Latest Update for Surgical Treatment of Lymphedema

1. Introduction

Lymphedema is a chronic, progressive condition caused by insufficient lymphatic drainage and the subsequent stasis of protein-rich interstitial fluid. A common symptom of the disease is the swelling of upper or lower extremities. In the early stages of the disease, patients feel heaviness or tightness of the affected extremity without swelling. As the disease progresses, significant swelling, inflammation, and fibrosis develop. Patients with lymphedema experience pain, discomfort, recurrent cellulitis, and overall decreased quality of life.

Peter C. Neligan, Jaume Masia, Neil B.Piller, Lymphedema complete medical and surgical management

Example of arm lymphedema

2. Causes

Lymphedema is classified into primary and secondary lymphedema. Primary lymphedema is caused by an intrinsic problem with the lymphatic system: dysplasia or agenesis of lymphatic vessels or lymph nodes. One of the leading causes of the secondary lymphedema is oncologic surgery with treatment including lymph node dissection, radiation, and chemotherapy. It is known that approximately 20% of breast cancer survivors experience lymphedema, and up to 50% of gynecologic cancer patients experience lymphedema after oncologic surgery. Overall, about 250 milion people worldwide suffer from lymphedema.

3. Diagnosis

Initial diagnosis of lymphedema can be performed by clinical examination. Lymphedema usually starts with unilateral extremity, following breast cancer or gynecologic cancer surgeries. It deteriorates in the evening after activity and gets better in the morning. Classical diagnosis was performed with lymphoscintigraphy, which has long been considered the gold standard in the diagnosis and evaluation of lymphedema. Radiolabeled tracer is injected subdermally at distal extremity. The tracer is then taken up by the lymphatic vessels and travels proximally along them to reach the lymph nodes. The transport is delayed or impaired in lymphedema patients. Although lymphoscintigraphy is helpful in the diagnosis of lymphedema, it has several drawbacks including painful injections and poor resolution.

ICG lymphography: normal arm

Recently, indocyanine green lymphography (ICG) has become a popular imaging technique for the diagnosis of lymphedema. ICG is injected subdermally in the distal extremity. The ICG binds to albumin and is taken up by lymphatic vessels. The lymphatic flow can be visualized in real time. This examination can be performed in an outpatient clinic room. The ICG lymphography is useful to evaluate stages of lymphedema and decide whether or not physiologic lymphatic surgery can be performed. New imaging techniques, including magnetic resonance angiography and ultrasound, have also been used.

Arm with lymphedema

4. Treatment

1. Lymphatico-Venular Anastomosis, LVA Llymphovenous Bypass LVB)

Because of recent advances in microsurgical technique and instruments, lymphatic vessels with a diameter of 0.3-0.8 mm can be anastomosed to venules or veins to create lympho-venous bypass. This surgery can restore physiologic lymphatic flow from lymphatic vessel to vein when the proximal part of the lymphatic flow is obstructed. Proximal obstruction of lymphatic flow is commonly developed in lymphedema following oncologic surgery.

Because LVA targets a superficial lymphatic vessel which is located in the superficial fat layer, the surgery is minimally invasive and causes little postoperative pain. The surgery can be performed with skin incisions less than 2-3 cm in length and can be performed by either local or general anesthesia. However, not all patients can be a candidate for this surgery since lymphatic vessels undergo degenerative change as the lymphedema progresses. An ICG lymphographic exam is a useful tool to evaluate whether or not lymphatic vessels are suitable for LVA surgery.

Lymphatic vessel anastomosed to side wall of vein. ICG lymphography shows flow from lymphatic vessel to vein after LVA.

2. Vascularized Lymph Node Transfer, VLNT

Free tissue transfer of lymph nodes has been the most recent development in the treatment of lymphedema. Currently, there are two hypotheses commonly accepted as the principle of VLNT. First, the “pump theory” suggests that the VLN flap absorbs the lymph fluid like a pump and drains it into the vein through natural lymphaticovenular connections inside the flap. The other hypothesis, known as the “lymphangiogenesis theory”, suggests that the transferred lymph node has a high capacity for spontaneous regeneration and improves the drainage by forming a bridge to the lymphatic pathway. Recently, VLNT has gained consensus as a promising operative technique for lymphedema based on excellent outcomes, especially in patients in advanced stages.

Schematic illustration of VLNT Lymph node flap is transplanted into the arms or legs with lymphedema in the form of a free flap.

"Korea’s medical system is well-equipped with a cooperative system, displaying the capacity to treat lymphedema"

Pre- and postoperative clinical image of patient underwent VLNT At 15 months, the postoperative circumference diameter of left leg was significantly decreased.

There are various donor sites for VLNT, such as groin, submental and supraclavicular areas. Just like the donor sites, the recipient sites also have great variability. In treating upper extremity lymphedema, recipient sites have included the wrist, elbow, and axillary regions. For lower extremity lymphedema, the ankle and groin are the most common recipient sites.While the literature for VLNT is still in its early stages, results have been favorable. Also, in many cases, it can be performed with simultaneous LVAs for better outcomes.

3. Debulking Procedure

(i) Liposuction

In late-stage cases, adipose tissue depositions and sometimes fibrosis are the prominent manifestations of the disease. In this case, liposuction can be used to remove hypertrophic tissues and lessen edematous symptoms. It is a useful treatment option in conjunction with controlled compression therapy.

(ii) Excisional Procedures

Intraoperative photo of immediate lymphatic reconstruction

Invasive reductive procedures such as the Charles operation can be used as a sole treatment option for patients with terminal refractory lymphedema. This method has not been used in a while because of extensive scarring and substantial morbidity including significant blood loss or infection. Recently, however, radical reduction of lymphedema with preservation of perforators (RRPP) and modified Charles procedure, composed of a negative dressing and delayed skin graft, provide optimal outcomes for patients with advanced extremity lymphedema.

4. Preventive Procedure: Immediate Lymphatic Reconstruction

Lymphedema is a refractory disease that is difficult to reverse once it occurs. Currently, immediate lymphatic reconstruction is drawing attention as a novel preventive technique. After reverse mapping with ICG lymphography, surgeons connect lymphatic vessels of upper/lower extremity to the surrounding vein. It can improve the drainage of lymphatic fluid and reduce the rate of lymphedema.

5. Basic Research in the Field of Lymphedema

Although the aforementioned surgical procedures exist to treat lymphedema, the disease is still considered to be a rare disease. In Korea, significant research has been conducted to develop animal models and research on stem cells and growth factors are also in progress to develop novel therapies. The ongoing research is showing the desired result and aiming to be approved for clinical trials soon.

6. Strengths of Korea

Lymphedema requires a systematic approach from diagnosis to surgery to rehabilitation due to the nature of the disease. Korea’s medical system is well-equipped with a cooperative system, displaying the capacity to treat lymphedema. Also, Korean plastic surgeons are well known for their academic achievements. Korean plastic surgeons have considerable clinical experience in microsurgery, consistently showing highly satisfactory outcomes.

December 6, 2021

Jae-Ho Chung, M.D., Ph.D.

• Acting Chief, Department of Plastic and Reconstructive Surgery, Korea University Anam Hospital

• Executive Assistant Secretary, Korean Society of Plastic and Reconstructive Surgeons

• Assistant Secretary at Surgery Committee, The Korean Society of Lymphedema

Jae-Ho Chung, M.D., Ph.D., is a physician, surgeon, assistant professor, and a researcher. He is now serving as an assistant secretary of surgery committee in the Korean society of Lymphedema. He is an expert in microsurgery and performs reconstructive surgeries such as head and neck or breast reconstruction. Since he was resident, he

has been interested in the field of lymphedema and visited the world’s leading center in lymphatic surgery such as the University of Chicago and the University of Tokyo. Based on these experiences, he performs various types of lymphatic surgery such as lymphovenous anastomosis, vascularized lymph node transfer, and prophylactic surgery. In addition, he has conducted animal experiments using stem cells and growth factor to find novel therapeutics for lymphedema, which is still considered a refractory disease. His research is supported as a national task. Also, in recognition of his research capabilities, he was awarded as an excellent basic researcher by the Korean Society of Plastic and Reconstructive Surgeons in 2021. Currently, he is recognized by the society as a young researcher with a promising future, publishing about 40 papers, including 23 SCI papers.

Kyong-Je Woo, M.D., Ph.D.

Assistant Professor and Chief of Department of Plastic and Reconstructive Surgery, Mokdong Hospital, Ewha Womans University

Kyong-Je Woo, M.D., Ph.D., is an assitant professor and chief of Department of Platic and Reconstructive Surgery, Mokdong Hospital, Ewha Womans University. He graduated from Seoul National University College of Medicine, and finished training and fellowship of plastic surgery at Samsung Medical Center, Seoul. His specialty is microsurgical lymphatic surgery, and breast reconstruction following mastectomy for breast cancer.

He established the surgical team at the lymphedema center at Mokdong Hospital and he has been actively performing surgical treatment of lymphedema of upper and lower extremities. The lymphedema center in Mokdong Hospital is one of the biggest lymphedema centers in Korea.