Urine based near-infrared spectroscopy analysis reveals a noninvasive and convenient diagnosis method for cancers: a pilot study.

Background: The challenges in cancer diagnosis underline the need for continued research and development of new diagnostic tools and methods. This study aims to explore an effective, noninvasive, and convenient diagnostic tool using urine based near-infrared spectroscopy (NIRS) analysis combined with machine learning algorithm. Methods: Urine samples were collected from a total of 327 participants, including 181 cancer cases and 146 healthy controls. These participants were randomly spit into train set (n = 218) and test set (n = 109). NIRS analysis (4,000 ∼10,000 cm-1) was performed for each sample in both train and test sets. Five pretreatment methods, including Savitzky-Golay (SG) smoothing, multiplicative scatter correction (MSC), baseline removal (BSL) with fitting polynomials to be used as baselines, the first derivative (DERIV1), and the second derivative (DERIV2), and combination with "scaling" and "center", were investigated. Then partial least-squares (PLS) and linear support-vector machine (SVM) classification models were established, and prediction performance was evaluated in test set. Results: NIRS had greatly overlapping in peaks, and PCA analysis failed in separation between cancers and healthy controls. In modeling with urine based NIRS data, PLS model showed its highest prediction accuracy of 0.780, with DERIV2, "scaling" and "center" pretreatment, while linear SVM displayed its best prediction accuracy of 0.844, with raw NIRS. With optimization in SVM, the prediction accuracy could improve to 0.862, when the top 262 features were involved as variables. Discussion: This pilot study combining urine based NIRS analysis and machine learning is effective and convenient that might facilitate in cancer diagnosis, encouraging further evaluation with a large-size multi-center study.

SGRT-based DIBH radiotherapy practice for right-sided breast cancer combined with RNI: A retrospective study on dosimetry and setup accuracy.

BACKGROUND: We retrospectively studied the dosimetry and setup accuracy of deep inspiration breath-hold (DIBH) radiotherapy in right-sided breast cancer patients with regional nodal irradiation (RNI) who had completed treatment based on surface-guided radiotherapy (SGRT) technology by Sentinel/Catalyst system, aiming to clarify the clinical application value and related issues. METHODS: Dosimetric indicators of four organs at risk (OARs), namely the heart, right coronary artery (RCA), right lung, and liver, were compared on the premise that the planning target volume met dose-volume prescription requirements. Meanwhile, the patients were divided into the edge of the xiphoid process (EXP), sternum middle (SM), and left breast wall (LBW) groups according to different positions of respiratory gating primary points. The CBCT setup error data of the three groups were contrasted for the treatment accuracy study, and the effects of different gating window heights on the right lung volume increases were compared among the three groups. RESULTS: Compared with free breath (FB), DIBH reduced the maximum dose of heart and RCA by 739.3 ± 571.2 cGy and 509.8 ± 403.8 cGy, respectively (p < 0.05). The liver changed the most in terms of the mean dose (916.9 ± 318.9 cGy to 281.2 ± 150.3 cGy, p < 0.05). The setup error of the EXP group in the anterior-posterior (AP) direction was 3.6 ± 4.5 mm, which is the highest among the three groups. The right lung volume increases in the EXP, SM, and LBW groups were 72.3%, 69.9%, and 67.2%, respectively (p = 0.08), and the corresponding breath-holding heights were 13.5 ± 3.7 mm, 10.3 ± 2.4 mm, and 9.6 ± 2.8 mm, respectively (p < 0.05). CONCLUSIONS: SGRT-based DIBH radiotherapy can better protect the four OARs of right-sided breast cancer patients with RNI. Different respiratory gating primary points have different setup accuracy and breath-hold height.

Prediction model for knee osteoarthritis using magnetic resonance-based radiomic features from the infrapatellar fat pad: data from the osteoarthritis initiative.

Background: The infrapatellar fat pad (IPFP) plays an important role in the incidence of knee osteoarthritis (OA). Magnetic resonance (MR) signal heterogeneity of the IPFP is related to pathologic changes. In this study, we aimed to investigate whether the IPFP radiomic features have predictive value for incident radiographic knee OA (iROA) 1 year prior to iROA diagnosis. Methods: Data used in this work were obtained from the osteoarthritis initiative (OAI). In this study, iROA was defined as a knee with a baseline Kellgren-Lawrence grade (KLG) of 0 or 1 that further progressed to KLG ≥2 during the follow-up visit. Intermediate-weighted turbo spin-echo knee MR images at the time of iROA diagnosis and 1 year prior were obtained. Five clinical characteristics-age, sex, body mass index, knee injury history, and knee surgery history-were obtained. A total of 604 knees were selected and matched (302 cases and 302 controls). A U-Net segmentation model was independently trained to automatically segment the IPFP. The prediction models were established in the training set (60%). Three main models were generated using (I) clinical characteristics; (II) radiomic features; (III) combined (clinical plus radiomic) features. Model performance was evaluated in an independent testing set (remaining 40%) using the area under the curve (AUC). Two secondary models were also generated using Hoffa-synovitis scores and clinical characteristics. Results: The comparison between the automated and manual segmentations of the IPFP achieved a Dice coefficient of 0.900 (95% CI: 0.891-0.908), which was comparable to that of experienced radiologists. The radiomic features model and the combined model yielded superior AUCs of 0.700 (95% CI: 0.630-0.763) and 0.702 (95% CI: 0.635-0.763), respectively. The DeLong test found no statistically significant difference between the receiver operating curves of the radiomic and combined models (P=0.831); however, both models outperformed the clinical model (P=0.014 and 0.004, respectively). Conclusions: Our results demonstrated that radiomic features of the IPFP are predictive of iROA 1 year prior to the diagnosis, suggesting that IPFP radiomic features can serve as an early quantitative prediction biomarker of iROA.

Two fully automated data-driven 3D whole-breast segmentation strategies in MRI for MR-based breast density using image registration and U-Net with a focus on reproducibility.

Presence of higher breast density (BD) and persistence over time are risk factors for breast cancer. A quantitatively accurate and highly reproducible BD measure that relies on precise and reproducible whole-breast segmentation is desirable. In this study, we aimed to develop a highly reproducible and accurate whole-breast segmentation algorithm for the generation of reproducible BD measures. Three datasets of volunteers from two clinical trials were included. Breast MR images were acquired on 3 T Siemens Biograph mMR, Prisma, and Skyra using 3D Cartesian six-echo GRE sequences with a fat-water separation technique. Two whole-breast segmentation strategies, utilizing image registration and 3D U-Net, were developed. Manual segmentation was performed. A task-based analysis was performed: a previously developed MR-based BD measure, MagDensity, was calculated and assessed using automated and manual segmentation. The mean squared error (MSE) and intraclass correlation coefficient (ICC) between MagDensity were evaluated using the manual segmentation as a reference. The test-retest reproducibility of MagDensity derived from different breast segmentation methods was assessed using the difference between the test and retest measures (Δ2-1), MSE, and ICC. The results showed that MagDensity derived by the registration and deep learning segmentation methods exhibited high concordance with manual segmentation, with ICCs of 0.986 (95%CI: 0.974-0.993) and 0.983 (95%CI: 0.961-0.992), respectively. For test-retest analysis, MagDensity derived using the registration algorithm achieved the smallest MSE of 0.370 and highest ICC of 0.993 (95%CI: 0.982-0.997) when compared to other segmentation methods. In conclusion, the proposed registration and deep learning whole-breast segmentation methods are accurate and reliable for estimating BD. Both methods outperformed a previously developed algorithm and manual segmentation in the test-retest assessment, with the registration exhibiting superior performance for highly reproducible BD measurements.

Preoperative prediction of lymph node metastasis using deep learning-based features.

Lymph node involvement increases the risk of breast cancer recurrence. An accurate non-invasive assessment of nodal involvement is valuable in cancer staging, surgical risk, and cost savings. Radiomics has been proposed to pre-operatively predict sentinel lymph node (SLN) status; however, radiomic models are known to be sensitive to acquisition parameters. The purpose of this study was to develop a prediction model for preoperative prediction of SLN metastasis using deep learning-based (DLB) features and compare its predictive performance to state-of-the-art radiomics. Specifically, this study aimed to compare the generalizability of radiomics vs DLB features in an independent test set with dissimilar resolution. Dynamic contrast-enhancement images from 198 patients (67 positive SLNs) were used in this study. Of these subjects, 163 had an in-plane resolution of 0.7 × 0.7 mm2, which were randomly divided into a training set (approximately 67%) and a validation set (approximately 33%). The remaining 35 subjects with a different in-plane resolution (0.78 × 0.78 mm2) were treated as independent testing set for generalizability. Two methods were employed: (1) conventional radiomics (CR), and (2) DLB features which replaced hand-curated features with pre-trained VGG-16 features. The threshold determined using the training set was applied to the independent validation and testing dataset. Same feature reduction, feature selection, model creation procedures were used for both approaches. In the validation set (same resolution as training), the DLB model outperformed the CR model (accuracy 83% vs 80%). Furthermore, in the independent testing set of the dissimilar resolution, the DLB model performed markedly better than the CR model (accuracy 77% vs 71%). The predictive performance of the DLB model outperformed the CR model for this task. More interestingly, these improvements were seen particularly in the independent testing set of dissimilar resolution. This could indicate that DLB features can ultimately result in a more generalizable model.

Optimizing the Peritumoral Region Size in Radiomics Analysis for Sentinel Lymph Node Status Prediction in Breast Cancer.

RATIONALE AND OBJECTIVES: Peritumoral features have been suggested to be useful in improving the prediction performance of radiomic models. The aim of this study is to systematically investigate the prediction performance improvement for sentinel lymph node (SLN) status in breast cancer from peritumoral features in radiomic analysis by exploring the effect of peritumoral region sizes. MATERIALS AND METHODS: This retrospective study was performed using dynamic contrast-enhanced MRI scans of 162 breast cancer patients. The effect of peritumoral features was evaluated in a radiomics pipeline for predicting SLN metastasis in breast cancer. Peritumoral regions were generated by dilating the tumor regions-of-interest (ROIs) manually annotated by two expert radiologists, with thicknesses of 2 mm, 4 mm, 6 mm, and 8 mm. The prediction models were established in the training set (∼67% of cases) using the radiomics pipeline with and without peritumoral features derived from different peritumoral thicknesses. The prediction performance was tested in an independent validation set (the remaining ∼33%). RESULTS: For this specific application, the accuracy in the validation set when using the two radiologists' ROIs could be both improved from 0.704 to 0.796 by incorporating peritumoral features. The choice of the peritumoral size could affect the level of improvement. CONCLUSION: This study systematically investigates the effect of peritumoral region sizes in radiomic analysis for prediction performance improvement. The choice of the peritumoral size is dependent on the ROI drawing and would affect the final prediction performance of radiomic models, suggesting that peritumoral features should be optimized in future radiomics studies.

A Potential Oncogenic Role for PFKFB3 Overexpression in Gastric Cancer Progression.

OBJECTIVES: PFKFB3 regulates glycolysis in tumor cells, might function as an oncogene, and is associated with cancer metastasis. However, its role in gastric cancer (GC) remains largely unknown. METHODS: PFKFB3 expression was assessed by immunohistochemistry (IHC) in GC tissues and paired paracancerous histological normal tissues (PCHNTs). The associations of PFKFB3 expression with clinical features and HIF-1α, Ki-67, E-cadherin, Snail, and Vimentin expression levels were assessed. A series of in vivo and in vitro experiments were performed to investigate the effects of PFKFB3 on the growth, migration, and invasion of GC cells. RESULTS: We found that PFKFB3 expression was significantly higher in GC tissues compared with PCHNTs (P = 0.000). PFKFB3 expression was positively correlated with tumor size (P = 0.000), differentiation (P = 0.025), venous invasion (P = 0.084), nerve invasion (P = 0.014), lymphatic invasion (P = 0.000), local invasion (P = 0.000), invasive depth (P = 0.000), nodal metastasis (P = 0.000), tumor-node-metastasis stage (P = 0.000), and patient survival (P = 0.000). Notably, PFKFB3 upregulation was highly correlated with increased epithelial-mesenchymal transition (EMT) in GC samples. PFKFB3 overexpression positively modulated cell proliferation, migration, and EMT in GC cells in vitro, with concomitant activation of NF-κB signaling. Administration of an NF-κB inhibitor attenuated PFKFB3-induced EMT in GC cells. PFKFB3 overexpression promoted tumor development and EMT in nude mice, which were attenuated by PFK-15, a PFKFB3 inhibitor. DISCUSSION: PFKFB3 could potentiate malignancy in GC cells through NF-κB pathway-mediated EMT, suggesting PFKFB3 represents a potential target for GC therapy.

Characterization of the Golgi scaffold protein PAQR3, and its role in tumor suppression and metabolic pathway compartmentalization.

The Golgi apparatus is critical in the compartmentalization of signaling cascades originating from the cytoplasmic membrane and various organelles. Scaffold proteins, such as progestin and adipoQ receptor (PAQR)3, specifically regulate this process, and have recently been identified in the Golgi apparatus. PAQR3 belongs to the PAQR family, and was recently described as a tumor suppressor. Accumulating evidence demonstrates PAQR3 is downregulated in different cancers to suppress its inhibitory effects on malignant potential. PAQR3 functions biologically through the pathological regulation of altered signaling pathways. Significant cell proliferation networks, including Ras proto-oncogene (Ras)/mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), insulin, and vascular endothelial growth factor, are closely controlled by PAQR3 for physiologically relevant effects. Meanwhile, genetic/epigenetic susceptibility and environmental factors, may have functions in the downregulation of PAQR3 in human cancers. This study aimed to assess the subcellular localization of PAQR3 and determine its topological features and functional domains, summarizing its effects on cell signaling compartmentalization. The pathophysiological functions of PAQR3 in cancer pathogenesis, metabolic diseases, and developmental ailments were also highlighted.

Polyamine synthesis enzyme AMD1 is closely associated with tumorigenesis and prognosis of human gastric cancers.

Adenosylmethionine decarboxylase 1 (AMD1) is a key enzyme involved in biosynthesis of polyamines including spermidine and spermine. The potential function of AMD1 in human gastric cancers is unknown. We analyzed AMD1 expression level in 319 human gastric cancer samples together with the adjacent normal tissues. The protein expression level of AMD1 was significantly increased in human gastric cancer samples compared with their corresponding para-cancerous histological normal tissues (P < 0.0001). The expression level of AMD1 was positively associated with Helicobactor pylori 16sRNA (P < 0.0001), tumor size (P < 0.0001), tumor differentiation (P < 0.05), tumor venous invasion (P < 0.0001), tumor lymphatic invasion (P < 0.0001), blood vessel invasion (P < 0.0001), and tumor lymph node metastasis (TNM) stage (P < 0.0001). Patients with high expression of AMD1 had a much shorter overall survival than those with normal/low expression of AMD1. Knockdown of AMD1 in human gastric cancer cells suppressed cell proliferation, colony formation and cell migration. In a tumor xenograft model, knockdown of AMD1 suppressed the tumor growth in vivo. Inhibition of AMD1 by an inhibitor SAM486A in human gastric cancer cells arrested cell cycle progression during G1-to-S transition. Collectively, our studies at the cellular, animal and human levels indicate that AMD1 has a tumorigenic effect on human gastric cancers and affect the prognosis of the patients.

Deregulation of CSMD1 targeted by microRNA-10b drives gastric cancer progression through the NF-κB pathway.

Aim: This study aimed to investigate the oncogenic activity of microRNA-10b by targeting CUB and sushi multiple domains protein 1 (CSMD1) in human gastric cancer (GC) and the underlying mechanisms. Methods: The expression of CSMD1 in human GC tissues was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemical analysis. The expressive abundance of microRNA-10b was detected by stem-loop RT-PCR. Molecular and cellular techniques, including lentiviral vector-mediated knockdown or overexpression, were used to elucidate the effect of microRNA-10b on the expression of CSMD1. Results: CSMD1 was targeted and downregulated by microRNA-10b in human GC tissues and cells, and the down-regulated expression of CSMD1 contributed to poor survival. The knockdown of microRNA-10b expression inhibited cell proliferation in GC cells in vitro and tumor growth in vivo. The inhibition of microRNA-10b expression repressed invasion and migration of HGC27 cells and retarded GC cells metastasis to the liver in Balb/c nude mice. The up-regulated expression of microRNA-10b promoted the proliferation and metastasis of MKN74 cell in vitro. Intratumoral injection of microRNA-10b mimic also promoted the growth and metastasis of tumor xenografts in Balb/c nude mice. Mechanistically, microRNA-10b promoted the invasion and metastasis of human GC cells through inhibiting the expression of CSMD1, leading to the activation of the nuclear factor-κB (NF-κB) pathway that links inflammation to carcinogenesis, subsequently resulting in the upregulation of c-Myc, cyclin D1 (CCND1), and epithelial-mesenchymal transition (EMT) markers. Conclusions: The findings established that microRNA-10b is an oncomiR that drives metastasis. Moreover, a set of critical tumor suppressor mechanisms was defined that microRNA-10b overcame to drive human GC progression.

Validation study of susceptibility loci for esophageal squamous cell carcinoma identified by GWAS in a Han Chinese subgroup from Eastern China.

Esophageal squamous cell carcinoma (ESCC) occurs at a relatively high frequency in China and is one of the most prevalent cancers in the world. Genome-wide association studies (GWAS) have identified 24 single-nucleotide polymorphisms (SNPs) that could be associated with ESCC in Chinese patients. This retrospective study aimed to validate the association between these 24 SNPs and ESCC in a Han Chinese subgroup from East China. A total of 2280 and 1900 patients with ESCC (case group) and non-esophageal cancer (control group) were included from a single center. Genotyping of the 24 polymorphisms was performed using the Sequenom MassARRAY system. Unconditional logistic regression analyses were conducted for every polymorphism. It was found that rs12188136 (P=0.027, OR=1.158, 95% CI=1.016-1.319 for AG/AA) was associated with ESCC. Binary logistic regression analyses revealed a significant negative association of rs875339 in RORA (P=0.014, OR=0.762, 95% CI=0.613-0.947 for TT/CC). Under the dominant model, rs6854472 was slightly associated with ESCC risk (P=0.048, OR=1.192, 95% CI=1.002-1.418). Under the recessive model, a significant negative association was observed for rs875339 (P=0.010, OR=0.758, 95% CI=0.615-0.935). In a word, this large-scale replication study validated that rs12188136 and rs6854472 are associated with ESCC in a Han Chinese subgroup from Eastern China, and that rs875339 is negative associated with ESCC.

Percutaneous full-endoscopic anterior transcorporeal cervical discectomy and channel repair: a technique note report.

BACKGROUND: Compared to anterior cervical discectomy and fusion (ACDF), cervical motion segment and disc was retained through anterior transcorporeal herniotomy (ATH). But surgical field and manipulation in traditional ATH was restricted by the narrow channel. Percutaneous full-endoscopic transdiscal cervical discectomy is a minimally invasive and functional spine surgery. However, significant loss of intervertebral disc height was inevitable. This study was done to illustrate the feasibility, safety, and efficacy and present our surgical experience of percutaneous full-endoscopic anterior transcorporeal cervical discectomy (PEATCD) and channel repair (CR) for the treatment of cervical disc herniation (CDH). METHODS: Four patients with CDH were chosen to undergo PEATCD and CR with a follow-up care for at least 22 months. The visual analogue score (VAS), Japanese Orthopedic Association (JOA), and modified Macnab criteria were recorded during the postoperative periods. CT images were obtained to observe the healing of the channel at 1 week and 3 months after the operation. RESULTS: The average operating time was 83.75 min. Drainage tubes were unnecessary. No procedure-related complications occurred. The postoperative VAS and JOA scores were improved compared to those of the preoperative assessment. The clinical efficacy was excellent in 3 patients and good in 1 patient at final follow up stage according to the modified Macnab criteria. The hernia was removed completely in all patients according to postoperative MRI. Migration of the repair implementation and collapse of the drilled vertebrae were not observed during the postoperative periods. The bony channel was nearly absent on CT images obtained at 3 months postoperative. CONCLUSION: This is the first time that the anterior transcorporeal cervical discectomy and CR have been performed simultaneously under endoscopy. Less damage to disc and the retained cervical motion segment were achieved through this method. This is a feasible, safe, and minimally invasive procedure. TRIAL REGISTRATION: Numbers: ChiCTR1800016383 . Registered 29 may 2018. Retrospectively registered. TRIAL REGISTRY: Chinese Clinical Trial Registry.

Soft-shelled turtle peptide modulates microRNA profile in human gastric cancer AGS cells.

Cancer prevention using natural micronutrition on epigenetic mechanisms primarily revolves around plant extracts. However, the role of macronutrition, including animal peptides, on epigenetic modification in cancer has been elusive. In traditional Chinese medicine, the soft-shelled turtle has a long-history of being a functional food that strengthens immunity through unknown mechanisms. The present study aimed to investigate the impact of soft-shelled turtle peptide on microRNA (miRNA) expression in gastric cancer (GC) cells and to analyze the potential anticancer mechanisms for GC. Affymetrix GeneChip miRNA 3.0 Array and quantitative polymerase chain reaction were used to detect the miRNA expression profile in human GC AGS cells treated with the soft-shelled turtle peptide. The results demonstrated that 101 miRNAs (49 upregulated miRNAs and 52 downregulated miRNAs) were significantly differentially expressed in the AGS cells following soft-shelled turtle peptide treatment. Several tumor suppressor miRNAs were upregulated markedly, including miRNA-375, let-7d, miRNA-429, miRNA-148a/148b and miRNA-34a. Pathway analysis indicated that soft-shelled turtle peptide may function with anticancer properties through the Hippo signaling pathway and the forkhead box O signaling pathway. Therefore, these results demonstrated that soft-shelled turtle peptide has the capacity to influence cancer-related pathways through the regulation of miRNA expression in GC cells.

Potential role of NDRG2 in reprogramming cancer metabolism and epithelial-to-mesenchymal transition.

Epithelial-to-mesenchymal transition (EMT) allows a cell with epithelial characteristics to transdifferentiate into a cell with mesenchymal characteristics, which is recognized as a key priming event for the initiation and evolvement of cancer metastasis. Accumulating data have shown that aberrant cancer metabolism contributes to the execution of EMT and cancer metastasis through multiple pathological pathways. Recently, the N-MYC downstream-regulated gene 2 (NDRG2), as a tumor suppressor and metabolism-related gene in various cancers, has been widely noted. NDGR2 is associated with energy metabolism, especially glycose metabolism. Hence, we propose a hypothesis that EMT is repressed by NDRG2 via cancer metabolic reprogramming, and summarize the pathological processes and molecular pathways related to the regulation of NDRG2.

Protective effects of oxymatrine against lipopolysaccharide/D­galactosamine­induced acute liver failure through oxidative damage, via activation of Nrf2/HO­1 and modulation of inflammatory TLR4­signaling pathways.

Oxymatrine has a variety of pharmacological functions, including anti-viral, anti-liver fibrotic, anti-cancer, anti­bacterial, anti­epidemic, analgesic, anti­allergy and anti­inflammatory properties. The present study aimed to investigate the protective effects of oxymatrine against lipopolysaccharide (LPS)/D­galactosamine (D­GalN)­induced acute liver failure and the associated underlying mechanisms. Mice were administrated 4 mg/kg LPS and 600 mg/kg D­GalN. Then, mice in the Oxymatrine group were treated with 120 mg/kg of oxymatrine for 4 weeks. Oxymatrine treatment increased survival rate, decreased plasma aspartate transaminase and alanine aminotransferase activity, increased superoxide dismutase and glutathione peroxidase and decreased malondialdehyde, tumor necrosis factor­ and myeloperoxidase activities in mice with LPS/D­GalN­induced liver failure. Furthermore, Oxymatrine activated nuclear factor erythroid 2­related factor (Nrf) 2 and heme oxygenase (HO)­1 protein expression, and suppressed Toll like receptor (TLR)4, myeloid differentiation primary response 88 and nuclear factor­κB protein expression in mice LPS/D­GalN mice. Overall, the present study suggests that oxymatrine effectively attenuates LPS/D­GalN­induced acute liver failure by oxidative damage via activation of Nrf2/HO­1 and modulation of TLR4­dependent inflammatory signaling pathways.

Intraoperative micro-computed tomography (micro-CT): a novel method for determination of primary tumour dimensions in breast cancer specimens.

OBJECTIVES: Micro-CT is a promising modality to determine breast tumour size in three dimensions in intact lumpectomy specimens. We compared the accuracy of tumour size measurements using specimen micro-CT with measurements using multimodality pre-operative imaging. METHODS: A tabletop micro-CT was used to image breast lumpectomy specimens. The largest tumour dimension on three-dimensional reconstructed micro-CT images of the specimen was compared with the measurements determined by pre-operative mammography, ultrasound and MRI. The largest dimension of pathologic invasive cancer size was used as the gold standard reference to assess the accuracy of imaging assessments. RESULTS: 50 invasive breast cancer specimens in 50 patients had micro-CT imaging. 42 were invasive ductal carcinoma, 6 were invasive lobular carcinoma and 2 were other invasive cancer. Median patient age was 63 years (range 33-82 years). When compared with the largest pathologic tumour dimension, micro-CT measurements had the best correlation coefficient (r = 0.82, p < 0.001) followed by MRI (r = 0.78, p < 0.001), ultrasound (r = 0.61, p < 0.001) and mammography (r = 0.40, p < 0.01). When compared with pre-operative modalities, micro-CT had the best correlation coefficient (r = 0.86, p < 0.001) with MRI, followed by ultrasound (r = 0.60, p < 0.001) and mammography (r = 0.54, p < 0.001). Overall, mammography and ultrasound tended to underestimate the largest tumour dimension, while MRI and micro-CT overestimated the largest tumour dimension more frequently. CONCLUSION: Micro-CT is a potentially useful tool for accurate assessment of tumour dimensions within a lumpectomy specimen. Future studies need to be carried out to see if this technology could have a role in margin assessment. ADVANCES IN KNOWLEDGE: Micro-CT is a promising new technique which could potentially be used for rapid assessment of breast cancer dimensions in an intact lumpectomy specimen in order to guide surgical excision.

Lumpectomy specimen margins are not reliable in predicting residual disease in breast conserving surgery.

BACKGROUND: In breast conserving surgery, the concordance between lumpectomy margin (LM) status and the status of the corresponding lumpectomy cavity remains uncertain. METHODS: We analyzed pathology reports of lumpectomies from 2004 to 2006. We included those which contained both ink-directed LM and complete (≥4) separate corresponding shaved cavity margins (SCMs). SCM pathology was used as a surrogate for lumpectomy cavity status, to determine the predictive value of LM for residual disease. RESULTS: Pathology from 1,201 pairs of LM and SCM from 242 patients was compared. LM status predicted corresponding lumpectomy cavity status with 50.9% sensitivity, 69.5% specificity, 35% positive predictive value, and 81.4% negative predictive value, giving an overall accuracy of 64.9%. CONCLUSIONS: Oriented LMs are not reliable for predicting lumpectomy cavity status, and therefore not reliable for directing re-excision. Taking complete, oriented SCMs at the time of lumpectomy may improve accuracy compared with traditional LM assessment.

Nipple-sparing mastectomy in BRCA1/2 mutation carriers: an interim analysis and review of the literature.

BACKGROUND: There are few large-scale studies that have examined outcomes for BRCA1/2 carriers who have undergone nipple-sparing mastectomy (NSM). The objective of our study was to examine incidental cancers, operative complications, and locoregional recurrences in BRCA1/2 mutation carriers who underwent NSM for both risk reduction and cancer treatment. METHODS: This was a retrospective review of pathology results and outcomes of 201 BRCA1/2 carriers from two different institutions who underwent NSM from 2007 to 2014. RESULTS: NSM was performed in 397 breasts of 201 BRCA1/2 carriers. One hundred and twenty-five (62.2 %) patients had a BRCA1 mutation and 76 (37.8 %) had a BRCA2 mutation; 150 (74.6 %) patients underwent NSM for risk reduction and 51 (25.4 %) for cancer. Incidental cancers were found in four (2.7 %) of the 150 risk-reduction patients and two (3.9 %) of the 51 cancer patients. The nipple-areolar complex (NAC) was involved with cancer in three (5.8 %) patients. No prophylactic mastectomy had a positive NAC margin. There was loss of the NAC in seven breasts (1.8 %) and flap necrosis in ten (2.5 %) breasts. With a mean follow-up of 32.6 months (1-76 months), there have been four cancer events-three in cancer patients and one in a risk-reduction patient but none at the NAC. CONCLUSION: NSM in BRCA1/2 carriers is associated with a low rate of complications and locoregional recurrence but these patients require long-term follow-up in both the cancer and risk-reduction setting.

Increasing eligibility for nipple-sparing mastectomy.

BACKGROUND: Eligibility for nipple-sparing mastectomy (NSM) varies widely on the basis of patient and tumor factors. METHODS: Review of patients undergoing NSM from June 2007 to December 2012 at our institution was performed. Patient and tumor characteristics, complications, and recurrences were collected. NSM from 2007 to 2010 and 2011 to 2012 were compared to assess trends in eligibility and outcomes over time. RESULTS: NSM was performed on 645 breasts in 370 patients. Indications were risk reduction in 330 (51.2 %), invasive cancer in 226 (35.0 %), and ductal carcinoma-in situ in 89 (13.8 %) breasts. Fifty-one (13.8 %) patients had positive lymph nodes. Twenty-seven (7.3 %) patients received neoadjuvant chemotherapy. Forty-eight (7.4 %) breasts had prior radiotherapy. Total nipple necrosis occurred in 11 (1.7 %) breasts. Twenty-four (3.7 %) breasts had nipples removed as a result of positive subareolar/nipple margins. At 22 months' mean follow-up, local recurrence occurred in 4 of 156 (2.6 %) breasts operated on for cancer through 2011. No recurrences involved the nipple. NSM performed in 2011-2012 (n = 475) compared to 2007-2010 (n = 170), were more often for cancer, in patients with higher body mass index, and on larger breasts (p < 0.001). There was no significant difference in total nipple necrosis rates between groups. Nipple loss due to positive subareolar/nipple margins was significantly less in 2011-2012 (p = 0.027). CONCLUSIONS: Eligibility for NSM has expanded to include women with higher body mass index and larger breasts, with no increase in nipple loss due to ischemia. Rates of positive subareolar margins have decreased over time, even though NSM is being performed more frequently for cancer, suggesting improved patient selection.

Micro-computed tomography (Micro-CT): a novel approach for intraoperative breast cancer specimen imaging.

Intraoperative radiographic examination of breast specimens is commonly performed to confirm excision of image-detected breast lesions, but it is not reliable for assessing margin status. A more accurate method of intraoperative breast specimen imaging is needed. Micro-CT provides quantitative imaging parameters, image rotation, and virtual "slicing" of intact breast specimens. We explored the use of micro-CT for assessment of a variety of clinical breast specimens. Specimens were evaluated with a table top micro-CT scanner, Skyscan 1173 (Skyscan, Belgium), with a 40-130 kV, 8 W X-ray source. Skyscan software for 3D image analysis (Dataviewer and CTVox) was employed to review 3D graphics of specimens. Scanning for 7 min and another 7 min for image reconstruction provided the desired resolution for breast specimens. Breast lumpectomy specimens, shaved cavity margins, mastectomy specimens, and axillary lymph nodes were imaged by micro-CT. The micro-CT images could be rotated in all directions and cross sections of internal portions of specimens could be visualized from any angle. This provided information about spatial orientation of masses and calcifications relative to margins in intact lumpectomy specimens. Micro-CT is a potentially useful tool for assessment of breast cancer specimens, allowing real-time analysis of tumor location in breast lumpectomy specimens or shaved cavity margins. Micro-CT may also be useful for assessing sentinel lymph nodes and mastectomy specimens.