Measuring body composition in dogs using bioelectrical impedance spectroscopy.

Assessment of body composition is an essential aspect of veterinary canine care, particularly as prevalence of overweight and obesity in dogs is increasing. Few quantitative objective methods for body composition measurement are available for routine clinical use. Bioelectrical impedance analysis is widely used in human medicine and nutritional assessment and although it has shown promise in production animals it has not yet been adopted for companion animals. The present study validated bioimpedance spectroscopy (BIS) against the reference method of dual-energy X-ray absorptiometry. Resistivity coefficients for use in BIS were determined: ρe = 444.8 and ρi = 1477.8 ohm.cm and used to predict fat-free mass (FFM) in a cohort of 35 mixed breed dogs. Overall, FFM was predicted to within 3.5% of reference values. At an individual level, FFM was predicted within 2 standard deviations (95% confidence) of 10%. BIS provides an objective quantitative alternative to the widely used semi-quantitative body condition scoring. In addition, BIS provides estimates of body water volumes (total, extra-and intracellular), information that can be useful in fluid management. BIS is inexpensive, and simple to perform but does require brief (<5 min) sedation of the animal.

Use of bioelectrical impedance spectroscopy to provide a measure of body composition in sows.

The ability to accurately estimate fat mass and fat-free mass (FFM) has the potential to improve the way in which sow body condition can be managed in a breeding herd. Bioelectrical impedance spectroscopy (BIS) has been evaluated as a practical technique for assessment of body composition in several livestock species, but similar work is lacking in sows. Bioelectrical impedance uses population-specific algorithms that require values for the apparent resistivities of body fluids and body proportion factors. This study comprised three major aims: (i) to derive apparent resistivity coefficients for extracellular water (ECW) and intracellular water (ICW) required for validation of BIS predictions of total body water (TBW) in live sows against standard reference tracer dilution methods; (ii) to develop predictions of TBW to body composition prediction algorithms, namely FFM, by developing a body geometry correction factor (Kb) and (iii) to compare the BIS predictions of FFM against existing impedance predictors and published prediction equations for use in sows, based on physical measurements of back-fat depth and BW (P2-based predictors). Whole body impedance measurements and the determination of TBW by deuterium dilution and ECW by bromide dilution were performed on 40 Large White x Landrace sows. Mean apparent resistivity coefficients of body fluids were 431.1 Ω.cm for ECW and 1827.8 Ω.cm for ICW. Using these coefficients, TBW and ECW were over-estimated by 6.5 and 3.3%, respectively, compared to measured reference values, although these differences were not statistically different (P > 0.05). Mean Kb was 1.09 ±â€¯0.14. Fat-free mass predictions were 194.9 kg, which equates to 60.9% of total sow weight, and 183.0 kg for BIS and the deuterium dilution method, respectively. Mean differences between the predicted and measured FFM values ranged from -8.2 to 32.7%, but were not statistically different (P > 0.05). Method validation (leave-one-out procedure) revealed that mean differences between predicted and measured values were not statistically significant (P > 0.05). Of the impedance-based predictors, equivalence testing revealed that BIS displayed the lowest test bias of 11.9 kg (8.2%), although the P2-based prediction equations exhibited the lowest bias and percentage equivalence, with narrow limits of agreement. Results indicate although differences between mean predicted and measured values were not significantly different, relatively wide limits of agreement suggest BIS as an impractical option for assessing body composition in individual sows compared to the use of existing prediction equations based on BW and back fat.

Reduction of breast lymphoedema secondary to breast cancer: a randomised controlled exercise trial.

BACKGROUND: Breast lymphoedema can occur following surgical treatment for breast cancer. We investigated whether an exercise program reduced breast lymphoedema symptoms compared to a non-exercise control group. METHODS: A single-blinded randomised controlled trial was conducted in which women with stable breast lymphoedema (n = 89) were randomised into an exercise (n = 41) or control (n = 47) group. The intervention comprised a 12-week combined aerobic and resistance training program, supervised weekly by an accredited exercise physiologist. All participants completed a weekly symptoms diary and were assessed monthly to ensure that there was no exacerbation of their lymphoedema. Changes in the breast were captured physically with ultrasound and bioimpedance spectroscopy and changes in symptoms were captured using European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer (BR23) and Lymphoedema Symptom Intensity and Distress questionnaires. RESULTS: The exercise group reported a greater reduction in breast-related symptoms than the control group, assessed by the EORTC BR23 breast symptom questions. Measures of extracellular fluid, assessed with bioimpedance spectroscopy ratio, decreased in the exercise group compared to the control group. No significant difference was detected in dermal thickness in the breast, assessed by ultrasound. Session attendance in the exercise sessions was high, with two musculoskeletal adverse events reported, but no exacerbations of lymphoedema observed. CONCLUSION: Combined resistance and aerobic exercise training is safe for women living with breast lymphoedema. Preliminary data suggest exercise training can reduce breast lymphoedema symptoms to a greater extent than usual care.

A randomized trial to examine the mechanisms of cognitive, behavioral and mindfulness-based psychosocial treatments for chronic pain: Study protocol.

This randomized trial will evaluate the mechanisms of three chronic pain treatments: cognitive therapy (CT), mindfulness meditation (MM), and activation skills (AS). We will determine the extent to which late-treatment improvement in primary outcome (pain interference) is predicted by early-treatment changes in cognitive content, cognitive process, and/or activity level. The shared versus specific role of these mechanisms across the three treatments will be evaluated during treatment (Primary Aim), and immediately post-treatment to examine relapse mechanisms (Secondary Aim). We will enroll 300 individuals with chronic pain (with low back pain as a primary or secondary condition), with 240 projected to complete the study. Participants will be randomly assigned to eight, 1.5 h telehealth group sessions of CT, MM, or AS. Mechanisms and outcomes will be assessed twice daily during 2-week baseline, 4-week treatment period, and 4-week post-treatment epoch via random cue-elicited ecological momentary assessment (EMA); activity level will be monitored during these time epochs via daily monitoring with ActiGraph technology. The primary outcome will be measured by the PROMIS 5-item Pain Interference scale. Structural equation modeling (SEM) will be used to test the primary aims. This study is pre-registered on clinicaltrials.gov (Identifier: NCT03687762). This study will determine the temporal sequence of lagged mediation effects to evaluate rates of change in outcome as a function of change in mediators. The findings will provide an empirical basis for enhancing and streamlining psychosocial chronic pain interventions. Further, results will guide future efforts towards optimizing maintenance of gains to effectively reduce relapse risk.

Screening for breast cancer-related lymphoedema: self-assessment of symptoms and signs.

INTRODUCTION: In the absence of monitoring programs, those at risk of developing breast cancer-related lymphoedema (BCRL) must detect its development. However, the efficacy of self-assessment for BCRL has not been widely investigated. This study will determine if symptoms and signs of BCRL are associated with lymphoedema detected by bioimpedance spectroscopy (BIS) and whether those with and without BCRL can accurately assess the signs of its presence. METHODS AND RESULTS: Participants with a history of breast cancer (n = 100) reported the presence/absence of symptoms associated with upper limb BCRL and underwent assessment for pitting oedema and differences in tissue texture between their arms (pinch). BIS detected BCRL in 48 women. Women were more likely to have BIS-detected BCRL if they reported swelling (odds ratio (OR), 58.8; 95% CI, 4.9 to 709.4; p = 0.001) or had inter-limb tissue texture differences in their forearm (OR, 73.5; 95% CI, 7.3 to 736.9; p = < 0.001) or upper arm (OR, 23.9; 95% CI, 2.8 to 201.7; p = 0.003). Agreement between therapist and self-assessment of signs of BCRL was almost perfect (kappa, 0.819 to 0.940). A combination of self-reported swelling and/or self-assessed forearm tissue texture difference identified all cases of BIS-detected BCRL. CONCLUSION: Participants accurately identified the presence or absence of physical signs of BCRL in their arm. Perceived swelling and differences in tissue texture in the affected arm were associated with, and sensitive to, BIS-detected BCRL. These findings support the use of self-assessment to determine if BCRL is developing, indicating the need for professional assessment.

Pediatric post-thrombotic syndrome in children: Toward the development of a new diagnostic and evaluative measurement tool.

OBJECTIVE: Our goal was to conduct the item generation and piloting phases of a new discriminative and evaluative tool for pediatric post-thrombotic syndrome. METHODS: We followed a formative model for the development of the tool, focusing on the signs/symptoms (items) that define post-thrombotic syndrome. For item generation, pediatric thrombosis experts and subjects diagnosed with extremity post-thrombotic syndrome during childhood nominated items. In the piloting phase, items were cross-sectionally measured in children with limb deep vein thrombosis to examine item performance. RESULT: Twenty-three experts and 16 subjects listed 34 items, which were then measured in 140 subjects with previous diagnosis of limb deep vein thrombosis (70 upper extremity and 70 lower extremity). The items with strongest correlation with post-thrombotic syndrome severity and largest area under the curve were pain (in older children), paresthesia, and swollen limb for the upper extremity group, and pain (in older children), tired limb, heaviness, tightness and paresthesia for the lower extremity group. CONCLUSION: The diagnostic properties of the items and their correlations with post-thrombotic syndrome severity varied according to the assessed venous territory. The information gathered in this study will help experts decide which item should be considered for inclusion in the new tool.

Measuring body composition in dogs using multifrequency bioelectrical impedance analysis and dual energy X-ray absorptiometry.

Thirty-five healthy, neutered, mixed breed dogs were used to determine the ability of multifrequency bioelectrical impedance analysis (MFBIA) to predict accurately fat-free mass (FFM) in dogs using dual energy X-ray absorptiometry (DXA)-measured FFM as reference. A second aim was to compare MFBIA predictions with morphometric predictions. MFBIA-based predictors provided an accurate measure of FFM, within 1.5% when compared to DXA-derived FFM, in normal weight dogs. FFM estimates were most highly correlated with DXA-measured FFM when the prediction equation included resistance quotient, bodyweight, and body condition score. At the population level, the inclusion of impedance as a predictor variable did not add substantially to the predictive power achieved with morphometric variables alone; in individual dogs, impedance predictors were more valuable than morphometric predictors. These results indicate that, following further validation, MFBIA could provide a useful tool in clinical practice to objectively measure FFM in canine patients and help improve compliance with prevention and treatment programs for obesity in dogs.

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

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.

Risk factors for lymphoedema in women with breast cancer: A large prospective cohort.

A prospective study was conducted to identify women at increased risk for lymphoedema (LE) based on axillary surgery. Assessment occurred prior to surgery, within 4 weeks, and at 6, 12 and 18 months following surgery. Following post-surgery assessment, women were asked to complete weekly diaries regarding events that occurred in the previous week. Risk factors were grouped into demographic, lifestyle, breast cancer treatment-related, arm swelling-related, and post-surgical activities. Bioimpedance spectroscopy thresholds were used to determine presence of LE. At 18-months, 241 women with <5 nodes removed and 209 women with ≥5 nodes removed were assessed. For those with <5 nodes removed, LE was present in 3.3% compared with 18.2% for those with ≥5 nodes removed. There were insufficient events to identify risk factors for those with <5 nodes removed; for those with >5 nodes removed, independent risk factors included presence of arm swelling at 12-months (Odds Ratio (OR): 13.5, 95% CI 4.8, 38.1; P < 0.01), at 6-months (5.6 (2.0, 16.9); P < 0.01), and radiotherapy to the axilla (2.6 (0.7, 8.9); P = 0.14). Arm swelling at 6 and 12 months was associated with taxane-based chemotherapy, high body weight at diagnosis and arm swelling within 4 weeks post-surgery. Of the post-surgical events assessed in a sub-group of women with >5 nodes removed and who maintained weekly diaries, only blood drawn from the 'at-risk' arm was identified as a potential risk (OR 2.0; 0.8, 5.2). For women with ≥5 nodes removed, arm swelling in the first year poses a very strong risk for presence of LE at 18-months.

Body composition assessment in horses using bioimpedance spectroscopy.

Assessment of equine body composition using objective measurements is difficult owing to the large size of the animals and the costs involved. Bioelectrical impedance spectroscopy (BIS), a technique widely used for the assessment of body composition in humans, was investigated for practicality of use in horses. BIS uses algorithms that require values for the apparent resistivities of body fluids and body proportion factors (Kb), currently not available for horses. Aims of the present study were to derive resistivity coefficients and body proportion factors and to validate their use for prediction of body composition horses. Validation of coefficients and predictive power using a split-sample agreement study design using correlation and limits of agreement analysis. Whole body impedance measurements were performed on 35 standardbred horses, yearlings to 14 yr, concurrently with determination of total body water volume (TBW) by deuterium dilution and extracellular water volume (ECW) by bromide dilution. Kb was determined in an independent group of 38 mixed-breed, age, and sex horses. Mean apparent resistivity coefficients were 511.4 and 1415.9 ohm.cm for intracellular water and TBW, respectively. Mean Kb was 1.52 ± 0.1. Using these coefficients, TBW and fat-free mass could be predicted with limits of agreement (2SD) of ± 11.6%; mean fat-free mass and fat mass were under- and overestimated by 3.1% and 14.1%, respectively, compared to measured reference values although these differences were not statistically significant. BIS is a practical technique for the assessment of body composition in equids, but the relatively wide limits of agreement, particularly for fat mass, may limit its usefulness for predicting body composition in individual horses.

Bioimpedance spectroscopy in the infant: effect of milk intake and extracellular fluid reservoirs on resistance measurements in term breastfed infants.

BACKGROUND/OBJECTIVES: Bioimpedance spectroscopy is an accurate non-invasive method for measuring body composition in adults, but in infants it requires further testing and validation. Of the few studies of bioimpedance conducted in infants, none have comprehensively investigated the effect of milk intake volume. This study assessed the effect of the milk intake, feed duration and the volume of the infant's stomach and bladder on the resistance values pre-/post-feed to establish the feasibility of using these values interchangeably during data collection. SUBJECTS/METHODS: Forty-eight breastfeeding infants were measured at 2, 5, 9 and/or 12 months (n=62 sessions) within 1-2 min before the start and after the end of breastfeed. Median (IQR) time between measurements was 24 (20.0-30.0) min. Resistance measurements at 0 and 50 kHz, and infinite frequency (R0, R50 and Rinf) and resistance of intracellular water (Ricw) were analysed with customised infant settings. Milk intake was measured by test weights. Free-water volumes and free-water change were determined from stomach and bladder volumes calculated from ultrasound images. RESULTS: Small pre-to-post-feed changes (median (IQR): R0 -3.7 (-14.8, 14.3); R50 0.3 (-10.4, 15.0); Rinf 2.8 (-13.3, 35.5); Ricw 20.8 (-98.1, 290.9)) were not significantly different from zero (R0: P=0.92; R50: P=0.48; Rinf: P=0.32; Ricw: P=0.097). No significant effect of milk intake or free-water change was detected. CONCLUSIONS: The lack of consistent change in resistance across a breastfeed provides flexibility in the timing of measurements of infants in the research setting, such that typically pre- and post-feed measures of resistance can be used interchangeably.

Estimation of body fluids with bioimpedance spectroscopy: state of the art methods and proposal of novel methods.

Determination of body fluids is a useful common practice in determination of disease mechanisms and treatments. Bioimpedance spectroscopy (BIS) methods are non-invasive, inexpensive and rapid alternatives to reference methods such as tracer dilution. However, they are indirect and their robustness and validity are unclear. In this article, state of the art methods are reviewed, their drawbacks identified and new methods are proposed. All methods were tested on a clinical database of patients receiving growth hormone replacement therapy. Results indicated that most BIS methods are similarly accurate (e.g. < 0.5 ± 3.0% mean percentage difference for total body water) for estimation of body fluids. A new model for calculation is proposed that performs equally well for all fluid compartments (total body water, extra- and intracellular water). It is suggested that the main source of error in extracellular water estimation is due to anisotropy, in total body water estimation to the uncertainty associated with intracellular resistivity and in determination of intracellular water a combination of both.

Resistivity coefficients for body composition analysis using bioimpedance spectroscopy: effects of body dominance and mixture theory algorithm.

Body composition is commonly predicted from bioelectrical impedance spectroscopy using mixture theory algorithms. Mixture theory algorithms require the input of values for the resistivities of intra-and extracellular water of body tissues. Various derivations of these algorithms have been published, individually requiring resistivity values specific for each algorithm. This study determined apparent resistivity values in 85 healthy males and 66 healthy females for each of the four published mixture theory algorithms. The resistivity coefficients determined here are compared to published values and the inter-individual (biological) variation discussed with particular reference to consequential error in prediction of body fluid volumes. In addition, the relationships between the four algorithmic approaches are derived and methods for the inter-conversion of coefficients between algorithms presented.

Slightly superior performance of bioimpedance spectroscopy over single frequency regression equations for assessment of total body water.

Electrical bioimpedance has been used for several decades to assess body fluid distribution and body composition by using single frequency and bioimpedance spectroscopic (BIS) techniques. It remains uncertain whether BIS methods have better performance compare to single frequency regression equations. In this work the performance of two BIS methods and four different 50 kHz single frequency prediction equations was studied in a data set of wrist-to-ankle tetrapolar BIS measurements (5-1000 kHz) together with reference values of total body water obtained by tritium dilution in 92 patients. Data were compared using regression techniques and Bland-Altman plots. The results of this study showed that all methods produced similarly high correlation and concordance coefficients, indicating good accuracy as a method. Limits of agreement analysis indicated that the population level performance of Sun's prediction equations was very similar to the performance of both BIS methods. However, BIS methods in practice have slightly better predictive performance than the single-frequency equations as judged by higher correlation and the limits of agreement from the Bland-Altman analysis. In any case, the authors believe that an accurate evaluation of performance of the methods cannot be done as long as the evaluation is done using Bland-Altman analysis, the commonly accepted technique for this kind of performance comparisons.

Segmental Impedance Thresholds for Early Detection of Unilateral Upper Limb Swelling.

BACKGROUND: Detection of early lymphedema is important for effective treatment outcome and reduction of disease burden. The aims of this study were to determine normal inter-limb variance in the hand and four segments of the arm using bioimpedance spectroscopy (BIS) to provide diagnostic thresholds for detection of early lymphedema development, to determine the intra-rater reliability of these measurements, and to compare the inter-limb BIS ratios to differences based on arm circumference measures. METHODS AND RESULTS: One hundred women, aged 49.1 (SD 13.8) years without history of breast cancer or lymphedema participated. Impedance measures for the hand and four 10 cm length arm segments were used to determine the inter-limb segment BIS ratios. Circumference difference and segment volumes were calculated from circumference measures obtained with a tape measure. A subgroup of women was measured on two occasions, one week apart. Thresholds were determined for the dominant and nondominant limb, based on two and three standard deviations (SD) above the mean. The 2SD and 3SD thresholds for the dominant arm ranged from 1.121 to 1.150 and 1.172 to 1.209, respectively, and for the nondominant limb ranged from 1.057 to 1.107 and 1.103 to 1.169, respectively. Intra-rater reliability was high (ICC: 0.945-0.983). BIS ratio and circumference-based measures did not identify the same segments as being over threshold. CONCLUSIONS: BIS diagnostic thresholds for the hand and four segments of the arm, based on normative data, taking into consideration arm dominance have been developed. Segmental BIS has been shown to be highly reliable.

Development of a single-frequency bioimpedance prediction equation for fat-free mass in an adult Indigenous Australian population.

BACKGROUND/OBJECTIVES: To describe the development of a single-frequency bioimpedance prediction equation for fat-free mass (FFM) suitable for adult Aboriginal and Torres Strait Islander peoples with and without diabetes or indicators of chronic kidney disease (CKD). SUBJECTS/METHODS: FFM was measured by whole-body dual-energy X-ray absorptiometry in 147 adult Indigenous Australians. Height, weight, body circumference and resistance were also measured. Adults with and without diabetes and indicators of CKD were examined. A random split sample with internal cross-validation approach was used to predict and subsequently validate FFM using resistance, height, weight, age and gender against measured FFM. RESULTS: Among 147 adults with a median body mass index of 31 kg/m(2), the final model of FFM was FFM (kg)=0.432 (height, cm(2)/resistance, ohm)-0.086 (age, years)+0.269 (weight, kg)-6.422 (if female)+16.429. Adjusted R(2) was 0.94 and the root mean square error was 3.33 kg. The concordance was high (rc=0.97) between measured and predicted FFM across a wide range of FFM (31-85 kg). CONCLUSIONS: In the context of the high burden of diabetes and CKD among adult Indigenous Australians, this new equation for FFM was both accurate and precise and based on easily acquired variables (height, weight, age, gender and resistance) among a heterogeneous adult cohort.

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.

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.

KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study.

BACKGROUND: Inhibitors of the epidermal growth factor (EGFR) signaling pathway have a major role in the treatment of KRAS wild-type colorectal cancer patients. The EGFR pathway has been shown to be activated in gastric cancer (GC). However, published data on KRAS and BRAF mutation status is limited in GC and has not been compared between GC from different geographic regions. METHODS: The prevalence of KRAS and BRAF mutations was established in 712 GC: 278 GC from the United Kingdom, 230 GC from Japan and 204 GC from Singapore. The relationship between KRAS/BRAF mutation status, DNA mismatch repair (MMR) status, clinicopathological variables and overall survival was analysed. RESULTS: Overall, 30 (4.2%) GC carried a KRAS mutation. In total, 5.8% of the UK GC, 4% of Japan GC and 1.5% of Singapore GC were KRAS mutant. KRAS mutant GC had fewer lymph node metastases in the UK cohort (P=0.005) and were more frequent in elderly patients in the Japan cohort (P=0.034). KRAS mutations were more frequent in MMR-deficient GC in the UK and the Japanese cohort (P<0.05). A BRAF mutation was only detected in a single Japanese GC. CONCLUSIONS: This large multicentre study demonstrated that KRAS mutations and DNA MMR deficiency have a role in a small subgroup of GC irrespective of country of origin, suggesting that this subgroup of GC may have developed along a common pathway. Further studies need to establish whether concomitant mutations or amplifications of other EGFR signalling pathway genes may contribute to the activation of this pathway in GC.