Background: Lymph is pumped through the collecting lymphatic vessels by both intrinsic and extrinsic forces, propelling it downstream back into circulation. The intrinsic lymph pump relies on the spontaneous contraction of lymphatic muscles to generate the force of pumping lymph (P lp ). However, the association between leg edema and reduced leg P lp in the general population is unknown. Therefore, this study determined the association of leg P lp and edema complaints and quality of life in healthy participants. Methods and Results: A total of 465 healthy volunteers (78 men and 387 women, age 30-85 years) filled out a questionnaire and medical history to rule out severe systemic diseases and local venous/lymphatic diseases. Quality of life was assessed using the Medical Outcome Study Short Form 36 (SF36). Leg P lp was measured using minimally invasive indocyanine green fluorescence lymphography and an occlusion cuff technique while sitting. All participants were divided into three groups according to the P lp values, as follows: Participants with P lp >40 mmHg in both legs, 20 mmHg-40 mmHg in either leg; and <20 mmHg in both legs were divided into the good (n = 100), moderate (n = 314), and poor (n = 51) P lp groups, respectively. The survey revealed the poor leg P lp group was associated with more frequently complaints of leg edema, as well as lower quality of life than the moderate and good P lp groups. Conclusion: Reduced leg P lp is significantly associated with leg edema complaints and lower quality of life in the general population.
Secondary lymphedema often develops after cancer surgery, and over 250 million patients suffer from this complication. A major symptom of secondary lymphedema is swelling with fibrosis, which lowers the patient's quality of life, even if cancer does not recur. Nonetheless, the pathophysiology of secondary lymphedema remains unclear, with therapeutic approaches limited to physical or surgical therapy. There is no effective pharmacological therapy for secondary lymphedema. Notably, the lack of animal models that accurately mimic human secondary lymphedema has hindered pathophysiological investigations of the disease. Here, we developed a novel rat hindlimb model of secondary lymphedema and showed that our rat model mimics human secondary lymphedema from early to late stages in terms of cell proliferation, lymphatic fluid accumulation, and skin fibrosis. Using our animal model, we investigated the disease progression and found that transforming growth factor‐beta 1 (TGFB1) was produced by macrophages in the acute phase and by fibroblasts in the chronic phase of the disease. TGFB1 promoted the transition of fibroblasts into myofibroblasts and accelerated collagen synthesis, resulting in fibrosis, which further indicates that myofibroblasts and TGFB1/Smad signaling play key roles in fibrotic diseases. Furthermore, the presence of myofibroblasts in skin samples from lymphedema patients after cancer surgery emphasizes the role of these cells in promoting fibrosis. Suppression of myofibroblast‐dependent TGFB1 production may therefore represent an effective pharmacological treatment for inhibiting skin fibrosis in human secondary lymphedema after cancer surgery.
Background: Lymph is pumped through the collecting lymphatic vessels by both intrinsic and extrinsic forces. The intrinsic pump relies on spontaneous lymphatic contraction, which generates the pumping lymph pressure (Plp). Among healthy people with daily leg edema, a considerable number of cases are accompanied with low leg Plp. Herein, a double-blinded controlled trial was conducted in healthy female volunteers with reduced leg Plp to compare the effectiveness of a 15–29 mmHg compression stocking (Stocking A) and a 8–16 mmHg stocking (Stocking B) on elevating Plp.Method and Results: Among 219 healthy female volunteers who underwent measurement of leg Plp, 80 participants (36.5%) had unilateral or bilateral legs with Plp < 20 mmHg (122 legs with Plp < 20 mmHg and 38 legs with Plp ≧ 20 mmHg). These 80 participants were assigned to wear either Stocking A (n = 40) or Stocking B (n = 40) for 16 weeks. Leg Plp was measured using indocyanine green fluorescence lymphography and an occlusion cuff technique while sitting. At 16 weeks, both Stockings A and B resulted in significantly elevated leg Plp, with the effect on elevating Plp being superior for Stocking A. Only Stocking A resulted in decreased prevalence of leg edema and improved Short Form-36 scores.Conclusion: Compression stockings may represent a therapeutic option to elevate leg Plp and ameliorate leg edema, thereby leading to improved quality of life in healthy females with low leg Plp.
Intraoperative lymph mapping and preoperative vein mapping are technically feasible and can positively contribute to the prevention of postoperative lymphorrhea after GSV harvesting.
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