LyMPHA and the Prevention of Lymphatic Injuries: A Rationale for Early Microsurgical Intervention

In response to the article by Lopez Penha et al[1] entitled “Microsurgical techniques for the treatment of breast cancer-related lymphedema: a systematic review,” the authors take the opportunity to discuss the role of lymphatic microsurgery (derivative and reconstructive multiple lymphatic-venous anastomoses [MLVA]) in the primary prevention of lymphatic injuries, with a particular reference to breast cancer patients.

We read with great interest the article by Lopez Penha et al[1] in which the authors reviewed studies from 2000 to 2012 related to microsurgical treatment of lymphedema secondary to breast cancer treatment. The authors identified 10 case series that met their inclusion criteria involving tissue and lymph node transfer or derivative “super” microlymphatic surgery. Both the surgical techniques resulted in postoperative volume or circumference reduction and very few complications, although the authors identified methodological shortcoming in the available literature, such as a lack of randomized controlled trials and patient inclusion criteria such as descriptions of lymphedema stage. Despite this, the authors concluded favorably that methodologically superior microsurgical techniques had a place in the treatment of breast cancer–related lymphedema and raised the question of the most appropriate time to apply these techniques. We discuss the role of lymphatic microsurgery (derivative and reconstructive MLVA[2] [3] [4]) in the primary prevention of lymphatic injuries with particular reference to breast cancer patients.

As noted by Lopez Penha et al, the incidence of lymphedema in patients treated for breast cancer ranges from 7 to 77% in the literature when patients undergo axillary node dissection, dropping to approximately 2 to 7% with sentinel lymph node biopsy.[5] [6] These wide ranges are clearly influenced not only by variations in study criteria, such as classification of lymphedema and length of follow-up, and patient characteristics, such as body mass index (BMI) and radiation treatment,[7] but also by anatomical variations in lymphatic pathways in the arm. That is, if the biopsied or treated lymph nodes are involved in drainage of the arm, then the development of lymphedema seems more likely. Recently, the axillary reverse mapping technique was developed in which dye is injected before biopsy to identify the lymphatic pathways in the arm and preserve them if possible.[8] This technique was based on the premise that the breast and arm drain through different lymphatic pathways and that breast cancer metastases would therefore not occur in the nodes involved in arm drainage and these nodes could be spared from dissection in the hope of preventing lymphedema. This has proven to be a viable prevention technique for patients with separate drainage pathways[9] but unfortunately, other studies revealed that a minority of women have coinvolved breast and arm lymphatic pathways and that it is possible for breast cancer to metastasize to lymph nodes involved in arm drainage.[5] In these cases, it is not appropriate to spare these lymph nodes during dissection.

For this reason, we conducted a prospective randomized controlled trial (RCT) to investigate the utility of using derivative lymphatic microsurgery (MLVA)[10] to create lymphaticovenous anastomoses (in contrast to the lymphatic-venular anastomoses used in the studies described by Lopez Penha et al) in patients undergoing axillary node dissection (AD) for breast cancer to prevent the development of lymphedema.[11] A total of 46 consecutive patients undergoing complete AD for breast cancer were randomly assigned into the following two groups: AD alone or AD in combination with MLVA. No compression bandaging was applied to either group. Lymphatic pathways were identified by injection of blue patent violet dye and patients in the MLVA group received anastomoses between the afferent lymphatics and a collateral branch of the axillary vein. The patients were followed for 1, 3, 6, 12, and 18 months after surgery. There was no difference in age, BMI, positive lymph nodes or number removed, or cellulitis between the two groups. There was a significant difference in the incidence of lymphedema (defined as a difference in arm volume of 100 mL or more) between the groups with 30.43% persistent lymphedema in the AD alone group compared with only 4.34% transitory lymphedema in the MLVA group.

In summary, we have developed a protocol (LyMPHA: lymphatic microsurgical preventive healing approach) for the prevention of lymphatic injury,[11] [12] and therefore, for increasing the possibility of preventing lymphedema, during axillary dissection for detection and treatment of breast cancer. The use of lymphatic microsurgery to create an alternative pathway for lymphatic drainage from the arm in patients where it is necessary to interrupt the natural pathways during cancer treatment represents a feasible preventive approach to minimize morbidity. Whereas previous research has advocated for the use of lymphatic microsurgery for lymphedema only after conservative measures have failed,[13] [14] we believe that this RCT study gives valid evidence for the appropriateness of applying lymphatic microsurgery very early, in patients with breast cancer at risk of developing lymphedema as identified by lymphatic mapping. We welcome further studies in this area to validate this premise and look forward to reading about the prospective study by Lopez Penha et al.

LyMPHA is an acronym for Lymphatic Microsurgical Preventive Healing Approach and is the technique of using lymphatic-venous anastomoses at the time of oncological surgery for the prevention of lymphatic injuries, including lymphedema.

• References

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