Quality of Life Improvements in Patients with Lymphedema After Surgical or Nonsurgical Interventions with 1-Year Follow-Up

Abstract

Background:

Lymphedema may impact patients' health-related quality of life (HRQoL). The purpose of this study was to evaluate HRQoL after two different treatments to the 12-month follow-up point.

Methods and Results:

Study participants were patients with moderate lymphedema in the upper or lower limb who attended a Swedish rehabilitation program (RP) undergoing conservative treatment, or those with severe, chronic lymphedema dominated by excess adipose tissue, who underwent liposuction (LS) combined with controlled compression therapy (CCT) in Australia, Scotland, or Sweden. The patients completed the Lymphedema Quality of Life Inventory (LyQLI) before intervention and after 1, 3, 6, and 12 months. Mean values and standard deviations were calculated for total limb volume and excess limb volume. Mean values were also calculated for the three LyQLI domains (physical, psychosocial, and practical). To detect and analyze differences in LyQLI responses in the three domains, the Wilcoxon signed rank test was performed. In the RP, 18 eligible patients completed the LyQLI. The results show improvements in HRQoL in physical (p = 0.003) and psychosocial domains (p = 0.002) at 1 month after the RP, with results remaining steady for 12 months for the physical domain (p = 0.024). Fifty-seven eligible LS patients completed the LyQLI. The results show improvements in HRQoL in all three domains (p < 0.001), with results remaining steady up to the 12-month follow-up (p < 0.001). The total volume in affected limb and the excess volume decreased significantly in both patient groups 1 month after intervention (p < 0.001).

Conclusions:

Treatment with a conservative RP in moderate lymphedema or with LS combined with CCT in severe lymphedema improves HRQoL.

Introduction

Lymphedema is a chronic disease and its impact on the patient's health-related quality of life (HRQoL) in the physical, psychosocial, and practical aspects is well documented.^1–9

The World Health Organization (WHO) has defined quality of life as “individuals' perception of their position in life in the context of the culture and value systems in which they live and in relationship to their goals, expectations, standards, and concerns.”¹⁰ To distinguish how patients experience quality of life specifically related to health, the concept HRQoL has been established.^11,12

Lymphedema is classified as primary or secondary. Primary lymphedema is caused by genetic mutations, which damage lymphatic vascular development, leading to a structural and/or functional abnormality that impairs drainage.¹³ Secondary lymphedema appears after damage to the lymphatic system by infection, inflammation, trauma, radiation, or surgical treatments.^13,14 The most common cause of secondary lymphedema in Western countries is cancer treatment of regional nodes.¹⁵ Lymphedema is characterized by swelling in different parts of the body, mostly the limbs, but swelling can also emerge in the trunk, head/neck, breast, or genital region.¹⁴

Early and accurate diagnosis is essential, since lymphedema is a chronic and progressive disease. Initially, the treatment for early lymphedema is often conservative, including compression garments. Additional commonly used conservative treatments are rehabilitation programs (RP), which often include complex (complete) decongestive therapy (CDT) traditionally comprising manual lymphatic drainage (MLD), multilayer limb bandaging, skin care and exercises to enhance lymphatic pumping.^14,16 However, the progress in surgical methods offer possibility to a reactive approach to treatment, such as lymphovenous anastomosis and vascularized lymph node transfer.¹⁷ Even then, the surgery is often combined with compression garments/stockings.¹⁷ Chronic lymphedema leads to the deposition of fat caused by chronic inflammation^18,19 and conservative treatments may fail to reduce the lymphedema volume.^20–22 Under these circumstances, the most effective treatment is surgery by liposuction (LS) followed by controlled compression therapy (CCT).^23–27

Since lymphedema is a chronic disease, it is vitally important to measure, evaluate, and, if possible, improve the patient's HRQoL. HRQoL after RP or CDT have been evaluated with different questionnaires, mostly generic or cancer specific.^3–6 However, in Sweden, HRQoL after RP has never been evaluated.

HRQoL after LS has been investigated with different instruments. In Scotland, Schaverien et al. performed LS on patients with upper limb lymphedema (ULL). They used the Hospital Anxiety and Depression scale (HADS) together with one single question about overall quality of life, to evaluate the patients' mental condition and well-being.²⁷ In Australia, Boyages et al. included patients with lower limb lymphedema (LLL), investigating both functional and psychological factors using the Patient-Specific Functional Scale (PSFS) after LS. In the PSFS, the patients, for example, rated the impact of lymphedema on six functional/emotional domains.²⁶ In Sweden, HRQoL after LS has been investigated with different instruments. An early investigation by Brorson et al.²⁸ used several HRQoL instruments: Nottingham Health Profile, Psychological Well-Being index, and HADS together with measurements of edema volume and visual analogue scale (VAS) to evaluate HRQoL, edema volume, and symptoms (pain, swelling, and difficulties in daily living activities) in patients with lymphedema following breast cancer treatment.²⁸ A recent Swedish study by Hoffner et al. used the generic HRQoL instrument 36-item Short Form Health Survey (SF-36) to investigate HRQoL in women with ULL after breast cancer treatment. They found improvements, but concluded that there is a need for a lymphedema-specific questionnaire for more accurate results.²⁹ Such a questionnaire, the Lymphedema Quality of Life Inventory (LyQLI), has recently been tested in Sweden and found to be valid and reliable,¹ as well as responsive and sensitive.² To our knowledge, the longitudinal impact on HRQoL after LS has never been examined with any lymphedema-specific questionnaire.

Aims

The main purpose of this study was to examine changes in HRQoL in patients with lymphedema before and after two different lymphedema treatments up to 12 months after intervention. A second purpose was to evaluate the effect of the interventions on lymphedema and lymphedema-related concerns (identified as high-impact factors).

Materials and Methods

This is a longitudinal multicenter study examining two different treatment concepts, an RP or surgery with LS, in three different countries, Australia, Scotland, and Sweden. The patients were included from 2013 to 2016.²

Ethical approvals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients provided informed consent before participating in the study. The Australian part was approved by the Macquarie University Human Research Ethics Committee (HREC [Medical Sciences]), Reference number 5201400124. In Scotland, treatment evaluation with questionnaires was already performed as a routine procedure, so ethical approval was not required. The Swedish part of the study was approved by the Regional Ethical Review Board in Lund, Sweden, Dnr 2013/628 and 2014/208.

Patients

The patients included in the two interventions had unilateral lymphedema in upper or lower limb.

Rehabilitation program

In this study, patients diagnosed with pitting lymphedema in the upper or lower limb are defined as moderate lymphedema; Bräcke Diakoni, Rehabcenter Sfären (Solna, Sweden). Inclusion criteria were adults, 18 years or older diagnosed with moderate lymphedema, and with no previous RP at the rehab center (Table 1). Patients with concurrent cancer disease or cognitive or communication difficulties were excluded. Patients were consecutively invited to the study when they were registered for a RP for 2 (ULL) or 3 (LLL) weeks. On the first day of the RP, the patients had arrival meetings with the different professionals and obtained an individual program. The program included the most common components in CDT,¹⁶ such as MLD, skin care, and multilayered bandaging, which were performed individually every day during the week. The RP was performed 5 days a week, 5–6 hours per day in 2 or 3 weeks depending on the severity of the lymphedema. Other important components in the program were water-based exercises, weightlifting, Nordic walking, and relaxation exercises (e.g., yoga), with each activity performed once or twice a week in group settings. The program also included lectures about the lymphatic system, ergonomic matters depending on part of body with lymphedema, information about different kinds of garments, dietary information, and self-care instructions. At the end of the program the lymph therapists usually supplied the patients with new compression garments. This concept is standardized in Region Stockholm, Sweden.

Table 1.

Clinical–Sociodemographic Characteristics of Patients at Baseline

Clinical–sociodemographic characteristics	RP (n = 18)	LS (n = 57)
Age, years, median (range)	61 (46–76)	53 (23–75)
Female/male, n (%)	15/3 (83/17)	52/5 (91/9)
Country of residence, n (%)
Australia		9 (16)
Scotland		29 (51)
Sweden	18 (100)	19 (33)
Years with lymphedema, median (range)	2.5 (0.5–57)	13 (2–66)
Primary lymphedema, n (%)	4 (22)	19 (33)
Secondary lymphedema, n (%)	14 (78)	38 (67)
Breast cancer	10	14
Gynecological cancer	2	15
Malignant melanoma		3
Other cancer diagnosis	1	1
Not cancer related	1	5
Body part affected, n (%)
Lower limb	7 (39)	41 (72)
Upper limb	11 (61)	16 (28)
Total volume of affected limb, mL, mean (SD)	6885 (5668)^a	10682 (5221)^a
Excess volume, mL, mean (SD)	934 (1398)^a	3117 (2543)^a

Differences between the RP patients and the LS patients in total volume of affected limb and excess volume at baseline were calculated with the Mann-Whitney test.

p ≤ 0.001.

LS, liposuction; RP, rehabilitation program; SD, standard deviation.

Liposuction

Patients who were operated on, had chronic lymphedema and had been treated conservatively, and thus showed minimal pitting (5–6 mm), and were in this study defined as severe lymphedema. Consecutive patients with ULL or LLL undergoing LS²³ for management of lymphedema through the Australian Lymphoedema Education Research Treatment (ALERT) program at Macquarie University in Sydney, Australia, the Plastic Surgery Clinic at Ninewells Hospital in Dundee, Scotland, or the Department of Plastic and Reconstructive Surgery, Lymphedema Center, Skåne University Hospital (Malmö, Sweden) participated in the study. LS for lymphedema is described in detail in several articles.^{23,25,26,30,31} In short, a tourniquet was utilized in combination with the tumescence technique to minimize blood loss³² and surgery was performed with around 10, 3- to 4-mm long incisions, and LS using 15- and 25-cm long cannulas with diameters of 3 and 4 mm. Circumferential LS was performed from wrist/ankles to axilla/inguinal region, and as much of the hypertrophied fat was removed as possible using previously measured circumferences of the healthy extremity as a control. When the extremity distal to the tourniquet had been treated, a sterilized custom-made compression sleeve was applied (Jobst Elvarex, compression class 2 or 3) to minimize bleeding and reduce postoperative edema. For the hand, a sterilized, standard interim glove (Cicatrex interim; Thuasne Begat) was put on. The tourniquet was then removed, and the most proximal part of the upper extremity was treated using the tumescent technique, where 1000 mL saline mixed with 1 mg adrenaline and 40 mL lidocaine 2% (Xylocaine; AstraZeneca PLC, London, United Kingdom) was infused subcutaneously. Finally, the proximal part of the compression garment was pulled up to compress the proximal part of the extremity. The incisions were left open to drain through the garment. An isoxazolyl penicillin was given intravenously for the first 24 hours and then orally until the incisions were healed, approximately during 10 days after surgery. In the case of penicillin allergy, clindamycin was used instead. The patient removed the garments after 2 days and then took a shower. The skin was lubricated with lotion, and the other set of garments was applied by the patient under supervision. The used garment was washed. On the fourth postoperative day, the second change was performed, and the patient was discharged. Thereafter, the patient changed the garments every other day during the first week at home, and then daily so that a clean set was always put on after showering and lubricating the limb. Used garments were washed to be used at the next change after drying, and so on. Thus, garments were worn continuously, night and day. Following surgery, renewal or compression garments were made at 1, 3, 6, and 12 months when necessary. The patients' clinical–sociodemographic characteristics are shown in Table 1.

Measurements

Lymphedema Quality of Life Inventory

The patients' used the LyQLI, which is a self-managed questionnaire, to assess HRQoL related to their lymphedema. Each item assesses the impact of lymphedema during the past 4 weeks on a 4-point Likert scale (0: none, 1: a little bit, 2: somewhat, 3: a lot). The scores are presented as mean scores in each domain, from 0.0 to 3.0, with a higher mean score indicating more impact on HRQoL. The questionnaire also includes four summary questions, of which item 44 assesses the overall experience of lymphedema and item 45 assesses the overall quality of life, both scored on a 4-point Likert scale ranging from 0: very bad to 3: very good. A higher score indicates higher HRQoL. The LyQLI has previously been tested in Sweden.^1,2

Clinical–sociodemographic characteristics questionnaire

Clinical-sociodemographic characteristics, lymphedema severity, and medical history were provided by the participants through hard copy surveys or a website link.

Visual analogue scale

The patients' subjective experiences of lymphedema symptoms in the affected limb were scored on a 100 mm horizontal VAS. The patients in the RP were asked to evaluate their average, least, and worst experience of tension and heaviness during the last week. The endpoints were “no discomfort” (0 mm) and “worst imaginable discomfort” (100 mm).^33,34 Because VAS measurements were repeated, the initial scores were made available to the patient at the second test.³⁵ It has been shown that patients with chronic disease tend to overestimate their experience of symptoms in long-term experiments if the initial scores are not made available at each assessment. Therefore, this procedure is recommended as more reliable when applying VAS in long-term studies.³⁵

Cylinder form method

In the RP patients, the volume of the extremities was calculated using the cylinder form method with circumferential measurements taken at 4 cm intervals and the contralateral arm/leg as control on each occasion.³⁶ The cylinder form method has been found valid in patients with LLL.³⁷ Sander et al.³⁸ found strong inter-rater and intrarater reliability for both water and geometric volumes in a study involving women with ULL.

Truncated cone method

In the LS patients in Australia and Scotland, the volume of the extremities was calculated using the truncated cone method with circumferential measurements taken at 4 cm intervals and the contralateral arm/leg as control on each occasion.^39,40 The method has been found reliable and valid.^39–41

Water displacement method

In the LS patients in Sweden, the volume of the extremities was measured with the water displacement method. On each occasion, each extremity was submerged in a container with water and the displaced water was weighed on a balance to the nearest 5 g (corresponding to 5 mL).⁴⁰ In a study involving women with ULL, both the water and truncated cone volume methods were found to be highly reliable.^40,42

Design

Follow-ups with LyQLI to assess the longitudinal experience of HRQoL were performed before and after 1, 3, 6, and 12 months for the two interventions. In the RP, limb volumes and experiences of tension and heaviness were obtained on the first and last day of the program and 6 months afterward. In the LS, the limb volume was measured before and at 1, 3, 6, 9, and 12 months afterward as a regular part of the usual clinical care.²³

Procedure

Rehabilitation program

Information about the study was included in the invitation to attend the planned RP and was sent to the patient about 3 weeks before the first appointment. Thereafter, the first author (P.K.) contacted the patients by telephone, and if they agreed to participate, they were sent the LyQLI, a consent form and a clinical-sociodemographic characteristics questionnaire together with a prepaid envelope. Patients were asked to return the questionnaire before starting the program. If the envelope was not returned after 1 week, a reminder was mailed. If they had still not responded after another week, P.K. contacted them by telephone. Experience of tension and heaviness, measured with VAS, and limb volume, measured using the cylinder method, were collated by P.K., who was not involved in the treatment program. During the RP, the patients were treated by a multidisciplinary team comprising a physician, nurses, lymphedema therapists, physiotherapists, and occupational therapists.

Liposuction

In Australia, the patients received information about the study and were invited to participate about 3 weeks before LS. The research assistant mailed a letter and sent an e-mail describing the purpose of the research to eligible patients. To join the study, the patients either followed a website link where they viewed and accepted the consent form or contacted the research assistant to request hard copies of the consent form, the clinical-sociodemographic questionnaire, and the LyQLI. In Scotland, patients received the forms in the morning, 4 hours before surgery. If they agreed to participate, they had to complete the forms before surgery. In Sweden, the patients received information about the study at their visit 2 weeks before surgery; thereafter, P.K. contacted the patients by telephone and invited them to participate. If they agreed, they received the LyQLI, a consent form, and a clinical-sociodemographic questionnaire by mail, together with a prepaid envelope, and were asked to return it before surgery. If the envelope was not returned after 1 week, a reminder was mailed. If they had still not responded after another week, P.K. contacted them by telephone before surgery. The surgeons were not involved in data collection.

Statistical analysis

Descriptive statistics reported for baseline variables include rates for mean scores, standard deviations (SDs), medians, ranges, and percentage. Mean values were calculated for the LyQLI responses for the three domains. There were few missing items, varying from 0.3% to 2%. The percentage of patients who experienced high impact (mean score ≥2.0) in one or more of the three domains was analyzed at baseline and after 1 and 12 months. Mean values and SD were calculated for the total volume of the affected limb as well as for the excess volume. The excess volume was defined as volume difference between the affected and nonaffected limb, expressed in milliliters. For the VAS measurements, mean values at the RP's first day, last day, and 6 months afterward were calculated in millimeters. To handle missing LyQLI forms, VAS measurements, and volume measurements, single imputation of the mean values was used for the follow-ups at 3, 6, and 12 months. The last-and-next imputation was used in patients with available assessments before and after the missing assessment.⁴³ Last-observation-carried-forward (LOCF) imputation was used in patients with no further assessments.⁴³ These methods allowed consistent number of patients from baseline to last follow-up measurement.

Since the patient groups were small, nonparametric tests were used. The Mann-Whitney test was used to detect significant differences between the RP patients and the LS patients at baseline, for the total volume of affected limb and excess volume. To detect and analyze differences in LyQLI responses in the three domains, from baseline to the 12-month follow-up, the Wilcoxon signed rank test was performed. The Wilcoxon sign rank test was also used to detect differences in experiences in tension and heaviness measured with VAS up to 6 months and for changes in total volume of the affected limb and excess volume up to the 12-month follow-up.

To detect which concerns mostly affected the patients' HRQoL and if that would change after the interventions, the responses were analyzed using 20 items with the highest mean score, identified in a previous study.² The items in physical domain were 1, 2, 3, 6, 9, 10, and 11, in psychosocial domain were 13, 14, 15, 16, 18, 20, and 27, and in practical domain were 30, 33, 36, 37, 38, and 39 (Tables 3 and 5). The responses were dichotomized into low impact (none/little impact), mean score <2.0, and high impact (somewhat/a lot impact), mean score ≥2.0. The percentage of patients who estimated a high impact on HRQoL in the 20 items at baseline and after 12 months was calculated. The differences between baseline and 12 months were calculated as a percentage. All statistical analyses were two tailed, and the significance level was set to 0.05. The statistical computer program IBM SPSS Statistics, version 22, was used for all tests.

Results

Rehabilitation program

Twenty patients fulfilled the criteria and were included in the study. Eighteen patients (Table 1) completed the LyQLI at 1 month and 16 at 3, 6, and 12 months. The reasons for dropout at 1 month were cancer recurrence in one patient and trauma in the other. At 3 months, one patient had died from cancer and one did not respond, with no reason given. Most in the study group were females with ULL secondary to cancer treatments.

The results show that the LyQLI scores decreased significantly compared to baseline, indicating improved HRQoL in the physical (p = 0.003) and psychosocial domains (p = 0.002) 1 month after the program. These results remained stable up to 6 months for the psychosocial domain (p = 0.012) and 12 months for the physical domain (p = 0.024). The scores in the practical domain also decreased, but not significantly (Fig. 1). At baseline, 21% of the participants scored ≥2.0 in at least one of the three domains, which indicates a high impact on HRQoL. After 1 month, HRQoL had improved and the number of patients who experienced high impact had decreased to 11%, but it increased again to 28% at the 12-month follow-up.

FIG. 1.

Scores of participants in the RP (n = 18) in the three domains of the LyQLI. The Figure shows changes in scores from baseline to the 12-month follow-up. A decrease in score indicates an increase in HRQoL. *p < 0.05; **p < 0.01. HRQoL, health-related quality of life; LyQLI, Lymphedema Quality of Life Inventory; RP, rehabilitation program.

The results from the volume measurements show that the total volume of the affected limb as well as the excess volume decreased significantly (p < 0.001) directly after the intervention, but by 6 months postintervention, the volume had started to increase (Table 2). The results from the VAS measurements show that six patients experience neither tension nor heaviness in their affected limb. For the remainder, the mean score decreased, indicating less discomfort. After 6 months, the impact increased again, except for heaviness–worst, which remained significantly better (p = 0.039) (Table 2).

Table 2.

Changes of Total Volume of the Affected Limb, Excess Volumes (n = 18), and Visual Analogue Scale Scores in the Rehabilitation Program Patients (n = 12)

	First day at the RP (baseline)	Last day at the RP	6 Months follow-up
Volume
Total volume of affected limb in mL, mean (SD)	6885 (5668)	6554 (5560), p < 0.001	6793 (5554), p = 0.472
Excess volume in mL, mean (SD)	934 (1398)	708 (1339), p < 0.001	770 (1336), p = 0.048
VAS
Tension-now in mm, mean (SD)	23 (22)	16 (17), p = 0.060	20 (23), p = 0.432
Tension-average in mm,^a mean (SD)	28 (28)	14 (16), p = 0.012	26 (23), p = 0.107
Tension-worst in mm, mean (SD)	42 (33)	26 (30), p = 0.016	37 (33), p = 0.530
Heaviness-now in mm, mean (SD)	19 (23)	10 (13), p = 0.041	15 (21), p = 0.722
Heaviness-average in mm,^a mean (SD)	28 (30)	16 (21), p = 0.012	23 (31), p = 0.208
Heaviness-worst in mm, mean (SD)	39 (36)	23 (26), p = 0.005	28 (32), p = 0.037

Lower VAS scores indicating less discomfort. For analysis of differences before and after intervention, the Wilcoxon signed rank test was used. p-Values presented are the difference in the follow-up measurements compared to baseline. Significant p-values (p < 0.05) are presented in bold.

n = 8.

VAS, visual analogue scale.

The 20 items with the highest impact on HRQoL and the changes in impact from baseline to the 12-month follow-up (sorted by impact at 12 months), are shown in Table 3.

Table 3.

The 20 Items with Most Impact on Health-Related Quality of Life Identified by the Lymphedema Quality of Life Inventory and the Percentage of the Participants (n = 18) Who Scored a High Impact on Health-Related Quality of Life Before and 12 Months After the Rehabilitation Program

Lymphedema-related concerns and problems, with high impact on HRQoL		Somewhat/a lot impact on HRQoL		Percentage improvements in HRQoL
		Percentage of patients		Baseline to 12 months
		Baseline	12 Months	Baseline to 12 months
20	Paying constant attention to my condition	72	39	46
18	Not being able to do the things I used to enjoy	50	28	44
27	Concerns about negative changes in my appearance	44	28	36
33	Having less energy to do activities (e.g., personal, normal daily, or employment)	47	33	30
36	Traveling long distances by car, train, plane, etc.	47	33	30
13	Feelings of frustration/feeling annoyed	61	44	28
10	Feeling physically aware of my lymphedema all the time	67	50	25
14	Feeling anxious about whether or not the lymphedema will get worse	67	50	25
15	Embarrassed by lymphedema/compression garments	44	33	25
38	Limitations in hot weather/sun	78	61	22
1	Pain/aches due to my lymphedema	56	44	21
3	A feeling of heaviness due to my lymphedema	56	44	21
16	Negative changes in how I see myself	56	44	21
37	Finding clothes and shoes that are comfortable and attractive, and the right size and type of material	61	50	18
30	Normal daily activities (e.g., doing housework, sports, and hobby activities)	33	28	15
2	Discomfort due to my lymphedema	61	56	8
6	Swelling/tightness due to my lymphedema	78	72	8
11	Feeling a loss of strength in the swollen part of my body	61	56	8
9	Movement difficulties due to my lymphedema	44	44	0
39	The constant self-care I need to do to stop my lymphedema from getting worse	56	67	−16

The items are presented in descending order, from highest increase in HRQoL at 12 months to the lowest increase among these 20 items. Items 1–12 relate to the physical domain, 13–28 to the psychosocial domain, and 29–41 to the practical domain.

HRQoL, health-related quality of life.

Liposuction

Sixty-four eligible patients were included in the study. Fifty-seven patients (89%) completed the LyQLI at 1 month (Table 1). Four patients did not respond to the second measurement, with no reasons given, one patient cancelled the surgery, and one patient gave a general lack of vigor as a reason. The seventh patient did respond and failed to complete the measurement. Fifty-two patients completed the LyQLI at 3 and 6 months and 46 patients at 12 months. The reasons for the dropouts are unknown. Most of the study group was female. More than half had secondary lymphedema and the absolute majority had lymphedema secondary to cancer treatment. Most patients had LLL, with ovarian or cervical cancer treatment the most common underlying cause.

The results show that the LyQLI scores decreased significantly (p < 0.001) compared to the baseline in all three domains, indicating improved HRQoL. These results remained stable up to the 12-month follow-up (Fig. 2). At baseline, 45% of the participants scored ≥2.0 in at least one of the three domains, which indicates a high impact on HRQoL. The patients' HRQoL improved after 1 month and the number that experienced high impact decreased to 19%, with a continued decrease to 5% by the 12-month follow-up. The results from the volume measurements show that the total volume of the affected limb and the excess volume decreased significantly (p < 0.001). The largest decrease was seen between baseline and follow-up at 1 month (Table 4).

FIG. 2.

Scores of participants in the LS program (n = 57) in the three domains of the LyQLI. The Figure shows changes in scores from baseline to the 12-month follow-up. A decrease in score indicates an increase in HRQoL. ***p < 0.001. LS, liposuction.

Table 4.

Changes of Affected Limb Volumes and Excess Volumes in the Liposuction Patients (n = 57)

Volume	Baseline	1 Month	3 Months	6 Months	12 Months
Total volume of affected limb in mL, mean (SD)	10682 (5221)	8537 (3980), p < 0.001	8419 (3898), p < 0.001	8085 (3646), p < 0.001	8021 (3643), p < 0.001
Excess volume in mL, mean (SD)	3117 (2543)	926 (1115), p < 0.001	656 (1023), p < 0.001	438 (828), p < 0.001	154 (579), p < 0.001

For analysis of differences before and after intervention, the Wilcoxon Signed rank test was used. p-Values presented are the difference for the follow-up measurements compared to baseline.

Significant p-values (p < 0.05) are presented in bold.

The 20 items with highest impact on HRQoL and the change of impact from baseline to 12-month follow-up are shown in Table 5.

Table 5.

The 20 Items with the Most Impact on Health-Related Quality of Life Identified by the Lymphedema Quality of Life Inventory and the Percentage of the Participants (n = 57) Who Scored High Impact on Health-Related Quality of Life Before and 12 Months After Liposuction

Lymphedema-related concerns and problems, with high impact on HRQoL		Somewhat/a lot impact on HRQoL		Percentage improvements in HRQoL
		Percentage of patients		Baseline to 12 months
		Baseline	12 Months	Baseline to 12 months
6	Swelling/tightness due to my lymphedema	89	12	86
14	Feeling anxious about whether or not the lymphedema will get worse	75	11	85
3	A feeling of heaviness due to my lymphedema	91	18	82
18	Not being able to do the things I used to enjoy	56	12	78
30	Normal daily activities (e.g., doing housework, sports, and hobby activities)	42	9	78
2	Discomfort due to my lymphedema	79	18	77
9	Movement difficulties due to my lymphedema	61	14	77
13	Feelings of frustration/feeling annoyed	66	16	76
33	Having less energy to do activities (e.g., personal, normal daily, or employment)	46	11	76
27	Concerns about negative changes in my appearance	63	16	75
16	Negative changes in how I see myself	70	18	74
10	Feeling physically aware of my lymphedema all the time	84	23	73
11	Feeling a loss of strength in the swollen part of my body	58	16	72
15	Embarrassed by lymphedema/compression garments	72	23	68
1	Pain/aches due to my lymphedema	54	18	67
20	Paying constant attention to my condition	55	18	67
37	Finding clothes and shoes that are comfortable and attractive, and the right size and type of material	91	39	57
39	The constant self-care I need to do to stop my lymphedema from getting worse	68	30	56
36	Traveling long distances by car, train, plane, etc.	63	30	52
38	Limitations in hot weather/sun	79	44	44

Discussion

The results show that treatment with a conservative RP in moderate lymphedema or LS combined with CCT in severe lymphedema improves HRQoL for patients with limb lymphedema.

Since data collection was performed independently for RP and LS and the participants were not randomized, the results are presented separately. Of note, however, is that patients undergoing LS were younger, had suffered from lymphedema for longer, and had significantly larger total volume and excess volume of the affected limb than the RP patients. The larger excess volumes in the LS patients may be explained by the circumstance that a longer duration of lymphedema in both upper and lower limb has been associated with greater excess volumes.⁴⁴

That is, the LS patients had more severe edema and greater impact on HRQoL at baseline than the RP patients. The percentage of the participants who had high impact on HRQoL because of lymphedema in one or more domains in LyQLI was 21% at baseline in the RP group and 45% in the LS group.

Rehabilitation program

One month after the RP, the number of participants who experienced high impact on HRQoL decreased from 21% to 11%, which implies that the intervention also improved HRQoL in those participants with many problems and concerns. However, after 12 months, high-impact HRQoL increased again to 28%. This suggests that repeated RP or psychosocial support may be required for patients with a high impact on HRQoL.

The results from the responses for the 20 high-impact items are equally represented across the three domains (Table 3). The three concerns that had the highest impact on HRQoL (>70% of patients) before the RP were as follows: “Swelling/tightness due to my lymphedema,” “Paying constant attention to my condition,” and “Limitations in hot weather/sun,” representing all three domains. The circumstance that the patients had high impact in all three domains of the LyQLI and that the issues involve physical, psychosocial, and practical problems for the patient may highlight the complexity of lymphedema impact.

The items that changed most from high impact to low impact on HRQoL were in the psychosocial domain, indicating an improved HRQoL. The improvements remained to the 12-month follow-up. This was for items such as “Paying constant attention to my condition,” “Not being able to do the things I used to enjoy,” “Concerns about negative changes in my appearance,” “Feeling of frustration/felling annoyed,” and “Feeling anxious about whether or not the lymphedema will get worse.”

In a systematic review, D'Egidio et al. concluded that health professionals can help to maintain and restore impaired physical and psychosocial health, for example, HRQoL, in women with breast cancer.⁴⁵ The rehabilitation in the RP was conducted by a multidisciplinary team with experienced therapists meeting patients face to face both individually and in groups. This circumstance could explain why the increases in psychosocial HRQoL occurred and were maintained. In the same study, the authors also concluded that peer support with educated breast cancer survivors could improve HRQoL for patients with newly diagnosed disease.⁴⁵ In this study, no such procedure was performed. However, most of the other patients who attended the RP had been to the RP before and were cancer survivors with a long history of lymphedema.

In particular, the item “The constant self-care I need to do to stop my lymphedema from getting worse” had a high impact on HRQoL and the impact increased up to 12 months. The negative impact of self-care on HRQoL is supported by other studies⁴⁶ with similar results. The impact of self-care or self-management is a known problem, since patients with chronic diseases must continue to perform self-care for the rest of their lives.^46,47 One way to improve HRQoL can be to give the patients regular access to supportive professional assistance so they can optimize their self-care and get help to decrease it to the minimum possible level to reduce the burden.⁴⁷

The results show that not all patients experienced tension or heaviness in their affected limb. For those who did, the mean score was relatively high (Table 2) on the first day of the RP and it decreased significantly by the last day. After 6 months, the discomfort had increased again, except for “Heaviness-worst” that remained significantly improved. The fact that tension increased may be due to insufficient supply of compression garments and it again highlights the need for frequent support to be provided to these patients.

Liposuction

The results show that HRQoL improved after 1 month in all three domains and the improvements of HRQoL remained up to 12 months in the physical, psychosocial, and practical domains. The proportion of participants that experienced negative impact on HRQoL in one or more domains decreased from 45% at baseline to 5% at the 12-month follow-up, indicating a very large improvement in HRQoL.

The results from the responses to the 20 high-impact items also reveal improved HRQoL, with more than 50% change from high impact to low impact, in all items, except for “Limitations in hot weather/sun” (Table 5).

The improvements were highest (>80%) in “Swelling/tightness due to my lymphedema,” “Feeling anxious about whether or not the lymphedema will get worse,” and “A feeling of heaviness due to my lymphedema,” indicating that the swelling itself and the worries patients had at baseline about the disease getting worse were almost gone 1 year after the surgery. The results show that change from high to low impact on HRQoL was highest in items belonging to the physical and psychosocial domains. The item in the practical domain, “Finding clothes and shoes that are comfortable and attractive, the right size, and type of material” had a high impact at baseline, but the change to low impact was only 57%, indicating that patients still recognized this as a problem.

The 10 items in which the HRQoL improved greatly (>70%) were from all three domains, physical, psychosocial, and practical. These findings emphasize that the problems in having lymphedema are multidimensional. The results also indicate that many of these concerns can be improved by LS, with improved HRQoL as a result. These results align with recent results from other studies where it was found that, for example, both physical and emotional impact decreased after intervention.^26,28,29

Among those 20 items, the improvement in the item “Limitations in hot weather/sun” was the lowest. The likely reason is probably that the patients must continue to wear compression garments after LS even in hot weather.²⁵

Strengths and limitations

Data collection was performed independently for RP and LS and the participants were not randomized; therefore, the results were presented separately and that can serve as a limitation. The main outcome of this study was HRQoL and we considered it important to measure HRQoL similarly in both patient groups, that is, 1 month after intervention, which was achieved. However, due to practical reasons, volume and VAS were measured on the last day of the RP and not 1 month after intervention. Volume and VAS were furthermore obtained 6 months after intervention for RP, but again due to practical reasons, it was not possible to review the patients at 3 and 12 months as for the LS patients. Neither was it possible to supply the RP patients with continuous change of compression garments as by LS combined with CCT.

A strength in the study is that all three volume measurement methods applied have been tested and found reliable.^36–42 Another strength is that all three sites used the same surgical method and rehabilitation protocol^25–27 following the surgical method introduced by H.B., Department of Plastic and Reconstructive Surgery, Skåne University Hospital, in 1987.^24,25,30 Both the Australian and Scottish teams underwent repeated training by his team in Sweden.

A third strength was the low dropout rate and the imputation through the last-and-next imputation and LOCF that makes the data more reliable by reducing the bias of missing data.⁴³

Conclusion

Treatment with a conservative RP in moderate lymphedema or LS combined with CCT in severe lymphedema increases HRQoL in patients with limb lymphedema. The improvements were found in all three domains (the physical, psychosocial, and practical domain) of the LyQLI. The results remained stable in the physical domain in the RP patients and in all three domains in the LS patients up to the 12-month follow-up. For the LS patients, the percentage that experienced high impact on HRQoL decreased from 45% to 19% at 6 months to 5% at 12 months, indicating a sustainable impact on HRQoL.

Footnotes

Acknowledgments

The authors are grateful to all the patients who took part in this study and to our colleagues for their assistance and support.

Author Disclosure Statement

The authors declare that they have no conflict of interest and that no competing financial interests exist.

Funding Information

This study was funded by the Swedish Cancer Society, Skåne County Council's Research, and the Swedish Association of Chronic Oedema.

References

Klernas

, Johnsson

, Horstmann

, Kristjanson

, Johansson

. Lymphedema Quality of Life Inventory (LyQLI)-Development and investigation of validity and reliability. Qual Life Res, 2015; 24:427–439.

Klernas

, Johnsson

, Horstmann

, Johansson

. Health-related quality of life in patients with lymphoedema—A cross-sectional study. Scand J Caring Sci, 2018; 32:634–644.

Jager

, Doller

, Roth

. Quality-of-life and body image impairments in patients with lymphedema. Lymphology, 2006; 39:193–200.

Cemal

, Jewell

, Albornoz

, Pusic

, Mehrara

. Systematic review of quality of life and patient reported outcomes in patients with oncologic related lower extremity lymphedema. Lymphat Res Biol, 2013; 11:14–19.

Chachaj

, Malyszczak

, Pyszel

, Lukas

, Tarkowski

, Pudelko

, Andrzejak

, Szuba

. Physical and psychological impairments of women with upper limb lymphedema following breast cancer treatment. Psychooncology, 2010; 19:299–305.

Pyszel

, Malyszczak

, Pyszel

, Andrzejak

, Szuba

. Disability, psychological distress and quality of life in breast cancer survivors with arm lymphedema. Lymphology, 2006; 39:185–192.

Bogan

, Powell

, Dudgeon

. Experiences of living with non-cancer-related lymphedema: Implications for clinical practice. Qual Health Res, 2007; 17:213–224.

Boyages

, Kalfa

, Xu

, Koelmeyer

, Mackie

, Viveros

, Taksa

, Gollan

. Worse and worse off: The impact of lymphedema on work and career after breast cancer. Springerplus, 2016; 5:657.

Boyages

, Xu

, Kalfa

, Koelmeyer

, Parkinson

, Mackie

, Viveros

, Gollan

, Taksa

. Financial cost of lymphedema borne by women with breast cancer. Psychooncology, 2017; 26:849–855.

10.

The World Health Organization Quality of Life assessment (WHOQOL): Position paper from the World Health Organization. Soc Sci Med, 1995; 41:1403–1409.

11.

Fayers

, Machin

: Quality of Life: The Assessment, Analysis and Reporting of Patient-Reported Outcomes. 3rd ed. West Sussex: John Wiley & Sons Ltd.; 2016.

12.

Ferrans

, Zerwic

, Wilbur

, Larson

. Conceptual model of health-related quality of life. J Nurs Scholarsh, 2005; 37:336–342.

13.

Mortimer

, Rockson

. New developments in clinical aspects of lymphatic disease. J Clin Invest, 2014; 124:915–921.

14.

The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology. Lymphology, 2013; 46:1–11.

15.

Szuba

, Rockson

. Lymphedema: Classification, diagnosis and therapy. Vasc Med, 1998; 3:145–156.

16.

Lasinski

, McKillip Thrift

, Squire

, Austin

, Smith

, Wanchai

, Green

, Stewart

, Cormier

, Armer

. A systematic review of the evidence for complete decongestive therapy in the treatment of lymphedema from 2004 to 2011. PM R, 2012; 4:580–601.

17.

Ciudad

, Sabbagh

, Agko

, Huang

TCT

, Manrique OJ

L C

R, Reynaga

, Delgado

, Maruccia

, Chen

. Surgical management of lower extremity lymphedema: A comprehensive review. Indian J Plast Surg, 2019; 52:81–92.

18.

Brorson

, Ohlin

, Olsson

, Karlsson

. Breast cancer-related chronic arm lymphedema is associated with excess adipose and muscle tissue. Lymphat Res Biol, 2009; 7:3–10.

19.

Brorson

, Ohlin

, Olsson

, Nilsson

. Adipose tissue dominates chronic arm lymphedema following breast cancer: An analysis using volume rendered CT images. Lymphat Res Biol, 2006; 4:199–210.

20.

Aschen

, Zampell

, Elhadad

, Weitman

, De Brot

, Mehrara

. Regulation of adipogenesis by lymphatic fluid stasis: Part II. Expression of adipose differentiation genes. Plast Reconstr Surg, 2012; 129:838–847.

21.

Rockson

. The lymphatics and the inflammatory response: Lessons learned from human lymphedema. Lymphat Res Biol, 2013; 11:117–120.

22.

Zampell

, Aschen

, Weitman

, Yan

, Elhadad

, De Brot

, Mehrara

. Regulation of adipogenesis by lymphatic fluid stasis: Part I. Adipogenesis, fibrosis, and inflammation. Plast Reconstr Surg, 2012; 129:825–834.

23.

Brorson

, Svensson

. Complete reduction of lymphoedema of the arm by liposuction after breast cancer. Scand J Plast Reconstr Surg Hand Surg, 1997; 31:137–143.

24.

Brorson

, Svensson

. Liposuction combined with controlled compression therapy reduces arm lymphedema more effectively than controlled compression therapy alone. Plast Reconstr Surg, 1998; 102:1058–1067; discussion 1068.

25.

Brorson

. Liposuction in lymphedema treatment. J Reconstr Microsurg, 2016; 32:56–65.

26.

Boyages

, Kastanias

, Koelmeyer

, Winch

, Lam

, Sherman

, Munnoch

, Brorson

, Ngo

, Heydon-White

, Magnussen

, Mackie

. Liposuction for advanced lymphedema: A multidisciplinary approach for complete reduction of arm and leg swelling. Ann Surg Oncol, 2015; 22(Suppl 3):S1263–S1270.

27.

Schaverien

, Munro

, Baker

, Munnoch

. Liposuction for chronic lymphoedema of the upper limb: 5 Years of experience. J Plast Reconstr Aesthet Surg, 2012; 65:935–942.

28.

Brorson

, Ohlin

, Olsson

, Langstrom

, Wiklund

, Svensson

. Quality of life following liposuction and conservative treatment of arm lymphedema. Lymphology, 2006; 39:8–25.

29.

Hoffner

, Bagheri

, Hansson

, Manjer

, Troeng

, Brorson

. SF-36 shows increased quality of life following complete reduction of postmastectomy lymphedema with liposuction. Lymphat Res Biol, 2017; 15:87–98.

30.

Brorson

, Svensson

, Norrgren

, Thorsson

. Liposuction reduces arm lymphedema without significantly altering the already impaired lymph transport. Lymphology, 1998; 31:156–172.

31.

Hoffner

, Ohlin

, Svensson

, Manjer

, Hansson

, Troeng

, Brorson

. Liposuction gives complete reduction of arm lymphedema following breast cancer treatment-A 5-year prospective study in 105 patients without recurrence. Plast Reconstr Surg Glob Open, 2018; 6:e1912.

32.

Wojnikow

, Malm

, Brorson

. Use of a tourniquet with and without adrenaline reduces blood loss during liposuction for lymphoedema of the arm. Scand J Plast Reconstr Surg Hand Surg, 2007; 41:243–249.

33.

Scott

, Huskisson

. Graphic representation of pain. Pain, 1976; 2:175–184.

34.

Wewers

, Lowe

. A critical review of visual analogue scales in the measurement of clinical phenomena. Res Nurs Health, 1990; 13:227–236.

35.

Scott

, Huskisson

. Accuracy of subjective measurements made with or without previous scores: An important source of error in serial measurement of subjective states. Ann Rheum Dis, 1979; 38:558–559.

36.

Kuhnke

. Volume determination from circumference measurements [In German]. Folia Angiolica, 1976; 24:228–232.

37.

Kaulesar Sukul

, den Hoed

, Johannes

, van Dolder

, Benda

. Direct and indirect methods for the quantification of leg volume: Comparison between water displacement volumetry, the disk model method and the frustum sign model method, using the correlation coefficient and the limits of agreement. J Biomed Eng, 1993; 15:477–480.

38.

Sander

, Hajer

, Hemenway

, Miller

. Upper-extremity volume measurements in women with lymphedema: A comparison of measurements obtained via water displacement with geometrically determined volume. Phys Ther, 2002; 82:1201–1212.

39.

Karges

, Mark

, Stikeleather

, Worrell

. Concurrent validity of upper-extremity volume estimates: Comparison of calculated volume derived from girth measurements and water displacement volume. Phys Ther, 2003; 83:134–145.

40.

Brorson

, Hoijer

. Standardised measurements used to order compression garments can be used to calculate arm volumes to evaluate lymphoedema treatment. J Plast Surg Hand Surg, 2012; 46:410–415.

41.

Taylor

, Jayasinghe

, Koelmeyer

, Ung

, Boyages

. Reliability and validity of arm volume measurements for assessment of lymphedema. Phys Ther, 2006; 86:205–214.

42.

Kettle

, Rundle

, Oddie

. Measurement of upper limb volumes: A clinical method. Aust N Z J Surg, 1958; 27:263–270.

43.

Sagberg

, Solheim

, Jakola

. Quality of survival the 1st year with glioblastoma: A longitudinal study of patient-reported quality of life. J Neurosurg, 2016; 124:989–997.

44.

Casley-Smith

. Alterations of untreated lymphedema and it's grades over time. Lymphology, 1995; 28:174–185.

45.

D'Egidio

, Sestili

, Mancino

, Sciarra

, Cocchiara

, Backhaus

, Mannocci

, De Luca

, Frusone

, Monti

, La Torre

; RETURN TO BREAST Collaborative group. Counseling interventions delivered in women with breast cancer to improve health-related quality of life: A systematic review. Qual Life Res, 2017; 26:2573–2592.

46.

Ridner

, Dietrich

, Kidd

. Breast cancer treatment-related lymphedema self-care: Education, practices, symptoms, and quality of life. Support Care Cancer, 2011; 19:631–637.

47.

Douglass

, Graves

, Gordon

. Self-care for management of secondary lymphedema: A systematic review. PLoS Negl Trop Dis, 2016; 10:e0004740.