCa Tx
2)≥ 2 cm swelling in affected arm
1) 3 month
2) SE ≥ 3 month
3) SE Dx/NR
Inclusion:
- no contraindications to laser
Exclusion:
- metastatic disease

Kessler
2003 [33]
Switzerland
Poor (3)
11 + 12 1) Ankle surgery
2) Clinically diagnosed post-operative swelling
1) NR
2) 2nd day post-surgery
3) Post-operative swelling/NR
- Age: 18-75 year
- good physical condition
- no contraindications for lymph drainage

Kozanoglu
2009 [34]
Turkey
Poor (3)
25 + 25 1) BCa Tx
2) Difference > 2 cm at 3/7 measurement points on limb
1)> 3 month
2) SE > 3 month
3) SE Dx/NR
Inclusion:
- arm SE ≥ 3 months
Exclusion:
- metastases or ongoing RT
- cellulitis
- venous thrombosis
- inflammatory disease
- history of severe trauma
- photosensitivity
- medications that affect electrolyte
balance
- limitation in UE joints
- physical therapy other than skin care
- home exercises for SE in past 6 months

Lau
2009 [35]
China
Good (6)
11 + 10 1) BCa Tx
2) Arm volume difference > 200 ml
1) 22-60 month post-BCa
2) Post-BCa Tx
3) SE Dx/NR
Inclusion:
-≥ 18 years
- unilateral mastectomy + CT or RT
Exclusion:
- metastases
- history of arm trauma
- kidney, heart, or lung disorder
- medications that alter body fluids
- primary SE of lower limb
- decrease shoulder movement
- cellulitis ≤ 3 months

Maiya
2008 [36]
India
Fair (5)
10 + 10 1) BCa Tx
2)≥ 2 cm difference at any 2 points between affected and unaffected limbs
1) NR
2) 3-6 week post-mastectomy
3) SE Dx/NR
Inclusion:
- mastectomy or RT completion
Exclusion:
- primary SE
- limb infection

McKenzie
2003 [37]
Canada
Poor (3)
7 + 7 1) BCa Tx
2) Circumference difference is > 2 cm and < 8 cm
1) NR
2)> 6 month post-cancer Tx
3) SE Dx/NR
Exclusion:
- stage III SE
- bilateral disease
- medications that affect swelling

McNeely
2004 [38]
Canada
Good (6)
22 + 20 1) BCa Tx
2)≥ 150 ml difference between affected and unaffected arms
1) NR
2) NR
3) SE Dx/NR
Inclusion:
- no sleeve use < 4 months
-≥ 6 months since SE T
XExclusion:
- new cancer D
X- receiving RT or CT
- infection in SE limb
- contraindications to T
X- uncontrolled hypertension
- heart disease
- renal insufficiency
- venous thrombosis

Pilch
2009 [39]
Poland
Poor (3)
17 + 9 + 11 + 20
1) BCa Tx
2) NR
1) NR
2) NR
3) SE Dx/NR
Inclusion:
-age 39-80 years

Radakovic
1998 [40]
Yugoslavia
Poor (1)
18 + 18 1) BCa Tx
2) NR
1) NR
2) post-RT
3) SE Dx/NR
Inclusion:
- no metastases

Schmitz
2009 [41]
U.S.
(companion Schmitz [42])
Good (7)
71 + 70 1) BCa Tx
2)≥ 10% volume or circumference difference between affected and unaffected arms
1) NR
2) 1-15 year post-BCa
3) SE Dx/SE exacerbation or cancer recurrence
Inclusion:
- 1-15 years since BCa D
X- no evidence of cancer
- unilateral SE
- BMI < 50 kg/m2
- not actively trying to lose weight
- no medical conditions to limit exercise
- no weight lifting ≤ 1 year
- removal of at least one lymph node

Shaw
2007 [43]
U.K.
Fair (5)
11 + 10 1) BCa Tx
2) Affected arm volume ≥ 15% than unaffected arm
1) NR
2)≥ 12 month post-CT or RT
3) SE Dx/completion of therapeutic regimen
Inclusion:
- remission
- BMI ≥ 25 kg/m2

Shaw
2007 [44]
U.K.
Fair (5)
19 + 17 + 15 1) BCa Tx
2) Affected arm volume ≥ 20% than unaffected arm
1) NR
2)≥ 12 month post-cancer Tx
3) SE Dx/NR
Inclusion:
- remission

Sitzia
2002 [45]
U.K.
Fair (5)
15 + 13 1) BCa Tx
2) Moderate or severe edema (≥ 20%)
1) NR
2) NR
3) SE Dx/NR
Inclusion:
-≥ 18 years
- no active disease
- no Tx except support garment

Szuba
2002 [46]
U.S.
Fair (4)
12 + 11 1) BCa Tx
2) Affected arm volume ≥ 20% than unaffected arm
1) NR
2)≥ 3 month from BCa Tx
3) SE Dx/NR
Inclusion:
-≥ 12 week post T
XExclusion:
- active infection
- recurrence
- venous occlusion

Szuba
2002 [47]††
U.S.
Fair (4)
12 + 13 1) BCa Tx
2) NR
1) NR
2) 1-12 month
3) SE Dx/NR
Inclusion
- CDT completed 1-12 months ago
Exclusion:
- active infection
- recurrence
- venous occlusion
- bilateral SE

Tsai
2009 [48]
China
Good (6)
20 + 21 1) BCa Tx
2) Affected arm circumference ≥ 2 cm than unaffected arm
1)≥ 3 month post-BCa Tx
2) 4 week after control period
3) SE Dx/NR
Inclusion:
- unilateral SE ≥ 3 months
Exclusion:
- active cancer
- use of diuretics or other SE influencing drugs
- skin disease
- decreased arm motion

Wilburn
2006 [49]††
U.S.
Good (7)
5 + 5 1) BCa Tx
2) Affected arm volume ≥ 20% than unaffected arm
1) 34 ± 34 month
2) 0-5 month after SE onset
3) SE Dx/NR
Exclusion:
- bilateral SE
- active cancer or infection
- venous obstruction or active thrombophlebitis
- pulmonary edema
- congestive heart failure
- history of pulmonary embolism
- contraindications to Tx

Williams
2002 [50]††
U.K.
Fair (4)
15 + 16 1) BCa Tx
2)> 10% excess volume measured two times
1)> 3 month
2)> 3 month
3) SE Dx/NR
Exclusion:
- active cancer
- use of edema-influencing
drugs

Observational

Balzarini
1993 [51]
Italy
Good (8)
50 + 100 1) BCa Tx
2)% difference between arms: ≤ 6.5% (mild), 6.5 to 13% (moderate), ≥ 13% (severe)
1) IG: 3-52 month; CG: 5-57 month
2) NR
3) SE Dx/NR
Exclusion:
- Tx with regional RT

Berlin
1999 [50]
Sweden
Fair (6)
28 + 8 +19 1) BCa Tx
2) Affected arm volume ≥ 100 ml than unaffected arm
1) NR
2) NR
3) SE Dx/NR
NR

Brambilla
2006 [53]
Italy
Good (8)
50 + 15 1) SE due to Kaposi's sarcoma
2) Grade II SE according to ISL
1) NR
2) NR
3) SE Dx/NR
Inclusion:
- SE below knee

Frischenschlager
1991 [54]
Austria
Fair (5)
15 + 15 1) BCa Tx
2) NR
1) ~5 year post-BCa Tx
2) NR
3) SE Dx/NR
Inclusion:
-female

Johansson
1999 [55]
Sweden
Fair (6)
20 + 18 1) BCa Tx
2) Affected arm volume ≥ 10% than unaffected arm
1) NR
2) NR
3) SE Dx/arm swelling resolution
Exclusion:
- previous contralateral breast disease
- comorbidity affecting swollen arm
- treatment ≤ 6 months (except compression sleeve)

Pinell
2007 [56]
U.S.
Good (7)
16 + 56 1) BCa Tx
2) Affected arm circumference ≥ 2 cm than unaffected arm
1) NR
2) NR
3) SE Dx/NR
Inclusion:
- referral to specific clinics

BCa Breast Cancer; BMI Body Mass Index; CDT Complex Decongestive Therapy; CG control group; CT chemotherapy; Dx Diagnosis; IG intervention group; ISL International Society of Lymphology; mo: months; NR Not Reported; RT Radiation Therapy; RCT Randomized Control Trial; SE Secondary Lymphedema; Tx Treatment; UE: Upper extremity; wk week; yr year

Rating (scale score)-RCT Jadad: poor (1-3), fair (4-5), good (6-8); Observational NOS: poor (0-3), fair (4-6), good (7-9)

††Crossover RCT (all other RCTs were randomized, parallel group)