Description
Lymphedema is an accumulation of fluid due to disruption of lymphatic drainage. Lymphedema can be caused by congenital or inherited abnormalities in the lymphatic system (primary lymphedema) but is most often caused by acquired damage to the lymphatic system (secondary lymphedema).
Diagnosis and Staging
A diagnosis of secondary lymphedema is based on history (e.g., cancer treatment, trauma) and physical examination (localized, progressive edema and asymmetric limb measurements) when other causes of edema can be excluded. Imaging, such as magnetic resonance imaging, computed tomography, ultrasound, or lymphoscintigraphy, may be used to differentiate lymphedema from other causes of edema in diagnostically challenging cases.
Table 1 lists International Society of Lymphology guidance for staging lymphedema based on "softness" or "firmness" of the limb and the changes with an elevation of the limb.
Table 1. Recommendations for Staging Lymphedema
| Populations |
Interventions |
Comparators |
Outcomes |
Individuals:
- With breast cancer-related secondary lymphedema
|
Interventions of interest are:
- Physiologic microsurgery to treat lymphedema along with continued conservative therapy
|
Comparators of interest are:
- Conservative therapy
- Complete decongestive therapy
- Pneumatic compression pumps
|
Relevant outcomes include:
- Symptoms
- Morbid events
- Functional outcomes
- Health status measures
- Quality of life
- Resource utilization
- Treatment-related morbidity
|
Individuals:
- Who are undergoing lymphadenectomy for breast cancer
|
Interventions of interest are:
- Physiologic microsurgery to prevent lymphedema
|
Comparators of interest are:
|
Relevant outcomes include:
- Symptoms
- Change in disease status
- Morbid events
- Quality of life
- Treatment-related morbidity
|
| Stage |
Description |
| Stage 0 (subclinical) |
Swelling is not evident and most individuals are asymptomatic despite impaired lymphatic transport |
| Stage I (mild) |
Accumulation of fluid that subsides (usually within 24 hours) with limb elevation; soft edema that may pit, without evidence of dermal fibrosis |
| Stage II (moderate) |
Does not resolve with limb elevation alone; limb may no longer pit on examination |
| Stage III (severe) |
Lymphostatic elephantiasis; pitting can be absent; skin has trophic changes |
Breast Cancer-Related Lymphedema
Breast cancer treatment is one of the most common causes of secondary lymphedema. Both the surgical removal of lymph nodes and radiotherapy are associated with development of lymphedema in individuals with breast cancer.
In a systematic review of 72 studies (N=29,612 women), DiSipio et al (2013) reported that approximately one (1) in five (5) women who survive breast cancer will develop arm lymphedema. Reviewers reported that risk factors for development of lymphedema that had a strong level of evidence were extensive surgery (i.e., axillary-lymph-node dissection, greater number of lymph nodes dissected, mastectomy) and being overweight or obese. The incidence of breast cancer-related lymphedema was found by DiSipio et al as well as other authors to be up to 30% at three (3) years after treatment.
Studies have also suggested that Black breast cancer survivors are nearly 2.2 times more likely to develop breast cancer-related lymphedema compared to White breast cancer survivors. These observations may be linked to racial disparities with regards to access to treatment and the types of treatments received. Black women are more likely than White women to undergo axillary lymph node dissection, which is associated with greater morbidity than the less invasive sentinel lymph node biopsy. While this may be explained in part by Black individuals having a higher likelihood of being diagnosed with more aggressive tumors, there is evidence that even when adjusting for stage and grade of tumors, Black women are more likely to undergo axillary lymph node dissection, putting Black women at greater risk of breast cancer-related lymphedema. Additionally, Black breast cancer survivors, on average, have higher body mass indexes than White breast cancer survivors, which could contribute to development of lymphedema in this setting as well.
Management and Treatment
Early and ongoing treatment of lymphedema is necessary. Conservative therapy may consist of several features depending on the severity of the lymphedema. Individuals are educated on the importance of self-care including hygiene practices to prevent infection, maintaining ideal body weight through diet and exercise, and limb elevation. Compression therapy consists of repeatedly applying padding and bandages or compression garments. Manual lymphatic drainage is a light pressure massage performed by trained physical therapists or by individuals designed to move fluid from obstructed areas into functioning lymph vessels and lymph nodes. Complete decongestive therapy is a multiphase treatment program involving all of the previously mentioned conservative treatment components at different intensities. Pneumatic compression pumps may also be considered as an adjunct to conservative therapy or as an alternative to self-manual lymphatic drainage in individuals who have difficulty performing self-manual lymphatic drainage. In individuals with more advanced lymphedema after fat deposition and tissue fibrosis has occurred, palliative surgery using reductive techniques such as liposuction may be performed.
Regulatory Status
Physiologic microsurgery for lymphedema is a surgical procedure and, as such, is not subject to regulation by the U.S. Food and Drug Administration.
For individuals who have breast cancer-related secondary lymphedema who receive physiologic microsurgery to treat lymphedema along with continued conservative therapy, the evidence includes a randomized controlled trial (RCT), observational studies, and systematic reviews. Relevant outcomes are symptoms, morbid events, functional outcomes, health status measures, quality of life, resource utilization, and treatment-related morbidity. Several physiologic microsurgeries have been developed; examples include lymphaticovenular anastomosis and vascularized lymph node transfer. No RCTs of lymphaticovenular anastomosis or similar surgeries involving the venous system were identified. One RCT of vascularized lymph node transfer with 36 participants has been conducted. Systematic reviews have indicated that the preponderance of the available evidence comes from single-arm clinical series from individual institutions. Surgical technique, outcomes metrics, and follow-up time have varied across these studies. These types of studies might be used for preliminary estimates of the amount of volume reduction expected from surgery, the durability of the reduction in volume, and the rates of adverse events. However, these studies are not adequate for determining the comparative efficacy of physiologic microsurgery versus conservative treatment or decongestive therapy, or the comparative efficacy of different microsurgery techniques. Randomized controlled trials are needed. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
For individuals who are undergoing lymphadenectomy for breast cancer who receive physiologic microsurgery to prevent lymphedema, the evidence includes a RCT, observational studies, and systematic reviews. Relevant outcomes are symptoms, change in disease status, morbid events, quality of life, and treatment-related morbidity. Lymphatic Microsurgical Preventing Healing Approach is a preventive lymphaticovenular anastomosis performed during nodal dissection. One RCT including 46 individuals has been conducted. The trial reported that lymphedema developed in 4% of women in the Lymphatic Microsurgical Preventing Healing Approach group and 30% in the control group by 18 months of follow-up. However, because the cumulative incidence of lymphedema after breast cancer treatment approximates 30% at three (3) years, longer follow-up is needed to assess the durability of the procedure. The trial methods of randomization and allocation concealment were not described and there was no blinding, potentially introducing bias. The remaining evidence consists of uncontrolled studies and systematic reviews of these studies. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.
