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Lymphedema is a complex clinical condition characterized by the malfunction of the lymphatic system responsible for moving tissue fluid from the interstitium into the venous system of the body. This causes retention of tissue fluid in the soft tissues, with associated swelling, inflammation, and destruction of lymphatic channels and chronic pathologic soft-tissue changes.
Lymphedema may be caused by genetic or developmental abnormalities (primary lymphedema) or postnatal insults, such as nodal surgery, radiation, and infection (secondary lymphedema). Lymphedema affects 2 to 3 million people in the US alone. Secondary lymphedema affects 1 in 6 survivors of cancer.1 In the US, breast cancer–associated lymphedema is the most common cause of secondary lymphedema. The reported incidence of lymphedema after sentinel lymph node biopsy is 0% to 23%, while that for axillary lymph node dissection is 11% to 57%.2 Patients who undergo postoperative radiation are at increased risk.
Patients with cancer-associated lymphedema typically present 6 months to 3 years after cancer treatment. Eighty percent of lymphedema onset occurs within the first 3 years of cancer treatment, and the incidence increases by 1% each year. Common symptoms and signs include limb swelling, skin tightness, heaviness, and infections (eg, cellulitis).
The most commonly used staging of lymphedema (per the International Society of Lymphology3) is based on clinical evaluation (Table).4 Patients with stage 0 (latent) disease have impaired lymphatic drainage but no clinical swelling. Patients in stage 1 have swelling that resolves with elevation or compression garments, while patients in stage 2 have swelling that does not resolve with elevation or compression and patients in stage 3 have chronic inflammatory tissue changes.
A full history and physical examination should be performed. Careful and precise measurements of limb circumferences (normal vs abnormal) should be documented.
Investigations are valuable for confirming the diagnosis and ruling out differential diagnoses. They include a venous Doppler ultrasonographic examination to rule out venous thrombosis and insufficiency, technetium (Tc 99m) lymphoscintigraphy to assess the baseline extent of lymphatic flow obstruction (partial vs total) and lymph node basins, and indocyanine green lymphangiography to assess superficial lymph drainage and identify blocked lymphatics for bypass. Other highly specific studies include magnetic resonance lymphangiography, which provides anatomic and volumetric information of a given limb and can evaluate honeycombing of soft tissues in patients with stage 2 and 3 lymphedema.
Nonsurgical treatment of lymphedema is typically the first modality. Numerous studies have shown that limb elevation, compression garments, manual lymphatic drainage, and complete decongestive therapy are all effective nonsurgical treatments.5 Complete decongestive therapy is a multimodality program administered by physical therapists involving manual lymphatic drainage, daily bandaging, exercise, and skin care. It helps to minimize accumulation of lymph fluid in soft tissue and decreases chronic inflammation. Optimal outcomes can be achieved with this mode of treatment in early-stage lymphedema.
Only patients who have demonstrated compliance with conservative therapy and whose cases have proven refractory to further complete decongestive therapy should be considered. Ideal candidates should optimize weight loss preoperatively, possess a patent and competent venous system in the extremity of interest, and be free of active infection at the time of surgery.
There are 3 main classes of lymphedema procedures. Excisional procedures help remove the deposited fibrofatty tissue and fluid but do not address the lymphatic drainage itself. They include extremity liposuction and excisional procedures, such as the Charles procedure, the Thompson procedure, and perforator-sparing resection.6 Extremity liposuction requires the patient to continue lifetime compression to minimize the recurrence of swelling but has a quick recovery and no associated major morbidity. The other excisional procedures are morbid procedures associated with operative blood loss and poor cosmesis because of the poor healing of scars and skin grafts.
Physiologic procedures include lymphovenous bypass and vascularized lymph node transfer. These procedures attempt to reconstruct the lymphatic drainage system to provide a path for drainage into the venous system.
Lymphovenous bypass surgery involves connecting obstructed superficial lymphatics to adjacent superficial veins to allow superficial drainage of lymph from the extremities. Vascularized lymph-node transfer harvests lymph nodes with their blood supply from a remote site (eg, the submental, supraclavicular, omentum, jejunum, superficial groin, and lateral chest areas) and reconnects them to the blood supply at the lymphedematous limb. Reverse lymphatic mapping is performed to minimize the incidence of donor site lymphedema (2%-3%).6 Scar release at the recipient site is important to optimize lymphatic regeneration. The transferred nodes stimulate lymphangiogenesis and drainage of the collected lymph into the venous system. A novel adjunct therapy with nanofibrillar collagen scaffolds has been shown to enhance lymphatic regeneration and augment outcomes of physiologic procedures.1
Lymphatic microsurgical preventive healing approach (LYMPHA) surgery is a preventive procedure that can be performed at the time of ablative breast surgery. It restores lymphatic continuity at the time of nodal surgery by identifying disrupted lymphatic channels using reverse axillary mapping and reconnecting them to upstream lymphatic vessels or bypassing them to available veins. One study describes a reduction of lymphedema incidence after axillary lymph node dissection from 19% to 3%.7
While studies show improvement in quality of life, rates of infections, and symptom relief with debulking procedures,8 there is a paucity of level 1 literature on outcomes of physiologic surgical lymphedema procedures. However, available evidence from retrospective cohorts from high-volume centers suggests volume reduction of 22.5% to 51% in upper-limb lymphedema and 7% to 42% in lower-limb lymphedema.4,9 Patients also report improvement in their quality of life and symptoms, and the incidence of cellulitis decreases significantly. Patients with early-stage disease have better mean results than those in later stages of disease. There is no clear evidence of the superiority of 1 physiologic procedure over another. The physiologic operations are associated with less risk of bleeding and other complications compared with the older debulking operations.
Lymphedema is a complex clinical condition associated with significant morbidity. Understanding symptoms, staging, workup, and treatment options is important for early diagnosis and referral of these patients to ensure prompt evaluation for treatment and improved outcomes.
Corresponding Author: Gordon K. Lee, MD, Stanford University Medical Center, 770 Welch Rd, Ste 400, Palo Alto, CA (firstname.lastname@example.org).
Published Online: March 25, 2020. doi:10.1001/jamasurg.2020.0015
Conflict of Interest Disclosures: None reported.
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Ogunleye AA, Nguyen DH, Lee GK. Surgical Treatment of Lymphedema. JAMA Surg. Published online March 25, 2020. doi:10.1001/jamasurg.2020.0015
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