Bruce Cornish

Lymphedema After Breast Cancer: Incidence, Risk Factors, and Effect on Upper Body Function

PURPOSE Secondary lymphedema is associated with adverse physical and psychosocial consequences among women with breast cancer (BC). This article describes the prevalence and incidence of lymphedema between 6 and 18 months after BC treatment; personal, treatment, and behavioral correlates of lymphedema status; and the presence of other upper-body symptoms (UBS) and function (UBF). PATIENTS AND METHODS A population-based sample of Australian women (n = 287) with recently diagnosed, invasive BC were evaluated on five occasions using bioimpedance spectroscopy. Lymphedema was diagnosed when the ratio of impedance values, comparing treated and untreated sides, was three standard deviations more than normative data. UBF was assessed using the validated Disability of the Arm, Shoulder, and Hand questionnaire. RESULTS From 6 to 18 months after surgery, 33% (n = 62) of the sample were classified as having lymphedema; of these, 40% had long-term lymphedema. Although older age, more extensive surgery or axillary node dissection, and experiencing one or more treatment-related complication(s) or symptom(s) at baseline were associated with increased odds, lower socioeconomic status, having a partner, greater child care responsibilities, being treated on the dominant side, participation in regular activity, and having good UBF were associated with decreased odds of lymphedema. Not surprisingly, lymphedema leads to reduced UBF; however, BC survivors report high prevalences of other UBS (34% to 62%), irrespective of their lymphedema status. CONCLUSION Lymphedema is a public health issue deserving greater attention. More systematic surveillance for earlier detection and the potential benefits of physical activity to prevent lymphedema and mitigate symptoms warrant further clinical integration and research.

Improved prediction of extracellular and total body water using impedance loci generated by multiple frequency bioelectrical impedance analysis

Bioelectrical impedance analysis (BIA) using a frequency of 50 kHz is an established method of predicting total body water (TBW). However, very little research has been performed to determine whether 50 kHz is the optimum frequency for the prediction of TBW from impedance measurements. This paper analyses a mathematical expression describing the equivalent electrical circuit for biological tissue, and derives a graphical representation of the resistive and reactive components. The nature of the resulting impedance locus was used in the analysis of measured whole-body impedance of 42 rats over a range of frequencies to determine the impedance at the characteristic frequency, Zc, and also the impedance at zero frequency, R0. The standard error associated with the prediction of TBW (determined by isotope dilution) using Zc was 5.9% compared with a standard error of prediction of 10.1% using the established BIA method at 50 kHz on the same data. Predictions of extracellular water (ECW) using the impedance at zero frequency, R0, yielded a standard error of 3.2% compared with standard errors of 4.8% and 4.2% using single frequency BIA measurements at 5 kHz and 1 kHz, respectively. These results demonstrate a significant (P < 0.01) improvement in the prediction of TBW and ECW using multiple frequency bioelectrical impedance analysis (MFBIA).

Comparison of methods to diagnose lymphoedema among breast cancer survivors: 6-month follow-up

SummaryOne of the more problematic and dreaded complications of breast cancer is lymphoedema. Our objective was to determine the prevalence of lymphoedema 6-months following breast cancer treatment and to examine potential risk factors among a population-based sample of women residing in South-East Queensland (n=176). Women were defined as having lymphoedema if the difference between the sum of arm circumferences (SOAC) of the treated and untreated sides was >5 cm (prevalence=11.9%) or >10% (prevalence=0.6%), their multi- frequency bioelectrical impedance (MFBIA) score was ≥3 standard deviations above the reference impedance score (prevalence=11.4%), or they reported ‘yes’ when asked if arm swelling had been present in the previous 6 months (prevalence=27.8%). Of those with lymphoedema defined by MFBIA, only 35% were detected using the SOAC method (difference > 5 cm), while 65% were identified via the self-report method (i.e., respective sensitivities). Specificities for SOAC (difference > 5 cm) and self-report were 88.5% and 76.9%, respectively. When examining associations between presence of lymphoedema and a range of characteristics, findings also varied depending on the method used to assess lymphoedema. Nevertheless, one of the more novel and significant findings was that being treated on the non-dominant, compared to dominant, side was associated with an 80% increased risk of having lymphoedema (MFBIA). Our work raises questions about the use of circumferences as the choice of measurement for lymphoedema in both research and clinical settings, and assesses MFBIA as a potential alternative.

Bioelectrical impedance for monitoring the efficacy of lymphoedema treatment programmes

The treatment of lymphoedema includes a combination of massage, compression bandaging, and exercise. To date the most common technique of assessing the efficacy of treatment has involved estimating the total limb volume from circumferential measurements at fixed intervals along the limb. This study investigated the application of multiple frequency bioelectrical impedance analysis, MFBIA, to monitor the volume of lymphoedema in the upper limb of patients who developed this disorder following surgery for cancer of the breast. Daily measurements of both circumference and impedance of both the affected and unaffected limbs were recorded for 20 patients throughout their 4 week treatment programmes. Twenty control subjects were also monitored daily over a similar 4 week period. Prior to the commencement of treatment the bioimpedance technique detected a significant (P < 0.01) asymmetry between the two limbs of the control subjects, associated with handedness (P < 0.001). Circumferential estimates of limb volumes in the control group detected no asymmetry. Impedance measures of extracellular fluid showed all of the patients to lie outside the 95% confidence interval determined from the data of the control group. The trends of the impedance measures and the circumferential estimates of volume throughout the 4 week program were found to be significantly different (P < 0.05); MFBIA exhibiting a greater sensitivity in the detection of lymphoedema. The results demonstrate that MFBIA is significantly more sensitive than circumferential measurement both in the early diagnosis of lymphoedema and in monitoring change.

Optimizing electrode sites for segmental bioimpedance measurements

Recent advances in the application of bioelectrical impedance analysis (BIA) have indicated that a more accurate approach to the estimation of total body water is to consider the impedance of the various body segments rather than simply that of the whole body. The segmental approach necessitates defining and locating the physical demarcation between both the trunk and leg and the trunk and arm. Despite the use of anatomical markers, these points of demarcation are difficult to locate with precision between subjects. There are also technical problems associated with the regional dispersion of the current distribution from one segment (cylinder) to another of different cross-sectional area. The concept of equipotentials in line with the proximal aspects of the upper (and lower) limbs along the contralateral limbs was investigated and, in particular, the utility of this concept in the measurement of segmental bioimpedance. The variation of measured segmental impedance using electrode sites along these equipotentials was less than 2.0% for all of the commonly used impedance parameters. This variation is approximately equal to that expected from biological variation over the measurement time. It is recommended that the electrode sites, for the measurement of segmental bioelectrical impedance in humans, described herein are adopted in accordance with the proposals of the NIH Technology Assessment Conference Statement.

Bioimpedance spectrometry in the determination of body water compartments: Accuracy and clinical significance

Bioelectrical impedance analysis (BIA) offers the potential for a simple, portable and relatively inexpensive technique for the in vivo measurement of total body water (TBW). The potential of BIA as a technique of body composition analysis is even greater when one considers that body water can be used as a surrogate measure of lean body mass. However, BIA has not found universal acceptance even with the introduction of multi-frequency BIA (MFBIA) which, potentially, may improve the predictive accuracy of the measurement. There are a number of reasons for this lack of acceptance, although perhaps the major reason is that no single algorithm has been developed which can be applied to all subject groups. This may be due, in part, to the commonly used wrist-to-ankle protocol which is not indicated by the basic theory of bioimpedance, where the body is considered as five interconnecting cylinders. Several workers have suggested the use of segmental BIA measurements to provide a protocol more in keeping with basic theory. However, there are other difficulties associated with the application of BIA, such as effects of hydration and ion status, posture and fluid distribution. A further putative advantage of MFBIA is the independent assessment not only of TBW but also of the extracellular fluid volume (ECW), hence heralding the possibility of being able to assess the fluid distribution between these compartments. Results of studies in this area have been, to date, mixed. Whereas strong relationships of impedance values at low frequencies with ECW, and at high frequencies with TBW, have been reported, changes in impedance are not always well correlated with changes in the size of the fluid compartments (assessed by alternative and more direct means) in pathological conditions. Furthermore, the theoretical advantages of Cole-Cole modelling over selected frequency prediction have not always been apparent. This review will consider the principles, methodology and applications of BIA. The principles and methodology will be considered in relation to the basic theory of BIA and difficulties experienced in its application. The relative merits of single and multiple frequency BIA will be addressed, with particular attention to the latters role in the assessment of compartmental fluid volumes.

A New Technique for the Quantification of Peripheral Edema with Application in Both Unilateral and Bilateral Cases

Current noninvasive techniques for the routine and frequent quantification of peripheral lymphedema in patients are total limb volume measurement (by water immersion or by circumferential measurements) and bioelectrical impedance analysis (BIA). However both of these techniques require standardizing the measurement using a contralateral measurement from the unaffected limb. Hence these techniques are essentially restricted to unilateral lymphedema. This paper describes the results from a preliminary study to investigate an alter native approach to the analysis of the data from multiple frequency BIA to produce an index of lymphedema without the need for normalization to another body segment. Twenty patients receiving surgical treatment for breast cancer were monitored prior to surgery and again after diagnosis with unilateral lymphedema. The data recorded were total limb volume, by circumferential measurements; and BIA measurements of both limbs. From these measure ments total limb volumes and extracellular fluid volumes were calculated and expressed as ratios of the affected limb to that of the unaffected limb. An index of the ratio of the extra cellular fluid volume to the intracellular fluid volume was determined. This ECW/ICW index was calculated for both the affected and unaffected limbs at both measurement times. Results confirmed that the established techniques of total limb volume and extracellular fluid volume normalized to the unaffected contralateral limb were accurate in the detection of lymphedema (p < 10-6). Comparison of the ECW/ICW index from the affected limb after diagnosis with that from the pre-surgery measurement revealed a significant (p < 10-6) and considerable (75%) increase. The results of this pilot study suggest that by using multiple frequency bioelectrical impedance analysis, an index of the ECW/ICW ratio can be obtained and this index appears to have an equal, or better, sensitivity than the other techniques in detecting lymphedema. More importantly, this index does not require normalization to another body segment and can be used to detect all types of peripheral edema including both unilateral and bilateral lymphedema.

Reliability of multiple frequency bioelectrical impedance analysis: An intermachine comparison

The technical reliability (i.e., interinstrument and interoperator reliability) of three SEAC‐swept frequency bioimpedance monitors was assessed for both errors of measurement and associated analyses. In addition, intraoperator and intrainstrument variability was evaluated for repeat measures over a 4‐hour period. The measured impedance values from a range of resistance‐capacitance circuits were accurate to within 3% of theoretical values over a range of 50–800 ohms. Similarly, phase was measured over the range 1°–19° with a maximum deviation of 1.3° from the theoretical value. The extrapolated impedance at zero frequency was equally well determined (±3%). However, the accuracy of the extrapolated value at infinite frequency was decreased, particularly at impedances below 50 ohms (approaching the lower limit of the measurement range of the instrument). The interinstrument/operator variation for whole body measurements were recorded on human volunteers with biases of less than ±1% for measured impedance values and less than 3% for phase. The variation in the extrapolated values of impedance at zero and infinite frequencies included variations due to operator choice of the analysis parameters but was still less than ±0.5%. Am. J. Hum. Biol. 9:63–72

Determination of Cole parameters in multiple frequency bioelectrical impedance analysis using only the measurement of impedances

Conventional bioimpedance spectrometers measure resistance and reactance over a range of frequencies and, by application of a mathematical model for an equivalent circuit (the Cole model), estimate resistance at zero and infinite frequencies. Fitting of the experimental data to the model is accomplished by iterative, nonlinear curve fitting. An alternative fitting method is described that uses only the magnitude of the measured impedances at four selected frequencies. The two methods showed excellent agreement when compared using data obtained both from measurements of equivalent circuits and of humans. These results suggest that operational equivalence to a technically complex, frequency-scanning, phase-sensitive BIS analyser could be achieved from a simple four-frequency, impedance-only analyser.

Effect of temperature and sweating on bioimpedance measurements

The effect of skin temperature and hydration status has been suggested by some researchers as a common cause of variation in bioimpedance measurements of the body. This paper details a simple method of measuring the transverse impedance of the skin. The measured resistance and reactance was found to decrease by 35% and 18% for an increase of 20 degrees C. Similarly a decrease in resistance and reactance of 20% and 25% respectively was detected after hydration of the skin. However, the changes in skin temperature and hydration were found to have no significant effect on the whole body bioimpedance measurements using the standard tetra-polar electrode technique.