Direct evidence of lymphatic function improvement after advanced pneumatic compression device treatment of lymphedema.
ABSTRACT: Lymphedema affects up to 50% of all breast cancer survivors. Management with pneumatic compression devices (PCDs) is controversial, owing to the lack of methods to directly assess benefit. This pilot study employed an investigational, near-infrared (NIR) fluorescence imaging technique to evaluate lymphatic response to PCD therapy in normal control and breast cancer-related lymphedema (BCRL) subjects. Lymphatic propulsion rate, apparent lymph velocity, and lymphatic vessel recruitment were measured before, during, and after advanced PCD therapy. Lymphatic function improved in all control subjects and all asymptomatic arms of BCRL subjects. Lymphatic function improved in 4 of 6 BCRL affected arms, improvement defined as proximal movement of dye after therapy. NIR fluorescence lymphatic imaging may be useful to directly evaluate lymphatic response to therapy. These results suggest that PCDs can stimulate lymphatic function and may be an effective method to manage BCRL, warranting future clinical trials.
Project description:Current treatment of unilateral breast cancer-related lymphedema (BCRL) is only directed to the afflicted arm. Near-infrared fluorescent imaging (NIRF) of arm lymphatic vessel architecture and function in BCRL and control subjects revealed a trend of increased lymphatic abnormalities in both the afflicted and unafflicted arms with increasing time after lymphedema onset. These pilot results show that BCRL may progress to affect the clinically "normal" arm, and suggest that cancer-related lymphedema may become a systemic, rather than local, malady. These findings support further study to understand the etiology of cancer-related lymphedema and lead to better diagnostics and therapeutics directed to the systemic lymphatic system.
Project description:To investigate the feasibility of assessing the efficacy of manual lymphatic drainage (MLD), a method for lymphedema (LE) management, by using near-infrared (NIR) fluorescence imaging.Exploratory pilot study.Primary care unit.Subjects (N=10; age, 18-68y) with a diagnosis of grade I or II LE and 12 healthy control subjects (age, 22-59y).Indocyanine green (25 ?g in 0.1 mL each) was injected intradermally in bilateral arms or legs of subjects. Diffused excitation light illuminated the limbs, and NIR fluorescence images were collected by using custom-built imaging systems. Subjects received MLD therapy, and imaging was performed pre- and posttherapy.Apparent lymph velocities and periods between lymphatic propulsion events were computed from fluorescence images. Data collected pre- and post-MLD were compared and evaluated for differences.By comparing pre-MLD lymphatic contractile function against post-MLD lymphatic function, results showed that average apparent lymph velocity increased in both the symptomatic (+23%) and asymptomatic (+25%) limbs of subjects with LE and control limbs (+28%) of healthy subjects. The average lymphatic propulsion period decreased in symptomatic (-9%) and asymptomatic (-20%) limbs of subjects with LE, as well as in control limbs (-23%).We showed that NIR fluorescence imaging could be used to quantify immediate improvement of lymphatic contractile function after MLD.
Project description:Previous studies have shown cost effectiveness and quality-of-life benefit of pneumatic compression therapy (PCT) for lymphedema. Insurers, such as the Centers for Medicare/Medicaid (CMS), however, desire visual proof that PCT moves lymph. Near-infrared fluorescence lymphatic imaging (NIRFLI) was used to visualize lymphatic anatomy and function in four subjects with primary and cancer treatment-related lymphedema (LE) of the lower extremities before, during, and after pneumatic compression therapy (PCT). Optically transparent and windowed PCT garments allowed visualization of lymph movement during single, one-hour PCT treatment sessions. Visualization revealed significant extravascular and lymphatic vascular movement of intradermally injected dye in all subjects. In one subject with sufficient patent lymphatic vessels to allow quantification of lymph pumping velocities and frequencies, these values were significantly increased during and after PCT as compared to pre-treatment values. Lymphatic contractile activity in patent lymphatic vessels occurred in concert with the sequential cycling of PCT. Direct visualization revealed increased lymphatic function, during and after PCT therapy, in all lymphedema-affected extremities. Further studies are warranted to assess the effects of PCT pressure and sequences on lymph uptake and movement.
Project description:To profile the prescription for and adherence to breast cancer-related lymphedema (BCRL) self-care modalities among breast cancer (BrCa) survivors with BCRL in a 12-month randomized weightlifting trial.We developed a questionnaire that assessed prescription for and adherence to 10 BCRL self-care modalities that included physical therapy exercise, pneumatic compression pump, medication, lymphedema bandaging, arm elevation, self-administered lymphatic drainage, therapist-administered lymphatic drainage, compression garments, skin care, and taping. We measured prescription for and adherence to BCRL self-care modalities at baseline, 3, 6, and 12 months. Longitudinal logistic regression was used to estimate the odds ratio (OR) and 95 % confidence interval (95 % CI) associated with prescription for and adherence to BCRL modalities over time.This study included 141 BrCa survivors with BCRL. Women were prescribed an average of 3.6?±?2.1 BCRL self-care modalities during the study. The prescription for therapist-administered lymphatic drainage (OR?=?0.92, 95 % CI 0.88-0.96), pneumatic compression pump use (OR?=?0.94, 95 % CI 0.89-0.98), and bandaging (OR?=?0.96, 95 % CI 0.93-0.99) decreased over 12 months of follow-up. No other prescribed BCRL self-care modalities changed during the study. Over 12 months, the average adherence to all BCRL self-care modalities varied with 13, 24, 32, and 31 % of women reporting <25, 25-49, 50-74, and ?75 % adherence, respectively. Over 12 months, there was a noticeable change from high to low adherence in self-administered lymphatic drainage, such that there was a 15 % increased likelihood of adherence <25 % compared to ?75 % (OR?=?1.15 (95 % CI 1.05-1.26); p?=?0.002). The adherence patterns of all other modalities did not change over follow-up.Our findings suggest the prescription for BCRL self-care modalities is variable. The average adherence to BCRL self-care was non-optimal. Future research is necessary to prepare BrCa survivors with the knowledge, skills, abilities, and resources necessary to care for this lifelong condition.
Project description:Although the importance of lymphatic function is well recognized, the lack of real-time imaging modalities limits our understanding of its role in many diseases. In a phase 0 exploratory study, we used dynamic, near-infrared (NIR) fluorescence imaging to assess the extremes of lymphatic architecture and transport in healthy human subjects and in subjects clinically diagnosed with unilateral lymphedema (LE), a disease that can be prevalent in cancer survivors.Active lymphatic propulsion was imaged after intradermal injections of 25 µg of indocyanine green (total maximum dose ?400 µg) bilaterally in the arms or legs of control and subjects. Images show well-defined lymphatic structures with propulsive dye transport in limbs of healthy subjects. In LE subjects, we observed extravascular dye accumulation, networks of fluorescent lymphatic capillaries, and/or tortuous lymphatic vessels in all symptomatic and some asymptomatic limbs. Statistical models indicate that disease status and/or limb significantly affect parameters of apparent lymph propagation velocity and contractile frequency.These clinical research studies demonstrate the potential of NIR fluorescence imaging as a diagnostic measure of functional lymphatics and as a new tool in translational research studies to decipher the role of the lymphatic system in cancer and other diseases.
Project description:Breast cancer treatment-related lymphedema (BCRL) arises from a mechanical insufficiency following cancer therapies. Early BCRL detection and personalized intervention require an improved understanding of the physiological processes that initiate lymphatic impairment. Here, internal magnetic resonance imaging (MRI) measures of the tissue microenvironment were paired with clinical measures of tissue structure to test fundamental hypotheses regarding structural tissue and muscle changes after the commonly used therapeutic intervention of manual lymphatic drainage (MLD).Measurements to identify lymphatic dysfunction in healthy volunteers (n = 29) and patients with BCRL (n = 16) consisted of (1) limb volume, tissue dielectric constant, and bioelectrical impedance (i.e., non-MRI measures); (2) qualitative 3 Tesla diffusion-weighted, T1-weighted and T2-weighted MRI; and (3) quantitative multi-echo T2 MRI of the axilla. Measurements were repeated in patients immediately following MLD. Normative control and BCRL T2 values were quantified and a signed Wilcoxon Rank-Sum test was applied (significance: two-sided p < 0.05). Non-MRI measures yielded significant capacity for discriminating between arms with versus without clinical signs of BCRL, yet yielded no change in response to MLD. Alternatively, a significant increase in deep tissue T2 on the involved (pre T2 = 0.0371 ± 0.003 seconds; post T2 = 0.0389 ± 0.003; p = 0.029) and contralateral (pre T2 = 0.0365 ± 0.002; post T2 = 0.0395 ± 0.002; p < 0.01) arms was observed. Trends for larger T2 increases on the involved side after MLD in patients with stage 2 BCRL relative to earlier stages 0 and 1 BCRL were observed, consistent with tissue composition changes in later stages of BCRL manifesting as breakdown of fibrotic tissue after MLD in the involved arm. Contrast consistent with relocation of fluid to the contralateral quadrant was observed in all stages.Quantitative deep tissue T2 MRI values yielded significant changes following MLD treatment, whereas non-MRI measurements did not vary. These findings highlight that internal imaging measures of tissue composition may be useful for evaluating how current and emerging therapies impact tissue function.
Project description:Secondary lymphedema is a chronic debilitating lifelong complication and early diagnosis is crucial. The Inbody 720, which is widely used, has no universal index of diagnostic criteria for test results. We aim to determine the normal range, cutoff values, and mean + standard deviation values of extracellular fluid (ECF) and the single frequency bioimpedance (SFBIA) ratios for the diagnosis of lymphedema and suggest the usefulness of these values for detecting lymphedema.Seventy patients with unilateral breast cancer-related lymphedema and 643 healthy subjects were enrolled. All patients with breast cancer underwent surgeries with dissection of lymph nodes. We analyzed the ECF volume, SFBIA at 1- and 5-kHz frequencies using Inbody 720.There were significant differences between patients with BCRL and healthy controls. The optimal cutoff values for ECF ratios were 1.010 for both the dominant and non-dominant arms. At 1?kHz, the cutoff values of SFBIA were 1.050 and 1.046, and at 5?kHz, those were 1.070 and 1.030 for the dominant and non-dominant affected arms, respectively. The mean + 2SD values for ECF ratio were 1.018 and 1.020 and at 1?kHz, the mean + 2SD values of SFBIA were 1.144 and 1.0135 and at 5?kHz, the cutoff values of SFBIA were 1.141 and 1.124 for the dominant and non-dominant affected arms, respectively. The mean + 3SD values for ECF ratio were 1.026 and 1.030 and at 1?kHz, the mean + 3SD values of SFBIA were 1.206 and 1.203 and at 5?kHz, those were 1.201 and 1.187 for the arms, respectively. The cutoff, mean + 2SD, and mean + 3SD values were applied to 70 patients with unilateral BCRL. When the cutoff values were applied, a higher proportion of BCRL patients were included.When these figures were applied to the patient group, the cutoff values included a higher proportion of patients with lymphedema. Further studies are needed to investigate whether bioimpedance analysis can accurately predict the development of lymphedema.
Project description:Lymphedema is a complication that may occur after surgical resection and radiation treatment in a number of cancer types and is especially debilitating in regions where treatment options are limited. Although upper and lower extremity lymphedema may be effectively treated with manual lymphatic drainage (MLD) therapies and devices that use compression to direct proximal flow of lymph fluids, head and neck lymphedema is more challenging.Herein, we describe the compassionate use of an investigatory technique of near-infrared (NIR) fluorescence imaging to understand the lymphatic anatomy and function, help direct MLD, and use 3-dimensional (3D) surface profilometry to monitor response to therapy in a patient with head and neck lymphedema after surgery and radiation treatment.NIR fluorescence imaging provides a mapping of functional lymph vessels for direction of efficient MLD therapy in the head and neck. Additional studies are needed to assess the efficacy of MLD therapy when directed by NIR fluorescence imaging.
Project description:Breast cancer-related lymphedema (BCRL) occurs in a significant number of breast cancer survivors as a consequence of the axillary lymphatics' impairment after therapy (mainly axillary surgery and irradiation). Despite the recent achievements in the clinical management of these patients, BCRL is often diagnosed at its occurrence. In most cases, it remains a progressive and irreversible condition, with dramatic consequences in terms of quality of life and on sanitary costs. There are still no validated pre-surgical strategies to identify individuals that harbor an increased risk of BCRL. However, clinical, therapeutic, and tumor-specific traits are recurrent in these patients. Over the past few years, many studies have unraveled the complexity of the molecular and transcriptional events leading to the lymphatic system ontogenesis. Additionally, molecular insights are coming from the study of the germline alterations involved at variable levels in BCRL models. Regrettably, there is a substantial lack of predictive biomarkers for BCRL, given that our knowledge of its molecular milieu remains extremely puzzled. The purposes of this review were (i) to outline the biology underpinning the ontogenesis of the lymphatic system; (ii) to assess the current state of knowledge of the molecular alterations that can be involved in BCRL pathogenesis and progression; (iii) to discuss the present and short-term future perspectives in biomarker-based patients' risk stratification; and (iv) to provide practical information that can be employed to improve the quality of life of these patients.
Project description:Background: Breast cancer-related lymphedema (BCRL) is hard to control. Management may include lymphatic drainage, skin care, bandaging, or even surgery. Since acupuncture has been proven to affect the neurophysiology and neuroendocrine systems, it has the potential to control BCRL. Aim: To evaluate the effect of acupuncture in BCRL in randomized controlled trials. Design: A literature search was performed, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and without language restrictions. Data Sources: Five databases were searched from inception tthrough September 2018. Only studies that fulfilled the eligibility criteria of evaluating the effect of acupuncture on lymphedema in breast cancer were included. The methodological quality of these trials was assessed using the Cochrane criteria, and meta-analysis software (RevMan 5.3) was used for analysis. Results: We examined 178 breast cancer patients from 6 trials. All included randomized controlled trials had medium to high quality, based on the modified Jadad scale. The systematic review showed that acupuncture is safe and has a trend to improve symptoms, but trials did not consistently measure outcomes. The meta-analysis showed that acupuncture produced no significant improvement in the extent of lymphedema as compared with the control intervention (-1.90; 95% confidence interval = -5.39 to 1.59, P = .29). None of the studies reported severe adverse events. Conclusions: Acupuncture is safe and has a trend to improve the lymphedema related to breast cancer, yet it did not significantly change arm circumference in BCRL. Future studies should include both subjective and objective measurements and large-scale studies are warranted.