Lymphangiogenesis: Molecular Mechanisms and Future Promise

Background Liposuction has been proposed as a potential treatment for the metabolic complications of obesity. We evaluated the effect of large-volume abdominal liposuction on metabolic risk factors for coronary heart disease in women with abdominal obesity. Methods We evaluated the insulin sensitivity of liver, skeletal muscle, and adipose tissue (with a euglycemic–hyperinsulinemic clamp procedure and isotope-tracer infusions) as well as levels of inflammatory mediators and other risk factors for coronary heart disease in 15 obese women before and 10 to 12 weeks after abdominal liposuction. Eight of the women had normal glucose tolerance (mean [±SD] body-mass index, 35.1±2.4), and seven had type 2 diabetes (body-mass index, 39.9±5.6). Results Liposuction decreased the volume of subcutaneous abdominal adipose tissue by 44 percent in the subjects with normal glucose tolerance and 28 percent in those with diabetes; those with normal oral glucose tolerance lost 9.1±3.7 kg of fat (18±3 percent decrease in tota...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa033179

Absence of an Effect of Liposuction on Insulin Action and Risk Factors for Coronary Heart Disease

Background: Lymphedema is a chronic, debilitating condition that has traditionally been seen as refractory or incurable. Recent years have brought new advances in the study of lymphedema pathophysiology. as well as diagnostic and therapeutic tools that are changing this perspective. Objective: To provide a systematic approach to evaluating and managing patients with lymphedema. Methods: We performed MEDLINE searches of the English-language literature (1966 to March 2006) using the terms lymphedema, breast cancer-associated lymphedema, lymphatic complications, lymphatic imaging, decongestive therapy, and surgical treatment of lymphedema. Relevant bibliographies and International Society of Lymphology guidelines were also reviewed. Results: In the United States, the populations primarily affected by lymphedema are patients undergoing treatment of malignancy, particularly women treated for breast cancer. A thorough evaluation of patients presenting with extremity swelling should include identification of prior surgical or radiation therapy for malignancy, as well as documentation of other risk factors for lymphedema, such as prior trauma to or infection of the affected limb. Physical examination should focus on differentiating signs of lymphedema from other causes of systemic or localized swelling. Lymphatic dysfunction can be visualized through lymphoscintigraphy; the diagnosis of lymphedema can also be confirmed through other imaging modalities, including CT or MRI. The mainstay of therapy in diagnosed cases of lymphedema involves compression garment use, as well as intensive bandaging and lymphatic massage. For patients who are unresponsive to conservative therapy; several surgical options with varied proven efficacies have been used in appropriate candidates, including excisional approaches, microsurgical lymphatic anastomoses, and circumferential suction-assisted lipectomy, an approach that has shown promise for long-term relief of symptoms. Conclusions: The diagnosis of lymphedema requires careful attention to patient risk factors and specific findings on physical examination. Noninvasive diagnostic tools and lymphatic imaging can be helpful to confirm the diagnosis of lymphedema or to address a challenging clinical presentation. Initial treatment with decongestive lymphatic therapy can provide significant improvement in patient symptoms and volume reduction of edematous extremities. Selected patients who are unresponsive to conservative therapy can achieve similar outcomes with surgical intervention, most promisingly suction-assisted lipectomy. (Less)

Lymphedema: a comprehensive review.

Multiple organs cooperate to regulate appetite, metabolism, and glucose and fatty acid homeostasis. Here, we identified and characterized lymphatic vasculature dysfunction as a cause of adult-onset obesity. We found that functional inactivation of a single allele of the homeobox gene Prox1 led to adult-onset obesity due to abnormal lymph leakage from mispatterned and ruptured lymphatic vessels. Prox1 heterozygous mice are a new model for adult-onset obesity and lymphatic vascular disease.

Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity

The improvement in the life expectancy of women with breast cancer raises important questions about how to improve the quality of life for women sustaining complications of breast cancer treatment. In particular, attention to common problems, such as arm edema, is of critical importance. We reviewed published breast cancer guidelines and literature identified via MEDLINE(R) searches in an effort to summarize the research literature pertinent to management of breast cancer-related arm edema, including incidence, prevalence, and timing; risk factors; morbidity; prevention; diagnosis; and efficacy of nonpharmacologic and pharmacologic interventions. We found that arm edema is a common complication of breast cancer therapy that can result in substantial functional impairment and psychological morbidity. The risk of arm edema increases when axillary dissection and axillary radiation therapy are used. Recommendations for preventive measures, such as avoidance of trauma, are available, but these measures have not been well studied. Nonpharmacologic treatments, such as massage and exercise, have been shown to be effective therapies for lymphedema, but the effect of pharmacologic interventions remains uncertain. Comparing results across studies is complicated by the fact that the definitions of interventions and measures of outcomes and risk stratification vary substantially among studies. As arm edema becomes more prevalent with the increasing survival of breast cancer patients, further research is needed to evaluate the efficacy of preventive strategies and therapeutic interventions.

/pdf/arm-edema-in-breast-cancer-patients-1uskpfirmu.pdf

Arm Edema in Breast Cancer Patients

Background: Arm lymphedema is a common complication after breast cancer treatment. Although conservative treatment can be used to reduce swelling, treatment often fails, possibly due to chronic edema being transformed from lymph fluid to subcutaneous fat, a condition called nonpitting lymphedema. It is currently unknown if the excess volume is solely due to excess in fat. This study evaluated whether dual energy X-ray absorptiometry (DXA) could be used to estimate the excess fat, muscle, and bone tissue in patients with arm lymphedema. Methods and Results: Eighteen women with arm lymphedema were investigated. Measurements were converted to volume values and compared with values obtained using plethysmography (PG). Linear regression equations and correlation equations were used to compare the DXA and the PG techniques in regard to total volume and excess volume in the lymphedematous arm. DXA was used to estimate excess fat, muscle, and bone volume in the lymphedematous arm. Both DXA and PG provided similar total arm volume and excess volume measurements for the lymphedematous arm. The lymphedematous arm showed 73% more fat, 47% more muscle, and 7% more bone by volume in the lymphedematous arm. Conclusions: Both excess fat and muscle volume contributed to the total excess volume in nonpitting arm lymphedema; excess soft tissue developed the first few years after breast cancer surgery. DXA can be used to identify patients with excess fat in their arms and thus unsuitable for conservative treatment and may be useful in estimating the amount of fat to remove in patients scheduled for liposuction. (Less)

Breast Cancer-Related Chronic Arm Lymphedema Is Associated with Excess Adipose and Muscle Tissue.

Arm lymphedema after breast cancer therapy has been treated with various forms of conservative and surgical treatment during recent years. The clinical results usually have been modest or, in some instances, even disappointing. In a previous series of patients treated with the new liposuction technique combined with controlled compression therapy, we found, however, an overall edema reduction of 106 percent after 1 year. The purpose of this study was both to investigate how much the surgical procedure contributes to the outcome and to clarify the importance of controlled compression therapy. Twenty-eight patients were, therefore, prospectively matched into two groups. One group received liposuction combined with controlled compression therapy, and one group received the therapy alone. Additionally, the therapy group was compared with our complete group of patients treated thus far with liposuction combined with therapy (n = 30). The prospective study using matched pairs (n = 14) showed that liposuction combined with controlled compression therapy is significantly more effective than the therapy alone (p < 0.0001), with a mean difference of about 1000 ml during the entire 1-year observation period. The beneficial effect of liposuction was confirmed by the comparison between the controlled compression therapy group and our complete group of patients treated with liposuction combined with the therapy, as the edema reduction figures after 1 year were 47 percent and 104 percent, respectively (p < 0.0001). In six patients who had surgery and a complete reduction of the edema, the compression garments were removed for 1 week, 1 year postoperatively. A marked increase in the arm volume was observed, which was immediately remedied by reapplying the garments. We conclude that liposuction combined with controlled compression therapy reduces arm lymphedema more efficiently than the therapy alone. Continued use of compression garments is, however, important to maintain the primary surgical outcome.

/pdf/liposuction-combined-with-controlled-compression-therapy-54fr2cprgm.pdf

Liposuction combined with controlled compression therapy reduces arm lymphedema more effectively than controlled compression therapy alone.

Background: Arm lymphedema is a common complication after breast cancer treatment. Various types of conservative and surgical treatments have aimed at reducing the arm swelling, but most of these have failed due to chronic edema eventually being transformed from an accumulation of lymph fluid to an increased deposition of subcutaneous fat (i.e., to a nonpitting lymphedema). Liposuction is a safe and reliable method for reducing the excess fat without recurring deposition of it. The objective of the present study was to obtain empirical evidence confirming clinical observations of the presence of excess adipose tissue in patients with chronic nonpitting arm lymphedema following breast cancer. Methods: A total of 11 women with nonpitting unilateral postmastectomy arm lymphedema were investigated and were treated as follows: The patient's excess arm volume was measured by plethysmography (PG) and, following treatment by liposuction, was observed until complete reduction of the excess volume was achieved. Vol...

Adipose Tissue Dominates Chronic Arm Lymphedema Following Breast Cancer: An Analysis Using Volume Rendered CT Images.

The incidence of lymphoedema of the arm after mastectomy ranges between 8% and 38%, and it is an appreciable problem from both functional and social aspects. Conservative and previous surgical regimens have not been completely successful. In the light of these experiences, liposuction clearly constitutes an interesting new surgical approach, which is potentially capable of effecting predictable and reliable improvements in patients with lymphoedema. Twenty eight women with lymphoedema of the arm after breast cancer were consecutively treated by liposuction. Limb compression with a compression garment was instituted immediately after operation. All patients had been given radiotherapy after the operation for breast cancer. Mean preoperative volume of oedema was 1845 ml (range 570-3915), and mean volume of aspirate was 2250 ml (range 1000-3850); volume of aspirate correlated linearly with the volume of preoperative oedema. There were no major surgical complications, but blood transfusion was necessary in eight patients whose volume of aspirate exceeded 2000 ml. After 12 months (n = 24), an average reduction in volume of oedema of 106% was found. Such a normalisation can be expected in patients with oedema that amounts to about 2500 ml. Although the oedema cannot be completely removed in more severe cases, substantial reduction is beneficial from both functional and cosmetic aspects. We conclude that liposuction is safe and effective for reducing lymphoedema of the arm after operations for breast cancer. In a one-stage procedure, oedematous and hypertrophic fat tissue can be removed with an excellent clinical outcome.

/pdf/complete-reduction-of-lymphoedema-of-the-arm-by-liposuction-4x4ajgebff.pdf

Håkan Brorson

Papers

Lymphedema: a comprehensive review.

Breast Cancer-Related Chronic Arm Lymphedema Is Associated with Excess Adipose and Muscle Tissue.

Liposuction combined with controlled compression therapy reduces arm lymphedema more effectively than controlled compression therapy alone.

Adipose Tissue Dominates Chronic Arm Lymphedema Following Breast Cancer: An Analysis Using Volume Rendered CT Images.

Complete reduction of lymphoedema of the arm by liposuction after breast cancer