Endothelial cells bud off from veins during early embryonic development and transdifferentiate to form the lymphatic vasculature.

The lymphatic primary plexus is composed of capillary-like vessels and is further remodeled to form pre-collecting, collecting, and ductal components. The major lymphatic ducts are formed by two paired lymph sacs (jugular and iliac) and two unpaired sacs (retroperitoneal and cisterna chyli).

Lymphatic channels are thin-walled vessels composed of endothelial cells connected by discontinuous junctions and surrounded by smooth muscle. The basement membranes of the larger, deeper lymphatic vessels have multiple intercellular gaps, which form valves through which fluid flows unidirectionally.

The superficial dermal lymphatics are unvalved and drain into the valved subfascial deep dermal system, which run with the superficial veins.

Lymphatic fluid is then transported through afferent lymphatic channels to lymph nodes, which are gathered in basins throughout the body. After undergoing immunological processes within the lymph nodes, the fluid flows out through efferent lymphatic channels and ultimately into the thoracic ducts and subclavian veins where they rejoin the venous circulation.

Lymph nodes are bean-shaped structures distributed along the lymphatic channels. They consist of a capsule, an outer cortex and an inner medulla. Multiple afferent lymphatics can enter via the outer cortex, and a lymph node is supplied by an artery and a vein at the hilar region, which accompany a single efferent lymphatic vessel. The lymph nodes contain lymphocytes and macrophages, which are responsible for removal of organisms, foreign substances, and tumor cells.

Lymph nodes are distributed deep in the body along the respiratory and gastrointestinal tract and superficial in the cervical, thoracic, and inguinal regions.

Lymphatic fluid transportation is under humoral influences and is propelled by a combination of:

Lymphatic homeostasis is a function of filtration of plasma across the capillary walls into the interstitial compartment and absorption by the lymphatic system. This rate of filtration is governed by the Starling equation whereby net filtration is determined by intra- and extracapillary hydrostatic and oncotic forces.

Lymphedema arises when the rate of filtration exceeds absorption by 2 to 4 L/d.

This disruption can occur at the level of the lymphatic vasculature or the lymph nodes and can arise due to a primary or secondary disease process.

True primary lymphedema can be classified as congenital (Milroy disease), pubertal/praecox (Meige disease), and tarda, which occurs in the adult age group. Lymphedema praecox is the most common form of primary lymphedema.

Lymphedema can also arise secondary to acquired damage to the lymphatic system. These include infection, trauma, malignancy, surgery, and radiation.

The most common cause worldwide is filariasis, caused by the parasite Wuchereria bancrofti. In the developed world, it is most commonly due to treatment for cancer.

When there is disruption in the lymphatic system and as lymphatic pressure builds, flow within the lymph vessels stagnates, leading to valvular incompetence and dermal backflow.

Lymphedema is confined to the subcutaneous compartment as the deeper lymphatics are driven by the skeletal muscle pump.

Over time, macromolecular protein and hyaluronan are deposited in the interstitium leading to increased tissue colloid osmotic pressure.

The cytokines arising from the inflammation and the disruption in lymphatic flow of lipids leads to adipose deposition and hypertrophy in the interstitium.

The verrucous appearance of long-standing lymphatic extremities is caused by hyperplasia of skin at the dermalepidermal junction.

Lymphatic stasis and decreased immunological function predispose the patient to an increased risk of local skin infections, erysipelas, and later, lymphangitis. The excess tissue can lead to symptoms of pain, heaviness, and decreased mobility. Long-standing chronic lymphedema can lead to development of lymphangiosarcoma (Stewart-Treves syndrome). Lymphedema has significant adverse impact on patients’ quality of life and psychosocial health.

The International Society of Lymphangology (ISL) has classified lymphedema into three stages:

The history is targeted at determining the diagnosis and etiology of lymphedema, duration, symptoms, and complications, and how the patient has been managing it.

The examination of the patient with lymphedema should include a general physical and a targeted examination of the affected part. The general examination is aimed at excluding any active infection or malignancy and general causes of extremity edema.

Lymphedema is typically unilateral, with the swelling beginning distally and progressing over months to years.

Reproducible measurements of the limb should be taken to help with accurate follow-up. These can include circumference measurements and volumetric measurements such as water displacement tests, perometry, and bioimpedance testing. Digital photographs are also useful for comparative analysis.

Lymphangiography is the visualization of lymphatic vessels using contrast medium. Vessels can be classified as anaplastic, hypoplastic, or hyperplastic. There are the direct and indirect forms of lymphangiography.

Isotopic lymphoscintigraphy is the current standard for lymphatic imaging. It injects Technetium-99-labeled albumin into the subepidermis of the distal affected extremity and timed post injection imaging to determine lymphatic anatomy and function. It has a sensitivity of 97% and specificity of 100%. However, when done awake, the injection can be painful, and the length of time required can be distressing to the patient.

The injection of indocyanine green (ICG) and imaging using an infrared camera have become widely used in the imaging of lymphatic vessels and are particularly useful intra-op when needing to delineate the superficial lymphatic system. A classification based on the appearance of the ICG has been developed and correlated with the Campisi classification (Table 1).¹

Computed tomography (CT) and magnetic resonance imaging (MRI) scanning are useful in determining the architecture of the affected limb and elucidating any underlying
cause such as neoplasm. There is commonly a “honeycomb” appearance above the deep subcutaneous fascia. MRI with contrast has proven promising in outlining lymphatic vasculature.²

Nonoperative management is aimed at reducing the amount of swelling and treating any resulting complications. The former is accomplished by compression and massage therapy, whereas the latter involves adequate skin care and early detection of infection and treatment with the appropriate antibiotics. In a compliant patient, this helps to slow down the progress of lymphedema.

Patients should be educated about lymphedema and its complications, and given responsibility for their own care.

Conservative treatment of lymphedema has been well researched and the regimen described is complete decongestive therapy (CDT). This should be started early to have the most benefit and is useful in cases of lesser than stage III lymphedema. Analyses have shown up to 40% to 60% reduction in lymphedema volume. It consists of two phases:

Weight loss may help with lymphedema by reducing the flow of fatty acids through lymphatic channels and decreasing fatty deposition in the subcutaneous tissue.

Exercises such as swimming can be useful in reducing the severity of lymphedema.

Unsubstantiated nonoperative measures include coumarin (5,6 benzo-a-pyrone), diuretic use, microwave heating, and intra-arterial injection of lymphocytes.

Although significant advances have been made in the surgical treatment of lymphedema, no surgical technique offers a cure, and an aggressive trial of nonsurgical therapy should first be done.

Indications for surgical treatment include failed conservative therapy, grossly impaired limb function, debilitating extremity size and weight, recurrent lymphangitis (greater than 3 episodes of infection per year), and uncontrolled pain.

Surgical techniques for the treatment of lymphedema are classified as excisional and physiological.

Excisional techniques aim to reduce the amount of lymphatic tissue and tighten the skin envelope. They are described elsewhere in this book and include but are not limited to excision and skin grafting (eg, Charles procedure), staged excision, liposuction, and, more recently, radical resection with preservation of perforators (RRPP).³ Unfortunately, as the primary disease process is not addressed, there is a high risk of recurrence with these techniques, and the appearance can be undesirable.

Physiological techniques attempt to replicate the normal lymphatic flow in the affected extremity. Procedures that have been developed and described elsewhere include buried dermal flaps, lymphovenolymphatic bypass, lymphatic bypass, and lymphovenous anastomosis (LVA).⁴

The vascularized lymph node transfer (VLNT) is a physiological technique that transfers intact autologous lymph nodes from a nonlymphedematous region of the body to the affected extremity. In a sense, this is the most physiological method of addressing the problem in a patient whose lymphedema is due to damage to or paucity of lymph nodes in a particular basin.

The lymph nodes are microsurgically anastomosed to the chosen recipient site vessels and allowed to develop collateral blood supply. Over time, reported mechanisms of lymphedema reduction include reduction of scarring at the recipient site, hydrostatic “pumping” of intraflap lymph via arterial inflow and venous outflow, and lymphangiogenesis aided by the production of VEGF-C by the transplanted lymph nodes.

Though not curative, physiological techniques have proven to alleviate symptoms and reduce lymphedema volume.