Introduction: Thromboprophylaxis recommendations for hospitalized cancer are based on trials done for the general medically patients, as there are no randomized clinical trials(RCTs) looking at thromboprophylaxis in medically ill patients with cancer. Methods: To determine if thromboprophylaxis is safe and effective to prevent VTE these patients, a Systematic Review(SR) was done. A survey was performed to assess: clinical equipoise, trial design and minimally clinically important difference(MCID) for a potential trial. Lastly, a pilot study for an RCT was designed. Results: The pooled RR of VTE was 0.91 (95%CI:0.21 to 4.0;I2:68%) among hospitalized cancer patients receiving thromboprophylaxis compared to placebo. 63.9% believe there is clinical equipoise and 58.3% would consider participating in a RCT comparing different agents/dosing. The MCID for absolute reduction in symptomatic VTE between two arms was 2% and for “acceptable” increase in major bleeding events was 1%. Conclusion: The risk-benefit ratio of current doses of thromboprophylaxis administered to hospitalized cancer patients is unclear and additional RCTs are necessary.

Introduction: Thromboprophylaxis recommendations for hospitalized cancer are based on trials done for the general medically patients, as there are no randomized clinical trials(RCTs) looking at thromboprophylaxis in medically ill patients with cancer. Methods: To determine if thromboprophylaxis is safe and effective to prevent VTE these patients, a Systematic Review(SR) was done. A survey was performed to assess: clinical equipoise, trial design and minimally clinically important difference(MCID) for a potential trial. Lastly, a pilot study for an RCT was designed. Results: The pooled RR of VTE was 0.91 (95%CI:0.21 to 4.0;I2:68%) among hospitalized cancer patients receiving thromboprophylaxis compared to placebo. 63.9% believe there is clinical equipoise and 58.3% would consider participating in a RCT comparing different agents/dosing. The MCID for absolute reduction in symptomatic VTE between two arms was 2% and for “acceptable” increase in major bleeding events was 1%. Conclusion: The risk-benefit ratio of current doses of thromboprophylaxis administered to hospitalized cancer patients is unclear and additional RCTs are necessary.

Two-dimensional (2-D) micro-autoradiography is typically used to identify the location of a radio-labeled ligand bound to a cellular target in tissue sections. Data, such as a histological image, combined with the autoradiographic data provide a spatial relationship of the radiolabel to cellular structures. However, the disadvantage of 2-D imaging is that it only provides a local distribution of the radiolabel within a tissue slice, and not a volumetric regional distribution in the structure of interest. The development of 3-D autoradiographic/histological visualizations would provide important information not otherwise apparent, such as the ability to visualize the distribution of the labeled agents in subcutaneous tissue. We plan to obtain digital micro-autoradiographic images and fuse them to their corresponding histological images using commercially available software. We plan to create a series of 2-D fused images. This series of 2-D fused images will then form a basis for creating 3-D visualization of autoradiographic/histological images using another commercially available software. These type of fused 3-D images, which we will refer to as micro-autoradiographic fusion tomography (MAFT), are not currently available. We will illustrate the use of MAFT with the distribution of vascular endothelial growth factor (VEGF) in subcutaneous tissue. [14C]-VEGF will be injected into rat subcutaneous tissue. VEGF has been found to stimulate angiogenesis, or the growth of new blood vessels, which could prove beneficial by aiding the function of an implantable blood glucose sensor. The diffusion coefficient for VEGF in subcutaneous tissue has not yet been characterized. MAFT would be an ideal technique to use for this type of study. My thesis will address the following specific aims: 1) To label the nicotine receptors in adult and adolescent rat brains, and to obtain digital micro-autoradiographic images and histological images; 2) To fuse a 2-D digital micro-autoradiographic image with a 2-D histological image; 3) To create a 3-D image from a series of 2-D fusion images; and 4) To assess the increased information value obtained using MAFT.