Computer-assisted liver surgery: clinical applications and technological trends

Oncological liver surgery and interventions aim for removal of tumor tissue while preserving a sufficient amount of functional tissue to ensure organ regeneration. This requires detailed understanding of the patient-specific internal organ anatomy (blood vessel system, bile ducts, tumor location). The introduction of computer support in the surgical process enhances anatomical orientation through patient-specific 3D visualization and enables precise reproduction of planned surgical strategies though stereotactic navigation technology. This article provides clinical background information on indications and techniques for the treatment of liver tumors, reviews the technological contributions addressing the problem of organ motion during navigated surgery on a deforming organ, and finally presents an overview of the clinical experience in computer-assisted liver surgery and interventions. The review concludes that several clinically applicable solutions for computer aided liver surgery are available and small-scale clinical trials have been performed. Further developments will be required more accurate and faster handling of organ deformation and large clinical studies will be required for demonstrating the benefits of computer aided liver surgery.

[Endobronchial ultrasound: practical aspects and clinical applications]

Endobronchial ultrasound (EBUS) has become a major advance in bronchoscopy. Substantial scientific evidence has confirmed its usefulness in lung cancer diagnosis and staging, as well as in other clinical settings. It is of growing importance that endoscopists perform and interpret this imaging method accurately, in order to optimize diagnosis and treatment of their patients. The present article provides a practical and comprehensible review of the two EBUS systems currently available and its main clinical indications.

Cardiovascular proteomics: implications for clinical applications

Proteomics is fulfilling its potential and beginning to impact the diagnosis and therapy of cardiovascular disease. As de novo proteomics analysis gets more streamlined, and robust high-throughput methods are developed, more and more attention is being directed toward the field of cardiovascular serum and plasma biomarker discovery. To take cardiovascular proteomics from bench to bedside, great care must be taken to achieve reproducible results. Despite technical advances, however, the absolute number of clinical biomarkers thus far discovered by a proteomics approach is small. Although several factors contribute to this lack, one step is to build "translation teams" involving a close collaboration between researchers and clinicians.

Dual energy subtraction: principles and clinical applications

Two technical solutions using single or dual shot offer different advantages and disadvantages for dual energy subtraction. The principles of these are explained and the main clinical applications with results are demonstrated. Elimination of overlaying bone and proof or exclusion of calcification are the primary aims of energy subtraction chest radiography, offering unique information in different clinical situations.

Gene therapy of cancer: Mechanisms of ``bystander effect'' killing in cells expressing the herpes simplex virus-thymidine kinase gene and its potential clinical applications

At the fore-front of cancer research, gene therapy offers the potential to either promote cell death or alter the behavior of tumor-cells. One example makes use of a toxic phenotype generated by the prodrug metabolizing gene, thymidine kinase (HSVtk) from the Herpes Simplex Virus. This gene confers selective toxicity to a relatively nontoxic prodrug, ganciclovir (GCV). Tumor cells transduced with the HSVtk gene are sensitive to 1-50 $\mu$M GCV; normal tissue is insensitive up to 150-250 $\mu$M GCV. Utilizing these different sensitivities, it is possible to selectively ablate tumor cells expressing this gene. Interestingly, if a HSVtk$\sp+$ expressing population is mixed with a HSVtk$\sp-$ population at high density, all the cells are killed after GCV administration. This phenomenon for killing all neighboring cells is termed the "bystander effect", which is well documented in HSVtk$\sp-$ GCV systems, though its exact mechanism of action is unclear.^ Using the mouse colon carcinoma cell line CT26, data are presented supporting possible mechanisms of "bystander effect" killing of neighboring CT26-tk$\sp-$cells. A major requirement for bystander killing is the prodrug GCV: as dead or dying CT26tk$\sp+$ cells have no toxic effect on neighboring cells in its absence. In vitro, it appears the bystander effect is due to transfer of toxic GCV-metabolites, through verapamil sensitive intracellular-junctions. Additionally, possible transfer of the HSVtk enzyme to bystander cells after GCV addition, may play a role in bystander killing. A nude mouse model suggests that in a 50/50 (tk$\sp+$/tk$\sp-$) mixture of CT26 cells the bystander eradication of tumors does not involve an immune component. Additionally in a possible clinical application, the "bystander effect" can be directly exploited to eradicate preexisting CT26 colon carcinomas in mice by intratumoral implantation of viable or lethally irradiated CT26tk$\sp+$ cells and subsequent GCV administration. Lastly, an application of this toxic phenotype gene to a clinical marking protocol utilizing a recombinant adenoviral vector carrying the bifunctional protein GAL-TEK to eradicate spontaneously-arisen or vaccine-induced fibrosarcomas in cats is demonstrated. ^

Diffusion-weighted imaging in musculoskeletal radiology-clinical applications and future directions

Diffusion-weighted imaging (DWI) is an established diagnostic tool with regards to the central nervous system (CNS) and research into its application in the musculoskeletal system has been growing. It has been shown that DWI has utility in differentiating vertebral compression fractures from malignant ones, assessing partial and complete tears of the anterior cruciate ligament (ACL), monitoring tumor response to therapy, and characterization of soft-tissue and bone tumors. DWI is however less useful in differentiating malignant vs. infectious processes. As of yet, no definitive qualitative or quantitative properties have been established due to reasons ranging from variability in acquisition protocols to overlapping imaging characteristics. Even with these limitations, DWI can still provide clinically useful information, increasing diagnostic accuracy and improving patient management when magnetic resonance imaging (MRI) findings are inconclusive. The purpose of this article is to summarize recent research into DWI applications in the musculoskeletal system.

Concise review:bone marrow for the treatment of spinal cord injury: mechanisms and clinical applications

Transplantation of bone marrow stem cells into spinal cord lesions enhances axonal regeneration and promotes functional recovery in animal studies. There are two types of adult bone marrow stem cell; hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs). The mechanisms by which HSCs and MSCs might promote spinal cord repair following transplantation have been extensively investigated. The objective of this review is to discuss these mechanisms; we briefly consider the controversial topic of HSC and MSC transdifferentiation into central nervous system cells but focus on the neurotrophic, tissue sparing, and reparative action of MSC grafts in the context of the spinal cord injury (SCI) milieu. We then discuss some of the specific issues related to the translation of HSC and MSC therapies for patients with SCI and present a comprehensive critique of the current bone marrow cell clinical trials for the treatment of SCI to date.

Interhemispheric differences of spectral power in expressive language:a MEG study with clinical applications

In the last decade we have seen an exponential growth of functional imaging studies investigating multiple aspects of language processing. These studies have sparked an interest in applying some of the paradigms to various clinically relevant questions, such as the identification of the cortical regions mediating language function in surgical candidates for refractory epilepsy. Here we present data from a group of adult control participants in order to investigate the potential of using frequency specific spectral power changes in MEG activation patterns to establish lateralisation of language function using expressive language tasks. In addition, we report on a paediatric patient whose language function was assessed before and after a left hemisphere amygdalo-hippocampectomy. Our verb generation task produced left hemisphere decreases in beta-band power accompanied by right hemisphere increases in low beta-band power in the majority of the control group, a previously unreported phenomenon. This pattern of spectral power was also found in the patient's post-surgery data, though not her pre-surgery data. Comparison of pre and post-operative results also provided some evidence of reorganisation in language related cortex both inter- and intra-hemispherically following surgery. The differences were not limited to changes in localisation of language specific cortex but also changes in the spectral and temporal profile of frontal brain regions during verb generation. While further investigation is required to establish concordance with invasive measures, our data suggest that the methods described may serve as a reliable lateralisation marker for clinical assessment. Furthermore, our findings highlight the potential utility of MEG for the investigation of cortical language functioning in both healthy development and pathology.