High-resolution fluorescence endomicroscopy for rapid evaluation of breast cancer margins

Breast cancer is a major public health problem world-wide and the second leading cause of cancer-related female deaths. Breast conserving surgery (BCS), in the form of wide local excision (WLE), allows complete tumour resection while maintaining acceptable cosmesis. It is the recommended treatment for a large number of patients with early stage disease or, in more advanced cases, following neoadjuvant chemotherapy. About 30% of patients undergoing BCS require one or more re-operative interventions, mainly due to the presence of positive margins. The standard of care for surgical margin assessment is post-operative examination of histopathological tissue sections. However, this process is invasive, introduces sampling errors and does not provide real-time assessment of the tumour status of radial margins. The objective of this thesis is to improve intra-operative assessment of margin status by performing optical biopsy in breast tissue. This thesis presents several technical and clinical developments related to confocal fluorescence endomicroscopy systems for real-time characterisation of different breast morphologies. The imaging systems discussed employ flexible fibre-bundle based imaging probes coupled to high-speed line-scan confocal microscope set-up. A preliminary study on 43 unfixed breast specimens describes the development and testing of line-scan confocal laser endomicroscope (LS-CLE) to image and classify different breast pathologies. LS-CLE is also demonstrated to assess the intra-operative tumour status of whole WLE specimens and surgical excisions with high diagnostic accuracy. A third study demonstrates the development and testing of a bespoke LS-CLE system with methylene blue (MB), an US Food and Drug Administration (FDA) approved fluorescent agent, and integration with robotic scanner to enable large-area in vivo imaging of breast cancer. The work also addresses three technical issues which limit existing fibre-bundle based fluorescence endomicroscopy systems: i) Restriction to use single fluorescence agent due to low-speed, single excitation and single fluorescence spectral band imaging systems; ii) Limited Field of view (FOV) of fibre-bundle endomicroscopes due to small size of the fibre tip and iii) Limited spatial resolution of fibre-bundle endomicroscopes due to the spacing between the individual fibres leading to fibre-pixelation effects. Details of design and development of a high-speed dual-wavelength LS-CLE system suitable for high-resolution multiplexed imaging are presented. Dual-wavelength imaging is achieved by sequentially switching between 488 nm and 660 nm laser sources for alternate frames, avoiding spectral bleed-through, and providing an effective frame rate of 60 Hz. A combination of hand-held or robotic scanning with real-time video mosaicking, is demonstrated to enable large-area imaging while still maintaining microscopic resolution. Finally, a miniaturised piezoelectric transducer-based fibre-shifting endomicroscope is developed to enhance the resolution over conventional fibre-bundle based imaging systems. The fibre-shifting endomicroscope provides a two-fold improvement in resolution and coupled to a high-speed LS-CLE scanning system, provides real-time imaging of biological samples at 30 fps. These investigations furthered the utility and applications of the fibre-bundle based fluorescence systems for rapid imaging and diagnosis of cancer margins.Open Acces

Medical Robotics

The first generation of surgical robots are already being installed in a number of operating rooms around the world. Robotics is being introduced to medicine because it allows for unprecedented control and precision of surgical instruments in minimally invasive procedures. So far, robots have been used to position an endoscope, perform gallbladder surgery and correct gastroesophogeal reflux and heartburn. The ultimate goal of the robotic surgery field is to design a robot that can be used to perform closed-chest, beating-heart surgery. The use of robotics in surgery will expand over the next decades without any doubt. Minimally Invasive Surgery (MIS) is a revolutionary approach in surgery. In MIS, the operation is performed with instruments and viewing equipment inserted into the body through small incisions created by the surgeon, in contrast to open surgery with large incisions. This minimizes surgical trauma and damage to healthy tissue, resulting in shorter patient recovery time. The aim of this book is to provide an overview of the state-of-art, to present new ideas, original results and practical experiences in this expanding area. Nevertheless, many chapters in the book concern advanced research on this growing area. The book provides critical analysis of clinical trials, assessment of the benefits and risks of the application of these technologies. This book is certainly a small sample of the research activity on Medical Robotics going on around the globe as you read it, but it surely covers a good deal of what has been done in the field recently, and as such it works as a valuable source for researchers interested in the involved subjects, whether they are currently “medical roboticists” or not

Exploration and Implementation of Augmented Reality for External Beam Radiotherapy

We have explored applications of Augmented Reality (AR) for external beam radiotherapy to assist with treatment planning, patient education, and treatment delivery. We created an AR development framework for applications in radiotherapy (RADiotherapy Augmented Reality, RAD-AR) for AR ready consumer electronics such as tablet computers and head mounted devices (HMD). We implemented in RAD-AR three tools to assist radiotherapy practitioners with: treatment plans evaluation, patient pre-treatment information/education, and treatment delivery. We estimated accuracy and precision of the patient setup tool and the underlying self-tracking technology, and fidelity of AR content geometric representation, on the Apple iPad tablet computer and the Microsoft HoloLens HMD. Results showed that the technology could already be applied for detection of large treatment setup errors, and could become applicable to other aspects of treatment delivery subject to technological improvements that can be expected in the near future. We performed user feedback studies of the patient education and the plan evaluation tools. Results indicated an overall positive user evaluation of AR technology compared to conventional tools for the radiotherapy elements implemented. We conclude that AR will become a useful tool in radiotherapy bringing real benefits for both clinicians and patients, contributing to successful treatment outcomes

Patients who decide to forgo Breast Cancer Treatment: Perspectives and Experiences of Cancer Professionals.

Background: Breast cancer is highly treatable if caught early, yet there are increasing numbers of women who decline treatment entirely, or in favour of alternative therapies. Previous research has demonstrated that such decisions can be troubling for health professionals, creating an ethical dilemma in which the bioethical mandate to respect patient autonomy must be offset against duties to act in the patient’s best interest. Previous research has indicated that health professionals may find it difficult to accept and understand such decisions; however, this research has predominantly focused on the experiences of different health professionals in isolation. Method: Qualitative, semi-structured interviews were carried out with eight oncology health professionals (Three oncologists, two breast surgeons and three clinical nurse specialists) to explore how health professionals understood and responded to these decisions. A critical realist epistemology was adopted and interviews were analysed using thematic analysis. Results: Four overarching themes were identified including ‘Head-Heart Lag’, ‘Tug of War’ ‘You Can’t Win Them All’ and ‘The Power and Privilege of Unbiased Expertise’. Themes yielded insights into how professionals navigate their responsibilities towards patients who decline treatment and the values, frameworks and resources that influence this process. Conclusion: Results indicated that health professionals’ responses were grounded in a commitment to evidence based practice, and that time and experience are important factors in professionals learning to accept a decision to decline breast cancer treatment. Findings are considered in the broader social context of contemporary healthcare and in relation to professional and patient needs. Recommendations are made for a more reflexive medical practice which transcends the constraints of the evidence-based paradigm and liberates health professionals to engage with the existential, as well as the medical within the clinical encounter

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p < 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p < 0.001). Males were significantly more likely to be admitted than females (p < 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

Design and fabrication of silicone-based composite tissue-mimicking phantoms for medical training

Silicone-based composite phantoms were fabricated to be used as an education model in medical training. A matrix of silicone formulations was tracked to mimic the ultrasonography, mammography, surgical, and microsurgical responses of different human tissue and organs. The performance of two different additives: i) silicone oil and ii) vinyl-terminated poly (dimethylsiloxane) (PDMS) were monitored with the acoustic setup and evaluated by the surgeons. Breast cancer is one of the most common types of cancer among women, and early diagnosis significantly improves the patient outcomes. The surgeons-in-training necessitate the vast amount of practice to facilitate a noteworthy contribution to this outcome. Therefore, breast simulation models that contain skin layer, inner breast tissue, and tumor structures which allow the collection of samples with biopsy needle were fabricated to be used in ultrasonography, as well as mammography models to be used in tumor diagnostics, and breast oncoplasty models for surgeons to practice their suturing skills. Development of microsurgical techniques signifies a foremost advance in the intervention of the injured peripheral nerves and with the aid of the operating microscopes; it is possible to evaluate the severity of the neural trauma. The advanced microsurgical skills of surgeons are essential for the success of the microsurgery, and in turn for the preservation of the nerve continuity. With this motive, a peripheral nerve phantom that contains skin layer, fascia tissue, epineurium, connective tissue, the fascicles, and the muscle layer has been designed. Herein, we highlight the fabrication of a realistic, durable, accessible, and cost-effective training platform that contains breast ultrasonography, mammography, and oncoplasty models, as well as peripheral nerve with complex hierarchical layers. For training purposes, closest media to reality, fresh cadavers, are hard to obtain due to their price and/or unavailability. Hence, a variety of synthetic tissues were also designed through the optimization of formulations of silicone. Surgical simulation models that mimic various human tissue and organs such as i) multi layers of skin, ii) axilla and axillary lymph nodes, iii) veins, iv) isthmus of the thyroid gland, cricoid cartilage, tongue, larynx, esophagus, tracheal rings, and bronchial tree for the tracheostomy and bronchoscopy models were fabricated

Complexity Reduction in Image-Based Breast Cancer Care

The diversity of malignancies of the breast requires personalized diagnostic and therapeutic decision making in a complex situation. This thesis contributes in three clinical areas: (1) For clinical diagnostic image evaluation, computer-aided detection and diagnosis of mass and non-mass lesions in breast MRI is developed. 4D texture features characterize mass lesions. For non-mass lesions, a combined detection/characterisation method utilizes the bilateral symmetry of the breast s contrast agent uptake. (2) To improve clinical workflows, a breast MRI reading paradigm is proposed, exemplified by a breast MRI reading workstation prototype. Instead of mouse and keyboard, it is operated using multi-touch gestures. The concept is extended to mammography screening, introducing efficient navigation aids. (3) Contributions to finite element modeling of breast tissue deformations tackle two clinical problems: surgery planning and the prediction of the breast deformation in a MRI biopsy device

Coping and stress management training with special focus on women with breast cancer

Background: People diagnosed with cancer are confronted with many stressors, such as worries about diagnosis and prognosis, demanding treatments, treatment decisions, and disruption of ordinary life functions and roles. Compared to other types of cancer, breast cancer affects relatively young women, half of them of working ages. Knowledge of effective strategies to cope with breast cancer, as well as development of interventions strengthening stress management skills among women with breast cancer, are important in order to decrease individual suffering and facilitate the transition back into everyday life, including work. Aims: The general aim of this thesis was to generate more knowledge regarding psychological and social aspects of being diagnosed with breast cancer. More specifically, the aims were to examine sickness absence and disability pension after diagnosis, how different ways of coping with breast cancer are linked to health outcomes, and ways to promote mental health after diagnosis. Methods: Study I: All 3547 women in Sweden aged 20-65 with a first breast cancer diagnosis in 2005 and a matched comparison group were followed by register linkage regarding annual levels of diagnosis-specific sickness absence and disability pension through 2010. Associations with disease-related and sociodemographic factors were estimated using logistic regression. Study II: 78 studies were included in a meta-analysis ofassociations between different strategies to cope with a breast cancer diagnosis and health outcomes. The influence ofpotential moderators was also studied. Study III: People with cancer (76% with breast cancer) were randomized to a mindfulness-based stress management training program (n=32) or a wait-list control condition (n=39). Effects on psychological processes and mental health outcomes after six months were analyzed. Study IV: University students participating in a feasibility study of an Internetbased version of the mindfulness-based stress management training program were randomized to the intervention (n=46) or an active control condition (n=44). Completion rate, participant experiences, and post-intervention effects on mental health were assessed. Results: Study I: Sickness absence, mainly due to breast cancer, increased markedly in the first year after breast cancer diagnosis, however, it approached the levels of breast cancer-free women five years later. Pre-diagnosis sickness absence and advanced cancer stage were associated with higher risk of sickness absence and disability pension, as were lower education and being born outside of Sweden. Study II: Adaptive coping, such as acceptance and positive reappraisal, was associated with better mental health in women with breast cancer. These associations were strongest among individuals under current treatment and women assessed soon after diagnosis. Study III: No significant effect of the mindfulness-based stress management training program on mental health outcomes was found at the six-month follow-up. However, a positive effect on self-reported mindfulness was observed. Study IV: The Internet-based mindfulness-based stress management training program was experienced as usable and acceptable and had potential for increasing psychological well-being for those completing it. However, only 39% of the participants completed the program. Conclusions: Among women diagnosed with breast cancer, levels of sickness absence were back to the same levels as before diagnosis in a few years. Adaptive coping was associated with better mental health among women with breast cancer, especially during treatment and in newly diagnosed women. Despite increase in mindfulness at six-month follow-up after a mindfulness-based stress management training program, no statistically significant improvement in mental health was found. More knowledge is needed on the underlying mechanisms and moderating factors for achieving long-term benefits ofthis kind oftraining. The Internet could be a promising way to disseminate programs and tools facilitating mindfulness training, but if retention and compliance is important, additional modification of the assessed Internet-based mindfulness-based stress management training program is needed

Clinical Management and Evolving Novel Therapeutic Strategies for Patients with Brain Tumors

A dramatic increase in knowledge regarding the molecular biology of brain tumors has been established over the past few years, and this has lead to the development of novel therapeutic strategies for these patients. In this book a review of the options available for the clinical management of patients with these tumors are outlined. In addition advances in radiology both for pre-operative diagnostic purposes along with surgical planning are described. Furthermore a review of newer developments in chemotherapy along with the evolving field of photodynamic therapy both for intra-operative management and subsequent therapy is provided. A discussion of certain surgical management issues along with tumor induced epilepsy is included. Finally a discussion of the management of certain unique problems including brain metastases, brainstem glioma, central nervous system lymphoma along with issues involving patients with a brain tumor and pregnancy is provided