Evidence Supporting BIS Over Conventional Methods
ImpediMed offer the following evidence based support to why a standardized, objective, cleared metric, is superior to conventional methods in aiding the assessing lymphedema.
Shortcomings associated with conventional methods
Conventional methods of detecting lymphedema include total limb volume assessment by visualization, water displacement, circumferential girth and self assessment. Their use should be seriously reconsidered because
i) they are non-standardized, subjective techniques, with significant operator error and wide variations in reported results - Hutson 2003 [1] and
ii) they fail to detect lymphedema when it is most easily treated and when treatment has the biggest impact in helping patients Lawenda 2009 [2], Bernas 2010 [3]
“Without intervention, lymphedema can lead to progressive swelling, fibrosis of the soft tissues, neurologic changes (eg, pain and/or paresthesias), and infection. Early identification of the signs and symptoms of lymphedema should be integral to the management of all patients who have received surgery and/or radiation, and are thus at high risk.When treated in the earliest stages, complications of this condition may be minimized”. Lawenda 2009 [2]
“It has become evident over the past decade that early detection and intervention hold the greatest promise of reducing the incidence of lymphedema”. Bernas 2010 [3]
The most widely used conventional method is circumferential girth using a tape measure .
“Volume based upon circumferential measurements performed with tape measure at pre-defined intervals, typically 4, 5 or 10cm along the limb; volume being calculated assuming a circular Casley-Smith 1994[4] or elliptical truncated cone geometry.” Mayrovitz, 2003[ 5]
“Furthermore, there is no standardization of the number of circumferential measurements (slices) that are required to provide a reasonably accurate measurement of volume. As a consequence, the method can lack accuracy and precision.” (Weissleder & Brauer, 2008). [6]
“Water displacement is equally inexpensive and can be less time-consuming but is messy for the patient, may be associated with infection control problems and is clearly not appropriate where the limb being measured has open wounds or skin conditions.” (Fu et al, 2009)[7]
“It would seem, despite the three and a half decades of lymphedema research that have passed …. that we are still no further forward. We continue to use outmoded measurement methods and detection criteria of uncertain provenance.” Ward L, 2009[8]
Conventional methods greatest short coming is that they measure the total limb volume and do not measure the specific extra-cellular compartment most relevant to lymphedema.
“Lymphedema is, at least in its early stages, an accumulation of lymph, an extracellular fluid. The total volume of an arm may change for other reasons. Obesity and work- or exercise-induced hypertrophy are cases in point, where a simple total volume measurement is not immediately related to the parameter of interest, i.e. lymph volume.” [8]
For this reason, lymphedema can be easily misdiagnosed with conventional methods – hence “it is frequently under diagnosed and under treated”. Warren et al: 2007[9]
The counter position to the recent expert review article in the Journal of Lymphoedema (JOL) titled, “Is BIS ready for prime time, as the gold standard measure?” (Ward 2009) [8] has really questioned the experts in the lymphedema field and their use of conventional methods.
“We had a paper in JOL about BIS (Ward, 2009) — but we had problems finding views of dissent” Piller 2010 [10].
In spite of the difficulties in finding a counter position from recognised leaders in the field, the Journal of Lymphoedema, recently published the rebuttal [10]. The global rebuttal from the experts challenging if BIS is the new gold standard, was basically a professional acceptance that BIS is the new standard.
“Rockson 2007[11] produced a summary of bioimpedance in the diagnosis and management of lymphedemas and summarised the literature indicating that bioimpedance (when performed correctly) may ‘antedate the appearance of clinically identifiable disease’ and be able to help in the identification of ‘at risk’ individual.” If we do not acknowledge and measure the variables Stanton et al (2001) know well, and if we only measure after the swelling is apparent, then we have some problems. In an earlier issue of JOL there was an interesting debate about this (Piller et al, 2009). It is clear that early detection and early recognition of lymphedema have significant benefits, such as reducing excess medical costs and the incidence of cellulitis, but the debate also revealed a paucity of evidence to indicate that early identification can really reduce the prevalence and severity of lymphedemas. Nevertheless, if there is one significant positive, maybe we should act on it. So, why don’t we?”[10]
Conventional methods are subject to wide variations
Conventional methods suffer from operator to operator variations, even when the definition of clinical lymphedema is consistent. Hutson quotes variation for repeat measurements of 2.1 +/-35%; and 1.4 +/- 31%; for circumference and volume measurements (calculated geometrically), respectively.[9] In contrast Hutson found variation for repeat bioimpedance measurements of 0.60 +/- 15.4%; Hutson also noted a low inter-operator variability in the use of bioimpedance instrumentation and a greater speed of use in a clinical setting. Hutson in conclusion, found that bioelectric impedance measurements were faster, better accepted by nursing personnel, and more consistent than either serial tape measurements or water displacement methods .[1]
Variation in measurement often leads to confusion and poor patient outcomes. There is a large body of scientific literature that is based off conventional methods and the data is inconsistent, confusing and often difficult to interpret. To highlight this issue resulting from the use of conventional methods, there are wide variations in the incidence of lymphedema.
“Although the incidence is generally accepted at approximately 30%, reported rates vary greatly, ranging between 2% and 83%....Differences in lymphedema measurement technique, definitions of what constitutes lymphedema, and timing of lymphedema assessments contribute to inconsistencies in the scientific literature and confusion surrounding clinical practice”.
“Most findings on incidence and risk factors have been derived from studies that use indirect measures of lymphedema, in particular, circumferences and water displacement”. Hayes et al 2008[12]
The European Journal of Clinical & Medical Oncology recently reported on this wide variation in results with conventional methods,
“The incidence of lymphedema is reported to range from 6% to 70% after axillary surgery for breast cancer; however, its true incidence has been difficult to quantify because of the lack of standard diagnostic and universal assessment criteria”. [13]
“The prevalence of chronic lymphoedema is difficult to assess due to the varying definitions, populations and methods of measurement. The reported prevalence varies from 0% to 16.8% with sentinel lymph node biopsy & from 7.1% to 56% with axillary lymph node dissection.” Dawes et al 2008 [14].
In a prospective study of breast cancer patients, the incidence rates of lymphedema have been shown to vary for the same patients according to four assessment tools administered over time. Armer et al 2009 [15] This last reference is a large prospective cohort study of breast cancer survivors followed over 30 months with validated objective measures for lymphedema as a control.
“Trends in LE occurrence are reported for data from 211 participants. At 30 months post-treatment, LE incidence ranged from 41-91%, with 2cm being the highest estimation method and self-reported signs and symptoms (SS) the lowest”[15]
Conventional methods fail to detect lymphedema when it is most easily treated
Cornish et al 1996 [16], demonstrated that volume techniques used in monitoring treatment can show that patients have returned to normal when a low lymphoedema using BIS (ECF) still exists.
“The applicability of repetitive quantitation of MFBIA (BIS) to assess the impact of therapy in lymphoedema patients has also been investigated. In this study, daily measurements of circumference and impedance of both the affected and unaffected limbs were recorded for a cohort of 20 lymphoedema patients throughout a four-week treatment programme. As expected, both volumes and impedance ratios (L-Dex values) declined during active treatment. Perhaps more notably, although volume ratios completely normalised by day 28 of treatment, the measured impedance ratio (L-Dex) remained detectably elevated. This observation can be interpreted to reflect a potentially greater sensitivity for impedance when compared with direct volumetric techniques”[11,16]
“Long-term population-based studies with standardized subjective and objective measures along with a consensus regarding classification and severity are needed in order to provide more accurate information on the incidence and outcomes following risk-reduction practices and treatment.”Bernas et al 2010 [3]
BIS delivers all these requirements today, in an Regulatory cleared device that through its portability and ease of use opens up clinical access to all key stakeholders in lymphedema prevention (surgeon & oncologists)
“The advantages of BIS are that it is simple to perform and it is rapid, reliable, and precise.” [3]
Today, depending on (a) who is conducting the method of measurement, (b) the technique being used, or (c) the assessment criteria employed, then conventional methods can deliver a different clinical assessment for the same patient. This can have a major impact for the patient for both the targeting and monitoring of treatment and for how long the treatment is needed. For this reason alone, a medical device that delivers (a) a direct measurement of extracellular fluid, (b) standardized, (c) objective, and (d) FDA cleared in its universal assessment criteria, is best positioned to deliver a superior result than the present conventional measures.
Bioimpedance Spectroscopy (BIS) - the clinical validation in lymphedema
“BIS measures the impedance of only the tissue compartment that changes in lymphedema, not all the tissues of the limb.”[8]
This review also notes that a normal arm has around 25% extracellular fluid, and that "total volume is attempting to quantify the small increment in extracellular water as lymph. BIS does this directly"[8]
Bioimpedance Spectroscopy (BIS) (also referred to as multiple frequency bioimpedance analysis or MFBIA in the early literature) provides an accurate measurement of extracellular fluid (ECF). BIS is not to be confused with BIA (bioelectrical impedance analysis) which generally uses a single frequency and prediction equations to estimate body composition. BIS provides a direct measure of fluid assessment. BIS passes a spectrum of frequencies through the body which are used to determine R0, the theoretical resistance at zero frequency or Direct Current, at which the current would travel only through extracellular fluid (ECF). Impedance is measured in Ohms and is inversely proportional to fluid volume: as fluid volume increases, impedance or resistance to the flow of the electrical current decreases. [17] [18] [19] [20] [21] Based on the fact it is more of a direct measure of lymphedema, BIS demonstrates better sensitivity and specificity.[22, 23]
“In 1992, Ward and colleagues published the results of a cross-sectional study of a cohort of women with post-mastectomy unilateral lymphedema and a comparable group of control subjects in which both impedance and limb volume, calculated from circumferences, were measured. Ward et al 1992[23] Whereas their data showed that the mean impedances of the two groups were significantly different, the overlap in individual impedance values did not discriminate totally between lymphedematous and control. In a subsequent study (1996), they were able to demonstrate, however, that the ratio of impedances between limbs clearly discriminated the affected individuals from the controls while the ratio of volume measurements overlapped.’[8, 16, 25]
Cornish et al 2001 [26] conducted a 3 year prospective trial that followed the progress of breast cancer survivors from a pre-surgical baseline. Patients were assessed at regular two (2) month intervals for two (2) years post surgery using BIS. The device reporting limb impedance ratios (now called L-Dex) between the affected and unaffected limbs. Each measurement was compared with the corresponding pre-surgery ratio and an increase of greater than three (3) standard deviations was validated to be predictive of the onset of lymphedema. This BIS ratio (which we now call L-Dex®) was compared to the current clinical practice of self reporting by symptomatic assessment and volumetric analysis using the tape measure. BIS was shown to assess lymphedema up to 10 months earlier than current clinical practice, with an average of 4 months earlier over the cohort. The trial assessed the diagnostic performance of each approach, by comparing the results to the clinical end point of physician diagnosed lymphedema.
“The sensitivity of the BIS ratio and tape measure for early detection were shown to be 100% and 5% respectively… Estimates of the sensitivity and specificity (for BIS) were both approximately 100%.” [26]
Hayes et. al. in 2005, showed,
“The sensitivities of the difference in sum of arm circumferences of greater than 5 cm or self-report as a criteria of lymphedema compared to BIA have been reported as 35% and 65%, respectively. The corresponding specificities were 88.5% and76.9% showed the specificity and sensitivity of the ratio approach to be 100%”. Hayes et al 2005[27]
In an editorial commentary preceding a Ward, et al BIS study in 2009, Drs. Hunt, Aksew and Cormier from M.D. Anderson Cancer Center offered the following statement:
“Ward et al. have responded to the need for more reliable measurement tools and standardized diagnostic criteria that will facilitate the early detection of lymphedema given the increasing number of breast cancer survivors.” Hunt et al 2009[28]
The 2008 study, by Hayes et. al., involved 287 women who were assessed using impedance ratios (BIS), self reporting through symptomatic assessment and SOAC (circumference measurement using a tape measure). Women were assessed at three (3) month intervals for a period of 18 months post surgery. Hayes et al made the following observations:
“Of those defined with lymphedema by BIS almost 40-60% went undetected and 40-12% were misclassified as having lymphedema based on the self report and SOAC respectively”. And
“Consequently, the BIS method has been shown to be a direct, accurate and reliable measure for lymphedema diagnosis, and is more sensitive to change than other objective measures. As such, BIS is our reference standard, against which we compared the other measures.” Hayes et al 2008[29]
Ward et al offered the following observations in their 2009 publication [30] regarding quantitative bioimpedance spectroscopy:
“The overwhelming advantage of BIS over total volume estimation techniques is that it measures a change in a variable, electrical resistance at zero frequency, that is directly and causally related being due solely to a change in extracellular volume. “ and,
“This implicitly implies a greater sensitivity of BIS compared to the alternative techniques, an observation borne out in practice. Additionally, impedance techniques are non-invasive, rapid to perform and have a high degree of reliability.” Ward et al 2009[30]
BIS comparison to a standardized volumetric measure - Perometry
To help standardize limb volume measurements, an optoelectronic device called a Perometer has been developed that uses arrays of infrared light and optoelectronic sensors to create a two-dimensional silhouette of the limb. Stanton et al 1997[31] In this way, it overcomes limitations inherent to the other operator dependant circumferential assessment method. Even though it is not FDA cleared, it does offer an objective metric for volume to offer consistent data to demonstrate the performance of BIS against objective volumetric measure.
In a recent publication, Jain et al, of the National Institutes of Health, evaluated BIS against perometry in a limited cohort of patients and concluded,
“We found that inter-rater reliability (r=0.987) and intra-rater reliability (r=0.993) were acceptably high for the BIS unit and concurrent validity was r=-0.904, when compared to perometry. These results confirm that BIS can produce valid and reliable data related to the assessment of upper limbs affected by lymphedema.” Jain et al 2010[32]
Another study conducted by Czerniec et al also demonstrated the early assessment capability of the L-Dex approach. This study found that patient self assessment is only moderately reliable and that Perometry comparisons were limited since the method could not measure the whole arm in many patients. BIS (L-Dex) detected fluid changes in lymphedema patients that went undetected by total arm volume metrics suggesting that;
“BIS may be particularly useful in the detection of early lymphedema, prior to arm volume changes." Czerniec et al 2009[33]
Kilbreath, et al, measured impedance ratios and arm volume by Perometry in patients with confirmed lymphedema and in a control group without lymphedema. Impedance indices were highly correlated with the arm limb volume differences assessed by the Perometer (r=0.926). This study concluded that;
“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.”
The paper concludes;
“Finally, the impedance technique would appear to be most suited for the early detection of or monitoring of the early stage of lymphedema when the changes are predominantly in extracellular fluid volume.”Kilbreath et al 2009 [34]
Czerniec et al., performed a cross sectional, observational, cohort study on 40 women: 29 with mild to severe lymphedema and 11 controls without lymphedema or breast cancer and compared BIS to perometry….They concluded,
“BIS can be used for localized measurement of lymphedema. BIS is more sensitive to localized LE due to its specificity in measuring extracellular fluid.”Czerniec et al. 2010[35]
Ridner et al. examined the relationship among self-reported arm symptoms, circumferential tape measurement, Perometry and bioelectrical impedance.
“The procedure implemented in this cross-sectional study resulted in bioelectrical impedance values that clearly distinguished between individuals with and without lymphedema and LIR (limb index ratio) means similar to those found in previous studies. These findings suggest that in addition to the ease of use and rapidity of measurement, bioelectrical impedance can be used outside laboratory settings to evaluate arm lymphedema.” Ridner et al 2007[36]
Cornish et al 2002, also has demonstrated the use of BIS against conventional methods for both unilateral and bilateral cases of lymphedema Cornish et al 2002[37]
Two NIH publications (Stout Gergich 2008 [38] and Jain 2010 [32]) cited bioimpedance as a viable alternative in the assessment of patients.
After 15 years of peer-reviewed science, Bioimpedance Spectroscopy is no longer experimental: it is now in routine clinical practice.
1. A Medscape CME by Dr. Pat Whitworth, Assist Professor of Surgery at Vanderbilt University discusses the use of BIS in the prospective management of lymphedema. In the first 6 weeks of the launch of this video, over 2000 surgeons and over 400 hematology/oncologists have reviewed, with 750 CME/CE certificates awarded. The outstanding demand is a clear indication of the level of interest in approaches to prevent lymphedema - http://cme.medscape.com/viewarticle/723452
2. The Medscape CME feedback to the question, “Your patient underwent an axillary dissection and chemotherapy for a high-risk, node-positive breast cancer in her left breast. Now that her adjuvant treatment is complete, what would be the best way to detect subclinical expansion in the extracellular space of her left arm, to prevent and/or mitigate lymphedema at an early stage?” 70% of surgeons and 65% of oncologists chose BIS as the best way to detect early lymphedema. [Medscape data on file].
3. Dr. Whitacre, American Society of Breast Surgeons current President, discusses the confusion around lymphedema data and his use of BIS:
4. Over 100 L-Dex devices are now in the offices of US surgeons and oncologists today, with over 85 devices with other care givers in this field.
5. Premier clinical institutions that have been using BIS and have published on it through the years include M.D. Anderson, Mayo Clinic in Rochester, the National Institutes of Health (NIH) in Bethesda, Stanford University, UCSF, Vanderbilt University, USC in California, University of Pittsburgh Medical Center and others.
6. The L-Dex U400 is specifically mentioned as a lymphedema assessment tool in the latest edition of Keurer’s Breast Surgical Oncology textbook (Chapter 104 – Lymphedema) published by McGraw-Hill.
In January/February 2009 issue of CA: A Cancer Journal for Clinicians, [2], Dr. Brian Lawenda, a noted radiation oncologist, wrote,
“Bioimpedance spectroscopy determines volume by comparing the composition of fluid compartments within the body using resistance to electrical current. This type of impedance analysis has been found to be a reliable and accurate tool with which to measure volume of both upper and lower extremities in the evaluation of lymphedema.”
A comprehensive overview of the cumulative scientific validation of the L-Dex (impedance ratio) can be found in Ward’s 2010 [8] review publication. He takes the accepted standards of other established fields of evidence based medicine to base his argument on defining a gold standard for lymphedema.
“A convincing argument can be made that on theoretical grounds, analytical and technical accuracy and precision and practicality in use, impedance technology is the method of choice when compared to competing technologies. The case is well made for its adoption for the assessment of lymphedema post-breast cancer treatment” [8]
The rebuttal to the review paper was basically an acceptance of BIS as the new gold standard.[10]
Summary
In conclusion, due to the use of conventional measures, the research in lymphedema is inconsistent and behind the evidence curve. It is for this reason that lymphedema as a condition has been largely ignored. Due to this lack of good objective metrics, little has advanced in the field for the last 35 years.[1] For the first time, BIS offers an Regulatory cleared standardized metric that can offer point of care assessment to aid in the early clinical assessment and prospective management of patients.
“When treated in the earliest stages, complications of this condition may be minimized”. [2]
We urge payers to consider the evidence presented. If you believe in the value of prospective care, education, and earlier treatment, then BIS offers the ability for lymphedema to be more effectively managed by:
1) Allowing new preemptive care approach utilizing a device cleared in the US which provides convenient and more accurate assessment of subclinical lymphedema,
2) Demonstrating clearly if intervention is successful, and
3) Assisting in the coordinated care between Surgeons, Oncologists and Physical Therapists.
References
[1] Hutson P. (2003) Assessing changes in arm lymphedema. Bioelectrical impedance vs. standard methods. Delivering the promise. Susan G. Komen Breast Cancer Foundation Conference.
[2] Lawenda B Mondry T and Johnstone P(2009)
[4] Casley-Smith JR (2003): Measuring and representing peripheral oedema and its alterations Lymphology 27:56-70.>
[5] Mayrovitz HN (2003): Limb Volume estimates based on limb elliptical vs. circular cross section models. Lymphology 31: 140-143
[6] Weissleder h and Brauer W (2008) Examination Methods. In WeisslederH & Schuchhardt C eds. Lymphedema Diagnosis and Therapy. 4th ed. Viavital Verlag Gmbh Publication Chapter 4 61-115.
[7] Fu M Ridner S and Armer J (2008): Post-breast cancer lymphedema Part 1 and 2. Am. J of Nurs. 109 pp. 48-54 and pp34-41.
[8] Ward L (2009): Is BIS ready for prime time as the gold standard measure? J Lymphoedema, 4:52–56.
[9] Warren AG (2007) - Lymphedema A Comprehensive Review - Annals of Plastic Surgery • Volume 594, pp. 464-72.
[27] Hayes S, Cornish B, Newman B. (2005) Comparison of methods to diagnose lymphedema among breast cancer survivors: 6-month follow-up. Breast Cancer Res Treat; 89:221–226.
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[30] Ward L, et al, (2009) Quantitative bioimpedance spectroscopy for the assessment of lymphoedema, Breast Cancer Research and Treatment, DOI 10.1007/s10549-008-0258-0
[34] Kilbreath et al. (2009), Operational Equivalence of Bioimpedance Indices and Perometry for the Assessment of Unilateral, Arm Lymphedema, Lymphatic Research and Biology, Volume 7, Number 2,.
[35] Czerniec S, Ward, L, Lee, M, Refshauge K, Beith J and Kilbreath S, (2010) Segmental Measurement of Breast Cancer-Related Arm Lymphoedema Using Perometry and Bioimpedance Spectroscopy, Support Care Cancer Published on-line 15 May 2010.
[36] Ridner et al, (2007) Comparison of upper limb volume measurement techniques and arm symptoms between healthy volunteers and individuals with known lymphedema, Lymphology, Volume 40, PP 35-46.
[3] Bernas M Askew R Armer J and Cormier J (2010): Lymphedema: How Do We Diagnose and Reduce the Risk of This Dreaded Complication of Breast Cancer Treatment? Curr Breast Cancer Rep 2:53–58
[4] Casley-Smith JR (2003): Measuring and representing peripheral oedema and its alterations Lymphology 27:56-70.>
[5] Mayrovitz HN (2003): Limb Volume estimates based on limb elliptical vs. circular cross section models. Lymphology 31: 140-143
[6] Weissleder h and Brauer W (2008) Examination Methods. In WeisslederH & Schuchhardt C eds. Lymphedema Diagnosis and Therapy. 4th ed. Viavital Verlag Gmbh Publication Chapter 4 61-115.
[7] Fu M Ridner S and Armer J (2008): Post-breast cancer lymphedema Part 1 and 2. Am. J of Nurs. 109 pp. 48-54 and pp34-41.
[8] Ward L (2009): Is BIS ready for prime time as the gold standard measure? J Lymphoedema, 4:52–56.
[9] Warren AG (2007) - Lymphedema A Comprehensive Review - Annals of Plastic Surgery • Volume 594, pp. 464-72.
[10] Piller N 2010 - Outcome measures for lymphoedema - Journal of Lymphoedema, 2010, Vol 5, No 2; rebuttal paper to Ward 2009 [1] calling BIS the new gold standard.
[11] Rockson S (2007) Bioimpedance analysis in the assessment of lymphoedema diagnosis and management; Journal of Lymphoedema, Vol 2, No 1 pp. 44-48.
[12] Hayes et al (2008) - Lymphedema After Breast Cancer: Incidence, Risk Factors, and Effect on Upper Body Function - Journal of Clinical Oncology, Vol 26, No 21 pp. 3536-3542.
[13] The Prevalence of Lymphedema and Changes in Practice to Reduce its Occurrence in Women with Breast Cancer: EUROPEAN JOURNAL OF CLINICAL & MEDICAL ONCOLOGY – June 2010 McLaughlin & Van Zee - Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, Evelyn H Lauder Breast Center, New York, NY, USA.
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[22] Ward L (2006) - Bioelectrical Impedance Analysis: Proven Utility in Lymphedema Risk Assessment and Therapeutic Monitoring –Lymphatic research and biology. Volume 4, Number 1, 2006
[23] Ward LC, Bunce IH, Cornish BH, Mirolo B, Thomas BJ, Jones LC. (1992) Multifrequency bioelectrical impedance augments the diagnosis and management of lymphedema in post-mastectomy patients. Eur J Clin Invest 22:751-754
[24] Ward LC, Bunce IH, Cornish BH, Mirolo BR, Thomas BJ, Jones LC (1992) Multifrequency bioelectrical impedance augments the diagnosis and management of lymphoedema in post-mastectomy patients. Eur J Clin Invest 22 (11): 751–4
[25] Cornish BH, Mirolo B, Bunce IH, Chapman M, Ward LC, Thomas BJ, Jones LC (1996) . Bioelectrical Impedance for Monitoring the Efficacy of Lymphedema Treatment Programs. Breast Cancer Res Treat;38:169–176.
[26] Cornish et al (2001)Early diagnosis of lymphedema using MFBIA, Lymphology, Volume 34, pp2-11.
[27] Hayes S, Cornish B, Newman B. (2005) Comparison of methods to diagnose lymphedema among breast cancer survivors: 6-month follow-up. Breast Cancer Res Treat; 89:221–226.
[28] Hunt, K. Askew, R. and Cormier, J. (2009) Measuring lymphedema in patients with breast cancer: Go with the flow? Breast Cancer Research and Treatment, (Published online)
[29] Hayes S et al, (2008) Lymphedema Secondary to breast cancer: how choice of measure influences diagnosis, prevalence, and identifiable risk factors, Lymphology, 41:pp18-28.
[30] Ward L, et al, (2009) Quantitative bioimpedance spectroscopy for the assessment of lymphoedema, Breast Cancer Research and Treatment, DOI 10.1007/s10549-008-0258-0
[31] Stanton A et al: (1997) Validation of an optoelectronic limb volumeter. 30 pp.77-97.
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[33] Czerniac et al, (2010) Assessment of Breast Cancer-Related Arm Lymphedema—Comparison of Physical Measurement Methods and Self-Report, Cancer Investigation, Volume 28, PP. 54-62
[34] Kilbreath et al. (2009), Operational Equivalence of Bioimpedance Indices and Perometry for the Assessment of Unilateral, Arm Lymphedema, Lymphatic Research and Biology, Volume 7, Number 2,.
[35] Czerniec S, Ward, L, Lee, M, Refshauge K, Beith J and Kilbreath S, (2010) Segmental Measurement of Breast Cancer-Related Arm Lymphoedema Using Perometry and Bioimpedance Spectroscopy, Support Care Cancer Published on-line 15 May 2010.
[36] Ridner et al, (2007) Comparison of upper limb volume measurement techniques and arm symptoms between healthy volunteers and individuals with known lymphedema, Lymphology, Volume 40, PP 35-46.
[37] Cornish BH, Thomas BJ, Ward LC, Hirst C, Bunce IH (2002) A new technique for the quantification of peripheral edema with application in both unilateral and bilateral cases. Angiology 53(1):41–7
[38] Stout-Gergich, et al, (2008) Preoperative Assessment Enables the Early Diagnosis and Successful Treatment of Lymphedema, Cancer, 2809-19.