Comparison of contrast enhanced color doppler targeted biopsy to conventional systematic biopsy in carcinoma prostate.

INTRODUCTION : One of the most common cancers diagnosed in men is carcinoma prostate. Because of improvements in diagnostic testing, its incidence has been increasing. In patients with carcinoma prostate, ultra sonogram guided biopsy has been the investigation of choice in men with increased serum prostate specific antigen or a nodular prostate. Targeted biopsies will be helpful in increasing the sensitivity of systematic biopsy. Micro-bubble contrast agents are used as innovative technology to enhance detection of prostate cancer. Several studies have demonstrated that contrast enhanced ultrasound (CEUS) of prostatic blood flow helps in visualization of cancerous lesion and to target biopsy. Biopsy from target lesion helps in detecting more cancers with lesser cores .CEUS has been shown to detect cancers with higher Gleason scores, which improves cancer grading. Micro bubble contrast agent images the microvasculature in the prostate, especially in carcinoma, these contrast agents increase the sensitivity in detecting carcinomatous lesions. We undertook this study to find the efficacy of CE sonography for detection of prostate in patients with PSA >4 ng/ml and compare this with conventional system. AIM AND OBJECTIVE : To assess the efficacy of contrast enhanced color Doppler ultrasound guided biopsy to detect prostate cancer. To compare prostate cancer detection with contrast enhanced ultrasound compared and conventional systematic biopsy and the impact on Gleason score. MATERIALS AND METHODS : Informed consent was obtained from all the patients. The patients were started on prophylactic antibiotic the night before biopsy. on the morning of biopsy, a cleansing enema was given for the patient. Aspirin or nonsteroidal anti-inflammatory agents are withheld for at least 5 days before biopsy. Transrectal ultrasound examination of the prostate, TRUS examination during infusion of contrast material, and biopsy of the prostate are all done during a single visit. Transrectal sonography was performed with Siemens ultrasound machine for all patients. Contrast enhanced sonography was done using sonovue, as the ultrasound contrast agent. The lyophilized powder is shaken with 5 mL of distilled water for 20 sec. By using a 20-gauge cannula, 1.5 ml contrast agent bolus was injected into the left antecubital vein manually. 1 ml solution contains 8ug/ml. 5 ml of normal saline is injected each time, after injecting the ultrasound contrast agent. Inclusion Criteria: Patients with serum prostate specific antigen > 4 ng/ml. Normal or abnormal digital rectal examination Exclusion Criteria: 1. Active UTI, 2. Prostatitis, 3. Un Co-Operative Patients, 4. Allergy to ultrasound contrast agents, 5. Contra-indications to ultrasound contrast agents like -Recent acute myocardial infarction (< 7 days), Right-to-left shunts, Class III / IV cardiac failure, and severe pulmonary hypertension. CONCLUSION : The results of this study shows that, The sensitivity and accuracy of cancer detection is improved by using ultrasound contrast agents for depicting microvessels in carcinoma prostate. The use contrast agents in TRUS will help in targeted biopsy of the enhancing lesions thereby decreasing the number of biopsy cores and associated complication. The use of CEUS also may be useful in patients with indeterminate serum PSA. Targeted biopsy has a definite impact on gleason scores, detecting high grade cancers with limited number of cores thus helping in planning the treatment in carcinoma prostate

Biomechanical Modeling and Inverse Problem Based Elasticity Imaging for Prostate Cancer Diagnosis

Early detection of prostate cancer plays an important role in successful prostate cancer treatment. This requires screening the prostate periodically after the age of 50. If screening tests lead to prostate cancer suspicion, prostate needle biopsy is administered which is still considered as the clinical gold standard for prostate cancer diagnosis. Given that needle biopsy is invasive and is associated with issues including discomfort and infection, it is desirable to develop a prostate cancer diagnosis system that has high sensitivity and specificity for early detection with a potential to improve needle biopsy outcome. Given the complexity and variability of prostate cancer pathologies, many research groups have been pursuing multi-parametric imaging approach as no single modality imaging technique has proven to be adequate. While imaging additional tissue properties increases the chance of reliable prostate cancer detection and diagnosis, selecting an additional property needs to be done carefully by considering clinical acceptability and cost. Clinical acceptability entails ease with respect to both operating by the radiologist and patient comfort. In this work, effective tissue biomechanics based diagnostic techniques are proposed for prostate cancer assessment with the aim of early detection and minimizing the numbers of prostate biopsies. The techniques take advantage of the low cost, widely available and well established TRUS imaging method. The proposed techniques include novel elastography methods which were formulated based on an inverse finite element frame work. Conventional finite element analysis is known to have high computational complexity, hence computation time demanding. This renders the proposed elastography methods not suitable for real-time applications. To address this issue, an accelerated finite element method was proposed which proved to be suitable for prostate elasticity reconstruction. In this method, accurate finite element analysis of a large number of prostates undergoing TRUS probe loadings was performed. Geometry input and displacement and stress fields output obtained from the analysis were used to train a neural network mapping function to be used for elastopgraphy imaging of prostate cancer patients. The last part of the research presented in this thesis tackles an issue with the current 3D TRUS prostate needle biopsy. Current 3D TRUS prostate needle biopsy systems require registering preoperative 3D TRUS to intra-operative 2D TRUS images. Such image registration is time-consuming while its real-time implementation is yet to be developed. To bypass this registration step, concept of a robotic system was proposed which can reliably determine the preoperative TRUS probe position relative to the prostate to place at the same position relative to the prostate intra-operatively. For this purpose, a contact pressure feedback system is proposed to ensure similar prostate deformation during 3D and 2D image acquisition in order to bypass the registration step

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

Ultrasound Imaging

This book provides an overview of ultrafast ultrasound imaging, 3D high-quality ultrasonic imaging, correction of phase aberrations in medical ultrasound images, etc. Several interesting medical and clinical applications areas are also discussed in the book, like the use of three dimensional ultrasound imaging in evaluation of Asherman's syndrome, the role of 3D ultrasound in assessment of endometrial receptivity and follicular vascularity to predict the quality oocyte, ultrasound imaging in vascular diseases and the fetal palate, clinical application of ultrasound molecular imaging, Doppler abdominal ultrasound in small animals and so on

Contrast-Enhanced Ultrasonography (CEUS) in Imaging of the Reproductive System in Dogs: A Literature Review

The use of contrast-enhanced ultrasound (CEUS) has been widely reported for reproductive imaging in humans and animals. This review aims to analyze the utility of CEUS in characterizing canine reproductive physiology and pathologies. In September 2022, a search for articles about CEUS in canine testicles, prostate, uterus, placenta, and mammary glands was conducted on PubMed and Scopus from 1990 to 2022, showing 36 total results. CEUS differentiated testicular abnormalities and neoplastic lesions, but it could not characterize tumors. In prostatic diseases, CEUS in dogs was widely studied in animal models for prostatic cancer treatment. In veterinary medicine, this diagnostic tool could distinguish prostatic adenocarcinomas. In ovaries, CEUS differentiated the follicular phases. In CEH-pyometra syndrome, it showed a different enhancement between endometrium and cysts, and highlighted angiogenesis. CEUS was shown to be safe in pregnant dogs and was able to assess normal and abnormal fetal–maternal blood flow and placental dysfunction. In normal mammary glands, CEUS showed vascularization only in diestrus, with differences between mammary glands. CEUS was not specific for neoplastic versus non-neoplastic masses and for benign tumors, except for complex carcinomas and neoplastic vascularization. Works on CEUS showed its usefulness in a wide spectrum of pathologies of this non-invasive, reliable diagnostic procedur

The role of STEAP2 in aggressive prostate cancer traits and androgen responses

The prognosis of localised prostate cancer is generally promising, as many tumours remain dormant and therefore do not require immediate intervention. In contrast, once metastasised, the prognosis for aggressive prostate cancer is often poor, highlighting the need for novel, effective treatment approaches. The expression of the six transmembrane epithelial antigen of the prostate2 (STEAP2) cell surface protein is increased in aggressive prostate cancer compared to normal prostate tissue. In vitro studies have shown STEAP2 to aid in prostate cancer progression, and as such this molecule shows promise as a potential novel therapeutic target in the treatment of advanced disease. The aim of this thesis was to develop a comprehensive understanding of the mechanistic role of STEAP2 in promoting aggressive prostate cancer traits and evaluate if its knock-out has the capacity to reduce the invasive potential of prostate cancer cells in vitro. As prostate cancer is a largely androgen dependent disease, this thesis also aimed to evaluate the effects of STEAP2 inhibition on the expression of the androgen receptor and androgen-regulated genes. This study developed and optimised a protocol for generating a set of 3D prostate cancer spheroids to provide more representative models of the in vivo prostate cancer environment. In this thesis, one commercial anti-STEAP2 polyclonal antibody and a panel of anti-STEAP2 monoclonal antibodies were selected for proof-of-concept studies where their effects on reducing prostate cancer cell viability were assessed. Receptor internalisation of STEAP2 was evaluated upon anti-STEAP2 monoclonal antibody binding to determine its suitability for use with antibody-drug conjugate technology. STEAP2 expression was knocked out using CRISPR/Cas9 genome engineering technology in two prostate cancer cell lines to evaluate its impact on cell proliferation, migration and invasion. Furthermore, gene expression profiling was conducted to explore interactions between STEAP2, the androgen receptor and a panel of androgen-regulated genes (PSA, FKBP5, GPRC6A and TMPRSS2) following: 1) anti-STEAP2 antibody treatment, 2) STEAP2-knockout and 3) the growth of prostate cancer cells in androgen-depleted conditions. The data presented in this thesis demonstrate that inhibition of STEAP2 by both the polyclonal anti-STEAP2 antibody and lead anti-STEAP2 monoclonal antibody significantly reduced prostate cancer cell viability. STEAP2 receptor internalisation was triggered following treatment of prostate cancer cells with the anti-STEAP2 monoclonal antibody, demonstrating its potential utility with antibody-drug conjugate technology in the future. STEAP2 knockout prostate cancer cells exhibited decreased cell proliferation, migration and invasion in comparison to wild-type cells. These promising findings highlight the therapeutic value of STEAP2-knockout in inhibiting invasive tumour cell traits. Gene expression data from both STEAP2-knockout cells and androgen-depleted cells suggest that STEAP2 may be involved in crosstalk between the androgen receptor and androgen-regulated genes. STEAP2 could therefore provide a novel target in conjunction with current conventional androgen deprivation therapy. In conclusion, the in vitro findings presented herein suggest STEAP2 as a viable target for the development of more tailored and personalised therapeutic agents to improve the clinical management of men with aggressive prostate cancer

Exploration of a xenograft model of human prostate cancer to predict patient treatment response

For several years, docetaxel was the only treatment to improve survival of patients with metastatic prostate cancer. There are now many novel agents available but the optimal sequence of treatments remains undefined. The emergence of prostate cancer stem cells has brought a new way to elucidate the molecular mechanisms behind treatment failure and recurrence. Traditionally cell lines have been used in preclinical studies but recently ‘near patient’ derived xenografts (PDX), have been suggested to be a better way to investigate new therapies and investigate pathways in metastatic spread. First we used a subcutaneous and an orthotopic PDX model to determine which is most feasible in looking at the differences in the expression of basal and luminal cell markers. We then looked at the effect of docetaxel on hormone naïve and castrate resistant PDXs specifically measuring changes in the numbers of basal and luminal cells determining docetaxel resistance. Finally we tried labelling and fluorescent cell sorting PDX cells to track metastatic spread and monitor chemotherapy effects.The mouse prostate microenvironment did not drastically change cellular phenotypes, allowing us to use the simpler subcutaneous method to assess chemotherapy effects on PDX. In fact the subcutaneous xenografts retained basal and luminal cells maintaining the clinical heterogeneity present in prostate cancers. In the docetaxel studies, alteration in AR expression and high levels of basal-like cells from the outset appeared to confer resistance. Although docetaxel had an overall detrimental effect, there was a typical decrease in the number of basal cells in both hormone naïve and resistant tumours. No trends were seen in the luminal populations. Side effects affecting continuation of treatment wereevident. Lentiviral transduction was successful in PC3 cells where they maintained high levels of fluorescent (RFP) reporter expression. Transduction of PDX cells proved more challenging and requires further optimisation.In the evolving area of new prostate cancer treatments, docetaxel chemotherapy continues to play an important role and could be given in hormone naïve cancers. This can also increase the chances of benefitting from the whole variety of new drugs. However, not all tumours are sensitive and resistance mechanisms remain unclear

A study of Raman spectroscopy for the early detection and characterization of prostate cancer using blood plasma and prostate tissue biopsy.

Prostate cancer (PC) is the most common cancer in men after non-melanoma skin cancer in the United Kingdom (Cancer Research UK, 2019). Current diagnostic methods (PSA, DRE, MRI & prostate biopsy) have limitations as these are unable to distinguish between low-risk cancers that do not need active treatment from cancers which are more likely to progress. In addition, prostate biopsy is invasive with potential side effects. There is an urgent need to identify new biomarkers for early diagnosis and prognostication in PC. Raman spectroscopy (RS) is an optical technique that utilises molecular-specific, inelastic scattering of light photons to interrogate biological samples. When laser light is incident on a biological sample, the photons from the laser light can interact with the intramolecular bonds present within the sample. The Raman spectrum is a direct function of the molecular composition of the tissue, providing a molecular fingerprint of the phenotypic expression of the cells and tissues, which can give good objective information regarding the pathological state of the biological sample under interrogation. We applied a technique of drop coating deposition Raman (DCDR) spectroscopy using both blood plasma and sera to see if a more accurate prediction of the presence and progression of prostate cancer could be achieved than PSA which would allow for blood sample triage of patients into at risk groups. 100 participants were recruited for this study (100 blood plasma and 100 serum samples). Secondly, 79 prostate tissue samples (from the same cohort) were interrogated with the aid of Raman micro-spectroscopy to ascertain if Raman spectroscopy can provide molecular fingerprint that can be utilised for real time in vivo analysis. Multivariate analysis of support vector machine (SVM) learning and linear discriminant analysis (LDA) were utilised differently to test the performance accuracy of the discriminant model for distinguishing between benign and malignant mean plasma spectra. SVM gave a better performance accuracy than LDA with sensitivity and specificity of 96% and 97% respectively and an area under the curve (AUC) of 0.98 as opposed to sensitivity and specificity of 51% and 80% respectively with AUC of 0.74 using LDA. Slightly lower performance accuracy was also observed when blood serum mean spectra analysis was compared with blood plasma mean spectra analysis for both machine learning algorithms (SVM & LDA). Tissue spectral analysis on the other hand recorded an overall accuracy of 80.8% and AUC of 0.82 with the SVM algorithm compared to performance accuracy of 75% and AUC of 0.77 with LDA algorithm (better performance noted with the SVM algorithm). The small sample size of 79 prostate biopsy tissues was responsible for the low sensitivity and specificity. Therefore, the tissues were insufficient to describe all the variances in each group as well as the variability of the gold standard technique. Conclusion: Raman spectroscopy could be a potentially useful technique in the management of Prostate Cancer in areas such as tissue diagnosis, assessment of surgical margin after radical prostatectomy, detection of metastasis, Prostate Cancer screening as well as monitoring and prognosticating patients with Prostate Cancer. However, more needs to be done to validate the approaches outlined in this thesis using prospective collection of new samples to test the classification models independently with sufficient statistical power. At this stage only the fluid-based models are likely to be large enough for this validation process

Diseases of the Abdomen and Pelvis 2018-2021: Diagnostic Imaging - IDKD Book

Gastrointestinal disease; PET/CT; Radiology; X-ray; IDKD; Davo