A Comprehensive Overview on the Surgical Management of Secondary Lymphedema of the Upper and Lower Extremities Related to Prior
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Garza et al. BMC Cancer (2017) 17:468 DOI 10.1186/s12885-017-3444-9 REVIEW Open Access A comprehensive overview on the surgical management of secondary lymphedema of the upper and lower extremities related to prior oncologic therapies Ramon Garza III1, Roman Skoracki2*, Karen Hock3 and Stephen P. Povoski4* Abstract Secondary lymphedema of the upper and lower extremities related to prior oncologic therapies, including cancer surgeries, radiation therapy, and chemotherapy, is a major cause of long-term morbidity in cancer patients. For the upper extremities, it is most commonly associated with prior oncologic therapies for breast cancer, while for the lower extremities, it is most commonly associated with oncologic therapies for gynecologic cancers, urologic cancers, melanoma, and lymphoma. Both non-surgical and surgical management strategies have been developed and utilized, with the primary goal of all management strategies being volume reduction of the affected extremity, improvement in patient symptomology, and the reduction/elimination of resultant extremity-related morbidities, including recurrent infections. Surgical management strategies include: (i) ablative surgical methods (i.e., Charles procedure, suction-assisted lipectomy/liposuction) and (ii) physiologic surgical methods (i.e., lymphaticolymphatic bypass, lymphaticovenular anastomosis, vascularized lymph node transfer, vascularized omental flap transfer). While these surgical management strategies can result in dramatic improvement in extremity-related symptomology and improve quality of life for these cancer patients, many formidable challenges remain for successful management of secondary lymphedema. It is hopeful that ongoing clinical research efforts will ultimately lead to more complete and sustainable treatment strategies and perhaps a cure for secondary lymphedema and its devastating resultant morbidities. Keywords: Lymphedema, Vascularized lymph node transfer, Lymphaticovenular bypass, Lymphogram, complete decongestive therapy Background when filtration rate exceeds the lymphatic system’s abil- Lymphedema is the buildup of protein rich extracellular ity to manage fluid balance. Changes in the interstitium fluid within the interstitial compartment of tissues that subsequently take place that ultimately progress to swell- arises from an imbalance of lymph production and ing of the extremity, adipocyte enlargement and irrevers- lymph transport to the systemic circulation. Fluid moves ible fibrosis. This process can create a cycle of fibrosis via ultrafiltration out of the capillary circulation into the leading to further lymphatic transport disruption and interstitium, then to the lymphatic system, and finally worsening lymphedema. Lymphedema is reported to into the systemic circulation [1, 2]. Edema develops affect 90 million people worldwide. The majority of these cases are secondary lymphedema caused by filiarial disease, a parasitic roundworm infection of the lymph- * Correspondence: [email protected]; [email protected] 2Department of Plastic Surgery, Arthur G. James Cancer Hospital and Richard atic system caused by Wuchereria bancrofti. However, in J. Solove Research Institute and Comprehensive Cancer Center, The Ohio the western world, the majority of cases of extremity State University Wexner Medical Center, Columbus, OH 43210, USA lymphedema occur after prior cancer-related surgeries 4Division of Surgical Oncology, Department of Surgery, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and Comprehensive and other adjuvant therapies. Most frequently, these in- Cancer Center, The Ohio State University Wexner Medical Center, Columbus, clude breast cancer and gynecologic malignancies, as well OH 43210, USA as melanoma, sarcoma, lymphoma, prostate cancer, Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Garza et al. BMC Cancer (2017) 17:468 Page 2 of 18 urologic cancers, and head and neck malignancies (Fig. 1) vessels (i.e., primary lymphatics) lack a smooth muscular [3]. This untoward complication has substantial morbidity layer in the vessel wall and thus are dependent on os- for patients and significantly impacts quality of life of those motic gradients and hydrostatic pressure differences to afflicted [1]. It also translates into a significant financial aid in movement and absorption of interstitial fluid and burden for the treatment and maintenance therapy of pa- proteins. Secondary lymphatic vessels are larger and tients afflicted with this life-long condition. In a study by their walls do have a muscular component (although Shih et al., treatment costs for patients with lymphedema much thinner than that found in arteries and veins) that were twice as much as non-lymphedema patients over the aids in propelling fluid in an afferent direction. Add- course of two years - $23,167 vs $14,877, respectively. It itionally, the secondary lymphatics have valves that assist can be assumed that patients will continue to incur costs in afferent fluid movement. Primary lymphatics lack related to their lymphedema treatment over the course of valves. Simplistically, the primary lymphatics may be their lifetime and that the total costs associated with these considered the French drains of the body’s immune sys- treatments would be significant. In addition to the monet- tem, collecting fluid, protein, cells and debris for trans- ary impact that lymphedema patients face, there are also port in the secondary lymphatics, which propel fluid significant psychosocial effects associated with lymph- unidirectionally to lymph nodes and eventual clearance edema. Patients with lymphedema are reported to feel de- into the blood stream. The lymphatic system has three pressed, angry, and frustrated. They also commonly have primary functions: maintaining fluid balance, serving as complaints of perceived diminished sexuality as well as so- a nutritional adjunct, and aiding host defenses against cial isolation. Some investigators are evaluating how treat- disease [6, 7]. ments effect the psychosocial well-being of lymphedema Lymph vessels are ubiquitous in the body with the ex- patients validating the importance of psychosocial health ception of skeletal muscle. These vessels aid in returning in this patient population [4, 5]. capillary ultrafiltrate and escaped plasma proteins from Currently, there is no cure for lymphedema. However, tissues back into the systemic circulation. This process is new surgical treatment options are showing promising important in maintaining balance between interstitial results. This comprehensive review will provide general fluid and intravascular volume. Lymphatic vessels are information about secondary lymphedema related to on- uniquely designed to do this because of fenestrations in cologic therapies and discuss treatment options with a their endothelium which allows diffusion of interstitial focus on surgical treatment. fluid and proteins into the lumen of the lymph vessel [8]. Lymph fluid is devoid of red blood cells and plate- The lymphatic system lets. Ultimately, these fluids will be returned to the Until the mid nineteenth century, the lymphatic system systemic circulation via the connection between the was poorly understood. Modern technology and imaging thoracic duct and the left subclavian vein as well as has allowed us to garner a greater understanding of the lymphatic connections to the right subclavian vein. lymphatic system in structure and function. The lymph- Thereisalsosomeevidencethatlymphfluidmay atic system is developed embryologically along with the enter the venous circulation at the level of the lymph vascular system. Lymphatic vessels parallel the venous nodes [9]. system in the extremities. The superficial lymphatic Primary lymphedema Primary lymphedema occurs when there is an intrinsic disruption in the lymphatic drainage system. This can be caused by an abnormality in the lymphatic vascular structure or function. The most common classification of primary lymphedema is based on timing of presenta- tion. Congenital lymphedema occurs at birth or shortly thereafter. Lymphedema praecox occurs after birth, but before age 35 (Fig. 2). After age 35, primary lymphedema is defined as lymphedema tarda. Recent studies have identified several genes associated with these syndromes including FLT4 and FOXC2. These associated genes have provided a better understanding of lymphatic sys- Fig. 1 Stage II breast cancer related lymphedema of the right upper tem development and structure. These genes may also extremity (left), uterine cancer related lymphedema of the left lower help with classifying the variations of primary lymph- extremities (right) edema [6, 7]. Garza et al. BMC Cancer (2017) 17:468 Page 3 of 18 upper extremity lymphedema [14]. Less invasive axillary lymph node surgery, such as a sentinel lymph node biopsy procedure, significantly reduces, but does not eliminate the