MR Imaging-Histology Correlation by Tailored 3D-Printed Slicer in Oncological Assessment.

3D printing and reverse engineering are innovative technologies that are revolutionizing scientific research in the health sciences and related clinical practice. Such technologies are able to improve the development of various custom-made medical devices while also lowering design and production costs. Recent advances allow the printing of particularly complex prototypes whose geometry is drawn from precise computer models designed on in vivo imaging data. This review summarizes a new method for histological sample processing (applicable to e.g., the brain, prostate, liver, and renal mass) which employs a personalized mold developed from diagnostic images through computer-aided design software and 3D printing. Through positioning the custom mold in a coherent manner with respect to the organ of interest (as delineated by in vivo imaging data), the cutting instrument can be precisely guided in order to obtain blocks of tissue which correspond with high accuracy to the slices imaged. This approach appeared crucial for validation of new quantitative imaging tools, for an accurate imaging-histopathological correlation and for the assessment of radiogenomic features extracted from oncological lesions. The aim of this review is to define and describe 3D printing technologies which are applicable to oncological assessment and slicer design, highlighting the radiological and pathological perspective as well as recent applications of this approach for the histological validation of and correlation with MR images.

Concordancia entre la medición directa y el valor estimado de colesterol de LDL en pacientes ambulatorios / Concordance between direct measurement and estimated LDL cholesterol in outpatients / Concordância entre medição direta e colesterol LDL estimado em pacientes ambulatoriais

Los laboratorios clínicos estiman la concentración del colesterol asociado a la lipoproteína de baja densidad (cLDL) mediante la ecuación de Friedewald; sin embargo, ésta presenta una notable desviación cuando la concentración sérica de triglicéridos se encuentra elevada. Se compararon 4.644 resultados de cLDL valorados en el laboratorio central del Hospital Edgardo Rebagliati Martins (Lima-Perú), mediante el ensayo directo homogéneo, con los valores estimados por las ecuaciones de Friedewald, Anandaraja, Chen, Vujovic, Córdova y de regresión múltiple. Además, se estratificaron los resultados en 5 grupos en función de las concentraciones de triglicéridos para determinar la influencia que ejerce el nivel de triglicéridos sobre dichas ecuaciones. En el total de las estimaciones, las ecuaciones de regresión y Vujovic mostraron los menores sesgos de -3,00 y -2,90 mg/dL, respectivamente. Asimismo, ambas ecuaciones presentaron un grado de acuerdo sustancial con la determinación directa y un menor error sistemático en los tres niveles de decisión clínica para el cLDL; sin embargo, la ecuación de regresión presentó una mejor performance para estimar el cLDL en concentraciones de triglicéridos ≥401 mg/dL. Se concluye que la ecuación de regresión presenta bajo error analítico, además de mostrar una buena concordancia con el método directo, incluso a concentraciones altas de triglicéridos.

Clinical laboratories estimate the concentration of low-density lipoprotein cholesterol (LDLc) associated with the Friedewald equation, but the latter shows a significant deviation when the serum triglyceride concentration is elevated. A total of 4644 LDLc values assessed at the central laboratory of the Edgardo Rebagliati Martins Lima-Perú Hospital were compared by means of the homogeneous direct assay with the values estimated by the Friedewald, Anandaraja, Chen, Vujovic, Córdova and multiple regression equations. Besides, the results were stratified into 5 groups based on triglyceride concentrations to determine the influence exerted by the triglyceride level on these equations. In the total of the estimates, the regression equations and Vujovic showed the lowest biases of -3.00 and -2.90 mg/dL respectively. Likewise, both equations presented a degree of substantial agreement with the direct determination and a smaller systematic error in the three levels of clinical decision for LDLc. However, the regression equation showed a better performance for estimating LDLc at triglyceride concentrations ≥401 mg/dL. It is concludeasdasdd that the regression equation presents low analytical error, besides showing a good concordance with the direct method even at high triglyceride concentrations.

Laboratórios clínicos calculam a concentração do colesterol associado à lipoproteína de baixa densidade (LDLc), utilizando a equação de Friedewald; no entanto ela apresenta um desvio significativo quando a concentração sérica de triglicerídeos está elevada. 4644 resultados de LDLc foram comparados avaliados no laboratório central do Hospital Edgardo Rebagliati Martins (Lima-Peru), por ensaio directo homogêneo, com os valores estimados pelas equações Friedewald, Anandaraja, Chen, Vujovic, Córdova e de regressão múltipla. Além disso, foram estratificados os resultados em cinco grupos com base nas concentrações de triglicerídeos para determinar a influência que exerce o nível de triglicerídeos sobre tais equações. No total das estimativas, as equações de regressão e Vujovic mostraram os menores vieses de -3,00 e -2,90 mg/DL, respectivamente. Também, ambas as equações apresentaram um grau substancial de acordo com a determinação direta e um menor erro sistemático nos três níveis de decisão clínica para o LDLc; contudo, a equação de regressão apresentou melhor desempenho para estimar o LDLc em concentrações de triglicerídeos ≥401 mg/dL. Conclui-se que a equação de regressão apresenta baixo erro analítico, além de mostrar boa concordância com o método direto, mesmo em altas concentrações de triglicerídeos.

[Integration of Internal and Clinical Laboratory Medicine].

The mission of our department is to contribute to diagnostic improvement in medicine in order to promote better outcomes. We have clinical expertise in internal medicine including primary care medicine, hematology, allergy, rheumatology, and nephrology. We also have expertise in clinical laboratory medicine and hospital infection control. Specific areas of academic interest include immune-mediated hematological diseases, allergic diseases, autoimmune diseases, and chronic kidney disease. Immune recovery following hematopoietic stem cell transplantation and the immunopathophysiology of bone marrow failure syndrome have been our main topics of interest, and we have been applying our knowledge of T-cell receptor diversity to these areas in order to explore the mechanisms of immunodeficiency and autoimmunity in hematological disorders. We have found that the peripheral expansion of mature T cells in grafts plays an important role in immune reconstitution after stem cell transplantation in humans, and have also found altered T-cell repertoires in immune-mediated chronic acquired pure red cell aplasia. Thus, quantitative and qualitative analyses of immune receptors could be a promising method for assessing immunocompetence and exploring the pathophysiology of autoimmune diseases. Research and development of novel approaches in this field should be intensively conducted.

[Clinical Personnel Training in Laboratory Medicine in Chiba University Hospital during the Past 15 Years].

During the past 15 years, various approaches have been adopted for medical personnel training in the Division of Laboratory Medicine, Chiba University Hospital. Medical personnel have been encouraged to enter the Graduate School of Medicine, Chiba University. At present, 14 of them have successfully completed the Ph.D. program and 16 have been awarded a master's degree. In our unit, clinical proteomics is a principal research subject, and we have identified a number of biomarker candidates in collaboration with clinical units. In Chiba University Hospital, all clinical laboratory physicians are certified as medical geneticists and are in charge of the Division of Clinical Genetics as well. We have treated a total of 1,009 patients, including those with hereditary neuromuscular diseases, familial cancers, and prenatal diagnoses. We have also encouraged medical technologists to become certified as genetic counselors, which may be a promising subspecialty for medical technologists. Mass spectrometry (MS) is a powerful analytical tool used in an increasing number of clinical laboratories around the world. Liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS) has been used for newborn screening, toxicology, therapeutic drug monitoring endocrinology, and, more recently, for the measurement of targeted proteins and peptides. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) has proven to be a rapid and reliable tool for identifying microorganisms. The Japanese Society for Medical Mass Spectrometry has started to certify medical mass spectrometrists, which could be another promising subspecialty for medical technologists.

[Circulating tumor cells: a new challenge for laboratory medicine]. / Les cellules tumorales circulantes : un nouveau challenge pour la biologie clinique oncologique.

Circulating tumor cells (CTCs) can be detected in the blood of patients with nearly all types of locally and metastatic adenocarcinomas. CTCs are epithelial cells whose release from a primitive tumor or a metastatic localization may be mediated by an epithelial-mesenchymal transition. Their pro-metastatic potential is still under debate because their phenotypes may be very heterogeneous, even within the same patient (expression of stem-cells markers, apoptotic status...). They often exhibit discrepancies with the primitive tumor, especially concerning the molecular basis of sensitivity/resistance to targeted therapies (expression of HER2 and hormone receptors, mutations responsible for resistance to tyrosine-kinase inhibitors). Many methods for CTCs analysis are commercially available but very few are evaluated and standardized enough for clinical applications. The CellSearch device is the only one which is validated by the FDA for managing metastatic breast, prostate and colo-rectal cancer. It was used in most of the studies having demonstrated the prognostic and predictive value of CTCs in many tumoral localizations. Other studies are wanted to assess the ability of CTCs to optimize the therapeutic choices, to monitor drug efficiency in real-time as well as to become a surrogate end-point for evaluation of new therapies. Beyond CTCs enumeration, their biological features will need to be investigated.

Radiation protection in pediatric interventional cardiology: An IAEA PILOT program in Latin America.

The aim of this work is to present a methodology and some initial results for a pilot program on radiation protection (RP) in pediatric interventional cardiology under the auspices of the International Atomic Energy Agency. The starting point of the program was a workshop involving several pediatric cardiologists leading this specialty in 11 Latin American countries. The workshop included a pilot RP training course and additional sessions during which the objectives of the program and the methodology to collect and process data on patient and staff radiation doses were discussed. Special attention was dedicated to agree on a common quality control (QC) protocol for the x-ray and imaging systems used in the different catheterization laboratories. The preliminary data showed that only 64% of the cardiologists used their personal dosimeters regularly and that only 36% were aware of their personal dose values. The data on pediatric interventional activity were collected from 10 centers from nine different countries. A total of 2,429 procedures (50% diagnostic and 50% therapeutic) were carried out during 2009 in these centers. Patient dose data were available in only a few centers and were not analyzed on a regular basis in any of the catheterization laboratories involved. Plans were developed for a basic QC protocol of the x-ray systems and construction of a Latin American database on pediatric cardiology with patient and staff dose values with the idea in mind of obtaining distributions of these dose values before promoting several optimization strategies.

Innovations in therapies for heart valve disease.

The burden of heart valve disease among adults is enormous in the developed world. Increased life expectancy and age-related valvular degeneration remain the predominant contributors to heart valve dysfunction, which if uncorrected lead to congestive heart failure and increased morbidity and mortality. Clinical evidence on the detrimental impact of valve disease on both pediatric and adult populations has fueled growing interest in diagnosis and therapy for heart valve disease, and also significant financial investment from hospitals and medical device manufacturers in hybrid operating rooms and novel medical device technologies. A wide array of surgical, minimally invasive and percutaneous heart valve technologies are available today, which have significantly enlarged the surgeon's armamentarium, and revolutionized the traditional role of a surgeon in correcting such lesions. Amid this revolution in heart valve technologies, we present recent advances in heart valve therapies, critically appraise their clinical need, and finally discuss the clinical experience and outcomes of some of these technologies. The expected outcome of this review is to provide the clinical reader with a reasonable scientific basis to enable appropriate adoption of these technologies into their clinical practice.

International Conference on Advances in Radiation Oncology (ICARO): outcomes of an IAEA meeting.

The IAEA held the International Conference on Advances in Radiation Oncology (ICARO) in Vienna on 27-29 April 2009. The Conference dealt with the issues and requirements posed by the transition from conventional radiotherapy to advanced modern technologies, including staffing, training, treatment planning and delivery, quality assurance (QA) and the optimal use of available resources. The current role of advanced technologies (defined as 3-dimensional and/or image guided treatment with photons or particles) in current clinical practice and future scenarios were discussed.ICARO was organized by the IAEA at the request of the Member States and co-sponsored and supported by other international organizations to assess advances in technologies in radiation oncology in the face of economic challenges that most countries confront. Participants submitted research contributions, which were reviewed by a scientific committee and presented via 46 lectures and 103 posters. There were 327 participants from 70 Member States as well as participants from industry and government. The ICARO meeting provided an independent forum for the interaction of participants from developed and developing countries on current and developing issues related to radiation oncology.

[Disappearing borders between visceral surgery and interventional endoscopy]. / Schwindende Fachgrenzen zwischen Viszeralchirurgie und interventioneller Endoskopie.

The tremendous increase in medical knowledge over the last decades and technical progress in medicine have caused further professional specialization. Numerous medical fields have evolved through the process of separation from the parent specialization and the traditional distinction between surgical and medical disciplines has been blurred. As a result of this development organ-specific interdisciplinary units have been formed and new partners have united, such as surgeons and gastroenterologists in the field of interventional endoscopy. The fading boundaries brought with them resistance and even resentment and called for a mutual regulation by the professional associations which took place 10 years ago. Nowadays, surgeons and gastroenterologists in Germany are trained in interventional endoscopy and are the foundation of endoscopic interdisciplinary teamwork in emergency care, diagnostics, therapy, complication management and palliative treatment. Technical innovations striving for a minimization of operative trauma like NOTES depend on the cooperation of both fields of expertise. The driving force behind these efforts should be the shared interest in further improvement of patient care at the highest level of individual expertise, patient-oriented process optimization and adequate use of resources.

[Diminishing borders between cardiology and cardiothoracic surgery: quo vadis?]. / Schwindende Fachgrenzen zwischen Kardiologie und Kardiochirurgie: Quo vadis?

UNLABELLED: Increasingly complex techniques in cardiovascular medicine lead to a competitive partnership between cardiology and cardiac surgery. Common challenges will arise in the fields of coronary heart disease, heart valves, heart failure and rhythm therapy. For instance, coronary revascularization in acute myocardial infarction is no longer considered to exclusively be an interventional option. In comparison, the implantation of heart valves is increasingly carried out by cardiologists using interventional techniques. The latest designs of sutureless valves try to combine the benefits of conventional and transcatheter heart valves. Heart failure is the most common reason for hospital admission and thus an important therapeutic target for cardiology and cardiac surgery. New approaches in diagnostics, heart assist devices and cellular therapy meet this challenge. CONCLUSION: In the future only a sensitive and transparent collaboration across transsectoral borders will offer optimal therapy in cardiovascular medicine.

[Disappearing borders between the disciplines vascular surgery and interventional radiology from the perspective of vascular surgeons]. / Schwindende Fachgrenzen zwischen Gefässchirurgie und interventioneller Radiologie aus Sicht des Gefässchirurgen.

Demographic development leads to an exponential increase of cardiovascular illness. Additionally, technical development of conservative and invasive treatment modalities adds to an increase of specified therapy. Both items lead to increased specialization and a new orientation of vascular specialties. This concept implies that specific contents are referred and contained to the partner specialties. Angiology, vascular surgery and radiology are primary partners in this concept, however, in the following article the focus lies on vascular surgery and radiology.

Transatlantic Innovations: a new approach to international ideas and technology.

BACKGROUND: In April of this past year, Transatlantic Innovations brought a variety of organizations and industry together for an international exchange of ideas, new technology, and current trends in plastic surgery. METHODS: The meeting was highly interactive and included audience response devices. The focus was on 10 major areas: (1) new surgical techniques; (2) composite allografts versus conventional techniques, facing the future; (3) interspecialty collaboration versus competition; (4) the business of plastic surgery, best practices; (5) the image of the plastic surgeon, branding yourself; (6) medical tourism; (7) publicity; (8) the regulation of innovation, U.S. Food and Drug Administration and European Medicines Agency perspective; (9) the future of plastic surgery, cutting edge technologies; and (10) applications and controversies in fat grafting. The meeting concluded with the 8th International Committee for Quality Assurance, Medical Technologies and Devices in Plastic Surgery Consensus Conference with the development of a consensus statement. RESULTS: Through an interactive audience response system, additional questions and attitudes were asked of the audience and, in real time, international differences were identified, which led to further discussions from panelists. Responses were identified in three major groups: European Union, North America, and the Rest of the World. Responses and data are included in this article. CONCLUSIONS: The meeting brought participants, industry, regulators, and educators from both sides of the Atlantic. The interaction of these groups in these outlined topics brought a unique perspective to the meeting and, in the end, volumes of data. We have more in common than we believe. It is our anticipation that as we as plastic surgeons move forward, we can use these interactions to help our own practices but more specifically the specialty as a whole.

Technology as a force for improved diagnosis and treatment of breast disease.

Increasing numbers of women are seeking evaluation of screen-detected breast abnormalities, and more women with breast cancer are living with the consequences of treatment. Improved technologies have helped to individualize diagnostic evaluation and treatment, improve efficacy and minimize morbidity. This article highlights some of these technologies. Superior imaging techniques have improved breast cancer screening and show promise for intraoperative surgical guidance and postoperative specimen evaluation. Digital mammography improves the sensitivity of mammography for women younger than 50 years with dense breasts, and tomosynthesis may improve specificity. Magnetic resonance imaging provides sensitive delineation of the extent of the disease and superior screening for women with a greater than 25% lifetime risk of breast cancer Minimally invasive techniques have been developed for the assessment of intraductal lesions, biopsy of imaging abnormalities, staging of the axilla and breast radiotherapy. Ductoscopy facilitates intraductal biopsy and localization of lesions for excision, sentinel lymph node biopsy is becoming standard for axillary staging, and intraoperative radiotherapy has the potential to reduce treatment time and morbidity. Three-dimensional imaging allows correlation of final histology with preoperative imaging for superior margin assessment. Related techniques show promise for translation to the intraoperative setting for surgical guidance. New classifications of breast cancers based on gene expression, rather than morphology, describe subtypes with different prognoses and treatment implications, and new targeted therapies are emerging. Genetic fingerprints that predict treatment response and outcomes are being developed to assign targeted treatments to individual patients likely to benefit. Surgeons play a vital role in the successful integration of new technologies into practice.

Progress in nanotechnology for healthcare.

This review based on the Wickham lecture given by AC at the 2009 SMIT meeting in Sinaia outlines the progress made in nano-technology for healthcare. It describes in brief the nature of nano-materials and their unique properties which accounts for the significant research both in scientific institutions and industry for translation into new therapies embodied in the emerging field of nano-medicine. It stresses that the potential of nano-medicine to make significant inroads for more effective therapies both for life-threatening and life-disabling disorders will only be achieved by high-quality life science research. The first generation of passive nano-diagnostics based on nanoparticle contrast agents for magnetic resonance imaging is well established in clinical practice and new such contrast agents are undergoing early clinical evaluation. Likewise active (second generation) nano-therapies, exemplified by targeted control drug release systems are undergoing early clinical evaluation. The situation concerning other nano-materials such as carbon nanotubes (CNTs) and boron nitride nanotubes (BNNTs) is less advanced although considerable progress has been made on their coating for aqueous dispersion and functionalisation to enable carriage of drugs, genes and fluorescent markers. The main problem related to the clinical use of these nanotubes is that there is no consent among scientists on the fate of such nano-materials following injection or implantation in humans. Provided carbon nanotubes are manufactured to certain medical criteria (length around 1 mum, purity of 97-99% and low Fe content) they exhibit no cytotoxicity on cell cultures and demonstrate full bio-compatibility on in vivo animal studies. The results of recent experimental studies have demonstrated the potential of technologies based on CNTs for low voltage wireless electro-chemotherapy of tumours and for electro-stimulation therapies for cardiac, neurodegenerative and skeletal and visceral muscle disorders.