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Sample records for tissue therapy

  1. Ultrasonic Histotripsy for Tissue Therapy

    Science.gov (United States)

    Pahk, K. J.; Dhar, D. K.; Malago, M.; Saffari, N.

    2015-01-01

    Hepatocyte transplantation has been considered and investigated as a promising and alternative method to liver transplantation for treating liver-based metabolic disorder in newborns over the past two decades. Although some clinical trials have been conducted and shown clinical benefits and outcomes, it is difficult to deliver and achieve a desired level of integration and transplantation of hepatocytes in the liver parenchyma. To overcome this problem, this work introduces an alternative method to a portal-infused-hepatocyte cell transplantation. To improve the level of engraftment of transplantable hepatocytes, these are injected directly into cavities generated by ultrasonic histotripsy. Histotripsy is an extracorporeal noninvasive technique which has been recently developed using high intensity focused ultrasound (HIFU) for inducing tissue fractionation with no coagulative necrosis. The exact mechanisms for the tissue fractionation are not well understood yet; but the possible mechanisms are thought to be a combination of nonlinear wave propagation effect, explosive bubble growth and ultrasonic atomization. The main objectives of this work are to demonstrate the feasibility of this new cell therapy and evaluate and distinguish between the different types of cavitation activity for either a thermally or a mechanically induced lesion. In the present work, numerical studies on the bubble dynamics (the Gilmore-Akulichev bubble model coupled with the Khokhlov-Zabolotskaya-Kuznetsov equation) and both ex- and in vivo liver experiments are conducted with histological analysis (haematoxylin and eosin stain). The numerical and the experimental results suggest that (a) the acoustic emissions emitted during the thermal ablation and the histotripsy exposure can be distinguished both numerically and experimentally and (b) the proposed cell therapy may potentially form an effective and safe clinical treatment for replacing and correcting disordered hepatocytes, although the

  2. Ultrasonic Histotripsy for Tissue Therapy

    International Nuclear Information System (INIS)

    Pahk, K J; Saffari, N; Dhar, D K; Malago, M

    2015-01-01

    Hepatocyte transplantation has been considered and investigated as a promising and alternative method to liver transplantation for treating liver-based metabolic disorder in newborns over the past two decades. Although some clinical trials have been conducted and shown clinical benefits and outcomes, it is difficult to deliver and achieve a desired level of integration and transplantation of hepatocytes in the liver parenchyma. To overcome this problem, this work introduces an alternative method to a portal-infused-hepatocyte cell transplantation. To improve the level of engraftment of transplantable hepatocytes, these are injected directly into cavities generated by ultrasonic histotripsy. Histotripsy is an extracorporeal noninvasive technique which has been recently developed using high intensity focused ultrasound (HIFU) for inducing tissue fractionation with no coagulative necrosis. The exact mechanisms for the tissue fractionation are not well understood yet; but the possible mechanisms are thought to be a combination of nonlinear wave propagation effect, explosive bubble growth and ultrasonic atomization. The main objectives of this work are to demonstrate the feasibility of this new cell therapy and evaluate and distinguish between the different types of cavitation activity for either a thermally or a mechanically induced lesion. In the present work, numerical studies on the bubble dynamics (the Gilmore-Akulichev bubble model coupled with the Khokhlov-Zabolotskaya-Kuznetsov equation) and both ex- and in vivo liver experiments are conducted with histological analysis (haematoxylin and eosin stain). The numerical and the experimental results suggest that (a) the acoustic emissions emitted during the thermal ablation and the histotripsy exposure can be distinguished both numerically and experimentally and (b) the proposed cell therapy may potentially form an effective and safe clinical treatment for replacing and correcting disordered hepatocytes, although the

  3. Focused sound: oncological therapy for transformed tissue

    International Nuclear Information System (INIS)

    Mares, C. E.; Cordova F, T.; Hernandez, A.

    2017-10-01

    The restlessness of the human being involves observing and being critical through their senses, in particular a disturbance in the environment cause vibrations that can be registered by the sense of hearing through the eardrum, if what it produces is in the frequency of the audible sound. The distinction of the sound of the other forms of energy transfer is that the waves of the same quickly involve the progressive return of displacements or vibrations of the molecules in the medium that propagates. In this work a sweep of frequencies was made from infra sound to ultrasound in plants of different types with different thicknesses and two people in order to find the resonance of each of them and compare it with the resonances registered in text, which allowed evaluate the secondary effect of sound focused on the tissue of the leaves and in particular of people. We consider that there is potential for this focused sound modality if it is at the resonance frequency of the transformed tissue as a means of oncological therapy without affecting the neighboring cells. (Author)

  4. Tissue Engineering in Regenerative Dental Therapy

    Directory of Open Access Journals (Sweden)

    Hiral Jhaveri-Desai

    2011-01-01

    Full Text Available Tissue engineering is amongst the latest exciting technologies having impacted the field of dentistry. Initially considered as a futuristic approach, tissue engineering is now being successfully applied in regenerative surgery. This article reviews the important determinants of tissue engineering and how they contribute to the improvement of wound healing and surgical outcomes in the oral region. Furthermore, we shall address the clinical applications of engineering involving oral and maxillofacial surgical and periodontal procedures along with other concepts that are still in experimental phase of development. This knowledge will aid the surgical and engineering researchers to comprehend the collaboration between these fields leading to extounding dental applications and to ever-continuing man-made miracles in the field of human science.

  5. Gene therapy for cartilage and bone tissue engineering

    CERN Document Server

    Hu, Yu-Chen

    2014-01-01

    "Gene Therapy for Cartilage and Bone Tissue Engineering" outlines the tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery, specifically for cartilage and bone engineering. It is intended for tissue engineers, cell therapists, regenerative medicine scientists and engineers, gene therapist and virologists. Dr. Yu-Chen Hu is a Distinguished Professor at the Department of Chemical Engineering, National Tsing Hua University and has received the Outstanding Research Award (National Science Council), Asia Research Award (Society of Chemical Engineers, Japan) and Professor Tsai-Teh Lai Award (Taiwan Institute of Chemical Engineers). He is also a fellow of the American Institute for Medical and Biological Engineering (AIMBE) and a member of the Tissue Engineering International & Regenerative Medicine Society (TERMIS)-Asia Pacific Council.

  6. Stem Cell Therapy in Wound Healing and Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2016-08-01

    a novel approach to many diseases. SUMMARY: Wound healing therapies continue to rapidly evolve, with advances in basic science and engineering research heralding the development of new therapies, as well as ways to modify existing treatments. Stem cell-based therapy is one of the most promising therapeutic concepts for wound healing. Advances in stem cell biology have enabled researchers and clinicians alike with access to cells capable of actively modulating the healing response.  KEYWORDS: wound healing, tissue regeneration, stem cells therapy

  7. Nano scaffolds and stem cell therapy in liver tissue engineering

    Science.gov (United States)

    Montaser, Laila M.; Fawzy, Sherin M.

    2015-08-01

    Tissue engineering and regenerative medicine have been constantly developing of late due to the major progress in cell and organ transplantation, as well as advances in materials science and engineering. Although stem cells hold great potential for the treatment of many injuries and degenerative diseases, several obstacles must be overcome before their therapeutic application can be realized. These include the development of advanced techniques to understand and control functions of micro environmental signals and novel methods to track and guide transplanted stem cells. A major complication encountered with stem cell therapies has been the failure of injected cells to engraft to target tissues. The application of nanotechnology to stem cell biology would be able to address those challenges. Combinations of stem cell therapy and nanotechnology in tissue engineering and regenerative medicine have achieved significant advances. These combinations allow nanotechnology to engineer scaffolds with various features to control stem cell fate decisions. Fabrication of Nano fiber cell scaffolds onto which stem cells can adhere and spread, forming a niche-like microenvironment which can guide stem cells to proceed to heal damaged tissues. In this paper, current and emergent approach based on stem cells in the field of liver tissue engineering is presented for specific application. The combination of stem cells and tissue engineering opens new perspectives in tissue regeneration for stem cell therapy because of the potential to control stem cell behavior with the physical and chemical characteristics of the engineered scaffold environment.

  8. Adaptive Breast Radiation Therapy Using Modeling of Tissue Mechanics: A Breast Tissue Segmentation Study

    International Nuclear Information System (INIS)

    Juneja, Prabhjot; Harris, Emma J.; Kirby, Anna M.; Evans, Philip M.

    2012-01-01

    Purpose: To validate and compare the accuracy of breast tissue segmentation methods applied to computed tomography (CT) scans used for radiation therapy planning and to study the effect of tissue distribution on the segmentation accuracy for the purpose of developing models for use in adaptive breast radiation therapy. Methods and Materials: Twenty-four patients receiving postlumpectomy radiation therapy for breast cancer underwent CT imaging in prone and supine positions. The whole-breast clinical target volume was outlined. Clinical target volumes were segmented into fibroglandular and fatty tissue using the following algorithms: physical density thresholding; interactive thresholding; fuzzy c-means with 3 classes (FCM3) and 4 classes (FCM4); and k-means. The segmentation algorithms were evaluated in 2 stages: first, an approach based on the assumption that the breast composition should be the same in both prone and supine position; and second, comparison of segmentation with tissue outlines from 3 experts using the Dice similarity coefficient (DSC). Breast datasets were grouped into nonsparse and sparse fibroglandular tissue distributions according to expert assessment and used to assess the accuracy of the segmentation methods and the agreement between experts. Results: Prone and supine breast composition analysis showed differences between the methods. Validation against expert outlines found significant differences (P<.001) between FCM3 and FCM4. Fuzzy c-means with 3 classes generated segmentation results (mean DSC = 0.70) closest to the experts' outlines. There was good agreement (mean DSC = 0.85) among experts for breast tissue outlining. Segmentation accuracy and expert agreement was significantly higher (P<.005) in the nonsparse group than in the sparse group. Conclusions: The FCM3 gave the most accurate segmentation of breast tissues on CT data and could therefore be used in adaptive radiation therapy-based on tissue modeling. Breast tissue segmentation

  9. Adaptive Breast Radiation Therapy Using Modeling of Tissue Mechanics: A Breast Tissue Segmentation Study

    Energy Technology Data Exchange (ETDEWEB)

    Juneja, Prabhjot, E-mail: Prabhjot.Juneja@icr.ac.uk [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom); Harris, Emma J. [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom); Kirby, Anna M. [Department of Academic Radiotherapy, Royal Marsden National Health Service Foundation Trust, Sutton (United Kingdom); Evans, Philip M. [Joint Department of Physics, Institute of Cancer Research, Sutton (United Kingdom)

    2012-11-01

    Purpose: To validate and compare the accuracy of breast tissue segmentation methods applied to computed tomography (CT) scans used for radiation therapy planning and to study the effect of tissue distribution on the segmentation accuracy for the purpose of developing models for use in adaptive breast radiation therapy. Methods and Materials: Twenty-four patients receiving postlumpectomy radiation therapy for breast cancer underwent CT imaging in prone and supine positions. The whole-breast clinical target volume was outlined. Clinical target volumes were segmented into fibroglandular and fatty tissue using the following algorithms: physical density thresholding; interactive thresholding; fuzzy c-means with 3 classes (FCM3) and 4 classes (FCM4); and k-means. The segmentation algorithms were evaluated in 2 stages: first, an approach based on the assumption that the breast composition should be the same in both prone and supine position; and second, comparison of segmentation with tissue outlines from 3 experts using the Dice similarity coefficient (DSC). Breast datasets were grouped into nonsparse and sparse fibroglandular tissue distributions according to expert assessment and used to assess the accuracy of the segmentation methods and the agreement between experts. Results: Prone and supine breast composition analysis showed differences between the methods. Validation against expert outlines found significant differences (P<.001) between FCM3 and FCM4. Fuzzy c-means with 3 classes generated segmentation results (mean DSC = 0.70) closest to the experts' outlines. There was good agreement (mean DSC = 0.85) among experts for breast tissue outlining. Segmentation accuracy and expert agreement was significantly higher (P<.005) in the nonsparse group than in the sparse group. Conclusions: The FCM3 gave the most accurate segmentation of breast tissues on CT data and could therefore be used in adaptive radiation therapy-based on tissue modeling. Breast tissue

  10. Clinical application of cell, gene and tissue therapies in Spain.

    Science.gov (United States)

    Gálvez-Martín, P; Ruiz, A; Clares, B

    2018-05-01

    Scientific and technical advances in the areas of biomedicine and regenerative medicine have enabled the development of new treatments known as "advanced therapies", which encompass cell therapy, genetics and tissue engineering. The biologic products that can be manufactured from these elements are classified from the standpoint of the Spanish Agency of Medication and Health Products in advanced drug therapies, blood products and transplants. This review seeks to provide scientific and administrative information for clinicians on the use of these biologic resources. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  11. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Shan Liu

    2016-06-01

    Full Text Available Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous. The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells, early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium, using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration, timing for cell therapy (immediate vs. a few days after injury, single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  12. Cell Therapy and Tissue Engineering Products for Chondral Knee Injuries

    Directory of Open Access Journals (Sweden)

    Adriana Flórez Cabrera

    2017-07-01

    Full Text Available The articular cartilage is prone to suffer lesions of different etiology, being the articular cartilage lesions of the knee the most common. Although most conventional treatments reduce symptoms they lead to the production of fibrocartilage, which has different characteristics than the hyaline cartilage of the joint. There are few therapeutic approaches that promote the replacement of damaged tissue by functional hyaline cartilage. Among them are the so-called advanced therapies, which use cells and tissue engineering products to promote cartilage regeneration. Most of them are based on scaffolds made of different biomaterials, which seeded or not with endogenous or exogenous cells, can be used as cartilage artificial replacement to improve joint function. This paper reviews some therapeutic approaches focused on the regeneration of articular cartilage of the knee and the biomaterials used to develop scaffolds for cell therapy and tissue engineering of cartilage.

  13. Current Molecular Targeted Therapies for Bone and Soft Tissue Sarcomas

    Directory of Open Access Journals (Sweden)

    Kenji Nakano

    2018-03-01

    Full Text Available Systemic treatment options for bone and soft tissue sarcomas remained unchanged until the 2000s. These cancers presented challenges in new drug development partly because of their rarity and heterogeneity. Many new molecular targeting drugs have been tried in the 2010s, and some were approved for bone and soft tissue sarcoma. As one of the first molecular targeted drugs approved for solid malignant tumors, imatinib’s approval as a treatment for gastrointestinal stromal tumors (GISTs has been a great achievement. Following imatinib, other tyrosine kinase inhibitors (TKIs have been approved for GISTs such as sunitinib and regorafenib, and pazopanib was approved for non-GIST soft tissue sarcomas. Olaratumab, the monoclonal antibody that targets platelet-derived growth factor receptor (PDGFR-α, was shown to extend the overall survival of soft tissue sarcoma patients and was approved in 2016 in the U.S. as a breakthrough therapy. For bone tumors, new drugs are limited to denosumab, a receptor activator of nuclear factor κB ligand (RANKL inhibitor, for treating giant cell tumors of bone. In this review, we explain and summarize the current molecular targeting therapies approved and in development for bone and soft tissue sarcomas.

  14. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    Science.gov (United States)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  15. Radiation therapy and late reactions in normal tissues

    International Nuclear Information System (INIS)

    Aoyama, Takashi; Kuroda, Yasumasa

    1998-01-01

    Recent developments in cancer therapy have made us increasingly aware that the quality of life of a patient is as valuable as other benefits received from therapy. This awareness leads to an emphasis on organ and/or function preservation in the course of therapy. In line with this new thinking, greater consideration is placed on radiation therapy as an appropriate modality of cancer therapy. Possible complications in normal tissues, especially those of late reaction type after the therapy must be overcome. This review, therefore, focuses on recent progress of studies on mechanisms of the complications of the late reaction type. An observation of a clinical case concerning a late reaction of spinal cord (radiation myelopathy) and surveys of experimental studies on the mechanisms of late reactions (including radiation pneumonitis and lung fibrosis, and radiation response of vascular endothelial cells) provide a hypothesis that apoptosis through the pathway starting with radiation-induced sphingomyelin hydrolysis may play an important role in causing a variety of late reactions. This insight is based on the fact that radiation also activates protein kinase C which appears to block apoptosis. The mechanisms of late reactions, therefore, may involve a balance between radiation-induced apoptotic death and its down regulation by suppressor mechanisms through protein kinase C. (author)

  16. Soft-tissue sarcomas. Current aspects of diagnosis and therapy

    International Nuclear Information System (INIS)

    Hohenberger, P.

    1996-01-01

    The decisive factor for promising therapy of soft-tissue sarcomas is primary therapy provided in an experienced tumour unit. This centre must offer the entire spectrum of surgery (vascular, reconstruction and orthopaedic surgery) leading into an interdisciplinary treatment regimen. Initially, MRI would appear to be sufficient for diagnosis. On the other hand, the presence of an experienced pathologist conversant with all means of cytogenetic tumour classification is essential. For interdisciplinary therapy, a radiotherapist with hyperthermia equipment, nuclear medicine specialists and medical oncologists are indispensable. All personnel must be familiar with the special problems associated with sarcomas. The current trend is indeed toward a select number of centres where such skills are focused. (orig.) [de

  17. 78 FR 44133 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-07-23

    ...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide... documents issued from the Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and...

  18. 77 FR 65693 - Cellular, Tissue and Gene Therapies Advisory Committee; Amendment of Notice

    Science.gov (United States)

    2012-10-30

    ...] Cellular, Tissue and Gene Therapies Advisory Committee; Amendment of Notice AGENCY: Food and Drug... notice of a meeting of the Cellular, Tissue and Gene Therapies Advisory Committee. This meeting was... announced that a meeting of the Cellular, Tissue and Gene Therapies Advisory Committee would be held on...

  19. 78 FR 79699 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-12-31

    ...] Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue, and Gene Therapies Advisory Committee. General Function of the Committee: To provide... updates on guidance documents issued from the Office of Cellular, Tissue, and Gene Therapies, Center for...

  20. Cardiac tissue engineering and regeneration using cell-based therapy

    Directory of Open Access Journals (Sweden)

    Alrefai MT

    2015-05-01

    Full Text Available Mohammad T Alrefai,1–3 Divya Murali,4 Arghya Paul,4 Khalid M Ridwan,1,2 John M Connell,1,2 Dominique Shum-Tim1,2 1Division of Cardiac Surgery, 2Division of Surgical Research, McGill University Health Center, Montreal, QC, Canada; 3King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, USA Abstract: Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. Keywords: stem cells, cardiomyocytes, cardiac surgery, heart failure, myocardial ischemia, heart, scaffolds, organoids, cell sheet and tissue engineering

  1. 76 FR 22405 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-04-21

    ...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide... June 29, 2011, the committee will discuss cellular and gene therapy products for the treatment of...

  2. Radiation-induced pseudotumor following therapy for soft tissue sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Lacey F.; Kransdorf, Mark J. [Mayo Clinic, Department of Radiology, Jacksonville, FL (United States); Buskirk, Steven J. [Mayo Clinic, Department of Radiation Oncology, Jacksonville, FL (United States); O' Connor, Mary I. [Mayo Clinic, Department of Orthopedic Surgery, Jacksonville, FL (United States); Menke, David M. [Mayo Clinic, Department of Pathology, Jacksonville, FL (United States)

    2009-06-15

    The purpose of this study was to describe the prevalence and imaging appearance of radiation induced pseudotumors in patients following radiation therapy for extremity soft tissue sarcomas. We retrospectively reviewed the serial magnetic resonance (MR) images of 24 patients following radiation therapy for extremity soft tissue sarcomas. A total of 208 exams were reviewed (mean, 8.7 exams per patient) and included all available studies following the start of radiation therapy. Exams were analyzed for the identification of focal signal abnormalities within the surgical bed suggesting local tumor recurrence. Histopathologic correlation was available in nine patients suspected of having local tumor recurrence. Additional information recorded included patient demographics, tumor type and location, radiation type, and dose. The study group consisted of 12 men and 12 women, having an average age of 63 years (range, 39-88 years). Primary tumors were malignant fibrous histiocytoma (n = 13), leiomyosarcoma (n = 6), liposarcoma (n = 3), synovial sarcoma (n = 1), and extraskeletal chondrosarcoma (n = 1). All lesions were high-grade sarcomas, except for two myxoid liposarcomas. Average patient radiation dose was 5,658 cGy (range, 4,500-8,040 cGy). Average follow-up time was 63 months (range, 3-204 months). Focal signal abnormalities suggesting local recurrence were seen in nine (38%) patients. Three of the nine patients with these signal abnormalities were surgically proven to have radiation-induced pseudotumor. The pseudotumors developed between 11 and 61 months following the initiation of radiation therapy (mean, 38 months), with an average radiation dose of 5,527 cGy (range, 5,040-6,500 cGy). MR imaging demonstrated a relatively ill-defined ovoid focus of abnormal signal and intense heterogeneous enhancement with little or no associated mass effect. MR imaging of radiation-induced pseudotumor typically demonstrates a relatively ill-defined ovoid mass-like focus of intense

  3. Normal tissue tolerance to external beam radiation therapy: Adult bone

    International Nuclear Information System (INIS)

    Sargos, P.; Mamou, N.; Dejean, C.; Henriques de Figueiredo, B.; Kantor, G.; Huchet, A.; Italiano, A.

    2010-01-01

    Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably under-evaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume. (authors)

  4. Histology-specific therapy for advanced soft tissue sarcoma and benign connective tissue tumors.

    Science.gov (United States)

    Silk, Ann W; Schuetze, Scott M

    2012-09-01

    Molecularly targeted agents have shown activity in soft tissue sarcoma (STS) and benign connective tissue tumors over the past ten years, but response rates differ by histologic subtype. The field of molecularly targeted agents in sarcoma is increasingly complex. Often, clinicians must rely on phase II data or even case series due to the rarity of these diseases. In subtypes with a clear role of specific factors in the pathophysiology of disease, such as giant cell tumor of the bone and diffuse-type tenosynovial giant cell tumor, it is reasonable to treat with newer targeted therapies, when available, in place of chemotherapy when systemic treatment is needed to control disease. In diseases without documented implication of a pathway in disease pathogenesis (e.g. soft tissue sarcoma and vascular endothelial growth factor), clear benefit from drug treatment should be established in randomized phase III trials before implementation into routine clinical practice. Histologic subtype will continue to emerge as a critical factor in treatment selection as we learn more about the molecular drivers of tumor growth and survival in different subtypes. Many of the drugs that have been recently developed affect tumor growth more than survival, therefore progression-free survival may be a more clinically relevant intermediate endpoint than objective response rate using Response Evaluation Criteria In Solid Tumors (RECIST) in early phase sarcoma trials. Because of the rarity of disease and increasing need for multidisciplinary management, patients with connective tissue tumors should be evaluated at a center with expertise in these diseases. Participation in clinical trials, when available, is highly encouraged.

  5. Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

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    Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Washington University School of Medicine, St Louis, MO (United States); Barthold, H. Joseph [Commonwealth Hematology and Oncology, Weymouth, MA (United States); Beth Israel Deaconess Medical Center, Boston, MA (Israel); O' Meara, Elizabeth [Radiation Therapy Oncology Group, Philadelphia, PA (United States); Bosch, Walter R. [Washington University School of Medicine, St Louis, MO (United States); El Naqa, Issam [Department of Radiation Oncology, McGill University Health Center, Montreal, Quebec (Canada); Al-Lozi, Rawan [Washington University School of Medicine, St Louis, MO (United States); Rosenthal, Seth A. [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); Lawton, Colleen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Lee, W. Robert [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Sandler, Howard [Cedars-Sinai Medical Center, Los Angeles, CA (United States); Zietman, Anthony [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Myerson, Robert [Washington University School of Medicine, St Louis, MO (United States); Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Willett, Christopher [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Kachnic, Lisa A. [Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA (United States); Jhingran, Anuja [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Portelance, Lorraine [University of Miami, Miami, FL (United States); Ryu, Janice [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); and others

    2012-07-01

    Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.

  6. Ultrasound therapy applicators for controlled thermal modification of tissue

    Science.gov (United States)

    Burdette, E. Clif; Lichtenstiger, Carol; Rund, Laurie; Keralapura, Mallika; Gossett, Chad; Stahlhut, Randy; Neubauer, Paul; Komadina, Bruce; Williams, Emery; Alix, Chris; Jensen, Tor; Schook, Lawrence; Diederich, Chris J.

    2011-03-01

    Heat therapy has long been used for treatments in dermatology and sports medicine. The use of laser, RF, microwave, and more recently, ultrasound treatment, for psoriasis, collagen reformation, and skin tightening has gained considerable interest over the past several years. Numerous studies and commercial devices have demonstrated the efficacy of these methods for treatment of skin disorders. Despite these promising results, current systems remain highly dependent on operator skill, and cannot effectively treat effectively because there is little or no control of the size, shape, and depth of the target zone. These limitations make it extremely difficult to obtain consistent treatment results. The purpose of this study was to determine the feasibility for using acoustic energy for controlled dose delivery sufficient to produce collagen modification for the treatment of skin tissue in the dermal and sub-dermal layers. We designed and evaluated a curvilinear focused ultrasound device for treating skin disorders such as psoriasis, stimulation of wound healing, tightening of skin through shrinkage of existing collagen and stimulation of new collagen formation, and skin cancer. Design parameters were examined using acoustic pattern simulations and thermal modeling. Acute studies were performed in 201 freshly-excised samples of young porcine underbelly skin tissue and 56 in-vivo treatment areas in 60- 80 kg pigs. These were treated with ultrasound (9-11MHz) focused in the deep dermis. Dose distribution was analyzed and gross pathology assessed. Tissue shrinkage was measured based on fiducial markers and video image registration and analyzed using NIH Image-J software. Comparisons were made between RF and focused ultrasound for five energy ranges. In each experimental series, therapeutic dose levels (60degC) were attained at 2-5mm depth. Localized collagen changes ranged from 1-3% for RF versus 8-15% for focused ultrasound. Therapeutic ultrasound applied at high

  7. Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure

    Science.gov (United States)

    Finosh, G.T.; Jayabalan, Muthu

    2012-01-01

    Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed. PMID:23507781

  8. Head and neck soft tissue sarcomas treated with radiation therapy

    Directory of Open Access Journals (Sweden)

    Lucas K. Vitzthum

    2016-06-01

    Full Text Available Head and neck soft tissue sarcomas (HNSTSs are rare and heterogeneous cancers in which radiation therapy (RT has an important role in local tumor control (LC. The purpose of this study was to evaluate outcomes and patterns of treatment failure in patients with HNSTS treated with RT. A retrospective review was performed of adult patients with HNSTS treated with RT from January 1, 1998, to December 31, 2012. LC, locoregional control (LRC, disease-free survival (DFS, overall survival (OS, and predictors thereof were assessed. Forty-eight patients with HNSTS were evaluated. Five-year Kaplan-Meier estimates of LC, LRC, DFS, and OS were 87, 73, 63, and 83%, respectively. Angiosarcomas were found to be associated with worse LC, LRC, DFS, and OS. Patients over the age of 60 had lower rates of DFS. HNSTSs comprise a diverse group of tumors that can be managed with various treatment regimens involving RT. Angiosarcomas have higher recurrence and mortality rates.

  9. 75 FR 66381 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-10-28

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide...

  10. 76 FR 49774 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-08-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide...

  11. 76 FR 64951 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-10-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide...

  12. 78 FR 15726 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-03-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of...

  13. Models for radiation-induced tissue degeneration and conceptualization of rehabilitation of irradiated tissue by cell therapy

    International Nuclear Information System (INIS)

    Phulpin, Berengere

    2011-01-01

    Radiation therapy induced acute and late sequelae within healthy tissue included in the irradiated area. In general, lesions are characterized by ischemia, cell apoptosis and fibrosis. In this context, cell therapy using bone marrow mesenchymal stem cells (BMSC) might represent an attractive new therapeutic approach, based partly on their angiogenic ability and their involvement in the natural processes of tissue repair. The first part of this work consisted in the development of experimental mouse model of radio-induced tissue degeneration similar to that occurring after radiotherapy. The aim was to better understand the physiopathological mechanisms of radiation-induced tissue damage and to determine the best treatment strategy. The second part of this work investigated the feasibility of autologous BMSC therapy on the murine model of radiation previously established with emphasis on two pre-requisites: the retention of the injected cells within the target tissue and the evaluation of the graft on bone metabolism. This preclinical investigation in a mouse model constitutes an essential step allowing an evaluation of the benefit of cell therapy for the treatment of radiation-induced tissue injury. Data from these studies could allow the proposal of clinical studies [fr

  14. Pivotal role of tissue plasminogen activator in the mechanism of action of electroconvulsive therapy.

    Science.gov (United States)

    Hoirisch-Clapauch, Silvia; Mezzasalma, Marco A U; Nardi, Antonio E

    2014-02-01

    Electroconvulsive therapy is an important treatment option for major depressive disorders, acute mania, mood disorders with psychotic features, and catatonia. Several hypotheses have been proposed as electroconvulsive therapy's mechanism of action. Our hypothesis involves many converging pathways facilitated by increased synthesis and release of tissue-plasminogen activator. Human and animal experiments have shown that tissue-plasminogen activator participates in many mechanisms of action of electroconvulsive therapy or its animal variant, electroconvulsive stimulus, including improved N-methyl-D-aspartate receptor-mediated signaling, activation of both brain-derived neurotrophic factor and vascular endothelial growth factor, increased bioavailability of zinc, purinergic release, and increased mobility of dendritic spines. As a result, tissue-plasminogen activator helps promote neurogenesis in limbic structures, modulates synaptic transmission and plasticity, improves cognitive function, and mediates antidepressant effects. Notably, electroconvulsive therapy seems to influence tissue-plasminogen activator metabolism. For example, electroconvulsive stimulus increases the expression of glutamate decarboxylase 65 isoform in γ-aminobutyric acid-releasing neurons, which enhances the release of tissue-plasminogen activator, and the expression of p11, a protein involved in plasminogen and tissue-plasminogen activator assembling. This paper reviews how electroconvulsive therapy correlates with tissue-plasminogen activator. We suggest that interventions aiming at increasing tissue-plasminogen activator levels or its bioavailability - such as daily aerobic exercises together with a carbohydrate-restricted diet, or normalization of homocysteine levels - be evaluated in controlled studies assessing response and remission duration in patients who undergo electroconvulsive therapy.

  15. Use of subatmospheric (VAC) therapy to improve bioengineered tissue grafting in diabetic foot wounds.

    Science.gov (United States)

    Espensen, Eric H; Nixon, Brent P; Lavery, Lawrence A; Armstrong, David G

    2002-01-01

    The use of bioengineered tissue and topical subatmospheric pressure therapy have both been widely accepted as adjunctive therapies for the treatment of noninfected, nonischemic diabetic foot wounds. This article describes a temporally overlapping method of care that includes a period of simultaneous application of bioengineered tissue (Apligraf, Novartis Pharmaceuticals Corp, East Hanover, New Jersey) and subatmospheric pressure therapy delivered through the VAC (Vacuum Assisted Closure) system (KCI, Inc, San Antonio, Texas). Future descriptive and analytic works may test the hypothesis that combined therapies used at different and often overlapping periods during the wound-healing cycle may be more effective than a single modality.

  16. Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

    International Nuclear Information System (INIS)

    Travis, Elizabeth L.

    1996-01-01

    Objective: This is the third part of a course designed for residents in radiation oncology preparing for their boards. This part of the course will focus on the mechanisms underlying damage in normal tissues. Although conventional wisdom long held that killing and depletion of a critical cell(s) in a tissue was responsible for the later expression of damage, histopathologic changes in normal tissue can now be explained and better understood in terms of the new molecular biology. The concept that depletion of a single cell type is responsible for the observed histopathologic changes in normal tissues has been replaced by the hypothesis that damage results from the interaction of many different cell systems, including epithelial, endothelial, macrophages and fibroblasts, via the production of specific autocrine, paracrine and endocrine growth factors. A portion of this course will discuss the clinical and experimental data on the production and interaction of those cytokines and cell systems considered to be critical to tissue damage. It had long been suggested that interindividual differences in radiation-induced normal tissue damage was genetically regulated, at least in part. Both clinical and experimental data supported this hypothesis but it is the recent advances in human and mouse molecular genetics which have provided the tools to dissect out the genetic component of normal tissue damage. These data will be presented and related to the potential to develop genetic markers to identify sensitive individuals. The impact on clinical outcome of the ability to identify prospectively sensitive patients will be discussed. Clinically it is well-accepted that the volume of tissue irradiated is a critical factor in determining tissue damage. A profusion of mathematical models for estimating dose-volume relationships in a number of organs have been published recently despite the fact that little data are available to support these models. This course will review the

  17. Stem cell-derived angiogenic/vasculogenic cells: Possible therapies for tissue repair and tissue engineering

    NARCIS (Netherlands)

    Zwaginga, J. J.; Doevendans, P.

    2003-01-01

    1. The recent ability to isolate stem cells and study their specific capacity of self-renewal with the formation of different cell types has opened up exciting vistas to help the repair of damaged tissue and even the formation of new tissue. In the present review, we deal with the characteristics

  18. Non-viral gene therapy for bone tissue engineering.

    Science.gov (United States)

    Wegman, Fiona; Oner, F Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

    2013-01-01

    The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future.

  19. Measurement of the tissue to A-150 tissue equivalent plastic kerma ratio at two p(66)Be neutron therapy facilities

    International Nuclear Information System (INIS)

    Langen, K M; Binns, P J; Schreuder, A N; Lennox, A J; Deluca, P M Jr.

    2003-01-01

    The ICRU tissue to A-150 tissue equivalent plastic kerma ratio is needed for neutron therapy dosimetry. The current ICRU protocol for neutron dosimetry recommends using a common conversion factor of 0.95 at all high-energy neutron therapy facilities. In an effort to determine facility specific ICRU tissue to A-150 plastic kerma ratios, an experimental approach was pursued. Four low pressure proportional counters that differed in wall materials (i.e. A-150, carbon, zirconium and zirconium-oxide) were used as dosimeters and integral kerma ratios were determined directly in the clinical beam. Measurements were performed at two p(66)Be facilities: iThemba LABS near Cape Town and Fermilab near Chicago. At the iThemba facility the clinical neutron beam is routinely filtered by a flattening and hardening filter combination. The influence of beam filtration on the kerma ratio was evaluated. Using two recent gas-to-wall dose conversion factor (r m,g value) evaluations a mean ICRU tissue to A-150 plastic kerma ratio of 0.93 ± 0.05 was determined for the clinical beam at iThemba LABS. The respective value for the Fermilab beam is 0.95 ± 0.05. The experimentally determined ICRU tissue to A-150 plastic kerma ratios for the two clinical beams are in agreement with theoretical evaluations. Beam filtration reduces the kerma ratio by 3 ± 2%

  20. Non-viral gene therapy for bone tissue engineering

    NARCIS (Netherlands)

    Wegman, F.

    2013-01-01

    In bone tissue engineering bone morphogentic protein-2 (BMP-2) is one of the most commonly used growth factors. It induces stem cells to differentiate into the osteogenic lineage to form new bone. Clinically however, high dosages of protein are administered due to fast degradation, which is

  1. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  2. Gene therapy with growth factors for periodontal tissue engineering–A review

    Science.gov (United States)

    Gupta, Shipra; Mahendra, Aneet

    2012-01-01

    The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. The aim of this paper is to review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Various such materials have been formulated into devices that can be used as vehicles for delivery of cells, growth factors and DNA. Different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral and tooth supporting structure. Key words: Periodontal disease, gene therapy, regeneration, tissue repair, growth factors, tissue engineering. PMID:22143705

  3. Determining the appropriate number and duration of leech therapy in congested tissues using tissue spectrophotometry and laser Doppler flowmetry.

    Science.gov (United States)

    Rothenberger, Jens; Petersen, Wiebke; Schaller, Hans-Eberhard; Held, Manuel

    2016-11-01

    A universal protocol determining the number of leeches and their application time does not exist. The aim of this study, therefore, is to quantify perfusion dynamics in venous congested tissues after leech application to get more detailed information about changes due to leech-induced skin microcirculation and to evaluate the usability of the Oxygen to See (O2C) device in terms of determining the appropriate number of leeches and the duration of therapy. Twelve patients with the need for leech therapy participated in the study. Perfusion dynamics of the congested tissue was assessed using the O2C device, which determines blood flow (BF), the relative amount of hemoglobin (rHB), and the oxygen saturation (SO2). Measurements were carried out before leech application and on various intervals like 10 minutes, one hour, and three hours after leech application. The leech application effectuated after 10 minutes a nonsignificant perfusion improvement, which further increased after one hour with a significant reduction of the relative amount of hemoglobin and a significant increase of blood flow and oxygen saturation (BF= +56.7%; rHB= -25.5%; SO2= +53.7%). After three hours, the values returned to the levels before leech administration. In two cases, in which further administration of leeches within the measurement period was necessary, no substantial perfusion changes were obtained. The results of this study forms a more precise pattern of microcirculatory changes of leech therapy in congested tissues. According to our measurements a venous drainage improvement can be expected in congested tissue one hour after leech administration. The O2C seems to be a useful method to determine the appropriate number and duration of leech therapy. © 2016 by the Wound Healing Society.

  4. Biomaterials and Culture Technologies for Regenerative Therapy of Liver Tissue.

    Science.gov (United States)

    Perez, Roman A; Jung, Cho-Rok; Kim, Hae-Won

    2017-01-01

    Regenerative approach has emerged to substitute the current extracorporeal technologies for the treatment of diseased and damaged liver tissue. This is based on the use of biomaterials that modulate the responses of hepatic cells through the unique matrix properties tuned to recapitulate regenerative functions. Cells in liver preserve their phenotype or differentiate through the interactions with extracellular matrix molecules. Therefore, the intrinsic properties of the engineered biomaterials, such as stiffness and surface topography, need to be tailored to induce appropriate cellular functions. The matrix physical stimuli can be combined with biochemical cues, such as immobilized functional groups or the delivered actions of signaling molecules. Furthermore, the external modulation of cells, through cocultures with nonparenchymal cells (e.g., endothelial cells) that can signal bioactive molecules, is another promising avenue to regenerate liver tissue. This review disseminates the recent approaches of regenerating liver tissue, with a focus on the development of biomaterials and the related culture technologies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Histologic response of soft tissue sarcoma to radiation therapy

    International Nuclear Information System (INIS)

    Willett, C.G.; Schiller, A.L.; Suit, H.D.; Mankin, H.J.; Rosenberg, A.

    1987-01-01

    Twenty-seven patients with soft tissue sarcoma had preoperative radiotherapy, limb-sparing marginal surgical resection and whole-mount tumor histologic analysis. Incisional biopsy specimens before radiotherapy were reviewed for tumor type, grade, and extent of necrosis. Preoperative radiotherapy was given in either of two regimens: 13 patients received a mean total dose of 5250 cGy in one daily 180 to 200 cGy fractions and 14 patients a mean total dose of 4770 cGy in two daily fractions of 180 to 200 cGy separated by 4 hours. Twenty-one specimens had at least 80% necrosis or severely altered cells, a 3+ to 4+ response. Grade and size of the tumor appeared to be indicators of response to treatment rather than histologic type. Three of five patients (60%) with Grade 1, eight of 11 patients (73%) with Grade 2 lesions, and ten of 11 patients (91%) with Grade 3 tumors had 80% or greater necrosis or severely altered cells. For tumors 10 cm or less in greatest diameter, the 3+ to 4+ histologic response was seen in 12 of 14 patients (86%) whereas for lesions greater than 10 cm, this response was observed in nine of 13 patients (69%). For patients with Grade 2 or 3 soft tissue sarcoma, 13 of 14 patients (93%) treated with two fractions per day and two of four patients (50%) receiving one fraction per day exhibited significant response. All six patients treated twice daily for lesions greater than 10 cm had 3+ to 4+ histologic response compared to three of seven (43%) patients treated once per day. Therefore, grade and size of soft tissue sarcoma are important predictors of response to radiotherapy and preoperative twice daily radiotherapy may more likely permit the conservative surgical excision of sarcomas of borderline resectability

  6. Normal tissue tolerance to external beam radiation therapy: Skin

    International Nuclear Information System (INIS)

    Ginot, A.; Doyen, J.; Hannoun-Levi, J.M.; Courdi, A.

    2010-01-01

    Acute skin toxicity is frequent during radiation therapy and can lead to temporary arrest of the treatment. Chronic toxicity can occur and conduct to cosmetic problems. Alopecia is the most frequent toxicity concerning hair and is most of the time reversible. Several factors linked to patients influence skin toxicity, such as under-nutrition, old age, obesity, smoking, skin diseases, autoimmune diseases, failure of DNA reparation. Skin, hair and nail toxicities depend also on radiation schedule. Acute toxicity is greater when dose per fraction increases. Chronic and acute toxicities are more often when total dose increases. Under 45 Gy, the risk of severe skin toxicity is low, and begins above 50 Gy. Skin toxicity depends also on the duration of radiotherapy and split course schedules are associated with less toxicities. Irradiation surface seems to influence skin toxicity but interaction is more complex. Reirradiation is often feasible in case of cancer recurrence but with a risk of grade 3-4 toxicity above all in head and neck cancer. The benefit/risk ratio has to be always precisely evaluated. Permanent alopecia is correlated with the follicle dose. Modern techniques of radiation therapy allow to spare skin. (authors)

  7. Normal tissue tolerance to external beam radiation therapy: The stomach

    International Nuclear Information System (INIS)

    Oberdiac, P.; Mineur, L.

    2010-01-01

    In the following article, we will discuss general issues relating to acute and late gastric's radiation toxicities. The tolerance of the stomach to complete or partial organ irradiation is more un-appreciated than for most other organs. We consulted the Medline database via PubMed and used the key words gastric - radiotherapy - toxicity. Currently, 60 Gy or less is prescribed in gastric radiation therapy. Acute clinical toxicity symptoms are predominantly nausea and vomiting. Although there is a general agreement that the whole stomach tolerance is for doses of 40 to 45 Gy without unacceptable complication, it is well established that a stomach dose of 35 Gy increases the risk of ulcer complications. (authors)

  8. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

    International Nuclear Information System (INIS)

    Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G.; Huchet, A.; Mamou, N.; Loiseau, H.

    2010-01-01

    Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

  9. Zinc therapy on children with Psoriasis modulates trace elements in serum and tissue

    International Nuclear Information System (INIS)

    El-Said, S. A.

    2013-01-01

    This study illustrates the effect of zinc therapy on some trace elements in either serum and skin which has been done on twenty patients with psoriasis with age range between 4 -13 years. They were under medical treatment with 5 milligram; oral zinc sulfate for 12 weeks. A significant increase in both serum and tissue copper and iron levels was detected by atomic absorption spectrophotometer . In addition, a significant decrease in both serum and tissue calcium and magnesium in psoriatic patients. It has been concluded that zinc therapy could be valuable through modulation of copper, calcium, iron and magnesium in psoriatic patients.

  10. Improvement of adipose tissue-derived cells by low-energy extracorporeal shock wave therapy.

    Science.gov (United States)

    Priglinger, Eleni; Schuh, Christina M A P; Steffenhagen, Carolin; Wurzer, Christoph; Maier, Julia; Nuernberger, Sylvia; Holnthoner, Wolfgang; Fuchs, Christiane; Suessner, Susanne; Rünzler, Dominik; Redl, Heinz; Wolbank, Susanne

    2017-09-01

    Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. In our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. After ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. Summarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  11. Adult soft tissue sarcomas: conventional therapies and molecularly targeted approaches.

    Science.gov (United States)

    Mocellin, Simone; Rossi, Carlo R; Brandes, Alba; Nitti, Donato

    2006-02-01

    The therapeutic approach to soft tissue sarcomas (STS) has evolved over the past two decades based on the results from randomized controlled trials, which are guiding physicians in the treatment decision-making process. Despite significant improvements in the control of local disease, a significant number of patients ultimately die of recurrent/metastatic disease following radical surgery due to a lack of effective adjuvant treatments. In addition, the characteristic chemoresistance of STS has compromised the therapeutic value of conventional antineoplastic agents in cases of unresectable advanced/metastatic disease. Therefore, novel therapeutic strategies are urgently needed to improve the prognosis of patients with STS. Recent advances in STS biology are paving the way to the development of molecularly targeted therapeutic strategies, the efficacy of which relies not only on the knowledge of the molecular mechanisms underlying cancer development/progression but also on the personalization of the therapeutic regimen according to the molecular features of individual tumours. In this work, we review the state-of-the-art of conventional treatments for STS and summarize the most promising findings in the development of molecularly targeted therapeutic approaches.

  12. Acute and late effects of multimodal therapy on normal tissues

    International Nuclear Information System (INIS)

    Phillips, T.L.; Fu, K.K.

    1977-01-01

    The increasing use of combined radiation, chemotherapy, and surgery has led to an increased incidence of acute and late complications. The complications are, in general, similar to those seen with each modality alone, but occur with increased incidence. Enhanced effects of combined radiation and surgery are modest in number and consist primarily of problems with wound healing and fibrosis, as well as late gastrointestinal damage. Combinations of radiotherapy and chemotherapy have shown a greater degree of enhanced acute and late reactions. Drugs, such as actinomycin-D and Adriamycin, are particularly dangerous if the marked enhancement of radiation effects caused by the drugs in almost all organs is not appreciated and the radiation dose not adjusted accordingly. Proper selection of drugs can lead to enhanced local control by radiotherapy and/or surgery, as well as eradication of microscopic distant metastases, without increased normal tissue injury. Late induction of malignancy can occur with either radiation or chemotherapy alone and, in some cases, this appears to be enhanced when they are combined

  13. Evaluation of Vacuum Assisted Closure Therapy for Soft Tissue Injury in Open Musculoskeletal Trauma.

    Science.gov (United States)

    Raj, Manish; Gill, S P S; Sheopaltan, Sunil Kumar; Singh, Pulkesh; Dinesh; Sigh, Jasveer; Rastogi, Prateek; Mishra, L N

    2016-04-01

    The application of controlled levels of negative or sub atmospheric pressure for a prolonged period of time on a wound had shown to accelerate removal of excess fluid and promote hyperaemia, which eventually promote wound healing. The study was conducted with the aim to evaluate the effectiveness of Vacuum Assisted Closure (VAC) therapy for soft tissue injury in open musculoskeletal trauma. Twenty cases of complex musculoskeletal wound involving different parts of body were included in this progressive randomized study. In patients, aggressive debridement was done before the application of VAC therapy. Controlled negative pressure was uniformly applied to the wound. Dressings were changed after every 4 to 5 days. The evaluation of results included healing rate of the wound, eradication of infection, complication rate, and number of secondary procedures. VAC therapy over the wound was administered for an average of 20.4 days ±6.72 days (range 14 to 42 days). There was decrease in wound size attained by VAC therapy ranged from 2.6 to 24.4cm(2), with an average reduction of 10.55 cm(2). Three wounds were infected at the start of VAC therapy. However, all patients were cleared of bacterial infection by the end of VAC therapy. VAC therapy using negative pressure promote Wound healing by increasing local capillary perfusion and increased rate of granulation tissue formation, decreases the duration of wound healing and requires fewer painful dressing change.

  14. Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

    Science.gov (United States)

    Yoshida, Toshiyuki; Washio, Kaoru; Iwata, Takanori; Okano, Teruo; Ishikawa, Isao

    2012-01-01

    It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy. PMID:22315604

  15. Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Toshiyuki Yoshida

    2012-01-01

    Full Text Available It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy.

  16. Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

    NARCIS (Netherlands)

    Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

    Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

  17. Stem cell therapy for the treatment of radiation-induced normal tissue damage

    International Nuclear Information System (INIS)

    Chapel, A.; Benderitter, M.; Gourmelon, P.; Lataillade, J.J.; Gorin, N.C.

    2013-01-01

    Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumour. In Europe, per year, 1.5 million patients undergo external radiotherapy. Acute adverse effect concern 80% of patients. The late adverse effect of radiotherapy concern 5 to 10% of them, which could be life threatening. Eradication of these manifestations is crucial. The French Institute of Radioprotection and Nuclear Safety (IRSN) contribute to understand effect of radiation on healthy tissue. IRSN is strongly implicated in the field of regeneration of healthy tissue after radiotherapy or radiological accident and in the clinical use of cell therapy in the treatment of irradiated patients. Our first success in cell therapy was the correction of deficient hematopoiesis in two patients. The intravenous injection of Mesenchymal Stem Cells (MSC) has restored bone marrow micro-environment after total body irradiation necessary to sustain hematopoiesis. Cutaneous radiation reactions play an important role in radiation accidents, but also as a limitation in radiotherapy and radio-oncology. We have evidenced for the first time, the efficiency of MSC therapy in the context of acute cutaneous and muscle damage following irradiation in five patients. Concerning the medical management of gastrointestinal disorder after irradiation, we have demonstrated the promising approach of the MSC treatment. We have shown that MSC migrate to damaged tissues and restore gut functions after radiation damage. The evaluation of stem cell therapy combining different sources of adult stem cells is under investigation

  18. Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation

    Science.gov (United States)

    2012-02-01

    10-1-0927 TITLE: Mesenchymal Stem Cell Therapy for Nerve Regeneration and Immunomodulation after Composite Tissue Allotransplantation...immunosuppression. Bone Marrow Derived Mesenchymal stem cells (BM-MSCs) are pluripotent cells, capable of differentiation along multiple mesenchymal lineages into...As part of implemented transition from University of Pittsburgh to Johns Hopkins University, we optimized our mesenchymal stem cell (MSC) isolation

  19. Tissue responses to postoperative laser therapy in diabetic rats submitted to excisional wounds.

    Directory of Open Access Journals (Sweden)

    Cristiano de Loura Santana

    Full Text Available In a previous study about low-level laser therapy biomodulation on a full-thickness burn model we showed that single and fractionated dose regimens increased wound healing and leukocyte influx similarly when compared with untreated control. In order to verify if this finding would be similar in an impaired wound model, we investigated the effect of single and multiple irradiations on wound closure rate, type of inflammatory infiltrate, myofibroblasts, collagen deposition, and optical retardation of collagen in diabetic rats. Female Wistar rats in the same estrous cycle had diabetes induced with streptozotocin and an 8-mm excisional wound performed with a punch. The experimental groups were: control group--untreated ulcer; single-dose group--ulcer submitted to single dose of diode laser therapy (λ = 660 ± 2 nm; P = 30 mW; energy density: 4 J/cm2 and fractionated-dose group--ulcer submitted to 1 J/cm2 laser therapy on Days 1, 3, 8, and 10. The ulcers were photographed on the experimental days and after euthanasia tissue samples were routinely processed for histological and immunohistochemistry analyses. Independently of the energy density, laser therapy accelerated wound closure by approximately 40% in the first three days in comparison to the control group. Laser therapy increased acute inflammatory infiltrate until Day 3. Both laser groups exhibited more myofibroblasts and better collagen organization than the control group. The findings demonstrate that low-level laser therapy in the immediate postoperative period can enhance the tissue repair process in a diabetes model. Similar effects were achieved with laser therapy applied a single time with an energy density of 4 J/cm2 and applied four times with an energy density of 1 J/cm2. The application of laser therapy in the inflammatory phase was the most important factor to the enhancement of the tissue repair process.

  20. Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure: new developments and challenges.

    Science.gov (United States)

    Finosh, G T; Jayabalan, Muthu

    2012-01-01

    Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed.

  1. Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

    Science.gov (United States)

    Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

    Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

  2. Tissue engineering and cell-based therapy toward integrated strategy with artificial organs.

    Science.gov (United States)

    Gojo, Satoshi; Toyoda, Masashi; Umezawa, Akihiro

    2011-09-01

    Research in order that artificial organs can supplement or completely replace the functions of impaired or damaged tissues and internal organs has been underway for many years. The recent clinical development of implantable left ventricular assist devices has revolutionized the treatment of patients with heart failure. The emerging field of regenerative medicine, which uses human cells and tissues to regenerate internal organs, is now advancing from basic and clinical research to clinical application. In this review, we focus on the novel biomaterials, i.e., fusion protein, and approaches such as three-dimensional and whole-organ tissue engineering. We also compare induced pluripotent stem cells, directly reprogrammed cardiomyocytes, and somatic stem cells for cell source of future cell-based therapy. Integrated strategy of artificial organ and tissue engineering/regenerative medicine should give rise to a new era of medical treatment to organ failure.

  3. An end-to-end assessment of range uncertainty in proton therapy using animal tissues

    Science.gov (United States)

    Zheng, Yuanshui; Kang, Yixiu; Zeidan, Omar; Schreuder, Niek

    2016-11-01

    Accurate assessment of range uncertainty is critical in proton therapy. However, there is a lack of data and consensus on how to evaluate the appropriate amount of uncertainty. The purpose of this study is to quantify the range uncertainty in various treatment conditions in proton therapy, using transmission measurements through various animal tissues. Animal tissues, including a pig head, beef steak, and lamb leg, were used in this study. For each tissue, an end-to-end test closely imitating patient treatments was performed. This included CT scan simulation, treatment planning, image-guided alignment, and beam delivery. Radio-chromic films were placed at various depths in the distal dose falloff region to measure depth dose. Comparisons between measured and calculated doses were used to evaluate range differences. The dose difference at the distal falloff between measurement and calculation depends on tissue type and treatment conditions. The estimated range difference was up to 5, 6 and 4 mm for the pig head, beef steak, and lamb leg irradiation, respectively. Our study shows that the TPS was able to calculate proton range within about 1.5% plus 1.5 mm. Accurate assessment of range uncertainty in treatment planning would allow better optimization of proton beam treatment, thus fully achieving proton beams’ superior dose advantage over conventional photon-based radiation therapy.

  4. Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults

    International Nuclear Information System (INIS)

    Blum, R.H.; Greenberger, J.S.; Wilson, R.E.; Corson, J.M.

    1979-01-01

    Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 mg/M 2 day 1, Adriamycin (ADR) 60 mg/M 2 day 2, and DTIC 400 mg/M 2 days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M 2 . Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000 to 5000 rad by megavoltage photons in 5 weeks, and in selected cases, an additional 1500 to 2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy. The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8 to 41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment

  5. Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies

    NARCIS (Netherlands)

    Jurgens, W.J.F.M.; Oedayrajsingh-Varma, M.J.; Helder, M.N.; Zandieh Doulabi, B.; Schouten, T.E.; Kuik, D.J.; Ritt, M.J.P.F.; van Milligen-Kummer, F.J.

    2008-01-01

    The stromal vascular fraction (SVF) of adipose tissue contains an abundant population of multipotent adipose-tissue-derived stem cells (ASCs) that possess the capacity to differentiate into cells of the mesodermal lineage in vitro. For cell-based therapies, an advantageous approach would be to

  6. Effect of ozone therapy on cell apoptosis and angiogenesis in retina tissue of diabetic retinopathy rats

    Institute of Scientific and Technical Information of China (English)

    Xiao Liu

    2016-01-01

    ABSTRACT Objective:To study the effect of ozone therapy on cell apoptosis and angiogenesis in retina tissue of diabetic retinopathy rats.Methods:SD rats were selected as experimental animals and divided into control group, model group and ozone group, and after diabetic models were built, ozone enema was conducted. Retina tissue was collected, TUNEL kits were used to detect the number of apoptotic cells, and Elisa kits were used to detect the contents of nerve damage molecules, angiogenesis-related molecules and endoplasmic reticulum stress molecules. Results:The number of apoptotic cells in retina tissue of model group was significantly more than that of control group, and the number of apoptotic cells in retina tissue of ozone group was significantly less than that of model group; NgR, NR2B, ERK1, ERK2, GFAP, VEGF, STAT-3, HIF-1α, Apelin, APJ, PERK, IRE-1α, ATF-6, eIF2α and XBP-1 contents in retina tissue of model group were significantly higher than those of control group, and PEDF content was lower than that of control group; NgR, NR2B, ERK1, ERK2, GFAP, VEGF, STAT-3, HIF-1α, Apelin, APJ, PERK, IRE-1α, ATF-6, eIF2α and XBP-1 contents in retina tissue of ozone group were significantly lower than those of model group, and PEDF content was higher than that of model group.Conclusion:Ozone therapy can reduce the number of apoptotic cells while reduce nerve cell injury and inhibit angiogenesis and endoplasmic reticulum stress in retina tissue of diabetic rats.

  7. Key Advances in the Systemic Therapy for Soft tissue Sarcomas: Current Status and Future Directions

    Directory of Open Access Journals (Sweden)

    Neelesh Soman

    2013-10-01

    Full Text Available Soft tissue sarcomas (STS represent a heterogeneous group of diverse neoplasms of mesenchymal origin. Once relapsed from standard therapy, STS patients have limited treatment options especially those that present with advanced or metastatic disease. In this review article, we highlight recent clinical data that led to the US Food and Drug Administration (FDA approval of pazopanib (Votrient® for STS and regorafenib (Stivarga®, BAY 73-4506 in gastrointestinal stromal tumours. We also review ongoing safety/efficacy data for trabectedin (Yondelis®, ET-743, and data from clinical studies of ridaforolimus (AP23573; MK-8669 and palifosfamide (ZIO-201. We provide a list of some promising ongoing trials in soft tissue sarcomas including first line studies of TH-302 and trabectedin. Finally, our article delves into recent advances in our understanding of the molecular pathogenesis of STS and novel therapies that might be explored as treatment options for specific STS histologies.

  8. The early career researcher's toolkit:translating tissue engineering, regenerative medicine and cell therapy products

    OpenAIRE

    Rafiq, Qasim A.; Ortega, Ilida; Jenkins, Stuart I.; Wilson, Samantha L.; Patel, Asha K.; Barnes, Amanda L.; Adams, Christopher F.; Delcassian, Derfogail; Smith, David

    2015-01-01

    Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in...

  9. Thermal distribution in biological tissue at laser induced fluorescence and photodynamic therapy

    Science.gov (United States)

    Krasnikov, I. V.; Seteikin, A. Yu.; Drakaki, E.; Makropoulou, M.

    2012-03-01

    Laser induced fluorescence spectroscopy and photodynamic therapy (PDT) are techniques currently introduced in clinical applications for visualization and local destruction of malignant tumours as well as premalignant lesions. During the laser irradiation of tissues for the diagnostic and therapeutic purposes, the absorbed optical energy generates heat, although the power density of the treatment light for surface illumination is normally low enough not to cause any significantly increased tissue temperature. In this work we tried to evaluate the utility of Monte Carlo modeling for simulating the temperature fields and the dynamics of heat conduction into the skin tissue under several laser irradiation conditions with both a pulsed UV laser and a continuous wave visible laser beam. The analysis of the results showed that heat is not localized on the surface, but it is collected inside the tissue. By varying the boundary conditions on the surface and the type of the laser radiation (continuous or pulsed) we can reach higher than normal temperature inside the tissue without simultaneous formation of thermally damaged tissue (e.g. coagulation or necrosis zone).

  10. Nanotechnology meets 3D in vitro models: tissue engineered tumors and cancer therapies.

    Science.gov (United States)

    da Rocha, E L; Porto, L M; Rambo, C R

    2014-01-01

    Advances in nanotechnology are providing to medicine a new dimension. Multifunctional nanomaterials with diagnostics and treatment modalities integrated in one nanoparticle or in cooperative nanosystems are promoting new insights to cancer treatment and diagnosis. The recent convergence between tissue engineering and cancer is gradually moving towards the development of 3D disease models that more closely resemble in vivo characteristics of tumors. However, the current nanomaterials based therapies are accomplished mainly in 2D cell cultures or in complex in vivo models. The development of new platforms to evaluate nano-based therapies in parallel with possible toxic effects will allow the design of nanomaterials for biomedical applications prior to in vivo studies. Therefore, this review focuses on how 3D in vitro models can be applied to study tumor biology, nanotoxicology and to evaluate nanomaterial based therapies. © 2013.

  11. 3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening

    Directory of Open Access Journals (Sweden)

    Michaela Thomas

    2017-11-01

    Full Text Available Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone, and poly(ethylene glycol. This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work.

  12. Expression of DMP-1 in the human pulp tissue using low level laser therapy

    International Nuclear Information System (INIS)

    Neto, Natalino Lourenço; Teixeira Marques, Nádia Carolina; Fernandes, Ana Paula; Silva, Thiago Cruvinel; Andrade Moreira Machado, Maria Aparecida; Oliveira, Thais Marchini; Rodini, Camila Oliveira

    2015-01-01

    This study aimed to evaluate the effects of low-level laser therapy (LLLT) on DMP-1 expression in pulp tissue repair of human primary teeth. Twenty mandibular primary molars were randomly assigned into the following groups: Group I—Buckley’s Formocresol (FC); Group II—Calcium Hydroxide (CH); Group III—LLLT + CH and Group IV—LLLT + Zinc oxide/Eugenol. The teeth at the regular exfoliation period were extracted for histological analysis and immunolocalization of DMP-1. Descriptive analysis was performed on the dentin pulp complex. Histopathological assessment showed internal resorption in group FC. Groups CH and LLLT + CH provided better pulpal repair due to the absence of inflammation and the formation of hard tissue barrier. These two groups presented odontoblastic layer expressing DMP-1. According to this study, low level laser therapy preceding the use of calcium hydroxide exhibited satisfactory bio-inductive activity on pulp tissue repair of human primary teeth. However, other histological and cellular studies are needed to confirm the laser tissue action and efficacy. (paper)

  13. The tolerance of skin grafts to postoperative radiation therapy in patients with soft-tissue sarcoma

    International Nuclear Information System (INIS)

    Lawrence, W.T.; Zabell, A.; McDonald, H.D.

    1986-01-01

    During the last ten years at the National Cancer Institute, 11 patients have received 12 courses of postoperative adjuvant radiation therapy to skin grafts used for wound closure after the resection of soft-tissue sarcomas. The intervals between grafting and the initiation of radiation ranged between 3 and 20 weeks, and 4 patients received chemotherapy at the same time as their radiation. Ten of the 12 irradiated grafts remained intact after the completion of therapy. One graft had several small persistently ulcerated areas that required no further surgical treatment, and one graft required a musculocutaneous flap for reconstruction of a persistent large ulcer. Acute radiation effects on the grafted skin sometimes developed at slightly lower doses than usually seen with normal skin, but these acute effects necessitated a break in therapy on only five occasions. Concurrent chemotherapy and a relatively short interval between grafting and the initiation of radiation seemed to contribute to more severe radiation reactions. This experience indicates that postoperative adjuvant radiation therapy can be delivered to skin grafted areas without undue fear of complications, especially if the graft is allowed to heal adequately prior to initiating therapy and if chemotherapy is not given in conjunction with radiation

  14. Can Bone Tissue Engineering Contribute to Therapy Concepts after Resection of Musculoskeletal Sarcoma?

    Directory of Open Access Journals (Sweden)

    Boris Michael Holzapfel

    2013-01-01

    Full Text Available Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology.

  15. Assessment of cone beam CT registration for prostate radiation therapy: fiducial marker and soft tissue methods.

    Science.gov (United States)

    Deegan, Timothy; Owen, Rebecca; Holt, Tanya; Fielding, Andrew; Biggs, Jennifer; Parfitt, Matthew; Coates, Alicia; Roberts, Lisa

    2015-02-01

    This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCTFM ) and the soft tissue prostate (CBCTST ). Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCTFM and CBCTST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland-Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoAmean ) were defined as ±2.0 mm for CBCTFM and ±3.0 mm for CBCTST . Differences between CBCTST alignment and the observer-averaged CBCTFM (AvCBCTFM ) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCTST and AvCBCTFM . CBCTFM and CBCTST alignments were performed for 185 images. The CBCTFM 95% LoAmean were within ±2.0 mm in all planes. CBCTST 95% LoAmean were within ±3.0 mm in all planes. Comparison of CBCTST with AvCBCTFM resulted in 95% LoA of -4.9 to 2.6, -1.6 to 2.5 and -4.7 to 1.9 mm in the superior-inferior, left-right and anterior-posterior planes, respectively. Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy. © 2014 The Royal Australian and New Zealand College of Radiologists.

  16. Assessment of cone beam CT registration for prostate radiation therapy: fiducial marker and soft tissue methods

    International Nuclear Information System (INIS)

    Deegan, Timothy; Owen, Rebecca; Holt, Tanya; Fielding, Andrew; Biggs, Jennifer; Parfitt, Matthew; Coates, Alicia; Roberts, Lisa

    2015-01-01

    This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCT FM ) and the soft tissue prostate (CBCT ST ). Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCT FM and CBCT ST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland–Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoA mean ) were defined as ±2.0 mm for CBCT FM and ±3.0 mm for CBCT ST . Differences between CBCT ST alignment and the observer-averaged CBCT FM (AvCBCT FM ) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCT ST and AvCBCT FM . CBCT FM and CBCT ST alignments were performed for 185 images. The CBCT FM 95% LoA mean were within ±2.0 mm in all planes. CBCT ST 95% LoA mean were within ±3.0 mm in all planes. Comparison of CBCT ST with AvCBCT FM resulted in 95% LoA of −4.9 to 2.6, −1.6 to 2.5 and −4.7 to 1.9 mm in the superior–inferior, left–right and anterior–posterior planes, respectively. Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy.

  17. Endovascular optical coherence tomography ex vivo: venous wall anatomy and tissue alterations after endovenous therapy

    International Nuclear Information System (INIS)

    Meissner, Oliver A.; Schmedt, Claus-Georg; Steckmeier, Bernd M.; Hunger, Kathrin; Reiser, Maximilian; Mueller-Lisse, Ullrich; Hetterich, Holger; Rieber, Johannes; Sroka, Ronald; Babaryka, Gregor; Siebert, Uwe

    2007-01-01

    Endovascular optical coherence tomography (OCT) is a new imaging modality providing histology-like information of the venous wall. Radiofrequency ablation (RFA) and laser therapy (ELT) are accepted alternatives to surgery. This study evaluated OCT for qualitative assessment of venous wall anatomy and tissue alterations after RFA and ELT in bovine venous specimens. One hundred and thirty-four venous segments were obtained from ten ex-vivo bovine hind limbs. OCT signal characteristics for different wall layers were assessed in 180/216 (83%) quadrants from 54 normal venous cross-sections. Kappa statistics (κ) were used to calculate intra- and inter-observer agreement. Qualitative changes after RFA (VNUS-Closure) and ELT (diode laser 980 nm, energy densities 15 Joules (J)/cm, 25 J/cm, 35 J/cm) were described in 80 venous cross-sections. Normal veins were characterized by a three-layered appearance. After RFA, loss of three-layered appearance and wall thickening at OCT corresponded with circular destruction of tissue structures at histology. Wall defects after ELT ranged from non-transmural punctiform damage to complete perforation, depending on the energy density applied. Intra- and inter-observer agreement for reading OCT images was very high (0.90 and 0.88, respectively). OCT allows for reproducible evaluation of normal venous wall and alterations after endovenous therapy. OCT could prove to be valuable for optimizing endovenous therapy in vivo. (orig.)

  18. 3D printing of biomaterials with mussel-inspired nanostructures for tumor therapy and tissue regeneration.

    Science.gov (United States)

    Ma, Hongshi; Luo, Jian; Sun, Zhe; Xia, Lunguo; Shi, Mengchao; Liu, Mingyao; Chang, Jiang; Wu, Chengtie

    2016-12-01

    Primary bone cancer brings patients great sufferings. To deal with the bone defects resulted from cancer surgery, biomaterials with good bone-forming ability are necessary to repair bone defects. Meanwhile, in order to prevent possible tumor recurrence, it is essential that the remaining tumor cells around bone defects are completely killed. However, there are few biomaterials with the ability of both cancer therapy and bone regeneration until now. Here, we fabricated a 3D-printed bioceramic scaffold with a uniformly self-assembled Ca-P/polydopamine nanolayer surface. Taking advantage of biocompatibility, biodegradability and the excellent photothermal effect of polydopamine, the bifunctional scaffolds with mussel-inspired nanostructures could be used as a satisfactory and controllable photothermal agent, which effectively induced tumor cell death in vitro, and significantly inhibited tumor growth in mice. In addition, owing to the nanostructured surface, the prepared polydopamine-modified bioceramic scaffolds could support the attachment and proliferation of rabbit bone mesenchymal stem cells (rBMSCs), and significantly promoted the formation of new bone tissues in rabbit bone defects even under photothermal treatment. Therefore, the mussel-inspired nanostructures in 3D-printed bioceramic exhibited a remarkable capability for both cancer therapy and bone regeneration, offering a promising strategy to construct bifunctional biomaterials which could be widely used for therapy of tumor-induced tissue defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Preclinical evaluation of oncolytic vaccinia virus for therapy of canine soft tissue sarcoma.

    Directory of Open Access Journals (Sweden)

    Ivaylo Gentschev

    Full Text Available Virotherapy using oncolytic vaccinia virus (VACV strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Lister VACV LIVP1.1.1 and GLV-1h68 strains against CSTS. Cell culture data demonstrated that both tested VACV strains efficiently infected and destroyed cells of the canine soft tissue sarcoma line STSA-1. In addition, in our new canine sarcoma tumor xenograft mouse model, systemic administration of LIVP1.1.1 or GLV-1h68 viruses led to significant inhibition of tumor growth compared to control mice. Furthermore, LIVP1.1.1 mediated therapy resulted in almost complete tumor regression and resulted in long-term survival of sarcoma-bearing mice. The replication of the tested VACV strains in tumor tissues led to strong oncolytic effects accompanied by an intense intratumoral infiltration of host immune cells, mainly neutrophils. These findings suggest that the direct viral oncolysis of tumor cells and the virus-dependent activation of tumor-associated host immune cells could be crucial parts of anti-tumor mechanism in STSA-1 xenografts. In summary, the data showed that both tested vaccinia virus strains and especially LIVP1.1.1 have great potential for effective treatment of CSTS.

  20. Potential of stem cell based therapy and tissue engineering in the regeneration of the central nervous system

    International Nuclear Information System (INIS)

    An Yihua; Tsang, Kent K S; Zhang Han

    2006-01-01

    The insufficiency of self-repair and regeneration of the central nervous system (CNS) leads to difficulty of rehabilitation of the injured brain. In the past few decades, the significant progress in cell therapy and tissue engineering has contributed to the functional recovery of the CNS to a great extent. The present review focuses on the potential role of stem cell based therapy and tissue engineering in the regeneration of the CNS. (topical review)

  1. Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

    International Nuclear Information System (INIS)

    Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

    2013-01-01

    the tumor motion trajectory and its final locations obtained from simulations with and without considering tissue incompressibility variation were very different. For example, tumor displacements in the z direction were −11.23 and −38.10 mm obtained with the Marlow hyperelastic material model in conjunction with constant and variable Poisson's ratio, respectively. By comparing the acquired 4D-CT image sequence of the porcine lung with their image sequence counterparts obtained from the hyperelastic model with constant and variable Poisson's ratio, it was shown that using variable tissue incompressibility reduced errors significantly in tumor motion prediction. Conclusions: This investigation demonstrates the importance of incompressibility variation estimation and utilization for accurate tumor tracking in computer assisted lung external beam radiation therapy. An optimization framework was developed to estimate a Poisson's ratio function in terms of respiration cycle time using experimental image data of the lung. Utilizing this function along with respiratory system FE modeling may lead to more effective tumor targeting, hence potentially improving the outcome of lung external beam radiation therapy techniques. This is particularly true for stereotactic body radiation therapy where only one or a few fraction treatments are applied, precluding the possibility of averaging out dosimetric deviations introduced by the respiratory motion.

  2. The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products.

    Science.gov (United States)

    Rafiq, Qasim A; Ortega, Ilida; Jenkins, Stuart I; Wilson, Samantha L; Patel, Asha K; Barnes, Amanda L; Adams, Christopher F; Delcassian, Derfogail; Smith, David

    2015-11-01

    Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization.

  3. Correction factors to convert microdosimetry measurements in silicon to tissue in 12C ion therapy.

    Science.gov (United States)

    Bolst, David; Guatelli, Susanna; Tran, Linh T; Chartier, Lachlan; Lerch, Michael L F; Matsufuji, Naruhiro; Rosenfeld, Anatoly B

    2017-03-21

    Silicon microdosimetry is a promising technology for heavy ion therapy (HIT) quality assurance, because of its sub-mm spatial resolution and capability to determine radiation effects at a cellular level in a mixed radiation field. A drawback of silicon is not being tissue-equivalent, thus the need to convert the detector response obtained in silicon to tissue. This paper presents a method for converting silicon microdosimetric spectra to tissue for a therapeutic 12 C beam, based on Monte Carlo simulations. The energy deposition spectra in a 10 μm sized silicon cylindrical sensitive volume (SV) were found to be equivalent to those measured in a tissue SV, with the same shape, but with dimensions scaled by a factor κ equal to 0.57 and 0.54 for muscle and water, respectively. A low energy correction factor was determined to account for the enhanced response in silicon at low energy depositions, produced by electrons. The concept of the mean path length [Formula: see text] to calculate the lineal energy was introduced as an alternative to the mean chord length [Formula: see text] because it was found that adopting Cauchy's formula for the [Formula: see text] was not appropriate for the radiation field typical of HIT as it is very directional. [Formula: see text] can be determined based on the peak of the lineal energy distribution produced by the incident carbon beam. Furthermore it was demonstrated that the thickness of the SV along the direction of the incident 12 C ion beam can be adopted as [Formula: see text]. The tissue equivalence conversion method and [Formula: see text] were adopted to determine the RBE 10 , calculated using a modified microdosimetric kinetic model, applied to the microdosimetric spectra resulting from the simulation study. Comparison of the RBE 10 along the Bragg peak to experimental TEPC measurements at HIMAC, NIRS, showed good agreement. Such agreement demonstrates the validity of the developed tissue equivalence correction factors and of

  4. Expression of HIF-1{alpha} in irradiated tissue is altered by topical negative-pressure therapy

    Energy Technology Data Exchange (ETDEWEB)

    Grimm, A.; Stange, S.; Labanaris, A.; Horch, R.E. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Plastic and Hand Surgery; Dimmler, A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Pathology; Sauer, R.; Grabenbauer, G. [Erlangen-Nuernberg Univ. (Germany). Dept. of Radiation Oncology

    2007-03-15

    Background and Purpose: Despite the enormous therapeutic potential of modern radiotherapy, common side effects such as radiation-induced wound healing disorders remain a well-known clinical phenomenon. Topical negative pressure therapy (TNP) is a novel tool to alleviate intraoperative, percutaneous irradiation or brachytherapy. Since TNP has been shown to positively influence the perfusion of chronic, poorly vascularized wounds, the authors applied this therapeutic method to irradiated wounds and investigated the effect on tissue oxygenation in irradiated tissue in five patients. Material and Methods: With informed patients' consent, samples prior to and 4 and 8 days after continuous TNP with -125 mmHg were obtained during routine wound debridements. Granulation tissue was stained with hematoxylin-eosin, and additionally with CD31, HIF-1{alpha} (hypoxia-inducible factor-1{alpha}), and D2-40 to detect blood vessels, measure indirect signs of hypoxia, and lymph vessel distribution within the pre- and post-TNP samples. Results: In this first series of experiments, a positive influence of TNP onto tissue oxygenation in radiation-induced wounds could be demonstrated. TNP led to a significant decrease of 53% HIF-1{alpha}-positive cell nuclei. At the same time, a slight reduction of CD31-stained capillaries was seen in comparison to samples before TNP. Immunostaining with D2-40 revealed an increased number of lymphatic vessels with distended lumina and an alteration of the parallel orientation within the post-TNP samples. Conclusion: This study is, to the authors' knowledge, the first report on a novel previously not described histological marker to demonstrate the effects of TNP on HIF-1{alpha} expression as an indirect marker of tissue oxygenation in irradiated wounds, as demonstrated by a reduction of HIF-1{alpha} concentration after TNP. Since this observation may be of significant value to develop possible new strategies to treat radiation-induced tissue

  5. Expression of HIF-1α in irradiated tissue is altered by topical negative-pressure therapy

    International Nuclear Information System (INIS)

    Grimm, A.; Stange, S.; Labanaris, A.; Horch, R.E.; Dimmler, A.; Sauer, R.; Grabenbauer, G.

    2007-01-01

    Background and Purpose: Despite the enormous therapeutic potential of modern radiotherapy, common side effects such as radiation-induced wound healing disorders remain a well-known clinical phenomenon. Topical negative pressure therapy (TNP) is a novel tool to alleviate intraoperative, percutaneous irradiation or brachytherapy. Since TNP has been shown to positively influence the perfusion of chronic, poorly vascularized wounds, the authors applied this therapeutic method to irradiated wounds and investigated the effect on tissue oxygenation in irradiated tissue in five patients. Material and Methods: With informed patients' consent, samples prior to and 4 and 8 days after continuous TNP with -125 mmHg were obtained during routine wound debridements. Granulation tissue was stained with hematoxylin-eosin, and additionally with CD31, HIF-1α (hypoxia-inducible factor-1α), and D2-40 to detect blood vessels, measure indirect signs of hypoxia, and lymph vessel distribution within the pre- and post-TNP samples. Results: In this first series of experiments, a positive influence of TNP onto tissue oxygenation in radiation-induced wounds could be demonstrated. TNP led to a significant decrease of 53% HIF-1α-positive cell nuclei. At the same time, a slight reduction of CD31-stained capillaries was seen in comparison to samples before TNP. Immunostaining with D2-40 revealed an increased number of lymphatic vessels with distended lumina and an alteration of the parallel orientation within the post-TNP samples. Conclusion: This study is, to the authors' knowledge, the first report on a novel previously not described histological marker to demonstrate the effects of TNP on HIF-1α expression as an indirect marker of tissue oxygenation in irradiated wounds, as demonstrated by a reduction of HIF-1α concentration after TNP. Since this observation may be of significant value to develop possible new strategies to treat radiation-induced tissue injury, further investigations of HIF

  6. Functional and psychosocial effects of multimodality limb-sparing therapy in patients with soft tissue sarcomas

    International Nuclear Information System (INIS)

    Chang, A.E.; Steinberg, S.M.; Culnane, M.

    1989-01-01

    We have documented functional and psychosocial changes in patients with extremity soft tissue sarcomas who have undergone multimodality limb-sparing treatments. In 88 patients, parameters related to economic status, sexual activity, pain, limb function, and global quality of life (QOL) were recorded prior to surgery and every 6 months postoperatively. Changes from the preoperative assessment for every parameter were analyzed in each patient. Six months after surgery, there was a decrease in employment status, sexual activity, and in limb function in a significant number of patients. At 12 months, these decreases were still evident. Despite these changes, global QOL measured by a standardized test showed at least some improvement in a significant proportion of patients at 12 months. These findings highlight the difficulty in defining QOL. It could not be ascertained if radiation therapy and/or chemotherapy were causative factors in specific changes because of the small numbers of patients in each subgroup. However, among 60 patients with high-grade sarcomas, significant wound problems developed in 10 of 33 who received postoperative radiation therapy in combination with adjuvant doxorubicin and cyclophosphamide chemotherapy compared with one of 27 patients who received adjuvant chemotherapy alone (P = .016). Also, among high-grade sarcoma patients with 12-month follow-up, six of 19 patients who received radiation therapy and chemotherapy developed joint contractures compared with zero of 15 patients who received chemotherapy alone (P less than .04). The combination of postoperative radiation therapy and chemotherapy appeared to be associated with significantly more tissue-related injury in patients with high-grade sarcomas compared with chemotherapy alone

  7. Functional and psychosocial effects of multimodality limb-sparing therapy in patients with soft tissue sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Chang, A.E.; Steinberg, S.M.; Culnane, M.; Lampert, M.H.; Reggia, A.J.; Simpson, C.G.; Hicks, J.E.; White, D.E.; Yang, J.J.; Glatstein, E. (National Cancer Institute, Bethesda, MD (USA))

    1989-09-01

    We have documented functional and psychosocial changes in patients with extremity soft tissue sarcomas who have undergone multimodality limb-sparing treatments. In 88 patients, parameters related to economic status, sexual activity, pain, limb function, and global quality of life (QOL) were recorded prior to surgery and every 6 months postoperatively. Changes from the preoperative assessment for every parameter were analyzed in each patient. Six months after surgery, there was a decrease in employment status, sexual activity, and in limb function in a significant number of patients. At 12 months, these decreases were still evident. Despite these changes, global QOL measured by a standardized test showed at least some improvement in a significant proportion of patients at 12 months. These findings highlight the difficulty in defining QOL. It could not be ascertained if radiation therapy and/or chemotherapy were causative factors in specific changes because of the small numbers of patients in each subgroup. However, among 60 patients with high-grade sarcomas, significant wound problems developed in 10 of 33 who received postoperative radiation therapy in combination with adjuvant doxorubicin and cyclophosphamide chemotherapy compared with one of 27 patients who received adjuvant chemotherapy alone (P = .016). Also, among high-grade sarcoma patients with 12-month follow-up, six of 19 patients who received radiation therapy and chemotherapy developed joint contractures compared with zero of 15 patients who received chemotherapy alone (P less than .04). The combination of postoperative radiation therapy and chemotherapy appeared to be associated with significantly more tissue-related injury in patients with high-grade sarcomas compared with chemotherapy alone.

  8. Does the application site of spinal manipulative therapy alter spinal tissues loading?

    Science.gov (United States)

    Funabashi, Martha; Nougarou, François; Descarreaux, Martin; Prasad, Narasimha; Kawchuk, Gregory N

    2018-01-31

    Previous studies found that the intervertebral disc (IVD) experiences the greatest loads during spinal manipulation therapy (SMT). Based on that, this study aimed to determine if loads experienced by spinal tissues are significantly altered when the application site of SMT is changed. A biomechanical robotic serial dissection study. Thirteen porcine cadaveric motion segments. Forces experienced by lumbar spinal tissues. A servo-controlled linear actuator provided standardized 300 N SMT simulations to six different cutaneous locations of the porcine lumbar spine: L2-L3 and L3-L4 facet joints (FJ), L3 and L4 transverse processes (TVP), and the space between the FJs and the TVPs (BTW). Vertebral kinematics were tracked optically using indwelling bone pins; the motion segment was removed and mounted in a parallel robot equipped with a six-axis load cell. Movements of each SMT application at each site were replayed by the robot with the intact specimen and following the sequential removal of spinal ligaments, FJs and IVD. Forces induced by SMT were recorded, and specific axes were analyzed using linear mixed models. Analyses yielded a significant difference (p<.05) in spinal structures loads as a function of the application site. Spinal manipulative therapy application at the L3 vertebra caused vertebral movements and forces between L3 and L4 spinal segment in the opposite direction to when SMT was applied at L4 vertebra. Additionally, SMT applications over the soft tissue between adjacent vertebrae significantly decreased spinal structure loads. Applying SMT with a constant force at different spinal levels creates different relative kinetics of the spinal segments and load spinal tissues in significantly different magnitudes. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Tissue As A Medium For Laser Light Transport-Implications For Photoradiation Therapy

    Science.gov (United States)

    Preuss, L. E.; Bolin, F. P.; Cain, B. W.

    1982-12-01

    An important medical laser application is in the emerging field of photoradiation therapy (PRT). PRT is the process in which malignant tissue is destroyed by administration of light to a specific photosensitized site. Filtered arcs, incandescents and dye lasers have been used as sources of activating light. We have carried out light experiments in tissue to study such PRT light distributions. The results of this research have shown that a number of important optical phenomena occurring within illuminated tissue must be accounted for in order to make good predictions of tumor light dosage. Among these are; tissue type, interface effects and anomalies due to composition. These effects substantially influence light levels in PRT and, thus, the therapeutic effect. The uniqueness of tissue as a medium for light transport presents special problems for optics research and instrumentation. Successful solutions necessarily will involve collaboration between the life sciences and optic specialists. Attempts at treatment of human disease using non-ionizing radiation have a history archaeologically traceable to archaic societies (in which the sun's photons were used and often worshipped).1 Western medicine in the past, has used visible light beneficially, albeit empirically, on a few ailments. However, in this century, a significant development in the understanding and in the therapeutic use of this electromagnetic radiation in the UV, visible and IR has occurred, based on scientific study. This utilization of radiation in the visible and ultraviolet can be by two distinct processes. One is through the direct action of the photons which serve as the sole treatment agent. In this case the photon interacts with the cell, or its components, in a single step, to produce a desired effect. An example is the successful use of blue light for treatment of bilirubinemia in newborns. The second process is a biological effect produced through the combination of electromagnetic radiation

  10. Tissue Pharmacologic and Virologic Determinants of Duodenal and Rectal Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution in HIV-Infected Patients Initiating Antiretroviral Therapy.

    Science.gov (United States)

    Asmuth, David M; Thompson, Corbin G; Chun, Tae-Wook; Ma, Zhong-Min; Mann, Surinder; Sainz, Talia; Serrano-Villar, Sergio; Utay, Netanya S; Garcia, Juan Carlos; Troia-Cancio, Paolo; Pollard, Richard B; Miller, Christopher J; Landay, Alan; Kashuba, Angela D

    2017-10-17

    Plasma, duodenal, and rectal tissue antiretroviral therapy (ART) drug concentrations, human immunodeficiency virus (HIV) RNA and HIV DNA copy numbers, and recovery of mucosal immunity were measured before and 9 months after initiation of 3 different ART regimens in 26 subjects. Plasma and tissue HIV RNA correlated at baseline and when 9-month declines were compared, suggesting that these compartments are tightly associated. Antiretroviral tissue:blood penetration ratios were above the 50% inhibitory concentration values in almost 100% of cases. There were no correlations between drug concentrations and HIV DNA/RNA. Importantly, no evidence was found for residual viral replication or deficient tissue drug penetration to account for delayed gastrointestinal-associated lymphoid tissue immune recovery. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  11. Original paper Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Joanna Świdrowska

    2015-04-01

    Full Text Available Objectives: Connective tissue diseases (CTD are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA. Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient’s clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS, it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. Material and methods: Data from 24 patients with CTD treated with tumor necrosis factor--blockers (etanercept, adalimumab, golimumab and an interleukin-6 receptor blocker (tocilizumab were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. Results : Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1% during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. Conclusions : In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS

  12. Radiation recall dermatitis with soft tissue necrosis following pemetrexed therapy: a case report

    Directory of Open Access Journals (Sweden)

    Spirig Christian

    2009-11-01

    Full Text Available Abstract Introduction Radiation recall dermatitis is a well known but still poorly understood inflammatory reaction. It can develop in previously irradiated areas and has been shown to be triggered by a variety of different drugs, including cytostatic agents. Pemetrexed may cause radiation recall dermatitis in pre-irradiated patients. Case presentation We present the case of a 49-year-old Caucasian woman with non-small cell lung cancer who was initially treated with carboplatin and paclitaxel concomitant with radiotherapy after suffering a painful plexus brachialis infiltration. Due to disease progression, a second-line treatment with pemetrexed was started. A severe soft tissue necrosis developed despite steroid treatment and plastic surgery. Conclusion To the best of our knowledge, we present the first case of a patient with severe soft tissue necrosis in a pre-irradiated area after pemetrexed therapy. We believe that physicians treating patients with pemetrexed should be aware of the severe, possibly life-threatening effects that may be induced by pemetrexed after previous radiation therapy.

  13. Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

    Science.gov (United States)

    Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

    1999-01-01

    Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

  14. Influence of the chemical composition of human tissues on dose distributions in hadron-therapy

    International Nuclear Information System (INIS)

    Batin, E.

    2008-06-01

    To compute the dose distribution, treatment planning systems require the exact anatomical location of tissues provided by computed tomography (CT) and the exact range of hadron beams in tissues based on the water equivalent ratio (WER). Since CT numbers are determined with x-rays and with an energy different from that used in hadron-therapy, a relation between CT numbers and the WER must to be established. We propose a determination of the WER with a Monte-Carlo simulation (GEANT4). We have determined the WER for 76 human tissues for a 135 MeV proton beam and for a 290 MeV/A carbon beam. The difference between the stoichiometric calibration and the simulated WER is lower than 1%. An additional 2% uncertainty that arises from the uncertainty in the CT numbers measurement should also be considered. The calculated WER were used to convert the deposited energy curve into the human tissue deposited energy curve for a 135 MeV proton beam and for a 290 MeV/A carbon beam. For both beams, the difference between the rescaled Bragg peak location and the one from the simulated curve is lower than 0.5 mm over the whole range of CT numbers. The differences between the maximum deposited energy can reach 3% for the proton beam in bones and vary between 1.5% and 3.5% for all tissues for the carbon beam. The scaling in two dimensions can be improved by using an additional factor that takes the scattering into account. (author)

  15. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States); Roeske, John C., E-mail: jroeske@lumc.edu [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States)

    2012-08-01

    Purpose: To implement the 'plan-do-check-act' (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues ('gold' contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes {>=}8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose

  16. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    International Nuclear Information System (INIS)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman; Roeske, John C.

    2012-01-01

    Purpose: To implement the “plan-do-check-act” (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues (“gold” contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes ≥8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose assessment in

  17. [Comparing effectivity of VAC therapy for treatment of infections following arthroplasty or soft-tissue surgery].

    Science.gov (United States)

    Schmal, H; Oberst, M; Hansen, S; Six-Merker, J; Südkamp, N P; Izadpanah, K

    2013-08-01

    Although vacuum-assisted wound closure (VAC) has been developed into a standard technique in septic surgery, reliable data about the efficacy of the treatment are still lacking. Postoperative infections after arthroplasty or soft-tissue surgery were identified using a prospective database for complications (Critical Incidence Reporting System) which was retrospectively supplemented with items for evaluation of VAC therapy. Eradication success of infection was analysed considering epidemiological parameters, course of treatment, and characteristics of causing bacterial strains. Furthermore, serological C-reactive protein (CRP) concentrations were evaluated for diagnostic and prognostic reliability. 92 patients with an average age of 60 ± 4 years were included in the study. Patients with soft tissue infections (STI, n = 53) were statistically significant younger compared to patients with infections following arthroplasty (AI, n = 39) (53 ± 6 vs. 70 ± 4 years; p infected endoprostheses were longer treated on intensive care units (6.1 ± 8.4 vs. 3.5 ± 6.5 days; p infection was with 81 % statistically significant higher in the STI group compared to 38 % in the AI group (p infections in the AI group were associated with a better healing success when compared to chronic infections (p infections (p infection, the probability for eradication of infection was impaired (p infection was reached. CRP values were higher in the AI group and associated with the prognosis (p VAC therapy is higher after soft-tissue infections compared to infections following arthroplasty. Accordingly, mortality is higher in this group. Chronic courses have worse chances for healing in both groups. For serological CRP values a prognostic relevance could be shown. Georg Thieme Verlag KG Stuttgart · New York.

  18. Tissue decomposition from dual energy CT data for MC based dose calculation in particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hünemohr, Nora, E-mail: n.huenemohr@dkfz.de; Greilich, Steffen [Medical Physics in Radiation Oncology, German Cancer Research Center, 69120 Heidelberg (Germany); Paganetti, Harald; Seco, Joao [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States); Jäkel, Oliver [Medical Physics in Radiation Oncology, German Cancer Research Center, 69120 Heidelberg, Germany and Department of Radiation Oncology and Radiation Therapy, University Hospital of Heidelberg, 69120 Heidelberg (Germany)

    2014-06-15

    Purpose: The authors describe a novel method of predicting mass density and elemental mass fractions of tissues from dual energy CT (DECT) data for Monte Carlo (MC) based dose planning. Methods: The relative electron density ϱ{sub e} and effective atomic number Z{sub eff} are calculated for 71 tabulated tissue compositions. For MC simulations, the mass density is derived via one linear fit in the ϱ{sub e} that covers the entire range of tissue compositions (except lung tissue). Elemental mass fractions are predicted from the ϱ{sub e} and the Z{sub eff} in combination. Since particle therapy dose planning and verification is especially sensitive to accurate material assignment, differences to the ground truth are further analyzed for mass density, I-value predictions, and stopping power ratios (SPR) for ions. Dose studies with monoenergetic proton and carbon ions in 12 tissues which showed the largest differences of single energy CT (SECT) to DECT are presented with respect to range uncertainties. The standard approach (SECT) and the new DECT approach are compared to reference Bragg peak positions. Results: Mean deviations to ground truth in mass density predictions could be reduced for soft tissue from (0.5±0.6)% (SECT) to (0.2±0.2)% with the DECT method. Maximum SPR deviations could be reduced significantly for soft tissue from 3.1% (SECT) to 0.7% (DECT) and for bone tissue from 0.8% to 0.1%. MeanI-value deviations could be reduced for soft tissue from (1.1±1.4%, SECT) to (0.4±0.3%) with the presented method. Predictions of elemental composition were improved for every element. Mean and maximum deviations from ground truth of all elemental mass fractions could be reduced by at least a half with DECT compared to SECT (except soft tissue hydrogen and nitrogen where the reduction was slightly smaller). The carbon and oxygen mass fraction predictions profit especially from the DECT information. Dose studies showed that most of the 12 selected tissues would

  19. Treatment Effects and Sequelae of Radiation Therapy for Orbital Mucosa-Associated Lymphoid Tissue Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Hata, Masaharu, E-mail: mhata@syd.odn.ne.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Omura, Motoko; Koike, Izumi [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Tomita, Naoto [Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Iijima, Yasuhito [Department of Ophthalmology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Tayama, Yoshibumi; Odagiri, Kazumasa; Minagawa, Yumiko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Ogino, Ichiro [Department of Radiation Oncology, Yokohama City University Medical Center, Yokohama, Kanagawa (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan)

    2011-12-01

    Purpose: Among extranodal lymphomas, orbital mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare presentation. We performed a review to ascertain treatment efficacy and toxicity of radiation therapy for orbital MALT lymphoma. We also evaluated changes in visual acuity after irradiation. Methods and Materials: Thirty patients with orbital MALT lymphoma underwent radiation therapy with curative intent. Clinical stages at diagnosis were stage I{sub E}A in 29 patients and stage II{sub E}A in 1 patient. Total doses of 28.8 to 45.8 Gy (median, 30 Gy) in 15 to 26 fractions (median, 16 fractions) were delivered to the tumors. Results: All irradiated tumors were controlled during the follow-up period of 2 to 157 months (median, 35 months) after treatment. Two patients had relapses that arose in the cervical lymph node and the ipsilateral palpebral conjunctiva outside the radiation field at 15 and 67 months after treatment, respectively. The 5-year local progression-free and relapse-free rates were 100% and 96%, respectively. All 30 patients are presently alive; the overall and relapse-free survival rates at 5 years were 100% and 96%, respectively. Although 5 patients developed cataracts of grade 2 at 8 to 45 months after irradiation, they underwent intraocular lens implantation, and their eyesight recovered. Additionally, there was no marked deterioration in the visual acuity of patients due to irradiation, with the exception of cataracts. No therapy-related toxicity of grade 3 or greater was observed. Conclusions: Radiation therapy was effective and safe for patients with orbital MALT lymphoma. Although some patients developed cataracts after irradiation, visual acuity was well preserved.

  20. Treatment Effects and Sequelae of Radiation Therapy for Orbital Mucosa-Associated Lymphoid Tissue Lymphoma

    International Nuclear Information System (INIS)

    Hata, Masaharu; Omura, Motoko; Koike, Izumi; Tomita, Naoto; Iijima, Yasuhito; Tayama, Yoshibumi; Odagiri, Kazumasa; Minagawa, Yumiko; Ogino, Ichiro; Inoue, Tomio

    2011-01-01

    Purpose: Among extranodal lymphomas, orbital mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare presentation. We performed a review to ascertain treatment efficacy and toxicity of radiation therapy for orbital MALT lymphoma. We also evaluated changes in visual acuity after irradiation. Methods and Materials: Thirty patients with orbital MALT lymphoma underwent radiation therapy with curative intent. Clinical stages at diagnosis were stage I E A in 29 patients and stage II E A in 1 patient. Total doses of 28.8 to 45.8 Gy (median, 30 Gy) in 15 to 26 fractions (median, 16 fractions) were delivered to the tumors. Results: All irradiated tumors were controlled during the follow-up period of 2 to 157 months (median, 35 months) after treatment. Two patients had relapses that arose in the cervical lymph node and the ipsilateral palpebral conjunctiva outside the radiation field at 15 and 67 months after treatment, respectively. The 5-year local progression-free and relapse-free rates were 100% and 96%, respectively. All 30 patients are presently alive; the overall and relapse-free survival rates at 5 years were 100% and 96%, respectively. Although 5 patients developed cataracts of grade 2 at 8 to 45 months after irradiation, they underwent intraocular lens implantation, and their eyesight recovered. Additionally, there was no marked deterioration in the visual acuity of patients due to irradiation, with the exception of cataracts. No therapy-related toxicity of grade 3 or greater was observed. Conclusions: Radiation therapy was effective and safe for patients with orbital MALT lymphoma. Although some patients developed cataracts after irradiation, visual acuity was well preserved.

  1. Spinal Tissue Loading Created by Different Methods of Spinal Manipulative Therapy Application.

    Science.gov (United States)

    Funabashi, Martha; Nougarou, François; Descarreaux, Martin; Prasad, Narasimha; Kawchuk, Gregory N

    2017-05-01

    Comparative study using robotic replication of spinal manipulative therapy (SMT) vertebral kinematics together with serial dissection. The aim of this study was to quantify loads created in cadaveric spinal tissues arising from three different forms of SMT application. There exist many distinct methods by which to apply SMT. It is not known presently whether different forms of SMT application have different effects on spinal tissues. Should the method of SMT application modulate spinal tissue loading, quantifying this relation may help explain the varied outcomes of SMT in terms of effect and safety. SMT was applied to the third lumbar vertebra in 12 porcine cadavers using three SMT techniques: a clinical device that applies forces through a hand-held instrument (INST), a manual technique of applying SMT clinically (MAN) and a research device that applies parameters of manual SMT through a servo-controlled linear actuator motor (SERVO). The resulting kinematics from each SMT application were tracked optically via indwelling bone pins. The L3/L4 segment was then removed, mounted in a parallel robot and the resulting kinematics from SMT replayed for each SMT application technique. Serial dissection of spinal structures was conducted to quantify loading characteristics of discrete spinal tissues. In terms of load magnitude, SMT application with MAN and SERVO created greater forces than INST in all conditions (P < 0.05). Additionally, MAN and SERVO created comparable posterior forces in the intact specimen, but MAN created greater posterior forces on IVD structures compared to SERVO (P < 0.05). Specific methods of SMT application create unique vertebral loading characteristics, which may help explain the varied outcomes of SMT in terms of effect and safety. N/A.

  2. Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

    Science.gov (United States)

    Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

    1993-06-01

    The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

  3. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    Science.gov (United States)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  4. Two-years therapy with bosentan of pulmonary arterial hypertension related to connective tissue diseases

    Directory of Open Access Journals (Sweden)

    M. Rizzo

    2011-09-01

    Full Text Available Objective: Pulmonary arterial hypertension (PAH is a rare but severe complication of connective tissue diseases (CTD, with a negative impact on patients survival. Bosentan, a receptor antagonist of endothelin, has been proved effective for the treatment of PAH. The aim of this study was to evaluate the effects and the safety of bosentan administered for 2 years in a group of patients with PAH related to CTD. Methods: Twelve patients with PAH related to systemic sclerosis (8 cases, SLE (2 cases, mixed connective tissue disease (1 case and polymyositis (1 case attending the Rheumatology Unit of Padova University were treated with bosentan for two years. Distance walked in 6 minutes, right ventricular systolic pressure and mean pulmonary artery pressure estimated by doppler echocardiography were evaluated at baseline and after 6, 12, 18 and 24 months of treatment. Safety was assessed by laboratory tests performed every two months. Results: During bosentan treatment, a significant decrease of right ventricular systolic pressure was observed after 6, 12, 18 and 24 months in comparison to baseline, whereas pulmonary artery mean pressure remained unchanged. Distance walked in 6 minutes slightly increased after 6 and 12 months, but significantly decreased after 18 and 24 months, mostly because complications of CTD which compromised the ability to walk arose in 4 patients. Adverse events related to bosentan were observed in 2 cases. Conclusions: Bosentan has been demonstrated effective in reducing pulmonary arterial pressure in a two-year period of treatment. Exercise capacity improved only in the first year of therapy and worsened thereafter, suggesting the opportunity of a combination therapy for a long-term treatment of PAH related to CTD.

  5. Non-damaging laser therapy of the macula: Titration algorithm and tissue response

    Science.gov (United States)

    Palanker, Daniel; Lavinsky, Daniel; Dalal, Roopa; Huie, Philip

    2014-02-01

    Retinal photocoagulation typically results in permanent scarring and scotomata, which limit its applicability to the macula, preclude treatments in the fovea, and restrict the retreatments. Non-damaging approaches to laser therapy have been tested in the past, but the lack of reliable titration and slow treatment paradigms limited their clinical use. We developed and tested a titration algorithm for sub-visible and non-damaging treatments of the retina with pulses sufficiently short to be used with pattern laser scanning. The algorithm based on Arrhenius model of tissue damage optimizes the power and duration for every energy level, relative to the threshold of lesion visibility established during titration (and defined as 100%). Experiments with pigmented rabbits established that lesions in the 50-75% energy range were invisible ophthalmoscopically, but detectable with Fluorescein Angiography and OCT, while at 30% energy there was only very minor damage to the RPE, which recovered within a few days. Patients with Diabetic Macular Edema (DME) and Central Serous Retinopathy (CSR) have been treated over the edematous areas at 30% energy, using 200μm spots with 0.25 diameter spacing. No signs of laser damage have been detected with any imaging modality. In CSR patients, subretinal fluid resolved within 45 days. In DME patients the edema decreased by approximately 150μm over 60 days. After 3-4 months some patients presented with recurrence of edema, and they responded well to retreatment with the same parameters, without any clinically visible damage. This pilot data indicates a possibility of effective and repeatable macular laser therapy below the tissue damage threshold.

  6. Effective photodynamic therapy against microbial populations in human deep tissue abscess aspirates.

    Science.gov (United States)

    Haidaris, Constantine G; Foster, Thomas H; Waldman, David L; Mathes, Edward J; McNamara, Joanne; Curran, Timothy

    2013-10-01

    The primary therapy for deep tissue abscesses is drainage accompanied by systemic antimicrobial treatment. However, the long antibiotic course required increases the probability of acquired resistance, and the high incidence of polymicrobial infections in abscesses complicates treatment choices. Photodynamic therapy (PDT) is effective against multiple classes of organisms, including those displaying drug resistance, and may serve as a useful adjunct to the standard of care by reduction of abscess microbial burden following drainage. Aspirates were obtained from 32 patients who underwent image-guided percutaneous drainage of the abscess cavity. The majority of the specimens (24/32) were abdominal, with the remainder from liver and lung. Conventional microbiological techniques and nucleotide sequence analysis of rRNA gene fragments were used to characterize microbial populations from abscess aspirates. We evaluated the sensitivity of microorganisms to methylene blue-sensitized PDT in vitro both within the context of an abscess aspirate and as individual isolates. Most isolates were bacterial, with the fungus Candida tropicalis also isolated from two specimens. We examined the sensitivity of these microorganisms to methylene blue-PDT. Complete elimination of culturable microorganisms was achieved in three different aspirates, and significant killing (P abscess treatment. © 2013 Wiley Periodicals, Inc.

  7. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Berg, Lise Charlotte; Betts, Dean H.

    2009-01-01

    This paper provides a bird's-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine.The understanding of equine stem cell biology, biofactors, and scaffolds...... mesenchymal stromal cells, unless there is proof that they exhibit the fundamental in vivo characteristics of pluripotency and the ability to self-renew. That said, these cells from various tissues hold great promise for therapeutic use in horses. The 3 components of tissue engineering - cells, biological...... factors, and biomaterials - are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources.The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently...

  8. Therapy-induced effects in normal tissue; Therapieinduzierte Effekte am Normalgewebe

    Energy Technology Data Exchange (ETDEWEB)

    Kaick, G. van; Delorme, S. [Deutsches Krebsforschungszentrum (DKFZ), Abteilung E010 - Radiologie, Heidelberg (Germany)

    2008-09-15

    More than 50% of cancer patients survive for more than 5 years, owing to modern and effective treatment. Therefore, long-term sequelae of treatment are more frequently seen than in the past. Such effects on normal tissue may both mimic and obscure tumor recurrences. Besides the direct consequences of surgery, tissue damage due to radiation or chemotherapy frequently cause problems in differential diagnosis. Among the numerous sequelae of radiotherapy, the most prominent are disturbance of the blood-brain barrier, radiation pneumonitis, osteodystrophy and osteoradionecrosis, fatty changes of bone marrow, or increased radiodensity of breast parenchyma. Chemotherapy may cause, e.g., diffuse abnormalities of white matter, pneumonitis and lung fibrosis, cardiomyopathy, or diffuse and patchy changes in bone marrow signals in MRI. The most devastating long-term complications are secondary cancers and leukemia induced by both radiotherapy and chemotherapy. (orig.) [German] Mehr als 50% der Tumorpatienten ueberleben dank moderner Therapie laenger als 5 Jahre, sodass die Spaetfolgen am gesunden Gewebe haeufiger und genauer erfasst werden. Diese koennen Tumorrezidive sowohl verschleiern als auch vortaeuschen. Neben den unmittelbaren Folgen operativer Eingriffe sind Auswirkungen der Chemo- und Strahlentherapie ein haeufiges differenzialdiagnostisches Problem. Wichtige Folgen einer Strahlentherapie sind z. B. Blut-Hirn-Schranken-Stoerungen, Strahlenpneumonitis, Osteodystrophie und -radionekrose, Verfettung des blutbildenden Knochenmarks oder Parenchymverdichtungen der Brust. Chemotherapie kann u. a. zur Leukenzephalopathie, Pneumonitis und Lungenfibrose, Kardiomyopathie sowie zu diffusen und fleckfoermigen Signalaenderungen des Knochenmarks in der MRT fuehren. Die schwerstwiegende Spaetkomplikation ist die Induktion solider Zweittumoren und Leukaemien sowohl nach Strahlen- als auch Chemotherapie. (orig.)

  9. Targeted photodynamic therapy of established soft-tissue infections in mice

    Science.gov (United States)

    Gad, Faten; Zahra, Touqir; Hasan, Tayyaba; Hamblin, Michael R.

    2004-06-01

    The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-negative bacteria in living mice. However these infected wound models used a short time after infection (30 min) before PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-positive bacteria. These engineered bacteria emitted bioluminescence allowing the progress of the infection to be monitored in both space and time with a lowlight imaging charged couple device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration. Twenty-four hours later the bacteria had multiplied more than one hundred-fold, and poly-L-lysine chlorin(e6) conjugate or free chlorin(e6) was injected into one area of infected muscle and imaged with the CCD camera. Thirty-minutes later red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a lightdose dependent loss of bioluminescence (to resistant soft-tissue infections.

  10. Generation and customization of biosynthetic excitable tissues for electrophysiological studies and cell-based therapies.

    Science.gov (United States)

    Nguyen, Hung X; Kirkton, Robert D; Bursac, Nenad

    2018-05-01

    We describe a two-stage protocol to generate electrically excitable and actively conducting cell networks with stable and customizable electrophysiological phenotypes. Using this method, we have engineered monoclonally derived excitable tissues as a robust and reproducible platform to investigate how specific ion channels and mutations affect action potential (AP) shape and conduction. In the first stage of the protocol, we combine computational modeling, site-directed mutagenesis, and electrophysiological techniques to derive optimal sets of mammalian and/or prokaryotic ion channels that produce specific AP shape and conduction characteristics. In the second stage of the protocol, selected ion channels are stably expressed in unexcitable human cells by means of viral or nonviral delivery, followed by flow cytometry or antibiotic selection to purify the desired phenotype. This protocol can be used with traditional heterologous expression systems or primary excitable cells, and application of this method to primary fibroblasts may enable an alternative approach to cardiac cell therapy. Compared with existing methods, this protocol generates a well-defined, relatively homogeneous electrophysiological phenotype of excitable cells that facilitates experimental and computational studies of AP conduction and can decrease arrhythmogenic risk upon cell transplantation. Although basic cell culture and molecular biology techniques are sufficient to generate excitable tissues using the described protocol, experience with patch-clamp techniques is required to characterize and optimize derived cell populations.

  11. Novel Stem Cell Therapies for Applications to Wound Healing and Tissue Repair.

    Science.gov (United States)

    Grada, Ayman; Falanga, Vincent

    2016-10-26

    The number of individuals with chronic cutaneous wounds has been increasing worldwide due to an aging population, diabetes, obesity, and cardiovascular disease. In the United States, almost seven million Americans have chronic skin ulcers. Many therapeutic approaches have been used. However, the treatment outcomes are not always ideal because of failure to achieve complete wound closure in around 60% of cases, scarring, and high rate of recurrence. Therefore, there is a need for more effective therapies. Stem cells offer promising possibilities. Pre-clinical studies have shown that bone- or adipose tissue-derived mesenchymal stem cells (MSCs) have a competitive advantage over other types of stem cells due to their better defined multipotent differentiating potential, paracrine effects, immunomodulatory properties, and safety. However, large controlled clinical trials are needed to examine the capabilities of MSCs in humans and to assess their safety profile. In this review, we highlight emerging treatments in tissue regeneration and repair and provide some perspectives on how to translate current knowledge about stem cells-both multipotent and pluripotent-into viable clinical approaches for treating patients with difficult to heal wounds.

  12. Tissue-Engineered Skin Substitute Enhances Wound Healing after Radiation Therapy.

    Science.gov (United States)

    Busra, Mohd Fauzi bin Mh; Chowdhury, Shiplu Roy; bin Ismail, Fuad; bin Saim, Aminuddin; Idrus, Ruszymah Bt Hj

    2016-03-01

    When given in conjunction with surgery for treating cancer, radiation therapy may result in impaired wound healing, which, in turn, could cause skin ulcers. In this study, bilayer and monolayer autologous skin substitutes were used to treat an irradiated wound. A single dose of 30 Gy of linear electron beam radiation was applied to the hind limb of nude mice before creating the skin lesion (area of 78.6 mm). Monolayer tissue-engineered skin substitutes (MTESSs) were prepared by entrapping cultured keratinocytes in fibrin matrix, and bilayer tissue-engineered skin substitutes (BTESSs) were prepared by entrapping keratinocytes and fibroblasts in separate layers. Bilayer tissue-engineered skin substitute and MTESS were implanted to the wound area. Gross appearance and wound area were analyzed to evaluate wound healing efficiency. Skin regeneration and morphological appearance were observed via histological and electron microscopy. Protein expressions of transforming growth factor β1 (TGF-β1), platelet-derived growth factor BB (PDGF-BB), and vascular endothelial growth factor (VEGF) in skin regeneration were evaluated by immunohistochemistry (IHC). Macroscopic observation revealed that at day 13, treatments with BTESS completely healed the irradiated wound, whereas wound sizes of 1.1 ± 0.05 and 6.8 ± 0.14 mm were measured in the MTESS-treated and untreated control groups, respectively. Hematoxylin-eosin (H&E) analysis showed formation of compact and organized epidermal and dermal layers in the BTESS-treated group, as compared with MTESS-treated and untreated control groups. Ultrastructural analysis indicates maturation of skin in BTESS-treated wound evidenced by formation of intermediate filament bundles in the dermal layer and low intercellular space in the epidermal layer. Expressions of TGF-β1, PDGF-BB, and VEGF were also higher in BTESS-treated wounds, compared with MTESS-treated wounds. These results indicate that BTESS is the preferred treatment for

  13. Collateral status and tissue outcome after intra-arterial therapy for patients with acute ischemic stroke.

    Science.gov (United States)

    Boers, Anna Mm; Jansen, Ivo Gh; Berkhemer, Olvert A; Yoo, Albert J; Lingsma, Hester F; Slump, Cornelis H; Roos, Yvo Bwem; van Oostenbrugge, Robert J; Dippel, Diederik Wj; van der Lugt, Aad; van Zwam, Wim H; Marquering, Henk A; Majoie, Charles Blm

    2017-11-01

    Intra-arterial therapy (IAT) for ischemic stroke aims to save brain tissue. Collaterals are thought to contribute to prolonged penumbra sustenance. In this study, we investigate the effect of collateral status on brain tissue salvage with IAT. In 500 patients randomized between IAT and standard care, collateral status was graded from 0 (absent) to 3 (good). Final infarct volumes (FIV) were calculated on post-treatment CT. FIVs were compared between treatment groups per collateral grade. Multivariable linear regression with interaction terms was performed to study whether collaterals modified IAT effect on FIV. Four-hundred-forty-nine patients were included in the analysis. Median FIV for the IAT group was significantly lower with 54.5 mL (95% IQR: 21.8-145.0) than for the controls with 81.8 mL (95% IQR: 40.0-154.0) ( p = 0.020). Treatment effect differed across collateral grades, although there was no significant interaction (unadjusted p = 0.054; adjusted p = 0.105). For grade 3, IAT resulted in a FIV reduction of 30.1 mL ( p = 0.024). For grade 2 and 1, this difference was, respectively, 28.4 mL ( p = 0.028) and 28.4 mL ( p = 0.29). For grade 0, this was 88.6 mL ( p = 0.28) in favour of controls. IAT saves substantially more brain tissue as compared to standard care. We observed a trend of increasing effect of IAT with higher collateral grades.

  14. Effect of low-level laser therapy on tissue repair after dental extraction in rats administered zoledronic acid and dexamethasone

    Science.gov (United States)

    Weber, João Batista Blessmann; Camilotti, Renata Stifelman; Jasper, Juliana; Casagrande, Liliane Cristina Onofre; Maito, Fábio Luiz Dal Moro

    2017-05-01

    Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic and oncological pathologies involving the skeletal system. Because of the severity of the BP associated osteonecrosis of the jaws, the difficulties of treatment, and patient discomfort, additional support methods for their management are needed. Laser therapy has an easy handling, photobiostimulator effect on tissues healing, so it can be considered a preferred therapy. The aim of this study was to evaluate the influence of low-level laser therapy in the 685- and 830-nm wavelength in the healing process of the bone and soft tissues in rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that underwent a surgery for the extraction of upper molars. There were statistically significant differences in the clinical evaluation of the wound and the weight of the animals. Regarding the histological evaluation, it was possible to observe the different maturations of the healing stage between groups. The effect of drug therapy with ZA and dexamethasone in the bone tissue repair process induces osteonecrosis of the jaw in rats and slows down the healing process. In the laser groups, at the stipulated dosimetry, a positive influence on the bone and soft tissue repair process was observed.

  15. Pilot study: whole body manual subcutaneous adipose tissue (SAT) therapy improved pain and SAT structure in women with lipedema.

    Science.gov (United States)

    Herbst, Karen L; Ussery, Christopher; Eekema, Alyna

    2017-09-20

    Background Lipedema is a common painful subcutaneous adipose tissue (SAT) disorder in women affecting the limbs. SAT therapy is a manual therapy to improve soft tissue quality. Objective Determine if SAT therapy improves pain and structure of lipedema SAT. Design Single arm prospective pilot study. Setting Academic medical center. Patients Seven women, 46 ± 5 years, weight 90 ± 19 kg, with lipedema. Intervention Twelve 90-min SAT therapy sessions over 4 weeks. Outcomes Dual X-ray absorptiometry (DXA) scans, SAT ultrasound (Vevo 2100), leg volumetrics, skin caliper assessment, tissue exam, weight, resting metabolic rate, pain assessment, lower extremity functional scale (LEFS) and body shape questionnaire (BSQ) at baseline and end of study. Results Weight, resting metabolic rate and BSQ did not change significantly. Limb fat over total body fat mass (p = 0.08) and trunk fat over total body mass trended down from baseline (p = 0.08) by DXA. Leg volume and caliper assessments in eight of nine areas (p < 0.007), LEFS (p = 0.002) and average pain (p = 0.007) significantly decreased from baseline. Fibrosis significantly decreased in the nodules, hips and groin. Ultrasound showed improved SAT structure in some subjects. Side effects included pain, bruising, itching, swelling and gastroesophageal reflux disease. All women said they would recommend SAT therapy to other women with lipedema. Limitations Small number of subjects. Conclusion SAT therapy in 4 weeks improved tissue structure, perceived leg function, and volume although shape was not affected. While side effects of SAT therapy were common, all women felt the therapy was beneficial.

  16. Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

    Science.gov (United States)

    Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D; Marini, Joan C; Caird, Michelle S; Morris, Michael D; Kozloff, Kenneth M

    2016-03-01

    Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and

  17. HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer.

    Science.gov (United States)

    Rose, Rebecca; Lamers, Susanna L; Nolan, David J; Maidji, Ekaterina; Faria, N R; Pybus, Oliver G; Dollar, James J; Maruniak, Samuel A; McAvoy, Andrew C; Salemi, Marco; Stoddart, Cheryl A; Singer, Elyse J; McGrath, Michael S

    2016-10-15

    While combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread. Combined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In

  18. Method for estimating optimal spectral and energy parameters of laser irradiation in photodynamic therapy of biological tissue

    Energy Technology Data Exchange (ETDEWEB)

    Lisenko, S A; Kugeiko, M M [Belarusian State University, Minsk (Belarus)

    2015-04-30

    We have solved the problem of layer-by-layer laser-light dosimetry in biological tissues and of selecting an individual therapeutic dose in laser therapy. A method is proposed for real-time monitoring of the radiation density in tissue layers in vivo, concentrations of its endogenous (natural) and exogenous (specially administered) chromophores, as well as in-depth distributions of the spectrum of light action on these chromophores. As the background information use is made of the spectrum of diffuse light reflected from a patient's tissue, measured by a fibre-optic spectrophotometer. The measured spectrum is quantitatively analysed by the method of approximating functions for fluxes of light multiply scattered in tissue and by a semi-analytical method for calculating the in-depth distribution of the light flux in a multi-layered medium. We have shown the possibility of employing the developed method for monitoring photosensitizer and oxyhaemoglobin concentrations in tissue, light power absorbed by chromophores in tissue layers at different depths and laser-induced changes in the tissue morphology (vascular volume content and ratios of various forms of haemoglobin) during photodynamic therapy. (biophotonics)

  19. Non-viral gene delivery strategies for cancer therapy, tissue engineering and regenerative medicine

    Science.gov (United States)

    Bhise, Nupura S.

    Gene therapy involves the delivery of deoxyribonucleic acid (DNA) into cells to override or replace a malfunctioning gene for treating debilitating genetic diseases, including cancer and neurodegenerative diseases. In addition to its use as a therapeutic, it can also serve as a technology to enable regenerative medicine strategies. The central challenge of the gene therapy research arena is developing a safe and effective delivery agent. Since viral vectors have critical immunogenic and tumorogenic safety issues that limit their clinical use, recent efforts have focused on developing non-viral biomaterial based delivery vectors. Cationic polymers are an attractive class of gene delivery vectors due to their structural versatility, ease of synthesis, biodegradability, ability to self-complex into nanoparticles with negatively charged DNA, capacity to carry large cargo, cellular uptake and endosomal escape capacity. In this thesis, we hypothesized that developing a biomaterial library of poly(betaamino esters) (PBAE), a newer class of cationic polymers consisting of biodegradable ester groups, would allow investigating vector design parameters and formulating effective non-viral gene delivery strategies for cancer drug delivery, tissue engineering and stem cell engineering. Consequently, a high-throughput transfection assay was developed to screen the PBAE-based nanoparticles in hard to transfect fibroblast cell lines. To gain mechanistic insights into the nanoparticle formulation process, biophysical properties of the vectors were characterized in terms of molecular weight (MW), nanoparticle size, zeta potential and plasmid per particle count. We report a novel assay developed for quantifying the plasmid per nanoparticle count and studying its implications for co-delivery of multiple genes. The MW of the polymers ranged from 10 kDa to 100 kDa, nanoparticle size was about 150 run, zeta potential was about 30 mV in sodium acetate buffer (25 mM, pH 5) and 30 to 100

  20. Effects of topical negative pressure therapy on tissue oxygenation and wound healing in vascular foot wounds.

    Science.gov (United States)

    Chiang, Nathaniel; Rodda, Odette A; Sleigh, Jamie; Vasudevan, Thodur

    2017-08-01

    Topical negative pressure (TNP) therapy is widely used in the treatment of acute wounds in vascular patients on the basis of proposed multifactorial benefits. However, numerous recent systematic reviews have concluded that there is inadequate evidence to support its benefits at a scientific level. This study evaluated the changes in wound volume, surface area, depth, collagen deposition, and tissue oxygenation when using TNP therapy compared with traditional dressings in patients with acute high-risk foot wounds. This study was performed with hospitalized vascular patients. Forty-eight patients were selected with an acute lower extremity wound after surgical débridement or minor amputation that had an adequate blood supply without requiring further surgical revascularization and were deemed suitable for TNP therapy. The 22 patients who completed the study were randomly allocated to a treatment group receiving TNP or to a control group receiving regular topical dressings. Wound volume and wound oxygenation were analyzed using a modern stereophotographic wound measurement system and a hyperspectral transcutaneous oxygenation measurement system, respectively. Laboratory analysis was conducted on wound biopsy samples to determine hydroxyproline levels, a surrogate marker to collagen. Differences in clinical or demographic characteristics or in the location of the foot wounds were not significant between the two groups. All patients, with the exception of two, had diabetes. The two patients who did not have diabetes had end-stage renal failure. There was no significance in the primary outcome of wound volume reduction between TNP and control patients on day 14 (44.2% and 20.9%, respectively; P = .15). Analyses of secondary outcomes showed a significant result of better healing rates in the TNP group by demonstrating a reduction in maximum wound depth at day 14 (36.0% TNP vs 17.6% control; P = .03). No significant findings were found for the other outcomes of changes

  1. Role of radiation therapy in management of patients with sarcoma of soft tissue

    International Nuclear Information System (INIS)

    Suit, Herman D.; Spiro, Ira J.

    1995-01-01

    -sparing procedures will be discussed. There are new accounts of impressive results of treatment with TNF and INF. Clinical and laboratory data are to be considered. Results of the several Phase III trials of adjuvant chemotherapy will be reviewed: trial design, patient numbers, implication for patient care. The role of radiation therapy in the management of a patient with sarcoma of soft tissue will be assessed with respect to radiation alone or in combination with surgery and/or chemotherapy or biological response modifiers. The radiation sensitivity measured in vitro for cells arising from sarcomas of soft tissue of human patients and experimental animals will be reviewed and compared with reference to clinical response patterns of epithelial tumors. Finally, there will be a brief coverage of the role of radiation in the treatment of several benign mesenchymal tumors, viz., desmoid tumors, atypical lipoma, fibrohistiocytoma, dermatofibrosarcoma protuberans, etc

  2. Performance tests and comparison of microdosimetric measurements with four tissue-equivalent proportional counters in scanning proton therapy

    Czech Academy of Sciences Publication Activity Database

    Farah, J.; De Saint-Hubert, M.; Mojzeszek, N.; Chiriotti, S.; Gryzinski, M.; Ploc, Ondřej; Trompier, F.; Turek, Karel; Vanhavere, F.; Olko, P.

    2017-01-01

    Roč. 96, JAN (2017), s. 42-52 ISSN 1350-4487 EU Projects: European Commission(XE) 662287 - CONCERT Institutional support: RVO:61389005 Keywords : tissue-equivalent proportional counters * microdosimetry * proton therapy * stray neutrons and prothons Subject RIV: JF - Nuclear Energetics OBOR OECD: Nuclear related engineering Impact factor: 1.442, year: 2016

  3. Subsurface thermal behaviour of tissue mimics embedded with large blood vessels during plasmonic photo-thermal therapy.

    Science.gov (United States)

    Paul, Anup; Narasimhan, Arunn; Das, Sarit K; Sengupta, Soujit; Pradeep, Thalappil

    2016-11-01

    The purpose of this study was to understand the subsurface thermal behaviour of a tissue phantom embedded with large blood vessels (LBVs) when exposed to near-infrared (NIR) radiation. The effect of the addition of nanoparticles to irradiated tissue on the thermal sink behaviour of LBVs was also studied. Experiments were performed on a tissue phantom embedded with a simulated blood vessel of 2.2 mm outer diameter (OD)/1.6 mm inner diameter (ID) with a blood flow rate of 10 mL/min. Type I collagen from bovine tendon and agar gel were used as tissue. Two different nanoparticles, gold mesoflowers (AuMS) and graphene nanostructures, were synthesised and characterised. Energy equations incorporating a laser source term based on multiple scattering theories were solved using finite element-based commercial software. The rise in temperature upon NIR irradiation was seen to vary according to the position of the blood vessel and presence of nanoparticles. While the maximum rise in temperature was about 10 °C for bare tissue, it was 19 °C for tissue embedded with gold nanostructures and 38 °C for graphene-embedded tissues. The axial temperature distribution predicted by computational simulation matched the experimental observations. A different subsurface temperature distribution has been obtained for different tissue vascular network models. The position of LBVs must be known in order to achieve optimal tissue necrosis. The simulation described here helps in predicting subsurface temperature distributions within tissues during plasmonic photo-thermal therapy so that the risks of damage and complications associated with in vivo experiments and therapy may be avoided.

  4. Improved Survival With Radiation Therapy in High-Grade Soft Tissue Sarcomas of the Extremities: A SEER Analysis

    International Nuclear Information System (INIS)

    Koshy, Matthew; Rich, Shayna E.; Mohiuddin, Majid M.

    2010-01-01

    Purpose: The benefit of radiation therapy in extremity soft tissue sarcomas remains controversial. The purpose of this study was to determine the effect of radiation therapy on overall survival among patients with primary soft tissue sarcomas of the extremity who underwent limb-sparing surgery. Methods and Materials: A retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included data from January 1, 1988, to December 31, 2005. A total of 6,960 patients constituted the study population. Overall survival curves were constructed using the Kaplan-Meir method and for patients with low- and high-grade tumors. Hazard ratios were calculated based on multivariable Cox proportional hazards models. Results: Of the cohort, 47% received radiation therapy. There was no significant difference in overall survival among patients with low-grade tumors by radiation therapy. In high-grade tumors, the 3-year overall survival was 73% in patients who received radiation therapy vs. 63% for those who did not receive radiation therapy (p < 0.001). On multivariate analysis, patients with high-grade tumors who received radiation therapy had an improved overall survival (hazard ratio 0.67, 95% confidence interval 0.57-0.79). In patients receiving radiation therapy, 13.5% received it in a neoadjuvant setting. The incidence of patients receiving neoadjuvant radiation did not change significantly between 1988 and 2005. Conclusions: To our knowledge, this is the largest population-based study reported in patients undergoing limb-sparing surgery for soft tissue sarcomas of the extremities. It reports that radiation was associated with improved survival in patients with high-grade tumors.

  5. Effect of red and infrared low-level laser therapy in endodontic sealer on subcutaneous tissue

    Science.gov (United States)

    Sivieri-Araujo, G.; Berbert, F. L. C. V.; Ramalho, L. T. O.; Rastelli, A. N. S.; Crisci, F. S.; Bonetti-Filho, I.; Tanomaru-Filho, M.

    2011-12-01

    This study evaluated the reactions of connective tissue after the implant of one endodontic sealer (Endofill) that was irradiated with low-level laser therapy (LLLT). Sixty mice were distributed into three Groups ( n = 20): GI—the tubes filled with Endofill were implanted in the animals and were not irradiated with LLLT; GII—the tubes containing Endofill were implanted in the animals and then irradiated with red LLLT (InGaAlP, λ = 685 nm, P = 35 mW, t = 58 s, D = 72 J/cm2, E = 2 J, Ø = 0.60 mm, continuous mode) and GIII—the tubes with Endofill were implanted and irradiated with infrared LLLT (AsGaAl, λ = 830 nm, P = 50 mW, t = 40 s, D = 70 J/cm2, E = 2 J, Ø = 0.60 mm, continuous wave) both are semiconductor diode laser device. The animals were killed after 7 and 30 days. Series sections of 6 μm thickness were obtained and stained with Hematoxylin-Eosin and Masson Trichrome. The data of the histopathological evaluation were submitted to Kruskal-Wallis and Dunn's tests at 5% significance level. At the 7th day: GI showed the presence of inflammation; GII and GIII reduced inflammation. At 30th day: GI showed low inflammation; GII and GII the absence of inflammation. It was possible show that LLLT reduced the irritating effect promoted by the Endofill, in the period of 7 days ( p > 0.05). The tissue repair occurred in 30 days, regardless of the use of LLLT.

  6. SU-F-T-181: Proton Therapy Tissue-Equivalence of 3D Printed Materials

    International Nuclear Information System (INIS)

    Taylor, P; Craft, D; Followill, D; Howell, R

    2016-01-01

    Purpose: This work investigated the proton tissue-equivalence of various 3D printed materials. Methods: Three 3D printers were used to create 5 cm cubic phantoms made of different plastics with varying percentages of infill. White resin, polylactic acid (PLA), and NinjaFlex plastics were used. The infills ranged from 15% to 100%. Each phantom was scanned with a CT scanner to obtain the HU value. The relative linear stopping power (RLSP) was then determined using a multi-layer ion chamber in a 200 MeV proton beam. The RLSP was measured both parallel and perpendicular to the print direction for each material. Results: The HU values of the materials ranged from lung-equivalent (−820 HU σ160) when using a low infill, to soft-tissue-equivalent 159 (σ12). The RLSP of the materials depended on the orientation of the beam relative to the print direction. When the proton beam was parallel to the print direction, the RLSP was generally higher than the RLSP in the perpendicular orientation, by up to 45%. This difference was smaller (less than 6%) for the materials with 100% infill. For low infill cubes irradiated parallel to the print direction, the SOBP curve showed extreme degradation of the beam in the distal region. The materials with 15–25% infill had wide-ranging agreement with a clinical HU-RLSP conversion curve, with some measurements falling within 1% of the curve and others deviating up to 45%. The materials with 100% infill all fell within 7% of the curve. Conclusion: While some materials tested fall within 1% of a clinical HU-RLSP curve, caution should be taken when using 3D printed materials with proton therapy, as the orientation of the beam relative to the print direction can result in a large change in RLSP. Further investigation is needed to measure how the infill pattern affects the material RLSP. This work was supported by PHS grant CA180803.

  7. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Partridge, Mike [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Carrington, Rhys [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff (United Kingdom); Crosby, Thomas [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hawkins, Maria A. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

  8. SU-F-T-181: Proton Therapy Tissue-Equivalence of 3D Printed Materials

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, P; Craft, D; Followill, D; Howell, R [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: This work investigated the proton tissue-equivalence of various 3D printed materials. Methods: Three 3D printers were used to create 5 cm cubic phantoms made of different plastics with varying percentages of infill. White resin, polylactic acid (PLA), and NinjaFlex plastics were used. The infills ranged from 15% to 100%. Each phantom was scanned with a CT scanner to obtain the HU value. The relative linear stopping power (RLSP) was then determined using a multi-layer ion chamber in a 200 MeV proton beam. The RLSP was measured both parallel and perpendicular to the print direction for each material. Results: The HU values of the materials ranged from lung-equivalent (−820 HU σ160) when using a low infill, to soft-tissue-equivalent 159 (σ12). The RLSP of the materials depended on the orientation of the beam relative to the print direction. When the proton beam was parallel to the print direction, the RLSP was generally higher than the RLSP in the perpendicular orientation, by up to 45%. This difference was smaller (less than 6%) for the materials with 100% infill. For low infill cubes irradiated parallel to the print direction, the SOBP curve showed extreme degradation of the beam in the distal region. The materials with 15–25% infill had wide-ranging agreement with a clinical HU-RLSP conversion curve, with some measurements falling within 1% of the curve and others deviating up to 45%. The materials with 100% infill all fell within 7% of the curve. Conclusion: While some materials tested fall within 1% of a clinical HU-RLSP curve, caution should be taken when using 3D printed materials with proton therapy, as the orientation of the beam relative to the print direction can result in a large change in RLSP. Further investigation is needed to measure how the infill pattern affects the material RLSP. This work was supported by PHS grant CA180803.

  9. Efficacious and safe tissue-selective controlled gene therapy approaches for the cornea.

    Directory of Open Access Journals (Sweden)

    Rajiv R Mohan

    2011-04-01

    Full Text Available Untargeted and uncontrolled gene delivery is a major cause of gene therapy failure. This study aimed to define efficient and safe tissue-selective targeted gene therapy approaches for delivering genes into keratocytes of the cornea in vivo using a normal or diseased rabbit model. New Zealand White rabbits, adeno-associated virus serotype 5 (AAV5, and a minimally invasive hair-dryer based vector-delivery technique were used. Fifty microliters of AAV5 titer (6.5×10(12 vg/ml expressing green fluorescent protein gene (GFP was topically applied onto normal or diseased (fibrotic or neovascularized rabbit corneas for 2-minutes with a custom vector-delivery technique. Corneal fibrosis and neovascularization in rabbit eyes were induced with photorefractive keratectomy using excimer laser and VEGF (630 ng using micropocket assay, respectively. Slit-lamp biomicroscopy and immunocytochemistry were used to confirm fibrosis and neovascularization in rabbit corneas. The levels, location and duration of delivered-GFP gene expression in the rabbit stroma were measured with immunocytochemistry and/or western blotting. Slot-blot measured delivered-GFP gene copy number. Confocal microscopy performed in whole-mounts of cornea and thick corneal sections determined geometric and spatial localization of delivered-GFP in three-dimensional arrangement. AAV5 toxicity and safety were evaluated with clinical eye exam, stereomicroscopy, slit-lamp biomicroscopy, and H&E staining. A single 2-minute AAV5 topical application via custom delivery-technique efficiently and selectively transduced keratocytes in the anterior stroma of normal and diseased rabbit corneas as evident from immunocytochemistry and confocal microscopy. Transgene expression was first detected at day 3, peaked at day 7, and was maintained up to 16 weeks (longest tested time point. Clinical and slit-lamp eye examination in live rabbits and H&E staining did not reveal any significant changes between AAV5

  10. Tissue Engineering in Osteoarthritis: Current Status and Prospect of Mesenchymal Stem Cell Therapy.

    Science.gov (United States)

    Im, Gun-Il

    2018-04-27

    Osteoarthritis (OA) is the most common form of arthritis. Over the last 20 years, attempts have been made to regenerate articular cartilage to overcome the limitations of conventional treatments. As OA is generally associated with larger and diffuse involvement of articular surfaces and alteration of joint homeostasis, a tissue engineering approach for cartilage regeneration is more difficult than in simple chondral defects. Autologous and allogeneic mesenchymal stem cells (MSCs) have rapidly emerged as investigational products for cartilage regeneration. This review outlines points to consider in MSC-based approaches for OA treatment, including allogeneic MSCs, sources of MSCs, dosages, feasibility of multiple injections, indication according to severity of OA lesion and patient age, and issues regarding implantation versus injection. We introduce possible mechanisms of action of implanted or injected MSCs as well as the immunological aspects of MSC therapy and provide a summary of clinical trials of MSCs in the treatment of OA. Given current knowledge, it is too early to draw conclusions on the ultimate effectiveness of intra-articular application of MSCs in terms of regenerative effects. Further radiological and histological data will be needed, with a larger pool of patients, before this question can be answered.

  11. Radiation Therapy for Control of Soft-Tissue Sarcomas Resected With Positive Margins

    International Nuclear Information System (INIS)

    DeLaney, Thomas F.; Kepka, Lucyna; Goldberg, Saveli I.; Hornicek, Francis J.; Gebhardt, Mark C.; Yoon, Sam S.; Springfield, Dempsey S.; Raskin, Kevin A.; Harmon, David C.; Kirsch, David G.; Mankin, Henry J.; Rosenberg, Andrew E.; Nielsen, G. Petur; Suit, Herman D.

    2007-01-01

    Purpose: Positive margins (PM) remain after surgery in some soft-tissue sarcoma (STS) patients. We investigated the efficacy of radiation therapy (RT) in STS patients with PM. Methods and Materials: A retrospective chart review was performed on 154 patients with STS at various anatomic sites with PM, defined as tumor on ink, who underwent RT with curative intent between 1970 and 2001. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated by univariate (log-rank) and multivariate analysis of prognostic and treatment factors. Results: At 5 years, actuarial LC, DFS, and OS rates were: 76%, 46.7%, and 65.2%, respectively. LC was highest with extremity lesions (p 64 Gy (p 64 Gy had higher 5-year LC, DFS, and OS rates of 85%, 52.1%, and 67.8% vs. 66.1%, 41.8%, and 62.9% if ≤64 Gy, p 50), also significantly influenced OS. By multivariate analysis, the best predictors of LC were site (extremity vs. other), p 64 vs. ≤64 Gy), p 64 Gy, superficial location, and extremity site are associated with improved LC. OS is worse in patients with tumors with lesions >5 cm, grossly positive margins, and after local failure

  12. Adjuvant therapy of chronic gastroduodenitis in children with dysplasia of connective tissue

    Directory of Open Access Journals (Sweden)

    О. М. Mukvich

    2018-04-01

    Full Text Available Chronic gastroduodenitis (CGD hold one of main places among leading diseases of gastro-intestinal tract (GIT in childhood. A special category is children who have CGD against the background of connective tissue (CT dysplasia (DCT. CGD in such children is characterized by early appearance, aggressive, gradient course with frequent acute conditions and recurrences with evident symptoms of nonspecific intoxication manifestations. Defect of collagen synthesis leads to pronounced morphological changes of proximal GIT mucous membrane (MM and decline in its cytoptotecive abilities. Challenges related to the qualitative and quantitative local ecosystem changes can aggravate immune and metabolic local processes and enhance the destruction of proximal GIT mucous membrane. Aforesaid defines the need to include multiprobiotics into the treatment schemes of patient with CGD, associated with congenital fibrogenesis disorders, as adjuvant therapy with complex therapeutic action; they positively influence the CT metabolism, improve reparative processes in MM, normalize immune processes and maintain composition and functions of physiological microbiota. Purposes – improvement of CGD treatment efficiency in children with DCT through inclusion of the multiprobiotic Symbiter® forte-M into the treatment schemes. Materials and methods. There were examined 33 children with CGD on the background of DCT and 32 healthy children (control from 11 to 17 years old. The state of the mucous barrier was estimated by certain mucin constituents (fucose, glycosaminoglycans, sialic acids assessing, antimicrobial peptides (ß2-defencins, non-specific humoral factors of the local immunity (immunoglobulins, lysozyme in mucous secretions (saliva, coprofiltrate (CF before and after probiotic therapy. Results. Increased concentrations of ß2-defencins (psaliva = 0.03, pCF = 0.03, sialic acids (P = 0.04 and lysozyme (P = 0.01 and decreased of fucose level (P = 0.03 in mucous secretions

  13. Statistical modeling of interfractional tissue deformation and its application in radiation therapy planning

    Science.gov (United States)

    Vile, Douglas J.

    In radiation therapy, interfraction organ motion introduces a level of geometric uncertainty into the planning process. Plans, which are typically based upon a single instance of anatomy, must be robust against daily anatomical variations. For this problem, a model of the magnitude, direction, and likelihood of deformation is useful. In this thesis, principal component analysis (PCA) is used to statistically model the 3D organ motion for 19 prostate cancer patients, each with 8-13 fractional computed tomography (CT) images. Deformable image registration and the resultant displacement vector fields (DVFs) are used to quantify the interfraction systematic and random motion. By applying the PCA technique to the random DVFs, principal modes of random tissue deformation were determined for each patient, and a method for sampling synthetic random DVFs was developed. The PCA model was then extended to describe the principal modes of systematic and random organ motion for the population of patients. A leave-one-out study tested both the systematic and random motion model's ability to represent PCA training set DVFs. The random and systematic DVF PCA models allowed the reconstruction of these data with absolute mean errors between 0.5-0.9 mm and 1-2 mm, respectively. To the best of the author's knowledge, this study is the first successful effort to build a fully 3D statistical PCA model of systematic tissue deformation in a population of patients. By sampling synthetic systematic and random errors, organ occupancy maps were created for bony and prostate-centroid patient setup processes. By thresholding these maps, PCA-based planning target volume (PTV) was created and tested against conventional margin recipes (van Herk for bony alignment and 5 mm fixed [3 mm posterior] margin for centroid alignment) in a virtual clinical trial for low-risk prostate cancer. Deformably accumulated delivered dose served as a surrogate for clinical outcome. For the bony landmark setup

  14. Localized Orbital Mucosa-Associated Lymphoma Tissue Lymphoma Managed With Primary Radiation Therapy: Efficacy and Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Goda, Jayant Sastri [Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Le, Lisa W. [Biostatistics, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Lapperriere, Normand J.; Millar, Barbara-Ann; Payne, David; Gospodarowicz, Mary K.; Wells, Woodrow; Hodgson, David C.; Sun, Alexander [Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Simpson, Rand [Ocular Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Tsang, Richard W., E-mail: richard.tsang@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada)

    2011-11-15

    Purpose: To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). Methods and Materials: From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. Results: The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade {>=}2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). Conclusions: POML responds favorably to moderate doses

  15. A Systematic Overview of Radiation Therapy Effects in Soft Tissue Sarcomas

    International Nuclear Information System (INIS)

    Strander, Hans; Turesson, Ingela; Cavallin-Staahl, Eva

    2003-01-01

    A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately. This synthesis of the literature on radiation therapy for soft tissue sarcomas (STS) is based on data from five randomized trials. Moreover, data from 6 prospective studies, 25 retrospective studies and 3 other articles were used. In total, 39 scientific articles are included, involving 4,579 patients. The results were compared with those of a similar overview from 1996 which included 3,344 patients. The conclusions reached can be summarized as follows: The well-established prognostic factors for tumour-related death from STS--histological grade, tumour size and age--are well documented. The importance of superficial versus deep site as well as the anatomic site is also reaffirmed to some extent. There is strong evidence that adjuvant radiotherapy improves the local control rate in combination with conservative surgery in the treatment of STS of extremities and trunk in patients with negative, marginal or minimal microscopic positive surgical margins. A local control rate of 90% has been achieved. Improvement is obtained with radiotherapy added in the case of intralesional surgery, but the local control rate is somewhat lower. More studies are needed on this issue. For STS in other anatomic sites, retroperitoneum, head and neck, breast and uterus, there is only weak indication of a benefit for the local control rate, with the use of adjuvant radiotherapy. There is still insufficient data to establish that preoperative radiotherapy is favourable compared to postoperative radiotherapy for local control in patients presenting primarily with large tumours. One small study has shown a possible survival benefit for preoperative radiotherapy. There is fairly good evidence to suggest that the preoperative setting results in more wound

  16. Cost-Effectiveness Analysis of Preoperative Versus Postoperative Radiation Therapy in Extremity Soft Tissue Sarcoma

    International Nuclear Information System (INIS)

    Qu, Xuanlu M.; Louie, Alexander V.; Ashman, Jonathan; Wasif, Nabil

    2017-01-01

    Purpose: Surgery combined with radiation therapy (RT) is the cornerstone of multidisciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or the postoperative setting with similar local recurrence and survival outcomes, the side effect profiles, costs, and long-term functional outcomes are different. The aim of this study was to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. Methods and Materials: A cost-effectiveness analysis was conducted using a state transition Markov model, with quality-adjusted life years (QALYs) as the primary outcome. A time horizon of 5 years, a cycle length of 3 months, and a willingness-to-pay threshold of $50,000/QALY was used. One-way deterministic sensitivity analyses were performed to determine the thresholds at which each strategy would be preferred. The robustness of the model was assessed by probabilistic sensitivity analysis. Results: Preoperative RT is a more cost-effective strategy ($26,633/3.00 QALYs) than postoperative RT ($28,028/2.86 QALYs) in our base case scenario. Preoperative RT is the superior strategy with either 3-dimensional conformal RT or intensity-modulated RT. One-way sensitivity analyses identified the relative risk of chronic adverse events as having the greatest influence on the preferred timing of RT. The likelihood of preoperative RT being the preferred strategy was 82% on probabilistic sensitivity analysis. Conclusions: Preoperative RT is more cost effective than postoperative RT in the management of resectable extremity STS, primarily because of the higher incidence of chronic adverse events with RT in the postoperative setting.

  17. Management of locally recurrent soft-tissue sarcoma after prior surgery and radiation therapy

    International Nuclear Information System (INIS)

    Torres, Mylin A.; Ballo, Matthew T.; Butler, Charles E.; Feig, Barry W.; Cormier, Janice N.; Lewis, Valerae O.; Pollock, Raphael E.; Pisters, Peter W.; Zagars, Gunar K.

    2007-01-01

    Purpose: The aim of this study was to evaluate outcome and treatment toxicity after wide local re-excision (WLE), with or without additional radiation therapy, for patients with isolated first local recurrence of soft-tissue sarcoma arising within a previously irradiated field. Methods: A retrospective review was performed of 62 consecutive patients. All patients underwent prior resection and external beam radiation. For recurrent disease, 25 patients were treated with WLE alone, and 37 patients were treated with WLE and additional radiation (45- 64 Gy). In 33 patients, the radiation was delivered via an afterloaded brachytherapy, single-plane implant. Results: The 5-year disease specific and distant metastasis-free survival rates were 65% and 73%, respectively. Local control (LC) at 5 years was 51%, and on multivariate analysis, a positive surgical resection margin (p< 0.001) was associated with a lower rate of LC. Reirradiation was not associated with improved LC; however complications requiring outpatient or surgical management were more common in patients who had undergone reirradiation (80% vs. 17%, p < 0.001). Amputation was also more common in the subgroup of patients who underwent extremity reirradiation (35% with radiation vs. 11% without, p = 0.05), although only one amputation was performed to resolve a treatment complication. Conclusion: Conservative surgery alone results in LC in a minority of patients who have failed locally after previous excision and external beam radiation. Although selection biases and small patient numbers confound the analysis, local treatment intensification with additional radiation does not clearly improve outcome after surgical excision alone, and is associated with an increase in complications

  18. Cost-Effectiveness Analysis of Preoperative Versus Postoperative Radiation Therapy in Extremity Soft Tissue Sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Xuanlu M. [Department of Oncology, Queen' s University, Kingston, Ontario (Canada); Louie, Alexander V. [Department of Radiation Oncology, London Health Sciences Center, London, Ontario (Canada); Ashman, Jonathan [Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, Arizona (United States); Wasif, Nabil, E-mail: wasif.nabil@mayo.edu [Department of General Surgery, Mayo Clinic Arizona, Phoenix, Arizona (United States)

    2017-02-01

    Purpose: Surgery combined with radiation therapy (RT) is the cornerstone of multidisciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or the postoperative setting with similar local recurrence and survival outcomes, the side effect profiles, costs, and long-term functional outcomes are different. The aim of this study was to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. Methods and Materials: A cost-effectiveness analysis was conducted using a state transition Markov model, with quality-adjusted life years (QALYs) as the primary outcome. A time horizon of 5 years, a cycle length of 3 months, and a willingness-to-pay threshold of $50,000/QALY was used. One-way deterministic sensitivity analyses were performed to determine the thresholds at which each strategy would be preferred. The robustness of the model was assessed by probabilistic sensitivity analysis. Results: Preoperative RT is a more cost-effective strategy ($26,633/3.00 QALYs) than postoperative RT ($28,028/2.86 QALYs) in our base case scenario. Preoperative RT is the superior strategy with either 3-dimensional conformal RT or intensity-modulated RT. One-way sensitivity analyses identified the relative risk of chronic adverse events as having the greatest influence on the preferred timing of RT. The likelihood of preoperative RT being the preferred strategy was 82% on probabilistic sensitivity analysis. Conclusions: Preoperative RT is more cost effective than postoperative RT in the management of resectable extremity STS, primarily because of the higher incidence of chronic adverse events with RT in the postoperative setting.

  19. Intralesional copper wire retention and pingyangmycin injection: an effective combinational therapy for complex venous malformation in soft tissue.

    Science.gov (United States)

    Yuan, S-M; Hong, Z-J; Jiang, H-Q; Wang, J; Hu, X-B

    2014-04-01

    Complex venous malformations (VMs) may extensively involve the soft tissue. The treatment remains a challenge till now. Here we introduce a combinational therapy of copper wires and pingyangmycin (bleomycin A5,PYM). Copper wires were retained in VMs by repeated penetration with a straight needle. Subsequently, PYM solution was injected into the lesion. Eight to 10 days later, copper wires were removed. The dressing was changed every day until the puncture pores healed. Magnetic resonance imaging scanning was performed to observe the change of VMs. From January 2001 to December 2011, 56 patients were treated. During the follow-up period, most of the VMs shrunk obviously. The symptoms were relieved or disappeared. The complications included local pain, temporary paraesthesia and moderate fever, which disappeared quickly after the removal of copper wires. This combinational therapy is a safe and effective approach for the complex VMs in soft tissue.

  20. Serum and tissue contents of copper, calcium, iron and magnesium elements in cases of acne vulgaris after zinc therapy

    International Nuclear Information System (INIS)

    El-Said, S.M.; El-Bedewi, A.F.

    2002-01-01

    The effect of zinc therapy on some trace elements contents in serum and skin was studied in normal group (forty) and patients group with acne vulgaris (26 males and 14 females) with age ranged between 14-30 year. They were under medical treatment with 330 mg oral zinc sulfate for 12 weeks. Highly significant decreases in both serum and tissue contents of copper and calcium were detected, as well as, highly significant decrease in the serum content of magnesium was recorded. The serum content of iron was highly significantly increased and that for tissue content was slightly significantly increased. It could be concluded that zinc therapy could be valuable through modulation of copper. calcium, iron and magnesium in acne patients

  1. Outcome and Toxicity of an Ifosfamide-Based Soft Tissue Sarcoma Treatment Protocol in Children. The Importance of Local Therapy

    Directory of Open Access Journals (Sweden)

    S. Murray Yule

    1998-01-01

    Full Text Available Background. Although the survival of children with soft tissue sarcoma (STS has improved considerably, the outcome of patients with metastatic disease, and those with primary tumours of the extremities or parameningeal sites remains disappointing. We describe the clinical outcome of an ifosfamide-based regimen with local therapy directed only to children who failed to achieve a complete response to initial chemotherapy.

  2. Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

    Science.gov (United States)

    Peterson, Christopher W; Wang, Jianbin; Deleage, Claire; Reddy, Sowmya; Kaur, Jasbir; Polacino, Patricia; Reik, Andreas; Huang, Meei-Li; Jerome, Keith R; Hu, Shiu-Lok; Holmes, Michael C; Estes, Jacob D; Kiem, Hans-Peter

    2018-04-01

    Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs) persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05), relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

  3. Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

    Directory of Open Access Journals (Sweden)

    Christopher W Peterson

    2018-04-01

    Full Text Available Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP model of latent infection using simian/human immunodeficiency virus (SHIV and combination antiretroviral therapy (cART in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05, relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

  4. Utility of Normal Tissue-to-Tumor {alpha}/{beta} Ratio When Evaluating Isodoses of Isoeffective Radiation Therapy Treatment Plans

    Energy Technology Data Exchange (ETDEWEB)

    Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Jin Jianyue [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Chang, Albert J. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-01-01

    Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and Materials: The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue {alpha}/{beta} ratio divided by the tumor {alpha}/{beta} times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified.

  5. Normal tissue complications after radiation therapy Las complicaciones de la radioterapia en los tejidos sanos

    Directory of Open Access Journals (Sweden)

    Jolyon H. Hendry

    2006-09-01

    Full Text Available This paper describes the biological mechanisms of normal tissue reactions after radiation therapy, with reference to conventional treatments, new treatments, and treatments in developing countries. It also describes biological reasons for the latency period before tissue complications arise, the relationship of dose to incidence, the effect of increasing the size of the irradiated volume, early and late tissue reactions, effects of changes in dose fractionation and dose rate, and combined chemotherapy and radiotherapy responses. Examples are given of increases in knowledge of clinical radiobiology from trials of new protocols. Potential modification to treatments include the use of biological response modifiers. The introduction of "response prediction" modifications to treatments might also be available in the near future. Finally, the paper points out that in some radiotherapy centers, the biologically-effective doses prescribed for combined brachytherapy and teletherapy treatment of cervix cancer are lower than those prescribed in other centers. This issue needs to be addressed further. The wealth of preclinical and clinical data has led to a much greater understanding of the biological basis to radiotherapy. This understanding has underpinned a variety of new approaches in radiotherapy, including both physical and biological strategies. There is also the important issue of treatment of a large number of cancers in developing countries, for which efficacious resource-sparing protocols are being continuously developed. A unified scoring system should be widely accepted as the new standard in reporting the adverse effects of radiation therapy. Likewise, late toxicity should be reported on an actuarial basis as a mandatory endpoint.En este artículo se describen los mecanismos biológicos que intervienen en las reacciones provocadas por la radioterapia, tanto con tratamientos convencionales como con los más nuevos, y los aplicados en países en

  6. Bremsstrahlung parameters of praseodymium-142 in different human tissues. A dosimetric perspective for 142Pr radionuclide therapy

    International Nuclear Information System (INIS)

    Bakht, M.K.; Jabal-Ameli, H.; Ahmadi, S.J.; Sadeghi, M.; Sadjadi, S.; Tenreiro, Claudio

    2012-01-01

    Praseodymium-142 [T 1/2 =19.12 h, E β -=2.162 MeV (96.3%), E γ =1575 keV (3.7%)] is one of the 141 Pr radioisotopes. Many studies have been attempted to assess the significance of usage 142 Pr in radionuclide therapy. In many studies, the dosimetric parameters of 142 Pr sources were calculated by modeling 142 Pr sources in the water phantom and scoring the energy deposited around it. However, the medical dosimetry calculations in water phantom consider Bremsstrahlung production, raising the question: ''How important is to simulate human tissues instead of using water phantom?'' This study answers these questions by estimation of 142 Pr Bremsstrahlung parameters. The Bremsstrahlung parameters of 142 Pr as therapeutic beta nuclides in different human tissues (adipose, blood, brain, breast, cell nucleus, eye lens, gastrointestinal tract, heart, kidney, liver, lung deflated, lymph, muscle, ovary, pancreas, cartilage, red marrow, spongiosa, yellow marrow, skin, spleen, testis, thyroid and different skeleton bones) were calculated by extending the national council for radiation protection model. The specific Bremsstrahlung constant (Γ Br ), probability of energy loss by beta during Bremsstrahlung emission (P Br ) and Bremsstrahlung activity (A release ) Br were estimated. It should be mentioned that Monte Carlo simulation was used for estimation of 142 Pr Bremsstrahlung activity based on the element compositions of different human tissues and the calculated exposures from the anthropomorphic phantoms. Γ Br for yellow marrow was smallest amount (1.1962 x 10 -3 C/kg-cm 2 /MBq-h) compared to the other tissues and highest for cortical bone (2.4764 x 10 -3 C/kg-cm 2 /MBq-h), and, overall, Γ Br for skeletal tissues were greater than other tissues. In addition, Γ Br breast was 1.8261 x 10 -3 C/kg-cm 2 /MBq-h which was greater than sacrum and spongiosa bones. Moreover, according to (A release ) Br of 142 Pr, the patients receiving 142 Pr do not have to be hospitalized for

  7. Clinical observations on the treatment of prolapsing hemorrhoids with tissue selecting therapy.

    Science.gov (United States)

    Wang, Zhi-Gang; Zhang, Yong; Zeng, Xian-Dong; Zhang, Tie-Hui; Zhu, Qi-Dong; Liu, De-Long; Qiao, Yun-Yu; Mu, Nan; Yin, Zhi-Tao

    2015-02-28

    To compare the effects and postoperative complications between tissue selecting therapy stapler (TST) and Milligan-Morgan hemorrhoidectomy (M-M). Four hundred and eighty patients with severe prolapsing hemorrhoids, who were admitted to the Shenyang Coloproctology Hospital between 2009 and 2012, were randomly divided into observation (n=240) and control (n=240) groups. Hemorrhoidectomies were performed with TST in the observation group and with the M-M technique in the control group. The therapeutic effects, operation security, and postoperative complications in the two groups were compared. The immediate and long-term complications were assessed according to corresponding criteria. Pain was assessed on a visual analogue scale. The efficacy was assessed by specialized criteria. The follow-up was conducted one year after the operation. The total effective rates of the observation and control groups were 99.5% (217/218) and 98.6% (218/221) respectively; the difference was not statistically significant (P=0.322). Their were significant differences between observation and control groups in intraoperative blood loss (5.07±1.14 vs 2.45±0.57, P=0.000), pain (12 h after the surgery: 5.08±1.62 vs 7.19±2.01, P=0.000; at first dressing change: 2.64±0.87 vs 4.34±1.15, P=0.000; first defecation: 3.91±1.47 vs 5.63±1.98, P=0.001), urine retention (n=22 vs n=47, P=0.001), anal pendant expansion after the surgery (2.35±0.56 vs 5.16±1.42, P=0.000), operation time (18.3±5.6 min vs 29.5±8.2 min, P=0.000), and the length of hospital stay (5.3±0.6 d vs 11.4±1.8 d, P=0.000). Moreover TST showed significant reductions compared to M-M in the rates of long-term complications such as fecal incontinence (n=3 vs n=16, P=0.003), difficult bowel movement (n=1 vs n=9, P=0.011), intractable pain (n=2 vs n=12, P=0.007), and anal discharge (n=3 vs n=23, P=0.000). TST for severe prolapsing hemorrhoids is a satisfactory technique for more rapid recovery, lower complication rates, and

  8. Costs Associated with Intravenous Cancer Therapy Administration in Patients with Metastatic Soft Tissue Sarcoma in a US Population

    Directory of Open Access Journals (Sweden)

    Mei Sheng Duh

    2013-01-01

    Full Text Available Background. The most common chemotherapies in metastatic soft tissue sarcoma (mSTS require intravenous (IV administration. This often requires patients to make multiple outpatient visits per chemotherapy cycle, possibly impeding patients’ daily activities and increasing caregiver burden and medical costs. This study investigated costs associated with IV cancer therapy administration in mSTS from the payer perspective of the health care system. Patients and Methods. From the Experian Healthcare database, 1,228 mSTS patients were selected. Data were analyzed on outpatient visits during 2005–2012 involving IV cancer therapy administration. Costs were estimated on a per patient per visit (PPPV and per patient per month (PPPM basis. Results. The mean (median cost of IV therapy was $2,427 ($1,532 PPPV and $5,468 ($4,310 PPPM, of which approximately 60% was IV drug costs. IV administration costs averaged $399 PPPV and $900 PPPM, representing 16.5% of total visit costs. Anthracycline and alkylating-agents-based therapies had the highest PPPV and PPPM IV administration costs, respectively (mean $479 and $1,336, resp.. Patients with managed care insurance had the highest IV administration costs (mean $504 PPPV; $1,120 PPPM. Conclusions. IV administration costs constitute a considerable proportion of the total costs of receiving an IV cancer therapy to treat mSTS.

  9. DRAGON score predicts functional outcomes in acute ischemic stroke patients receiving both intravenous tissue plasminogen activator and endovascular therapy.

    Science.gov (United States)

    Wang, Arthur; Pednekar, Noorie; Lehrer, Rachel; Todo, Akira; Sahni, Ramandeep; Marks, Stephen; Stiefel, Michael F

    2017-01-01

    The DRAGON score, which includes clinical and computed tomographic (CT) scan parameters, predicts functional outcomes in ischemic stroke patients treated with intravenous tissue plasminogen activator (IV tPA). We assessed the utility of the DRAGON score in predicting functional outcome in stroke patients receiving both IV tPA and endovascular therapy. A retrospective chart review of patients treated at our institution from February 2009 to October 2015 was conducted. All patients with computed tomography angiography (CTA) proven large vessel occlusions (LVO) who underwent intravenous thrombolysis and endovascular therapy were included. Baseline DRAGON scores and modified Rankin Score (mRS) at the time of hospital discharge was calculated. Good outcome was defined as mRS ≤3. Fifty-eight patients with LVO of the anterior circulation were studied. The mean DRAGON score of patients on admission was 5.3 (range, 3-8). All patients received IV tPA and endovascular therapy. Multivariate analysis demonstrated that DRAGON scores ≥7 was associated with higher mRS ( P DRAGON scores ≤6. Patients with DRAGON scores of 7 and 8 on admission had a mortality rate of 3.8% and 40%, respectively. The DRAGON score can help predict better functional outcomes in ischemic stroke patients receiving both IV tPA and endovascular therapy. This data supports the use of the DRAGON score in selecting patients who could potentially benefit from more invasive therapies such as endovascular treatment. Larger prospective studies are warranted to further validate these results.

  10. Tissue engineering for lateral ridge augmentation with recombinant human bone morphogenetic protein 2 combination therapy: a case report.

    Science.gov (United States)

    Mandelaris, George A; Spagnoli, Daniel B; Rosenfeld, Alan L; McKee, James; Lu, Mei

    2015-01-01

    This case report describes a tissue-engineered reconstruction with recombinant human bone morphogenetic protein 2/acellular collagen sponge (rhBMP-2/ ACS) + cancellous allograft and space maintenance via Medpor Contain mesh in the treatment of a patient requiring maxillary and mandibular horizontal ridge augmentation to enable implant placement. The patient underwent a previously unsuccessful corticocancellous bone graft at these sites. Multiple and contiguous sites in the maxilla and in the mandibular anterior, demonstrating advanced lateral ridge deficiencies, were managed using a tissue engineering approach as an alternative to autogenous bone harvesting. Four maxillary and three mandibular implants were placed 9 and 10 months, respectively, after tissue engineering reconstruction, and all were functioning successfully after 24 months of follow-up. Histomorphometric analysis of a bone core obtained at the time of the maxillary implant placement demonstrated a mean of 76.1% new vital bone formation, 22.2% marrow/cells, and 1.7% residual graft tissue. Tissue engineering for lateral ridge augmentation with combination therapy requires further research to determine predictability and limitations.

  11. Numerical simulation of time fractional dual-phase-lag model of heat transfer within skin tissue during thermal therapy.

    Science.gov (United States)

    Kumar, Dinesh; Rai, K N

    2017-07-01

    In this paper, we investigated the thermal behavior in living biological tissues using time fractional dual-phase-lag bioheat transfer (DPLBHT) model subjected to Dirichelt boundary condition in presence of metabolic and electromagnetic heat sources during thermal therapy. We solved this bioheat transfer model using finite element Legendre wavelet Galerkin method (FELWGM) with help of block pulse function in sense of Caputo fractional order derivative. We compared the obtained results from FELWGM and exact method in a specific case, and found a high accuracy. Results are interpreted in the form of standard and anomalous cases for taking different order of time fractional DPLBHT model. The time to achieve hyperthermia position is discussed in both cases as standard and time fractional order derivative. The success of thermal therapy in the treatment of metastatic cancerous cell depends on time fractional order derivative to precise prediction and control of temperature. The effect of variability of parameters such as time fractional derivative, lagging times, blood perfusion coefficient, metabolic heat source and transmitted power on dimensionless temperature distribution in skin tissue is discussed in detail. The physiological parameters has been estimated, corresponding to the value of fractional order derivative for hyperthermia treatment therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. PML expression in soft tissue sarcoma: prognostic and predictive value in alkylating agents/antracycline-based first line therapy.

    Science.gov (United States)

    Vincenzi, Bruno; Santini, Daniele; Schiavon, Gaia; Frezza, Anna Maria; Silletta, Marianna; Crucitti, Pierfilippo; Casali, Paolo; Dei Tos, Angelo P; Rossi, Sabrina; Rizzo, Sergio; Badalamenti, Giuseppe; Tomasino, Rosa Maria; Russo, Antonio; Butrynski, James E; Tonini, Giuseppe

    2012-04-01

    Soft tissue sarcomas are aggressive tumors representing alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. PML expression was significantly reduced in synovial sarcomas (P < 0.0001), in myofibroblastic sarcomas (P < 0.0001), angiosarcomas (P < 0.0001), in leiomyosarcomas (P = 0.003), in mixoid liposarcomas (P < 0.0001), and in dedifferentiated liposarcomas (P < 0.0001). No significant difference was found for pleomorphic sarcoma [31.8 (95% CI: 16.7-41.0); P = 0.21]. and pleomorphic liposarcomas (P = 0.51). Loss of PML expression was found to be statistically correlated with TTP (P < 0.0001), median duration of response (P = 0.007), and OS (P = 0.02). No correlation was observed between PML expression and treatment efficacy. PML IHC expression is down-regulated in synovial sarcomas, myofibroblastic sarcomas, angiosarcomas, liposarcoma, and leiomyosarcomas and its expression correlated with prognosis. Copyright © 2011 Wiley Periodicals, Inc.

  13. Early Tissue Effects of Stereotactic Body Radiation Therapy for Spinal Metastases

    NARCIS (Netherlands)

    Steverink, Jasper G.; Willems, Stefan M.; Philippens, Marielle E.P.; Kasperts, Nicolien; Eppinga, Wietse S.C.; Versteeg, Anne L.; van der Velden, Joanne M.; Faruqi, Salman; Sahgal, Arjun; Verlaan, Jorrit Jan

    2018-01-01

    Purpose: Stereotactic body radiation therapy (SBRT) is a highly effective and potentially ablative treatment for complex spinal metastases. Recent data have suggested radiobiologic effects of SBRT that expand beyond the traditional concept of DNA damage. Antitumor immunity, vascular damage leading

  14. Engineered Biomaterials to Enhance Stem Cell-Based Cardiac Tissue Engineering and Therapy.

    Science.gov (United States)

    Hasan, Anwarul; Waters, Renae; Roula, Boustany; Dana, Rahbani; Yara, Seif; Alexandre, Toubia; Paul, Arghya

    2016-07-01

    Cardiovascular disease is a leading cause of death worldwide. Since adult cardiac cells are limited in their proliferation, cardiac tissue with dead or damaged cardiac cells downstream of the occluded vessel does not regenerate after myocardial infarction. The cardiac tissue is then replaced with nonfunctional fibrotic scar tissue rather than new cardiac cells, which leaves the heart weak. The limited proliferation ability of host cardiac cells has motivated investigators to research the potential cardiac regenerative ability of stem cells. Considerable progress has been made in this endeavor. However, the optimum type of stem cells along with the most suitable matrix-material and cellular microenvironmental cues are yet to be identified or agreed upon. This review presents an overview of various types of biofunctional materials and biomaterial matrices, which in combination with stem cells, have shown promises for cardiac tissue replacement and reinforcement. Engineered biomaterials also have applications in cardiac tissue engineering, in which tissue constructs are developed in vitro by combining stem cells and biomaterial scaffolds for drug screening or eventual implantation. This review highlights the benefits of using biomaterials in conjunction with stem cells to repair damaged myocardium and give a brief description of the properties of these biomaterials that make them such valuable tools to the field. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. A new tissue segmentation method to calculate 3D dose in small animal radiation therapy.

    Science.gov (United States)

    Noblet, C; Delpon, G; Supiot, S; Potiron, V; Paris, F; Chiavassa, S

    2018-02-26

    In pre-clinical animal experiments, radiation delivery is usually delivered with kV photon beams, in contrast to the MV beams used in clinical irradiation, because of the small size of the animals. At this medium energy range, however, the contribution of the photoelectric effect to absorbed dose is significant. Accurate dose calculation therefore requires a more detailed tissue definition because both density (ρ) and elemental composition (Z eff ) affect the dose distribution. Moreover, when applied to cone beam CT (CBCT) acquisitions, the stoichiometric calibration of HU becomes inefficient as it is designed for highly collimated fan beam CT acquisitions. In this study, we propose an automatic tissue segmentation method of CBCT imaging that assigns both density (ρ) and elemental composition (Z eff ) in small animal dose calculation. The method is based on the relationship found between CBCT number and ρ*Z eff product computed from known materials. Monte Carlo calculations were performed to evaluate the impact of ρZ eff variation on the absorbed dose in tissues. These results led to the creation of a tissue database composed of artificial tissues interpolated from tissue values published by the ICRU. The ρZ eff method was validated by measuring transmitted doses through tissue substitute cylinders and a mouse with EBT3 film. Measurements were compared to the results of the Monte Carlo calculations. The study of the impact of ρZ eff variation over the range of materials, from ρZ eff  = 2 g.cm - 3 (lung) to 27 g.cm - 3 (cortical bone) led to the creation of 125 artificial tissues. For tissue substitute cylinders, the use of ρZ eff method led to maximal and average relative differences between the Monte Carlo results and the EBT3 measurements of 3.6% and 1.6%. Equivalent comparison for the mouse gave maximal and average relative differences of 4.4% and 1.2%, inside the 80% isodose area. Gamma analysis led to a 94.9% success rate in the 10% isodose

  16. Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Skouby, S O.; Andersen, L F

    2002-01-01

    BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen......: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed...

  17. In vivo study on influence of the heterogeneity of tissues in the dose distribution in high energy X ray therapy

    International Nuclear Information System (INIS)

    Aldred, M.A.

    1987-01-01

    Several authors investigated the effect of the heterogeneity of tissue in the dose distribution in a radiation-therapy. Practically all of them carried out ''in vitro'' measurements using a solid body immersed in a water phantom, in order to simulate the inhomogeneity, such as bone, air cavity, etc. In the present work, ''in vivo'' measurements were performed utilizing thermoluminescent dosimeters, whose appropriateness and convenience are well known. Eight patients at Instituto de Radioterapia Oswaldo Cruz were selected, that were under irradiation treatments in their pelvic region. The ratio between body entry radiation dose and the corresponding exit dose, when compared to the same ratio for a homogeneous phantom, gives the influence of the heterogeneity of the tissue the radiation crosses. The results found in those eight patients have shown that ''in vivo'' measurements present a ratio about 8% smaller that in homogeneous phantom case. (author) [pt

  18. Impact of Computed Tomography Image Quality on Image-Guided Radiation Therapy Based on Soft Tissue Registration

    International Nuclear Information System (INIS)

    Morrow, Natalya V.; Lawton, Colleen A.; Qi, X. Sharon; Li, X. Allen

    2012-01-01

    Purpose: In image-guided radiation therapy (IGRT), different computed tomography (CT) modalities with varying image quality are being used to correct for interfractional variations in patient set-up and anatomy changes, thereby reducing clinical target volume to the planning target volume (CTV-to-PTV) margins. We explore how CT image quality affects patient repositioning and CTV-to-PTV margins in soft tissue registration-based IGRT for prostate cancer patients. Methods and Materials: Four CT-based IGRT modalities used for prostate RT were considered in this study: MV fan beam CT (MVFBCT) (Tomotherapy), MV cone beam CT (MVCBCT) (MVision; Siemens), kV fan beam CT (kVFBCT) (CTVision, Siemens), and kV cone beam CT (kVCBCT) (Synergy; Elekta). Daily shifts were determined by manual registration to achieve the best soft tissue agreement. Effect of image quality on patient repositioning was determined by statistical analysis of daily shifts for 136 patients (34 per modality). Inter- and intraobserver variability of soft tissue registration was evaluated based on the registration of a representative scan for each CT modality with its corresponding planning scan. Results: Superior image quality with the kVFBCT resulted in reduced uncertainty in soft tissue registration during IGRT compared with other image modalities for IGRT. The largest interobserver variations of soft tissue registration were 1.1 mm, 2.5 mm, 2.6 mm, and 3.2 mm for kVFBCT, kVCBCT, MVFBCT, and MVCBCT, respectively. Conclusions: Image quality adversely affects the reproducibility of soft tissue-based registration for IGRT and necessitates a careful consideration of residual uncertainties in determining different CTV-to-PTV margins for IGRT using different image modalities.

  19. Impact of Computed Tomography Image Quality on Image-Guided Radiation Therapy Based on Soft Tissue Registration

    Energy Technology Data Exchange (ETDEWEB)

    Morrow, Natalya V.; Lawton, Colleen A. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Qi, X. Sharon [Department of Radiation Oncology, University of Colorado Denver, Denver, Colorado (United States); Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

    2012-04-01

    Purpose: In image-guided radiation therapy (IGRT), different computed tomography (CT) modalities with varying image quality are being used to correct for interfractional variations in patient set-up and anatomy changes, thereby reducing clinical target volume to the planning target volume (CTV-to-PTV) margins. We explore how CT image quality affects patient repositioning and CTV-to-PTV margins in soft tissue registration-based IGRT for prostate cancer patients. Methods and Materials: Four CT-based IGRT modalities used for prostate RT were considered in this study: MV fan beam CT (MVFBCT) (Tomotherapy), MV cone beam CT (MVCBCT) (MVision; Siemens), kV fan beam CT (kVFBCT) (CTVision, Siemens), and kV cone beam CT (kVCBCT) (Synergy; Elekta). Daily shifts were determined by manual registration to achieve the best soft tissue agreement. Effect of image quality on patient repositioning was determined by statistical analysis of daily shifts for 136 patients (34 per modality). Inter- and intraobserver variability of soft tissue registration was evaluated based on the registration of a representative scan for each CT modality with its corresponding planning scan. Results: Superior image quality with the kVFBCT resulted in reduced uncertainty in soft tissue registration during IGRT compared with other image modalities for IGRT. The largest interobserver variations of soft tissue registration were 1.1 mm, 2.5 mm, 2.6 mm, and 3.2 mm for kVFBCT, kVCBCT, MVFBCT, and MVCBCT, respectively. Conclusions: Image quality adversely affects the reproducibility of soft tissue-based registration for IGRT and necessitates a careful consideration of residual uncertainties in determining different CTV-to-PTV margins for IGRT using different image modalities.

  20. SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

    International Nuclear Information System (INIS)

    Zhang, Q; Lei, Y; Zheng, D; Zhu, X; Wahl, A; Lin, C; Zhou, S; Zhen, W

    2015-01-01

    Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness were created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing

  1. Limb sparing approach: Adjuvant radiation therapy in adults with intermediate or high-grade limb soft tissue sarcoma

    International Nuclear Information System (INIS)

    Merimsky, Ofer; Soyfer, Vjacheslav; Kovner, Felix; Bickels, Jacob; Issakov, Josephine; Flusser, Gideon; Meller, Isaac; Ofer, Oded; Kollender, Yehuda

    2005-01-01

    Background: Limb soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). Patients and methods: Between October 1994 and October 2002, 133 adult patients with intermediate or high-grade limb STS were approached by LSS+RT. Results: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II vs I, primary site in the upper limb vs lower limb, MPNST vs other types, induction therapy vs no induction, adequate resection vs marginal resection or involved margins, and good response to induction therapy vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. Conclusions: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS are satisfactory

  2. Prevalence of oral soft tissue lesions in HIV-infected minority children treated with highly active antiretroviral therapies.

    Science.gov (United States)

    Flanagan, M A; Barasch, A; Koenigsberg, S R; Fine, D; Houpt, M

    2000-01-01

    This project studied the prevalence of oral soft tissue disease in HIV-infected children treated with highly active antiretroviral therapy (HAART). Thirty-eight HIV-infected children participated in the study. Twenty-three of these patients were treated with HAART while 14 received exclusively reverse transcriptase inhibitors (RTI) and served as controls. The children were examined three times at approximately one-month intervals while their health history and laboratory data were abstracted from medical charts. Analyses were performed to determine differences in lesion prevalence between treatment groups as well as between lesion and no lesion groups with regard to immune differences. Thirty patients (79%) had oral lesions detected in at least one visit. There were no differences in specific lesion prevalence between HAART compared with RTI-treated children. However, a trend for more oral candidiasis in the latter group was observed. Subjects with oral soft tissue lesions had lower CD4 counts (P = 0.04) and percentage (P = 0.01) but similar viral loads when compared to patients without oral soft tissue disease. HAART does not appear to significantly affect oral soft tissue disease prevalence in HIV-infected children. Presence of lesions was associated with decreased immunity and may signal advancing disease.

  3. Spot-scanning proton therapy for malignant soft tissue tumors in childhood: First experiences at the Paul Scherrer Institute

    International Nuclear Information System (INIS)

    Timmermann, Beate; Schuck, Andreas; Niggli, Felix; Weiss, Markus; Lomax, Antony Jonathan; Pedroni, Eros; Coray, Adolf; Jermann, Martin; Rutz, Hans Peter; Goitein, Gudrun

    2007-01-01

    Purpose: Radiotherapy plays a major role in the treatment strategy of childhood sarcomas. Consequences of treatment are likely to affect the survivor's quality of life significantly. We investigated the feasibility of spot-scanning proton therapy (PT) for soft tissue tumors in childhood. Methods and Materials: Sixteen children with soft tissue sarcomas were included. Median age at PT was 3.3 years. In 10 children the tumor histology was embryonal rhabdomyosarcoma. All tumors were located in the head or neck, parameningeal, or paraspinal, or pelvic region. In the majority of children, the tumor was initially unresectable (Intergroup Rhabdomyosarcoma Study [IRS] Group III in 75%). In 50% of children the tumors exceeded 5 cm. Fourteen children had chemotherapy before and during PT. Median total dose of radiotherapy was 50 cobalt Gray equivalent (CGE). All 16 children were treated with spot-scanning proton therapy at the Paul Scherrer Institute, and in 3 children the PT was intensity-modulated (IMPT). Results: After median follow-up of 1.5 years, local control was achieved in 12 children. Four children failed locally, 1 at the border of the radiation field and 3 within the field. All 4 children died of tumor recurrence. All 4 showed unfavorable characteristic either of site or histopathology of the tumor. Acute toxicity was low, with Grade 3 or 4 side effects according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria occurring in the bone marrow only. Conclusions: Proton therapy was feasible and well tolerated. Early local control rates are comparable to those being achieved after conventional radiotherapy. For investigations on late effect, longer follow-up is needed

  4. Prognosis of critical limb ischemia patients with tissue loss after achievement of complete wound healing by endovascular therapy.

    Science.gov (United States)

    Kobayashi, Norihiro; Hirano, Keisuke; Nakano, Masatsugu; Ito, Yoshiaki; Ishimori, Hiroshi; Yamawaki, Masahiro; Tsukahara, Reiko; Muramatsu, Toshiya

    2015-04-01

    Critical limb ischemia (CLI) patients with tissue loss have been recognized to have a poor survival rate. In this study, we aimed to determine whether the prognosis of CLI patients with tissue loss improves after complete wound healing is achieved by endovascular therapy. We treated 187 CLI patients with tissue loss by endovascular therapy from April 2007 to December 2012. Among these patients, 113 patients who achieved complete wound healing were enrolled. The primary end point was survival rate at 3 years. The secondary end points were limb salvage rate and recurrence rate of CLI at 3 years. The mean follow-up period after achievement of complete wound healing was 32 ± 18 months. At 1 year, 2 years, and 3 years, the survival rates were 86%, 79%, and 74%; the limb salvage rates were 100%, 100%, and 100%; the recurrence rates of CLI were 2%, 6%, and 9%, respectively. On multivariate Cox proportional hazard analysis, age >75 years (hazard ratio, 3.18; 95% confidence interval, 1.23-8.24; P = .017) and nonambulatory status (hazard ratio, 2.46; 95% confidence interval, 1.08-5.65; P = .035) were identified as independent predictors of death for CLI patients with tissue loss even after complete wound healing was achieved. The Kaplan-Meier curve for the overall survival rate at 3 years showed that CLI patients of older age (>75 years) had a significantly decreased survival rate compared with CLI patients of younger age (≤75 years) (58% vs 87%; log-rank test, P wound healing was achieved. Nonambulatory status and age >75 years can serve as predictors of death even after complete wound healing is achieved. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  5. VACUUM THERAPY – PREVENTION OF HYPOXIA OF CAVERNOUS TISSUE PATIENTS AFTER RADICAL PROSTATECTOMY

    Directory of Open Access Journals (Sweden)

    A. E. Osadchinskii

    2018-01-01

    Full Text Available Patients, after radical prostatectomy with the use of nerve-sparing techniques, without carrying out penile rehabilitation, are at risk of forming cavernous fibrosis with the emergence of subsequent persistent erectile dysfunction. In order to minimize damage to cavernous tissue and early restoration of erectile function during the period of neuropraxia, it is necessary to ensure a sufficient level of oxygenation. The role of applying vacuum in penile rehabilitation for the prevention of hypoxia of cavernous tissue is not fully understood, due to the lack of data on the gaseous composition of the blood at the time of reaching the vacuum of erection. The purpose of this work was to review the scientific studies devoted to the study of vacuum induced penile erection in animals or humans, which indicates high results due to increased oxygenation of cavernous tissue.

  6. Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapy.

    Science.gov (United States)

    Yamaguchi, Shintaro; Yoshino, Jun

    2017-05-01

    Nicotinamide adenine dinucleotide (NAD + ) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD + biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT-mediated NAD + biosynthesis, together with its key downstream mediator, namely the NAD + -dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue-dependent manner. These discoveries have provided novel mechanistic and therapeutic insights into obesity and its metabolic complications, such as insulin resistance, an important risk factor for developing type 2 diabetes and cardiovascular disease. This review will focus on the importance of adipose tissue NAMPT-mediated NAD + biosynthesis and SIRT1 in the pathophysiology of obesity and insulin resistance. We will also critically explore translational and clinical aspects of adipose tissue NAD + biology. © 2017 WILEY Periodicals, Inc.

  7. Normal tissue tolerance to external beam radiation therapy: Brain and hypophysis

    International Nuclear Information System (INIS)

    Haberer, S.; Assouline, A.; Mazeron, J.J.

    2010-01-01

    Anticancer treatments-induced central nervous system neurotoxicity has become a major problem in recent years. Real advances in therapeutic results for cancer treatments have improved patients survival. Nowadays, central nervous system radiation therapy is widely prescribed, both for palliative and curative treatments in the management of malignant or benign tumors. Recent data on tolerance of normal central nervous system to radiation therapy are reviewed here, early and delayed radiation-induced effects are described and dose recommendations are suggested for clinical practice. (authors)

  8. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

    Directory of Open Access Journals (Sweden)

    Ting Gong

    2016-01-01

    Full Text Available Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration.

  9. A Standardized Rat Model of Volumetric Muscle Loss Injury for the Development of Tissue Engineering Therapies

    Science.gov (United States)

    2012-12-01

    appropriate sample size and dura- tion required to adequately characterize a treatment. Further compounding the need for a standard preclinical VML...al. In vivo tissue engineer- ing of functional skeletal muscle by freshly isolated satellite cells embedded in a photopolymerizable hydrogel. FASEB J

  10. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

    Science.gov (United States)

    Gong, Ting; Heng, Boon Chin; Lo, Edward Chin Man; Zhang, Chengfei

    2016-01-01

    Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration. PMID:27069484

  11. Biomarker expression in rectal cancer tissue before and after neoadjuvant therapy

    Directory of Open Access Journals (Sweden)

    Boogerd LS

    2018-03-01

    Full Text Available Leonora SF Boogerd,1 Maxime JM van der Valk,1 Martin C Boonstra,1 Hendrica AJM Prevoo,1 Denise E Hilling,1 Cornelis JH van de Velde,1 Cornelis FM Sier,1 Arantza Fariña Sarasqueta,2 Alexander L Vahrmeijer1 1Department of Surgery, 2Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands Purpose: Intraoperative identification of rectal cancer (RC can be challenging, especially because of fibrosis after treatment with preoperative chemo- and radiotherapy (CRT. Tumor-targeted fluorescence imaging can enhance the contrast between tumor and normal tissue during surgery. Promising targets for RC imaging are carcinoembryonic antigen (CEA, epithelial cell adhesion molecule (EpCAM and the tyrosine-kinase receptor Met (c-Met. The effect of CRT on their expression determines their applicability for imaging. Therefore, we investigated whether CRT modifies expression patterns in tumors, lymph node (LN metastases and adjacent normal rectal tissues. Patients and methods: Preoperative biopsies, primary tumor specimens and metastatic LNs were collected from 38 RC patients who did not receive CRT (cohort 1 and 34 patients who did (cohort 2. CEA, EpCAM and c-Met expression was determined using immunohistochemical staining and was semiquantified by a total immunostaining score (TIS, consisting of the percentage and intensity of stained tumor cells (0–12. Results: In both cohorts CEA, EpCAM and c-Met were significantly highly expressed in >60% of tumor tissues compared with adjacent normal epithelium (T/N ratio, P<0.01. EpCAM showed the most homogenous expression in tumors, whereas CEA showed the highest T/N ratio. Most importantly, CEA and EpCAM expression did not significantly change in normal or neoplastic RC tissue after CRT, whereas levels of c-Met changed (P=0.02. Tissues of eight patients with a pathological complete response after CRT showed expression of all biomarkers with TIS close to normal epithelium. Conclusion: Histological

  12. Assessment of the Effectiveness of Extracorporeal Shock Wave Therapy (ESWT) For Soft Tissue Injuries (ASSERT): An Online Database Protocol.

    Science.gov (United States)

    Maffulli, G; Hemmings, S; Maffulli, N

    2014-09-01

    Soft tissue injuries and tendinopathies account for large numbers of chronic musculoskeletal disorders. Extracorporeal shockwave therapy (ESWT) is popular, and effective in the management of chronic tendon conditions in the elbow, shoulder, and pain at and around the heel. Ethical approval was granted from the South East London Research Ethics Committee to implement a database for the Assessment of Effectiveness of Extracorporeal Shock Wave Therapy for Soft Tissue Injuries (ASSERT) to prospectively collect information on the effectiveness of ESWT across the UK. All participants will give informed consent. All clinicians follow a standardised method of administration of the ESWT. The primary outcome measures are validated outcome measures specific to the condition being treated. A Visual Analogue Score for pain and the EuroQol will be completed alongside the condition specific outcome tool at baseline, 3, 6, 12 and 24 months post treatment. The development of the ASSERT database will enable the evaluation of the effectiveness of ESWT for patients suffering from chronic conditions (plantar fasciopathy, tennis elbow, Achilles tendinopathy, greater trochanter pain syndrome and patellar tendinopathy). The results will aid the clinicians in the decision making process when managing these patients.

  13. Role of radiation therapy in management of patients with sarcoma of soft tissue

    International Nuclear Information System (INIS)

    Spiro, Ira J.

    1996-01-01

    Soft tissue sarcomas (STS) are relatively rare malignant neoplasms arising from the mesenchymal connective tissues. There are some 5600 newly diagnosed patients with STS per year. These tumors occur at all anatomic sites within the body and are of many histologic subtypes. Etiologic factors, including occupational risks, the role of environmental carcinogens, radiation and genetic diseases in the development of these tumors will be mode. The molecular biology of soft tissue sarcomas including the role of several oncogenes and suppressor genes (e.g. Rb, p53, MDM2) will be reviewed. Cytogenetic alternations with an emphasis on molecular diagnostic techniques will be reviewed. The natural history of these tumors will be described with reference to local invasion and spread to regional and distal sites. The evaluation of the patients suspected of having a sarcoma of soft tissue will then be considered including the relative roles of various imaging modalities. The timing and type of biopsy (including FNA, core needle biopsy, incisional biopsy or excisional biopsy) for tumors at various sites and sizes will be addressed. Assessment of histopathologic subtype of the tumor by standard H and E stains, immunohistochemistry, electron microscopy and cytogenetic studies will then be discussed. The principal role for radiation in the management of patients with sarcoma of soft tissue is in combination with surgery. This may be: 1) pre-operative and or post-operative use of external beam photons, electrons, and protons, and 2) intra-operative use of electron beam techniques, or 3) post-operative brachytherapy. Results of these various treatment options with respect to local control, disease-free survival and overall survival will be considered for each of the various techniques with respect to size, grade, histologic type, surgical margin status, anatomic site, primary vs. recurrent disease. Similarly, the factors associated with delay in wound healing are to be considered and

  14. Role of radiation therapy in management of patients with sarcoma of soft tissue

    International Nuclear Information System (INIS)

    Spiro, Ira J.; Suit, Herman D.

    1997-01-01

    Soft tissue sarcomas (STS) are relatively rare malignant neoplasms arising from the mesenchymal connective tissues. There are some 5600 newly diagnosed patients with STS per year. These tumors occur at all anatomic sites within the body and are of many histologic subtypes. Etiologic factors, including occupational risks, the role of environmental carcinogens, radiation and genetic diseases in the development of these tumors will be made. The molecular biology of soft tissue sarcomas including the role of several oncogenes and suppressor genes (e.g. Rb, p53, MDM2) will be reviewed. Cytogenetic alternations with an emphasis on molecular diagnostic techniques will be reviewed. The natural history of these tumors will be described with reference to local invasion and spread to regional and distal sites. The evaluation of the patients suspected of having a sarcoma of soft tissue will then be considered including the relative roles of various imaging modalities. The timing and type of biopsy (including FNA, core needle biopsy, incisional biopsy or excisional biopsy) for tumors at various sites and sizes will be addressed. Assessment of histopathologic subtype of the tumor by standard H and E stains, immunohistochemistry, electron microscopy and cytogenetic studies will then be discussed. The principal role for radiation in the management of patients with sarcoma of soft tissue is in combination with surgery. This may be: 1) pre-operative and or post-operative use of external beam photons, electrons, and protons, and 2) intra-operative use of electron beam techniques, or 3) post-operative brachytherapy. Results of these various treatment options with respect to local control, disease-free survival and overall survival will be considered for each of the various techniques with respect to size, grade, histologic type, surgical margin status, anatomic site, primary vs. recurrent disease. Similarly, the factors associated with delay in wound healing are to be considered and

  15. External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

    International Nuclear Information System (INIS)

    Cho, Eunpi; Mostaghel, Elahe A.; Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A.; Kurland, Brenda F.; Marck, Brett T.; Matsumoto, Alvin M.; Dalkin, Bruce L.; Montgomery, R. Bruce

    2015-01-01

    Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

  16. External Beam Radiation Therapy and Abiraterone in Men With Localized Prostate Cancer: Safety and Effect on Tissue Androgens

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Eunpi [University of Washington School of Medicine, Seattle, Washington (United States); Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Mostaghel, Elahe A. [Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Russell, Kenneth J.; Liao, Jay J.; Konodi, Mark A. [University of Washington School of Medicine, Seattle, Washington (United States); Kurland, Brenda F. [University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Marck, Brett T. [Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Matsumoto, Alvin M. [University of Washington School of Medicine, Seattle, Washington (United States); Veterans Affairs Puget Sound Health Care System, Seattle, Washington (United States); Dalkin, Bruce L. [University of Washington School of Medicine, Seattle, Washington (United States); Montgomery, R. Bruce, E-mail: rbmontgo@uw.edu [University of Washington School of Medicine, Seattle, Washington (United States)

    2015-06-01

    Purpose: Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression. Methods and Materials: A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Results: A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse. Conclusions: Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression

  17. Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering

    Science.gov (United States)

    Fernández-Robredo, P.; Sancho, A.; Johnen, S.; Recalde, S.; Gama, N.; Thumann, G.; Groll, J.; García-Layana, A.

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. PMID:24672707

  18. Online Image-based Monitoring of Soft-tissue Displacements for Radiation Therapy of the Prostate

    International Nuclear Information System (INIS)

    Schlosser, Jeffrey; Salisbury, Kenneth; Hristov, Dimitre

    2012-01-01

    Purpose: Emerging prolonged, hypofractionated radiotherapy regimens rely on high-dose conformality to minimize toxicity and thus can benefit from image guidance systems that continuously monitor target position during beam delivery. To address this need we previously developed, as a potential add-on device for existing linear accelerators, a novel telerobotic ultrasound system capable of real-time, soft-tissue imaging. Expanding on this capability, the aim of this work was to develop and characterize an image-based technique for real-time detection of prostate displacements. Methods and Materials: Image processing techniques were implemented on spatially localized ultrasound images to generate two parameters representing prostate displacements in real time. In a phantom and five volunteers, soft-tissue targets were continuously imaged with a customized robotic manipulator while recording the two tissue displacement parameters (TDPs). Variations of the TDPs in the absence of tissue displacements were evaluated, as was the sensitivity of the TDPs to prostate translations and rotations. Robustness of the approach to probe force was also investigated. Results: With 95% confidence, the proposed method detected in vivo prostate displacements before they exceeded 2.3, 2.5, and 2.8 mm in anteroposterior, superoinferior, and mediolateral directions. Prostate pitch was detected before exceeding 4.7° at 95% confidence. Total system time lag averaged 173 ms, mostly limited by ultrasound acquisition rate. False positives (FPs) (FP) in the absence of displacements did not exceed 1.5 FP events per 10 min of continuous in vivo imaging time. Conclusions: The feasibility of using telerobotic ultrasound for real-time, soft-tissue–based monitoring of target displacements was confirmed in vivo. Such monitoring has the potential to detect small clinically relevant intrafractional variations of the prostate position during beam delivery.

  19. Evaluation of mortality and length of therapy in patients with soft tissue infections 1989-99

    Directory of Open Access Journals (Sweden)

    Geranmayeh L

    2002-07-01

    Full Text Available Background: Necrotizing soft tissue infections are one of the most dreaded infections in human and result in a very high rate of mortality. The treatment of these infections must be very aggressive and consists of radical debridement of all necrotic tissue accompanied by appropriate antibiotics. Materials and Methods: This study was undertaken to assess the mortality rate, the time from diagnosis to cure, and some of the parameters which may affect mortality in our patients. In this descriptive, retrospective study first files from patients attended by necrotizing soft tissue infections including Fournier's gangrene or disease, gas gangrene, hemolytic streptococcal infections, myonecrosis, necrotizing fascitis and related subjects in Sina and Amir-Alam hospitals from 1989 to 1999 were studied. Data were extracted and analyzed by SPSS. Results: The total number of cases was 36. The median age was 47.69 years. Seven of the patients were female. The median time from onset to cure was 10 days. The most common site affected was the perineum and the most common etiology was perianal abscess. Diabetes mellitus was the underlying disease mostly observed. Half of the patients had received inappropriate treatments. In this group mortality was higher. Conclusion: It is crucial that general practitioners be acquainted with the diagnosis of necrotizing soft tissue infections so that patients are referred immediately to surgical centers. In our referral center the mortality was acceptable but it can be lowered further. The sex, sites of infection, underlying disease and etiologies in our patients were similar to patient in other countries except for alcoholism. It appears that data in foreign texts can be attributed to Iranian patients.

  20. Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Richard, Patrick, E-mail: patrjr@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Phillips, Mark; Smith, Wade [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Davidson, Darin [Department of Orthopedic Surgery, University of Washington, Seattle, Washington (United States); Kim, Edward; Kane, Gabrielle [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States)

    2016-07-01

    Purpose: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. Methods and Materials: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with the largest impact on the ICER. Results: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. Conclusions: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.

  1. Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas

    International Nuclear Information System (INIS)

    Richard, Patrick; Phillips, Mark; Smith, Wade; Davidson, Darin; Kim, Edward; Kane, Gabrielle

    2016-01-01

    Purpose: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. Methods and Materials: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with the largest impact on the ICER. Results: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. Conclusions: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.

  2. Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy

    Science.gov (United States)

    Berndt, Bianca; Landry, Guillaume; Schwarz, Florian; Tessonnier, Thomas; Kamp, Florian; Dedes, George; Thieke, Christian; Würl, Matthias; Kurz, Christopher; Ganswindt, Ute; Verhaegen, Frank; Debus, Jürgen; Belka, Claus; Sommer, Wieland; Reiser, Maximilian; Bauer, Julia; Parodi, Katia

    2017-03-01

    The purpose of this work was to evaluate the ability of single and dual energy computed tomography (SECT, DECT) to estimate tissue composition and density for usage in Monte Carlo (MC) simulations of irradiation induced β + activity distributions. This was done to assess the impact on positron emission tomography (PET) range verification in proton therapy. A DECT-based brain tissue segmentation method was developed for white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF). The elemental composition of reference tissues was assigned to closest CT numbers in DECT space (DECTdist). The method was also applied to SECT data (SECTdist). In a validation experiment, the proton irradiation induced PET activity of three brain equivalent solutions (BES) was compared to simulations based on different tissue segmentations. Five patients scanned with a dual source DECT scanner were analyzed to compare the different segmentation methods. A single magnetic resonance (MR) scan was used for comparison with an established segmentation toolkit. Additionally, one patient with SECT and post-treatment PET scans was investigated. For BES, DECTdist and SECTdist reduced differences to the reference simulation by up to 62% when compared to the conventional stoichiometric segmentation (SECTSchneider). In comparison to MR brain segmentation, Dice similarity coefficients for WM, GM and CSF were 0.61, 0.67 and 0.66 for DECTdist and 0.54, 0.41 and 0.66 for SECTdist. MC simulations of PET treatment verification in patients showed important differences between DECTdist/SECTdist and SECTSchneider for patients with large CSF areas within the treatment field but not in WM and GM. Differences could be misinterpreted as PET derived range shifts of up to 4 mm. DECTdist and SECTdist yielded comparable activity distributions, and comparison of SECTdist to a measured patient PET scan showed improved agreement when compared to SECTSchneider. The agreement between predicted and measured PET

  3. Studies on implantation of 198Au-grain as a radiation therapy to cancer tissue

    International Nuclear Information System (INIS)

    Machida, Seiro

    1975-01-01

    The most effective dose of 198 Au-grain to be implanted and the clinicopathological findings after treatment are discussed. A safe dose of 198 Au-grain which could be implanted subcutaneously in rats, was under 2 mCi migration of 198 Au-grain was not recognized. In Yoshida sarcoma, transplanted subcutaneously into the backs of rats the most effective dose of 198 Au-grain was 2mCi/g of tumour tissue. However, about half of the rats implanted with this dosage died from the growing tumour. Histological examination of the implanted tumour tissue, revealed necrosis within a distance of only 0.4 mm from 198 Au-grain particles. In small metastatic tumours after 198 Au-grain implantation, there was necrosis i.e. pyknosis and karyolysis of the tumour cells, fibrosis and hyaline degeneration of the stroma. However, hardly any change in tumour size was detectable because of swelling and induration around the tumour. In some of the cases treated with 198 Au-grain combined with 60 Co or with chemotherapeutics, the tumour size was evidently reduced and became non-palable. Side effects were minimal except in one case which was afflicted temporarily with radiation sickness after an implantation of 200 mCi 198 Au-grain. In conclusion, the implantation of 198 Au-grain into the tumour was found to be very safe for the patients with surgically incurable cancer. Because of the short range of 198 Au-grain radioactivity, homogeneous density of 198 Au-grain into the whole tumour tissue is required. A combination with other radiations and/or with chemotherapeutics is also recommended. (author)

  4. Hepatoblastoma: A Need for Cell Lines and Tissue Banks to Develop Targeted Drug Therapies

    Directory of Open Access Journals (Sweden)

    Rishi Raj Rikhi

    2016-03-01

    Full Text Available Limited research exists regarding the most aggressive forms of hepatoblastoma. Cell lines of the rare subtypes of hepatoblastoma with poor prognosis are not only difficult to attain, but are challenging to characterize histologically. A community approach to educating parents and families of the need for donated tissue is necessary for scientists to have access to resources for murine models and drug discovery. Herein we describe the currently available resources, the today’s existing gaps in research, and the path to move forward for uniform cure of hepatoblastoma.

  5. Magnetic nanoparticle-based approaches to locally target therapy and enhance tissue regeneration in vivo.

    Science.gov (United States)

    Sensenig, Richard; Sapir, Yulia; MacDonald, Cristin; Cohen, Smadar; Polyak, Boris

    2012-09-01

    Magnetic-based systems utilizing superparamagnetic nanoparticles and a magnetic field gradient to exert a force on these particles have been used in a wide range of biomedical applications. This review is focused on drug targeting applications that require penetration of a cellular barrier as well as strategies to improve the efficacy of targeting in these biomedical applications. Another focus of this review is regenerative applications utilizing tissue engineered scaffolds prepared with the aid of magnetic particles, the use of remote actuation for release of bioactive molecules and magneto-mechanical cell stimulation, cell seeding and cell patterning.

  6. Impact of tissue specific parameters on the predition of the biological effectiveness for treatment planning in ion beam therapy

    International Nuclear Information System (INIS)

    Gruen, Rebecca Antonia

    2014-01-01

    Treatment planning in ion beam therapy requires a reliable estimation of the relative biological effectiveness (RBE) of the irradiated tissue. For the pilot project at GSI Helmholtzzentrum fuer Schwerionenforschung GmbH and at other European ion beam therapy centers RBE prediction is based on a biophysical model, the Local Effect Model (LEM). The model version in use, LEM I, is optimized to give a reliable estimation of RBE in the target volume for carbon ion irradiation. However, systematic deviations are observed for the entrance channel of carbon ions and in general for lighter ions. Thus, the LEM has been continuously developed to improve accuracy. The recent version LEM IV has proven to better describe in-vitro cell experiments. Thus, for the clinical application of LEM IV it is of interest to analyze potential differences compared to LEM I under treatment-like conditions. The systematic analysis presented in this work is aiming at the comparison of RBE-weighted doses resulting from different approaches and model versions for protons and carbon ions. This will facilitate the assessment of consequences for clinical application and the interpretation of clinical results from different institutions. In the course of this thesis it has been shown that the RBE-weighted doses predicted on the basis of LEM IV for typical situations representing chordoma treatments differ on average by less than 10 % to those based on LEM I and thus also allow a consistent interpretation of the clinical results. At Japanese ion beam therapy centers the RBE is estimated using their clinical experience from neutron therapy in combination with in-vitro measurements for carbon ions (HIMAC approach). The methods presented in this work allow direct comparison of the HIMAC approach and the LEM and thus of the clinical results obtained at Japanese and European ion beam therapy centers. Furthermore, the sensitivity of the RBE on the model parameters was evaluated. Among all parameters the

  7. Alpha-1-antitrypsin augmentation therapy in deficient individuals enrolled in the Alpha-1 Foundation DNA and Tissue Bank

    Directory of Open Access Journals (Sweden)

    Adriano R Tonelli

    2009-12-01

    Full Text Available Adriano R Tonelli1, Farshid Rouhani1, Ning Li2, Pam Schreck1, Mark L Brantly11Alpha-1 Research Program, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Department of Epidemiology and Biostatistics, University of Florida, Gainesville, Florida, USAIntroduction: Intravenous augmentation therapy with purified intravenous alpha-1 antitrypsin replaces the deficient protein and is the only currently approved treatment for alpha-1 antitrypsin deficiency (AATD related lung disease. While augmentation therapy has been available for more than 20 years, there are a limited number of studies evaluating the effect of augmentation on lung function.Material and methods: We examined the decline in forced expiratory volume in one second (FEV1 in patients enrolled in the Alpha-1 Foundation DNA and Tissue Bank in relation to the use or not of alpha-1 antitrypsin augmentation therapy. For the purpose of our analysis we included 164 patients with AATD and PI ZZ genotype.Results: Mean age of the patients was 60 years, 52% were females, 94% were white and 78% ex-smokers. The mean FEV1 at baseline was 1.7 L and the mean FEV1 % of predicted was 51.3%. The mean follow-up time was 41.7 months. A total of 124 (76% patients received augmentation therapy (augmented group while 40 patients (24% did not received it (non-augmented group. When adjusted by age at baseline, sex, smoking status, baseline FEV1 % of predicted, the mean overall change in FEV1 was 47.6 mL/year, favoring the augmented group (?FEV1 10.6 ± 21.4 mL/year in comparison with the non-augmented group (?FEV1 −36.96 ± 12.1 mL/year (P = 0.05. Beneficial ?FEV1 were observed in ex-smokers and the group with initial FEV1 % of predicted of <50%. No differences were observed in mortality.Conclusions: In conclusion, augmentation therapy improves lung function in subjects with AATD when adjusted by age, gender, smoking status and baseline FEV1 % of predicted. The beneficial

  8. Nonthermal Ablation by Using Intravascular Oxygen Radical Generation with WST11: Dynamic Tissue Effects and Implications for Focal Therapy

    Science.gov (United States)

    Kimm, Simon Y.; Tarin, Tatum V.; Monette, Sébastien; Srimathveeravalli, Govindarajan; Gerber, Daniel; Durack, Jeremy C.; Solomon, Stephen B.; Scardino, Peter T.; Scherz, Avigdor

    2016-01-01

    Purpose To examine the hypothesis that vascular-targeted photodynamic therapy (VTP) with WST11 and clinically relevant parameters can be used to ablate target tissues in a non–tumor-bearing large-animal model while selectively sparing blood vessels and collagen. Materials and Methods By using an institutional animal care and use committee–approved protocol, 68 ablations were performed in the kidneys (cortex and medulla) and livers of 27 adult pigs. Posttreatment evaluation was conducted with contrast material–enhanced computed tomography in the live animals at 24 hours. Immunohistochemistry was evaluated and histologic examination with hematoxylin-eosin staining was performed at 4 hours, 24 hours, and 7 days. Intravenous infusion of WST11 (4 mg per kilogram of body weight) was followed by using near-infrared illumination (753 nm for 20 minutes) through optical fibers prepositioned in target tissues by using a fixed template. Treated areas were scanned, measured, and statistically analyzed by using the Student t test and two-way analysis of variance. Results Focal WST11 VTP treatment in the liver and kidney by using a single optical fiber resulted in well-demarcated cylindrical zones of nonthermal necrosis concentrically oriented around the light-emitting diffuser, with no intervening viable parenchymal cells. The radius of ablated tissue increased from approximately 5 mm at 150 mW to approximately 7 mm at 415 mW (P necrosis. Patterns of acute injury within 24 hours were consistent with microcirculatory flow arrest and collagen preservation (demonstrated with trichrome staining). In the peripheral ablation zone, blood vessels at least 40 μm in diameter were selectively preserved and remained functional at 7 days. Ablated tissues exhibited progressive fibrosis and chronic inflammatory cell infiltrates. No histologic changes consistent with thermal injury were observed in blood vessels or collagen. The renal hilum and collecting system did not show treatment

  9. Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus.

    Science.gov (United States)

    Cucchiarini, M; McNulty, A L; Mauck, R L; Setton, L A; Guilak, F; Madry, H

    2016-08-01

    Meniscal lesions are common problems in orthopaedic surgery and sports medicine, and injury or loss of the meniscus accelerates the onset of knee osteoarthritis (OA). Despite a variety of therapeutic options in the clinics, there is a critical need for improved treatments to enhance meniscal repair. In this regard, combining gene-, cell-, and tissue engineering-based approaches is an attractive strategy to generate novel, effective therapies to treat meniscal lesions. In the present work, we provide an overview of the tools currently available to improve meniscal repair and discuss the progress and remaining challenges for potential future translation in patients. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  10. Radiation absorbed dose and expected risk in head and neck tissues after thyroid radioiodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hamed, A [National Center for Nuclear and Radiation Control, AEA., Cairo (Egypt); Farag, H I [National Cancer instiute, Cairo University, Cairo (Egypt); Saleh, A [Al-hussien Hospital, Al-Azhar University, Cairo (Egypt)

    1997-12-31

    Measurement of absorbed dose in head and neck phantom after applying I-131 therapeutic dose for the treatment of thyroid malignancies was conducted. The measurement were carried out at several sites of phantom using TL dosimeters. The absorbed doses were also measured on the skin of four patients during their administration of I-131 therapeutic doses 1.332 GBq (36 mci) I-131. The measurements were taken over 69 hours exposure at different sites of phantom. The same measurements were carried out on the four patients. At five sites of the patients head and neck, the absorbed dose were measured and compared with that measured on the phantom. The values measured are discussed in the light of the published individual absorbed doses in the organs by ICRP tables. High absorbed doses were absorbed in the different sites of the head and neck during the I-131 therapy (0.14-9.68 mGy/mCi). 3 figs., 2 tabs.

  11. Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project.

    Science.gov (United States)

    Popowicz, Natalia; Bintcliffe, Oliver; De Fonseka, Duneesha; Blyth, Kevin G; Smith, Nicola A; Piccolo, Francesco; Martin, Geoffrey; Wong, Donny; Edey, Anthony; Maskell, Nick; Lee, Y C Gary

    2017-06-01

    Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22-58] to 16% [8-31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247-2,984] over 72 h of therapy; P <  0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent

  12. Vasculatures in Tumors Growing From Preirradiated Tissues: Formed by Vasculogenesis and Resistant to Radiation and Antiangiogenic Therapy

    International Nuclear Information System (INIS)

    Chen, Fang-Hsin; Chiang, Chi-Shiun; Wang, Chun-Chieh; Fu, Sheng-Yung; Tsai, Chien-Sheng; Jung, Shih-Ming; Wen, Chih-Jen; Lee, Chung-Chi; Hong, Ji-Hong

    2011-01-01

    Purpose: To investigate vasculatures and microenvironment in tumors growing from preirradiated tissues (pre-IR tumors) and study the vascular responses of pre-IR tumors to radiation and antiangiogenic therapy. Methods and Materials: Transgenic adenocarcinoma of the mouse prostate C1 tumors were implanted into unirradiated or preirradiated tissues and examined for vascularity, hypoxia, and tumor-associated macrophage (TAM) infiltrates by immunohistochemistry. The origin of tumor endothelial cells was studied by green fluorescent protein-tagged bone marrow (GFP-BM) transplantation. The response of tumor endothelial cells to radiation and antiangiogenic agent was evaluated by apoptotic assay. Results: The pre-IR tumors had obvious tumor bed effects (TBE), with slower growth rate, lower microvascular density (MVD), and more necrotic and hypoxic fraction compared with control tumors. The vessels were dilated, tightly adhered with pericytes, and incorporated with transplanted GFP-BM cells. In addition, hypoxic regions became aggregated with TAM. As pre-IR tumors developed, the TBE was overcome at the tumor edge where the MVD increased, TAM did not aggregate, and the GFP-BM cells did not incorporate into the vessels. The vessels at tumor edge were more sensitive to the following ionizing radiation and antiangiogenic agent than those in the central low MVD regions. Conclusions: This study demonstrates that vasculatures in regions with TBE are mainly formed by vasculogenesis and resistant to radiation and antiangiogenic therapy. Tumor bed effects could be overcome at the edge of larger tumors, but where vasculatures are formed by angiogenesis and sensitive to both treatments. Vasculatures formed by vasculogenesis should be the crucial target for the treatment of recurrent tumors after radiotherapy.

  13. Risk for molecular contamination of tissue samples evaluated for targeted anti-cancer therapy.

    Directory of Open Access Journals (Sweden)

    Eyal Asor

    Full Text Available With the increasing usage of sensitive PCR technology for pharmacogenetics, cross contamination becomes a significant concern. Researchers employed techniques which basically include replacing laboratory equipment after each sample preparation; however, there are no recommended guidelines. In the present work we wanted to evaluate the risk of cross contamination during tissue processing using the routine precaution measures. Twenty-one surgical samples of lung adenocarcinoma were used, of which 7 contained EGFR exon 19 mutation, 7 contained EGFR exon 21 mutation (p.L858R and 7 were EGFR wild-type. The samples were ordered by alternating the mutation group to maximize the potential for cross contamination and underwent tissue sectioning and de-paraffinization. The entire process was performed using the same tools. Following DNA extraction all samples underwent PCR amplification and were scrutinized for small fractions of EGFR mutation using deep sequencing with the Ion torrent PGM technology. Twenty samples yielded results. The fraction of mutated copies was 41 ± 23% (range 11-66 for the cases with known exon 19 mutation and 48±24% (range 0-65 for the cases with known exon 21 mutations. No in-frame exon 19 deletion mutations were identified in the wild-type (WT and exon 21 groups. The fraction of EGFR exon 21 (codon 858 mutations was 0.018±0.014% (range 0-0.05% in the WT and exon 19 groups, which was not statistically different than the background sequencing artifact noise for the same base-pair alteration (p = 0.21. Our results suggest that standard precautions are sufficient for molecular pathology diagnosis of surgical samples and are not associated with increased risk of cross contamination.

  14. The immediate effect of soft tissue manual therapy intervention on lung function in severe chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Cruz-Montecinos C

    2017-02-01

    Full Text Available Carlos Cruz-Montecinos,1–3 Diego Godoy-Olave,4 Felipe A Contreras-Briceño,5 Paulina Gutiérrez,4 Rodrigo Torres-Castro,2 Leandro Miret-Venegas,3 Roger M Engel6 1Laboratory of Biomechanics and Kinesiology, San José Hospital, Santiago, Chile; 2Department of Physical Therapy, Faculty of Medicine, University of Chile, Santiago, Chile; 3Unit of Kinesiology and Physical Therapy, San José Hospital, Santiago, Chile; 4Departamento de Kinesiología, Universidad Metropolitana de Ciencias de la Educación, Santiago, Chile; 5Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; 6Department of Chiropractic, Macquarie University, Sydney, Australia Background and objective: In chronic obstructive pulmonary disease (COPD, accessory respiratory muscles are recruited as a compensatory adaptation to changes in respiratory mechanics. This results in shortening and overactivation of these and other muscles. Manual therapy is increasingly being investigated as a way to alleviate these changes. The aim of this study was to measure the immediate effect on lung function of a soft tissue manual therapy protocol (STMTP designed to address changes in the accessory respiratory muscles and their associated structures in patients with severe COPD.Methods: Twelve medically stable patients (n=12 with an existing diagnosis of severe COPD (ten: GOLD Stage III and two: GOLD Stage IV were included. Residual volume, inspiratory capacity and oxygen saturation (SpO2 were recorded immediately before and after administration of the STMTP. A Student’s t-test was used to determine the effect of the manual therapy intervention (P<0.05.Results: The mean age of the patients was 62.4 years (range 46–77. Nine were male. Residual volume decreased from 4.5 to 3.9 L (P=0.002, inspiratory capacity increased from 2.0 to 2.1 L (P=0.039 and SpO2 increased from 93% to 96% (P=0.001.Conclusion: A single application of an STMTP appears to have the potential to produce

  15. Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

    Science.gov (United States)

    Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

    2017-02-01

    Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

  16. High throughput screening for small molecule therapy for Gaucher disease using patient tissue as the source of mutant glucocerebrosidase.

    Directory of Open Access Journals (Sweden)

    Ehud Goldin

    Full Text Available Gaucher disease (GD, the most common lysosomal storage disorder, results from the inherited deficiency of the lysosomal enzyme glucocerebrosidase (GCase. Previously, wildtype GCase was used for high throughput screening (HTS of large collections of compounds to identify small molecule chaperones that could be developed as new therapies for GD. However, the compounds identified from HTS usually showed reduced potency later in confirmatory cell-based assays. An alternate strategy is to perform HTS on mutant enzyme to identify different lead compounds, including those enhancing mutant enzyme activities. We developed a new screening assay using enzyme extract prepared from the spleen of a patient with Gaucher disease with genotype N370S/N370S. In tissue extracts, GCase is in a more native physiological environment, and is present with the native activator saposin C and other potential cofactors. Using this assay, we screened a library of 250,000 compounds and identified novel modulators of mutant GCase including 14 new lead inhibitors and 30 lead activators. The activities of some of the primary hits were confirmed in subsequent cell-based assays using patient-derived fibroblasts. These results suggest that primary screening assays using enzyme extracted from tissues is an alternative approach to identify high quality, physiologically relevant lead compounds for drug development.

  17. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy.

    Science.gov (United States)

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory's development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery.

  18. Mechanical Dyssynchrony by Tissue Doppler Cross-Correlation is Associated with Risk for Complex Ventricular Arrhythmias after Cardiac Resynchronization Therapy

    DEFF Research Database (Denmark)

    Tayal, Bhupendar; Gorcsan, John; Delgado-Montero, Antonia

    2015-01-01

    BACKGROUND: Tissue Doppler cross-correlation analysis has been shown to be associated with long-term survival after cardiac resynchronization defibrillator therapy (CRT-D). Its association with ventricular arrhythmia (VA) is unknown. METHODS: From two centers 151 CRT-D patients (New York Heart...... Association functional classes II-IV, ejection fraction ≤ 35%, and QRS duration ≥ 120 msec) were prospectively included. Tissue Doppler cross-correlation analysis of myocardial acceleration curves from the basal segments in the apical views both at baseline and 6 months after CRT-D implantation was performed...... with a substantially increased risk for VA (hazard ratio [HR], 4.4; 95% CI, 1.2-16.3; P = .03) and VA or death (HR, 4.0; 95% CI, 1.7-9.6; P = .002) after adjusting for other covariates. Similarly, patients with new dyssynchrony had increased risk for VA (HR, 10.6; 95% CI, 2.8-40.4; P = .001) and VA or death (HR, 5...

  19. Normal tissue complication probability modeling of radiation-induced hypothyroidism after head-and-neck radiation therapy.

    Science.gov (United States)

    Bakhshandeh, Mohsen; Hashemi, Bijan; Mahdavi, Seied Rabi Mehdi; Nikoofar, Alireza; Vasheghani, Maryam; Kazemnejad, Anoshirvan

    2013-02-01

    To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with α/β = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D(50) estimated from the models was approximately 44 Gy. The implemented normal tissue complication probability models showed a parallel architecture for the

  20. Normal Tissue Complication Probability Modeling of Radiation-Induced Hypothyroidism After Head-and-Neck Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bakhshandeh, Mohsen [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Hashemi, Bijan, E-mail: bhashemi@modares.ac.ir [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Mahdavi, Seied Rabi Mehdi [Department of Medical Physics, Faculty of Medical Sciences, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Nikoofar, Alireza; Vasheghani, Maryam [Department of Radiation Oncology, Hafte-Tir Hospital, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Kazemnejad, Anoshirvan [Department of Biostatistics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of)

    2013-02-01

    Purpose: To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Methods and Materials: Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with {alpha}/{beta} = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Results: Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D{sub 50} estimated from the models was approximately 44 Gy. Conclusions: The implemented

  1. * Tissue-Specific Extracellular Matrix Enhances Skeletal Muscle Precursor Cell Expansion and Differentiation for Potential Application in Cell Therapy.

    Science.gov (United States)

    Zhang, Deying; Zhang, Yong; Zhang, Yuanyuan; Yi, Hualin; Wang, Zhan; Wu, Rongpei; He, Dawei; Wei, Guanghui; Wei, Shicheng; Hu, Yun; Deng, Junhong; Criswell, Tracy; Yoo, James; Zhou, Yu; Atala, Anthony

    2017-08-01

    Skeletal muscle precursor cells (MPCs) are considered a key candidate for cell therapy in the treatment of skeletal muscle dysfunction due to injury, disease, or age. However, expansion of a sufficient number of functional skeletal muscle cells in vitro from a small tissue biopsy has been challenging due to changes in phenotypic expression of these cells under traditional culture conditions. Thus, the aim of the study was to develop a better culture system for the expansion and myo-differentiation of MPCs that could further be used for therapy. For this purpose, we developed an ideal method of tissue decellularization and compared the ability of different matrices to support MPC growth and differentiation. Porcine-derived skeletal muscle and liver and kidney extracellular matrix (ECM) were generated by decellularization methods consisting of distilled water, 0.2 mg/mL DNase, or 5% fetal bovine serum. Acellular matrices were further homogenized, dissolved, and combined with a hyaluronic acid-based hydrogel decorated with heparin (ECM-HA-HP). The cell proliferation and myogenic differentiation capacity of human MPCs were assessed when grown on gel alone, ECM, or each ECM-HA-HP substrate. Human MPC proliferation was significantly enhanced when cultured on the ECM-HA-HP substrates compared to the other substrates tested, with the greatest proliferation on the muscle ECM-HA-HP (mECM-HA-HP) substrate. The number of differentiated myotubes was significantly increased on the mECM-HA-HP substrate compared to the other gel-ECM substrates, as well as the numbers of MPCs expressing specific myogenic cell markers (i.e., myosin, desmin, myoD, and myf5). In conclusion, skeletal mECM-HA-HP as a culture substrate provided an optimal culture microenvironment potentially due to its similarity to the in vivo environment. These data suggest a potential use of skeletal muscle-derived ECM gel for the expansion and differentiation of human MPCs for cell-based therapy for skeletal muscle

  2. Effects of negative pressure wound therapy on the expression of EDA+ FN in granulation tissues of human diabetic foot wounds

    Directory of Open Access Journals (Sweden)

    Shao-ling YANG

    2017-04-01

    Full Text Available Objective  To investigate the effects of negative pressure wound therapy (NPWT on the expression of EDA+ FN in granulation tissues of human diabetic foot wounds. Methods  Forty patients with diabetic foot wounds fitting the inclusion criteria, admitted from Jan. 2014 to Jun. 2016, were randomly and equally apportioned to receive either NPWT or conventional gauze therapy (control for 14 days. Granulated tissue biopsies were collected before (0 day and after (14 day treatment in both groups. All biopsies were subdivided into two parts. One part was preserved in 4% paraformaldehyde for immunocytochemical staining of EDA+ FN, and the other part was stored at –80℃for Western blotting and PCR analysis of EDA+ FN. Results  The immunohistochemical analysis revealed that the mean area density of EDA+ FN increased in both NPWT group and control group at day 14 relative to day 0, but the change value of mean area density was higher in NPWT group than in control group (P<0.01. Western blotting showed that the relative protein levels of EDA+ FN increased in both NPWT group and control group at day 14 relative to day 0, but the change value of relative protein levels of EDA+ FN was higher in NPWT group than in control group (P<0.01. The real time PCR analysis demonstrated that the relative mRNA levels of EDA+ FN increased in both NPWT group and control group at day 14 relative to day 0, but the change value of relative mRNA levels of EDA+ FN was higher in NPWT group than in control group (P<0.01. The results demonstrated the higher protein and mRNA levels of EDA+ FN in NPWT group than that in control group. Conclusion  NPWT obviously enhances EDA+ FN expression in granulation tissue of diabetic foot wound, as a result promotes wound healing. DOI: 10.11855/j.issn.0577-7402.2017.03.09

  3. Intensity-Modulated Proton Therapy Further Reduces Normal Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Gomez, Daniel; Palmer, Matthew B.; Riley, Beverly A.; Mayankkumar, Amin V.; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Dong, Lei; Zhu, X. Ronald [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Likhacheva, Anna; Liao, Zhongxing [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Cox, James D. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

    2011-12-01

    Purpose: We have previously found that {<=} 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Patients and Methods: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Results: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p < .0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p {<=} .0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p < .001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p {<=} .02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p < .0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p {<=} .005), heart (p {<=} .003), and liver (p {<=} .04). Conclusions: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for

  4. Tissue Engineering Based Therapy for Articular Cartilage Defects - A New Approach

    Directory of Open Access Journals (Sweden)

    Abraham S

    2007-01-01

    Full Text Available Background: Articular cartilage, the load-bearing tissue in diarthrodial joints, when damaged due to trauma could lead to osteoarthritis. At present Autologous Cartilage Implantation is an established method in which patients own chondrocytes are isolated and then implanted after in vitro expansion over the affected area with bovine or porcine collagen matrix. This procedure results in more of Collagen Type I during in vitro expansion, which eventually becomes fibrocartilage. Also it requires growth factors. We have in this study tried growing human Chondrocytes without growth factors using synthetic scaffolds to grow more Collagen Type II Materials and Methods: Human cartilage specimens were harvested through arthroscopy from the non-weight bearing area of the knee joint from 13 patients who underwent surgical procedures of the knee joint after getting their informed consent. The tissues were transported in saline taking 1 hour to laboratory and subjected to digestion with Collagenase type II for 16~18 Hrs. The chondrocyte cells obtained after dissociation were divided into two groups for culture. Gr. I were embedded in a Thermogelation polymer (TGP and Gr. II in basal culture media (DMEM + Ascorbic Acid without using any growth factors. The Group II cells were viable only for 4 weeks and then started degenerating. The TGP-Chondrocytes scaffolds were grown for 16 weeks and the specimens were harvested at 4, 8, 12 and 16-week intervals and their morphology and molecular characteristics were studied by H&E staining, S-100 protein analysis and RT-PCR.Results: Human chondrocytes could be cultured in both TGP (group I and Basal culture media (group II. The Gr. I cells were viable upto the 16th week while the Group II chondrocytes started degenerating after the 4 week. Both the groups were proven positive for S-100 protein, a Chondrocyte specific marker protein; Gr. II specimens after 4 weeks, and Gr. I specimens after 4, 8, 12 and 16 weeks. RT

  5. Intraoperative Radiation Therapy for Locally Advanced and Recurrent Soft-Tissue Sarcomas in Adults

    International Nuclear Information System (INIS)

    Tran, Phuoc T.; Hara, Wendy; Su Zheng; Lin, H. Jill; Bendapudi, Pavan K.; Norton, Jeffrey; Teng, Nelson; King, Christopher R.; Kapp, Daniel S.

    2008-01-01

    Purpose: To analyze the outcomes of and identify prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for locally advanced and recurrent soft-tissue sarcoma in adults from a single institution. Methods and Materials: We retrospectively reviewed 50 consecutive patients treated with IORT to 62 sites of disease. Primary sites included retroperitoneum-pelvis (78%), extremity (8%), and other (14%). Seventy percent of patients had recurrent disease failing prior surgery (70%) and/or radiation (32%). Mean disease-free interval (DFI) before IORT was 1.9 years (range, 2 weeks-5.4 years). The IORT was delivered with orthovoltage X-rays using individually sized beveled cone applicators. Clinical characteristics were as follows: mean tumor size, 10 cm (range, 1-25 cm); high-grade histologic subtype (72%); and mean dose, 1,159 cGy (range, 600-1,600 cGy). Postoperative radiation or chemotherapy was administered to 37% of IORT Sites and 32% of patients, respectively. Outcomes measured were infield control (IFC), locoregional control (LRC), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and treatment-related complications. Mean and median follow-up of alive patients were 59 and 35 months, respectively. Results: Kaplan-Meier 5-year IFC, LRC, DMFS, and DSS probabilities for the entire group were 55%, 26%, 51%, and 25%, respectively. Prognostic factors found to be significant (p < 0.05) on multivariate analysis were prior DFI and tumor size for LRC, extremity location and leiomyosarcoma histologic subtype for DMFS, and prior DFI for DSS. Our cohort had five Grade 3/4 complications associated with treatment or a 5-year Kaplan-Meier Grade 3/4 complication-free survival rate of 85%. Conclusions: IORT after tumor reductive surgery is well tolerated and seems to confer IFC in carefully selected patients

  6. Particle Therapy Using Protons or Carbon Ions for Unresectable or Incompletely Resected Bone and Soft Tissue Sarcomas of the Pelvis

    Energy Technology Data Exchange (ETDEWEB)

    Demizu, Yusuke, E-mail: y_demizu@nifty.com [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Jin, Dongcun; Sulaiman, Nor Shazrina; Nagano, Fumiko; Terashima, Kazuki; Tokumaru, Sunao [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Akagi, Takashi [Department of Radiation Physics, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan); Fujii, Osamu [Department of Radiation Oncology, Hakodate Goryokaku Hospital, Hakodate, Hokkaido (Japan); Daimon, Takashi [Department of Biostatistics, Hyogo College of Medicine, Nishinomiya, Hyogo (Japan); Sasaki, Ryohei [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Fuwa, Nobukazu [Department of Radiation Oncology, Ise Red Cross Hospital, Ise, Mie (Japan); Okimoto, Tomoaki [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno, Hyogo (Japan)

    2017-06-01

    Purpose: To retrospectively analyze the treatment outcomes of particle therapy using protons or carbon ions for unresectable or incompletely resected bone and soft tissue sarcomas (BSTSs) of the pelvis. Methods and Materials: From May 2005 to December 2014, 91 patients with nonmetastatic histologically proven unresectable or incompletely resected pelvic BSTSs underwent particle therapy with curative intent. The particle therapy used protons (52 patients) or carbon ions (39 patients). All patients received a dose of 70.4 Gy (relative biologic effectiveness) in 32 fractions (55 patients) or 16 fractions (36 patients). Results: The median patient age was 67 years (range 18-87). The median planning target volume (PTV) was 455 cm{sup 3} (range 108-1984). The histologic type was chordoma in 53 patients, chondrosarcoma in 14, osteosarcoma in 10, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma in 5, and other in 9 patients. Of the 91 patients, 82 had a primary tumor and 9 a recurrent tumor. The median follow-up period was 32 months (range 3-112). The 3-year rate of overall survival (OS), progression-free survival (PFS), and local control was 83%, 72%, and 92%, respectively. A Cox proportional hazards model revealed that chordoma histologic features and a PTV of ≤500 cm{sup 3} were significantly associated with better OS, and a primary tumor and PTV of ≤500 cm{sup 3} were significantly associated with better PFS. Ion type and number of fractions were not significantly associated with OS, PFS, or local control. Late grade ≥3 toxicities were observed in 23 patients. Compared with the 32-fraction protocol, the 16-fraction protocol was associated with significantly more frequent late grade ≥3 toxicities (18 of 36 vs 5 of 55; P<.001). Conclusions: Particle therapy using protons or carbon ions was effective for unresectable or incompletely resected pelvic BSTS, and the 32-fraction protocol was effective and relatively less toxic. Nevertheless, a

  7. The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure.

    Science.gov (United States)

    Sherlock, Mark; Behan, Lucy Ann; Hannon, Mark J; Alonso, Aurora Aragon; Thompson, Christopher J; Murray, Robert D; Crabtree, Nicola; Hughes, Beverly A; Arlt, Wiebke; Agha, Amar; Toogood, Andrew A; Stewart, Paul M

    2015-11-01

    Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy. To assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition. We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body composition (clinical parameters and full body DXA) of 53 patients (19 female, median age 46 years) with hypopituitarism (33 ACTH-deficient/20 ACTH-replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity was assessed by urinary THF+5α-THF/THE. Endocrine Centres within University Teaching Hospitals in the UK and Ireland. Urinary corticosteroid metabolite profile and body composition assessment. In study A, when patients were divided into three groups - patients not receiving HC and patients receiving HC≤20 mg/day or HC>20 mg/day - patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (WHR) than the ACTH replete group. They also had significantly elevated THF+5α-THF/THE (P=0.0002) and total cortisol metabolites (P=0.015). In study B, patients on the highest HC dose had significantly elevated total cortisol metabolites and all patients on HC had elevated THF+5α-THF/THE ratios when compared to controls. In ACTH-deficient patients daily HC doses of >20 mg/day have increased WHR, THF+5α-THF/THE ratios and total cortisol metabolites. GC metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype. © 2015 European Society of Endocrinology.

  8. Spectral pulsed-wave tissue Doppler imaging lateral-to-septal delay fails to predict clinical or echocardiographic outcome after cardiac resynchronization therapy

    NARCIS (Netherlands)

    O.I.I. Soliman (Osama Ibrahim Ibrahim); D.A.M.J. Theuns (Dominic); M.L. Geleijnse (Marcel); A. Nemes (Attila); K. Caliskan (Kadir); W.B. Vletter (Wim); L.J.L.M. Jordaens (Luc); F.J. ten Cate (Folkert)

    2007-01-01

    textabstractAims: The current study sought to assess if pre-implantation lateral-to-septal delay (LSD) ≥60 ms assessed by spectral pulsed-wave myocardial tissue Doppler imaging (PW-TDI) could predict successful long-term outcome after cardiac resynchronization therapy (CRT). Methods and results

  9. Effect of negative pressure therapy on repair of soft tissues of the lower extremities in patients with neuropathic and neuroischaemic forms of diabetic foot syndrome

    Directory of Open Access Journals (Sweden)

    Ekaterina Leonidovna Zaytseva

    2014-06-01

    Full Text Available Aim. To evaluate the efficiency of topical negative pressure wound therapy (NPWT compared with standard therapy for the regeneration of the soft tissues of the lower extremities in patients with diabetic foot syndrome. Materials and Methods. The effects of negative pressure therapy on the clinical (size, tissue oxygenation, histological (light microscopy and immunohistochemical (CD68, MMP-9, TIMP-1 aspects of repair of the soft tissue of the lower extremities in patients with diabetes mellitus were compared with those of standard treatment. Thirty-one patients with diabetic foot ulcers were included in the study from the moment of debridement until the plastic closure of the wound. During the perioperative period, 13 patients received NPWT (-90 to -120 mmHg and 18 patients received standard therapy. Results. A reduction of the wound area (26.6%?17.2% and the depth of the defects (40.5%?25.6% were achieved with negative pressure therapy compared with baseline data. In the control group, the corresponding values were 25.3%?19.4% and 21.8%?21.6%, respectively. The results of transcutaneous oximetry showed a greater increase in the level of local hemodynamics in the study group (p

  10. Low-level laser therapy (LLLT) does not reduce subcutaneous adipose tissue by local adipocyte injury but rather by modulation of systemic lipid metabolism.

    Science.gov (United States)

    Jankowski, Marek; Gawrych, Mariusz; Adamska, Urszula; Ciescinski, Jakub; Serafin, Zbigniew; Czajkowski, Rafal

    2017-02-01

    Low-level laser (light) therapy (LLLT) has been applied recently to body contouring. However the mechanism of LLLT-induced reduction of subcutaneous adipose tissue thickness has not been elucidated and proposed hypotheses are highly controversial. Non-obese volunteers were subject to 650nm LLLT therapy. Each patient received 6 treatments 2-3 days apart to one side of the abdomen. The contralateral side was left untreated and served as control. Subjects' abdominal adipose tissue thickness was measured by ultrasound imaging at baseline and 2 weeks post-treatment. Our study is to the best of our knowledge, the largest split-abdomen study employing subcutaneous abdominal fat imaging. We could not show a statistically significant reduction of abdominal subcutaneous adipose tissue by LLLT therapy. Paradoxically when the measurements of the loss of fat thickness on treated side was corrected for change in thickness on non treated side, we have observed that in 8 out of 17 patients LLLT increased adipose tissue thickness. In two patients severe side effect occurred as a result of treatment: one patient developed ulceration within appendectomy scar, the other over the posterior superior iliac spine. The paradoxical net increase in subcutaneous fat thickness observed in some of our patients is a rationale against liquefactive and transitory pore models of LLLT-induced adipose tissue reduction. LLLT devices with laser diode panels applied directly on the skin are not as safe as devices with treatment panels separated from the patient's skin.

  11. Uric acid therapy improves the outcomes of stroke patients treated with intravenous tissue plasminogen activator and mechanical thrombectomy.

    Science.gov (United States)

    Chamorro, Ángel; Amaro, Sergio; Castellanos, Mar; Gomis, Meritxell; Urra, Xabier; Blasco, Jordi; Arenillas, Juan F; Román, Luis S; Muñoz, Roberto; Macho, Juan; Cánovas, David; Marti-Fabregas, Joan; Leira, Enrique C; Planas, Anna M

    2017-06-01

    Background Numerous neuroprotective drugs have failed to show benefit in the treatment of acute ischemic stroke, making the search for new treatments imperative. Uric acid is an endogenous antioxidant making it a drug candidate to improve stroke outcomes. Aim To report the effects of uric acid therapy in stroke patients receiving intravenous thrombolysis and mechanical thrombectomy. Methods Forty-five patients with proximal vessel occlusions enrolled in the URICO-ICTUS trial received intravenous recombinant tissue plasminogen activator within 4.5 h after stroke onset and randomized to intravenous 1000 mg uric acid or placebo (NCT00860366). These patients also received mechanical thrombectomy because a brain computed tomogaphy angiography confirmed the lack of proximal recanalization at the end of systemic thrombolysis. The primary outcome was good functional outcome at 90 days (modified Rankin Score 0-2). Safety outcomes included mortality, symptomatic intracerebral bleeding, and gout attacks. Results The rate of successful revascularization was >80% in the uric acid and the placebo groups but good functional outcome was observed in 16 out of 24 (67%) patients treated with uric acid and 10 out of 21 (48%) treated with placebo (adjusted Odds Ratio, 6.12 (95% CI 1.08-34.56)). Mortality was observed in two out of 24 (8.3%) patients treated with uric acid and one out of 21 (4.8%) treated with placebo (adjusted Odds Ratio, 3.74 (95% CI 0.06-226.29)). Symptomatic cerebral bleeding and gout attacks were similar in both groups. Conclusions Uric acid therapy was safe and improved stroke outcomes in stroke patients receiving intravenous thrombolysis followed by thrombectomy. Validation of this simple strategy in a larger trial is urgent.

  12. Biomechanical and histological effects of augmented soft tissue mobilization therapy on achilles tendinopathy in a rabbit model.

    Science.gov (United States)

    Imai, Kan; Ikoma, Kazuya; Chen, Qingshan; Zhao, Chunfeng; An, Kai-Nan; Gay, Ralph E

    2015-02-01

    Augmented soft tissue mobilization (ASTM) has been used to treat Achilles tendinopathy and is thought to promote collagen fiber realignment and hasten tendon regeneration. The objective of this study was to evaluate the biomechanical and histological effects of ASTM therapy on rabbit Achilles tendons after enzymatically induced injury. This study was a non-human bench controlled research study using a rabbit model. Both Achilles tendons of 12 rabbits were injected with collagenase to produce tendon injury simulating Achilles tendinopathy. One side was then randomly allocated to receive ASTM, while the other received no treatment (control). ASTM was performed on the Achilles tendon on postoperative days 21, 24, 28, 31, 35, and 38. Tendons were harvested 10 days after treatment and examined with dynamic viscoelasticity and light microscopy. Cross-sectional area in the treated tendons was significantly greater than in controls. Storage modulus tended to be lower in the treated tendons but elasticity was not significantly increased. Loss modulus was significantly lower in the treated tendons. There was no significant difference found in tangent delta (loss modulus/storage modulus). Microscopy of control tendons showed that the tendon fibers were wavy and type III collagen was well stained. The tendon fibers of the augmented soft tissue mobilization treated tendons were not wavy and type III collagen was not prevalent. Biomechanical and histological findings showed that the Achilles tendons treated with ASTM had better recovery of biomechanical function than did control tendons. Copyright © 2015 National University of Health Sciences. Published by Elsevier Inc. All rights reserved.

  13. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Li T

    2015-06-01

    Full Text Available Tianyuzi Li,1 Howard E Gendelman,1,2 Gang Zhang,1 Pavan Puligujja,1 JoEllyn M McMillan,1 Tatiana K Bronich,2 Benson Edagwa,1 Xin-Ming Liu,1,2 Michael D Boska3 1Department of Pharmacology and Experimental Neuroscience, 2Department of Pharmaceutical Sciences, 3Department of Radiology, University of Nebraska Medical Center, Omaha, NE, USA Abstract: Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART. Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK, pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO] particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. Keywords: folic acid, decorated nanoparticles, magnetite, theranostics, magnetic resonance imaging

  14. Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

    Directory of Open Access Journals (Sweden)

    Renata Miossi

    2013-01-01

    phosphokinase (p = 0.40 and ribonucleoprotein antibody levels (p = 0.98, remained largely unchanged pre and post-vaccination. No severe side effects were reported. CONCLUSIONS: The non-adjuvanted influenza A/H1N1 vaccination immune response in mixed connective tissue disease patients is adequate and does not depend on the disease manifestations and therapy.

  15. Increased expression of heat shock protein 70 and heat shock factor 1 in chronic dermal ulcer tissues treated with laser-aided therapy.

    Science.gov (United States)

    Zhou, Jian-da; Luo, Cheng-qun; Xie, Hui-qing; Nie, Xin-min; Zhao, Yan-zhong; Wang, Shao-hua; Xu, Yi; Pokharel, Pashupati Babu; Xu, Dan

    2008-07-20

    Chronic dermal ulcers are also referred to as refractory ulcers. This study was conducted to elucidate the therapeutic effect of laser on chronic dermal ulcers and the induced expression of heat shock factor 1 (HSF1) and heat shock protein 70 (HSP70) in wound tissues. Sixty patients with 84 chronic dermal ulcers were randomly divided into traditional therapy and laser therapy groups. Laser treatment was performed in addition to traditional therapy in the laser therapy group. The treatment efficacy was evaluated after three weeks. Five tissue sections of healing wounds were randomly collected along with five normal skin sections as controls. HSP70-positive cells from HSP70 immunohistochemical staining were counted and the gray scale of positive cells was measured for statistical analysis. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the mRNA and protein expressions of HSF1 and HSP70. The cure rate of the wounds and the total efficacy in the laser therapy group were significantly higher than those in the traditional therapy group (P ulcers plays a facilitating role in healing due to the mechanism of laser-activated endogenous heat shock protection in cells in wound surfaces.

  16. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads.

    Science.gov (United States)

    Lamers, Susanna L; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J; Fogel, Gary B; Salemi, Marco; Garcia, Debra L; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A; McGrath, Michael S; Singer, Elyse J

    2016-10-15

    HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is

  17. Distribution patterns of Gd-DTPA-enhanced magnetic resonance imaging after intravenous tissue plasminogen activator therapy for acute myocardial infarction

    International Nuclear Information System (INIS)

    Fukuzawa, Shigeru; Watanabe, Hiroyuki; Shimada, Kazuhiro; Katagiri, Nakoto; Ozawa, Shun

    1994-01-01

    In patients who received thrombolytic therapy for acute myocardial infarction (AMI), we observed 3 distinct patterns in gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance (MR) imaging. To clarify the significance of these distribution patterns of Gd-DTPA, 20 consecutive patients underwent Gd-DTPA-enhanced MR imaging 7-10 days after AMI. All of the patients received intravenous recombinant tissue plasminogen activator (IVTPA) within 6 h of onset. Echocardiograms were obtained prior to and serially over 10 days, and interpreted for regional wall motion. Coronary angiograms were obtained the day before discharge. None of the 6 patients with a closed infarct-related artery, and 9 of the 14 patients with an open artery, demonstrated subendocardial enhancement (p<0.05). All of these latter 9 patients demonstrated a significant improvement in wall motion between days 1 and 10 after AMI. In contrast, only 1 of the 7 patients with transmural enhancement and none of the 4 patients with non-homogeneous enhancement demonstrated improvement of wall motion on day 10 (p<0.05). We concluded that subendocardial enhancement was a fair prognostic sign for restoration of regional cardiac function in patients who received IVTPA during AMI. (author)

  18. Radiological changes of bones and soft tissues after irradiation therapy in patients with Wilms' tumor and neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, Hiroaki; Okabe, Ikuo

    1989-04-01

    Late effects of tele cobalt 60 therapy on bones and soft tissues were studied radiologically in 24 patients with neuroblastoma and Wilms' tumor. The degree of changes in spinal bodies was influenced by the dose of irradiation as well as the age of patients at the time of irradiation. In patients who had 15 to 19 Gy of irradiation at the ages under one year old, a moderate to severe degree of changes was observed. Many patients showed atrophies of iliac bone, ribs, and erector spinae and psoas muscles on the side of the irradiation. In patients who were equal to or over 12 y.o. at the time of the examination, the degree of atrophy of erector spinae muscles on the side of the irradiation was greater than that of the patients who were less than 12 y.o.. Scoliosis was observed in 71% of patients and it had a tendency to aggravate at puberty. Because there was a significant correlation between the degree of scoliosis and the severity of the atrophic erector spinae muscle, the latter was thought to contribute much to the development of the former. At present, all patients are living with no limitation of their daily activities and no one needs medical care. (author).

  19. Influence of radiation therapy on lung tissue in breast cancer patients. CT-assessed density changes 4 years after completion of radiotherapy

    International Nuclear Information System (INIS)

    Svane, G.; Rotstein, S.; Lax, I.

    1995-01-01

    CT-assessed density changes in lung tissues were measured in 22 disease-free breast cancer patients 4 years after completion of radiation therapy. All patients had previously undergone similar CT-examinations before treatment, 3 months, and 9 months after radiotherapy. In patients with visible areas of increased lung density at earlier CT-examinations a decrease of focal findings was observed at 4 years. In patients without focal findings, an increase in density relative to that before therapy was observed. The difference between the mean lung density values among those with visible radiological findings and those without was statistically significant both at 3 and 9 months after therapy. However, this difference did not persist at 4 years. These results may indicate a 2-phase development of radiation-induced lung damages - an acute phase and a late phase; the late phase emerging slowly, and in this study detectable 4 years after completion of radiation therapy. (orig.)

  20. Effect of negative pressure therapy on repair of soft tissues of the lower extremities in patients with neuropathic and neuroischaemic forms of diabetic foot syndrome

    Directory of Open Access Journals (Sweden)

    Ekaterina Leonidovna Zaytseva

    2014-06-01

    Full Text Available AimTo evaluate the efficiency of topical negative pressure wound therapy (NPWT compared with standard therapy for the regeneration of the soft tissues of the lower extremities in patients with diabetic foot syndrome.Materials and MethodsThe effects of negative pressure therapy on the clinical (size, tissue oxygenation, histological (light microscopy and immunohistochemical (CD68, MMP-9, TIMP-1 aspects of repair of the soft tissue of the lower extremities in patients with diabetes mellitus were compared with those of standard treatment. Thirty-one patients with diabetic foot ulcers were included in the study from the moment of debridement until the plastic closure of the wound. During the perioperative period, 13 patients received NPWT (-90 to -120 mmHg and 18 patients received standard therapy.ResultsA reduction of the wound area (26.6%±17.2% and the depth of the defects (40.5%±25.6% were achieved with negative pressure therapy compared with baseline data. In the control group, the corresponding values were 25.3%±19.4% and 21.8%±21.6%, respectively. The results of transcutaneous oximetry showed a greater increase in the level of local hemodynamics in the study group (p <0.04. An important criterion for wound preparation for a plastic closure is filling it with granulation tissue by more than 75%. In the study group, 95% of patients had wounds filled with 89.9%±17% of abundant granulation tissue. The histological data of the study group show a significant reduction of oedema by 80% (p <0.05, improved extracellular matrix organization (p <0.05, 90% (p <0.05 dissolution of inflammatory infiltrate and the formation of healthy granulation tissue (p <0.05. Immunohistochemical analysis demonstrated a significant decrease in the number of macrophages in the dermis (CD68 expression (p <0.05. In both groups, the level of MMP-9 was decreased. However, the ratio of MMP-9:TIMP-1 was lower in the study group (p <0.05.ConclusionThe findings suggest that

  1. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Adam J., E-mail: adam_olszewski@brown.edu; Desai, Amrita

    2014-03-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas.

  2. Radiation Therapy Administration and Survival in Stage I/II Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue

    International Nuclear Information System (INIS)

    Olszewski, Adam J.; Desai, Amrita

    2014-01-01

    Purpose: To determine the factors associated with the use of radiation therapy and associated survival outcomes in early-stage marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT). Methods and Materials: We extracted data on adult patients with stage I/II MALT lymphoma diagnoses between 1998 and 2010 recorded in the Surveillance, Epidemiology, and End Results (SEER) database. We studied factors associated with radiation therapy administration in a logistic regression model and described the cumulative incidence of lymphoma-related death (LRD) according to receipt of the treatment. The association of radiation therapy with survival was explored in multivariate models with adjustment for immortal time bias. Results: Of the 7774 identified patients, 36% received radiation therapy as part of the initial course of treatment. Older patients; black or Hispanic men; white, Hispanic, and black women; and socioeconomically disadvantaged and underinsured patients had a significantly lower chance of receiving radiation therapy. Radiation therapy administration was associated with a lower chance of LRD in most sites. In cutaneous, ocular, and salivary MALT lymphomas, the 5-year estimate of LRD after radiation therapy was 0%. The association of radiation therapy with overall survival in different lymphoma sites was heterogeneous, and statistically significant in cutaneous (hazard ratio 0.45, P=.009) and ocular (hazard ratio 0.47, P<.0001) locations after multivariate adjustment. Conclusions: Demographic factors are associated with the use of radiation therapy in MALT lymphoma. Clinicians should be sensitive to those disparities because the administration of radiation therapy may be associated with improved survival, particularly in cutaneous and ocular lymphomas

  3. Effect of metformin therapy on the levels of certain adipose tissue hormones and mediators of nonspecific generalized inflammation in patients with newly diagnosed type 2 diabetes

    Directory of Open Access Journals (Sweden)

    A.M. Urbanovych

    2015-05-01

    Full Text Available The aim of the study was to investigate the influence of the drug metformin on the levels of adipose tissue hormones and generalized nonspecific mediators of inflammation in type 2 diabetes. 38 patients with newly diagnosed type 2 diabetes were followed up before and after 12 months of hypoglycemic monotherapy with glucophage. The results indicate that the normalization of carbohydrate metabolism indices and decreased body weight of patients in the presence of the therapy is due not only to direct effects of metformin in improving glucose uptake by peripheral tissues, but by the ability of the drug to modulate adipocytokine secretion.

  4. SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Y [DCH Reg. Medical Center, Tuscaloosa, AL (United States)

    2016-06-15

    Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. The margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.

  5. Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

    International Nuclear Information System (INIS)

    Deman, Pierre; Vautrin, Mathias; Edouard, Magali; Stupar, Vasile; Bobyk, Laure; Farion, Régine; Elleaume, Hélène; Rémy, Chantal; Barbier, Emmanuel L.; Estève, François; Adam, Jean-François

    2012-01-01

    Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 × 5 × 4.8 mm 3 volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 × 8 × 7.8 mm 3 volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 ± 12.5 days versus 23.3 ± 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

  6. Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Deman, Pierre [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Vautrin, Mathias [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); DOSIsoft, Cachan (France); Edouard, Magali [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Stupar, Vasile [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Bobyk, Laure; Farion, Regine [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Elleaume, Helene [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Remy, Chantal; Barbier, Emmanuel L. [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Esteve, Francois [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Adam, Jean-Francois, E-mail: adam@esrf.fr [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France)

    2012-03-15

    Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 Multiplication-Sign 5 Multiplication-Sign 4.8 mm{sup 3} volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 Multiplication-Sign 8 Multiplication-Sign 7.8 mm{sup 3} volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 {+-} 12.5 days versus 23.3 {+-} 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

  7. Determination of optical properties, drug concentration, and tissue oxygenation in human pleural tissue before and after Photofrin-mediated photodynamic therapy

    Science.gov (United States)

    Ong, Yi Hong; Padawer-Curry, Jonah; Finlay, Jarod C.; Kim, Michele M.; Dimofte, Andreea; Cengel, Keith; Zhu, Timothy C.

    2018-02-01

    PDT efficacy depends on the concentration of photosensitizer, oxygen, and light delivery in patient tissues. In this study, we measure the in-vivo distribution of important dosimetric parameters, namely the tissue optical properties (absorption μa (λ) and scattering μs ' (λ) coefficients), photofrin concentration (cphotofrin), blood oxygen saturation (%StO2), and total hemoglobin concentration (THC), before and after PDT. We characterize the inter- and intra-patient heterogeneity of these quantities and explore how these properties change as a result of PDT treatment. The result suggests the need for real-time dosimetry during PDT to optimize the treatment condition depending on the optical and physiological properties.

  8. Tissue oxygenation as a target for goal-directed therapy in high-risk surgery : a pilot study

    NARCIS (Netherlands)

    van Beest, Paul A.; Vos, Jaap Jan; Poterman, Marieke; Kalmar, Alain F.; Scheeren, Thomas W. L.

    2014-01-01

    Background:  Tissue hypoperfusion occurs frequently during surgery and may contribute to postoperative organ dysfunction. There is a need for perioperative treatment protocols aiming at improving tissue oxygenation (StO(2)). We hypothesised that intra-operative optimisation of StO(2) improves tissue

  9. Treatment of tension-type headache with articulatory and suboccipital soft tissue therapy: A double-blind, randomized, placebo-controlled clinical trial.

    Science.gov (United States)

    Espí-López, Gemma V; Gómez-Conesa, Antonia; Gómez, Anna Arnal; Martínez, Josep Benítez; Pascual-Vaca, Angel Oliva; Blanco, Cleofás Rodríguez

    2014-10-01

    This study researches the effectiveness of two manual therapy treatments focused on the suboccipital region for tension-type headache. A randomized double-blind clinical trial was conducted over a period of four weeks with a follow-up at one month. Eighty-four patients with a mean age of 39.7 years (SD 11.4) with tension-type headache were assigned to 4 groups which included the following manual therapy treatment: suboccipital soft tissue inhibition; occiput-atlas-axis global manipulation; combination of both techniques; and a control group. The primary assessment consisted of collecting socio-demographic data and headache characteristics in a one-month base period, data such as age, gender, severity of pain, intensity and frequency of headache, among other. Outcome secondary assessment were: impact of headache, disability, ranges of motion of the craniocervical junction, frequency and intensity of headache, and pericranial tenderness. In the month prior to the study, average pain intensity, was rated at 6.49 (SD 1.69), and 66.7% subjects suffered headaches of moderate intensity. After 8 weeks, statistically significant improvements were noted. OAA manipulative treatment and combined therapy treatments proved to be more effective than suboccipital soft tissue inhibition for tension-type headache. The treatment with suboccipital soft tissue inhibition, despite producing less significant results, also has positive effects on different aspects of headache. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Boron neutron capture therapy (BNCT) inhibits tumor development from precancerous tissue: An experimental study that supports a potential new application of BNCT

    International Nuclear Information System (INIS)

    Monti Hughes, A.; Heber, E.M.; Pozzi, E.; Nigg, D.W.; Calzetta, O.; Blaumann, H.; Longhino, J.; Nievas, S.I.; Aromando, R.F.; Itoiz, M.E.; Trivillin, V.A.; Schwint, A.E.

    2009-01-01

    We previously demonstrated the efficacy of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-10 (Na 2 10 B 10 H 10 ) and (GB-10+BPA) to control tumors, with no normal tissue radiotoxicity, in the hamster cheek pouch oral cancer model. Herein we developed a novel experimental model of field-cancerization and precancerous lesions (globally termed herein precancerous tissue) in the hamster cheek pouch to explore the long-term potential inhibitory effect of the same BNCT protocols on the development of second primary tumors from precancerous tissue. Clinically, second primary tumor recurrences occur in field-cancerized tissue, causing therapeutic failure. We performed boron biodistribution studies followed by in vivo BNCT studies, with 8 months follow-up. All 3 BNCT protocols induced a statistically significant reduction in tumor development from precancerous tissue, reaching a maximum inhibition of 77-100%. The inhibitory effect of BPA-BNCT and (GB-10+BPA)-BNCT persisted at 51% at the end of follow-up (8 months), whereas for GB-10-BNCT it faded after 2 months. Likewise, beam-only elicited a significant but transient reduction in tumor development. No normal tissue radiotoxicity was observed. At 8 months post-treatment with BPA-BNCT or (GB-10+BPA)-BNCT, the precancerous pouches that did not develop tumors had regained the macroscopic and histological appearance of normal (non-cancerized) pouches. A potential new clinical application of BNCT would lie in its capacity to inhibit local regional recurrences.

  11. Tumor development in field-cancerized tissue is inhibited by a double application of Boron neutron capture therapy (BNCT) without exceeding radio-tolerance

    International Nuclear Information System (INIS)

    Monti Hughes, Andrea; Heber, Elisa M.; Itoiz, Maria E.; Molinari, Ana J.; Garabalino, Marcela A.; Trivillin, Veronica A.; Schwint, Amanda E.; Aromando, Romina F.

    2009-01-01

    Introduction: BNCT is based on the capture reaction between boron, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue, sparing normal tissue. We previously evidenced a remarkable therapeutic success of a 'single' application of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-1(Na 2 10 B 10 H 10 ) or (GB-10+BPA) to treat hamster cheek pouch tumors with no normal tissue radiotoxicity. Based on these results, we developed a model of precancerous tissue in the hamster cheek pouch for long-term studies. Employing this model we evaluated the long-term potential inhibitory effect on the development of second primary tumors from precancerous tissue and eventual radiotoxicity of a single application of BNCT mediated by BPA, GB-10 or (GB-10+BPA), in the RA-6. The clinical rationale of this study was to search for a BNCT protocol that is therapeutic for tumor, not radio-toxic for the normal tissue that lies in the neutron beam path, and exerts the desired inhibitory effect on the development of second primary tumors, without exceeding the radio-tolerance of precancerous tissue, the dose limiting tissue in this case. Second primary tumors that arise in precancerous tissue (also called locoregional recurrences) are a frequent cause of therapeutic failure in head and neck tumors. Aim: Evaluate the radiotoxicity and inhibitory effect of a 'double' application of the same BNCT protocols that were proved therapeutically successful for tumor and precancerous tissue, with a long term follow up (8 months). A 'double' application of BNCT is a potentially useful strategy for the treatment of tumors, in particular the larger ones, but the cost in terms of side-effects in dose-limiting tissues might preclude its application and requires cautious evaluation. Materials and methods: We performed a double application of 1) BPA-BNCT; 2) (GB

  12. Development of Causative Treatment Strategies for Lacrimal Gland Insufficiency by Tissue Engineering and Cell Therapy. Part 2: Reconstruction of Lacrimal Gland Tissue: What Has Been Achieved So Far and What Are the Remaining Challenges?

    Science.gov (United States)

    Massie, Isobel; Dietrich, Jana; Roth, Mathias; Geerling, Gerd; Mertsch, Sonja; Schrader, Stefan

    2016-10-01

    The lacrimal gland is located in the upper temporal compartment of the orbita, and along with the ocular surface, eye lids, and sensory and motor nerves forms the lacrimal functional unit (LFU). The LFU is responsible for producing, distributing, and maintaining the tear film in order to maintain a smooth, moist, and regular ocular surface epithelium such that appropriate refractive properties are achieved and the eyeball is protected against dust, debris, and pathogens. If the main lacrimal gland is impaired (due to either disease or injury), this balance is disrupted, and severe quantitative dry eye syndrome (DES) can develop. DES treatments remain palliative, with the most commonly used therapies being based on tear substitution, tear retention, and control of inflammation on the ocular surface. Causative treatments such as salivary gland transplantation have shown to reduce symptoms in very severe cases, however can cause problems on the ocular surface due to different properties of saliva and tears. Therefore, causative approaches for treating DES by regeneration or reconstruction of lacrimal gland tissue depending on disease severity seem highly appealing. This article reviews current approaches for in vitro reconstruction of lacrimal gland tissue. Finally, the limitations that must be overcome before a new, tissue-engineered therapy may be delivered to clinic will be discussed.

  13. Determination of gold accumulation in human tissues caused by gold therapy using x-ray fluorescence analysis

    International Nuclear Information System (INIS)

    Bacso, J.; Uzonyi, I.; Dezsoe, B.

    1986-08-01

    Human autopsy tissues from five patients with rheumatoid arthritis treated earlier with aqueous solution of gold and those from untreated control with the same disease were analyzed by x-ray fluorescence spectrometry using a conventional Si(Li) detection system. The gold and zinc concentrations of tissues were determined and compared with literature data. Correlation was found between Zn and Au concentrations in heart, lung, kidney and liver tissues. (author)

  14. Rescue localized intra-arterial thrombolysis for hyperacute MCA ischemic stroke patients after early non-responsive intravenous tissue plasminogen activator therapy

    International Nuclear Information System (INIS)

    Kim, Dong Joon; Kim, Dong Ik; Kim, Seo Hyun; Lee, Kyung Yeol; Heo, Ji Hoe; Han, Sang Won

    2005-01-01

    The outcome of patients who show no early response to intravenous (i.v.) tissue plasminogen activator (tPA) therapy is poor. The objective of this study was to evaluate the feasibility of rescue localized intra-arterial thrombolysis (LIT) therapy for acute ischemic stroke patients after an early non-responsive i.v. tPA therapy. Patients with proximal MCA occlusions who were treated by LIT (n=10) after failure of early response [no improvement or improvement of National Institute of Health Stroke Scale (NIHSS) scores of ≤3] to i.v. tPA therapy (0.9 mg/kg - 10% bolus and 90% i.v. infusion over 60 min) were selected. The recanalization rates, incidence of post-thrombolysis hemorrhage and clinical outcomes [baseline and discharge NIHSS scores, mortality, 3 months Barthel index (BI) and modified Rankin score (mRS)] were evaluated. Rescue LIT therapy was performed on ten MCA occlusion patients (male:female=3:7, mean age 71 years). The mean time between the initiation of i.v. tPA therapy and the initiation of intra-arterial urokinase (i.a. UK) was 117±25.0 min [time to i.v. tPA 137±32 min; time to digital subtraction angiography (DSA) 221±42 min; time to i.a. UK 260±46 min]. The baseline NIHSS scores showed significant improvement at discharge (median from 18 to 6). Symptomatic hemorrhage and, consequent, mortality were noted in 2/10 (20%) patients. Three months good outcome was noted in 4/10 (40%, mRS 0-2) and 3/10 (30%, BI ≥95). In conclusion, rescue LIT therapy can be considered as a treatment option for patients not showing early response to full dose i.v. tPA therapy. Larger scale studies for further validation of this protocol may be necessary. (orig.)

  15. Role of outpatient parenteral antibiotic therapy in the treatment of community acquired skin and soft tissue infections in Singapore.

    Science.gov (United States)

    Chan, Monica; Ooi, Chee Kheong; Wong, Joshua; Zhong, Lihua; Lye, David

    2017-07-06

    Treatment of community acquired skin and soft tissue infections (SSTIs) is a common indication for outpatient parenteral antibiotic therapy (OPAT) in USA, UK and Australasia, however data from Asia are lacking. OPAT is well established within the Singapore healthcare since 2002, however, systematic use of OPAT for the treatment of SSTIs remains infrequent. In this report, we describe the treatment and outcome of patients with SSTIs referred directly from Emergency Department (ED) to OPAT for continuation of intravenous (IV) antibiotics in Singapore, thus avoiding potential hospital admission. This is a single center university hospital retrospective study of patients with SSTIs presenting to ED who were assessed to require IV antibiotics and accepted to the OPAT clinic for continuation of IV treatment. Exclusion criteria were: haemodynamic instability, uncontrolled or serious underlying co-morbidities, necessity for inpatient surgical drainage, facial cellulitis and cephalosporin allergy. Patients returned daily to the hospital’s OPAT clinic for administration of IV antibiotics and review, then switched to oral antibiotics on improvement. From 7 February 2012 to 31 July 2015, 120 patients with SSTIs were treated in OPAT. Median age was 56 years and 63% were male. Lower limbs were affected in 91%. Diabetes was present in 20%. Sixty-seven (56%) had been treated with oral antibiotics for a median duration of 3 days prior to OPAT treatment. Common symptoms were erythema (100%), swelling (96%), pain (88%) and fever (55%). Antibiotics administered were IV cefazolin with oral probenecid (71%) or IV ceftriaxone (29%) for median 3 days then oral cloxacillin (85%) for median 7 days. Clinical improvement occurred in 90%. Twelve patients (10%) were hospitalized for worsening cellulitis, with 4 patients requiring surgical drainage of abscess. Microbiological cultures from 2 patients with drained abscess grew methicillin sensitive Staphylococcus aureus (MSSA) and Klebsiella

  16. The prevalence of thyroid tissue along the thyroglossal tract on SPECT/CT following I131 ablation therapy after total thyroidectomy for thyroid cancer

    International Nuclear Information System (INIS)

    Barber, T.W.; Cherk, M.H.; Yap, K.S.K.; Kalff, V.; Topliss, D.J.; Serpell, J.W.

    2015-01-01

    Full text of publication follows. Aim: the aims of this study are first to determine the prevalence of thyroid tissue along the thyroglossal tract on SPECT/CT and secondly to assess the contribution of this tissue to total neck I-131 activity in patients treated with I-131 ablation therapy after total thyroidectomy for thyroid cancer. Materials and methods: a total of 63 consecutive patients with well differentiated thyroid cancer treated with total thyroidectomy underwent whole body planar imaging and SPECT/CT of the neck 48 hours following ablative I-131 therapy. On SPECT/CT, thyroglossal tract thyroid tissue was defined as radioiodine activity in the anterior neck, superior to the thyroid bed in close proximity to the midline without evidence of localisation to lymph nodes. On planar imaging, thyroglossal tract thyroid tissue was defined as linear radioiodine activity in the midline of the neck superior to the thyroid bed. SPECT/CT and planar images were classified by two independent reviewers as positive, negative or equivocal with interobserver agreement quantified using a Kappa score. Disagreement was resolved using a third reviewer. Quantitation of thyroglossal tract thyroid tissue and total neck I-131 activity was performed using region of interest analysis on planar imaging following localisation on SPECT/CT. Results: thyroglossal tract thyroid tissue was present in 31/63 (49%; 95% CI: 37-61%) patients on SPECT/CT. In these 31 patients, thyroglossal tract thyroid tissue contributed to an average of 49% of total neck activity. Interobserver agreement was substantial on SPECT/CT (Kappa = 0.76; 95% CI: 0.61-0.91) and fair on planar imaging (Kappa = 0.31; 95% CI: 0.15-0.47). Conclusion: thyroid tissue along the thyroglossal tract was present in one half of patients in our study population and can contribute to a significant amount of total neck I-131 activity. Given the high prevalence of thyroglossal tract thyroid tissue, our results suggest that total neck

  17. Influence of Spinal Manipulative Therapy Force Magnitude and Application Site on Spinal Tissue Loading: A Biomechanical Robotic Serial Dissection Study in Porcine Motion Segments.

    Science.gov (United States)

    Funabashi, Martha; Nougarou, François; Descarreaux, Martin; Prasad, Narasimha; Kawchuk, Greg

    In order to define the relation between spinal manipulative therapy (SMT) input parameters and the distribution of load within spinal tissues, the aim of this study was to determine the influence of force magnitude and application site when SMT is applied to cadaveric spines. In 10 porcine cadavers, a servo-controlled linear actuator motor provided a standardized SMT simulation using 3 different force magnitudes (100N, 300N, and 500N) to 2 different cutaneous locations: L3/L4 facet joint (FJ), and L4 transverse processes (TVP). Vertebral kinematics were tracked optically using indwelling bone pins, the motion segment removed and mounted in a parallel robot equipped with a 6-axis load cell. The kinematics of each SMT application were replicated robotically. Serial dissection of spinal structures was conducted to quantify loading characteristics of discrete spinal tissues. Forces experienced by the L3/L4 segment and spinal structures during SMT replication were recorded and analyzed. Spinal manipulative therapy force magnitude and application site parameters influenced spinal tissues loading. A significant main effect (P < .05) of force magnitude was observed on the loads experienced by the intact specimen and supra- and interspinous ligaments. The main effect of application site was also significant (P < .05), influencing the loading of the intact specimen and facet joints, capsules, and ligamentum flavum (P < .05). Spinal manipulative therapy input parameters of force magnitude and application site significantly influence the distribution of forces within spinal tissues. By controlling these SMT parameters, clinical outcomes may potentially be manipulated. Copyright © 2017. Published by Elsevier Inc.

  18. Magnetic resonance imaging and morphometric histologic analysis of prostate tissue composition in predicting the clinical outcome of terazosin therapy in benign prostatic hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Isen, K. [Karaelmas Univ., Zonguldak (Turkey). School of Medicine; Sinik, Z.; Alkibay, T.; Sezer, C.; Soezen, S.; Atilla, S.; Ataoglu, O.; Isik, S.

    2001-02-01

    The purpose of this study was to determine whether magnetic resonance imaging (MRI) or quantitative color-imaged morphometric analysis (MA) of the prostate gland are related to the clinical response to terazosin. Thirty-six male patients with symptomatic benign prostatic hyperplasia (BPH) with a serum prostate-specific antigen level of 4-10 ng/mL underwent MRI with body coil, transrectal prostate unltrasonography and biopsy prior to terazosin therapy. For MRI-determined stromal and non-stromal BPH, the ratio of the signal intensity of the inner gland to the obturator internus muscle was evaluated. Histologic sections were stained with hematoxylin and eosin. The MA of the specimens was performed by Samba 2000. Results of the two techniques were interpreted according to the terazosin therapy results. The mean stromal percentage was 60.5{+-}18.0%. No statistically significant relationship was found between the clinical outcome of terazosin and the MRI findings. The MA results showed a significant relationship between the percentage of stroma and the percent change of the peak urinary flow rate, but not with the percent change of the international prostate symptom score after terazosin therapy (P<0.05). Magnetic resonance imaging alone is not sufficient in predicting the response to terazosin therapy. Morphometric analysis of BPH tissue composition can be used in predicting the clinical outcome of terazosin therapy but it is suitable only in patients for whom prostatic biopsy is necessary in order to rule out prostate cancer. (author)

  19. Magnetic resonance imaging and morphometric histologic analysis of prostate tissue composition in predicting the clinical outcome of terazosin therapy in benign prostatic hyperplasia

    International Nuclear Information System (INIS)

    Isen, K.; Sinik, Z.; Alkibay, T.; Sezer, C.; Soezen, S.; Atilla, S.; Ataoglu, O.; Isik, S.

    2001-01-01

    The purpose of this study was to determine whether magnetic resonance imaging (MRI) or quantitative color-imaged morphometric analysis (MA) of the prostate gland are related to the clinical response to terazosin. Thirty-six male patients with symptomatic benign prostatic hyperplasia (BPH) with a serum prostate-specific antigen level of 4-10 ng/mL underwent MRI with body coil, transrectal prostate unltrasonography and biopsy prior to terazosin therapy. For MRI-determined stromal and non-stromal BPH, the ratio of the signal intensity of the inner gland to the obturator internus muscle was evaluated. Histologic sections were stained with hematoxylin and eosin. The MA of the specimens was performed by Samba 2000. Results of the two techniques were interpreted according to the terazosin therapy results. The mean stromal percentage was 60.5±18.0%. No statistically significant relationship was found between the clinical outcome of terazosin and the MRI findings. The MA results showed a significant relationship between the percentage of stroma and the percent change of the peak urinary flow rate, but not with the percent change of the international prostate symptom score after terazosin therapy (P<0.05). Magnetic resonance imaging alone is not sufficient in predicting the response to terazosin therapy. Morphometric analysis of BPH tissue composition can be used in predicting the clinical outcome of terazosin therapy but it is suitable only in patients for whom prostatic biopsy is necessary in order to rule out prostate cancer. (author)

  20. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies.

    LENUS (Irish Health Repository)

    Moran, Ellen M

    2009-01-01

    INTRODUCTION: The aim of this study was to examine IL-17A in patients, following anti-TNF-alpha therapy and the effect of IL-17A on matrix turnover and cartilage degradation. METHODS: IL-17A expression was examined by ELISA and immunohistology in the rheumatoid arthritis (RA) joints. RA whole synovial tissue explant (RA ST), primary synovial fibroblasts (RASFC), human cartilage and chondrocyte cultures were stimulated with IL-17A +\\/- TNF-alpha and Oncostatin M (OSM). Matrix metalloproteinase (MMP) and tissue inhibitor (TIMP-1) were assessed by ELISA and zymography. Cartilage proteoglycan release was assessed histologically by Safranin-O staining. Clinical parameters, IL-17A, MMP\\/TIMP were assessed in patients pre\\/post biologic therapy. RESULTS: IL-17A levels were higher in RA vs osteoarthritis (OA)\\/normal joints (P < 0.05). IL-17A up-regulated MMP-1, -2, -9, and -13 in RA ST, RASFC, cartilage and chondrocyte cultures (P < 0.05). In combination with TNF-alpha and OSM, IL-17A shifted the MMP:TIMP-1 ratio in favor of matrix degradation (all P < 0.05). Cartilage proteoglycan depletion in response to IL-17A was mild; however, in combination with TNF-alpha or OSM showed almost complete proteoglycan depletion. Serum IL-17A was detected in 28% of patients commencing biologic therapy. IL-17A negative patients demonstrated reductions post therapy in serum MMP1\\/TIMP4, MMP3\\/TIMP1 and MMP3\\/TIMP4 ratios and an increase in CS846 (all P < 0.05). No significant changes were observed in IL-17A positive patients. CONCLUSIONS: IL-17A is produced locally in the inflamed RA joint. IL-17A promotes matrix turnover and cartilage destruction, especially in the presence of other cytokines, mimicking the joint environment. IL-17A levels are modulated in vivo, following anti-TNF therapy, and may reflect changes in matrix turnover.

  1. SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D [M.D. Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

  2. Efficacy and safety of extracorporeal shock wave therapy for acute and chronic soft tissue wounds: A systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Li; Fu, Xiao-Bing; Chen, Shuo; Zhao, Zhan-Bo; Schmitz, Christoph; Weng, Chang-Shui

    2018-04-19

    This study aimed to evaluate and compare the effects of extracorporeal shock wave therapy (ESWT) and conventional wound therapy (CWT) for acute and chronic soft tissue wounds. All English-language articles on ESWT for acute and chronic soft tissue wounds indexed in PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, Physiotherapy Evidence Database, and HealthSTAR published prior to June 2017 were included, as well as corresponding articles cited in reference lists of related review articles. The methodological quality of the selected studies was assessed with the Cochrane Collaboration's "risk of bias" tool. Study design, subject demographics, wound aetiology, treatment protocols, assessment indexes, and follow-up duration were extracted. The fixed or random-effects model was used to calculate the pooled effect sizes according to studies' heterogeneity. Ten randomised controlled trials (RCTs) involving 473 patients were included in this systematic review and meta-analysis. The meta-analysis showed that ESWT statistically significantly increased the healing rate of acute and chronic soft tissue wounds 2.73-fold (odds ratio, OR = 3.73, 95% confidence interval, CI: 2.30-6.04, P SMD) = 30.45; 95% CI: 23.79-37.12; P SMD = -2.86, 95% CI:-3.78 to -1.95, P SMD = -19.11, 95% CI: -23.74 to -14.47, P infection by 53% (OR = 0.47, 95% CI: 0.24-0.92, P = .03) when compared with CWT alone. Serious adverse effects were not reported. ESWT showed better therapeutic effects on acute and chronic soft tissue wounds compared with CWT alone. However, higher-quality and well-controlled RCTs are needed to further assess the role of ESWT for acute and chronic soft tissue wounds. © 2018 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  3. SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

    International Nuclear Information System (INIS)

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

    2015-01-01

    Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted

  4. Therapy-refractory Panton Valentine Leukocidin-positive community-acquired methicillin-sensitive Staphylococcus aureus sepsis with progressive metastatic soft tissue infection: a case report

    Directory of Open Access Journals (Sweden)

    Schefold Joerg C

    2007-12-01

    Full Text Available Abstract We report a case of fulminant multiple organ failure including the Acute Respiratory Distress Syndrome (ARDS, haemodynamic, and renal failure due to community-acquired methicillin-sensitive Panton Valentine Leukocidin (PVL positive spa-type 284 (ST121 Staphylococcus aureus septic shock. The patient's first clinical symptom was necrotizing pneumonia. Despite organism-sensitive triple antibiotic therapy with linezolid, imipenem and clindamycin from the first day of treatment, progressive abscess formation in multiple skeletal muscles was observed. As a result, repeated surgical interventions became necessary. Due to progressive soft tissue infection, the anti-microbial therapy was changed to a combination of clindamycin and daptomycin. Continued surgical and antimicrobial therapy finally led to a stabilisation of the patients' condition. The clinical course of our patient underlines the existence of a "PVL-syndrome" which is independent of in vitro Staphylococcus aureus susceptibility. The PVL-syndrome should not only be considered in patients with soft tissue or bone infection, but also in patients with pneumonia. Such a condition, which may easily be mistaken for uncomplicated pneumonia, should be treated early, aggressively and over a long period of time in order to avoid relapsing infection.

  5. Distally based saphenous neurocutaneous perforator flap combined with vac therapy for soft tissue reconstruction and hardware salvage in the lower extremities.

    Science.gov (United States)

    Wen, Gen; Wang, Chun-Yang; Chai, Yi-Min; Cheng, Liang; Chen, Ming; Yi-Min, L V

    2013-11-01

    The complex wound with the exposed hardware and infection is one of the common complications after the internal fixation of the tibia fracture. The salvage of hardware and reconstruction of soft tissue defect remain challenging. In this report, we presented our experience on the use of the distally based saphenous neurocutaneous perforator flap combined with vacuum-assisted closure (VAC) therapy for the coverage of the soft tissue defect and the exposed hardware in the lower extremity with fracture. Between January 2008 and July 2010, seven patients underwent the VAC therapy followed by transferring a reversed saphenous neurocutaneous perforator flap for reconstruction of the wound with exposed hardware around the distal tibia. The sizes of the flaps ranged from 6 × 3 cm to 15 × 6 cm. Six flaps survived completely. Partial necrosis occurred in one patient. There were no other complications of repair and donor sites. Bone healing was achieved in all patients. In conclusion, the reversed saphenous neurocutaneous perfortor flaps combined with the VAC therapy might be one of the options to cover the complex wound with exposed hardware in the lower extremities. © 2013 Wiley Periodicals, Inc.

  6. CdSe/ZnS Quantum Dots-Labeled Mesenchymal Stem Cells for Targeted Fluorescence Imaging of Pancreas Tissues and Therapy of Type 1 Diabetic Rats.

    Science.gov (United States)

    Liu, Haoqi; Tang, Wei; Li, Chao; Lv, Pinlei; Wang, Zheng; Liu, Yanlei; Zhang, Cunlei; Bao, Yi; Chen, Haiyan; Meng, Xiangying; Song, Yan; Xia, Xiaoling; Pan, Fei; Cui, Daxiang; Shi, Yongquan

    2015-12-01

    Mesenchymal stem cells (MSCs) have been used for therapy of type 1 diabetes mellitus. However, the in vivo distribution and therapeutic effects of transplanted MSCs are not clarified well. Herein, we reported that CdSe/ZnS quantum dots-labeled MSCs were prepared for targeted fluorescence imaging and therapy of pancreas tissues in rat models with type 1 diabetes. CdSe/ZnS quantum dots were synthesized, their biocompatibility was evaluated, and then, the appropriate concentration of quantum dots was selected to label MSCs. CdSe/ZnS quantum dots-labeled MSCs were injected into mouse models with type 1 diabetes via tail vessel and then were observed by using the Bruker In-Vivo F PRO system, and the blood glucose levels were monitored for 8 weeks. Results showed that prepared CdSe/ZnS quantum dots owned good biocompatibility. Significant differences existed in distribution of quantum dots-labeled MSCs between normal control rats and diabetic rats (p quantum dots-labeled MSC injection. Statistical differences existed between the blood glucose levels of the diabetic rat control group and MSC-injected diabetic rat group (p < 0.01), and the MSC-injected diabetic rat group displayed lower blood glucose levels. In conclusion, CdSe/ZnS-labeled MSCs can target in vivo pancreas tissues in diabetic rats, and significantly reduce the blood glucose levels in diabetic rats, and own potential application in therapy of diabetic patients in the near future.

  7. Usefulness of 99mTc(V)-dimercaptosuccinic acid scintigraphy in the assessment of response to external radiation therapy in soft tissue sarcoma in Giant Schnauzer dog

    International Nuclear Information System (INIS)

    Chaudhari, P. R.; Mathe, D.; Balogh, L.; Andocs, G.; Janoki, G. A.

    2005-01-01

    A nine-year-old male black Giant Schnauzer dog was referred for the scintigraphic evaluation with a history of malignant fibrosarcoma with a rapidly growing non painful mass on the left shoulder region quite near to the site of an operation performed four months ago. We carried out oncological scintigraphy using pentavalent 99mT echnetium labelled dimercaptosuccinic acid [ 99mT c(V)-DMSA], a tumour localising radiopharmaceutical agent. The study was performed to assess the margins, vascularity of the tumour and response to the cancer therapy. Uniform intense radiopharmaceutical uptake was observed in the lesion indicating its margins, vascularity and malignant nature. The dog was subjected to external radiation therapy to control the growth of the cancer and to bring the tumour mass to an operable size. The dog was followed up with 99mT c(V)-DMSA scintigraphy pre-irradiation and post-irradiation. Immediately after the post-irradiation scintigraphy, the dog was operated on. During the surgery, resection of the tumour margins was performed carefully using a hand held gamma probe to assure that no tumour tissue was left inside. In conclusion, the authors would like to state that 99mT c(V)-DMSA oncoscintigraphy is valuable in the assessment and evaluation of therapy in canine soft tissue cancer. (author)

  8. CdSe/ZnS Quantum Dots-Labeled Mesenchymal Stem Cells for Targeted Fluorescence Imaging of Pancreas Tissues and Therapy of Type 1 Diabetic Rats

    Science.gov (United States)

    Liu, Haoqi; Tang, Wei; Li, Chao; Lv, Pinlei; Wang, Zheng; Liu, Yanlei; Zhang, Cunlei; Bao, Yi; Chen, Haiyan; Meng, Xiangying; Song, Yan; Xia, Xiaoling; Pan, Fei; Cui, Daxiang; Shi, Yongquan

    2015-06-01

    Mesenchymal stem cells (MSCs) have been used for therapy of type 1 diabetes mellitus. However, the in vivo distribution and therapeutic effects of transplanted MSCs are not clarified well. Herein, we reported that CdSe/ZnS quantum dots-labeled MSCs were prepared for targeted fluorescence imaging and therapy of pancreas tissues in rat models with type 1 diabetes. CdSe/ZnS quantum dots were synthesized, their biocompatibility was evaluated, and then, the appropriate concentration of quantum dots was selected to label MSCs. CdSe/ZnS quantum dots-labeled MSCs were injected into mouse models with type 1 diabetes via tail vessel and then were observed by using the Bruker In-Vivo F PRO system, and the blood glucose levels were monitored for 8 weeks. Results showed that prepared CdSe/ZnS quantum dots owned good biocompatibility. Significant differences existed in distribution of quantum dots-labeled MSCs between normal control rats and diabetic rats ( p pancreas of rats in the diabetes group, and was about 32 %, while that in the normal control group rats was about 18 %. The blood glucose levels were also monitored for 8 weeks after quantum dots-labeled MSC injection. Statistical differences existed between the blood glucose levels of the diabetic rat control group and MSC-injected diabetic rat group ( p pancreas tissues in diabetic rats, and significantly reduce the blood glucose levels in diabetic rats, and own potential application in therapy of diabetic patients in the near future.

  9. The effect of customized beam shaping on normal tissue complications in radiation therapy of parotid gland tumors

    International Nuclear Information System (INIS)

    Keus, R.; Boer, R. de; Lebesque, J.; Noach, P.

    1991-01-01

    The impact of customized beam shaping was studied for 5 patients with parotid tumors treated with a paired wedged field technique. For each patient 2 plans were generated. The standard plan had unblocked portals with field sizes defined by the largest target contour found in any CT slice. In the 2nd plan customized beam's view (BEV) designed blocks were added to both beams. The differences in those distributions between the 2 types of plans were evaluated using dose-volume histograms (DVH). As expected, the dose distribution within the target volume showed no difference. However, a considerable sparing of normal tissue was observed for the plans with customized blocks. The volume of un-necessary exposed normal tissue that received more than 90 percent of the prescribed dose, was reduced by a factor of about 4: from 165 to 44 percent on an average, if the volume is expressed as a percentage of the target volume in each patient. In particular, the homolateral mandible showed a mean decrease of 21 percent of integral dose when blocks were used. Normal tissue complication probabilities (NTCP) were calculated. For a tumor dose of 70 Gy, the average bone necrosis probability was reduced from 8.4 percent (no blocks) to 4.1. percent (blocks). For other normal tissues such as nervous tissue, other soft tissues and bones a substantial reduction of integral dose was found for al patients when individual blocks were used. (author). 10 refs.; 4 figs.; 2 tabs

  10. Killing effect of EGFR-TKI combined with 125I seed implantation therapy on ⅢB-Ⅳ stage lung cancer tissue

    Directory of Open Access Journals (Sweden)

    Ai-Sheng Xiang

    2016-12-01

    Full Text Available Objective: To analyze the killing effect of EGFR-TKI combined with 125I seed implantation therapy on ⅢB-Ⅳ stage lung cancer tissue. Methods: A total of 78 patients with ⅢB-Ⅳ stage lung cancer were randomly divided into observation group and control group (n=39, control group received EGFR-TKI treatment and observation group received EGFR-TKI combined with 125I seed implantation therapy. Differences in apoptosis gene, invasion gene and autophagy gene expression in lung tissue were compared between two groups after 1 month of treatment. Results: Apoptosis genes PDCD5, bax and bcl-xS mRNA expression levels in lung tissue of observation group after 1 month of treatment were higher than those of control group while Bag-1, survivin and bcl-xL mRNA expression levels were lower than those of control group; invasion genes CD147, EGFR and DDX17 mRNA expression levels were lower than those of control group while Bin1, E-cadherin and Ovol2 mRNA expression levels were higher than those of control group; autophagy genes ARHI, Beclin1, Atg5, LC3B, pULK and PI3KC3 mRNA expression levels were higher than those of control group. Conclusions: EGFR-TKI combined with 125I seed implantation therapy can enhance the tumor killing effect on patients with ⅢB-Ⅳ stage lung cancer, and contribute to the optimization of overall condition and the extension of survival time.

  11. Combined therapy for critical limb ischemia: biomimetic PLGA microcarriers potentiates the pro-angiogenic effect of adipose tissue stromal vascular fraction cells.

    Science.gov (United States)

    Hoareau, Laurence; Fouchet, Florian; Planesse, Cynthia; Mirbeau, Sophie; Sindji, Laurence; Delay, Emmanuel; Roche, Régis; Montero-Menei, Claudia N; Festy, Franck

    2018-04-14

    We propose a regenerative solution in the treatment of critical limb ischemia. Poly-lactic/glycolic acid (PLGA) microcarriers were prepared and coated with laminin to be sterilized through γ-irradiation of 25 kGy at low temperature. Stromal vascular fraction (SVF) cells were extracted through enzymatic digestion of adipose tissue. Streptozotocin-induced diabetic mice underwent arteriotomy and received an administration of SVF cells combined or not with biomimetic microcarriers. Functional evaluation of the ischemic limb was then reported and tissue reperfusion was evaluated through fluorescence molecular tomography (FMT). Microcarriers were stable and functional after γ-irradiation until at least 12 months storage. Mice which received an injection of SVF cells in the ischemic limb have 22 % of supplementary blood supply within this limb 7 days after surgery compared to vehicle, whereas no difference was observed at day 14. With the combined therapy, the improvement of blood flow is significantly higher compared to vehicle, of about 31 % at day 7 and of about 11 % at day 14. Injection of SVF cells induces a significant 27 % decrease of necrosis compared to vehicle. This effect is more important when SVF cells were mixed with biomimetic microcarriers: - 37% compared to control. Although SVF cells injection leads to a non-significant 22 % proprioception recovery, the combined therapy induces a significant recovery of about 27 % compared to vehicle. We show that the combination of SVF cells from adipose tissue with laminin-coated PLGA microcarriers is efficient for CLI therapy in a diabetic mouse model. This article is protected by copyright. All rights reserved.

  12. Differences in Normal Tissue Response in the Esophagus Between Proton and Photon Radiation Therapy for Non-Small Cell Lung Cancer Using In Vivo Imaging Biomarkers.

    Science.gov (United States)

    Niedzielski, Joshua S; Yang, Jinzhong; Mohan, Radhe; Titt, Uwe; Mirkovic, Dragan; Stingo, Francesco; Liao, Zhongxing; Gomez, Daniel R; Martel, Mary K; Briere, Tina M; Court, Laurence E

    2017-11-15

    To determine whether there exists any significant difference in normal tissue toxicity between intensity modulated radiation therapy (IMRT) or proton therapy for the treatment of non-small cell lung cancer. A total of 134 study patients (n=49 treated with proton therapy, n=85 with IMRT) treated in a randomized trial had a previously validated esophageal toxicity imaging biomarker, esophageal expansion, quantified during radiation therapy, as well as esophagitis grade (Common Terminology Criteria for Adverse Events version 3.0), on a weekly basis during treatment. Differences between the 2 modalities were statically analyzed using the imaging biomarker metric value (Kruskal-Wallis analysis of variance), as well as the incidence and severity of esophagitis grade (χ 2 and Fisher exact tests, respectively). The dose-response of the imaging biomarker was also compared between modalities using esophageal equivalent uniform dose, as well as delivered dose to an isotropic esophageal subvolume. No statistically significant difference in the distribution of esophagitis grade, the incidence of grade ≥3 esophagitis (15 and 11 patients treated with IMRT and proton therapy, respectively), or the esophageal expansion imaging biomarker between cohorts (P>.05) was found. The distribution of imaging biomarker metric values had similar distributions between treatment arms, despite a slightly higher dose volume in the proton arm (P>.05). Imaging biomarker dose-response was similar between modalities for dose quantified as esophageal equivalent uniform dose and delivered esophageal subvolume dose. Regardless of treatment modality, there was high variability in imaging biomarker response, as well as esophagitis grade, for similar esophageal doses between patients. There was no significant difference in esophageal toxicity from either proton- or photon-based radiation therapy as quantified by esophagitis grade or the esophageal expansion imaging biomarker. Copyright © 2017 Elsevier

  13. [Ru(bipy)3]2+ nanoparticle-incorporate dental light cure resin to promote photobiomodulation therapy for enhanced vital pulp tissue repair

    Science.gov (United States)

    Mosca, Rodrigo C.; Young, Nicholas; Zeituni, Carlos A.; Arany, Praveen R.

    2018-02-01

    The use of nanoparticle on dental light cure resin is not new, currently several compounds (nanoadditives) are used to promote better communication between the restorative material and biological tissues. The interest for this application is growing up to enhance mechanical proprieties to dental tissue cells regeneration. Bioactive nanoparticles and complex compounds with multiple functions are the major target for optimizing the restorative materials. In this work, we incorporate [Ru(bipy)3]2+ nanoparticles, that absorbs energy at 450 nm (blue-light) and emits strongly at 620 nm (red-light), in PLGA Microspheres and insert it in Dental Light Cure Resin to promote the Photobiomodulation Therapy (PBM) effects to accelerate dental pulp repair by in vitro using cytotoxicity and proliferation assay.

  14. Boron neutron capture therapy (BNCT) inhibits tumor development from precancerous tissue: An experimental study that supports a potential new application of BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Monti Hughes, A.; Heber, E.M. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Pozzi, E. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Department of Research and Production Reactors, Ezeiza Atomic Center, CNEA, Buenos Aires (Argentina); Nigg, D.W. [Idaho National Laboratory, Idaho Falls, Idaho (United States); Calzetta, O.; Blaumann, H.; Longhino, J. [Department of Nuclear Engineering, Bariloche Atomic Center, CNEA, Rio Negro (Argentina); Nievas, S.I. [Department of Chemistry, CNEA, Buenos Aires (Argentina); Aromando, R.F. [Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Itoiz, M.E. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Department of Oral Pathology, Faculty of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Trivillin, V.A. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina); Schwint, A.E. [Department of Radiobiology, National Atomic Energy Commission (CNEA), Buenos Aires (Argentina)], E-mail: schwint@cnea.gov.ar

    2009-07-15

    We previously demonstrated the efficacy of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-10 (Na{sub 2}{sup 10}B{sub 10}H{sub 10}) and (GB-10+BPA) to control tumors, with no normal tissue radiotoxicity, in the hamster cheek pouch oral cancer model. Herein we developed a novel experimental model of field-cancerization and precancerous lesions (globally termed herein precancerous tissue) in the hamster cheek pouch to explore the long-term potential inhibitory effect of the same BNCT protocols on the development of second primary tumors from precancerous tissue. Clinically, second primary tumor recurrences occur in field-cancerized tissue, causing therapeutic failure. We performed boron biodistribution studies followed by in vivo BNCT studies, with 8 months follow-up. All 3 BNCT protocols induced a statistically significant reduction in tumor development from precancerous tissue, reaching a maximum inhibition of 77-100%. The inhibitory effect of BPA-BNCT and (GB-10+BPA)-BNCT persisted at 51% at the end of follow-up (8 months), whereas for GB-10-BNCT it faded after 2 months. Likewise, beam-only elicited a significant but transient reduction in tumor development. No normal tissue radiotoxicity was observed. At 8 months post-treatment with BPA-BNCT or (GB-10+BPA)-BNCT, the precancerous pouches that did not develop tumors had regained the macroscopic and histological appearance of normal (non-cancerized) pouches. A potential new clinical application of BNCT would lie in its capacity to inhibit local regional recurrences.

  15. SU-F-T-684: Analysis of Cherenkov Excitation in Tissue and the Feasibility of Cherenkov Excited Photodynamic Therapy

    International Nuclear Information System (INIS)

    Saunders, Sara L; Andreozzi, Jacqueline M; Pogue, Brian W; Glaser, Adam K

    2016-01-01

    Purpose: The irradiation of photodynamic agents with radiotherapy beams has been demonstrated to enhance tumor killing in various studies, and one proposed mechanism is the optical fluence of Cherenkov emission activating the photosensitizer. This mechanism is explored in Monte Carlo simulations of fluence as well as laboratory measurements of fluence and radical oxygen species. Methods: Simulations were completed using GAMOS/GEANT4 with a 6 MV photon beam in tissue. The effects of blood vessel diameter, blood oxygen saturation, and beam size were examined, recording spectral fluence. Experiments were carried out in solutions of photosensitizer and phantoms. Results: Cherenkov produced by a 100×100um"2 6 MV beam resulted in fluence of less than 1 nJ/cm"2/Gy per 1 nm wavelength. At this microscopic level, differences in absorption of blood and water in the tissue affected the fluence spectrum, but variation in blood oxygenation had little effect. Light in tissue resulting from larger (10mm ×10mm) 6 MV beams had greater fluence due to light transport and elastic scattering of optical photons, but this transport process also resulted in higher absorption shifts. Therefore, the spectrum produced by a microscopic beam was weighted more heavily in UV/blue wavelengths than the spectrum at the macroscopic level. At the macroscopic level, the total fluence available for absorption by Verteporfin (BPD) in tissue approached uJ/cm"2 for a high radiation dose, indicating that photodynamic activation seems unlikely. Tissue phantom confirmation of these light levels supported this observation, and photosensitization measurements with a radical oxygen species reporter are ongoing. Conclusion: Simulations demonstrated that fluence produced by Cherenkov in tissue by 6 MV photon beams at typical radiotherapy doses appears insufficient to activate photosensitizers to the level required for threshold effects, yet this disagrees with published biological experiments. Experimental

  16. SU-F-T-684: Analysis of Cherenkov Excitation in Tissue and the Feasibility of Cherenkov Excited Photodynamic Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Saunders, Sara L; Andreozzi, Jacqueline M; Pogue, Brian W [Dartmouth College, Hanover, NH (United States); Glaser, Adam K [University of Washington, Seattle, WA (United States)

    2016-06-15

    Purpose: The irradiation of photodynamic agents with radiotherapy beams has been demonstrated to enhance tumor killing in various studies, and one proposed mechanism is the optical fluence of Cherenkov emission activating the photosensitizer. This mechanism is explored in Monte Carlo simulations of fluence as well as laboratory measurements of fluence and radical oxygen species. Methods: Simulations were completed using GAMOS/GEANT4 with a 6 MV photon beam in tissue. The effects of blood vessel diameter, blood oxygen saturation, and beam size were examined, recording spectral fluence. Experiments were carried out in solutions of photosensitizer and phantoms. Results: Cherenkov produced by a 100×100um{sup 2} 6 MV beam resulted in fluence of less than 1 nJ/cm{sup 2}/Gy per 1 nm wavelength. At this microscopic level, differences in absorption of blood and water in the tissue affected the fluence spectrum, but variation in blood oxygenation had little effect. Light in tissue resulting from larger (10mm ×10mm) 6 MV beams had greater fluence due to light transport and elastic scattering of optical photons, but this transport process also resulted in higher absorption shifts. Therefore, the spectrum produced by a microscopic beam was weighted more heavily in UV/blue wavelengths than the spectrum at the macroscopic level. At the macroscopic level, the total fluence available for absorption by Verteporfin (BPD) in tissue approached uJ/cm{sup 2} for a high radiation dose, indicating that photodynamic activation seems unlikely. Tissue phantom confirmation of these light levels supported this observation, and photosensitization measurements with a radical oxygen species reporter are ongoing. Conclusion: Simulations demonstrated that fluence produced by Cherenkov in tissue by 6 MV photon beams at typical radiotherapy doses appears insufficient to activate photosensitizers to the level required for threshold effects, yet this disagrees with published biological experiments

  17. TU-H-BRC-08: Use and Validation of Flexible 3D Printed Tissue Compensators for Post-Mastectomy Radiation Therapy

    International Nuclear Information System (INIS)

    Craft, D; Kry, S; Salehpour, M; Howell, R; Woodward, W; Kanke, J

    2016-01-01

    Purpose: Patient-specific tissue equivalent compensators can be used for post-mastectomy radiation therapy (PMRT) to achieve homogenous dose distributions with single-field treatments. However, current fabrication methods are time consuming and expensive. 3D-printing technology could overcome these limitations. The purposes of this study were to [1] evaluate materials for 3D-printed compensators [2] design and print a compensator to achieve a uniform thickness to a clinical target volume (CTV), and [3] demonstrate that a single-field electron compensator plan is a clinically feasible treatment option for PMRT. Methods: Blocks were printed with three materials; print accuracy, density, Hounsfield units (HU), and percent depth doses (PDD) were evaluated. For a CT scan of an anthropomorphic phantom, we used a ray-tracing method to design a compensator that achieved uniform thickness from compensator surface to CTV. The compensator was printed with flexible tissue equivalent material whose physical and radiological properties were most similar to soft tissue. A single-field electron compensator plan was designed and compared with two standard-of-care techniques. The compensator plan was validated with thermoluminescent dosimeter (TLD) measurements. Results: We identified an appropriate material for 3D-printed compensators that had high print accuracy (99.6%) and was similar to soft tissue; density was 1.04, HU was - 45 ± 43, and PDD curves agreed with clinical curves within 3 mm. We designed and printed a compensator that conformed well to the phantom surface and created a uniform thickness to the CTV. In-house fabrication was simple and inexpensive (<$75). Compared with the two standard plans, the compensator plan resulted in overall more homogeneous dose distributions and performed similarly in terms of lung/heart doses and 90% isodose coverage of the CTV. TLD measurements agreed well with planned doses (within 5 %). Conclusions: We have demonstrated that 3D

  18. Tissue Oxygenation and Negative-Pressure Wound Therapy When Applied to the Feet of Persons With Diabetes Mellitus: An Observational Study.

    Science.gov (United States)

    Lee, Ye-Na; Lee, Jong Seok; Han, Seung-Kyu; Jung, Hye-Kyung

    Our group has reported that negative-pressure wound therapy (NPWT) decreases tissue oxygenation by 84% in the foot of diabetic patients because the pad of the connecting drainage tube and foam sponge of the NPWT system compress the wound bed. The purpose of this study was to determine whether an NPWT modified dressing application reduces tissue oxygenation in the feet of persons with diabetes mellitus. A prospective, clinical, observational study. We enrolled 30 patients with diabetic mellitus; their mean age was 63.9 ± 11.2 years (mean ± standard deviation). All were cared for at the diabetic wound center at an academic tertiary medical center in South Korea between 2014 and January 2015. Transcutaneous partial oxygen pressures (TcpO2) were measured to determine tissue oxygenation levels beneath modified NPWT dressings. A TcpO2 sensor was fixed at the tarsometatarsal area of the contralateral unwounded foot. A negative pressure of -125 mm Hg was applied until TcpO2 reached a plateau state; values were measured before, during, and after the modified NPWT. The Wilcoxon' and Mann-Whitney U tests were used to compare differences between these measurements. TcpO2 levels decreased by 26% during the modified NPWT. Mean TcpO2 values before, during, and after turning off the therapy were 54.3 ± 15.3 mm Hg, 41.6 ± 16.3 mm Hg, and 53.3 ± 15.6 mm Hg (P drainage tube significantly reduces the amount of tissue oxygenation loss beneath foam dressings on the skin of the foot dorsum in diabetic patients.

  19. TU-H-BRC-08: Use and Validation of Flexible 3D Printed Tissue Compensators for Post-Mastectomy Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Craft, D; Kry, S; Salehpour, M; Howell, R [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX (United States); The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX (United States); Woodward, W [The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX (United States); Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Kanke, J [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: Patient-specific tissue equivalent compensators can be used for post-mastectomy radiation therapy (PMRT) to achieve homogenous dose distributions with single-field treatments. However, current fabrication methods are time consuming and expensive. 3D-printing technology could overcome these limitations. The purposes of this study were to [1] evaluate materials for 3D-printed compensators [2] design and print a compensator to achieve a uniform thickness to a clinical target volume (CTV), and [3] demonstrate that a single-field electron compensator plan is a clinically feasible treatment option for PMRT. Methods: Blocks were printed with three materials; print accuracy, density, Hounsfield units (HU), and percent depth doses (PDD) were evaluated. For a CT scan of an anthropomorphic phantom, we used a ray-tracing method to design a compensator that achieved uniform thickness from compensator surface to CTV. The compensator was printed with flexible tissue equivalent material whose physical and radiological properties were most similar to soft tissue. A single-field electron compensator plan was designed and compared with two standard-of-care techniques. The compensator plan was validated with thermoluminescent dosimeter (TLD) measurements. Results: We identified an appropriate material for 3D-printed compensators that had high print accuracy (99.6%) and was similar to soft tissue; density was 1.04, HU was - 45 ± 43, and PDD curves agreed with clinical curves within 3 mm. We designed and printed a compensator that conformed well to the phantom surface and created a uniform thickness to the CTV. In-house fabrication was simple and inexpensive (<$75). Compared with the two standard plans, the compensator plan resulted in overall more homogeneous dose distributions and performed similarly in terms of lung/heart doses and 90% isodose coverage of the CTV. TLD measurements agreed well with planned doses (within 5 %). Conclusions: We have demonstrated that 3D

  20. Biological therapy of strontium-substituted bioglass for soft tissue wound-healing: responses to oxidative stress in ovariectomised rats.

    Science.gov (United States)

    Jebahi, S; Oudadesse, H; Jardak, N; Khayat, I; Keskes, H; Khabir, A; Rebai, T; El Feki, H; El Feki, A

    2013-07-01

    New synthetic biomaterials are constantly being developed for wound repair and regeneration. Bioactive glasses (BG) containing strontium have shown successful applications in tissue engineering account of their biocompatibility and the positive biological effects after implantation. This study aimed to assess whether BG-Sr was accepted by the host tissue and to characterize oxidative stress biomarker and antioxidant enzyme profiles during muscle and skin healing. Wistar rats were divided into five groups (six animals per group): the group (I) was used as negative control (T), after ovariectomy, groups II, III, IV and V were used respectively as positive control (OVX), implanted tissue with BG (OVX-BG), BG-Sr (OVX-BG-Sr) and presented empty defects (OVX-NI). Soft tissues surrounding biomaterials were used to estimate superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) concentration. Our results show that 60 days after operation, treatment of rats with BG-Sr significantly increased MDA concentration and caused an increase of SOD, CAT and GPx activities in both skin and muscular tissues. BG-Sr revealed maturation of myotubes followed a normal appearance of muscle regenerated with high density and mature capillary vessels. High wound recovery with complete re-epithelialization and regeneration of skin was observed. The results demonstrate that the protective action against reactive oxygen species (ROS) was clearly observed in soft tissue surrounding BG-Sr. Moreover, the potential use of BG-Sr rapidly restores the wound skin and muscle structural and functional properties. The BG advantages such as ion release might make BG-Sr an effective biomaterial choice for antioxidative activity. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  1. Technical Note: Radiation properties of tissue- and water-equivalent materials formulated using the stoichiometric analysis method in charged particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yohannes, Indra; Vasiliniuc, Stefan [Radiation Oncology, University Hospital Erlangen, Erlangen 91054 (Germany); Hild, Sebastian [Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91054, Germany and Department of Biophysics, GSI - Helmholtz Centre for Heavy Ion Research, Darmstadt 64291 (Germany); Langner, Oliver [QRM - Quality Assurance in Radiology and Medicine GmbH, Möhrendorf 91096 (Germany); Graeff, Christian [Department of Biophysics, GSI - Helmholtz Centre for Heavy Ion Research, Darmstadt 64291 (Germany); Bert, Christoph, E-mail: christoph.bert@uk-erlangen.de [Radiation Oncology, University Hospital Erlangen, Erlangen 91054 (Germany); Faculty of Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91054 (Germany); Department of Biophysics, GSI - Helmholtz Centre for Heavy Ion Research, Darmstadt 64291 (Germany)

    2016-01-15

    Purpose: Five tissue- and water-equivalent materials (TEMs) mimicking ICRU real tissues have been formulated using a previously established stoichiometric analysis method (SAM) to be applied in charged particle therapy. The purpose of this study was an experimental verification of the TEMs-SAM against charged particle beam measurements and for different computed tomography (CT) scanners. The potential of the TEMs-SAM to be employed in the dosimetry was also investigated. Methods: Experimental verification with three CT scanners was carried out to validate the calculated Hounsfield units (HUs) of the TEMs. Water-equivalent path lengths (WEPLs) of the TEMs for proton (106.8 MeV/u), helium (107.93 MeV/u), and carbon (200.3 MeV/u) ions were measured to be compared with the computed relative stopping powers. HU calibration curves were also generated. Results: Differences between the measured HUs of the TEMs and the calculated HUs of the ICRU real tissues for all CT scanners were smaller than 4 HU except for the skeletal tissues which deviated up to 21 HU. The measured WEPLs verified the calculated WEPLs of the TEMs (maximum deviation was 0.17 mm) and were in good agreement with the calculated WEPLs of the ICRU real tissues (maximum deviation was 0.23 mm). Moreover, the relative stopping powers converted from the measured WEPLs differed less than 0.8% and 1.3% from the calculated values of the SAM and the ICRU, respectively. Regarding the relative nonelastic cross section per unit of volume for 200 MeV protons, the ICRU real tissues were generally well represented by the TEMs except for adipose which differed 3.8%. Further, the HU calibration curves yielded the mean and the standard deviation of the errors not larger than 0.5% and 1.9%, respectively. Conclusions: The results of this investigation implied the potential of the TEMs formulated using the SAM to be employed for both, beam dosimetry and HU calibration in charged particle therapy.

  2. Technical Note: Radiation properties of tissue- and water-equivalent materials formulated using the stoichiometric analysis method in charged particle therapy

    International Nuclear Information System (INIS)

    Yohannes, Indra; Vasiliniuc, Stefan; Hild, Sebastian; Langner, Oliver; Graeff, Christian; Bert, Christoph

    2016-01-01

    Purpose: Five tissue- and water-equivalent materials (TEMs) mimicking ICRU real tissues have been formulated using a previously established stoichiometric analysis method (SAM) to be applied in charged particle therapy. The purpose of this study was an experimental verification of the TEMs-SAM against charged particle beam measurements and for different computed tomography (CT) scanners. The potential of the TEMs-SAM to be employed in the dosimetry was also investigated. Methods: Experimental verification with three CT scanners was carried out to validate the calculated Hounsfield units (HUs) of the TEMs. Water-equivalent path lengths (WEPLs) of the TEMs for proton (106.8 MeV/u), helium (107.93 MeV/u), and carbon (200.3 MeV/u) ions were measured to be compared with the computed relative stopping powers. HU calibration curves were also generated. Results: Differences between the measured HUs of the TEMs and the calculated HUs of the ICRU real tissues for all CT scanners were smaller than 4 HU except for the skeletal tissues which deviated up to 21 HU. The measured WEPLs verified the calculated WEPLs of the TEMs (maximum deviation was 0.17 mm) and were in good agreement with the calculated WEPLs of the ICRU real tissues (maximum deviation was 0.23 mm). Moreover, the relative stopping powers converted from the measured WEPLs differed less than 0.8% and 1.3% from the calculated values of the SAM and the ICRU, respectively. Regarding the relative nonelastic cross section per unit of volume for 200 MeV protons, the ICRU real tissues were generally well represented by the TEMs except for adipose which differed 3.8%. Further, the HU calibration curves yielded the mean and the standard deviation of the errors not larger than 0.5% and 1.9%, respectively. Conclusions: The results of this investigation implied the potential of the TEMs formulated using the SAM to be employed for both, beam dosimetry and HU calibration in charged particle therapy

  3. Technical Note: Radiation properties of tissue- and water-equivalent materials formulated using the stoichiometric analysis method in charged particle therapy.

    Science.gov (United States)

    Yohannes, Indra; Hild, Sebastian; Vasiliniuc, Stefan; Langner, Oliver; Graeff, Christian; Bert, Christoph

    2016-01-01

    Five tissue- and water-equivalent materials (TEMs) mimicking ICRU real tissues have been formulated using a previously established stoichiometric analysis method (SAM) to be applied in charged particle therapy. The purpose of this study was an experimental verification of the TEMs-SAM against charged particle beam measurements and for different computed tomography (CT) scanners. The potential of the TEMs-SAM to be employed in the dosimetry was also investigated. Experimental verification with three CT scanners was carried out to validate the calculated Hounsfield units (HUs) of the TEMs. Water-equivalent path lengths (WEPLs) of the TEMs for proton (106.8 MeV/u), helium (107.93 MeV/u), and carbon (200.3 MeV/u) ions were measured to be compared with the computed relative stopping powers. HU calibration curves were also generated. Differences between the measured HUs of the TEMs and the calculated HUs of the ICRU real tissues for all CT scanners were smaller than 4 HU except for the skeletal tissues which deviated up to 21 HU. The measured WEPLs verified the calculated WEPLs of the TEMs (maximum deviation was 0.17 mm) and were in good agreement with the calculated WEPLs of the ICRU real tissues (maximum deviation was 0.23 mm). Moreover, the relative stopping powers converted from the measured WEPLs differed less than 0.8% and 1.3% from the calculated values of the SAM and the ICRU, respectively. Regarding the relative nonelastic cross section per unit of volume for 200 MeV protons, the ICRU real tissues were generally well represented by the TEMs except for adipose which differed 3.8%. Further, the HU calibration curves yielded the mean and the standard deviation of the errors not larger than 0.5% and 1.9%, respectively. The results of this investigation implied the potential of the TEMs formulated using the SAM to be employed for both, beam dosimetry and HU calibration in charged particle therapy.

  4. Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair: a combined gene therapy-cell transplantation approach.

    Science.gov (United States)

    Jabbarzadeh, Ehsan; Starnes, Trevor; Khan, Yusuf M; Jiang, Tao; Wirtel, Anthony J; Deng, Meng; Lv, Qing; Nair, Lakshmi S; Doty, Steven B; Laurencin, Cato T

    2008-08-12

    One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue-engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors, and optimal factor doses. This study reports an approach as a step forward to resolving this dilemma by combining an ex vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated by using 3D poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose-derived stromal cells (ADSCs) with adenovirus encoding the cDNA of VEGF. We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We thereby delineate the potential of ADSCs to promote vascular growth into biomaterials.

  5. Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Ken, E-mail: keharada@ncc.go.jp [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Murakami, Naoya; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Inaba, Koji; Morota, Madoka; Ito, Yoshinori; Sumi, Minako [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Suzuki, Shigenobu [Department of Ophthalmic Oncology, National Cancer Center Hospital, Tokyo (Japan); Tobinai, Kensei [Department of Hematologic Oncology, National Cancer Center Hospital, Tokyo (Japan); Uno, Takashi [Department of Radiology, Chiba University School of Medicine, Chiba (Japan); Itami, Jun [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)

    2014-03-01

    Purpose: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). Methods and Materials: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. Results: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). Conclusions: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract.

  6. Localized Ocular Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy: A Long-Term Outcome in 86 Patients With 104 Treated Eyes

    International Nuclear Information System (INIS)

    Harada, Ken; Murakami, Naoya; Kitaguchi, Mayuka; Sekii, Shuhei; Takahashi, Kana; Yoshio, Kotaro; Inaba, Koji; Morota, Madoka; Ito, Yoshinori; Sumi, Minako; Suzuki, Shigenobu; Tobinai, Kensei; Uno, Takashi; Itami, Jun

    2014-01-01

    Purpose: To evaluate the natural history, behavior of progression, prognostic factors, and treatment-related adverse effects of primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML). Methods and Materials: Eighty-six patients with histologically proven stage I POAML treated with radiation therapy at National Cancer Center Hospital, Tokyo between 1990 and 2010 were retrospectively reviewed. The median age was 56 years (range, 18-85 years). The median dose administered was 30 Gy (range, 30-46 Gy). Seventy-seven patients (90%) were treated by radiation therapy alone. Results: The median follow-up duration was 9 years (range, 0.9-22 years). The 5- and 10-year overall survival (OS) rates were 97.6% and 93.5%, respectively, and no patients died of lymphoma. Patients with tumor sizes ≥4 cm showed a greater risk of contralateral relapse (P=.012). Six patients with contralateral relapse were seen and treated by radiation therapy alone, and all the lesions were controlled well, with follow-up times of 3 to 12 years. There was 1 case of local relapse after radiation therapy alone, and 3 cases of relapse occurred in a distant site. Cataracts developed in 36 of the 65 eyes treated without lens shielding and in 12 of the 39 patients with lens shielding (P=.037). Conclusions: The majority of patients with POAML showed behavior consistent with that of localized, indolent diseases. Thirty gray of local irradiation seems to be quite effective. The initial bilateral involvement and contralateral orbital relapses can be also controlled with radiation therapy alone. Lens shielding reduces the risk of cataract

  7. The role of cyclooxygenase-2 in the malignant tissue and possible applicability of cyclooxygenase-2 inhibitors in the therapy of cancer

    International Nuclear Information System (INIS)

    Legan, M.

    2003-01-01

    Cyclooxygenase-2 (COX-2), an inducible prostaglandin (PG) synthase, is elevated in many types of malignant and pre-malignant tissues. This enzyme is localized in neoplastic (epithelial) cells, microvascular endothelial cells, and stromal fibroblasts. Through the released PG it enhances carcinogenesis with increasing angiogenesis, inhibiting apoptosis, activating matrix metalloproteinases, suppressing of cell mediated antitumor immune response and protection against damage by cytotoxic agents. Evidences from in vitro studies, studies on animal models as well as first clinical outcomes suggest that the inhibition of COX-2 may suppress carcinogenesis by affecting a number of pathways: inhibiting angiogenesis, invasiveness of tumors and promoting apoptosis. References forecast that COX-2 inhibitors, mostly COX-2 selective inhibitors, may get a role in the therapy of cancer as an adjuvant therapy or as an co-chemotherapeutic agent. The purpose of the present article is to summarize the most important facts about the role of COX-2 in the malignant tissue and discuss possible ways for potential therapeutic place of COX-2 inhibitors in clinical practice. (author)

  8. Correlation of the findings of thallium-201 chloride scans with those of other imaging modalities and histology following therapy in patients with bone and soft tissue sarcomas

    International Nuclear Information System (INIS)

    Kostakoglu, L.; Panicek, D.M.; Divgi, C.R.; Botet, J.; Healy, J.; Larson, S.M.; Abdel-Dayem, H.M.

    1995-01-01

    We performed a prospective study to evaluate the imaging potential of thallium-201 as compared with other imaging modalities in differentiating residual/recurrent tumors from post-therapy changes in patients with musculoskeletal sarcomas. 201 Tl scans, magnetic resonance imaging (17), X-ray computed tomography (6) or contrast angiography (6) studies in 29 patients previously treated for musculoskeletal sarcomas were correlated with either histopathologic findings (26 patients) or 2-year clinical follow-up (three patients). All imaging studies were acquired within 2 weeks. Ratios of 201 Tl tumor uptake to the contralateral (28 patients) or adjacent region of interest were calculated. When qualitative interpretation was in doubt, only those cases with a ratio of 1.5 or more were considered suggestive of recurrent or residual viable tumor tissue. Residual or recurrent tumor tissue was verified in 21 patients by biopsy. All had true-positive 201 Tl scans while the other imaging modalities were true-positive in 20 and equivocal in one. In eight patients, there was no evidence of viable tumor tissue as proven by biopsy in five and long-term clinical follow-up in three. 201 Tl scan was false-positive (ratio 1.5) in one patient and true-negative in seven while the other imaging modalities had four false-positives. The average 201 Tl ratios were 3.8 ± 1.1 in the true-positive cases and 1.3 ± 0.3 in the true-negative cases. The percentage sensitivities, specificities, and accuracy for 201 Tl were 100%, 87.5%, and 96.5% versus 95%, 50%, and 82.7% respectively for other imaging modalities. These results indicate that 201 Tl scintigraphy is more accurate than other imaging modalities in differentiating residual/recurrent musculoskeletal sarcomas from post-therapy changes. (orig.)

  9. Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial.

    Science.gov (United States)

    Coghlan, John Gerry; Galiè, Nazzareno; Barberà, Joan Albert; Frost, Adaani E; Ghofrani, Hossein-Ardeschir; Hoeper, Marius M; Kuwana, Masataka; McLaughlin, Vallerie V; Peacock, Andrew J; Simonneau, Gérald; Vachiéry, Jean-Luc; Blair, Christiana; Gillies, Hunter; Miller, Karen L; Harris, Julia H N; Langley, Jonathan; Rubin, Lewis J

    2017-07-01

    Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH. To explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial. This was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response). In the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups. This post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy. NCT01178073, post results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jakobi, Annika, E-mail: Annika.Jakobi@OncoRay.de [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Bandurska-Luque, Anna [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Stützer, Kristin; Haase, Robert; Löck, Steffen [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Wack, Linda-Jacqueline [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); Mönnich, David [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); German Cancer Research Center, Heidelberg (Germany); German Cancer Consortium, Tübingen (Germany); Thorwarth, Daniela [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); and others

    2015-08-01

    Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.

  11. Gingival crevicular fluid tissue/blood vessel-type plasminogen activator and plasminogen activator inhibitor-2 levels in patients with rheumatoid arthritis: effects of nonsurgical periodontal therapy.

    Science.gov (United States)

    Kurgan, Ş; Önder, C; Balcı, N; Fentoğlu, Ö; Eser, F; Balseven, M; Serdar, M A; Tatakis, D N; Günhan, M

    2017-06-01

    The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type plasminogen activator (t-PA) and plasminogen activator inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p periodontitis groups (p periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the plasminogen activating system plays a role in the disease process of periodontitis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

    Science.gov (United States)

    Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz

    2016-07-01

    Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation. © 2016 Blackwell Verlag GmbH.

  13. Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

    International Nuclear Information System (INIS)

    Jakobi, Annika; Bandurska-Luque, Anna; Stützer, Kristin; Haase, Robert; Löck, Steffen; Wack, Linda-Jacqueline; Mönnich, David; Thorwarth, Daniela

    2015-01-01

    Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons

  14. Advantages and disadvantages of using intravenous tissue Plasminogen activator as salvage therapy for inoperable HeartWare thrombosis.

    Science.gov (United States)

    Basken, Robyn; Bazzell, Charles M; Smith, Richard; Janardhanan, Rajesh; Khalpey, Zain

    2017-07-01

    Device thrombosis is a devastating complication of left ventricular assist devices. The definitive treatment has been device exchange or explant. Evidence of increasing morbidity and mortality with device exchange has shifted strategies toward conservative management. In this report, we detail the use of thrombolytics as salvage therapy in a patient with an occlusive HeartWare ventricular assist device (HeartWare Inc., Framingham, MA) thrombus, resulting in long-term survival without further intervention. © 2017 Wiley Periodicals, Inc.

  15. Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

    Energy Technology Data Exchange (ETDEWEB)

    Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.; Barnes, M.; DeLuca, A.M.; Terrill, R.; Matthews, D.; Johnstone, P.A.S. [National Institutes of Health, Bethesda, MD (United States); Anderson, W.J. [Terre Haute Center for Medical Education, IN (United States); Bollinger, B.K. [National Naval Medical Center, Bethesda, MD (United States)

    1994-07-01

    The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through a 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.

  16. Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

    International Nuclear Information System (INIS)

    Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.; Barnes, M.; DeLuca, A.M.; Terrill, R.; Matthews, D.; Johnstone, P.A.S.; Anderson, W.J.; Bollinger, B.K.

    1994-01-01

    The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through a 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses ≥30 Gy. Radiation changes were present in the aorta and vena cava at doses ≥40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs

  17. Mortality and length of therapy in soft tissue infections, Sina and Amir-Alam Hospitals (1989-99

    Directory of Open Access Journals (Sweden)

    Geranpaieh L

    2002-11-01

    Full Text Available Introduction: Necrotizing soft tissue infections are one of the most dreaded infections in human and result in a very high rate of mortality. The treatment of these infections must be very aggressive and consists of radical debridement of all necrotic tissue accompanied by appropriate antibiotics. Materials and methods: This study was undertaken to assess the mortality rate, the time from diagnosis to cure, and some of the parameters which may affect mortality in our patients. In this descriptive, retrospective study first files from patients attended by necrotizing soft tissue infections including Fournier's gangrene or disease, gas gangrene, hemolytic streptococcal infections, myonecrosis, necrotizing fascitis and related subjects in Sina and Amir-Alam hospitals from 1989 to 1999 were studied. Data were extracted and analyzed by SPSS. Results: The total number of cases was 36. The median age was 47.69 years. Seven of the patients were female. The median time from onset to cure was 10 days. The most common site affected was the perineum and the most common etiology was perianal abscess. Diabetes mellitus was the underlying disease mostly observed. Half of the patients had received inappropriate treatments. In this group mortality was higher. Conclusion: It is crucial that general practitioners be acquainted with the diagnosis of necrotizing soft tissue infections so that patients are referred immediately to surgical centers. In our referral center the mortality was acceptable but it can be lowered further. The sex, sites of infection, underlying disease and etiologies in our patients were similar to patient in other countries except for alcoholism. It appears that data in foreign texts can be attributed to Iranian patients.

  18. Hormone replacement therapy dependent changes in breast cancer-related gene expression in breast tissue of healthy postmenopausal women.

    Science.gov (United States)

    Sieuwerts, Anieta M; De Napoli, Giuseppina; van Galen, Anne; Kloosterboer, Helenius J; de Weerd, Vanja; Zhang, Hong; Martens, John W M; Foekens, John A; De Geyter, Christian

    2011-12-01

    Risk assessment of future breast cancer risk through exposure to sex steroids currently relies on clinical scorings such as mammographic density. Knowledge about the gene expression patterns in existing breast cancer tumors may be used to identify risk factors in the breast tissue of women still free of cancer. The differential effects of estradiol, estradiol together with gestagens, or tibolone on breast cancer-related gene expression in normal breast tissue samples taken from postmenopausal women may be used to identify gene expression profiles associated with a higher breast cancer risk. Breast tissue samples were taken from 33 healthy postmenopausal women both before and after a six month treatment with either 2mg micronized estradiol [E2], 2mg micronized estradiol and 1mg norethisterone acetate [E2+NETA], 2.5mg tibolone [T] or [no HRT]. Except for [E2], which was only given to women after hysterectomy, the allocation to each of the three groups was randomized. The expression of 102 mRNAs and 46 microRNAs putatively involved in breast cancer was prospectively determined in the biopsies of 6 women receiving [no HRT], 5 women receiving [E2], 5 women receiving [E2+NETA], and 6 receiving [T]. Using epithelial and endothelial markers genes, non-representative biopsies from 11 women were eliminated. Treatment of postmenopausal women with [E2+NETA] resulted in the highest number of differentially (pbreast tissue with a change in the expression of genes putatively involved in breast cancer. Our data suggest that normal mammary cells triggered by [E2+NETA] adjust for steroidogenic up-regulation through down-regulation of the estrogen-receptor pathway. This feasibility study provides the basis for whole genome analyses to identify novel markers involved in increased breast cancer risk. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  19. An update clinical application of amniotic fluid-derived stem cells (AFSCs) in cancer cell therapy and tissue engineering.

    Science.gov (United States)

    Gholizadeh-Ghaleh Aziz, Shiva; Fathi, Ezzatollah; Rahmati-Yamchi, Mohammad; Akbarzadeh, Abolfazl; Fardyazar, Zahra; Pashaiasl, Maryam

    2017-06-01

    Recent studies have elucidated that cell-based therapies are promising for cancer treatments. The human amniotic fluid stem (AFS) cells are advantageous cells for such therapeutic schemes that can be innately changed to express therapeutic proteins. HAFSCs display a natural tropism to cancer cells in vivo. They can be useful in cancer cells targeting. Moreover, they are easily available from surplus diagnostic samples during pregnancy and less ethical and legal concern are associated with the collection and application than other putative cells are subjected. This review will designate representatives of amniotic fluid and stem cell derived from amniotic fluid. For this propose, we collect state of human AFS cells data applicable in cancer therapy by dividing this approach into two main classes (nonengineered and engineered based approaches). Our study shows the advantage of AFS cells over other putative cells types in terms differentiation ability to a wide range of cells by potential and effective use in preclinical studies for a variety of diseases. This study has shown the elasticity of human AFS cells and their favorable potential as a multipotent cell source for regenerative stem cell therapy and capable of giving rise to multiple lineages including such as osteoblasts and adipocyte.

  20. Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Reinhardt, Michael J; Joe, Alexius Y; Mallek, Dirk von; Ezziddin, Samer; Palmedo, Holger [Department of Nuclear Medicine, University Hospital of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Brink, Ingo [Department of Nuclear Medicine, University Hospital of Freiburg (Germany); Krause, Thomas M [Department of Nuclear Medicine, Inselspital Bern (Switzerland)

    2002-09-01

    This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15{+-}9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256{+-}80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses. (orig.)

  1. Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome

    International Nuclear Information System (INIS)

    Reinhardt, Michael J.; Joe, Alexius Y.; Mallek, Dirk von; Ezziddin, Samer; Palmedo, Holger; Brink, Ingo; Krause, Thomas M.

    2002-01-01

    This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15±9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256±80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses. (orig.)

  2. A case of cardiac cancer diagnosed after 30 Gy radiation therapy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma without helicobacter pylori (H. pylori) infection

    International Nuclear Information System (INIS)

    Ito, Kazuhiro; Akamatsu, Taiji; Shinji, Akihiro

    2005-01-01

    An 80-year-old man was referred to Shinshu University Hospital in April 2001 for treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. He had received anti-biotic therapy in spite of no evidence of H. pylori infection in the former hospital 3 years ago, but no remarkable improvement was recognized and endoscopic findings were progressive. An esophagogastroduodenoscopy (EGD) revealed mucosal redness on the greater curvature and the anterior wall of the body. Biopsy specimens taken from the lesions showed remarkable infiltration of atypical small lymphocytes, and this lesions were diagnosed MALT lymphoma by an immunophenotypic studies. Endoscopic ultrasonography (EUS) showed that MALT lymphoma was limited within the mucosa and submucosa. Staging work up revealed stage I. After written informed consent, he was treated by 30 Gy radiation therapy for gastric MALT lymphoma. Response assessment was performed by EGD, EUS, and biopsy specimens, and a complete remission was confirmed. After that, he was followed up with regular intervals, and EGD was performed every 6 months. He was diagnosed to have O I type cardiac cancer at 21 months after radiation therapy. He underwent proximal partial gastrectomy, and histopathological findings showed as follows: O I type, 17 x 12 mm, tub 2, SM, ly 1, v 1, n 0, PM (-), DM (-), INFγ, stage I A. No residual lesion of gastric MALT lymphoma and no dysplasia of gastric mucosa was recognized. Causal relationship between radiation therapy and carcinogenesis in this case is unclear. However, it might be suggested by the facts that cancer occurred in the radiation field where MALT lymphoma had been presented and gastric cancer was rare in the stomach without H. pylori infection. (author)

  3. A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

    International Nuclear Information System (INIS)

    Zhou, Rachel; Ng, Angela; Constine, Louis S.; Stovall, Marilyn; Armstrong, Gregory T.; Neglia, Joseph P.; Friedman, Debra L.; Kelly, Kara; FitzGerald, Thomas J.; Hodgson, David C.

    2016-01-01

    Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohort and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.

  4. A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT and intraoperative radiation therapy (IORT in patients with retroperitoneal soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Roeder Falk

    2012-07-01

    Full Text Available Abstract Background Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT are considered. Methods/design The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy followed by surgery and IORT (10–12 Gy in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. Discussion The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. Trial registration NCT01566123

  5. A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma

    International Nuclear Information System (INIS)

    Roeder, Falk; Hensley, Frank W; Buechler, Markus W; Debus, Juergen; Koch, Moritz; Weitz, Juergen; Bischof, Marc; Schulz-Ertner, Daniela; Nikoghosyan, Anna V; Huber, Peter E; Edler, Lutz; Habl, Gregor; Krempien, Robert; Oertel, Susanne; Saleh-Ebrahimi, Ladan

    2012-01-01

    Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS) remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT) has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT) has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT) are considered. The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50–56 Gy) followed by surgery and IORT (10–12 Gy) in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. NCT01566123

  6. Feasibility of salvage interstitial microwave thermal therapy for prostate carcinoma following failed brachytherapy: studies in a tissue equivalent phantom

    International Nuclear Information System (INIS)

    McCann, Claire; Kumaradas, J Carl; Gertner, Mark R; Davidson, Sean R H; Dolan, Alfred M; Sherar, Michael D

    2003-01-01

    Thermal therapy is an experimental treatment to destroy solid tumours by heating them to temperatures ranging from 55 deg C to 90 deg C, inducing thermal coagulation and necrosis of the tumour. We are investigating the feasibility of interstitial microwave thermal therapy as a salvage treatment for prostate cancer patients with local recurrence following failed brachytherapy. Due to the electrical and thermal conductivity of the brachytherapy seeds, we hypothesized that the seeds could scatter the microwave energy and cause unpredictable heating. To investigate this, a 915 MHz helical antenna was inserted into a muscle-equivalent phantom with and without brachytherapy seeds. Following a 10 W, 5 s input to the antenna, the temperature rise was used to calculate absorbed power, also referred to as specific absorption rate (SAR). Plane wave models based on Maxwell's equations were also used to characterize the electromagnetic scattering effect of the seeds. In addition, the phantom was heated with 8 W for 5 min to quantify the effect of the seeds on the temperature distribution during extended heating. SAR measurements indicated that the seeds had no significant effect on the shape and size of the SAR pattern of the antenna. However, the plane wave simulations indicated that the seeds could scatter the microwave energy resulting in hot spots at the seed edges. Lack of experimental evidence of these hot spots was probably due to the complex polarization of the microwaves emitted by the helical antenna. Extended heating experiments also demonstrated that the seeds had no significant effect on the temperature distributions and rates of temperature rise measured in the phantom. The results indicate that brachytherapy seeds are not a technical impediment to interstitial microwave thermal therapy as a salvage treatment following failed brachytherapy

  7. Adjunctive Systemic Antimicrobial Therapy vs Asepsis in Conjunction with Guided Tissue Regeneration: A Randomized, Controlled Clinical Trial.

    Science.gov (United States)

    Abu-Ta'a, Mahmoud

    2016-01-01

    This randomized clinical trial compares the usefulness of adjunctive antibiotics, while strict asepsis was followed during periodontal surgery involving guided tissue regeneration. Two groups of 20 consecutive patients each with advanced periodontal disease were randomly assigned to treatment. They displayed one angular defect each with an intrabony component ≥3 mm, probing pocket depth and probing attachment level (PAL) ≥7 mm. Test group included 13 males, mean age 60 years, treated with enamel matrix derivative (EMD) and demineralized freeze-dried bone allograft with modified papilla preservation technique, received oral amoxicillin 1 gm, 1 hour preoperatively and 2 gm for 2 days postoperatively. Control group included 10 males, mean age 57 years, treated with EMD and demineralized freeze-dried bone allograft with modified papilla preservation technique, received no antibiotics. Outcome measures were clinical attachment level (CAL) gain, residual periodontal pocket depth (res. PD), gingival recession (GR), bleeding on probing (BOP), adverse events and postoperative complications. Patients were followed up to 12 months after periodontal surgery involving guided tissue regeneration. There were no significant differences between both groups for CAL gain, res. PD, GR, BOP nor other clinical parameters, though patients' subjective perception of postoperative discomfort was significantly smaller in the group receiving antibiotics. Antibiotics do not provide significant advantages concerning clinical periodontal parameters nor concerning postoperative infections in case of proper asepsis. It does, on the contrary, reduce postoperative discomfort. Regarding the results of this study, adjunc-tive systemic antibiotics in combination with guided tissue regeneration may be useful in reducing postoperative discomfort but may not be helpful for improving periodontal regeneration outcomes.

  8. Precision IORT - Image guided intraoperative radiation therapy (igIORT) using online treatment planning including tissue heterogeneity correction.

    Science.gov (United States)

    Schneider, Frank; Bludau, Frederic; Clausen, Sven; Fleckenstein, Jens; Obertacke, Udo; Wenz, Frederik

    2017-05-01

    To the present date, IORT has been eye and hand guided without treatment planning and tissue heterogeneity correction. This limits the precision of the application and the precise documentation of the location and the deposited dose in the tissue. Here we present a set-up where we use image guidance by intraoperative cone beam computed tomography (CBCT) for precise online Monte Carlo treatment planning including tissue heterogeneity correction. An IORT was performed during balloon kyphoplasty using a dedicated Needle Applicator. An intraoperative CBCT was registered with a pre-op CT. Treatment planning was performed in Radiance using a hybrid Monte Carlo algorithm simulating dose in homogeneous (MCwater) and heterogeneous medium (MChet). Dose distributions on CBCT and pre-op CT were compared with each other. Spinal cord and the metastasis doses were evaluated. The MCwater calculations showed a spherical dose distribution as expected. The minimum target dose for the MChet simulations on pre-op CT was increased by 40% while the maximum spinal cord dose was decreased by 35%. Due to the artefacts on the CBCT the comparison between MChet simulations on CBCT and pre-op CT showed differences up to 50% in dose. igIORT and online treatment planning improves the accuracy of IORT. However, the current set-up is limited by CT artefacts. Fusing an intraoperative CBCT with a pre-op CT allows the combination of an accurate dose calculation with the knowledge of the correct source/applicator position. This method can be also used for pre-operative treatment planning followed by image guided surgery. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  9. α-Fetoprotein promoter-driven Cre/LoxP-switched RNA interference for hepatocellular carcinoma tissue-specific target therapy.

    Directory of Open Access Journals (Sweden)

    Yuan-Fei Peng

    Full Text Available RNA interference (RNAi has recently emerged as a potential treatment modality for hepatocellular carcinoma (HCC therapy, but the lack of cellular targets and sustained efficacy limits its application. The purpose of this study is to develop an HCC tissue-specific RNAi system and investigate its possibility for HCC treatment.Two different HCC-specific RNAi systems in which therapeutic miRNA or shRNA against target gene (Beclin 1 was directly or indirectly driven by alpha-fetoprotein promoter (AFP-miRNA and AFP-Cre/LoxP-shRNA were constructed. Human HCC cell lines (HepG2, Hep3B and HCCLM3 and non-HCC cell lines (L-02, Hela and SW1116 were infected with the systems. The effectiveness and tissue-specificity of the systems were examined by Q-PCR and western blot analysis. The efficacy of the systems was further tested in mouse model of HCC by intravenous or intratumoral administration. The feasibility of the system for HCC treatment was evaluated by applying the system as adjuvant therapy to enhance sorafenib treatment. An AFP-Cre/LoxP-shRNA system targeting Atg5 gene (AFP-Cre/LoxP-shRNA-Atg5 was constructed and its efficacy in sensitizing HCC cells (MHCC97L/PLC to sorafenib treatment was examined by apoptosis assay in vitro and tumorigenesis assay in vivo.The AFP-miRNA system could silence target gene (Beclin 1 but required a high titer which was lethal to target cells. The AFP-Cre/LoxP-shRNA system could efficiently knockdown target gene while maintain high HCC specificity. Intratumoral injection of the AFP-Cre/LoxP-shRNA system could efficiently silence target gene (Beclin 1 in vivo while intravenous administration could not. The AFP-Cre/LoxP-shRNA system target Atg5 gene could significantly sensitize MHCC97L/PLC cells to sorafenib-induced apoptosis in vitro and tumor growth suppression in vivo.An efficient HCC tissue-specific RNAi system (AFP-Cre/LoxP-shRNA was successfully established. The system provides a usable tool for HCC-specific RNAi

  10. Normal tissue tolerance to external beam radiation therapy: Skin; Dose de tolerance des tissus sains: la peau et les phaneres

    Energy Technology Data Exchange (ETDEWEB)

    Ginot, A.; Doyen, J.; Hannoun-Levi, J.M.; Courdi, A. [Service d' oncologie-radiotherapie, centre Antoine-Lacassagne, 06 - Nice (France)

    2010-07-15

    Acute skin toxicity is frequent during radiation therapy and can lead to temporary arrest of the treatment. Chronic toxicity can occur and conduct to cosmetic problems. Alopecia is the most frequent toxicity concerning hair and is most of the time reversible. Several factors linked to patients influence skin toxicity, such as under-nutrition, old age, obesity, smoking, skin diseases, autoimmune diseases, failure of DNA reparation. Skin, hair and nail toxicities depend also on radiation schedule. Acute toxicity is greater when dose per fraction increases. Chronic and acute toxicities are more often when total dose increases. Under 45 Gy, the risk of severe skin toxicity is low, and begins above 50 Gy. Skin toxicity depends also on the duration of radiotherapy and split course schedules are associated with less toxicities. Irradiation surface seems to influence skin toxicity but interaction is more complex. Reirradiation is often feasible in case of cancer recurrence but with a risk of grade 3-4 toxicity above all in head and neck cancer. The benefit/risk ratio has to be always precisely evaluated. Permanent alopecia is correlated with the follicle dose. Modern techniques of radiation therapy allow to spare skin. (authors)

  11. Normal tissue tolerance to external beam radiation therapy: Cardiac structures; Dose de tolerance des tissus sains: le coeur

    Energy Technology Data Exchange (ETDEWEB)

    Doyen, J. [Service d' oncologie-radiotherapie, centre Antoine-Lacassagne, 06 - Nice (France); Giraud, P. [Universite Rene-Descartes Paris 5, 75 - Paris (France); Service d' oncologie-radiotherapie, hopital europeen Georges-Pompidou, 75 - Paris (France); Belkacemi, Y. [Faculte de medecine de Creteil, universite Paris 12, 94 - Creteil (France); Service d' oncologie-radiotherapie, CHU Henri-Mondor, 94 - Creteil (France)

    2010-07-15

    Radiation thoracic tumors may be associated with cardiac toxicity because of the central position of the heart in the thorax. The present review aims to describe the cardiotoxicity during radiotherapy of different tumor sites most associated with this complication and the risk factors of cardiotoxicity during radiation therapy. Medline literature searches were performed using the following cardiac - heart - radiotherapy - toxicity - cardiotoxicity - breast cancer - lymphoma. Cardiac toxicity after breast cancer and mediastinal lymphoma is the most reported radiation-induced complication. The most frequent clinical complications are pericarditis, congestive heart failure, and heart infarction. These events are mostly asymptomatic. Thus clinicians have to give particular attention to these complications. Anthracycline treatment is a major risk factor for additional cardiotoxicity during radiotherapy with a synergistic effect. Correction of cardiovascular risk is an important point of the prevention of heart complications. Total dose delivered to the planned target volume (PTV), the dose per fraction and the irradiated volume were correlated to the risk of cardiotoxicity. Volume of heart receiving 35 Gy must be inferior to 30% and dose per fraction should not exceed 2 Gy when dose of prescription exceeds 30 Gy. Maximum heart distance (maximal thickness of heart irradiated) must be less than 1 cm during irradiation of breast cancer. Modern irradiation techniques seem to be associated with a limited risk of heart complication. The use of anthracycline, other cardio-toxic chemotherapies and targeted therapies should incite for great caution by performing a careful treatment planning and optimisation. (authors)

  12. Soluble TGF-β type II receptor gene therapy reduces TGF-β activity in irradiated lung tissue and protects lungs from radiation-induced injury

    International Nuclear Information System (INIS)

    Vujaskovic, Z.; Rabbani, Z.; Zhang, X.; Samulski, T.V.; Li, C.-Y.; Anscher, M.S.

    2003-01-01

    Full text: The objective was to determine whether administration of recombinant human adenoviral vector carrying soluble TGF-β1 type II receptor (TβR-II) gene reduces availability of active TGFβ1 and protects lung from radiation-induced injury. Female Fisher-344 rats were randomized into four groups to receive: 1) Control 2) Adenoviral green fluorescent protein vector (AdGFP) alone 3) Radiation (RT) + Adenoviral vector with TGF-β1 type II receptor gene (AdexTβR-II-Fc) 4) RT alone. Animals were irradiated to right hemithorax using a single dose of 30 Gy. The packaging and production of a recombinant adenovirus carrying the fused human TβR-II-IgG1 Fc gene was achieved by use of the AdEasy system. The treatment vector AdexTbR-II-Fc (1.5*1010 PFU) and control vector AdGFP (1*109 PFU) were injected i.v. 24 hrs after RT. Respiratory rate was measured as an index of pulmonary function weekly for 5 weeks post RT. Structural damage was scored histologically. Immunohistochemistry was performed to identify activated macrophages. ELISA was used to quantify active TGF-β1 in tissue homogenate. Western blot was used to determine TβR-II expression in plasma and lung tissue. Animals receiving treatment vector AdexTbR-II-Fc have elevated plasma levels of soluble TβR-II at 24 and 48 hours after injection. In the RT+AdexTbR-II-Fc group, there was a significant reduction in respiratory rate (p = 0.002) at four weeks after treatment compared to RT alone group. Histology revealed a significant reduction in lung structural damage in animals receiving gene therapy after RT vs RT alone (p=0.0013). There was also a decrease in the number of activated macrophage (p= 0.02) in RT+AdexTbR-II-Fc group vs RT alone. The tissue protein expression of active TGF-β1 was significantly reduced in rats receiving RT+AdexTbR-II-Fc treatment (p<0.05). This study shows the ability of adenovirus mediated soluble TβR-II gene therapy to reduce tissue levels of active TGF-β1 and ameliorate radiation

  13. Thickening of the epicardial adipose tissue can be alleviated by thyroid hormone replacement therapy in patients with subclinical hypothyroidism.

    Science.gov (United States)

    Sayin, Irmak; Erkan, Aycan Fahri; Ekici, Berkay; Kutuk, Utku; Corakci, Ahmet; Tore, Hasan Fehmi

    2016-01-01

    Subclinical hypothyroidism (SCH) is a common disorder which has adverse cardiovascular effects. Epicardial adipose tissue (EAT), a novel marker of cardiovascular risk, is increased in SCH. We aimed to investigate whether L-thyroxine treatment can reverse the thickening of EAT in SCH. Forty-four patients with SCH and 42 euthyroid control subjects were included. EAT thickness was measured using transthoracic echocardiography at baseline and after restoration of the euthyroid status with 3 months of L-thyroxine treatment. At baseline, mean EAT thickness was significantly greater in the SCH group when compared to the control group (6.3 ± 1.7 mm vs. 4.1 ± 0.9 mm, respectively, p treatment (6.3 ± 1.7 mm vs. 5.1 ± 1.4 mm, p treatment when compared to baseline (DEAT) significantly correlated to the difference in TSH levels before and after treatment (DTSH; r = 0.323; p = 0.032). Epicardial adipose tissue thickness is increased in patients with SCH. This thickening was alleviated with restoration of the euthyroid status with L-thyroxine treatment in our study population of predominantly male, relatively old subjects with greater baseline EAT thickness.

  14. Relationship between opioid therapy, tissue-damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates.

    Science.gov (United States)

    Angeles, Danilyn M; Ashwal, Stephen; Wycliffe, Nathaniel D; Ebner, Charlotte; Fayard, Elba; Sowers, Lawrence; Holshouser, Barbara A

    2007-05-01

    To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection.

  15. Antibiotics for methicillin-resistant Staphylococcus aureus skin and soft tissue infections: the challenge of outpatient therapy.

    Science.gov (United States)

    Pate, Amy J; Terribilini, Reno Giovonni; Ghobadi, Farzaneh; Azhir, Alaleh; Barber, Andre; Pearson, Julie Marie; Kalantari, Hossein; Hassen, Getaw W

    2014-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections are becoming increasingly prevalent in both community and hospital settings. Certain strains are notorious for causing skin and soft tissue infections in patients with no established risk factors. In this article, we report our findings on the dynamic antibiotic resistance pattern of MRSA and outpatient prescription trend for skin and soft tissue infections within our community. We conducted a retrospective medical record review of 1876 patients evaluated in the emergency department of an urban community hospital from 2003 to 2012. Data regarding culture isolates and associated antimicrobial resistance, antibiotic treatment, site of specimen collection, age, race, and sex were collected and analyzed. Analysis of 1879 culture specimens yielded 2193 isolates. In some cases, a single specimen yielded polymicrobial growth. Staphylococcus aureus represented 996 isolates (45.4%); 463 were methicillin-susceptible (21.1%) and 533 (24.3%) were methicillin-resistant. Most patients were prescribed a single- or poly-drug regimen of trimethoprim/sulfamethoxazole, cephalexin, and clindamycin. Antimicrobial resistance analysis indicated that MRSA became increasingly resistant to the aforementioned antibiotics over time: 10% and 6% in 2012 vs 3.5% and 3.4% in 2007 for clindamycin and trimethoprim/sulfamethoxazole, respectively. Methicillin-resistant Staphylococcus aureus is a particularly virulent, rapidly adaptive pathogen that is becoming increasingly difficult to combat with existing antibiotics. Care must be taken to ensure appropriate treatment and follow-up of patients with known MRSA infections. © 2013.

  16. Concomitant radiation therapy and doxorubicin by continuous Infusion in advanced malignancies - A phase I-II study - evidence of synergistic effect in Soft tissue sarcomas and hepatomas

    International Nuclear Information System (INIS)

    Rosenthal, C.J.; Bhutiani, I.; Rotman, M.

    1986-01-01

    This paper attempts to establish the dose and the duration of administration of doxorubicin infusion having the best therapeutic index and to determine the dose of radiation which in combination with the optimal dose of doxorubicin administered by continuous infusion would have the best therapeutic index. The authors attempt to find the nature and the incidence of side effects of these combined modalities of therapy. The therapeutic effect of the optimal doxorubicin infusion dose in combination with concomitant radiotherapy is assessed in a preliminary study and it was found to have a significant enhancing effect in a few cases of hepatomas and in most of the cases of recurrent and metastatic soft tissue sarcomas

  17. Increase in tumor control and normal tissue complication probabilities in advanced head-and-neck cancer for dose-escalated intensity-modulated photon and proton therapy

    Directory of Open Access Journals (Sweden)

    Annika eJakobi

    2015-11-01

    Full Text Available Introduction:Presently used radio-chemotherapy regimens result in moderate local control rates for patients with advanced head and neck squamous cell carcinoma (HNSCC. Dose escalation (DE may be an option to improve patient outcome, but may also increase the risk of toxicities in healthy tissue. The presented treatment planning study evaluated the feasibility of two DE levels for advanced HNSCC patients, planned with either intensity-modulated photon therapy (IMXT or proton therapy (IMPT.Materials and Methods:For 45 HNSCC patients, IMXT and IMPT treatment plans were created including DE via a simultaneous integrated boost (SIB in the high-risk volume, while maintaining standard fractionation with 2 Gy per fraction in the remaining target volume. Two DE levels for the SIB were compared: 2.3 Gy and 2.6 Gy. Treatment plan evaluation included assessment of tumor control probabilities (TCP and normal tissue complication probabilities (NTCP.Results:An increase of approximately 10% in TCP was estimated between the DE levels. A pronounced high-dose rim surrounding the SIB volume was identified in IMXT treatment. Compared to IMPT, this extra dose slightly increased the TCP values and to a larger extent the NTCP values. For both modalities, the higher DE level led only to a small increase in NTCP values (mean differences < 2% in all models, except for the risk of aspiration, which increased on average by 8% and 6% with IMXT and IMPT, respectively, but showed a considerable patient dependence. Conclusions:Both DE levels appear applicable to patients with IMXT and IMPT since all calculated NTCP values, except for one, increased only little for the higher DE level. The estimated TCP increase is of relevant magnitude. The higher DE schedule needs to be investigated carefully in the setting of a prospective clinical trial, especially regarding toxicities caused by high local doses that lack a sound dose response description, e.g., ulcers.

  18. Utilization pattern and survival outcomes of adjuvant therapies in high-grade nonretroperitoneal abdominal soft tissue sarcoma: A population-based study.

    Science.gov (United States)

    Green, William Ross; Chokshi, Ravi; Jabbour, Salma K; DeLaney, Thomas F; Mahmoud, Omar

    2018-02-01

    Nonretroperitoneal abdominal soft tissue sarcoma (NRA-STS) is a rare disease with limited data supporting its management. Our study aimed to reveal the utilization patterns of adjuvant therapy and its potential survival benefits using the National Cancer Data Base. The analysis included patients with resected high-grade NRA-STS. Chi-square analysis was used to evaluate distribution of patient and tumor-related factors within treatment groups. The Kaplan-Meier and Cox proportional hazards model were utilized to evaluate overall survival according to treatment approach. Multivariate analysis was used to determine the impact of these factors on patients' outcome. Matched propensity score analysis was implemented to control for imbalance of confounding variables. At median follow-up of 49 months, 5-year overall survival improved from 46% without adjuvant radiation therapy to 52% (P = 0.009) with radiotherapy delivery with a 30% reduction in hazard of death (95% confidence interval = 0.58-0.84). On multivariate analysis, age <50, tumor <8 cm, negative margins and radiotherapy delivery were significant predictors of improved survival. Chemotherapy was not associated with significant survival improvement (Hazard Ratios [HR]: 0.89, P = 0.28). Adjuvant radiotherapy was associated with improved survival in high-grade NRA-STS. Chemotherapy was not associated with a survival improvement; however, further studies are needed to refine treatment strategies. © 2017 John Wiley & Sons Australia, Ltd.

  19. In vitro cultivation of canine multipotent mesenchymal stromal cells on collagen membranes treated with hyaluronic acid for cell therapy and tissue regeneration

    Directory of Open Access Journals (Sweden)

    T.I. Wodewotzky

    2012-12-01

    Full Text Available Support structures for dermal regeneration are composed of biodegradable and bioresorbable polymers, animal skin or tendons, or are bacteria products. The use of such materials is controversial due to their low efficiency. An important area within tissue engineering is the application of multipotent mesenchymal stromal cells (MSCs to reparative surgery. The combined use of biodegradable membranes with stem cell therapy may lead to promising results for patients undergoing unsuccessful conventional treatments. Thus, the aim of this study was to test the efficacy of using membranes composed of anionic collagen with or without the addition of hyaluronic acid (HA as a substrate for adhesion and in vitro differentiation of bone marrow-derived canine MSCs. The benefit of basic fibroblast growth factor (bFGF on the differentiation of cells in culture was also tested. MSCs were collected from dog bone marrow, isolated and grown on collagen scaffolds with or without HA. Cell viability, proliferation rate, and cellular toxicity were analyzed after 7 days. The cultured cells showed uniform growth and morphological characteristics of undifferentiated MSCs, which demonstrated that MSCs successfully adapted to the culture conditions established by collagen scaffolds with or without HA. This demonstrates that such scaffolds are promising for applications to tissue regeneration. bFGF significantly increased the proliferative rate of MSCs by 63% when compared to groups without the addition of the growth factor. However, the addition of bFGF becomes limiting, since it has an inhibitory effect at high concentrations in culture medium.

  20. In vitro cultivation of canine multipotent mesenchymal stromal cells on collagen membranes treated with hyaluronic acid for cell therapy and tissue regeneration

    International Nuclear Information System (INIS)

    Wodewotzky, T.I.; Lima-Neto, J.F.; Pereira-Júnior, O.C.M.; Sudano, M.J.; Lima, S.A.F.; Bersano, P.R.O.; Yoshioka, S.A.; Landim-Alvarenga, F.C.

    2012-01-01

    Support structures for dermal regeneration are composed of biodegradable and bioresorbable polymers, animal skin or tendons, or are bacteria products. The use of such materials is controversial due to their low efficiency. An important area within tissue engineering is the application of multipotent mesenchymal stromal cells (MSCs) to reparative surgery. The combined use of biodegradable membranes with stem cell therapy may lead to promising results for patients undergoing unsuccessful conventional treatments. Thus, the aim of this study was to test the efficacy of using membranes composed of anionic collagen with or without the addition of hyaluronic acid (HA) as a substrate for adhesion and in vitro differentiation of bone marrow-derived canine MSCs. The benefit of basic fibroblast growth factor (bFGF) on the differentiation of cells in culture was also tested. MSCs were collected from dog bone marrow, isolated and grown on collagen scaffolds with or without HA. Cell viability, proliferation rate, and cellular toxicity were analyzed after 7 days. The cultured cells showed uniform growth and morphological characteristics of undifferentiated MSCs, which demonstrated that MSCs successfully adapted to the culture conditions established by collagen scaffolds with or without HA. This demonstrates that such scaffolds are promising for applications to tissue regeneration. bFGF significantly increased the proliferative rate of MSCs by 63% when compared to groups without the addition of the growth factor. However, the addition of bFGF becomes limiting, since it has an inhibitory effect at high concentrations in culture medium

  1. In vitro cultivation of canine multipotent mesenchymal stromal cells on collagen membranes treated with hyaluronic acid for cell therapy and tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Wodewotzky, T.I.; Lima-Neto, J.F. [Departamento de Reprodução Animal e Radiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil); Pereira-Júnior, O.C.M. [Departamento de Reprodução Animal e Radiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil); Departamento de Cirurgia e Anestesiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil); Sudano, M.J.; Lima, S.A.F. [Departamento de Reprodução Animal e Radiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil); Bersano, P.R.O. [Departamento de Patologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil); Yoshioka, S.A. [Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP (Brazil); Landim-Alvarenga, F.C. [Departamento de Reprodução Animal e Radiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual de São Paulo, Botucatu, SP (Brazil)

    2012-09-21

    Support structures for dermal regeneration are composed of biodegradable and bioresorbable polymers, animal skin or tendons, or are bacteria products. The use of such materials is controversial due to their low efficiency. An important area within tissue engineering is the application of multipotent mesenchymal stromal cells (MSCs) to reparative surgery. The combined use of biodegradable membranes with stem cell therapy may lead to promising results for patients undergoing unsuccessful conventional treatments. Thus, the aim of this study was to test the efficacy of using membranes composed of anionic collagen with or without the addition of hyaluronic acid (HA) as a substrate for adhesion and in vitro differentiation of bone marrow-derived canine MSCs. The benefit of basic fibroblast growth factor (bFGF) on the differentiation of cells in culture was also tested. MSCs were collected from dog bone marrow, isolated and grown on collagen scaffolds with or without HA. Cell viability, proliferation rate, and cellular toxicity were analyzed after 7 days. The cultured cells showed uniform growth and morphological characteristics of undifferentiated MSCs, which demonstrated that MSCs successfully adapted to the culture conditions established by collagen scaffolds with or without HA. This demonstrates that such scaffolds are promising for applications to tissue regeneration. bFGF significantly increased the proliferative rate of MSCs by 63% when compared to groups without the addition of the growth factor. However, the addition of bFGF becomes limiting, since it has an inhibitory effect at high concentrations in culture medium.

  2. Measurements of free and total PSA, tissue polypeptide-specific antigen (TPS), and CYFRA 21-1 in prostate cancer patients under intermittent androgen suppression therapy.

    Science.gov (United States)

    Theyer, G; Dürer, A; Theyer, U; Haberl, I; Ulsperger, E; Baumgartner, G; Hamilton, G

    1999-10-01

    The present study evaluated monthly measurements of free and total prostate-specific antigen (PSA), and the tumor proliferation markers tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 21-1 (CYFRA 21-1) in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Thirty-four men received alternating cycles of 8 month androgen suppression and treatment cessation (mean duration, 10.3 months) until PSA increased to >20 microg/l. Measurements of testosterone, percentage of free PSA, TPS, and CYFRA 21-1 were performed using ELISA and RIA assays. Periods of androgen suppression resulted in reversible reductions of testosterone (from 6 +/- 0.8 to IAS cycle. TPS showed a decrease of 50% after 3 months, and CYFRA 21-1 a 25% decrease after 7 months of androgen suppression treatment. During treatment cessation, TPS exceeded the normal cutoff value of 90 U/l late in tumor regrowth (9-11 months), whereas CYFRA 21-1 remained below the normal cutoff value of 3.3 ng/ml. PSA is the best and most sensitive marker of prostate cancer regression and regrowth during IAS cycles of the markers tested in this study. Free PSA constitutes approximately 15% of total PSA (range, 5-32%), and its percentage showed no significant change during IAS cycles. The TPS and CYFRA 21-1 proliferation marker changes in IAS seem to be related mainly to effects on normal androgen-dependent tissues. Copyright 1999 Wiley-Liss, Inc.

  3. Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

    Science.gov (United States)

    Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

    2014-03-01

    There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

  4. Bio-Engineering tissue and V.A.C. therapy: A new method for the treatment of extensive necrotizing infection in the diabetic foot.

    Science.gov (United States)

    Armenio, Andrea; Cutrignelli, Daniela Anna; Nardulli, Maria Luisa; Maggio, Giulio; Memeo, Giuseppe; De Santis, Valerio; Giudice, Giuseppe; Ressa, Cosmo Maurizio

    2017-01-01

    The aim of the study is to compare the standard care for progressive necrotizing infection in diabetic foot with a treatment protocol based on the association between autologous fibroblast grafts and vacuum-assisted closure therapy (V.A.C.). A retrospective matched Case-Control study was carried out on 20 patients with diabetic foot infection, 10 treated with the standard care and 10 with our new protocol. Inclusion criteria were: acute diabetic foot necrosis (Wagner III and IV), ulcer size (30 to 80 cm2), tendon and bone exposure. Success in the treatment was evaluated as: percentage of healing at the 20th week, time of healing, deambulation, recurrence and major amputation rate. A 90% healing rate was observed after 20 weeks in the study group, compared to a 28.6% in the control group. The recurrence rate in the treated areas was 20% in the study group and 100% in the control group. None of the patients in either group required major amputations. We achieved very promising results by associating autologous fibroblasts grafts and V.A.C. therapy, in comparison with standard care. V.A.C. therapy seems to improve the growth rate of the fibroblasts, probably by sealing the wound and providing a moist environment following the fibroblast graft. The improved neoangiogenesis of the neo-dermis could explain the reduced recurrence rate of the study group. Despite the low number of patients involved and the retrospective nature of the analysis, this study showed a reliable, safe and cost-effective method of treating extensive infection in the diabetic foot. Bio-Engineered Tissue, Diabetic foot, Fibroblast graft, V.A.C.

  5. Role of vitamin C as an adjuvant therapy to different iron chelators in young β-thalassemia major patients: efficacy and safety in relation to tissue iron overload.

    Science.gov (United States)

    Elalfy, Mohsen S; Saber, Maha M; Adly, Amira Abdel Moneam; Ismail, Eman A; Tarif, Mohamed; Ibrahim, Fatma; Elalfy, Omar M

    2016-03-01

    Vitamin C, as antioxidant, increases the efficacy of deferoxamine (DFO). To investigate the effects of vitamin C as an adjuvant therapy to the three used iron chelators in moderately iron-overloaded young vitamin C-deficient patients with β-thalassemia major (β-TM) in relation to tissue iron overload. This randomized prospective trial that included 180 β-TM vitamin C-deficient patients were equally divided into three groups (n = 60) and received DFO, deferiprone (DFP), and deferasirox (DFX). Patients in each group were further randomized either to receive vitamin C supplementation (100 mg daily) or not (n = 30). All patients received vitamin C (group A) or no vitamin C (group B) were followed up for 1 yr with assessment of transfusion index, hemoglobin, iron profile, liver iron concentration (LIC) and cardiac magnetic resonance imaging (MRI) T2*. Baseline vitamin C was negatively correlated with transfusion index, serum ferritin (SF), and LIC. After vitamin C therapy, transfusion index, serum iron, SF, transferrin saturation (Tsat), and LIC were significantly decreased in group A patients, while hemoglobin and cardiac MRI T2* were elevated compared with baseline levels or those in group B without vitamin C. The same improvement was found among DFO-treated patients post-vitamin C compared with baseline data. DFO-treated patients had the highest hemoglobin with the lowest iron, SF, and Tsat compared with DFP or DFX subgroups. Vitamin C as an adjuvant therapy possibly potentiates the efficacy of DFO more than DFP and DFX in reducing iron burden in the moderately iron-overloaded vitamin C-deficient patients with β-TM, with no adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yen-Wen [National Taiwan University Hospital, Department of Internal Medicine, Taipei (China); National Taiwan University Hospital, Department of Nuclear Medicine, Taipei (China); Kao, Hsian-Li; Chen, Ming-Fong; Lin, Lian-Yu; Wang, Yi-Chih; Lin, Yen-Hung; Lin, Hung-Ju; Huang, Por-Jau [National Taiwan University Hospital, Department of Internal Medicine, Taipei (China); Huang, Chi-Lun [Tao-Yuan General Hospital, Department of Internal Medicine, Tao-Yuan (China); Tzen, Kai-Yuan; Yen, Ruoh-Fang [National Taiwan University Hospital, Department of Nuclear Medicine, Taipei (China); Chi, Yu-Chiao [National Taiwan University, Graduate Institute of Clinical Medicine, College of Medicine, Taipei (China); Yang, Wei-Shiung [National Taiwan University Hospital, Department of Internal Medicine, Taipei (China); National Taiwan University, Graduate Institute of Clinical Medicine, College of Medicine, Taipei (China)

    2012-03-15

    {sup 18}F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has the potential to track vascular inflammation and monitor therapeutic response. The purpose of this study was to determine the association between arterial inflammation, calcification and serological biomarkers in subjects with atherosclerosis, and to assess their therapeutic response to 12-week atorvastatin treatment. Forty-three statin-naive subjects with atherosclerosis received atorvastatin (40 mg/day) for 12 weeks and underwent {sup 18}F-FDG PET/CT, coronary calcification and abdominal adipose tissue volume measurements. A panel of serological biomarkers was analysed. Arterial inflammation was measured at seven arterial segments and normalized to venous FDG activity to produce target to background ratios (TBR). Thirty-four subjects without cardiovascular disease who repeated PET 1-4 years apart for routine health check-ups were retrospectively evaluated for comparison. The baseline mean TBR values in atherosclerotic patients were positively correlated with age (R = 0.36), body mass index (R = 0.54), abdominal visceral adipose tissue volume (R = 0.65), coronary calcification score (R = 0.40), levels of low-density lipoprotein cholesterol (R = 0.54), matrix metalloproteinase (MMP)-9 (R = 0.46) and fatty acid binding protein 4 (FABP4) (R = 0.67, all p < 0.05). The TBR as well as high-sensitivity C-reactive protein (hsCRP), E-selectin, MMP-9, monocyte chemotactic protein 1, FABP4 and follistatin values were reduced significantly after the 12-week atorvastatin treatment. The TBR reduction marginally correlated with changes in MMP-9 levels (R = 0.56, p = 0.05). The control group, whose median age was younger, by comparison had lower hsCRP and arterial TBR than the subjects with atherosclerosis (all p < 0.05), and moreover had a slight but insignificant increase in mean TBR at their 2.5{+-}0.8 year follow-up. The medium dose of atorvastatin over a 12-week period resulted in a significant

  7. The effects of 3-month atorvastatin therapy on arterial inflammation, calcification, abdominal adipose tissue and circulating biomarkers

    International Nuclear Information System (INIS)

    Wu, Yen-Wen; Kao, Hsian-Li; Chen, Ming-Fong; Lin, Lian-Yu.; Wang, Yi-Chih; Lin, Yen-Hung; Lin, Hung-Ju; Huang, Por-Jau; Huang, Chi-Lun; Tzen, Kai-Yuan; Yen, Ruoh-Fang; Chi, Yu-Chiao; Yang, Wei-Shiung

    2012-01-01

    18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT has the potential to track vascular inflammation and monitor therapeutic response. The purpose of this study was to determine the association between arterial inflammation, calcification and serological biomarkers in subjects with atherosclerosis, and to assess their therapeutic response to 12-week atorvastatin treatment. Forty-three statin-naive subjects with atherosclerosis received atorvastatin (40 mg/day) for 12 weeks and underwent 18 F-FDG PET/CT, coronary calcification and abdominal adipose tissue volume measurements. A panel of serological biomarkers was analysed. Arterial inflammation was measured at seven arterial segments and normalized to venous FDG activity to produce target to background ratios (TBR). Thirty-four subjects without cardiovascular disease who repeated PET 1-4 years apart for routine health check-ups were retrospectively evaluated for comparison. The baseline mean TBR values in atherosclerotic patients were positively correlated with age (R = 0.36), body mass index (R = 0.54), abdominal visceral adipose tissue volume (R = 0.65), coronary calcification score (R = 0.40), levels of low-density lipoprotein cholesterol (R = 0.54), matrix metalloproteinase (MMP)-9 (R = 0.46) and fatty acid binding protein 4 (FABP4) (R = 0.67, all p < 0.05). The TBR as well as high-sensitivity C-reactive protein (hsCRP), E-selectin, MMP-9, monocyte chemotactic protein 1, FABP4 and follistatin values were reduced significantly after the 12-week atorvastatin treatment. The TBR reduction marginally correlated with changes in MMP-9 levels (R = 0.56, p = 0.05). The control group, whose median age was younger, by comparison had lower hsCRP and arterial TBR than the subjects with atherosclerosis (all p < 0.05), and moreover had a slight but insignificant increase in mean TBR at their 2.5±0.8 year follow-up. The medium dose of atorvastatin over a 12-week period resulted in a significant reduction of

  8. SU-F-T-187: Quantifying Normal Tissue Sparing with 4D Robust Optimization of Intensity Modulated Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Newpower, M; Ge, S; Mohan, R [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: To report an approach to quantify the normal tissue sparing for 4D robustly-optimized versus PTV-optimized IMPT plans. Methods: We generated two sets of 90 DVHs from a patient’s 10-phase 4D CT set; one by conventional PTV-based optimization done in the Eclipse treatment planning system, and the other by an in-house robust optimization algorithm. The 90 DVHs were created for the following scenarios in each of the ten phases of the 4DCT: ± 5mm shift along x, y, z; ± 3.5% range uncertainty and a nominal scenario. A Matlab function written by Gay and Niemierko was modified to calculate EUD for each DVH for the following structures: esophagus, heart, ipsilateral lung and spinal cord. An F-test determined whether or not the variances of each structure’s DVHs were statistically different. Then a t-test determined if the average EUDs for each optimization algorithm were statistically significantly different. Results: T-test results showed each structure had a statistically significant difference in average EUD when comparing robust optimization versus PTV-based optimization. Under robust optimization all structures except the spinal cord received lower EUDs than PTV-based optimization. Using robust optimization the average EUDs decreased 1.45% for the esophagus, 1.54% for the heart and 5.45% for the ipsilateral lung. The average EUD to the spinal cord increased 24.86% but was still well below tolerance. Conclusion: This work has helped quantify a qualitative relationship noted earlier in our work: that robust optimization leads to plans with greater normal tissue sparing compared to PTV-based optimization. Except in the case of the spinal cord all structures received a lower EUD under robust optimization and these results are statistically significant. While the average EUD to the spinal cord increased to 25.06 Gy under robust optimization it is still well under the TD50 value of 66.5 Gy from Emami et al. Supported in part by the NCI U19 CA021239.

  9. Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group Response Score

    International Nuclear Information System (INIS)

    Schaefer, Inga-Marie; Hornick, Jason L.; Barysauskas, Constance M.; Raut, Chandrajit P.; Patel, Sagar A.; Royce, Trevor J.; Fletcher, Christopher D.M.; Baldini, Elizabeth H.

    2017-01-01

    Purpose: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). Methods and Materials: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. Results: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Conclusion: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.

  10. Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group Response Score

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, Inga-Marie; Hornick, Jason L. [Department of Pathology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Barysauskas, Constance M. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Raut, Chandrajit P. [Division of Surgical Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Patel, Sagar A.; Royce, Trevor J. [Department of Radiation Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Fletcher, Christopher D.M. [Department of Pathology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Baldini, Elizabeth H., E-mail: ebaldini@partners.org [Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Department of Radiation Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2017-06-01

    Purpose: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). Methods and Materials: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. Results: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Conclusion: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.

  11. Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response Score.

    Science.gov (United States)

    Schaefer, Inga-Marie; Hornick, Jason L; Barysauskas, Constance M; Raut, Chandrajit P; Patel, Sagar A; Royce, Trevor J; Fletcher, Christopher D M; Baldini, Elizabeth H

    2017-06-01

    To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Rates of Reconstruction Failure in Patients Undergoing Immediate Reconstruction With Tissue Expanders and/or Implants and Postmastectomy Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fowble, Barbara, E-mail: BFowble@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Park, Catherine [Department of Radiation Oncology, University of California San Francisco, San Francisco, California (United States); Wang, Frederick; Peled, Anne [Division of Plastic and Reconstructive Surgery, University of California San Francisco, San Francisco, California (United States); Alvarado, Michael; Ewing, Cheryl; Esserman, Laura [Carol Franc Buck Breast Care Center, Department of Surgery, University of California San Francisco, San Francisco, California (United States); Foster, Robert; Sbitany, Hani [Division of Plastic and Reconstructive Surgery, University of California San Francisco, San Francisco, California (United States); Hanlon, Alex [University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania (United States)

    2015-07-01

    Objectives: Mastectomy rates for breast cancer have increased, with a parallel increase in immediate reconstruction. For some women, tissue expander and implant (TE/I) reconstruction is the preferred or sole option. This retrospective study examined the rate of TE/I reconstruction failure (ie, removal of the TE or I with the inability to replace it resulting in no final reconstruction or autologous tissue reconstruction) in patients receiving postmastectomy radiation therapy (PMRT). Methods and Materials: Between 2004 and 2012, 99 women had skin-sparing mastectomies (SSM) or total nipple/areolar skin-sparing mastectomies (TSSM) with immediate TE/I reconstruction and PMRT for pathologic stage II to III breast cancer. Ninety-seven percent had chemotherapy (doxorubicin and taxane-based), 22% underwent targeted therapies, and 78% had endocrine therapy. Radiation consisted of 5000 cGy given in 180 to 200 cGy to the reconstructed breast with or without treatment to the supraclavicular nodes. Median follow-up was 3.8 years. Results: Total TE/I failure was 18% (12% without final reconstruction, 6% converted to autologous reconstruction). In univariate analysis, the strongest predictor of reconstruction failure (RF) was absence of total TE/I coverage (acellular dermal matrix and/or serratus muscle) at the time of radiation. RF occurred in 32.5% of patients without total coverage compared to 9% with coverage (P=.0069). For women with total coverage, the location of the mastectomy scar in the inframammary fold region was associated with higher RF (19% vs 0%, P=.0189). In multivariate analysis, weight was a significant factor for RF, with lower weight associated with a higher RF. Weight appeared to be a surrogate for the interaction of total coverage, thin skin flaps, interval to exchange, and location of the mastectomy scar. Conclusions: RFs in patients receiving PMRT were lowered with total TE/I coverage at the time of radiation by avoiding inframammary fold incisions and

  13. The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy.

    Science.gov (United States)

    Kilinc, Mehmet Okyay; Santidrian, Antonio; Minev, Ivelina; Toth, Robert; Draganov, Dobrin; Nguyen, Duong; Lander, Elliot; Berman, Mark; Minev, Boris; Szalay, Aladar A

    2018-02-07

    Stromal vascular fraction (SVF) represents an attractive source of adult stem cells and progenitors, holding great promise for numerous cell therapy approaches. In 2017, it was reported that 1524 patients received autologous SVF following the enzymatic digestion of liposuction fat. The treatment was safe and effective and patients showed significant clinical improvement. In a collaborative study, we analyzed SVF obtained from 58 patients having degenerative, inflammatory, autoimmune diseases, and advanced stage cancer. Flow analysis showed that freshly isolated SVF was very heterogeneous and harbored four major subsets specific to adipose tissue; CD34 high CD45 - CD31 - CD146 - adipose-derived stromal/stem cells (ADSCs), CD34 low CD45 + CD206 + CD31 - CD146 - hematopoietic stem cell-progenitors (HSC-progenitors), CD34 high CD45 - CD31 + CD146 + adipose tissue-endothelial cells and CD45 - CD34 - CD31 - CD146 + pericytes. Culturing and expanding of SVF revealed a homogenous population lacking hematopoietic lineage markers CD45 and CD34, but were positive for CD90, CD73, CD105, and CD44. Flow cytometry sorting of viable individual subpopulations revealed that ADSCs had the capacity to grow in adherent culture. The identity of the expanded cells as mesenchymal stem cells (MSCs) was further confirmed based on their differentiation into adipogenic and osteogenic lineages. To identify the potential factors, which may determine the beneficial outcome of treatment, we followed 44 patients post-SVF treatment. The gender, age, clinical condition, certain SVF-dose and route of injection, did not play a role on the clinical outcome. Interestingly, SVF yield seemed to be affected by patient's characteristic to various extents. Furthermore, the therapy with adipose-derived and expanded-mesenchymal stem cells (ADE-MSCs) on a limited number of patients, did not suggest increased efficacies compared to SVF treatment. Therefore, we tested the hypothesis that a certain combination

  14. Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: quality and safety data.

    Science.gov (United States)

    Martins, José Paulo; Santos, Jorge Miguel; de Almeida, Joana Marto; Filipe, Mariana Alves; de Almeida, Mariana Vargas Teixeira; Almeida, Sílvia Cristina Paiva; Água-Doce, Ana; Varela, Alexandre; Gilljam, Mari; Stellan, Birgitta; Pohl, Susanne; Dittmar, Kurt; Lindenmaier, Werner; Alici, Evren; Graça, Luís; Cruz, Pedro Estilita; Cruz, Helder Joaquim; Bárcia, Rita Nogueira

    2014-01-17

    Standardization of mesenchymal stromal cells (MSCs) manufacturing is urgently needed to enable translational activities and ultimately facilitate comparison of clinical trial results. In this work we describe the adaptation of a proprietary method for isolation of a specific umbilical cord tissue-derived population of MSCs, herein designated by its registered trademark as UCX®, towards the production of an advanced therapy medicinal product (ATMP). The adaptation focused on different stages of production, from cell isolation steps to cell culturing and cryopreservation. The origin and quality of materials and reagents were considered and steps for avoiding microbiological and endotoxin contamination of the final cell product were implemented. Cell isolation efficiency, MSCs surface markers and genetic profiles, originating from the use of different medium supplements, were compared. The ATMP-compliant UCX® product was also cryopreserved avoiding the use of dimethyl sulfoxide, an added benefit for the use of these cells as an ATMP. Cells were analyzed for expansion capacity and longevity. The final cell product was further characterized by flow cytometry, differentiation potential, and tested for contaminants at various passages. Finally, genetic stability and immune properties were also analyzed. The isolation efficiency of UCX® was not affected by the introduction of clinical grade enzymes. Furthermore, isolation efficiencies and phenotype analyses revealed advantages in the use of human serum in cell culture as opposed to human platelet lysate. Initial decontamination of the tissue followed by the use of mycoplasma- and endotoxin-free materials and reagents in cell isolation and subsequent culture, enabled the removal of antibiotics during cell expansion. UCX®-ATMP maintained a significant expansion potential of 2.5 population doublings per week up to passage 15 (P15). They were also efficiently cryopreserved in a DMSO-free cryoprotectant medium with

  15. Photobiomodulation Therapy Decreases Oxidative Stress in the Lung Tissue after Formaldehyde Exposure: Role of Oxidant/Antioxidant Enzymes

    Directory of Open Access Journals (Sweden)

    Rodrigo Silva Macedo

    2016-01-01

    Full Text Available Formaldehyde is ubiquitous pollutant that induces oxidative stress in the lung. Several lung diseases have been associated with oxidative stress and their control is necessary. Photobiomodulation therapy (PBMT has been highlighted as a promissory treatment, but its mechanisms need to be better investigated. Our objective was to evaluate the effects of PBMT on the oxidative stress generated by FA exposure. Male Wistar rats were submitted to FA exposure of 1% or vehicle (3 days and treated or not with PBMT (1 and 5 h after each FA exposure. Rats treated only with laser were used as control. Twenty-four hours after the last FA exposure, we analyzed the effects of PBMT on the generation of nitrites and hydrogen peroxide, oxidative burst, glutathione reductase, peroxidase, S-transferase enzyme activities, the gene expression of nitric oxide, cyclooxygenase, superoxide dismutase, the catalase enzyme, and heme oxygenase-1. PBMT reduced the generation of nitrites and hydrogen peroxide and increased oxidative burst in the lung cells. A decreased level of oxidant enzymes was observed which were concomitantly related to an increased level of antioxidants. This study provides new information about the antioxidant mechanisms of PBMT in the lung and might constitute an important tool for lung disease treatment.

  16. Hyperbaric oxygen therapy in the treatment of radio-induced lesions in normal tissues: a literature review

    International Nuclear Information System (INIS)

    Pasquier, David; Hoelscher, Tobias; Schmutz, Jorg; Dische, Stanley; Mathieu, Daniel; Baumann, Michael; Lartigau, Eric

    2004-01-01

    Late complications are one of the major factors limiting radiotherapy treatment, and their treatment is not codified. Hyperbaric oxygen (HBO) has been used in combination with radiotherapy for over half a century, either to maximise its effectiveness or in an attempt to treat late complications. In this latter case, retrospective trials and case reports are prevailing in literature. This prompted European Society for Therapeutic Radiotherapy and Oncology and European Committee for Hyperbaric Medicine to organise a consensus conference in October 2001, dealing with the HBO indications on radiotherapy for the treatment and prevention of late complications. This updated literature review is part of the documents the jury based its opinion on. A systematic search was done on literature from 1960 to 2004, by only taking into account the articles that appeared in peer review journals. Hyperbaric oxygen treatment involving complications to the head and neck, pelvis and nervous system, and the prevention of complications after surgery in irradiated tissues have been studied. Despite the small number of controlled trials, it may be indicated for the treatment of mandibular osteoradionecrosis in combination with surgery, haemorrhagic cystitis resistant to conventional treatments and the prevention of osteoradionecrosis after dental extraction, whose level of evidence seems to be the most significant though randomised trials are still necessary. The other treatment methods are also outlined for each location

  17. Radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma: Dose-volumetric analysis and its clinical implications

    International Nuclear Information System (INIS)

    Lim, Hyeon Won; Kim, Tae Hyun; Choi, Il Ju; Kim, Chan Gyoo; Lee, Jong Yeul; Cho, Soo Jeong; Eom, Hyeon Seok; Moon, Sung Ho; Kim, Dae Yong

    2016-01-01

    To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, Dmax and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and Dmean and V15 for right kidney and Dmean for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys

  18. High-density lipoprotein-based therapy reduces the hemorrhagic complications associated with tissue plasminogen activator treatment in experimental stroke.

    Science.gov (United States)

    Lapergue, Bertrand; Dang, Bao Quoc; Desilles, Jean-Philippe; Ortiz-Munoz, Guadalupe; Delbosc, Sandrine; Loyau, Stéphane; Louedec, Liliane; Couraud, Pierre-Olivier; Mazighi, Mikael; Michel, Jean-Baptiste; Meilhac, Olivier; Amarenco, Pierre

    2013-03-01

    We have previously reported that intravenous injection of high-density lipoproteins (HDLs) was neuroprotective in an embolic stroke model. We hypothesized that HDL vasculoprotective actions on the blood-brain barrier (BBB) may decrease hemorrhagic transformation-associated with tissue plasminogen activator (tPA) administration in acute stroke. We used tPA alone or in combination with HDLs in vivo in 2 models of focal middle cerebral artery occlusion (MCAO) (embolic and 4-hour monofilament MCAO) and in vitro in a model of BBB. Sprague-Dawley rats were submitted to MCAO, n=12 per group. The rats were then randomly injected with tPA (10 mg/kg) or saline with or without human plasma purified-HDL (10 mg/kg). The therapeutic effects of HDL and BBB integrity were assessed blindly 24 hours later. The integrity of the BBB was also tested using an in vitro model of human cerebral endothelial cells under oxygen-glucose deprivation. tPA-treated groups had significantly higher mortality and rate of hemorrhagic transformation at 24 hours in both MCAO models. Cotreatment with HDL significantly reduced stroke-induced mortality versus tPA alone (by 42% in filament MCAO, P=0.009; by 73% in embolic MCAO, P=0.05) and tPA-induced intracerebral parenchymal hematoma (by 92% in filament MCAO, by 100% in embolic MCAO; Phemorrhagic transformation in rat models of MCAO. Both in vivo and in vitro results support the vasculoprotective action of HDLs on BBB under ischemic conditions.

  19. Radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma: Dose-volumetric analysis and its clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyeon Won; Kim, Tae Hyun; Choi, Il Ju; Kim, Chan Gyoo; Lee, Jong Yeul; Cho, Soo Jeong; Eom, Hyeon Seok; Moon, Sung Ho; Kim, Dae Yong [Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

    2016-09-15

    To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, Dmax and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and Dmean and V15 for right kidney and Dmean for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys.

  20. Prognostic Value of External Beam Radiation Therapy in Patients Treated With Surgical Resection and Intraoperative Electron Beam Radiation Therapy for Locally Recurrent Soft Tissue Sarcoma: A Multicentric Long-Term Outcome Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Calvo, Felipe A. [Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); School of Medicine, Complutense University, Madrid (Spain); Sole, Claudio V., E-mail: cvsole@uc.cl [Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); School of Medicine, Complutense University, Madrid (Spain); Service of Radiation Oncology, Instituto de Radiomedicina, Santiago (Chile); Cambeiro, Mauricio [Service of Radiation Oncology, Clínica Universitaria, Universidad de Navarra, Pamplona (Spain); Montero, Angel; Polo, Alfredo [Service of Radiation Oncology, Hospital Universitario Ramón y Cajal, Universidad de Alcala, Madrid (Spain); Gonzalez, Carmen [School of Medicine, Complutense University, Madrid (Spain); Service of Radiation Oncology, Instituto de Radiomedicina, Santiago (Chile); Service of Radiation Oncology, Clínica Universitaria, Universidad de Navarra, Pamplona (Spain); Service of Radiation Oncology, Hospital Universitario Ramón y Cajal, Universidad de Alcala, Madrid (Spain); Service of Radiation Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Cuervo, Miguel [Service of Orthopedics and Traumatology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); San Julian, Mikel [Service of Orthopedics and Traumatology, Clínica Universitaria, Universidad de Navarra, Pamplona (Spain); and others

    2014-01-01

    Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy.

  1. Prognostic Value of External Beam Radiation Therapy in Patients Treated With Surgical Resection and Intraoperative Electron Beam Radiation Therapy for Locally Recurrent Soft Tissue Sarcoma: A Multicentric Long-Term Outcome Analysis

    International Nuclear Information System (INIS)

    Calvo, Felipe A.; Sole, Claudio V.; Cambeiro, Mauricio; Montero, Angel; Polo, Alfredo; Gonzalez, Carmen; Cuervo, Miguel; San Julian, Mikel

    2014-01-01

    Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P=.02) and microscopically involved margin resection status (P=.04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P=.03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy

  2. Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Reinhardt, Michael J.; Joe, Alexius Y.; Mallek, Dirk von; Ezziddin, Samer; Palmedo, Holger [Department of Nuclear Medicine, University Hospital of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany); Brink, Ingo [Department of Nuclear Medicine, University Hospital of Freiburg (Germany); Krause, Thomas M. [Department of Nuclear Medicine, Inselspital Bern (Switzerland)

    2002-09-01

    This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15{+-}9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256{+-}80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses

  3. Design of polymeric carrier containing boron for boron neutron capture therapy and its use in tissue cultures

    International Nuclear Information System (INIS)

    Kahraman, G.

    2004-01-01

    The aim of this study is the synthesis of a new alternative boron containing polymer carrier to be used for Boron Neutron Capture Therapy (BNCT) (one of the treatment methods for brain tumours) and to investigate its use in cell cultures. First of all, B-containing copolymer were synthesized by complex-radical copolymerization of vinylphenylboronic acid and maleic anhydride with 2, 2- azobisisobutyronitrile as an initiator in DMF solvent at 65 degree Celsius under nitrogen atmosphere. Macro branched derivatives of these polymers were synthesized by the partial grafting with α-hydroxy,ω -methoxy-poly(ethylene oxide). Characterization of Poly(VPBA-co-MA) and these macro branched copolymers were performed by FTIR, 1 H NMR spectroscopy, X-Ray diffraction, DSC and TGA analyses. As a result of these analyses, it was observed that these macro branched copolymers had a higher crystallinity and thermal stability than the copolymer. These properties of macro branched copolymers are explained by self-organized H-bonding effect in radical copolymerization and grafting reactions and by the formation of self assembled supramolecular architecture. The selected macro branched copolymer was incorporated by poly(ethylene imine) in order to uptake to cell and thus, this synthesized macro complex copolymer [(VFBA-co-MA)-g-PEG/PEI] was charged with positive charge. As a result of FTIR analysis, it was observed that COO - .NH + complex was formed. After the cell culture experiment, it was observed that this macro complex copolymer labelled with fluorescein up took to HeLa cells with 7 % efficiency. And then, folic acid was incorporated in [(VFBA-co-MA)-g-PEG/PEI] macro complex in order to provide selective targeting properties with tumour cells. As a result of the experiment of cell culture containing mixture of HeLa and fibroblast cell, it was observed that [(VFBA-co-MA)-g-PEG/PEI]-FA macro complex went towards to HeLa cells selectively by means of fluorescence microscopy. Poly

  4. Favorable effect of optimal lipid-lowering therapy on neointimal tissue characteristics after drug-eluting stent implantation: qualitative optical coherence tomographic analysis.

    Science.gov (United States)

    Jang, Ji-Yong; Kim, Jung-Sun; Shin, Dong-Ho; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

    2015-10-01

    Serial follow-up optical coherence tomography (OCT) was used to evaluate the effect of optimal lipid-lowering therapy on qualitative changes in neointimal tissue characteristics after drug-eluting stent (DES) implantation. DES-treated patients (n = 218) who received statin therapy were examined with serial follow-up OCT. First and second follow-up OCT evaluations were performed approximately 6 and 18 months after the index procedure, respectively. Patients were divided into two groups, based on the level of low-density lipoprotein-cholesterol (LDL-C), which was measured at the second follow-up. The optimal lipid-lowering group (n = 121) had an LDL-C reduction of ≥50% or an LDL-C level ≤70 mg/dL, and the conventional group (n = 97). Neointimal characteristics were qualitatively categorized as homogeneous or non-homogeneous patterns using OCT. The non-homogeneous group included heterogeneous, layered, or neoatherosclerosis patterns. Qualitative changes in neointimal tissue characteristics between the first and second follow-up OCT examinations were assessed. Between the first and second follow-up OCT procedures, the neointimal cross-sectional area increased more substantially in the conventional group (0.4 mm(2) vs. 0.2 mm(2) in the optimal lipid-lowering group, p = 0.01). The neointimal pattern changed from homogeneous to non-homogeneous less often in the optimal lipid-lowering group (1.3%, 1/77, p < 0.001) than in the conventional group (15.3%, 11/72, p = 0.44). Optimal LDL-C reduction was an independent predictor for the prevention of neointimal pattern change from homogeneous to non-homogeneous (odds ratio: 0.05, 95% confidence interval: 0.01∼0.46, p = 0.008). Our findings suggest that an intensive reduction in LDL-C levels can prevent non-homogeneous changes in the neointima and increases in neointimal cross-sectional area compared with conventional LDL-C controls. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. 3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms.

    Science.gov (United States)

    Burtnyk, Mathieu; N'Djin, William Apoutou; Kobelevskiy, Ilya; Bronskill, Michael; Chopra, Rajiv

    2010-11-21

    MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 × 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm(-2). Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ± 1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 °C and 0

  6. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

    International Nuclear Information System (INIS)

    Simpson, Daniel R.; Song, William Y.; Moiseenko, Vitali; Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2012-01-01

    Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I–III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade ≥2 GI toxicity and the volume of bowel receiving ≥45 Gy (V 45 ) using the logistic model. Results: Twenty-three patients (46%) had Grade ≥2 GI toxicity. The mean (SD) V 45 was 143 mL (99). The mean V 45 values for patients with and without Grade ≥2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V 45 >150 mL. The proportion of patients with Grade ≥2 GI toxicity with and without V 45 >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and γ were 161 mL (95% confidence interval [CI] 60–399) and 0.31 (95% CI 0.04–0.63), respectively. On multivariable logistic regression, increased V 45 was associated with an increased odds of Grade ≥2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04–4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V 45 is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V 45 could reduce the risk of Grade ≥2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  7. Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

    Energy Technology Data Exchange (ETDEWEB)

    Jebsen, Nina L., E-mail: nina.louise.jebsen@helse-bergen.no [Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen (Norway); Department of Oncology, Haukeland University Hospital, Bergen (Norway); Engellau, Jacob [Department of Oncology, Skåne University Hospital, Lund (Sweden); Engström, Katarina [Department of Oncology, Sahlgrenska University Hospital, Gothenburg (Sweden); Bauer, Henrik C. [Department of Molecular Medicine and Surgery, Section for Orthopaedics and Sports Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm (Sweden); Monge, Odd R. [Department of Oncology, Haukeland University Hospital, Bergen (Norway); Muren, Ludvig P. [Department of Physics and Technology, University of Bergen, Bergen (Norway); Department of Medical Physics, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Eide, Geir E. [Centre for Clinical Research, Haukeland University Hospital, Bergen (Norway); Department of Public Health and Primary Health Care, University of Bergen, Bergen (Norway); Trovik, Clement S. [Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen (Norway); Department of Oncology, Haukeland University Hospital, Bergen (Norway); Bruland, Øyvind S. [Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo (Norway); Institute of Clinical Medicine, University of Oslo, Oslo (Norway)

    2013-08-01

    Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.

  8. Development and validation of a new scoring system to predict wound healing after endovascular therapy in critical limb ischemia with tissue loss.

    Science.gov (United States)

    Kobayashi, Norihiro; Hirano, Keisuke; Nakano, Masatsugu; Muramatsu, Toshiya; Tsukahara, Reiko; Ito, Yoshiaki; Ishimori, Hiroshi; Yamawaki, Masahiro; Araki, Motoharu; Takimura, Hideyuki; Sakamoto, Yasunari

    2015-02-01

    To develop a scoring system to predict wound healing in critical limb ischemia (CLI) patients treated with endovascular therapy (EVT). Between July 2007 and January 2013, 184 patients (118 men; mean age 73.0 years) with CLI (217 limbs) and tissue loss underwent EVT. From this cohort 236 separate wounds were divided into development (n = 118) and validation (n = 118) groups. Predictors of wound healing were identified using multivariable analysis. Each predictor was assigned a score based on its regression coefficient, and total scores were calculated, ranging from 0 to 1 for low risk up to ≥ 4 for high risk of a nonhealing wound. The performance of the scoring system in the prediction of wound healing was evaluated by calculating the area under the receiver operating characteristics (ROC) curve. By multivariable analysis, a University of Texas grade ≥ 2 (HR 0.524, 95% CI 0.288-0.951, p = 0.034), an infected wound (HR 0.497, 95% CI 0.276-0.894, p = 0.020), dependence on hemodialysis (HR 0.459, 95% CI 0.259-0.814, p = 0.008), no visible blood flow to the wound (HR 0.343, 95% CI 0.146-0.802, p = 0.014), and major tissue loss (HR 0.322, 95% CI 0.165-0.630, p = 0.001) predicted a non-healing wound. The 1-year rates of wound healing in the low-, intermediate-, and high-risk groups were 94.6%, 67.6%, and 9.1%, respectively, in the development group (p wound healing in CLI patients after endovascular revascularization and is potentially helpful in deciding if additional adjuncts or revascularization should be considered. © The Author(s) 2015.

  9. Patterns of Local Recurrence and Dose Fractionation of Adjuvant Radiation Therapy in 462 Patients With Soft Tissue Sarcoma of Extremity and Trunk Wall

    International Nuclear Information System (INIS)

    Jebsen, Nina L.; Engellau, Jacob; Engström, Katarina; Bauer, Henrik C.; Monge, Odd R.; Muren, Ludvig P.; Eide, Geir E.; Trovik, Clement S.; Bruland, Øyvind S.

    2013-01-01

    Purpose: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. Methods and Materials: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. Results: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. Conclusions: No significant dose–response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma

  10. Forcing lateral electron disequilibrium to spare lung tissue: a novel technique for stereotactic body radiation therapy of lung cancer

    International Nuclear Information System (INIS)

    Disher, Brandon; Hajdok, George; Gaede, Stewart; Mulligan, Matthew; Battista, Jerry J

    2013-01-01

    Stereotactic body radiation therapy (SBRT) has quickly become a preferred treatment option for early-stage lung cancer patients who are ineligible for surgery. This technique uses tightly conformed megavoltage (MV) x-ray beams to irradiate a tumour with ablative doses in only a few treatment fractions. Small high energy x-ray fields can cause lateral electron disequilibrium (LED) to occur within low density media, which can reduce tumour dose. These dose effects may be challenging to predict using analytic dose calculation algorithms, especially at higher beam energies. As a result, previous authors have suggested using low energy photons ( 5 × 5 cm 2 ) for lung cancer patients to avoid the negative dosimetric effects of LED. In this work, we propose a new form of SBRT, described as LED-optimized SBRT (LED-SBRT), which utilizes radiotherapy (RT) parameters designed to cause LED to advantage. It will be shown that LED-SBRT creates enhanced dose gradients at the tumour/lung interface, which can be used to manipulate tumour dose, and/or normal lung dose. To demonstrate the potential benefits of LED-SBRT, the DOSXYZnrc (National Research Council of Canada, Ottawa, ON) Monte Carlo (MC) software was used to calculate dose within a cylindrical phantom and a typical lung patient. 6 MV or 18 MV x-ray fields were focused onto a small tumour volume (diameter ∼1 cm). For the phantom, square fields of 1 × 1 cm 2 , 3 × 3 cm 2 , or 5 × 5 cm 2 were applied. However, in the patient, 3 × 1 cm 2 , 3 × 2 cm 2 , 3 × 2.5 cm 2 , or 3 × 3 cm 2 field sizes were used in simulations to assure target coverage in the superior–inferior direction. To mimic a 180° SBRT arc in the (symmetric) phantom, a single beam profile was calculated, rotated, and beams were summed at 1° segments to accumulate an arc dose distribution. For the patient, a 360° arc was modelled with 36 equally weighted (and spaced) fields focused on the tumour centre. A planning target volume (PTV) was generated

  11. A histological study on the effect of pressure therapy on the activities of myofibroblasts and keratinocytes in hypertrophic scar tissues after burn.

    Science.gov (United States)

    Li-Tsang, Cecilia W P; Feng, Beibei; Huang, Lin; Liu, Xusheng; Shu, Bin; Chan, Yvonne T Y; Cheung, Kwok-Kuen

    2015-08-01

    Although pressure therapy (PT) has been widely used as the first-line treatment for hypertrophic scars (HS), the histopathological changes involved have seldom been studied. This study aimed to examine the longitudinal effect of PT on the histopathological changes in HS. Ten scar samples were selected from six patients with HS after burn and they were given a standardized PT intervention for 3 months while 16 scar samples were obtained on those without PT. The scar biopsies were collected pre-treatment, 1 and 3 months post-intervention for both clinical and histopathological examinations. Clinical assessments demonstrated significant improvement in the thickness and redness of the scars after PT. Histological examination revealed that cell density in the dermal layer was markedly reduced in the 3-months post-pressurized scar tissues, while the arrangement of the collagen fiber was changed from nodular to wave-like pattern. The α-smooth muscle actin immunoreactivity was significantly decreased after 1-month pressure treatment. There was a significant reduction of myofibroblasts population and a concomitant increase in the apoptotic index in the dermal layer in the 3-months' post-pressurized scars. A significant negative correlation was found between the myofibroblasts population and the apoptotic index. The keratinocyte proliferation was found inhibited after PT. Results demonstrated that PT appeared to promote HS maturation by inhibiting the keratinocyte proliferation and suppressing myofibroblasts population, the latter possibly via apoptosis. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  12. Dose--effect relationships for femoral fractures after multimodality limb-sparing therapy of soft-tissue sarcomas of the proximal lower extremity.

    Science.gov (United States)

    Pak, Daniel; Vineberg, Karen A; Griffith, Kent A; Sabolch, Aaron; Chugh, Rashmi; Ben-Josef, Edgar; Biermann, Janet Sybil; Feng, Mary

    2012-07-15

    We investigated the clinical and dosimetric predictors for radiation-associated femoral fractures in patients with proximal lower extremity soft tissue sarcomas (STS). We examined 131 patients with proximal lower extremity STS who received limb-sparing surgery and external-beam radiation therapy between 1985 and 2006. Five (4%) patients sustained pathologic femoral fractures. Dosimetric analysis was limited to 4 fracture patients with full three-dimensional dose information, who were compared with 59 nonfracture patients. The mean doses and volumes of bone (V(d)) receiving specified doses (≥30 Gy, 45 Gy, 60 Gy) at the femoral body, femoral neck, intertrochanteric region, and subtrochanteric region were compared. Clinical predictive factors were also evaluated. Of 4 fracture patients in our dosimetric series, there were three femoral neck fractures with a mean dose of 57.6 ± 8.9 Gy, V30 of 14.5 ± 2.3 cc, V45 of 11.8 ± 1.1 cc, and V60 of 7.2 ± 2.2 cc at the femoral neck compared with 22.9 ± 20.8 Gy, 4.8 ± 5.6 cc, 2.5 ± 3.9 cc, and 0.8 ± 2.7 cc, respectively, for nonfracture patients (p fracture rate was higher than at the subtrochanteric region despite lower mean doses at these subregions. All fracture sites received mean doses greater than 40 Gy. Also, with our policy of prophylactic femoral intramedullary nailing for high-risk patients, there was no significant difference in fracture rates between patients with and without periosteal excision. There were no significant differences in age, sex, tumor size, timing of radiation therapy, and use of chemotherapy between fracture and nonfracture patients. These dose-volume toxicity relationships provide RT optimization goals to guide future efforts for reducing pathologic fracture rates. Prophylactic femoral intramedullary nailing may also reduce fracture risk for susceptible patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Dose-Effect Relationships for Femoral Fractures After Multimodality Limb-Sparing Therapy of Soft-Tissue Sarcomas of the Proximal Lower Extremity

    Energy Technology Data Exchange (ETDEWEB)

    Pak, Daniel; Vineberg, Karen A. [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States); Griffith, Kent A. [Biostatistics Unit, Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI (United States); Sabolch, Aaron [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States); Chugh, Rashmi [Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States); Biermann, Janet Sybil [Department of Orthopedic Surgery, University of Michigan, Ann Arbor, MI (United States); Feng, Mary, E-mail: maryfeng@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States)

    2012-07-15

    Purpose: We investigated the clinical and dosimetric predictors for radiation-associated femoral fractures in patients with proximal lower extremity soft tissue sarcomas (STS). Methods and Materials: We examined 131 patients with proximal lower extremity STS who received limb-sparing surgery and external-beam radiation therapy between 1985 and 2006. Five (4%) patients sustained pathologic femoral fractures. Dosimetric analysis was limited to 4 fracture patients with full three-dimensional dose information, who were compared with 59 nonfracture patients. The mean doses and volumes of bone (V{sub d}) receiving specified doses ({>=}30 Gy, 45 Gy, 60 Gy) at the femoral body, femoral neck, intertrochanteric region, and subtrochanteric region were compared. Clinical predictive factors were also evaluated. Results: Of 4 fracture patients in our dosimetric series, there were three femoral neck fractures with a mean dose of 57.6 {+-} 8.9 Gy, V30 of 14.5 {+-} 2.3 cc, V45 of 11.8 {+-} 1.1 cc, and V60 of 7.2 {+-} 2.2 cc at the femoral neck compared with 22.9 {+-} 20.8 Gy, 4.8 {+-} 5.6 cc, 2.5 {+-} 3.9 cc, and 0.8 {+-} 2.7 cc, respectively, for nonfracture patients (p < 0.03 for all). The femoral neck fracture rate was higher than at the subtrochanteric region despite lower mean doses at these subregions. All fracture sites received mean doses greater than 40 Gy. Also, with our policy of prophylactic femoral intramedullary nailing for high-risk patients, there was no significant difference in fracture rates between patients with and without periosteal excision. There were no significant differences in age, sex, tumor size, timing of radiation therapy, and use of chemotherapy between fracture and nonfracture patients. Conclusions: These dose-volume toxicity relationships provide RT optimization goals to guide future efforts for reducing pathologic fracture rates. Prophylactic femoral intramedullary nailing may also reduce fracture risk for susceptible patients.

  14. Dose–Effect Relationships for Femoral Fractures After Multimodality Limb-Sparing Therapy of Soft-Tissue Sarcomas of the Proximal Lower Extremity

    International Nuclear Information System (INIS)

    Pak, Daniel; Vineberg, Karen A.; Griffith, Kent A.; Sabolch, Aaron; Chugh, Rashmi; Ben-Josef, Edgar; Biermann, Janet Sybil; Feng, Mary

    2012-01-01

    Purpose: We investigated the clinical and dosimetric predictors for radiation-associated femoral fractures in patients with proximal lower extremity soft tissue sarcomas (STS). Methods and Materials: We examined 131 patients with proximal lower extremity STS who received limb-sparing surgery and external-beam radiation therapy between 1985 and 2006. Five (4%) patients sustained pathologic femoral fractures. Dosimetric analysis was limited to 4 fracture patients with full three-dimensional dose information, who were compared with 59 nonfracture patients. The mean doses and volumes of bone (V d ) receiving specified doses (≥30 Gy, 45 Gy, 60 Gy) at the femoral body, femoral neck, intertrochanteric region, and subtrochanteric region were compared. Clinical predictive factors were also evaluated. Results: Of 4 fracture patients in our dosimetric series, there were three femoral neck fractures with a mean dose of 57.6 ± 8.9 Gy, V30 of 14.5 ± 2.3 cc, V45 of 11.8 ± 1.1 cc, and V60 of 7.2 ± 2.2 cc at the femoral neck compared with 22.9 ± 20.8 Gy, 4.8 ± 5.6 cc, 2.5 ± 3.9 cc, and 0.8 ± 2.7 cc, respectively, for nonfracture patients (p < 0.03 for all). The femoral neck fracture rate was higher than at the subtrochanteric region despite lower mean doses at these subregions. All fracture sites received mean doses greater than 40 Gy. Also, with our policy of prophylactic femoral intramedullary nailing for high-risk patients, there was no significant difference in fracture rates between patients with and without periosteal excision. There were no significant differences in age, sex, tumor size, timing of radiation therapy, and use of chemotherapy between fracture and nonfracture patients. Conclusions: These dose–volume toxicity relationships provide RT optimization goals to guide future efforts for reducing pathologic fracture rates. Prophylactic femoral intramedullary nailing may also reduce fracture risk for susceptible patients.

  15. Late Consequential Surgical Bed Soft Tissue Necrosis in Advanced Oropharyngeal Squamous Cell Carcinomas Treated With Transoral Robotic Surgery and Postoperative Radiation Therapy

    International Nuclear Information System (INIS)

    Lukens, J. Nicholas; Lin, Alexander; Gamerman, Victoria; Mitra, Nandita; Grover, Surbhi; McMenamin, Erin M.; Weinstein, Gregory S.; O'Malley, Bert W.; Cohen, Roger B.; Orisamolu, Abimbola; Ahn, Peter H.; Quon, Harry

    2014-01-01

    Purpose: A subset of patients with oropharyngeal squamous cell carcinoma (OP-SCC) managed with transoral robotic surgery (TORS) and postoperative radiation therapy (PORT) developed soft tissue necrosis (STN) in the surgical bed months after completion of PORT. We investigated the frequency and risk factors. Materials and Methods: This retrospective analysis included 170 consecutive OP-SCC patients treated with TORS and PORT between 2006 and 2012, with >6 months' of follow-up. STN was defined as ulceration of the surgical bed >6 weeks after completion of PORT, requiring opioids, biopsy, or hyperbaric oxygen therapy. Results: A total of 47 of 170 patients (28%) had a diagnosis of STN. Tonsillar patients were more susceptible than base-of-tongue (BOT) patients, 39% (41 of 104) versus 9% (6 of 66), respectively. For patients with STN, median tumor size was 3.0 cm (range 1.0-5.6 cm), and depth of resection was 2.2 cm (range 1.0-5.1 cm). Median radiation dose and dose of fraction to the surgical bed were 6600 cGy and 220 cGy, respectively. Thirty-one patients (66%) received concurrent chemotherapy. Median time to STN was 2.5 months after PORT. All patients had resolution of STN after a median of 3.7 months. Multivariate analysis identified tonsillar primary (odds ratio [OR] 4.73, P=.01), depth of resection (OR 3.12, P=.001), total radiation dose to the resection bed (OR 1.51 per Gy, P<.01), and grade 3 acute mucositis (OR 3.47, P=.02) as risk factors for STN. Beginning May 2011, after implementing aggressive avoidance of delivering >2 Gy/day to the resection bed mucosa, only 8% (2 of 26 patients) experienced STN (all grade 2). Conclusions: A subset of OP-SCC patients treated with TORS and PORT are at risk for developing late consequential surgical bed STN. Risk factors include tonsillar location, depth of resection, radiation dose to the surgical bed, and severe mucositis. STN risk is significantly decreased with carefully avoiding a radiation dosage of >2 Gy/day to

  16. Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bazan, Jose G.; Luxton, Gary; Kozak, Margaret M.; Anderson, Eric M.; Hancock, Steven L.; Kapp, Daniel S.; Kidd, Elizabeth A.; Koong, Albert C.; Chang, Daniel T., E-mail: dtchang@stanford.edu

    2013-12-01

    Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Results: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0tissue complication probability curve compared with treatment with Cis. Dose tolerance of PBM and the LSS subsite may be lower for

  17. Dosimetric feasibility of magnetic resonance imaging-guided tri-cobalt 60 preoperative intensity modulated radiation therapy for soft tissue sarcomas of the extremity.

    Science.gov (United States)

    Kishan, Amar U; Cao, Minsong; Mikaeilian, Argin G; Low, Daniel A; Kupelian, Patrick A; Steinberg, Michael L; Kamrava, Mitchell

    2015-01-01

    The purpose of this study was to investigate the dosimetric differences of delivering preoperative intensity modulated radiation therapy (IMRT) to patients with soft tissue sarcomas of the extremity (ESTS) with a teletherapy system equipped with 3 rotating (60)Co sources and a built-in magnetic resonance imaging and with standard linear accelerator (LINAC)-based IMRT. The primary study population consisted of 9 patients treated with preoperative radiation for ESTS between 2008 and 2014 with LINAC-based static field IMRT. LINAC plans were designed to deliver 50 Gy in 25 fractions to 95% of the planning target volume (PTV). Tri-(60)Co system IMRT plans were designed with ViewRay system software. Tri-(60)Co-based IMRT plans achieved equivalent target coverage and dosimetry for organs at risk (long bone, skin, and skin corridor) compared with LINAC-based IMRT plans. The maximum and minimum PTV doses, heterogeneity indices, and ratio of the dose to 50% of the volume were equivalent for both planning systems. One LINAC plan violated the maximum bone dose constraint, whereas none of the tri-(60)Co plans did. Using a tri-(60)Co system, we were able to achieve equivalent dosimetry to the PTV and organs at risk for patients with ESTS compared with LINAC-based IMRT plans. The tri-(60)Co system may be advantageous over current treatment platforms by allowing PTV reduction and by elimination of the additional radiation dose associated with daily image guidance, but this needs to be evaluated prospectively. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  18. TU-H-CAMPUS-TeP2-05: Selective Protection of Normal Tissue by Cerium Oxide Nanoparticles During Radiation Therapy

    International Nuclear Information System (INIS)

    Ouyang, Z; Ngwa, W; Yasmin-Karim, S; Strack, G; Sajo, E

    2016-01-01

    Purpose: Cerium oxide nanoparticles (CONPs) have unique pH dependent properties such that they act as a radical modulator. These properties may be used in radiation therapy (RT) to protect normal tissue. This work investigates the selective radioprotection of CONPs in-vitro and potential for in-situ delivery of CONPs in prostate cancer RT. Methods: i) Normal human umbilical vein endothelial cells (HUVEC) and human prostate cancer cells (PC-3) were treated with 0 or 2 ng/mL CONPs (NP size: 5 nm). 2 Gy of 100 kVp radiation was delivered to the cells 4 hours after the CONP treatment. Cell viability was checked 48 hours later using MTS assays. ii) A prostate tumor was modeled as a 2-cm diameter sphere. CONPs were proposed to be loaded in a hollow radiotherapy fiducial marker. The concentration profile for the CONPs within the tumor was modeled with a previously validated diffusion equation employed in other studies for nanoparticles 10 nm or less. Results: i) Without radiation, cell viability was above 90% when treated with 2 ng/mL CONPs for both HUVEC and PC-3. After irradiation, a slightly higher viability was observed in HUVEC with CONPs than the ones without CONPs, and this effect was not observed in PC-3. ii) Based on the calculations, 2 ng/mL of CONPs could be delivered to normal cells by diffusion with a 1 µg/mL initial concentration within two weeks. Conclusion: We conclude that CONPs can provide selective radioprotection. The delivery of needed concentrations of CONPs is feasible via in-situ release from radiotherapy biomaterials (e.g. fiducials) loaded with the CONPs.

  19. Early initiation of highly active antiretroviral therapy fails to reverse immunovirological abnormalities in gut-associated lymphoid tissue induced by acute HIV infection.

    Science.gov (United States)

    Tincati, Camilla; Biasin, Mara; Bandera, Alessandra; Violin, Michela; Marchetti, Giulia; Piacentini, Luca; Vago, Gian Luca; Balotta, Claudia; Moroni, Mauro; Franzetti, Fabio; Clerici, Mario; Gori, Andrea

    2009-01-01

    During the acute phase of HIV infection, large CD4+ T-cell depletion occurs in the gastrointestinal tract. The kinetics of CD4+ T-cell decrease and highly active antiretroviral therapy (HAART)-mediated immune reconstitution were evaluated. Rectosigmoid colonic (RSC) biopsies and blood samples of nine patients with acute HIV infection were collected. CD4+ T-cell count, HIV RNA, intracellular HIV DNA and messenger RNA cytokine expression were evaluated before and after 6 months of HAART. All nine patients presented symptomatic retroviral infection. Early HAART was associated with a sustained and comparable reduction of HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs) and RSC biopsies. HIV DNA decreased in PBMCs, but was only marginally reduced in RSC biopsies. Comparisons between reduction rates of HIV DNA in these two compartments confirmed that HIV DNA clearance was less efficient in RSC biopsies compared with PBMCs. Assessment of immunological profiles in PBMCs and RSC biopsies showed that the T-helper (Th)1-like/Th2-like ratio was sharply decreased in RSC biopsies and increased in PBMCs throughout the study period. A persistent Th2-like profile was detected in RSC biopsies. Efficient clearing of HIV DNA observed in PBMCs correlated with the establishment of a more favourable Th1-like profile. A less efficient clearance of intracellular HIV DNA following early introduction of HAART is associated with persistent immunological impairment in gut-associated lymphoid tissue (GALT), which is reflected by the skewed expression of cytokines in this reservoir. The present study shows that early initiation of HAART, in the short-term, is not effective in containing the establishment of HIV infection and in reversing associated immunological GALT abnormalities.

  20. Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy

    International Nuclear Information System (INIS)

    Lee, Tsair-Fwu; Yeh, Shyh-An; Chao, Pei-Ju; Chang, Liyun; Chiu, Chien-Liang; Ting, Hui-Min; Wang, Hung-Yu; Huang, Yu-Jie

    2015-01-01

    Radiation-induced tinnitus is a side effect of radiotherapy in the inner ear for cancers of the head and neck. Effective dose constraints for protecting the cochlea are under-reported. The aim of this study is to determine the cochlea dose limitation to avoid causing tinnitus after head-and-neck cancer (HNC) intensity-modulated radiation therapy (IMRT). In total 211 patients with HNC were included; the side effects of radiotherapy were investigated for 422 inner ears in the cohort. Forty-nine of the four hundred and twenty-two samples (11.6 %) developed grade 2+ tinnitus symptoms after IMRT, as diagnosed by a clinician. The Late Effects of Normal Tissues–Subjective, Objective, Management, Analytic (LENT-SOMA) criteria were used for tinnitus evaluation. The logistic and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models were used for the analyses. The NTCP-fitted parameters were TD 50 = 46.31 Gy (95 % CI, 41.46–52.50), γ 50 = 1.27 (95 % CI, 1.02–1.55), and TD 50 = 46.52 Gy (95 % CI, 41.91–53.43), m = 0.35 (95 % CI, 0.30–0.42) for the logistic and LKB models, respectively. The suggested guideline TD 20 for the tolerance dose to produce a 20 % complication rate within a specific period of time was TD 20 = 33.62 Gy (95 % CI, 30.15–38.27) (logistic) and TD 20 = 32.82 Gy (95 % CI, 29.58–37.69) (LKB). To maintain the incidence of grade 2+ tinnitus toxicity <20 % in IMRT, we suggest that the mean dose to the cochlea should be <32 Gy. However, models should not be extrapolated to other patient populations without further verification and should first be confirmed before clinical implementation

  1. TU-H-CAMPUS-TeP2-05: Selective Protection of Normal Tissue by Cerium Oxide Nanoparticles During Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, Z; Ngwa, W [University of Massachusetts Lowell, Lowell, MA (United States); Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (United States); Yasmin-Karim, S [Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (United States); Strack, G; Sajo, E [University of Massachusetts Lowell, Lowell, MA (United States)

    2016-06-15

    Purpose: Cerium oxide nanoparticles (CONPs) have unique pH dependent properties such that they act as a radical modulator. These properties may be used in radiation therapy (RT) to protect normal tissue. This work investigates the selective radioprotection of CONPs in-vitro and potential for in-situ delivery of CONPs in prostate cancer RT. Methods: i) Normal human umbilical vein endothelial cells (HUVEC) and human prostate cancer cells (PC-3) were treated with 0 or 2 ng/mL CONPs (NP size: 5 nm). 2 Gy of 100 kVp radiation was delivered to the cells 4 hours after the CONP treatment. Cell viability was checked 48 hours later using MTS assays. ii) A prostate tumor was modeled as a 2-cm diameter sphere. CONPs were proposed to be loaded in a hollow radiotherapy fiducial marker. The concentration profile for the CONPs within the tumor was modeled with a previously validated diffusion equation employed in other studies for nanoparticles 10 nm or less. Results: i) Without radiation, cell viability was above 90% when treated with 2 ng/mL CONPs for both HUVEC and PC-3. After irradiation, a slightly higher viability was observed in HUVEC with CONPs than the ones without CONPs, and this effect was not observed in PC-3. ii) Based on the calculations, 2 ng/mL of CONPs could be delivered to normal cells by diffusion with a 1 µg/mL initial concentration within two weeks. Conclusion: We conclude that CONPs can provide selective radioprotection. The delivery of needed concentrations of CONPs is feasible via in-situ release from radiotherapy biomaterials (e.g. fiducials) loaded with the CONPs.

  2. Anticipated Intraoperative Electron Beam Boost, External Beam Radiation Therapy, and Limb-Sparing Surgical Resection for Patients with Pediatric Soft-Tissue Sarcomas of the Extremity: A Multicentric Pooled Analysis of Long-Term Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Sole, Claudio V., E-mail: cvsole@uc.cl [Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); School of Medicine, Complutense University, Madrid (Spain); Service of Radiation Oncology, Instituto de Radiomedicina, Santiago (Chile); Calvo, Felipe A. [Department of Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); School of Medicine, Complutense University, Madrid (Spain); Polo, Alfredo [Service of Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid (Spain); Cambeiro, Mauricio [Service of Radiation Oncology, Clínica Universidad de Navarra, Pamplona (Spain); Alvarez, Ana; Gonzalez, Carmen [Service of Radiation Oncology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); Gonzalez, Jose [Service of Pediatric Orthopedics and Traumatology, Hospital General Universitario Gregorio Marañón, Madrid (Spain); San Julian, Mikel [Service of Orthopedics and Traumatology, Clínica Universidad de Navarra, Pamplona (Spain); Martinez-Monge, Rafael [Service of Radiation Oncology, Clínica Universidad de Navarra, Pamplona (Spain)

    2014-09-01

    Purpose: To perform a joint analysis of data from 3 contributing centers within the intraoperative electron-beam radiation therapy (IOERT)-Spanish program, to determine the potential of IOERT as an anticipated boost before external beam radiation therapy in the multidisciplinary treatment of pediatric extremity soft-tissue sarcomas. Methods and Materials: From June 1993 to May 2013, 62 patients (aged <21 years) with a histologic diagnosis of primary extremity soft-tissue sarcoma with absence of distant metastases, undergoing limb-sparing grossly resected surgery, external beam radiation therapy (median dose 40 Gy) and IOERT (median dose 10 Gy) were considered eligible for this analysis. Results: After a median follow-up of 66 months (range, 4-235 months), 10-year local control, disease-free survival, and overall survival was 85%, 76%, and 81%, respectively. In multivariate analysis after adjustment for other covariates, tumor size >5 cm (P=.04) and R1 margin status (P=.04) remained significantly associated with local relapse. In regard to overall survival only margin status (P=.04) retained association on multivariate analysis. Ten patients (16%) reported severe chronic toxicity events (all grade 3). Conclusions: An anticipated IOERT boost allowed for external beam radiation therapy dose reduction, with high local control and acceptably low toxicity rates. The combined radiosurgical approach needs to be tested in a prospective trial to confirm these results.

  3. Anticipated Intraoperative Electron Beam Boost, External Beam Radiation Therapy, and Limb-Sparing Surgical Resection for Patients with Pediatric Soft-Tissue Sarcomas of the Extremity: A Multicentric Pooled Analysis of Long-Term Outcomes

    International Nuclear Information System (INIS)

    Sole, Claudio V.; Calvo, Felipe A.; Polo, Alfredo; Cambeiro, Mauricio; Alvarez, Ana; Gonzalez, Carmen; Gonzalez, Jose; San Julian, Mikel; Martinez-Monge, Rafael

    2014-01-01

    Purpose: To perform a joint analysis of data from 3 contributing centers within the intraoperative electron-beam radiation therapy (IOERT)-Spanish program, to determine the potential of IOERT as an anticipated boost before external beam radiation therapy in the multidisciplinary treatment of pediatric extremity soft-tissue sarcomas. Methods and Materials: From June 1993 to May 2013, 62 patients (aged <21 years) with a histologic diagnosis of primary extremity soft-tissue sarcoma with absence of distant metastases, undergoing limb-sparing grossly resected surgery, external beam radiation therapy (median dose 40 Gy) and IOERT (median dose 10 Gy) were considered eligible for this analysis. Results: After a median follow-up of 66 months (range, 4-235 months), 10-year local control, disease-free survival, and overall survival was 85%, 76%, and 81%, respectively. In multivariate analysis after adjustment for other covariates, tumor size >5 cm (P=.04) and R1 margin status (P=.04) remained significantly associated with local relapse. In regard to overall survival only margin status (P=.04) retained association on multivariate analysis. Ten patients (16%) reported severe chronic toxicity events (all grade 3). Conclusions: An anticipated IOERT boost allowed for external beam radiation therapy dose reduction, with high local control and acceptably low toxicity rates. The combined radiosurgical approach needs to be tested in a prospective trial to confirm these results

  4. SU-C-213-01: 3D Printed Patient Specific Phantom Composed of Bone and Soft Tissue Substitute Plastics for Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ehler, E; Sterling, D; Higgins, P [University of Minnesota, Minneapolis, MN (United States)

    2015-06-15

    Purpose: 3D printed phantoms constructed of multiple tissue approximating materials could be useful in both clinical and research aspects of radiotherapy. This work describes a 3D printed phantom constructed with tissue substitute plastics for both bone and soft tissue; air cavities were included as well. Methods: 3D models of an anonymized nasopharynx patient were generated for air cavities, soft tissues, and bone, which were segmented by Hounsfield Unit (HU) thresholds. HU thresholds were chosen to define air-to-soft tissue boundaries of 0.65 g/cc and soft tissue-to-bone boundaries of 1.18 g/cc based on clinical HU to density tables. After evaluation of several composite plastics, a bone tissue substitute was identified as an acceptable material for typical radiotherapy x-ray energies, composed of iron and PLA plastic. PET plastic was determined to be an acceptable soft tissue substitute. 3D printing was performed on a consumer grade dual extrusion fused deposition model 3D printer. Results: MVCT scans of the 3D printed heterogeneous phantom were acquired. Rigid image registration of the patient and the 3D printed phantom scans was performed. The average physical density of the soft tissue and bone regions was 1.02 ± 0.08 g/cc and 1.39 ± 0.14 g/cc, respectively, for the patient kVCT scan. In the 3D printed phantom MVCT scan, the average density of the soft tissue and bone was 1.01 ± 0.09 g/cc and 1.44 ± 0.12 g/cc, respectively. Conclusion: A patient specific phantom, constructed of heterogeneous tissue substitute materials was constructed by 3D printing. MVCT of the 3D printed phantom showed realistic tissue densities were recreated by the 3D printing materials. Funding provided by intra-department grant by University of Minnesota Department of Radiation Oncology.

  5. SU-C-213-01: 3D Printed Patient Specific Phantom Composed of Bone and Soft Tissue Substitute Plastics for Radiation Therapy

    International Nuclear Information System (INIS)

    Ehler, E; Sterling, D; Higgins, P

    2015-01-01

    Purpose: 3D printed phantoms constructed of multiple tissue approximating materials could be useful in both clinical and research aspects of radiotherapy. This work describes a 3D printed phantom constructed with tissue substitute plastics for both bone and soft tissue; air cavities were included as well. Methods: 3D models of an anonymized nasopharynx patient were generated for air cavities, soft tissues, and bone, which were segmented by Hounsfield Unit (HU) thresholds. HU thresholds were chosen to define air-to-soft tissue boundaries of 0.65 g/cc and soft tissue-to-bone boundaries of 1.18 g/cc based on clinical HU to density tables. After evaluation of several composite plastics, a bone tissue substitute was identified as an acceptable material for typical radiotherapy x-ray energies, composed of iron and PLA plastic. PET plastic was determined to be an acceptable soft tissue substitute. 3D printing was performed on a consumer grade dual extrusion fused deposition model 3D printer. Results: MVCT scans of the 3D printed heterogeneous phantom were acquired. Rigid image registration of the patient and the 3D printed phantom scans was performed. The average physical density of the soft tissue and bone regions was 1.02 ± 0.08 g/cc and 1.39 ± 0.14 g/cc, respectively, for the patient kVCT scan. In the 3D printed phantom MVCT scan, the average density of the soft tissue and bone was 1.01 ± 0.09 g/cc and 1.44 ± 0.12 g/cc, respectively. Conclusion: A patient specific phantom, constructed of heterogeneous tissue substitute materials was constructed by 3D printing. MVCT of the 3D printed phantom showed realistic tissue densities were recreated by the 3D printing materials. Funding provided by intra-department grant by University of Minnesota Department of Radiation Oncology

  6. Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection.

    Directory of Open Access Journals (Sweden)

    Teresa H Evering

    2012-02-01

    Full Text Available Mucosal mononuclear (MMC CCR5+CD4+ T cells of the gastrointestinal (GI tract are selectively infected and depleted during acute HIV-1 infection. Despite early initiation of combination antiretroviral therapy (cART, gut-associated lymphoid tissue (GALT CD4+ T cell depletion and activation persist in the majority of HIV-1 positive individuals studied. This may result from ongoing HIV-1 replication and T-cell activation despite effective cART. We hypothesized that ongoing viral replication in the GI tract during cART would result in measurable viral evolution, with divergent populations emerging over time. Subjects treated during early HIV-1 infection underwent phlebotomy and flexible sigmoidoscopy with biopsies prior to and 15-24 months post initiation of cART. At the 2(nd biopsy, three GALT phenotypes were noted, characterized by high, intermediate and low levels of immune activation. A representative case from each phenotype was analyzed. Each subject had plasma HIV-1 RNA levels <50 copies/ml at 2(nd GI biopsy and CD4+ T cell reconstitution in the peripheral blood. Single genome amplification of full-length HIV-1 envelope was performed for each subject pre- and post-initiation of cART in GALT and PBMC. A total of 280 confirmed single genome sequences (SGS were analyzed for experimental cases. For each subject, maximum likelihood phylogenetic trees derived from molecular sequence data showed no evidence of evolved forms in the GALT over the study period. During treatment, HIV-1 envelope diversity in GALT-derived SGS did not increase and post-treatment GALT-derived SGS showed no substantial genetic divergence from pre-treatment sequences within transmitted groups. Similar results were obtained from PBMC-derived SGS. Our results reveal that initiation of cART during acute/early HIV-1 infection can result in the interruption of measurable viral evolution in the GALT, suggesting the absence of de-novo rounds of HIV-1 replication in this compartment

  7. Non-randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema and tissue fibrosis after radiotherapy for early breast cancer

    International Nuclear Information System (INIS)

    Gothard, Lone; Stanton, Anthony; MacLaren, Julie; Lawrence, David; Hall, Emma; Mortimer, Peter; Parkin, Eileen; Pritchard, Joyce; Risdall, Jane; Sawyer, Robert; Woods, Mary; Yarnold, John

    2004-01-01

    Background: Radiation-induced arm lymphoedema is a common and distressing complication of curative treatment for early breast cancer. Hyperbaric oxygen (HBO 2 ) therapy promotes healing in bone rendered ischaemic by radiotherapy, and may help some soft-tissue injuries too, but is untested in arm lymphoedema. Methods: Twenty-one eligible research volunteers with a minimum 30% increase in arm volume in the years after axillary/supraclavicular radiotherapy (axillary surgery in 18/21 cases) were treated with HBO 2 . The volunteers breathed 100% oxygen at 2.4 ATA for 100 min in a multiplace hyperbaric chamber on 30 occasions over a period of 6 weeks. The volume of the ipsilateral limb, measured opto-electronically by a perometer and expressed as a percentage of contralateral limb volume, was selected as the primary endpoint. A secondary endpoint was local lymph drainage expressed as fractional removal rate of radioisotopic tracer, measured using lymphoscintigraphy. Results: Three out of 19 evaluable patients experienced >20% reduction in arm volume at 12 months. Six out of 13 evaluable patients experienced a >25% improvement in 99 Tc-nanocolloid clearance rate from the ipsilateral forearm measured by quantitative lymphoscintigraphy at 12 months. Overall, there was a statistically significant, but clinically modest, reduction in ipsilateral arm volume at 12 months follow-up compared with baseline (P=0.005). The mean percentage reduction in arm volume from baseline at 12 months was 7.51. Moderate or marked lessening of induration in the irradiated breast, pectoral fold and/or supraclavicular fossa was recorded clinically in 8/15 evaluable patients. Twelve out of 19 evaluable patients volunteered that their arms felt softer, and six reported improvements in shoulder mobility at 12 months. No significant improvements were noted in patient self-assessments of quality of life. Conclusion: Interpretation is limited by the absence of a control group. However, measurement of

  8. SU-E-T-417: The Impact of Normal Tissue Constraints On PTV Dose Homogeneity for Intensity Modulated Radiotherapy (IMRT), Volume Modulated Arc Therapy (VMAT) and Tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Peng, J; McDonald, D; Ashenafi, M; Ellis, A; Vanek, K [Medical University of South Carolina, Charleston, SC (United States)

    2014-06-01

    Purpose: Complex intensity modulated arc therapy tends to spread low dose to normal tissue(NT)regions to obtain improved target conformity and homogeneity and OAR sparing.This work evaluates the trade-offs between PTV homogeneity and reduction of the maximum dose(Dmax)spread to NT while planning of IMRT,VMAT and Tomotherapy. Methods: Ten prostate patients,previously planned with step-and-shoot IMRT,were selected.To fairly evaluate how PTV homogeneity was affected by NT Dmax constraints,original IMRT DVH objectives for PTV and OARs(femoral heads,and rectal and bladder wall)applied to 2 VMAT plans in Pinnacle(V9.0), and Tomotherapy(V4.2).The only constraint difference was the NT which was defined as body contours excluding targets,OARs and dose rings.NT Dmax constraint for 1st VMAT was set to the prescription dose(Dp).For 2nd VMAT(VMAT-NT)and Tomotherapy,it was set to the Dmax achieved in IMRT(~70-80% of Dp).All NT constraints were set to the lowest priority.Three common homogeneity indices(HI),RTOG-HI=Dmax/Dp,moderated-HI=D95%/D5% and complex-HI=(D2%-D98%)/Dp*100 were calculated. Results: All modalities with similar dosimetric endpoints for PTV and OARs.The complex-HI shows the most variability of indices,with average values of 5.9,4.9,9.3 and 6.1 for IMRT,VMAT,VMAT-NT and Tomotherapy,respectively.VMAT provided the best PTV homogeneity without compromising any OAR/NT sparing.Both VMAT-NT and Tomotherapy,planned with more restrictive NT constraints,showed reduced homogeneity,with VMAT-NT showing the worst homogeneity(P<0.0001)for all HI.Tomotherapy gave the lowest NT Dmax,with slightly decreased homogeneity compared to VMAT. Finally, there was no significant difference in NT Dmax or Dmean between VMAT and VMAT-NT. Conclusion: PTV HI is highly dependent on permitted NT constraints. Results demonstrated that VMAT-NT with more restrictive NT constraints does not reduce Dmax NT,but significantly receives higher Dmax and worse target homogeneity.Therefore, it is critical

  9. Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection.

    Science.gov (United States)

    Evering, Teresa H; Mehandru, Saurabh; Racz, Paul; Tenner-Racz, Klara; Poles, Michael A; Figueroa, Amir; Mohri, Hiroshi; Markowitz, Martin

    2012-02-01

    Mucosal mononuclear (MMC) CCR5+CD4+ T cells of the gastrointestinal (GI) tract are selectively infected and depleted during acute HIV-1 infection. Despite early initiation of combination antiretroviral therapy (cART), gut-associated lymphoid tissue (GALT) CD4+ T cell depletion and activation persist in the majority of HIV-1 positive individuals studied. This may result from ongoing HIV-1 replication and T-cell activation despite effective cART. We hypothesized that ongoing viral replication in the GI tract during cART would result in measurable viral evolution, with divergent populations emerging over time. Subjects treated during early HIV-1 infection underwent phlebotomy and flexible sigmoidoscopy with biopsies prior to and 15-24 months post initiation of cART. At the 2(nd) biopsy, three GALT phenotypes were noted, characterized by high, intermediate and low levels of immune activation. A representative case from each phenotype was analyzed. Each subject had plasma HIV-1 RNA levels <50 copies/ml at 2(nd) GI biopsy and CD4+ T cell reconstitution in the peripheral blood. Single genome amplification of full-length HIV-1 envelope was performed for each subject pre- and post-initiation of cART in GALT and PBMC. A total of 280 confirmed single genome sequences (SGS) were analyzed for experimental cases. For each subject, maximum likelihood phylogenetic trees derived from molecular sequence data showed no evidence of evolved forms in the GALT over the study period. During treatment, HIV-1 envelope diversity in GALT-derived SGS did not increase and post-treatment GALT-derived SGS showed no substantial genetic divergence from pre-treatment sequences within transmitted groups. Similar results were obtained from PBMC-derived SGS. Our results reveal that initiation of cART during acute/early HIV-1 infection can result in the interruption of measurable viral evolution in the GALT, suggesting the absence of de-novo rounds of HIV-1 replication in this compartment during

  10. Tissue engineering in dentistry.

    Science.gov (United States)

    Abou Neel, Ensanya Ali; Chrzanowski, Wojciech; Salih, Vehid M; Kim, Hae-Won; Knowles, Jonathan C

    2014-08-01

    of this review is to inform practitioners with the most updated information on tissue engineering and its potential applications in dentistry. The authors used "PUBMED" to find relevant literature written in English and published from the beginning of tissue engineering until today. A combination of keywords was used as the search terms e.g., "tissue engineering", "approaches", "strategies" "dentistry", "dental stem cells", "dentino-pulp complex", "guided tissue regeneration", "whole tooth", "TMJ", "condyle", "salivary glands", and "oral mucosa". Abstracts and full text articles were used to identify causes of craniofacial tissue loss, different approaches for craniofacial reconstructions, how the tissue engineering emerges, different strategies of tissue engineering, biomaterials employed for this purpose, the major attempts to engineer different dental structures, finally challenges and future of tissue engineering in dentistry. Only those articles that dealt with the tissue engineering in dentistry were selected. There have been a recent surge in guided tissue engineering methods to manage periodontal diseases beyond the traditional approaches. However, the predictable reconstruction of the innate organisation and function of whole teeth as well as their periodontal structures remains challenging. Despite some limited progress and minor successes, there remain distinct and important challenges in the development of reproducible and clinically safe approaches for oral tissue repair and regeneration. Clearly, there is a convincing body of evidence which confirms the need for this type of treatment, and public health data worldwide indicates a more than adequate patient resource. The future of these therapies involving more biological approaches and the use of dental tissue stem cells is promising and advancing. Also there may be a significant interest of their application and wider potential to treat disorders beyond the craniofacial region. Considering the

  11. Antiproton Cancer Therapy

    DEFF Research Database (Denmark)

    Bassler, Niels

    An essential part in cancer radiotherapy, is to direct a sufficiently high dose towards the tumour, without damaging the surrounding tissue. Different techniques such as intensity modulated radiation therapy and proton therapy have been developed, in order to reduce the dose to the normal tissue...

  12. Differentiation between healthy thyroid remnants and tumor tissue after radioiodine therapy in patients with differentiated thyroid carcinoma using in-vitro phosphorus-31 magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Moka, D.; Dietlein, M.; Schicha, H.; Raffelt, K.; Hahn, J.

    2002-01-01

    Full text: In many tumors, tumor growth and spread is triggered by changes in cell membrane metabolism, which can lead to systemic alterations in levels of phospholipids. The aim of this study was to differentiate between healthy remnants of thyroid tissue and residual/recurrent tumor tissue or metastases in patients with thyroid carcinoma by measurement of plasma levels of various phospholipids. Phospholipid concentrations was measured by in-vitro phosphorus-31-magnetic resonance spectroscopy ( 31 P-MRS) in blood samples from 30 patients with thyroid cancer, who had been rendered hypothyroid in preparation for diagnostic/therapeutic administration of iodine-131. All patients were already thyroidectomized. 131 I-whole-body scintigraphy and measurements of thyroglobulin values in a 2-year-follow-up were used to distinguish between patients in remission, patients with only healthy thyroid remnants and patients with cancerous thyroid tissue and/or metastases. Significantly lower blood plasma levels of systemic sphingomyelin (0.33±0.06 vs. 0.46±0.03 (controls) mmol/l; p 31 P-MRS can be used to differentiate between the presence of tumor tissue, healthy remnants of thyroid tissue not requiring further treatment and remission in patients with thyroid cancer. In future, therefore, plasma 31 P-MRS could be developed as an additional diagnostic tool for the follow-up of differentiated thyroid cancer. (author)

  13. A retrospective study of 5-year outcomes of radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication therapy

    International Nuclear Information System (INIS)

    Abe, Seiichiro; Oda, Ichiro; Inaba, Koji

    2013-01-01

    The favorable response rate of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication has been demonstrated. However, there are limited data available on the long-term outcomes. The aim of this retrospective study was to evaluate the long-term outcomes of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication. Thirty-four consecutive patients with localized gastric mucosa-associated lymphoid tissue lymphoma that were refractory to eradication were treated with radiotherapy (a total dose of 30 Gy). The response and adverse events of radiotherapy were retrospectively analyzed as short-term outcomes, and recurrence-free, overall and disease-specific survival rates were calculated as long-term outcomes. Thirty-three (97.1%) patients achieved complete remission and radiotherapy was well tolerated. One patient underwent emergency gastrectomy due to severe hematemesis. Of the 34 patients during the median follow-up period of 7.5 (1.2-13.0) years, one patient had local recurrence after 8.8 years, one patient underwent surgery for bowel obstruction secondary to small bowel metastasis after 5.1 years and one patient had pulmonary metastasis after 10.9 years. Pathologically, all three recurrences revealed mucosa-associated lymphoid tissue lymphoma without any transformation to high-grade lymphoma. None died of gastric mucosa-associated lymphoid tissue lymphoma. The 5-year recurrence-free survival rate was 97.0%. The 5-year overall survival rates and disease-specific survival rates were 97.0 and 100%, respectively. Radiotherapy in patients with localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication can achieve excellent overall survival. However, long-term surveillance is necessary to identify late recurrences. (author)

  14. A retrospective study of 5-year outcomes of radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication therapy.

    Science.gov (United States)

    Abe, Seiichiro; Oda, Ichiro; Inaba, Koji; Suzuki, Haruhisa; Yoshinaga, Shigetaka; Nonaka, Satoru; Morota, Madoka; Murakami, Naoya; Itami, Jun; Kobayashi, Yukio; Maeshima, Akiko Miyagi; Saito, Yutaka

    2013-09-01

    The favorable response rate of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication has been demonstrated. However, there are limited data available on the long-term outcomes. The aim of this retrospective study was to evaluate the long-term outcomes of radiotherapy for localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication. Thirty-four consecutive patients with localized gastric mucosa-associated lymphoid tissue lymphoma that were refractory to eradication were treated with radiotherapy (a total dose of 30 Gy). The response and adverse events of radiotherapy were retrospectively analyzed as short-term outcomes, and recurrence-free, overall and disease-specific survival rates were calculated as long-term outcomes. Thirty-three (97.1%) patients achieved complete remission and radiotherapy was well tolerated. One patient underwent emergency gastrectomy due to severe hematemesis. Of the 34 patients during the median follow-up period of 7.5 (1.2-13.0) years, one patient had local recurrence after 8.8 years, one patient underwent surgery for bowel obstruction secondary to small bowel metastasis after 5.1 years and one patient had pulmonary metastasis after 10.9 years. Pathologically, all three recurrences revealed mucosa-associated lymphoid tissue lymphoma without any transformation to high-grade lymphoma. None died of gastric mucosa-associated lymphoid tissue lymphoma. The 5-year recurrence-free survival rate was 97.0%. The 5-year overall survival rates and disease-specific survival rates were 97.0 and 100%, respectively. Radiotherapy in patients with localized gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication can achieve excellent overall survival. However, long-term surveillance is necessary to identify late recurrences.

  15. Acute and long-term adverse effects of postoperative irradiation on limb function of combined modality limb sparing therapy for extermity of soft tissue sarcoma

    International Nuclear Information System (INIS)

    Glinski, B.; Dymek, P.; Walasek, T.; Pecak, M.; Rogowska, M.

    2008-01-01

    The aim of this study is to focus on the aspect of functional outcome for early and late normal tissues damage for patients undergoing postoperative radiotherapy after limb preservation surgery for extremity soft tissues sarcoma (ESTS). The review of the literature suggests that approximately 50% of patients with ESTS have significant impairments, but synthesis of the results is difficult because of the heterogeneity of outcomes used to evaluate function. Future studies require the use of standardized definitions, and reliable and functional outcome measures. (author)

  16. Rationale and Design of the First Double-Blind, Placebo-Controlled Trial with Allogeneic Adipose Tissue-Derived Stromal Cell Therapy in Patients with Ischemic Heart Failure

    DEFF Research Database (Denmark)

    Kastrup, Jens; Schou, Morten; Gustafsson, Ida

    2017-01-01

    BACKGROUND: Ischemic heart failure (IHF) has a poor prognosis in spite of optimal therapy. We have established a new allogeneic Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors. It is produced without animal products, in closed bioreactor systems...

  17. Reasons for the lack of benefit of immediate angioplasty during recombinant tissue plasminogen activator therapy for acute myocardial infarction: a regional wall motion analysis. European Cooperative Study Group

    NARCIS (Netherlands)

    Arnold, A. E.; Serruys, P. W.; Rutsch, W.; Simoons, M. L.; de Bono, D. P.; Tijssen, J. G.; Lubsen, J.; Verstraete, M.

    1991-01-01

    Regional ventricular wall motion analysis utilizing three different methods was performed on predischarge left ventriculograms from 291 of 367 patients enrolled in a randomized trial of single chain recombinant tissue-type plasminogen activator (rt-PA), aspirin and heparin with and without immediate

  18. Significant reduction of normal tissue dose by proton radiotherapy compared with three-dimensional conformal or intensity-modulated radiation therapy in Stage I or Stage III non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Chang, Joe Y.; Zhang Xiaodong; Wang Xiaochun; Kang Yixiu; Riley, Beverly C.; Bilton, Stephen C.; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.

    2006-01-01

    Purpose: To compare dose-volume histograms (DVH) in patients with non-small-cell lung cancer (NSCLC) treated by photon or proton radiotherapy. Methods and Materials: Dose-volume histograms were compared between photon, including three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and proton plans at doses of 66 Gy, 87.5 Gy in Stage I (n = 10) and 60-63 Gy, and 74 Gy in Stage III (n 15). Results: For Stage I, the mean total lung V5, V10, and V20 were 31.8%, 24.6%, and 15.8%, respectively, for photon 3D-CRT with 66 Gy, whereas they were 13.4%, 12.3%, and 10.9%, respectively, with proton with dose escalation to 87.5 cobalt Gray equivalents (CGE) (p = 0.002). For Stage III, the mean total lung V5, V10, and V20 were 54.1%, 46.9%, and 34.8%, respectively, for photon 3D-CRT with 63 Gy, whereas they were 39.7%, 36.6%, and 31.6%, respectively, for proton with dose escalation to 74 CGE (p = 0.002). In all cases, the doses to lung, spinal cord, heart, esophagus, and integral dose were lower with proton therapy even compared with IMRT. Conclusions: Proton treatment appears to reduce dose to normal tissues significantly, even with dose escalation, compared with standard-dose photon therapy, either 3D-CRT or IMRT

  19. Synovial tissue research

    DEFF Research Database (Denmark)

    Orr, Carl; Sousa, Elsa; Boyle, David L

    2017-01-01

    The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the past few decades from arthroplasty and blind needle biopsy to the use of arthroscopic and ultrasonographic technologies that enable...... easier visualization and improve the reliability of synovial biopsies. Rapid progress has been made in using synovial tissue to study disease pathogenesis, to stratify patients, to discover biomarkers and novel targets, and to validate therapies, and this progress has been facilitated by increasingly...... diverse and sophisticated analytical and technological approaches. In this Review, we describe these approaches, and summarize how their use in synovial tissue research has improved our understanding of rheumatoid arthritis and identified candidate biomarkers that could be used in disease diagnosis...

  20. A Comparative Evaluation of Normal Tissue Doses for Patients Receiving Radiation Therapy for Hodgkin Lymphoma on the Childhood Cancer Survivor Study and Recent Children's Oncology Group Trials

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Rachel; Ng, Angela [Department of Radiation Therapy, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Constine, Louis S. [Department of Radiation Oncology, University of Rochester, Rochester, New York (United States); Stovall, Marilyn [Division of Radiation Oncology, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Armstrong, Gregory T. [Epidemiology/Cancer Control Department, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Neglia, Joseph P. [Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota (United States); Friedman, Debra L. [Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Kelly, Kara [Division of Pediatric Hematology/Oncology/Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); FitzGerald, Thomas J. [Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, Massachusetts (United States); Imaging and Radiation Oncology Core Group, Lincoln, Rhode Island (United States); Hodgson, David C., E-mail: David.hodgson@rmp.uhn.on.ca [Department of Radiation Oncology, University of Toronto, and Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario (Canada)

    2016-06-01

    Purpose: Survivors of pediatric Hodgkin lymphoma (HL) are recognized to have an increased risk of delayed adverse health outcomes related to radiation therapy (RT). However, the necessary latency required to observe these late effects means that the estimated risks apply to outdated treatments. We sought to compare the normal tissue dose received by children treated for HL and enrolled in the Childhood Cancer Survivor Study (CCSS) (diagnosed 1970-1986) with that of patients treated in recent Children's Oncology Group (COG) trials (enrolled 2002-2012). Methods and Materials: RT planning data were obtained for 50 HL survivors randomly sampled from the CCSS cohort and applied to computed tomography planning data sets to reconstruct the normal tissue dosimetry. For comparison, the normal tissue dosimetry data were obtained for all 191 patients with full computed tomography–based volumetric RT planning on COG protocols AHOD0031 and AHOD0831. Results: For early-stage patients, the mean female breast dose in the COG patients was on average 83.5% lower than that for CCSS patients, with an absolute reduction of 15.5 Gy. For advanced-stage patients, the mean breast dose was decreased on average by 70% (11.6 Gy average absolute dose reduction). The mean heart dose decreased on average by 22.9 Gy (68.6%) and 17.6 Gy (56.8%) for early- and advanced-stage patients, respectively. All dose comparisons for breast, heart, lung, and thyroid were significantly lower for patients in the COG trials than for the CCSS participants. Reductions in the prescribed dose were a major contributor to these dose reductions. Conclusions: These are the first data quantifying the significant reduction in the normal tissue dose using actual, rather than hypothetical, treatment plans for children with HL. These findings provide useful information when counseling families regarding the risks of contemporary RT.

  1. Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Granzotto, Adeline [INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon (France); Benadjaoud, Mohamed Amine [INSERM UMRS 1018, Institut Gustave-Roussy, Villejuif (France); Vogin, Guillaume [INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon (France); Institut de Cancérologie de Lorraine, Vandoeuvre-les-Nancy (France); Devic, Clément; Ferlazzo, Mélanie L. [INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon (France); Bodgi, Larry [INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon (France); Université Saint-Joseph, Beirut (Lebanon); Pereira, Sandrine; Sonzogni, Laurène [INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon (France); Forcheron, Fabien [Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge (France); Viau, Muriel; Etaix, Aurélie; Malek, Karim; Mengue-Bindjeme, Laurence [INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon (France); Escoffier, Clémence; Rouvet, Isabelle; Zabot, Marie-Thérèse [Centre de Biotechnologie Cellulaire et Biothèque, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron (France); Joubert, Aurélie [Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses (France); Vincent, Anne; Venezia, Nicole Dalla [INSERM, UMR1052, Cancer Research Centre of Lyon, Lyon (France); Bourguignon, Michel [Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses (France); and others

    2016-03-01

    Purpose: Whereas post–radiation therapy overreactions (OR) represent a clinical and societal issue, there is still no consensual radiobiological endpoint to predict clinical radiosensitivity. Since 2003, skin biopsy specimens have been collected from patients treated by radiation therapy against different tumor localizations and showing a wide range of OR. Here, we aimed to establish quantitative links between radiobiological factors and OR severity grades that would be relevant to radioresistant and genetic hyperradiosensitive cases. Methods and Materials: Immunofluorescence experiments were performed on a collection of skin fibroblasts from 12 radioresistant, 5 hyperradiosensitive, and 100 OR patients irradiated at 2 Gy. The numbers of micronuclei, γH2AX, and pATM foci that reflect different steps of DNA double-strand breaks (DSB) recognition and repair were assessed from 10 minutes to 24 hours after irradiation and plotted against the severity grades established by the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group. Results: OR patients did not necessarily show a gross DSB repair defect but a systematic delay in the nucleoshuttling of the ATM protein required for complete DSB recognition. Among the radiobiological factors, the maximal number of pATM foci provided the best discrimination among OR patients and a significant correlation with each OR severity grade, independently of tumor localization and of the early or late nature of reactions. Conclusions: Our results are consistent with a general classification of human radiosensitivity based on 3 groups: radioresistance (group I); moderate radiosensitivity caused by delay of nucleoshuttling of ATM, which includes OR patients (group II); and hyperradiosensitivity caused by a gross DSB repair defect, which includes fatal cases (group III).

  2. Pitfalls in Prediction Modeling for Normal Tissue Toxicity in Radiation Therapy: An Illustration With the Individual Radiation Sensitivity and Mammary Carcinoma Risk Factor Investigation Cohorts

    Energy Technology Data Exchange (ETDEWEB)

    Mbah, Chamberlain, E-mail: chamberlain.mbah@ugent.be [Department of Basic Medical Sciences, Faculty of Health Sciences, Ghent University, Ghent (Belgium); Department of Mathematical Modeling, Statistics, and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Ghent (Belgium); Thierens, Hubert [Department of Basic Medical Sciences, Faculty of Health Sciences, Ghent University, Ghent (Belgium); Thas, Olivier [Department of Mathematical Modeling, Statistics, and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Ghent (Belgium); National Institute for Applied Statistics Research Australia, University of Wollongong, Wollongong, New South Wales (Australia); De Neve, Jan [Department of Data Analysis, Faculty of Psychology and Educational Sciences, Ghent University, Ghent (Belgium); Chang-Claude, Jenny; Seibold, Petra; Botma, Akke [Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg (Germany); West, Catharine [Translational Radiobiology Group, Institute of Cancer Sciences, Radiotherapy Related Research, Christie Hospital NHS Trust, University of Manchester, Manchester (United Kingdom); De Ruyck, Kim [Department of Basic Medical Sciences, Faculty of Health Sciences, Ghent University, Ghent (Belgium)

    2016-08-01

    Purpose: To identify the main causes underlying the failure of prediction models for radiation therapy toxicity to replicate. Methods and Materials: Data were used from two German cohorts, Individual Radiation Sensitivity (ISE) (n=418) and Mammary Carcinoma Risk Factor Investigation (MARIE) (n=409), of breast cancer patients with similar characteristics and radiation therapy treatments. The toxicity endpoint chosen was telangiectasia. The LASSO (least absolute shrinkage and selection operator) logistic regression method was used to build a predictive model for a dichotomized endpoint (Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer score 0, 1, or ≥2). Internal areas under the receiver operating characteristic curve (inAUCs) were calculated by a naïve approach whereby the training data (ISE) were also used for calculating the AUC. Cross-validation was also applied to calculate the AUC within the same cohort, a second type of inAUC. Internal AUCs from cross-validation were calculated within ISE and MARIE separately. Models trained on one dataset (ISE) were applied to a test dataset (MARIE) and AUCs calculated (exAUCs). Results: Internal AUCs from the naïve approach were generally larger than inAUCs from cross-validation owing to overfitting the training data. Internal AUCs from cross-validation were also generally larger than the exAUCs, reflecting heterogeneity in the predictors between cohorts. The best models with largest inAUCs from cross-validation within both cohorts had a number of common predictors: hypertension, normalized total boost, and presence of estrogen receptors. Surprisingly, the effect (coefficient in the prediction model) of hypertension on telangiectasia incidence was positive in ISE and negative in MARIE. Other predictors were also not common between the 2 cohorts, illustrating that overcoming overfitting does not solve the problem of replication failure of prediction models completely

  3. In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. possible implications for measurements in vivo after heparin therapy

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Larsen, L F; Ostergaard, P

    2000-01-01

    The coagulant activity of blood coagulation factor VII (FVII:C) can be lowered by changes in lifestyle and by therapeutic intervention, e.g. heparin infusion. The question is, however, whether FVII:C determined ex vivo is a valid measure of the FVII activity in vivo. We measured plasma FVII......:C, activated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after infusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 healthy subjects. Additionally, we conducted in vitro experiments...

  4. Spread of community-acquired meticillin-resistant Staphylococcus aureus skin and soft-tissue infection within a family: implications for antibiotic therapy and prevention.

    LENUS (Irish Health Repository)

    Amir, N H

    2010-04-01

    Outbreaks or clusters of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) within families have been reported. We describe a family cluster of CA-MRSA skin and soft-tissue infection where CA-MRSA was suspected because of recurrent infections which failed to respond to flucloxacillin. While the prevalence of CA-MRSA is low worldwide, CA-MRSA should be considered in certain circumstances depending on clinical presentation and risk assessment. Surveillance cultures of family contacts of patients with MRSA should be considered to help establish the prevalence of CA-MRSA and to inform the optimal choice of empiric antibiotic treatment.

  5. Normal tissue tolerance to external beam radiation therapy: Spinal cord; Tolerance a l'irradiation des tissus sains: moelle epiniere

    Energy Technology Data Exchange (ETDEWEB)

    Habrand, J.L. [Departement de radiotherapie, institut Gustave-Roussy, 94 - Villejuif (France); Centre de protontherapie, institut Curie, 91 - Orsay (France); Drouet, F. [Departement de radiotherapie, centre Rene-Gauducheau, 44 - Nantes (France)

    2010-07-15

    Radiation myelopathy is one of the most dreadful complications of radiation therapy. Despite multiple animal experiments and human autopsic series, its pathogenesis remains largely unknown. In most instances, the classical aspect of myelomalacia combines glial and vascular injuries in various sequences. Recent studies point out the role of oligo-dendrocytes and their precursors, as well as of intercellular mediators (cytokines and stress molecules). The clinical presentation comprises a spectrum of non specific neurological symptoms whose evolution is sometimes regressive but more commonly progressive and life-threatening. Usually, it occurs following a latent period of six months to two years after irradiation of the cervical, thoracic or upper lumbar spine to a dose in excess of 50 Gy, conventionally fractionated. Nonetheless, these typical features can be altered by extrinsic factors, such as hypo fractionation/acceleration of the dose, multiple surgical procedures, chemotherapy especially mega therapy, or neurotoxic drugs. Conversely, hyperfractionated regimens that take into account protracted half-time repair of sublethal damages to the CNS, as well as sophisticated estimates of the dose to the cord and QA programs during the treatment course minimize such risks. (authors)

  6. Tissue engineering

    CERN Document Server

    Fisher, John P; Bronzino, Joseph D

    2007-01-01

    Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

  7. Mechanical dyssynchrony evaluated by tissue Doppler cross-correlation analysis is associated with long-term survival in patients after cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Risum, Niels; Williams, Eric S; Khouri, Michel G

    2013-01-01

    Aims Pre-implant assessment of longitudinal mechanical dyssynchrony using cross-correlation analysis (XCA) was tested for association with long-term survival and compared with other tissue Doppler imaging (TDI)-derived indices. Methods and results In 131 patients referred for cardiac resynchroniz......Aims Pre-implant assessment of longitudinal mechanical dyssynchrony using cross-correlation analysis (XCA) was tested for association with long-term survival and compared with other tissue Doppler imaging (TDI)-derived indices. Methods and results In 131 patients referred for cardiac......-max was independently associated with improved survival when adjusted for QRS > 150 ms and aetiology {hazard ratio (HR) 0.35 [95% confidence interval (CI) 0.16-0.77], P = 0.01}. Maximal activation delay performed significantly better than Yu index, OWD, and the presence of left bundle branch block (P ..., for difference between parameters). In subgroup analysis, patients without dyssynchrony and QRS between 120 and 150 ms showed a particularly poor survival [HR 4.3 (95% CI 1.46-12.59), P

  8. Development and characterization of a PHB-HV-based 3D scaffold for a tissue engineering and cell-therapy combinatorial approach for spinal cord injury regeneration.

    Science.gov (United States)

    Ribeiro-Samy, Silvina; Silva, Nuno A; Correlo, Vitor M; Fraga, Joana S; Pinto, Luísa; Teixeira-Castro, Andreia; Leite-Almeida, Hugo; Almeida, Armando; Gimble, Jeffrey M; Sousa, Nuno; Salgado, António J; Reis, Rui L

    2013-11-01

    Spinal cord injury (SCI) leads to devastating neurological deficits. Several tissue engineering (TE)-based approaches have been investigated for repairing this condition. Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV) is found to be particularly attractive for TE applications due to its properties, such as biodegradability, biocompatibility, thermoplasticity and piezoelectricity. Hence, this report addresses the development and characterization of PHB-HV-based 3D scaffolds, produced by freeze-drying, aimed to SCI treatment. The obtained scaffolds reveal an anisotropic morphology with a fully interconnected network of pores. In vitro studies demonstrate a lack of cytotoxic effect of PHB-HV scaffolds. Direct contact assays also reveal their ability to support the culture of CNS-derived cells and mesenchymal-like stem cells from different sources. Finally, histocompatibility studies show that PHB-HV scaffolds are well tolerated by the host tissue, and do not negatively impact the left hindlimb locomotor function recovery. Therefore results herein presented suggest that PHB-HV scaffolds may be suitable for SCI treatment. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Normal tissue tolerance to external beam radiation therapy: Adult bone; Dose de tolerance a l'irradiation des tissus sains: l'os chez l'adulte

    Energy Technology Data Exchange (ETDEWEB)

    Sargos, P.; Mamou, N.; Dejean, C.; Henriques de Figueiredo, B.; Kantor, G. [Departement de radiotherapie, Centre regional de lutte contre le cancer, institut Bergonie, 33 - Bordeaux (France); Huchet, A. [Departement de radiotherapie, hopital Saint-Andre, 33 - Bordeaux (France); Italiano, A. [Service d' oncologie medicale, Centre regional de lutte contre le cancer, institut Bergonie, 33 - Bordeaux (France)

    2010-07-15

    Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably under-evaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume. (authors)

  10. Immunosenescence of the CD8(+) T cell compartment is associated with HIV-infection, but only weakly reflects age-related processes of adipose tissue, metabolism, and muscle in antiretroviral therapy-treated HIV-infected patients and controls

    DEFF Research Database (Denmark)

    Tavenier, Juliette; Langkilde, Anne; Haupt, Thomas Huneck

    2015-01-01

    of immunosenescence is not well established. Studying immunosenescence in HIV-infection could give insight into its role in ageing processes. In this cross-sectional study, we aimed to investigate whether ART-treated HIV-infected patients exhibit immunosenescence; and whether immunosenescence is associated with age......BACKGROUND: Despite effective antiretroviral therapy (ART), HIV-infected patients exhibit systemic inflammation, early onset of age-related diseases, and features of immunosenescence. The role of inflammation in the development of age-related diseases is widely recognized. However, the role......-related processes of inflammation, metabolism, adipose tissue, and muscle. T cell immunosenescence and exhaustion were assessed by flow cytometry analysis of CD8 (+) cells from 43 ART-treated HIV-infected patients (HIV(+)) and ten Controls using markers of differentiation: CD27/CD28; maturation: CD27/CD45RA...

  11. Normal tissue tolerance to external beam radiation therapy: The stomach; Dose de tolerance a l'irradiation des tissus sains: l'estomac

    Energy Technology Data Exchange (ETDEWEB)

    Oberdiac, P. [Service de radiotherapie, hopital de Bellevue, CHU de Saint-Etienne, 42 - Saint-Etienne (France); Mineur, L. [Unite d' oncologie digestive et radiotherapie, institut Sainte-Catherine, 84 - Avignon (France)

    2010-07-15

    In the following article, we will discuss general issues relating to acute and late gastric's radiation toxicities. The tolerance of the stomach to complete or partial organ irradiation is more un-appreciated than for most other organs. We consulted the Medline database via PubMed and used the key words gastric - radiotherapy - toxicity. Currently, 60 Gy or less is prescribed in gastric radiation therapy. Acute clinical toxicity symptoms are predominantly nausea and vomiting. Although there is a general agreement that the whole stomach tolerance is for doses of 40 to 45 Gy without unacceptable complication, it is well established that a stomach dose of 35 Gy increases the risk of ulcer complications. (authors)

  12. The effect of 6 and 15 MV on intensity-modulated radiation therapy prostate cancer treatment: plan evaluation, tumour control probability and normal tissue complication probability analysis, and the theoretical risk of secondary induced malignancies

    Science.gov (United States)

    Hussein, M; Aldridge, S; Guerrero Urbano, T; Nisbet, A

    2012-01-01

    Objective The aim of this study was to investigate the effect of 6 and 15-MV photon energies on intensity-modulated radiation therapy (IMRT) prostate cancer treatment plan outcome and to compare the theoretical risks of secondary induced malignancies. Methods Separate prostate cancer IMRT plans were prepared for 6 and 15-MV beams. Organ-equivalent doses were obtained through thermoluminescent dosemeter measurements in an anthropomorphic Aldersen radiation therapy human phantom. The neutron dose contribution at 15 MV was measured using polyallyl-diglycol-carbonate neutron track etch detectors. Risk coefficients from the International Commission on Radiological Protection Report 103 were used to compare the risk of fatal secondary induced malignancies in out-of-field organs and tissues for 6 and 15 MV. For the bladder and the rectum, a comparative evaluation of the risk using three separate models was carried out. Dose–volume parameters for the rectum, bladder and prostate planning target volume were evaluated, as well as normal tissue complication probability (NTCP) and tumour control probability calculations. Results There is a small increased theoretical risk of developing a fatal cancer from 6 MV compared with 15 MV, taking into account all the organs. Dose–volume parameters for the rectum and bladder show that 15 MV results in better volume sparing in the regions below 70 Gy, but the volume exposed increases slightly beyond this in comparison with 6 MV, resulting in a higher NTCP for the rectum of 3.6% vs 3.0% (p=0.166). Conclusion The choice to treat using IMRT at 15 MV should not be excluded, but should be based on risk vs benefit while considering the age and life expectancy of the patient together with the relative risk of radiation-induced cancer and NTCPs. PMID:22010028

  13. Number needed to treat to benefit and to harm for intravenous tissue plasminogen activator therapy in the 3- to 4.5-hour window: joint outcome table analysis of the ECASS 3 trial.

    Science.gov (United States)

    Saver, Jeffrey L; Gornbein, Jeffrey; Grotta, James; Liebeskind, David; Lutsep, Helmi; Schwamm, Lee; Scott, Phillip; Starkman, Sidney

    2009-07-01

    Measures of a therapy's effect size are important guides to clinicians, patients, and policy-makers on treatment decisions in clinical practice. The ECASS 3 trial demonstrated a statistically significant benefit of intravenous tissue plasminogen activator for acute cerebral ischemia in the 3- to 4.5-hour window, but an effect size estimate incorporating benefit and harm across all levels of poststroke disability has not previously been derived. Joint outcome table specification was used to derive number needed to treat to benefit (NNTB) and number needed to treat to harm (NNTH) values summarizing treatment impact over the entire outcome range on the modified Rankin scale of global disability, including both expert-dependent and expert-independent (algorithmic and repeated random sampling) array generation. For the full 7-category modified Rankin scale, algorithmic analysis demonstrated that the NNTB for 1 additional patient to have a better outcome by >or=1 grades than with placebo must lie between 4.0 and 13.0. In bootstrap simulations, the mean NNTB was 7.1. Expert joint outcome table analyses indicated that the NNTB for improved final outcome was 6.1 (95% CI, 5.6-6.7) and the NNTH 37.5 (95% CI, 34.6-40.5). Benefit per 100 patients treated was 16.3 and harm per 100 was 2.7. The likelihood of help to harm ratio was 6.0. Treatment with tissue plasminogen activator in the 3- to 4.5-hour window confers benefit on approximately half as many patients as treatment <3 hours, with no increase in the conferral of harm. Approximately 1 in 6 patients has a better and 1 in 35 has a worse outcome as a result of therapy.

  14. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves; Dose de tolerance a l'irradiation des tissus sains: les nerfs peripheriques

    Energy Technology Data Exchange (ETDEWEB)

    Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G. [Departement de radiotherapie, institut Bergonie, centre regional de lutte contre le cancer, 33 - Bordeaux (France); Huchet, A.; Mamou, N. [Service d' oncologie medicale et de radiotherapie, CHU Saint-Andre, 33 - Bordeaux (France); Loiseau, H. [Service de neurochirurgie, CHU Pellegrin, 33 - Bordeaux (France)

    2010-07-15

    Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

  15. Morbidity of a combined modality therapy of I.A. Doxorubicin, neoadjuvant radiotherapy and surgery for locally advanced high grade Soft Tissue Sarcomas (STS) of the extremities

    International Nuclear Information System (INIS)

    Nijhuis, Paul; Pras, Betty; Sleijfer, Dirk Th.; Molenaar, Ineke M.; Schraffordt, Koops Heimen; Hoekstra, Harald J.

    1997-01-01

    Purpose/objective: In the early eighties a combined modality therapy of intra-arterial doxorubicin, neo-adjuvant radiotherapy and surgery was introduced as limb-saving treatment for 'unresectable' grade III high grade STS of the extremities. We studied short and long-term morbidity of this combined modality treatment. Materials and methods: Between 1982 and 1986 11 patients, 9 male and 2 female, median age 52 (range 24-70) years, with 'unresectable' grade III STS of the extremities were treated by preoperative i.a. infusion of doxorubicin for three consecutive days (daily dose 20 mg/m 2 ). Within 24 hours after infusion preoperative radiation of the compartment (10 x 350 cGy) was started. After chemo-radiotherapy the tumor was resected. Non-radical resections received additionally 20-30 Gy radiotherapy (9 patients). Results: No local recurrences (median follow-up 110 months); pulmonary metastases in five patients (45%). Local skin toxicity due to doxorubicin in three patients (27%). Preoperative 35 Gy radiotherapy was well tolerated. Limb-saving treatment was possible in ten patients (91%); in one patient an exarticulation of the hip had to be performed. Three of the five long-term survivors (follow-up > 10 years) developed a severe fibrosis of the affected limb (60%). Two severe long-term complications: a stress fracture of the affected femur (91 months after treatment), and a severe radiation-induced motor and sensory neuropathy of the sciatic nerve. Conclusion: The long-term results show a limb-saving rate of 91%, without increasing the risk of a local recurrence. Especially the long-term morbidity is extremely high (60%). This combination therapy should therefore no longer be advocated as a limb-saving treatment modality for these primarily 'unresectable' high grade STS of the extremities

  16. Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients

    Directory of Open Access Journals (Sweden)

    Stenman Ulf-Håkan

    2011-08-01

    Full Text Available Abstract Background We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI in both tumour tissue (t-TATI and in serum (s-TATI are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT on concentrations of t-TATI and s-TATI in patients with rectal cancer. Methods TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term preoperative RT and 21 patients 25 × 2 Gy (long-term preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test. Results RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P Conclusions The results presented here further validate the utility of t-TATI and s-TATI as prognostic biomarkers in patients with rectal cancer, independent of neoadjuvant RT.

  17. The effects of tissue-non-specific alkaline phosphatase gene therapy on craniosynostosis and craniofacial morphology in the FGFR2C342Y/+ mouse model of Crouzon craniosynostosis.

    Science.gov (United States)

    Wang, E; Nam, H K; Liu, J; Hatch, N E

    2015-04-01

    Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue-non-specific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs. Neonatal Crouzon (FGFRC342Y/+) and wild-type (FGFR+/+) mice were injected with lentivirus to deliver a recombinant form of TNAP. Mice were sacrificed at 4 weeks postnatal. Serum was collected to test for alkaline phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and morphology were assessed by micro-computed tomography. Injection with the TNAP lentivirus significantly increased serum AP levels (increased serum AP levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphological analysis revealed craniofacial form differences for inferior surface (p=0.023) and cranial height (p=0.014) regions between TNAP lentivirus-injected and vehicle-injected Crouzon mice. With each unit increase in AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (p=0.068). These results suggest that TNAP deficiency may mediate FGFR2-associated craniosynostosis. Future studies should incorporate injection of recombinant TNAP protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: Viable therapy for type III.C. a diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Umang G Thakkar

    2014-12-01

    Full Text Available Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC along with his bone marrow derived hematopoietic stem cells (BM-HSC. Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus.

  19. Soft-tissue injuries from sports activities and traffic accidents--treatment with low-level laser therapy: a multicenter double-blind placebo-controlled clinical study on 132 patients

    Science.gov (United States)

    Simunovic, Zlatko; Trobonjaca, Tatjana

    2000-06-01

    The aim of current multicenter clinical study was to assess the efficacy of low energy-level laser therapy (LLLT) in the treatment of soft tissue injuries compared to the placebo and classical phyiotherapeutic procedures. This clinical study was conducted in two centers located in Locarno, Switzerland and Opatija, Croatia. Two types of irradiation techniques were used: (1) direct, skin contact technique for treatment of trigger points where IR diode laser 830 nm continuous wave was applied; and (2) scanning technique for irradiation of larger surface area with use of Helium Neon laser 632.8 nm combined with IR diode laser 904 nm pulsed wave. Results were evaluated according to clinical parameters like: hematoma, swelling, heat, pan and loss of function. The findings were statistically analyzed via chi- square test. Results have demonstrated that the recovery process was accelerated in 85 percent of patients treated with LLLT compared to the control group of patients. The results and advantages obtained proved once again the efficacy of LLLT as a new and successful way to treat soft tissue injuries.

  20. Tissue types (image)

    Science.gov (United States)

    ... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

  1. Long-term outcome of combined modality therapy in retroperitoneal and deep-trunk soft-tissue sarcoma: analysis of prognostic factors

    International Nuclear Information System (INIS)

    Youssef, Emad; Fontanesi, James; Mott, Michael; Kraut, Michael; Lucas, David; Mekhael, Hany; Ben-Josef, Edgar

    2002-01-01

    Purpose: To evaluate the long-term outcome of surgery and postoperative radiotherapy (RT) in retroperitoneal and deep-trunk soft-tissue sarcoma, and to identify the prognostic factors for local control, disease-free survival, and overall survival. Methods and Materials: Between January 1980 and December 1998, 60 patients with nonmetastatic retroperitoneal and deep-trunk soft-tissue sarcoma were treated at Wayne State University using combined surgery and RT. The location was retroperitoneal in 38 patients (63%) and deep trunk in 22 (27%). Forty-six patients (76%) were treated for primary disease and 14 (24%) for recurrent disease. The resection margins were negative in 24 patients (40%), close in 3 (5%), and positive in 33 (55%; 18 microscopic and 15 macroscopic). The median tumor size was 8.6 cm (range 2-55). External beam RT (EBRT; median dose 5220 cGy) was given to 44 patients (73%) and combined EBRT (median dose 4200 cGy) and brachytherapy (median dose 1600 cGy) to 16 patients (27%). Univariate and multivariate Cox regression analyses were conducted to identify the possible associations between patient age, race, gender, tumor site, histologic features, grade, size, stage, surgical margin, RT dose, modality (EBRT vs. EBRT plus brachytherapy), and presentation (primary vs. recurrent) and disease control. Results: The actuarial 5- and 10-year disease-free survival rate was 53% and 44%, respectively. Disease-free survival was significantly associated with female gender on univariate analysis (67% for female patients and 37% for male patients at 5 years, p=0.05). On multivariate analysis, both gender and surgical margin had borderline significance (p=0.06). The actuarial local control rate was 71% and 54% at 5 and 10 years, respectively. The median time to local relapse was 10.2 months, with 75% of all failures occurring within 29 months. The surgical margin status was significantly associated with local control (78% for patients with negative or close margins vs

  2. Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity

    Energy Technology Data Exchange (ETDEWEB)

    Bahig, Houda [Department of Radiation Oncology, Centre Hospitalier de l' Université de Montréal, Montreal, QC (Canada); Roberge, David, E-mail: david.roberge.chum@ssss.gouv.qc.ca [Department of Radiation Oncology, Centre Hospitalier de l' Université de Montréal, Montreal, QC (Canada); Bosch, Walter [Department of Radiation Oncology, Washington University, St Louis, Missouri (United States); Levin, William [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Petersen, Ivy; Haddock, Michael [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Freeman, Carolyn [Division of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada); DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Indelicato, Danny J. [Department of Radiation Oncology, University of Florida Medical Center, Jacksonville, Florida (United States); Baldini, Elizabeth H. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Hitchcock, Ying [Department of Radiation Oncology, University of Utah Medical Center, Salt Lake City, Utah (United States); Kirsch, David G. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Kozak, Kevin R. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Wolfson, Aaron [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); and others

    2013-06-01

    Purpose: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Methods and Materials: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm{sup 3} (7-413 cm{sup 3}), 280 cm{sup 3} and 360 cm{sup 3}. The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm{sup 3} (24-565 cm{sup 3}) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm{sup 3} (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm{sup 3}, respectively. There were 3 large tumors with >30 cm{sup 3} of SE not included in the CTV3cm volume. Conclusion: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant

  3. Agreement among RTOG sarcoma radiation oncologists in contouring suspicious peritumoral edema for preoperative radiation therapy of soft tissue sarcoma of the extremity.

    Science.gov (United States)

    Bahig, Houda; Roberge, David; Bosch, Walter; Levin, William; Petersen, Ivy; Haddock, Michael; Freeman, Carolyn; Delaney, Thomas F; Abrams, Ross A; Indelicato, Danny J; Baldini, Elizabeth H; Hitchcock, Ying; Kirsch, David G; Kozak, Kevin R; Wolfson, Aaron; Wang, Dian

    2013-06-01

    Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm(3) (7-413 cm(3)), 280 cm(3) and 360 cm(3). The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm(3) (24-565 cm(3)) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm(3) (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm(3), respectively. There were 3 large tumors with >30 cm(3) of SE not included in the CTV3cm volume. Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE. Copyright © 2013 Elsevier Inc. All rights

  4. Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity

    International Nuclear Information System (INIS)

    Bahig, Houda; Roberge, David; Bosch, Walter; Levin, William; Petersen, Ivy; Haddock, Michael; Freeman, Carolyn; DeLaney, Thomas F.; Abrams, Ross A.; Indelicato, Danny J.; Baldini, Elizabeth H.; Hitchcock, Ying; Kirsch, David G.; Kozak, Kevin R.; Wolfson, Aaron

    2013-01-01

    Purpose: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Methods and Materials: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm 3 (7-413 cm 3 ), 280 cm 3 and 360 cm 3 . The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm 3 (24-565 cm 3 ) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm 3 (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm 3 , respectively. There were 3 large tumors with >30 cm 3 of SE not included in the CTV3cm volume. Conclusion: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE

  5. Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients

    International Nuclear Information System (INIS)

    Gaber, Alexander; Jirström, Karin; Stene, Christina; Hotakainen, Kristina; Nodin, Björn; Palmquist, Ingrid; Bjartell, Anders; Stenman, Ulf-Håkan; Jeppsson, Bengt; Johnson, Louis B

    2011-01-01

    We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI) in both tumour tissue (t-TATI) and in serum (s-TATI) are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT) on concentrations of t-TATI and s-TATI in patients with rectal cancer. TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term) preoperative RT and 21 patients 25 × 2 Gy (long-term) preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z) test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R) test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS) according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test. RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P < 0.001). T-TATI expression correlated with male gender (R = 0.406, P = 0.008). High t-TATI expression in surgical specimens was associated with a significantly shorter OS (P = 0.045). S-TATI concentrations in serum drawn at all time points were associated with an impaired OS (P = 0.035 before RT, P = 0.001 prior to surgery, P = 0.043 post surgery). At all time points, s-TATI correlated with higher age (P < 0

  6. Esoteric Connective Tissue Therapy for chronic low back pain to reduce pain, and improve functionality and general well-being compared with physiotherapy: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Schnelle, Christoph; Messerschmidt, Steffen; Minford, Eunice J; Greenaway-Twist, Kate; Szramka, Maxine; Masiorski, Marianna; Sheldrake, Michelle; Jones, Mark

    2017-07-17

    Low back pain causes more global disability than any other condition. Once the acute pain becomes chronic, about two-thirds of sufferers will not fully recover after 1-2 years. There is a paucity of effective treatments for non-specific, chronic low back pain. It has been noted that low back pain is associated with changes in the connective tissue in the affected area, and a very low-impact treatment, Esoteric Connective Tissue Therapy (ECTT), has been developed to restore flexibility in connective tissue. ECTT uses patterns of very small, circular movements, to the legs, arms, spine, sacrum and head, which anecdotally are effective in pain relief. In an unpublished single-arm phase I/II trial with chronic pain patients, ECTT showed a 56% reduction in pain after five treatments and 45% and 54% improvements at 6 months and 7-9 years of follow-up respectively. The aim of this randomised controlled trial is to compare ECTT with physiotherapy for reducing pain and improving physical function and physical and mental well-being in patients with chronic low back pain. The trial will be held at two hospitals in Vietnam. One hundred participants with chronic low back pain greater than or equal to 40/100 on the visual analogue scale will be recruited and randomised to either ECTT or physiotherapy. Four weekly treatments will be provided by two experienced ECTT practitioners (Treatment Group, 40 minutes each) and hospital-employed physiotherapy nurses (Control Group, 50 minutes). The primary outcomes will be changes in pain, physical function per the Quebec Pain Functionality Questionnaire and physical and mental well-being recorded by the Short Form Health Survey (SF-36), with mixed modelling used as the primary statistical tool because the data are longitudinal. Initial follow-up will be at either 4 or 8 months, with a second follow-up after 12 months. The trial design has important strengths, because it is to be conducted in hospitals under medical supervision

  7. Synthetic Phage for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2014-01-01

    Full Text Available Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy.

  8. Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats

    Directory of Open Access Journals (Sweden)

    Bei Zhang

    2015-01-01

    Full Text Available Motor function impairment is a common outcome of stroke. Constraint-induced movement therapy (CIMT involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of ′learned non-use′ and improve limb function after stroke. However, the underlying mechanism of CIMT remains unclear. In the present study, rats were randomly divided into a middle cerebral artery occlusion (model group, a CIMT + model (CIMT group, or a sham group. Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups. Compared with the model group, CIMT significantly improved the forelimb functional performance in rats. By western blot assay, the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group, and was similar to sham group levels. These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi.

  9. In vivo study of necrosis on the liver tissue of Wistar rats: a combination of photodynamic therapy and carbon dioxide laser ablation

    International Nuclear Information System (INIS)

    Rego, R F; Nicolodelli, G; Bagnato, V S; Araujo, M T; Tirapelli, L F; Araujo-Moreira, F M

    2013-01-01

    Photodynamic therapy (PDT) is known to be limited to applications in large volume tumors due to its limited penetration. Therefore, a combination of PDT and carbon dioxide (CO 2 ) laser ablation may constitute a potential protocol to destroy bulk tumors because it involves an association of these two techniques allowing the removal of visible lesions with a high selectivity of destruction of remnant tumors. The main aim of this study is to investigate the most appropriate procedure to combine use of a CO 2 laser and PDT on livers of healthy rats, and to analyze different techniques of this treatment using three types of photosensitizers (PSs). Forty eight animals were separated to form six groups: (1) only CO 2 laser ablation, (2) drug and CO 2 laser ablation, (3) only PDT, (4) drug and light (PDT) followed by CO 2 laser ablation, (5) ablated with CO 2 laser followed by PDT, and (6) drug followed by CO 2 laser ablation and light. For each group, three types of photosensitization were used: topical 5-aminolevulinic acid (ALA), intravenous ALA and intravenous Photogem ® . Thirty hours after the treatments, the animals were sacrificed and the livers removed. The depth of necrosis was analyzed and measured, considering microscopic and macroscopic aspects. The results show that the effects of the PDT were considerably enhanced when combined with CO 2 laser ablation, especially when the PDT was performed before the CO 2 laser ablation. (paper)

  10. Thoracic mobilisation and periscapular soft tissue manipulations in the management of chronic Prolapsed Intervertebral Disc (PIVD - An innovative manual therapy approach

    Directory of Open Access Journals (Sweden)

    Raj Kiran

    2017-10-01

    Full Text Available Background The most common cause of CLBP is discogenic lower back pain. Researches haveshown that connective tissue remodelling occurs in CLBP and thoracic spinal mobility and thoracolumbar mobility have higher correlations with LBP. Aims To see the effect of upper back fascia and periscapular muscles stretching and thoracic mobilisation to reduce symptoms in subjects with CLBP due to lumbar disk herniation. Methods A total of 40 subjects with CLBP due to Prolapsed Intervertebral Disc (PIVD were recruited and randomly distributed in two groups. Group 1 was given stretching of upper back fascia and periscapular muscles and thoracic mobilization along with conventional exercises (Cyriax listing correction -I followed by repeated McKenzie back extension exercise and Core muscle strengthening. Group 2 received only conventional exercises. Outcome Measures: visual analog scale, Oswestry Disability Index and Modified Schober's Test. Measurements were taken before and after three weeks of treatment, for five days/week. Results Overall results of the study, both Group 1 and Group 2 showed improvement in pain, function and lumbar Range of Motion (ROM after three weeks of intervention. However, Group 1 improved significantly to a greater extent in pain, ROM and function than the Group 2. Conclusion Stretching of periscapular muscles and fascia of the upper back and mobilisation of upper thoracic spine is found to be effective for the management of chronic low back pain due to PIVD.

  11. Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma

    International Nuclear Information System (INIS)

    Xu ZhiYong; Liang Shixiong; Zhu Ji; Zhu Xiaodong; Zhao Jiandong; Lu Haijie; Yang Yunli; Chen Long; Wang Anyu; Fu Xiaolong; Jiang Guoliang

    2006-01-01

    Purpose: To describe the probability of RILD by application of the Lyman-Kutcher-Burman normal-tissue complication (NTCP) model for primary liver carcinoma (PLC) treated with hypofractionated three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: A total of 109 PLC patients treated by 3D-CRT were followed for RILD. Of these patients, 93 were in liver cirrhosis of Child-Pugh Grade A, and 16 were in Child-Pugh Grade B. The Michigan NTCP model was used to predict the probability of RILD, and then the modified Lyman NTCP model was generated for Child-Pugh A and Child-Pugh B patients by maximum-likelihood analysis. Results: Of all patients, 17 developed RILD in which 8 were of Child-Pugh Grade A, and 9 were of Child-Pugh Grade B. The prediction of RILD by the Michigan model was underestimated for PLC patients. The modified n, m, TD 5 (1) were 1.1, 0.28, and 40.5 Gy and 0.7, 0.43, and 23 Gy for patients with Child-Pugh A and B, respectively, which yielded better estimations of RILD probability. The hepatic tolerable doses (TD 5 ) would be MDTNL of 21 Gy and 6 Gy, respectively, for Child-Pugh A and B patients. Conclusions: The Michigan model was probably not fit to predict RILD in PLC patients. A modified Lyman NTCP model for RILD was recommended

  12. Engineering vascular development for tissue regeneration

    NARCIS (Netherlands)

    Rivron, N.C.

    2010-01-01

    Tissue engineering and regenerative medicine aim at restoring a damaged tissue by recreating in vitro or promoting its regeneratin in vovo. The vasculature is central to these therapies for the irrigation of the defective tissue (oxygen, nutrients or circulating regenerative cells) and as an

  13. A CMR study of the effects of tissue edema and necrosis on left ventricular dyssynchrony in acute myocardial infarction: implications for cardiac resynchronization therapy

    Directory of Open Access Journals (Sweden)

    Manka Robert

    2012-07-01

    Full Text Available Abstract Background In acute myocardial infarction (AMI, both tissue necrosis and edema are present and both might be implicated in the development of intraventricular dyssynchrony. However, their relative contribution to transient dyssynchrony is not known. Cardiovascular magnetic resonance (CMR can detect necrosis and edema with high spatial resolution and it can quantify dyssynchrony by tagging techniques. Methods Patients with a first AMI underwent percutaneous coronary interventions (PCI of the infarct-related artery within 24 h of onset of chest pain. Within 5–7 days after the event and at 4 months, CMR was performed. The CMR protocol included the evaluation of intraventricular dyssynchrony by applying a novel 3D-tagging sequence to the left ventricle (LV yielding the CURE index (circumferential uniformity ratio estimate; 1 = complete synchrony. On T2-weighted images, edema was measured as high-signal (>2 SD above remote tissue along the LV mid-myocardial circumference on 3 short-axis images (% of circumference corresponding to the area-at-risk. In analogy, on late-gadolinium enhancement (LGE images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. Necrosis was also quantified on LGE images covering the entire LV (expressed as %LV mass. Finally, salvaged myocardium was calculated as the area-at-risk minus necrosis (expressed as % of LV circumference. Results After successful PCI (n = 22, 2 female, mean age: 57 ± 12y, peak troponin T was 20 ± 36ug/l and the LV ejection fraction on CMR was 41 ± 8%. Necrosis mass was 30 ± 10% and CURE was 0.91 ± 0.05. Edema was measured as 58 ± 14% of the LV circumference. In the acute phase, the extent of edema correlated with dyssynchrony (r2 = −0.63, p 2 = −0.19, p = 0.05. PCI resulted in salvaged myocardium of 27 ± 14%. LV dyssynchrony (=CURE decreased at 4 months from 0.91

  14. SU-E-T-321: The Effects of a Dynamic Collimation System On Proton Pencil Beams to Improve Lateral Tissue Sparing in Spot Scanned Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hill, P; Wang, D; Flynn, R; Hyer, D [University Of Iowa, Iowa City, IA (United States)

    2014-06-01

    Purpose: To evaluate the lateral beam penumbra in pencil beam scanning proton therapy delivered using a dynamic collimator device capable of trimming a portion of the primary beam in close proximity to the patient. Methods: Monte Carlo simulations of pencil beams were performed using MCNPX. Each simulation transported a 125 MeV proton pencil beam through a range shifter, past acollimator, and into a water phantom. Two parameters were varied among the simulations, the source beam size (sigma in air from 3 to 9 mm), and the position of the edge of the collimator (placed from 0 to 30 mm from the central axis of the beam). Proton flux was tallied at the phantom surface to determine the effective beam sizefor all combinations of source beam size and collimator edge position. Results: Quantifying beam size at the phantom surface provides a useful measure tocompare performance among varying source beam sizes and collimation conditions. For arelatively large source beam size (9 mm) entering the range shifter, sigma at thesurface was found to be 10 mm without collimation versus 4 mm with collimation. Additionally, sigma at the surface achievable with collimation was found to be smallerthan for any uncollimated beam, even for very small source beam sizes. Finally, thelateral penumbra achievable with collimation was determined to be largely independentof the source beam size. Conclusion: Collimation can significantly reduce proton pencil beam lateral penumbra.Given the known dosimetric disadvantages resulting from large beam spot sizes,employing a dynamic collimation system can significantly improve lateral tissuesparing in spot-scanned dose distributions.

  15. Does treatment of split-thickness skin grafts with negative-pressure wound therapy improve tissue markers of wound healing in a porcine experimental model?

    Science.gov (United States)

    Ward, Christopher; Ciraulo, David; Coulter, Michael; Desjardins, Steven; Liaw, Lucy; Peterson, Sarah

    2012-08-01

    Negative-pressure wound therapy (NPWT) has been used for to treat wounds for more than 15 years and, more recently, has been used to secure split-thickness skin grafts. There are some data to support this use of NPWT, but the actual mechanism by which NPWT speeds healing or improves skin graft take is not entirely known. The purpose of this project was to assess whether NPWT improved angiogenesis, wound healing, or graft survival when compared with traditional bolster dressings securing split-thickness skin grafts in a porcine model. We performed two split-thickness skin grafts on each of eight 30 kg Yorkshire pigs. We took graft biopsies on postoperative days 2, 4, 6, 8, and 10 and submitted the samples for immunohistochemical staining, as well as standard hematoxylin and eosin staining. We measured the degree of vascular ingrowth via immunohistochemical staining for von Willenbrand's factor to better identify blood vessel epithelium. We determined the mean cross-sectional area of blood vessels present for each representative specimen, and then compared the bolster and NPWT samples. We also assessed each graft for incorporation and survival at postoperative day 10. Our analysis of the data revealed that there was no statistically significant difference in the degree of vascular ingrowth as measured by mean cross-sectional capillary area (p = 0.23). We did not note any difference in graft survival or apparent incorporation on a macroscopic level, although standard hematoxylin and eosin staining indicated that microscopically, there seemed to be better subjective graft incorporation in the NPWT samples and a nonsignificant trend toward improved graft survival in the NPWT group. We were unable to demonstrate a significant difference in vessel ingrowth when comparing NPWT and traditional bolster methods for split-thickness skin graft fixation. More studies are needed to elucidate the manner by which NPWT exerts its effects and the true clinical magnitude of these

  16. Application of monomer/polymer gel dosimetry to study the effects of tissue inhomogeneities on intensity-modulated radiation therapy (IMRT) dose distributions.

    Science.gov (United States)

    Vergote, Koen; De Deene, Yves; Claus, Filip; De Gersem, Werner; Van Duyse, Bart; Paelinck, Leen; Achten, Eric; De Neve, Wilfried; De Wagter, Carlos

    2003-04-01

    When planning an intensity-modulated radiation therapy (IMRT) treatment in a heterogeneous region (e.g. the thorax), the dose computation algorithm of a treatment planning system may need to account for these inhomogeneities in order to obtain a reliable prediction of the dose distribution. An accurate dose verification technique such as monomer/polymer gel dosimetry is suggested to verify the outcome of the planning system. The effects of low-density structures: (a) on narrow high-energy (18 MV) photon beams; and (b) on a class-solution IMRT treatment delivered to a thorax phantom have been examined using gel dosimetry. The used phantom contained air cavities that could be filled with water to simulate a homogeneous or heterogeneous configuration. The IMRT treatment for centrally located lung tumors was delivered on both cases, and gel derived dose maps were compared with computations by both the GRATIS and Helax-TMS planning system. Dose rebuildup due to electronic disequilibrium in a narrow photon beam is demonstrated. The gel measurements showed good agreement with diamond detector measurements. Agreement between measured IMRT dose maps and dose computations was demonstrated by several quantitative techniques. An underdosage of the planning target volume (PTV) was revealed. The homogeneity of the phantom had only a minor influence on the dose distribution in the PTV. An expansion of low-level isodoses in the lung volume was predicted by collapsed cone computations in the heterogeneous case. For the class-solution described, the dose in centrally located mediastinal tumors can be computed with sufficient accuracy, even when neglecting the lower lung density. Polymer gel dosimetry proved to be a valuable technique to verify dose calculation algorithms for IMRT in 3D in heterogeneous configurations.

  17. WE-F-16A-05: Use of 3D-Printers to Create a Tissue Equivalent 3D-Bolus for External Beam Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Burleson, S; Baker, J; Hsia, A; Xu, Z [Stony Brook Medicine, Stony Brook, NY (United States)

    2014-06-15

    Purpose: The purpose of this project is to demonstrate that a non-expensive 3D-printer can be used to manufacture a 3D-bolus for external beam therapy. The printed bolus then can be modeled in our treatment planning system to ensure accurate dose delivery to the patient. Methods: We developed a simple method to manufacture a patient-specific custom 3Dbolus. The bolus is designed using Eclipse Treatment Planning System, contoured onto the patients CT images. The bolus file is exported from Eclipse to 3D-printer software, and then printed using a 3D printer. Various tests were completed to determine the properties of the printing material. Percent depth dose curves in this material were measured with electron and photon beams for comparison to other materials. In order to test the validity of the 3D printed bolus for treatment planning, a custom bolus was printed and tested on the Rando phantom using film for a dose plane comparison. We compared the dose plane measured on the film to the same dose plane exported from our treatment planning system using Film QA software. The gamma-dose distribution tool was used in our film analysis. Results: We compared point measurements throughout the dose plane and were able to achieve greater than 95% passing rate at 3% dose difference and 3 mm distance to agreement, which is our departments acceptable gamma pixel parameters. Conclusion: The printed 3D bolus has proven to be accurately modeled in our treatment planning system, it is more conformal to the patient surface and more durable than other bolus currently used (wax, superflab etc.). It is also more convenient and less costly than comparable bolus from milling machine companies.

  18. WE-F-16A-05: Use of 3D-Printers to Create a Tissue Equivalent 3D-Bolus for External Beam Therapy

    International Nuclear Information System (INIS)

    Burleson, S; Baker, J; Hsia, A; Xu, Z

    2014-01-01

    Purpose: The purpose of this project is to demonstrate that a non-expensive 3D-printer can be used to manufacture a 3D-bolus for external beam therapy. The printed bolus then can be modeled in our treatment planning system to ensure accurate dose delivery to the patient. Methods: We developed a simple method to manufacture a patient-specific custom 3Dbolus. The bolus is designed using Eclipse Treatment Planning System, contoured onto the patients CT images. The bolus file is exported from Eclipse to 3D-printer software, and then printed using a 3D printer. Various tests were completed to determine the properties of the printing material. Percent depth dose curves in this material were measured with electron and photon beams for comparison to other materials. In order to test the validity of the 3D printed bolus for treatment planning, a custom bolus was printed and tested on the Rando phantom using film for a dose plane comparison. We compared the dose plane measured on the film to the same dose plane exported from our treatment planning system using Film QA software. The gamma-dose distribution tool was used in our film analysis. Results: We compared point measurements throughout the dose plane and were able to achieve greater than 95% passing rate at 3% dose difference and 3 mm distance to agreement, which is our departments acceptable gamma pixel parameters. Conclusion: The printed 3D bolus has proven to be accurately modeled in our treatment planning system, it is more conformal to the patient surface and more durable than other bolus currently used (wax, superflab etc.). It is also more convenient and less costly than comparable bolus from milling machine companies

  19. Primary Radiation Therapy in Patients With Localized Orbital Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma)

    International Nuclear Information System (INIS)

    Son, Seok Hyun; Choi, Byung Ock; Kim, Gi Won; Yang, Suk Woo; Hong, Young Seon; Choi, Ihl Bohng; Kim, Yeon Sil

    2010-01-01

    Purpose: To evaluate the outcomes of patients with localized orbital marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who were treated with radiotherapy (RT). Methods and Materials: We retrospectively reviewed the records of 46 patients who were treated with RT for pathologically confirmed localized stage IE marginal zone B-cell lymphoma of MALT. The radiation dose ranged from 21.6 to 45 Gy (median, 30.6 Gy) at 1.8-2.0 Gy per fraction. Median follow-up duration was 32.3 months (range, 3.1-113.6 months). Results: Forty-three patients (93%) achieved complete remission (CR), and three patients (7%) achieved partial remission (PR). Five-year relapse-free survival, cause-specific survival, and overall survival were 93%, 100%, and 100%, respectively. Among the patients with CR, two had recurrence at three sites. One patient relapsed locally and was successfully salvaged with reirradiation. The other patient relapsed in a distant site and was successfully treated with six cycles of CHOP chemotherapy. Late complications were noted in four patients. Two patients developed cataracts at 26 and 37 months after completion of RT. The other two patients developed nasolacrimal duct obstructions at 4 and 11 months after completion of RT. Conclusion: Our study showed that a modest dose of RT is an excellent treatment modality with low complication and recurrence rates. We suggest that a dose of 30.6 Gy is tolerable and sufficient for treating orbital MALT lymphoma. Even following recurrence, successful salvage is possible with RT or chemotherapy.

  20. Fiducial-free CyberKnife stereotactic body radiation therapy (SBRT) for single vertebral body metastases: acceptable local control and normal tissue tolerance with 5 fraction approach

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Beant; Oermann, Eric; Ju, Andrew; Suy, Simeng; Yu, Xia; Rabin, Jennifer [Department of Radiation Medicine, Georgetown University Hospital,, Washington, DC (United States); Kalhorn, Christopher; Nair, Mani N.; Voyadzis, Jean-Marc [Department of Neurosurgery, Georgetown University Hospital,, Washington, DC (United States); Unger, Keith; Collins, Sean P.; Harter, K. W.; Collins, Brian T., E-mail: collinsb@gunet.georgetown.edu [Department of Radiation Medicine, Georgetown University Hospital,, Washington, DC (United States)

    2012-04-26

    This retrospective analysis examines the local control and toxicity of five-fraction fiducial-free CyberKnife stereotactic body radiation therapy (SBRT) for single vertebral body (VB) metastases. All patients had favorable performance status (ECOG 0–1), oligometastatic disease, and no prior spine irradiation. A prescribed dose of 30–35 Gy was delivered in five fractions to the planning target volume (PTV) using the CyberKnife with X-sight spine tracking. Suggested maximum spinal cord and esophagus point doses were 30 and 40 Gy, respectively. A median 30 Gy (IQR, 30–35 Gy) dose was delivered to a median prescription isodose line of 70% (IQR, 65–77%) to 20 patients. At 34 months median follow-up (IQR, 25–40 months) for surviving patients, the 1- and 2-year Kaplan–Meier local control estimates were 80 and 73%, respectively. Two of the five local failures were infield in patients who had received irradiation to the gross tumor volume and three were paravertebral failures just outside the PTV in patients with prior corpectomy. No local failures occurred in patients who completed VB radiation alone. The 1- and 2-year Kaplan–Meier overall survival estimates were 80 and 57%, respectively. Most deaths were attributed to metastatic disease; one death was attributed to local recurrence. The mean maximum point doses were 26.4 Gy (SD, 5.1 Gy) to the spinal cord and 29.1 Gy (SD, 8.9 Gy) to the esophagus. Patients receiving maximum esophagus point doses greater than 35 Gy experienced acute dysphagia (Grade I/II). No spinal cord toxicity was documented. Five-fraction fiducial-free CyberKnife SBRT is an acceptable treatment option for newly diagnosed VB metastases with promising local control rates and minimal toxicity despite the close proximity of such tumors to the spinal cord and esophagus. A prospective study aimed at further enhancing local control by targeting the intact VB and escalating the total dose is planned.

  1. Preoperative therapy with pazopanib in high-risk soft tissue sarcoma: a phase II window-of-opportunity study by the German Interdisciplinary Sarcoma Group (GISG-04/NOPASS).

    Science.gov (United States)

    Ronellenfitsch, Ulrich; Dimitrakopoulou-Strauss, Antonia; Jakob, Jens; Kasper, Bernd; Nowak, Kai; Pilz, Lothar R; Attenberger, Ulrike; Gaiser, Timo; Egerer, Gerlinde; Fröhling, Stefan; Derigs, Hans-Günter; Schwarzbach, Matthias; Hohenberger, Peter

    2016-01-06

    For resectable soft tissue sarcoma (STS), radical surgery, usually combined with radiotherapy, is the mainstay of treatment and the only potentially curative modality. Since surgery is often complicated by large tumour size and extensive tumour vasculature, preoperative treatment strategies with the aim of devitalising the tumour are being explored. One option is treatment with antiangiogenic drugs. The multikinase inhibitor pazopanib, which possesses pronounced antiangiogenic effects, has shown activity in metastatic and unresectable STS, but has so far not been tested in the preoperative setting. This open-label, multicentre phase II window-of-opportunity trial assesses pazopanib as preoperative treatment of resectable STS. Participants receive a 21-day course of pazopanib 800 mg daily during wait time for surgery. Major eligibility criteria are resectable, high-risk adult STS of any location, or metachronous solitary STS metastasis for which resection is planned, and adequate organ function and performance status. The trial uses an exact single-stage design. The primary end point is metabolic response rate (MRR), that is, the proportion of patients with >50% reduction of the mean standardised uptake value (SUVmean) in post-treatment compared to pre-treatment fluorodeoxyglucose positron emission tomography CT. The MRR below which the treatment is considered ineffective is 0.2. The MRR above which the treatment warrants further exploration is 0.4. With a type I error of 5% and a power of 80%, the sample size is 35 evaluable patients, with 12 or more responders as threshold. Main secondary end points are histopathological and MRI response, resectability, toxicity, recurrence-free and overall survival. In a translational substudy, endothelial progenitor cells and vascular epithelial growth factor receptor are analysed as potential prognostic and predictive markers. Approval by the ethics committee II, University of Heidelberg, Germany (2012-019F-MA), German Federal

  2. Tissue Classification

    DEFF Research Database (Denmark)

    Van Leemput, Koen; Puonti, Oula

    2015-01-01

    Computational methods for automatically segmenting magnetic resonance images of the brain have seen tremendous advances in recent years. So-called tissue classification techniques, aimed at extracting the three main brain tissue classes (white matter, gray matter, and cerebrospinal fluid), are now...... well established. In their simplest form, these methods classify voxels independently based on their intensity alone, although much more sophisticated models are typically used in practice. This article aims to give an overview of often-used computational techniques for brain tissue classification...

  3. Bioprinting for Neural Tissue Engineering.

    Science.gov (United States)

    Knowlton, Stephanie; Anand, Shivesh; Shah, Twisha; Tasoglu, Savas

    2018-01-01

    Bioprinting is a method by which a cell-encapsulating bioink is patterned to create complex tissue architectures. Given the potential impact of this technology on neural research, we review the current state-of-the-art approaches for bioprinting neural tissues. While 2D neural cultures are ubiquitous for studying neural cells, 3D cultures can more accurately replicate the microenvironment of neural tissues. By bioprinting neuronal constructs, one can precisely control the microenvironment by specifically formulating the bioink for neural tissues, and by spatially patterning cell types and scaffold properties in three dimensions. We review a range of bioprinted neural tissue models and discuss how they can be used to observe how neurons behave, understand disease processes, develop new therapies and, ultimately, design replacement tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. External-beam radiation therapy combined with limb-sparing surgery in elderly patients (>70 years) with primary soft tissue sarcomas of the extremities. A retrospective analysis

    Energy Technology Data Exchange (ETDEWEB)

    Andrae, Claudia; Rauch, Josefine; Belka, Claus [University Hospital of Munich (LMU), Department of Radiation Oncology, Munich (Germany); Klein, Alexander; Duerr, Hans Roland [University Hospital of Munich (LMU), Department of Orthopedics, Munich (Germany); Lindner, Lars Hartwin [University Hospital of Munich (LMU), Deparment of Internal Medicine, Munich (Germany); Knoesel, Thomas [University Hospital of Munich (LMU), Institute of Pathology, Munich (Germany); Angele, Martin [University Hospital of Munich (LMU), Department of Surgery, Munich (Germany); Baur-Melnyk, Andrea [University Hospital of Munich (LMU), Department of Radiology, Munich (Germany); Roeder, Falk [University Hospital of Munich (LMU), Department of Radiation Oncology, Munich (Germany); German Cancer Research Center (DKFZ), CCU Molecular Radiation Oncology, Heidelberg (Germany)

    2017-08-15

    To report our experience with EBRT combined with limb-sparing surgery in elderly patients (>70 years) with primary extremity soft tissue sarcomas (STS). Retrospectively analyzed were 35 patients (m:f 18:17, median 78 years) who all presented in primary situation without nodal/distant metastases (Charlson score 0/1 in 18 patients; ≥2 in 17 patients). Median tumor size was 10 cm, mainly located in lower limb (83%). Stage at presentation (UICC7th) was Ib:3%, 2a:20%, 2b:20%, and 3:57%. Most lesions were high grade (97%), predominantly leiomyosarcoma (26%) and undifferentiated pleomorphic/malignant fibrous histiocytoma (23%). Limb-sparing surgery was preceded (median 50 Gy) or followed (median 66 Gy) by EBRT. Median follow-up was 37 months (range 1-128 months). Margins were free in 26 patients (74%) and microscopically positive in 9 (26%). Actuarial 3- and 5-year local control rates were 88 and 81% (4 local recurrences). Corresponding rates for distant control, disease-specific survival, and overall survival were 57/52%, 76/60%, and 72/41%. The 30-day mortality was 0%. Severe postoperative complications were scored in 8 patients (23%). Severe acute radiation-related toxicity was observed in 2 patients (6%). Patients with Charlson score ≥2 had a significantly increased risk for severe postoperative complications and acute radiation-related side effects. Severe late toxicities were found in 7 patients (20%), including fractures in 3 (8.6%). Final limb preservation rate was 97%. Combination of EBRT and limb-sparing surgery is feasible in elderly patients with acceptable toxicities and encouraging but slightly inferior outcome compared to younger patients. Comorbidity correlated with postoperative complications and acute toxicities. Late fracture risk seems slightly increased. (orig.) [German] Erfahrungsbericht zur perkutanen Radiotherapie (EBRT) kombiniert mit extremitaetenerhaltender Operation bei Patienten >70 Jahre mit Weichteilsarkom der Extremitaet. Retrospektiv

  5. Particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.

    1993-09-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics.

  6. Particle therapy

    International Nuclear Information System (INIS)

    Raju, M.R.

    1993-01-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics

  7. Isolation of an X-ray-responsive element in the promoter region of tissue-type plasminogen activator: Potential uses of X-ray-responsive elements for gene therapy

    International Nuclear Information System (INIS)

    Boothman, D.A.; Lee, I.W.; Sahijdak, W.M.

    1994-01-01

    Tissue-type plasminogen activator (t-PA) was induced over 50-fold after X irradiation in radioresistant human melanoma cells. Activities of t-PA were induced 14-fold in ataxia telangiectasia, 9-fold in Bloom's syndrome and 6-fold in Fanconi's anemia cells, compared to normal human fibroblasts. X-ray-inducible synthesis of the protease, t-PA, may play a role(s) in damage-inducible repair processes in mammalian cells, similar to the SOS repair systems in lower eukaryotes and prokaryotes. DNA band shift and DNase I footprinting assays were used to determine binding if transcription factors to a previously unknown X-ray-responsive element (XRE) in the t-PA promoter. The major goals of our research with XREs are to understand (a) which transcription factor(s) regulates to-PA induction after X-rays, and (b) the role(s) of t-PA in DNA repair, apoptosis or other responses to X rays. The purpose of this paper is to discuss the potential use of an XRE, such as the one in the t-PA promoter, for gene radiotherapy. Several gene therapy strategies are proposed. 22 refs., 3 figs

  8. Co-infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and bone marrow derived hematopoietic stem cells, a viable therapy for post-traumatic brachial plexus injury: A case report

    Directory of Open Access Journals (Sweden)

    Umang G Thakkar

    2014-08-01

    Full Text Available Stem cell therapy is emerging as a viable approach in regenerative medicine. A 31-year-old male with brachial plexus injury had complete sensory-motor loss since 16 years with right pseudo-meningocele at C5