Breast Cancer

In breast cancer the extent of axillary surgery is an important prognostic factor for lymphedema. Both ALND and sentinel lymph node biopsy (SLNB) put patients at a lifelong risk for lymphedema. Disipio et al. estimated that the rate of arm lymphedema is about four times more likely with ALND as compared to SLNB (19.9% and 5.6%, respectively).

Clinical studies have found that radiotherapy is a risk factor for the development of lymphedema with a synergistic effect when combined with ALND. Shaitelman et al. in a recent metaanalysis concluded that the risk for lymphedema in breast cancer patients is significantly higher among patients treated with regional lymph node radiation (RLNR) as compared to those treated with whole breast radiation alone, with the highest risk associated with patients who receive RLNR following ALND. The study calculates the pooled incidence of lymphedema as stratified by radiation targets with a pooled incidence of 7.4% for patients treated with breast/chest wall radiation and a range of 10.8%–15.5% for different combinations of RLNR. Further stratification was performed to include the extent of axillary surgery and radiation targets with a 4.1% pooled incidence for patients treated with SLNB and breast/chest wall radiation with an increase to 5.7% with the addition of RLNR to breast/chest wall radiation. For patients treated with ALND, there was an increased risk for lymphedema with a pooled incidence of 9.4% with ALND and breast/chest wall radiation with a significant increase in risk to 18.2% with the addition of RLNR to breast/chest wall radiation.

It is suggested that breast cancer patients who undergo RLNR even without ALND ought to be considered as high risk for lymphedema.

McDuff et al. in a recent large prospective cohort study of 2171 women estimated a 5-year cumulative incidence of 13.7% for lymphedema. The overall risk peaked between 12 and 30 months postoperatively depending on the treatment received. ALND was associated with early onset lymphedema, while late-onset lymphedema (>12 months) was associated with RLNR. These findings can inform clinical practice and provide information that may be used for patient education and surveillance practices.

Other Risk Factors

Evidence shows other BCRL risk factors, including chemotherapy with taxanes, cellulitis, subclinical edema, and lack of breast reconstruction. There is growing evidence of genetics as a predisposing factor in the development of secondary lymphedema, with evidence of genetic mutations as a risk factor in lymphedema following breast cancer treatment.

Gynecologic Cancer

For gynecologic cancers the risk of lower limb lymphedema (LLL) varies based on the extent of surgery and lymphadenectomy, the removal of specific nodes, radiotherapy treatment, and the disease site (endometrial, vulvar, ovarian, cervical).

Inguinofemoral lymph node dissection as is often the case with vulvar cancer is correlated with the highest risk of LLL in gynecologic cancers, ranging from 30% to 70%, and includes most of the cases of genital lymphedema. Cormier et al. estimate a lymphedema risk of 22% in patients undergoing pelvic dissection. The removal of the circumflex iliac lymph nodes to the level of the distal external iliac node (CINDEIN) is associated with a significantly higher level of postoperative lower extremity lymphedema. Lymphadenectomy of the pelvic and para-aortic lymph nodes are often involved in endometrial cancer with a variation in node dissection from a sampling of a few nodes to median of 10–30 nodes. A 12-year retrospective study showed that removal of ≥10 nodes and in another study ≥15 nodes were indicative of an increased risk for LLL in women with endometrial cancer, however, Yost et al. in a large retrospective study did not find a lymphedema risk associated with the number of nodes removed. SLNB is a safe and effective alternative to complete dissection in vulvar cancer. Promising evidence of SLNB in endometrial and cervical cancers continue to emerge. While it is estimated that the overall incidence for gynecologic cancer is 25%, Shaitelman et al. estimate an overall pooled incidence of 9% in patients who receive SLNB as part of their gynecologic cancer treatment.

There is a higher risk of LLL reported in patients treated with adjuvant radiotherapy. In a metaanalysis of 1193 patients with gynecologic cancer, there was a reported 34% pooled incidence of lymphedema in patients who received radiation treatment

Obesity

There is strong evidence associated with a high body mass index at the time of breast cancer diagnosis and an increased risk of developing lymphedema. Most of the studies related to body mass index (BMI) and cancer-related lymphedema risk involve the upper extremity secondary to breast cancer treatment. These findings may also be applicable to patients at risk for LLL following inguinal lymphadenectomy.

As early as 1957, from a study of 1007 postradical mastectomy cases, obesity was identified as a predisposing factor for lymphedema. In a prospective study, Ridner et al. reported that breast cancer survivors with a BMI ≥30 at the time of diagnosis were 3.6 times more likely to develop lymphedema as compared to those patients with a BMI <30. Jammallo et al. prospectively found a preoperative BMI ≥30 as an independent risk factor for lymphedema and an associated increased risk of BCRL with postoperative weight fluctuations with loss or gain of greater than 10 lb.

Mehrara and Greene suggest evidence that obesity impairs lymphatic transport and a clear relationship between obesity and lymphedema, although the cellular mechanisms are currently not known. In a randomized clinical trial, it was found that a weight reduction diet over a span of 12 weeks in patients with BCRL resulted in significant reduction in arm volumes relative to the control group that received no specific dietary interventions. It is recommended that weight management and weight reduction efforts should be integrated into lymphedema management of patients at risk or with a diagnosis of lymphedema.

Medical Chart Review

A thorough chart review is an essential starting point in the assessment of the patient for lymphedema. It is important to review the patient’s cancer history, including the location of the cancer, presence and location of metastatic disease, diagnostic testing results such as PET/CT scans, bone scans, CT of chest, abdomen, and pelvis if available. Since swelling of the affected limb can also be due to other causes such as deep vein thrombosis, results of venous ultrasound tests can also be beneficial.

Surgical treatment is often a part of the treatment of breast and gynecologic cancers. A review of the surgical report that includes information on whether or not lymph nodes were removed and if so, which ones (i.e., lymph node dissection) can be very helpful information.

If radiation therapy was part of the treatment, a review of the radiation therapy treatment plan or radiation oncology consultation report is important to determine which structures were irradiated, including lymph nodes as well as dose and number of fractions.

Lymphedema History

Pertinent information to gather from the patient includes (1) when and how long ago did they notice swelling of the extremity? (2) were there any associated circumstances around the time that the swelling was first noticed—cuts, bruises, redness of skin, trauma to limb, etc.? (3) did the swelling start gradually or suddenly? (4) is this the first time that the patient has noticed swelling of the limb or have there been other times as well? (5) was there a recent change in their cancer history such as progression of disease? (6) is the swelling present in one extremity or more? (7) has the patient experienced a perception of heaviness of the limb accompanied by difficulty wearing jewelry, a watch or a long sleeve shirt? (8) is there any associated weakness, numbness, or tingling sensation of the affected limb? It is also important to determine the impact of the limb swelling on the patient’s function. In BCRL, does the patient have a difficult time performing self-care, household chores, work, childcare, or hobby activities due to the swelling of the limb? In LLL, does the patient have difficulty wearing pants, walking or has noticed an impaired balance, falls, or “near-falls” due to the swelling of the leg?

In patients with a history of lymphedema, other important information are to obtain: (1) is the current limb swelling different or worse than previous lymphedema flare-ups? (2) are there any other or new symptoms or signs such as weakness, pain in ipsilateral joints or muscles or sensory complaints? (3) recent history of weight gain? (4) history of treatment for the lymphedema, including manual lymphatic drainage (MLD), compression sleeves or bandage use, or intermittent pneumatic compression (IPC)?

Physical Examination

Inspection : (1) is the patient obese? (2) any cuts, bruises, erythema, skin changes such as cobblestoning, skin overgrowth, and wart-like changes indicative of more advanced disease deformities of the limb as well as distribution of the swelling. Palpation : tissue fibrosis, tender points, pitting versus nonpitting edema, presence of axillary cords, or regional lymphadenopathy (i.e., axillary or supraclavicular lymphadenopathy). Range of motion : any restrictions in the range of motion of proximal and/or distal joints in the affected extremity. In addition, circumferential measurements of the affected and nonaffected limb as well as assessment of muscle strength and sensory deficits are important components of the physical examination. Lastly, a functional assessment of the person’s ability to use the affected limb can provide relevant information, for example, the ability of the person with BCRL to put on a shirt or the assessment of gait abnormality in person with LLL.

Staging

The International Society of Lymphology (ISL) describes a three stage scale (Stage 0/Ia–Stage III) for the classification of lymphedema. ( Table 21.1 ). It considers the extent of swelling and evidence or absence of pitting. It describes the progression from a latent state where there may be changes in tissue fluid with no apparent swelling to more advanced disease characterized by trophic skin changes, tissue hypertrophy, fibrosis, and fat deposition. Based on the classification, Stage 0 signifies a latent or subclinical state where there is no overt swelling despite impaired lymph transport. Subjective symptoms may be present. This stage may persist for months or years. Stage I describes an early accumulation of high protein fluid that abates with limb elevation. Pitting may occur. Stage II is further classified into an early and late stage. In the early stage, elevation seldom reduces the swelling and pitting is manifest. In the later stage, there may be no pitting due to increasing fat and fibrotic tissue deposition. Stage III also described as lymphostatic elephantiasis is the most advanced stage of the disease where pitting is absent and the presence of pronounced skin changes, including acanthosis, thickening and loss of skin flexibility, and other dystrophic changes are evident. There is further deposition of fat and fibrotic tissue. A limb may exhibit more than one stage affecting different lymphatic territories within the limb.

A functional severity assessment utilizing volume differences is often used along with the ISL staging to provide another aspect of severity within each stage. Whereby a volume difference of >5–<20% increase is assessed as minimal, 20%–40% increase moderate, and >40% increase severe. The volume measurements are a gross measurement and do not define the composition of the swelling. Clinicians in describing severity may also include other factors such as extensiveness, erysipelas, and inflammation.

The ISL recognizes the need for a more detailed and inclusive staging system that goes beyond describing only the physical condition of the extremities and to include other areas such as radiographic and pathogenic components of lymphedema, genetic considerations, disability, and QOL.

Diagnosis

In most cases the diagnosis of lymphedema can be made based on a thorough clinical history and physical examination, including assessment of tissue quality and a measurement of increased limb volume along with a patient-reported symptom assessment. The patient’s risk status is also considered. The clinical signs and symptoms of lymphedema are influenced by the duration and severity of the disease.

In the early stages the symptoms may be subtle and there may be mild swelling with pitting edema due to the increasing volume of fluid in the interstitial spaces. In a subclinical condition, swelling may not be evident despite impaired lymph transport.

As the disease progresses over time, there is increased cellular proliferation, fibrosis, and adipose deposition that are associated with a nonpitting edema along with thickening and loss of flexibility of the skin. ( Fig. 21.3 )

Stage II lymphedema of the left upper limb.

In the chronic/late stages, there are characteristic cutaneous changes that distinguish lymphedema from nonlymphatic forms of edema. There may be a positive Stemmer sign that is the inability to tent the skin at the base of digits. A positive sign is diagnostic of lymphedema of the extremities; however, the absence of a Stemmer sign does not rule out lymphedema. Other characteristics distinguishing physical findings for late stage lymphedema may include peau d’orange, papillomatosis, cobblestone deformities, lymph cysts, and chronic inflammatory changes.

Conditions such as morbid obesity, venous insufficiency, unrecognized trauma, and repeated infections may complicate the clinical presentation of lymphedema.

Malignant lymphedema should always be considered where there is a possibility of cancer recurrence. Progression of cancer or metastases may obstruct or infiltrate the proximal lymphatics resulting in impaired lymph flow and development of lymphedema. Clinically, malignant lymphedema is more likely to begin centrally with pronounced vascular changes, the development of symptoms is more rapid and progressive, the edema and tissues tend to be firm from the outset, and there may be more pain as compared to benign forms of lymphedema.

Accurate and objective measurement techniques together with patient-reported symptoms are required not only for evaluation and diagnosis but also to track the progress or regression of both the disease and treatment interventions.

BIS, water displacement, tape measurement, perometry, and imaging are current options of objective measures used in the diagnosis and monitoring of lymphedema.

Water Displacement

Water displacement is a volume measurement and is considered the reference standard due to its excellent reliability and validity. It is accurate and inexpensive but is limited by clinical utility. It is time-consuming, and there are concerns for cross contamination in individuals with open wounds and skin breakdown.

Circumferential Measurements

Circumferential measurements utilizing a measuring tape is the most common practice method for girth and volume measurements. The American Physical Therapy Association (APTA) Clinical Practice Guidelines for the Diagnosis of Upper Quadrant Lymphedema recommend that when circumferential measurements are used, the measurement of each limb should be calculated to a volume measurement. using a mathematical formula, with a summed truncated frustum cone formula as the preferred method. Calculated limb volumes derived from circumferential measurements show excellent interrater and intrarater reliability for the upper limb. A volume differential between sides of ≥200 mL will help rule in lymphedema, however values below 200 mL do not rule out lymphedema. The guidelines further specify that a 2 cm circumferential difference lacks accuracy and should not be used as a diagnostic standard for upper extremity lymphedema. A volume ratio of 1.04 of affected:unaffected limb may be indicative of upper limb lymphedema. If preoperative measurements were performed, a 5% volume change from the baseline measurement is a diagnostic criterion for lymphedema. Also to be considered, is that volume calculated circumferential measurements may not capture subclinical and early stage lymphatic transport deficits.

Perometry

Perometry is a volume measurement that uses infrared light and optoelectronic sensors to create a three-dimensional silhouette of the limb from which limb volume is calculated. Perometry may be used for volume assessment in the early, moderate, and late stages of lymphedema. It has excellent inter/intrarater reliability and psychometric properties. The time to measure and setup is approximately 5 minutes, and the accompanying software enables easy documentation and comparison of results. It is highly reproducible, accurate and provides segmental volumes. Disadvantages include bulkiness, lack of portability, and expense of the equipment.

Bioimpedance Spectroscopy

BIS is a noninvasive method for detection of early/subclinical stages of edema. The 2017 APTA Clinical Practice Guidelines for the Diagnosis of Upper Quadrant Lymphedema, recommends the use of BIS to detect subclinical/early stage lymphedema. It further suggests the use of BIS to assist in the diagnosis of early/subclinical lymphedema (stages 0 and 1) in patients at risk for BCRL. In 2008 the FDA approved the L- Dex U400 (ImpediMed, Limited) BIS device for clinical use. By means of skin electrodes, it passes an alternating low-frequency current through the limb, and the impedance to the current is then used to detect and measure the extracellular fluid in a limb. It derives a lymphedema L-Dex value (L-Dex score) that measures the ratio of fluid differences between the affected and unaffected limb. For a patient without lymphedema, the L-Dex defines the normal range of −10 to 10. L-Dex values that lie outside the normal range or reflect a shift of +10 units from preoperative baseline measurements are regarded as clinically significant and may indicate subclinical lymphedema. L-Dex scores of more than 7.1 is a diagnostic criterion when no preoperative assessment is available. A preoperative BIS measurement may improve the ability for earlier detection of post operative tissue fluid changes which may be indicative of lymphedema.

The clinical utility advantages of BIS includes portability, is easily performed, takes less than 8 minutes and requires minimal technical training. The machine is relatively inexpensive; however, a new set of electrodes that are costly are required for each assessment. Recently, a new BIS unit with L-Dex technology was introduced, which does not require electrodes. It is a standing unit with scanning technology that measures fluid status in seconds ( Fig. 21.4 ).

Bioimpedence spectroscopy device

(Reprinted with permission from SOZO® Bioimpedance Spectroscopy Device, Copyright © ImpediMed Limited and ImpediMed Inc.)

BIS is sensitive, specific and noninvasive and is being increasingly utilized for detection of early stage edema and is also used in prospective screening for early/subclinical edema in patients at risk for lymphedema. The BIS device however, measures fluid content only and does not capture the secondary tissue changes of fibrosis and adipose deposition that are characteristic in the moderate and later stages of lymphedema. It is therefore recommended that a volume measurement, for example, circumferential measurements should also be taken even though it may show no volume increase in the early/subclinical stage of the disease. A baseline volume measurement is useful for ongoing monitoring to identify increased volume due to secondary tissue changes.

Near-Infrared Fluorescent Lymphography

Near-infrared fluorescent (NIRF) lymphography or indocyanine green (ICG) lymphography, is gaining popularity as it enables visualization of superficial lymph flow in real time without radiation exposure. The ICG dye is injected intradermally in the second web space of the extremity, illuminating the superficial lymphatic flow. The light emitted by ICG in the lymph vessels, is imaged using a specialized camera.

It measures lymph pump function and dermal backflow. Dermal backflow is a sign unique to lymphedema and indicates lymphatic fluid congestion in the subcutaneous and dermal space secondary to the rerouting of the lymphatic fluid.

There are various classification systems utilizing ICG lymphography. The MD Anderson ICG classification system has four stages based on ICG findings and the severity of dermal backflow. In Stage 1 the patient has several patent lymphatics and minimal dermal backflow; in Stage 2, there are a moderate number of patent lymphatics with segmental dermal backflow; in Stage 3, there are few patent lymphatics with extensive dermal backflow throughout the arm; and lastly, in Stage 4, there are no patent lymphatics and severe dermal backflow of the entire arm and hand ( Fig. 21.5 ). The Pathophysiological Severity Staging System is another ICG classification system that includes the extremities, the genitals, and the lower abdominal area. ICG lymphography patterns change from a normal linear pattern with no dermal backflow (Stage 0) to abnormal dermal backflow patterns (Stages I–V) ranging from splash (Stage I mild dermal backflow), stardust (Stages II–IV moderate dermal backflow), and diffuse (Stage V severe dermal backflow) patterns.

MD Anderson lymphedema ICG classification system. ICG , Indocyanine green. (A) Stage 1: many patent lymphatic vessels, with minimal, patchy dermal backflow. (B) Stage 2: moderate number of patent lymphatic vessels, with segmental dermal backflow. (C) Stage 3: few patent lymphatic vessels, with extensive dermal backflow involving the entire arm. (D) Stage 4: no patent lymphatic vessels, with severe dermal backflow involving the entire arm and extending to the dorsum of the hand.

(Reprinted with permission from Chang DW, Suami H, Skoracki R. A prospective analysis of 100 consecutive lymphovenous bypass cases for treatment of extremity lymphedema. Plast Reconstr Surg . 2013; 132(5): 1305–1314.)

NIRF lymphography provides information that can be useful in the decision-making for lymphedema evaluation and a guide to determine conservative, surgical, or combined treatments.

Self-Report/Subjective Symptoms

Patients at risk or who have lymphedema may present with symptoms such as heaviness, fatigue, perceived sensations of swelling, tingling, pain, sensory changes, and changes in fit of clothing. Patient-reported symptoms are important as these may indicate volume and pressure changes in the interstitial space before there are measurable volume changes. Patients are often the first to describe symptoms in their limb before physical or detectable volume changes occur. Self-reported measures may therefore assist with the identification of subclinical or early lymphedema and also a trigger for further examination and objective measures.

There are several self-report assessment tools available. The APTA Clinical Practice Guidelines suggest the Norman Questionnaire and the Morbidity Screening Tool (MST) should be considered. Other assessment tools reported in the guidelines include the Lymphedema and Breast Cancer Questionnaire (LBCQ), the Visual Analogue Scale (VAS), and The Lymphedema Symptom Intensity and Distress Survey (LSIDS).

For evaluation of LLL in gynecologic patients the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) is a self-reporting assessment tool analyzing physical function and symptoms of numbness, swelling, heaviness, and aching.

A recent study of 100 patients with a history of breast cancer showed that symptoms of perceived arm swelling, along with differences in tissue texture determined by a patient-administered basic self-assessment forearm pinch test, were associated with and sensitive to BIS-detected BCRL. The findings support the use of self-assessment to help identify the early development of BCRL, and an indication for the patient to seek further professional evaluation.

Additional Diagnostic Measures

As discussed, the diagnosis of lymphedema in most cases can be determined clinically through observation, the patient’s history, physical examination, an objective measurement, and self-reported symptoms. If there is unclear etiology or need for further clarification, there are other imaging diagnostic measures that may be utilized which are able to detect tissue quality, visualize edema, or evaluate structural lymphatic transport capacity. These measures include lymphoscintigraphy, magnetic resonance imaging, ultrasonography, CT, and NIRF spectroscopy. Lymphoscintigraphy is regarded as a standard investigation technique in lymphedema diagnosis. In a study of 227 patients (454 limbs), lymphoscintigraphy was found to be very sensitive (96%) and specific (100%) for lymphedema. It is useful in confirming the diagnosis of lymphedema in patients with an equivocal clinical diagnosis, can verify normal lymphatic function, and can document the severity of lymphatic dysfunction. Magnetic resonance imaging is being considered more for diagnosis of lymphedema. A recent small population study reported greater sensitivity with MRI (100%) for depiction of lymph vessels as compared to lymphoscintigraphy (83.3%). The study also demonstrated concordance in the MRI and lymphoscintigraphy results for axillary lymph node enhancement and lymphatic drainage in the upper extremities. Venous duplex ultrasound is a simple, noninvasive imaging technique. It should be performed on patients with lymphedema to assess the venous system for possible deep vein thrombosis which could also present with limb swelling. Ultrasound may be used in the later stages of lymphedema to detect underlying tissue changes. It is able to detect fluid collection, subcutaneous tissue thickness, and fibrosis. There is a potential advantage for ultrasound to be used to measure areas such as the chest wall, breast, or genitalia. Tonometry evaluates tissue tension, the tissue resistance to pressure. It is not a volume measurement. It assesses compliance of the dermis and is an index of fibrotic induration. Tissue dielectric constant (TDC) assesses localized skin to fat tissue water changes. It uses a high-frequency electromagnetic wave via a probe to the skin to measure the water content in the tissue. TDC is a clinically efficient procedure, measurement takes approximately 10 seconds at multiple sites, and it can be used to measure at almost any body site. Mayrovitz et al. in a study of 80 women treated for breast cancer demonstrated that with TDC a greater number of patients were found to have interarm ratio increases exceeding 10% that were not identified using BIS ratios. This may suggest a greater sensitivity to localized tissue water changes and may play a role in detection of subclinical edema.

Screening and Prevention

There has been a shift in the diagnosis and surveillance of lymphedema away from the traditional impairment-based model with a now growing consensus for a preventative, prospective screening model. This approach facilitates the detection of subclinical lymphedema that is thought to be associated with more effective treatment and prevention of disease progression. However, there needs to be further research to lend support to this theory. Nevertheless, recognized practice guidelines recommend prospective surveillance. The ISL supports a prospective surveillance model and early lymphedema detection and intervention as strategies for greater success with treatment and potential cost savings. The National Lymphedema Network (NLN) position paper on screening and early detection of BCRL contends that a screening model for early detection and treatment of lymphedema, even in the subclinical stage, may reverse the progression to chronic lymphedema.

Although large randomized control trials (RCTs) are lacking, there is mounting evidence in the research literature that surveillance leads to subclinical detection, earlier diagnosis, and subsequent earlier treatment interventions that may prevent progression to a more advanced stage of lymphedema.

Stout et al. prospectively screened via perometry 196 patients for BCRL. Patients diagnosed with subclinical lymphedema were prescribed a compression garment intervention for 4 weeks (in this study the diagnosis of lymphedema was defined as an increase >3% in arm volume compared to preoperative measurements). After the 4 weeks of compression, there was a significant volume reduction, and this was maintained at an average follow-up of 4.8 months after the completion of the intervention. In another prospective study by Soran et al., 186 patients with breast cancer and ALND were screened with either BIS or circumferential measurements. Patients with a diagnosis of subclinical lymphedema received interventions of compression garments, physical therapy, and education. In the BIS surveillance group, 33% of patients were diagnosed with subclinical lymphedema, of which only 4.4% developed clinical lymphedema over an average of 20 months follow-up, whereas in the control group, there was a 36.4% incidence of clinical lymphedema.

Prospective screening and early intervention may also have implications for health-care costs. Stout et al. by estimating costs from the Medicare 2009 physician fee schedule found the cost per year per patient to manage early stage BCRL through prospective surveillance was $636.19 as compared to $3124.92 per year to manage late stage BCRL using a traditional model of care.

Important components that should be considered in a surveillance program for lymphedema include (1) a reliable and valid objective measurement instrument such as circumferential measurements, perometry, and BIS. Whichever tool is chosen, it should be used consistently, they are not interchangeable, and accuracy will be improved if a standardized measurement protocol is established; (2) baseline preoperative measurements , Sun et al. analyzed 1028 patients and reported that without a preoperative baseline measurement diagnosis of subclinical and clinical lymphedema are missed 40%–50% of the time. The study further reported that approximately half of lymphedema cases that are diagnosed without a baseline measurement are most likely overdiagnoses as arms are rarely symmetrical at baseline; (3) an ongoing serial follow up measurement protocol at regular intervals Ostby et al. proposed a prospective surveillance program for BCRL (PROSURV-BCRL), whereby assessment and measurements are coordinated with doctors’ visits at intervals of 1, 3, 6, 9, 12 months followed by semiannual visits for 1–3 years; (4) the use of measurement methods/formulas that factors in natural arm asymmetry and weight changes . Recommended quantification formulas include the relative volume change equation for patients with unilateral breast surgery and the weight change–adjusted equation for patients with bilateral breast surgery; and finally, (5) patient symptom report should always be used together with objective measures and can be invaluable in identifying subclinical lymphedema.

Complete Decongestive Therapy

Complete decongestive therapy (CDT) is a combination therapy for the management of lymphedema that includes MLD, compression, exercise, skin care, patient education, and self-management. CDT is a two-phase therapy: Phase I may be considered as the reduction phase that is aimed at volume reduction, mobilizing high protein interstitial fluid and reduction of increased connective tissue utilizing MLD, short-stretch compression wrappings, exercise to promote lymph flow and skin care. Phase II is described as the maintenance or self-management phase aimed at optimizing and preserving the gains made in Phase I. Interventions are based on the stage of lymphedema and may include the use of compression garments, MLD, and ongoing exercise and skin care. CDT has long been considered the standard of care and is recognized as the therapy of choice by several organizations, including the ISL. CDT can effectively reduce limb volume and provide long-term benefits of an enhanced transport capacity of the lymph vascular system and removal of accumulated protein from the interstitium. The goal of CDT as described by Földi et al. is to improve lymphatic function and lymph drainage, soften fibrotic tissue, decrease collagen deposition, and skin care to reduce the risk of opportunistic infections. Lasinski et al. in a systematic review evaluated 27 studies on the effectiveness of CDT and concluded that CDT was effective in limb volume reduction and was beneficial in mild, moderate, or severe lymphedema. The majority of research is focused on CDT in its totality, but the relative contribution and efficacy of each of the components of CDT is not well understood. There are some less robust studies that suggest the benefit of techniques such as MLD as possible monotherapies especially in the subclinical and early stages of lymphedema. The efficacy of the individual components of CDT in lymphedema management is relevant especially with the current shift toward prevention, subclinical diagnosis, early intervention, and consideration of treatment costs. The ISL 2016 consensus document acknowledges compression garments alone as treatment for subclinical and early stage lymphedema particularly in BCRL. It recognizes published reports supporting MLD as a monotherapy but underlines the need for further research and convincing evidence.

Manual Lymphatic Drainage

MLD is a specialized manual therapy technique centered on the anatomy of the lymphatic system. The light tissue compression used in the course of MLD is aimed at reducing swelling through improved lymphatic contractility, uptake of interstitial fluid, rerouting of lymph into nonobstructed lymphatics, and development of accessory lymph collectors.

MLD is regarded as an important component of CDT. However, in the literature, there is discussion and debate on the function and efficacy of MLD with a lack of supporting objective data. A recent Cochrane review of trials concluded that MLD is safe and well tolerated and beneficial to patients with mild-to-moderate BCRL. It further demonstrated that MLD may offer benefit when added to compression bandaging. Compression bandaging alone resulted in a significant reduction in volume of 30%–38.6% with a further gain of 7.11% reduction with the addition of MLD. In addition, it was found that those with mild-to-moderate BCRL may be the ones who benefit from adding MLD to compression bandaging versus individuals with moderate-to-severe BCRL. The authors suggest that there should be more trials that include volumetric outcomes in truncal and breast lymphedema. MLD may play an important role in truncal/chest wall or breast swelling, areas that may not be as amenable to compression therapy.

Tan et al. used NIRF imaging to compare lymphatic contractile function pre- and post-MLD treatment in both the symptomatic and asymptomatic limbs of 10 patients with Stages I or II lymphedema. The research showed an increase in the average lymph velocity in both the affected and unaffected limbs of 23% and 25%, respectively. The study also included a control group of 12 healthy participants with a reported 28% increase in lymph velocity post-MLD.

In an RCT of 120 patients, Torres Lacomba et al. showed that early physical therapy, including MLD, could be effective in preventing secondary lymphedema for at least 1 year in women following breast cancer surgery and ALND. In the study the control group received education only and the intervention group MLD, scar massage, and shoulder exercises. Risk factors for lymphedema were similar between groups. At 1 year follow-up the difference was significant ( P =.01). In the control group, 25% developed lymphedema compared to 7% in the intervention group. It may be argued in the study MLD was combined with other therapy modalities so there was no clear contribution from MLD.

There is an emerging new approach using fluroroscopy guided MLD to enable more specific application of MLD treatment. In a recent study Suami et al. developed a prospective protocol using ICG fluorescent lymphography to identify lymphatic drainage pathways in patients with BCRL. The protocol is intended to assist with the diagnosis and treatment interventions of BCRL including ICG- directed MLD. In the imaging procedures for the protocol MLD is performed by a therapist to facilitate movement of ICG through the lymphatics. The study cohort included 103 upper limbs examined in 100 patients of which ALND was performed in 99 limbs. The ICG lymphographic findings of the study demonstrate that MLD can advance the transit of ICG by way of dermal backflow and lymph vessels; it identified various lymphatic drainage pathway patterns including the ipsilateral axilla, clavicular, parasternal and contralateral axilla regions; although the majority of patients had undergone ALND, the ipsilateral axilla drainage pathway was found to be the the most commonly used pathway in 67% of the upper limbs, suggesting that there are patent lymph vessels that traverse the axilla and provided drainage in over 2/3 of the patients in the study. The MD Anderson ICG classification/staging system ( Fig. 21.5 ) was incorporated into the study to investigate the correlation between the identified lymphatic drainage pathways and the severity. As the severity of the disease increased there was a decrease in ipsilateral axilla drainage and increased drainage to the parasternal and contralateral axilla as found in Stage 4 of the MD Anderson ICG staging. MLD is a central component of lymphedema management. The ICG lymphograpy protocol identifies the individuals lymphatic drainage pathways enabling a personalized approach to MLD which may potentially improve MLD application and techniques.

The relative contribution of MLD to complete decongestive therapy (CDT) should be further examined. This would address the question as to whether MLD alone would be of benefit especially in participants with mild BCRL.

Compression

Compression is an important and indispensable component of CDT and is necessary for both initial and long-term lymphedema management. It is considered a cornerstone of lymphedema treatment.

Compression modalities most commonly used in lymphedema treatment are compression bandages (CBs), Adjustable Velcro compression devices (AVCDs), and compression garments.

Compression therapy is always included in CDT. Studies have been conducted to unbundle compression from the other components of CDT to determine the efficacy and contribution of compression as a first-line therapy in the management of lymphedema. This is relevant as CDT is both labor intensive and costly to both the patient and health-care sector. In a small randomized controlled study McNeely et al. assessed 50 women with BCRL and demonstrated that 4 weeks of CB reduced arm volume effectively with or without the addition of MLD. Andersen et al. conducted an RCT of 42 patients with mild or early onset BCRL and found that MLD was not a significant factor contributing to further reduction in volume compared to compression alone. Another trial by Dayes et al. randomly assigned 103 women with lymphedema to either CDT (daily MLD, bandaging, followed by compression garments) or compression garments alone. The study demonstrated no significant difference in volume reduction, arm function, and QOL measures between the two groups. Study results suggest that a subgroup of patients with a diagnosis of lymphedema exceeding 1 year benefited more from CDT compared to compression garments alone. Conversely, women with a history of lymphedema of less than 1 year the treatment benefit was almost identical in both groups. Finally, Zasadzka et al. in a recent randomized trial in elderly patients with unilateral LLL, compared CDT to CB alone. The study measured 103 patients, 50 treated with CDT, and 53 with CB, reduction in swelling in both groups, were achieved but with no significant difference in volume reduction between the two groups.

These studies provide data that suggest CB as a possible first line therapy in the management of lymphedema. However, although most of the studies are RCTs the findings are limited due to small sample sizes.

In a consensus document a classification system for compression was introduced to describe the deciding characteristics of compression bandaging. Pressure, LAyers, Components, and Elastic properties (PLACE) as the primary variables to consider when applying a CB. The elastic properties of a bandage may be inelastic (rigid bandages or short-stretch bandages) or elastic (long-stretch bandages). The static stiffness index (SSI) may be a helpful parameter to specify stiffness for CBs, including multicomponent multilayer short-stretch compression bandaging. The SSI is the subbandage pressure when changing from a supine to standing position. This is measured at approximately 12 cm above the medial malleolus. A pressure >10 mm Hg is considered a stiff product (inelastic) and <10 mm Hg marks elasticity.

Short-stretch bandages are the preferred choice in the management of lymphedema especially during the reduction phase of therapy due to its low resting pressure that is comfortable at rest and a high working pressure that will maximize the pressure generated with muscle contraction during movement. This allows for a reduction in limb volume and a massaging effect on the tissues and softening of fibrosclerotic skin areas. The use of special padding materials may be added to the bandages to provide a local massaging effect to indurated tissue. The most significant volume reduction usually occurs during the first week of treatment.

In many studies over the years a strong pressure was defined from 40 to 60 mm Hg and very strong as greater than 60 mm Hg with high stiffness, but the compression was not often measured. There is now a debate in the literature of optimal pressure for edema reduction, stiffness, and other variables related to efficacy and comfort. Mosti and Cavezzi in a recent review of the literature describe a trend toward the use of lower pressure for both upper and lower extremities with a range of 20–30 mm Hg in arm lymphedema and 40–60 mm Hg for LLL as effective parameters and suggest that high stiffness may not be an essential prerequisite. A randomized controlled trial compared the effect of low (20–30 mm Hg) versus high pressure (44–58 mm Hg) short stretch, multilayer CBs in patients with moderate-to-severe BCRL. In the first 24 hours the lower pressure bandages were shown to be better tolerated and were equally effective as bandages applied at a higher pressure.

Short-stretch, multilayered CBs are an essential component of CDT and are a mainstay in lymphedema management particularly in the acute treatment phase. However, there is a pressure drop that will occur with short-stretch bandages requiring reapplication of bandages on a regular basis often on a daily basis in order to maintain optimal pressure. AVCDs can be used in both the initial and maintenance phase of treatment ( Fig. 21.6 ). These adjustable devices were once recommended for the maintenance treatment phase only; however, research studies have shown them to be also effective in the initial treatment phase. Damstra and Partsch conducted a randomized controlled trial comparing AVCDs to CBs during the initial treatment of leg lymphedema and demonstrated significant leg volume reduction with the use of the AVCDs as compared to conventional bandaging. In a recent RCT, Mosti et al. demonstrated AVCDs to be effective in reducing venous edema in the initial treatment phase. The study demonstrated that both compression systems (AVCDs and CBs) achieved a significant reduction of total lower leg volume as compared to baseline measurements; however, in comparing effects of both devices the AVCD group showed a significant volume reduction after both 1 and 7 days as compared to the CB group ( P <.001). The authors concluded AVCDs to be an effective and well-tolerated option in both the initial and maintenance phase of treatment. Advantages of AVCDs include the ease and handling of the device by the patient or caregiver, and if there is a pressure loss, it can be readjusted by the patient according to subjective sensations. Patients were also found to avoid the use of unacceptable high and low pressures during self-application or readjustment of the devices.

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