Lymphedema Interventions: Exercise, Surgery, and Compression Devices

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Seminars in Oncology Nursing, Vol 29, No 1 (February), 2013: pp 28-40

LYMPHEDEMA INTERVENTIONS: EXERCISE, SURGERY, AND COMPRESSION DEVICES CHRISTINE J. CHANG AND JANICE N. CORMIER OBJECTIVES: To review exercise, surgical treatment, and intermittent pneumatic compression in the risk reduction and treatment of lymphedema, and to provide applications of the evidence to the care of the oncology patient with or at risk for lymphedema.

DATA SOURCES: Systematic reviews of the contemporary literature (20042010) examining exercise, surgical treatment, and intermittent pneumatic compression use in lymphedema therapy, peer-reviewed publications, and web sites of professional organizations. CONCLUSION: Exercise and intermittent pneumatic compression are effective therapies and can be safely implemented in appropriate patients as an adjunct to complete decongestive therapy. Surgical treatments have proven beneficial in carefully selected patients, but require continued use of life-long compression therapy. Intermittent pneumatic compression devices are a safe adjunctive treatment option for in-home use in appropriate patients at low to moderate pressure ranges, following and in conjunction with complete decongestive therapy.

IMPLICATIONS FOR NURSING PRACTICE: Informed oncology nurses can assist patients in an individualized, integrated multimodality approach to lymphedema therapy. KEY WORDS: Lymphedema, systematic review, exercise, surgery, intermittent pneumatic compression

L

YMPHEDEMA is a chronic condition of the lymphatic system that results from obstruction or disruption of the flow of lymph fluid. Disturbance of the lymph

flow leads to the accumulation of protein-rich fluid in interstitial tissues, thus resulting in swelling of the affected body part. The resultant swelling can range from mild to severe and, when left untreated,

Christine J. Chang, RN, MSN, ACNP-BC: Nurse Practitioner, Multidisciplinary Thoracic Oncology, Ellis Fischel Cancer Center, Columbia, MO. Janice N. Cormier, MD, MPH, FACS: Professor, Departments of Surgical Oncology and Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX.

Address correspondence to Christine J. Chang, RN, MSN, ACNP-BC, Ellis Fischel Cancer Center, 115 Business Loop 70W, DC 116.05 Suite 408, Columbia, MO 65203. e-mail: [email protected] Ó 2013 Elsevier Inc. All rights reserved. 0749-2081/2901-$36.00/0. http://dx.doi.org/10.1016/j.soncn.2012.11.005

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can lead to skin changes, impaired function, loss of normal sensation, discomfort, pain, and chronic infections that affect quality of life.1 Lymphedema is classified as either primary or secondary. Primary lymphedema is caused by a congenital dysfunction or abnormality of the lymphatic system, while secondary lymphedema results from obstruction or disruption of the normal lymph flow because of tumors or damage to lymphatic channels. This disruption or damage is most commonly the result of surgery including lymph node surgery, radiation therapy, trauma, or infection. The most common cause of secondary lymphedema in the United States and developed countries is breast cancer treatment.2 Although awareness of breast cancerassociated lymphedema is increasing, lymphedema is also reported following the treatment of other solid tumors including head and neck (4%), gynecologic (20%), melanoma (16%), and genitourinary (10%).3,4 The gold standard for the treatment of lymphedema is complete decongestive therapy (CDT), which should be performed by a trained, certified lymphedema therapist.5 CDT is a two-phased, sixcomponent treatment regimen. An initial reductive phase (phase I) aims at reducing the size of the affected area and emphasizing proper skin care. Once maximum fluid volume reduction has been reached, the maintenance phase (phase II) begins and requires life-long self-maintenance. While there is no cure for lymphedema, it can be successfully managed with CDT. Early diagnosis is important because lymphedema is most successfully treated and complications minimized when therapies are introduced early.6,7 Beyond conventional treatment, exercise, surgical interventions, and intermittent pneumatic compression (IPC) devices have evolved as potentially effective treatment modalities. This article will discuss the role of exercise in lymphedema management, describe current research in surgical approaches to the management of lymphedema, and review the evidence for IPC in the treatment of lymphedema.

EXERCISE AND LYMPHEDEMA Exercise is an important component in cancer prevention and control.8,9 Cancer survivors can receive many benefits from exercise, including reduced fatigue, increased strength and flexibility, and improved body image and quality of life.10 Because the number of cancer survivors continues to increase, patient education regarding an appro-

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priate exercise regimen for long-term health and cancer prevention is essential. Approximately 2.5 million female breast cancer survivors reside in the United States.11 The incidence of breast cancer-related lymphedema (BCRL) is conservatively estimated to be approximately 26% at 2 years post-operatively.12 In addition to the previously noted benefits of exercise in cancer survivors in general, exercise and maintaining a healthy weight are specifically relevant to breast cancer survivors because weight gain and/or obesity are known to increase the risk of lymphedema in breast cancer survivors posttreatment.3 Postoperatively, breast cancer survivors are often instructed on various restrictions and lifestyle modifications, including avoidance of trauma, phlebotomy, injections, blood pressure monitoring, tight-fitting clothing, as well as proper skin care, with the goal of lymphedema prevention. In the past, there was limited high-level research in the form of studies that specifically addressed exercise in relation to lymphedema. This left clinicians without conclusive evidence on which to advise patients about exercise, and patients were commonly instructed to avoid exercise to the affected extremity or were told that there was no clear answer, leaving the patient to decide on his/her own. This often resulted in frustration and fear in breast cancer survivors as to what level of exercise they could safely perform without increasing the risk of lymphedema occurrence or exacerbation.13 Physiologically, exercise activates the musculoskeletal pumping mechanism that increases venous and lymphatic return in the extremity affected by lymphedema. It has been suggested that upper body exercises may reset the sympathetic nervous system drive to the lymph vessels and thus provide a benefit in the long-term management of lymphedema.14 In recent years; additional research has been conducted to specifically address the issues of exercise and lymphedema. The dragon boat racing study in breast cancer survivors was among the first to demonstrate that there is no association between upper body exercise and the onset or exacerbation of BCRL15,16 In an effort to update the International Lymphoedema Framework Best Practices document,17 which summarized the literature up to the year 2004, the American Lymphedema Framework Project in partnership with the International Lymphoedema Framework commissioned a systematic review of 2004-2010 literature on exercise

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and lymphedema that was performed by Kwan et al.10 Publications were retrieved from 11 major medical indices for articles published from 2004 to 2010 using search terms for lymphedema and exercise. Approximately 1,303 articles were selected, of which 659 were reviewed by clinical lymphedema experts for inclusion, yielding 35 articles in the area of exercise. After applying predefined exclusion criteria, 19 articles were selected for final review. Of the 19 articles reviewed, seven addressed resistance exercise,18-24 seven addressed aerobic and resistance exercises,25-31 and five addressed other exercise modalities.32-36 The evidence was rated using the Oncology Nursing Society’s research grading system, Putting Evidence into Practice (presented elsewhere in this issue by Lasinski).37 This article will summarize the findings of the systematic review and discuss application to clinical practice. Resistance Exercise Of the seven studies that addressed resistance exercise and lymphedema, six of the studies were randomized controlled trials (RCT)18-23 and one was a case crossover series.24 All focused on breast cancer survivors. The studies provided strong evidence that resistance exercises can be performed with minimal risk of onset or exacerbation of lymphedema in the upper extremity.10 Resistance exercises were initiated at various times postoperatively, ranging from 4 weeks to at least 1 year postoperatively, and no significant increase in the development of BCRL was observed in any of the studies, supporting the implementation of a progressive resistance exercise program at any time after surgery for breast cancer.10 The weight of the evidence was rated ‘‘Likely to be Effective’’ according to the Putting Evidence into Practice grading system. The physical activity and lymphedema (PAL) trial is the largest RCT to date, with the longest follow-up that examines the safety of progressive strength training in breast cancer survivors both with and without BCRL.38 Approximately 295 breast cancer survivors were enrolled and followed for 1 year. Of these, 141 participants had BCRL at study entry18 and 154 were considered at risk for the development of BCRL.19 Those randomized to the intervention group participated in a twice-weekly weight lifting program with no upper limit on weight progression. The main outcome examined was change in arm and hand swelling at 1 year, which was defined as an absolute increase of 5% or more by water displacement of the affected and unaffected limbs.

In those with BCRL at the time of study entry, it was found that weight lifting did not significantly affect the severity of BCRL. It was also noted that the severity of arm and hand symptoms decreased, as did the incidence of lymphedema exacerbations, while muscular strength was increased.18 In the study of breast cancer survivors at risk for development of BCRL at the time of study entry, progressive weight lifting did not increase the incidence of BCRL. The researchers reported that 11% in the weight lifting group and 17% in the control group experienced BCRL onset. An additional finding in this study was that in those who had $5 lymph nodes removed, 7% in the intervention group, and 22% in the control group had BCRL onset.19 The PAL trial provides the strongest evidence to date in support of the efficacy of progressive resistance exercises in reducing the risk of BCRL and not exacerbating pre-existing BCRL. Resistance and Aerobic Exercises In the systematic review, three RCTs25,30,31 and four literature reviews26-29 were identified that addressed combined regimens of resistance and aerobic exercise in lymphedema. The conclusions drawn were that combined resistance and aerobic exercise regimens did not lead to an increase in the incidence of lymphedema.10 Exercise interventions were initiated at various times in the three RCTs, from during chemotherapy,25 and at least 231 and 6 months30 after treatment. The weight of the evidence was rated as ‘‘Benefits Balanced with Harms.’’ Two of the RCTs examined had small sample sizes,30,31 while the third had a larger sample size, but was hindered by a low adherence rate.25 Additional larger and more rigorous studies are needed. Other Exercises Five studies, four RCTs32-35 and one case study,36 were identified that evaluated the effect of physical therapy programs on shoulder dysfunction after breast cancer treatment and the onset of BCRL symptoms. Comparison among studies was limited because of small sample sizes, BCRL evaluated as a secondary outcome and varied interventions. Kwan et al10 rated the weight of the evidence for this group of studies as ‘‘Effectiveness not Established.’’ Compression Garments The role of compression garments during exercise is not clearly established. Of the RCTs included in

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Kwan et al’s10 systematic review, only two18,23 required participants to wear compression garments during exercise. Two other studies19,30 noted that the use of compression garments was optional for at-risk patients or required if they developed lymphedema while participating in the exercise arm of the study. The remaining studies did not address the use of compression. In its Position Statement, The National Lymphedema Network (NLN)6 currently supports the use of compression garments during exercise in patients with lymphedema and supports that the decision for compression use during exercise in patients at risk for lymphedema be made by the individual patient, with guidance from a therapist/clinician. The NLN also recommends that compression garments should be professionally fitted, and be at least Class I compression (18-21 mmHg [European Standards]; 20-30 mmHg [U.S. Standards]) for upper extremity lymphedema, with the possibility of higher classes being needed for lower extremity lymphedema.39 A clear evidence-based recommendation regarding use of compression garments during exercise cannot be made from the systematic review. Kwan et al10 found that there is strong evidence for the safety of breast cancer survivors both with and at risk for lymphedema to participate in slowly progressive resistance exercise throughout their cancer experience without an increase in risk for the onset or exacerbation of existing lymphedema. The authors advised that clinicians and patients should weigh the individual benefits versus harms of participating in a combined resistance and aerobic exercise regimen, as the current evidence only demonstrates some benefit. There is very limited evidence to support the effectiveness of other types of exercises.

Application to Practice Recent studies are providing evidence that breast cancer patients with or at risk for developing lymphedema can participate in a slowly progressive resistance exercise program without an increased risk of developing or exacerbating lymphedema. Patients with lymphedema should be educated on the benefits of exercise on their general health and in cancer prevention. Although studies primarily address breast cancer survivors, the general principles may be transferable to other cancer survivors with lymphedema. However, additional research to establish the generalizability of these findings needs to be done. Before initiating an exercise program, other health conditions (heart disease, hypertension, diabetes, etc.) should also be taken into consideration and risks/benefits discussed. Exercise regimens should be tailored to the individual patient’s needs and ideally be developed in collaboration with a certified lymphedema therapist or trainer who has experience working with patients with or at risk for lymphedema. Self-monitoring for physical signs of lymphedema onset or flare up during exercise, including changes in arm swelling, changes in skin texture, changes in range of motion or skin tone, as well as sensation changes, including limb heaviness, and change in fit of garments and numbness40 is imperative to aid in the early identification and prompt evaluation by a lymphedema specialist. Ongoing follow-up with an experienced clinician for symptom assessment and limb volume measurements to monitor the lymphedematous limb’s response to exercise should be maintained. Until further studies specifically examine the use of compression devices, compliance with the NLN’s position on garment use during exercise should be strongly considered.

Future Studies Evidence supporting the safety of exercise in patients with and at risk for developing lymphedema is amassing, especially in breast cancer survivors, but the need for further research remains. Additional RCTs examining exercise and lymphedema in other patient populations with or at risk for developing lymphedema are needed, particularly studies that include lymphedema of other areas (lower extremity, head, trunk, and genital). Furthermore, there is not enough evidence to provide a clear recommendation for or against the use of compression garments during exercise for patients with and at risk for lymphedema, and further studies are needed.

SURGICAL TREATMENTS The surgical treatment of lymphedema is generally reserved as an option for patients with pronounced lymphedema who have failed standard treatment trials. While surgery for lymphedema is not curative, in carefully selected patients it can serve to reduce limb volume when adequate trials of conservative treatment methods have not been adequate. Indications for surgical intervention include recurrent lymphangitis and cellulitis, refractory pain, impaired movement and function of the affected extremity due to its size and weight, and to improve cosmesis.41 A variety of surgical techniques have been investigated for the

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treatment of chronic lymphedema. Three categories of surgical treatment and their effectiveness as found in the literature will be discussed: (1) excisional procedures, (2) lymphatic reconstruction, and (3) tissue transfer procedures. In an effort to update the International Lymphoedema Framework Best Practices document10 that summarized the literature up to 2004, the American Lymphedema Framework Project again commissioned a systematic review of the literature published between 2004 and 2010 on the surgical treatment of lymphedema.42 As with the exercise systematic review, publications were retrieved from 11 major medical indices (2004 to 2010) using search terms to identify literature related to lymphedema. Inclusion and exclusion criteria were applied and peerreviewed articles related to the surgical treatment of lymphedema were selected. Some 20 articles were selected for final review and were categorized according to the type of procedure: excisional procedures (n ¼ 8),43-50 lymphatic reconstruction (n ¼ 8),51-58 and tissue transfer (n ¼ 4).59-62 The quality of each study was scored implementing the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) scale, which evaluates quality based on a 14-item index to evaluate internal and external validity and allow for consistent interrater reliability between ratings (total potential score of 14).63 This article will summarize the findings of the systematic review and discuss application to practice. Excisional Procedures Excisional procedures for treatment of lymphedema that has failed standard treatment are designed to remove fibrofatty tissue that has formed secondary to sustained lymphatic fluid collection and reduce the bulk of the affected area. Procedures include debulking, liposuction, and amputation. Debulking has been performed for lymphedema as early as 191242 and involves removal of excess adipose tissue, fibrosclerotic connective tissue, and excess skin to decrease the volume of the affected region. A more recently implemented technique, liposuction removes subcutaneous fat to decrease the size of the affected limb. Potential complications after excisional procedures include infection, loss of limb function, skin/flap necrosis, hematoma, infection, chronic wounds, delayed wound healing, and recurrence of lymphedema.64 Cormier et al42 reviewed eight studies, seven prospective43,44,46-50 and one retrospective,45 that addressed excisional procedures for the treatment

of lymphedema. A total of 155 patients with lymphedema of various sites: upper extremity (n ¼ 116), lower extremity (n ¼ 22), and genital (n ¼ 17), were identified. Three studies addressed excisional procedures in patients with upper extremity (n ¼ 11), lower extremity (n ¼ 22) and genital (n ¼ 17) lymphedema.43-45 The remaining five studies addressed liposuction as the primary surgical technique in patients with upper extremity lymphedema (n ¼ 105).46-50 Of the studies reviewed, five reported volume reductions ranging from 18% to 118%, with a weighted average of 91.1% volume reduction.42 Three of the five studies that examined liposuction in the upper extremity reported volume reduction of >100% at 6 to 12 months’ follow-up. 46,47,49 The mean  standard deviation (SD) of the quality scores for the eight studies was 7.7  3.2.42 Lymphatic Reconstruction Lymphatic reconstruction involves microsurgical and supramicrosurgical techniques to reconstruct or bypass the regions of the lymphatic obstruction to improve drainage. Microsurgical techniques include the creation of anastamoses from the lymph vessels to veins, lymph nodes to veins, or distal to proximal lymphatics.65 At the supramicrosurgical level, anastamoses are made between distal subdermal lymphatics and subdermal venules <0.8 mm in diameter, a procedure known as lymphaticovenular anastamosis (LVA). A complication of lymphatic-to-venular anastamosis is that venous pressure can be higher than the lymph vessel pressure, and a higher rate of thrombosis at the anastamosis site can occur.66 This pressure imbalance between the lymphatic and venular anastamosis is eliminated and thus the potential for backflow and thrombosis is decreased when LVA is performed because of the subdermal location of the selected vessels. LVA offers the benefit of smaller incisions (<3 cm) and the use of local versus general anesthesia as well as a shorter hospitalization (<24 h).42 Cormier et al42 reviewed eight studies that examined the use of LVA in the treatment of upper and lower extremity edema.51-58 The authors noted that of the six studies that reported volume reduction,51,52,54,55,57,58 the weighted average volume reduction was 54.9%.42 The largest study (n ¼ 1,800), by Campisi et al,57 was a retrospective study that examined LVA in the treatment of a large, heterogeneous group of patients with both upper and lower extremity lymphedema.

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A reported 67% reduction in limb volume was noted in 83% of patients. This study provided the longest follow-up time of 10 years compared with six studies that reported follow-up times of 8.9 to 18 months.51-55,58 Mean  SD quality score for the eight studies was 6.1  1.1.42 Tissue Transfer Procedures Tissue transfer techniques aim to remove excess interstitial fluid associated with lymphedema by transferring lymph tissue into a congested area with anastamosis of the lymphatic vessels to re-establish a new pathway of lymph flow. Techniques include lymph node transplantation, pedicled omentum, and bone marrow stromal cell transplantation. Lymphatic grafting entails harvesting normal lymph nodes from an unaffected nodal region and transplanting them into a lymphedematous area.42 Pedicled omentum, skin and muscle flaps have also been posed as options to create lymphatic bridges to increase lymphatic flow in areas of obstruction.67-70 Tissue transfers are not without risk, including flap failure and potential donor site complications, and the risk of damage of the lymphatics at the donor site leading to lymphedema at the site of harvest.42 Four studies that addressed tissue transfer procedures were examined in Cormier et al’s42 systematic review. These included lymph node transfer/transplantation and autologous bone marrow stromal cell transplantation in upper extremity lymphedema (three studies) and lower extremity lymphedema (one study). A total of 61 patients were included in the studies. Of the three studies that reported percent volume reduction, the weighted average was 47.6%. One study by Hou et al60 had one of the highest quality scores (11 on a scale of 1 to 14) among all of the studies in the systematic review. In their RCT, Hou et al60 examined volume reduction in patients with upper extremity lymphedema treated with bone marrow stromal cell transplantation (n ¼ 15) versus CDT (n ¼ 35). At 12-month follow-up, patients treated with bone marrow stromal cell transplantation had an 81% volume reduction.60 In their 2008 retrospective case control series, Belcaro et al61 reported an increase in lower extremity limb volume of 13% after lymphatic tissue transplantation when compared with a control group. The studies reviewed were limited by small cohorts of nine to 24 patients, but two studies did have control groups allowing for comparison of outcomes.60,61 Mean  SD quality score of the four studies was 6.8  3.0.42

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Most studies showed a marked reduction of limb volume. Excisional procedures resulted in the greatest volume reduction (91.1%), followed by lymphatic reconstruction (54.9%) and tissue transfer procedures (47.6%). Although surgical treatments for lymphedema are promising, the need for conventional compression therapy postoperatively remained throughout all studies, other than one retrospective study of patients who underwent LVA.51 Cormier et al42 noted that given the lack of RCTs with larger cohorts, objective standardized measurements, long-term follow-up and assessment of risk, the findings of the studies were difficult to generalize to all patients with lymphedema. Future Studies Future studies with larger cohorts of patients and longer follow-up are needed. Prospective studies comparing nonsurgical (CDT) and surgical treatments for lymphedema and long-term outcomes are warranted. Application to Practice Patients considering surgical treatment for lymphedema should first be educated that surgery should not be considered a first-line treatment option, but rather an option to be considered when CDT has failed. Surgical treatment is associated with significant risks. Counseling on the risks and benefits of specific procedures should be considered and weighed against the individual needs of the patient. The surgical treatment of lymphedema is not curative and lifelong compression garments are generally required postoperatively for maintenance. Compliance with follow-up assessments and refitting of compression garments to assure that proper compression is maintained will be required. Microvascular procedures demand a high level of skill and should be performed by a surgeon with expertise in microvascular surgery. It is essential that patients with lymphedema be treated by surgeons who are experienced in lymphedema care and who offer ongoing care after surgery with support from certified lymphedema providers.

INTERMITTENT PNEUMATIC COMPRESSION THERAPY IPC therapy is widely used in the treatment of lymphedema as an adjunct to CDT. It has

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also been used as an alternative to manual lymph drainage (MLD) in patients who have difficulty or are unable to perform the techniques required in MLD self-care. The inflation and deflation of IPC applies pressure that mimics the action of the muscle pump, which is an important mechanism in lymph transport. IPC also reduces lymphedema by decreasing capillary filtration and therefore decreasing lymph formation.71 Devices may be either single or multiple chambered (Table 1).72 In recent years, the selection of pumps has trended toward the use of multiple chamber pumps as single chamber pumps have been found to move fluid bi-directionally leading to fluid build-up in an area that is already swollen. Multi-chambered pumps function by inflating sequentially from distal to proximal anatomic regions producing a wave of pressure that moves up the extremity. There are two-phase pumps that simulate MLD with a preparation phase, applying pressure in a proximal-to-distal gradient, followed by a drainage phase, applying pressure in a distal to proximal gradient. Initiation of IPC therapy requires evaluation by a physician or health care provider experienced in lymphedema care. A prescription with specific pressure settings and duration of therapy individualized to the patient’s specific needs is required. Contraindications to the use of IPC include local or proximal malignancy, infection in the limb, deep vein thrombosis, and anticoagulated patients.73 A variety of issues related to IPC therapy, including physiologic changes with IPC use, optimal pressure ranges, frequency and duration of treatments, volume changes post therapy and cost considerations remain unclear and will be explored in this article. A systematic review of literature evaluating the use of IPC therapy in the treatment of lymphedema was performed by Feldman et al.72 As in the earlier systematic reviews, publications were retrieved from 11 major medical indices for articles published from 2004 to 2011 using search terms for lymphedema management. After applying key words for IPC, 13 studies were selected for final review. Of the articles reviewed, two were systematic reviews,74,75 one was an overview of the literature,76 two were RCTs,77,78 six were controlled trials,79-84 and two were case studies.85,86 The evidence was rated using the Bandolier Strength of Evidence Guidelines from The Oxford Medical

Journal87 (Table 2). This article will summarize the findings of the systematic review and discuss application to practice. Previous Reported Evidence Two systematic reviews that provided level I evidence to support the use of IPC for lymphedema treatment addressed the role of compression pumps in women with breast cancer-related upper extremity lymphedema. In her 2010 systematic review, Rinehart-Ayres et al75 addressed whether compression pumps decrease lymphedema when compared with other treatments and examined what the recommended treatment parameters are for use of compression pumps. Although a small number of studies (eight) met inclusion criteria, findings were that there was no evidence to suggest that the use of an IPC pump is better than education about arm care and hygiene in the treatment of upper extremity lymphedema. They also found no consensus on pressures to be used or evidence to support whether an intermittent compression pump was any better or worse than a sequential compression pump. In their 2007 systematic review, Moseley et al74 investigated common conservative therapies for arm lymphedema, including five studies that examined the effect of IPC. Two studies demonstrated volume reductions with IPC therapy alone, while three studies demonstrated better results in volume reduction when IPC was used in combination with other therapies (MLD, compression garments, and self-massage). The overall finding was that IPC was one of the therapies considered most likely to provide larger percentage volume reductions. Physiologic Changes With IPC Use An understanding of the effect of external pressure applied by compression devices on the movement of fluid in the lymphedematous tissue is necessary when considering IPC therapy. Two studies ranked level II and III evidence that evaluated physiotherapy of lymphedema. In a nonrandomized, controlled, pre-test/post-test study, Olszewski et al80 measured tissue fluid pressure and flow under the skin in the subcutaneous tissue both at rest and during manual and pneumatic compression using various pressures in 25 patients with unilateral, lower extremity lymphedema and five normal controls. The compression device used was constructed with eight segments that were 9 cm in length that sequentially inflated with pressures from 50 to 125 mmHg. Tissue fluid

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TABLE 1. Characteristics of Intermittent Pneumatic Compression (IPC) Devices IPC Device Single chamber

Multi-chamber segmented without manual control

Unique Characteristics       

Multi-chamber segmented, calibrated

   

Advanced compression systems

    

Single cuff that expands and contracts applying pressure against the limb No manual control over pressure distribution No pressure gradient exists Not optimal for lymphedema management at this time Commonly have 3 to 4 chambers that inflate sequentially from distal to proximal until all are inflated and then all deflate together May have limited pressure programming options and are not typically independently adjustable May be constructed so that each chamber has the same pressure and pressure gradient is achieved by virtue of the limb contours These pumps can treat one or two legs or arms Gradient of pressure exists; higher pressure in the distal chambers and lower pressures in the proximal chambers Exhibit at least three zones of pressure; some pumps allow adjustment of each chamber Typically manually programmable, enabling adjustment of the level and location of compression May have from four to 36 chambers Enable digital programming May simulate, through adjacent pneumatic truncal applications, the action of clearing the proximal trunk and extremity The truncal and proximal chambers enable clearing of the lymphatic pathways Only 1 to 2.5 chambers at a time are active as compression progresses in a distal-to-proximal direction, simulating the action of manual lymphatic drainage

Reprinted with permission from Lymphology.72

pressures generated by pneumatic compression varied depending on the sleeve inflation pressures, but were on average 20% less than pressures in the inflated chambers. Factors such as skin rigidity (fibrosis) and dissipation of the applied force to the proximal non-compressed regions were noted as likely contributors to the pressure gradient variance. Pneumatic compression was found to have an advantage over manual compression as it produced unidirectional flow of fluid toward the groin without backflow. In a pilot study of six women with unilateral BCRL and three normal controls, Adams et al81 examined lymphatic response to IPC therapy. Subjects received near-infrared fluorescent contrast injections before IPC therapy. The rate of lymphatic propulsion, apparent lymph velocity, and lymphatic vessel recruitment were measured before, during, and after 2.5 hours of IPC therapy. Lymphatic function improved in all control subjects and in asymptomatic arms of BCRL subjects. The affected arms of four of the six BCRL subjects showed improved lymphatic function. Adams et al81 concluded that

results suggested that IPC may be an effective method to manage BCRL. Pressure Level The pressure within normal skin lymphatic vessels range from 4 mmHg to 8 mmHg in comparison to pressure measurements in edematous lymphatics and tissues which range from 15 mmHg to 18 mmHg.84 Lymph vessel damage can occur if pressures that are too high are applied in both MLD and IPC. Pressures applied to limb models by IPC have been shown to exceed the pressure anticipated from the pump setting.88 There is no consensus on standard pressure settings for use in IPC therapy. There is level I to III evidence that supported compression pressures in the range between 30 and 60 mmHg. A randomized study by Szolnoky et al78 compared subjects (n ¼ 13) who received MLD alone and subjects (n ¼ 14) who received MLD and IPC at 50 mmHg as part of a CDT protocol. Significant decrease in symptoms was found in both groups and it was concluded that IPC with MLD in combination enhances the

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TABLE 2. Bandolier Ranking System for Level of Evidence Weight of Evidence Category I

II

III

IV

Description Strong evidence from at least one published systematic review of multiple well-designed randomized controlled trials Strong evidence from at least one published properly designed randomized controlled trials of appropriate size and in an appropriate clinical setting Evidence from published well-designed trials without randomization, single group, pre-post, cohort, time series or matched case-controlled studies Evidence from well-designed non-experimental studies from more than one center or research group Opinions of respected authorities, based on clinical evidence, descriptive studies or reports of experts consensus committees

protocol, with 7% reporting use more than once daily. Of the cancer-related lymphedema group, 32% followed the protocol, and 21% used the IPC more than once daily. Some 47% of the cancerrelated lymphedema group reported use below the protocol or not at all. In the non-cancer group, 37% used the IPC less than prescribed and 7% did not use it at all. No statistically significant association was found between reported use patterns and age group, gender, lymphedema severity, or time since diagnosis. Patient preference plays a significant role in determining the frequency of IPC use. Attention should be paid to variables such as patient level of adherence and barriers to IPC treatment and individualize treatment plans tailored accordingly.72

effect of CDT in arm volume reduction. Partsch et al76 conducted a literature review on the topic of compression therapy in venous and lymphatic disease. Levels of compression shown to be effective in reviewed studies using varied compression devices ranged from 5 to 10 mmHg and >120 mmHg. A sustained pressure of 60 to 70 mmHg was suggested as a maximum upper limit to prevent damage. Strong levels of evidence supporting the use of IPC for thrombosis prevention after surgery, in the treatment of post-thrombotic syndrome, and in lymphedema were reported.

Subjective Reported Changes Three studies with level III and V evidence addressed subjective reported changes after implementation of IPC therapy. Overall findings were reports of improvement in symptoms of tightness and heaviness in the affected area, selfperceived limb volume reduction, and a decrease in the use of clinician-administered MLD. One study of interest was Hammond’s85 case study of a woman with BCRL who, despite diligent performance of prescribed home therapy, had difficulty controlling her lymphedema, with resultant cellulitis requiring hospitalization, intravenous antibiotics, and repeated visits to skilled therapy. Following the initiation of home IPC, she experienced no additional episodes of cellulitis, required less frequent medical follow-up and had improvement in quality of life over the 3-year follow-up period.

Treatment Times and Frequency Optimal frequency and duration of IPC therapy is unclear.72 One study offered level III evidence for IPC frequency and duration. Ridner et al82 compared treatment protocol adherence, satisfaction, and perceived changes in emotional and functional status between patients with cancerrelated (n ¼ 93) and non-cancer–related lymphedema (n ¼ 62) using the Flexitouch (Tactile Systems Technology, Inc., Minneapolis, MN) system for lymphedema self-care in the home. Patients were instructed to use the IPC pump for an hour twice a day for the first month, then for 1 hour once a day as maintenance. Approximately 56% of the non-cancer–related lymphedema patients reported following the once per day

Volumetric Changes Pilch et al’s77 RCT comparing the efficacy of single-chambered sleeve and three-chambered sleeve IPC devices at two cycle settings (90 second compression: 90 second decompression, and 45 second compression: 15 second decompression) on edema volume reduction was included in the systematic review. Approximately 57 women with BCRL were randomly assigned to two study groups and underwent treatment for 5 weeks, five times a week for 1 hour. Significant edema volume reduction was observed in all subgroups. No significant difference in volume reduction was observed between devices or cycle settings. The author concluded that IPC is an effective method of volume reduction in women with BCRL, regardless

V

Adapted from ‘‘Type & strength of evidence.’’87

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of the number of sleeve chambers or cycle time. The level of evidence was rated II for this study. Adverse Events There were no significant adverse events reported with IPC treatments. There were reports of discomfort in two patients with chronic venous edema treated with IPC at 60 mmHg, but not at 40 or 50 mmHg.79 Another patient in Vanscheidt et al’s79 study reported skin irritation during IPC treatment and three patients reported discomfort at least once during therapy. Current literature indicates that IPC devices have little detrimental effect on patient safety.72 Cost Considerations IPC devices are estimated to range in price from several hundred to several thousand dollars. In a case study, Hammond85compared costs of lymphedema-related treatment in a patient with difficult-to-control lymphedema with costs for lymphedema-related treatment after implementation of IPC. Costs for lymphedema-related treatments over a 4-month period before IPC therapy were more than four times greater than the cost of the IPC system. The patient was followed for 3 years while undergoing continued IPC home treatments and incurred no further lymphedemarelated costs. While this was a single case study, it underscores the significance of future studies to compare cost-effectiveness of IPC in patients using self-MLD with those using IPC. Other direct and indirect costs, including device cost, the number and severity of infections, cost of treating infections, cost of clinician-based MLD or CDT, and other resources utilized should be studied. IPC can be effective as an adjunct treatment modality in lymphedema management.72 Review of the literature indicated that IPC devices are well-tolerated in low-to-moderate pressure ranges and are a safe option for home use in appropriate patients.72 There was no clear Best Practice guideline that emerged from the literature, but an individualized, multi-modality approach was noted to be optimal to treat lymphedema, and evidence shows that IPC devices may play a role in this approach. Future Studies Further studies assessing the cost benefit of IPC are needed, as are further studies to address specific pressure settings and the length of treatment sessions.

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Application to Practice IPC is a potentially valuable adjunctive therapy in the management of lymphedema. Before initiating IPC therapy, patients should be aware that it is not a stand-alone treatment and compression garments are required between treatments and after completion of therapy to maintain control of lymphedema. IPC should only be prescribed by practitioners who have received training at a specialist level and who will maintain continued follow-up to monitor response to therapy and make necessary adjustments in pump settings. When applying IPC to an extremity, it is important to monitor for increased edema or fibrotic tissue proximally, at the level just above the sleeve. The area of fibrotic tissue is termed a fibrosclerotic ring79 and requires clinical evaluation and consideration of changing to a device that treats both the trunk and the extremity. As previously discussed, there are no clear guidelines for use when selecting pressure settings. The NLN currently recommends pump pressures from 30 to 60 mmHg,6 which is consistent with those observed in the systematic review.72

CONCLUSION While CDT remains the gold standard in lymphedema therapy, evidence supporting consideration of adjunctive therapies such as exercise, IPC, and surgery. Consideration of non-CDT adjunctive interventions for lymphedema should be made on a case-by-case basis. There is strong evidence for the safety of breast cancer survivors both with and at risk for lymphedema to participate in supervised, slowly progressive resistance exercise throughout their cancer experience without an increase in risk for the onset or exacerbation of existing lymphedema. Additional RCTs examining exercise and lymphedema in other patient populations with or at risk for developing lymphedema are needed, particularly studies that include lymphedema of other areas (lower extremity, head, trunk, and genital), as are studies examining the role of compression garments during exercise. Surgical treatments for lymphedema are promising in patients with pronounced lymphedema who have not been responsive to standard treatment, but require careful patient selection and life-long use of compression garments postoperatively. IPC devices are well-tolerated in

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low-to-moderate pressure ranges and are a safe adjunctive treatment option for in-home use in

appropriate patients, following and in conjunction with CDT.

REFERENCES 1. Morgan PA, Franks PJ, Moffatt CJ. Health-related quality of life with lymphoedema: a review of the literature. Int Wound J 2005;2:47-62. 2. Armer JM. The problem of post-breast cancer lymphedema: Impact and measurement issues. Cancer Invest 2005;23:76-83. 3. Warren AG. Lymphedema: A comprehensive review. Ann Plast Surg 2007;59:464-472. 4. Cormier JN, Askew RL, Mungovan KS, et al. Lymphedema beyond breast cancer: a systemic review of cancer-related secondary lymphedema. Cancer 2010;116:5138-5149. 5. International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2009 consensus document of the International Society of Lymphology. Lymphology 2009;42:51-60. 6. National Lymphedema Network. Position statement of the National Lymphedema Network. Topic: the diagnosis and treatment of lymphedema. Available at: http://www.lymphnet.org/ pdfDocs/nlntreatment.pdf. (accessed March 21, 2012). 7. Lawenda BD, Mondry TE, Johnstone PA. Lymphedema: a primer on the identification and management of a chronic condition in oncologic treatment. CA Cancer J Clin 2009;59:8-24. 8. Doyle C, Kushi LH, Byers T, et al. Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. CA Cancer J Clin 2006;56: 323-353. 9. World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity and the prevention of cancer: a global perspective. Washington, DC: World Cancer Research Fund/American Institute for Cancer Research; 2007. 10. Kwan ML, Cohn JC, Armer JM, et al. Exercise in patients with lymphedema: a systematic review of the contemporary literature. J Cancer Surviv 2011;5:320-336. 11. American Cancer Society. Breast cancer facts & figures 2009-2010. Atlanta, GA: American Cancer Society; 2010. 12. Erickson VS, Pearson ML, Ganz PA, et al. Arm edema in breast cancer patients. J Natl Cancer Inst 2001;93:96-111. 13. Rockson SG. Precipitating factors in lymphedema: myths and realities. Cancer 1998;83(suppl 12):2814-2816. 14. McKenzie DC, Kalda AL. Effect of upper extremity exercise on secondary lymphedema in breast cancer patients: a pilot study. J Clin Oncol 2003;21:463-466. 15. McKenzie DC. Abreast in a boat – a race against breast cancer. CMAJ 1998;159:376-378. 16. Unruh AM, Elvin N. In the eye of the dragon: women’s experience of breast cancer and the occupation of dragon boat racing. Can J Occup Ther 2004;71:138-149. 17. Lymphedema Framework. Best practice for the management of lymphedema: international consensus. London, UK: MEP Ltd; 2006. 18. Schmitz KH, Ahmed RL, Troxel A, et al. Weight lifting in women with breast-cancer-related lymphedema. N Engl J Med 2009;361:664-673. 19. Schmitz KH, Ahmed RL, Troxel AB, et al. Weight lifting for women at risk for breast cancer-related lymphedema: a randomized trial. JAMA 2010;304:2699-2705.

20. Ahmed RL, Thomas W, Yee D, et al. Randomized controlled trial of weight training and lymphedema in breast cancer survivors. J Clin Oncol 2006;24:2765-2772. 21. Sagen A, Karesen R, et al. Physical activity for the affected limb and arm lymphedema after breast cancer surgery. A prospective, randomized controlled trial with two years follow-up. Acta Oncol 2009;48:1102-1110. 22. Kilbreath SL, Refshauge KM, Beith JM, et al. Progressive resistance training and stretching following surgery for breast cancer: study protocol for a randomised controlled trial. BMC Cancer 2006;6:273. 23. Irdesel J, Celikatas SK. Effectiveness of exercise and compression garments in the treatment of breast cancer related lymphedema. Turk J Phys Med Rehab 2007;53:16-21. 24. Sander AP. A safe and effective upper extremity resistive exercise program for woman post breast cancer treatment. Rehabil Oncol 2008;26:3-10. 25. Courneya KS, Segal RJ, Mackey JR, et al. Effects of aerobic and resistance exercise in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. J Clin Oncol 2007;25:4396-4404. 26. Bicego D, Brown K, Ruddick M, et al. Exercise for women with or at risk for breast cancer-related lymphedema. Phys Ther 2006;86:1398-1405. 27. Cheema B, Gaul CA, Lane K, et al. Progressive resistance training in breast cancer: a systematic review of clinical trials. Breast Cancer Res Treat 2008;109:9-26. 28. De Backer IC, Schep G, Backx FJ, et al. Resistance training in cancer survivors: a systematic review. Int J Sports Med 2009;30:703-712. 29. Poage E, Singer M, Armer J, et al. Demystifying lymphedema: development of the lymphedema putting evidence into practice card. Clin J Oncol Nurs 2008;12: 951-964. 30. Hayes SC, Reul-Hirche H, Turner J. Exercise and secondary lymphedema: safety, potential benefits, and research issues. Med Sci Sports Exerc 2009;41:483-489. 31. Portela ALM, Santaella CLC, Gomez CC, et al. Feasibility of an exercise program for Puerto Rican women who are breast cancer survivors. Rehabil Oncol 2008;26:20-31. 32. Torres Lacomba M, Yuste Sanchez MJ, Zapico Goni A, et al. Effectiveness of early physiotherapy to prevent lymphoedema after surgery for breast cancer: randomised, single blinded, clinical trial. BMJ 2010;340:b5396. 33. Kilgour RD, Jones DH, Keyserlingk JR. Effectiveness of a self-administered, home-based exercise rehabilitation program for women following a modified radical mastectomy and axillary node dissection: a preliminary study. Breast Cancer Res Treat 2008;109:285-295. 34. Beurskens CH, van Uden CJ, Strobbe LJ, et al. The efficacy of physiotherapy upon shoulder function following axillary dissection in breast cancer, a randomized controlled study. BMC Cancer 2007;7:166. 35. de Rezende LF, Franco RL, de Rezende MF, et al. Two exercise schemes in postoperative breast cancer: comparison

ADJUNCT INTERVENTIONS FOR LYMPHEDEMA

of effects on shoulder movement and lymphatic disturbance. Tumori 2006;92:55-61. 36. Moseley AL, Piller NB, Carati CJ. The effect of gentle arm exercise and deep breathing on secondary arm lymphedema. Lymphology 2005;38:136-145. 37. Mitchell S, Friese C. Oncology Nursing Society. Putting evidence into practice. Weight of evidence classification schema. Decision rules for summative evaluation of a body of evidence. Available at: http://www.ons.org/Research/media/ons/docs/research/ outcomes/weight-of-evidence-table.pdf (accessed December 14, 2012). 38. Schmitz KH, Troxel AB, Cheville A, et al. Physical activity and lymphedema (the PAL trial): assessing the safety of progressive strength training in breast cancer survivors. Contemp Clin Trials 2009;30:233-245. 39. National Lymphedema Network. Position statement of the National Lymphedema Network. Topic: exercise. Available at: http://www.lymphnet.org/pdfDocs/nlnexercise.pdf (accessed December 14, 2012). 40. Armer JM, Radina ME, Porock D, et al. Predicting breast cancer-related lymphedema using self-reported symptoms. Nurs Res 2003;52:370-379. 41. Gloviczki P. Principles of surgical treatment of chronic lymphoedema. Int Angiol 1999;218:42-46. 42. Cormier JN, Rourke L, Crosby M, et al. The surgical treatment of lymphedema: a systematic review of the contemporary literature (2004-2010). Ann Surg Oncol 2012;19: 642-651. 43. Salgado CJ, Sassu P, Gharb BB, et al. Radical reduction of upper extremity lymphedema with preservation of perforators. Ann Plast Surg 2009;63:302-306. 44. Modolin M, Mitre AI, da Silva JC, et al. Surgical treatment of lymphedema of the penis and scrotum. Clinics (Sao Paulo) 2006;61:289-294. 45. Lee BB, Kim YW, Kim DI, et al. Supplemental surgical treatment to end stage (stage IV-V) of chronic lymphedema. Int Angiol 2008;27:389-395. 46. Brorson H, Ohlin K, Olsson G, et al. Quality of life following liposuction and conservative treatment of arm lymphedema. Lymphology 2006;39:8-25. 47. Brorson H, Ohlin K, Olsson G, et al. Adipose tissue dominates chronic arm lymphedema following breast cancer: an analysis using volume rendered CT images. Lymphat Res Biol 2006;4:199-210. 48. Qi F, Gu J, Shi Y, et al. Treatment of upper limb lymphedema with combination of liposuction, myocutaneous flap transfer, and lymph-fascia grafting: a preliminary study. Microsurgery 2009;29:29-34. 49. Damstra RJ, Voesten HG, Klinkert P, et al. Circumferential suction-assisted lipectomy for lymphoedema after surgery for breast cancer. Br J Surg 2009;96:859-864. 50. Liu Q, Zhou X, Wei Q. Treatment of upper limb lymphedema after radical mastectomy with liposuction technique and pressure therapy. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2005;19:344-345. 51. Damstra RJ, Voesten HG, van Schelven WD, et al. Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature. Breast Cancer Res Treat 2009;113:199-206. 52. Demirtas Y, Ozturk N, Yapici O, et al. Supermicrosurgical lymphaticovenular anastomosis and lymphaticovenous implan-

39

tation for treatment of unilateral lower extremity lymphedema. Microsurgery 2009;29:609-618. 53. Matsubara S, Sakuda H, Nakaema M, et al. Long-term results of microscopic lymphatic vessel-isolated vein anastomosis for secondary lymphedema of the lower extremities. Surg Today 2006;36:859-864. 54. Koshima I, Nanba Y, Tsutsui T, et al. Minimal invasive lymphaticovenular anastomosis under local anesthesia for leg lymphedema: is it effective for stage III and IV? Ann Plast Surg 2004;53:261-266. 55. Narushima M, Mihara M, Yamamoto Y, et al. The intravascular stenting method for treatment of extremity lymphedema with multiconfiguration lymphaticovenous anastomoses. Plast Reconstr Surg 2010;125:935-943. 56. Maegawa J, Mikami T, Yamamoto Y, et al. Types of lymphoscintigraphy and indications for lymphaticovenous anastomosis. Microsurgery 2010;30:437-442. 57. Campisi C, Bellini C, Accogli S, et al. Microsurgery for lymphedema: clinical research and long-term results. Microsurgery 2010;30:256-260. 58. Chang DW. Lymphaticovenular bypass for lymphedema management in breast cancer patients: a prospective study. Plast Reconstr Surg 2010;126:752-758. 59. Lin CH, Ali R, Chen SC, et al. Vascularized groin lymph node transfer using the wrist as a recipient site for management of postmastectomy upper extremity lymphedema. Plast Reconstr Surg 2009;123:1265-1275. 60. Hou C, Wu X, Jin X. Autologous bone marrow stromal cells transplantation for the treatment of secondary arm lymphedema: a prospective controlled study in patients with breast cancer related lymphedema. Jpn J Clin Oncol 2008; 38:670-674. 61. Belcaro G, Errichi BM, Cesarone MR, et al. Lymphatic tissue transplant in lymphedema–a minimally invasive, outpatient, surgical method: a 10-year follow-up pilot study. Angiology 2008;59:77-83. 62. Becker C, Assouad J, Riquet M, et al. Postmastectomy lymphedema: Long-term results following microsurgical lymph node transplantation. Ann Surg 2006;243:313-315. 63. Whiting P, Rutjes A, Reitsma J, et al. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003;3:25. 64. Gloviczki P. Principles of surgical treatment. In: Browse N, Burnand KG, Mortimer P, eds. Diseases of the lymphatics. London: Arnold; 2003: pp. 179-204. 65. Campisi C, Davini D, Bellini C, et al. Lymphatic microsurgery for the treatment of lymphedema. Microsurgery 2006;26:65-69. 66. Baumeister RG, Siuda S. Treatment of lymphedemas by microsurgical lymphatic grafting: what is proved? Plast Reconstr Surg 1990;85:64-74. discussion 75-66. 67. Classen DA, Irvine L. Free muscle flap transfer as a lymphatic bridge for upper extremity lymphedema. J Reconst Microsurg 2005;21:93-99. 68. Slavin SA, Van den Abbeele AD, Losken A, et al. Return of lymphatic function after flap transfer for acute lymphedema. Ann Surg 1999;229:421-427. 69. Medgyesi S. A successful operation for lymphoedema using a myocutaneous flap as a "wick". Br J Plast Surg 1983;36:64-66. 70. Slavin SA, Upton J, Kaplan WD, et al. An investigation of lymphatic function following free-tissue transfer. Plast Reconstr Surg 1997;99:730-741. discussion 742-733.

40

C.J. CHANG AND J.N. CORMIER

71. Miranda FJ, Perez MC, Castiglioni ML, et al. Effect of sequential intermittent pneumatic compression on both leg lymphedema volume and on lymph transport as semi-quantitatively evaluated by lymphoscintigraphy. Lymphology 2001;34:135-141. 72. Feldman JL, Stout NL, Wanchai A, et al. Intermittent pneumatic compression therapy: a systematic review. Lymphology 2012;45:13-25. 73. Brennan MJ, Miller LT. Overview of treatment options and review of the current role and use of compression garments, intermittent pumps, and exercise in the management of lymphedema. Cancer 1998;83(suppl 12):2821-2827. 74. Moseley AL, Carati CJ, Piller NB. A systematic review of common conservative therapies for arm lymphoedema secondary to breast cancer treatment. Ann Oncol 2007;18: 639-646. 75. Rinehart-Ayres M, Fish K, Lapp K, et al. Use of compression pumps for treatment of upper extremity lymphedema following treatment for breast cancer: a systematic review. Rehabil Oncol 2010;28:10-18. 76. Partsch H, Flour M, Smith PC. Indications for compression therapy in venous and lymphatic disease consensus based on experimental data and scientific evidence. Under the auspices of the IUP. Int Angiol 2008;27:193-219. 77. Pilch U, Wozniewski M, Szuba A. Influence of compression cycle time and number of sleeve chambers on upper extremity lymphedema volume reduction during intermittent pneumatic compression. Lymphology 2009;42:26-35. 78. Szolnoky G, Lakatos B, Keskeny T, et al. Intermittent pneumatic compression acts synergistically with manual lymphatic drainage in complex decongestive physiotherapy for breast cancer treatment-related lymphedema. Lymphology 2009;42:188-194. 79. Vanscheidt W, Ukat A, Partsch H. Dose-response of compression therapy for chronic venous edema-higher

pressures are associated with greater volume reduction: two randomized clinical studies. J Vasc Surg 2009;49: 395-402. 80. Olszewski WL, Jain P, Ambujam G. Tissue fluid pressure and flow in the subcutaneious tiisue in lymphedema-hints for manual and pneumatic compression therapy. Phlebolymphology 2010;17:144-150. 81. Adams KE, Rasmussen JC, Darne C, et al. Direct evidence of lymphatic function improvement after advanced pneumatic compression device treatment of lymphedema. Biomed Opt Exp 2010;1:114-125. 82. Ridner S, Dietrich MS, Hoy S, et al. Home-based lymphedema treatment in patients with cancer-related lymphedema or noncancer-related lymphedema. Oncol Nurs Forum 2008;35: 671-680. 83. Ridner SH, Murphy B, Deng J, et al. Advanced pneumatic therapy in self-care of chronic lymphedema of the trunk. Lymphat Res Biol 2010;8:209-215. 84. Mayrovitz HN. Interface pressures produced by two different types of lymphedema therapy devices. Phys Ther 2007;87:1379-1388. 85. Hammond T. Reductions of complications and associated costs with flexitouch therapy for lymphedema. Open Rehabil J 2009;2:54-57. 86. Hammond T, Mayrovitz HN. Programmable intermittent pneumatic compression of therapy for breast cancer treatmentrelated truncal and arm lymphedema. Home Hlth Care Mgmt Prac 2010;22:397-402. 87. Type & strength of evidence. Bandolier. Available at: http://www.medicine.ox.ac.uk/bandolier/band6/b6-5.html. (accessed March 21, 2012). 88. Segers P, Belgrado JP, Leduc A, et al. Excessive pressure in multichambered cuffs used for sequential compression therapy. Phys Ther 2002;82:1000-1008.