Developments in Lymphedema Research

In the United States, an estimated 10 million people are affected by lymphedema. This is more than the number of people diagnosed with multiple sclerosis, amyotrophic lateral sclerosis, muscular dystrophy, Parkinson’s disease, and AIDS combined.

While this condition can be painful and debilitating, it is encouraging to know that there have been advancements in the treatment of lymphedema.

Julie Pederson, BSW, RN, OCN, CBCN, of the Baylor Scott & White McClinton Cancer Center in Waco, Texas, shared her excitement about some promising results of the study and procedures in the treatment of lymphedema at the PER^® 36th Annual CFS^® nursing track session in New York City, held on Nov. 7.¹

Lymphovascular Bypass

Lymphovascular bypass surgery, also known as “lymphaticovenous anastomosis,”² is a relatively new surgery which is performed post axillary dissection by a trained plastic surgeon and only extends surgery time by approximately 45 minutes.

“The breast surgeon injects dye to identify the lymph nodes to in the axilla needing excision. The plastic surgeon also uses a dye to distally inject the arm which identifies lymphatic vasculature that were lysed from the nodes,” Pederson explained. “A vein is selected and the plastic surgeon will anastomose the tiny lymphatic vessel to the vein allowing continued lymphatic drainage. So far this is showing efficacy in preventing lymphedema.”

However, Pederson acknowledged that it is early to know the lasting effects of this surgery.

Ketogenic Diet

The ketogenic diet has shown efficacy in helping people lose weight. In one small study, 12 obese women with a mean BMI of 38.38 received intervention strategies over the course of 3 months.³ Six went on a 12-week ketogenic diet, 4 did not, and two women dropped out in the middle of the study.

Among those on the ketogenic diet, the average weight loss was about 18 pounds compared with about 1 pound among those who did not go on the diet.⁴

The most striking effect of the ketogenic diet was the volume of lymph fluid loss where 4 out of the 6 women who were on the ketogenic diet lost more than 1100 ml of lymphatic fluid, and others lost 183 and 467 ml. Comparatively, of those not on the ketogenic diet, only 1 woman lost more than 1000 ml of fluid, 1 lost 115 ml and 2 actually showed a small increase.⁴

Autologous Lymph Node Transplant

Pederson also touched on the use of autologous lymph node transplant which she said has a 30% to 50% success rate. “When it works, it works great, but there can be issues with lymph angiogenesis and engraftment to the new lymph nodes,” she added. “If it does not occur within a certain time frame, it might not prevent lymphedema.”

Lymfactin is clinical stage gene therapy that repairs damage of the lymphatic system.⁵ Lymfactin expresses the human growth factor VEGF-C, which is natural and specific for the development of lymphatic vessels, according to Herantis, the gene therapy’s manufacturer located in Finland. Based on preclinical studies, Lymfactin, transferred by an adenovirus vector, triggers the growth of new functional lymphatic vasculature in the damaged area, repairing the underlying cause of lymphedema. “If you just give VEGF-C, it will remain in the system for approximately 30 minutes. Lymfactin given distally, will stay in the system for about 2 weeks, which is effective in stimulating lymphatic vasculature growth and engraftment into the lymph node.”

Anti-Inflammatory Treatment

An inflammatory molecule called leukotriene B4 has been shown to play a part in inflammation in relation to lymphedema. Some studies have seen success treating lymphedema with ketoprofen, a non-steroidal anti-inflammatory agent. Aspirin and ibuprofen do not target leukotriene B4 and are ineffective in treating lymphedema, Pederson said.

Previous studies have shown that ketoprofen reduced the thickness of the patient’s skin in the affected limb by unblocking the molecular pathway that was causing the inflammation and restricting the body’s ability to repair its own lymphatic system.⁶

“When using calipers, the normal skin measurement is about 1 to 2 millimeters. When you have a stage III -IV lymphedema, the skin fold can measure up to 38 millimeters. After taking ketoprofen for 4 to 6 months, measurements have decreased down to 3 to 4 millimeters of skin thickness.” Pederson said.

Exercise

Patients express concern about exercise inducing or worsening lymphedema. A small study conducted at Baylor Scott & White McClinton Cancer Center was designed to determine if exercise does increase lymphedema in women diagnosed with breast cancer who had axillary and/or sentinel node dissection. An exercise physiologist assessed 20 patients, determined fitness levels and designed exercise programs starting with 20 minutes of aerobic activity, escalating to 40 minutes. Core training and light resistance training with 2-, 3-, or 5-pound weights were also employed during the 6-week study.

Investigators used circumferential measurements, weight, grip strength, and bioimpedance measurements to assess the effects of exercise on patients’ affected arms. Results of the study indicated that exercise did not induce or increase patients’ lymphedema. Exercise had the benefit of increasing energy level and quality of life. Pederson noted that it was a small study, however, it could provide hope that, with more study and education, patients’ fears about exercise can be reduced, and they could reap the other benefits that exercise can provide.

References

• Pederson J. Latest practices in lymphedema. Presented at: PER® 36th Annual CFS®; November 7-9, 2018; New York, NY.
• Baltzer H, Winocour S, Harless C, Saint-Cyr M. Lymphaticovenous bypass: adaptations and lessons learned. Plast Reconstr Surg Glob Open. 2017;5(6): e1328. doi: 10.1097/GOX.0000000000001328.
• Keith L, Rowsemitt C, Richards L. Lifestyle modification group for lymphedema and obesity results in significant health outcomes. doi.org/10.1177/1559827617742108.
• Keith L. Diet and lifestyle for lymphatic disorders: Implementing a ketogenic diet. Lymphatic Education and Research Network website. lymphaticnetwork.org/symposium-series/diet-and-lifestyle-for-lymphatic-disorders-implementing-a-ketogenic-diet. Published August 28,2017. Accessed December 3, 2018.
• Lymfactin® for lymphedema. Herantis website. herantis.com/pipeline/lymfactin-for-lymphedema/. Accessed November 30, 2018.
• Rockson S, Tian W, Jian X, et al. Pilot studies demonstrate the potential benefits of antiinflammatory therapy in human lymphedema. JCI Insight. 2018;3(20):e123775. doi: 10.1172/jci.insight.123775.