Elizabeth Dylke

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.

Effects of Mastectomy on Shoulder and Spinal Kinematics During Bilateral Upper-Limb Movement

Background Shoulder movement impairment is a commonly reported consequence of surgery for breast cancer. Objective The aim of this study was to determine whether shoulder girdle kinematics, including those of the scapula, spine, and upper limb, in women who have undergone a unilateral mastectomy for breast cancer are different from those demonstrated by an age-matched control group. Design An observational study using 3-dimensional kinematic analysis was performed. Methods Women who had a unilateral mastectomy on their dominant-arm side (n=29, mean [±SD] age=62.4±8.9 years) or nondominant-arm side (n=24, mean [±SD] age=59.8±9.9 years), as well as a control group of age-matched women without upper-limb, shoulder, or spinal problems (n=22, mean [±SD] age=58.1±11.5 years), were measured while performing bilateral arm movements in the sagittal, scapular, and coronal planes. All of the women were free of shoulder pain at the time of testing. Data were collected from the glenohumeral joint, the scapulothoracic articulation, and the spine (upper and lower thoracic and lumbar regions) using an electromagnetic tracking system. Results Women following mastectomy displayed altered patterns of scapular rotation compared with controls in all planes of movement. In particular, the scapula on the mastectomy side rotated upward to a markedly greater extent than that on the nonmastectomy side, and women following mastectomy displayed greater scapular excursion than controls. Conclusions The findings suggest that altered motor patterns of the scapula are associated with mastectomy on the same side. Whether these changes are harmful or not is unclear. Investigation of interventions designed to restore normal scapulohumeral relationships on the affected side following unilateral mastectomy for breast cancer is warranted.

Normative volume difference between the dominant and nondominant upper limbs in healthy older women

BACKGROUND Upper limb lymphedema is a possible consequence of the treatment for breast cancer. Accurate detection of swelling is important in implementing appropriate treatment. Currently used diagnostic cut-offs for excess volume have been chosen for ease of use and are not based on normative differences. The aim of this study, therefore, was to determine the normal inter-limb variance for healthy older women and identify statistically-based diagnostic cut-offs for both circumference and volume. METHODS AND RESULTS Two hundred and four healthy women, over the age of 40 years, with no history of treatment for breast cancer or lymphedema, underwent measurement of their upper limbs with a perometer. Using the associated software, the circumference of the limb was determined at a number of set points along the limb and the volume of the intervening segments recorded. Segment volumes were also calculated from the circumferential measurements using the formulae for a truncated cone and cylinder. The mean inter-limb difference found was small but a large range was seen for all of the circumference and volume measurements. Dominance was found to have a significant effect on the limb size. Regression analysis showed that an individuals age was negatively related to their inter-limb difference. Diagnostic cut-offs, set at three standard deviations above the mean, were determined. CONCLUSIONS New circumference and volume criteria based on normative data, taking arm dominance into consideration, will allow for more accurate diagnosis of changes in limb volume, allowing treatment to be started and monitored appropriately.

Tissue Composition Changes and Secondary Lymphedema

BACKGROUND The aim of this study was to determine the impact of dominance and severity on tissue composition changes with lymphedema using dual-energy X-ray absorptiometry (DXA), and to determine the relationships between the DXA-determined tissue volumes and the clinical outcomes determined by perometry and bioimpedance spectroscopy. METHODS AND RESULTS Fifty-six women with secondary lymphedema and 44 women without a history of breast cancer or lymphedema underwent measurement of their upper limbs with DXA, perometry, and bioimpedance spectroscopy. Whether the affected side was the dominant or nondominant arm influenced inter-limb tissue volumes differences (F=16.31 to 35.14; all p<0.001) and interacted with the severity of lymphedema (F=3.22 to 11.07; all p<0.05). In the control group, the dominant limb had more lean tissue but less fat than the nondominant limb. In the lymphedema group, increases in fat in the affected arm were not related to generalized increases in whole body adiposity when the dominant arm was affected. Perometry-measured volumes and BIS ratios were moderately to highly correlated with inter-limb fat, volume, and total tissue differences found by DXA (r=0.39 to 0.86). CONCLUSIONS The direction and magnitude of limb composition changes in those with lymphedema are impacted by whether the affected side is the dominant or nondominant limb, as well as the severity of the condition. The stage of tissue composition change may impact on the diagnosis and monitoring as well as treatment of secondary 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.

Diagnosis of upper limb lymphedema: development of an evidence-based approach

Abstract Background: The diagnosis of secondary upper limb lymphedema (LE) is complicated by the lack of an agreed-upon measurement tool and diagnostic threshold. The aim of this study was to determine which of the many commonly used and normatively determined clinical diagnostic thresholds has the best diagnostic accuracy of secondary upper limb LE, when compared to diagnosis by an appropriate reference standard, lymphoscintigraphy. Material and methods: The arms of women treated for breast cancer with and without a previous diagnosis of LE, as well as healthy controls, were assessed using lymphoscintigraphy, bioimpedance spectroscopy (BIS) and perometry. Dermal backflow score determined from lymphoscintigraphy imaging assessment (reference standard) was compared with diagnosis by both commonly used and normatively determined diagnostic thresholds for volume and circumference measurements as well as BIS. Results: For those with established dermal backflow, all commonly used and normatively determined diagnostic thresholds accurately identified presence of LE compared with lymphoscintigraphy diagnosis. In participants with mild to moderate changes in dermal backflow, only a normatively determined diagnostic threshold, set at two standard deviations above the norm, for arm circumference and full arm BIS were found to have both high sensitivity (81% and 76%, respectively) and specificity (96% and 93%, respectively). For this group, strong, and clinically useful, positive (23 and 10, respectively) and negative likelihood (0.2 and 0.3) ratios were found for both the circumference and bioimpedance diagnostic thresholds. Conclusion: For the first time, evidence-based clinical diagnostic thresholds have been established for secondary LE. With mild LE, normatively determined circumference and BIS thresholds are superior to the commonly used thresholds.

Measurement of hand volume by bioelectrical impedance spectroscopy.

BACKGROUND Assessment of lymphedema is frequently based upon measuring the increase in volume of the affected region compared to that of a comparable unaffected region. This requires methods that can measure the volume of body regions that are not only accurate and sensitive but also suitable for use in clinical practice. To date, bioimpedance spectroscopy has been used to measure volume increase due to lymphedema in whole arms but excluding the hand. We report here an impedance-based method for the measurement of hand volume. METHODS Impedance measurement electrodes were located on the dorsum of the hand, with the sense electrodes at the level of ulnar styloid and metacarpal-phalangeal joint of the third finger and current drive electrodes on the forearm and at the nail bed of the third finger. The impedances of the hands of 50 participants were measured and hand volumes computed. These were compared with the hand volumes measured by perometry. The region of the hand defined by the impedance measurements was determined, both in vivo and using a hand phantom. RESULTS The region of the hand measured by the impedance technique was limited to the palmar volume (i.e., excluding the thumb). Palmar volumes computed from impedance measurements were significantly correlated (r=0.88) with those measured by perometry but were, on average, 8% larger. The impedance technique was sufficiently sensitive to detect the change in hand volume elicited by decrease in vascular volume due to blood draining from the hand on elevation. CONCLUSIONS An impedance technique was developed that has the potential to measure the change in hand volume when affected by lymphedema. Bioimpedance spectroscopy has the advantage over currently used perometric or water displacement techniques in that it can measure specifically the change in extracellular fluid, including lymph, rather than simply total hand volume.

Inter-rater reliability of arm circumference measurement.

BACKGROUND Arm lymphedema is routinely assessed by clinicians and researchers, using arm circumference measurements. A protocol was developed for measuring arm circumference independent of medically trained professionals. The aim of this project was to assess the protocols inter-rater reliability and its coherence with perometry measures. METHODS AND RESULTS Community-dwelling adults (n = 57), aged 60.2  ± 12.8 years, in good general health, were included in this study. Circumference of both arms were measured at the ulnar styloid of the wrist and at four 10 cm intervals up the arm by a friend of the participant, as well as the trained assessor using a tape measure. The same measures were also obtained with a perometer. The assessment tools had moderate to high concordance (r(c) = 0.84-0.94 for assessor vs. perometer and r(c) = 0.68-0.93 for assessor vs. participant). Limits of agreement analysis revealed that the mean difference between methods varied based on the measurement location; the bias ranged from -5.5% to 1.5% for assessor-measured vs. perometer methods and from -2.4% to 4.0% for assessor-measured vs. participant-measured methods. CONCLUSIONS The written instructions and cartoons are reliable tools that could be used by women at risk of lymphedema as well as those with lymphedema following treatment for breast cancer to measure their arm circumference reliably independent of medically trained personnel.

Use of impedance ratios to assess hand swelling in lymphoedema

Objectives To determine whether bioimpedance spectroscopy was suitable for detection of hand lymphoedema. Methods The hands of 50 participants without a history of lymphoedema were measured with perometry and bioimpedance spectroscopy after positioning two ways for three minutes: (a) both hands rested at heart height and (b) the dominant hand at heart height and the non-dominant hand at head height. In addition, 10 women with secondary hand lymphoedema were also measured. Results Impedance and volume measurements were found to be strongly related (dominant hand r = −0.794). Both measurements were reliable (ICC2,1 = 0.900–0.967 and 0.988–0.996, respectively). Impedance was more sensitive to small changes in hand volume due to the postural change (position × device interaction: F = 23.9, P < 0.001). Finally, impedance measurements had better discrimination of women with lymphoedema than volume measurements. Conclusions Bioimpedance spectroscopy is a promising tool for the detection of secondary hand lymphoedema.