bluuebunny/crossref_metadata_2025 huggingface dataset:
Localized Prostate Cancer—What the Medical Oncologist Needs to Know
Authors: Bardia Aditya , Carducci Michael A ,   Clinical Fellow, Division of Medical Oncology,   Professor of Oncology and Urology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University
Published: October 2015

Prostate cancer is the most commonly diagnosed cancer among men and the second leading cause of cancer-related deaths among men in the US. In the post-prostate specific antigen (PSA) era, about 85% of all prostate cancers diagnosed are clinically localized prostate cancers. Most cancers are diagnosed in asymptomatic men, and T1c (stage I) is the most commonly diagnosed stage of prostate cancer. Consequently, medical oncologists are increasingly being asked to participate in multidisciplinary prostate cancer clinics and provide recommendations on localized prostate cancer, particularly related to active surveillance as well as neoadjuvant and adjuvant therapies such as androgen deprivation therapy (ADT) and chemotherapy. This article reviews the potential role of the medical oncologist as a team member in the management of localized prostate cancer. The role of active surveillance as well as neo-adjuvant and adjuvant therapies such as ADT and chemotherapy is discussed in detail. The long-term adverse effects of ADT and potential supportive measures are also reviewed.
Relevance of Weight Loss, Splenomegaly, and Hypocholesterolemia in the Treatment of Myeloproliferative Neoplasms— Implications for a JAK2 Inhibitor Era
Authors: Scherber Robyn M , Mesa Ruben A ,   Medical Student, Chicago Medical School, Rosalind Franklin University of Medicine and Science,   Consultant Hematologist and Chair, Department of Hematology and Oncology, Mayo Clinic
Published: October 2015

Myeloproliferative neoplasms (MPNs) encompass a diverse yet homogenous classification of hematologic malignancies including primary myelofibrosis (MF), essential thrombocythemia (ET), and polycythemia vera (PV). Although clinically distinct, these three entities share similar clinical and prognostic features and are characterized by clonal stem cell proliferation with recurrent chromosomal abnormalities. MPNs can be accompanied by symptomatic worsening, particularly weight loss and splenomegaly. However, of these symptoms only splenomegaly is targeted by conventional therapy. With the key discovery of the JAK2V617F mutation, there has been renewed focus on effective treatment strategies aimed at counteracting the debilitating side effects accompanying this disease. In this brief article, we describe the clinical features, course, treatment approaches, and monitoring utility of progressive splenomegaly and cachexia in MPNs.
The Effect of Sickle Cell Genetic Markers on Geographic Distribution and Relation to Pain Outcomes in the Multicenter Study of Hydroxyurea in Sickle Cell Anemia
Authors: Ballas Samir K , Bauserman Robert L , McCarthy William F , Waclawiw Myron A ,   Cardeza Foundation for Hematologic Research, Department of Medicine, Jefferson Medical College, Thomas Jefferson University,   Maryland Medical Research Institute,   Maryland Medical Research Institute,   National Heart, Lung and Blood Institute
Published: October 2015

Some genetic markers known to play a role in sickle cell disease were associated with classification as a treatment responder, pain-related outcomes, and equi-analgesic dosing in the Multicenter Study of Hydroxurea (MSH) cohort. However, when examined by sex, associations with equi-analgesic dosing were statistically significant for males only. Factors that increase the hemoglobin/hematocrit levels seem not to be beneficial. Future research should focus on factors that increase fetal hemoglobin level.
Internal Hemipelvectomy for Musculoskeletal Tumors—Indications and Options for Reconstruction
Authors: Schwartz Adam J , Eckardt Jeffrey J , Beauchamp Christopher P ,   Instructor of Orthopedics,   Professor of Orthopedic Surgery,   Associate Professor of Orthopedics, University of California, Los Angeles Medical Center and Mayo Clinic Arizona
Published: October 2015

Resection of all or part of the bony pelvis is commonly referred to as internal hemipelvectomy. This procedure is a common treatment for various localized primary tumors of the hemipelvis, and rarely for metastatic lesions. Options for reconstruction following tumor resection include allograft, allograft-prosthetic composite (APC), and endoprosthetic reconstruction. An alternative method of limb salvage following resection of the hemipelvis is resection arthroplasty. Controversy exists among musculoskeletal oncologists regarding the most durable and functional method of reconstruction. As primary musculoskeletal tumors involving the pelvis are rare, there are few well-designed studies from which to draw definitive conclusions. The purpose of this paper is to review the indications for internal hemipelvectomy and to examine the risks and benefits of the available reconstruction methods.
Treatment Options for Myelodysplastic Syndromes
Authors: Prescott Hillary , Jabbour Elias , Bryan Jeffrey , Kantarjian Hagop ,   Clinical Pharmacy Specialist,   Assistant Professor,   Clinical Pharmacy Specialist,   Chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center
Published: October 2015

Myelodysplastic syndromes (MDS) are a group of heterogeneous hematopoietic stem cell disorders characterized by peripheral blood cytopenias and a risk of transformation to acute myeloid leukaemia. Until recently, treatment of MDS predominately consisted of supportive care measures. However, three agents for the treatment of MDS have recently been approved: lenalidomide, decitabine, and azacitidine. These agents have dramatically improved the outcomes for patients with MDS. To date, azacitidine is the only agent that has demonstrated a survival advantage when compared with conventional care. Novel agents and combination regimens including lenalidomide, decitabine and azacitidine are being explored in an effort to further improve patient outcomes.
Chemotherapy Options for Metastatic HER2-Negative Breast Cancer after Prior Exposure to Anthracyclines and Taxanes
Authors: Liu Minetta C ,   Associate Professor, Breast Cancer Program, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center
Published: October 2015

Metastatic breast cancer (MBC) remains incurable despite the many advances in cancer treatment. While anthracycline- and/or taxane-based regimens are the preferred first-line chemotherapies for MBC, many patients develop disease that is either resistant or becomes refractory to these agents. Currently, there is no single standard of care for women who experience disease progression after treatment with anthracyclines and taxanes. A number of chemotherapeutics have been evaluated as single agents and as part of combination regimens, with varying results. The US Food and Drug Administration has approved capecitabine, ixabepilone, and eribulin as single agents for third-line therapy and beyond. Combination regimens such as capecitabine plus ixabepilone or gemcitabine plus carboplatin are also available for pre-treated MBC patients. The present article will review the options available to MBC patients following prior treatment with anthracyclines and taxanes.
Conventional Pre-operative Chemoradiotherapy and Post-operative Adjuvant Chemotherapy with Induction Chemotherapy Followed by Chemoradiotherapy and Surgery in Locally Advanced Rectal Cancer
Authors: Fernández-Martos Carlos , Estevan Rafael , Maurel Joan ,   Head, Gastrointestinal Oncology Unit, Medical Oncology Department, Valencia Oncology Institute,   Head, Surgery Department, Valencia Oncology Institute,   Head, Gastrointestinal Oncology Service, Medical Oncology Department, Hospital Clinic, Barcelona
Published: October 2015

In locally advanced rectal cancer, pre-operative combined-modality treatment with 5-fluorouracil and radiation has become standard, as it improves locoregional control. However, to date, no improvement has been demonstrated in terms of survival outcomes. Phase III trials published in the past decade included clinically staged populations of heterogeneous risk, and one recurring finding was that there was poor adherence to the adjuvant chemotherapy treatment after surgery. No randomized studies have been able to show that the administration of adjuvant chemotherapy in patients undergoing pre-operative radiochemotherapy improves outcomes, compared to observation. One strategy to address this is to give upfront chemotherapy prior to pre-operative chemoradiotherapy. Compared with post-operative chemotherapy, the upfront strategy does not appear to improve pathological complete response, but it has been found to have a better toxicity profile, improve compliance with treatment, and provide greater exposure to systemic treatment. This can be important for patients at higher risk of distant disease relapse. Introducing a systemically active combination chemotherapy prior to chemoradiotherapy and surgery in an appropriately selected high-risk population may well be the next step in phase III testing in order to improve disease-free survival.
Peri-operative Therapies for Localized Retroperitoneal Soft Tissue Sarcoma
Authors: Radaelli Stefano , Desai Anant , Colombo Chiara , Fiore Marco , Gronchi Alessandro ,   Fellow Surgeon, Department of Surgery, National Cancer Institute, Milan,   Attending Surgeon, Department of Surgery, National Cancer Institute, Milan and Queen Elizabeth Medical Centre, Birmingham,   Attending Surgeon, Department of Surgery, National Cancer Institute, Milan,   Attending Surgeon, Department of Surgery, National Cancer Institute, Milan,   Chief, Sarcoma Service, Department of Surgery, National Cancer Institute, Milan
Published: October 2015

Retroperitoneal soft tissue sarcomas are rare solid tumors that usually arise in the retroperitoneum or the pelvis. They are often large at presentation and push adjacent structures, displacing them, anatomically. The most common adult histotypes are liposarcoma and leiomyosarcoma. Five-year overall survival is less than 50 % and is mainly determined by the high incidence of local relapse and to a lesser extent by their capacity to metastasize. Radical surgery is still the most effective treatment. While an aggressive surgical policy consisting of multivisceral resections ‘en bloc’ with the mass has undoubtedly decreased, the rate of local recurrence, prognosis remains poor. Retrospective analyses and early prospective data suggest a benefit from using neoadjuvant radiotherapy in order to improve local control. Chemotherapy plays an important role in advanced disease, but very little evidence supports a real advantage in delivering it prior to surgery to make the resection more likely to achieve clear margins or postoperatively to decrease the risk of systemic recurrence. Further studies are required to explore the role of these neoadjuvant/adjuvant therapies, particularly in the context of new developments in molecular therapeutic agents.
A Review of Sleep Concerns in Pediatric Sickle Cell Disease
Authors: Daniel Lauren C , Barakat Lamia P ,   Postdoctoral Researcher, Division of Oncology, The Children’s Hospital of Philadelphia,   Director of Psychosocial Services, The Children’s Hospital of Philadelphia and Associate Professor of Clinical Psychology, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania
Published: October 2015

Children with sickle cell disease (SCD) are at an increased risk of sleep disorders as compared with healthy children, possibly because of disease processes, pain, ethnic minority status, and living in an urban environment. Adequate sleep is an essential component of typical child development, mood-and-affect regulation, and health maintenance, but more research is needed to understand the contribution of sleep to health outcomes in children with SCD. SCD is a chronic disease that can be influenced by environmental, health, and behavioral factors. Understanding the impact of the disease on sleep is important to maximise the quality of life in these children. If SCD causes poor sleep quality, then children may be at risk of a host of developmental and psychosocial problems beyond those caused by the disease. Also, poor sleep may affect the disease course, thus exacerbating symptoms. In this article, prevalent sleep disorders in this population are reviewed, including sleep-disordered breathing, periodic limb movement disorder, restless legs syndrome, and nocturnal enuresis. Also, the contribution of the disease symptoms—such as pain, hypoxemia, and daytime tiredness and fatigue—to disrupted sleep are examined. Finally, the effects of sociodemographic factors, such as poverty and ethnic minority status, are described, as these contextual factors significantly impact sleep across several chronic conditions in pediatric patients. Frequent monitoring for sleep disruptions can be essential to improving health outcomes and quality of life in children with SCD.
Iron Deficiency Anemia in Cancer Patients
Authors: Janis Mark ,   Attending Hematologist/Oncologist, Los Alamitos Hematology Oncology Medical Group, Los Alamitos, California, US
Published: October 2015

Anemia is highly prevalent, affecting approximately 40 % of cancer patients, and results in a significant decrease in health-related quality of life while also being associated with shorter cancer survival times. A recent survey of 15,000 cancer patients in Europe found that 39 % were anemic at the time of enrolment. In addition, anemia is a recognized complication of myelosuppressive chemotherapy, and it has been estimated that, in the US, around 1.3 million cancer patients who are not anemic at the time of diagnosis will develop anemia during the course of their disease. The etiology of anemia in cancer patients is variable and often multifactorial, and may be the result of an absolute or a functional iron deficiency. Cancer produces an enhanced inflammatory state within the bodycausing hepcidin levels to increase and erythropoietin production to decreaseand results in a reduction in erythropoiesis due to impaired iron transport. This type of anemia is known as functional iron deficiency, where the body has adequate iron stores but there are problems with mobilization and transport of the iron. Absolute iron deficiency is when both iron stores and iron transport are low. The National Comprehensive Cancer Network (NCCN) treatment guidelines for cancer-related anemia recommend intravenous (IV) iron products alone for iron repletion in cancer patients with absolute iron deficiency, and erythropoiesis-stimulating agents (ESAs) in combination with IV iron in cancer patients (currently undergoing palliative chemotherapy) with functional iron deficiency. Although IV iron has been demonstrated to enhance the hematopoietic response to ESA therapy, the use of supplemental iron has not yet been optimized in oncology. Here we discuss the significance of iron deficiency anemia in cancer patients and the need to implement tools to properly diagnose this condition, and we provide an overview of the management strategies and recommendations for patients with iron deficiency anemia as outlined in the NCCN guidelines.
Aging Influences the Value of Serum Leptin as Prostate Cancer Risk Factor
Authors: Bologna Mauro , Sanità Patrizia , Vicentini Carlo , Angelucci Adriano ,   Professor of General Pathology, Department of Life, Health and Environmental Sciences,   PhD Fellow in Biotechnology, Department of Biotechnological and Applied Clinical Sciences,   Chief of Urology Clinic, Department of Life, Health and Environmental Sciences,   Assistant Professor of General Pathology, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Italy.
Published: October 2015

Depository fat functions as endocrine tissue able to regulate whole-body energy homeostasis. Obesity and aging are independently associated with a deregulation of adipose tissue, resulting in pro-inflammatory status and excessive release of adipokines. These events are under investigation for a possible synergism in determining chronic diseases, including cardiovascular illnesses and several types of cancer. Our data, obtained through an observational study conducted with prostate cancer patients, confirmed the association of leptin, an adipose tissue-derived adipokine, with cancer, and suggested that serum leptin represents a stronger risk factor for prostate cancer (PCa) in older than in younger subjects. In elderly patients, visceral obesity measured by waist to hip ratio provided a better correlation with serum leptin in terms of body mass index (BMI) measurements and appeared to be a more adequate indicator for obesity. The expression of leptin receptor mainly observed in invasive prostate carcinoma tissue and in aggressive prostate cancer cell lines suggests a possible molecular link between persistently high leptin levels, seen in aged obese subjects, and PCa progression.
Multi-modality Therapy for Rectal Cancer—Past, Present, and Future
Authors: Overton Lindsay C , Thomas Jr Charles R , Herzig Dan O , Lopez Charles D ,   Division of Hematology and Medical Oncology, Department of Medicine and the Knight Cancer Institute,   Department of Radiation Medicine and the Knight Cancer Institute,   Department of Surgery and the Knight Cancer Institute, Oregon Health and Science University, Portland, OR, US.,   Division of Hematology and Medical Oncology, Department of Medicine and the Knight Cancer Institute
Published: October 2015

The treatment of rectal cancer currently involves coordinated efforts for combined modality therapy with pre-operative chemoradiation followed by surgical management and additional adjuvant chemotherapy. The landscape of rectal cancer has shifted significantly over the past 30 years. This review aims to track this changing landscape, with a particular focus on current research and future endeavors.
Late Complications of Cancer in Childhood and Adolescence
Authors: Chowdhury Tanzina , Levitt Gill A ,   Consultant in Paediatric Oncology,   Honorary Consultant in Oncology, Department of Paediatric Oncology, Great Ormond Street Hospital, London, UK.
Published: October 2015

Overall survival for all childhood cancers has substantially increased with nearly 80 % of children surviving to five years following diagnosis, compared with 30 % 50 years ago. Unfortunately this comes at a cost; the overall Standardised Mortality Ratio (SMR) was 8.4 for childhood cancer survivors compared with the general population and increases in cause-specific mortality were seen for deaths due to second malignancy and cardiotoxicity. The incidence of chronic morbidities in the US Childhood Cancer Survivor Study (CCSS) cohort was 62.3 % after follow-up for 26.6 years. While many children will escape these organ toxicities, a significant proportion will require surveillance and management of treatment morbidities. It is the responsibility of those who treat childhood cancer to understand the effects of treatment and provide effective services to maximise the potential of these young people.
Supportive and Palliative Oncology—A New Paradigm for Comprehensive Cancer Care
Authors: Hui David , Bruera Eduardo ,   Department of Palliative Care and Rehabilitation Medicine, MD Anderson Cancer Center, Houston, TX, US.,   Department of Palliative Care and Rehabilitation Medicine, MD Anderson Cancer Center, Houston, TX, US.
Published: October 2015

Patients with advanced cancer often experience symptoms related to increasing tumor burden, cancer treatments, and psychosocial stressors. They also have significant social, informational, and decision-making needs. Palliative care practitioners have developed expertise to address many of these supportive care concerns through interprofessional teamwork, validated assessments, multidimensional interventions, and frequent communication. In this article, we aim to provide an evidence-based update on several important palliative care topics, including management of pain, fatigue, anorexiacachexia, depression, and anxiety, as well as patientclinician communication and decision-making. Multiple randomized controlled trials have demonstrated that palliative care can improve symptom burden, quality of life, quality of care, satisfaction, and possibly survival and cost of care. To enhance the level of care for patients with advanced cancer, oncologists need to have a good working knowledge of the major palliative care principles, and to refer patients to palliative care programs often and early in the disease trajectory.
New Molecular Targets in Lung Adenocarcinoma
Authors: Kelleher Fergal C , Colebatch Andrew J , Rao Aparna ,   Lecturer in Medical Oncology, St Vincents University Hospital and University College Dublin, Dublin, Ireland,   Registrar in Anatomical Pathology, Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia,   Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia,   PhD Candidate and Medical Oncologist, Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Published: October 2015

Lung cancer is designated as either non-small-cell lung cancer (NSCLC) or small-cell lung cancer. There are three subtypes of NSCLC: adenocarcinoma (48 %), squamous cell carcinoma (28 %), and large-cell carcinoma (24 %). Epidermal growth factor receptor(EGFR)mutations, anaplastic lymphoma kinase(ALK)rearrangements, andROS1rearrangements are co-associated with lung adenocarcinoma in never-smokers. Histologically, lung adenocarcinoma is sub-divided into papillary, acinar, bronchioalveolar, and solid subtypes. A superseding molecular subclassification is emerging with important therapeutic implications. Secondary resistance to medications targeting these molecular abnormalities does invariably occur. It is anticipated that strategies including drugs with increased receptor binding affinity, altered medication pharmacodynamic profiles, and combinatorial approaches will emerge.
Bevacizumab in the Management of Epithelial Ovarian Cancer
Authors: Markman Maurie ,   Senior Vice President of Clinical Affairs, National Director for Medical Oncology, Cancer Treatment Centers of America, Philadelphia, US; Clinical Professor of Medicine, Drexel University College of Medicine, Philadelphia, US
Published: October 2015

Preclinical investigations have provided strong support for the hypothesis that angiogenesis is a potent driver of epithelial ovarian cancer progression. Phase II data have revealed the activity of single-agent bevacizumab in previously treated and clinically defined platinum-resistant ovarian cancer. Several reported phase III randomized trials, involving primary and both ‘platinum-sensitive’ recurrent and platinum-resistant disease, have demonstrated the addition of bevacizumab to a cytotoxic chemotherapy regimen improves progression-free survival compared with chemotherapy alone. While there continues to be considerable debate regarding the optimal dose, timing, and duration of bevacizumab administration in ovarian cancer, the existing data provide strong support for an important role for this agent in the overall management paradigm for this malignancy.
Advances in Adjuvant Therapy for the Treatment of High-risk Melanoma
Authors: Grossmann Kenneth F , Christiansen Shelley ,   Huntsman Cancer Institute, Division of Medical Oncology,   Department of Internal Medicine, University of Utah,   Department of Internal Medicine, University of Utah
Published: October 2015

The global incidence of melanoma is increasing, and the prognosis for patients remains poor. High-dose interferon-alpha (HD-IFN-a) and pegylated IFN are the only US Food and Drug Administration (FDA)-approved agents for adjuvant therapy for high-risk melanoma, and an improvement in relapse-free survival (RFS) has been observed consistently across nearly all published studies and meta-analyses. Some studies and meta-analyses have also supported an overall survival (OS) benefit. However, despite a number of adjuvant studies, controversy remains regarding the role of this treatment. As the benefits in OS are modest with IFN treatment, there is therefore a need for new therapeutic targets, new drugs, and optimum patient selection. Current research is investigating new adjuvant agents, either individually or in combination, which may advance the standard of care beyond HD-IFN. Additionally, identifying biomarkers of patients with greater likelihood of response may allow patient-specific therapeutic approaches. Following the recent FDA approval of ipilimumab, vemurafenib, dabrafenib, and trametenib for metastatic melanoma, ongoing adjuvant trials are now underway.
The Role of Anaplastic Lymphoma Kinase in Human Cancers
Authors: García-Regalado Alejandro , González-De la Rosa Claudia Haydée ,   Postdoctoral Researcher of Natural Sciences Department,   Professor and Researcher of Natural Sciences Department, Metropolitan Autonomous University, Mexico City, Mexico
Published: October 2015

The anaplastic lymphoma kinase (ALK) is a receptor with tyrosine kinase activity, which regulates the development and maintenance of the nervous system. Mutations or amplification in ALK promote tumorogenesis and progression of diverse types of cancer, which makes it an attractive therapeutic target against cancer diseases. Inhibition of its tyrosine kinase activity with small molecules, such as crizotinib, reveals tumor reversion; however, secondary mutations and amplification of the gene mediate resistance to treatment. In this article, we discuss the emerging role of possible therapeutic targets that could overcome the resistance to ALK inhibition in cancer, such as inhibition of other kinases involved in the pathway, inhibition of ALK mutant proteins through the development of new drugs based on its crystallography, and the use of antibodies against ALK.
Diagnosis and Work-up of Malignant Melanoma in the Age of Fine Needle Aspiration and Molecular Testing
Authors: Layfield Lester J ,   Professor and Chair, Department of Pathology & Anatomical Sciences, University of Missouri, Columbia, US
Published: October 2015

Melanoma is one of the most aggressive skin cancers and is prone to both local recurrence and distant metastases. Primary treatment usually includes wide excision and sentinel lymph node biopsy. Clinical and pathologic staging is important for estimating the potential for metastasis and influences post-resection follow-up protocols. Because stage I and II melanomas metastasize infrequently, asymptomatic patients with these low-stage malignancies do not require routine imaging studies. Patients with positive sentinel lymph nodes often undergo routine examination (for staging) using computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) despite evidence showing a very low yield for such testing. Patients with stage III disease and local recurrence should undergo further testing including serum lactate dehydrogenase (LDH), chest radiograph, CT, and PET due to increased risk for systemic metastases. Imaging abnormalities may undergo fine needle aspiration, core biopsy, or open biopsy for confirmation of diagnosis and to obtain tissue for ancillary studies. Depending on the availability of treatment protocols ancillary testing may include mutational analysis for BRAF V600-E, CKIT, and NRAS.
Androgen Deprivation Therapy and the Re-emergence of Parenteral Estrogen in Prostate Cancer
Authors: Phillips Iain , A Shah Syed I , Duong Trinh , Abel Paul , Langley Ruth E ,   Clinical Fellow,   Clinical Research Fellow,   Senior Statistician,   Professor and Honorary Consultant Urologist, Imperial College, London, UK,   Medical Oncologist, Medical Research Council Clinical Trials Unit, University College, London, UK
Published: October 2015

Androgen deprivation therapy (ADT) resulting in testosterone suppression is central to the management of prostate cancer (PC). As PC incidence increases, ADT is more frequently prescribed, and for longer periods of time as survival improves. Initial approaches to ADT included orchiectomy or oral estrogen (diethylstilbestrol [DES]). DES reduces PC-specific mortality, but causes substantial cardiovascular (CV) toxicity. Currently, luteinizing hormone-releasing hormone agonists (LHRHa) are mainly used; they produce low levels of both testosterone and estrogen (as estrogen in men results from the aromatization of testosterone), and many toxicities including osteoporosis, fractures, hot flashes, erectile dysfunction, muscle weakness, increased risk for diabetes, changes in body composition, and CV toxicity. An alternative approach is parenteral estrogen, it suppresses testosterone, appears to mitigate the CV complications of oral estrogen by avoiding first-pass hepatic metabolism, and avoids complications caused by estrogen deprivation. Recent research on the toxicity of ADT and the rationale for revisiting parenteral estrogen is discussed.
Immunologic Therapy of Renal Cell Carcinoma
Authors: Agarwal Neeraj , Fishman Mayer ,   Assistant Professor, Division of Medical Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City, Utah, US,   Senior Member, Department of Genitourinary Oncology, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, US
Published: October 2015

Interleukin-2 (IL-2) has been the mainstay of immunotherapy of metastatic renal cell carcinoma (mRCC) therapy for over 20 years. Although IL-2 treatment is limited to fit patients, a select group of these patients have derived substantial, durable benefit from it, for some translating into cures with no ongoing therapy or chronic toxicity. While targeted therapies are applicable to most patients, improvements of median survival have been measured in months. Immunotherapy, encompassing not only IL-2 but also newer checkpoint and vaccine approaches, therefore still has an important role for many as a main choice in RCC treatment. Enhanced patient selection techniques have evolved over time, and the overall response rate to high-dose (HD) IL-2 has improved among those selected patients. An increased understanding of immunotherapy has led to other novel approaches. These include checkpoint inhibitors mediating changes of T-cell behavior acting at the lymphocyte protein receptor programmed death-1 (PD-1), such as nivolumab, and vaccine immunotherapies, including peptide and dendritic cell vaccines in pivotal trials, and coordinated use of radiation therapy with IL-2, encouraging in early phase testing. Such approaches have the potential to expand the immune approach to achieve outcomes with better overall survival for many patients with mRCC.
Potential Use of Biomarkers to Augment Clinical Decisions for the Early Detection of Breast Cancer
Authors: Hollingsworth Alan B , Reese David E ,   Medical Director, Mercy Women’s Center, Mercy Hospital–OKC, Oklahoma City, OK, US,   Chief Scientific Officer and Chief Executive Officer, Provista Diagnostics, Inc., New York, NY, US
Published: October 2015

Breast cancer remains a significant worldwide health problem, despite the fact that early detection is associated with excellent survival rates. Currently, a substantial proportion of breast cancers are not detected using routine screening. Therefore, there is a need to identify a technology that can improve the precision and accuracy of early breast cancer detection. Biomarkers are attractive in that they can potentially detect early cancers with high sensitivity, while distinguishing between benign disease and invasive cancers. Many commonly used serum biomarkers have limited use in screening assays for breast cancer as single agents due to the heterogeneous nature of breast cancer. However, the use of protein panels that detect multiple serum biomarkers offer the potential for enhanced sensitivity and specificity in a clinical setting. Recently, a serum biomarker test comprising five serum biomarkers for breast cancer was clinically validated and showed high sensitivity and specificity. Additional panels have been developed that combine serum protein biomarkers (SPB) and tumor-associated autoantibodies (TAb) to further enhance the clinical utility of the assay. Serum biomarkers are currently not the standard of care and are not recommended in any detection guidelines. However, tumor biomarkers are used in the breast cancer setting to determine the course of care. The purpose of this article is to review recent advances in SPB, TAb, and biomarkers used in breast cancer detection to provide a perspective on how these technologies may offer benefit when combined with current imaging modalities.
Recent Developments in Androgen Deprivation Therapy for Locally Advanced Prostate Cancer
Authors: Bader David A , Cerne Jasmina Z , McGuire Sean E ,   MD/PhD Student,   Post-Doctoral Fellow,   Assistant Professor, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, US,   Assistant Professor, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, US
Published: October 2015

Locally advanced prostate cancer (LAPC) is often managed with a combination of external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT). Clinical protocols combining ADT and EBRT for the treatment of LAPC were developed based on clinical trials that used conventional-dose EBRT (~70 Gy) and luteinizing hormone-releasing hormone (LHRH) analog monotherapy. However, dose-escalated EBRT (>74 Gy) is in widespread clinical use and potent second-generation agents targeting the androgen axis have recently received US Food and Drug Administration (FDA) approval. These and other recent developments challenge the current standard of care for LAPC. Determining the optimal duration and potency of ADT in combination with dose-escalated EBRT in LAPC is an active area of clinical research seeking to balance the side-effect profile of ADT with its well-established therapeutic benefits. Prospective randomized clinical trials incorporating dose-escalated EBRT and second-generation androgen axis inhibitors are necessary to clarify the role of ADT in this new arena. Further, since biochemical response to neoadjuvant ADT predicts for efficacy of EBRT, new trials should seek to achieve maximal androgen suppression prior to EBRT to increase clinical benefit. Last, recent clinical and preclinical research efforts hold significant promise and seek to provide better predictive markers and expand the therapeutic target spectrum in prostate cancer.
Future of Radiotherapy Delivery in Rectal Cancer— European and US Approaches
Authors: Torok Jordan A , Czito Brian G , Willett Christopher G , Palta Manisha ,   Resident,   Associate Professor,   Professor and Chair,   Assistant Professor, Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, US
Published: October 2015

Neoadjuvant radiation therapy is integral in the management of patients with localized rectal cancer. In parts of Europe, patients with operable rectal cancer are treated with short-course radiation therapy delivered in five daily, 5 Gy fractions to a total dose of 25 Gy, followed by surgery within 1 week. In the US, the standard for locally advanced rectal cancer is neoadjuvant chemoradiotherapy. This approach is principally based on the results of the German Rectal Cancer Study Group trial evaluating preoperative compared with postoperative chemoradiation. Surgery is typically performed at 4–8 weeks following completion of long-course chemoradiotherapy, facilitating tumor downstaging, and potential sphincter sparing surgery. No significant difference in clinical outcomes has been observed between these two approaches in two randomized clinical trials; however, further follow-up of these studies and new results from ongoing trials are anticipated to further clarify the optimal neoadjuvant treatment strategy.
Thyroid Cancer—Risks and Causes
Authors: Bonnefond Simon , Davies Terry F ,   Visiting Research Fellow,   Baumritter Professor of Medicine, Thyroid Research Unit, James J Peters VA Medical Center, The Icahn School of Medicine at Mount Sinai, New York, US
Published: October 2015

The incidence of thyroid cancer has almost doubled in recent years and over 60,000 people will be diagnosed in the US in 2015. While the prognosis for most such patients is excellent, a significant proportion die of thyroid cancer from local tumor progression and above all from metastases. Here we review the different types of thyroid cancers and their molecular changes with a special emphasis on the currently known susceptibility and precipitating factors. With the recent clinical introduction of tyrosine kinase inhibitors for the treatment of metastatic thyroid cancer it is clear that a simple cure is not at hand and further understanding of the molecular mechanisms of these tumors is urgently needed.
EGFR Inhibition in the Treatment of Squamous Cell Carcinoma of the Head and Neck
Authors: Hadziahmetovic Mersiha , Machtay Mitchell ,   Assistant Professor of Radiation Oncology, University Hospitals Seidman Cancer Center, Firelands Regional Medical Center, Sandusky, Ohio, US,   Chairman, Department of Radiation Oncology, UH Case Medical Center and Professor, Radiation Oncology, CWRU School of Medicine, Cleveland, Ohio, US
Published: October 2015

Squamous cell carcinoma of the mucosal surfaces in the head and neck (SCCHN) remains a therapeutic challenge in much of the world. Most patients present with locally and/or regionally advanced disease, and are offered curative (definitive) therapy in the form of external beam radiotherapy with a concurrent radiosensitizing systemic agent, most commonly platinum-based or targeting an epidermal growth factor receptor (EGFR). In this review, we will cover the literature and published data evaluating the use of EGFR inhibitors as part of the concurrent or postoperative regimen in the context of definitive treatment for patients with SCCHN, as well as its use in patients with recurrent or distantly metastatic disease.
Yoga for the Treatment of Insomnia Among Cancer Patients— Evidence, Mechanisms of Action, and Clinical Recommendations
Authors: Mustian Karen M , Janelsins Michelle , Peppone Luke J , Kamen Charles ,   Associate Professor,   Assistant Professor,   Assistant Professor,   Research Assistant Professor, Department of Surgery, University of Rochester School of Medicine and Dentistry, Wilmot Cancer Institute, Rochester, New York, US
Published: October 2015

Up to 90 % of cancer patients report symptoms of insomnia during and after treatment. Symptoms of insomnia include excessive daytime sleepiness, difficulty falling asleep, difficulty staying asleep, and waking up too early. Insomnia symptoms are among the most prevalent, distressing, and persistent cancer- and cancer treatment-related toxicities reported by patients and can be severe enough to increase cancer morbidity and mortality. Despite the ubiquity of insomnia symptoms, they are underscreened, underdiagnosed, and undertreated in cancer patients. When insomnia symptoms are identified, providers are hesitant to prescribe pharmaceuticals, and patients are reluctant to take them due to polypharmacy concerns. In addition, sleep medications do not cure insomnia. Yoga is a well-tolerated mode of exercise with promising evidence for its efficacy in improving insomnia symptoms among cancer patients. This article reviews existing clinical research on the effectiveness of yoga for treating insomnia among cancer patients. The article also provides clinical recommendations for prescribing yoga for the treatment of insomnia in this population.
Cancer Pain and Opioids—Past, Present, and Future
Authors: Crawford Gregory B ,   Senior Consultant in Palliative Medicine, Director of Research & Education, Northern Adelaide Palliative Service, Adelaide, Australia; Associate Professor of Palliative Medicine, Discipline of Medicine, University of Adelaide, Australia
Published: October 2015

The Cancer Council Australia and Cancer Institute New South Wales are two Australian organizations that are providing useful resources to support evidence-based prescribing of opioids in cancer pain. Morphine remains the preeminent medication for nociceptive cancer pain. Our understanding of the action of opioids, and how relatively recently these developments are, assists in putting pain and suffering in the context of total pain. Increasing understanding of the how pain is understood is leading to new insights with an increasing emphasis on the neuroimmuno- pharmacology of pain.
The Role of Vacuum Device Therapy in the Management of Erectile Dysfunction
Authors: Lewis Ronald W , Newell Mark M
Published: October 2015

In November 1996, the American Urological Association (AUA) handed down guidelines for treating erectile dysfunction (ED), and urged all physicians to give sound and unbiased explanations of all ED treatments to their patients.1Currently, nearly all urologists and many primary care physicians routinely ask whether their patients are experiencing erectile problems. If the answer is positive, then treatment options are discussed.
Adding to the Armamentarium for the Treatment of Diabetes Mellitus
Authors: Triplitt Curtis
Published: October 2015

Current estimates are that more than 20 million people in the US have diabetes. Diabetes mellitus, especially type-2 diabetes mellitus (T2DM), is an increasingly common chronic disease with the potential for significant morbidity and mortality. People with diabetes are at an increased risk of both macrovascular complications, such as myocardial infarction and stroke, and microvascular complications, including retinopathy, neuropathy and nephropathy. The prevention and early detection of complications is paramount to improving outcomes, as diabetes and its complications are estimated to cost over US$100 billion per year in the US.
Diabetic Foot Complications
Authors: M Boulton Andrew J
Published: October 2015

Diabetic foot complications comprise foot ulceration, Charcot neuroarthropathy, and amputation. Foot complications are exceedingly common and it is estimated that more than 5% of diabetic patients will have a history of foot ulcers, whilst the cumulative lifetime risk of foot ulceration may be as high as 25%.1

As up to 85% of all amputations are preceded by foot ulcers, it is safe to presume that any success in reducing foot ulcer incidence will be followed by a reduction in amputation. The economic consequences of diabetic foot lesions to the healthcare providers are vast: a recent global review2estimated that diabetic foot problems (ulcers and amputations) cost the US healthcare payers US$10.9 billion in 2001, with the equivalent figure for the UK being £252 million.This paper will therefore focus on the causation and potential for prevention of diabetic foot ulcers followed by a small note on Charcot neuroarthropathy, which is much rarer than foot ulceration.
An Update on Female Puberty
Authors: Sanfilippo Joseph S
Published: October 2015

Puberty is best defined at the period of life during which one acquires reproductive capabilities. As a female transitions from childhood to adulthood, one witnesses a significant reactivation of the hypothalamicpituitary- ovarian (HPO) axis; this axis is functional in utero.The hallmarks of pubertal development include:

All this may take three to five years for completion.The American Academy of Pediatrics Pediatric Research in Office Settings (PROS) Study has provided the latest information regarding age of onset of specific pubertal milestones. PROS focused on breast development— thelarche (an early sign of the onset of puberty) occurs in African-American girls at 8.87 years and in white American girls at 9.96 years of age; the onset of pubic and axillary hair development, i.e. pubarche, occurs in African-American girls at 8.78 years and in white girls at 10.51 years of age.1,2Additional information is detailed inTable 1.
Womens Sexual Health Update on Testosterone Therapy
Authors: Goldstein Irwin
Published: October 2015

There are limited numbers of healthcare facilities offering comprehensive psychological and biological sexual healthcare for women. This, however, is expected to change over the next few years for the following reasons:
Diabetes in Sub-Saharan Africa – Overview of a Looming Health Challenge
Authors: Assah Felix K , Mbanya Jean-Claude ,   Doctoral Student, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge,   Professor of Medicine and Endocrinology, Department of Internal Medicine and Specialities, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I
Published: October 2015

The number of people living with diabetes in the world is increasing rapidly. Most of the increase will occur in developing countries such as those in sub-Saharan Africa. Diabetes is currently recognised as a real and imminent threat to social and economic development globally and is set to be a major public health challenge in the 21st century. In sub-Saharan Africa, the challenge posed by diabetes is even more overwhelming since diabetes will have to share scarce resources with infections and malnutrition. Even worse, diabetes still has to gain sufficient political and social recognition in order to warrant aggressive national policies for prevention and treatment. In this article we present an overview of the burden of diabetes in sub-Saharan Africa and the specificities of care and control, and highlight the importance of developing effective national diabetes programmes.
The Role of Insulin in the Regulation of PEPCK and Gluconeogenesis In Vivo
Authors: Ramnanan Christopher J , Edgerton Dale S , Cherrington Alan D ,   Post-doctoral Fellow,   Research Assistant Professor,   Professor, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine
Published: October 2015

The regulation of gluconeogenesis by insulin is complex and can involve insulin-mediated events in the liver, as well as in several non-hepatic tissues. Given the complexity of this regulation, it is no surprise that there is considerable debate regarding insulin’s ability to regulate the rate of gluconeogenic formation of glucose-6-phosphate (GNG flux to G6P)in vivo. Conventional ‘textbook’ teaching (based onin vitrostudies of rat liver) depicts that insulin can inhibit this pathway by suppressing the transcription of the enzyme phosphoenolpyruvate carboxykinase (PEPCK). PEPCK is widely considered to be a ‘rate-limiting’ enzyme with high control strength. Additionally, recent data in rodents have led to the conclusion that hyperinsulinemia in the brain can inhibit GNG flux to G6P, likely through transcriptional regulation of PEPCK. Recent data from the authors’ lab have confirmed that the molecular regulation of PEPCK messenger RNA (mRNA) and protein by insulin is conserved in large animals. Acute physiological hyperinsulinemia does not alter gluconeogenic formation of G6P, however, despite substantial reductions in PEPCK protein. This indicates that PEPCK has poor regulatory control over the pathwayin vivo. A physiological rise in insulin suppresses hepatic glucose production by inhibiting glycogenolysis and promoting glycogen synthesis, stimulating glycolytic flux, and redirecting gluconeogenically derived carbon to glycogen. This review documents the relevant ways in which insulin can regulate GNG flux to G6Pin vivo.