Multi-modal ultrasound imaging for breast cancer detection

This work describes preliminary results of a two-modality imaging system aimed at the early detection of breast cancer. The first technique is based on compounding conventional echographic images taken at regular angular intervals around the imaged breast. The other modality obtains tomographic images of propagation velocity using the same circular geometry. For this study, a low-cost prototype has been built. It is based on a pair of opposed 128-element, 3.2 MHz array transducers that are mechanically moved around tissue mimicking phantoms. Compounded images around 360 degrees provide improved resolution, clutter reduction, artifact suppression and reinforce the visualization of internal structures. However, refraction at the skin interface must be corrected for an accurate image compounding process. This is achieved by estimation of the interface geometry followed by computing the internal ray paths. On the other hand, sound velocity tomographic images from time of flight projections have been also obtained. Two reconstruction methods, Filtered Back Projection (FBP) and 2D Ordered Subset Expectation Maximization (2D OSEM), were used as a first attempt towards tomographic reconstruction. These methods yield useable images in short computational times that can be considered as initial estimates in subsequent more complex methods of ultrasound image reconstruction. These images may be effective to differentiate malignant and benign masses and are very promising for breast cancer screening. (C) 2015 The Authors. Published by Elsevier B.V.

Advances in skin cancer early detection and diagnosis

OBJECTIVES: To provide an overview of 1) traditional methods of skin cancer early detection, 2) current technologies for skin cancer detection, and 3) evolving practice models of early detection. DATA SOURCES: Peer-reviewed databased articles and reviews, scholarly texts, and Web-based resources. CONCLUSION: Early detection of skin cancer through established methods or newer technologies is critical for reducing both skin cancer mortality and the overall skin cancer burden. IMPLICATIONS FOR NURSING PRACTICE: A basic knowledge of recommended skin examination guidelines and risk factors for skin cancer, traditional methods to further examine lesions that are suspicious for skin cancer and evolving detection technologies can guide patient education and skin inspection decisions.

Circulating tumor cell detection in high-risk non-metastatic prostate cancer

Purpose The detection of circulating tumor cells (CTCs) provides important prognostic information in men with metastatic prostate cancer. We aim to determine the rate of detection of CTCs in patients with high-risk non-metastatic prostate cancer using the CellSearch® method. Method Samples of peripheral blood (7.5 mL) were drawn from 36 men with newly diagnosed high-risk non-metastatic prostate cancer, prior to any initiation of therapy and analyzed for CTCs using the CellSearch® method. Results The median age was 70 years, median PSA was 14.1, and the median Gleason score was 9. The median 5-year risk of progression of disease using a validated nomogram was 39 %. Five out of 36 patients (14 %, 95 % CI 5–30 %) had CTCs detected in their circulation. Four patients had only 1 CTC per 7.5 mL of blood detected. One patient had 3 CTCs per 7.5 mL of blood detected, which included a circulating tumor microemboli. Both on univariate analysis and multivariate analysis, there were no correlations found between CTC positivity and the classic prognostic factors including PSA, Gleason score, T-stage and age. Conclusion This study demonstrates that patients with high-risk, non-metastatic prostate cancer present infrequently with small number of CTCs in peripheral blood. This finding is consistent with the limited literature available in this setting. Other CTC isolation and detection technologies with improved sensitivity and specificity may enable detection of CTCs with mesenchymal phenotypes, although none as yet have been validated for clinical use. Newer assays are emerging for detection of new putative biomarkers for prostate cancer. Correlation of disease control outcomes with CTC detection will be important.

Improving the early diagnostic of prostate cancer by multiple biomarker detection with new biosensing devices

Prostate cancer (PCa) is the most common form of cancer in men, in Europe (World Health Organization data). The most recent statistics, in Portuguese territory, confirm this scenario, which states that about 50% of Portuguese men may suffer from prostate cancer and 15% of these will die from this condition. Its early detection is therefore fundamental. This is currently being done by Prostate Specific Antigen (PSA) screening in urine but false positive and negative results are quite often obtained and many patients are sent to unnecessary biopsy procedures. This early detection protocol may be improved, by the development of point-of-care cancer detection devices, not only to PSA but also to other biomarkers recently identified. Thus, the present work aims to screen several biomarkers in cultured human prostate cell lines, serum and urine samples, developing low cost sensors based on new synthetic biomaterials. Biomarkers considered in this study are the following: prostate specific antigen (PSA), annexin A3 (ANXA3), microseminoprotein-beta (MSMB) and sarcosine (SAR). The biomarker recognition may occurs by means of molecularly imprinted polymers (MIP), which are a kind of plastic antibodies, and enzymatic approaches. The growth of a rigid polymer, chemically stable, using the biomarker as a template allows the synthesis of the plastic antibody. MIPs show high sensitivity/selectivity and present much longer stability and much lower price than natural antibodies. This nanostructured material was prepared on a carbon solid. The interaction between the biomarker and the sensing-material produces electrical signals generating quantitative or semi-quantitative data. These devices allow inexpensive and portable detection in point-of-care testing.

Early detection of ovarian cancer in samples pre-diagnosis using CA125 and MALDI-MS peaks

Aim: A nested case-control discovery study was undertaken 10 test whether information within the serum peptidome can improve on the utility of CA125 for early ovarian cancer detection. Materials and Methods: High-throughput matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS) was used to profile 295 serum samples from women pre-dating their ovarian cancer diagnosis and from 585 matched control samples. Classification rules incorporating CA125 and MS peak intensities were tested for discriminating ability. Results: Two peaks were found which in combination with CA125 discriminated cases from controls up to 15 and 11 months before diagnosis, respectively, and earlier than using CA125 alone. One peak was identified as connective tissue-activating peptide III (CTAPIII), whilst the other was putatively identified as platelet factor 4 (PF4). ELISA data supported the down-regulation of PF4 in early cancer cases. Conclusion: Serum peptide information with CA125 improves lead time for early detection of ovarian cancer. The candidate markers are platelet-derived chemokines, suggesting a link between platelet function and tumour development.

Development of a novel probe integrated with a micro-structured impedance sensor for the detection of breast cancer

The work described in this thesis focuses on the development of an innovative bioimpedance device for the detection of breast cancer using electrical impedance as the detection method. The ability for clinicians to detect and treat cancerous lesions as early as possible results in improved patient outcomes and can reduce the severity of the treatment the patient has to undergo. Therefore, new technology and devices are continually required to improve the specificity and sensitivity of the accepted detection methods. The gold standard for breast cancer detection is digital x-ray mammography but it has some significant downsides associated with it. The development of an adjunct technology to aid in the detection of breast cancers could represent a significant patient and economic benefit. In this project silicon substrates were pattern with two gold microelectrodes that allowed electrical impedance measurements to be recorded from intact tissue structures. These probes were tested and characterised using a range of in vitro and ex vivo experiments. The end application of this novel sensor device was in a first-in-human clinical trial. The initial results of this study showed that the silicon impedance device was capable of differentiating between normal and abnormal (benign and cancerous) breast tissue. The mean separation between the two tissue types 4,340 Ω with p < 0.001. The cancer type and grade at the site of the probe recordings was confirmed histologically and correlated with the electrical impedance measurements to determine if the different subtypes of cancer could each be differentiated. The results presented in this thesis showed that the novel impedance device demonstrated excellent electrochemical recording potential; was biocompatible with the growth of cultured cell lines and was capable of differentiating between intact biological tissues. The results outlined in this thesis demonstrate the potential feasibility of using electrical impedance for the differentiation of biological tissue samples. The novelty of this thesis is in the development of a new method of tissue determination with an application in breast cancer detection.

Detection and Grading of Prostate Cancer in Temporal Enhanced Ultrasound using Convolutional Neural Networks

Prostate cancer is the most common non-dermatological cancer amongst men in the developed world. The current definitive diagnosis is core needle biopsy guided by transrectal ultrasound. However, this method suffers from low sensitivity and specificity in detecting cancer. Recently, a new ultrasound based tissue typing approach has been proposed, known as temporal enhanced ultrasound (TeUS). In this approach, a set of temporal ultrasound frames is collected from a stationary tissue location without any intentional mechanical excitation. The main aim of this thesis is to implement a deep learning-based solution for prostate cancer detection and grading using TeUS data. In the proposed solution, convolutional neural networks are trained to extract high-level features from time domain TeUS data in temporally and spatially adjacent frames in nine in vivo prostatectomy cases. This approach avoids information loss due to feature extraction and also improves cancer detection rate. The output likelihoods of two TeUS arrangements are then combined to form our novel decision support system. This deep learning-based approach results in the area under the receiver operating characteristic curve (AUC) of 0.80 and 0.73 for prostate cancer detection and grading, respectively, in leave-one-patient-out cross-validation. Recently, multi-parametric magnetic resonance imaging (mp-MRI) has been utilized to improve detection rate of aggressive prostate cancer. In this thesis, for the first time, we present the fusion of mp-MRI and TeUS for characterization of prostate cancer to compensates the deficiencies of each image modalities and improve cancer detection rate. The results obtained using TeUS are fused with those attained using consolidated mp-MRI maps from multiple MR modalities and cancer delineations on those by multiple clinicians. The proposed fusion approach yields the AUC of 0.86 in prostate cancer detection. The outcomes of this thesis emphasize the viable potential of TeUS as a tissue typing method. Employing this ultrasound-based intervention, which is non-invasive and inexpensive, can be a valuable and practical addition to enhance the current prostate cancer detection.

Association of heparan sulfate proteoglycans SDC1 and SDC4 polymorphisms with breast cancer in an Australian Caucasian population

Breast cancer is a common disease in both developing and developed countries with early identification and treatment improving prognosis and survival. Heparan sulfate proteoglycans (HSPGs) are key components of the extracellular matrix (ECM) that mediate cell adhesion, motility, proliferation, invasion and cell signalling. Members of the syndecan family of HSPGs have been identified to be involved in breast cancer progression through their varied interactions with a number of growth factors, ligands and receptors. Specifically, high expression levels of syndecan-1 (SDC1) have been demonstrated in more invasive breast tumours while elevated syndecan-4 (SDC4) levels have been identified to correspond with improved prognosis. With genetic changes in the syndecans and their association with breast cancers plausible, we examined two single nucleotide polymorphisms in SDC1 (rs1131351) and SDC4 (rs67068737) within an Australian Caucasian breast cancer case/control population. No association was found with SDC4 and breast cancer in our population. However, a significant association between SDC1 and breast cancer was identified in both our case/control population and in a replication cohort. When both populations were combined for analysis, this association became more significant (genotype, p = 0.0003; allele, p = 0.0001). This data suggests an increased risk of developing breast cancer associated with the presence of the C allele of the SDC1 rs1131351 single nucleotide polymorphism (SNP) and may provide a marker toward early breast cancer detection.

Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

Clinical tips: Bowel cancer screening

So, when was the last time you checked your poo? Checking your poo – it probably is not a conversation many patients want to have with their pharmacists. But bowel cancer screening remains an important tool in cancer detection...

Evaluation of Alpha 1-Antitrypsin and the Levels of mRNA Expression of Matrix Metalloproteinase 7, Urokinase Type Plasminogen Activator Receptor and COX-2 for the Diagnosis of Colorectal Cancer

8 p.

Computer technology in detection and staging of prostate carcinoma: a review

Y. Zhu, S. Williams and R. Zwiggelaar, 'Computer technology in detection and staging of prostate carcinoma: a review', Medical Image Analysis 10 (2), 178-199 (2006)