The Johns Hopkins Medical Institutions

Bryans Road, MD, United States

The Johns Hopkins Medical Institutions

Bryans Road, MD, United States
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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.

Berman D.M.,Queen's 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.

Westra W.H.,The Johns Hopkins Medical Institutions
Otolaryngologic Clinics of North America | Year: 2012

The confirmation of human papillomavirus (HPV) as a causative agent for a subset of squamous cell carcinomas of the head and neck has resulted in a growing expectation for HPV testing in head and neck cancers. An increasing understanding of HPV-related tumorigenesis has informed this evaluation process in a manner that is moving wide scale, indiscriminant, and nonstandardized testing toward a more directed, clinically relevant, and standardized approach. This review addresses the current state of HPV detection and focuses on the importance, appropriate time, and need for HPV testing. © 2012 Elsevier Inc.

Bishop J.A.,The Johns Hopkins Medical Institutions | Sharma R.,The Johns Hopkins Medical Institutions | Illei P.B.,The Johns Hopkins Medical Institutions
Human Pathology | Year: 2010

Recent advances in the treatment of pulmonary adenocarcinoma have increased the need for accurate typing of non-small cell carcinomas. Immunohistochemistry for thyroid transcription factor-1 is widely used in the diagnosis of pulmonary adenocarcinomas because it marks approximately 75% of lung adenocarcinomas and is negative in most squamous cell carcinomas and adenocarcinomas of other organs. Napsin A is an aspartic proteinase involved in the maturation of surfactant protein B. It is detected in the cytoplasm of type 2 pneumocytes and alveolar macrophages and is a putative marker for pulmonary adenocarcinomas. We performed immunohistochemistry for napsin A and thyroid transcription factor-1 using tissue microarrays of 95 adenocarcinomas, 48 squamous cell carcinomas, 6 neuroendocrine tumors of the lung, as well as 5 colonic, 31 pancreatic, and 17 breast adenocarcinomas, 38 malignant mesotheliomas, 118 renal cell carcinomas, and 81 thyroid tumors. The tissue microarrays also included 15 different benign tissues. Pulmonary adenocarcinomas were napsin A positive in 79 (83%) of 95 cases compared with 69 (73%) of 95 cases that were thyroid transcription factor-1 positive. There were 13 napsin A-positive/thyroid transcription factor-1-negative and 2 thyroid transcription factor-1-positive/napsin A-negative tumors, increasing the number of cases that were positive with at least one of the markers to 81 (85%) of 95. The limited number of neuroendocrine tumors tested was napsin A negative. All squamous cell carcinomas, adenocarcinomas of the colon, pancreas and breast, and mesotheliomas were negative for both markers. Of the renal tumors, napsin A was positive in most of papillary renal cell carcinomas (79%), about one third (34%) of clear cell renal cell carcinomas, and in a single case of chromophobe renal cell carcinoma (3%). In the thyroid, only 2 cases of papillary thyroid carcinoma (5%), both with tall cell morphology, were positive for napsin A, whereas all other papillary and follicular carcinomas were negative. As expected, all renal tumors were thyroid transcription factor-1 negative, and all thyroid tumors, except for one papillary carcinoma, were thyroid transcription factor-1 positive. Napsin A is a sensitive marker for pulmonary adenocarcinoma and is also expressed in a subset of renal cell carcinomas, particularly of the papillary type, as well as in rare cases of papillary thyroid carcinomas. The combined use of napsin A and thyroid transcription factor-1 results in improved sensitivity and specificity for identifying pulmonary adenocarcinoma in primary lung tumors and in a metastatic setting. © 2010 Elsevier Inc. All rights reserved.

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.

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.

Molena D.,The Johns Hopkins Medical Institutions | Yang S.C.,The Johns Hopkins Medical Institutions
Seminars in Thoracic and Cardiovascular Surgery | Year: 2012

Esophageal achalasia is a chronic and progressive motility disorder that leads to massive esophageal dilation when left untreated. Treatment for achalasia is palliative and aimed to relieve the outflow obstruction at the level of the lower esophageal sphincter, yet protecting the esophageal mucosa from refluxing gastric acids. The best way to accomplish this goal is through an esophageal myotomy and partial fundoplication, with a success rate >90%. Progression of disease, treatment failure, and complications from gastroesophageal reflux disease cause progressive deterioration of the esophageal function to an end stage in about 5% of patients. The only chance to improve symptoms in this small group of patients is through an esophageal resection. This article will review the indications for esophagectomy in end-stage achalasia, present the different types of surgical approach and possibilities for reconstruction of the alimentary tract, and summarize the short-term and long-term postoperative results. © 2012.

Westra W.H.,The Johns Hopkins Medical Institutions
Seminars in Diagnostic Pathology | Year: 2015

A subset of head and neck squamous cell carcinomas are caused by the human papillomavirus (HPV). This HPV-related form of head and neck squamous cell carcinoma (HPV-HNSCC) has captured the attention of the oncology community for its rising incidence, its link to non-traditional risk factors, and its divergent clinical behavior. To diagnose this special form of head and neck squamous cell carcinoma is to provide important prognostic information and, in some instances, redirect clinical therapy. The diagnosis of HPV-HNSCC is aided by a strong appreciation for its characteristic microscopic findings and by an awareness of aberrant features that set apart a growing list of HPV-HNSCC morphologic variants. 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, offer recommendations for appropriate terminology when diagnosing HPV-HNSCC, and provide examples of specific diagnostic scenarios where HPV testing can inform the diagnostic process. © 2015 Elsevier Inc.

Goldstein S.D.,The Johns Hopkins Medical Institutions | Yang S.C.,The Johns Hopkins Medical Institutions
Annals of Thoracic Surgery | Year: 2010

Background: Robotic thymectomy is an emerging treatment for myasthenia gravis. However, the Myasthenia Gravis Foundation of America clinical research standards have been infrequently adopted in the surgical literature. Methods: Twenty-six patients underwent robotic thymectomy for myasthenia gravis between 2003 and 2008, performed by a single surgeon using the da Vinci system (Intuitive Surgical; Sunnyvale, CA) through a four-port right-sided approach. Results: Mean operative times were 68 ± 25 minutes of robotic system activation and 127 ± 35 minutes from incision to closure. There were no intraoperative or postoperative mortalities; the most common intraoperative complication was desaturation after single-lung ventilation, for which four procedures were converted to open. On histologic examination, there were five thymomas. The average follow-up after surgery was 26 months. Median preoperative and postoperative Myasthenia Gravis Foundation of America disease classifications were 2 and 0, respectively, reflecting a statistically significant decrease in symptoms (p < 0.01). Additionally, the average daily dose of cholinesterase inhibitor decreased by 63% postoperatively. Overall, 82% of patients improved and 18% were unchanged; no worsening disease was observed. Conclusions: Robotic thymectomy is a safe and efficacious treatment option for myasthenia gravis. There were no notable differences in patient demographics compared with previously published reports of open thymectomies. Furthermore, surgical and neurologic outcomes in this series compare favorably with conventional approaches in the literature. Of those with follow-up greater than 6 months, 82% of patients undergoing robotic thymectomy demonstrated significant clinical improvement postoperatively, indicating that this approach in concert with optimized medical management is an effective treatment for myasthenia gravis. © 2010 The Society of Thoracic Surgeons.

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.

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