Background: Carotid body tumor (CBT) is a rare lesion of the neuroendocrine system. Chronic hypoxia has long been recognized as an etiology of CBT and other paragangliomas. Recent biogenetic discoveries reveal that mutations in oxygen-sensing genes are another etiology, accounting for approximately 35% of cases, and that these 2 etiologies are probably additive. Data Sources: (1) A retrospective analysis of fifteen cases of CBT in a 6-year period occurring in the mountains of Southern Appalachia; (2) an extensive review of the literature on the surgery of CBT and on the expansive biogenetic understanding of the disease. Conclusions: Improved imaging, vascular surgical techniques, and understanding of the disease have vastly improved outcomes for patients. The necessities for long-term follow-up and appropriate genetic testing and counseling of patients and their families are documented. Surgeon and institutional competence are critical in achieving maximal outcomes.

Thesis (Doctor of Radiography)--Cape Peninsula University of Technology, 2020 / Radiation therapy has undergone significant changes with regard to new medical imaging technologies, including computerised tomography (CT) and magnetic resonance imaging (MRI). Practitioners now have access to technologies that provide anatomical information in an infinite selection of views. Earlier advances in three-dimensional conformal radiation therapy (3D-CRT) allowed for the site of treatment to be accurately located. Intensity modulated radiotherapy (IMRT) enabled practitioners to accurately focus the ionising radiation beam, while modulating the intensity of the dose being administered. Currently, using image-guided radiotherapy (IGRT) methods, radiation therapists can track the effectiveness of treatment in real-time to provide better protection for the organs and tissue that are not targeted for treatment. The changes described above have fundamentally changed radiation therapy practice, and thus have implications for the training of radiation therapists. This thesis argues that without a deep understanding of the science underpinning the advancements in radiation therapy techniques, practitioners will be unlikely to achieve the necessary level of accuracy and consistency in treatment. Radiation physics concepts, such as sources and types of ionising radiation, ionisation, the isocentre and the Inverse Square Law underpin competent and safe practice. Threshold concepts, such as those listed above, have been identified as concepts that pose difficulty to students due to its complexity and the increased levels of cognitive challenge required to master a threshold concept. In applied disciplines, such as radiation physics, threshold concepts are strongly associated with competent practice. This study focused on the first year radiation physics curriculum and addressed the overarching research question: What is the relationship between threshold concepts in the radiation physics curriculum and radiation therapy practice? The study was guided by a translation device that combined two conceptual frameworks namely the Threshold Concept Framework and Legitimation Code Theory’s (LCT) Semantics dimension. LCT is a knowledge base theory that explains the complexity of knowledge structures. The Semantics dimension provided an explanation of the difficulty of concepts and proposed five pedagogies for the cumulative learning of complex concepts. A case study research design and methodology guided the research process. Data for the study comprised curriculum documents, and semi structured focus group and individual interviews with students, academic staff and clinical educators. The data were analysed using a translation device to show the semantic profile of curriculum documents, pedagogies and participants’ different understandings of the threshold concepts in radiation physics. The study found that threshold concepts in radiation physics underpin competent and safe practice. An external language of description was developed to identify the characteristics of threshold concepts. A virtual clinical environment was proposed as one of the pedagogies to aid mastering of threshold concepts through visualisation of the unseen by facilitating students’ understanding of threshold concepts for competent and safe radiation therapy practice. The study showed that students’ mastery of threshold concepts in radiation physics is critical for practice.

Breast cancer is one of the leading causes of death among women. In 2017, breast, lung and bronchus, prostate, and colorectal cancers accounted for almost 50% of all new cancer cases in the United States. Breast conservation therapy with lumpectomy (i.e., surgery) and adjuvant radiation therapy is commonly used as treatment for early stage breast cancer. However, side effects such as pain and poor sleep quality can affect quality of life for breast cancer patients undergoing radiation treatment. The main purpose of this quantitative study, using the health belief model (HBM) theoretical framework, was to investigate the correlations between the independent variable of exercise and the dependent variables of pain and sleep quality during radiation treatment. To examine these possible relationships, secondary data from another study were used, Self-Reported Exercise Behavior and Short-Term Patients Outcomes in Women Undergoing Radiation Treatment for Operable Breast Cancer by principal investigator Janet K. Horton of the Duke University Health System. The secondary data were analyzed using logistic regression and multiple linear regression statistical models. The findings from this study indicate that mild exercise is positively associated with reduced pain level and improved sleep quality and that vigorous exercise does not have a positive association with improved sleep quality. This study provides health practitioners with resources to encourage physical activity in breast cancer patients while undergoing and after radiation treatment. In this way, the study may serve to promote positive social change not only for breast cancer patients, but also for patients with other types of cancer to reduce side effects from radiation treatment.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12916号 / 論医博第2091号 / 新制||医||1009(附属図書館) / 32126 / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 伊達 洋至, 教授 鈴木 実 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13032号 / 論医博第2114号 / 新制||医||1016(附属図書館) / 32990 / 横浜市立大学大学院医科学専攻 / (主査)教授 増永 慎一郎, 教授 坂井 義治, 教授 小川 修 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20997号 / 医博第4343号 / 新制||医||1027(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 鈴木 実, 教授 平井 豊博, 教授 伊達 洋至 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Purpose: Tumour hypoxia is the result of uncontrolled growth of the tumour and its vasculature and is often found in solid tumours. It has been known for some time that tumour hypoxia is associated with increased radio resistance and poorer treatment outcomes. While there are several techniques to image the tumour’s oxygenation, no metric or guideline exists that helps in automatically delineating those hypoxic cells into target volumes. Even though several hypoxic biomarkers have been developed and tested to detect visualise and localise hypoxic areas, most of these delineated areas show volumes that are not immediately suitable for dose planning (i.e. a speckled hypoxia distribution). This work deals with 18 cases of tumour hypoxia in patients with non-small cell lung cancer (NSCLC) and presents a method that gives guidance on how to construct hypoxic target volumes feasible for dose planning. Materials and Methods: PET-CT scans have been taken with the hypoxic biomarker 18F-HX4. Hypoxic volumes have been extracted using a threshold of 10mmHg. A region growing algorithm was used to develop the HTV delineation method. Individually calculated doses based on the pO2-distribution within the hypoxic target volume have been used for the construction of dose plans with 24 fractions. Results: Treatment plans that boost the hypoxic target volume whilst sparing surrounding organs at risk were possible to construct for those tumours lying outside the mediastinum. Tumours which volumes were partially or fully overlapping with the mediastinum showed conflicts with delivering the dose necessary for a tumour control probability (TCP) of at least 95% and not exceeding the dose constraints set for the mediastinum.

Side effects of radiation therapy (RT) remain the most challenging issue for pancreatic cancer treatment. In this report we determined whether and how cerium oxide nanoparticles (CONPs) sensitize pancreatic cancer cells to RT. CONP pretreatment enhanced radiation-induced reactive oxygen species (ROS) production preferentially in acidic cell-free solutions as well as acidic human pancreatic cancer cells. In acidic environments, CONPs favor the scavenging of superoxide radical over the hydroxyl peroxide resulting in accumulation of the latter whereas in neutral pH CONPs scavenge both. CONP treatment prior to RT markedly potentiated the cancer cell apoptosis both in culture and in tumors and the inhibition of the pancreatic tumor growth without harming the normal tissues or host mice. Mechanistically, CONPs were not able to significantly impact RT-induced DNA damage in cancer cells, thereby ruling out sensitization through increased mitotic catastrophe. However, JNK activation, which is known to be a key driver of RT-induced apoptosis, was significantly upregulated by co-treatment with CONPs and RT in pancreatic cancer cells in vitro and human pancreatic tumors in nude mice in vivo compared to CONPs or RT treatment alone. Further, CONP-driven increase in RT-induced JNK activation was associated with marked increases in Caspase 3/7 activation, indicative of apoptosis. We have shown CONPs increase ROS production in cancer cells; ROS has been shown to drive the oxidation of thioredoxin (TRX) 1 which results in the activation of Apoptosis Signaling iv Kinase (ASK) 1. The dramatic increase in ASK1 activation following the co-treatment of pancreatic cancer cells with CONPs followed by RT in vitro suggests that increased the c-Jun terminal kinase (JNK) activation is the result of increased TRX1 oxidation. The ability of CONPs to sensitize pancreatic cancer cells to RT was mitigated when the TRX1 oxidation was prevented by mutagenesis of a cysteine residue, or the JNK activation was blocked by an inhibitor,. Additionally, angiogenesis in pancreatic tumors treated with CONPs and RT was significantly reduced compared to other treatment options. Taken together, these data demonstrate an important role and mechanisms for CONPs in specifically killing cancer cells and provide novel insight into the utilization of CONPs as a radiosensitizer and therapeutic agent for pancreatic cancer.

This thesis contributes to the topic of image-based feature localization and tracking in fluoroscopic (2D x-ray) image sequences. Such tracking is needed to automatically measure organ motion in cancer patients treated with radiation therapy. While the use of 3D cone-beam computed tomography (CBCT) images is a standard clinical practice for verifying the agreement of the patient's position to a plan, it is done before the treatment procedure. Hence, measurement of the motion during the procedure could improve plan design and the accuracy of treatment delivery. Using an existing CBCT imaging system is one way of collecting fluoroscopic sequences for such analysis. Since x-ray images of soft tissues are typically characterized with low contrast and high noise, radio-opaque fiducial markers are often inserted in or around the target. This thesis describes techniques that comprise a complete system for automated detection and tracking of the markers in fluoroscopic image sequences. One of the cornerstone design ideas in this thesis is the use of the 3D CBCT image of the patient, from which the markers can be extracted more easily, to initialize the tracking in the fluoroscopic image sequences. To do this, a specific marker-based image registration framework was proposed. It includes multiple novel techniques, such as marker segmentation and modelling, the marker enhancement filter, and marker-specific template image generation approaches. Through extensive experiments on testing data sets, these novel techniques were combined with appropriate state-of-the-art methods to produce a sleek, computationally efficient, fully automated system that achieved reliable marker localization and tracking. The accuracy of the system is sufficient for clinical implementation. The thesis demonstrates an application of the system to the images of prostate cancer patients, and includes examples of statistical analysis of organ motion that can be used to improve treatment planning. / Dissertation / Doctor of Philosophy (PhD) / This thesis presents the development of a software system that analyzes sequences of 2D x-ray images to automatically measure organ motion in patients undergoing radiation therapy for cancer treatment. The knowledge of motion statistics obtained from this system creates opportunities for patient-specific treatment design that may lead to a better outcome. Automated processing of organ motion is challenging due to the low contrast and high noise levels in the x-ray images. To achieve reliable detection, the proposed system was designed to make use of 3D cone-beam computed tomography images of the patient, where the features (markers) are easier to identify. This required the development of a specific image registration framework for aligning the images, including a number of novel feature modelling and image processing techniques. The proposed motion tracking approach was implemented as a complete software system that was extensively validated on phantom and patient studies. It achieved a level of accuracy and reliability that is suitable for clinical implementation.