Approach to Lymphedema Management

Abstract

Millions of people worldwide suffer from lymphedema. In developed nations, lymphedema most commonly stems secondarily from oncologic treatment, but may also result from trauma. More recently, lymphedema has been identified in patients after gender-affirmation phalloplasty reconstruction. Regardless of the etiology, the underlying pathophysiology involves blockage of lymphatic flow, resulting in lymph stasis, thus triggering a cascade of inflammation culminating in fibrosis and adipose deposition. Recent technical advances led to the refinement of physiologic and reductive surgeries—including lymphovenous anastomosis and free functional lymphatic transfer, which collectively encompass a variety of flap procedures including lymph node transfer, lymph channel transfer, and lymphatic system transfer. This article provides a summary of our approach in the assessment and management of the lymphedema patient, including detailed intraoperative photography and imaging, in addition to advanced technical considerations in physiologic reconstruction.

Despite medical advances over the last century, lymphedema remains as a chronic progressive disease that continues to affect hundreds of millions of people worldwide. In developed countries, lymphedema is most commonly iatrogenic in nature following cancer treatment, but may also be developmentally primary lymphedema, or secondary to trauma or surgical treatment of other conditions. An estimated 5 to 6 million Americans must cope with lymphedema, exceeding the prevalence of Parkinson's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis combined. ¹ The most common malignancies associated with lymphedema include breast, gynecologic, head and neck, neurologic, melanoma, sarcoma, prostate, and lymphoma. Trauma remains another significant contributor to lymphedema. As gender-affirmation surgery grows in prevalence, lymphedema has been increasingly observed in patients undergoing gender-affirmation phalloplasty reconstruction and is an area of ongoing research as well.

Numerous developments have been made over the last decades that have improved the diagnostic capabilities, assessment, and available surgical treatment options to alleviate the symptoms of lymphedema. This article provides an overview of lymphedema epidemiology and pathophysiology, along with our approach in assessment and management. We discuss procedure selection, including supermicrosurgical lymphovenous anastomosis (LVA) and free functional lymphatic transfer (FFLT), along with special technical considerations.

Epidemiology

Oncologic

In breast cancer treatment, an estimated 20 to 50% of patients undergoing complete axillary lymph node dissection will develop lymphedema, but fortunately the incidence decreases to an estimated 5 to 7% with sentinel lymph node biopsy. ¹ In other forms of cancer, meta-analysis examination suggested an overall incidence of lymphedema of 15.5%, which varied by malignancy. The highest incidence was 30% along those with sarcoma, followed by 28% of gynecologic cancers, 16% melanoma, 10% genitourinary cancers, and 4% head and neck cancers. ² Examining gynecologic malignancies further, 27% were related to cervical, 30% vulvar, and 1% to endometrial cancers. ² After solid tumor treatment, it is estimated that 1 in 6 patients will develop lymphedema, likely due to a common progression with regional lymphatic metastases before distant metastases, and treatment often including dissection of the involved lymph node basins.

Lymphedema onset after tumor treatment develops in a highly variable delayed fashion, varying between breast cancer-related upper extremity lymphedema and tumor-related lower extremity lymphedema. Within breast cancer lymphedema, diagnoses have been reported ranging from 30 days to 30 years postoperatively, with an average of 8 months after cancer treatment. However, 80% of cases present within the first 3 years of surgery, with an additional 1% per year presenting after 3 years. The severity and rate of progression are difficult to predict.

Risk factors for development of lymphedema in breast cancer patients include 10 or more lymph nodes removed during biopsy, adjuvant chemotherapy, supraclavicular radiation therapy, and obesity. ³ Patients with body mass index greater than 30 are 3.6 times more likely to develop lymphedema, and interestingly it is obesity at the time of breast cancer diagnosis that correlates with a higher risk, rather than those patients with weight gain after diagnosis. Unfortunately, losing weight after diagnosis of breast cancer did not alter this risk in this study.

Within lower extremity cancer-related lymphedema, presentation has been found to have an earlier onset. In contrast to an average of 8 months to time of diagnosis in breast cancer, lower extremity onset tends to develop 3 to 6 months postoperatively. Approximately 80% of patients present within 12 months after tumor treatment, far more rapidly than those with breast cancer as well. ⁴

Risk factors for development of lower extremity lymphedema include inguinal, pelvic, and periaortic lymph node dissection local radiation therapy; and chemotherapy. ² Similar to breast cancer, obesity remains a risk factor as well. Risk is unaffected by the number of lymph nodes sampled, lymph node status, or open versus laparoscopic approach. ⁴ Combining data from melanoma, gynecologic, and genitourinary cancer patients, pelvic lymph node basin dissection confers a risk of 22%, and pelvic radiation therapy was correlated with a 31% risk. ²

Posttraumatic

Post-traumatic lymphedema has not been scrutinized to the extent that cancer related onset has, likely in part due to such a high variability among injury mechanisms, patterns, and treatment. Extremity edema occurs even without disruption of the superficial lymphatic system as a result of local inflammation and increased lymphatic production. ⁵ The lymphatic system reacts by attempting to evacuate excess fluid, eliminate cellular debris and microorganisms, and transport immune-mediated cells to the site of injury. ⁵

Szczesny and Olszewski examined posttraumatic edema in the lower limbs in closed injuries using lymphoscintigraphy and did not identify dermal backflow or disruption of lymphatics, but did observe dilatation of collecting lymphatics with a decrease in lymph flow rate. ⁶ It has been estimated that up to 20 to 25% of patients with traumatic injuries of the limbs involving bone fracture and/or soft tissue trauma will go on to have chronic edema following the inciting trauma, although the mechanisms are not fully understood. ⁵

Lohrmann et al. examined posttraumatic edema of the lower extremities using magnetic resonance lymphangiography (MRL), confirming dilatation of lymphatic vessels and fast lymphatic flow. ⁷ Collateral lymphatic flow involved both the suprafascial and subfascial lymphatic systems. Lu et al. used MRL to examine lower extremity lymphedema specifically within gynecology oncology-related patients ⁸ and while comparing the affected and contralateral lower extremities, their group again found a significantly larger diameter in lymphatic channels, but also found a greater number of visualized lymphatic vessels. These parallels suggest potentially similar underlying pathology, but further studies are necessary to more clearly identify risk factors in posttraumatic lymphedema.

Postsurgical Lymphedema in Gender-Affirmation Phalloplasty

Outside of oncologic and traumatic etiologies, lymphedema is increasingly being observed in donor sites following complex reconstruction, including phalloplasty for gender affirmation ( Fig. 1 ). It is well-known that the risk of donor site lymphedema increases with increasingly larger flap size harvest within the extremity. Although the circumferential forearm skin can be harvested as a microvascular flap based on the radial artery angiosome, this can be highly morbid because of the disruption of the superficial lymphatic drainage from the hand. In practice, a strip at least 3 to 5 cm in width overlying the posterior extensor compartment and the ulnar subcutaneous border should be kept intact at a minimum. ⁹ However, radial forearm phalloplasty reconstruction oftentimes requires a large skin paddle and it is most often not feasible to leave a large section of an intact skin bridge. Global microsurgery centers use varying flap skin paddle designs, and in some cases very little intact skin remains after flap harvest, consequently causing severely compromised lymphatic drainage after flap harvest ( Fig. 2A, B ) leading to postoperative lymphedema ( Fig. 2C ). A meta-analysis examining patients undergoing gender-affirmation radial forearm phalloplasty reconstruction identified lymphedema or limb swelling in 3.9% among 255 patients in 3 articles. ¹⁰ However, these outcomes were subjective reported outcomes without objective measurements and further detailed study would be beneficial.

Fig. 1.

Donor site lymphedema and cellulitis in a radial forearm phalloplasty donor extremity.

Fig. 2.

Lymphatic mapping ( A ) intraoperatively after radial forearm flap harvest ( B ) demonstrating lymphatic disruption and leakage with indocyanine green (ICG) mapping intraoperatively. ( C ) Severe dermal backflow in a separate postoperative patient demonstrates lymphatic obstruction at the interface with the skin graft.

In our experience in over 500 primary phalloplasty reconstructions, and occasional revision of those performed by other groups, preservation of an ulnar-sided skin bridge is typically helpful in prevention of edema. However, the ulnar skin-bridge alone is not sufficient to predict or guarantee prevention of donor site lymphedema after radial forearm flap harvest. Despite measures to preserve draining lymphatic channels along the ulnar hand and forearm with the aid of preoperative indocyanine green (ICG) lymphatic mapping at the time of flap design ( Fig. 3 ), a very small subset of patients still developed lymphedema. Lymphedema after anterolateral thigh phalloplasty is far rarer. Data collection is ongoing.

Fig. 3.

Indocyanine green (ICG) lymphatic mapping for preservation at the time of radial forearm flap design.

Anatomic studies have not identified lymphatic communication penetrating the deep fascia to permit drainage between the superficial and deep lymphatic systems, ⁹ but our findings suggest that lymphatic drainage may have a dominant laterality, and certain anatomic variances among patients have insufficient compensatory lymphatic drainage. Anatomic studies by Suami and Scaglioni have examined lymphatic territories in the upper limb and found that lymphatic territories among dominant lymph nodes do not overlap, ¹¹ but no studies to our knowledge have assessed functional capacity to compensate for focal blockage in vivo. We suspect a test may exist—analogous to the Allen's test for radial and ulnar arterial perfusion to the hand—that would assess the compensatory lymphatic drainage capacity between the radial and ulnar hand and forearm. Identification of anatomic variants with insufficient compensatory capability would enable prevention of donor site lymphedema. If high-risk patients could be readily identified, they would be potential candidates for immediate lymphatic reconstruction at the time of radial forearm flap harvest, as previously described by our group. ¹²

Symptoms

Regardless of the underlying etiology of lymphedema, the millions affected worldwide experience a similar constellation of symptoms that may vary widely depending on disease progression. Complaints include pain ranging from a dull ache to severe discomfort. Often vague, the symptoms are sometimes described as a burning or bursting sensation within the limbs; a feeling of “pins-and-needles” and heat and altitude sensitivity. These disturbances are thought to result from stretching of terminal nerve fibers due to the associated edema. Furthermore, fluid stasis within the extremity causes objective and subjective heaviness, impairing limb function as well. Skin changes occur with severity progression, ranging from skin dehydration with flakiness, to trophic skin changes including hyperkeratosis, acanthosis, papillomatous plaques, and ulcerations, as well as excoriation and skin breakdown with associated weeping and infection.

Due to impaired lymphatic function, the immune-mediated protection within the limb is compromised and increases susceptibility to infection from minor trauma that would otherwise be insignificant. Patients may experience recurrent cellulitis and lymphangitis, which in severe cases requires hospitalization and intravenous antibiotics as in Fig. 4 . Recurrent cases may necessitate long-term prophylactic antibiotics. Combined, these progressive symptoms and increased risk of infection impair extremity function and decrease quality of life on a constant daily basis.

Fig. 4.

Severe hand cellulitis in lymphedema requiring inpatient intravenous (IV) antibiotics.

Societal Impact

Despite the constant burden affecting patients, the impact of lymphedema often goes underappreciated. Unfortunately, the prevalence of lymphedema and lifelong symptoms combine to form a significant burden both for the patient and society. Treatment remains costly from both monetary and time utilization standpoints among office visits, lymphedema therapy, as well as mental health-related services, diagnostic imaging, and durable medical equipment. The psychosocial burden contributes as well, with patients experiencing depression, anger, and frustration, in addition to diminished perceived sexuality and social isolation. Economic analysis has estimated the difference in health care costs were nearly double in women with breast cancer-related lymphedema compared with those without over a 2-year study period. ¹³ Without proper lymphedema management, the permanent nature of the disease, disease progression, and need for ongoing treatment combine to generate long-term economic and societal impact.

Pathophysiology

As treatment of lymphedema evolves, understanding of the available options requires awareness of key elements of the structure and function of lymphatics. The lymphatic system is a series of vessels distributed throughout the surface of the body, also lining the internal surface of the gastrointestinal and respiratory tract, primarily functioning to maintain fluid balance in the body. Lymphatic channels provide a conduit for transport of fluid, hormones, nutrients, and waste products. Secondarily, the lymphatic system plays an important role in the immune system function, transporting bacteria and pathogens to the lymph nodes, thus assisting with activation of the immune system reaction.

Lymphatics mediate fluid regulation by returning proteinaceous deposits and extracellular fluid back into the central blood circulation. Estimates suggest the lymphatic system filtrates roughly 24 L of fluid per day, of which 85% is reabsorbed into the capillaries, and 15% is returned via the lymphatics. Fluid originates with extravasation from the blood circulation, which causes increased volume in the surrounding tissue. This fluid is then passively captured by the lymphatic capillaries, which have a fenestrated structure to allow diffusion of fluid and proteins, and thus rely on osmotic gradients and hydrostatic pressure to function. The lymphatic capillaries then feed into lymphatic precollectors in the deeper layer of the dermis, which then converge and course deeper through the subcutaneous tissue as superficial lymph collecting vessels. Superficial lymph collecting vessel walls contain smooth muscle cells and valves, and actively propel lymphatic fluid centrally toward lymph nodes. Deep lymph collecting vessels, in contrast, are located deep to the fascial layer and accompany arteries. A crucial consideration in lymphedema pathophysiology is the observation that deep lymphatics are not known to have connections to the superficial system. ¹¹ From the lymph nodes, fluid then passes via lymphatic trunks into lymphatic ducts, and then returns to the general circulation via connections to the subclavian veins, including the thoracic duct.

Structurally, the lymphatic system and venous structures share a common embryologic origin. Although they appear parallel to the venous system in the extremities, they have several crucial differences that impact treatment options. As mentioned, there are no bridging connections between the superficial and deep left collecting vessel systems, and thus disruption to the superficial lymphatic system does not necessarily imply compensatory function through the deep system. Furthermore, lymph collecting vessels run more independently and have fewer interconnections, again demonstrating a decreased compensatory capability compared with the venous system.

Due to such limited compensatory capability, lymphedema develops from disruption and blockage of flow. Chronic fluid buildup and fluid stasis causes extremity edema in addition to activation of chronic inflammatory pathways, which ultimately result in adipose deposition, adipocyte enlargement, and irreversible fibrosis. Together, these changes create a feedback loop by damaging the remaining functional lymphatics—leading to progressively worsened lymphatic disruption and lymphedema ( Fig. 5 ). Cellulitis feeds further into this cycle by contributing additional inflammation. Because of this feedback loop, it is well established that early intervention is important in disease management.

Fig. 5.

Feedback loop between fluid stasis, inflammation, and worsened lymphatic function.

Assessment, Diagnosis, and Evaluation

Management of lymphedema aims to prevent fluid stasis and prevent progression of the resulting inflammatory cascade. Due to the progressive nature of lymphedema, noninvasive management should begin as early as possible in suspected cases. This includes compression garments, pneumatic lymphedema pumps, and referral to lymphedema therapy for complex decongestive therapy (CDT).

Initial management begins with examination and workup for other causes of extremity swelling. Examination should note the degree of edema. It is of critical importance to identify the presence of fibrosis, adipose, or fluid dominance by assessment of pitting edema. Trophic skin changes and skin breakdown also provide information regarding severity. Patients are commonly assessed for the Stemmer sign, which describes the inability to pinch or lift the skin from the dorsum of the toe or finger. This accounts for the fact that lymphedema affects the entire extremity, whereas lipodystrophy or lipedema end at the level of the ankles and will not affect the feet or toes.

Other frequent misdiagnoses—including venous stasis, lipedema, obesity, trauma, vascular malformation, and rheumatologic disease—must be ruled out. Further basic workup assesses for recurrent or primary malignancy causing lymphatic or venous obstruction, deep vein thrombosis (DVT), venous insufficiency, and congestive heart failure.

Typical initial workup includes duplex ultrasound to assess for superficial and deep venous insufficiency and venous thrombosis, and computed tomography venogram to assess for venous obstruction within the pelvis, including mass effect, thrombosis, or May–Thurner syndrome. These measures can be important due to potential complications of initiating mechanical compression or massage in the setting of undetected DVT.

Lymphoscintigraphy confirms lymphatic blockage or delayed transit by assessing rate and pattern of transit of Tc99 Technetium 99 sulfur colloid. This is indicated by the lymphatic transport index wherein TI = 0 shows optimal lymphatic outflow and TI = 45 indicates no visible flow, with a normal TI < 10. Alternatively, MRL provides higher resolution and can assess the superficial and deep lymphatic systems in detail, measure lymphatic vessel caliber, and provide information regarding lymphatic transport time. However, MRL is expensive, time consuming, and not widely available as of this publication, and has limited application in real-time surgery. High-resolution ultrasound shows significant promise in real-time dynamic assessment of lymphatic channels including function, but similarly has limited availability at this time.

Initial Management

After lymphatic disruption has been confirmed, lymphedema therapy is initiated with CDT. CDT is composed of several elements, including manual lymphatic drainage, graduated compression wrapping, therapeutic decongestive exercises, skin care, and patient education. CDT is not curative, but aids with symptom management and prevention of disease progression by decreasing the burden of lymphedematous fluid in the affected area. While in therapy, progress can be tracked using objective limb measurement evaluation. Whether using serial circumference or volumetric measurements, the most important element remains reproducibility and availability of the selected technique for the duration of long-term treatment for ongoing monitoring. Limb circumference measurements are typically taken at multiple reproducible, defined anatomic locations in relation to extremity joints, for example. Classically, diagnosis is established based on a 2-cm difference compared with the contralateral limb. However, measurements have high interrater variability, and the utility is limited in patients with a high body mass. Volumetric measurements are considered superior and are typically obtained using a perometer infrared limb scanner, as opposed to water displacement methods or mathematical methods such as the truncated cone formula. Diagnostic criteria classically include a 200-mL or 10% difference between limbs. Bioimpedance is another method to serially track improvement in edema within the affected extremity by assessing differences in electrical current transmission due to edema.

Simultaneous with lymphedema therapy, further first-line treatment includes compression garments and lymphedema pumps. In many instances, custom fabricated garments are helpful due to unusual limb sizes that do not fit properly within off-the-shelf garments. Available compression levels vary, and although 20 to 30 mm Hg is typical, patient comfort and the resulting compliance dictate the actual compression level selected. If compression wraps are used, short-stretch bandages—as opposed to over-the-counter sports wraps or ace bandages—are most useful because they have limited excursion and thus limit the extent of limb edema permitted. This results in a low baseline pressure with a high working pressure, and accordingly may be worn throughout the day and night. Compression pumps are helpful for home decongestion, and both pneumatic and nonpneumatic versions are available. In both instances, a specially designed garment is worn over the affected area. A series of chambers or compressive elements activate in sequence, creating a gentle wavelike motion to promote transit of lymphedematous fluid toward the central circulation.

Patients are counseled regarding weight loss and exercise as well. An interplay appears to exist between adipose tissue and inflammation, as evidenced by the increased risk of lymphedema in obesity at the time of tumor diagnosis, and the observation that lymphatic stasis promotes adipose deposition, and inflamed adipose impairs lymphatic function. Accordingly, aerobic exercise may help to decrease disease severity by decreasing the body's adipose burden, thus reducing subcutaneous tissue inflammation and negative effects on lymphatic function.

No medications have been definitively proven to improve lymphedema, although some continue to undergo research. A common misconception revolves around diuretics aiding with edema, but in fact the opposite holds true—diuretics do not remove protein from the extracellular space, causing them to increase in concentration, thus increasing oncotic pressure and fluid extravasation, leading to additional edema and fibrosis over time. Prophylactic antibiotics may be helpful in select instances and are indicated for three or more episodes of cellulitis in 1 year. Infection prevention is particularly important due to the significant inflammatory contributions associated with cellulitis, which further the progression of lymphedema.

First-line noninvasive measures are universally instituted in all patients with suspected lymphedema after initial workup, as these measures pose minimal to no risk and aim to halt disease progression while providing symptom management. Unfortunately, these noninvasive measures rely upon patient compliance and are time consuming, often requiring multiple hours daily for care and therapy. In warmer climates, garments and pumps may be intolerable due to the warm environment. Furthermore, patient expenses compound rapidly, as the combination of garments, therapy, and lymphedema pumps may prove to be costly over time due to the need for ongoing treatment as well as product replacement from mechanical wear and tear. As insurance coverage is not widely standardized in the United States, the expense of ongoing first-line treatment alone is often cost prohibitive. Due to these numerous barriers surrounding patient compliance, discussion regarding surgical management may be explored.

Surgical Management

When patients find first-line measures to be intolerable or insufficient, then consideration for surgical treatment may be given. In general, a minimum of 4 to 6 months of noninvasive measures are trialed due to the potential for spontaneous regression, which is uncommon but has been observed.

To determine surgical candidacy, real-time detailed assessment of the superficial lymphatic system is performed using ICG lymphangiography, which can be performed either in the clinic or procedural setting. ICG is a water-soluble dye that is activated once bound to protein, emitting energy in the near-infrared range of 750 to 810 nm; the transit of this activated dye is then detected using near-infrared imaging systems. Imaging provides real-time high-resolution assessment of the anatomic location of lymphatic vessels, and provides dynamic information regarding their level of function based on the visualized pattern and flow rates. Intact channels have a crisp linear appearance, but lymphedema is demonstrated when abnormal flow, leakage, or blockage is visualized in conjunction with dermal backflow, punctate lymphatic vessel leaks, and hyperplastic and abnormal lymphatic vessels, as demonstrated in Figs. 6 7 8 9 . Multiple ICG staging systems have been proposed but in our experience the critical element is identification of normal versus abnormal lymphatic channels, and the specific anatomic site where the transition occurs for surgical planning purposes.

Fig. 6.

Indocyanine green (ICG) lymphatic mapping showing linear intact channels along the dorsal hand.

Fig. 7.

Flow proximally shows diffusion and leaking, suggestive of lymphatic vessel damage.

Fig. 8.

Diffusion and leakage of indocyanine green (ICG) demonstrates dermal backflow due to damage and fibrosis of the lymphatic channels, and confirms lymphedema.

Fig. 9.

Lower extremity lymphedema in gynecologic cancer-related lymphedema. Note transition from linear flow to dermal backflow.

Treatment options depend on the disease severity. The most common system used to grade severity is likely the International Society of Lymphology (ISL) staging system, which utilizes clinical criteria describing the presence of fluid versus fibroadipose dominance:

• Stage 0: Subclinical lymphedema, in which patients experience symptoms but have no measurable edema.

• Stage 1: Reversible limb swelling and pitting edema, indicating fluid predominance.

• Stage 2: Irreversible limb swelling, without pitting edema, indicating fibrotic or adipose dominance.

• Stage 3: End-stage lymphedema with severe swelling, trophic skin changes, and elephantiasis.

Procedure Selection

Procedure selection depends on disease staging and degree of fibrofatty deposition, both of which reflect the working condition of the remaining functioning lymphatics. As the severity of lymphedema progresses, the remaining lymphatic channels demonstrate progressively decreased function. When determining treatment options, it may be simplest to determine whether the edema is clinically primarily a dominance of fluid, versus fibrotic and adipose tissue. In general, surgical management falls within physiologic versus debulking techniques as shown in Fig. 10 .

Fig. 10.

International Society of Lymphology staging system of disease severity with associated treatment options, including physiologic (lymphovenous anastomosis [LVA], vascularized lymph node transfer [VLNT], free functional lymphatic transfer) and reductive (liposuction, excision) techniques.

Physiologic techniques aim to improve fluid drainage by restoring lymphatic drainage and some element of function. These techniques are thought to be most effective in fluid-dominant lymphedema, such as in those in ISL Stage 0 and 1 with pitting edema indicating the presence of fluid. Decreasing lymphatic fluid stasis results in lower subsequent inflammation and less damage to the remaining functioning lymphatics, thus slowing disease progression. Improved fluid mobility also decreases susceptibility to lymphedema-related cellulitis, thus decreasing the risk for limb-threatening infection requiring hospitalization. Furthermore, decreased fluid provides symptom relief by decreasing the weight of the extremity; improving cosmetic appearance with reduction in extremity volume and potentially reducing pain by decreasing stretch on terminal nerve fibers. Treatment timing relies on the presence of remaining functioning lymphatics and should be performed early in management. If treatment is delayed, the remaining lymphatics may be injured past the point of utility due to disease progression, as suggested by research demonstrating better outcomes with earlier interventions. ¹⁴

Reductive techniques, in contrast, do not attempt to restore lymphatic function or decrease inflammation, but rather remove excess fibroadipose tissue. As with physiologic techniques, reductive techniques provide symptom relief by decreasing extremity size and weight, improving cosmesis, and can decrease painful stretching on nerve fibers. Patients must be committed to life-long compression to prevent recurrent accumulation of fibrofatty deposition.

Physiologic Reconstruction

Options for physiologic reconstruction include supermicrosurgical techniques to directly manipulate lymphatic channels, and microvascular flaps containing various lymphatic elements, collectively referred to as FFLT.

Lymphovenous Anastomosis

Supermicrosurgical reconstruction is composed of LVA, also known as lymphovenous bypass, and requires meticulous manipulation of vessels as small as 0.3 mm in diameter. LVA critically relies on remaining function lymphatics that still carry sufficient flow to transport fluid effectively. With this technique, lymph flow is diverted from the lymphatic vessels into the venous system upstream of the identified lymphatic blockage, thus providing an outlet for lymph flow and leading to decreased fluid stasis and edema, as depicted in Fig. 11A–D . The lymphatic blockage is bypassed by using the bloodstream as a surrogate conduit. Lymph fluid reenters the blood circulation peripherally in the extremity as opposed to centrally via the thoracic duct and attachments to the right subclavian vein, and has no negative physiologic consequence. Proper function depends on the pressure gradient between high pressure lymphedema congestion and the lower pressure venous system. High pressure in the lymphatic system results from fluid congestion, and is augmented with muscle contraction and external forces such as lymphedema pumps and compression garments, which help divert lymph into the recipient vein of the LVA.

Fig. 11.

Preop and 1-month postop demonstration of lymphovenous anastomosis bypassing focal lymphatic blockage. ( A , B ) Preoperative indocyanine green (ICG) lymphatic mapping showing complete blockage and severe dermal backflow at the ankle. ( C , D ) View of lymphovenous anastomosis (LVA) located just inferior to the scabbed wound 1 month postop, with ICG lymphatic mapping showing restoration of lymphatic flow via the LVA into a superficial venule, with decreased dermal backflow.

Aside from direct mechanical action of lymphatic decongestion, research by Torrisi et al. suggests that lymphovenous anastomoses induce physiologic and histologic changes via attenuation of CD4-mediated inflammatory response and decreased transforming growth factor beta 1 expression. ¹⁵ They suggest these changes may decrease the fibrotic response and dermal collagen deposition in lymphedema, thus blunting secondary trophic changes in lymphedema including skin thickening and increased lymphatic capillary density. Although LVA may alter the pathophysiology of lymphedema, they are not able to reverse changes.

When preparing for LVA, ICG lymphatic mapping is first performed to assess the severity of lymphedema and identify intact lymphatic channels that are suitable candidates for bypass. Fig. 12 demonstrates an ideal candidate lymphatic, with identification of a healthy linear lymphatic vessel with a focal obstruction causing dermal backflow and lymph stasis.

Fig. 12.

Example of a linear lymphatic transitioning to dermal backflow, demonstrating focally identifiable lymphatic blockage.

After identification of candidate lymphatics, nearby recipient superficial venules are identified, commonly with the assistance of a vein finder. Ideal targets are absent from venous reflux, and may be assessed for reflux by using a “strip test” similar to that used to assess microsurgical anastomosis patency. High-power operating microscopes are required for anastomosis, in addition to superfine instruments and superfine suture typically consisting of 10–0, 11–0, and 12–0 suture as exemplified in Fig. 13 .

Fig. 13.

( A ) Comparative size between a penny and 10–0 nylon suture with superfine needle. ( B ) Scaled comparison with a lymphovenous anastomosis. Each blue square indicates 1 mm.

LVA are well-tolerated procedures with numerous advantages including: minimal pain, commonly without any need for postoperative narcotics; a superficial, minimally invasive dissection; a low risk of complications; and ease of performance in an outpatient setting. In many instances when a lymphatic channel already demonstrates complete focal obstruction as in Fig. 12 , failure of LVA poses little to no risk of worsening lymphatic flow. Disadvantages to LVA include requirement of supermicrosurgical expertise, specialized superfine instruments, and a high-power operating microscope.

Growing literature supports symptom improvement with LVA with improvements in limb circumference and lower incidence of cellulitic infections, particularly in earlier stages of disease. ^{14 16} Gaining popularity is the LYMPHA (Lymphatic Microsurgical Preventive Healing Approach) technique, utilizing LVA as a preventive measure at the time of lymph node dissection. Advantages include direct repair in the lymph node basin at the time of dissection, with larger caliber vessels due to the more central location in the axilla; and anastomoses are technically easier due to the lack of fibrosis and sclerosis from chronic lymphedema inflammation. Data are promising although technique may vary highly between centers.

Free Functional Lymphatic Transfer

Microsurgical tissue transfer brings healthy noncritical lymphatic organs to the affected area and can be performed using a variety of flap designs, which we collectively refer to as FFLT. Vascularized lymph node transfers (VLNTs) remain the most common, but other techniques gaining popularity include vascularized lymph channel transfer (VLCT) as described by Koshima et al, and lymphatic system transfer (LYST) as popularized by Yoshimatsu et al., which include afferent lymph channels and their natural connections to the dominant draining lymph nodes. Regardless of the technique, microvascular anastomosis is only performed for the flap artery and vein, but not the lymphatic channels. Outcomes from multiple groups worldwide are consistent with clinical improvement after VLNT, with reduced extremity volume, decreased pain and heaviness, improved extremity function, and decreased incidence of cellulitis. ¹⁴

Various flap designs and donor sites are available to take advantage of nonessential donor lymph nodes—including those from the supraclavicular, omental, groin, lateral thoracic, submental, and axillary regions, for example—but ultimately the flap selection depends on surgeon and patient preference, available donor sites, and patient anatomy. There is no agreement regarding the optimal recipient site placement. Flap placement proximally in the axilla or groin has better cosmesis, allows for scar release from prior oncologic lymph node dissection, and may permit remaining lymphatics to drain; but the proximal location is not able to take advantage of gravity to enhance lymph drainage through flap-mediated action. Flap placement distally in the extremity has worse cosmesis, but permits gravity-assisted flap drainage, brings growth factors to the most congested area, and brings immune organs to the sites of recurrent infection. Direct comparison between differing flap types is difficult due to the variability among patient disease severity and anatomy, as well as surgeon technique and flap design.

It has been proposed that transferred lymph nodes exert function via several proposed mechanisms, including induction of new lymphatic vessel formation via secretion of growth factors such as vascular endothelial growth factor C, ^{17 18} functioning as an active pump to shunt lymph fluid drainage into the efferent flap vein, by serving as a local immune organism to aid the immune response and decrease cellulitis, and by potentially freeing sclerotic lymphatics and permitting further drainage. ¹⁹ Accordingly, patients appear to have a bimodal improvement in symptoms. Early improvement results from a direct pump action and fluid drainage augmentation as shown in Fig. 14 , while later improvement results from gradual induction of lymphangiogenesis and may take greater than 1 year.

Fig. 14.

Example of ( A ) preoperative lymphedema and ( B ) early improvement 3 weeks after microvascular vascularized lymph node transfer, likely due to direct lymphatic drainage through the flap.

Microvascular tissue transfer is generally regarded as a more powerful technique than LVA, but takes significantly more investment by the patient regarding the magnitude of surgery in terms of hospitalization and recovery. Drawbacks compared with LVA include the general risks of microvascular flap transfer—including lengthier surgery and inpatient admission. Donor site morbidity is another consideration, including seroma, chronic pain, and even iatrogenic donor site lymphedema, which may be mitigated by reverse sentinel node mapping as described by Dayan et al. ²⁰ Recipient site cosmesis may be a concern as well due to the addition of soft tissue bulk, but may be lessened by placement within the axilla or groin, or by local tissue debulking at the time of flap inset.

Reductive Techniques

Reductive techniques are generally reserved for patients with significant adipose and fibrotic deposits from longstanding disease and are most appropriate for patients with nonpitting lymphedema. Although physiologic techniques do not have significant impact on the burden of existing fibrotic tissue and adipose deposits, they may improve the soft tissue characteristics and improve the effectiveness of reductive techniques. Thus, physiologic techniques are performed first to enhance decongestion and improve suppleness in the affected extremity; and if necessary, reductive techniques are used to remove the remaining adipose deposition.

Liposuction-assisted debulking achieves dramatic improvement but 24-hour compression garment compliance postoperatively is required to prevent recurrence, which can recur rapidly within 3 months of noncompliance. ¹ Various technique modifications distinguish debulking in lymphedema from routine liposuction, as described by Schaverien et al and Brorson. ^{21 22} In general, power-assisted liposuction and ultrasound-assisted liposuction both enhance adipose removal in the fibrotic extremities, and blood loss can be minimized with use of a tourniquet and addition of tranexamic acid to the tumescent solution as well. Care must be taken to prevent damage to remaining superficial lymphatics, and it may be helpful to perform liposuction under ICG guidance to identify functioning channels. Direct excision using a Charles procedure is associated with significant morbidity and deformity and is typically only performed in severe end-stage lymphedema.

Special Technical Considerations for Physiologic Reconstruction

Lymphovenous Anastomosis

Lymphatic anastomoses are minimally invasive, well-tolerated outpatient procedures that may provide significant symptom relief. Surgical technique varies among centers, but preoperative preparation preferably includes optimized fluid decongestion. Postoperative care varies, and no standardized pathway has been established regarding postoperative compression, antiplatelet therapy, and antibiotic usage.

ICG lymphatic mapping may be performed preoperatively or intraoperatively, and adjacent superficial venules are identified using a vein finder. Reflux-free veins are preferred and are assessed using a strip test like that used to assess microvascular anastomosis patency. When selecting candidate LVA sites, consideration is given to the planned configuration: end-to-end, end-to-side, side-to-end, and side-to-side.

The end-to-end ( Figs. 13 and 15 ) or end-to-side (end-of-lymphatic to side-of-vein) configuration ( Fig. 16 ) is most useful for LVA performed immediately upstream of focal lymphatic blockage transitioning to dermal backflow, as in Fig. 17 . Between these two options, there may be a theoretical preference for end-to-side configuration. In the end-to-side anastomosis, ongoing venous flow is thought to maintain venous patency, and higher velocity outflow may create a zone of lower pressure due to Bernoulli's principle and ultimately augment lymphatic drainage from the high-pressure lymphatic congestion.

Fig. 15.

Steps during end-to-end lymphovenous anastomosis. ( A ) The lymphatic is identified with isosulfan blue dye, adjacent to a superficial venule. ( B ) The lymphatic is divided and anastomosed to the end of a side branch of the venule. ( C ) Indocyanine green (ICG) confirms patent lymphatic flow without leakage. ( D ) Isosulfan blue dye similarly confirms patency without leakage.

Fig. 16.

End-to-side lymphovenous anastomosis (LVA) demonstrating passage of lymphatic fluid into the venous system. ( A ) Patency viewed with isosulfan blue. ( B ) Patency viewed by indocyanine green (ICG).

Fig. 17.

Lymphatic mapping and indocyanine green (ICG) tracing showing abrupt transition to dermal backflow, indicating an ideal candidate site for lymphovenous anastomosis (LVA).

Side-to-end (side-of-lymphatic to end-of-vein) LVA ( Fig. 18 ) are useful when the lymphatic is linear both distal and proximal to the target site. This configuration has the advantage of providing both antegrade and retrograde lymphatic flow, and has been shown to have similar effectiveness to multiple end-to-end anastomoses in serial configuration. ²³ The side-to-side configuration ( Fig. 19 ) similarly allows antegrade and retrograde lymphatic flow, and additionally may potentially have the benefits from constant venous flow. However, this design is technically demanding and requires the lymphatic and venule to be favorably situated anatomically.

Fig. 18.

Side-to-end lymphovenous anastomosis (LVA), from the side of the lymphatic (blue) to the end of the vein.

Fig. 19.

Side-to-side lymphovenous anastomosis (LVA) from the smaller lymphatic to the larger diameter vein.

After target site selection, dissection is performed under the operating microscope. The lymphatics identified preoperatively with ICG mapping are again identified using isosulfan blue dye and ICG under microscope magnification. Hemostasis is crucial for visualization, and is provided by lidocaine and epinephrine without use of a tourniquet. The vessels are dissected meticulously, and handsewn using the planned configuration ( Fig. 15A, B ). Adjacent adipose tissue is excised to prevent any compressive forces on the LVA that may risk thrombosis. Patency is again assessed using ICG and isosulfan blue dye ( Fig. 15C, D ).

Free Functional Lymphatic Transfer

Among microvascular FFLT, various designs and configurations are available which utilize varying components of the lymphatic system. Isolated VLNT flaps are the most common and focus on transfer of lymph nodes and larger afferent lymphatic vessels, and have the advantage of small flap bulk which is easier for inset and cosmesis. In contrast, vascularized lymph vessel transfer (VLVT), also referred to as VLCT, was originally proposed by Koshima et al ²⁴ and does not contain lymph nodes, but rather transfers healthy, contractile superficial lymph collecting vessels containing smooth muscle cells and valves to transport lymph fluid into the venous system. It is hypothesized that VLVT also work via a pump mechanism as with VLNT. Yoshimatsu et al. describe a combination of these techniques, utilizing LYST composed of vascularized afferent lymphatic vessels together with their vascularized draining lymph nodes. ²⁵ Although VLNT with skin paddles likely contain afferent lymphatic vessels, LYST flaps have more emphasis on flap design to capture and orient superficial afferent lymphatic vessels physiologically, and in theory have a lower dependence on delayed lymphangiogenesis for physiologic function.

Other variations have been proposed, but regardless of the flap type and lymphatic components included in the design, all functional lymphatic microvascular flaps rely on the theoretical pump mechanism. The microvascular flap elements absorb lymphatic fluid, which is then shunted back into the bloodstream via the efferent flap vein.

Considering the importance of flap perfusion on physiologic function, in our opinion the planned arterial and venous flap architecture deserves special attention. Functional lymphatic microvascular flaps typically lack intrinsic arteriovenous connections, and thus are high-resistance systems to flow through the flap. Consequently, end-to-end or end-to-side arterial inflow results in arterial flow into a blind arterial ending and is likely to cause a high-pressure gradient and a water-hammer effect, predisposing the flap to congestion, or even thrombosis due to slow flow. In our opinion, it is theoretically preferable to perform two arterial anastomoses in flow-through fashion, including both an arterial inflow and outflow, as shown in Figs. 20 21 22 . This may be done in end-to-end fashion to arterial side branches, or end-to-side to the named artery, but if possible not end-to-end to the larger named artery. The outflow artery thus acts as a “pop-off valve” and relieves the high pressure gradient against the flap, thus decreasing the risk of flap congestion. Furthermore, the constant arterial flow prevents risk of thrombosis from hemostasis, as might be found in a blind-ending artery. We prefer functional lymphatic microvascular flaps that have one contiguous inflow artery that allow this design, such as supraclavicular lymph node flaps. This flow-through arterial design is also more likely to present physiologic levels of blood flow to the transferred lymph nodes as they would experience in situ prior to harvest. Of course, flow-through design is not always possible, depending on the donor and recipient area anatomy.

Fig. 20.

Supraclavicular vascularized lymph node transfer (VLNT) with proximal artery and vein (right), and distal artery and vein (left) with anastomoses to the radial artery and radial vena comitans.

Fig. 21.

Close up of vascularized lymph node transfer (VLNT) proximal artery and vein. The inflow arterial anastomosis is end-to-side to the radial artery. The outflow venous anastomosis is end-to-end to a venous side branch of a radial vena comitans.

Fig. 22.

Close up of vascularized lymph node transfer (VLNT) distal artery and vein. The outflow arterial anastomosis is end-to-side to the radial artery. The inflow venous anastomosis is end to side to a radial vena comitans.

In similar fashion, we recommend that the flap veins be performed in flow-through fashion as well, for analogous reasons. Due to the high-resistance anatomy in FFLT flap arteriovenous connections, the flap vein has slow venous outflow. To prevent venous stasis and risk of thrombosis, an inflow venous anastomosis is performed when feasible to permit constant flow. This design is again more consistent with physiologic blood flow in situ prior to harvest. We further suspect that the higher rate of constant outflow may have a beneficial effect via the Bernoulli principle, in which the higher velocity venous flow creates a lower pressure system, thus augmenting flap drainage of blood and collected lymph, and enhancing the pump mechanism.

During flap inset, preference should be given to avoid skin graft placement directly over the FFLT, since this decreases the available surface area contact for afferent lymphatics to drain the surrounding subcutaneous tissue. In most instances, this requires local direct excision of fibroadipose tissue in the subcutaneous layer to allow for primary closure. If skin grafts are necessary, then second stage revision is recommended for graft excision and subcutaneous flap advancement.

Conclusion

Lymphedema persists as one of few remaining fields within medicine that has yet to emerge from relative infancy, with much awaiting to be discovered regarding the pathogenesis and treatment. Surgical management is particularly challenging due to the unique demands that encompass aesthetics, technically challenging small vessel supermicrosurgery, and restoration of complex lymphatic organ function, including physiologic drainage, immune function, and extremity function. Supermicrosurgical LVA, microvascular FFLT, and debulking strategies show promising results. Treatment strategies vary among groups worldwide and no consensus has yet been reached regarding optimal management algorithms, but ongoing favorable outcomes bring hope that the most effective methods will soon be discovered. The future of lymphedema treatment remains bright and should prove to be exciting as new developments continue to evolve over the coming decades.

Funding Statement

Funding None.