Organ-based Approach Research Articles

Quality of Life in Patients Undergoing Surgery for Upper GI Malignancies.

Upper gastrointestinal (GI) conditions vastly affect each individual's physical, social, and emotional status. The decision-making process by the medical personnel about these patients is currently based on a patient's life quality evaluation scale, HRQL scales. By utilizing HRQL scales, a better understanding of the various surgical and non-surgical treatment options, as well as their long-term consequences, can be achieved. In our study, an organ-based approach is used in an attempt to examine and characterized the effect of upper GI surgery on HRQL. Therefore, HRQL scales' function as a prognostic tool is useful, and the need for future research, the creation of valid training programs, and modern guidelines is highlighted.

Inflammatory and Infectious Disorders in Endocrine Pathology.

A variety of inflammatory conditions may directly involve the endocrine glands, leading to endocrine dysfunction that can cause severe consequences on patients' health, if left untreated. Inflammation of the endocrine system may be caused by either infectious agents or other mechanisms, including autoimmune and other immune-mediated processes. Not infrequently, inflammatory and infectious diseases may appear as tumor-like lesions of endocrine organs and simulate neoplastic processes. These diseases may be clinically under-recognized and not infrequently the diagnosis is suggested on pathological samples. Thus, the pathologist should be aware of the basic principles of their pathogenesis, as well as of their morphological features, clinicopathological correlates, and differential diagnosis. Interestingly, several systemic inflammatory conditions show a peculiar tropism to the endocrine system as a whole. In turn, organ-specific inflammatory disorders are observed in endocrine glands. This review will focus on the morphological aspects and clinicopathological features of infectious diseases, autoimmune disorders, drug-induced inflammatory reactions, IgG4-related disease, and other inflammatory disorders involving the endocrine system. A mixed entity-based and organ-based approach will be used, with the aim to provide the practicing pathologist with a comprehensive and practical guide to the diagnosis of infectious and inflammatory disorders of the endocrine system.

Integrating a Comprehensive Cancer Genome Profiling into Clinical Practice: A Blueprint in an Italian Referral Center.

The implementation of cancer molecular characterization in clinical practice has improved prognostic re-definition, extending the eligibility to a continuously increasing number of targeted treatments. Broad molecular profiling technologies better than organ-based approaches are believed to serve such dynamic purposes. We here present the workflow our institution adopted to run a comprehensive cancer genome profiling in clinical practice. This article describes the workflow designed to make a comprehensive cancer genome profiling program feasible and sustainable in a large-volume referral hospital.

General and custom deep learning autosegmentation models for organs in head and neck, abdomen, and male pelvis.

To reduce workload and inconsistencies in organ segmentation for radiation treatment planning, we developed and evaluated general and custom autosegmentation models on computed tomography (CT) for three major tumor sites using a well-established deep convolutional neural network (DCNN). Five CT-based autosegmentation models for 42 organs at risk (OARs) in head and neck (HN), abdomen (ABD), and male pelvis (MP) were developed using a full three-dimensional (3D) DCNN architecture. Two types of deep learning (DL) models were separately trained using either general diversified multi-institutional datasets or custom well-controlled single-institution datasets. To improve segmentation accuracy, an adaptive spatial resolution approach for small and/or narrow OARs and a pseudo scan extension approach, when CT scan length is too short to cover entire organs, were implemented. The performance of the obtained models was evaluated based on accuracy and clinical applicability of the autosegmented contours using qualitative visual inspection and quantitative calculation of dice similarity coefficient (DSC), mean distance to agreement (MDA), and time efficiency. The five DL autosegmentation models developed for the three anatomical sites were found to have high accuracy (DSC ranging from 0.8 to 0.98) for 74% OARs and marginally acceptable for 26% OARs. The custom models performed slightly better than the general models, even with smaller custom datasets used for the custom model training. The organ-based approaches improved autosegmentation accuracy for small or complex organs (e.g., eye lens, optic nerves, inner ears, and bowels). Compared with traditional manual contouring times, the autosegmentation times, including subsequent manual editing, if necessary, were substantially reduced by 88% for MP, 80% for HN, and 65% for ABD models. The obtained autosegmentation models, incorporating organ-based approaches, were found to be effective and accurate for most OARs in the male pelvis, head and neck, and abdomen. We have demonstrated that our multianatomical DL autosegmentation models are clinically useful for radiation treatment planning.

Towards real-time free-hand biopsy navigation.

Performing a transrectal ultrasound (TRUS) prostate biopsy is at the heart of the current prostate cancer detection procedure. With today's two-dimensional (2D) live ultrasound (US) imaging equipment, this task remains complex due to the poor visibility of cancerous tissue on TRUS images and the limited anatomical context available in the 2D TRUS plane. This paper presents a rigid 2D/3DUS registration method for navigated prostate biopsy. This allows continuous localization of the biopsy trajectory during the procedure. We proposed an organ-based approach to achieve real-time rigid registration without the need for any probe localization device. The registration method combines image similarity and geometric proximity of detected features. Additions to our previous work include a multi-level approach and the use of a rejection rate favouring the best matches. Their aim is to increase the accuracy and time performances. These modifications and their in-depth evaluation on real clinical cases and comparison to this previous work are described. We performed static and dynamic evaluations along biopsy trajectories on a very large amount of data acquired under uncontrolled routine conditions. The computed transforms are compared to a ground truth obtained either from corresponding manually detected fiducials or from an already evaluated registration method. All results show that the current method outperforms its previous version, both in terms of accuracy (the average error reported here is 12 to 17% smaller depending on the experiment) and processing time (from 20 to 60 times faster compared to the previous implementation). The dynamic registration experiment demonstrates that the method can be successfully used for continuous tracking of the biopsy location w.r.t the prostate at a rate that varies between 5 and 15Hz. This work shows that on the fly 2D/3DUS registration can be performed very efficiently on biopsy trajectories. This allows us to plan further improvements in prostate navigation and a clinical transfer.

Complications of Hematologic Malignancies in the Emergency Department: A Primer for the Radiologist

Hematologic malignancies, including diseases such as Hodgkin and non-Hodgkin lymphoma, acute and chronic lymphocytic and myelogenous leukemia, and multiple myeloma, comprise a set of prevalent and clinically diverse diseases that can affect any organ system.1 Acute life-threatening oncologic emergencies can result secondary to the underlying disease or as a result of complications of therapy, and they are common in patients with hematologic malignancies. Oncologic emergencies can be categorized as metabolic, hematologic, and structural conditions.2 Although metabolic and hematologic emergencies are diagnosed most often on the basis of clinical and laboratory findings, imaging plays a significant role in determining the underlying cause for these entities. Imaging studies play a critical role in diagnosing structural pathologic conditions, which can result in bleeding, mechanical compression, or obstruction to the hollow organs. Radiologists should be aware of the acute clinical presentations of hematologic malignancies to make an accurate, timely diagnosis and provide appropriate patient care. This article reviews, in a systematic, organ-based approach, the acute metabolic and mechanical emergencies encountered in the emergency department in patients with hematologic malignancies.

Extrahepatic Fat-Containing Lesions of the Abdomen and Pelvis: An Organ-Based Approach to Differential Diagnoses.

The presence of intralesional fat provides an invaluable tool for narrowing the differential diagnosis for both benign and malignant neoplasms of the abdomen and pelvis. The ability to characterize intralesional fat is further expanded by the ability of magnetic resonance imaging to detect small quantities (intravoxel) of fat. While the presence of intralesional fat can help to provide a relatively narrow set of diagnostic possibilities, depending on the type of fat (macroscopic vs intravoxel) that is present and the organ of origin, radiologists must be aware of uncommon mimickers of pathology, both benign and malignant.

Imaging of Metastatic Germ Cell Tumors in Male Patients From Initial Diagnosis to Treatment-Related Toxicities: A Primer for Radiologists.

OBJECTIVE. This review describes the influence of histology and metastatic sites on prognosis in male patients with metastatic germ cell tumors (GCTs) and explains the role imaging in assessing therapeutic response, residual disease, recurrence, sand treatment-related toxicities. CONCLUSION. Seminomatous and nonseminomatous GCTs differ in imaging appearance, pattern of spread, and prognosis, and an organ-based approach is helpful in prognostication. Multimodality imaging aids in accurate staging, prognostication, characterization of treatment response, and identification of therapy-related toxicity.

Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases.

Microsatellite Instability: A Predictive Biomarker for Cancer Immunotherapy.

Immunotherapy has shown promising results in various types of cancers. Checkpoint inhibitor drugs developed for cancer immunotherapy have been approved by the US Food and Drug Administration (FDA) for patients with advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin lymphoma. In the latest announcement, the FDA has granted accelerated approval to pembrolizumab for pediatric and adult patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient solid tumors. This is the first time the agency has approved a cancer treatment based on a common biomarker rather than organ-based approach. MSI-H, either due to inherited germline mutations of mismatch repair genes or epigenetic inactivation of these genes, is found in a subset of colorectal and noncolorectal carcinomas. It is known that MSI-H causes a build up of somatic mutations in tumor cells and leads to a spectrum of molecular and biological changes including high tumor mutational burden, increased expression of neoantigens and abundant tumor-infiltrating lymphocytes. These changes have been linked to increased sensitivity to checkpoint inhibitor drugs. In this mini review, we provide an update on MSI-related solid tumors with special focus on the predictive role of MSI for checkpoint immunotherapy.

Established and novel approaches for teaching and learning of veterinary parasitology in Berlin

The teaching of veterinary parasitology to the large number of students at the Freie Universität Berlin is mainly limited to conventional face-to-face lectures, supplemented by practical classes. Extensive parasite descriptions and diagnostic techniques are at the core of the practical classes, which are also intended to emphasise key biological and veterinary aspects covered in lectures. Further in-depth and specific learning is achieved within a detailed framework of elective courses, with defined learning outcomes for small groups of students, focusing on themes such as ‘diagnosis and treatment of ectoparasites in companion animals’ or ‘zoonotic parasites’. Additionally, structured excursions are designed to offer experience through collaborative international investigations. Organ-based approaches are also an integral part of our veterinary parasitology teaching, done in collaboration with the clinical and para-clinical departments, either via face-to-face interactions or online. Wide-ranging themes, such as ‘causes of colic in horses’ or ‘atopic dermatitis in dogs’ are covered. Recently, diverse blended learning elements were introduced into the curriculum (e.g., QuerVet), which makes teaching and learning more flexible, in terms of time and space, and fosters self-directed learning and participation among the students. A new platform to provide online lectures for students, termed VET Talks, was launched in 2015 by the International Veterinary Student’s Association (IVSA), and is as a publicly available educational support system for students. Provided free to veterinary students throughout the world, this platform offers students the opportunity to access lectures on interesting topics by outstanding speakers who are nominated by their students. Finally, continuing education (CE) opportunities are provided through specific Masters courses (Master of Equine Medicine, Master of Small Animal Sciences), classical seminars and recent webinars.

Metabolic Effects of Bariatric Surgery.

Obesity can be defined as a chronic subcortical brain disease, as there is an important neurophysiological component to its etiology based on changes in the functioning of those areas of the brain controlling food intake and reward. Extensive metabolic changes accompany bariatric surgery-based treatment of obesity. Consequently, the term "metabolic" surgery is being increasingly adopted in relation to the beneficial effects these procedures have on chronic diseases like type 2 diabetes. In the present review, we focus on the key biochemical and physiological changes induced by metabolic surgery and highlight the beneficial effects accrued systemically with the use of an organ-based approach. Understanding the impact on and interactions between the gut, brain, adipose tissue, liver, muscle, pancreas, and kidney is key to understanding the sum of the metabolic effects of these operations. Further mechanistic studies are essential to assess the true potential of metabolic surgery to treat metabolic comorbidities of obesity beyond type 2 diabetes. Approaches that may mitigate the metabolic side effects of surgery also require attention. Understanding the positive impact of metabolic surgery on metabolic health may result in a wider acceptance of this intervention as treatment for metabolic, comorbid conditions.

Whole-Body Voxel-Based Personalized Dosimetry: The Multiple Voxel S-Value Approach for Heterogeneous Media with Nonuniform Activity Distributions.

Personalized dosimetry with high accuracy is becoming more important because of the growing interest in personalized medicine and targeted radionuclide therapy. Voxel-based dosimetry using dose point kernel or voxel S-value (VSV) convolution is available. However, these approaches do not consider the heterogeneity of the medium. Here, we propose a new method for whole-body voxel-based personalized dosimetry in heterogeneous media with nonuniform activity distributions-a method we refer to as the multiple VSV approach. Instead of using only a single VSV, as found in water, the method uses multiple numbers (N) of VSVs to cover media of various density ranges, as found in the whole body. Methods: The VSVs were precalculated using GATE Monte Carlo simulation and were convoluted with the time-integrated activity to generate density-specific dose maps. CT-based segmentation was performed to generate a binary mask image for each density region. The final dose map was acquired by the summation of N segmented density-specific dose maps. We tested several sets of VSVs with different densities: N = 1 (single water VSV), 4, 6, 8, 10, and 20. To validate the proposed method, phantom and patient studies were conducted and compared with the direct Monte Carlo approach, which was considered the ground truth. Finally, dosimetry on 10 patients was performed using the multiple VSV approach and compared with the single VSV and organ-based approaches. Errors at the voxel and organ levels were reported for 8 organs. Results: In the phantom and patient studies, the multiple VSV approach showed significant decreases in voxel-level errors, especially for the lung and bone regions. As the number of VSVs increased, voxel-level errors decreased, although some overestimations were observed at the lung boundaries. For the multiple VSVs (N = 8), we achieved a voxel-level error of 2.06%. In the dosimetry study, our proposed method showed greatly improved results compared with single VSV and organ-based dosimetry. Errors at the organ level were -6.71%, 2.17%, and 227.46% for single VSV, multiple VSV, and organ-based dosimetry, respectively. Conclusion: The multiple VSV approach for heterogeneous media with nonuniform activity distributions offers fast personalized dosimetry at the whole-body level, yielding results comparable to those of the direct Monte Carlo approach.

Imaging Spectrum of Invasive Fungal and Fungal-like Infections.

Invasive fungal and fungal-like infections contribute to substantial morbidity and mortality in immunocompromised individuals. The incidence of these infections is increasing-largely because of rising numbers of immunocompromised patients, including those with neutropenia, human immunodeficiency virus, chronic immunosuppression, indwelling prostheses, burns, and diabetes mellitus, and those taking broad-spectrum antibiotics. Invasive fungal pathogens include primary mycotic organisms such as Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, and Paracoccidioides brasiliensis, which are true pathogens and inherently virulent. Secondary mycotic organisms such as Candida and Aspergillus species, Cryptococcus neoformans, Pneumocystis jirovecii, and Mucorales fungi are opportunistic, less virulent pathogens. Nocardia and Actinomyces species are gram-positive bacteria that behave like fungi in terms of their growth pattern and cause fungal-like invasive indolent infections; thus, these organisms are included in this review. Fungal and fungal-like infections can affect a variety of organ systems and include conditions such as meningitis, sinusitis, osteomyelitis, and enteritis. As awareness of these infections increases, timely diagnosis and treatment will become even more important. Imaging has a critical role in the evaluation of disease activity, therapy response, and related complications. Using an organ-based approach with computed tomography, magnetic resonance imaging, and ultrasonography to gain familiarity with the appearances of these infections enables timely and accurate diagnoses. ©RSNA, 2017.

Using concept maps in a modified team-based learning exercise.

Medical school education has traditionally been driven by single discipline teaching and assessment. Newer medical school curricula often implement an organ-based approach that fosters integration of basic science and clinical disciplines. Concept maps are widely used in education. Through diagrammatic depiction of a variety of concepts and their specific connections with other ideas, concept maps provide a unique perspective into learning and performance that can complement other assessment methods commonly used in medical schools. In this innovation, we describe using concepts maps as a vehicle for a modified a classic Team-Based Learning (TBL) exercise. Modifications to traditional TBL in our innovation included replacing an individual assessment using multiple-choice questions with concept maps as well as combining the group assessment and application exercise whereby teams created concept maps. These modifications were made to further assess understanding of content across the Fundamentals module (the introductory module of the preclerkship curriculum). While preliminary, student performance and feedback from faculty and students support the use of concept maps in TBL. Our findings suggest concept maps can provide a unique means of determining assessment of learning and generating feedback to students. Concept maps can also demonstrate knowledge acquisition, organization of prior and new knowledge, and synthesis of that knowledge across disciplines in a unique way providing an additional means of assessment in addition to traditional multiple-choice questions.

Abstract 5401: Investigation of sub-tumor accumulation of PRINT nanoparticles reveals dose and route of administration dependence on particle association

Abstract The assessment of nanoparticle accumulation in tumors and other organs uses a whole organ-based approach. These techniques, however, neglect the complex composition of tumors which multiple types of cells other than cancer cells(e.g. endothelial cells, macrophages). For delivery of certain therapeutics, identification of precisely which cells are associating with particles is critical. Using an orthotopic model of melanoma and fluorescently labeled 80x320nm PRINT nanoparticles, we assessed nanoparticle distribution in a cell-type specific manner by flow cytometry. We found that although cancer cells make up 90% of the tumor cells, only a small fraction (1-7%) associate the nanoparticles following intravenous dosing. The fractional association was dependent on the dose used and a plateau is seemingly reached, suggesting a limited number of cells are able to associate with 80x320nm particles. In addition, particle-positive tumor-associated macrophages associated with 4-fold more particles than cancer cells despite constituting approximately 1% of all cells in the tumor. When particles were administered intratumorally, cancer cell association doubles as compared to intravenous dosing. Fluoresence intensity suggests that when dosed intratumorally cancer cells associated with a greater amount of particles, similar to macrophages. Together, these data suggest a biological limitation on the ability of intravenous administration of nanoparticles for nucleic acid delivery and reveal the potential for therapeutic targeting of macrophages. Citation Format: Luke Roode, Tao Bo, Jillian Perry, J. Chris Luft, James E. Bear, Ian J. Davis, Joseph M. DeSimone. Investigation of sub-tumor accumulation of PRINT nanoparticles reveals dose and route of administration dependence on particle association. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5401. doi:10.1158/1538-7445.AM2014-5401

“Toward a system plan for transforming cancer care to a molecular-based approach”: Recommendations from an expert panel

Leading cancer experts convened for a one day Think Tank to develop practical recommendations for transforming cancer care from an organ-based approach to a molecular-based approach. The event took place on May 30, 2013 in Chicago prior to ASCO and was keynoted by Dr. Richard Wilson, Director, The Genome Institute at Washington University School of Medicine.

Multi-modality organ-based approach to expected imaging findings, complications and recurrent tumour in the genitourinary tract after radiotherapy

PurposeRadiotherapy (RT) is an integral component in the management of many abdominal and pelvic malignancies. Imaging follow-up in patients who have received RT is performed to assess for treatment response, evaluate for tumour recurrence and to diagnose complications related to treatment. The purpose of this pictorial review is to depict the expected imaging findings and potential complications following RT in the genitourinary (GU) tract using an organ-based approach and to review the diagnosis of locally recurrent tumour in the GU tract following RT.ConclusionsSome GU malignancies, namely cervical and prostatic carcinoma, can be treated with radical RT with intent to cure. More frequently, the GU tract is indirectly treated as a result of RT to adjacent cancers. Expected imaging findings, RT-related complications and the diagnosis of recurrent tumour following RT in the GU tract often necessitate a multi-modality imaging approach, the incorporation of functional imaging techniques and an organ-based approach for diagnosis.

An organ-based approach to dose calculation in the assessment of dose-dependent biological effects of ionising radiation in Arabidopsis thaliana

There is a need for a better understanding of biological effects of radiation exposure in non-human biota. Correct description of these effects requires a more detailed model of dosimetry than that available in current risk assessment tools, particularly for plants. In this paper, we propose a simple model for dose calculations in roots and shoots of Arabidopsis thaliana seedlings exposed to radionuclides in a hydroponic exposure setup. This model is used to compare absorbed doses for three radionuclides, 241Am (α-radiation), 90Sr (β-radiation) and 133Ba (γ radiation). Using established dosimetric calculation methods, dose conversion coefficient values were determined for each organ separately based on uptake data from the different plant organs. These calculations were then compared to the DCC values obtained with the ERICA tool under equivalent geometry assumptions. When comparing with our new method, the ERICA tool appears to overestimate internal doses and underestimate external doses in the roots for all three radionuclides, though each to a different extent. These observations might help to refine dose–response relationships. The DCC values for 90Sr in roots are shown to deviate the most. A dose–effect curve for 90Sr β-radiation has been established on biomass and photosynthesis endpoints, but no significant dose-dependent effects are observed. This indicates the need for use of endpoints at the molecular and physiological scale.

NIH Signals Intent to Boost Funding of Emergency Care Research and Training

EMERGENCY CARE RESEARCH SHOULD be getting a financial and prestige boost, thanks to the National Institutes of Health (NIH). The federal agency, which provides about $30 billion annually in medical research, announced July 31 it was forming the Office of Emergency Care Research (OECR). Although the office will not directly fund research projects, it is intended to serve as the focal point for basic, clinical, and translational emergency care research and training across the NIH. The need for such an office arose because the NIH comprises 27 institutes and centers, each with a specific research agenda, often focusing on a particular disease or organ system. Emergency care, however, is not tied to a specific disease or organ system. ArthurKellermann,MD,MPH,asenior researcherwith theRandCorporation in Santa Monica, Calif, defined emergency care research as that which “focuses on the discovery and application of timecriticaldiagnostics,decisionmaking,and treatments that save lives, prevent or reducedisability,andrestorehumanhealth” (Kellermann AL. Ann Emerg Med. 2010; 56[5]:568-570). Kellermann, who has workedwith theNIHfor several years to bring more attention to emergency care research,calledtheformationoftheOECR ahistoricdevelopmentthatwillhelpcountertheprevailingenvironmentattheNIH. “The NIH takes an organ-based approach to funding research, so if you’re proposing a study that cuts across institutes, it is very hard to find a home for that,” Kellermann said. “If you had an emergency care research proposal to be reviewed,youwouldhear, ‘That’snotfrom myspecialtyordiscipline, sowhywould we support that here?’”