Standardization of lower extremity quantitative lymphedema measurements and associated patient-reported outcomes in gynecologic cancers.

Practice changing standardization of lower extremity lymphedema quantitative measurements with integrated patient reported outcomes will likely refine and redefine the optimal risk-reduction strategies to diminish the devastating limb-related dysfunction and morbidity associated with treatment of gynecologic cancers. The National Cancer Institute (NCI), Division of Cancer Prevention brought together a diverse group of cancer treatment, therapy and patient reported outcomes experts to discuss the current state-of-the-science in lymphedema evaluation with the potential goal of incorporating new strategies for optimal evaluation of lymphedema in future developing gynecologic clinical trials.

Bioimpedance Spectroscopy for Assessment of Breast Cancer-Related Lymphedema: A Systematic Review.

Bioimpedance spectroscopy is currently used to evaluate patients with breast cancer-related lymphedema (BCRL). We aimed to describe published studies on the use of bioimpedance spectroscopy for assessment for BCRL. We queried the PubMed, Ovid Medline, and Embase databases to identify studies that evaluated the use of bioimpedance spectroscopy as an assessment tool. We searched for the keywords "bioimpedance" AND ("lymphedema" OR "lymphoedema"). We included English-language studies that reported the use of bioimpedance spectroscopy for assessment of BCRL. Out of 152, 116, and 235 articles identified in each database, respectively, only a total of 11 articles were included. Bioimpedance spectroscopy was studied as a method to assess and predict response to BCRL treatment, assess volume changes, and calibrate L-Dex scores for conversion to units of volume. All studies reported that bioimpedance spectroscopy is a promising tool for predicting response to BCRL treatment and measuring volume changes. Bioimpedance spectroscopy can be used for assessment of BCRL. However, the accuracy of bioimpedance spectroscopy for BCRL assessment has not been determined, and consequently further studies are needed.

Design, Construction and Validation of an Electrical Impedance Probe with Contact Force and Temperature Sensors Suitable for in-vivo Measurements.

Bioimpedance spectroscopy measurements can be used for tissue characterization. These measurements can be performed in soft tissues by direct contact of a non-invasive probe consisting of two or four electrodes. The amount of force applied by users can be quite different, and the measurements can vary as a result. To compensate for this, we have built an electrical impedance probe (diameter 3.2 mm) with fibre optic contact-force and temperature sensors built in it. The different sensors of the probe were tested individually. The errors in magnitude and phase angle of the probe are <0.9% and <4°, respectively, for a 0.9% NaCl solution. The linear dynamic range of the force sensor was from 0 to 100 grams. An ex-vivo experiment on a section of proximal colon from a guinea-pig was performed. Twenty bioimpedance measurements were taken in a frequency range of 5 kHz to 1 MHz, while simultaneously recording the force applied. For an increase in contact pressure applied to tissue from 0 to 15.4 kPa, the maximum change in resistivity was 33% at 5 kHz and the minimum was 6.6% at 142 kHz. The probe is small enough to be introduced via the instrument port of an endoscope.

Normative Interlimb Impedance Ratios: Implications for Early Diagnosis of Uni- and Bilateral, Upper and Lower Limb Lymphedema.

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.

Correlation of Bioimpedance Spectroscopy with Risk Factors for the Development of Breast Cancer-Related Lymphedema.

Background: We reviewed serial bioimpedance measurements in order to quantify the relationship between changes in these scores and a patient's risk for developing breast cancer-related lymphedema (BCRL). Methods and Results: From April 2010 through November 2016, 505 patients were prospectively evaluated using bioimpedance spectroscopy (BIS/L-Dex). Patients received preoperative and postoperative L-Dex measurements and were categorized based upon risk for BCRL with respect to axillary staging procedure, radiation use, taxane use, and body mass index (BMI). L-Dex change was associated with the type and number of BCRL risk factors. Both axillary lymph node dissection (ALND) and regional nodal irradiation (RNI) were associated with a greater change in L-Dex (p < 0.001), although elevated BMI was not associated. The median, maximal change in L-Dex for patients treated with ALND, RNI, and taxanes was 16.7 versus 5.2 for ALND alone and 3.7 for sentinel lymph node biopsy (SLNB) alone (p = 0.016). In a model using all four risk factors to predict the maximal change in L-Dex, ALND and RNI remained significantly associated with maximum change (p < 0.05). The time required to reach maximal change in L-Dex was shorter in patients treated with ALND or RNI (the time for 25% of patients achieving an L-Dex ≥7 was 4.3 months for ALND, RNI, and taxanes patients versus 30.8 months for SLNB-alone patients). Conclusions: Risk factors for development of BCRL were associated with both the magnitude and timing of change in L-Dex scores. These findings demonstrate the utility of serial L-Dex measurements in providing an objective assessment of a patient's lymphedema status and the value of L-Dex serial measurements to assist in monitoring patients for the development of BCRL. This supports the clinical utilization of serial L-Dex scores to follow patients at risk for BCRL.

Reference Values for Assessing Localized Hand Lymphedema Using Interhand Tissue Dielectric Constant Ratios.

BACKGROUND: Early detection and tracking of breast cancer treatment-related lymphedema have been helped by quantitative assessment methods and parameters, including bioelectrical impedance spectroscopy and tissue dielectric constant (TDC). Such measurements are evaluated with respect to interarm differences or ratios that (when exceeding specified thresholds) are suggestive of lymphedema. Specific threshold ratios depend on the assessment method and have been reported for arms. However, there is far less information available on thresholds to assess lymphedema that manifests in at-risk hands and essentially nothing known about TDC ratios in healthy hands. Such information is essential to establish reference values from which lymphedema threshold TDC values may be estimated. The specific aim of this research was to determine such interhand TDC ratios applicable to both young and mature women. METHODS AND RESULTS: A total of 70 women (35 under 30 years of age, YOUNG, and 35 over 50 years of age, MATURE) participated after signing an approved institutional review board informed consent. TDC values of the hand dorsum web were measured bilaterally in triplicate with participants in a supine resting position. Results showed MATURE TDC values to be about 15% less than YOUNG (p < 0.01) on dominant and nondominant hands, but no statistical difference in dominant/nondominant interarm ratios (1.026 ± 0.100). CONCLUSIONS: Based on this data set's overall mean and two standard deviation value, an age-independent interhand TDC threshold ratio of 1.23 emerges as potentially useful for lymphedema detection. This is a good initial start threshold that is usable in future clinical and research assessments.

Reference Ranges Using Bioimpedance for Detection of Lymphedema in Chinese Women.

BACKGROUND: Bioimpedance is a commonly used technique for detection of early lymphedema. The thresholds used for detection are based on impedance measurements obtained in Western populations. It is unknown whether these thresholds are applicable to a Chinese population. METHODS AND RESULTS: Impedance measurements were obtained for both arms in 391 women, ranging in age from 20 to 84 years, using a standardized protocol. Frequency distributions of interlimb impedance arm ratios for both dominant:non-dominant and non-dominant:dominant were used to determine thresholds at two and three standard deviations (SDs) above the mean. Absolute impedance was significantly higher in the youngest group (20-39 years) compared to other age groups. However, there was no significant effect of age on impedance ratios. Similarly, there was no significant difference between impedance ratios determined in this study and those from recent studies in the Australia and the United States, which used similar protocols. New two and three SDs above the mean thresholds, using a weighted average from the pooled data of these studies are 1.108 and 1.153 for use when the dominant limb is at-risk and 1.072 and 1.116 when the non-dominant limb is at-risk. CONCLUSION: There was no effect of ethnicity on impedance ratios. Consequently, the proposed pooled thresholds can be used, irrespective of ethnicity.

Bioimpedance analysis vs. DEXA as a screening tool for osteosarcopenia in lean, overweight and obese Caucasian postmenopausal females.

BACKGROUND-OBJECTIVES: We aimed at evaluating the efficiency of a newly developed, advanced Bioimpedance Analysis (BIA-ACC®) device as a screening tool for determining the degree of obesity and osteosarcopenia in postmenopausal women with normal or decreased bone density determined by Dual-Energy X-Ray absorptiometry (DEXA) in a representative sample of Greek postmenopausal women. METHODS: This is a single-gate cross-sectional study of body composition measured by BIA-ACC® and DEXA. Postmenopausal females with BMI ranging from 18.5 to 40 kg/m2 were subjected to two consecutive measurements of DEXA and BIA-ACC® within 5-10 minutes of each other. We used Pearson's co-efficient to examine linear correlations, the intraclass correlation co-efficient (ICC) to test reliability, Bland-Atman plots to assess bias and Deming regressions to establish the agreement in parameters measured by BIA-ACC® and DEXA. Last, we used ANOVA, with Bonferroni correction and Dunnett T3 post hoc tests, for assessing the differences between quantitative and Pearson's x2 between qualitative variables. SAMPLE AND RESULTS: Our sample consisted of 84 overweight/obese postmenopausal women, aged 39-83 years, of whom 22 had normal bone density, 38 had osteopenia and 24 had osteoporosis based on DEXA measurements, using quota sampling. ICCs and Deming regressions showed strong agreement between BIA-ACC® and DEXA and demonstrated minimal proportional differences of no apparent clinical significance. Bland-Altman plots indicated minimal biases. Fat, skeletal and bone mass measured by BIA-ACC® and DEXA were increased in the non-osteopenic/non-osteoporotic women compared with those of the osteopenic and osteoporotic groups. CONCLUSIONS: BIA-ACC® is a rapid, bloodless and useful screening tool for determining body composition adiposity and presence of osteo-sarcopenic features in postmenopausal women. Women with osteopenia and osteoporosis evaluated by DEXA had decreased fat, skeletal and bone mass compared with normal bone density women, suggesting concordance in the change of these three organ masses in postmenopausal women.

Modeling the microscopic electrical properties of thrombin binding aptamer (TBA) for label-free biosensors.

Aptamers are chemically produced oligonucleotides, able to bind a variety of targets such as drugs, proteins and pathogens with high sensitivity and selectivity. Therefore, aptamers are largely employed for producing label-free biosensors (aptasensors), with significant applications in diagnostics and drug delivery. In particular, the anti-thrombin aptamers are biomolecules of high interest for clinical use, because of their ability to recognize and bind the thrombin enzyme. Among them, the DNA 15-mer aptamer (TBA), has been widely explored around the possibility of using it in aptasensors. This paper proposes a microscopic model of the electrical properties of TBA and of the aptamer-thrombin complex, combining information from both structure and function, following the issues addressed in an emerging branch of electronics known as proteotronics. The theoretical results are compared and validated with measurements reported in the literature. Finally, the model suggests resistance measurements as a novel tool for testing aptamer-target affinity.

Age-related changes in male forearm skin-to-fat tissue dielectric constant at 300 MHz.

Prior research suggests that tissue dielectric constant (TDC) values are useful to assess localized skin water in females for early diagnosing breast cancer treatment-related lymphoedema and TDC values in young adults have shown gender differences. However, no TDC data are available for older males nor have ageing effects been studied despite known shifts in water state and other skin age-related changes. Thus our goals were to (i) characterize TDC values at various skin depths in young and older males, (ii) determine the dependence of these values on body composition parameters and (iii) establish inter-arm TDC ratios for use as normal male reference values. TDC measurements were made to depths of 0·5, 1·5, 2·5 and 5·0 mm bilaterally on volar forearm skin in 60 males in three groups of 20 that had mean ages ± SD of 24·0 ± 0·9, 40·0 ± 12·9 and 71·0 ± 8·0 years. Total body fat and water percentages were determined via bioimpedance at 50 KHz. Results showed that (i) for all age groups TDC values decreased with increasing depth, (ii) TDC values were not statistically different among age groups except at a depth of 0·5 mm, (iii) TDC values were highly negatively correlated with total body fat and (iv) inter-arm ratios varied little among age groups and depths. It is concluded that (i) age-related larger TDC values at only the shallowest depth is consistent with skin water shifting state from bound to more mobile in the oldest group and (ii) inter-arm ratios at any depth provide a basis to test for unilateral oedema.

Improved electrode positions for local impedance measurements in the lung-a simulation study.

Impedance spectroscopy can be used to analyze the dielectric properties of various materials. In the biomedical domain, it is used as bioimpedance spectroscopy (BIS) to analyze the composition of body tissue. Being a non-invasive, real-time capable technique, it is a promising modality, especially in the field of lung monitoring. Unfortunately, up to now, BIS does not provide any regional lung information as the electrodes are usually placed in hand-to-hand or transthoracic configurations. Even though transthoracic electrode configurations are in general capable of monitoring the lung, no focusing to specific regions is achieved. In order to resolve this issue, we use a finite element model (FEM) of the human body to study the effect of different electrode configurations on measured BIS data. We present evaluation results and show suitable electrode configurations for eight lung regions. We show that, using these optimized configurations, BIS measurements can be focused to desired regions allowing local lung analysis.

Validation of Bioelectrical Impedance Spectroscopy to Measure Total Body Water in Resistance-Trained Males.

The three-compartment (3-C) model of physique assessment (fat mass, fat-free mass, water) incorporates total body water (TBW) whereas the two-compartment model (2-C) assumes a TBW of 73.72%. Deuterium dilution (D2O) is the reference method for measuring TBW but is expensive and time consuming. Multifrequency bioelectrical impedance spectroscopy (BIS SFB7) estimates TBW instantaneously and claims high precision. Our aim was to compare SFB7 with D2O for estimating TBW in resistance trained males (BMI >25kg/m2). We included TBWBIS estimates in a 3-C model and contrasted this and the 2-C model against the reference 3-C model using TBWD2O. TBW of 29 males (32.4 ± 8.5 years; 183.4 ± 7.2 cm; 92.5 ± 9.9 kg; 27.5 ± 2.6 kg/m2) was measured using SFB7 and D2O. Body density was measured by BODPOD, with body composition calculated using the Siri equation. TBWBIS values were consistent with TBWD2O (SEE = 2.65L; TE = 2.6L) as were %BF values from the 3-C model (BODPOD + TBWBIS) with the 3-C reference model (SEE = 2.20%; TE = 2.20%). For subjects with TBW more than 1% from the assumed 73.72% (n = 16), %BF from the 2-C model differed significantly from the reference 3-C model (Slope 0.6888; Intercept 5.093). The BIS SFB7 measured TBW accurately compared with D2O. The 2C model with an assumed TBW of 73.72% introduces error in the estimation of body composition. We recommend TBW should be measured, either via the traditional D2O method or when resources are limited, with BIS, so that body composition estimates are enhanced. The BIS can be accurately used in 3C equations to better predict TBW and BF% in resistance trained males compared with a 2C model.

A critical evaluation of bioimpedance spectroscopy analysis in estimating body composition during GH treatment: comparison with bromide dilution and dual X-ray absorptiometry.

OBJECTIVE: To compare estimates by bioimpedance spectroscopy analysis (BIS) of extracellular water (ECW), fat mass (FM), and fat-free mass (FFM) against standard techniques of bromide dilution and dual energy X-ray absorptiometry (DXA) during intervention that causes significant changes in water compartments and body composition. METHODS: Body composition analysis using BIS, bromide dilution, and DXA was performed in 71 healthy recreational athletes (43 men, 28 women; aged 18-40 years; BMI 24 ± 0.4 kg/m(2)) who participated in a double-blinded, randomized, placebo-controlled study of GH and testosterone treatment. The comparison of BIS with bromide dilution and DXA was analyzed using linear regression and the Bland-Altman method. RESULTS: At baseline, there was a significant correlation between BIS and bromide dilution-derived estimates for ECW, and DXA for FM and FFM (P<0.001). ECW by BIS was 3.5 ± 8.1% lower compared with bromide dilution, while FM was 22.4 ± 26.8% lower and FFM 13.7 ± 7.5% higher compared with DXA (P<0.01). During treatment, the change in ECW was similar between BIS and bromide dilution, whereas BIS gave a significantly greater reduction in FM (19.4 ± 44.8%) and a greater increase in FFM (5.6 ± 3.0%) compared with DXA (P<0.01). Significant differences in body composition estimates between the BIS and DXA were observed only in men, particularly during the treatment that caused greatest change in water compartments and body composition. CONCLUSION: In healthy adults, bioimpedance spectroscopy is an acceptable tool for measuring ECW; however, BIS overestimates FFM and substantially underestimates FM compared with DXA.

Clinical performance of the Nevisense system in cutaneous melanoma detection: an international, multicentre, prospective and blinded clinical trial on efficacy and safety.

BACKGROUND: Even though progress has been made, the detection of melanoma still poses a challenge. In light of this situation, the Nevisense electrical impedance spectroscopy (EIS) system (SciBase AB, Stockholm, Sweden) was designed and shown to have the potential to be used as an adjunct diagnostic tool for melanoma detection. OBJECTIVES: To assess the effectiveness and safety of the Nevisense system in the distinction of benign lesions of the skin from melanoma with electrical impedance spectroscopy. METHODS: This multicentre, prospective, and blinded clinical study was conducted at five American and 17 European investigational sites. All eligible skin lesions in the study were examined with the EIS-based Nevisense system, photographed, removed by excisional biopsy and subjected to histopathological evaluation. A postprocedure clinical follow-up was conducted at 7 ± 3 days from the initial measurement. A total of 1951 patients with 2416 lesions were enrolled into the study; 1943 lesions were eligible and evaluable for the primary efficacy end point, including 265 melanomas - 112 in situ and 153 invasive melanomas with a median Breslow thickness of 0·57 mm [48 basal cell carcinomas (BCCs) and seven squamous cell carcinomas (SCCs)]. RESULTS: The observed sensitivity of Nevisense was 96·6% (256 of 265 melanomas) with an exact one-sided 95% lower confidence bound estimated at 94·2% and an observed specificity of 34·4%, and an exact two-sided 95% confidence bound estimated at 32·0-36·9%. The positive and negative predictive values of Nevisense were 21·1% and 98·2%, respectively. The observed sensitivity for nonmelanoma skin cancer was 100% (55 of 48 BCCs and seven SCCs) with an exact two-sided 95% confidence bound estimated at 93·5-100·0%. CONCLUSIONS: Nevisense is an accurate and safe device to support clinicians in the detection of cutaneous melanoma.

Evaluation of a new dielectric barrier discharge excitation source for the determination of arsenic with atomic emission spectrometry.

A low power dielectric barrier discharge excitation source was developed to determine arsenic in a cost-effective manner. Arsenic in water was reduced to AsH3 by hydride generation (HG), which was transported to the miniature dielectric barrier discharge (DBD) excitation source for excitation and optical detection at As 193.7 nm atomic line. The DBD source consists of a quartz tube, a tungsten rod electrode, and a copper coil electrode. The main operation parameters and the potential interferences affecting the determination were investigated. The detection limit for arsenic with the proposed DBD-AES was 4.8 µg L(-1) when the HG products were dried with concentrated H2SO4 before introducing to DBD. Repeatability, expressed as the relative standard deviation of the spectral peak height, was 2.8% (n=11) for 0.1 mg L(-1) arsenic solution. The proposed method was successfully applied to the determinations of certified reference material (GBW08605) and nature water samples.

Titanium dioxide nanotube films: Preparation, characterization and electrochemical biosensitivity towards alkaline phosphatase.

Titania nanotubes (TNTs) were prepared by anodization on different substrates (titanium, Ti6Al4V and Ti6Al7Nb alloys) in ethylene glycol and glycerol. The influence of the applied potential and processing time on the nanotube diameter and length is analyzed. The as-formed nanotube layers are amorphous but they become crystalline when subjected to subsequent thermal treatment in air at 550°C; TNT layers grown on titanium and Ti6Al4V alloy substrates consist of anatase and rutile, while those grown on Ti6Al7Nb alloy consist only of anatase. The nanotube layers grown on Ti6Al7Nb alloy are less homogeneous, with supplementary islands of smaller diameter nanotubes, spread across the surface. Better adhesion and proliferation of osteoblasts was found for the nanotubes grown on all three substrates by comparison to an unprocessed titanium plate. The sensitivity towards bovine alkaline phosphatase was investigated mainly by electrochemical impedance spectroscopy in relation to the crystallinity, the diameter and the nature of the anodization electrolyte of the TNT/Ti samples. The measuring capacity of the annealed nanotubes of 50nm diameter grown in glycerol was demonstrated and the corresponding calibration curve was built for the concentration range of 0.005-0.1mg/mL.

Effects of the electrode size and modification protocol on a label-free electrochemical biosensor.

In the present work, the effect of a surface modification protocol along with the electrode size has been investigated for developing an efficient, label-free electrochemical biosensing method for diagnosis of traumatic brain injury (TBI) biomarkers. A microdisk electrode array (MDEA) and a macroelectrode with a comb structure (MECS) were modified with an anti-GFAP (GFAP = glial fibrillary acidic protein) antibody using two protocols for optimum and label-free detection of GFAP, a promising acute-phase TBI biomarker. For the MDEA, an array of six microdisks with a 100 µm diameter and, for the MECS, a 3.2 mm × 5.5 mm electrode 5 µm wide with 10 µm spaced comb fingers were modified using an optimized protocol for dithiobis(succinimidyl propionate) (DSP) self-assembled monolayer formation. Anti-GFAP was covalently bound, and the remaining free DSP groups were blocked using ethanolamine (Ea). Sensors were exposed to solutions with different GFAP concentrations, and a label-free electrochemical impedance spectroscopy (EIS) technique was used to determine the concentration. EIS results confirmed that both types of Ea/anti-GFAP/DSP/Au electrodes modified with an optimized DSP-based protocol can accurately detect GFAP in the range of 1 pg mL(-1) to 100 ng mL(-1) with a detection limit of 1 pg mL(-1). However, the cross-use of the MDEA protocol on the MECS and vice versa resulted in very low sensitivity or poor signal resolution, underscoring the importance of proper matching of the electrode size and type and the surface modification protocol.

Ultrasensitive label free electrical detection of insulin in neat blood serum.

Electrical assays potentially offer a highly sensitive, cheap, portable, automated, and multiplexed means of protein biomarker detection, characteristics with an ability to underpin both disease stratification and the development of point of care diagnostics. Most conveniently applied in a reagent free manner, all sensitive assays such as these suffer, however, from profound problems when applied in complex fluids such as blood serum. We report herein, the development, and clinical application, of a highly sensitive and selective electrical insulin biosensor based on a chemisorbed zwittorionic polymer support and a novel reagentless sensing technique based on phase monitoring electrochemical impedance spectroscopy. The polymer adlayer is exceptionally effective in both reducing background response and maintaining receptive antibody binding efficacy, while the non-Faradaic analysis avoids potential interference from background electro-active molecules. Applied to the detection of even a low molecular weight protein (here, insulin), a linear range from 0.1 to 200 pM and an unprecedented femtomolar detection limit are possible in undiluted blood serum.

Accuracy of detection of high-grade cervical intraepithelial neoplasia using electrical impedance spectroscopy with colposcopy.

OBJECTIVE: To determine if electrical impedance spectroscopy (EIS) improves the diagnostic accuracy of colposcopy when used as an adjunct. DESIGN: Prospective, comparative, multi-centre clinical study. SETTING: Three colposcopy clinics: two in England and one in Ireland. POPULATION: Women referred with abnormal cytology. METHODS: In phase 1, EIS was assessed against colposcopic impression and histopathology of the biopsies taken. In phase 2, a probability index and cut-off value for the detection of high-grade cervical intraepithelial neoplasia (HG-CIN, i.e. grade CIN2+) was derived to indicate sites for biopsy. EIS data collection and analyses were performed in real time and blinded to the clinician. The phase-2 data were analysed using different cut-off values to assess performance of EIS as an adjunct. MAIN OUTCOME MEASURE: Histologically confirmed HG-CIN (CIN2+). RESULTS: A total of 474 women were recruited: 214 were eligible for analysis in phase 1, and 215 were eligible in phase 2. The average age was 33.2 years (median age 30.3 years, range 20-64 years) and 48.5% (208/429) had high-grade cytology. Using the cut-off from phase 1 the accuracy of colposcopic impression to detect HG-CIN when using EIS as an adjunct at the time of examination improved the positive predictive value (PPV) from 78.1% (95% CI 67.5-86.4) to 91.5%. Specificity was also increased from 83.5% (95% CI 75.2-89.9) to 95.4%, but sensitivity was significantly reduced from 73.6% (95% CI 63.0-82.5) to 62.1%, and the negative predictive value (NPV) was unchanged. The positive likelihood ratio for colposcopic impression alone was 4.46. This increased to 13.5 when EIS was used as an adjunct. The overall accuracy of colposcopy when used with EIS as an adjunct was assessed by varying the cut-off applied to a combined test index. Using a cut-off set to give the same sensitivity as colposcopy in phase 2, EIS increased the PPV to detect HG-CIN from 53.5% (95% CI 45.0-61.8) to 67%, and specificity increased from 38.5% (95% CI 29.4-48.3) to 65.1%. NPV was not significantly increased. Alternatively, applying a cut-off to give the same specificity as colposcopy alone increased EIS sensitivity from 88.5% (95% CI 79.9-94.4) to 96.6%, and NPV from 80.8% (95% CI 67.5-90.4) to 93.3%. PPV was not significantly increased. The receiver operator characteristic (ROC) to detect HG-CIN had an area under the curve (AUC) of 0.887 (95% CI 0.840-0.934). CONCLUSIONS: EIS used as an adjunct to colposcopy improves colposcopic performance. The addition of EIS could lead to more appropriate patient management with lower intervention rates.

Non-invasive identification of melanoma with near-infrared and skin impedance spectroscopy.

BACKGROUND/PURPOSE: An early diagnosis of cutaneous malignant melanoma is of high importance for good prognosis. An objective, non-invasive instrument could improve the diagnostic accuracy of melanoma and decrease unnecessary biopsies. The aim of this study was to investigate the use of Near-infrared and skin impedance spectroscopy in combination as a tool to distinguish between malignant and benign skin tumours. METHODS: Near-infrared and skin impedance spectra were collected in vivo on 50 naevi or suspect melanomas prior to excision. Received data were analysed using multivariate techniques and the results were compared to histopathology analyses of the tumours. A total of 12 cutaneous malignant melanomas, 19 dysplastic naevi and 19 benign naevi were included in the study. RESULTS: The observed sensitivity and specificity of the proposed method were 83% and 95%, respectively, for malignant melanoma. CONCLUSION: The results indicate that the combination of near-infrared and skin impedance spectroscopy is a promising tool for non-invasive diagnosis of suspect cutaneous malignant melanomas.