Clinical impact of molecular breast imaging as adjunct diagnostic modality in evaluation of indeterminate breast abnormalities and unresolved diagnostic concerns

Purpose Improvements in molecular breast imaging (MBI) have increased the use of MBI as adjunct diagnostic modality and alternative to MRI. We aimed to assess the value of MBI in patients with equivocal breast lesions on conventional imaging, especially in terms of its ability to rule out malignancy. Methods We selected patients who underwent MBI in addition to conventional diagnostics due to equivocal breast lesions between 2012 and 2015. All patients underwent digital mammography, target ultrasound and MBI. MBI was performed using a single-head Dilon 6800 gamma camera after administration of 600 MBq 99mTc-sestamibi. Imaging was reported according to BI-RADS classification and compared with pathology or follow-up of ≥6 months. Results Of 226 women included, pathology was obtained in 106 (47%) and (pre)malignant lesions were found in 25 (11%). Median follow-up was 5.4 years (IQR 3.9-7.1). Sensitivity was higher for MBI compared to conventional diagnostics (84% vs. 32%; P = 0.002), identifying malignancy in 21 and 6 patients, respectively, but specificity did not differ (86% vs. 81%; P = 0.161). Positive and negative predictive value were 43% and 98% for MBI and 17% and 91% for conventional diagnostics. MBI was discordant with conventional diagnostics in 68 (30%) patients and correctly changed diagnosis in 46 (20%) patients, identifying 15 malignant lesions. In subgroups with nipple discharge (N = 42) and BI-RADS 3 lesions (N = 113) MBI detected 7 of 8 occult malignancies. Conclusion MBI correctly adjusted treatment in 20% of patients with diagnostic concerns after conventional work-up, and could rule out malignancy with a high negative predictive value of 98%.</p

The impact of using BARCIST 1.0 criteria on quantification of BAT volume and activity in three independent cohorts of adults

Human brown adipose tissue (BAT) is commonly assessed by cold-induced 18F-fluorodeoxyglucose (FDG) PET-CT using several quantification criteria. Uniform criteria for data analysis became available recently (BARCIST 1.0). We compared BAT volume and activity following BARCIST 1.0 criteria against the most commonly used criteria [Hounsfield Units (HU):-250, -50, standardized uptake value (SUV):2.0; HU: Not applied, SUV:2.0 and HU:-180, -10, SUV:1.5] in a prospective study using three independent cohorts of men including young lean adults, young overweight/obese adults and middle-aged overweight/obese adults. BAT volume was the most variable outcome between criteria. While BAT volume calculated using the HU: NA; SUV: 2.0 criteria was up to 207% higher than the BAT volume calculated based on BARCIST 1.0 criteria, it was up to 57% lower using the HU: -250, -50; SUV: 2.0 criteria compared to the BARCIST 1.0. Similarly, BAT activity (expressed as SUVmean) also differed between different thresholds mainly because SUVmean depends on BAT volume. SUVpeak was the most consistent BAT outcome across the four study criteria. Of note, we replicated these findings in three independent cohorts. In conclusion, BAT volume and activity as determined by 18F-FDG-PET/CT highly depend on the quantification criteria used. Future human BAT studies should conduct sensitivity analysis with different thresholds in order to understand whether results are driven by the selected HU and/or SUV thresholds. The design of the present study precludes providing any conclusive threshold, but before more definitive thresholds for HU and SUV are available, we support the use of BARCIST 1.0 criteria to facilitate interpretation of BAT characteristics between research groups

Effect of sitagliptin on energy metabolism and brown adipose tissue in overweight individuals with prediabetes:a randomised placebo-controlled trial

Aims/hypothesis: The aim of this study was to evaluate the effect of sitagliptin on glucose tolerance, plasma lipids, energy expenditure and metabolism of brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle in overweight individuals with prediabetes (impaired glucose tolerance and/or impaired fasting glucose). Methods: We performed a randomised, double-blinded, placebo-controlled trial in 30 overweight, Europid men (age 45.9 \xc2\xb1 6.2\xc2\xa0years; BMI 28.8 \xc2\xb1 2.3\xc2\xa0kg/m2) with prediabetes in the Leiden University Medical Center and the Alrijne Hospital between March 2015 and September 2016. Participants were initially randomly allocated to receive sitagliptin (100\xc2\xa0mg/day) (n = 15) or placebo (n = 15) for 12\xc2\xa0weeks, using a randomisation list that was set up by an unblinded pharmacist. All people involved in the study as well as participants were blinded to group assignment. Two participants withdrew from the study prior to completion (both in the sitagliptin group) and were subsequently replaced with two new participants that were allocated to the same treatment. Before and after treatment, fasting venous blood samples and skeletal muscle biopsies were obtained, OGTT was performed and body composition, resting energy expenditure and [18F] fluorodeoxyglucose ([18F]FDG) uptake by metabolic tissues were assessed. The primary study endpoint was the effect of sitagliptin on BAT volume and activity. Results: One participant from the sitagliptin group was excluded from analysis, due to a distribution error, leaving 29 participants for further analysis. Sitagliptin, but not placebo, lowered glucose excursion (\xe2\x88\x9240%; p < 0.003) during OGTT, accompanied by an improved insulinogenic index (+38%; p < 0.003) and oral disposition index (+44%; p < 0.003). In addition, sitagliptin lowered serum concentrations of triacylglycerol (\xe2\x88\x9229%) and very large (\xe2\x88\x9246%), large (\xe2\x88\x9235%) and medium-sized (\xe2\x88\x9224%) VLDL particles (all p < 0.05). Body weight, body composition and energy expenditure did not change. In skeletal muscle, sitagliptin increased mRNA expression of PGC1\xce\xb2 (also known as PPARGC1B) (+117%; p < 0.05), a main controller of mitochondrial oxidative energy metabolism. Although the primary endpoint of change in BAT volume and activity was not met, sitagliptin increased [18F] FDG uptake in subcutaneous WAT (sWAT; +53%; p < 0.05). Reported side effects were mild and transient and not necessarily related to the treatment. Conclusions/interpretation: Twelve weeks of sitagliptin in overweight, Europid men with prediabetes improves glucose tolerance and lipid metabolism, as related to increased [18F] FDG uptake by sWAT, rather than BAT, and upregulation of the mitochondrial gene PGC1\xce\xb2 in skeletal muscle. Studies on the effect of sitagliptin on preventing or delaying the progression of prediabetes into type 2 diabetes are warranted. Trial registration: ClinicalTrials.gov NCT02294084. Funding: This study was funded by Merck Sharp & Dohme Corp, Dutch Heart Foundation, Dutch Diabetes Research Foundation, Ministry of Economic Affairs and the University of Granada

Changes in Avidity and Level of Immunoglobulin G Antibodies to Mycobacterium tuberculosis in Sera of Patients Undergoing Treatment for Pulmonary Tuberculosis

Much is known about specific antibodies and their titers in patients with tuberculosis. However, little is known about the avidity of these antibodies or whether changes in avidity occur during the progression of the disease or during treatment. The aims of this study were to determine the avidity of antibodies to Mycobacterium tuberculosis in patients with pulmonary tuberculosis, to explore the value of avidity determination for the diagnosis of tuberculosis, and to study changes in levels of antibodies and their avidity during treatment. Antibody avidity was measured by an enzyme-linked immunosorbent assay with thiocyanate elution. Avidity indices and serum levels of immunoglobulin G to M. tuberculosis were determined for 22 patients with pulmonary tuberculosis before and during treatment and for 24 patients with other pulmonary diseases. Antibody levels and avidity were both significantly higher in untreated tuberculosis patients than in the controls. Avidity determination had more diagnostic potential than determination of the antibody levels. Tuberculosis patients with a long duration of symptoms had higher antibody avidity than those with a recent onset of symptoms, indicating affinity maturation of specific antibodies during active disease. In the early phase of treatment, a decrease in antibody avidity was observed for 73% of all tuberculosis patients, accompanied by an initial increase in antibody levels in 36% of these patients. These phenomena could be explained by an intense stimulation of the humoral response by antigens released from killed bacteria, reflecting early bactericidal activity of antituberculous drugs leading to the production of low-affinity antibodies against these released antigens

Is Technetium-99m Sestamibi Imaging Able to Predict Pathologic Nonresponse to Neoadjuvant Chemotherapy in Breast Cancer?: A Meta-analysis Evaluating Current Use and Shortcomings

Background: Interest in technetium-99m (99mTc)-sestamibi imaging for neoadjuvant chemotherapy (NAC) response monitoring in locally advanced breast cancer (LABC) is increasing but remains matter of discussion. The present study conducted a meta-analysis of the diagnostic performance of 99mTc-sestamibi to predict pathologic nonresponse to NAC for primary LABC. Materials and Methods: A systematic data search was performed. Studies with a minimum of 10 LABC patients that had evaluated 99mTc-sestamibi imaging for NAC nonresponse using conventional planar scintimammography, breast-specific γ-imaging, and/or single photon emission computed tomography/computed tomography (SPECT/CT) were included. The histopathologic findings were the reference standard. The meta-analysis was performed using a mixed logistic regression model. Results: The search revealed 14 eligible studies with 529 patients. Of the 14 studies, 11 had evaluated scintimammography and 3 breast-specific γ-imaging. No studies examining SPECT or SPECT/CT were found. The overall estimated pooled sensitivity, specificity, and positive and negative likelihood ratios of 99mTc-sestamibi imaging to predict nonresponsiveness to NAC were 70.3% (95% confidence interval [CI], 56.5%-81.3%%), 90.1% (95% CI, 77.5%-96.0%), 7.13 (95% CI, 3.08-16.53), and 0.33 (95% CI, 0.22-0.49), respectively. Only 3 studies (107 patients) evaluated 99mTc-sestamibi imaging during NAC, reported an estimated pooled sensitivity of 87% (95% CI, 72%-100%) and specificity of 93% (95% CI, 85%-100%). Conclusion: Only planar 99mTc-sestamibi imaging has been investigated for NAC nonresponse in LABC but showed low sensitivity to predict pathologic nonresponse. However, most studies focused on the prediction of pathologic complete response after NAC. Although experience is limited, 99mTc-sestamibi uptake during NAC seems highly sensitivity for the prediction of nonresponsiveness. Features such as SPECT/CT imaging, standardized quantification, relation to tumor subtypes, and proper timing have been insufficiently evaluated and require further investigation

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The clinical impact of molecular breast imaging in women with proven invasive breast cancer scheduled for breast-conserving surgery

Purpose: To investigate the clinical utility of molecular breast imaging (MBI) in patients with proven invasive breast cancer scheduled for breast-conserving surgery (BCS). Methods: Following approval by the institutional review board and written informed consent, records of patients with newly diagnosed breast cancer scheduled for BCS who had undergone MBI for local staging in the period from March 2012 till December 2014 were retrospectively reviewed. Results: A total of 287 women (aged 30–88 years) were evaluated. MBI showed T stage migration in 26 patients (9%), with frequent detection of in situ carcinoma around the tumor. Surgical management was adjusted in 14 of these patients (54%). In 17 of 287 patients (6%), MBI revealed 21 proven additional lesions in the ipsilateral, contralateral breast or both. In 18 of these additional foci (86%), detected in 15 patients, malignancy was found. Thirteen of these 15 patients had ipsilateral cancer and 2 patients bilateral malignancy. In total, MBI revealed a larger tumor extent, additional tumor foci or both in 40 patients (14%), leading to treatment adjustment in 25 patients (9%). Conclusion: MBI seems to be a useful imaging modality with a high predictive value in revealing ipsilateral and bilateral disease not visualized by mammography and ultrasound. It may play an important role in delineating the extent of the index lesion during preoperative planning. Incorporation of MBI in the clinical work-up as an adjunct modality to mammography and ultrasound may lead to better selection of patients who could benefit from BCS