Background: This study aimed at testing whether arm-to-leg ratios of extracellular water (ECW) and ECW normalized to intracellular water (ICW), measured by bioimpedance spectroscopy (BIS), can accurately detect bilateral, lower-limb lymphedema, and whether accounting for sex, age, and body mass index (BMI) improves the diagnostic performance of cut-offs. Methods and Results: We conducted a dual-approach, case-control study consisting of cases of bilateral, lower-limb lymphedema and healthy controls who self-reported absence of lymphedema. The diagnostic performance using normative data-derived cut-offs (i.e., mean + 0.5 standard deviation [SD] to mean + 3 SD; n = 136, 66% controls) and receiver operating characteristic (ROC) curve-derived cut-offs (n = 746, 94% controls) was assessed. The impact of sex, age, and BMI was investigated by comparing stratified and nonstratified normative data-derived cut-offs, and ROC curves generated from adjusted and unadjusted logistic regression models. Arm-to-leg ratios of ECW between mean + 0.5 SD and mean + 1 SD showed fair to good sensitivity (0.73-0.84) and poor to good specificity (0.64 to 0.84). Arm-to-leg ratios of ECW/ICW failed to detect lymphedema (sensitivity <0.5). Stratification by sex, or by sex and age, yielded similar results to nonstratified cut-offs. Cut-offs derived from adjusted ROC curves showed both good sensitivity (0.83-0.89) and specificity (0.8-0.84). Conclusion: These findings represent new BIS criteria for diagnosing lower-limb lymphedema that do not rely on comparison to baseline measures or the presence of a nonaffected, contralateral limb.

Background: Bioimpedance spectroscopy detects unilateral lymphedema if the ratio of extracellular fluid (ECF) between arms or between legs is outside three standard deviations (SDs) of the normative mean. Detection of bilateral lymphedema, common after bilateral breast or gynecological cancer, is complicated by the unavailability of an unaffected contralateral limb. The objectives of this work were to (1) present normative values for interarm, interleg, and arm-to-leg impedance ratios of ECF and ECF normalized to intracellular fluid (ECF/ICF); (2) evaluate the influence of sex, age, and body mass index on ratios; and (3) describe the normal change in ratios within healthy individuals over time. Methods: Data from five studies were combined to generate a normative data set (n = 808) from which mean and SD were calculated for interarm, interleg, and arm-to-leg ratios of ECF and ECF/ICF. The influence of sex, age, and body mass index was evaluated using multiple linear regression, and normative change was calculated for participants with repeated measures by subtracting their lowest ratio from their highest ratio. Results: Mean (SD) interarm, interleg, dominant arm-to-leg, and nondominant arm-to-leg ratios were 0.987 (0.067), 1.005 (0.072), 1.129 (0.160), and 1.165 (0.174) for ECF ratios; and 0.957 (0.188), 1.024 (0.183), 1.194 (0.453), and 1.117 (0.367) for ECF/ICF ratios, respectively. Arm-to-leg ratios were significantly affected by sex, age, and body mass index. Mean normative change ranged from 7.2% to 14.7% for ECF ratios and from 14.7% to 67.1% for ECF/ICF ratios. Conclusion: These findings provide the necessary platform for extending bioimpedance-based screening beyond unilateral lymphedema.

OBJECTIVE:Cancer-related lymphedema is a debilitating condition that adversely influences function, health and quality of life. The purpose of this study was to assess the prevalence, incidence, and risk factors of lower-limb lymphedema pre- through to 24months post-surgery for gynecological cancer. METHODS:A clinic-based sample of women (n=408) with gynecological cancer participated in a prospective, longitudinal study (2008-2011) using self-reported measures (swelling in one or both legs) and objectively measured lymphedema (bioimpedance spectroscopy) at baseline (pre-surgery), six weeks-three months, 6-12months, and 15-24months post-surgery. RESULTS:At pre-surgery, 15% of women self-reported lymphedema and 27% had measurable evidence of lymphedema. By 24months post-surgery, incidence of new self-reported or measured lymphedema was 45% and 37%, respectively. Three-quarters of these new cases presented by 12-months post-treatment. While lymphedema was transient for some women, 60% had persistent lymphedema. More extensive lymph node dissection, receipt of chemotherapy and radiation therapy, increasing body mass index, insufficient levels of physical activity, diagnosis of vulvar/vaginal cancer and presence of pre-treatment lymphedema were identified as potential risk factors (p<0.05). CONCLUSION:Findings support the need for integration of pre-surgical assessment, and prospective, post-treatment surveillance of lymphedema into gynecological cancer care. Future research exploring the role of maintaining healthy body weight, regular physical activity and education about early detection of lymphedema to improve gynecological cancer survivorship is warranted.

Background. Resistance exercise is emerging as a potential adjunct therapy to aid in the management of breast cancer–related lymphedema (BCRL). However, the mechanisms underlying the relationships between the acute and long-term benefits of resistance exercise on BCRL are not well understood. Purpose. To examine the acute inflammatory response to upper-body resistance exercise in women with BCRL and to compare these effects between resistance exercises involving low, moderate, and high loads. The impact on lymphedema status and associated symptoms was also compared. Methods. A total of 21 women, 62 ± 10 years old, with BCRL participated in the study. Participants completed low-load (15-20 repetition maximum [RM]), moderate-load (10-12 RM), and high-load (6-8 RM) exercise sessions consisting of 3 sets of 6 upper-body resistance exercises. Sessions were completed in a randomized order separated by a 7- to 10-day wash-out period. Venous blood samples were obtained to assess markers of exercise-induced muscle damage and inflammation. Lymphedema status was assessed using bioimpedance spectroscopy and arm circumferences, and associated symptoms were assessed using Visual Analogue Scales for pain, heaviness, and tightness. Measurements were conducted before and 24 hours after the exercise sessions. Results. No significant changes in creatine kinase, C-reactive protein, interleukin-6, and tumor necrosis factor-α were observed following the 3 resistance exercise sessions. There were no significant changes in arm swelling or symptom severity scores across the 3 resistance exercise conditions. Conclusions. The magnitude of acute exercise-induced inflammation following upper-body resistance exercise in women with BCRL does not vary between resistance exercise loads.

BACKGROUND Bioimpedance spectroscopy (BIS) assesses resistance (impedance) to the flow of an electrical current. Through the measurement of impedance to currents at low (R0) and high (Rinf) frequencies, extracellular fluid (ECF) and total body fluid (TBF) can be measured, respectively, and intracellular fluid (Ri = ICF) subsequently extrapolated (TBW = ECF + ICF). Measuring bilateral upper-limb or lower-limb secondary lymphoedema following cancer is complicated by the unavailability of a comparable, unaffected limb. Availability of normative BIS data for all 4 limb segments would enable an extension of BIS in the diagnosis of bilateral upper-, as well as lower-limb lymphoedema. The purpose of this study was to describe normative arm to leg, arm to arm and leg to leg impedance ratios and to determine optimal cut-off thresholds for diagnosing lymphoedema by testing the accuracy of cut-offs based on normative means plus or minus 0.5 to 3 SDs to diagnose known cases of lymphoedema.

Background - The use of compression garments during exercise is recommended for women with breast cancer-related lymphoedema, but the evidence behind this clinical recommendation is unclear. The aim of this randomised, cross-over trial was to compare the acute effects of wearing versus not wearing compression during a single bout of moderate-load resistance exercise on lymphoedema status and its associated symptoms in women with breast cancer-related lymphoedema. Methods - Twenty-five women with clinically diagnosed, stable unilateral breast cancer-related lymphoedema completed two resistance exercise sessions, one with compression and one without, in a randomised order separated by a 14 day wash-out period. The resistance exercise session consisted of six upper-body exercises, with each exercise performed for three sets at a moderate-load (10-12 repetition maximum). Primary outcome was lymphoedema, assessed using bioimpedance spectroscopy (L-Dex score). Secondary outcomes were lymphoedema as assessed by arm circumferences (percent inter-limb difference and sum-of-circumferences), and symptom severity for pain, heaviness and tightness, measured using visual analogue scales. Measurements were taken pre-, immediately post- and 24 hours post-exercise. Results - There was no difference in lymphoedema status (i.e., L-Dex scores) pre- and post-exercise sessions or between the compression and non-compression condition [Mean (SD) for compression pre-, immediately post- and 24 hours post-exercise: 17.7 (21.5), 12.7 (16.2) and 14.1 (16.7), respectively; no compression: 15.3 (18.3), 15.3 (17.8), and 13.4 (16.1), respectively]. Circumference values and symptom severity were stable across time and treatment condition. Conclusions - An acute bout of moderate-load, upper-body resistance exercise performed in the absence of compression does not exacerbate lymphoedema in women with breast cancer-related lymphoedema.

The use of compression garments during exercise is recommended for women with breast cancer-related lymphedema, but the evidence behind this clinical recommendation is unclear. The aim of this randomized, cross-over trial was to compare the acute effects of wearing versus not wearing compression during a single bout of moderate-load resistance exercise on lymphedema status and its associated symptoms in women with breast cancer-related lymphedema (BCRL). Twenty-five women with clinically diagnosed, stable unilateral breast cancer-related lymphedema completed two resistance exercise sessions, one with compression and one without, in a randomized order separated by a minimum 6 day wash-out period. The resistance exercise session consisted of six upper-body exercises, with each exercise performed for three sets at a moderate-load (10-12 repetition maximum). Primary outcome was lymphedema, assessed using bioimpedance spectroscopy (L-Dex score). Secondary outcomes were lymphedema as assessed by arm circumferences (percent inter-limb difference and sum-of-circumferences), and symptom severity for pain, heaviness and tightness, measured using visual analogue scales. Measurements were taken pre-, immediately post- and 24 hours post-exercise. There was no difference in lymphedema status (i.e., L-Dex scores) pre- and post-exercise sessions or between the compression and non-compression condition [Mean (SD) for compression pre-, immediately post- and 24 hours post-exercise: 17.7 (21.5), 12.7 (16.2) and 14.1 (16.7), respectively; no compression: 15.3 (18.3), 15.3 (17.8), and 13.4 (16.1), respectively]. Circumference values and symptom severity were stable across time and treatment condition. An acute bout of moderate-load, upper-body resistance exercise performed in the absence of compression does not exacerbate lymphedema in women with BCRL.

BACKGROUND Bioimpedance techniques provide a reliable method of assessing unilateral lymphedema in a clinical setting. Bioimpedance devices are traditionally used to assess body composition at a current frequency of 50 kHz. However, these devices are not transferable to the assessment of lymphedema, as the sensitivity of measuring the impedance of extracellular fluid is frequency dependent. It has previously been shown that the best frequency to detect extracellular fluid is 0 kHz (or DC). However, measurement at this frequency is not possible in practice due to the high skin impedance at DC, and an estimate is usually determined from low frequency measurements. This study investigated the efficacy of various low frequency ranges for the detection of lymphedema. METHODS AND RESULTS Limb impedance was measured at 256 frequencies between 3 kHz and 1000 kHz for a sample control population, arm lymphedema population, and leg lymphedema population. Limb impedance was measured using the ImpediMed SFB7 and ImpediMed L-Dex(®) U400 with equipotential electrode placement on the wrists and ankles. The contralateral limb impedance ratio for arms and legs was used to calculate a lymphedema index (L-Dex) at each measurement frequency. The standard deviation of the limb impedance ratio in a healthy control population has been shown to increase with frequency for both the arm and leg. Box and whisker plots of the spread of the control and lymphedema populations show that there exists good differentiation between the arm and leg L-Dex measured for lymphedema subjects and the arm and leg L-Dex measured for control subjects up to a frequency of about 30 kHz. CONCLUSIONS It can be concluded that impedance measurements above a frequency of 30 kHz decrease sensitivity to extracellular fluid and are not reliable for early detection of lymphedema.

Velocity dependent changes observed in the impedance of flowing blood is one of the reasons the physiological source of Impedance Cardiography waveforms has been widely disputed in the literature. This study investigates the experimental relationship between the impedance and pulsatile velocity of blood. Experimental measurements of impedance and velocity were recorded for bovine blood; pumped through rigid tubes in a mock circulatory system as cardiac parameters were varied. From the data collected, the time constant and system gain have been modeled. Results show that the time constant is influenced by the pulse rate and the peak pulse velocity as well as the hematocrit of the blood. The system gain is also influenced by the peak pulse velocity and the hematocrit of the blood. This information may aid in further understanding of the fine details of an Impedance Cardiogram (ICG).

In a letter published in Cancer, Schonholz acknowledged the work by Stout Gergich et al that suggested that the early detection of lymphedema leads to successful treatment. Schonholz reported the 2 limitations of the work to be the lack of a control group and the lymphedema assessment method used. It is generally accepted that the lack of treatment for lymphedema leads to disease progression. Although, to the best of our knowledge, the scientific evidence to support this theory remains scarce, withholding treatment means that the development and implementation of a true randomized controlled trial with which to assess lymphedema strategies is unlikely. Nonetheless, randomized controlled trials comparing the effectiveness of various treatment strategies are plausible. The work of Stout Gergich et al provides the necessary preliminary information to support compression as a treatment strategy worthy of further investigation. As highlighted by the correspondence between Schonholz and Stout Gergich, lymphedema can be assessed using several self–report and objective methods, and there is controversy regarding which method(s) represent the ‘‘gold standard.’’ This is a major issue in lymphedema research because the manner by which lymphedema is measured significantly influences the results and conclusions derived from research relating to its incidence and potential risk factors as well as the effectiveness of prevention and/or treatment strategies. The work from our group has demonstrated this in several publications that have involved prospectively designed studies that make use of objective (including bioimpedance spectroscopy, circumference measurements, and perometry) as well as self–report measures. When deciding which method(s) are optimal, research and clinically relevant factors must be considered. Is it accurate, sensitive, and specific? Can it detect ‘‘subclinical’’ lymphedema (before patients report symptoms)? Is it affordable? Is it transportable? Is intertester error low? Is the measurement fast and noninvasive? Bioimpedance spectroscopy is a technology that demonstrates all these features and therefore will remain our primary measurement tool in the investigation of lymphedema after breast cancer.