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Complementary, Alternative, and Other Noncomplete Decongestive Therapy Treatment Methods in the Management of Lymphedema: A Systematic Search and Review
Accepted Manuscript Complementary, Alternative, and Other Non-Complete Decongestive Therapy (CDT) Treatment Methods in the Management of Lymphedema: A Systematic Search and Review Julia R. Rodrick, OTR, CLT-LANA/WCC Ellen Poage, MSN, MPH,NP-C,CLT-LANA Ausanee Wanchai, RN, PhD Bob R. Stewart, EdD Janice N. Cormier, MD, MPH, FACS Jane M. Armer, RN, PhD, CLT, FAAN PII:
S1934-1482(13)01082-4
DOI:
10.1016/j.pmrj.2013.09.008
Reference:
PMRJ 1133
To appear in:
PM&R
Received Date: 15 July 2013 Revised Date:
8 September 2013
Accepted Date: 11 September 2013
Please cite this article as: Rodrick JR, Poage E, Wanchai A, Stewart BR, Cormier JN, Armer JM, Complementary, Alternative, and Other Non-Complete Decongestive Therapy (CDT) Treatment Methods in the Management of Lymphedema: A Systematic Search and Review, PM&R (2013), doi: 10.1016/j.pmrj.2013.09.008. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Title: Complementary, Alternative, and Other Non-Complete Decongestive Therapy (CDT) Treatment Methods in the Management of Lymphedema: A Systematic Search and Review
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Julia R. Rodrick, OTR; CLT-LANA/WCC;1 Ellen Poage, MSN, MPH,NP-C,CLT-LANA;2 Ausanee Wanchai, RN, PhD,;3,4 Bob R Stewart. EdD;3 Janice N. Cormier, MD, MPH, FACS;5 Jane M Armer, RN, PhD, CLT, FAAN3
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(1) St. John’s Hospital Rehabilitation South, Springfield, IL. (2) Rehabilitation Associates of Naples, Naples, FL (3) University of Missouri Sinclair School of Nursing, Columbia, MO (4) Boromarajonani College of Nursing, Buddhachinaraj, Thailand (5) University of Texas MD Anderson Cancer Center, Houston, TX
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Authors’ Financial Disclosures: None
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Disclaimers This systematic review of contemporary peer-reviewed lymphedema literature (2004 to 2012) in the areas of complementary and alternative therapies was commissioned by the American Lymphedema Framework Project (ALFP) to evaluate the level of evidence in support of complementary and alternative therapies in the management of lymphedema. The objectives of the ALFP are to provide evidence of the best practice of lymphedema care, assist in establishing guidelines for the management of lymphedema, and to increase awareness of this condition in the U.S. and worldwide.
Source of Support: ALFP staff and reference librarian time were supported by industry donations to the ALFP. Authors donated their time in preparation of this manuscript.
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Corresponding Author (contact info): Jane M. Armer, PhD, RN, CLT, FAAN Professor at Sinclair School of Nursing, University of Missouri Director, Nursing Research, Ellis Fischel Cancer Center Contact address: Ellis Fischel Cancer Center, EFCC 408 DC 116.05 Columbia, MO, USA 65212 Telephone Number: 573-882-0287 E-mail Address: [email protected] (preferred contact)
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Running Head: Review of Non-CDT LE Treatment Methods Word Count: 8,458
Figures & Tables: 1 Figure, 2 Tables ** Named devices are for reference only. No authors participated in development of nor benefitted from the review of these devices. **
ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods Synopsis
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The goal of this paper is to provide expert guidance for health professionals in caring for patients with and at risk for lymphedema. It will summarize the current evidence in the literature and provide recommendations for management using complementary, alternative, and other non-complete decongestive therapies (CDT).
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Abstract
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Objectives: 1) Provide a critical analysis of the contemporary published research pertaining to complementary, alternative, and other non-Complete Decongestive Therapies (CDT) for treatment of lymphedema (LE); and 2) Provide practical applications of that evidence to improve care of patients with or at risk for LE.
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Type: This study meets the defining criteria as a systematic search and review since it includes varied study types. All studies that met the inclusion criteria were evaluated for weight of evidence and value.
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Literature Survey: The systematic search and review includes manuscripts published in the contemporary literature (2004-2012). Publications published from 2004-2011 were retrieved from 11 major medical indices using search terms for LE and management approaches. Literature archives were examined through 2012. Data extraction included study design, objectives pertaining to LE, number and characteristics of participants, interventions, and outcomes. Study strengths and weaknesses were summarized. Study evidence was categorized according to the Oncology Nursing Society Putting Evidence into Practice (PEP) level-of-evidence guidelines after achieving consensus among the authors. No authors participated in development of nor benefitted from the review of these modality methods or devices.
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Methodology: Data extraction from 85 studies was reviewed in four sub-categories: Botanical, Pharmaceutical, Physical Agent Modality (PAM), and Modalities of Contemporary Value (MCV). After review, 47 articles were excluded, leaving 16 articles on botanicals and pharmaceuticals and 22 articles for PAM/MCV. Pharmaceuticals were later excluded. The authors concluded Botanicals had generated sufficient studies to support a second, more specific systematic review; thus, Botanicals are reported elsewhere.
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Synthesis: It was found that limited high-level evidence was available for all categories. Wellconstructed randomized control trials (RCT) related specifically to LE were limited. Objective outcome measures over time were absent from several studies. Rationale for the use and benefits of the specific modality, as related to LE, was often anecdotal. Subject sizes were less than 50 for most studies.
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Conclusions: No interventions were ranked as “recommended for practice” based on the PEP guidelines. Two treatment modalities in three studies were ranked as “likely to be effective” in reducing LE, or in managing secondary LE complications. Consideration should be given that many of the PAM demonstrate long-standing support within the literature with broad parameters for therapeutic application and benefit for secondary conditions associated with LE. However, further investigation as to their individual, contributory value and the factors that contribute to their efficacy, specific to LE, have not been determined. It is also significant to mention that the majority of these studies focused on breast cancer-related lymphedema. Studies exploring treatment interventions for lymphedema-related vascular disorders (e.g., chronic venous insufficiency, congenital dysphasia, trauma) were sparse. Limitations of the literature support
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods the recommendations for future research to further examine the level of evidence in these modalities for LE management.
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Key Words: lymphedema, systematic review, complementary therapies, alternative therapies, non-CDT treatment modalities, physical agent modalities, hyperbaric oxygen therapy, diathermy, elastic taping, low level laser, aqua-therapy, ultrasound, High Volt Electrical Stimulation, Electrical stimulated lymphatic drainage (ESD), and acupuncture
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 51 Introduction
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Microcirculation describes the process by which the vasculature delivers nutrients and removes waste products from the tissues, as well as regulates blood flow and pressure, tissue perfusion, body temperature and tissue fluid (edema). Until recently, the focus of the microcirculation has been limited to the arterial and vascular components including the arterioles, capillaries, and venules. Through advancements in technology and research, it is now evident that the lymphatic system plays a major role in the dynamics of microcirculation, specifically in returning interstitial proteins back to the circulation and in the regulation of tissue fluid (1). Lymphedema (LE) occurs when there is a mechanical or metabolic failure affecting the lymphatic’s ability to complete this function. Mechanical failure is due to anatomical deficits of lymph nodes, vessel or tissue, either inherent (primary LE) or due to tissue trauma (secondary LE). Metabolic disorders can also progress to symptomatic LE (1, 2, 3, 4). LE can cause pathological changes to musculoskeletal structures, causing added dysfunction (1, 5). Qualified rehabilitation therapists can provide adjunctive therapy techniques to reduce swelling and pain, increase tissue and joint mobility, as well as improve muscle strength and stability. According to a study completed in 2008, the population prevalence of LE is estimated in the range of 1.3-1.4 per 1000, and the authors note that data collection regarding incidence and prevalence of LE is challenging and “relevant medical literature is scanty” (6). A research review for a patient-focused website offered that, beyond the estimated 10-40% incidence among breast cancer survivorship, the potential LE incidence related to other cancer surgeries (e.g., melanoma), conditions (e.g., cellulitis), and surgeries (e.g., hip replacements) may exceed 6.8 million patients in the U.S (7). LE has been shown to have significant impact on functional abilities, psychosocial issues and quality of life (8). Therefore, the need for early diagnosis and effective treatment is evident.
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Purpose/Exploring Treatment Options: Clinical evidence suggests that many conventional types of therapies for LE fall short in providing optimal functional outcomes and management. The most widely accepted treatment involves a multi-faceted form of intensive therapeutic intervention known as Complete Decongestive Therapy (CDT) (9). Manual lymph drainage (MLD), a component of CDT, is a specialized form of manual skin mobilization designed to facilitate lymphatic drainage, which aims to decongest lymphostatic regions in order to reduce the swelling and support tissue remodeling and healing. A customized application of layered (short-stretch) compression bandaging is utilized to protect the tissue from re-fill following MLD. Exercise contributes to the reduction of lymphostatic fluid trapped in the tissue through recruitment of muscle and joint “pumping.” Finally, skin care is used to promote healing of the compromised tissue (1). Goals of treatment are to improve the quality of life by reducing the swelling and improving functional mobility, to provide strategies to avoid recurrence and to prevent the development of infections (8, 10) .The successful use of this treatment method requires the skills of a trained therapist who demonstrates high competency. Today, CDT is one of the most recognized treatment methods by Best Practice standards (8, 10). Although considered effective, many insurance providers do not recognize or reimburse for the compression supplies required for this treatment. Patient tolerance to the compression is also an issue for many individuals and the treatment approach is time intensive, costly and limited by the number of qualified medical professionals available to perform CDT. Recognizing that today’s standard treatment is costly, time consuming, and poorly accepted by LE patients, those involved in the provision of care are continuingly seeking alternatives and adjuncts. The purpose of this paper is to review the scientific evidence of complementary, alternative, and other nonCDT treatment modalities in the management of LE.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 98
Methods A research librarian assisted with initial searches using the terms utilized in the Best Practice for the Management of Lymphoedema, 2006 (8) plus expanded terms, for all literature related to LE (2004-2009). The databases searched included: PubMed, CINAHL, the Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, PapersFirst, ProceedingsFirst, Worldcat, PEDro, National Guidelines Clearing House, ACP Journal Club, and DARE, as well as articles from searches by and the archives of the authors. Literature was sorted (Figure 1) and selected references were sent to ALFP research associates who reviewed abstracts to apply broad inclusion and exclusion criteria of LE/non-LE. ALFP authors (BRS, JNC, JMA) sorted relevant literature passing screen #1 into included and excluded articles and topical areas. Full articles were requested for these selected abstracts. Studies were grouped by topic and assigned to authors (EP, JR) for data extraction and quality assessment of the level of evidence using a consensus process. Articles from 2010-2012 were identified by the co-authors, screened, and included, as appropriate. The level of evidence for each study was assessed using the research grading system from the PEP® level of evidence guidelines (Table 1), a system judged to be both reliable and accessible (11, 12, 13). Each author rated all of the articles and the final rating was agreed upon by a consensus process based on this system (screen #2).
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No gray literature was included; non-refereed articles, abstracts, and dissertations were excluded. Eighty-five articles were extracted from the initial collection of 659 articles. Exclusion of 574 articles by the authors took place due to duplication, inability to obtain English translation, inadequate sample size, insufficient level of evidence due to study design, and failure to meet inclusion criteria. The remaining eighty-five articles were placed into four categories (screen #3) which included Botanical, Pharmaceutical, Physical Agent Modalities (PAM) and Modalities of Contemporary Value (MCV). Following further review, 47 articles were rejected, falling outside the systematic review inclusion criteria by definition of these four categories, by design or for lack of English translation. This left 16 articles for the topics of botanicals and pharmaceuticals and 22 total articles for the topics of PAM and MCV. The category of pharmaceuticals was excluded, as the authors recognized the definition of complementary or alternative treatments with regards to the prescription and distribution of medications was not applicable or within the scope of practice for most practicing LE therapists in the United States. It was determined by the authors that the category of Botanicals had generated a significant body of knowledge to support a second, more specific systematic review resulting in the evolution of two separate topic papers. The remaining 22 articles were further evaluated for PEP ranking, specific to their value as a clinically effective treatment for the reduction and management of secondary LE and/or the musculoskeletal complications as they related to LE. A detailed synopsis of the PAM and MCV studies is found in Table 2.
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Physical Agent Modalities
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For the purpose of this review, PAM was defined as those physically-applied agents that produce a bio-physiological response to tissue through the use of light, water, temperature, sound, electricity and/or mechanical device (14, 15). More specifically, a PAM can be defined as a form of energy and materials which may be applied to the body part to produce effect or desired bio-physiological change, as in the reduction of symptoms (15). These may be categorized as thermal, mechanical or electromagnetic. Some, well-documented musculoskeletal pathologies associated with LE include tissue hypoxia, lymphostatic arthropathy, tendinosis, and ligamentosis. These conditions can manifest as chronic wounds, fallen arches of the feet, plantar fasciitis, weak muscle pump and gait disturbances, pain, and
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods joints that are limited in active motion leading to poor fine/gross motor function (1, 2, 5, 16, 17). The PAM selected for review as adjunctive treatment methods which may offer positive effects for the management of these pathologies, as they relate to LE included ultrasound, electrically stimulated lymphatic drainage (ESD), high volt electrical stimulation (HVES), diathermy, low level laser therapy (LLLT), hyperbaric oxygen therapy (HBOT), elastic taping, acupuncture, and a sub-group categorized as Miscellaneous Modalities of Contemporary Value and Possible Benefit (MCV). These included Endermologie®, the Lymphease® Massage Unit, the Sun Ancon® Chi Machine® Aerobic Exercise, the Deep Oscillation device, the Tidar Method® of Aqua-Lymphatic Therapy, and Extracorporeal Shock wave therapy.
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Applying the principles of the PEP ranking system, it was found that interventions of ultrasound, ESD, HVES, short wave electromagnetic diathermy, acupuncture, and HBOT as treatment for LE were ranked as meeting level of evidence of ‘Effectiveness not established’ due to the studies’ small sample sizes, lack of RCT and/or statistically insignificant results. However, the rigor of two studies supporting low level laser therapy and one study which supported elastic taping for LE treatment led to these interventions being ranked as ‘Likely to be effective’ (screen #3).
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It is important to note that the use of these PAM requires the additional training necessary for the appropriate clinical application and consideration of precautions and contraindications for the safety of the patient.
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Ultrasound
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Therapeutic ultrasound (US) is classified as a PAM which employs acoustic energy. It is defined as high-frequency sound composed of alternating waves of compression and rarefaction. It can produce both thermal and non-thermal effects when applied to tissue. The greatest heat is produced in tissues with high ultrasound absorption coefficients, such as dense tissue, tendon, and bone. It can also affect deeper, dense tissue through non-thermal mechanical effects, including cavitation, micro-streaming, and acoustic streaming produced by continuous and pulsed ultrasound delivery. The hypothesis for using US for the treatment of LE explores its thermal effects on edema reduction by indirectly increasing ultrafiltration, thereby increasing circulation (15). Non-thermal and thermal US effects may also increase tissue extensibility (15) and contribute to a reduction of fibrosis, a characteristic of stage 2 and 3 LE. Current literature is sparse regarding the role of ultrasound as a therapeutic intervention for the reduction of LE swelling, but some studies exist.
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A systematic review by Oremus, et al (18) examined the effectiveness of conservative treatments for secondary LE, as well as harms, in studies published between 1990 and 2010. The researchers reviewed 36 English and 8 non-English RCT and an observational study with comparison groups of various treatment interventions, including ultrasound. They found there was limited follow-up beyond 6 months and inadequate study designs. Several failed to report precautions to avoid harm, based on general treatment protocols, with the proposed treatment intervention (18). One small, non-randomized study by Balzarini et al (19), investigated the use of ultrasound therapy for chronic arm LE, secondary to breast cancer treatment (BCT) without radiation. The experiment compared the efficacy of ultrasound (study group n=50) versus mechanical pressure therapy, using a pneumatic pump (control/comparison n=100) and combining both with compression sleeves (19). The control group received pneumatic compression for 6 hours a day for 5 days (30-40 mmHg) at 4 month intervals. The study group (n=50) received pulsed ultrasound for 30 minutes a day for 10 days at 2 W/cm2 at a 3MHz
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods frequency; 5-second cycle with 0.5 second time. Further, a randomized, comparison sample (n=50) used a compression sleeve between cycles.
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The results are inconclusive as the method of limb measurement is unclear. Nevertheless, initially the ultrasound group showed greater reduction, at one year follow-up, however, there was no statistical difference. Balzarini et al (19) noted that the members of the study group reported “greater softening of the arm, patient satisfaction by avoidance of an uncomfortable and constrictive device, better relief of osteomyofascial pain, greater scapulohumeral motion and less intercostobrachial pain-dysesthesia.“ Interestingly, ultrasound is sometimes applied to injured tissues in order to soften them, to increase tissue mobility and reduce pain (15).
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Oremus et al (18) concluded there is no specific evidence to support the use of US for LE. Although the outcomes of the study showed limited limb volume reduction, the benefits associated with the reduction of pain, the improvement of tissue pliability and joint mobility suggest ultrasound may provide an indirect therapeutic contribution to support return of limb function.
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Due to small sample sizes, non-randomized design of the studies and unclear measurement outcomes, this treatment is ranked as ‘effectiveness not established.’
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Electrically stimulated lymphatic drainage/ High Volt Electrical Stimulation
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Electrical stimulation (ES) is a PAM which uses various electrical wave forms, intensities, and polarities to treat musculoskeletal and neurological conditions. Evidence supports their use for pain management, wound healing, muscle strengthening, and even edema reduction for post surgical and traumatic swelling (20).
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Researchers have continued to explore ES’s diverse therapeutic potentials, using varied treatment parameters to target specific treatment objectives and benefits (14, 15).
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In the case of LE, it is hypothesized that ES alters vascular permeability to plasma proteins (12) and that, by stimulating muscle contraction, a pumping effect occurs, thereby facilitating lymphangion activity. A lymphangion is defined as a motor unit of lymphatic collector vessels which propels lymphatic fluid along drainage pathways (1).
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Kligman et al (21) performed a systematic review investigating the treatment options for women with breast cancer-related LE. In one small RCT (N=68), Bertilli et al (22) explored the use of a form of electrical stimulation for the treatment of LE. Patients were randomized into two groups. Group A wore a compression sleeve for six hours daily for nine weeks, while group B wore both the sleeve and received electrically stimulated lymphatic drainage (ESD). Eight electrodes were placed between the supraclavicular region and the wrist over “lymphatic stations or motor points” (22). A sequence of electrical impulses at 4.5 kHz was administered over 30 minutes. No other therapy was allowed over the 9-week intervention. A comparison of LE reduction was observed at two months and then at six months. The mean absolute difference was 12.6 versus 12.1 cm, respectively, for treatment and control group. At 6 months, (4 months after the end of treatment) the mean results were 12.4 cm versus 11.6 cm, respectively. Response rates at two months were 38.3% reduction with ESD and 29.4% without. None of these differences between groups were statistically significant (22).
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A more contemporary systematic review by Leal et al (23) included a RCT by Garcia et al (24, 25) which explored high volt electrical stimulation (HVES) as a treatment option for LE. HVES is defined as electrical stimulation using a monophasic twin-peak wave form with an output greater
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods than 150 volts (20). Leal et al (23) reported limited details regarding this RCT which explored the effectiveness of lymphatic drainage massage with compression (CDT), when combined with HVES. It included a sample size of 20 patients undergoing mastectomy. Weaknesses identified in both the Kligman et al (21) and Leal et al (23) systematic reviews are the generally small and underpowered sample size and the lack of blinding. Leal et al (23) himself concluded that larger randomized controlled studies are needed to demonstrate the efficacy of HVES as a valuable modality in the treatment of LE. The PEP assigned ranking for this intervention of ES based on the evidence reported in these two systematic reviews is ‘effectiveness not established.’
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Electromagnetic diathermy (shortwave)
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Electromagnetic diathermy (ED), also known as Short wave diathermy (SWD), is a PAM that generates a deep heating tissue response through the use of high-frequency electrical or electromagnetic current. “Different frequency ranges are used to achieve clinical effects in different tissue waves and at different depths” (15, p.388). The appeal of this form of PAM is that the potential treatment field is larger compared to conventional ultrasound. In SWD, the treated region is sandwiched between two condenser applicators with higher temperatures affecting deeper tissues.
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Electromagnetic diathermy has been investigated for its effects on lymphatic flow and venous circulation (15). Van der Veen et al (27) evaluated lymphatic and venous dynamics of 10 healthy subjects using lymphoscintigraphy and light reflection rheography of the legs. He concluded that, although diathermy had an accelerating effect on venous return, there was no increase in lymph flow (27). These finding were disputed by a pilot study by Mayrovitz et al (28) who assessed the use of diathermy on post-mastectomy arm LE and skin blood flow on seven patients. Using adjusted treatment protocols with an intensity of 12% of the maximum, initial edema volume decreased and skin blood profusion rates increased (28). Precautions and considerations regarding the safe use of diathermy are many (15).
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Since 2004, little research using Short wave diathermy (SWD) to treat LE was found. A single case study (26) indirectly connected the use of this modality to relief of complicating pathologies related to breast cancer. The study, however, was confounded with too many variables and this intervention of SWD is therefore ranked in this systematic review as ‘effectiveness not established.’
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Low Level Laser Therapy
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The use of low-level laser therapy (LLLT) as a therapeutic tool for the treatment of breast cancer-related LE has gained popularity in the United States since its approval by the FDA in 2007. The science supporting this modality has expanded since its introduction in the 1970s (29). The term ‘low-level laser or cold laser’ refers to the form and intensity of energy used to treat a long list of musculoskeletal disorders. Many labels are used to describe this modality, primarily due to manufacturer’s differentiation in terms and marketing strategies for similar devices. Low-level laser therapy uses energy within the spectrum of light to create biochemical changes to injured tissue, causing physiochemical effects following controlled exposure (29). It is hypothesized that this technique stimulates photochemical reactions in the cells creating an anti-inflammatory, analgesic, and regenerative effect (30).
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Clinical applications for LLLT include pain management, musculoskeletal symptoms relief, wound healing, and the management of inflammatory conditions such as repetitive strain disorders (20). Some effects of LLLT postulated to benefit LE include the softening of scar
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods tissue by affecting fibroblasts, and the reduction of interstitial fluid by stimulating lymphatic motoricity, lymphangiogenesis, and macrophage activity (20, 29, 31) LLLT can potentially unblock the lymph system and restore lymphatic flow, something not associated with Complete Decongestive Therapy (CDT) or pneumatic compression (31). Standard therapies for LE can be both time-consuming and burdensome to the patient, and some patients achieve only limited benefits even when they strictly adhere to therapy protocols (32).
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Low-level laser therapy has been studied for its potential benefits and ease of use, and a few recent studies have been conducted to evaluate the influence of LLLT on LE in breast cancer survivors. Six such studies were found to match the review inclusion criteria (32, 33, 34, 35, 36, 37). Two studies reviewed had 20 or fewer subjects (32, 34) and four (33, 35, 36, 37) included a larger number of subjects, greater than 20 but less than 75. In each of these studies, evaluating LLLT as an effective method of symptom relief was specific to patients with breast cancerrelated LE. While four studies (32, 34, 35, 36) had characteristics which alone would lead level of evidence to be assessed as ‘effectiveness not established’ due to small sample size, limited measurement assessment techniques, and variable dosing of LLLT, the rigorous designs and findings of studies by Kozanoglu et al (33) and Ahmed Omar et al (37) led to the rating of the LLLT intervention as ‘likely to be effective.’ Ahmed Omar et al (37) and Kozanoglu et al (33) are examined separately and in detail for they supported the ranking of ‘likely to be effective,’ while the other four will be discussed collectively prior to the conclusion.
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‘Likely to be effective’ was the quality assessment assigned to LLLT based on the study by Ahmed Omar et al (37), in which a prospective, double-blind, randomized placebo-controlled trial was conducted to investigate the effects of LLLT on limb volume reduction, shoulder mobility, and grip strength of the involved upper extremity. Participants included 50 women with LE (affected arm circumference greater than 2 cm and less than 8 cm from the unaffected arm) and a history of breast cancer surgery with complete or partial axillary lymph node dissection, with or without radiation or chemotherapy. Therapists and patients were blinded to the treatment that included sham or LLLT. The therapy cycle was three times a week for 12 weeks with a GaAs 904 nm Rian Corp laser with an energy dose of 1.5 J/cm2 per intervention. LLLT was delivered at three points on the antecubetal fossa and at seven points in the axilla continuously for 20 min with pulse. Each point was treated for two minutes. In addition to laser therapy, both groups were instructed on daily limb and movement therapies and wore a class II compression sleeve (40-60 mmHg). Measurements were taken at pre-treatment, 4 weeks, 8 weeks and 12 weeks. At completion, there was a significant 93% reduction in limb volume in the LLLT group compared to the control group. Although still a small study, the study design and measurements were of high quality; however, additional multisite studies with larger sample sizes are needed to establish efficacy.
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Kozanoglu et al. (33) conducted an earlier RCT with LLLT with a similar sample size (N=47) which contributed to LLLT’s ranking as ‘likely to be effective.’ Although not a double-blind study, LLLT was compared to another contemporary therapy, pneumatic compression (PC). A more homogeneous patient population was included in this study: all were status post modified radical mastectomy, axillary lymph node dissection, and radiation. The women were randomly allocated to pneumatic compression Group I (n=24) or LLLT Group II (n=23). Group I received 2 hours of pneumatic compression therapy at 60 mmHg pressure daily for 4 weeks and Group II was treated with 20 minutes of LLLT three times a week for 4 weeks. Laser therapy was administered using a Ga-As 904 nm Electronica Pagani IR 27/4 with an energy dose of 1.5 J/cm2 per intervention. LLLT was delivered at three points on the antecubetal fossa and at seven points in the axilla continuously for 20 min with pulse. Information pertaining to timed dose per point was not provided. As was the case in the Ahmed Omar et al study, (37) all
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods patients were given daily exercises and self care instruction, although no compression sleeves were assigned. Measurements included the difference between sum of the circumferences of affected and un-affected limbs, pain assessment using a visual analogue scale, grip strength, and shoulder ROM. The sum of the circumferences reduction in Group II was greater than that in Group I at post-treatment. Circumference reduction occurred in both groups at one, three, and six months (The statistical significant decrease (pretreatment Group I = 18.9 cm versus Group II=16.8 cm, Sum C) and post treatment Group (I=13.9 cm versus Group II=11.1cm). The centimeter decrease, however, was still significant at month 12 only in group II (p=0.004) (At 12 months Group 1= 18.2 cm versus Group II=11.4 cm). Although small, the strengths of this study include comparison of LLLT with a standard modality (pneumatic compression versus sham), homogeneous participants, and long-term follow-up after 1-, 3-, 6-, and 12 months.
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Evaluating the benefits of LLLT for LE or other physical problems such as pain, wound healing, or trauma-related swelling is often difficult to determine because of the variability of the laser dose, frequency and duration used in the research (38, 39, 40). A number of well-designed LLLT RCTs have used a laser dose that is insufficient to produce the response desired, with an end result of reporting no benefit from LLLT when a proper dose or duration may have shown benefit. (38, 40). For example, the designs of the four ‘effectiveness not established’ LLLT studies (32, 33, 34, 36) differed in laser type as well as dose and duration of the beam application, suggesting a need to compare two different laser types or doses. Ahmed Omar et al (37) thoughtfully referred to cellular studies to select the dose (1.5J/cm2) for his trial and described this in his research. Again, more attention needs to be placed on studying the effects of dose, frequency, pulse, non-pulse, wave length, watts and duration to get a better understanding of the practical application of LLLT prior to its use in mainstream medicine.
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A possible short-coming of all the studies presented in the LLLT discussion (32, 33, 34, 35, 36, 37) is that none of them identified funding sources or whether those with a potential conflict of interest had a stake in the treatment outcomes. Although the current LLLT studies (2004-2011) continue to include small sample sizes and most have non-uniform protocols, there appears to be a trend toward drawing the conclusion that arm volume reduction is achievable with LLLT (35, 37, 41, 59). These benefits occur whether LLLT is independent of compression (33, 34, 35, 36) or when it is used as an adjunctive therapy with compression (37) or with CDT (32). Benefits observed with LLLT include reduction in volume, improvement in self-reported symptoms like pain and limb function, increased quality of life, and softening of tissue (32, 35, 41).
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Hyperbaric Oxygen Therapy (HBOT)
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Hyperbaric oxygen therapy (HBOT) involves the breathing of pure oxygen while in a sealed chamber that has been pressurized at 1.5 to 3 times normal atmospheric pressure (42). In the early 1900s researchers speculated on the clinical benefits of HBOT. They observed that patients who suffered from secondary cardiac disease experienced improved symptoms when re-located from higher altitudes to accommodation at sea level. The clinical application of HBOT did not occur until the 1940’s when it was used to treat deep sea divers who suffered from decompression sickness (15). Curiosity about clinical applications of HBOT continue.
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Two contemporary studies by Gothard, et al (43, 44) reported outcomes using HBOT for patients with chronic arm LE and tissue fibrosis following radiotherapy for earlier breast cáncer. The 2004 non-randomized clinical trial (N=21) included subjects with ipsilateral arm LE, equal to or greater than 30%. The participants breathed 100% O2 at 2.4 ATA for 100 minutes on 30 occasions over 6 weeks. The follow-up assessments at 12 months involved 19 of the remaining subjects (n=19/21). A significant reduction in arm volume was noted compared to baseline
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods measures in 5 subjects. In addition, six of the 13 evaluable patients who gave consent experienced a greater than 25% improvement in 99TC nanocloid clearance rate from the ipsilateral forearm measured by quantitative lymphosintgraphy at 12 months (43). The lymphoscintigraphy findings support a strong argument for further investigation as to the longterm treatment benefits of HBOT for secondary LE.
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A phase II randomized trial (44) using a similar intervention design as the 2004 study further explored this modality’s value in the treatment of LE (44). The design included a subject group of 58 patients with arm volume differential greater than to or equal to 15% following axillary surgery were randomized into 2:1 ratio (38/20) study and control groups. Subjects breathed 100% O2 at 2.4 ATA for 100 minutes on 30 occasions over 6 weeks. Both established baseline measure, with follow-up at 12 months. At that time the median limb volume was 131.2% in the control group and 133.5% in the treatment group. Both trials by Gothard offer small sample sizes (2004: N=19 finished, 2010: N=58) and one lacks a randomized control group. Outcomes were similar for the groups in the RCT. Gothard (44) concluded, “No evidence has been found of a beneficial effect of HBOT in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer. There are no beneficial treatment effects of HBOT for this population.” This conclusion supports the PEP ranking of this intervention as ‘effectiveness not established.’ Nevertheless, advances in HBOT technology and further examination of treatment parameters may allow further examination into the application of HBOT for LE (42).
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Acupuncture
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No consensus was found on the precise definition of the acupuncture intervention modality, (45) due in part to the historically diverse styles and the transition of this modality of treatment from the Eastern to the Western world. Following a National Institutes of Health (NIH) consensus conference in 1997, the following general definition was accepted: “Acupuncture describes a family of procedures involving stimulation of anatomical locations on the skin by a variety of techniques. There are a variety of approaches to diagnosis and treatment in American acupuncture which incorporates medical traditions from China, Japan, Korea, and other countries” (46). More specifically, acupuncture or acupoint stimulation modalities are procedures of applied pressure or needle placement on or in the skin which creates levels of stimulation to improve health and/or reduce pain (46).
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A study by Alem et al (46) involving (n=29) women diagnosed with upper limb LE following unilateral breast cancer and mastectomy or segmentectomy with axillary node dissection explored acupuncture as a treatment for LE reduction. The subjects were treated once a week for 30-minute needle retention over six months. No other treatment intervention was given. The authors documented that, while arm circumference did not reduce after treatment, there were significant improvements in shoulder range of motion. Alem et al (46) also documented subjective reports of improved altered sensory issues and less density of the tissue was perceived.
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Further investigation into the secondary benefits beyond girth reduction may eventually demonstrate that acupuncture is ‘likely to be effective’ as an adjunct therapy option to improve post-operative mobility and pain; however, due to the small sample size, lack of randomization, and the lack of evidence to support direct benefit, this level of evidence was ranked as ‘effectiveness not established’. (46)
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A systematic review completed by Chao et al (47) explored the efficacy of acupoint stimulation (APS) for treatment of breast cancer treatment-associated morbidity. The term acupoint
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods stimulation was used to represent various methods of acupuncture including manual needling, needling combined with electric stimulation, wrist band, magnet, laser or heat applications (47) Twenty-six article were reviewed which assessed the application of acupoint stimulation on six conditions associated with cancer therapies. The conditions included vasomotor syndrome, chemotherapy-induced nausea, LE, post-operative pain, aromatase inhibitors-related joint pain, and leukopenia. Acupoint stimulation was applied with varied methods which included traditional, palpating acupressure, electroacupuncture, and magnetic acupressure. The review reported that only 35% of trials were of high quality based on the modified Jadad methodological quality scoring system. Chao et al (47) noted only one study which explored the direct effects of acupuncture on breast cancer-related LE. This was the Alem et al (46) study. It was stated that the study presented with a small sample size, lack of control, and lack of reported long-term outcomes which “increased doubts about the conclusions” (47), supporting the previous acupuncture ranking as ‘effectiveness not established.’
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Elastic-taping
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The use of taping and wrapping to support injured tissue is not a new concept. The most common taping technique recognized in the United States is traditional white athletic taping which are generic, rigid products that require a pre-tape application over the skin to prevent skin irritation. Generally, the irritation is from moisture entrapment, latex, and applied compression over the skin, muscle belly, and joints. Another widely recognized taping technique is McConnell® Taping which uses a cotton mesh tape under a rigid, high-adhesive tape to provide positioning for muscular re-education. It is recommended that the tape stay on the skin less than 18 hours to avoid skin irritation and constriction of muscle fibers which can increase pain. In general, most taping materials are designed to immobilize injured tissue for short periods of time in order to provide rest, prevent re-injury, and allow a level of lifestyle participation in spite of the injury. Controlling muscle motion and limb positioning to promote functional recovery is a foundational concept of rehabilitation basics (16, 48, 49).
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Kinesio-tec® (KMS,LLC, Albuquerque, NM.) tape, the predecessor to similar elastic tape products, was originally conceptualized by Dr. Kenso Kase in the early 1970’s. In 1998, Dr. Kase reported that the application of Kinesio tape in a distal to proximal direction of tension had a positive effect on peripheral blood flow for those with physical disorders, thereby supporting the healing continuum. This specialized tape is a latex-free, elastic product which is reported to allow early motion, while providing tissue correction and realignment, thus reducing pain and inflammation (50, 51). Elastic tape is also referred to as kinaesthetic tape, kinesiotape, lymph taping, or kinesthetic tape. All refer to the effect the tape produces or the sensation by which bodily position, weight, muscle tension, and movement are perceived (52). The application of elastic tape products has been proposed for “lymphatic correction,” claiming it lifts the superficial (initial lymph capillaries) lymphatic structures in the epidermis. This tape is hypothesized to decrease lymphostatic pressure while improving the function of deeper lymphatic vessels (50, 51). Shim et al (52) reported that, in addition to vascular effects (53), elastic taping also affected lymphatic flow in the hind leg of rabbit test subjects. Kase and Stockheimer (53) describe that the directional pull of the tape guides the lymphatic fluid in the desired direction of drainage. It is also reported that the tape can be applied to weak upper extremity musculature to enhance the strength of contraction and support lymphatic peristalsis. It is postulated that the tape can also be used as an alternative to standard compression methods to control the edema (54) although no strong analysis to support this claim was found. The randomized, double-blind, clinical trial (RCT) by Thelen et al (55) documented immediate improvement from impingement pain with pain-free shoulder abduction. These findings suggest elastic taping may be effective treatment
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods for associated symptoms for LE patients presenting with related issues of limited joint mobility, core weakness, or tissue restrictions.
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Evidence-based research to support the use of elastic taping as an adjunctive treatment for LE was limited to those discussing the direct effect of the tape for the treatment of secondary LE and the secondary musculoskeletal dysfunctions that may be associated with this condition. Three studies met the topic criteria and were ranked using the PEP card system. No study presented with a sample size greater than 50 (56, 57, 58).
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Elastic taping is ranked ‘likely to be effective’ due to the rigorous design and potential benefits reported in the single-blinded, randomized control trial (RCT) by Tsai et al (58) which posed the question of whether forms of elastic taping could replace bandaging in decongestive lymphatic therapy for breast-cancer-related LE. The RCT consisted of 41 patients with unilateral breastcancer-related LE of at least 3 months with the affected limb circumference being 2cm or greater in bilateral limb comparison. Participants were randomized to a decongestion lymphatic therapy (DLT) group using compression bandages and pneumatic compression (N=21) or a modified DLT group (N=20) using Kinesio tape (K-tape) instead of compression bandages, combined with pneumatic compression. Both groups were directed through a 20 minute exercise regimen following DLT and bandage/K-Tape application. Four evaluations were performed, including before and after the control period, after intervention and at a 3 month follow-up (59). Outcomes included objective limb size measurements using volumetrics and circumference, water composition of the upper extremity using an 8-pt. tactile-electrode impedance meter, LE-related symptoms using a visual analog scale (VAS), quality of life questionnaire (QLQ-C30 and QLQ-BR23), and patients' acceptance of the bandage or tape assessed by recorded length of time it was tolerated daily. There were no significant differences between the two groups in all outcome variables (p>0.05). Both groups presented with reduced volumetric and circumference measures, but acceptance scores were higher with the taping group (p<0.05) (58). The study results suggest that K-tape could potentially replace the bandages in DLT, and it could be an alternative choice for the breast-cancer-related LE patient with poor short-stretch bandage compliance after 1-month intervention (58).
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Bosman and Pillar (56) performed a non-blinded RCT of nine women treated for breast cancer. Of the nine, four (n=4) had developed seroma. The study examined the use of lymph taping as a treatment to reduce extracellular fluid (ECF) accumulation and improved a range of quality of life measures. Measurements included bio-impedance spectroscopy, active range of motion (AROM), and Quality of Life questionnaire (QOL). Two of the four subjects were taped over “watershed” regions (1) to facilitate fluid reduction while two were treated by “best practice” involving skin care and gentle exercises (56). The study subjects presented with a greater decrease of ECF, improved QOL, and functional AROM scores than others receiving best practice treatment. This small study offers a possible solution for truncal edemas associated with breast cancer treatment, an area where further studies are needed.
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A single case presentation by Pyszora and Krajnik (57) presents an interesting discussion for Kinesio taping in the palliative care setting. Objectives of treatment for this challenging patient population include “symptom management without decreasing the patient’s quality of life” (57). When patients are not able to tolerate compression garments, bandages or devices, the application of elastic taping may provide tissue tension relief with reduction of pain and alternative means of tissue fluid decongestion for truncal, genital, head and/or neck regions where compression is difficult to apply. Because of small size of the last two studies (56, 57), they support a ranking of ‘effectiveness not established’ for Kinesio taping in the palliative care setting.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods The research question to consider for future studies is whether the severity of fibrotic tissue presentation or LE stage alters outcomes, as limited tissue assessment data were made available in these studies. Also, is the tape effective in long-term management? In areas of the world where climate comfort is an issue, elastic taping may provide an alternative to the currently used layered compression bandages. Future research with more patients and controlled study designs are needed to provide higher levels of evidence to assist in the development of effective LE treatment protocols using this modality.
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Miscellaneous Modalities of Contemporary Value (MCV) and possible benefit
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Beyond the traditional modalities of treatment for LE are contemporary interventions which have been explored for their benefits in reducing the debilitating symptoms of LE. Modalities of contemporary value (MCV), as defined by the authors, include treatment interventions and/or devices which have been developed over the time span explored in the design of this systematic search and review and which have drawn the attention of the medical community for the evaluation of their effectiveness in the treatment of LE. These seven modalities included four device modalities, the Endermologie® system, the Lymphease® Massage Unit, the Sun Ancon® Chi Machine® Aerobic Exercise, and the Deep Oscillation device. Two other studies supporting therapeutic modalities of contemporary value were also explored. They included The Tidhar Method® of Aqua-Lymphatic Therapy and Extracorporeal Shock wave therapy.
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Please note that these MCV may require additional training for the appropriate application to support the patient’s plan of care without causing harm.
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The Endermologie® System. The primary use of The Endermologie® System is to reduce the appearance of cellulite. In its application for the treatment of LE, the system uses two motorized, cylinder-type rollers which are applied to the affected region, using lymphatic drainage patterns (59). Moseley et al. (59) conducted a comparative study of 34 women with unilateral breast cancer related arm LE with the established fibrotic induration for greater than one year. Two protocols, in two trials which differed in the lymphatic drainage patterns, time spent and the size of the treatment area were used for four days a week for four weeks (59). Following treatment, compression bandaging was applied to gain the “greatest reduction” and maintain the treatment’s benefits. Perometry was used to assess arm volume. Bio-impedance and tonometry were used to assess changes in tissue fluid and fibrosis of the arm and trunk. A 10-point likertscale was used to measure subjective improvements. Overall reductions in limb volume were noted in both trials (134mls; 18.3% p=0.000 and 185mls; 28% p=0.002) There was also improvement in the induration of some lymphatic territories and perceptions of improvements by study participants. The authors emphasized that the use of this device, along with the application of compression bandages, should be administered by a trained LE professional who shows competency in the concepts of lymphatic pathophysiology and who will monitor the patient’s treatment (59). A small sample size and lack of long-term follow-up were limitations of the study. In addition, the two protocols were not completed simultaneously, but rather the first protocol was altered after it was determined that the regimen did not provide adequate drainage to lymph static regions.
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The Lymphease® Massage Unit. A single pilot study by Moseley et al (60) reported the result of using a hand-held massage device called the Lymphease® Massage Unit. This device produces light intensity (32-45 Hz) vibration to lymphedematous tissue to manage the symptoms and reduce LE in the home setting. Thirty women with breast cancer-related LE for more than one year with a contralateral arm volume difference of 200 mls were recruited to participate. Out of the 30 initial subjects, 25 completed the study, with 21 completing 1-month
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods follow-up assessment. The instructions for using the device, based on the principles of manual lymph drainage, were documented with detail in a handout. Each subject was issued the handout and checked for competency of use prior to issue. The recommendation was for the device to be used for 25 minutes each evening for one month. Compliance was tracked using a log book. Measurements to assess the results included bio-impedance, tonometry, and perometry. Improvements in subjective symptoms were assessed using the likert Scale (60). After the initial treatment month, bio-impedance demonstrated a 43mls fluid loss to the affected arm initially, with reduction of 96mls in truncal fluid by four weeks. Improvements in subjective symptoms were documented, as well. Retention at four-week follow-up showed a significant increase in limb size and return of subjective symptoms; however, pain was still improved, as well as limb mobility (60). There was no mention of the use of compression garments during the trial. It would be of interest to explore the use of this device and the protocols of manual lymph drainage (MLD) in combination with compression garments used to retain the benefits of the treatment.
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The Sun Ancon® Chi. A third study was found by Moseley et al. (61) which explored the use of The Sun Ancon® Chi Machine® Aerobic Exerciser as a “new patient-focused, home-based therapy” to reduce chronic secondary leg LE. Thirty-three patients with a 95% compliance rate used the machine through a gradually-increasing regimen twice a day, in their homes. Perometry was used for measurement of volume reduction. Bio-impedance and tonometry were used to measure tissue density changes and lymphscintigraphy was used to evaluate lymph drainage in eight of the 33 subjects. The McGill Quality of Life Questionnaire was also administered to assess subjective perception of symptoms (61). After using the device for three weeks, the total leg volume reduction was reported as significant (p=0.001) and subjective perceptions of pain, tightness, heaviness, and skin dryness were improved. Post-treatment lymphscintigraphy demonstrated increased lymphatic transport function in only three of eight patients. A limitation of the study was the heterogeneity of the patients with respect to type of cancer and treatment which may alter lymph flow patterns and influence the degree to which lymph transport can recover (1). The results of the study suggested this device might show promise as an adjunct component for maintenance after reduction is achieved. Although objective measures were reliable, this small study lacked control and blinding.
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Deep Oscillation®. Jahr et al (62) completed an RCT to evaluate the possible benefits of Deep Oscillation® therapy for breast cancer treatment-related pain, swelling, and loss of function of 21 patients. Deep oscillation (DO) therapy is said to stimulate lymphatic flow to reduce edema (62), an action that is accomplished by an electrical device which applies an intermittent electrostatic field of low intensity to a target treatment area. The deep oscillation device is connected to the therapist and the patient simultaneously, producing a vibration to the tissue. There are specific protocols for the treatment, requiring the therapist to perform manual lymph drainage (MLD) with gloved hands to protect the skin from electrical charges (62). In the study, the designed intervention included 12 one-hour sessions over a 4-week period consisting of MLD for 15 minutes, supplemented by the DO device for an additional 45 minutes at varied intensity. This was followed by MLD only for an additional eight weeks. The control group received one to two treatment sessions per week of MLD alone. The patients were evaluated prior, mid-point, and at the conclusion of the study using reliable measures. The study group experienced reduced pain and breast volume reduction during the first four weeks, but not at follow-up at eight weeks. Joint mobility remained unchanged. In contrast, the control group had no improvement in pain reporting and demonstrated less mobility at eight weeks (62). There appears to be some inconsistency regarding the study’s design as the control group received fewer treatments for a shorter duration than the study group, making it difficult to compare outcomes. In summary, all four MCV device studies led to the intervention being ranked as
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods ‘effectiveness not established’ due to design, lack of strong objective measure, and/or small sample size.
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Aqua-Lymphatic Therapy (The Tidhar® Method). Exercise is one of the five basic treatment components of complete decongestive therapy (CDT). It is used in conjunction with compression to promote lymph drainage (1). Active muscle contraction supports re-absorption of lymph through superficial and deep lymphatic drainage pathways during the initial treatment phase of CDT. Long established is the knowledge that exercise will improve muscle tone, mobilize joint structures, and increase functional endurance (63). Although aqua therapies may be categorized as a type of exercise, the direct effects of water emersion produce biophysiological changes using energy, in the forms of heat, buoyancy, and resistant forces, which directly or indirectly reduce symptoms (12, 64,65), [thereby meeting the qualifications set by Cannon]. The concepts and principles of aqua-therapy are not new. “Healing water” as a form of therapeutic intervention has been considered throughout history and cultural experience (64). Aqua therapy has been supported in biblical references found in 2 Kings 5:14: “So he went down and dipped himself in the Jordan seven times, as the man of God had told him, and his flesh was restored and became clean like that of a young boy.”
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In recent years, researchers have looked at aquatic exercise to determine if it can control LErelated symptoms and whether it has an added benefit over standard exercise (66, 67). A single-blind RCT by Tidhar et al (68) involved 48 women with unilateral breast cancer-related LE (n=48) who had completed the intensive phase (initial treatment) of complex physical therapy (CPT). It explored whether Aqua-Lymphatic therapy (The Tidhar® Method) is a safe method to treat breast cancer-related LE and to determine if the addition of Aqua-Lymphatic therapy (ALT) to a phase two management protocol would improve adherence, control of limb volume, and quality of life (68). The exercise patterns of ALT are thought to utilize specific forces of the aquatic environment to promote strengthening and lymphatic decongestion (68). The control group (n=32) were directed to perform the self-management protocols set at the initiation of the study. The ALT group (n=16) met for weekly sessions of 45 minutes and were directed to follow self-management treatment between sessions. Circumference of the effected limb were taken and calculated before and after each session. Each patient was expected to log adherence. The study reported that ALT had a significant positive and immediate effect on limb volume and quality of life. It was also found to be safe and promoted a high adherence to a self-directed management program. Although the aquatic environment is not a comfortable venue for some, these outcomes support incorporating ALT into the plan of care for patients who struggle to manage LE. Some weakness of the study included a small sample size, limited adherence (75%) and no long-term effect at three months (68). Therefore, this intervention is currently ranked as ‘effectiveness not established.’
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Extracorporeal Shock Wave Therapy. Animal studies have suggested that Extracorporeal shock wave therapy can increase growth factors which may promote lymphangiogenesis. Kubo et al (69) reported that low-energy, short-wave treatments could promote lymphangiogenesis, thereby reducing secondary LE in a rabbit ear model. Serizawa et al (70) found that Extracorporeal Shock Wave Therapy promoted lymphangiogenesis in a rat model of secondary LE. To date, there has been limited correlation in human application, and further investigation exploring the differences between anatomical and physiological tissue healing characteristics between animal models and human subjects is needed. Because these studies have no direct evidence for effectively treating human subjects, a PEP ranking of ‘benefits balanced with harms’ is assigned this intervention.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods All the studies reviewed for this section create the anticipation for supportive, alternative treatment options for LE with further investigation.
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Summary
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LE is a chronic health condition resulting from the accumulation of protein-rich interstitial fluid due to an impairment of the lymphatic system. It can be progressive and resistant to treatment (1, 4, 5). If left untreated, LE can contribute to fibrotic tissue changes, infection, severe limitations in physical function, and activities of daily living, as well as dramatically impact quality of life. The standard of care for the treatment of LE is CDT (9) which can be labor intensive, cost prohibitive, and too-frequently unavailable due to the lack of medical personal qualified to treat it. It is important, therefore, to explore adjunctive treatment approaches, including modalities, which may enhance CDT. This systematic review of the literature identified new applications for traditional treatment modalities, as well as newer, more contemporary alternative treatments. The primary goal for treatment is to reduce edema; however, the secondary effects of LE such as musculoskeletal dysfunction and poor skin integrity should not be ignored as these effects can often significantly reduce quality of life and function for these patients. Alternative treatment modalities should be considered not only as stand-alone treatment, but also in the context of adjunctive therapies. This may require adjusting parameters and protocols for traditional application techniques to optimally support lymphatic function. There is a critical need for welldesigned, randomized trials to examine the broad range of alternative modalities to determine which ones may be the best for managing LE.
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The current body of published literature lacks sufficient quality to provide the evidence to support the majority of alternative treatment modalities to enhance current LE treatment protocols. The systematic search and review evaluated twenty-six studies which explored the use of PAM and modalities of contemporary value. No interventions reviewed met the PEP standards to be ‘recommended for practice’. Only three studies and two interventions (LLLT [33, 37] and kinesio taping combined with decongestive lymphatic therapy and pneumatic compression, with kinesio taping compared to compression bandaging [58]) met the PEP card systems criteria for ‘likely to be effective.’ The authors challenge the LE medical community to forge ahead in this area of more rigorous human research in alternative modalities to optimize patient outcomes. It is also encouraged to address the need to study effective treatment interventions for other types of lymphedema, beyond that which is related to breast cancer.
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13. Mitchell SA, Friese CR. ONS PEP (putting evidence into practice) weight of evidence classification schema: decision rules for summative evaluation of a body of evidence. 2011; http://www.ons.org/Research/media/ons/docs/research/outcomes/weight-of-evidencetable.pdf. Accessed March 23, 2012.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 15. Cameron MH. Physical Agents in Rehabilitation: From research to practice. 2nd ed. St. Louis: Saunders; 2003.
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26. Johnson W, Draper DO. Increased range of motion and function in an individual with breast cancer and necrotizing fasciitis-manual therapy and pulsed short-wave diathermy treatment. Case Rep Med. 2010;2010.
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27. van der Veen P, Kempenaers F, Vermijlen S, et al. Electromagnetic diathermia: a lymphoscintigraphic and light reflection rheographic study of leg lymphatic and venous dynamics in healthy subjects. Lymphology. Mar 2000;33(1):12-18.
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28. Mayrovitz HN, Sims N, Macdonald J. Effects of Pulsed Radio Frequency Diathermy on Postmastectomy Arm Lymphedema and Skin Blood Flow: A pilot investigation. Lymphology. 2002;35(suppl):353-356.
755 756
29. Tuner J, Hode L. The Laser Therapy Handbook. Grängesberg, Sweden: Prima Books AB; 2004.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 30. Wang G. Low Level Laser Therapy (LLLT): Technology assessment. Olympia, WA: Washington State Department of Labor and Industries: Office of the Medical Director; May 3 2004.
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31. Leal NF, Carrara HH, Vieira KF, Ferreira CH. Physiotherapy treatments for breast cancerrelated lymphedema: a literature review. Rev. Lat. Am. Enfermagem. Sep-Oct 2009;17(5):730-736.
763 764 765
32. Dirican A, Andacoglu O, Johnson R, McGuire K, Mager L, Soran A. The short-term effects of low-level laser therapy in the management of breast-cancer-related lymphedema. Support. Care Cancer. 2011;19:685-690.
766 767 768
33. Kozanoglu E, Basaran S, Paydas S, Sarpel T. Efficacy of pneumatic compression and lowlevel laser therapy in the treatment of postmastectomy lymphoedema: a randomized controlled trial. Clin. Rehabil. Feb 2009;23(2):117-124.
769 770 771
34. Kaviani A, Fateh M, Yousefi Nooraie R, Alinaqi-zadeh MR, Ataie-Fashtami L. Low-level laser therapy in management of postmastectomy lymphedema. Lasers Med Sci. Jul 2006;21(2):90-94.
772 773
35. Lau RWL, Cheing GLY. Managing postmastectomy lymphedema with low-level laser therapy. Photomedicine and Laser Surgery. Oct 2009;27(5):763-769.
774 775
36. Maiya AG, Olivia ED, Dibya A. Effect of low energy laser therapy in the management of post-mastectomy lymphoedema. Physiotherapy Singapore. 2008;11:2-5.
776 777 778
37. Ahmed Omar MT, Abd-El-Gayed Ebid A, El Morsy AM. Treatment of post-mastectomy lymphedema with laser therapy: double blind placebo control randomized study. J. Surg. Res. Jan 2011;165(1):82-90.
779 780 781
38. Bjordal JM, Johnson MI, Iversen V, Aimbire F, Lopes-Martins RA. Low-level laser therapy in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo-controlled trials. Photomed Laser Surg. Apr 2006;24(2):158-168.
782 783
39. Stergioulas A. Low-level laser treatment can reduce edema in second degree ankle sprains. J. Clin. Laser Med. Surg. Apr 2004;22(2):125-128.
784 785
40. Pinheiro AL. Advances and perspectives on tissue repair and healing. Photomed Laser Surg. Dec 2009;27(6):833-836.
786 787 788
41. Poage EG, Singer M, Armer JM, Poundall MD, Shellabarger MJ. Demystifying lymphedema: Development of the lymphedema putting evidence into practice card. Clin. J. Oncol. Nurs. 2008;12(6):951-964.
789 790
42. Bennett MH, Feldmeier J, Hampson N, Smee R, Milross C. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2005(3):CD005005.
791 792 793
43. Gothard L, Stanton A, MacLaren J, et al. Non-randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema and tissue fibrosis after radiotherapy for early breast cancer Radiother. Oncol. 2004;70(3):217-224.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 44. Gothard L, Haviland J, Bryson P, et al. Randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer. Radiother. Oncol. 2010;97(1):101-107.
797 798
45. Rotchford JK, Kobrin LE. The importance of a modern and comprehensive definition for acupuncture in clinical research: preliminary perspectives. Med Acup. 2002;13(3):38-40.
799 800
46. Alem M, Gurgel MS. Acupuncture in the rehabilitation of women after breast cancer surgery-a case series. Acupunct Med. Jun 2008;26(2):87-93.
801 802 803
47. Chao LF, Zhang AL, Liu HE, Cheng MH, Lam HB, Lo SK. The efficacy of acupoint stimulation for the management of therapy-related adverse events in patients with breast cancer: a systematic review. Breast Cancer Res. Treat. Nov 2009;118(2):255-267.
804 805
48. Greene WB. Rehabilitation. In: Greene WB, ed. Netter's Orthopaedics. 1st ed. Philadelphia, PA: Saunders; 2006:239-250.
806 807
49. Kendall FP, McCreary EK, Provance PG. Posture: Alignment and Muscle Balance. Muscles: Testing and function. 4th ed. Baltimore, MD: Lippincott Williams & Wilkins; 1993.
808 809
50. Cooper RA. Kinesio taping. In: Mackin E, Callahan A, Skirvan T, eds. Rehabilitation of the Hand and Upper Extremity. St. Louis, MO: Mosby Inc; 2002:1796-1807.
810 811
51. Jeffs E. Treating breast cancer-related lymphoedema at the London Haven: clinical audit results. Eur. J. Oncol. Nurs. 2006;10(1):71-79.
812 813
52. Shim JY, Lee HR, Lee DC. The use of elastic adhesive tape to promote lymphatic flow in the rabbit hind leg. Yonsei Med. J. 2003;44(6):1045-1052.
814 815
53. Kase K, Stockheimer KR. Kinesio Taping for Lymphoedema and Chronic Swelling: Kinesio USA, LLC;2006.
816 817 818
54. Stockheimer KR. Kinesio Taping & Lymphedema: Applied kinesio taping for lymphoedema/chronic swelling of the arm and/or breast after a mastectomy and axilla lymph node removal. Advance Healing. 2006;summer:22-23.
819 820 821
55. Thelen MD, Dauber JA, Stoneman PD. The clinical efficacy of kinesio tape for shoulder pain: a randomized, double-blinded, clinical trial. J. Orthop. Sports Phys. Ther. Jul 2008;38(7):389-395.
822 823
56. Bosman J, Piller N. Lymph taping and seroma formation post breast cancer. Journal of Lymphoedema. 2010;5(2):46-52.
824 825
57. Pyszora A, Krajnik M. Is kinesio taping useful for advanced cancer lymphedema treatment? A case study. Advances in Palliative Medicine. 2010;9(4):141-144.
826 827 828
58. Tsai HJ, Hung HC, Yang JL, Huang CS, Tsauo JY. Could Kinesio tape replace the bandage in decongestive lymphatic therapy for breast-cancer-related lymphedema? A pilot study. Support. Care Cancer. Nov 2009;17(11):1353-1360.
829 830 831
59. Moseley AL, Esplin M, Piller NB, Douglass J. Endermologie (with and without compression bandaging)--a new treatment option for secondary arm lymphedema. Lymphology. Sep 2007;40(3):129-137.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 60. Moseley A, Piller N, Heidenreich B, Douglass J. Pilot study of a handheld massage unit. Journal of Lymphoedema. 2009;4(1):24-28.
834 835 836
61. Moseley AL, Piller N, Esterman A, Carati C. The Sun Ancon Chi Machine Aerobic Exerciser: a new patient focused, home based therapy for people with chronic secondary leg lymphedema. Lymphology. Jun 2004;37(2):53-61.
837 838 839
62. Jahr S, Schoppe B, Reisshauer A. Effect of treatment with low-intensity and extremely lowfrequency electrostatic fields (Deep Oscillation) on breast tissue and pain in patients with secondary breast lymphoedema. J Rehabil Med. Aug 2008;40(8):645-650.
840 841 842
63. Hayes SC, Rye S, Battistutta D, Newman B. Prevalence of upper-body symptoms following breast cancer and its relationship with upper-body function and lymphedema. Lymphology. Dec 2010;43(4):178-187.
843 844
64. Becker BE, Cole AJ. Comprehensive Aquatic Therapy. Newton, MA: ButterworthHeinemann; 1997.
845 846
65. Bates A, Hanson N. The Principles and Properties of Water. Aquatic Exercise Therapy. 1st ed. Philadelphia, PA: Saunders; 1996.
847 848 849
66. Letellier M, Towers A, Cohen R. Aqualymphatic exercise as an alternative therapy for lymphedema management following breast cancer: A randomized controlled pilot study. J. Palliat. Care. 2008;10(3):215, 338.
850 851
67. Tidhar D, Shimony A, Drouin J. Aqua lymphatic therapy for postsurgical breast cancer lymphedema. Rehabilitation Oncology. 2004;22(3):6-14.
852 853 854
68. Tidhar D, Katz-Leurer M. Aqua lymphatic therapy in women who suffer from breast cancer treatment-related lymphedema: A randomized controlled study. Support. Care Cancer. 2010;18(3):383-392.
855 856 857
69. Kubo M, Li TS, Kamota T, Ohshima M, Shirasawa B, Hamano K. Extracorporeal shock wave therapy ameliorates secondary lymphedema by promoting lymphangiogenesis. J. Vasc. Surg. Aug 2010;52(2):429-434.
858 859 860
70. Serizawa F, Ito K, Matsubara M, Sato A, Shimokawa H, Satomi S. Extracorporeal shock wave therapy induces therapeutic lymphangiogenesis in a rat model of secondary lymphoedema. Eur. J. Vasc. Endovasc. Surg. Aug 2011;42(2):254-260.
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Figure 1. Literature Review Process
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Table 1. Putting Evidence into Practice (PEP) Weight-of-Evidence Classification Schema
Likely to be Effective
Effectiveness has been demonstrated by supportive evidence from a single rigorously conducted controlled trial, consistent supportive evidence from welldesigned controlled trials using small samples or guidelines developed from evidence and supported by expert opinion. Clinicians and patients should weigh the beneficial and harmful effects according to individual circumstances and priorities. Data currently are insufficient or are of inadequate quality.
RCTs, meta-analysis or systematic reviews with documented adverse effects in certain populations.
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Benefits Balance with harms
Examples -At least two multisite, wellconducted, randomized, controlled trials (RCTs) with at least 100 subjects -Panel of expert recommendation derived from explicit literature search strategy; includes thorough analysis; quality rating and synthesis of evidence -One well-conducted RCT with fewer than 100 patients or at one or more study sites -Guidelines developed by consensus or expert opinion without synthesis or quality rating.
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Description Effectiveness is demonstrated by strong evidence from rigorously designed studies, meta-analysis, or systematic reviews. Expected benefit exceeds harms.
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Weight of Evidence Category Recommended for Practice
Effectiveness not established
Lack of effectiveness is less well established than those listed under not recommended for practice.
Not Recommended For Practice
Ineffectiveness or harm clearly is demonstrated or cost or burden exceeds potential benefit.
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Effectiveness unlikely
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Adapted from information from Mitchell & Friese, 2011
-Well-conducted case control study or poorly controlled RCT -Conflicting evidence or statistically insignificant results. -Single RCT with at least 100 subjects that showed no benefit -No benefit and unacceptable toxicities found in observational or experimental studies. -No benefit or excess costs or burden from at least two multisite, well-conducted RCTs with at least 100 subjects. -Discouraged by expert recommendation derived from explicit literature search strategy; includes thorough analysis, quality rating and synthesis of evidence.
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Table 2. Summary Table of Physical Agent Modalities and Modalities of Contemporary Value Physical Agent Modalities PEP Ranking- Likely to be Effective Design
Sample
Intervention
LE Defined
Measurements
Omar et al, 2011
DBRCT; Placebo Evaluate effect of LLLT for LE symptoms
Female, BCRL N=50 (25/25)
Swelling >2cm but<8cm
-Circumference @ 6 points, -Jamr® strength test, mean of 3; dynamometer -AROM using standard plastic goniometer -Measurements taken @ pre-treatment, 4,8,&12 weeks
Kozanoglu et al, (2009).
RCT Evaluate effect of LLLT for LE management
N=47 (G1=24 PCP; G2=23 LLLT)
Therapy cycle 3x/wk x 12 Ga-As 904 nm, 5 mW spot size 0.2cm². average 1.5 J/cm² continuous for 20min./pulsed 50ns @frequency of 28000 Hz @ 3 pts. To anti-cubital fossa & 7 pts. Over axilla; daily limb and movement therapies. (5 times each set). compression sleeves (40-60 mmHg) G1= 2 hrs. PCP@ 60 mmHg; G2 = 20 mins. LLLT; 4wks (20 sessions).
Tsai et al,
SBRCT Efficacy of KT to replace bandages in DLT for BCRLE
41 women with uni-lateral BCRLE for at least 3 mos N=21 in standard decongestive lymphatic therapy (DLT group: & N=20 in the modified DLT (K tape) group.
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Unilateral BCRLE >=3 mos. 2 cm girth measure in one or more points
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Both groups received DLT (skin care, MLD, with 1 hr. pneumatic compression (PC) @ 40 mmHg + 20mins. of exercise. DLT used short stretch bandages. KT group used K-tape instead of bandages. - Each group was treated for 2 hours/session 5 sessions/wk in 4-week period.
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Calculated difference of >2cm in 3 of 7 anatomical UE points (effected vs non-effected)
Outcome Results/conclusion
Strength
Weakness
LLLT was found to be effective in reducing limb volume, increased limb mobility and grip strength in 93% of patients tested Conclusion: : LLLT may be useful modality in the treatment of LE
Double blinding & sham laser; All patients wore compression sleeves following treatment
Small sample size
Circumference reduced in both groups at 1,3 and 6 mos.; Decrease was still significant at 12 mos. only in LLLT group (p=0.004). Reduction G2 was greater than G1 at posttreatment. Conclusion: LLLT may be useful modality in the treatment of LE No significant difference between groups in all outcome variables (p>0.05) - DLT=excess limb size, water composition, and circumference of lower part of upper arm significantly reduced. KT= only excess circumference of arm & water composition significantly reduced. The acceptance of K-tape was better than DLT( bandage). Patients reported using the Ktape longer, with a greater ease of use, increased comfort, convenience. Conclusion: The K-tape could replace the bandage in DLT for BCRLE
Comparative results over 12 mos.
Lacks control group; small sample; “pain” was not well defined, patients with functional mobility (pain with motion) were excluded. Small sample size - Lack of longterm follow-up
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-Difference between sum of circumferences of affected vs unaffected limbs; -Pain Visual Analogue Scale -dynamometer measure grip strength
-Volumetric Water displacement circum. measurement - An eight-polar tactileelectrode impedance meter - Visual Analogue Scale to measure lymphedema-related symptoms - The EORTC QLQ-C30 and QLQ-BR23 to measure health-related quality of life - A Visual Analogue Scale to measure patients’ acceptance to the bandage or tape
Physical Agent Modalities PEP Ranking-Effectiveness not established
Blinding sample into study groups
ACCEPTED MANUSCRIPT Design
Sample
Intervention
LE Defined
Measurements
Oremus et al, (2012)
SR examined the efficacy of conservative tx. methods for secondary LE, as well as harms related to treatment
36 English and 8 non-English RCT or comparison studies from 1990-Jan. 19, 2010 reporting efficacy data
1 Applicable to this SR: (Balzarini et al. 1993) Comparison pilot study for ultrasound therapy for chronic arm BCRLE without radiation. Compared the efficacy of US vs. MPT using a pneumatic pump (control/comparison n=100) and combining both with compression sleeves. The control group received pneumatic compression for 6 hrs/day x 5 days (30-40 mmHg) at 4 month intervals. The study group (n=50) received pulsed ultrasound for 30 minutes/day x10 days at 2 W/cm2 at a 3MHz frequency; 5 second cycle with 0.5 second time. Further, a randomized, comparison sample (n=50) used a compression sleeve between cycles. (Balzarini et al,1993)
LE quantified % >=6.5 slight >=12% moderate .>=13% severe. (Balzarini et al,1993)
Significant variation in assessment methods.
Leal et al
SR present/
18 articles,
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10 RCT measured the effect of therapy BCRLE included compression garments, MLD, CDT, CP, ESD and medical therapies.
1 Applicable to this SR: (Bertelli et al, 1991) N=74 ESD +compression garment vs. compression garment used alone. Both groups wore a standard elastic sleeve for 6 h/day/6 mos. ESD group= 8 electrodes placed between the supraclavicular region and the wrist A sequence of electrical impulses at 4.5 kHz was administered over 30 minutes. No other treatment for lymphedema was per-mitted for duration of trial.
No specific definition
1 Applicable to this SR:
No specific
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SR to provide evidence summary regarding treatment options for woman with BCRLE
Favorable reporting that study group reported *“greater softening of the arm, *patient satisfaction by avoidance of an uncomfortable and constrictive device, *better relief of osteo-myofascial pain, greater scapulohumeral motion and less intercostobrachial paindysesthesia. (Balzarini et al,1993)
Significant variation in assessment methods.
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Outcome Results/conclusion
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Initially, the ultrasound group showed greater reduction but, at 1 year follow up, there was no statistical difference. Conclusion: No specific evidence to support the use of US for lymphedema volume reduction but showed beneficial effects for related functional conditions (Oremus et al, 2012)
Conclusion: Compression therapy and MLD may improve lymphedema, but further studies are needed. Compression garments should be worn daily /removed at bedtime. No current evidence to support the use of medical therapies for lymphedema. No statistically significant differences between the 2 groups specific to ESD ( Bertelli et al, 1991)
Strength
Weakness
Control group comparison *Qualifying % of LE per specific measure (6.5=slight, 712.5=mod >13=severe Girth % was consistently measured *Duration/ effects over 1 year *Scoring of edema “firmness” is defined. *Small dropout rate (reoccurrence or poor compliance) *Similar patient profiles (Balzarini et al,1993)
Small samples;
Varied measures reflected standardized measurement Examined potential harms (Oremus et al, 2012) There was a formal external review process to validate the relevance of the opinions. Reviewers were oncologists, nurses and physiotherapists
No double blinded studies of weighted evidence.
Studies were small/underpowered, ranged from 25 to 104 patients. None of these studies used blinded outcome assessments; QOL not assessed
More and better designed, larger trials are needed. Need to establish consistency in defining LE (Kligman, et al 2004)
Significant variation
Both Tx. groups reduced
7/18 RCT, Cohort
No uniformity
ACCEPTED MANUSCRIPT examined the results of varies physio-therapy modalities used for treating lymphedema, Data was collected from textbooks & LILACS, PubMed & SciELO databases from 19512009
inclusion of varied design included DBRCT, RCT, Cohort studies and case presentations which addressed physiotherapy approaches for LE Tx.
(Garcia et al., 2005) Randomized study N=20 BCRLE; Analysis of the effects of HVES and MLD with compression sleeves vs. MLD with compression sleeves alone.
Johnson & Draper, 2010
Single Case study
N=1 female
Pulsed short-wave diathermy (PSWD) 48 watts/20 mins. 4-5 ̊C @ 35 cm. depth over painful, restricted LE tissue areas 3x/wk3, then 1-2x/wk 3
No specific definition
Kaviani et al (2006).
RCT, double blinding
N=11 women with unilateral post mastectomy lymphedema N=6 laser group; N=5 placebo
Study group rec’d LLLT over the five points applied to the axillary areas 3x/wk /3 weeks. After 8-week interval,Tx repeated for 3-week (18 Tx). GA-As laser device wavelength 890 nm over arm and axilla - Patients in the sham group received sham irradiation under strictly controlled double-blinded conditions.
No specific definition
Lau,et al 2009.
Prospective, single blinded RCT LLLT, no concurrent treatment.
N=21 female, unilateral BCRLE with radiation therapy. Random allocation study group n= 11; Control n=10
LLLT for four weeks (3x/week) study group. Control group= no therapy LLLT to axillary region alone for 20 min. Comby 3 Terza Serie, Model D; ASA S.r.l., Vicenza, Italy.
No specific definition
in assessment methods.
definition
“lymphedema perimeters and Severity” without any significant difference in the 2 groups. Volume reduction was greater with the use of HVES. (Garcia et al., 2005) Exercise modes and PC may not be beneficial without MLD and compression. MLD alone is not effective for lymphedema treatment unless compression and exercises are combined. Conclusion: The use of MLD/CDT with HVES are effective & offers greatest reduction of lymphedema. Pt. experienced increased ROM, reduced pain & improved function after Tx. Individuals with cancer ,those have experienced severe infection, post radiation pain or scarring restriction may have significant improvement in ROM, in quality of life, & functional outcomes using PSWD; Conclusion: No direct benefit for lymphedema reduction All patients completed 10 days of treatment without any adverse reactions. - The study group showed significant improvement in the reduction in pain and limb Conclusion: Need for further study
sample sizes were >130
stated to determined definition for LE, Lacks clarity in assessment tools used.
Established Tx. Parameters
Single case study. Data insufficient evidence, statistically insignificant
Adherence to treatment is 100% Well designed RCT
Lack of longterm followup; Small sample size
Only 1 intervention. The result was consistent with previous studies which showed a progressive
small sample size, short follow up, singleblinded study. They
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Other modalities examined included PC, MDT/CDT, LLLT, and exercise (Leal et al 2009)
Goniometer MNS= tissue changes
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A tape measure to measure limb circumference. Subjective symptoms, such as pain, range of motion of the arm, heaviness of affected limb, and patient’s desire to continue with their treatment were expressed by patients using visual analogue scale
Volumetry: minimum arm volume Tonometry: tissue resistance. Disabilities of Arm, Shldr. , Hand questionnaire
Reduction in arm volume and increased tissue softening in LLLT group only. Significant difference between groups (p<0.05).Laser group: 16% arm volume reduction. At 4 week follow up: 28%
ACCEPTED MANUSCRIPT (DASH). Outcome measures were assessed before and after the treatment period and week follow
Gothard,
1 group control design/ case study
N=21 BCRL patients w/tissue fibrosis s/p radiotherapy
Hyperbaric oxygen therapy (HBOT): Patients breathed 100% oxygen at 2.4 ATA for 100 mins. In a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks.
specific to secondary conditions of LE symptom- logy
58 subjects with axillary dissection and RD
52/58 patients) were randomized in a 2:1 ratio to HBOT (n=38) or to best standard care (n=20). The HBOT group breathed 100% oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks
≥ 15% increase in arm volume after supraclavicular ± axillary RD
Limb volume using perometer; Lymphoscintigraphy; EORTC core questionnaire QLQ-C30) and BR23 measure quality of life.MRI to SC fossa, axilla and brachial plexus to exclude cancer recurrence, clinical assessment of subcutaneous induration, Photos
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A non-randomised phase II study to examine effect of hyperbaric oxygen (HBO) therapy on arm LE following adjuvant radiotherapy for early BC
Ipsilateral limb volume shown as a percentage of contra-lateral limb volume. Fractional removal rate of radioisotopic tracer from the arm,extracellular water content, patient selfassessments and UK SF-36 Health Survey Questionnaire.
Alem, et al 2008
Case controlled study to examine the effects of acupuncture as a therapeutic Tx. intervention for improving motor function, reduce lymphedema and improve to sensory symptoms of heaviness and tissue tightness in the affected UE of woman undergoing
29 women undergone unilateral breast cancer surgery (mastectomy or segmentectomy with axillary dissection), presenting with lymphedema (N=23) and/or a decrease in movement amplitude of upper limb (age ranged from 43 to
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Acupuncture (APS) was performed by an acupuncture specialist/ PT once a week with a 30 minute needle retention time for six months; total Tx. N=24 Pt. rec’d 11 stainless steel needle placements; points based on the theory of Traditional Chinese Medicine for lymphedema reduction, altered sensation, increasing blood flow, and gynecological
+2cm UE circumference comparison with a differential @ 3 different anatomical points, wrist to olecranon process (10 cm above and below)
reduction. LLLT was effective for the management of PMLE and the effects were maintained at 4 week follow up. Conclusion: Recommend LLLT be used in conjunction with CDT. (WHY?) Significantly reduced arm volume at 12 mos follow-up, compared to baseline (p=0.005) Six of 13 evaluable patients experienced a >25% improvement in 99TC nanocolloid clearance rate from the ipsilateral forearm measure by quantitative lymphoscintgraphy at 12 months. No significant improvements noted in QOL. Conclusion: Need for further study
reduction of average arm volume after cessation of LLLT (Piller, 1998; Kaviani, 006; Carati, 2003)
(91.4%) patients with baseline assessments, (86.8%) @ 12 mos assessment; Median volume of ipsilateral limb at baseline was 133.5% (IQR 126.0-152.3%) in the control group, and 135.5% (IQR 126.5-146.0%) in the treatment group. @ 12 mos.after baseline the median (IQR) volume of ipsilateral limb was 131.2% (IQR 122.7151.5%) in the control group and 133.5% (IQR 122.3144.9%) in the Tx. group treatment group.
Well designed study with structured intervention protocols. Objective, reliable measure; 12 mos follow-up with high retention
Small sample,
Strict patient compliance, no other treatment variable
Lack of information about previous treatments correct
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Scanning head. Three infrared laser heads sources with one emitting at a wavelength of 808nm and two emitting at a wavelength of 905nm. (2J/cm2).
Goniometry to evaluate shoulder range of motion (ROM) - A flexible metric tape to measure Circumferences of arm, forearm, and wrist: One , Three and 6 months after tx.
Conclusion: No evidence for beneficial effect - ROM of shoulder, degree of lymphedema, and sense of heaviness and tightness in the affected limb were significantly improved at the end of treatment (p< 0.001, p = 0.016, p < 0.001). - No improvement in the difference of circumferences of arm, forearm, and wrist. Conclusion: Acupuncture may help to improve ROM of shoulder, symptoms of heaviness, and tightness in
Reliable instruments Compliance with treatment protocols 100% more than one study site. Well designed case/ control study
Reliable constructs
recommend the control group get sham treatment to rule out placebo effect. Lack of randomized control group Small sample size Cost may be prohibitive
Lacks blinding or randomized design
Lack of a control group Small sample size Lack of longterm observation
ACCEPTED MANUSCRIPT arm, and degree of lymphedema. No influence for direct girth reduction
26 studies; 18 English studies 8 Chinese studies *Inclusion : adults diagnosed with B/C at any stage of Tx.(surgery, radio-therapy, chemo-therapy, hormonal therapy, or palliative treatment, and with treatmentinduced adverse effects).
Varied . Traditional Acupuncture - Acupressure - Electro-acupuncture - The use of magnetic device on acupuncture points
Specific to the Alem et al ,2008 study: +2cm UE circumference comparison with a differential using 3 different anatomical points (wrist to olecranon process;10 cm above and below)
- A questionnaire with a visual analogue scale (VAS) to measure perceived heaviness and tightness in the arm - Palpation and visual inspection to classify degree of lymphedema
Varied symptom scores and general health status outcomes
RCT to investigate the potential of lymph taping (Elastic taping) to combat seroma formation
9 subjects
One day post-taping was applied every five days to the study group. The tape was cut into three strips and applied over the watershed between the posterior thoracic skin territories & from spine to axilla, in skin stretch positioning. The participants were encouraged to perform early arm motion, including abduction of the arm at 90° and “arm raising”. Participants were also encouraged to resume their normal daily activities.
Specific to secondary conditions of LE symptom- logy
Anna Pyszora, Małgorzata Krajnik, 2010
Single case study of an advanced cancer patient whose painful skin tension, caused by LE was successfully reduced with the use of Kinesio Taping. (elastic tape method)
Conventional methods of CDT but, due to tissue sensitivity, Kinesio tape was used as an alternative to compression wrap
A lateral anterior lower leg taping application was used. The “’fan tape” anchored at the lateral aspect of the knee with no tension. The tails of the tape were applied to the anterior, medial and posterior aspects of the lower leg with 15–25% tension The tapes were left on the patient’s skin for the next three days
specific to secondary conditions of LE symptom- logy
Bio-impedance spectroscopy of the breast was used to assess intra and extracellular fluid levels in each of the four quadrants of the breast. Measurements were repeated at five, nine and 16 days.
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Jadad scale; 35% of the studies selected were determined high quality but only one related to lymphedema treatment (see Alem et al ). The results of the study were favorable for Acupoint stimuli for secondary musculoskeletal and sensory deficits related to lymphedema. The article referenced reported improved mobility and relief of sensory discomfort but not in circumference.
Both English and Chinese published articles were included for reviewing - Quality of study was evaluated by using a modified Jadad scale
Only 35% of trials were determined as high quality. -*Only one study in this review examined the effect of acupuncture on breast cancerrelated lymphedema.
The extracellular fluid value at t16 was 0.1037 ± 0.0324 (15.3 % decrease) over t1 in the lymph taping group and 0.1066 ± 0.0227 (4.6 % decrease) in the current best practice group (n=4 in each group).After 16 days of treatment, substantial changes were found in burning sensations, tightness and heaviness in favor of the lymph taping group. In particular, pain perception in the lymph taping group improved. Conclusions: lymph taping has the ability to reduce extracellular fluid accumulation and improve a range of quality of life measures. The patient claimed that the oedema, pain and feeling of heaviness had decrease. Conclusion: The study suggests that forms of elastic Taping could replace the bandage in CDT, and could be an alternative choice for LE patients with poor short-stretch bandage compliance. The authors emphasized the need for more clinical trials evaluating the effectiveness of
Strong measures, subjects followed over 16 days; Standard tape application
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patient compliance
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92 years)
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mastectomy or segmentectomy with axillary dissection associated with BC A literature review of the efficacy of Acupoint stim. (APS) for BCRL and adverse effects
No objective measure reported
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Kinesio (elastic) Taping.
Modalities of Contemporary Value PEP Ranking-Effectiveness not established Sample
Intervention
LE Defined
Measurements
Outcome Results/conclusion
Moseley, et al (2007).
Comparative study with two groups to explore effectacy of a new treatment option for secondary UE LE
34 women with unilateral UE BCRLE with the presence of established fibrotic induration (>1 yr) 24 women in the first protocol 10 women in the second protocol
Volume difference >200mls determined by perometry
Moseley et al, (2009)
One Group Study to explore the use of the HandHeld (Lymphease massage unit as an effective tool for the management of LE in the home.
26 women with BCRLE of the UE
Endermologie system applied over the same period (4 day/wk x4 wks Using the same measurement schedule, variation in protocol II time spent treating clearing trunk adjacent to the swollen limb Used larger treatment head After each treatment session, compression bandaging was applied to arm. Use of Hand held unit for a total of 25 mins. Every evening with specific MLD protocols for 1 mos.
Multi-frequency (5-500 Hz) bio-impedance to measure arm & truncal fluid Opto-electronic perometry to measure arm volume - Tonometry to measure fibrotic induration in the of arm & anterior thorax. A 10 point Likert Scale to rate pt. subjective complaints, such as pain, heaviness, tightness, hardness, ROM , and limb size Bioimpedance to measure arm and truncal volume - Perometer to measure total arm volume - Tonometry to measure tissue compliance - Subjective arm symptoms
Moseley, et al (2004).
An experimental study with one group
N=33 patients with secondary lymphedema of the LE, related to CA surgery with various type of CA, such as bowel, cervical, reproductive, prostate, and melanoma cancer (age ranged 3988 years).
Both protocols showed overall reductions in limb volume, limb fluid, and truncal fluid, improvements in fibrotic induration in some lymphatic territories, and improvements in subject reporting of heaviness, tightness, tissue hardness, and limb size. Conclusion: The self-massage and compression are helpful for patients with secondary lymphedema related to breast cancer. @ 4 weeks S/P initial Tx. reduction in arm fluid of 51 ml. - Participants who previously c/o irradiation, or who were moderately compliant in conservative Tx., experienced significant reductions in arm fluid volume (p = 0.015, 0.018, and 0.019, respectively). -improvements in limb size (p = 0.007) and range of movement (p = 0.000). - Conclusion: The device may help to maintain their arm lymphedema @ home. There was a significant total leg volume reduction over 3 weeks (p = 0.001), and at 1 month follow-up leg volume remained significant lower than pretreatment level (p = 0.032). - Bio-impedance showed a significant fluid reduction in the affected leg(s) at 3 weeks of treatment (p = 0.021). - There were significant improvements in subjective leg symptoms, including pain, tightness, heaviness, skin dryness, and perceived leg size at 3 weeks. - No significance differences were found in the leg tissues as
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Participants used the Sun Ancon Chi Machine Aerobic Exerciser in their own home, morning and evening for three weeks adhering to the following regimens: day 1-2: 5-min per session, day 3-7: 8min per session, day 821: 12-min per session.
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- Perometer to measure limb volume - InBody 3.0 system to measure body biopedance - Tonometry measures tissure resistance to pressure - Lymphscintigraphy - McGill Quality of life Questionnaire to measure: pain, heaviness, tightness, pins, and needles, cramping, burning sensations, and perceived leg size
Strength
Weakness
Validated techniques /measures
Unequal # of pts. /group. Small sample size No long-term follow-up Design flaw in protocol I
Reliable measures
Lack of a control group Small sample size Adverse effects from handheld device use included headache, discomfort, heavy to use.
Overall 95% compliance rate with the regime.
The most commonly reported side effects were knee pain, dizziness, and neck pain Caution should be noted for patients with pre-existing joint/bone problems. - Lack of a control group - Lack of longterm evaluation
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Tidhar et al (2009)
RCT to examine safe efficacy of Aqua-lymphatic Therapy (ALT);explore improvements in adherence, limb volume & QOL between selfmanaged Tx. group vs. ALT group *The therapist who performed outcome assessment was blinded to group allocation
N=48 women with BCRL (age ranged 31-81 years) n=16 women in the aqua lymphatic therapy (ALT) group n=32 women in the control group
The study group joined a weekly session of ALT for 3 months in addition to self-management therapy. Each session lasts 45 minutes. - The control group was instructed to continue performing as usual, selfdirected management .
DX of breast LE by palpation of the effected breast Photo and 3D measure
Pre-test measure of Relative volume (severity of LE) LRV= EVx100 Volume of contra-lateral limb; ULL27 to measure QOL; Assessment ; body weight (scale)
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- The treatment group 12 sessions (MLD) supplemented by deep Oscillation for 4 weeks (23 sessions per week). 15 mins. MLD, 45 mins. DO to the breast, chest wall and arm consisting of 100 HZ for 30 MIN & 30 HZ for 15 MIN. Then the patients returned to manual lymphatic drainage alone for the next 8 weeks. - The control group received MLD alone, consisting of 1 or 2 of 3045-min/ week.
VAS to - Breast edema documented by photos. - Functional testing to assess ROM shoulder and cervical spine. - Analysis of breast volume using 3D measuring system (called Scan Mobile®). Done before the 4 week intervention, at completion then 8 weeks. (evals: 3 times)
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Breast LE and pain N=21 patients BCRL with SLND and 1 had melanoma/tissue excision with ax node dissection; n=11 in treatment group n=12 in control group
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RCT Block randomization evaluated the additive benefits of Deep Oscillation® therapy (DO)
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measured by tonometry. - Of eight participants who underwent lymphscintigraphy, three participants showed increased lymphatic transport function in the post-treatment scan.. Conclusion: The Sun Ancon Chi Machine Aerobic Exerciser is an effective adjunct therapy that can be used in the patient’s own home. - Treatment group significantly reduced pain & breast volume @ 4 weeks after treatment (p < 0.05), not @ follow-up at 8 weeks. - Control group: no change in pain scores. Objective confirmation by breast 3D measuring treatment group only (of symptom relief of swelling) at follow-up the difference lost significance. - Both group subjectively reported reduction of swelling. - The range of mobility in treatment group was unchanged, whereas there was a significant reduction in shoulder mobility in the control group (p < 0.05). Conclusion: Deep Oscillation ® supplementary to MLD MAY relieve pain and reduce swelling in patients with breast cancerrelated lymphedema ALT had a positive significant immediate effect of limb volume but no long-term effect (at 3 months follow-up) was found. - The adherence rate to ALT was significantly higher than the adherence to self-management therapy. - Quality of life improved in the ALT group. Conclusion: ALT was found to be a safe method, with high adherence for treating breast cancer-related lymphedema.
- Water displacement to measure limb volume - The Upper Limb lymphedema Questionnaire (ULL27) to measure quality of life - A self-reported diary to measure adherence, Body weight
Using blocked RCT
- Small sample size - Number of treatment sessions per week in the treatment group is higher than those in the control group. This is not completely clear: (The control group received MLD 1-2 tx per week or “usual care.”
RCT
Unequal of number of sample in each group - Small sample size - The clinical physical therapist, who performed the limb volume assessment at the first and the last sessions in the pool were not blinded to the group allocation. - Low adherence for completing the
ACCEPTED MANUSCRIPT adherence diaries (75%). Unclear as to (self-managed control group methods used
Modalities of Contemporary Value
Sample
Intervention
LE Defined
Comparative study for the efficacy of low energy extracorporeal shock wave therapy (ESWT) to promote lymphangiogenesis to improve lymphedema
A rabbit ear model with “created” secondary lymphedema
surgical disruption of lymphatic vessels to the ear of a rabbit. 2 weeks after disruption, the ear was treated (with/without) ESWT (0.9mj/mm;10%, 200 shots to effected tissue) 3x/wk4
Not defined
Serizawa et al (2011)
Comparative study to investigate effect of ESWT for improving condition of secondary Le with increased lymphogenesis
Rat Tail Model with “created” secondary lymphedema (n=15/group)
Tissue in study group was treated with ESWT using 0.25mj mm, 500 impulses 4 times (day 3,5,7 & 9) Control did not
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Measurements Ear thickness measured following surgery 1x/wk2; measured 1cm distal and medial to site using vernier caliper
Outcome Results/conclusion
Strength
Weakness
VEGF-C and VEGF receptor 3 were significantly increased in the treated ears vs. untreated. Conclusion: ESWT may be a promising noninvasive strategy for the Tx. of LE; Further study is needed including effects versus harm for human subjects
Controlled variable with structured lab environment reproducible
Tail volume increased in control group, showed significant improvement in test subjects. VEGF-C & bFGF. ESWT may be a promising noninvasive strategy for the Tx. of LE; Further study is needed; effects vs harm for human tests
Controlled variable with structured lab environment; reproducible
Non-human study, unknown harms to human subjects. Confirmation is needed to differentiate “created” secondary LE from inflammatory edema Non-human study, unknown harms to human subjects. Confirmation is needed to differentiate “created” LE from inflammatory edema
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Kubo et al (2010)
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Observed through fluorescence/ measure drainage function of lymphatic fluid. Tail volume measured using water displacement volumetry every 3 days (n=15/group)
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CG: compression garments ES = elastic sleeve ESD: Electrical Stimulation Drainage f/u: follow-up VEGF: vascular endothelial growth factor bFGF: basic fibroblast growth factor HVES: High Volt Electrical Stimulation LDM: lymph Drainage Massge LLLT: Low Level Laser therapy L/E: lower extremity LE: lymphedema MPT: mechanical pressure therapy MLD: Manual Lymph Drainage MNS: Measurements not standardized PCP or PC: pneumatic compression, pump PSWD: Pulsed Short Wave Diathermy QOL: quality of life QT: Qualified therapist noted ROM: Range of Motion RD: Radiation RCT: Randomized controlled trial SR: systematic review SI: Standardized intervention SLD: simplified/self-MLD SS: Small sample size TC: truncated cone formula used to figure volume Tx.= treatment TM: q__ cm:: tape measurements each __ cm UE: upper extremity US or UST: Ultrasound therapy Vod. MLD: Vodder MLD Vod. Var. MLD: a variation of the Vodder method Volumetry.: water displacement
S1934-1482(13)01082-4
DOI:
10.1016/j.pmrj.2013.09.008
Reference:
PMRJ 1133
To appear in:
PM&R
Received Date: 15 July 2013 Revised Date:
8 September 2013
Accepted Date: 11 September 2013
Please cite this article as: Rodrick JR, Poage E, Wanchai A, Stewart BR, Cormier JN, Armer JM, Complementary, Alternative, and Other Non-Complete Decongestive Therapy (CDT) Treatment Methods in the Management of Lymphedema: A Systematic Search and Review, PM&R (2013), doi: 10.1016/j.pmrj.2013.09.008. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Title: Complementary, Alternative, and Other Non-Complete Decongestive Therapy (CDT) Treatment Methods in the Management of Lymphedema: A Systematic Search and Review
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Julia R. Rodrick, OTR; CLT-LANA/WCC;1 Ellen Poage, MSN, MPH,NP-C,CLT-LANA;2 Ausanee Wanchai, RN, PhD,;3,4 Bob R Stewart. EdD;3 Janice N. Cormier, MD, MPH, FACS;5 Jane M Armer, RN, PhD, CLT, FAAN3
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(1) St. John’s Hospital Rehabilitation South, Springfield, IL. (2) Rehabilitation Associates of Naples, Naples, FL (3) University of Missouri Sinclair School of Nursing, Columbia, MO (4) Boromarajonani College of Nursing, Buddhachinaraj, Thailand (5) University of Texas MD Anderson Cancer Center, Houston, TX
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Authors’ Financial Disclosures: None
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Disclaimers This systematic review of contemporary peer-reviewed lymphedema literature (2004 to 2012) in the areas of complementary and alternative therapies was commissioned by the American Lymphedema Framework Project (ALFP) to evaluate the level of evidence in support of complementary and alternative therapies in the management of lymphedema. The objectives of the ALFP are to provide evidence of the best practice of lymphedema care, assist in establishing guidelines for the management of lymphedema, and to increase awareness of this condition in the U.S. and worldwide.
Source of Support: ALFP staff and reference librarian time were supported by industry donations to the ALFP. Authors donated their time in preparation of this manuscript.
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Corresponding Author (contact info): Jane M. Armer, PhD, RN, CLT, FAAN Professor at Sinclair School of Nursing, University of Missouri Director, Nursing Research, Ellis Fischel Cancer Center Contact address: Ellis Fischel Cancer Center, EFCC 408 DC 116.05 Columbia, MO, USA 65212 Telephone Number: 573-882-0287 E-mail Address: [email protected] (preferred contact)
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Running Head: Review of Non-CDT LE Treatment Methods Word Count: 8,458
Figures & Tables: 1 Figure, 2 Tables ** Named devices are for reference only. No authors participated in development of nor benefitted from the review of these devices. **
ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods Synopsis
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The goal of this paper is to provide expert guidance for health professionals in caring for patients with and at risk for lymphedema. It will summarize the current evidence in the literature and provide recommendations for management using complementary, alternative, and other non-complete decongestive therapies (CDT).
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Abstract
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Objectives: 1) Provide a critical analysis of the contemporary published research pertaining to complementary, alternative, and other non-Complete Decongestive Therapies (CDT) for treatment of lymphedema (LE); and 2) Provide practical applications of that evidence to improve care of patients with or at risk for LE.
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Type: This study meets the defining criteria as a systematic search and review since it includes varied study types. All studies that met the inclusion criteria were evaluated for weight of evidence and value.
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Literature Survey: The systematic search and review includes manuscripts published in the contemporary literature (2004-2012). Publications published from 2004-2011 were retrieved from 11 major medical indices using search terms for LE and management approaches. Literature archives were examined through 2012. Data extraction included study design, objectives pertaining to LE, number and characteristics of participants, interventions, and outcomes. Study strengths and weaknesses were summarized. Study evidence was categorized according to the Oncology Nursing Society Putting Evidence into Practice (PEP) level-of-evidence guidelines after achieving consensus among the authors. No authors participated in development of nor benefitted from the review of these modality methods or devices.
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Methodology: Data extraction from 85 studies was reviewed in four sub-categories: Botanical, Pharmaceutical, Physical Agent Modality (PAM), and Modalities of Contemporary Value (MCV). After review, 47 articles were excluded, leaving 16 articles on botanicals and pharmaceuticals and 22 articles for PAM/MCV. Pharmaceuticals were later excluded. The authors concluded Botanicals had generated sufficient studies to support a second, more specific systematic review; thus, Botanicals are reported elsewhere.
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Synthesis: It was found that limited high-level evidence was available for all categories. Wellconstructed randomized control trials (RCT) related specifically to LE were limited. Objective outcome measures over time were absent from several studies. Rationale for the use and benefits of the specific modality, as related to LE, was often anecdotal. Subject sizes were less than 50 for most studies.
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Conclusions: No interventions were ranked as “recommended for practice” based on the PEP guidelines. Two treatment modalities in three studies were ranked as “likely to be effective” in reducing LE, or in managing secondary LE complications. Consideration should be given that many of the PAM demonstrate long-standing support within the literature with broad parameters for therapeutic application and benefit for secondary conditions associated with LE. However, further investigation as to their individual, contributory value and the factors that contribute to their efficacy, specific to LE, have not been determined. It is also significant to mention that the majority of these studies focused on breast cancer-related lymphedema. Studies exploring treatment interventions for lymphedema-related vascular disorders (e.g., chronic venous insufficiency, congenital dysphasia, trauma) were sparse. Limitations of the literature support
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods the recommendations for future research to further examine the level of evidence in these modalities for LE management.
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Key Words: lymphedema, systematic review, complementary therapies, alternative therapies, non-CDT treatment modalities, physical agent modalities, hyperbaric oxygen therapy, diathermy, elastic taping, low level laser, aqua-therapy, ultrasound, High Volt Electrical Stimulation, Electrical stimulated lymphatic drainage (ESD), and acupuncture
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 51 Introduction
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Microcirculation describes the process by which the vasculature delivers nutrients and removes waste products from the tissues, as well as regulates blood flow and pressure, tissue perfusion, body temperature and tissue fluid (edema). Until recently, the focus of the microcirculation has been limited to the arterial and vascular components including the arterioles, capillaries, and venules. Through advancements in technology and research, it is now evident that the lymphatic system plays a major role in the dynamics of microcirculation, specifically in returning interstitial proteins back to the circulation and in the regulation of tissue fluid (1). Lymphedema (LE) occurs when there is a mechanical or metabolic failure affecting the lymphatic’s ability to complete this function. Mechanical failure is due to anatomical deficits of lymph nodes, vessel or tissue, either inherent (primary LE) or due to tissue trauma (secondary LE). Metabolic disorders can also progress to symptomatic LE (1, 2, 3, 4). LE can cause pathological changes to musculoskeletal structures, causing added dysfunction (1, 5). Qualified rehabilitation therapists can provide adjunctive therapy techniques to reduce swelling and pain, increase tissue and joint mobility, as well as improve muscle strength and stability. According to a study completed in 2008, the population prevalence of LE is estimated in the range of 1.3-1.4 per 1000, and the authors note that data collection regarding incidence and prevalence of LE is challenging and “relevant medical literature is scanty” (6). A research review for a patient-focused website offered that, beyond the estimated 10-40% incidence among breast cancer survivorship, the potential LE incidence related to other cancer surgeries (e.g., melanoma), conditions (e.g., cellulitis), and surgeries (e.g., hip replacements) may exceed 6.8 million patients in the U.S (7). LE has been shown to have significant impact on functional abilities, psychosocial issues and quality of life (8). Therefore, the need for early diagnosis and effective treatment is evident.
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Purpose/Exploring Treatment Options: Clinical evidence suggests that many conventional types of therapies for LE fall short in providing optimal functional outcomes and management. The most widely accepted treatment involves a multi-faceted form of intensive therapeutic intervention known as Complete Decongestive Therapy (CDT) (9). Manual lymph drainage (MLD), a component of CDT, is a specialized form of manual skin mobilization designed to facilitate lymphatic drainage, which aims to decongest lymphostatic regions in order to reduce the swelling and support tissue remodeling and healing. A customized application of layered (short-stretch) compression bandaging is utilized to protect the tissue from re-fill following MLD. Exercise contributes to the reduction of lymphostatic fluid trapped in the tissue through recruitment of muscle and joint “pumping.” Finally, skin care is used to promote healing of the compromised tissue (1). Goals of treatment are to improve the quality of life by reducing the swelling and improving functional mobility, to provide strategies to avoid recurrence and to prevent the development of infections (8, 10) .The successful use of this treatment method requires the skills of a trained therapist who demonstrates high competency. Today, CDT is one of the most recognized treatment methods by Best Practice standards (8, 10). Although considered effective, many insurance providers do not recognize or reimburse for the compression supplies required for this treatment. Patient tolerance to the compression is also an issue for many individuals and the treatment approach is time intensive, costly and limited by the number of qualified medical professionals available to perform CDT. Recognizing that today’s standard treatment is costly, time consuming, and poorly accepted by LE patients, those involved in the provision of care are continuingly seeking alternatives and adjuncts. The purpose of this paper is to review the scientific evidence of complementary, alternative, and other nonCDT treatment modalities in the management of LE.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 98
Methods A research librarian assisted with initial searches using the terms utilized in the Best Practice for the Management of Lymphoedema, 2006 (8) plus expanded terms, for all literature related to LE (2004-2009). The databases searched included: PubMed, CINAHL, the Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, PapersFirst, ProceedingsFirst, Worldcat, PEDro, National Guidelines Clearing House, ACP Journal Club, and DARE, as well as articles from searches by and the archives of the authors. Literature was sorted (Figure 1) and selected references were sent to ALFP research associates who reviewed abstracts to apply broad inclusion and exclusion criteria of LE/non-LE. ALFP authors (BRS, JNC, JMA) sorted relevant literature passing screen #1 into included and excluded articles and topical areas. Full articles were requested for these selected abstracts. Studies were grouped by topic and assigned to authors (EP, JR) for data extraction and quality assessment of the level of evidence using a consensus process. Articles from 2010-2012 were identified by the co-authors, screened, and included, as appropriate. The level of evidence for each study was assessed using the research grading system from the PEP® level of evidence guidelines (Table 1), a system judged to be both reliable and accessible (11, 12, 13). Each author rated all of the articles and the final rating was agreed upon by a consensus process based on this system (screen #2).
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No gray literature was included; non-refereed articles, abstracts, and dissertations were excluded. Eighty-five articles were extracted from the initial collection of 659 articles. Exclusion of 574 articles by the authors took place due to duplication, inability to obtain English translation, inadequate sample size, insufficient level of evidence due to study design, and failure to meet inclusion criteria. The remaining eighty-five articles were placed into four categories (screen #3) which included Botanical, Pharmaceutical, Physical Agent Modalities (PAM) and Modalities of Contemporary Value (MCV). Following further review, 47 articles were rejected, falling outside the systematic review inclusion criteria by definition of these four categories, by design or for lack of English translation. This left 16 articles for the topics of botanicals and pharmaceuticals and 22 total articles for the topics of PAM and MCV. The category of pharmaceuticals was excluded, as the authors recognized the definition of complementary or alternative treatments with regards to the prescription and distribution of medications was not applicable or within the scope of practice for most practicing LE therapists in the United States. It was determined by the authors that the category of Botanicals had generated a significant body of knowledge to support a second, more specific systematic review resulting in the evolution of two separate topic papers. The remaining 22 articles were further evaluated for PEP ranking, specific to their value as a clinically effective treatment for the reduction and management of secondary LE and/or the musculoskeletal complications as they related to LE. A detailed synopsis of the PAM and MCV studies is found in Table 2.
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Physical Agent Modalities
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For the purpose of this review, PAM was defined as those physically-applied agents that produce a bio-physiological response to tissue through the use of light, water, temperature, sound, electricity and/or mechanical device (14, 15). More specifically, a PAM can be defined as a form of energy and materials which may be applied to the body part to produce effect or desired bio-physiological change, as in the reduction of symptoms (15). These may be categorized as thermal, mechanical or electromagnetic. Some, well-documented musculoskeletal pathologies associated with LE include tissue hypoxia, lymphostatic arthropathy, tendinosis, and ligamentosis. These conditions can manifest as chronic wounds, fallen arches of the feet, plantar fasciitis, weak muscle pump and gait disturbances, pain, and
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods joints that are limited in active motion leading to poor fine/gross motor function (1, 2, 5, 16, 17). The PAM selected for review as adjunctive treatment methods which may offer positive effects for the management of these pathologies, as they relate to LE included ultrasound, electrically stimulated lymphatic drainage (ESD), high volt electrical stimulation (HVES), diathermy, low level laser therapy (LLLT), hyperbaric oxygen therapy (HBOT), elastic taping, acupuncture, and a sub-group categorized as Miscellaneous Modalities of Contemporary Value and Possible Benefit (MCV). These included Endermologie®, the Lymphease® Massage Unit, the Sun Ancon® Chi Machine® Aerobic Exercise, the Deep Oscillation device, the Tidar Method® of Aqua-Lymphatic Therapy, and Extracorporeal Shock wave therapy.
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Applying the principles of the PEP ranking system, it was found that interventions of ultrasound, ESD, HVES, short wave electromagnetic diathermy, acupuncture, and HBOT as treatment for LE were ranked as meeting level of evidence of ‘Effectiveness not established’ due to the studies’ small sample sizes, lack of RCT and/or statistically insignificant results. However, the rigor of two studies supporting low level laser therapy and one study which supported elastic taping for LE treatment led to these interventions being ranked as ‘Likely to be effective’ (screen #3).
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It is important to note that the use of these PAM requires the additional training necessary for the appropriate clinical application and consideration of precautions and contraindications for the safety of the patient.
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Ultrasound
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Therapeutic ultrasound (US) is classified as a PAM which employs acoustic energy. It is defined as high-frequency sound composed of alternating waves of compression and rarefaction. It can produce both thermal and non-thermal effects when applied to tissue. The greatest heat is produced in tissues with high ultrasound absorption coefficients, such as dense tissue, tendon, and bone. It can also affect deeper, dense tissue through non-thermal mechanical effects, including cavitation, micro-streaming, and acoustic streaming produced by continuous and pulsed ultrasound delivery. The hypothesis for using US for the treatment of LE explores its thermal effects on edema reduction by indirectly increasing ultrafiltration, thereby increasing circulation (15). Non-thermal and thermal US effects may also increase tissue extensibility (15) and contribute to a reduction of fibrosis, a characteristic of stage 2 and 3 LE. Current literature is sparse regarding the role of ultrasound as a therapeutic intervention for the reduction of LE swelling, but some studies exist.
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A systematic review by Oremus, et al (18) examined the effectiveness of conservative treatments for secondary LE, as well as harms, in studies published between 1990 and 2010. The researchers reviewed 36 English and 8 non-English RCT and an observational study with comparison groups of various treatment interventions, including ultrasound. They found there was limited follow-up beyond 6 months and inadequate study designs. Several failed to report precautions to avoid harm, based on general treatment protocols, with the proposed treatment intervention (18). One small, non-randomized study by Balzarini et al (19), investigated the use of ultrasound therapy for chronic arm LE, secondary to breast cancer treatment (BCT) without radiation. The experiment compared the efficacy of ultrasound (study group n=50) versus mechanical pressure therapy, using a pneumatic pump (control/comparison n=100) and combining both with compression sleeves (19). The control group received pneumatic compression for 6 hours a day for 5 days (30-40 mmHg) at 4 month intervals. The study group (n=50) received pulsed ultrasound for 30 minutes a day for 10 days at 2 W/cm2 at a 3MHz
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods frequency; 5-second cycle with 0.5 second time. Further, a randomized, comparison sample (n=50) used a compression sleeve between cycles.
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The results are inconclusive as the method of limb measurement is unclear. Nevertheless, initially the ultrasound group showed greater reduction, at one year follow-up, however, there was no statistical difference. Balzarini et al (19) noted that the members of the study group reported “greater softening of the arm, patient satisfaction by avoidance of an uncomfortable and constrictive device, better relief of osteomyofascial pain, greater scapulohumeral motion and less intercostobrachial pain-dysesthesia.“ Interestingly, ultrasound is sometimes applied to injured tissues in order to soften them, to increase tissue mobility and reduce pain (15).
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Oremus et al (18) concluded there is no specific evidence to support the use of US for LE. Although the outcomes of the study showed limited limb volume reduction, the benefits associated with the reduction of pain, the improvement of tissue pliability and joint mobility suggest ultrasound may provide an indirect therapeutic contribution to support return of limb function.
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Due to small sample sizes, non-randomized design of the studies and unclear measurement outcomes, this treatment is ranked as ‘effectiveness not established.’
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Electrically stimulated lymphatic drainage/ High Volt Electrical Stimulation
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Electrical stimulation (ES) is a PAM which uses various electrical wave forms, intensities, and polarities to treat musculoskeletal and neurological conditions. Evidence supports their use for pain management, wound healing, muscle strengthening, and even edema reduction for post surgical and traumatic swelling (20).
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Researchers have continued to explore ES’s diverse therapeutic potentials, using varied treatment parameters to target specific treatment objectives and benefits (14, 15).
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In the case of LE, it is hypothesized that ES alters vascular permeability to plasma proteins (12) and that, by stimulating muscle contraction, a pumping effect occurs, thereby facilitating lymphangion activity. A lymphangion is defined as a motor unit of lymphatic collector vessels which propels lymphatic fluid along drainage pathways (1).
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Kligman et al (21) performed a systematic review investigating the treatment options for women with breast cancer-related LE. In one small RCT (N=68), Bertilli et al (22) explored the use of a form of electrical stimulation for the treatment of LE. Patients were randomized into two groups. Group A wore a compression sleeve for six hours daily for nine weeks, while group B wore both the sleeve and received electrically stimulated lymphatic drainage (ESD). Eight electrodes were placed between the supraclavicular region and the wrist over “lymphatic stations or motor points” (22). A sequence of electrical impulses at 4.5 kHz was administered over 30 minutes. No other therapy was allowed over the 9-week intervention. A comparison of LE reduction was observed at two months and then at six months. The mean absolute difference was 12.6 versus 12.1 cm, respectively, for treatment and control group. At 6 months, (4 months after the end of treatment) the mean results were 12.4 cm versus 11.6 cm, respectively. Response rates at two months were 38.3% reduction with ESD and 29.4% without. None of these differences between groups were statistically significant (22).
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A more contemporary systematic review by Leal et al (23) included a RCT by Garcia et al (24, 25) which explored high volt electrical stimulation (HVES) as a treatment option for LE. HVES is defined as electrical stimulation using a monophasic twin-peak wave form with an output greater
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods than 150 volts (20). Leal et al (23) reported limited details regarding this RCT which explored the effectiveness of lymphatic drainage massage with compression (CDT), when combined with HVES. It included a sample size of 20 patients undergoing mastectomy. Weaknesses identified in both the Kligman et al (21) and Leal et al (23) systematic reviews are the generally small and underpowered sample size and the lack of blinding. Leal et al (23) himself concluded that larger randomized controlled studies are needed to demonstrate the efficacy of HVES as a valuable modality in the treatment of LE. The PEP assigned ranking for this intervention of ES based on the evidence reported in these two systematic reviews is ‘effectiveness not established.’
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Electromagnetic diathermy (shortwave)
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Electromagnetic diathermy (ED), also known as Short wave diathermy (SWD), is a PAM that generates a deep heating tissue response through the use of high-frequency electrical or electromagnetic current. “Different frequency ranges are used to achieve clinical effects in different tissue waves and at different depths” (15, p.388). The appeal of this form of PAM is that the potential treatment field is larger compared to conventional ultrasound. In SWD, the treated region is sandwiched between two condenser applicators with higher temperatures affecting deeper tissues.
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Electromagnetic diathermy has been investigated for its effects on lymphatic flow and venous circulation (15). Van der Veen et al (27) evaluated lymphatic and venous dynamics of 10 healthy subjects using lymphoscintigraphy and light reflection rheography of the legs. He concluded that, although diathermy had an accelerating effect on venous return, there was no increase in lymph flow (27). These finding were disputed by a pilot study by Mayrovitz et al (28) who assessed the use of diathermy on post-mastectomy arm LE and skin blood flow on seven patients. Using adjusted treatment protocols with an intensity of 12% of the maximum, initial edema volume decreased and skin blood profusion rates increased (28). Precautions and considerations regarding the safe use of diathermy are many (15).
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Since 2004, little research using Short wave diathermy (SWD) to treat LE was found. A single case study (26) indirectly connected the use of this modality to relief of complicating pathologies related to breast cancer. The study, however, was confounded with too many variables and this intervention of SWD is therefore ranked in this systematic review as ‘effectiveness not established.’
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Low Level Laser Therapy
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The use of low-level laser therapy (LLLT) as a therapeutic tool for the treatment of breast cancer-related LE has gained popularity in the United States since its approval by the FDA in 2007. The science supporting this modality has expanded since its introduction in the 1970s (29). The term ‘low-level laser or cold laser’ refers to the form and intensity of energy used to treat a long list of musculoskeletal disorders. Many labels are used to describe this modality, primarily due to manufacturer’s differentiation in terms and marketing strategies for similar devices. Low-level laser therapy uses energy within the spectrum of light to create biochemical changes to injured tissue, causing physiochemical effects following controlled exposure (29). It is hypothesized that this technique stimulates photochemical reactions in the cells creating an anti-inflammatory, analgesic, and regenerative effect (30).
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Clinical applications for LLLT include pain management, musculoskeletal symptoms relief, wound healing, and the management of inflammatory conditions such as repetitive strain disorders (20). Some effects of LLLT postulated to benefit LE include the softening of scar
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods tissue by affecting fibroblasts, and the reduction of interstitial fluid by stimulating lymphatic motoricity, lymphangiogenesis, and macrophage activity (20, 29, 31) LLLT can potentially unblock the lymph system and restore lymphatic flow, something not associated with Complete Decongestive Therapy (CDT) or pneumatic compression (31). Standard therapies for LE can be both time-consuming and burdensome to the patient, and some patients achieve only limited benefits even when they strictly adhere to therapy protocols (32).
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Low-level laser therapy has been studied for its potential benefits and ease of use, and a few recent studies have been conducted to evaluate the influence of LLLT on LE in breast cancer survivors. Six such studies were found to match the review inclusion criteria (32, 33, 34, 35, 36, 37). Two studies reviewed had 20 or fewer subjects (32, 34) and four (33, 35, 36, 37) included a larger number of subjects, greater than 20 but less than 75. In each of these studies, evaluating LLLT as an effective method of symptom relief was specific to patients with breast cancerrelated LE. While four studies (32, 34, 35, 36) had characteristics which alone would lead level of evidence to be assessed as ‘effectiveness not established’ due to small sample size, limited measurement assessment techniques, and variable dosing of LLLT, the rigorous designs and findings of studies by Kozanoglu et al (33) and Ahmed Omar et al (37) led to the rating of the LLLT intervention as ‘likely to be effective.’ Ahmed Omar et al (37) and Kozanoglu et al (33) are examined separately and in detail for they supported the ranking of ‘likely to be effective,’ while the other four will be discussed collectively prior to the conclusion.
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‘Likely to be effective’ was the quality assessment assigned to LLLT based on the study by Ahmed Omar et al (37), in which a prospective, double-blind, randomized placebo-controlled trial was conducted to investigate the effects of LLLT on limb volume reduction, shoulder mobility, and grip strength of the involved upper extremity. Participants included 50 women with LE (affected arm circumference greater than 2 cm and less than 8 cm from the unaffected arm) and a history of breast cancer surgery with complete or partial axillary lymph node dissection, with or without radiation or chemotherapy. Therapists and patients were blinded to the treatment that included sham or LLLT. The therapy cycle was three times a week for 12 weeks with a GaAs 904 nm Rian Corp laser with an energy dose of 1.5 J/cm2 per intervention. LLLT was delivered at three points on the antecubetal fossa and at seven points in the axilla continuously for 20 min with pulse. Each point was treated for two minutes. In addition to laser therapy, both groups were instructed on daily limb and movement therapies and wore a class II compression sleeve (40-60 mmHg). Measurements were taken at pre-treatment, 4 weeks, 8 weeks and 12 weeks. At completion, there was a significant 93% reduction in limb volume in the LLLT group compared to the control group. Although still a small study, the study design and measurements were of high quality; however, additional multisite studies with larger sample sizes are needed to establish efficacy.
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Kozanoglu et al. (33) conducted an earlier RCT with LLLT with a similar sample size (N=47) which contributed to LLLT’s ranking as ‘likely to be effective.’ Although not a double-blind study, LLLT was compared to another contemporary therapy, pneumatic compression (PC). A more homogeneous patient population was included in this study: all were status post modified radical mastectomy, axillary lymph node dissection, and radiation. The women were randomly allocated to pneumatic compression Group I (n=24) or LLLT Group II (n=23). Group I received 2 hours of pneumatic compression therapy at 60 mmHg pressure daily for 4 weeks and Group II was treated with 20 minutes of LLLT three times a week for 4 weeks. Laser therapy was administered using a Ga-As 904 nm Electronica Pagani IR 27/4 with an energy dose of 1.5 J/cm2 per intervention. LLLT was delivered at three points on the antecubetal fossa and at seven points in the axilla continuously for 20 min with pulse. Information pertaining to timed dose per point was not provided. As was the case in the Ahmed Omar et al study, (37) all
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods patients were given daily exercises and self care instruction, although no compression sleeves were assigned. Measurements included the difference between sum of the circumferences of affected and un-affected limbs, pain assessment using a visual analogue scale, grip strength, and shoulder ROM. The sum of the circumferences reduction in Group II was greater than that in Group I at post-treatment. Circumference reduction occurred in both groups at one, three, and six months (The statistical significant decrease (pretreatment Group I = 18.9 cm versus Group II=16.8 cm, Sum C) and post treatment Group (I=13.9 cm versus Group II=11.1cm). The centimeter decrease, however, was still significant at month 12 only in group II (p=0.004) (At 12 months Group 1= 18.2 cm versus Group II=11.4 cm). Although small, the strengths of this study include comparison of LLLT with a standard modality (pneumatic compression versus sham), homogeneous participants, and long-term follow-up after 1-, 3-, 6-, and 12 months.
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Evaluating the benefits of LLLT for LE or other physical problems such as pain, wound healing, or trauma-related swelling is often difficult to determine because of the variability of the laser dose, frequency and duration used in the research (38, 39, 40). A number of well-designed LLLT RCTs have used a laser dose that is insufficient to produce the response desired, with an end result of reporting no benefit from LLLT when a proper dose or duration may have shown benefit. (38, 40). For example, the designs of the four ‘effectiveness not established’ LLLT studies (32, 33, 34, 36) differed in laser type as well as dose and duration of the beam application, suggesting a need to compare two different laser types or doses. Ahmed Omar et al (37) thoughtfully referred to cellular studies to select the dose (1.5J/cm2) for his trial and described this in his research. Again, more attention needs to be placed on studying the effects of dose, frequency, pulse, non-pulse, wave length, watts and duration to get a better understanding of the practical application of LLLT prior to its use in mainstream medicine.
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A possible short-coming of all the studies presented in the LLLT discussion (32, 33, 34, 35, 36, 37) is that none of them identified funding sources or whether those with a potential conflict of interest had a stake in the treatment outcomes. Although the current LLLT studies (2004-2011) continue to include small sample sizes and most have non-uniform protocols, there appears to be a trend toward drawing the conclusion that arm volume reduction is achievable with LLLT (35, 37, 41, 59). These benefits occur whether LLLT is independent of compression (33, 34, 35, 36) or when it is used as an adjunctive therapy with compression (37) or with CDT (32). Benefits observed with LLLT include reduction in volume, improvement in self-reported symptoms like pain and limb function, increased quality of life, and softening of tissue (32, 35, 41).
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Hyperbaric Oxygen Therapy (HBOT)
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Hyperbaric oxygen therapy (HBOT) involves the breathing of pure oxygen while in a sealed chamber that has been pressurized at 1.5 to 3 times normal atmospheric pressure (42). In the early 1900s researchers speculated on the clinical benefits of HBOT. They observed that patients who suffered from secondary cardiac disease experienced improved symptoms when re-located from higher altitudes to accommodation at sea level. The clinical application of HBOT did not occur until the 1940’s when it was used to treat deep sea divers who suffered from decompression sickness (15). Curiosity about clinical applications of HBOT continue.
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Two contemporary studies by Gothard, et al (43, 44) reported outcomes using HBOT for patients with chronic arm LE and tissue fibrosis following radiotherapy for earlier breast cáncer. The 2004 non-randomized clinical trial (N=21) included subjects with ipsilateral arm LE, equal to or greater than 30%. The participants breathed 100% O2 at 2.4 ATA for 100 minutes on 30 occasions over 6 weeks. The follow-up assessments at 12 months involved 19 of the remaining subjects (n=19/21). A significant reduction in arm volume was noted compared to baseline
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods measures in 5 subjects. In addition, six of the 13 evaluable patients who gave consent experienced a greater than 25% improvement in 99TC nanocloid clearance rate from the ipsilateral forearm measured by quantitative lymphosintgraphy at 12 months (43). The lymphoscintigraphy findings support a strong argument for further investigation as to the longterm treatment benefits of HBOT for secondary LE.
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A phase II randomized trial (44) using a similar intervention design as the 2004 study further explored this modality’s value in the treatment of LE (44). The design included a subject group of 58 patients with arm volume differential greater than to or equal to 15% following axillary surgery were randomized into 2:1 ratio (38/20) study and control groups. Subjects breathed 100% O2 at 2.4 ATA for 100 minutes on 30 occasions over 6 weeks. Both established baseline measure, with follow-up at 12 months. At that time the median limb volume was 131.2% in the control group and 133.5% in the treatment group. Both trials by Gothard offer small sample sizes (2004: N=19 finished, 2010: N=58) and one lacks a randomized control group. Outcomes were similar for the groups in the RCT. Gothard (44) concluded, “No evidence has been found of a beneficial effect of HBOT in the treatment of arm lymphoedema following primary surgery and adjuvant radiotherapy for early breast cancer. There are no beneficial treatment effects of HBOT for this population.” This conclusion supports the PEP ranking of this intervention as ‘effectiveness not established.’ Nevertheless, advances in HBOT technology and further examination of treatment parameters may allow further examination into the application of HBOT for LE (42).
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Acupuncture
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No consensus was found on the precise definition of the acupuncture intervention modality, (45) due in part to the historically diverse styles and the transition of this modality of treatment from the Eastern to the Western world. Following a National Institutes of Health (NIH) consensus conference in 1997, the following general definition was accepted: “Acupuncture describes a family of procedures involving stimulation of anatomical locations on the skin by a variety of techniques. There are a variety of approaches to diagnosis and treatment in American acupuncture which incorporates medical traditions from China, Japan, Korea, and other countries” (46). More specifically, acupuncture or acupoint stimulation modalities are procedures of applied pressure or needle placement on or in the skin which creates levels of stimulation to improve health and/or reduce pain (46).
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A study by Alem et al (46) involving (n=29) women diagnosed with upper limb LE following unilateral breast cancer and mastectomy or segmentectomy with axillary node dissection explored acupuncture as a treatment for LE reduction. The subjects were treated once a week for 30-minute needle retention over six months. No other treatment intervention was given. The authors documented that, while arm circumference did not reduce after treatment, there were significant improvements in shoulder range of motion. Alem et al (46) also documented subjective reports of improved altered sensory issues and less density of the tissue was perceived.
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Further investigation into the secondary benefits beyond girth reduction may eventually demonstrate that acupuncture is ‘likely to be effective’ as an adjunct therapy option to improve post-operative mobility and pain; however, due to the small sample size, lack of randomization, and the lack of evidence to support direct benefit, this level of evidence was ranked as ‘effectiveness not established’. (46)
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A systematic review completed by Chao et al (47) explored the efficacy of acupoint stimulation (APS) for treatment of breast cancer treatment-associated morbidity. The term acupoint
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods stimulation was used to represent various methods of acupuncture including manual needling, needling combined with electric stimulation, wrist band, magnet, laser or heat applications (47) Twenty-six article were reviewed which assessed the application of acupoint stimulation on six conditions associated with cancer therapies. The conditions included vasomotor syndrome, chemotherapy-induced nausea, LE, post-operative pain, aromatase inhibitors-related joint pain, and leukopenia. Acupoint stimulation was applied with varied methods which included traditional, palpating acupressure, electroacupuncture, and magnetic acupressure. The review reported that only 35% of trials were of high quality based on the modified Jadad methodological quality scoring system. Chao et al (47) noted only one study which explored the direct effects of acupuncture on breast cancer-related LE. This was the Alem et al (46) study. It was stated that the study presented with a small sample size, lack of control, and lack of reported long-term outcomes which “increased doubts about the conclusions” (47), supporting the previous acupuncture ranking as ‘effectiveness not established.’
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Elastic-taping
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The use of taping and wrapping to support injured tissue is not a new concept. The most common taping technique recognized in the United States is traditional white athletic taping which are generic, rigid products that require a pre-tape application over the skin to prevent skin irritation. Generally, the irritation is from moisture entrapment, latex, and applied compression over the skin, muscle belly, and joints. Another widely recognized taping technique is McConnell® Taping which uses a cotton mesh tape under a rigid, high-adhesive tape to provide positioning for muscular re-education. It is recommended that the tape stay on the skin less than 18 hours to avoid skin irritation and constriction of muscle fibers which can increase pain. In general, most taping materials are designed to immobilize injured tissue for short periods of time in order to provide rest, prevent re-injury, and allow a level of lifestyle participation in spite of the injury. Controlling muscle motion and limb positioning to promote functional recovery is a foundational concept of rehabilitation basics (16, 48, 49).
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Kinesio-tec® (KMS,LLC, Albuquerque, NM.) tape, the predecessor to similar elastic tape products, was originally conceptualized by Dr. Kenso Kase in the early 1970’s. In 1998, Dr. Kase reported that the application of Kinesio tape in a distal to proximal direction of tension had a positive effect on peripheral blood flow for those with physical disorders, thereby supporting the healing continuum. This specialized tape is a latex-free, elastic product which is reported to allow early motion, while providing tissue correction and realignment, thus reducing pain and inflammation (50, 51). Elastic tape is also referred to as kinaesthetic tape, kinesiotape, lymph taping, or kinesthetic tape. All refer to the effect the tape produces or the sensation by which bodily position, weight, muscle tension, and movement are perceived (52). The application of elastic tape products has been proposed for “lymphatic correction,” claiming it lifts the superficial (initial lymph capillaries) lymphatic structures in the epidermis. This tape is hypothesized to decrease lymphostatic pressure while improving the function of deeper lymphatic vessels (50, 51). Shim et al (52) reported that, in addition to vascular effects (53), elastic taping also affected lymphatic flow in the hind leg of rabbit test subjects. Kase and Stockheimer (53) describe that the directional pull of the tape guides the lymphatic fluid in the desired direction of drainage. It is also reported that the tape can be applied to weak upper extremity musculature to enhance the strength of contraction and support lymphatic peristalsis. It is postulated that the tape can also be used as an alternative to standard compression methods to control the edema (54) although no strong analysis to support this claim was found. The randomized, double-blind, clinical trial (RCT) by Thelen et al (55) documented immediate improvement from impingement pain with pain-free shoulder abduction. These findings suggest elastic taping may be effective treatment
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods for associated symptoms for LE patients presenting with related issues of limited joint mobility, core weakness, or tissue restrictions.
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Evidence-based research to support the use of elastic taping as an adjunctive treatment for LE was limited to those discussing the direct effect of the tape for the treatment of secondary LE and the secondary musculoskeletal dysfunctions that may be associated with this condition. Three studies met the topic criteria and were ranked using the PEP card system. No study presented with a sample size greater than 50 (56, 57, 58).
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Elastic taping is ranked ‘likely to be effective’ due to the rigorous design and potential benefits reported in the single-blinded, randomized control trial (RCT) by Tsai et al (58) which posed the question of whether forms of elastic taping could replace bandaging in decongestive lymphatic therapy for breast-cancer-related LE. The RCT consisted of 41 patients with unilateral breastcancer-related LE of at least 3 months with the affected limb circumference being 2cm or greater in bilateral limb comparison. Participants were randomized to a decongestion lymphatic therapy (DLT) group using compression bandages and pneumatic compression (N=21) or a modified DLT group (N=20) using Kinesio tape (K-tape) instead of compression bandages, combined with pneumatic compression. Both groups were directed through a 20 minute exercise regimen following DLT and bandage/K-Tape application. Four evaluations were performed, including before and after the control period, after intervention and at a 3 month follow-up (59). Outcomes included objective limb size measurements using volumetrics and circumference, water composition of the upper extremity using an 8-pt. tactile-electrode impedance meter, LE-related symptoms using a visual analog scale (VAS), quality of life questionnaire (QLQ-C30 and QLQ-BR23), and patients' acceptance of the bandage or tape assessed by recorded length of time it was tolerated daily. There were no significant differences between the two groups in all outcome variables (p>0.05). Both groups presented with reduced volumetric and circumference measures, but acceptance scores were higher with the taping group (p<0.05) (58). The study results suggest that K-tape could potentially replace the bandages in DLT, and it could be an alternative choice for the breast-cancer-related LE patient with poor short-stretch bandage compliance after 1-month intervention (58).
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Bosman and Pillar (56) performed a non-blinded RCT of nine women treated for breast cancer. Of the nine, four (n=4) had developed seroma. The study examined the use of lymph taping as a treatment to reduce extracellular fluid (ECF) accumulation and improved a range of quality of life measures. Measurements included bio-impedance spectroscopy, active range of motion (AROM), and Quality of Life questionnaire (QOL). Two of the four subjects were taped over “watershed” regions (1) to facilitate fluid reduction while two were treated by “best practice” involving skin care and gentle exercises (56). The study subjects presented with a greater decrease of ECF, improved QOL, and functional AROM scores than others receiving best practice treatment. This small study offers a possible solution for truncal edemas associated with breast cancer treatment, an area where further studies are needed.
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A single case presentation by Pyszora and Krajnik (57) presents an interesting discussion for Kinesio taping in the palliative care setting. Objectives of treatment for this challenging patient population include “symptom management without decreasing the patient’s quality of life” (57). When patients are not able to tolerate compression garments, bandages or devices, the application of elastic taping may provide tissue tension relief with reduction of pain and alternative means of tissue fluid decongestion for truncal, genital, head and/or neck regions where compression is difficult to apply. Because of small size of the last two studies (56, 57), they support a ranking of ‘effectiveness not established’ for Kinesio taping in the palliative care setting.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods The research question to consider for future studies is whether the severity of fibrotic tissue presentation or LE stage alters outcomes, as limited tissue assessment data were made available in these studies. Also, is the tape effective in long-term management? In areas of the world where climate comfort is an issue, elastic taping may provide an alternative to the currently used layered compression bandages. Future research with more patients and controlled study designs are needed to provide higher levels of evidence to assist in the development of effective LE treatment protocols using this modality.
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Miscellaneous Modalities of Contemporary Value (MCV) and possible benefit
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Beyond the traditional modalities of treatment for LE are contemporary interventions which have been explored for their benefits in reducing the debilitating symptoms of LE. Modalities of contemporary value (MCV), as defined by the authors, include treatment interventions and/or devices which have been developed over the time span explored in the design of this systematic search and review and which have drawn the attention of the medical community for the evaluation of their effectiveness in the treatment of LE. These seven modalities included four device modalities, the Endermologie® system, the Lymphease® Massage Unit, the Sun Ancon® Chi Machine® Aerobic Exercise, and the Deep Oscillation device. Two other studies supporting therapeutic modalities of contemporary value were also explored. They included The Tidhar Method® of Aqua-Lymphatic Therapy and Extracorporeal Shock wave therapy.
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Please note that these MCV may require additional training for the appropriate application to support the patient’s plan of care without causing harm.
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The Endermologie® System. The primary use of The Endermologie® System is to reduce the appearance of cellulite. In its application for the treatment of LE, the system uses two motorized, cylinder-type rollers which are applied to the affected region, using lymphatic drainage patterns (59). Moseley et al. (59) conducted a comparative study of 34 women with unilateral breast cancer related arm LE with the established fibrotic induration for greater than one year. Two protocols, in two trials which differed in the lymphatic drainage patterns, time spent and the size of the treatment area were used for four days a week for four weeks (59). Following treatment, compression bandaging was applied to gain the “greatest reduction” and maintain the treatment’s benefits. Perometry was used to assess arm volume. Bio-impedance and tonometry were used to assess changes in tissue fluid and fibrosis of the arm and trunk. A 10-point likertscale was used to measure subjective improvements. Overall reductions in limb volume were noted in both trials (134mls; 18.3% p=0.000 and 185mls; 28% p=0.002) There was also improvement in the induration of some lymphatic territories and perceptions of improvements by study participants. The authors emphasized that the use of this device, along with the application of compression bandages, should be administered by a trained LE professional who shows competency in the concepts of lymphatic pathophysiology and who will monitor the patient’s treatment (59). A small sample size and lack of long-term follow-up were limitations of the study. In addition, the two protocols were not completed simultaneously, but rather the first protocol was altered after it was determined that the regimen did not provide adequate drainage to lymph static regions.
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The Lymphease® Massage Unit. A single pilot study by Moseley et al (60) reported the result of using a hand-held massage device called the Lymphease® Massage Unit. This device produces light intensity (32-45 Hz) vibration to lymphedematous tissue to manage the symptoms and reduce LE in the home setting. Thirty women with breast cancer-related LE for more than one year with a contralateral arm volume difference of 200 mls were recruited to participate. Out of the 30 initial subjects, 25 completed the study, with 21 completing 1-month
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods follow-up assessment. The instructions for using the device, based on the principles of manual lymph drainage, were documented with detail in a handout. Each subject was issued the handout and checked for competency of use prior to issue. The recommendation was for the device to be used for 25 minutes each evening for one month. Compliance was tracked using a log book. Measurements to assess the results included bio-impedance, tonometry, and perometry. Improvements in subjective symptoms were assessed using the likert Scale (60). After the initial treatment month, bio-impedance demonstrated a 43mls fluid loss to the affected arm initially, with reduction of 96mls in truncal fluid by four weeks. Improvements in subjective symptoms were documented, as well. Retention at four-week follow-up showed a significant increase in limb size and return of subjective symptoms; however, pain was still improved, as well as limb mobility (60). There was no mention of the use of compression garments during the trial. It would be of interest to explore the use of this device and the protocols of manual lymph drainage (MLD) in combination with compression garments used to retain the benefits of the treatment.
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The Sun Ancon® Chi. A third study was found by Moseley et al. (61) which explored the use of The Sun Ancon® Chi Machine® Aerobic Exerciser as a “new patient-focused, home-based therapy” to reduce chronic secondary leg LE. Thirty-three patients with a 95% compliance rate used the machine through a gradually-increasing regimen twice a day, in their homes. Perometry was used for measurement of volume reduction. Bio-impedance and tonometry were used to measure tissue density changes and lymphscintigraphy was used to evaluate lymph drainage in eight of the 33 subjects. The McGill Quality of Life Questionnaire was also administered to assess subjective perception of symptoms (61). After using the device for three weeks, the total leg volume reduction was reported as significant (p=0.001) and subjective perceptions of pain, tightness, heaviness, and skin dryness were improved. Post-treatment lymphscintigraphy demonstrated increased lymphatic transport function in only three of eight patients. A limitation of the study was the heterogeneity of the patients with respect to type of cancer and treatment which may alter lymph flow patterns and influence the degree to which lymph transport can recover (1). The results of the study suggested this device might show promise as an adjunct component for maintenance after reduction is achieved. Although objective measures were reliable, this small study lacked control and blinding.
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Deep Oscillation®. Jahr et al (62) completed an RCT to evaluate the possible benefits of Deep Oscillation® therapy for breast cancer treatment-related pain, swelling, and loss of function of 21 patients. Deep oscillation (DO) therapy is said to stimulate lymphatic flow to reduce edema (62), an action that is accomplished by an electrical device which applies an intermittent electrostatic field of low intensity to a target treatment area. The deep oscillation device is connected to the therapist and the patient simultaneously, producing a vibration to the tissue. There are specific protocols for the treatment, requiring the therapist to perform manual lymph drainage (MLD) with gloved hands to protect the skin from electrical charges (62). In the study, the designed intervention included 12 one-hour sessions over a 4-week period consisting of MLD for 15 minutes, supplemented by the DO device for an additional 45 minutes at varied intensity. This was followed by MLD only for an additional eight weeks. The control group received one to two treatment sessions per week of MLD alone. The patients were evaluated prior, mid-point, and at the conclusion of the study using reliable measures. The study group experienced reduced pain and breast volume reduction during the first four weeks, but not at follow-up at eight weeks. Joint mobility remained unchanged. In contrast, the control group had no improvement in pain reporting and demonstrated less mobility at eight weeks (62). There appears to be some inconsistency regarding the study’s design as the control group received fewer treatments for a shorter duration than the study group, making it difficult to compare outcomes. In summary, all four MCV device studies led to the intervention being ranked as
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods ‘effectiveness not established’ due to design, lack of strong objective measure, and/or small sample size.
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Aqua-Lymphatic Therapy (The Tidhar® Method). Exercise is one of the five basic treatment components of complete decongestive therapy (CDT). It is used in conjunction with compression to promote lymph drainage (1). Active muscle contraction supports re-absorption of lymph through superficial and deep lymphatic drainage pathways during the initial treatment phase of CDT. Long established is the knowledge that exercise will improve muscle tone, mobilize joint structures, and increase functional endurance (63). Although aqua therapies may be categorized as a type of exercise, the direct effects of water emersion produce biophysiological changes using energy, in the forms of heat, buoyancy, and resistant forces, which directly or indirectly reduce symptoms (12, 64,65), [thereby meeting the qualifications set by Cannon]. The concepts and principles of aqua-therapy are not new. “Healing water” as a form of therapeutic intervention has been considered throughout history and cultural experience (64). Aqua therapy has been supported in biblical references found in 2 Kings 5:14: “So he went down and dipped himself in the Jordan seven times, as the man of God had told him, and his flesh was restored and became clean like that of a young boy.”
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In recent years, researchers have looked at aquatic exercise to determine if it can control LErelated symptoms and whether it has an added benefit over standard exercise (66, 67). A single-blind RCT by Tidhar et al (68) involved 48 women with unilateral breast cancer-related LE (n=48) who had completed the intensive phase (initial treatment) of complex physical therapy (CPT). It explored whether Aqua-Lymphatic therapy (The Tidhar® Method) is a safe method to treat breast cancer-related LE and to determine if the addition of Aqua-Lymphatic therapy (ALT) to a phase two management protocol would improve adherence, control of limb volume, and quality of life (68). The exercise patterns of ALT are thought to utilize specific forces of the aquatic environment to promote strengthening and lymphatic decongestion (68). The control group (n=32) were directed to perform the self-management protocols set at the initiation of the study. The ALT group (n=16) met for weekly sessions of 45 minutes and were directed to follow self-management treatment between sessions. Circumference of the effected limb were taken and calculated before and after each session. Each patient was expected to log adherence. The study reported that ALT had a significant positive and immediate effect on limb volume and quality of life. It was also found to be safe and promoted a high adherence to a self-directed management program. Although the aquatic environment is not a comfortable venue for some, these outcomes support incorporating ALT into the plan of care for patients who struggle to manage LE. Some weakness of the study included a small sample size, limited adherence (75%) and no long-term effect at three months (68). Therefore, this intervention is currently ranked as ‘effectiveness not established.’
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Extracorporeal Shock Wave Therapy. Animal studies have suggested that Extracorporeal shock wave therapy can increase growth factors which may promote lymphangiogenesis. Kubo et al (69) reported that low-energy, short-wave treatments could promote lymphangiogenesis, thereby reducing secondary LE in a rabbit ear model. Serizawa et al (70) found that Extracorporeal Shock Wave Therapy promoted lymphangiogenesis in a rat model of secondary LE. To date, there has been limited correlation in human application, and further investigation exploring the differences between anatomical and physiological tissue healing characteristics between animal models and human subjects is needed. Because these studies have no direct evidence for effectively treating human subjects, a PEP ranking of ‘benefits balanced with harms’ is assigned this intervention.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods All the studies reviewed for this section create the anticipation for supportive, alternative treatment options for LE with further investigation.
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Summary
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LE is a chronic health condition resulting from the accumulation of protein-rich interstitial fluid due to an impairment of the lymphatic system. It can be progressive and resistant to treatment (1, 4, 5). If left untreated, LE can contribute to fibrotic tissue changes, infection, severe limitations in physical function, and activities of daily living, as well as dramatically impact quality of life. The standard of care for the treatment of LE is CDT (9) which can be labor intensive, cost prohibitive, and too-frequently unavailable due to the lack of medical personal qualified to treat it. It is important, therefore, to explore adjunctive treatment approaches, including modalities, which may enhance CDT. This systematic review of the literature identified new applications for traditional treatment modalities, as well as newer, more contemporary alternative treatments. The primary goal for treatment is to reduce edema; however, the secondary effects of LE such as musculoskeletal dysfunction and poor skin integrity should not be ignored as these effects can often significantly reduce quality of life and function for these patients. Alternative treatment modalities should be considered not only as stand-alone treatment, but also in the context of adjunctive therapies. This may require adjusting parameters and protocols for traditional application techniques to optimally support lymphatic function. There is a critical need for welldesigned, randomized trials to examine the broad range of alternative modalities to determine which ones may be the best for managing LE.
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The current body of published literature lacks sufficient quality to provide the evidence to support the majority of alternative treatment modalities to enhance current LE treatment protocols. The systematic search and review evaluated twenty-six studies which explored the use of PAM and modalities of contemporary value. No interventions reviewed met the PEP standards to be ‘recommended for practice’. Only three studies and two interventions (LLLT [33, 37] and kinesio taping combined with decongestive lymphatic therapy and pneumatic compression, with kinesio taping compared to compression bandaging [58]) met the PEP card systems criteria for ‘likely to be effective.’ The authors challenge the LE medical community to forge ahead in this area of more rigorous human research in alternative modalities to optimize patient outcomes. It is also encouraged to address the need to study effective treatment interventions for other types of lymphedema, beyond that which is related to breast cancer.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 15. Cameron MH. Physical Agents in Rehabilitation: From research to practice. 2nd ed. St. Louis: Saunders; 2003.
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16. Foldi E, Freud RE, Streicher E. Additive therapy in lymphedema of the lower extremities. National Lymphedema Network LymphLink. Apr-Jun 2000;12(2).
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19. Balzarini A, Pirovano C, Diazzi G, et al. Ultrasound therapy of chronic arm lymphedema after surgical treatment of breast cancer. Lymphology. 1993;26:128-134.
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21. Kligman L, Wong RK, Johnston M, Laetsch NS. The treatment of lymphedema related to breast cancer: a systematic review and evidence summary. Support. Care Cancer. Jun 2004;12(6):421-431.
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22. Bertelli G, Venturini M, Forno G, Macchiavello F, Dini D. Conservative treatment of postmastectomy lymphedema: a controlled, randomized trial.[see comment]. Ann. Oncol. 1991;2(8):575-578.
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24. Garcia LB, Guirro ECO. Efeitos da Estimulação de AltaVoltagem no Linfedema Pósmastectomia. Rev Bras Fisioter. 2005;9(2):243-248.
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25. Garcia LB, Guirro ECO, Montebello MIL. Avaliação de diferentes recursos fisioterapêuticos no controle do linfedema pós-mastectomia. Rev Bras Mastol. 2005;15(2):64-70.
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26. Johnson W, Draper DO. Increased range of motion and function in an individual with breast cancer and necrotizing fasciitis-manual therapy and pulsed short-wave diathermy treatment. Case Rep Med. 2010;2010.
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27. van der Veen P, Kempenaers F, Vermijlen S, et al. Electromagnetic diathermia: a lymphoscintigraphic and light reflection rheographic study of leg lymphatic and venous dynamics in healthy subjects. Lymphology. Mar 2000;33(1):12-18.
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28. Mayrovitz HN, Sims N, Macdonald J. Effects of Pulsed Radio Frequency Diathermy on Postmastectomy Arm Lymphedema and Skin Blood Flow: A pilot investigation. Lymphology. 2002;35(suppl):353-356.
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29. Tuner J, Hode L. The Laser Therapy Handbook. Grängesberg, Sweden: Prima Books AB; 2004.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 30. Wang G. Low Level Laser Therapy (LLLT): Technology assessment. Olympia, WA: Washington State Department of Labor and Industries: Office of the Medical Director; May 3 2004.
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31. Leal NF, Carrara HH, Vieira KF, Ferreira CH. Physiotherapy treatments for breast cancerrelated lymphedema: a literature review. Rev. Lat. Am. Enfermagem. Sep-Oct 2009;17(5):730-736.
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32. Dirican A, Andacoglu O, Johnson R, McGuire K, Mager L, Soran A. The short-term effects of low-level laser therapy in the management of breast-cancer-related lymphedema. Support. Care Cancer. 2011;19:685-690.
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33. Kozanoglu E, Basaran S, Paydas S, Sarpel T. Efficacy of pneumatic compression and lowlevel laser therapy in the treatment of postmastectomy lymphoedema: a randomized controlled trial. Clin. Rehabil. Feb 2009;23(2):117-124.
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34. Kaviani A, Fateh M, Yousefi Nooraie R, Alinaqi-zadeh MR, Ataie-Fashtami L. Low-level laser therapy in management of postmastectomy lymphedema. Lasers Med Sci. Jul 2006;21(2):90-94.
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35. Lau RWL, Cheing GLY. Managing postmastectomy lymphedema with low-level laser therapy. Photomedicine and Laser Surgery. Oct 2009;27(5):763-769.
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36. Maiya AG, Olivia ED, Dibya A. Effect of low energy laser therapy in the management of post-mastectomy lymphoedema. Physiotherapy Singapore. 2008;11:2-5.
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37. Ahmed Omar MT, Abd-El-Gayed Ebid A, El Morsy AM. Treatment of post-mastectomy lymphedema with laser therapy: double blind placebo control randomized study. J. Surg. Res. Jan 2011;165(1):82-90.
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38. Bjordal JM, Johnson MI, Iversen V, Aimbire F, Lopes-Martins RA. Low-level laser therapy in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo-controlled trials. Photomed Laser Surg. Apr 2006;24(2):158-168.
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39. Stergioulas A. Low-level laser treatment can reduce edema in second degree ankle sprains. J. Clin. Laser Med. Surg. Apr 2004;22(2):125-128.
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40. Pinheiro AL. Advances and perspectives on tissue repair and healing. Photomed Laser Surg. Dec 2009;27(6):833-836.
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41. Poage EG, Singer M, Armer JM, Poundall MD, Shellabarger MJ. Demystifying lymphedema: Development of the lymphedema putting evidence into practice card. Clin. J. Oncol. Nurs. 2008;12(6):951-964.
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42. Bennett MH, Feldmeier J, Hampson N, Smee R, Milross C. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2005(3):CD005005.
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43. Gothard L, Stanton A, MacLaren J, et al. Non-randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema and tissue fibrosis after radiotherapy for early breast cancer Radiother. Oncol. 2004;70(3):217-224.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 44. Gothard L, Haviland J, Bryson P, et al. Randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer. Radiother. Oncol. 2010;97(1):101-107.
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45. Rotchford JK, Kobrin LE. The importance of a modern and comprehensive definition for acupuncture in clinical research: preliminary perspectives. Med Acup. 2002;13(3):38-40.
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46. Alem M, Gurgel MS. Acupuncture in the rehabilitation of women after breast cancer surgery-a case series. Acupunct Med. Jun 2008;26(2):87-93.
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47. Chao LF, Zhang AL, Liu HE, Cheng MH, Lam HB, Lo SK. The efficacy of acupoint stimulation for the management of therapy-related adverse events in patients with breast cancer: a systematic review. Breast Cancer Res. Treat. Nov 2009;118(2):255-267.
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48. Greene WB. Rehabilitation. In: Greene WB, ed. Netter's Orthopaedics. 1st ed. Philadelphia, PA: Saunders; 2006:239-250.
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49. Kendall FP, McCreary EK, Provance PG. Posture: Alignment and Muscle Balance. Muscles: Testing and function. 4th ed. Baltimore, MD: Lippincott Williams & Wilkins; 1993.
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50. Cooper RA. Kinesio taping. In: Mackin E, Callahan A, Skirvan T, eds. Rehabilitation of the Hand and Upper Extremity. St. Louis, MO: Mosby Inc; 2002:1796-1807.
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51. Jeffs E. Treating breast cancer-related lymphoedema at the London Haven: clinical audit results. Eur. J. Oncol. Nurs. 2006;10(1):71-79.
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52. Shim JY, Lee HR, Lee DC. The use of elastic adhesive tape to promote lymphatic flow in the rabbit hind leg. Yonsei Med. J. 2003;44(6):1045-1052.
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53. Kase K, Stockheimer KR. Kinesio Taping for Lymphoedema and Chronic Swelling: Kinesio USA, LLC;2006.
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54. Stockheimer KR. Kinesio Taping & Lymphedema: Applied kinesio taping for lymphoedema/chronic swelling of the arm and/or breast after a mastectomy and axilla lymph node removal. Advance Healing. 2006;summer:22-23.
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55. Thelen MD, Dauber JA, Stoneman PD. The clinical efficacy of kinesio tape for shoulder pain: a randomized, double-blinded, clinical trial. J. Orthop. Sports Phys. Ther. Jul 2008;38(7):389-395.
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56. Bosman J, Piller N. Lymph taping and seroma formation post breast cancer. Journal of Lymphoedema. 2010;5(2):46-52.
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57. Pyszora A, Krajnik M. Is kinesio taping useful for advanced cancer lymphedema treatment? A case study. Advances in Palliative Medicine. 2010;9(4):141-144.
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58. Tsai HJ, Hung HC, Yang JL, Huang CS, Tsauo JY. Could Kinesio tape replace the bandage in decongestive lymphatic therapy for breast-cancer-related lymphedema? A pilot study. Support. Care Cancer. Nov 2009;17(11):1353-1360.
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59. Moseley AL, Esplin M, Piller NB, Douglass J. Endermologie (with and without compression bandaging)--a new treatment option for secondary arm lymphedema. Lymphology. Sep 2007;40(3):129-137.
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ACCEPTED MANUSCRIPT Review of Non-CDT LE Treatment Methods 60. Moseley A, Piller N, Heidenreich B, Douglass J. Pilot study of a handheld massage unit. Journal of Lymphoedema. 2009;4(1):24-28.
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61. Moseley AL, Piller N, Esterman A, Carati C. The Sun Ancon Chi Machine Aerobic Exerciser: a new patient focused, home based therapy for people with chronic secondary leg lymphedema. Lymphology. Jun 2004;37(2):53-61.
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62. Jahr S, Schoppe B, Reisshauer A. Effect of treatment with low-intensity and extremely lowfrequency electrostatic fields (Deep Oscillation) on breast tissue and pain in patients with secondary breast lymphoedema. J Rehabil Med. Aug 2008;40(8):645-650.
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63. Hayes SC, Rye S, Battistutta D, Newman B. Prevalence of upper-body symptoms following breast cancer and its relationship with upper-body function and lymphedema. Lymphology. Dec 2010;43(4):178-187.
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64. Becker BE, Cole AJ. Comprehensive Aquatic Therapy. Newton, MA: ButterworthHeinemann; 1997.
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65. Bates A, Hanson N. The Principles and Properties of Water. Aquatic Exercise Therapy. 1st ed. Philadelphia, PA: Saunders; 1996.
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66. Letellier M, Towers A, Cohen R. Aqualymphatic exercise as an alternative therapy for lymphedema management following breast cancer: A randomized controlled pilot study. J. Palliat. Care. 2008;10(3):215, 338.
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67. Tidhar D, Shimony A, Drouin J. Aqua lymphatic therapy for postsurgical breast cancer lymphedema. Rehabilitation Oncology. 2004;22(3):6-14.
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68. Tidhar D, Katz-Leurer M. Aqua lymphatic therapy in women who suffer from breast cancer treatment-related lymphedema: A randomized controlled study. Support. Care Cancer. 2010;18(3):383-392.
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69. Kubo M, Li TS, Kamota T, Ohshima M, Shirasawa B, Hamano K. Extracorporeal shock wave therapy ameliorates secondary lymphedema by promoting lymphangiogenesis. J. Vasc. Surg. Aug 2010;52(2):429-434.
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70. Serizawa F, Ito K, Matsubara M, Sato A, Shimokawa H, Satomi S. Extracorporeal shock wave therapy induces therapeutic lymphangiogenesis in a rat model of secondary lymphoedema. Eur. J. Vasc. Endovasc. Surg. Aug 2011;42(2):254-260.
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Figure 1. Literature Review Process
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Table 1. Putting Evidence into Practice (PEP) Weight-of-Evidence Classification Schema
Likely to be Effective
Effectiveness has been demonstrated by supportive evidence from a single rigorously conducted controlled trial, consistent supportive evidence from welldesigned controlled trials using small samples or guidelines developed from evidence and supported by expert opinion. Clinicians and patients should weigh the beneficial and harmful effects according to individual circumstances and priorities. Data currently are insufficient or are of inadequate quality.
RCTs, meta-analysis or systematic reviews with documented adverse effects in certain populations.
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Benefits Balance with harms
Examples -At least two multisite, wellconducted, randomized, controlled trials (RCTs) with at least 100 subjects -Panel of expert recommendation derived from explicit literature search strategy; includes thorough analysis; quality rating and synthesis of evidence -One well-conducted RCT with fewer than 100 patients or at one or more study sites -Guidelines developed by consensus or expert opinion without synthesis or quality rating.
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Description Effectiveness is demonstrated by strong evidence from rigorously designed studies, meta-analysis, or systematic reviews. Expected benefit exceeds harms.
SC
Weight of Evidence Category Recommended for Practice
Effectiveness not established
Lack of effectiveness is less well established than those listed under not recommended for practice.
Not Recommended For Practice
Ineffectiveness or harm clearly is demonstrated or cost or burden exceeds potential benefit.
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Effectiveness unlikely
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Adapted from information from Mitchell & Friese, 2011
-Well-conducted case control study or poorly controlled RCT -Conflicting evidence or statistically insignificant results. -Single RCT with at least 100 subjects that showed no benefit -No benefit and unacceptable toxicities found in observational or experimental studies. -No benefit or excess costs or burden from at least two multisite, well-conducted RCTs with at least 100 subjects. -Discouraged by expert recommendation derived from explicit literature search strategy; includes thorough analysis, quality rating and synthesis of evidence.
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Table 2. Summary Table of Physical Agent Modalities and Modalities of Contemporary Value Physical Agent Modalities PEP Ranking- Likely to be Effective Design
Sample
Intervention
LE Defined
Measurements
Omar et al, 2011
DBRCT; Placebo Evaluate effect of LLLT for LE symptoms
Female, BCRL N=50 (25/25)
Swelling >2cm but<8cm
-Circumference @ 6 points, -Jamr® strength test, mean of 3; dynamometer -AROM using standard plastic goniometer -Measurements taken @ pre-treatment, 4,8,&12 weeks
Kozanoglu et al, (2009).
RCT Evaluate effect of LLLT for LE management
N=47 (G1=24 PCP; G2=23 LLLT)
Therapy cycle 3x/wk x 12 Ga-As 904 nm, 5 mW spot size 0.2cm². average 1.5 J/cm² continuous for 20min./pulsed 50ns @frequency of 28000 Hz @ 3 pts. To anti-cubital fossa & 7 pts. Over axilla; daily limb and movement therapies. (5 times each set). compression sleeves (40-60 mmHg) G1= 2 hrs. PCP@ 60 mmHg; G2 = 20 mins. LLLT; 4wks (20 sessions).
Tsai et al,
SBRCT Efficacy of KT to replace bandages in DLT for BCRLE
41 women with uni-lateral BCRLE for at least 3 mos N=21 in standard decongestive lymphatic therapy (DLT group: & N=20 in the modified DLT (K tape) group.
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Unilateral BCRLE >=3 mos. 2 cm girth measure in one or more points
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Both groups received DLT (skin care, MLD, with 1 hr. pneumatic compression (PC) @ 40 mmHg + 20mins. of exercise. DLT used short stretch bandages. KT group used K-tape instead of bandages. - Each group was treated for 2 hours/session 5 sessions/wk in 4-week period.
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Calculated difference of >2cm in 3 of 7 anatomical UE points (effected vs non-effected)
Outcome Results/conclusion
Strength
Weakness
LLLT was found to be effective in reducing limb volume, increased limb mobility and grip strength in 93% of patients tested Conclusion: : LLLT may be useful modality in the treatment of LE
Double blinding & sham laser; All patients wore compression sleeves following treatment
Small sample size
Circumference reduced in both groups at 1,3 and 6 mos.; Decrease was still significant at 12 mos. only in LLLT group (p=0.004). Reduction G2 was greater than G1 at posttreatment. Conclusion: LLLT may be useful modality in the treatment of LE No significant difference between groups in all outcome variables (p>0.05) - DLT=excess limb size, water composition, and circumference of lower part of upper arm significantly reduced. KT= only excess circumference of arm & water composition significantly reduced. The acceptance of K-tape was better than DLT( bandage). Patients reported using the Ktape longer, with a greater ease of use, increased comfort, convenience. Conclusion: The K-tape could replace the bandage in DLT for BCRLE
Comparative results over 12 mos.
Lacks control group; small sample; “pain” was not well defined, patients with functional mobility (pain with motion) were excluded. Small sample size - Lack of longterm follow-up
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Author
-Difference between sum of circumferences of affected vs unaffected limbs; -Pain Visual Analogue Scale -dynamometer measure grip strength
-Volumetric Water displacement circum. measurement - An eight-polar tactileelectrode impedance meter - Visual Analogue Scale to measure lymphedema-related symptoms - The EORTC QLQ-C30 and QLQ-BR23 to measure health-related quality of life - A Visual Analogue Scale to measure patients’ acceptance to the bandage or tape
Physical Agent Modalities PEP Ranking-Effectiveness not established
Blinding sample into study groups
ACCEPTED MANUSCRIPT Design
Sample
Intervention
LE Defined
Measurements
Oremus et al, (2012)
SR examined the efficacy of conservative tx. methods for secondary LE, as well as harms related to treatment
36 English and 8 non-English RCT or comparison studies from 1990-Jan. 19, 2010 reporting efficacy data
1 Applicable to this SR: (Balzarini et al. 1993) Comparison pilot study for ultrasound therapy for chronic arm BCRLE without radiation. Compared the efficacy of US vs. MPT using a pneumatic pump (control/comparison n=100) and combining both with compression sleeves. The control group received pneumatic compression for 6 hrs/day x 5 days (30-40 mmHg) at 4 month intervals. The study group (n=50) received pulsed ultrasound for 30 minutes/day x10 days at 2 W/cm2 at a 3MHz frequency; 5 second cycle with 0.5 second time. Further, a randomized, comparison sample (n=50) used a compression sleeve between cycles. (Balzarini et al,1993)
LE quantified % >=6.5 slight >=12% moderate .>=13% severe. (Balzarini et al,1993)
Significant variation in assessment methods.
Leal et al
SR present/
18 articles,
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10 RCT measured the effect of therapy BCRLE included compression garments, MLD, CDT, CP, ESD and medical therapies.
1 Applicable to this SR: (Bertelli et al, 1991) N=74 ESD +compression garment vs. compression garment used alone. Both groups wore a standard elastic sleeve for 6 h/day/6 mos. ESD group= 8 electrodes placed between the supraclavicular region and the wrist A sequence of electrical impulses at 4.5 kHz was administered over 30 minutes. No other treatment for lymphedema was per-mitted for duration of trial.
No specific definition
1 Applicable to this SR:
No specific
EP
SR to provide evidence summary regarding treatment options for woman with BCRLE
Favorable reporting that study group reported *“greater softening of the arm, *patient satisfaction by avoidance of an uncomfortable and constrictive device, *better relief of osteo-myofascial pain, greater scapulohumeral motion and less intercostobrachial paindysesthesia. (Balzarini et al,1993)
Significant variation in assessment methods.
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Outcome Results/conclusion
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Author
Initially, the ultrasound group showed greater reduction but, at 1 year follow up, there was no statistical difference. Conclusion: No specific evidence to support the use of US for lymphedema volume reduction but showed beneficial effects for related functional conditions (Oremus et al, 2012)
Conclusion: Compression therapy and MLD may improve lymphedema, but further studies are needed. Compression garments should be worn daily /removed at bedtime. No current evidence to support the use of medical therapies for lymphedema. No statistically significant differences between the 2 groups specific to ESD ( Bertelli et al, 1991)
Strength
Weakness
Control group comparison *Qualifying % of LE per specific measure (6.5=slight, 712.5=mod >13=severe Girth % was consistently measured *Duration/ effects over 1 year *Scoring of edema “firmness” is defined. *Small dropout rate (reoccurrence or poor compliance) *Similar patient profiles (Balzarini et al,1993)
Small samples;
Varied measures reflected standardized measurement Examined potential harms (Oremus et al, 2012) There was a formal external review process to validate the relevance of the opinions. Reviewers were oncologists, nurses and physiotherapists
No double blinded studies of weighted evidence.
Studies were small/underpowered, ranged from 25 to 104 patients. None of these studies used blinded outcome assessments; QOL not assessed
More and better designed, larger trials are needed. Need to establish consistency in defining LE (Kligman, et al 2004)
Significant variation
Both Tx. groups reduced
7/18 RCT, Cohort
No uniformity
ACCEPTED MANUSCRIPT examined the results of varies physio-therapy modalities used for treating lymphedema, Data was collected from textbooks & LILACS, PubMed & SciELO databases from 19512009
inclusion of varied design included DBRCT, RCT, Cohort studies and case presentations which addressed physiotherapy approaches for LE Tx.
(Garcia et al., 2005) Randomized study N=20 BCRLE; Analysis of the effects of HVES and MLD with compression sleeves vs. MLD with compression sleeves alone.
Johnson & Draper, 2010
Single Case study
N=1 female
Pulsed short-wave diathermy (PSWD) 48 watts/20 mins. 4-5 ̊C @ 35 cm. depth over painful, restricted LE tissue areas 3x/wk3, then 1-2x/wk 3
No specific definition
Kaviani et al (2006).
RCT, double blinding
N=11 women with unilateral post mastectomy lymphedema N=6 laser group; N=5 placebo
Study group rec’d LLLT over the five points applied to the axillary areas 3x/wk /3 weeks. After 8-week interval,Tx repeated for 3-week (18 Tx). GA-As laser device wavelength 890 nm over arm and axilla - Patients in the sham group received sham irradiation under strictly controlled double-blinded conditions.
No specific definition
Lau,et al 2009.
Prospective, single blinded RCT LLLT, no concurrent treatment.
N=21 female, unilateral BCRLE with radiation therapy. Random allocation study group n= 11; Control n=10
LLLT for four weeks (3x/week) study group. Control group= no therapy LLLT to axillary region alone for 20 min. Comby 3 Terza Serie, Model D; ASA S.r.l., Vicenza, Italy.
No specific definition
in assessment methods.
definition
“lymphedema perimeters and Severity” without any significant difference in the 2 groups. Volume reduction was greater with the use of HVES. (Garcia et al., 2005) Exercise modes and PC may not be beneficial without MLD and compression. MLD alone is not effective for lymphedema treatment unless compression and exercises are combined. Conclusion: The use of MLD/CDT with HVES are effective & offers greatest reduction of lymphedema. Pt. experienced increased ROM, reduced pain & improved function after Tx. Individuals with cancer ,those have experienced severe infection, post radiation pain or scarring restriction may have significant improvement in ROM, in quality of life, & functional outcomes using PSWD; Conclusion: No direct benefit for lymphedema reduction All patients completed 10 days of treatment without any adverse reactions. - The study group showed significant improvement in the reduction in pain and limb Conclusion: Need for further study
sample sizes were >130
stated to determined definition for LE, Lacks clarity in assessment tools used.
Established Tx. Parameters
Single case study. Data insufficient evidence, statistically insignificant
Adherence to treatment is 100% Well designed RCT
Lack of longterm followup; Small sample size
Only 1 intervention. The result was consistent with previous studies which showed a progressive
small sample size, short follow up, singleblinded study. They
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Other modalities examined included PC, MDT/CDT, LLLT, and exercise (Leal et al 2009)
Goniometer MNS= tissue changes
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A tape measure to measure limb circumference. Subjective symptoms, such as pain, range of motion of the arm, heaviness of affected limb, and patient’s desire to continue with their treatment were expressed by patients using visual analogue scale
Volumetry: minimum arm volume Tonometry: tissue resistance. Disabilities of Arm, Shldr. , Hand questionnaire
Reduction in arm volume and increased tissue softening in LLLT group only. Significant difference between groups (p<0.05).Laser group: 16% arm volume reduction. At 4 week follow up: 28%
ACCEPTED MANUSCRIPT (DASH). Outcome measures were assessed before and after the treatment period and week follow
Gothard,
1 group control design/ case study
N=21 BCRL patients w/tissue fibrosis s/p radiotherapy
Hyperbaric oxygen therapy (HBOT): Patients breathed 100% oxygen at 2.4 ATA for 100 mins. In a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks.
specific to secondary conditions of LE symptom- logy
58 subjects with axillary dissection and RD
52/58 patients) were randomized in a 2:1 ratio to HBOT (n=38) or to best standard care (n=20). The HBOT group breathed 100% oxygen at 2.4 atmospheres absolute for 100 min on 30 occasions over 6 weeks
≥ 15% increase in arm volume after supraclavicular ± axillary RD
Limb volume using perometer; Lymphoscintigraphy; EORTC core questionnaire QLQ-C30) and BR23 measure quality of life.MRI to SC fossa, axilla and brachial plexus to exclude cancer recurrence, clinical assessment of subcutaneous induration, Photos
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A non-randomised phase II study to examine effect of hyperbaric oxygen (HBO) therapy on arm LE following adjuvant radiotherapy for early BC
Ipsilateral limb volume shown as a percentage of contra-lateral limb volume. Fractional removal rate of radioisotopic tracer from the arm,extracellular water content, patient selfassessments and UK SF-36 Health Survey Questionnaire.
Alem, et al 2008
Case controlled study to examine the effects of acupuncture as a therapeutic Tx. intervention for improving motor function, reduce lymphedema and improve to sensory symptoms of heaviness and tissue tightness in the affected UE of woman undergoing
29 women undergone unilateral breast cancer surgery (mastectomy or segmentectomy with axillary dissection), presenting with lymphedema (N=23) and/or a decrease in movement amplitude of upper limb (age ranged from 43 to
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Acupuncture (APS) was performed by an acupuncture specialist/ PT once a week with a 30 minute needle retention time for six months; total Tx. N=24 Pt. rec’d 11 stainless steel needle placements; points based on the theory of Traditional Chinese Medicine for lymphedema reduction, altered sensation, increasing blood flow, and gynecological
+2cm UE circumference comparison with a differential @ 3 different anatomical points, wrist to olecranon process (10 cm above and below)
reduction. LLLT was effective for the management of PMLE and the effects were maintained at 4 week follow up. Conclusion: Recommend LLLT be used in conjunction with CDT. (WHY?) Significantly reduced arm volume at 12 mos follow-up, compared to baseline (p=0.005) Six of 13 evaluable patients experienced a >25% improvement in 99TC nanocolloid clearance rate from the ipsilateral forearm measure by quantitative lymphoscintgraphy at 12 months. No significant improvements noted in QOL. Conclusion: Need for further study
reduction of average arm volume after cessation of LLLT (Piller, 1998; Kaviani, 006; Carati, 2003)
(91.4%) patients with baseline assessments, (86.8%) @ 12 mos assessment; Median volume of ipsilateral limb at baseline was 133.5% (IQR 126.0-152.3%) in the control group, and 135.5% (IQR 126.5-146.0%) in the treatment group. @ 12 mos.after baseline the median (IQR) volume of ipsilateral limb was 131.2% (IQR 122.7151.5%) in the control group and 133.5% (IQR 122.3144.9%) in the Tx. group treatment group.
Well designed study with structured intervention protocols. Objective, reliable measure; 12 mos follow-up with high retention
Small sample,
Strict patient compliance, no other treatment variable
Lack of information about previous treatments correct
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Scanning head. Three infrared laser heads sources with one emitting at a wavelength of 808nm and two emitting at a wavelength of 905nm. (2J/cm2).
Goniometry to evaluate shoulder range of motion (ROM) - A flexible metric tape to measure Circumferences of arm, forearm, and wrist: One , Three and 6 months after tx.
Conclusion: No evidence for beneficial effect - ROM of shoulder, degree of lymphedema, and sense of heaviness and tightness in the affected limb were significantly improved at the end of treatment (p< 0.001, p = 0.016, p < 0.001). - No improvement in the difference of circumferences of arm, forearm, and wrist. Conclusion: Acupuncture may help to improve ROM of shoulder, symptoms of heaviness, and tightness in
Reliable instruments Compliance with treatment protocols 100% more than one study site. Well designed case/ control study
Reliable constructs
recommend the control group get sham treatment to rule out placebo effect. Lack of randomized control group Small sample size Cost may be prohibitive
Lacks blinding or randomized design
Lack of a control group Small sample size Lack of longterm observation
ACCEPTED MANUSCRIPT arm, and degree of lymphedema. No influence for direct girth reduction
26 studies; 18 English studies 8 Chinese studies *Inclusion : adults diagnosed with B/C at any stage of Tx.(surgery, radio-therapy, chemo-therapy, hormonal therapy, or palliative treatment, and with treatmentinduced adverse effects).
Varied . Traditional Acupuncture - Acupressure - Electro-acupuncture - The use of magnetic device on acupuncture points
Specific to the Alem et al ,2008 study: +2cm UE circumference comparison with a differential using 3 different anatomical points (wrist to olecranon process;10 cm above and below)
- A questionnaire with a visual analogue scale (VAS) to measure perceived heaviness and tightness in the arm - Palpation and visual inspection to classify degree of lymphedema
Varied symptom scores and general health status outcomes
RCT to investigate the potential of lymph taping (Elastic taping) to combat seroma formation
9 subjects
One day post-taping was applied every five days to the study group. The tape was cut into three strips and applied over the watershed between the posterior thoracic skin territories & from spine to axilla, in skin stretch positioning. The participants were encouraged to perform early arm motion, including abduction of the arm at 90° and “arm raising”. Participants were also encouraged to resume their normal daily activities.
Specific to secondary conditions of LE symptom- logy
Anna Pyszora, Małgorzata Krajnik, 2010
Single case study of an advanced cancer patient whose painful skin tension, caused by LE was successfully reduced with the use of Kinesio Taping. (elastic tape method)
Conventional methods of CDT but, due to tissue sensitivity, Kinesio tape was used as an alternative to compression wrap
A lateral anterior lower leg taping application was used. The “’fan tape” anchored at the lateral aspect of the knee with no tension. The tails of the tape were applied to the anterior, medial and posterior aspects of the lower leg with 15–25% tension The tapes were left on the patient’s skin for the next three days
specific to secondary conditions of LE symptom- logy
Bio-impedance spectroscopy of the breast was used to assess intra and extracellular fluid levels in each of the four quadrants of the breast. Measurements were repeated at five, nine and 16 days.
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Jadad scale; 35% of the studies selected were determined high quality but only one related to lymphedema treatment (see Alem et al ). The results of the study were favorable for Acupoint stimuli for secondary musculoskeletal and sensory deficits related to lymphedema. The article referenced reported improved mobility and relief of sensory discomfort but not in circumference.
Both English and Chinese published articles were included for reviewing - Quality of study was evaluated by using a modified Jadad scale
Only 35% of trials were determined as high quality. -*Only one study in this review examined the effect of acupuncture on breast cancerrelated lymphedema.
The extracellular fluid value at t16 was 0.1037 ± 0.0324 (15.3 % decrease) over t1 in the lymph taping group and 0.1066 ± 0.0227 (4.6 % decrease) in the current best practice group (n=4 in each group).After 16 days of treatment, substantial changes were found in burning sensations, tightness and heaviness in favor of the lymph taping group. In particular, pain perception in the lymph taping group improved. Conclusions: lymph taping has the ability to reduce extracellular fluid accumulation and improve a range of quality of life measures. The patient claimed that the oedema, pain and feeling of heaviness had decrease. Conclusion: The study suggests that forms of elastic Taping could replace the bandage in CDT, and could be an alternative choice for LE patients with poor short-stretch bandage compliance. The authors emphasized the need for more clinical trials evaluating the effectiveness of
Strong measures, subjects followed over 16 days; Standard tape application
Small sample
patient compliance
Limited sample size
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mastectomy or segmentectomy with axillary dissection associated with BC A literature review of the efficacy of Acupoint stim. (APS) for BCRL and adverse effects
No objective measure reported
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Kinesio (elastic) Taping.
Modalities of Contemporary Value PEP Ranking-Effectiveness not established Sample
Intervention
LE Defined
Measurements
Outcome Results/conclusion
Moseley, et al (2007).
Comparative study with two groups to explore effectacy of a new treatment option for secondary UE LE
34 women with unilateral UE BCRLE with the presence of established fibrotic induration (>1 yr) 24 women in the first protocol 10 women in the second protocol
Volume difference >200mls determined by perometry
Moseley et al, (2009)
One Group Study to explore the use of the HandHeld (Lymphease massage unit as an effective tool for the management of LE in the home.
26 women with BCRLE of the UE
Endermologie system applied over the same period (4 day/wk x4 wks Using the same measurement schedule, variation in protocol II time spent treating clearing trunk adjacent to the swollen limb Used larger treatment head After each treatment session, compression bandaging was applied to arm. Use of Hand held unit for a total of 25 mins. Every evening with specific MLD protocols for 1 mos.
Multi-frequency (5-500 Hz) bio-impedance to measure arm & truncal fluid Opto-electronic perometry to measure arm volume - Tonometry to measure fibrotic induration in the of arm & anterior thorax. A 10 point Likert Scale to rate pt. subjective complaints, such as pain, heaviness, tightness, hardness, ROM , and limb size Bioimpedance to measure arm and truncal volume - Perometer to measure total arm volume - Tonometry to measure tissue compliance - Subjective arm symptoms
Moseley, et al (2004).
An experimental study with one group
N=33 patients with secondary lymphedema of the LE, related to CA surgery with various type of CA, such as bowel, cervical, reproductive, prostate, and melanoma cancer (age ranged 3988 years).
Both protocols showed overall reductions in limb volume, limb fluid, and truncal fluid, improvements in fibrotic induration in some lymphatic territories, and improvements in subject reporting of heaviness, tightness, tissue hardness, and limb size. Conclusion: The self-massage and compression are helpful for patients with secondary lymphedema related to breast cancer. @ 4 weeks S/P initial Tx. reduction in arm fluid of 51 ml. - Participants who previously c/o irradiation, or who were moderately compliant in conservative Tx., experienced significant reductions in arm fluid volume (p = 0.015, 0.018, and 0.019, respectively). -improvements in limb size (p = 0.007) and range of movement (p = 0.000). - Conclusion: The device may help to maintain their arm lymphedema @ home. There was a significant total leg volume reduction over 3 weeks (p = 0.001), and at 1 month follow-up leg volume remained significant lower than pretreatment level (p = 0.032). - Bio-impedance showed a significant fluid reduction in the affected leg(s) at 3 weeks of treatment (p = 0.021). - There were significant improvements in subjective leg symptoms, including pain, tightness, heaviness, skin dryness, and perceived leg size at 3 weeks. - No significance differences were found in the leg tissues as
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Participants used the Sun Ancon Chi Machine Aerobic Exerciser in their own home, morning and evening for three weeks adhering to the following regimens: day 1-2: 5-min per session, day 3-7: 8min per session, day 821: 12-min per session.
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- Perometer to measure limb volume - InBody 3.0 system to measure body biopedance - Tonometry measures tissure resistance to pressure - Lymphscintigraphy - McGill Quality of life Questionnaire to measure: pain, heaviness, tightness, pins, and needles, cramping, burning sensations, and perceived leg size
Strength
Weakness
Validated techniques /measures
Unequal # of pts. /group. Small sample size No long-term follow-up Design flaw in protocol I
Reliable measures
Lack of a control group Small sample size Adverse effects from handheld device use included headache, discomfort, heavy to use.
Overall 95% compliance rate with the regime.
The most commonly reported side effects were knee pain, dizziness, and neck pain Caution should be noted for patients with pre-existing joint/bone problems. - Lack of a control group - Lack of longterm evaluation
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Tidhar et al (2009)
RCT to examine safe efficacy of Aqua-lymphatic Therapy (ALT);explore improvements in adherence, limb volume & QOL between selfmanaged Tx. group vs. ALT group *The therapist who performed outcome assessment was blinded to group allocation
N=48 women with BCRL (age ranged 31-81 years) n=16 women in the aqua lymphatic therapy (ALT) group n=32 women in the control group
The study group joined a weekly session of ALT for 3 months in addition to self-management therapy. Each session lasts 45 minutes. - The control group was instructed to continue performing as usual, selfdirected management .
DX of breast LE by palpation of the effected breast Photo and 3D measure
Pre-test measure of Relative volume (severity of LE) LRV= EVx100 Volume of contra-lateral limb; ULL27 to measure QOL; Assessment ; body weight (scale)
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- The treatment group 12 sessions (MLD) supplemented by deep Oscillation for 4 weeks (23 sessions per week). 15 mins. MLD, 45 mins. DO to the breast, chest wall and arm consisting of 100 HZ for 30 MIN & 30 HZ for 15 MIN. Then the patients returned to manual lymphatic drainage alone for the next 8 weeks. - The control group received MLD alone, consisting of 1 or 2 of 3045-min/ week.
VAS to - Breast edema documented by photos. - Functional testing to assess ROM shoulder and cervical spine. - Analysis of breast volume using 3D measuring system (called Scan Mobile®). Done before the 4 week intervention, at completion then 8 weeks. (evals: 3 times)
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Breast LE and pain N=21 patients BCRL with SLND and 1 had melanoma/tissue excision with ax node dissection; n=11 in treatment group n=12 in control group
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measured by tonometry. - Of eight participants who underwent lymphscintigraphy, three participants showed increased lymphatic transport function in the post-treatment scan.. Conclusion: The Sun Ancon Chi Machine Aerobic Exerciser is an effective adjunct therapy that can be used in the patient’s own home. - Treatment group significantly reduced pain & breast volume @ 4 weeks after treatment (p < 0.05), not @ follow-up at 8 weeks. - Control group: no change in pain scores. Objective confirmation by breast 3D measuring treatment group only (of symptom relief of swelling) at follow-up the difference lost significance. - Both group subjectively reported reduction of swelling. - The range of mobility in treatment group was unchanged, whereas there was a significant reduction in shoulder mobility in the control group (p < 0.05). Conclusion: Deep Oscillation ® supplementary to MLD MAY relieve pain and reduce swelling in patients with breast cancerrelated lymphedema ALT had a positive significant immediate effect of limb volume but no long-term effect (at 3 months follow-up) was found. - The adherence rate to ALT was significantly higher than the adherence to self-management therapy. - Quality of life improved in the ALT group. Conclusion: ALT was found to be a safe method, with high adherence for treating breast cancer-related lymphedema.
- Water displacement to measure limb volume - The Upper Limb lymphedema Questionnaire (ULL27) to measure quality of life - A self-reported diary to measure adherence, Body weight
Using blocked RCT
- Small sample size - Number of treatment sessions per week in the treatment group is higher than those in the control group. This is not completely clear: (The control group received MLD 1-2 tx per week or “usual care.”
RCT
Unequal of number of sample in each group - Small sample size - The clinical physical therapist, who performed the limb volume assessment at the first and the last sessions in the pool were not blinded to the group allocation. - Low adherence for completing the
ACCEPTED MANUSCRIPT adherence diaries (75%). Unclear as to (self-managed control group methods used
Modalities of Contemporary Value
Sample
Intervention
LE Defined
Comparative study for the efficacy of low energy extracorporeal shock wave therapy (ESWT) to promote lymphangiogenesis to improve lymphedema
A rabbit ear model with “created” secondary lymphedema
surgical disruption of lymphatic vessels to the ear of a rabbit. 2 weeks after disruption, the ear was treated (with/without) ESWT (0.9mj/mm;10%, 200 shots to effected tissue) 3x/wk4
Not defined
Serizawa et al (2011)
Comparative study to investigate effect of ESWT for improving condition of secondary Le with increased lymphogenesis
Rat Tail Model with “created” secondary lymphedema (n=15/group)
Tissue in study group was treated with ESWT using 0.25mj mm, 500 impulses 4 times (day 3,5,7 & 9) Control did not
Not defined
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Measurements Ear thickness measured following surgery 1x/wk2; measured 1cm distal and medial to site using vernier caliper
Outcome Results/conclusion
Strength
Weakness
VEGF-C and VEGF receptor 3 were significantly increased in the treated ears vs. untreated. Conclusion: ESWT may be a promising noninvasive strategy for the Tx. of LE; Further study is needed including effects versus harm for human subjects
Controlled variable with structured lab environment reproducible
Tail volume increased in control group, showed significant improvement in test subjects. VEGF-C & bFGF. ESWT may be a promising noninvasive strategy for the Tx. of LE; Further study is needed; effects vs harm for human tests
Controlled variable with structured lab environment; reproducible
Non-human study, unknown harms to human subjects. Confirmation is needed to differentiate “created” secondary LE from inflammatory edema Non-human study, unknown harms to human subjects. Confirmation is needed to differentiate “created” LE from inflammatory edema
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Kubo et al (2010)
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Observed through fluorescence/ measure drainage function of lymphatic fluid. Tail volume measured using water displacement volumetry every 3 days (n=15/group)
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CG: compression garments ES = elastic sleeve ESD: Electrical Stimulation Drainage f/u: follow-up VEGF: vascular endothelial growth factor bFGF: basic fibroblast growth factor HVES: High Volt Electrical Stimulation LDM: lymph Drainage Massge LLLT: Low Level Laser therapy L/E: lower extremity LE: lymphedema MPT: mechanical pressure therapy MLD: Manual Lymph Drainage MNS: Measurements not standardized PCP or PC: pneumatic compression, pump PSWD: Pulsed Short Wave Diathermy QOL: quality of life QT: Qualified therapist noted ROM: Range of Motion RD: Radiation RCT: Randomized controlled trial SR: systematic review SI: Standardized intervention SLD: simplified/self-MLD SS: Small sample size TC: truncated cone formula used to figure volume Tx.= treatment TM: q__ cm:: tape measurements each __ cm UE: upper extremity US or UST: Ultrasound therapy Vod. MLD: Vodder MLD Vod. Var. MLD: a variation of the Vodder method Volumetry.: water displacement