State-of-the-Art Lymphedema Surgery Treatment Program

Abstract

The purpose of this article is to describe the multidisciplinary lymphedema surgery treatment program at Washington University in St. Louis. In this article, we discuss our collaboration with colleagues in medicine and therapy for conservative management and lymphedema staging. We describe our preferred imaging modalities for diagnosis, staging, and surgical treatment. Finally, we provide an overview of the surgical procedures we perform and our surgical treatment algorithm.

Introduction

Lymphedema is a progressive, debilitating condition that affects up to 250 million people worldwide.¹ Lymphedema is characterized by an accumulation of fat or fluid—most commonly in the upper or lower extremity—that results in progressive swelling, pain, numbness and tingling.^1,2 Eventually, patients develop hypertrophy, acanthosis, and hyperkeratosis that results in skin breakdown.² A feared consequence of lymphedema is the development of cellulitis, lymphangitis, and lymphatic malignancies.² To prevent such complications, clinicians aim to diagnose and treat lymphedema at its early stages. The International Society of Lymphology staging guidelines are provided in Figure 1.

Figure 1.

International Society of Lymphology Lymphedema Staging Guidelines

Lymph fluid flows throughout the network of lymphatic channels, moving by contraction of skeletal muscles. An insult to the transport of lymphatic fluid results in the accumulation of protein-rich fluid, excess water, blood cells, and cellular products.³ As flow of lymphatic fluid becomes impaired, the remaining lymphatic vessels dilate and valves fail to maintain unidirectional flow of fluid. Persistent lymphatic stasis results in the accumulation of proteinaceous fluid and induces inflammation—causing cellular proliferation, deposition of fat, and fibrosis of lymphatic vessels.^3,4 Lymphedema results when the lymphatic pumping potential becomes overwhelmed, resulting in the accumulation of fluid in the subcutaneous tissue.³

Etiology

Causes of lymphedema can be divided into two groups: primary and secondary lymphedema. Primary lymphedema is caused by a developmental abnormality and may present at birth, during adolescence, or during adulthood. A genetic mutation is implicated in 30% of patients, most commonly the vascular endothelial growth factor (VEGF) signaling pathway is implicated.⁵

However, most cases of lymphedema amenable to surgical management are caused by an insult to the lymphatic system which may be infectious, cancerous, or traumatic. In the developing world, secondary lymphedema is primarily caused by infection with microfilaria Wuchereria bancrofti, which affects up to 300 million people world-wide.^3,5 In the Western world, lymphedema is iatrogenic, most commonly secondary to the treatment of breast, gynecologic, and skin cancer.⁵ Most commonly, lymphedema results secondary to breast cancer. The risk of breast cancer-related lymphedema (BCRL) increases with axillary lymph node dissection, adjuvant radiotherapy, and regional nodal irradiation.⁵ The combination of lymphadenectomy and post-radiation scarring damages the lymphatic system and results in lymphadematous swelling of the upper or lower extremity.⁶ The incidence of BCRL after mastectomy ranges from 24%–49% and from 4%–28% after lumpectomy.⁴ Historically 20%–50% of patients undergoing axillary lymph node dissection developed secondary lymphedema, but this number has decreased to 5%–7% with the advent of sentinel lymph node biopsy.³

As a result of fluid accumulation patients experience heaviness, numbness, tingling, and pain of the extremity (Figure 2).^3,7 Lymphedema is associated with a decreased quality of life, embarrassment due to the cosmetic appearance of the affected limb, and financial burden. Patients report a decreased ability to perform activities of daily living and maintain employment.^3,8,9

Figure 2.

Presenting Symptoms of Lymphedema

Multidisciplinary Lymphatic Disease Diagnosis

Surgical planning for the management of lymphatic disorders requires advanced imaging techniques for lymphatic mapping. Historically, the gold standard for the diagnosis of lymphedema was lymphoscintigraphy.¹⁰ First introduced in 1953, it has been the primary imaging modality used to definitively diagnose patients with extremity lymphedema. Lymphoscintigraphy uses radioactive contrast, Technetium-99m sulfur-colloid, to provide images of the lymphatic system and assess lymphatic flow. The colloid tracer is injected into the first webspace of the hands or feet; is taken up by lymph nodes; and then enters the lymph ducts. A gamma scanner is used to follow the movement of radioactive material. The amount of radiotracer absorbed throughout the lymphatic system indicates the function of lymphatic channels and drainage of lymph to nodal basins. Lymphoscintigraphy assesses the speed of lymph node drainage (transport index) to semi-quantitatively understand the severity of lymphedema and identify lymphatic channel blockage. The measurement is based on the speed of uptake and time to reach the lymph nodal basin. Delayed uptake indicates partial blockage; absent uptake indicates complete blockage of lymphatic flow.¹¹ Lymphoscintigraphy does not provide a dynamic visualization of lymphatic vessels and lymph nodes. Due to the slow movement and absorption of colloid, lymphoscintigraphy has limited temporal and spatial resolution.^{12, 13}

In recent years, Magnetic Resonance Imaging (MRI) has emerged as a new method for the diagnosis of lymphatic diseases due to its high sensitivity for depiction of abnormal lymph vessels without the use of a radioactive isotope.^13,14 At our institution, Magnetic Resonance Lymphangiography (MRL), which uses Gd-BOPTA (gadolinium benzyloxypropionictetraacetate) has emerged as the preferred imaging modality for the visualization and diagnosis of lymphatic disorders. This modality allows for the dynamic assessment of lymphatic architecture and drainage. Three-dimensional visualization of lymphatic channels assesses for morphological abnormalities. Due to the specificity of gadolinium contrast for the lymphatic system, it is possible to visualize finely detailed morphological abnormalities in lymphatic vessels—even for vessels as small as 1mm. MRL is able to visualize distinct intranodal structural pathology and allow for real-time lymph flow monitoring. The high spatial resolution of MRL has profound implications for the surgical management of lymphedema: MRL can localize the damage to the lymphatic system so that the appropriate vessels for lymphovenous anastomosis can be determined preoperatively. The 3D assessment of lymph vessels helps guide intraoperative lymph node and vessel transplantation.¹⁴ Volumetric assessment of the limb and the 3D depiction of the relationship between lymphatic vessels and the venous system is a useful guide both pre- and intraoperatively. Additional information on the severity of lymphedema, degree of fat accumulation, and volume of muscle is also beneficial for surgical planning.¹⁴ MLR demonstrates extra-lymphatic abnormalities, including: the location of edema, deposition of fat, and tissue fibrosis to distinguish lymphedema from other types of edema. The higher spatial resolution; depiction of structurally abnormal lymphatic channels; 3D images; and absence of ionizing radiation have positively impacted our clinical practice and microsurgical outcomes.

We use fluorescent lymphangiography for intraoperative lymphatic mapping. Indocyanine Green (ICG) is injected into the web space of the digits. Fluorescence lymphangiography detects the near-infrared light emitted by the indocyanine green dye which demonstrates the path of lymphatic vessels.^15,16 Only functioning lymphatics take up ICG which allows clinicians to distinguish functioning lymphatics from non-functioning lymphatics. ICG can demonstrate disruption of lymphatic flow, tortuous abnormal lymphatics, and dermal backflow—which is diffuse leakage of dye into the interstitium as a result of lymphatic vessel abnormality. The subdermal pattern of ICG uptake correlates the degree of dilatation and fibrosis in the lymphatics.⁶ Most commonly, ICG is used for evaluating lymphatic transport, the presence of functional lymphatics, and the distribution of dermal backflow.^5,15,16 Intraoperative ICG allows surgeons to make incisions precisely over the functional lymphatic vessels for the lymphovenous anastomosis. Identifying the appropriate functioning lymphatic vessel for bypass is the step most important for success of the operation.^15,16 The use of ICG has been shown to reduce operative times and improve outcomes while simultaneously allowing for the accurate assessment of disease severity and ISL staging.¹⁵ ICG findings positively correlate with lymphoscintigraphy when used to determine disease severity, while being a less invasive and lower cost test.

We obtain MRI lymphangiography preoperatively for disease staging and treatment planning. We use the ICG intra-operatively to identify dermal lymphatics for lymphovenous anastomosis. In the operating room, it is our practice to confer all ICG findings with the MRI lymphangiography such that all channels identified on MRI assessment are also marked out with ICG before incision.

We have partnered with lymphedema therapists in both the physical and occupational therapy department for preoperative optimization and disease staging. Our therapists perform circumferential measurements to compare volume differences between the affected and unaffected limbs and monitor the progression of symptoms over time.

We have begun to use bioimpedance spectroscopy using the SOZO® bioimpedance spectroscopy device (ImpediMed) in the assessment of lymphedema. The Sozo device produces an L-Dex score in 30 seconds by passing a small, painless electrical current through the limb. The amount of interstitial fluid is inversely proportional to the resistance in the circuit. As lymphedema develops, the amount of fluid will increase, making it easier for the signal to travel through the extremity. The L-Dex score represents the difference in extracellular fluid volume in the diseased limb compared to an unaffected limb. We obtain L- Dex scores at baseline at each postoperative visit to monitor changes to lymphedema. The L-dex score may be the most sensitive test to detect lymphedema in the earliest stages, even before symptoms become apparent.¹⁷

Multidisciplinary Management of Lymphatic Diseases

Prior to surgical workup, our patients undergo medical and therapeutic optimization of their lymphedema symptoms as surgical results are optimized when combined with therapy. Decongestive treatment, performed by our Certified Lymphedema Therapists (CLTs), is commonly recommended for patients with ISL stages I–II lymphedema. Our CLTs are specifically trained in manual lymphatic drainage to manually move lymph fluid away from the obstructed portion of the limb towards the center of the body. Concurrently, multilayer low-stretch bandages are applied to the limb to prevent refilling of the evacuated fluid. Our therapists work with patients to develop specific exercise regiments to restore flexibility and strength which improves lymphatic drainage through muscle contraction. Patients are encouraged to use a lymphatic drainage pump which forces excess lymph fluid out of the affected limb and into the central body circulation. We work with patients to establish a well-balanced diet and control body weight for symptom management.

Surgical Treatment

Historically, lymphatic surgery was reserved for the most severe cases. However, over the past several decades, “supermicrosurgery” on lymphatic vessels has allowed for the development of techniques to treat lymphedema in the early stages.³ Surgical management of lymphedema is divided into physiologic procedures and debulking or reductive procedures. Both procedures aim to restore lymphatic flow. Physiologic procedures rewire the lymphatic system to restore lymphatic flow and improve the clearance of excess lymphatic fluid. Excisional procedures focus on removing diseased tissue. Physiologic procedures are indicated for early stages of lymphedema; these procedures restore anterograde flow of lymphatic fluid. Lymphovenous anastomosis (LVA) and vascularized lymph node transplant (VLNT) are common physiologic procedures. Debulking procedures are indicated in later stages of lymphedema; these procedures remove fibro-fatty tissue. A brief surgical guide of the procedures we offer is provided in Figure 3.

Figure 3.

Brief Surgical Guide of Operative Procedures

Lymphovenous anastomosis was originally pioneered in 1952 by Sherman and colleagues and subsequently modified by Koshima, who introduced supermicrosurgical LVA which utilizes lymphatics and venules less than 0.8mm in diameter.¹¹ This operative technique is a bypass operation that redirects the flow of lymphatic fluid into the venous circulation.² The lymphatic channel is connected directly to the venous system for venous drainage, bypassing the area of obstruction. This procedure is indicated for patients who still have functionality of the lymphatic system as demonstrated by ICG lymphography. Flow of lymphatic fluid is only partially obstructed. ICG is used to visualize the flow of dye from the distal extremity toward the trunk. Using a near-infrared camera, the course of functioning lymphatic vessels is traced by following uptake of the dye and correlated with the findings of MRL. ICG and MRL is used to visualize the most functional lymphatic channels and these are chosen for anastomoses. Once optimal vessels are identified, short transverse incisions are planned over the marked channels. Isosulfan blue dye is injected subcutaneously for improved visualization of the lymphatic during anastomosis. Once a lymphatic is identified, a subdermal venule of similar caliber is chosen (between 0.3mm and 0.8 mm in diameter).¹¹ The anastomosis between the lymphatic and vein is created end-to-end or end-to-side using 11-0 or 12-0 nylon suture.² Once the anastomosis has been created, patency can be assessed by visualizing the prompt, anterograde flow of blue-stained fluid across the suture line. Increased pressure in the lymphatic vessel forces fluid into the venous system. Increasing the number of LVAs created maximizes symptom relief.² This procedure carries high therapeutic benefits for patients with ISL stage I–II lymphedema with minimal morbidity. It is an outpatient procedure that utilizes minimal incisions and absent blood loss.

For patients with a more advanced stage of disease (ISL stages II–III), vascularized lymph node transfer (VLNT) is recommended. During this procedure, healthy lymph nodes, along with their vascular supply, are transferred to the affected area. Care is taken to maintain vascularity of the lymph nodes for greater improvement of edema and better lymphatic function. The newly transplanted lymph nodes act as a sponge to absorb lymphatic fluid and direct it into the vascular system. These lymph nodes secrete growth factors (VEGF) that stimulate the generation of new lymphatic pathways and channels at the site of disease.³ Vascularized lymph node transfer is performed for patients who have suffered from damage to the lymph node basins secondary to lymphadenectomy or radiation therapy.² As a result, patients have complete blockage of lymphatic fluid at the site of insult.

Vascularized lymph node transfer typically utilizes groin, thoracic, submental and supraclavicular node, though recently mesenteric lymph node transfer and omental transfer has been reported.¹¹ Most commonly, supraclavicular lymph nodes based off the transverse cervical artery and vein and the superficial inguinal lymph nodes supplied by the superficial circumflex iliac artery are used.² Recently, Dayan introduced reverse lymphatic mapping to aid in the identification of donor nodes from the groin and axilla that are expandable and whose harvest will not cause subsequent lymphedema at the donor-site. ¹⁸ This involves injecting technitium into the web spaces of the hand or foot and identifying nodes using the gamma probe.^3,11 Furthermore, technical modifications for lymph node placement have evolved to improve post-operative outcomes. Since upper extremity lymphedema occurs as a result of previous surgery to the axilla with or without radiation, wide excision of scar tissue, to prevent impingement on surrounding vasculature, is advocated. This will create optimal conditions for lymphangiogenesis and aid in creating a patent connection between the nodes and the recipient bed, such as the thoracodorsal artery.¹¹

For lymphedema of the lower extremity, the ankle and the groin are the most common recipient sites. As in the axilla, it is important to remove scar tissue in the groin caused by previous surgery and radiation. The superficial circumflex iliac vessels are used for the anastomosis. When lymphedema occurs distal to the groin, the ankle is the optimal recipient site due to its dependent position. Gravitational forces pull fluid into the ankle, so lymph nodes in this region can facilitate drainage. When the ankle is used for anastomosis the anterior tibialis or dorsalis pedis arteries are often used.¹¹ For optimal surgical outcomes, when performing, VLNT flap inset, minimal tension should be used.¹¹

VLNT is an effective procedure for patients with total occlusion of lymph channels based on lymphoscintigraphy; ISL stage II lymphedema, history of cellulitis; and for patients who have failed 12 months of conservative therapy.¹¹ For these patients, results have shown up to 30–60% reduction of excess volume when compared with the unaffected limb.^2,11 In a systematic review that captured 305 patients, almost 50% of patients did not require postoperative compression garments.³

Finally, for patients with severe lymphedema, ISL stage III, excisional treatment is recommended. Excisional treatment can be performed with liposuction, during which tissue is removed by vacuum aspiration. Liposuction for the treatment of lymphedema is most useful in addressing large adipose tissue deposits and volume excess of upwards of 600 ml. Liposuction results in immediate reduction in volume and lymphatic pressure of the extremity and improved lymphatic flow. All patients must wear a compressive garment immediately after the procedure and are encouraged to wear compression garments indefinitely. One study has found that liposuction achieved an average excess volume reduction of 96.6% and patients report an immediate improvement in well-being and quality of life.^3,19

The Charles procedure is performed at our institution for patients with elephantiasis and significant fibrosis of the extremities. This procedure involves the radical excision of skin and subcutaneous tissue down to muscle fascia or underlying epimysium which is subsequently covered by skin grafts. This is an ablative procedure that disrupts remaining lymphatic function and results in ulceration, hyperkeratosis of overlying skin.^2,3 Due to the risk of complications, this approach is reserved for very severe cases that are not amenable to therapy or any other approach. Patients stay in the Intensive Care Unit postoperatively.

Surgical modifications have evolved to combine the procedures mentioned above. For patients with BCRL it is possible to perform LVA at the time of microvascular free tissue breast reconstruction. If a lymph node transfer is required, we recommend performing this in a subsequent procedure such that the breast reconstruction is complete and the thoracodorsal vessels can be used for the VLNT without concern.² In our practice, the senior author of this report has experience harvesting lower abdominal flaps with the attached inguinal lymph nodes for the treatment of lymphedema among patients undergoing concurrent delayed breast reconstruction. The thoracodorsal vessels are used as recipients in the axilla.¹¹

Conclusion

Our state-of-the-art multidisciplinary lymphedema treatment program offers conservative, medical, and therapeutic management. Our partners in therapy are crucial for baseline lymphedema measurements, preoperative optimization, postoperative therapy, and limb volume surveillance. We have developed an imaging protocol that utilizes MRI lymphangiography to stage lymphedema and guide surgical planning. ICG is used for intraoperative lymph channel identification. Patients with ISL stage I–II lymphedema are offered LVA, and patients with more advanced stages of disease are offered VLNT. Our surgical algorithm is provided in Figure 4. Improving the quality of life for patients with lymphedema is central to our goal. Clinical and basic science research focused on the pathophysiology of lymphedema propels our mission forward. Though conservative management with therapy is our first-line treatment, surgical management offers an exciting and innovative way to approach an oftentimes difficult and recalcitrant problem.

Figure 4.

Washington University in St. Louis Lymphedema Surgery Algorithm ISL, International Society of Lymphology; LVA, lymphovenous anastomosis; PT, physical therapy; VLNT, vascularized lymph node transfer