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1.
Vitamin D (25-0H D3) status and pathological response to neoadjuvant chemotherapy in stage II/III breast cancer: Data from the NEOZOTAC trial (BOOG 10-01).
Charehbili, A, Hamdy, NA, Smit, VT, Kessels, L, van Bochove, A, van Laarhoven, HW, Putter, H, Meershoek-Klein Kranenbarg, E, van Leeuwen-Stok, AE, van der Hoeven, JJ, et al
Breast (Edinburgh, Scotland). 2016;:69-74
Abstract
BACKGROUND Serum levels of 25-OH vitamin D3 (vitamin D) have been shown to be prognostic for disease-free survival in patients with breast cancer. We investigated the predictive value of these levels for pathological response after neoadjuvant chemotherapy in patients with breast cancer taking part in the NEOZOTAC phase-III trial. Additionally, the effect of chemotherapy on vitamin D levels was studied. MATERIALS AND METHODS Serum vitamin D was measured at baseline and before the last cycle of chemotherapy. The relationship between these measurements and clinical outcome, as defined by pathological complete response in breast and lymph nodes (pCR) was examined. RESULTS Baseline and end of treatment vitamin D data were available in 169 and 91 patients, respectively. Median baseline vitamin D values were 58.0 nmol/L. In patients treated with chemotherapy only, serum vitamin D levels decreased during neoadjuvant chemotherapy (median decrease of 16 nmol/L, P = 0.003). The prevalence of vitamin D levels < 50 nmol/L increased from 38.3% at baseline to 55.9% after chemotherapy. In the total population, baseline and end of therapy vitamin D levels were not related to pathological response. No associations were found between pCR and vitamin D level changes. CONCLUSION The significant decrease in vitamin D post-neoadjuvant chemotherapy suggests that vitamin D levels should be monitored and in case of decrease of vitamin D levels, correction may be beneficial for skeletal health and possibly breast cancer outcome.
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2.
The Central-European SentiMag study: sentinel lymph node biopsy with superparamagnetic iron oxide (SPIO) vs. radioisotope.
Thill, M, Kurylcio, A, Welter, R, van Haasteren, V, Grosse, B, Berclaz, G, Polkowski, W, Hauser, N
Breast (Edinburgh, Scotland). 2014;(2):175-9
Abstract
Sentinel lymph node biopsy (SLNB) is the standard surgical procedure for the axilla in early node-negative breast cancer. To date, the "gold standard" to localize the sentinel lymph node (SLN) is the radiotracer (99m)Tc with or without blue dye. The aim of this study was to evaluate potential equivalency of the new SentiMag(®) technique in comparison to the "gold standard". Within this prospective, multicentric and multinational non-inferiority study including 150 patients (99m)Tc was compared with the magnetic technique, using superparamagnetic iron oxide particles (SPIOs, Sienna+(®)) for localization of SLNs. The results showed a detection rate per patient of 97.3% (146/150) for (99m)Tc vs. 98.0% (147/150) for Sienna+(®) with a similar average number of removed SLNs per patient and a higher per patient malignancy detection rate for the SPIO tracer. We obtained convincing results that magnetic SLNB can be performed easily, safely and equivalently well in comparison to the radiotracer method.
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3.
Viability of lymph node samples obtained by echobronchoscopy in the study of epigenetic alterations in patients with lung cancer.
Leiro-Fernández, V, De Chiara, L, Botana-Rial, M, González-Piñeiro, A, Tardio-Baiges, A, Núñez-Delgado, M, Valverde Pérez, D, Fernández-Villar, A
Archivos de bronconeumologia. 2014;(6):213-20
Abstract
INTRODUCTION The diagnosis of microscopic lymph node metastasis in lung cancer is challenging despite the constant advances in tumor staging. The analysis of the methylation status of certain genes in lymph node samples could improve the diagnostic capability of conventional cyto-histological methods. The aim of this study was to demonstrate the feasibility of methylation studies using cytological lymph node samples. METHODS Prospective study including 88 patients with a diagnosis or strong suspicion of non-small cell lung cancer, in which an echobronchoscopy was performed on mediastinal or hilar lymph nodes for diagnostic and/or staging. DNA was extracted from cytological lymph node samples and sodium bisulfite modification was performed. Methylation studies for p16/INK4a and SHOX2 were accomplished by MS-qPCR and pyrosequencing. RESULTS The methodology used in our study yielded optimal/good DNA quality in 90% of the cases. No differences in DNA concentration were observed with respect to the lymph node biopsied and final diagnosis. Methylation analyses using MS-qPCR and pyrosequencing were not possible in a small number of samples mainly due to low DNA concentration, inadequate purity, fragmentation and/or degradation as a consequence of bisulfite conversion. CONCLUSION Methylation quantification using MS-qPCR and pyrosequencing of cytological lymph node samples obtained using echobronchoscopy is feasible if an appropriate DNA concentration is obtained, notably contributing to the identification of epigenetic biomarkers capable of improving decision-making for the benefit of potentially curable lung cancer patients.
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4.
Pre-operative prediction of cervical nodal metastasis in papillary thyroid cancer by 99mTc-MIBI SPECT/CT; a pilot study.
Tangjaturonrasme, N, Vasavid, P, Sombuntham, P, Keelawat, S
Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2013;(6):696-702
Abstract
OBJECTIVE Papillary thyroid cancer has a high prevalence of cervical nodal metastasis. There is no "gold standard" imaging for pre-operative diagnosis. The aim of the present study was to assess the accuracy of pre-operative 99mTc-MBI SPECT/CT in diagnosis of cervical nodal metastasis in patients with papillary thyroid cancer MATERIAL AND METHOD Fifteen patients were performed 99Tc-MlBI SPECT/CT pre-operatively. Either positive pathological report of neck dissection or positive post-treatment I-131 whole body scan with SPECT/CT of neck was concluded for definite neck metastasis. The PPV, NPV, and accuracy of 99mTc-MIBI SPECT/CT were analyzed. RESULTS The PPV NPV and accuracy were 80%, 88.89%, and 85.71%, respectively. 99mTc-MIBI SPECT/CT could localize the abnormal lymph nodes groups correctly in most cases when compared with pathological results. However the authors found one false positive case with caseating granulomatous lymphadenitis and one false negative case with positive post-treatment 1-131 whole body scan with SPECT/CT of neck on cervical nodes zone II and IV CONCLUSION 99mTc-MIBI SPECT/CTseem promising for pre-operative staging of cervical nodal involvement in patients with papillary thyroid cancer without the need of using iodinated contrast that may complicate subsequence 1-131 treatment. However, false positive result in granulomatous inflammatory nodes should be aware of especially in endemic areas. 99mTc-MIBI SPECT/CT scan shows a good result when compared with previous study of CT or MRI imaging. The comparative study between different imaging modality and the extension of neck dissection according to MIBI result seems interesting.
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5.
Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging facilitates detection of metastases in normal-sized pelvic lymph nodes of patients with bladder and prostate cancer.
Birkhäuser, FD, Studer, UE, Froehlich, JM, Triantafyllou, M, Bains, LJ, Petralia, G, Vermathen, P, Fleischmann, A, Thoeny, HC
European urology. 2013;(6):953-60
Abstract
BACKGROUND Conventional cross-sectional imaging with computed tomography and magnetic resonance imaging (MRI) has limited accuracy for lymph node (LN) staging in bladder and prostate cancer patients. OBJECTIVE To prospectively assess the diagnostic accuracy of combined ultrasmall superparamagnetic particles of iron oxide (USPIO) MRI and diffusion-weighted (DW) MRI in staging of normal-sized pelvic LNs in bladder and/or prostate cancer patients. DESIGN, SETTING, AND PARTICIPANTS Examinations with 3-Tesla MRI 24-36 h after administration of USPIO using conventional MRI sequences combined with DW-MRI (USPIO-DW-MRI) were performed in 75 patients with clinically localised bladder and/or prostate cancer staged previously as N0 by conventional cross-sectional imaging. Combined USPIO-DW-MRI findings were analysed by three independent readers and correlated with histopathologic LN findings after extended pelvic LN dissection (PLND) and resection of primary tumours. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Sensitivity and specificity for LN status of combined USPIO-DW-MRI versus histopathologic findings were evaluated per patient (primary end point) and per pelvic side (secondary end point). Time required for combined USPIO-DW-MRI reading was assessed. RESULTS AND LIMITATIONS At histopathologic analysis, 2993 LNs (median: 39 LNs; range: 17-68 LNs per patient) with 54 LN metastases (1.8%) were found in 20 of 75 (27%) patients. Per-patient sensitivity and specificity for detection of LN metastases by the three readers ranged from 65% to 75% and 93% to 96%, respectively; sensitivity and specificity per pelvic side ranged from 58% to 67% and 94% to 97%, respectively. Median reading time for the combined USPIO-DW-MRI images was 9 min (range: 3-26 min). A potential limitation is the absence of a node-to-node correlation of combined USPIO-DW-MRI and histopathologic analysis. CONCLUSIONS Combined USPIO-DW-MRI improves detection of metastases in normal-sized pelvic LNs of bladder and/or prostate cancer patients in a short reading time.
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6.
Clinical relevance of positron emission tomography/computed tomography-positive inguinal nodes in rectal cancer after neoadjuvant chemoradiation.
Perez, RO, Habr-Gama, A, São Julião, GP, Proscurshim, I, Ono, CR, Lynn, P, Bailão Aguilar, P, Nahas, SC, Gama-Rodrigues, J, Buchpiguel, CA
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. 2013;(6):674-82
Abstract
AIM: Inguinal nodes may be a possible route for lymphatic spread in patients with distal rectal cancer. The outcome was examined for patients with distal rectal cancer undergoing neoadjuvant chemoradiation (CRT) and having 2-fluorine-18-fluoro-2-deoxy-d-glucose (FDG)-avid inguinal nodes using positron emission tomography/computed tomography (PET/CT) imaging. METHOD Ninety-nine consecutive patients with cT2-4N0-2M0 distal rectal adenocarcinoma were enrolled in a clinical trial (NCT00254683) and underwent baseline PET/CT followed by 54 Gy and 5-fluorouracil-based CRT. After CRT, patients underwent 6- and 12-week PET/CT. Patients with positive inguinal node uptake were compared with patients with negative uptake. The inguinal region was not included in the field of radiation therapy. RESULTS Seventeen (17%) patients had baseline positive inguinal node FDG uptake. They were more likely to have the tumour closer to the anal verge (2.0 vs 4.2 cm; P = 0.001). Of these, eight (47%) demonstrated a positive inguinal uptake at PET/CT after 12 weeks from CRT. Patients with inguinal node FDG uptake after CRT (positive PET at baseline and 12 weeks) had a significantly worse 3-year overall and disease-free survival (P = 0.02 and P = 0.03). After a median follow-up period of 22 months, none of these patients had developed inguinal recurrence. CONCLUSION Uptake of inguinal nodes at PET/CT may be present in up to 17% of patients with distal rectal cancer, particularly with ultra-low tumours. Nearly half of these nodes no longer show uptake after CRT despite the groin area not being included in the radiation field. Persistence of inguinal node uptake 12 weeks after CRT completion may be a marker for worse oncological outcome.
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7.
Application of MR mammography beyond local staging: is there a potential to accurately assess axillary lymph nodes? evaluation of an extended protocol in an initial prospective study.
Baltzer, PA, Dietzel, M, Burmeister, HP, Zoubi, R, Gajda, M, Camara, O, Kaiser, WA
AJR. American journal of roentgenology. 2011;(5):W641-7
Abstract
OBJECTIVE The purpose of our study was to clinically test an extended MR mammography (MRM) protocol for combined local staging (T-staging) and locoregional staging (N-staging) of breast cancer within one single examination using a dedicated whole-body scanner. SUBJECTS AND METHODS Fifty-six consecutive primary breast cancer patients without prior treatment underwent MRM and surgicopathological N-staging. The MRM protocol (10 minutes; axial T1-weighted gradient-recalled echo; dynamic contrast-enhanced; T2-weighted; turbo spin-echo) was extended to evaluate axillary lymph nodes (90 seconds; coronal T2-weighted HASTE; T1-weighted volumetric breath-hold examination; field of view, both axillae, supraclavicular nodes, and cervical nodes). A dedicated whole-body scanner was used. First, two experienced radiologists independently rated the presence of lymph node metastasis (present or absent, weighted kappa). Second, predefined descriptors were applied by both readers to differentiate lymph node status. These were statistically analyzed using univariate chi-square statistics, sensitivity and specificity, positive likelihood ratio, diagnostic odds ratio (OR), and multivariate statistics (binary logistic-regression, receiver operating characteristics, and chi-squared automatic interaction detection [CHAID] tree). RESULTS Most significant predictors (p < 0.001) of present metastasis were "irregular margin" (diagnostic OR, 14.0), "inhomogeneous cortex" (diagnostic OR, 8.4), "perifocal edema" (positive likelihood ratio, 100) and "asymmetry" (diagnostic OR, 19.5). CHAID tree identified "asymmetry" and "irregular margin" as significant predictors (adjusted-p < 0.05) for present metastasis (PPV: 100%), whereas absence of "asymmetry" and "homogeneous internal structure" were highly predictive of absent metastasis (negative predictive value, 94.3%). Combination of significant descriptors using binary logistic regression revealed an area under the receiver operating characteristic curve of 0.93 (p < 0.001). Interrater agreement was "almost-perfect" (κ = 0.95). CONCLUSION Combined T-staging and locoregional staging (N-staging) was possible within one imaging session using the proposed protocol. Despite a minimal increase in examination time, high diagnostic accuracy and excellent interrater reliability were achieved.
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8.
High-resolution MR lymphography using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in patients with early stage breast cancer: preliminary results.
Kimura, K, Tanigawa, N, Matsuki, M, Nohara, T, Iwamoto, M, Sumiyoshi, K, Tanaka, S, Takahashi, Y, Narumi, Y
Breast cancer (Tokyo, Japan). 2010;(4):241-6
Abstract
BACKGROUND The purpose of this study was to examine the utility of high-resolution magnetic resonance (MR) lymphography using ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation of axillary lymph nodes in patients with early stage breast cancer. METHODS Ten women with breast cancer without swollen axillary lymph nodes were enrolled in this study. High-resolution MR lymphography was performed 24 h after administration of USPIO. On the MR examination, a 3-inch surface coil was placed on the sentinel lymph node (SLN) parts as defined by a radioisotope (RI) scintigraphy method, and T2*-weighted (T2*W) and T1-weighted (T1W) images were obtained. Detected nodes were differentiated as normal or diseased nodes by the enhancement patterns. The day after MR examination, SLN biopsy (SNB) was performed. The imaging results were compared to the histopathologic findings. RESULTS On MR images, the mean number of detectable nodes was 7.9 per patient. Eight patients who histopathologically had no metastatic lymph nodes were diagnosed as nonmetastatic and two patients who had 3- and 6-mm metastatic areas in the node, respectively, were diagnosed as metastatic preoperatively. No side effects were noted. CONCLUSIONS High-resolution MR lymphography using USPIO enabled us to obtain good axillary lymph node evaluation results. These results suggest that this method of imaging may contribute to better preoperative lymph node staging.
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9.
Sentinel lymph node identification in breast cancer: a comparison study of deep versus superficial injection of radiopharmaceutical.
Clímaco, F, Coelho-Oliveira, A, Djahjah, MC, Gutfilen, B, Correia, AH, Noé, R, da Fonseca, LM
Nuclear medicine communications. 2009;(7):525-32
Abstract
OBJECTIVES Sentinel lymph node biopsy (SLNB) has been performed for purposes of disease staging. SLN is usually located in the axillary region and internal mammary chain (IMC). Metastasis in internal mammary nodes can be an important prognostic factor and an indication for systemic treatment in patients with small carcinomas. The SLNB technique continues to evolve and the proper radiopharmaceutical injection route remains under discussion. This study evaluated the success rate of deep injection to identify axillary and extra-axillary SLNs and compared the results with superficial injection technique. METHODS Forty-six patients diagnosed with breast cancer (stages I and II) were submitted to radiopharmaceutical injection. Deep injection of technetium-99m-dextran 500 was carried out in 20 patients (group A) and periareolar injection of technetium-99m-phytate was carried out in 26 patients (group B). All SLNs were studied by imprint cytology and hematoxylin and eosin staining. RESULTS SLN identification rate was 76.1% (35 of 46). The SLN identification rate was 75% (15 of 20) for group A and 76.9% (20 of 26) for group B. Axillary SLNs were identified in 65% (13 of 20) of group A and 76.9% (20 of 26) of group B, with no statistical difference (P = 0.75). Extra-axillary SLNs were only identified in group A, and IMC was the principal extra-axillary location. CONCLUSION Deep injection of radiopharmaceutical achieved a good SLN identification rate in axillary and extra-axillary locations and it is an important method for detecting IMC sentinel nodes.
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10.
Metabolic fingerprinting of fresh lymphoma samples used to discriminate between follicular and diffuse large B-cell lymphomas.
Barba, I, Sanz, C, Barbera, A, Tapia, G, Mate, JL, Garcia-Dorado, D, Ribera, JM, Oriol, A
Experimental hematology. 2009;(11):1259-65
Abstract
OBJECTIVE To investigate if proton nuclear magnetic resonance ((1)H NMR) spectroscopy-based metabolic profiling was able to differentiate follicular lymphoma (FL) from diffuse large B-cell lymphoma (DLBCL) and to study which metabolites were responsible for the differences. MATERIALS AND METHODS High-resolution (1)H NMR spectra was obtained from fresh samples of lymph node biopsies obtained consecutively at one center (14 FL and 17 DLBCL). Spectra were processed using pattern-recognition methods. RESULTS Discriminant models were able to differentiate between the two tumor types with a 86% sensitivity and a 76% specificity; the metabolites that most contributed to the discrimination were a relative increase of alanine in the case of DLBCL and a relative increase of taurine in FL. Metabolic models had a significant but weak correlation with Ki67 expression (r(2)=0.42; p=0.002) CONCLUSIONS We have proved that it is possible to differentiate between FL and DLBCL based on their NMR metabolic profiles. This approach may potentially be applicable as a noninvasive tool for diagnostic and treatment follow-up in the clinical setting using conventional magnetic resonance systems.