The lymphatic system is an important biologic system that regulates metabolism of lipids, fluid homeostasis, and immune mechanics. Its mechanics rely on networks of lymphatic vessels and lymph nodes to transport extracellular fluid, immune cells, as well as molecules and macromolecules, which may be packaged into a variety of carriers.

This afferent (prenodal) lymph fluid enters lymphatic capillaries, drains into lymph nodes, and then is transported via efferent (postnodal) lymphatic vessels. The systemic efferent lymphatic vessels meet at either the thoracic duct, which then drains into the venous system via the junction of the left internal jugular and subclavian veins, or the right lymphatic duct, which drains into the right subclavian vein (4,5).

Flow in the thoracic duct is about 100 mL per hour, and total body flow of lymph is around 4 to 5 L per day (6). Given the incredible volume of flow, any disruption can easily lead to edema.

Lymphedema is the pathologic process by which this transport and drainage of proteinaceous lymph fluid is deranged. This lymphostasis creates lymphatic vessel hypertension and dilation, which can lead to lymphatic leakage into the interstitial compartment and, ultimately, dermal backflow and lymphedema. Primary lymphedema usually becomes apparent within the first 2 years of life, and occurs when there are structurally or physiologically abnormal lymphatics (7,8,9). Secondary lymphedema occurs due to physical injury of the lymphatic system. Globally, the most common cause of secondary lymphedema is filariasis (10); in the United States, secondary lymphedema is usually secondary to ablative cancer treatments.

The International Society of Lymphology has defined a classification system to describe the progression of lymphedema (11). Stage 0 is a subclinical or latent condition, defined as the impairment of lymphatic fluid transportation without any clinical manifestations of lymphedema. Stages I to III describe the progression of lymphedema. Stage I is defined as the early accumulation of edema which resolves with elevation of the affected extremity. Pitting edema may occur at this early stage. Stage II represents continued limb edema that rarely improves with limb elevation alone and pitting is present. Stage III describes limb edema classified as lymphostatic elephantiasis, wherein pitting can be absent and certain skin changes, such as fibrosis, increased skin thickness, fat deposition, and acanthosis are present. Interestingly, an affected limb may exhibit more than one stage of lymphedema, which demonstrates the complicated nature of this disease.

Moreover, further clinical descriptions of lymphedema exist. The extent of lymphedema and frequency of erysipelas, an infection of the superficial lymphatic system and the upper dermis, may be factored into the clinical description of lymphedema. Likewise, the circumference or volume (11) of the affected limb may be measured and compared to unaffected limbs. Using the above staging classification system, minimal lymphedema
is considered when limb volume is between 5% and 20% greater than the unaffected side. A 20% to 40% volumetric increase in affected limb volume is considered moderate lymphedema, and severe lymphedema is seen when the limb volume is more than 40% of the unaffected side.

By taking disease progression and clinical manifestations of lymphedema into account, clinicians can usually diagnose lymphedema by history and physical examination. If, however, diagnosis is difficult to make on account of confounding factors such as obesity or other causes of extremity edema including cardiac or renal failure, or if further information about the affected limb is otherwise useful in treatment or staging of the disease, imaging modalities may be warranted.

Multiple studies have demonstrated that BCRL has a negative impact on quality of life (12,13,14,15,16,17,18,19,20). BCRL has been shown to cause impairments in the glenohumeral joint, and has been associated with rotator cuff tendonitis (21). Despite the overall diminished quality of life in patients with lymphedema, the severity of clinical lymphedema does not seem to have a direct effect on the impact on one’s quality of life (22).

The treatment of lymphedema may be surgical or nonsurgical. Many patients will start conservative therapy prior to undergoing a surgical procedure (23). Conservative therapy consists of multiple modalities, usually employed over several months. Decongestive therapy is one such modality, which aims to decrease the interstitial fluid burden on the affected limb. Compression therapy may include customized garments, bandages, and wraps. Some will also employ intermittent pneumatic compression devices to the affected limb. Supervised exercise regimens have also proven to be helpful in the conservative treatment of lymphedema.

Alternatively, surgical treatment may be the best option for some patients. Surgical treatment may include reductive or debulking procedures, such as liposuction and direct excision, or may change the physiology of the lymphedematous limb, in the case of lymphaticovenous bypass or lymph node transplant. Vascularized lymph node transplant (VLNT) moves lymph nodes from a donor site as a flap, via their artery and vein, to the lymphedematous limb, where the microsurgical anastomoses are created. The remainder of this chapter will focus on VLNT, specifically in regard to the treatment of upper extremity lymphedema.

No one treatment algorithm exists, so timing of surgical intervention varies widely. Some surgeons argue that surgical intervention should be employed when lymphedema is refractory to conservative treatment or causes severe deformity or physical impairment (24,25). Alternatively, others will prefer to offer surgical treatment, such as VLNT, prior to the onset of permanent fibrosis (26,27,28,29). Still yet, others advocate for preventative surgical intervention with lymphaticovenous shunt at the time of breast cancer extirpation (30). Preventative surgical intervention has not yet become widespread because of the concern over iatrogenic donor site lymphedema, and because all those at risk for lymphedema will not develop the disease.

The mechanism of action of VLNT is based on two physiologic hypotheses: improved lymphatic drainage, whereby bringing in new, nondiseased lymph tissue decreases interstitial pressure within the affected area, and lymphangiogenesis, which describes the growth of new lymphatic channels in the affected area.

The action of a lymphatic pump system has been proposed (31). High pressure inflow from the donor artery creates a favorable environment from which the donor vein drains. New, healthy lymph nodes and associated lymphatic capillaries from the VLNT provide low pressure within the flap, and excess lymphatic fluid from the hypertensive surrounding interstitial fluid is then recruited into the new flap via the high-pressure artery. This fluid is then mobilized into the venous drainage system via the native lymphaticovenous connections within the transplanted flap itself. Overall, this decreases the pressure in the affected area, and will allow for old and damaged lymph channels to reopen. Long-term evidence has demonstrated, clinically and via indocyanine green (ICG) imaging, that this physiologic lymphatic pump system remains functional as long as the venous and arterial anastomoses remain patent (32,33).

Likewise, the theory of a lymphatic sink has also been described (34). Akin to arterial and venous pumping of lymphatic fluid, it is proposed that the new, healthy lymphatic tissue brought with the VLNT flap creates a low-pressure system into which the surrounding lymphatic fluid may drain. As such, the lymph nodes within the VLNT flap provide a lymphatic sink for the surrounding hypertensive interstitial compartment of the lymphedematous limb. Imaging studies have shown this to be the case: ICG is immediately taken up into the transplanted lymph node and is then distributed into the venous system (35).

Lastly, the idea of lymphangiogenesis, or the creation of new lymphatic channels in the affected area, has been described as a possible mechanism of action of VLNT. Lymph nodes secrete a human lymphangiogenic growth factor, vascular endothelial growth factor C (VEGF-C), which has been shown to be an instrumental growth factor in lymphatic channel creation in the embryonic stage (36,37,38). This VEGF-C, which is secreted from the newly transplanted lymph nodes, may help create connections
between the transplanted new lymphatic channels and the diseased lymph channels in the recipient tissue. This theory is promoted by imaging with MR lymphography and lymphoscintigraphy, which have demonstrated that transplanted lymph nodes become incorporated into the recipient site postoperatively (26).