Westra W.H.,The Johns Hopkins Medical Institutions
Head and Neck Pathology | Year: 2012
Much recent attention has highlighted a subset of head and neck squamous cell carcinomas (HNSCCs) related to the human papillomavirus (HPV) that is characterized by an epidemiologic, demographic, and clinical profile that deviates from the profile of conventional non-HPV-related HNSCC. Lost in the dash to develop and implement diagnostic assays to detect the presence of HPV in HNSCCs is the unpretentious observation that these HPV-HNSCCs are also distinctive with respect to their microscopic appearance, and that an awareness of these characteristic morphologic features can facilitate the diagnosis of HPV-related HNSCC (HPV-HNSCC). This review will delineate the microscopic appearance of HPV-HNSCC, spotlight ways in which the misinterpretation of these microscopic features can lead to diagnostic confusion, and provide recommendations for appropriate terminology when diagnosing HPV-HNSCC. © 2012 Springer Science+Business Media, LLC.
Laube B.L.,The Johns Hopkins Medical Institutions
Respiratory Care | Year: 2015
Inhalation therapy has matured to include drugs that: (1) deliver nucleic acids that either lead to the restoration of a gene construct or protein coding sequence in a population of cells or suppress or disrupt production of an abnormal gene product (gene therapy); (2) deliver peptides that target lung diseases such as asthma, sarcoidosis, pulmonary hypertension, and cystic fibrosis; and (3) deliver peptides to treat diseases outside the lung whose target is the systemic circulation (systemic drug delivery). These newer applications for aerosol therapy are the focus of this paper, and I discuss the status of each and the challenges that remain to their successful development. Drugs that are highlighted include: small interfering ribonucleic acid to treat lung cancer and Mycobacterium tuberculosis; vectors carrying the normal alpha-1 antitrypsin gene to treat alpha-1 antitrypsin deficiency; vectors carrying the normal cystic fibrosis transmembrane conductance regulator gene to treat cystic fibrosis; vasoactive intestinal peptide to treat asthma, pulmonary hypertension, and sarcoidosis; glutathione to treat cystic fibrosis; granulocyte-macrophage colony-stimulating factor to treat pulmonary alveolar proteinosis; calcitonin for postmenopausal osteoporosis; and insulin to treat diabetes. The success of these new aerosol applications will depend on many factors, such as: (1) developing gene therapy formulations that are safe for acute and chronic administrations to the lung, (2) improving the delivery of the genetic material beyond the airway mucus barrier and cell membrane and transferring the material to the cell cytoplasm or the cell nucleus, (3) developing aerosol devices that efficiently deliver genetic material and peptides to their lung targets over a short period of time, (4) developing devices that increase aerosol delivery to the lungs of infants, (5) optimizing the bioavailability of systemically delivered peptides, and (6) developing peptide formulations for systemic delivery that do not cause persistent cough or changes in lung function. © 2015 Daedalus Enterprises.
Berman D.M.,Queens University |
Epstein J.I.,The Johns Hopkins Medical Institutions
Urologic Clinics of North America | Year: 2014
Several investigators have challenged the idea that low-grade cancers are a cause for concern, suggesting that the term cancer should not be applied to these tumors. This article reviews the defining features of cancer, and the diagnostic and prognostic classification systems currently used for prostate cancer. Logical, morphologic, and molecular evidence is presented to show that low-grade prostate cancers are correctly classified as cancer. The authors suggest, however, that 6 out of 10 on an aggressiveness scale is inappropriate for indolent cancer, and that a proposed reinterpretation of Gleason grading categories is a more logical way to address overtreatment. © 2014 Elsevier Inc.
Reyes D.K.,Brady Urological Institute and Oncology |
Pienta K.J.,Brady Urological Institute and Oncology |
Pienta K.J.,The Johns Hopkins Medical Institutions
Oncotarget | Year: 2015
Clinical reports of limited and treatable cancer metastases, a disease state that exists in a transitional zone between localized and widespread systemic disease, were noted on occasion historically and are now termed oligometastasis. The ramification of a diagnosis of oligometastasis is a change in treatment paradigm, i.e. if the primary cancer site (if still present) is controlled, or resected, and the metastatic sites are ablated (surgically or with radiation), a prolonged disease-free interval, and perhaps even cure, may be achieved. Contemporary molecular diagnostics are edging closer to being able to determine where an individual metastatic deposit is within the continuum of malignancy. Preclinical models are on the outset of laying the groundwork for understanding the oligometastatic state. Meanwhile, in the clinic, patients are increasingly being designated as having oligometastatic disease and being treated owing to improved diagnostic imaging, novel treatment options with the potential to provide either direct or bridging therapy, and progressively broad definitions of oligometastasis.
Sodha N.R.,The Johns Hopkins Medical Institutions
Plastic and reconstructive surgery | Year: 2012
Surgeons are faced with increasingly complex and larger chest wall defects as a result of a variety of pathologies, the majority of which are oncologic. Skeletal reconstruction of these resulting defects and subsequent soft-tissue coverage remain a challenge for thoracic and plastic and reconstructive surgeons. A variety of techniques and grafts have been utilized to support the thoracic cage. This review focuses on the use of acellular dermal matrices in thoracic skeletal reconstruction, with a focus on the indications, published data, and surgical techniques for utilizing acellular dermal matrices in chest wall reconstruction.