Sharon Czerniec

Confirmation of the Reference Impedance Ratios Used for Assessment of Breast Cancer-Related Lymphedema by Bioelectrical Impedance Spectroscopy

BACKGROUND Breast cancer-related lymphedema in the arm is commonly detected by bioelectrical impedance spectroscopy as an increased inter-arm impedance ratio due to the presence of excess lymph in the at-risk arm relative to that of the unaffected arm. The presence of lymphedema is determined by a value of this ratio greater than the mean ratio, plus three standard deviations observed in a comparable healthy population. This threshold value has not been established using the measurement protocols in current practice. The aim of the present study was to determine the reference range of the inter-arm impedance ratio to allow a cut-off value to be established as a criterion for the detection of breast cancer-related lymphedema. METHODS The mean and variation (3 SD) of the inter-arm impedance ratio for the arms of 172 healthy female control participants were determined from an accumulated database of impedance data obtained using present generation impedance instrumentation and methodology. This reference range and threshold value was compared to the original threshold ratio determined a decade ago but still in current use. RESULTS The presence of lymphedema is indicated when the impedance ratio exceeded 1.106 when the nondominant limb is at risk, and 1.134 when the dominant limb is at risk compared with the currently used values of 1.066 and 1.139, respectively. Although the difference in these values was statistically significant, this difference was determined to be of minor importance to clinical practice. CONCLUSIONS The impedance ratio thresholds for early detection of lymphedema remain suitable for clinical use with present day bioimpedance spectroscopy analyzers and measurement protocols.

Operational equivalence of bioimpedance indices and perometry for the assessment of unilateral arm lymphedema

BACKGROUND The aim was to assess the agreement between bioimpedance indices and inter-limb volume differences, as assessed by perometry, for assessment of unilateral arm lymphedema. METHODS Impedance was measured in the arms of 45 women with lymphedema and a separate control group without lymphedema (n = 21). Arm volume was measured at the same time by perometry. The impedance indices, (ratio of impedances between limbs and the L-dex scores) were compared to the inter-limb volume differences using concordance correlation analysis. RESULTS Impedance indices were highly correlated (r = 0.926) with the difference in arm volume measured by perometry. CONCLUSIONS Bioelectrical impedance analysis, although not providing a quantitative volume measurement of lymphedema, provides a measurement index that is highly correlated with quantitative measurements of the volume increase in limb size seen in lymphedema. The speed and ease of the impedance technique renders it a suitable alternative to perometry for the assessment of lymphedema.

Reference ranges for assessment of unilateral lymphedema in legs by bioelectrical impedance spectroscopy

BACKGROUND Secondary unilateral lymphedema in the leg may occur as a consequence of pelvic surgery and/or radiation therapy, which causes damage to the pelvic lymphatic system. To date, assessment has been typically by manual measurement of the volume excess of the affected leg compared to the contralateral leg. In contrast, the assessment of unilateral arm lymphedema is readily accomplished by the use of bioelectrical impedance spectroscopy (BIS) as an increased inter-arm impedance ratio due to the presence of excess lymph in the affected arm relative to that of the unaffected arm. The presence of lymphedema is defined by a value of this ratio greater than the mean ratio plus three standard deviations (SD) observed in a comparable healthy population. The aim of the present study was to determine the equivalent reference range of the impedance ratio for the legs. This would allow a cut-off value to be established as a criterion for the detection and assessment of lower limb lymphedema. METHODS The impedances of the legs of 172 healthy females and 150 healthy males, measured by BIS, were extracted from an accumulated database of impedance data. These data were used to determine the normal distribution of inter-leg impedance ratios and the reference range and threshold value (mean + 3 SD). RESULTS The presence of lymphedema is indicated when the impedance ratio exceeds 1.167 in males and 1.136 in females. Unlike in the arms, the effect of limb dominance in the legs is minimal and it is suggested that no correction for limb dominance is warranted. CONCLUSIONS The impedance ratio thresholds for lymphedema of the legs have been established, opening the way for BIS to become established clinically for the early detection and assessment of lower limb lymphedema.

Assessment of bilateral limb lymphedema by bioelectrical impedance spectroscopy

Objective: The aim of the present study was to determine if the ratio of extracellular fluid (ECF), including the lymph, to that of intracellular fluid (ICF), as measured by bioimpedance spectroscopy (BIS), could be used to assess bilateral lymphedema (LE). Background: The presence of LE is commonly determined as an increase in tissue volume due to the presence of excess lymph relative to the volume of a comparable unaffected body region or to comparative normative data. However, in bilateral LE of the limbs, a comparable body region, the contralateral limb, is also affected, precluding normalization. An alternative is to normalize the increase in lymph volume, as ECF, to that of ICF volume. Methods: Extracellular/intracellular fluid ratios, expressed as the ratio of intracellular impedance (R i) to extracellular impedance (R 0), for the limbs of 277 female and 224 male controls were determined from an accumulated database of impedance data. Equivalent data were obtained for an opportunistic cross-sectional sample of 37 female and 5 male participants with bilateral LE of the legs. The ratios of R i/R 0 in the lymphedematous legs of the affected participants were compared with the equivalent ratios in the unaffected arms of the same participants and with those of the controls using box plots and visualized as bivariate data using tolerance ellipses. Results: Despite R i/R 0 ratios varying with age, sex, and limb dominance, comparison of the ratio for affected legs (normalized to the ratio in the unaffected arms) with equivalent ratios observed in a control population (as bivariate tolerance plots) was capable of discriminating between 70% and 89% of the participants with LE. Conclusions: Bioelectrical impedance spectroscopy and determination of Ri/R0 ratios as indices of ECF/ICF ratios holds promise for the semiquantitative assessment of bilateral LE.

Reliability and Concurrent Validity of the Perometer for Measuring Hand Volume in Women With and Without Lymphedema

BACKGROUND Lymphedema of hand after breast cancer treatment causes significant loss of hand function. Although there are several ways of assessing limb volume, measuring hand volume has been problematic due to technical difficulties associated with assessment of finger volumes. The aim of this study was to investigate the criterion validity and reliability of Perometer™ for measuring hand volume in woman with and without lymphedema. METHODS AND RESULTS Hand volume of forty women with (n = 20) and without lymphedema (n = 20) was assessed twice by one rater and once by another rater using the Perometer, and once by one rater using the water volumetry method. Intra- and inter-rater reliability was determined from the intraclass correlation coefficients and Percent Close Agreement. Agreement between the Perometer and water volumetry was determined using a limit of agreement and Lins concordance correlation. The Perometer had high intra [ICC(2,1) = 0.989 (95% CI: 0.98-0.99)] and inter-rater reliability [ICC(2,1) = 0.993 (95% CI: 0.99-1.0)]. Percent close agreement revealed that 80% of the measures were within 9 ml for inter-rater reliability and within 15 ml for intra-rater reliability. In addition, there was high concordance between hand volumes obtained with the Perometer and water volumetry method (R(c) = 0.88). However, the Perometer overestimated the volume of hand compared to water volumetry method (bias: 7.5%). CONCLUSIONS The Perometer can be used with high reliability to measure hand volume but caution should be exercised when data are compared with measures derived from the water volumetry method.

Assessment of Breast Cancer-Related Lymphedema: A Comparison of Moisture Meter and Spot Bioimpedance Measurement

BACKGROUND Tissue dielectric constant (TDC) and spot bioimpedance measurement (BIA) have a role in the assessment of tissue composition changes in breast cancer-related lymphedema (BCRL). Our aims were to determine whether TDC and spot BIA measures could detect inter-limb differences in BCRL, explore the relationship between methods, and establish the intra-rater reliability and technical error of measurement for TDC. METHODS AND RESULTS Women with (n=20) and without (n=4) unilateral BCRL participated. Circumference, TDC, and spot BIA measures were completed on the most affected region of the arm for BCRL participants and at a standardized forearm point in women without lymphedema. All measures were compared to measurements from an identical location on the contralateral arm. The affected arm differed significantly to the unaffected arm of women with BCRL for TDC and spot BIA measures. The median (IQR) differences were: extra-small probe 5.75 (3.10-8.21), small probe 3.50 (1.16-6.89), medium probe 5.08 (0.88-10.91), and for spot BIA measurement (-35.20 Ω; -59.75 to -14.85 Ω). The small and medium TDC probe measures were moderately correlated to spot bioimpedance measurements (r=-0.54 and r=-0.43, respectively). Intra-rater reliability coefficients (ICC2,1) of TDC measures ranged from 0.50 (95% CI: 0.12-0.75) to 0.92 (0.82-0.96). TDC technical error of measurement for women with lymphedema varied from 10.5% to 13.3%. CONCLUSIONS Both TDC and spot bioimpedance may have a role in clinical assessment of tissue compositional change in BCRL. Their relationship with tissue composition, assessed by imaging, is now required.

Assessment of segmental arm soft tissue composition in breast cancer-related lymphedema : A pilot study using dual energy X-ray absorptiometry and bioimpedance spectroscopy

BACKGROUND Changes in arm soft tissue composition, especially increased adipose tissue, has been found in advanced, non-pitting breast cancer-related lymphedema (BCRL). The aim of this study was to examine whether these changes were localized to any particular region of the arm and whether they occurred in lymphedema which still pitted to pressure. Secondary aims were to explore relationships between arm segment volumes, bioimpedance spectroscopy (BIS) measurements of extracellular fluid (ECF), and dual-energy X-ray absorptiometry (DXA) measurements of tissue composition. METHODS AND RESULTS Nine women with unilateral BCRL participated. The dominant arm was affected in 4 women, and all presented with lymphedema that pitted to pressure. Arm volume was calculated from circumferences by the truncated cone method, ECF was determined with BIS and fat and lean tissue content measured by DXA. BIS and DXA measurements for women with lymphedema were made of the whole arm and also of four 10 cm-segments measured from the ulnar styloid at the wrist. Whole arm DXA data were compared to those of 45 women of similar age and body mass index without lymphedema. All women with lymphedema had a significantly larger absolute fat mass in their affected arm compared to their unaffected arm, (median difference between arms 146.9 g). The forearm segment 10 - 20 cm proximal to the wrist had the highest median inter-limb fat difference of all four arm segments. CONCLUSIONS The soft tissue composition changes associated with BCRL may occur in the presence of pitting and predominantly affect the proximal forearm.

Breast Cancer-Related Arm Lymphedema: Fluctuation over Six Months and the Effect of the Weather

BACKGROUND An understanding of normal fluctuation of lymphedema over time is important to identify real change, whether it is from response to treatment or worsening of the condition. The weather is another factor that possibly influences lymphedema but has had minimal investigation to date. The purpose of this study was to determine the extent to which breast cancer-related lymphedema (BCRL) fluctuated over a 6-month period and the influence of temperature, humidity, and barometric pressure. METHOD AND RESULTS Women with unilateral BCRL (n = 26) and without BCRL (n = 17) were measured on nine occasions over 6 months using a standardized protocol. Measures included self-reported arm swelling, arm volume, and extracellular fluid with bioimpedance. Daily weather data were obtained for analysis of effects on lymphedema. Neither arm volume nor extracellular fluid varied significantly for women with lymphedema; coefficients of variation were 2.3% and 3.7%, respectively. Women without lymphedema had even less fluctuation, with coefficient of variation of 1.9% for arm volume and 2.9% for ECF. Correlation of weather and lymphedema data showed that temperature was the only aspect of the weather to have any effect on BCRL, with the maximum temperature on the day before measurement slightly affecting ECF (r = 0.27, p < 0.001), arm volume (r = 0.23, p < 0.001), and self-reported swelling (r = 0.26, p < 0.001). For women without lymphedema, the weather did not affect any measure. CONCLUSIONS Established BCRL is relatively stable over a 6-month period. Temperature was the only aspect of the weather found to impact lymphedema.

Estimation of Arm Adipose Tissue Quotient Using Segmental Bioimpedance Spectroscopy

BACKGROUND Breast cancer-related lymphedema (BCRL) is a chronic condition characterized by accumulation of lymph fluid that may subsequently become fibrotic with infiltration of adipose tissue. Bioimpedance spectroscopy (BIS) is the preferred method for early detection of lymphedema as it can estimate extracellular lymph fluid. This study developed a modified impedance technique that concurrently estimates both lymph accumulation and increases in adipose tissue. METHODS AND RESULTS BIS was used to estimate the adipose tissue volume in a cohort of healthy women (n = 171), which was found to be highly correlated (r > 0.87) with measurements of adipose tissue obtained using the reference method of dual-energy X-ray absorptiometry (DXA). In a separate cohort of women with BCRL (n = 16), adipose volumes measured by BIS and reference method, respectively, were 2452.9 ± 933.3 mL and 2109.1 ± 824 6 mL for affected arms; 1770.9 ± 747.8 mL and 1801.4 ± 775.7 mL for unaffected arms; and comparable values for a group of age-matched controls were 1862.5 ± 661.6 mL and 1657.0 ± 641.1 mL for age-matched control arms. The increase in adipose tissue in affected arms was significant irrespective of the method of measurement, p < 0.02 and p < 0.001 for BIS and DXA, respectively. CONCLUSIONS An impedance method is described that can estimate increase both in lymph accumulation and adipose tissue in breast cancer-related lymphedema.

Estimation of limb adiposity by bioimpedance spectroscopy in lymphoedema

Lymphoedema is a chronic debilitating condition that may occur in approximately 25% of women treated for breast cancer. As the condition progresses, accumulated lymph fluid becomes fibrotic with infiltration of adipose tissue. Bioelectrical impedance spectroscopy is the preferred method for early detection of lymphoedema based on the measurement of impedance of extracellular fluid. The present study assessed whether these impedance measurements could also be used to estimate the adipose tissue content of the arm based on a model previously used to predict whole body composition. Estimates of arm adipose tissue in a cohort of women with lymphoedema were found to be highly correlated (r > 0.82) with measurements of adipose tissue obtained using the reference method of dual energy X-ray absorptiometry. Paired t-tests confirmed that there was no significant difference between the adipose tissue volumes obtained by the two methods. These results support the view that the method shows promise for the estimation of arm adiposity in lymphoedema.