Lymphedema (PDQ®): Supportive care - Health Professional Information [NCI]
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Purpose of This PDQ Summary
This PDQ cancer information summary provides comprehensive, peer-reviewed information for health professionals about the pathophysiology and treatment of lymphedema. This information is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board.
Information about the following is included in this summary:
- Risk factors.
This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients during and after cancer treatment. It does not provide formal guidelines or recommendations for making health care decisions. Information in this summary should not be used as a basis for reimbursement determinations.
This summary will soon be available in a patient version, which is written in less technical language, and is available in Spanish.
Lymphedema is swelling that occurs when protein-rich lymph fluid accumulates in the interstitial tissue. This lymph fluid may contain plasma proteins, extravascular blood cells, excess water, and parenchymal products. Lymphedema is one of the most poorly understood, relatively underestimated, and least researched complications of cancer or its treatment. The Institute of Medicine of the National Academies published a report in 2006 recommending a "survivorship care plan" for cancer patients that incorporates information about late effects of treatment, health management behaviors, disease management, and recurrence monitoring. The Institute of Medicine also highlighted critical shortfalls in the transition to survivorship, particularly in providing education about late effects of treatment.
Lymphedema is an important consideration for clinicians who care for cancer patients because of its relatively high frequency and significant functional and quality of life implications for patients. Lymphedema is an independent predictor of decreased quality of life, even when other predictive factors such as socioeconomic status, decreased range of motion, age, and obesity are taken into account.
This summary will review issues related to anatomy and pathophysiology of lymphedema related to cancer, its clinical manifestations, diagnosis, and treatment. Primary (congenital) lymphedema and non–cancer-related lymphedema (i.e., recurrent cellulitis, connective tissue disease, and infection) will not be reviewed here.
Anatomy and Pathophysiology of the Lymphatic System
The human lymphatic system generally includes superficial or primary lymphatic vessels that form a complex dermal network of capillarylike channels that drain into larger, secondary lymphatic vessels located in the subdermal space. These primary and secondary lymphatic vessels parallel the superficial veins and drain into a deeper third layer of lymphatic vessels located in the subcutaneous fat adjacent to the fascia. A muscular wall and numerous valves aid active, unidirectional lymphatic flow in secondary and subcutaneous lymphatic vessels. Primary lymphatic vessels lack a muscular wall and do not have valves. An intramuscular system of lymphatic vessels that parallels the deep arteries and drains the muscular compartment, joints, and synovium also exists. The superficial and deep lymphatic systems probably function independently, except in abnormal states, although there is evidence that they communicate near lymph nodes. Lymph drains from the lower limbs into the lumbar lymphatic trunk, which joins the intestinal lymphatic trunk and cisterna chyli to form the thoracic duct that empties into the left subclavian vein. The lymphatic vessels of the left arm drain into the left subclavian lymphatic trunk and then into the left subclavian vein. Lymph channels of the right arm drain into the right subclavian lymphatic trunk and then into the right subclavian vein.
One function of the lymphatic system is to return excess fluid and protein from interstitial spaces to the blood vascular system. Because lymphatic vessels often lack a basement membrane, they can resorb molecules too large for venous uptake. Mechanisms of clinical edema include increased arteriovenous capillary filtration and reduced interstitial fluid absorption. Causes of increased capillary filtration include increased hydrostatic pressure in capillaries, decreased tissue pressure, and increased membrane permeability. Reduced interstitial fluid resorption can be caused by decreased plasma oncotic pressure, increased oncotic pressure of tissue fluid, and lymphatic obstruction.
The onset of secondary lymphedema is often insidious. However, it may be suddenly provoked by local inflammation from causes such as infection or limb injury. Therefore, patients should be evaluated for evidence of cellulitis. Classically, lymphedema is characterized by nonpitting swelling of an extremity, usually with involvement of the digits. Early stages of lymphedema manifest with pitting edema until fibrosis develops. The distribution of the swelling may be restricted only in the proximal or distal portion of the limb. Lymphedema may also predispose to recurrent skin infections.
Patients with lymphedema may report a wide variety of complaints: heaviness or fullness related to the weight of the limb, a tight sensation of the skin, or decreased flexibility of the affected joint. The texture of the skin may become hyperkeratotic, with verrucous and vesicular skin lesions. With upper extremity involvement, the patient may have difficulty fitting the affected area into clothing or wearing previously well-fitting rings, watches, or bracelets. Similar difficulties with lower extremity lymphedema include a sensation of tightness or difficulty wearing shoes, itching of the legs or toes, burning sensation in the legs, or sleep disturbance and loss of hair. Ambulation can be affected because of the increased size and weight of the affected limb. Activities of daily living, hobbies, and the ability to perform previous work tasks may also be affected.
Breast cancer survivors with arm lymphedema have been found to be more disabled, experience a poorer quality of life, and have more psychological distress than do survivors without lymphedema.[6,7] In addition, women reporting swelling have reported significantly lower quality of life with multiple functional assessments.
Lymphedema can occur after any cancer or its treatment that affects lymph node drainage. It has been reported to occur within days and up to 30 years after treatment for breast cancer. Eighty percent of patients experience onset within 3 years of surgery; the remainder develop edema at a rate of 1% per year. Upper-extremity lymphedema most often occurs after breast cancer; lower-extremity lymphedema most often occurs with uterine cancer, prostate cancer, lymphoma, or melanoma. A large population-based study supports the evidence that lower-limb lymphedema is experienced by a significant proportion of women after treatment for gynecological cancer, with the highest prevalence (36%) among vulvar cancer survivors and lowest prevalence (5%) among ovarian cancer survivors.
There is no consistency in the data on the incidence and prevalence of lymphedema after breast cancer, probably because of differences in diagnosis, the different characteristics of the patients studied, and inadequate follow-up to capture delayed development of the disorder. The overall incidence of arm lymphedema can range from 8% to 56% at 2 years postsurgery.
Patients undergoing axillary surgery and/or axillary radiation therapy for breast cancer are at higher risk for developing lymphedema of the arm. Previous convention suggested that nodal positivity was a predisposing factor for the development of lymphedema in breast cancer patients. Controlling for axillary radiation, one study actually found an inverse relationship between nodal positivity and arm volume.
Axillary node removal
Compared with axillary sampling alone, partial or total mastectomy followed by full axillary lymph node dissection significantly increases a patient's chance of developing arm edema. For example, in one series of 100 women who underwent partial or total mastectomy and then full axillary lymph node dissection or axillary sampling, arm edema developed in more patients who underwent axillary lymph node dissection compared with sampling alone (30% vs. none). In addition, the extent of axillary lymph node dissection increases the risk for developing arm edema. For example, in one series involving 381 women undergoing segmental mastectomy and axillary lymph node dissection, women who had ten or more lymph nodes removed were more likely than women who had few lymph nodes in the specimen to develop arm symptoms within the first year (53% vs. 33%) and within the next 2 years (33% vs. 20%).
Sentinel node biopsy
For patients with breast cancer, sentinel lymph node dissection has gained favor over axillary lymph node dissection for the axillary staging of early disease because of decreased morbidity and because of the questionable survival benefits of axillary lymph node dissection, as shown in a phase III randomized study (ACOSOG-Z0011) of axillary lymph node dissection in women who had stage I or IIA breast cancer and a positive sentinel node. Several studies have shown that lymphedema is more prevalent in breast cancer patients who undergo axillary lymph node dissection than in those who undergo sentinel lymph node biopsy. One study evaluated 30 patients with unilateral invasive breast carcinoma who underwent sentinel lymph node biopsy and 30 patients who underwent axillary lymph node dissection. This study found a 20% rate of developing lymphedema in the axillary lymph node dissection group compared with none in the sentinel lymph node biopsy group.
Among all breast cancer patients, being obese or overweight may predispose women to developing lymphedema after treatment for breast cancer. Some studies have correlated the degree of lymphedema with the level of obesity. Similarly, among young breast cancer survivors, persistent swelling was related to having more lymph nodes removed and being obese.
Other risk factors for developing lymphedema include the following:
- Extent of local surgery.
- Local radiation (axillary, inguinal, pelvic, or supraclavicular regions).
- Delayed wound healing.
- Tumor causing lymphatic obstruction of the anterior cervical, thoracic, axillary, pelvic, or abdominal nodes.
- Scarring of the left or right subclavian lymphatic ducts by either surgery or radiation.
- Intrapelvic or intra-abdominal tumors that involve or directly compress lymphatic vessels and/or the cisterna chyli and thoracic duct.
Diagnosis and Evaluation
Lymphedema is typically evident by clinical findings such as nonpitting edema, usually with involvement of the digits, in a patient with known risk factors such as previous axillary dissection. Other causes of limb swelling, including deep venous thrombosis, malignancy, and infection, should be considered in the differential diagnosis and excluded with appropriate studies, if indicated.
If the diagnosis is not evident on the basis of clinical assessment, imaging of the lymphatic system with lymphoscintigraphy (radionuclide imaging) may be necessary. Lymphangiography is generally no longer a favored diagnostic test and may be contraindicated in patients with malignancy because of concern that it may contribute to metastatic spread of tumor. Additional imaging techniques such as magnetic resonance imaging may complement information obtained via lymphoscintigraphy by providing anatomic and nodal detail.
The wide variety of methods described in the literature for evaluating limb volume and lack of standardization makes it difficult for the clinician to assess the at-risk limb. Options include water displacement, tape measurement, infrared scanning, and bioelectrical impedance measures.
The most widely used method to diagnose upper extremity lymphedema is circumferential upper extremity measurement using specific anatomical landmarks. Arm circumference measures are used to estimate volume differences between the affected and unaffected arms. Sequential measurements are taken at four points on both arms: the metacarpal-phalangeal joints, the wrist, 10 cm distal to the lateral epicondyles, and 15 cm proximal to the lateral epicondyles. Differences of 2 cm or more at any point compared with the contralateral arm are considered by some experts to be clinically significant. However, measuring specific differences between arms may have limited clinical relevance because of implications, for example, of a 3-cm difference between the arm of an obese woman and the arm of a thin woman. In addition, there can be inherent anatomic variations in circumference between the dominant and nondominant limb related to differences in muscle mass and variations after breast cancer treatment that may occur with atrophy of the ipsilateral arm or hypertrophy of the contralateral arm. A small study comparing various methods of assessing upper limb lymphedema did not show any superiority of any one method. Sequential measurements over time, including pretreatment measurements, may prove to be more clinically meaningful.
The water displacement method is another way to evaluate arm edema. A volume difference of 200 mL or more between the affected and opposite arms is typically considered to be a cutoff point to define lymphedema.
One common method of lymphedema classification uses three stages based on severity. Stage I is spontaneously reversible and typically is marked by pitting edema, increase in upper extremity girth, and heaviness. Stage II is characterized by a spongy consistency of the tissue without signs of pitting edema. Tissue fibrosis can then cause the limbs to harden and increase in size. Stage III, also called lymphostatic elephantiasis, is the most advanced stage, but is rarely seen following breast cancer treatment.
Ideally, prevention should begin before treatment, by educating the patient and family in a sensitive fashion about the potential risk of developing lymphedema. Proceeding in this way may diminish a breast cancer survivor's dissatisfaction with the educational information received about lymphedema, and could serve as a foundation for making decisions and coping with lymphedema, should it develop later. Patients should be taught to recognize the early signs of edema because treatment outcomes may be significantly improved if the problem is detected early.
Traditionally, patients with breast cancer and axillary dissection have been warned against vigorous, repetitive, or excessive upper-body exercise because of concern about inducing lymphedema. Several reports have questioned this historical recommendation. One case series evaluated arm circumferences of 20 breast cancer patients who had a history of axillary dissection (level I–II), many of whom also received breast or axillary radiation therapy. While training and competing in the vigorous upper-body sport of dragon boat racing, none of the women showed a clinically significant difference in arm circumference after approximately 7 or 8 months. As a precaution, however, the women were advised to wear compression sleeves on the affected upper extremity during exercise training.
A randomized trial examined the effects of a supervised upper- and lower-body weight training program on the incidence and symptoms of lymphedema in 45 breast cancer survivors. All patients had axillary dissection as part of their treatment, and 13 women had lymphedema at baseline. A 6-month, twice-a-week weight training program did not increase the risk of lymphedema or exacerbate symptoms.
Additional research with larger samples, more rigorous designs, and more sophisticated outcome tools to measure lymphatic flow is needed to address the safety and effectiveness of exercises for women with breast cancer–related lymphedema.
Generally anecdotal recommendations for taking preventive measures include the following:
Hygiene: Skin and Nail Care
- Maintain meticulous skin hygiene and nail care to prevent a portal of entry for infection which may result in cellulitis.
- Cut toenails straight across; see a podiatrist as needed to prevent ingrown nails and infections.
- Use skin moisturizers and topical antibiotic solutions after small breaks in the skin, such as paper cuts.
- Use sunscreen and suntan gradually.
- Wear cotton socks; keep feet clean and dry.
- Wear gardening and cooking gloves and use thimbles for sewing.
- Avoid going barefoot outdoors.
- Avoid blood draws (including finger sticks), vaccinations, or intravenous lines in the affected arm.
- Use the unaffected extremity to test temperatures (e.g., for bath water or cooking), as sensation may be diminished.
- Be aware of the signs of infection (fever, swelling, redness, pain, and heat) and see a physician for evaluation immediately.
- Keep the arm or leg elevated above the level of the heart when possible.
- Avoid constrictive pressure on the affected arm or leg:
- Do not cross legs while sitting.
- Wear loose jewelry and clothes with no constricting bands.
- Carry a handbag on the opposite arm.
- Do not use elastic bandages and stockings with constrictive bands.
- Do not sit in one position for longer than 30 minutes.
Avoiding the Pooling of Blood in the Involved Extremity
- Avoid rapid circular movements that cause centrifugal pooling of fluid in distal parts of the limb.
- Avoid local application of heat to the limb, which may increase blood flow.
- Do not maintain the limb in a gravity-dependent position for long periods of time.
- Avoid tight-fitting clothing or blood pressure monitoring in the affected arm, which could cause a tourniquet effect and obstruct lymph flow.
The goal of lymphedema treatment centers on controlling limb swelling and minimizing complications; the underlying lymphatic vessel interruption cannot be corrected. Because clinical trials evaluating pharmacologic measures are generally not found to be effective, nonpharmacologic measures are the mainstay of treatment, with the goal of maximizing the activities of daily living, decreasing pain, increasing range of motion, and improving function.
Nonfatiguing exercises may induce sufficient muscle contraction to move lymph into terminal lymphangioles and reduce swelling. Aerobic exercise may also increase the tone of the sympathetic nervous system, which causes the lymph collector vessels to pump more vigorously.
Gradient pressure garments
Gradient pressure garments (also known as lymphedema sleeves or stockings) generate greater pressures distally than proximally, which enhances mobilization of edema fluid. Some patients may require custom-made sleeves to achieve an appropriate fit. The use of these garments may be especially important at high altitudes, such as during air travel, because the ambient atmospheric pressure is less than the outlet transcapillary pressure within the superficial tissues, which can lead to worsening edema.
Bandaging involves the use of inelastic material to discourage reaccumulation of lymph by reducing capillary ultrafiltration and optimizing the efficacy of the intrinsic muscle pump. Bandaging may change an initially resistant limb to one with less edema, resulting in decreased limb volume and allowing a garment to be applied successfully.
Manual lymphedema therapy
Manual lymphedema therapy (or massage therapy) involves the use of a very light superficial massage with gentle, rhythmic skin distention limited ideally to pressures of approximately 30 mmHg to 45 mmHg. Manual lymphedema therapy decreases congested lymph by directing it to lymphotomes, or anatomic regions drained by a specific lymph node bed, with preserved drainage. Massage begins on the unaffected lymphotome areas to direct the lymph away from the affected extremity.
Possible contraindications to massage therapy include the following:
- Active cellulitis or other inflammations of the infected limb.
- Active neoplasia.
- Acute deep venous thrombosis.
- Congestive heart failure.
- Local massage over radiated soft tissue.
The goal of skin care is to minimize dermal colonization by bacteria and fungus, especially in the crevices, and hydrate the skin to control dryness and cracking.
Complex decongestive therapy
Complex decongestive therapy is a multimodality program that consists of manual lymphedema drainage therapy, low-stretch bandaging, exercises, and skin care. This approach has been recommended as a primary treatment by consensus panels and as an effective therapy for lymphedema unresponsive to standard elastic compression therapy.[10,11]
Complex decongestive therapy is divided into two successive phases. The first phase consists of intensive treatment to allow substantive reduction of lymphedema volume. The second phase consists of maintenance treatment at home. Compliance with the use of the elastic sleeve and low-stretch bandage has been found to be an important determinant of success with maintenance therapy at home. Complex decongestive therapy has also been shown to improve lymphedema following groin dissection. Patients should be referred to a properly trained therapist for optimal results.
Intermittent external pneumatic compression
Intermittent external pneumatic compression may also provide additional improvement with lymphedema management when used adjunctively with decongestive lymphatic therapy. One small randomized trial of 23 women with new breast cancer–associated lymphedema found an additional significant volume reduction when compared with manual lymphatic drainage alone (45% vs. 26%). Similarly, improvements were also found in the maintenance phase of therapy. Concerns regarding the use of intermittent pneumatic compression include the optimum amount of pressure and treatment schedule and whether maintenance therapy is needed after the initial reduction in edema. There is a theoretical concern that pressures higher than 60 mmHg and long-term use may actually injure lymphatic vessels.
No chronic pharmacologic therapy is recommended for patients with lymphedema. Diuretics are typically of little benefit and may promote intravascular volume depletion because the lymphedema fluid cannot be easily mobilized into the vascular space. Coumarin is associated with significant hepatotoxicity and has not been found to have any benefit in controlled trials. Antibiotics should be used promptly for patients with evidence of cellulitis; intravenous use may sometimes be required for severe cellulitis, lymphangitis, or septicemia.
The results of a randomized trial have suggested that lymphedema may improve with weight loss. The mechanism by which obesity may predispose to lymphedema is unclear, but proposed mechanisms include an increased risk of postoperative complications, including infection, reduced muscle pumping efficiency, and separation of lymphatic channels by subcutaneous fat.
Low-level laser therapy
Studies suggest that low-level laser therapy may be effective in reducing lymphedema in a clinically meaningful way for some women. Two cycles of laser treatment were found to be effective in reducing the volume of the affected arm, extracellular fluid, and tissue hardness in approximately one-third of patients with postmastectomy lymphedema at 3 months posttreatment. Suggested rationales for laser therapy include a potential decrease in fibrosis, stimulation of macrophages and the immune system, and a possible role in encouraging lymphangiogenesis.
Surgery is rarely performed on patients who have cancer-related lymphedema. The primary surgical method for treating lymphedema consists of removing the subcutaneous fat and fibrous tissue with or without creation of a dermal flap within the muscle to encourage superficial-to-deep lymphatic anastomoses. These methods have not been evaluated in prospective trials, with adequate results for only 30% of patients in one retrospective review. In addition, many patients face complications such as skin necrosis, infection, and sensory abnormalities. The oncology patient is usually not a candidate for these procedures. Other surgical options include the following:
- Microsurgical lymphaticovenous anastomoses, in which the lymph is drained into the venous circulation or the lymphatic collectors above the area of lymphatic obstruction.
- Superficial lymphangiectomy.
Refractory Lymphedema and Complications
If lymphedema is massive and refractory to treatment, or has an onset several years after the primary surgery without obvious trauma, a search for other etiologies should be undertaken. Of particular importance is exclusion of the recurrence of tumor or the development of lymphangiosarcoma, which should be excluded with computed tomography or magnetic resonance imaging. The complication of lymphangiosarcoma is classically seen in the postmastectomy lymphedematous arm (Stewart-Treves syndrome). The mean time between mastectomy and lymphangiosarcoma is 10.2 years, with a median survival of 1.3 years. Clinically, the lesions of lymphangiosarcoma may initially appear as blue-red or purple with a macular or papular shape in the skin. Multiple lesions are common; subcutaneous nodules may appear and should be carefully evaluated in the patient who has chronic lymphedema.
Current Clinical Trials
Check NCI's PDQ Cancer Clinical Trials Registry for U.S. supportive and palliative care trials about lymphedema that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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Date Last Modified: 2009-06-30