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Over the last 20 years, cancer clinicians have begun to improve the efficacy of cancer care through tumor boards, meetings of multidisciplinary patient care teams used to educate attendees and align treatment plans. In addition to the potential for collaboration between different disciplines, these meetings allow for the incorporation of information from peer-reviewed literature. Despite their use, very little research has been done on the effect of tumor boards on treatment efficacy. Within this small body of work, the indicators used are often inherently biased, and little concern is given to their confounding effects. This document will discuss alternative metrics that provide a less biased estimate of the impact of tumor boards. Given their educational aspects, tumor boards are beginning to be used in an international context to support clinicians in developing nations. Despite the relative lack of evidence supporting use of tumor boards, they provide a low-cost method for improving clinician education in a setting where treatment protocols vary greatly. Moreover, international tumor boards provide a way for low-resource hospitals to tap into facilities of high-resource hospitals, receive resource-sensitive guidelines for future practice, and collaborate with clinicians from other hospitals. However, there are serious barriers to implementing international tumor boards, including technological, logistical, linguistic, and oversight issues. This document outlines potential issues and methods to circumvent them, as well as benefits of international tumor boards (including future collaboration).

<p>The purpose of this thesis was to evaluate the diagnostic potential of a new ultrasound contrast agent,Sonazoid^TM, intended for use in patients with suspicion of prostate cancer.</p><p>The sonographic appearance of normal prostatic vascularity in dogs was evaluated before and after injection of Sonazoid,using different Doppler flow detection modes.The use of Sonazoid significantly improved the visibility of the vascular pattern in normal dog prostate,both with colour and power Doppler imaging.There was a significant difference in the depiction of blood flow in the prostate between the two imaging modalities,showing the power Doppler superior to colour Doppler imaging.The contrast revealed a radial,spoke-like intraprostatic pattern,not seen prior to contrast injection.</p><p>Different ultrasound imaging modalities were tested in a small group of young healthy male volunteers to evaluate the visibility of the normal prostate blood flow with and without Sonazoid.</p><p>The ultrasound contrast agent improved the visibility of the normal human prostate vascular anatomy for both colour and power Doppler imaging.Again,the improvement was significantly better for power Doppler than for colour Doppler imaging.Using fundamental B-mode,there was no major difference in the ultrasound appearance of the prost ate vascular it y before and after i njection of Sonazoid.Cont rast dynamic st udies of blood flow wit hi n t he normal gland showed a filling from the periphery towards the centre in all subjects,demonstrating a symmetric, radial vascular pattern.</p><p>A canine prostate model was used to investigate if Sonazoid,could improve the visualisation of prostatic vessels to better delineate areas on normal and decreased blood flow.Both 2D and 3D power Doppler imaging was performed in this study.The visibility of the prostate blood flow improved significantly following injection of Sonazoid for both 2D and 3D power Doppler imaging.There was,however,no major difference in depicting the vascularity using 2D and 3D imaging.After injection of Sonazoid,a disturbance of the radial vascular pattern and a lack of blood flow symmetry between the two prostate lobes were possible to identify.The added information gained by injection of Sonazoid made it possible to identify areas of decreased blood flow not seen prior to contrast injection.</p><p>The vascular pattern of lesions,identified with B-mode imaging in patients with suspicion of prostate cancer,was studied,using Sonazoid.Contrast dynamic inflow in the lesions,compared to the adjacent tissue was investigated in the same study.Prostate cancer lesions appeared hypervasuclar prior to ultrasound contrast agent.Three of six cancer lesions changed from hypervascular to marked hypervascular following injection of Sonazoid,a finding that might be interpreted as a higher level of confidence.None of the non-cancer lesions were assessed as hypervascular after Sonazoid injection,a possible increased value of a negative finding.Four of the cancer lesions enhanced earlier compared to the surrounding prostate tissue,following ultrasound contrast injection.The results indicate that changes in vascular architecture,e.g.induction of angiogenesis by tumour cells,can be observed by ultrasonographically determining the inflow pattern of an intravenously injected ultrasound contrast agent.</p>

The purpose of this thesis was to evaluate the diagnostic potential of a new ultrasound contrast agent,SonazoidTM, intended for use in patients with suspicion of prostate cancer. The sonographic appearance of normal prostatic vascularity in dogs was evaluated before and after injection of Sonazoid,using different Doppler flow detection modes.The use of Sonazoid significantly improved the visibility of the vascular pattern in normal dog prostate,both with colour and power Doppler imaging.There was a significant difference in the depiction of blood flow in the prostate between the two imaging modalities,showing the power Doppler superior to colour Doppler imaging.The contrast revealed a radial,spoke-like intraprostatic pattern,not seen prior to contrast injection. Different ultrasound imaging modalities were tested in a small group of young healthy male volunteers to evaluate the visibility of the normal prostate blood flow with and without Sonazoid. The ultrasound contrast agent improved the visibility of the normal human prostate vascular anatomy for both colour and power Doppler imaging.Again,the improvement was significantly better for power Doppler than for colour Doppler imaging.Using fundamental B-mode,there was no major difference in the ultrasound appearance of the prost ate vascular it y before and after i njection of Sonazoid.Cont rast dynamic st udies of blood flow wit hi n t he normal gland showed a filling from the periphery towards the centre in all subjects,demonstrating a symmetric, radial vascular pattern. A canine prostate model was used to investigate if Sonazoid,could improve the visualisation of prostatic vessels to better delineate areas on normal and decreased blood flow.Both 2D and 3D power Doppler imaging was performed in this study.The visibility of the prostate blood flow improved significantly following injection of Sonazoid for both 2D and 3D power Doppler imaging.There was,however,no major difference in depicting the vascularity using 2D and 3D imaging.After injection of Sonazoid,a disturbance of the radial vascular pattern and a lack of blood flow symmetry between the two prostate lobes were possible to identify.The added information gained by injection of Sonazoid made it possible to identify areas of decreased blood flow not seen prior to contrast injection. The vascular pattern of lesions,identified with B-mode imaging in patients with suspicion of prostate cancer,was studied,using Sonazoid.Contrast dynamic inflow in the lesions,compared to the adjacent tissue was investigated in the same study.Prostate cancer lesions appeared hypervasuclar prior to ultrasound contrast agent.Three of six cancer lesions changed from hypervascular to marked hypervascular following injection of Sonazoid,a finding that might be interpreted as a higher level of confidence.None of the non-cancer lesions were assessed as hypervascular after Sonazoid injection,a possible increased value of a negative finding.Four of the cancer lesions enhanced earlier compared to the surrounding prostate tissue,following ultrasound contrast injection.The results indicate that changes in vascular architecture,e.g.induction of angiogenesis by tumour cells,can be observed by ultrasonographically determining the inflow pattern of an intravenously injected ultrasound contrast agent.

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on March 25, 2010). Vita. Thesis advisor: Carolyn J. Henry. "December 2009" Includes bibliographical references.

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<p> Initial approaches to cancer treatment have involved classifying cancer by the site in which it is first formed, and treating it with drugs and other therapies that have very broad targeting. These therapies are often prone to damaging healthy cells in the process, which may lead to additional health complications. With the advent of high-throughput sequencing, and the development of computational tools and software to process the subsequent deluge of sequencing data, much progress has been made on functionally annotating the human genome. Many genomes have been cost-effectively sequenced, providing insight into genetic variation between various human populations. The methods used to study population variation may also be used to study the basis of genetic disease, including cancer. It has now been demonstrated that there are many molecular subtypes of cancer, where each subtype is differentiated based on which important cellular molecule or DNA sequence has been disrupted. Hence, understanding the genetic basis of cancer is paramount to the development of new, personalized molecular therapies to treat cancer.</p><p> Noncoding variants are known to be associated with disease, but they are not as commonly investigated as coding variants since assessing the functional impact of a mutation is difficult. For rare mutations, background mutation models have been set up for burden tests to discover highly mutated regions, which might be potential drivers of cancer. This has been developed for coding regions, leading to the successful use of burden tests to find highly mutated genes. However, this is challenging for noncoding regions because of mutation rate heterogeneity and potential correlations across regions, which give rise to huge overdispersion in the mutation count data. If not corrected, such overdispersions may suggest artefactual mutational hotspots. We address these issues with the development of a new computational framework called LARVA. LARVA intersects whole genome single nucleotide variant (SNV) calls with a comprehensive set of noncoding regulatory elements, and models these elements' mutation counts with a beta-binomial distribution to handle the overdispersion in a principled fashion. Furthermore, in estimating this distribution and determining the local mutation rate, LARVA incorporates regional genomic features like replication timing.</p><p> The LARVA framework can be extended in certain ways to facilitate the analysis of its results. By storing information on highly mutated annotations in a relational database, it is possible to quickly extract the most interesting results for further analysis. Furthermore, results from multiple LARVA runs can be combined for a meta-analysis that could involve, for example, finding highly mutated pathways in cancer and other types of genetic disease. Since LARVA's computation consists of many independent units of work, it can benefit from various forms of parallel computation. These forms of computation include distributed computing with a large number of commodity processors, as well as more esoteric types of parallelization, such as general purpose graphics processing unit (GPU) computation.</p><p> We make LARVA available as free software tool at larva.gersteinlab.org. We demonstrate the effectiveness of LARVA by showing how it identifies the well-known noncoding drivers, such as TERT promoter, on 760 cancer whole genomes. Furthermore, we show it is able to highlight several novel noncoding regulators that could be potential new noncoding drivers. We also make all of the highly mutated annotations available online.</p><p> We also describe the Aggregation and Correlation Toolbox (ACT), a collection of software tools that facilitates the analysis of genomic signal tracks. The aggregation component takes a signal track and a series of genome regions, and creates an aggregate profile of the signal over the given regions. This enables the discovery of consistent signal patterns over related sets of annotations, implying potential connections between the signal and the regions. The correlation component of ACT takes two or more signal tracks and computes all pairwise track correlations. Correlation analyses are useful for finding similarities between various experiments, such as the binding sites of transcription factors as determined by ChIP-seq. The final component of ACT is a saturation tool designed to determine the number of experiments necessary to cover genomic features to saturation. This type of analysis can be illustrated with a ChIP-seq experiment where the inclusion of additional cell lines will reveal more binding sites for a transcription factor of interest: with each new cell line, a smaller fraction of the sites will be newly discovered, and a larger fraction will overlap discovered sites from previously used cell lines. The objective of ACT's saturation tool is to find the point of diminishing returns in the discovery of new sites, which may result in more efficiently planned experiments.</p>

The following brief and imperfect statement is based chiefly upon the official statistics of which it is an exposition and slight expansion. The material available for such an enquiry in this country is somewhat limited, but in view of the importance attached to the subject, particularly that aspect of it relating to the increase of this dread disease, the writer has collected available information and has sought to give it intelligible form.

<p> Diet is a modifiable risk factor that strongly influences colorectal cancer (CRC) risk. Previous studies have associated CRC with impaired nutrient intakes including calcium, selenium and folate intakes. This study sought to investigate relationships between calcium, selenium and folate intakes and CRC. Calcium, selenium, and folate intakes and incidence of CRC from a selected cohort within the National Health and Nutrition Examination Survey (NHANES) 1999&ndash;2014 were analyzed. A total of 2,130 men and women aged 31 to 85 with and without CRC were included in the analysis. The relationships between daily intakes of calcium, selenium and folate and CRC incidence were analyzed using &chi;² test and logistic regression. Correlations between calcium, selenium and folate intakes and CRC were also assessed using Pearson&rsquo;s correlation coefficient.</p>