Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer

Background: Marking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node-positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment-positive marked lymph nodes (MLNs) together with SLNs. Methods: This was a multicentre retrospective analysis of patients with clinically node-positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately. Results: At least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent). Conclusion: Excision of the pretreatment-positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node-positive disease resulted in a higher identification rate and improved detection of residual axillary disease

LysoPC-acyl C16:0 is associated with brown adipose tissue activity in men.

INTRODUCTION: Brown adipose tissue (BAT) recently emerged as a potential therapeutic target in the treatment of obesity and associated disorders due to its fat-burning capacity. The current gold standard in assessing BAT activity is [(18)F]FDG PET-CT scan, which has severe limitations including radiation exposure, being expensive, and being labor-intensive. Therefore, indirect markers are needed of human BAT activity and volume. OBJECTIVE: We aimed to identify metabolites in serum that are associated with BAT volume and activity in men. METHODS: We assessed 163 metabolites in fasted serum of a cohort of twenty-two healthy lean men (age 24.1 (21.7-26.6) years, BMI 22.1 (20.5-23.4) kg/m(2)) who subsequently underwent a cold-induced [(18)F]FDG PET-CT scan to assess BAT volume and activity. In addition, we included three replication cohorts consisting of in total thirty-seven healthy lean men that were similar with respect to age and BMI compared to the discovery cohort. RESULTS: After correction for multiple testing, fasting concentrations of lysophosphatidylcholine-acyl (LysoPC-acyl) C16:1, LysoPC-acyl C16:0 and phosphatidylcholine-diacyl C32:1 showed strong positive correlations with BAT volume (β= 116 (85-148) mL, R(2) = 0.81, p = 4.6 × 10(-7); β = 79 (93-119) mL, R(2) = 0.57, p = 5.9 × 10(-4) and β= 91 (40-141) mL, R(2) = 0.52, p = 1.0 × 10(-3), respectively) as well as with BAT activity (β= 0.20 (0.11-0.29) g/mL, R(2) = 0.59, p = 1.9 × 10(-4); β = 0.15 (0.06-0.23) g/mL, R(2) = 0.47, p = 2.0 × 10(-3) and β= 0.13 (0.01-0.25) g/mL, R(2) = 0.28, p = 0.04, respectively). When tested in three independent replication cohorts (total n = 37), the association remained significant between LysoPC-acyl C16:0 and BAT activity in a pooled analysis (β= 0.15 (0.07-0.23) g/mL, R(2) = 0.08, p = 4.2 × 10(-4)). CONCLUSIONS: LysoPC-acyl C16:0 is associated with BAT activity in men. Since BAT is regarded as a promising tool in the battle against obesity and related disorders, the identification of such a noninvasive marker is highly relevant

Brown adipose tissue volume in healthy lean south Asian adults compared with white Caucasians: A prospective, case-controlled observational study

Background: Individuals of south Asian origin have a very high risk of developing type 2 diabetes compared with white Caucasians. We aimed to assess volume and activity of brown adipose tissue (BAT), which is thought to have a role in energy metabolism by combusting fatty acids and glucose to produce heat and might contribute to the difference in incidence of type 2 diabetes between ethnic groups. Methods: We enrolled Dutch nationals with south Asian ancestry and matched Caucasian participants at The Rijnland Hospital (Leiderdorp, Netherlands). Eligible participants were healthy lean men aged 18-28 years, and we matched groups for BMI. We measured BAT volume and activity with cold-induced 18F-fluorodeoxyglucose (18F-FDG) PET CT scans, and assessed resting energy expenditure, non-shivering thermogenesis, and serum parameters. This study is registered with the Netherlands Trial Register, number 2473. Findings: Between March 1, 2013, and June 1, 2013, we enrolled 12 participants in each group; one Caucasian participant developed hyperventilation after 18F-FDG administration, and was excluded from all cold-induced and BAT measurements. Compared with Caucasian participants, south Asian participants did not differ in age (mean 23·6 years [SD 2·8] for south Asians vs 24·6 years [2·8] for Caucasians) or BMI (21·5 kg/m2 [2·0] vs 22·0 kg/m2 [1·6]), but were shorter (1·74 m [0·06] vs 1·85 m [0·04]) and lighter (65·0 kg [8·5] vs 75·1 kg [7·2]). Thermoneutral resting energy expenditure was 1297 kcal per day (SD 123) in south Asian participants compared with 1689 kcal per day (193) in white Caucasian participants (difference -32%, p=0·0008). On cold exposure, shiver temperature of south Asians was 2·0°C higher than Caucasians (p=0·0067) and non-shivering thermogenesis was increased by 20% in white Caucasians (p<0·0001) but was not increased in south Asians. Although the maximum and mean standardised uptake values of 18F-FDG in BAT did not differ between groups, total BAT volume was lower in south Asians (188 mL [SD 81]) than it was in Caucasians (287 mL [169]; difference -34%, p=0·04). Overall, BAT volume correlated positively with basal resting energy expenditure in all assessable individuals (β=0·44, p=0·04). Interpretation: Lower resting energy expenditure, non-shivering thermogenesis, and BAT volumes in south Asian populations might underlie their high susceptibility to metabolic disturbances, such as obesity and type 2 diabetes. Development of strategies to increase BAT volume and activity might help prevent and treat such disorders, particularly in south Asian individuals. © 2014 Elsevier Ltd. Chemicals/CAS: fluorodeoxyglucose f 18, 63503-12-8; glucose, 50-99-7, 84778-64-