Systematic review: conservative treatments for secondary lymphedema

Oremus et al. BMC Cancer 2012, 12:6 http://www.biomedcentral.com/1471-2407/12/6 RESEARCH ARTICLE Open Access Systematic review: conservative treatments for secondary lymphedema Mark Oremus1,2, Ian Dayes3, Kathryn Walker1,2 and Parminder Raina1,2* Abstract Background: Several conservative (i.e., nonpharmacologic, nonsurgical) treatments exist for secondary lymphedema. The optimal treatment is unknown. We examined the effectiveness of conservative treatments for secondary lymphedema, as well as harms related to these treatments. Methods: We searched MEDLINE®, EMBASE®, Cochrane Central Register of Controlled Trials®, AMED, and CINAHL from 1990 to January 19, 2010. We obtained English- and non-English-language randomized controlled trials or observational studies (with comparison groups) that reported primary effectiveness data on conservative treatments for secondary lymphedema. For English-language studies, we extracted data in tabular form and summarized the tables descriptively. For non-English-language studies, we summarized the results descriptively and discussed similarities with the English-language studies. Results: Thirty-six English-language and eight non-English-language studies were included in the review. Most of these studies involved upper-limb lymphedema secondary to breast cancer. Despite lymphedema’s chronicity, lengths of follow-up in most studies were under 6 months. Many trial reports contained inadequate descriptions of randomization, blinding, and methods to assess harms. Most observational studies did not control for confounding. Many studies showed that active treatments reduced the size of lymphatic limbs, although extensive betweenstudy heterogeneity in areas such as treatment comparisons and protocols, and outcome measures, prevented us from assessing whether any one treatment was superior. This heterogeneity also precluded us from statistically pooling results. Harms were rare (< 1% incidence) and mostly minor (e.g., headache, arm pain). Conclusions: The literature contains no evidence to suggest the most effective treatment for secondary lymphedema. Harms are few and unlikely to cause major clinical problems. Background Secondary lymphedema (SE) is an acquired condition resulting from disease, trauma, or an iatrogenic process such as surgery or radiation that damages the lymphatic system [1,2]. Clinically, SE may present as edema [3]. Globally, the major cause of SE is lymphatic filariasis resulting from infection with the nematode Wusheria Bancrofti. In the United States (U.S.), the most common cause of SE is treatment for malignancy (i.e., surgery, radiation) [4], especially breast cancer. SE incidence rates following mastectomy range from 24% to 49%, with lower rates of 4% to 28% following lumpectomy [1]. The literature is bereft of reliable prevalence * Correspondence: 1 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada Full list of author information is available at the end of the article estimates, although some suggest approximately 10 million persons in the U.S. have SE http://www.shlnews. org/?p=67. Several types of conservative therapy exist to treat SE. Compression techniques, including multilayer bandaging, and pressure garments are thought to restore hydrostatic pressure and improve lymph flow in affected limbs [5]. Manual lymphatic drainage (MLD), a form of massage, is administered using light strokes to direct lymph flow from blocked to open lymphatics [5-7]. Exercise helps increase lymph flow via muscle contraction around the lymphatics [8]. Complex (or complete) decongestive therapy (CDT) includes MLD, limb compression with low stretch bandages, skin care, and exercise. The intent of CDT is to decrease fluid in affected limbs, prevent infection, and improve tissue integrity © 2011 Oremus et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Oremus et al. BMC Cancer 2012, 12:6 http://www.biomedcentral.com/1471-2407/12/6 [5,9]. Dieting (e.g., low-fat diet) is also used as a conservative therapy for SE. Mechanical treatments for SE include intermittent pneumatic compression (IPC) devices and low-level laser therapy (LLLT). IPC devices are pneumatic cuffs connected to pumps that mimic the naturally occurring muscle pump effect of muscles contracting around peripheral lymphatics [10]. LLLT employs low intensity laser waves and appears to encourage formation of lymphatic vessels, promote lymph flow, and stimulate immune systems [11,12]. This systematic review is based on a peer-reviewed technology report [13] commissioned by the Agency for Healthcare Research and Quality (AHRQ) and the Centers for Medicare and Medicaid Services (CMS). A copy of the technology report is available on the AHRQ website http://www.cms.gov/determinationprocess/downloads/id66aTA.pdf. The technology report served as background material for a Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) Meeting held in November 2009. One purpose of the meeting was to discuss the available evidence for treatment methods in SE. This review addresses two key questions: 1. How effective are conservative treatments for SE in pediatric or adult populations who developed SE following any type of illness except filariasis infection? 2. What harms are associated with conservative treatments for SE? Page 2 of 15 except filariasis infection. We excluded case series, case reports, narrative and systematic reviews, editorials, comments, letters, opinion pieces, abstracts, conference proceedings, and animal experiments. We also excluded studies involving pharmacologic or surgical treatments for SE. Trained raters independently applied the inclusion and exclusion criteria to the articles retrieved in the literature search. The criteria were applied at three levels of screening: I-title and abstract first review; II-title and abstract second review; III-full text. We extracted data from articles that passed full text screening. Raters managed the screening process electronically using standardized screening forms and Distiller SR systematic review software (Evidence Partners, Ottawa, Canada). Methodological quality assessment Two raters independently assessed the quality of the extracted English-language articles. Raters used the eight-point Jadad scale for RCTs [17,18] and the Newcastle-Ottawa Scale (NOS) [19] for observational studies. The overall quality of each extracted article was rated ‘good’, ‘fair’, or ‘poor’ in accordance with the recommendations outlined in the AHRQ’s methods guide for systematic reviews [20]. Issues of methodological quality often preclude the inclusion of observational studies in systematic reviews. However, observational (...truncated)